OBJECTIVES: To evaluate the internal adaptation of recent pulp capping materials (TheraCal and Biodentine) relative to MTA when used as indirect pulp capping for primary teeth. MATERIALS AND METHODS: Thirty primary molars were randomly allocated into three groups, group (A) was TheraCal, group (B) was Biodentine, and MTA was the control group (C). A standardized round class-V cavity (1.5 mm diameter and 2 mm depth) was prepared using a milling machine on the buccal surface of each tooth with the pulpal floor located on the dentin. Then, pulp-capping materials were applied. Finally, all teeth were restored by composite restoration. The internal adaptation of the pulp-capping materials to the dentinal surface was investigated by microcomputed tomography (Micro-CT) to determine the internal gap volume, and by optical coherence tomography (OCT) to determine the high-intensity reflection of light from the floor. RESULTS: Based on Micro-CT findings, TheraCal showed significantly higher internal gap volume than both MTA and Biodentine (p < 0.001), while MTA and Biodentine did not show a significant difference in the gap volume. Based on the OCT findings, TheraCal showed a significantly higher intensity of light reflection than both MTA and Biodentine (p < 0.001); however, there was no significant difference between MTA and Biodentine. Pearson's correlation test showed that there was a strong positive correlation between Micro-CT and OCT (r = 0.686, N = 30, p < 0.001). CONCLUSIONS: Biodentine and MTA showed a comparable result in terms of their internal adaptation on the dentinal surface of the primary teeth, and both were better than TheraCal. There is a moderate to a strong positive correlation between Micro-CT and OCT in the measurement of internal adaptation of the tested pulp capping materials. OCT can be helpful and beneficial for the clinical setting and allow dentists to screen and evaluate restorations during follow-up.

OBJECTIVE: This study is aimed at providing a nonbridging external fixation technique with pinning fixation for the pronation-abduction stage III ankle fracture. The secondary purpose was to evaluate its effect on anatomic reduction and fracture fragment stability against cadaveric models' rotation. METHOD: A paired design study was conducted using 14 pairs of the cadaveric model which had been modeled for pronation-abduction stage III ankle fracture. One fracture model from each pair was randomly allocated to receive an open reduction and internal fixation, while the other was reduced and stabilized with the external fixation technique. After the surgery, the antirotational stability tests were performed with external rotation torques of 10 nm, 15 nm, and 20 nm applied, respectively. The postoperation reduction rate and ankle parameters were recorded in anteroposterior and lateral radiographs before and after the antirotational stability experiment. RESULT: The outcomes were assessed according to Burwell-Charnley's radiographic criteria of reduction. It showed no statistically significant differences in reduction between the two groups (P < 0.05). The displacement of lateral fragment following a reduction in the external fixation group was significantly larger than that of the internal fixation group (3.14 ± 0.56 vs. 1.49 ± 0.39, P < 0.05). After applying rotational torques of 10 nm, 15 nm, and 20 nm, the results of other parameters showed no significant differences between the two groups. CONCLUSION: This nonbridging external fixation method with pin fixation of fracture fragments might have the same effect as that of internal fixation on the reduction rate of pronation-abduction stage III ankle fracture.

Acute graft-versus-host disease (aGVHD) remains a significant and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to the occurrence of aGVHD, allo-HSCT significantly increases the mortality rate compared with autologous hematopoietic stem cell transplantation (auto-HSCT). In this study, auto-HSCT and allo-HSCT aGVHD mouse models were built to detect the difference in CD4+ lymphocyte in different tissues based on ribonucleic acid sequencing (RNA-Seq) analysis. Clustering analysis, functional annotation, and pathway enrichment analysis were performed on differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was used to find hub genes. CD4+T cells were activated by MLR and cytokine stimulation. Cells were sorted out by a flow cell sorter. The selected genes were verified by qRT-PCR, histology, and immunofluorescence staining. The GSE126518 GEO dataset was used to verify the hub genes. Enrichment analysis revealed four immune-related pathways that play an important role in aGVHD, including immunoregulatory interactions between a lymphoid and a nonlymphoid cell, chemokine receptors binding chemokines, cytokine and cytokine receptor interaction, and the chemokine signaling pathway. At the same time, with the PPI network, 11 novel hub genes that were most likely to participate in immunoregulation in aGVHD were identified, which were further validated by qRT-PCR and the GSE126518 dataset. Besides, the protein expression level of Cxcl7 was consistent with the sequencing results. In summary, this study revealed that immunoregulation-related DEGs and pathways played a vital role in the onset of aGVHD. These findings may provide some new clues for probing the pathogenesis and treatment of aGVHD.

OBJECTIVES: The aim of our study was to investigate the association of single-nucleotide polymorphism (SNP) and mRNA expression profile of single immunoglobulin IL-1-related receptor (SIGIRR) in rheumatoid arthritis (RA) in a Chinese population. METHODS: SIGIRR rs7396562 polymorphism was genotyped using TaqMan allelic discrimination assay in 517 RA patients and 601 healthy controls. Simultaneously, the SIGIRR mRNA expression levels of 79 RA patients and 76 healthy controls were examined by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The frequency of SIGIRR rs7396562 T allele was significantly higher in RA patients compared with healthy controls (T versus G: OR = 1.277, 95%CI = 1.079 - 1.511, P = 0.004). The TT genotype of SIGIRR rs7396562 was more frequent in RA patients than in healthy controls (OR = 1.547, 95%CI = 1.107 - 2.163, P = 0.011). Moreover, we also found a significant difference in the recessive model (TT versus TG+GG: OR = 1.439, 95%CI = 1.122 - 1.847, P = 0.004). However, no significant evidence was observed for the association of the SIGIRR rs7396562 with RA in dominant model (TT+TG versus GG: OR = 1.275, 95%CI = 0.947 - 1.717, P = 0.109). Further analysis showed no association between SIGIRR rs7396562 polymorphism and laboratory parameters of RA patients (all P > 0.05). The mRNA expression of SIGIRR was decreased in PBMCs of patients with RA when compared to healthy controls (Z = -2.459, P = 0.014). No significant differences in SIGIRR mRNA expression levels were observed in patients with RA with different genotypes (P = 0.280). CONCLUSIONS: Our findings demonstrated that the dysregulation of SIGIRR might be associated with the pathogenesis of RA, and SIGIRR rs7396562 polymorphism might contribute to RA susceptibility in the Chinese population.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most life-threatening malignancies. The crucial role of bone morphogenetic protein (BMP)/BMP receptors reveals the significance of exploring BMP protein-related prognostic predictors in LUAD. METHODS: The mRNA expression of BMPs/BMP receptors was investigated in LUAD and normal lung tissues. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed, and the prognostic values were assessed by Kaplan-Meier Plotter. Univariate and multivariate Cox regression analyses were executed to ascertain the correlation between overall survival (OS) and the mRNA expression of BMPs/BMP receptors. The receiver operating characteristic (ROC) curves were implemented to evaluate the predictive power of the prognostic model. Then, the prognostic model was validated in the GEO cohort. Furthermore, a nomogram comprising the prognostic model was established. RESULTS: The mRNA expression of BMP2/5/6/R2, ACVRL1, and TGFBR2/3 was lower in LUAD tissues than in normal lung tissues. High expression of BMP2/4/5/R1A/R2, ACVR1/2A/L1, and TGFBR1/3 was associated with better OS, while BMP7 and ACVR1C/2B were associated with poorer OS. Three genes (BMP5, BMP7, and ACVR2A) were screened by univariate and multivariate Cox regression analyses to develop the prognostic model in TCGA. Significantly better survival was observed in LUAD patients with a low-risk score than those with a high-risk score. The ROC curves confirmed the good performance of the prognostic model, then, the prognostic model was validated in the GSE31210 dataset. A nomogram was constructed (AUCs>0.7). And hub genes were further evaluated, including gene set enrichment analysis and immune cell infiltration. CONCLUSIONS: BMP5, BMP7, and ACVR2A are potential therapeutic targets in LUAD. The three-gene prognostic model and the nomogram are reliable tools for predicting the OS of LUAD patients.

Perioperative bleeding is one of the major comorbidities associated with surgery. While anesthesia is a critical component to perform surgery, a number of clinical studies supported the contribution of anesthetic drugs to perioperative bleeding. Here, we reviewed the literature on this topic including the underlying mechanism and discussed the future direction on coagulation research in anesthesia.

This paper describes a convenient and straightforward method developed to extract keratin particles (KPs) from human hair. It also involves their characterization by several methods and encapsulation of the anticancer drug Paclitaxel (Taxol) within them, aiming for targeted delivery to cancerous sites and slow release at their vicinity. The KPs obtained were in micrometer in size. They are capable of encapsulating Taxol within them with a high encapsulation efficiency of 56% and a drug loading capacity of 2.360 g of Taxol per g keratin. As revealed by the SEM elemental analysis, KPs do not contain any toxic metal ion, and hence, they pose no toxicity to human cells. The pH-dependent release kinetics of the drug from KPs indicates that the drug is released faster when the pH of the solution is increased in the 5.0 to 7.0 pH range. The release kinetics obtained is impressive, and once targeted to the cancerous sites, using cancer directing agents, such as folic acid; a glutamate urea ligand known as DUPA; aminopeptidase N, also known as CD13; and FAP-α-targeting agents, the slow release of the drug is expected to destroy only the cancerous cells. The Noyes-Whitney dissolution model was used to analyze the release behavior of Taxol from KPs, which shows excellent fitting with experimental data. The pH dependence of drug release from keratin is also explained using the 3-D structures and keratin stability at different pH values.

BACKGROUND: Malnutrition accounts for almost half of the global under-five child mortality. Worm infections are one of the immediate and commonest causes that affect the nutritional status of children. There is limited data related to the magnitude of wasting and associated factors among children. Therefore, this study was aimed at assessing the magnitude of wasting and associated factors among children aged 2 to 5 years in the Wonago district of Gedeo Zone, southern Ethiopia. METHODS: Community-based cross-sectional study design was conducted. A total of 3324 children aged 2-5 years were included in the study. A pretested semistructured questionnaire was used for data collection, and anthropometric measurements were computed using the World Health Organization Anthro-nutritional software. The multivariate logistic regression analyses with adjusted odds ratio, 95% confidence interval, and P value less than 0.05 were used to identify the factors significantly associated with wasting. RESULTS: A total of 3273 children aged 2-5 years participated with a 98.5% response rate. The magnitude of wasting was 13%. The factors like government-employed fathers [AOR = 1.93; 95% CI (1.08, 3.46)], child's age range between 48 and 59 months [AOR = 1.46; 95% CI (1.01, 2.09)], being a male child [AOR = 1.42; 95% CI (1.07, 1.88)], having diarrheal disease in the past two weeks [AOR = 0.39; 95% CI (0.17, 0.90)], and bathing less than two times per week [AOR = 1.42; 95% CI (1.03, 1.96)] were factors significantly associated with wasting. CONCLUSION: Undernutrition in children is still a problem, and the proportion of wasting was 13%. Government-employed fathers, child's age range between 48 and 59 months, being a male child, having diarrheal disease in the past two weeks, and bathing below two times per week were significantly associated with children's nutritional status warranting close attention by policymakers and stakeholders. For researchers, a further longitudinal study is recommended to get strong evidence.

OBJECTIVE: Alveolar echinococcosis (AE) is a zoonosis caused by the larval stage of the metacestode Echinococcosis multilocularis with a tumor-like behavior in the targeted organ, especially in the liver. Surgery with albendazole is first-line modality for AE. Drug discontinuation is usually based upon the parasitic viability shown by the positron emission tomography (PET) scan. However, as a demanding and expensive method, it is not widely practiced in majority of the endemic regions. Further understanding on the cytokine and chemokine response profiles in AE patients may provide an interesting insight for potential markers in viability assessment. METHODS: Mice were inoculated with Echinococcus multilocularis intrahepatically to develop the hepatic AE murine model. Oral albendazole administration was then applied for three months after the first inoculation, and peripheral and regional immune cells including type 1 T helper cells (Th), Th2, Th17, regulatory T (Treg) cells, related cytokines, and chemokines were examined. RESULTS: The hepatic AE lesion was confirmed by ultrasound examination resulting in a successful rate of 70%. Among the 17 cytokines and chemokines detected, plasma levels of IL-23 were significantly higher in E. multilocularis-infected mice when compared to the control group; furthermore, more obvious increasing levels were found after albendazole treatment (p < 0.05). All chemokine levels other than eotaxin and MCP-3 were slightly higher in E. multilocularis-infected mice compared to the control group (p > 0.05). Eotaxin levels were significantly decreased in mice with E. multilocularis infection followed by albendazole treatment (p < 0.05). Both IL-17A and IL-23 expressions in hepatic AE lesions were significantly higher and related with disease activity. CONCLUSION: Albendazole administration influenced the balance of immune response and promotes the secretion of proinflammatory factors which is beneficial to parasite clearance. IL-23 seems to be associated with the successful albendazole treatment in mice with E. multilocularis infection; such a change could be translated into clinical application in the near future.

OBJECTIVE: This study is aimed at exploring the role of vitamin D in the treatment of children with OSAHS by comparing the clinical symptoms, serum indicators, and behavioral changes of vitamin D intervention. METHOD: Healthy children who were examined physically in Rizhao People's Hospital were selected as the control group, and their sex, age, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, serum 25-OHD levels, and Conners' parental scale were measured. In addition, children diagnosed as OSAHS in the otolaryngology department of Rizhao People's Hospital were selected as experimental subjects. Their body mass index, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, serum 25-OHD levels, sleep apnea hypopnea index, minimum oxygen saturation, and Conners' parental scale were measured. The experimental subjects were treated with Rocaltrol intervention therapy (0.25 g/QD) for 4 weeks and reanalyzing their triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, serum 25-OHD levels, sleep apnea hypopnea index, minimum oxygen saturation, and Conners' parental scale. RESULT: OSAHS children commonly have the situation of obesity, dyslipidemia, and vitamin D deficiency. Behavioral and cognitive dysfunction is common in OSAHS children. There were no significant changes in body mass index, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, sleep apnea, hypopnea index, and minimum oxygen saturation for OSAHS children after vitamin D treatment, but the serum 25-OHD level is significantly improved, and children with conduct problems, learning problems, and hyperactivity index decrease. CONCLUSION: (1) OSAHS children commonly have the situation of obesity, dyslipidemia, vitamin D deficiency, and behavioral and cognitive impairment. (2) Vitamin D supplementation has no therapeutic effect on obesity and dyslipidemia of OSAHS children, but has obvious protective and improving effects on neuron damage caused by hypoxia. Obstructive sleep apnea syndrome (OSAHS) is a common disease. Patients with OSAHS usually have many clinical features, such as obesity, metabolic syndrome, and cardiovascular disease. The decline of cognitive function and learning ability is one of the serious complications of OSAHS patients [1]. Vitamin D (VitD) deficiency is associated with many diseases. Recent studies have shown that the serum 25-OHD level of OSAHS patients is relatively insufficient and related to the disease severity. However, there are few reports on explaining whether vitamin D supplementation can alleviate the clinical symptoms and improve serum indicators and behavioral and cognitive dysfunction in children with OSAHS.

Contact dermatitis is a frequent skin disorder related to environmental and occupational etiological factors, which could potentially affect all age groups, as well as both genders. The current study is aimed at exploring the patterns of contact sensitization with respect to the population's occupational patterns in Greece. A retrospective analysis was performed in a cohort of 1978 patients from 2014 to 2016. Patients were divided into two categories; blue collars (BlC) and white collars (WhC), as well as detailed occupation was considered. Separation was performed on the basis of their profession, i.e., labor workers and handicraftsmen were sorted to the BlC group, while office employees were sorted to the WhC group. The common allergen in all occupational subgroups was nickel sulphate. The three most prevalent allergens in both BlC and WhC were nickel sulphate 5%, fragrance mix (I) 8%, and Balsam of Peru 25%. WhC males were uniquely sensitized to colophony 20% and formaldehyde 2%, and WhC females were uniquely sensitized to 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and neomycin sulphate 20%. Sensitization to allergens manifested occupation-specific patterns. Allergic contact dermatitis surveillance is of great importance towards the clinical and systematic understanding of the disease, especially with respect to the patient's occupational profile.

In clinical treatment, the analytical quality assessment of the delivery of chemotherapeutic preparations is required to guarantee the patient's safety regarding the dose and most importantly the appropriate anticancer drug. On its own, the development of rapid analytical methods allowing both qualitative and quantitative control of the formulation of prepared solutions could significantly enhance the hospital's workflow, reducing costs, and potentially providing optimal patient care. UV-visible spectroscopy is a nondestructive, fast, and economical technique for molecular characterization of samples. A discrimination and quantification study of three chemotherapeutic drugs doxorubicin, daunorubicin, and epirubicin was conducted, using clinically relevant concentration ranges prepared in 0.9% NaCl solutions. The application of the partial least square discriminant analysis PLS-DA method on the UV-visible spectral data shows a perfect discrimination of the three drugs with a sensitivity and specificity of 100%. The use of partial least square regression PLS shows high quantification performance of these molecules in solution represented by the low value of root mean square error of calibration (RMSEC) and root mean square error of cross validation (RMSCECV) on the one hand and the high value of R-square on the other hand. This study demonstrated the viability of UV-visible fingerprinting (routine approach) coupled with chemometric tools for the classification and quantification of chemotherapeutic drugs during clinical preparation.

Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B6 and B12 deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.

Management of endometrial cancer, an adenocarcinoma of the endometrium which occupies most uterine corpus neoplasms, including uterine sarcomas, has been more relevant due to its increasing incidence. Extensive research on tumorigenesis molecular mechanisms and molecular characterization across cancers has brought paradigm shifts in the treatment of various malignant tumors. Endometrial cancer treatment has been traditionally guided according to the disease extent or histology types, while recent studies on molecular features have led to the introduction of targeted agents into clinical use, along with conventional chemotherapeutic agents in patients with recurrent or metastatic disease. Considering the proven efficacy and relatively tolerable toxicities of targeted therapies across malignant tumors, improvement of treatment outcomes is also expected in endometrial cancer by adopting an individualized therapy depending on the specific molecular features. Efficacy assessment of new biological agents is still ongoing based on previous preclinical data on endometrial cancer molecular features. Here, endometrial cancer molecular characterization will be reviewed, and then, we will introduce preclinical data, directing the adoption of new biological agents.

Substance P (SP) is a peptide involved in many biological processes, including nociception and inflammation. SP has a high affinity for its receptor neurokinin-1 (NK-1R). SP/NK-1R complex plays a major role in the interactions going on during the onset of dental pain and inflammation. Objective. To identify the expression of NK-1R in healthy and inflamed human dental pulp, as well as to identify any association with severity of dental pain. Methods. This case-control study included ten irreversibly inflamed samples of dental pulp, which were extirpated from patients presenting with chief complaint of dental pain due to caries. Ten healthy pulps, extirpated from those teeth which were indicated for extraction due to orthodontic reasons, were used as the control group. Visual analog scale (VAS) and modified McGill Pain Questionnaire were used to assess the characteristic and severity of pain. Immunohistochemical study was performed using monoclonal antibodies against NK-1R. Results. The results showed that the NK-1R was expressed intensely in patients with higher pain score. The mean pain score in cases was 7.0 ± 2.0. The healthy dental pulps had negative or mild NK-1R staining of +1 intensity. The NK-1R score in cases was 2.4 ± 0.516 and 0.2 ± 0.4216 in controls. There was significant difference in NK-1R score between both groups (p value <0.05). There was a strong positive correlation between the pain score and NK-1R expression score. As the pain increased, the NK-1R expression score was also increased (0.95∗∗, p value 0.000). Conclusions. NK-1R is overexpressed in inflamed dental pulp. SP/NK-1R modulation may provide a novel approach for the treatment of pulpal inflammation and pain.

BACKGROUND: The growth or multiplication of harmful microorganisms in addition to harmful human activities has led to many disorders in humans. Consequently, there is a search for medications to treat these disorders. Interestingly, medicines of plant origin are known to be among the most attractive sources of new drugs and have shown promising results in the treatment of various diseases including peptic ulcers. This review, therefore, is aimed at obtaining knowledge on some Ghanaian ethnomedicinal plants used to treat peptic ulcers, their folkloric uses, their phytochemicals, and their antiulcer and related pharmacological activities as well as finding areas for prospective studies. METHODS: Published peer-reviewed articles on ethnomedicinal plants used for the management of peptic ulcers in Ghana from 1967 to 2020 were sourced and used for the study. RESULTS: In this review, 13 plants were identified which belong to 10 different families including Sapindaceae, Apocynaceae, and Bignoniaceae. The parts most often used for most preparations were the leaves (53%), followed by stem bark and roots (both having the same percentage of use of 17.6%), the whole plant (5.9%), and the rhizomes (5.9%). Azadirachta indica was the only plant that had undergone some patient studies in addition to animal studies. Conclusion. A discussion of various antiulcer activity studies using ulcer models carried out on selected medicinal plants used for the management of peptic ulcer disease in addition to brief information on their folkloric uses and their phytochemical and other pharmacological properties is presented. These medicinal plants may be used in developing herbal products for the management of peptic ulcer disease.

Chromosomal abnormalities are the main genetic risk factor associated with reproductive and sexual development disorders (DSD). The goal of this study is to retrospectively evaluate the frequency of chromosomal aberrations in Moroccan subjects with problems of procreation or sexual ambiguity. A total of 1005 individuals, including 170 infertile couples, underwent cytogenetic analysis in the Cytogenetic Laboratory of the Pasteur Institute of Morocco. Heparinized blood samples were processed according to the standard karyotype method. A total (81.5%) of the patients studied had a normal karyotype, while the remaining (18.5%) patients had an abnormal karyotype. Female patients had more chromosomal abnormalities (52%) than male patients (48%). These chromosomal aberrations included 154 cases (83%) of sex chromosomal abnormalities, the most common being Turner's syndrome and Klinefelter's syndrome, and 31 cases (17%) had autosomal aberrations, especially chromosome 9 reversal (inv(9)(p12;q13)). The present data shows that among 170 couples, 10.6% had chromosomal abnormalities mainly involved in the occurrence of recurrent miscarriages. Genotype-phenotype correlations could not be made, and therefore, studies using more resolutive molecular biology techniques would be desirable.

This study is aimed at assessing the influence of Nd:YAG, Er,Cr:YSGG laser irradiation, and adjunctive photodynamic therapy (aPDT) on the bond strength of zirconia posts to radicular dentin. Eighty extracted anterior teeth were randomly categorized into 4 groups (n = 20) based on varying laser irradiation treatments, i.e., conventional cleaning and shaping (CCS), Nd:YAG, Er,Cr:YSGG, and aPDT group, respectively. Using a cutting machine, the samples were prepared for push-out bond strength analysis; 4 sections (2 on each apical and cervical) of around 1 mm thickness were sectioned for all roots at a right angle to the long axis of the post. After making the space for the post, they were incorporated into the root system and were subjected to different laser treatments. The universal testing machine was utilized to assess the push-out bond strength, which had a defined 1 mm/minute crosshead speed until the failure was encountered. Specimens in the aPDT group (8.20 ± 2.14 MPa) demonstrated the highest mean push-out bond strength, whereas the lowest was shown by samples in the CCS group (7.08 ± 1.11 MPa). According to the independent t-test, the mean push-out bond strength scores of the cervical segments were higher as compared to the apical segments in research groups (p < 0.05). Overall, the adhesive type was the most frequently encountered failure mode in all of the experimental groups, with the least number of failures observed in aPDT treated teeth samples. In conclusion, the push-out bond strength to radicular dentin was not much influenced by Nd:YAG, Er,Cr:YSGG laser, and aPDT in comparison with CCS. Although statistically not significant, however, the application of aPDT provided better outcomes as compared to other research groups.

Molecular characterization of oil palm germplasm is crucial in utilizing and conserving germplasm with promising traits. This study was conducted to evaluate the genetic diversity structures and relationships among 26 families of MPOB-Senegal oil palm germplasm using thirty-five microsatellite markers. High level of polymorphism (P = 96.26%), number of effective allele (N e = 2.653), observed heterozygosity (H o = 0.584), expected heterozygosity (H e = 0.550), total heterozygosity (H T = 0.666), and rare alleles (54) were observed which indicates that MPOB-Senegal germplasm has a broad genetic variation. Among the SSR markers, sMo00053 and sMg00133 were the most informative markers for discrimination among the MPOB-Senegal oil palm germplasm for having the highest private alleles and the rare alleles. For selection and conservation, oil palm populations with high rare alleles and Nei's gene diversity index should be considered as these populations may possess unique genes for further exploitation.

Traditional screening of cervical cancer type classification majorly depends on the pathologist's experience, which also has less accuracy. Colposcopy is a critical component of cervical cancer prevention. In conjunction with precancer screening and treatment, colposcopy has played an essential role in lowering the incidence and mortality from cervical cancer over the last 50 years. However, due to the increase in workload, vision screening causes misdiagnosis and low diagnostic efficiency. Medical image processing using the convolutional neural network (CNN) model shows its superiority for the classification of cervical cancer type in the field of deep learning. This paper proposes two deep learning CNN architectures to detect cervical cancer using the colposcopy images; one is the VGG19 (TL) model, and the other is CYENET. In the CNN architecture, VGG19 is adopted as a transfer learning for the studies. A new model is developed and termed as the Colposcopy Ensemble Network (CYENET) to classify cervical cancers from colposcopy images automatically. The accuracy, specificity, and sensitivity are estimated for the developed model. The classification accuracy for VGG19 was 73.3%. Relatively satisfied results are obtained for VGG19 (TL). From the kappa score of the VGG19 model, we can interpret that it comes under the category of moderate classification. The experimental results show that the proposed CYENET exhibited high sensitivity, specificity, and kappa scores of 92.4%, 96.2%, and 88%, respectively. The classification accuracy of the CYENET model is improved as 92.3%, which is 19% higher than the VGG19 (TL) model.

RESULTS: KIR2DL1 and ILT-2 expression on idNK cells was higher in healthy women than in RPL patients. Sildenafil enhanced NKG2A expression in RPL patients. VEGF concentration was higher in fertile woman idNK cell cultures. idNK cells were more sensitive for necrosis in RPL than in fertile women. SC did not influence VEGF production or idNK cell apoptosis. CONCLUSIONS: A combination of hypoxia, IL-15, and AZA promotes the conversion of pbNK into idNK cells CD56+CD16--expressing KIR receptors and produces VEGF. Alterations in KIR2DL1 and ILT-2 expression as well as impaired VEGF production were associated with RPL. SC affects NKG2A expression on RPL idNK cells. SC had no effect on VEGF release or idNK cell apoptosis.

Repulsive guidance molecule-a (RGMa) is a member of glycosylphosphatidylinositol- (GPI-) anchored protein family, which has axon guidance function and is widely involved in the development and pathological processes of the central nervous system (CNS). On the one hand, the binding of RGMa and its receptor Neogenin can regulate axonal guidance, differentiation of neural stem cells into neurons, and the survival of these cells; on the other hand, RGMa can inhibit functional recovery of CNS by inhibiting axonal growth. A number of studies have shown that RGMa may be involved in the pathogenesis of CNS diseases, such as multiple sclerosis, neuromyelitis optica spectrum diseases, cerebral infarction, spinal cord injury, Parkinson's disease, and epilepsy. Targeting RGMa can enhance the functional recovery of CNS, so it may become a promising target for the treatment of CNS diseases. This article will comprehensively review the research progression of RGMa in various CNS diseases up to date.

BACKGROUND: Genomic testing gives guidance to the treatment options in lung adenocarcinoma patients, but some patients are unable to obtain tissue samples due to lesion location or intolerance. Cell-free circulating tumor DNA (ctDNA) tested in plasma or pleural effusion is an advanced access to solve the problem. Our study descriptively identified the genetic variations of advanced Chinese lung adenocarcinoma patients and analyzed the overall survival of patients with EGFR mutations. METHODS: A total of 152 patients' plasma samples were included, and gene mutations were detected by NGS using an Illumina Miseq tabletop sequencer. RESULTS: Frequencies of altered were EGFR 46.05%, ALK 7.24%, KRAS 6.58%, PIK3CA 6.58%, PTEN 2.63%, HER2 1.97%, MET 1.97%, BRAF 1.32%, NF1 1.32%, and ROS1 0.66%. We identified 48 cases with double or triple driver gene mutations. Multiple mutations were more frequently observed in EGFR and PIK3CA genes. Patients harboring coexistent mutations with an EGFR mutation tended to have a shorter overall survival than those with exclusively EGFR mutations. CONCLUSION: EGFR, ALK, and KRAS were common driver gene in Chinese patients with stage IV lung adenocarcinoma. Multiple mutations were detected in the ctDNA samples and involve more EGFR and PIK3CA mutations. The existence of coexisting gene mutations may have adverse effects on the prognosis of patients with EGFR mutation. The unknown mutations discovered by NGS may provide new targets for gene targeting therapy, and ctDNA test by NGS is an effective method for making appropriate treatment choices.

PURPOSE: Obstructive sleep apnea is a condition involving repetitive partial or complete collapse of the pharyngeal airway, especially in patient with mandibular hypoplasia. The present study investigated the differences between the volume of the oropharyngeal airway and the minimum axial area in three skeletal patterns through the use of cone-beam computed tomography (CBCT). MATERIALS AND METHODS: CBCT scans of 147 patients were collected to measure the upper oropharyngeal airway volume (UOV), lower oropharyngeal airway volume (LOV), upper oropharyngeal airway area (UOA), minimum upper oropharyngeal airway area (MUOA), lower oropharyngeal airway area (LOA), minimum lower oropharyngeal airway area (MLOA), anatomical structures (orbitale, Or; porion, Po; pogonion, Pog; hyoid, H; second cervical vertebra, C2; fourth cervical vertebra, C4), and relevant angles. Statistical analysis was performed using analysis of variance and Pearson's test. RESULTS: Compared with patients in Class II, those in Class III and Class I exhibited a significantly anterior position of H and Pog. The vertical positions of H and Pog revealed no significant difference between the three skeletal patterns. Patients in skeletal Class III exhibited significantly larger oropharyngeal area (UOA, MUOA, LOA, MLOA) and oropharyngeal airway (UOV and LOV) than those in skeletal Class II did. The horizontal position of Pog had a moderately significant correlation with UOA (r = 0.471) and MUOA (r = 0.455). CONCLUSION: Patients in skeletal Class II had significantly smaller oropharyngeal airway areas and volumes than those in Class III did. The minimum oropharyngeal cross-sectional area had a 67% probability of occurrence in the upper oropharyngeal airway among patients in Class I and Class II and a 50% probability of occurrence among patients in Class III.

Anethum graveolens, belonging to the family Apiaceae, has been extensively used for medicinal and therapeutic purposes since long. Plants encompass rich number of effective constituents with less toxicity. Thus, nowadays, the attempts are being made to search plant constituents that can prevent and reverse the chronic diseases, such as cancer. In this study, an in vitro antioxidant and anticancer efficacies of Anethum graveolens (AG-ME) were studied on human breast (MCF-7), lung (A-549), and cervical (HeLa) carcinoma cell lines. The antioxidant efficacies of AG-ME were evaluated by total antioxidant, DPPH radical scavenging, H2O2 scavenging, and ferrous reducing antioxidant assays. Further, the anticancer potential of AG-ME was also determined against different cancer cell lines. The AG-ME exhibited strong antioxidant activities as observed by antioxidant assays. AG-ME also showed a dose-dependent anticancer/cytotoxic potential against MCF-7, A-549, and HeLa cell lines. The AG-ME-induced reduction in GSH and increase in SOD activities indicates the role of oxidative stress in AG-ME-induced MCF-7 cell death. The results also exhibited that AG-ME triggered ROS production and significantly reduced MMP level. Moreover, a dose-dependent increase in caspase-3 and caspase-9 activities suggests that the AG-ME-induced MCF-7 cell death is caspase-dependent. Together, the present study provides reasoning and reassurance for the uses of A. graveleons for medical purposes as an antioxidant and anticancer agent. Additional investigations are required to examine biological and anticancer activities under an in vivo system to discover a possible beneficial use of AG-ME against diseases.

The main objective of this study was to device-assess the levels of physical activity and sedentary behaviour patterns of older adults during the situation prior to the COVID-19 pandemic, home confinement, and phase-0 of the deescalation. We also aimed to analyse the effectiveness of an unsupervised home-based exercise routine to counteract the potential increase in sedentary behaviour during the periods within the pandemic. A total of 18 noninstitutionalized older adults(78.4 ± 6.0 y.), members of the Spanish cohort of the EXERNET-Elder 3.0 project, participated in the study. They were recommended to perform an exercise prescription based on resistance, balance, and aerobic exercises during the pandemic. Wrist triaxial accelerometers (ActiGraph GT9X) were used to assess the percentage of sedentary time, physical activity, sedentary bouts and breaks of sedentary time. An ANOVA for repeated measures was performed to analyse the differences between the three different periods. During home quarantine, older adults spent more time in sedentary behaviours (71.6 ± 5.3%) in comparison with either the situation prior to the pandemic (65.5 ± 6.7%) or the ending of isolation (67.7 ± 7.1%) (all p < 0.05). Moreover, participants performed less bouts of physical activity and with a shorter duration during home quarantine (both p < 0.05). Additionally, no differences in the physical activity behaviours were found between the situation prior to the pandemic and the phase-0 of deescalation. According to our results, the home confinement could negatively affect health due to increased sedentary lifestyle and the reduction of physical activity. Therefore, our unsupervised exercise program does not seem to be a completely effective strategy at least in this period.

PURPOSE: The purpose of this study was to compare postintervention pain related to orthodontic treatment and orthognathic surgery. Material and Methods. One hundred patients who received only orthodontic treatment are the nonsurgical group. One hundred other patients were separated equally into the following four orthognathic surgical subgroups. The visual analog scale (VAS) score was used to measure postoperative pain. Patient- and operation-related factors were compared among the four surgical subgroups. The null hypothesis was that there was no difference between orthodontic treatment and orthognathic surgery in terms of posttreatment pain. RESULTS: There were no significant differences between the nonsurgical and surgical groups for gender (P = 0.780) or age (P = 0.473). The VAS scores of the nonsurgical group (mean: 3.59) were significantly (P = 0.007) higher than those of the surgical group (mean: 3.06). The null hypothesis was rejected. Within the surgical subgroups, no significant differences were observed between the men and women for age, operation time, blood loss volume, or blood laboratory values. CONCLUSIONS: The VAS scores of the orthodontic (nonsurgical) group were significantly higher than those of the surgical group. No significant differences in VAS scores were found between the four surgical subgroups.

Tissue decellularization has rapidly developed to be a practical approach in tissue engineering research; biological tissue is cleared of cells resulting in a protein-rich husk as a natural scaffold for growing transplanted cells as a donor organ therapy. Minimally processed, acellular extracellular matrix reproduces natural interactions with cells in vitro and for tissue engineering applications in animal models. There are many decellularization techniques that achieve preservation of molecular profile (proteins and sugars), microstructure features such as organization of ECM layers (interstitial matrix and basement membrane) and organ level macrofeatures (vasculature and tissue compartments). While structural and molecular cues receive attention, mechanical and material properties of decellularized tissues are not often discussed. The effects of decellularization on an organ depend on the tissue properties, clearing mechanism, chemical interactions, solubility, temperature, and treatment duration. Physical characterization by a few labs including work from the authors provides evidence that decellularization protocols should be tailored to specific research questions. Physical characterization beyond histology and immunohistochemistry of the decellularized matrix (dECM) extends evaluation of retained functional features of the original tissue. We direct our attention to current technologies that can be employed for structure function analysis of dECM using underutilized tools such as atomic force microscopy (AFM), cryogenic electron microscopy (cryo-EM), dynamic mechanical analysis (DMA), Fourier-transform infrared spectroscopy (FTIR), mass spectrometry, and rheometry. Structural imaging and mechanical functional testing combined with high-throughput molecular analyses opens a new approach for a deeper appreciation of how cellular behavior is influenced by the isolated microenvironment (specifically dECM). Additionally, the impact of these features with different decellularization techniques and generation of synthetic material scaffolds with desired attributes are informed. Ultimately, this mechanical profiling provides a new dimension to our understanding of decellularized matrix and its role in new applications.

Erratum for Biomed Res Int. 2021 Feb 8;2021:3948638.

Phosphoglycerate mutase 1 (PGAM1) is considered as a novel target for multiple types of cancer drugs for the upregulation in tumor, cell prefoliation, and cell migration. During aerobic glycolysis, PGAM1 plays a critical role in cancer cell metabolism by catalyzing the conversion of 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG). In this computational-based study, the molecular docking approach was used with the best binding active sites of PGAM1 to screen 5,000 Chinese medicinal phytochemical library. The docking results were three ligands with docking score, RMSD-refine, and residues. Docking scores were -16.57, -15.22, and -15.74. RMSD values were 0.87, 2.40, and 0.98, and binding site residues were Arg 191, Arg 191, Arg 116, Arg 90, Arg 10, and Tyr 92. The best compounds were subjected to ADMETsar, ProTox-2 server, and Molinspiration analysis to evaluate the toxicological and drug likeliness potential of such selected compounds. The UCSF-Chimera tool was used to visualize the results, which shows that the three medicinal compounds named N-Nitrosohexamethyleneimine, Subtrifloralactone-K, and Kanzonol-N in chain-A were successfully binding with the active pockets of PGAM1. The study might facilitate identifying the hit molecules that could be beneficial in the development of antidrugs against various types of cancer treatment. These hit phytochemicals could be beneficial for further investigation of a novel target for cancer.

The PadiU Putra rice line is a blast-resistant and high-yield rice line with high potential. The application of topdressing and the foliar applied method of silicon (Si) treatments could strengthen the culm to resist breakage and ultimately increase yield production. Treatments which consisted of a control, a Si topdressing, and a Si foliar applied were arranged in a randomised complete block design. At 55 days after transplanting (DAT), the foliar applied Si treatments had 59% higher dry matter partitioning to the roots. Meanwhile, at 75 DAT, both Si foliar applied and topdressing method showed increased assimilate partitioning into the culm sheath by 29% and 49%, respectively. Dark green and light yellowish colours were obtained in both Si treatments using UAV, indicating similar results to physiological responses. Remarkably, Si foliar applied treatments enhanced the diameter and width of the outer and inner layers of the diameter of vascular bundles at 75 DAT by 58, 181, and 80%, respectively. The yield production of rice increased by 53% in the Si foliar applied, compared to the control, and produced a 1.63 benefit-cost ratio.

Passive movement is an important mean of rehabilitation for stroke survivors in the early stage or with greater paralysis. The upper extremity robot is required to assist therapists with passive movement during clinical rehabilitation, while customizing is one of the crucial issues for robot-assisted upper extremity training, which fits the patient-centeredness. Robot-assisted teaching training could address the need well. However, the existing control strategies of teaching training are usually commanded by position merely, having trouble to achieve the efficacy of treatment by therapists. And deficiency of flexibility and compliance comes to the training trajectory. This research presents a novel motion control strategy for customized robot-assisted passive neurorehabilitation. The teaching training mechanism is developed to coordinate the movement of the shoulder and elbow, ensuring the training trajectory correspondence with human kinematics. Furthermore, the motion trajectory is adjusted by arm strength to realize dexterity and flexibility. Meanwhile, the torque sensor employed in the human-robot interactive system identifies movement intention of human. The goal-directed games and feedbacks promote the motor positivity of stroke survivors. In addition, functional experiments and clinical experiments are investigated with a healthy adult and five recruited stroke survivors, respectively. The experimental results present that the suggested control strategy not only serves with safety training but also presents rehabilitation efficacy.

Background. Magnolia officinalis Rehd. and Wils. is widely used in Asian countries because of its multiple pharmacological effects. This study investigated the gastroprotective effect and mechanisms of the ethanol extracts from the bark of Magnolia officinalis (MOE) against ethanol-induced gastric mucosal damage in rats. Methods. MOE was prepared by reflux extraction with 70% ethanol, and its main compounds were analyzed by UPLC-Q-Exactive Orbitrap-MS. DPPH, ABTS, and FRAP methods were used to evaluate the antioxidant capacity of MOE in vitro. The gastroprotective effects of MOE were evaluated by the area of gastric injury, H&E (hematoxylin-eosin), and PAS (periodic acid-Schiff). The mechanism was explored by measuring the levels of cytokines and protein in the NF-κB signaling pathway. Results. 30 compounds were identified from MOE, mainly including lignans and alkaloids. MOE presented a high antioxidant activity in several oxidant in vitro systems. Gastric ulcer index and histological examination showed that MOE reduced ethanol-induced gastric mucosal injury in a dose-dependent manner. MOE pretreatment significantly restored the depleted activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzymes, reduced malondialdehyde (MDA), and prostaglandin E2 (PGE2) levels in the gastric tissue in rats. In addition, MOE also inhibited the activation of nuclear factor kappa B (NF-κB) pathway and decreased the production of proinflammatory cytokines. Conclusions. The gastroprotective effect of MOE was attributed to the inhibition of oxidative stress and the NF-κB inflammatory pathway. The results provided substantial evidence that MOE could be a promising phytomedicine for gastric ulcer prevention.

BACKGROUND: This study is aimed at determining the predictive value of the gray-matter-white-matter ratio (GWR) on brain computed tomography for delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP). METHODS: This retrospective cohort study reviewed 352 patients with acute CO poisoning and who underwent the brain computed tomography test. These patients were admitted to Cangzhou Central Hospital from May 2010 to May 2020. The patients were divided into the DEACMP (n = 16) and non-DEACMP (n = 336) groups. Pearson's correlation coefficients were computed for correlation analysis. The predictive value of GWR for DEACMP was evaluated by using logistic regression analysis and receiver operator characteristic curves. RESULTS: The morbidity of DEACMP was 4.5% (16/352). The GWR-basal ganglia, GWR-cerebrum, and GWR-average in the DEACMP group were lower than those in the non-DEACMP group. Correlation analysis indicated that GWR-basal ganglia (r = 0.276; P < 0.001), GWR-cerebrum (r = 0.163; P = 0.002), and GWR-average (r = 0.200; P < 0.001) were correlated with DEACMP. Multivariate logistic regression analysis revealed that reduced GWR-basal ganglia, GWR-cerebrum, and GWR-average were independent risk factors (P < 0.001; P = 0.008; P = 0.001; respectively). Compared with GWR-cerebrum and GWR-average, GWR-basal ganglia had a higher area under the curve of 0.881 (95% confidence interval: 0.783-0.983) with sensitivity and specificity of 93.8% and 68.7%, respectively. The cut-off value of GWR-basal ganglia was 1.055. CONCLUSION: GWR, especially GWR-basal ganglia, is an early useful predictor for DEACMP.

OBJECTIVE: To evaluate the safety and efficacy of surgical ligation and endovascular embolization for the treatment of type II congenital extrahepatic portosystemic shunt (CEPS). METHODS: In this retrospective study, 23 patients diagnosed with type II CEPS between March 2011 and April 2019 were divided into either a surgical group (n = 13; 41.5 ± 19.9 years) or the interventional group (n = 10; 44.9 ± 19.7 years). The surgical group underwent laparoscopic surgical ligation of the shunt alone or ligation of the shunt and splenic artery and/or vein. The interventional group underwent endovascular embolization using microcoils, detachable coils, and vascular plug. RESULTS: All 23 patients received a one-step shunt closure, and their clinical symptoms were significantly improved within 3-month postprocedure and without recurrence during follow-up. The serum ammonia levels in both groups decreased after the procedure and dropped to normal level at 6- to 12-month postprocedure. Compared with baseline, the portal vein diameter in interventional group increased significantly at 3-, 6-, 12-, and 36-month postocclusion (P = 0.01 for all). The procedure time was shorter in the interventional group (127.0 ± 43.2 minutes) than the surgical group (219.8 ± 56.7 minutes; P < 0.001). The intraoperative blood loss in the interventional group (32.0 ± 62.5 mL) was less than that in the surgical group (238.5 ± 396.9 mL; P = 0.001). CONCLUSION: Both surgical ligation and endovascular embolization are effective in the treatment of type II CEPS. Endovascular embolization has the advantages of shorter procedure time and less intraoperative blood loss. The ligation of the portosystemic shunt and splenic artery and vein is feasible with apparent safety, and it could avoid a second surgical treatment.

BACKGROUND: Kinesio tape (KT) may be useful for the treatment of delayed onset muscle soreness (DOMS), but there has been no systematic review assessing their efficacy. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate the efficacy of KT on DOMS. METHODS: We searched seven databases for randomized controlled trials (RCTs) and crossover randomized trials of KT in DOMS, from the earliest date available to December 31, 2019. The primary outcome was muscle soreness. The secondary outcome was muscle strength and serum creatine kinase (CK) level. The risk of bias was evaluated based on the Cochrane criteria. Data were analyzed using RevMan version 5.3.0 software. P values < 0.05 were considered statistically significant. Systematic review registration number is CRD42020157052. RESULTS: Eight trials (six RCTs and two crossover randomized trials) with 289 participants were included. KT use significantly reduced muscle soreness at 48 h (mean difference (MD): -0.67, 95% confidence interval (CI): -1.10 to 0.24, P = 0.002) and 72 h postexercise (MD: -0.81, 95% CI: -1.45 to -0.17, P = 0.01) but not at 24 h. KT use improved muscle strength at 72 h postexercise (standardized mean difference: 0.35, 95% CI: 0.02 to 0.69, P = 0.04) but not at 24 or 48 h. However, the serum CK level at 24, 48, and 72 h postexercise was not better in the KT group relative to the control group. CONCLUSIONS: Current evidence suggests that KT might help to alleviate DOMS after strenuous exercise to improve muscle strength. Thus, using KT on the skin for more than 48 hours postexercise, but not for 24 h, appears more effective at relieving pain and improving muscle strength.

OBJECTIVE: Secretion of glucagon-like peptide 1 (GLP-1) and its effect on target organs were impaired in individuals with obesity. However, its mechanism needs to be further studied. We aim to explore the roles of the receptor of GLP-1 (GLP-1R) involved in high-fat-diet- (HFD-) induced kidney damage improved by emodin. METHODS: Male C57bl/6 mice were fed with HFD diet and therapied by emodin. NRK-52E cells were cultured and treated with palmitic acid or low-density lipoprotein cholesterol (LDL-C). Emodin was used to remedy the NRK-52E cell damage. GW9662 was administrated to block the function of peroxisome proliferator-activated receptor γ (PPAR-γ). GLP-1 in the plasma was measured by ELISA. PPAR-γ and GLP-1R in the kidney and NRK-52E cells were detected by western blotting. The interaction between PPAR-γ protein and GLP-1R promoter regions was observed by chromatin immunoprecipitation (ChIP). RESULTS: Postprandial GLP-1 levels in plasma, as well as PPAR-γ and GLP-1R, decreased in kidney tissue of HFD mice, while they were reserved by emodin treatment. Although PPAR-γ and GLP-1R were not downregulated by LDL-C, they were suppressed by palmitic acid. Interestingly, GLP-1R mRNA was detected by PCR in the mixture pulled down with PPAR-γ antibody. Additionally, downregulation of PPAR-γ and GLP-1R by palmitic acid was remanded by emodin. Moreover, GW9662, an inhibitor of PPAR-γ, abolished the protective effect of emodin. CONCLUSION: The kidney damage of HFD mice seems to be alleviated by emodin via the upregulation of GLP-1R in kidney tissue.

Previous studies have indicated that radiation resistance of glioma is one of the leading causes of radiotherapy failure. Mounting evidence suggests that long non-coding RNA (lncRNA) plays an important role in regulating radiosensitivity of cancer cells via implicating in various cell processes. However, the underlying mechanisms remain unclear and need further study, especially at the molecular level. We found that the expression level of lncRNA H19 was elevated by radiation, and then, the modulation of H19 affected the resistant of glioma cells to X-rays. Dual-luciferase reporter analyses showed that H19 was transcriptionally activated by CREB1 in glioma cells after irradiation. In addition, both flow cytometry and 5-ethynyl-2'-deoxyuridine (EdU) assay suggested that H19 was involved in the cell cycle arrest, apoptosis, and DNA synthesis to modulate the radiation response of glioma cells and influenced their radioresistance. Therefore, H19 might play a crucial role in enhancing the radioresistance of glioma.

Taxillus chinensis (DC.) Danser, a parasitic plant that belongs to the Loranthaceae family, has a long history of being used in the Chinese medicine. We observed that the loranthus seeds were sensitive to temperature and could lose viability below 0°C quickly. Thus, we performed small RNA sequencing to study the microRNA (miRNA) regulation in the loranthus seeds under cold stress. In total, we identified 600 miRNAs, for the first time, in the loranthus seeds under cold stress. Then, we detected 224, 229, and 223 miRNAs (TPM > 1) in A0 (control), A1 (cold treatment for 12 h at 0°C), and A2 (cold treatment for 36 h at 0°C), respectively. We next identified 103 differentially expressed miRNAs (DEmiRs) in the loranthus seeds in response to cold. Notably, miR408 was upregulated during the cold treatment, which can regulate genes encoding phytocyanin family proteins and phytophenol oxidases. Some DEmiRs were specific to A1 and may function in early response to cold, such as gma-miR393b-3p, miR946, ath-miR779.2-3p, miR398, and miR9662. It is interesting that ICE3, IAA13, and multiple transcription factors (e.g., WRKY and CRF4 and TCP4) regulated by the DEmiRs have been reported to respond cold in other plants. We further identified 4, 3, and 4 DEmiRs involved in the pathways "responding to cold," "responding to abiotic stimulus," and "seed development/germination," respectively. qRT-PCR was used to confirm the expression changes of DEmiRs and their targets in the loranthus seeds during the cold treatment. This is the first time to study cold-responsive miRNAs in loranthus, and our findings provide a valuable resource for future studies.

BACKGROUND: ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the safety of ML171 after a single intraperitoneal (IP) injection in mice. METHODS: The toxicity of a single dose of ML171 was evaluated in 6-week-old Institute of Cancer Research (ICR) mice in a good laboratory practice (GLP) laboratory. Twenty-five mice of each sex were assigned to five groups: negative control, vehicle control, and 125, 250, and 500 mg/kg of ML171. All mice were acclimatized for one week before beginning the study. Mice received an IP injection of ML171 or vehicle. The general condition and mortality of the animals were observed. The mice were sacrificed to evaluate histopathology 14 days after the administration of ML171 or vehicle. RESULTS: Bodyweights were not significantly different in any group. Three males and one female died due to ML171 administration in the 500 mg/kg dose group. Autopsies of the surviving mice did not reveal any significant abnormalities after the injection of 125 mg/kg of ML171. However, the anterior lobe edge of the liver was thickened and adhesions between the liver and adjacent organs were observed in mice treated with 250 or 500 mg/kg of ML171. In addition, hypertrophy of centrilobular hepatocytes and inflammatory cell infiltration were observed after injection of 250 and 500 mg/kg of ML171. CONCLUSION: Our results indicate that the lethal IP injection dose of ML171 is 500 mg/kg for both males and females. Mortality were not observed for lower doses of ML171. The safe dose of single IP ML171 in ICR mice was 250 mg/kg or less. Further studies are needed to confirm the safety of ML171 in the human body.

INTRODUCTION: Illicium verum commonly known as star anise has been widely used in many Asian countries for pharmaceutical treatment for many diseases. The aim of the present study was to investigate the anti-inflammatory, astringent, and antimicrobial properties of an Illicium verum mouthwash. METHODS: The present double blinded randomized clinical trial was conducted on fifty subjects, divided into groups A and B. Illicium verum mouthwash (group A) and placebo (group B) were provided to subjects for 21 days; after 14 days, washout period mouthwashes were switched as per crossover design between groups for 21 days. The gingival index (GI), papillary bleeding index (PBI), and oral microbial count were recorded at each stage of study. RESULTS: The significant intragroup difference was observed, before crossover in group A and after crossover in group B for GI, PBI, and oral microbial count at different stages of study. On comparing both group A and group B at the first and second follow-up for GI, PBI, and oral microbial count, a statistically significant difference (p < 0.05) was observed. A statistically highly significant mean intergroup and intragroup difference was seen for all the clinical parameters at different stages of study. CONCLUSION: The study revealed that the Illicium verum/star anise has potent antibacterial, anti-inflammatory, and astringent properties.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease with an eczematous rash and itching. Due to undesired adverse effects of traditional systemic treatment, there is still an unmet need for safe and effective long-term therapy for refractory AD. As our understanding of the pathogenesis underlying AD grows, novel treatments targeting specific molecules have been developed. Here, we discuss the efficacy and safety profiles of these drugs in recent clinical trials. Among their adverse effects, of particular note is AD acceleration. Although there is still debate about whether certain adverse reactions can be said to be paradoxical adverse events (PAEs), a wide range of PAEs have been reported during biological treatment for chronic immune-mediated diseases. Close surveillance of novel biologics is crucial to detect new undescribed paradoxical reactions and to shed light on the convoluted pathogenesis of AD.

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature babies, especially affecting those with very low or extremely low birth weights. Survivors experience adverse lung and neurological defects including cognitive dysfunction. This impacts the prognosis of children with BPD and may result in developmental delays. The currently available options for the treatment of BPD are limited owing to low efficacy or several side effects; therefore, there is a lack of effective treatments for BPD. The treatment for BPD must help in the repair of damaged lung tissue and promote further growth of the lung tissue. In recent years, the emergence of stem cell therapy, especially mesenchymal stem cell (MSC) therapy, has improved the treatment of BPD to a great extent. This article briefly reviews the advantages, research progress, and challenges faced with the use of MSCs in the treatment of BPD. Stem cell therapy is beneficial as it repairs damaged tissues by reducing inflammation, fibrosis, and by acting against oxidative stress damage. Experimental trials have also proven that MSCs provide a promising avenue for BPD treatment. However, there are challenges such as the possibility of MSCs contributing to tumorous growths, the presence of heterogeneous cell populations resulting in variable efficacy, and the ethical considerations regarding the use of this treatment in humans. Therefore, more research must be conducted to determine whether MSC therapy can be approved as a treatment option for BPD.

BACKGROUND: The preoperative platelet-to-lymphocyte ratio (PLR) evaluates the prognosis of gastric cancer patients. However, whether preoperative PLR may be used to evaluate the prognosis of mucinous gastric carcinoma (MGC) patients is poorly investigated. The present study evaluated the effect of preoperative PLR on overall survival in gastric cancer patients with a mucinous component. METHODS: A total of 336 MGC were enrolled in this study, and the characteristics of the tumor, including pathological features and clinical data, were retrospectively analyzed. RESULTS: A high PLR was associated with larger tumor size, advanced tumor invasion, lymph node metastasis, advanced TNM stage, tumor location, total gastrectomy, low hemoglobin level, low albumin level, high fibrinogen level, high platelet level, and high neutrophil-to-lymphocyte ratio (NLR, all P's < 0.05). Multivariate analysis identified age (HR = 1.876; 95% CI 1.361-2.585, P < 0.001), TNM stage (HR = 2.350; 95% CI 1.216-4.542, P = 0.011), globulin (HR = 1.520; 95% CI 1.067-2.165, P = 0.020), total gastrectomy (HR = 0.537; 95% CI 0.373-0.772, P = 0.001), and PLR (HR = 1.582; 95% CI 1.066-2.348, P = 0.023) as independent prognostic factors for OS. CONCLUSION: Preoperative PLR is related to pathological features and may independently evaluate the survival of MGC. Therefore, preoperative PLR may help physicians develop treatment plans and evaluate survival in these patients.

BACKGROUND: Addressing inequalities in accessing emergency obstetric care is crucial for reducing the maternal mortality ratio. This study was undertaken to examine the time trends and sociodemographic correlates of cesarean section (CS) utilization in Nepal between 2006 and 2016. Methods. Data from the Nepal Demographic and Health Surveys (NDHS) 2006, 2011, and 2016 were sourced for this study. Women who had a live birth in the last five years of the survey were the unit of analysis for this study. Absolute and relative inequalities in CS utilization were expressed in terms of rate difference and rate ratios, respectively. We used multivariable regression models to assess the CS rate by background sociodemographic characteristics of women. RESULTS: Age and parity-adjusted CS rates were found to have increased almost threefold (from 3.2%, 95% CI: 2.1-4.3 in 2006 to 10.5%; 95% CI: 8.9-11.9 in 2016) over the decade. In 2016, women from mountain region (3.0%), those from the lowest wealth quintile (2.4%), and those living in Karnali province (2.4%) had CS rate below 5%. Whereas women from the highest wealth quintile (25.1%), with higher education (21.2%), and those delivering in private facilities (37.1%) had CS rate above 15%. Women from the highest wealth quintile (OR-3.3; 95% CI: 1.6-7.0) compared to women from the lowest wealth quintile and those delivered in private/NGO-run facilities (OR-3.6; 95% CI: 2.7-4.9) compared to women delivering in public facilities were more than three times more likely to deliver by CS. CONCLUSION: To improve maternal and newborn health, strategies need to be revised to address the underuse of CS among poor, those living in mountain region and Province 2, Lumbini province, Karnali province, and Sudhurpaschim province. Simultaneously, there is a pressing need for policies, guidelines, and continuous monitoring of CS rates to reduce overuse among rich women, women with higher education, and those giving childbirth in private facilities.

INTRODUCTION: Microribonucleic acids (miRNAs) have short (approximately 18 to 25) nucleotides and are evolutionarily conserved and endogenously expressed RNAs belonging to a family of noncoding RNA molecules. miRNA-373 regulates cell proliferation, migration, apoptosis, invasion, and repairing damaged DNA after hypoxia stress. Neonatal hypoxic-ischemic encephalopathy (HIE) refers to perinatal asphyxia caused by partial or complete hypoxia, reduced or suspended cerebral blood flow, and fetal or neonatal brain damage. We aim to investigate the relationship between miRNA-373 and HIF-1α, between miRNA-373 MMP-9, and between miRNA-373 VEGF in the occurrence and development of HIE. METHODS: Human (children) samples were divided into four groups (n = 15 in each group) according to HIE severity. The patient group was divided into middle, moderate, and severe HIE groups. The control group included healthy children or children with nonneurological diseases. The expressions of miRNA-373, HIF-1α, MMP-9, and VEGF were assayed in the serum samples. RESULTS: Our study showed a strong relationship between miRNA-373 and HIF-1α, between miRNA-373 and MMP-9, and between miRNA-373 and VEGF. The expression levels of miRNA-373, HIF-1α, MMP-9, and VEGF in the HIE groups were much higher than those of the control group. CONCLUSION: The increased change in miRNA-373 expression has a certain diagnostic significance on neonatal HIE. In the occurrence and development of HIE, miRNA-373 is positively correlated with HIF-1α, MMP-9, and VEGF.

This study is aimed at investigating the features of fasciculation potentials (FPs) in amyotrophic lateral sclerosis (ALS) and peripheral nerve hyperexcitability syndromes (PNH). Needle electrophysiologic examination (EMG) was performed for 5-15 muscles in the ALS and PNH patients. The spontaneous activity of fasciculations and fibrillations/sharp-waves (fibs-sw) was recorded. The distribution, firing frequency, and waveform parameters of FPs in muscles were calculated and compared. In total, 361 muscles in ALS patients and 124 muscles in PNH patients were examined, with the FP detection rates of 45.1% and 53.2%. Moreover, the ALS patients with the upper limb onset had the highest FP detection rate. Fasciculations occurred more frequently in the upper limbs than in the lower limbs in ALS and PNH. The detection rate of fibs-sw in the bulbar muscle was relatively low, which could be elevated when combining fibs-sw and FPs. Benign FPs in PNH were of smaller amplitude, shorter duration, and fewer phases/turns, compared with malignant FPs in ALS. The FP area in PNH was significantly smaller than that in ALS. The incidence of polyphasic FPs in ALS was distinctly greater than that in PNH. The firing frequency of FPs in PNH was higher than that in ALS. There was no significant difference in the amplitude, duration, phases and turns, and area of FPs between groups with and without fibs-sw in the muscles of normal strength in ALS. Conclusively, it is necessary to detect the FPs in the thoracic and bulbar muscles of patients suspected having ALS. FP parameters in ALS are significantly different from PNH.

BACKGROUND: Fibrinogen and interleukin-1β as a proinflammatory cytokine and interleukin-10 and nesfatin-1 as an anti-inflammatory cytokine have an important role in the development and prevention of systemic inflammation and incidence of obesity-induced diseases. Thus, this study is aimed at the interaction effects of aerobic training and oak husk hydroalcoholic extract consumption on plasma levels of fibrinogen, interleukin-1β, nesfatin-1, and interleukin-10 in obese elderly male mice. MATERIALS AND METHODS: In this experimental study, 40 fat male mice were fed a high-fat diet for 4 weeks to induce obesity, and subsequently, they were divided randomly into four groups: control, supplement, exercise-placebo, and exercise-supplement. The training groups performed aerobic exercise 5 days a week for 6 weeks (approximately 80-75% VOmax 2). The supplement groups received a solution of oak husk hydroalcoholic extract at a dose of 20 milligram per kilogram of body weight for 6 weeks. Blood samples were taken 48 h after the last training session, and the levels of IL-10, fibrinogen, IL-1β, and nesfatin-1 were measured. Data were analyzed using one-way ANOVA and LSD post hoc tests. RESULTS: The results showed that six-week training and oak husk hydroalcoholic extract consumption significantly increased the levels of IL-10 and nesfatin-1 in experimental groups (P < 0.001). Also, the levels of fibrinogen and IL-1β decreased significantly in training groups. Averages between group variations of all indicators were statistically significant, and they were more meaningfully pronounced in the exercise-supplement group than other groups (P ≤ 0.05). CONCLUSIONS: Considering the results of the present study, the use of moderate aerobic exercise and oak husk hydroalcoholic extract is recommended to reduce the risk of obesity; it may also have a positive effect on inflammatory factors.

Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), a member of the 3-hydroxyacyl-CoA dehydrogenase family, were previously demonstrated to be involved in the tumorigenesis of various cancer types. This study is aimed at determining of the diagnostic and prognostic value of EHHADH in osteosarcoma (OS). The overexpression of EHHADH was found both in OS and also other sarcoma types, and according to the retrospective cohort study, the EHHADH level was related to the overall survival and disease-free survival of the OS patients. Furthermore, knockdown of EHHADH under the influence of EHHADH small interfering RNA significantly suppressed the proliferation ability of the tumor cells. Moreover, EHHADH overexpressed was found in human OS tissues. In summary, the progression of OS could be enhanced by EHHADH, which may be a potential diagnostic and prognostic biomarker for OS patients.

BACKGROUND: Over recent years, an increasing body of literature has focused on the relationship between erectile dysfunction (ED) and migraine. However, the specific mechanism is unclear. MATERIALS AND METHODS: We used a bioinformatic database to predict the targets and pathways associated with migraine and ED. Twenty male SD rats were randomly divided into a blank group (Group A, n = 10) and a migraine model group (Group B, n = 10). The rats in Group A were subcutaneously injected with normal saline (2 ml/kg) into the back of the neck. Rats in Group B were subcutaneously injected with nitroglycerin 10 mg/kg (5 mg/ml) into the back of the neck in order to create an animal model of migraine. Next, we carried out the measurement of erectile function. We used hematoxylin and eosin (HE) to compare the tissue structure of the cavernous body of the penis. Western blotting was used to determine the expression levels of PI3K, p-AKT, and p-mTOR in the protein; Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was used to determine the expression levels of PI3K, AKT, and mTOR in the messenger ribonucleic acid (mRNA). RESULTS: There are 117 intersection targets of migraine and ED, involving 188 cell biological processes (BP), 21 cellular components (CC), 31 molecular functions (MF), and 65 signaling pathways. HE staining results show that there were no significant differences between Group A and Group B with regard to any of the parameters. Compared with Group A, the levels of the PI3K, p-AKT, and p-mTOR proteins and PI3K, AKT, and mTOR mRNAs in Group B decreased (P < 0.01). CONCLUSIONS: The decline of erectile function in a rat model of migraine was associated with the PI3K/Akt/mTOR signaling pathway.

PURPOSE: The potential of UV-mediated photofunctionalization to enhance the resin-based luting agent bonding performance to aged materials was investigated. METHODS: Sixty samples of each material were prepared. Yttria-stabilized zirconia (YZr) and Pd-Au alloy (Pd-Au) plates were fabricated and sandblasted. Lithium disilicate glass-ceramic (LDS) was CAD-CAM prepared and ground with #800 SiC paper. Half of the specimens were immersed in machine oil for 24 h to simulate the carbon adsorption. Then, all of the specimens (noncarbon- and carbon-adsorbed) were submitted to UV-mediated photofunctionalization with a 15 W UV-LED (265 nm, 300 mA, 7692 μW/cm2) for 0 (control groups), 5, and 15 min and subjected to contact angle (Ɵ) measurement and bonded using a resin cement (Panavia™ V5, Kuraray Noritake, Japan). The tensile bond strength (TBS) test was performed after 24 h. The Ɵ (°) and TBS (MPa) data were statistically analyzed using two-way ANOVA and Bonferroni correction tests (α = 0.05). RESULTS: In the carbon-adsorbed groups, UV-mediated photofunctionalization for 5 min significantly decreased Ɵ of all materials and increased TBS of YZr, and UV for 15 min significantly increased the TBS of LDS and Pd-Au. In noncarbon-adsorbed groups, UV-photofunctionalization did not significantly change the Ɵ or TBS except YZr specimens UV-photofunctionalized for 15 min. CONCLUSION: UV-mediated photofunctionalization might have removed the adsorbed hydrocarbon molecules from the materials' surfaces and enhanced bond strengths of Panavia™ V5 to YZr, LDS, and Pd-Au. Additionally, UV-mediated photofunctionalization improved the overall TBS of YZr. Further investigation on the optimum conditions of UV photofunctionalization on indirect restorative materials should be conducted.

Selenium nanoparticles (SeNPs) are well-known bioactive compounds. Various chemical and biological methods have been applied to SeNP synthesis. Spirulina platensis is a widely used blue-green microalgae in various industries. In this study, the biosynthesis of SeNPs using sodium selenite and Spirulina platens has been developed. The SeNP synthesis was performed at different cultivation condition including pH and illumination schedule variation. The SeNPs were characterized by FT-IR, XRD, size, and zeta potential measurements, and the antioxidant activities of selected SeNPs were evaluated by DPPH and FRAP assays. FT-IR analysis showed the production of SeNPs. The 12 h dark/12 h light cycles and continuous light exposure at pH 5 led to the production of stable SeNPs with sizes of 145 ± 6 and 171 ± 13 nm, respectively. Antioxidant activity of selected SeNPs was higher than sodium selenite. It seems that green synthesis is a safe method to produce SeNPs as well as a convenient method to scale-up this production.

Erratum for Biomed Res Int. 2021 Feb 9;2021:5545078.

As one of important epigenetic modifications, DNA N4-methylcytosine (4mC) plays a crucial role in controlling gene replication, expression, cell cycle, DNA replication, and differentiation. The accurate identification of 4mC sites is necessary to understand biological functions. In the paper, we use ensemble learning to develop a model named i4mC-EL to identify 4mC sites in the mouse genome. Firstly, a multifeature encoding scheme consisting of Kmer and EIIP was adopted to describe the DNA sequences. Secondly, on the basis of the multifeature encoding scheme, we developed a stacked ensemble model, in which four machine learning algorithms, namely, BayesNet, NaiveBayes, LibSVM, and Voted Perceptron, were utilized to implement an ensemble of base classifiers that produce intermediate results as input of the metaclassifier, Logistic. The experimental results on the independent test dataset demonstrate that the overall rate of predictive accurate of i4mC-EL is 82.19%, which is better than the existing methods. The user-friendly website implementing i4mC-EL can be accessed freely at the following.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the world. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in GC development are still unclear. It is of great significance to explore the prognostic value of LncRNA signatures for GC. METHODS: LncRNAs differently expressed in GC and their prognostic value were studied based on The Cancer Genome Atlas (TCGA) database. The functional regulatory network and immune infiltration of RP11-357H14.17 were further studied using a variety of bioinformatics tools and databases. RESULTS: We found that the high expression of RP11-357H14.17 was closely associated with shortened overall survival (OS) and poor prognosis in gastric cancer patients. We also found that its expression was related to clinical features including tumor volume, metastasis, and differentiation. Functional enrichment analysis revealed that RP11-357H14.17 is closely related to enhanced DNA replication and metabolism; ssGSEA analysis implied the oncogenic roles of RP11-357H14.17 was related to ATF2 signaling and Treg cell differentiation. Furthermore, we verified such link by using real-time PCR and IHC staining in human GC samples. CONCLUSION: We demonstrate that RP11-357H14.17 may play a crucial role in the occurrence, development, and malignant biological behavior of gastric cancer as a potential prognostic marker for gastric cancer.

After the announcement of a new coronavirus in China in December 2019, which was then called SARS-CoV-2, this virus changed to a global concern and it was then declared as a pandemic by WHO. Human leukocyte antigen (HLA) alleles, which are one of the most polymorphic genes, play a pivotal role in both resistance and vulnerability of the body against viruses and other infections as well as chronic diseases. The association between HLA alleles and preexisting medical conditions such as cardiovascular diseases and diabetes mellitus is reported in various studies. In this review, we focused on the bioinformatic HLA studies to summarize the HLA alleles which responded to SARS-CoV-2 peptides and have been used to design vaccines. We also reviewed HLA alleles that are associated with comorbidities and might be related to the high mortality rate among COVID-19 patients. Since both genes and patients' medical conditions play a key role in both severity of the disease and the mortality rate in COVID-19 patients, a better understanding of the connection between HLA alleles and SARS-CoV-2 can provide a wider perspective on the behavior of the virus. Such understanding can help scientists, especially in terms of protecting healthcare workers and designing effective vaccines.

The pathogenesis of the osteoarthritis (OA) is complex. Abnormal subchondral bone metabolism is an important cause of this disease. Further understanding on the pathology of the subchondral bone in OA may provide a new therapy. This research is about to investigate the role of SDF-1 in the subchondral bone during the pathological process of OA. In vitro, Transwell was used to test the migratory ability of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs). Western blot presented the protein level after SDF-1 treatment in BMSCs and HUVESs. Alizarin red was used to assess the ability of osteogenic differentiation. To inhibit SDF-1 signaling pathway in vivo, AMD3100 (SDF-1 receptor blocker) was continuously delivered via miniosmotic pump for 4 weeks in mice after performing anterior cruciate ligament transaction surgery. Micro-CT, histology staining, immunofluorescence, immunohistochemistry, and TRAP staining were used to assess the role of SDF-1 on osteogenesis and angiogenesis in the subchondral bone. Our results showed that SDF-1 could recruit BMSCs, activate the p-ERK pathway, and enhance osteogenic differentiation. SDF-1 promoted the ability of proliferation, migration and tube formation of HUVECs by activating the ERK and AKT signaling pathways. In an animal study, inhibition of SDF-1/CXCR4 axis could significantly reduce subchondral osteogenesis differentiation and H-type vessel formation. Furthermore, the AMD3100-treated group showed less cartilage destruction and bone resorption. Our research shows that SDF-1 alters the microenvironment of the subchondral bone by promoting osteoid islet formation and abnormal H-type angiogenesis in the subchondral bone, resulting in articular cartilage degeneration.

BACKGROUND: Emerging threat of drug resistance among pathogens causing ventilator-associated pneumonia (VAP) has resulted in higher hospital costs, longer hospital stays, and increased hospital mortality. Biofilms in the endotracheal tube of ventilated patients act as protective shield from host immunity. They induce chronic and recurrent infections that defy common antibiotics. This study intended to determine the biofilm produced by pathogens causing VAP and their relation with drug resistance. METHODS: Bronchoalveolar lavage and deep tracheal aspirates (n = 70) were obtained from the patients mechanically ventilated for more than 48 hours in the intensive care units of Tribhuvan University Teaching Hospital, Kathmandu, and processed according to the protocol of the American Society for Microbiology (ASM). Antibiotic susceptibility testing was done following Clinical and Laboratory Standards Institute (CLSI) 2017 guidelines. Biofilm formation was determined using the microtiter plate method described by Christensen and modified by Stepanovoic et al. RESULTS: Significant microbial growth was seen in 78.6% of the total samples with 52.7% monomicrobial, 45.5% polymicrobial, and 1.8% fungal infection. Among the 71 isolates obtained, bulk was gram-negative (n = 64, 90.1%). Pseudomonas aeruginosa (31.0%) was the predominant isolate followed by Acinetobacter calcoaceticus baumannii complex (16.9%), Klebsiella pneumoniae (16.9%), Citrobacter freundii (15.5%), Staphylococcus aureus (7.0%), Escherichia coli (5.6%), Citrobacter koseri (2.8%), Enterococcus faecalis (1.4%), Burkholderia cepacia complex (1.4%), and Candida albicans (1.4%). Of the total isolates, 56.3% were biofilm producers. Multidrug-resistant (MDR) organisms, extended-spectrum β-lactamase (ESBL), and metallo-β-lactamase (MBL) producers were preeminent among the biofilm producers. The highest producer of biofilm was P. aeruginosa (19.7%). Among gram-negative biofilm producers, 42.2% were MDR, 21.9% were ESBL producers, and 7.8% were MBL producers. CONCLUSION: Gram-negative nonfermenter bacteria account for the bulk of nosocomial pneumonia. MDR, ESBL, and MBL production was preponderant among the biofilm producers. The rampant spread of drug resistance among biofilm producers is summoning novel interventions to combat multidrug resistance.

BACKGROUND: Vulvovaginal candidiasis caused by Candida species is a prevalent fungal infection among women. It is believed that the pathogenesis of Candida species is linked with the production of biofilm which is considered a virulence factor for this organism. The aim of this study was molecular identification, antifungal susceptibility, biomass quantification of biofilm, and detection of virulence markers of Candida species. METHODS: We investigated the molecular identification of 70 vaginal isolates of Candida species, antifungal resistance to amphotericin B, fluconazole, itraconazole, and voriconazole according to CLSI M27-A3 and M27-S4, biofilm formation, and frequency analysis of biofilm-related ALS1, ALS3, and HWP1 genes. RESULTS: Our findings showed that the most common yeast isolated from vaginal discharge was C. albicans (67%), followed by the non-Candida albicans species (33%). All C. albicans complex isolates were confirmed as C. albicans by HWP-PCR, and all isolates of the C. glabrata complex were revealed to be C. glabrata sensu stricto using the multiplex PCR method. FLC resistance was observed in 23.4% of C. albicans and 7.7% of C. glabrata. The resistance rate to ITC was found in 10.6% of C. albicans. The frequency of ALS1, ALS3, and HWP1 genes among Candida species was 67.1%, 80%, and 81.4%, respectively. Biofilm formation was observed in 54.3% of Candida species, and the highest frequency detected as a virulence factor was for the ALS3 gene (97.3%) in biofilm-forming species. Discussion. Our results showed the importance of molecular epidemiology studies, investigating antifungal susceptibility profiles, and understanding the role of biofilm-related virulence markers in the pathogenesis of Candida strains.

Two novel Algerian field-collected isolates were selected for their antifungal activity against Zymoseptoria tritici (teleomorph Mycosphaerella graminicola). The novel strains, termed Alg.24B1 and Alg.24B2, were identified as Bacillus subtilis and Bacillus simplex since their respective nucleotide sequences of the 16S rRNA gene were 100% and 99.93% identical to those of B. subtilis and B. simplex, respectively. The antifungal activities of Alg.24B1 and Alg.24B2 were evaluated by the well diffusion method and compared to those of other Bacillus species. The maximum activity was obtained after two days of confrontation of the bacterial strain supernatants with the fungus for Alg.24B1 and three days for Alg.24B2. Furthermore, the metabolites responsible for the antifungal activity of both strains were detected by the investigation of either gene presence (PCR) or molecule production (activity detection of lytic enzymes and HPLC detection of lipopeptides). Overall, this study showed that in addition to their ability to produce lytic enzymes (protease and β-glucanase), both strains coproduce three types of lipopeptides viz. surfactin, iturin, and fengycin. Thus, the biofungicide activity of both strains may be a result of a combination of different mechanisms. Therefore, they had a great potential to be used as biocontrol agents to effectively manage septoria tritici blotch of wheat (STB).

BACKGROUND: This study is aimed at confirming the effectiveness of nonpharmaceutical interventions during the COVID-19 outbreak in Hubei, China. METHODS: The data are all from the epidemic information released by the National Health Commission of the People's Republic of China and the Health Commission of Hubei Province. We used the multivariable linear regression by the SPSS 19.0 software: the cumulative number of confirmed cases, the cumulative number of cured cases, and the number of daily severe cases were taken as dependent variables, and the six policies, including the Joint Prevention and Control Mechanism of the State Council, lockdown Wuhan city, the first-level response to public health emergencies, the expansion of medical insurance coverage to suspected patients, mobile cabin hospitals, and counterpart assistance in Hubei province, were gradually entered into multiple linear regression models as independent variables. RESULTS: The factors influencing the cumulative number of diagnosed cases ranged from large to small: mobile cabin hospitals and the expansion of medical insurance coverage to suspected patients. The factors influencing the cumulative number of cured cases ranged from large to small: counterpart support medical teams in Hubei province and mobile cabin hospitals. The factors influencing the number of daily severe cases ranged from large to small: mobile cabin hospitals and the expansion of medical insurance coverage to suspected patients. CONCLUSION: The mobile cabin hospital is a major reason for the successfully defeating COVID-19 in China. As COVID-19 pandemic spreads globally, the mobile cabin hospital is a successful experience in formulating policies to defeat COVID-19 for other countries in the outbreak phase.

OBJECTIVE: Driver gene mutation in lung adenocarcinoma patients in Zunyi and its relationship with clinical features were probed in this investigation. METHODS: In total, with 244 patients with lung adenocarcinoma as study subjects, including 141 males and 103 females, amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) was utilized for detecting multigene mutations. Subsequently, the relationship between gene mutation and clinical characteristics was analyzed. RESULTS: The total mutation rate of driver genes was 65.17%, including 48.36% EGFR, 6.15% KRAS, 5.74% ALK, 2.05% HER-2, 1.23% ROS1, 0.82% RET, 0.41% NRAS, and 0.41% BRAF. Among EGFR mutations, 47.46% were EGFR-19-deletion, 42.37% EGFR-21-L858R mutation, 4.24% EGFR-20-T790M mutation, 2.54% EGFR-21-L861Q mutation, 2.54% EGFR-20-insertion, and 0.85% EGFR-18-G719X mutation. Both female patients and nonsmoking patients with lung adenocarcinoma had a higher rate of EGFR mutation. Additionally, 15 patients with multiple mutations in EGFR, including 13 patients with 2 mutations in EGFR and 2 patients with 3 mutations in EGFR, were found. CONCLUSION: Among driver gene mutations in patients with lung adenocarcinoma in Zunyi, EGFR mutation has the highest incidence, followed by ALK fusion and KRAS mutation. Although both mutations and multisite mutations in the other driver genes account for a low proportion, they still have great clinical significance. Multigene mutation detection contributes to the rapid screening of patients with lung adenocarcinoma who respond to targeted therapy.

Lysine succinylation is a typical protein post-translational modification and plays a crucial role of regulation in the cellular process. Identifying succinylation sites is fundamental to explore its functions. Although many computational methods were developed to deal with this challenge, few considered semantic relationship between residues. We combined long short-term memory (LSTM) and convolutional neural network (CNN) into a deep learning method for predicting succinylation site. The proposed method obtained a Matthews correlation coefficient of 0.2508 on the independent test, outperforming state of the art methods. We also performed the enrichment analysis of succinylation proteins. The results showed that functions of succinylation were conserved across species but differed to a certain extent with species. On basis of the proposed method, we developed a user-friendly web server for predicting succinylation sites.

OBJECTIVE: To investigate the etiology, clinical as well as neuroimaging characteristics, and outcomes after proper treatment in a series of 18 patients with osmotic demyelination syndrome. METHODS: Medical records, including video records, of 18 patients with osmotic demyelination syndrome were retrospectively examined. Demographic and clinical information, imaging results, plans of management, and outcomes during the follow-up period were collected and analyzed. RESULTS: Eighteen patients, including 10 males and 8 females, were included in the present study. The mean age at diagnosis of CNS insult was 47.4 ± 13.3 years (ranged from 30 to 78 years). Etiologies included rapidly corrected hyponatremia (50%), alcoholism (27.8%), and others. Neurological manifestations included encephalopathy (61.1%), dysphonia (50%), extrapyramidal symptoms (38.9%), and seizures (22.2%). Neuroimaging results showed that 6 patients (33.3%) had central pontine myelinolysis, 5 (27.8%) had extrapontine myelinolysis, and 7 (38.9%) had both. After treatment, 12 patients showed improvement and the other 6 did not. Among these patients, those who showed symptoms of encephalopathy had a favorable outcome. The majority of those who presented with mental retardation, seizures, and no other symptoms recovered better than their counterparts who had other symptoms. Nine out of 11 patients with pseudobulbar paralysis and/or extrapyramidal symptoms showed improvement, but the other 2 did not show improvement. Five patients who did not improve after treatment during admission were followed up for 1-3 months with rehabilitation training recommended, and it was found that 3 showed significant improvement after training, and the other 2 did not respond to this training. CONCLUSIONS: Osmotic demyelination syndrome is a complex disease entity due to a variety of etiologies, manifesting with symptoms involving diverse systems of the brain. Early identification and removal/correction of conditions leading to osmotic demyelination syndrome are the key to prevent and/or manage this disease.

BACKGROUND: Respiratory syncytial virus (RSV) infection is a public health epidemic, leading to around 3 million hospitalization and about 66,000 deaths each year. It is a life-threatening condition exclusive to children with no effective treatment. METHODS: In this study, we used system-level and vaccinomics approaches to design a polyvalent vaccine for RSV, which could stimulate the immune components of the host to manage this infection. Our framework involves data accession, antigenicity and subcellular localization analysis, T cell epitope prediction, proteasomal and conservancy evaluation, host-pathogen-protein interactions, pathway studies, and in silico binding affinity analysis. RESULTS: We found glycoprotein (G), fusion protein (F), and small hydrophobic protein (SH) of RSV as potential vaccine candidates. Of these proteins (G, F, and SH), we found 9 epitopes for multiple alleles of MHC classes I and II bear significant binding affinity. These potential epitopes were linked to form a polyvalent construct using AAY, GPGPG linkers, and cholera toxin B adjuvant at N-terminal with a 23.9 kDa molecular weight of 224 amino acid residues. The final construct was a stable, immunogenic, and nonallergenic protein containing cleavage sites, TAP transport efficiency, posttranslation shifts, and CTL epitopes. The molecular docking indicated the optimum binding affinity of RSV polyvalent construct with MHC molecules (-12.49 and -10.48 kcal/mol for MHC classes I and II, respectively). This interaction showed that a polyvalent construct could manage and control this disease. CONCLUSION: Our vaccinomics and system-level investigation could be appropriate to trigger the host immune system to prevent RSV infection.

Aging affects the brain function in elderly individuals, and Dushen Tang (DST) is widely used for the treatment of senile diseases. In this study, the protective effect of DST against memory impairment was evaluated through the Morris water maze (MWM) test and transmission electron microscopy (TEM). A joint analysis was also performed using LC-MS metabolomics and the microbiome. The MWM test showed that DST could significantly improve the spatial memory and learning abilities of rats with memory impairment, and the TEM analysis showed that DST could reduce neuronal damage in the hippocampus of rats with memory impairment. Ten potential biomarkers involving pyruvate metabolism, the synthesis and degradation of ketone bodies, and other metabolic pathways were identified by the metabolomic analysis, and it was found that 3-hydroxybutyric acid and lactic acid were involved in the activation of cAMP signaling pathways. The 16S rDNA sequencing results showed that DST could regulate the structure of the gut microbiota in rats with memory impairment, and these effects were manifested as changes in energy metabolism. These findings suggest that DST exerts a good therapeutic effect on rats with memory impairment and that this effect might be mainly achieved by improving energy metabolism. These findings might lead to the potential development of DST as a drug for the treatment of rats with memory impairment.

The objective of this study was to observe the curative effect of combined arteriovenous approach embolization on complex carotid-cavernous fistulas. The clinical data of 13 patients with complex carotid-cavernous fistulas treated with combined arteriovenous approach embolization in our department between January 2017 and January 2020 were analyzed retrospectively. All 13 patients received the combined arteriovenous approach embolization with coil combined with Onyx glue. The intraoperative angiography immediately showed that the fistula could be completely blocked, and the carotid artery was/got unobstructed. The patients had no clinical symptoms recurring during a follow-up period of 3-18 months, on average 9.1 ± 6.3 months. A combined arteriovenous approach embolization on complex carotid-cavernous fistulas is safe and effective since it can improve the occlusion rate and reduce the relapse rate.

The aim of this study was to investigate the effect of cardiac troponin I-interacting kinase (TNNI3K) on sepsis-induced myocardial dysfunction (SIMD) and further explore the underlying molecular mechanisms. In this study, a lipopolysaccharide- (LPS-) induced myocardial injury model was used. qRT-PCR was performed to detect the mRNA expression of TNNI3K. Western blot was conducted to quantitatively detect the expression of TNNI3K and apoptosis-related proteins (Bcl-2, Bax, and caspase-3). ELISA was performed to detect the content of lactate dehydrogenase (LDH) and creatine kinase (CK). TUNEL assay was used to detect the apoptosis of H9C2 cells. In LPS-induced H9C2 cells, TNNI3K was up regulated. Besides, the CK activity, the content of LDH, and the apoptosis of H9C2 cells were significantly increased after treatment with LPS. Silencing TNNI3K decreased the LDH release activity and CK activity and inhibited apoptosis of H9C2 cell. Further research illustrated that si-TNNI3K promoted the protein expression of Bcl-2 and decreased the protein expression of Bax and cleaved caspase-3. The study concluded that TNNI3K was upregulated in LPS-induced H9C2 cells. Importantly, functional research findings indicated that silencing TNNI3K alleviated LPS-induced H9C2 cell injury by regulating apoptosis-related proteins.

The new Coronavirus Disease 19, officially known as COVID-19, originated in China in 2019 and has since spread worldwide. We presented an age-structured Susceptible-Latent-Mild-Critical-Removed (SLMCR) compartmental model of COVID-19 disease transmission with nonlinear incidence during the pandemic period. We provided the model calibration to estimate parameters with day-wise COVID-19 data, i.e., reported cases by worldometer from 15th February to 30th March 2020 in six high-burden countries, including Australia, Italy, Spain, the USA, the UK, and Canada. We estimate transmission rates for each country and found that the country with the highest transmission rate is Spain, which may increase the new cases and deaths than the other countries. We found that saturation infection negatively impacted the dynamics of COVID-19 cases in all the six high-burden countries. The study used a sensitivity analysis to identify the most critical parameters through the partial rank correlation coefficient method. We found that the transmission rate of COVID-19 had the most significant influence on prevalence. The prediction of new cases in COVID-19 until 30th April 2020 using the developed model was also provided with recommendations to control strategies of COVID-19. We also found that adults are more susceptible to infection than both children and older people in all six countries. However, in Italy, Spain, the UK, and Canada, older people show more susceptibility to infection than children, opposite to the case in Australia and the USA. The information generated from this study would be helpful to the decision-makers of various organisations across the world, including the Ministry of Health in Australia, Italy, Spain, the USA, the UK, and Canada, to control COVID-19.

INTRODUCTION: In the recent decade, the increased immunocompromised population such as diabetic patients makes a high incidence of invasive Candida infections. Diabetes mellitus is the most common endocrine metabolic disorder, and diabetic patients are more susceptible to oral candidiasis infection. Candidiasis is an opportunistic fungal infection caused by many species of Candida. Secretion of exoenzymes plays an important role in the virulence and pathogenesis of Candida species. The aim of this study was to evaluate the potential role of phospholipase, esterase, and hemolytic activity of Candida species isolated from oral cavity lesions of diabetic patients. METHODS: A total of 108 Candida species including 75 Candida albicans and 33 non-Candida albicans species were recovered from the oral cavity of diabetic patients included in our study. Egg yolk agar, Tween 80 opacity medium, and blood agar plate assays were used for determining phospholipase, esterase, and hemolytic activities, respectively. RESULTS: Candida albicans species had the most exoenzyme activity in comparison to non-albicans isolates. Candida albicans isolates showed 97.3%, 100%, and 77.3% phospholipase, hemolysin, and esterase activities, respectively. The difference between Candida albicans and non-Candida albicans was significant in phospholipase (P < 0.001) and hemolytic activity (P = 0.027), but not significant in esterase activity (P = 0.076). CONCLUSION: This study showed that most of the isolates had different enzymatic patterns, and Candida albicans isolates had the most exoenzyme activity. So due to the potential effects of these enzymes in pathogenesis and virulence effects of Candida species, we can conclude that the severity of extracellular enzymes may play a role in the severity of signs and symptoms of Candida oral cavity infections in diabetic patients.

Aortic stenosis is a disease that is increasing in prevalence and manifests as decreased cardiac output, which if left untreated can result in heart failure and ultimately death. It is primarily a disease of the elderly who often have multiple comorbidities. The advent of transcatheter aortic valve therapies has changed the way we treat these conditions. However, long-term results of these therapies remain uncertain. Recently, there has been an increasing number of studies examining the role of both surgical aortic valve replacement and transcatheter aortic valve replacement. We therefore performed a systematic review using Ovid MEDLINE, Ovid Embase, and the Cochrane Library. Two investigators searched papers published between January 1, 2007, and to date using the following terms: "aortic valve stenosis," "aortic valve operation," and "transcatheter aortic valve therapy." Both strategies in aortic stenosis treatment highlighted specific indications alongside the pitfalls such as structural valve degeneration and valve thrombosis which have a bearing on clinical outcomes. We propose some recommendations to help clinicians in the decision-making process as technological improvements make both surgical and transcatheter therapies viable options for patients with aortic stenosis. Finally, we assess the role of finite element analysis in patient selection for aortic valve replacement. THVT and AVR-S are both useful tools in the armamentarium against aortic stenosis. The decision between the two treatment strategies should be best guided by a strong robust evidence base, ideally with a long-term follow-up. This is best performed by the heart team with the patient as the center of the discussion.

OBJECTIVE: To evaluate the efficacy and safety of an endoscopic bag during laparoscopic morcellation of leiomyoma or myomatous uterus. MATERIALS AND METHODS: A total of 48 patients with symptomatic leiomyoma were randomized for laparoscopic morcellation in two groups: group A with a specific endoscopic bag or group B without any bag. The primary outcome measure was the detection of smooth muscle cells from washing after power morcellation determined by peritoneal cytology and immunohistochemistry (IHC). RESULTS: Cytology and IHC from group A did not revealed any smooth muscle cells, while 29% of cases (7/24) from group B were positive (p = .009). The duration of the surgical procedure was the same in both groups. The duration of positioning the bag did not change significantly during the study. Only in one case the use of the bag was difficult due to a low pneumoperitoneum. CONCLUSIONS: The use of a morcellation bag is efficient to prevent the spread of smooth muscle cells during the morcellation of leiomyoma or myomatous uterus. This study confirms the feasibility and the safety of the laparoscopic inbag morcellation versus open morcellation.

Pyruvate kinase (PK), a key enzyme that determines glycolytic activity, has been known to support the metabolic phenotype of tumor cells, and specific pyruvate kinase isoform M2 (PKM2) has been reported to fulfill divergent biosynthetic and energetic requirements of cancerous cells. PKM2 is overexpressed in several cancer types and is an emerging drug target for cancer during recent years. Therefore, this study was carried out to identify PKM2 inhibitors from natural products for cancer treatment. Based on the objectives of this study, firstly, plant extract library was established. In order to purify protein for the establishment of enzymatic assay system, pET-28a-HmPKM2 plasmid was transformed to E. coli BL21 (DE3) cells for protein expression and purification. After the validation of enzymatic assay system, plant extract library was screened for the identification of inhibitors of PKM2 protein. Out of 51 plant extracts screened, four extracts Mangifera indica (leaf, seed, and bark) and Bombex ceiba bark extracts were found to be inhibitors of PKM2. In the current study, M. indica (leaf, seed, and bark) extracts were further evaluated dose dependently against PKM2. These extracts showed different degrees of concentration-dependent inhibition against PKM2 at 90-360 μg/ml concentrations. We have also investigated the anticancer potential of these extracts against MDA-MB231 cells and generated dose-response curves for the evaluation of IC50 values. M. indica (bark and seed) extracts significantly halted the growth of MDA-MB231 cells with IC50 values of 108 μg/ml and 33 μg/ml, respectively. Literature-based phytochemical analysis of M. indica was carried out, and M. indica-derived 94 compounds were docked against three binding sites of PKM2 for the identification of PKM2 inhibitors. The results of in silico based screening have unveiled various PKM2 modulators; however, further studies are recommended to validate their PKM2 inhibitory potential via in vitro biochemical assay. The results of this study provide novel findings for possible mechanism of action of M. indica (bark and seed) extracts against TNBC via PKM2 inhibition suggesting that M. indica might be of therapeutic interest for the treatment of TNBC.

The clinical significance of the family with sequence similarity 189 member B (FAM189B) gene remains largely unknown in gastric cancer (GC). A comprehensive investigation combining multiple detection methods was carried out in the current study to unveil the clinical implications and prospective molecular characterization of FAM189B protein and mRNA in GC. The protein level of FAM189B was clearly upregulated in the tumor tissues of GC as compared to noncancerous gastric tissues with 179 GC cases and 147 noncancerous gastric controls assessed by immunohistochemistry. The upregulation of the FAM189B protein was also found in the more deteriorating period of the tumor, as there were increasing trends in the groups of larger tumors, with lymph node metastasis, a further advanced clinical stage, and a higher histological grade. Next, we focused on the mRNA level of FAM189B in GC tissues using various high-throughput data. After the screening of GEO, ArrayExpress, and SRA, we finally achieved 18 datasets, including an RNA sequencing dataset of TCGA. Altogether, 1095 cases of GC tissue samples were collected, with 305 unique examples of noncancerous controls. Concerning the mRNA level of FAM189B in GC, the final standard mean difference (SMD) was 0.46 and the area under the curve (AUC) was 0.79 for the upregulation of FAM189B mRNA, which confirmed that the FAM189B mRNA level was also markedly upregulated in GC tissues and comparable to its protein level. The survival analysis showed that the higher expression of FAM189B was a risk factor for the overall survival, first progression, and postprogression survival of GC. For the Affymetrix ID 1555515_a_at of FAM189B, the higher expression level of FAM189B predicted a lower overall survival, first progression survival, and postprogression survival with the hazard ratio (HR) being 1.56 (1.24, 1.95), 1.69 (1.32, 2.17), and 1.97 (1.5, 2.6), respectively. For the Affymetrix ID 203550_s_at of FAM189B, a similar result could be found with corresponding HR being 1.49 (1.24, 1.8), 1.49 (1.21, 1.83), and 1.66 (1.32, 2.08), respectively. The interaction of MEM, COXPRESdb coexpressed genes, and DEGs of GC finally generated 368 genes, and the pathway of the cell cycle was the top pathway enriched by KEGG. In conclusion, the overexpression of the FAM189B protein and mRNA might enhance the incidence of GC.

A global pandemic has emerged following the appearance of the new severe acute respiratory virus whose official name is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), strongly affecting the health sector as well as the world economy. Indeed, following the emergence of this new virus, despite the existence of a few approved and known effective vaccines at the time of writing this original study, a sense of urgency has emerged worldwide to discover new technical tools and new drugs as soon as possible. In this context, many studies and researches are currently underway to develop new tools and therapies against SARS CoV-2 and other viruses, using different approaches. The 3-chymotrypsin (3CL) protease, which is directly involved in the cotranslational and posttranslational modifications of viral polyproteins essential for the existence and replication of the virus in the host, is one of the coronavirus target proteins that has been the subject of these extensive studies. Currently, the majority of these studies are aimed at repurposing already known and clinically approved drugs against this new virus, but this approach is not really successful. Recently, different studies have successfully demonstrated the effectiveness of artificial intelligence-based techniques to understand existing chemical spaces and generate new small molecules that are both effective and efficient. In this framework and for our study, we combined a generative recurrent neural network model with transfer learning methods and active learning-based algorithms to design novel small molecules capable of effectively inhibiting the 3CL protease in human cells. We then analyze these small molecules to find the correct binding site that matches the structure of the 3CL protease of our target virus as well as other analyses performed in this study. Based on these screening results, some molecules have achieved a good binding score close to -18 kcal/mol, which we can consider as good potential candidates for further synthesis and testing against SARS-CoV-2.

INTRODUCTION: Sexually transmitted infections (STIs) are prevalent in Ethiopia and elsewhere among different population groups particularly among female sex workers (FSWs). Because of their work and their behavior, FSWs are at high risk to acquire STIs. The aim of the study was to assess the seroprevalence and associated factors of HIV, HBV, HCV, and T. pallidum among FSWs in Dessie City, Northeast Ethiopia. METHODS: This cross-sectional study was conducted in Dessie City, Amhara Region, Northeastern Ethiopia, from November 2017 to April 2018. A total of 360 FSWs whose age is greater than or equal to 18 years and who are willing to participate were recruited by simple random sampling technique. Interview-based questionnaire was administered, and 5 ml of venous blood from each participant was drawn under aseptic conditions. The rapid test was performed to obtain the result of the four STIs (HIV, T. pallidum, HBV, and HCV). The collected data were entered and analyzed by SPSS version 20.0. From the bivariable analysis, variables having P value < 0.2 were retained into multivariable analysis. From the multivariable analysis, variables with P value < 0.05 were affirmed as statistically associated factors. Adjusted odds ratios and their 95% confidence intervals were used as indicators of the strength of association. RESULTS: Majority of study participants were urban dwellers, 10 (2.8%) respondents were married, 61 (16.9%) have more than two children, and more than half of them were at the age range between 18 and 27 years. Any infection with STIs was 84 (23.3%), whereas 27 (7.5%), 47 (13.1%), 2 (0.6%), and 45 (12.5%) study participants were positive for laboratory test of HIV, HBV, HCV, and T. pallidum, respectively. Marital status, sharing of sharp materials, breakage of condom, number of customers per week, genital discharge, and pain had significant association with any STI. CONCLUSIONS: In comparison with different research works in Ethiopia and abroad, the prevalence of any STI, HIV, HBV, and T. pallidum was found to be relatively high. Preventive approach and appropriate treatment of STIs should be developed. Concerned body should work together to alleviate the problem by counseling and recruiting them on other productive job sectors in the country.

PURPOSE: This study was aimed at comparing the effects of TheraBand and theratube eccentric exercises on quadriceps muscle strength in young adults. METHODS: Thirty young adults (19 females, 11 males) participated in this pretest-posttest experimental study. Participants were randomly assigned to one of the two groups: TheraBand and theratube groups. They received the training intervention 3 times a week for 4 weeks (12 sessions) with progression after 2 weeks. Maximum eccentric quadriceps strength was assessed using the Biodex isokinetic dynamometer system. Additionally, quadriceps muscle mass was measured using a tape. RESULTS: Both groups showed a significant improvement in the peak torque of the eccentric isokinetic quadriceps' strength after weeks 2 and 4. Strength change in the quadriceps was nonsignificant in the theratube group compared to the TheraBand group after 4 weeks of training (p < 0.05). There was no increase in muscle mass during the 4 weeks of training in any group (p > 0.05). CONCLUSION: Both the TheraBand and theratube are equally effective in the strengthening of the quadriceps muscle in young adults. Therefore, either the TheraBand or theratube may be used according to the availability and feasibility of the subjects for training intervention.

BACKGROUND: Almost every sector in the health care is affected by the COVID-19 pandemic. Many studies already investigated the effect on different aspects in orthopedic and trauma care. However, the current literature lacks data regarding the consequence on daily surgical business. Thus, the aim of the present study was to analyze the development of knee-related pathologies and surgical procedures in a German university level-one trauma center during the lockdown phase and early lockdown phase to investigate the impact of the COVID-19 lockdown on orthopedic and trauma knee surgery. Material and Methods. The amount of knee joint surgeries performed during the high-peak COVID-19 crisis in the period of January to May 2020 was evaluated retrospectively and compared to the corresponding time periods of the previous years (2017-2019). RESULTS: The COVID-19 lockdown led to a significant decrease in the number of knee injuries in March and April 2020 by 83.3%. Surgical procedures were reduced by 84.8% during the same period. In May 2020, the number of knee joint procedures returned to an almost prepandemic level. The distribution of urgent and elective knee surgery changed to predominantly acute trauma care at the beginning of the COVID-19 lockdown and persisted through to May 2020. CONCLUSION: The COVID-19 pandemic had a high impact on emergency and elective knee surgery in a level-one trauma center in Germany during the lockdown phase. It also showed that a level-one trauma center in the German healthcare system is able to handle urgent trauma and orthopedic operations during a worldwide medical crisis and to return to a prepandemic level within a short phase.

BACKGROUND: We aimed to examine the differences of clinical characteristics between patients with ischemic stroke with active cancer and those without cancer to develop a clinical score for predicting the presence of occult cancer in patients with ischemic stroke. METHODS: This retrospective study enrolled consecutive adult patients with acute ischemic stroke who were admitted to our department between December 2017 and January 2019. The demographic, clinical, laboratory, and neuroimaging characteristics were compared between patients with ischemic stroke with active cancer and those without cancer. Multivariate analysis was performed to identify independent factors associated with active cancer. Subsequently, a predictive score was developed using the areas under the receiver operating characteristic curves based on these independent factors. Finally, Bayesian decision theory was applied to calculate the posterior probability of active cancer for finding the best scoring system. RESULTS: Fifty-three (6.63%) of 799 patients with ischemic stroke had active cancer. The absence of a history of hyperlipidemia (odds ratio (OR) = 0.17, 95% confidence interval (CI): 0.06-0.48, P < 0.01), elevated serum fibrinogen (OR = 1.72, 95% CI: 1.33-2.22, P < 0.01) and D-dimer levels (OR = 1.43, 95% CI: 1.24-1.64, P <0.01), and stroke of undetermined etiology (OR = 22.87, 95% CI: 9.91-52.78, P < 0.01) were independently associated with active cancer. A clinical score based on the absence of hyperlipidemia, serum fibrinogen level of ≥4.00 g/L, and D-dimer level of ≥2.00 μg/mL predicted active cancer with an area under the curve of 0.83 (95% CI: 0.77-0.89, P < 0.01). The probability of active cancer was 59% at a supposed prevalence of 6.63%, if all three independent factors were present in a patient with ischemic stroke. CONCLUSIONS: We devised a clinical score to predict active cancer in patients with ischemic stroke based on the absence of a history of hyperlipidemia and elevated serum D-dimer and fibrinogen levels. The use of this score may allow for early intervention. Further research is needed to confirm the implementation of this score in clinical settings.

Gynecological malignancies are tumors of the female reproductive system, mainly cervical cancer, endometrial cancer, and ovarian cancer. Endometrial cancer (EC) is the most common gynecological malignant tumor in developed countries. The aim of this study was to construct a network of programmed cell death protein 1 (PD-1) coexpressed genes through bioinformatics analysis and screen the potential biomarkers of PD-1 in endometrial cancer. In addition, genes and pathways involved in PD-1 and modulating tumor immune status were identified. We select the EC transcriptomic dataset in TCGA to retrieve gene sets on the cBioPortal platform, and the PD-1 coexpressed genes were obtained on the platform. GO and KEGG enrichment analysis of coexpressed genes was performed using the DAVID database. The target protein-protein interaction (PPI) network was constructed using Cytoscape 3.7.1 software, and the hub genes were then screened. A total of 976 coexpression genes were obtained. The enrichment analysis showed that PD-1 coexpressed genes were significantly enriched in overall components of the cell structure, the interaction of cytokines with cytokine receptors, chemokine signaling pathways, and cell adhesion molecules (CAMs). Ten hub genes were obtained by node degree analysis. CD3E gene is involved in the prognosis and immune process of EC, and the expression level is related to PD-1 (Pearson correlation coefficient is 0.82, P < 0.01). Patients with low CD3E gene expression in EC have a poor prognosis. The coexpression hub genes of PD-1 are related to immunity, in which CD3E is a prognostic marker that is involved in the PD-1/PD-L1-induced tumor immune escape. This study provides a new area to study the mechanism of PD-1/PD-L1 in EC and the precise treatment with targeted drugs.

Pediatric lymphoma is a kind of malignant tumor with high mortality. The complexity of pediatric lymphoma shows a great challenge for effective diagnosis and treatment. In order to meet the challenge, the combination of pseudotargeted and targeted metabolomics was used to analyze the serum metabolites in pediatric lymphoma patients and healthy controls for discovering the metabolites related to pediatric lymphoma. The serum samples were obtained from the treatment group (n = 43), the control group (n = 26), and the patients group (n = 18). A total of 17 serum metabolites, including carnitine, leucine, creatine, urea, (6Z,9Z,12Z)-octadecatrienoic acid, linoleate, octadecenoic acid, L-palmitoylcarnitine, hexadecanoic acid, tetradecanoic acid, (9Z)-hexadecenoic acid, uric acid, glucose, 1-methylnicotinamide, hypoxanthine, L-glutamine, and taurine, were found to be related to pediatric lymphoma. They could provide a scientific diagnostic basis and therapeutic target for pediatric lymphoma and elucidate the mechanism of pediatric lymphoma.

Aiming at the current problem of insufficient extraction of small retinal blood vessels, we propose a retinal blood vessel segmentation algorithm that combines supervised learning and unsupervised learning algorithms. In this study, we use a multiscale matched filter with vessel enhancement capability and a U-Net model with a coding and decoding network structure. Three channels are used to extract vessel features separately, and finally, the segmentation results of the three channels are merged. The algorithm proposed in this paper has been verified and evaluated on the DRIVE, STARE, and CHASE_DB1 datasets. The experimental results show that the proposed algorithm can segment small blood vessels better than most other methods. We conclude that our algorithm has reached 0.8745, 0.8903, and 0.8916 on the three datasets in the sensitivity metric, respectively, which is nearly 0.1 higher than other existing methods.

Knowledge of anatomical variations of the limb's main arteries is significant for the clinicians. Thus, this study is aimed at examining the branching pattern and anatomical variations of the axillary artery. We conducted research on 59 upper limbs of adult human donated cadavers. All axillary artery branches' origins were assessed, and the correlations between points of origins and variations of specific branches were evaluated. The average length of the axillary artery was found to be 11.22 cm, and this length was defined as reference line. Based on this reference line, the first, second, and third parts were 37.56%, 39%, and 30.05%, respectively. The STA was originated from 25.11%. The TAA and LTA were 42.67% and 54.82%, respectively. The SSA, ACHA, and PCHA were 64.72%, 83.89%, and 84.53%, respectively. The origin of LTA was correlated with that of SSA (R = 0.473, P < 0.05) and AHCA (R = 0.307, P < 0.05), respectively. And there was a positive correlation between AHCA and PHCA (R = 0.705, P < 0.05). The number of branches ranged from 3~6, and 9 types were shown. The most frequent branching pattern was common origin of the LTA and SSA (22/59). And AHCA and PHCA were originated together in 19 cases, and both patterns were combined in 12 cases. TTA and LTA branched together in 9 cases, and common trunk for the SSA, PHCA, and AHCA was found in 2 cases. According to this pattern, the origin of LTA and PCHA was significantly different. This information is particularly useful for surgeons and clinicians.

The growth and development of facial bones are closely related to each other. The present study investigated the differences in the nasomaxillary and mandibular morphology among different skeletal patterns. Cephalograms of 240 participants were divided into 3 groups based on the skeletal pattern (Class I, Class II, and Class III). The dimensions of nasomaxilla (nasal bone length, nasal ridge length, nasal depth, palatal length, and maxillary height) and mandible (condylar length, ramus length, body length, symphysis length, and entire mandibular length) were measured. One-way analysis of variance and Pearson's correlation test were used for statistical analysis. No significant differences were observed among the skeletal patterns in terms of nasal bone length, palatal length, maxillary height, or condylar length. Class II had a significantly shorter ramus, mandibular body, and entire mandibular length compared with those of Class I and Class III. Nasal ridge length exhibited a significant moderate correlated with nasal bone length (correlation coefficient: 0.433) and maxillary height (correlation coefficient: 0.535). The entire mandibular length exhibited a significant moderate correlated with ramus length (correlation coefficient: 0.485) and body length (correlation coefficient: 0.536). In conclusion, nasal and maxillary dimensions exhibited no significant difference among the 3 skeletal patterns. Mandibular body and entire mandibular lengths were significantly positively correlations with Class III skeletal patterns.

BACKGROUND: Investigating the viability and proliferative rates of fibroblast cells on human amniotic membrane (HAM) as a scaffold will be an important subject for further research. The aim of this study was to assess the fibroblast viability seeded on acellular HAM, since foreskin neonatal allogenic fibroblasts seeded on HAM accelerate the wound healing process. METHODS: Fibroblasts were retrieved from the foreskin of a genetically healthy male infant, and we exploited AM of healthy term neonates to prepare the amniotic scaffold for fibroblast transfer. After cell culture, preparation of acellular HAM, and seeding of cells on HAM based on the protocol, different methods including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI), and propidium iodide (PI) staining were employed for assessment of fibroblast viability on HAM. RESULTS: Based on the results obtained from the DAPI and PI staining, the percentage of viable cells in the former staining was clearly higher than that of the dead cells in the latter one. The results of DAPI and PI staining were in accordance with the findings of MTT assay, confirming that fibroblasts were viable and even proliferate on HAM. CONCLUSION: Our findings showed the viability of fibroblasts seeded on the acellular HAM using MTT assay, DAPI, and PI staining; however, this study had some limitations. It would be an interesting subject for future research to compare the viability and proliferation rate of fibroblasts seeded on both cellular and acellular HAM.

BACKGROUND: Manganese superoxide dismutase (MnSOD) has been reported to promote stemness of lung cancer stem-like cells (LCSLCs) which had higher glycolytic rates compared with non-CSLCs. Isovitexin exhibited an inhibitory effect on the stemness of hepatocellular carcinoma cells. However, whether isovitexin could inhibit the promotion of stemness of LCSLCs mediated by MnSOD through glycolysis remains unclear. OBJECTIVE: Our study was aimed at investigating whether isovitexin inhibits lung cancer stem-like cells (LCSLCs) through MnSOD signaling blockage and glycolysis suppression. METHODS: Sphere formation and soft agar assays were conducted to determine self-renewal ability. The migration and invasion of LCSLCs were determined by wound healing and transwell assay. The glycolytic activity was assessed by determination of L-lactate metabolism rate. The influences of isovitexin on MnSOD, CaMKII, and AMPK activations as well as the metabolic shift to glycolysis were determined by manipulating MnSOD expression. RESULTS: It was found that MnSOD and glycolysis enhanced simultaneously in LCSLCs compared with parental H460 cells. Overexpression of MnSOD activated CaMKII/AMPK signaling and glycolysis in LCSLCs with increased self-renewal, migration, invasion, and expression of stemness-associated markers in vitro and elevated carcinogenicity in vivo. Knockdown of MnSOD induced an inverse effect in LCSLCs. Isovitexin blocked MnSOD/CaMKII/AMPK signaling axis and suppressed glycolysis in LCSLCs, resulting in inhibition of stemness features in LCSLCs. The knockdown of MnSOD significantly augmented isovitexin-associated inhibition of CaMKII/AMPK signaling, glycolysis, and stemness in LCSLCs. However, the overexpression of MnSOD could attenuate the inhibition of isovitexin on LCSLCs. Importantly, isovitexin notably suppressed tumor growth in nude mice bearing LCSLCs by downregulation of MnSOD expression. CONCLUSION: MnSOD promotion of stemness of LCSLCs derived from H460 cell line is involved in the activation of the CaMKII/AMPK pathway and induction of glycolysis. Isovitexin-associated inhibition of stemness in LCSLCs is partly dependent on blockage of the MnSOD/CaMKII/AMPK signaling axis and glycolysis suppression.

Erratum in Biomed Res Int. 2021 Oct 12;2021:9858140.

PURPOSE: To evaluate the effects of anti-VEGF treatment of neovascular age-related macular degeneration (nAMD) in a real-life clinical setting. METHODS: Study design is a retrospective case series. Naïve nAMD patients treated with intravitreal injection of aflibercept or ranibizumab were analyzed over a 24-month follow-up. Each patient received the loading dose, followed by a PRN regimen. Patients were further subdivided into subgroups according to macular neovascularization type, best corrected visual acuity (BCVA) at baseline (BCVA > 0.3 LogMAR and BCVA ≤ 0.3 LogMAR), and different anti-VEGF drugs. Primary outcome was the changes in BCVA and central macular thickness (CMT) over 24 months. Secondary outcomes included the influence of the selected drug and of the baseline BCVA on the final outcomes. RESULTS: 439 patients (224 males; 51%) with naïve AMD-related macular neovascularization were included in the analyses. Mean age was 78 ± 8 years old. Compared to baseline evaluations, not significant BCVA changes were found at 1-year and 2-year examinations. CMT was significantly reduced at both 1-year and 2-year follow-ups (p < 0.01). Classic, polypoidal choroidal vasculopathy and mixed subtypes significantly correlated with worse visual outcome (p < 0.01). Overall, baseline BCVA significantly correlated with both 1-year and 2-year follow-up changes (p < 0.01). Moreover, BCVA at 1-year significantly correlated with BCVA changes at 2-year follow-up (p < 0.01). Furthermore, CMT changes from baseline significantly correlated with both 1-year and 2-year follow-up measurements (p < 0.01). CONCLUSION: Anti-VEGF approach is generally effective in stopping nAMD progression in our real-life analysis. No difference was found comparing patients treated with ranibizumab and aflibercept, nor in patients with drug switching.

INTRODUCTION: Dental anxiety is a common occurrence in patients undergoing dental treatments, especially in children. The success in paedriatric dental treatments and patient comfort depends on controlling the level of patient's anxiety in clinical settings. This study is aimed at evaluating the efficacy of different techniques applied for the reduction of dental anxiety in paediatric patients. Material and Methods. One hundred and sixty participants were divided into 4 groups; each group having 40 patients as follows: group I: mobile application "little lovely dentist," group II: YouTube® "dental video songs," group III "tell-show-do," and group IV "control." Dental prophylaxis treatments were provided to all the participants. Initial anxiety levels were noted during the patient's education phase by measuring heart rate with pulse oximeter and distress level with facial image scale, at the same time in each group, respectively. The postoperative anxiety was noted later with the same methods, after the application of anxiety reduction techniques. The data obtained were entered in the statistical package for the social sciences software, version 25. One-way ANOVA and paired t-test for matched groups were used to compare mean values of the 4 groups, in this study to determine their effectiveness. A p value of ≤0.05 was considered as statistically significant. RESULTS: The mean age of patients in group 1 was 6.8 ± 2.1 years, group 2: 8.15 ± 2.27 years, group 3: 7.5 ± 2.3 years, and group 4: 7.27 ± 1.68 years. The intragroup comparisons of heart rate and facial image scores have shown a significant difference in before and after dental treatment procedures. Marked reduction in heart rate and facial image scale scores were found in patients belonging to group 1 (mobile applications) and group 2 (dental video songs). An increase in heart rate and facial image scale scores was seen in group 3 (tell-show-do) and the control group. CONCLUSION: The paediatric dental anxiety is a common finding in dental clinics. Behavior modification techniques like smartphone applications, "little lovely dentist," and "dental songs" can alleviate dental anxiety experienced by paediatric patients. The "tell-show-do" technique although most commonly used did not prove to be beneficial in the reduction of the anxiety levels.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process known as cytokine storm. Xuebijing injection (hereinafter referred to as Xuebijing) is a patent drug that was used to treat ARDS or severe pneumonia (SP) in China. However, its efficacy and mechanism of actions remain unclear. In this study, we used meta-analysis and network pharmacology to assess these traits of Xuebijing. METHODS: We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases for randomized controlled trials (RCTs) that evaluated Xuebijing therapy for ARDS or SP. The outcomes were total mortality, intensive care unit (ICU) stay time, and TNF-α and IL-6 levels. We performed a meta-analysis using RevMan 5.3 software. The putative targets, top 10 proteins, and possible pathway of Xuebinjing on ARDS were analyzed by network pharmacology. TNF-α and IL-6 were further docked with the six main active components of Xuebinjing using AutoDock 4.2.6 and PyMol 1.5.0.3 software. RESULTS: Fifteen RCTs involving 2778 patients (13 ARDS and 2 SP) were included. Compared with the control, Xuebijing treatment significantly reduced the mortality rate (risk ratio, 0.64 (95% credible interval (CrI), 0.54-0.77)), reduced the ICU stay time (mean difference (MD), -4.51 (95% CrI, -4.97--4.06)), reduced the TNF-α ((MD), -1.23 (95% CrI, -1.38--1.08)) and IL-6 ((MD), -1.15 (95% CrI, -1.52--0.78)) levels. The 56 putative targets, top 10 proteins (MAPK1 (mitogen-activated protein kinase 1), MAPK8 (mitogen-activated protein kinase 8), RELA (transcription factor p65), NFKB1 (nuclear factor NF-kappa-B p105 subunit), JUN (transcription factor AP-1), SRC (proto-oncogene tyrosine-protein kinase), TNF (tumor necrosis factor), HRAS (GTPase HRas), IL6 (interleukin-6), and APP (amyloid-beta A4 protein)), and possible pathways (Ret tyrosine kinase, IL2-mediated signaling events, CD4+/CD8+ T cell-related TCR signaling, p75(NTR)-mediated signaling, CXCR4-mediated signaling events, LPA receptor-mediated events, IL12-mediated signaling events, FAS (CD95) signaling pathway, and immune system) of Xuebinjing's action on ARDS were obtained. The molecular docking results showed that all the six components of Xuebinjing docked with TNF-α, and two components docked with IL-6 got the binding energies lower than -5. CONCLUSION: Our results recommended Xuebijing treatment for patients with ARDS. Xuebijing has therapeutic effects on ARDS patients partly by regulating the immune cell/cytokine pathways and thus inhibiting the cytokine storm. TNF-α is the cytokine both directly and indirectly inhibited by Xuebijing, and IL-6 is the cytokine mainly indirectly inhibited by Xuebijing.

Prostate cancer is currently associated with higher morbidity and mortality in men in the United States and Western Europe, so it is important to identify genes that regulate prostate cancer. The high-dimension gene expression profile impedes the discovery of biclusters which are of great significance to the identification of the basic cellular processes controlled by multiple genes and the identification of large-scale unknown effects hidden in the data. We applied the biclustering method MCbiclust to explore large biclusters in the TCGA cohort through a large number of iterations. Two biclusters were found with the highest silhouette coefficient value. The expression patterns of one bicluster are highly similar to those found by the gene expression profile of the known androgen-regulated genes. Further gene set enrichment revealed that mitochondrial function-related genes were negatively correlated with AR regulation-related genes. Then, we performed differential analysis, AR binding site analysis, and survival analysis on the core genes with high phenotypic contribution. Among the core genes, NDUFA10 showed a low expression value in cancer patients across different expression profiles, while NDUFV2 showed a high expression value in cancer patients. Survival analysis of NDUFA10 and NDUFV2 demonstrated that both genes were unfavorable prognostic markers.

BACKGROUND: The aim of this study is to retrospectively evaluate the efficacy of 3D navigational template for Salter osteotomy of DDH in children. METHODS: Thirty-two consecutive patients with DDH who underwent Salter osteotomy were evaluated between July 2014 and August 2017, and they were divided into the conventional group (n = 16) and navigation template group (n = 16) according to different surgical methods. The corrective acetabular degrees, radiation exposure, and operation time were compared between the two groups. RESULTS: No nerve palsy or redislocation was reported in the navigation template group. Compared with the conventional group, the navigation template group had the advantages of more accurate acetabular degrees, less radiation exposure, and shorter operation time (P < 0.05). Meanwhile, the navigation template group achieved a better surgical outcome than the conventional group (McKay, P = 0.0293; Severin, P = 0.0949). CONCLUSIONS: The 3D navigational template for Salter osteotomy of DDH is simple and effective, which could be an alternative approach to improve the Salter osteotomy accuracy and optimize the efficacy.

BACKGROUND: Colon cancer (CC) is a malignant tumor with a high incidence and poor prognosis. Accumulating evidence shows that the immune signature plays an important role in the tumorigenesis, progression, and prognosis of CC. Our study is aimed at establishing a novel robust immune-related gene pair signature for predicting the prognosis of CC. METHODS: Gene expression profiles and corresponding clinical information are obtained from two public data sets: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO, GSE39582). We screened out immune-related gene pairs (IRGPs) associated with prognosis in the discovery cohort. Lasso-Cox proportional hazard regression was used to develop the best prognostic signature model. According to this, the patients in the validation cohort were divided into high immune-risk group and low immune-risk group, and the prediction ability of the signature model was verified by survival analysis and independent prognostic analysis. RESULTS: A total of 17 IRGPs composed of 26 IRGs were used to construct a prognostic-related risk scoring model. This model accurately predicted the prognosis of CC patients, and the patients in the high immune-risk group indicated poor prognosis in the discovery cohort and validation cohort. Besides, whether in univariate or multivariate analysis, the IRGP signature was an independent prognostic factor. T cell CD4 memory resting in the low-risk group was significantly higher than that in the high-risk group. Functional analysis showed that the biological processes of the low-risk group included "TCA cycle" and "RNA degradation," while the high-risk group was enriched in the "CAMs" and "focal adhesion" pathways. CONCLUSION: We have successfully established a signature model composed of 17 IRGPs, which provides a novel idea to predict the prognosis of CC patients.

OBJECTIVE: Curcumin, a major bioactive curcuminoid derived from the rhizome of Curcuma longa, is known to have anticancer potential and is still under investigation. In this study, we investigated the cytotoxic mechanism(s) of curcumin against acidity-tolerant prostate cancer PC-3AcT cells in lactic acid-containing medium. METHODS: Using 2D-monolyer and 3D spheroid culture models, MTT assay, annexin V-PE binding assay, flow cytometric analysis, measurement of ATP content, and Western blot analysis were used for this study. RESULTS: At nontoxic concentrations in normal prostate epithelial RWPE-1 and HPrEC cells, curcumin led to strong cytotoxicity in PC-3AcT cells, including increases in sub-G0/G1 peak, annexin V-PE-positive cells, and ROS levels; loss of mitochondrial membrane potential; reduction of cellular ATP content; DNA damage; and concurrent induction of apoptosis and necroptosis. A series of changes induced by curcumin were effectively reversed by reducing ROS levels or replenishing ATP. Pretreatment with apoptosis inhibitor Q-VD-Oph-1 or necroptosis inhibitor necrostatin-1 restored cell viability inhibited by curcumin. Treatment of 3D spheroids with curcumin decreased cell viability, accompanied by an increase in mediators of apoptosis and necroptosis, including cleaved caspase-3 and cleaved PARP, phospho (p)-RIP3, and p-MLKL proteins. CONCLUSION: This study shows that curcumin simultaneously induces apoptosis and necroptosis by oxidative mitochondrial dysfunction and subsequent ATP depletion, providing a mechanistic basis for understanding the novel role of curcumin for prostate carcinoma cells.

BACKGROUND: Research has previously been done into the risk factors for mortality in septic shock patients. However, there has been no epidemiological study investigating the effect of the blood urea nitrogen/creatinine ratio (BCR) on the prognosis of critically ill septic shock patients. This study is aimed at determining the relationship between BCR and all-cause mortality in adult septic shock patients. METHODS: Data were extracted from the MIMIC-III database. The clinical endpoints were 28-, 90-, and 365-day all-cause mortality rates in critically ill septic shock patients. Cox proportional hazards models and subgroup analyses were used to analyze the relationship between BCR quartiles and all-cause mortality in septic shock patients. Receiver operator characteristic (ROC) curves and areas under the ROC curves (AUCs) were calculated to evaluate how accurately BCR predicts the mortality of septic shock patients. RESULTS: Among the 2484 septic shock patients extracted from the database, 619, 563, 677, and 625 fell into the first (<14.4 mg/dL), second (≥14.4 mg/dL and <20.0 mg/dL), third (≥20.0 mg/dL and <27.3 mg/dL), and fourth (≥27.3 mg/dL) quartiles of BCR, respectively. Male and white patients accounted for 53.8% (1336 patients) and 74.8% (1857 patients) of the population, respectively. The mean age of the population was 67.7 ± 15.8 years. An inverse M-shaped relationship between BCR and mortality in septic shock patients was identified, with a value of ≥27.3 mg/dL providing the highest risk (HR = 1.596, 95% CI: 1.396-1.824, P < 0.001). In the Cox regression model adjusted for different confounding variables, BCR values in the fourth quartiles were significantly associated with increased mortality, using the first quartiles as a reference. The areas under the ROC curves (AUCs) for BCR plus the Sequential Organ Failure Assessment (SOFA) score and BCR plus Acute Physiology Score III (APSIII) were 0.694 (95% CI: 0.673-0.716) and 0.724 (95% CI: 0.703-0.744), respectively. CONCLUSION: An inverse M-shaped curve was determined between BCR and the mortality of septic shock patients. BCR was identified as a readily available and independent prognostic biomarker for septic shock patients, and higher BCRs were associated with increased mortality in these patients.

BACKGROUND: Teaching is one of the professions where incidence and prevalence of neck pain is high. Prolonged use of computers, which has further increased due to online teaching amid pandemic, is known to cause neck pain and alter posture, while people with forward head posture (FHP) are prone to develop neck pain and related disability. Research has shown that impairment of deep cervical flexor (DCF) muscles leads to insufficiency in coordination, activation, overload, and poor support on cervical structures that further lead to development of neck pain and altered neck posture. The objective of this study was to see the effect of DCF muscle training using pressure biofeedback on pain and FHP in school teachers with neck pain. METHODS: This observational study was conducted at medical center in school premises. Fifty-five school teachers aged between 25 and 40 years with experience of more than 5 years were invited to participate in this study. Subjects were divided in two groups. Both the groups received conventional exercises while in experimental group DCF muscle training using pressure biofeedback was given additionally. Pain and FHP were assessed using NPRS and cranio-vertebral angle using digital photograph technique, respectively, at baseline and end of four weeks of treatment. RESULTS: Although pain and FHP improved in both the groups, mean improvement in both the measures was more in the group that also received DCF training using pressure biofeedback. CONCLUSIONS: This study shows that although pain and FHP improved following conventional exercises in school teachers with neck pain, mean improvement was more significant among those who received additional DCF muscle training using pressure biofeedback.

INTRODUCTION: Antimicrobial resistance represents a growing public health threat. One of the World Health Organization's strategic objectives is "strengthening knowledge through surveillance and research." Sub-Saharan African countries are still far from achieving this objective. We aimed to estimate and compare the prevalence of antibacterial resistance in 2010 and 2017 in Cameroon. METHODS: We conducted a retrospective study on all clinical specimens cultured in Centre Pasteur du Cameroun (CPC) in 2010 and 2017. Data were extracted from the CPC's laboratory data information system software and then managed and analyzed using R. Bacterial resistance rates were calculated in each year and compared using chi-square or Fisher's tests, and relative changes were calculated. Outcomes included acquired resistance (AR), WHO priority resistant pathogens, some specific resistances of clinical interest, and resistance patterns (multi, extensively, and pan drug resistances) for five selected pathogens. RESULTS: A total of 10,218 isolates were analyzed. The overall AR rate was 96.0% (95% CI: 95.4-96.6). Most of WHO priority bacterial resistance rates increased from 2010 to 2017. The most marked increases expressed as relative changes concerned imipenem-resistant Acinetobacter (6.2% vs. 21.6%, +248.4%, p = 0.02), imipenem-resistant Pseudomonas aeruginosa (13.5% vs. 23.5%, +74.1%, p < 0.01), 3rd generation-resistant Enterobacteriaceae (23.8% vs. 40.4%, +65.8%, p < 10-15), methicillin-resistant Staphylococcus aureus (27.3% vs. 46.0%, +68.6%, p < 0.002), fluoroquinolone-resistant Salmonella (3.9% vs. 9.5%, +142.9%, p = 0.03), and fluoroquinolone-resistant Enterobacteriaceae (32.6% vs. 54.0%, +65.8%, p < 10-15). For selected pathogens, global multidrug resistance was high in 2010 and 2017 (74.9% vs. 78.0% +4.1%, p = 0.01), intensively drug resistance rate was 5.8% (7.0% vs. 4.7%; p = 0.07), and no pan drug resistance has been identified. CONCLUSION: Bacterial resistance to antibiotics of clinical relevance in Cameroon was high and appeared to increase between 2010 and 2017. There is a need for regular surveillance of antibacterial resistance to inform public health strategies and empirically inform prescription practices.

BACKGROUND: Pyrethroid insecticides are widely used in many countries for chemical-based control of Ae. aegypti. Regardless of their efficacy, the constant use of insecticides has induced insecticide resistance mechanisms, such as knockdown resistance (kdr) in mosquitoes. Sri Lankan Vector Controlling Entities (VCE) have been using a variety of pyrethroid insecticides as the primary approach for dengue control. However, development of any resistance among the Aedes mosquitoes has been limitedly studied in the country. Therefore, the current study was conducted to evaluate the prevalence of F1534C, V1016G, and S989P mutations among Ae. aegypti mosquito populations in three dengue endemic high-risk regions of Sri Lanka. Methodology. Immature (both pupae and larvae) stages of Ae. aegypti mosquitoes were collected from Colombo, Gampaha, and Kandy districts of Sri Lanka from February 2018 to December 2019. Polymerase Chain Reaction- (PCR-) based assay for molecular genotyping of mutations was performed to identify the prevalence of kdr mutations in collected Ae. aegypti populations, separately. The frequencies of the resistant and susceptible kdr alleles were determined by using the Hardy-Weinberg equilibrium. RESULTS: The Ae. aegypti populations from Colombo, Gampaha, and Kandy districts showed 46%, 42%, and 22% of F1534C mutation allele frequencies, along with 15%, 12%, and 6% of V1016G mutation allele frequencies, respectively. The mutation allele frequencies of S989 in Colombo, Gampaha, and Kandy districts were 9.5%, 8.5%, and 4.5%, respectively. The wild-type (PP) genotype remained predominant within all the three districts, whereas the homogenous (QQ) mutation genotype occurred only in minority. The abundance of Q allele frequency in Ae. aegypti mosquitoes was relatively higher for all the three mutations in Colombo. CONCLUSIONS: The findings clearly indicate that long-term insecticide applications and multiple use of pyrethroids have led to the acquisition of kdr mutations, leading to the development of insecticide resistance among local Ae. aegypti populations, especially in the Colombo and Gampaha districts. Therefore, evaluation of the prevalence levels of these kdr mutations highlights the necessity for shifting towards novel vector control strategies.

Advanced single-cell profiling technologies promote exploration of cell heterogeneity, and clustering of single-cell RNA (scRNA-seq) data enables discovery of coexpression genes and network relationships between genes. In particular, single-cell profiling of circulating tumor cells (CTCs) can provide unique insights into tumor heterogeneity (including in triple-negative breast cancer (TNBC)), while scRNA-seq leads to better understanding of subclonal architecture and biological function. Despite numerous reports suggesting a direct correlation between circulating tumor cells (CTCs) and poor clinical outcomes, few studies have provided a thorough heterogeneity characterization of CTCs. In addition, TNBC is a disease with not only intertumor but also intratumor heterogeneity and represents various biological distinct subgroups that may have relationships with immune functions that are not clearly established yet. In this article, we introduce a new scheme for detecting genotypic characterization of single-cell heterogeneities and apply it to CTC and TNBC single-cell RNA-seq data. First, we use an existing mixture exponential family graph model to partition the cell-cell network; then, with the Markov random field model, we obtain more flexible network rewiring. Finally, we find the cell heterogeneity and network relationships according to different high coexpression gene modules in different cell subsets. Our results demonstrate that this scheme provides a reasonable and effective way to model different cell clusters and different biological enrichment gene clusters. Thus, using different internal coexpression genes of different cell clusters, we can infer the differences in tumor composition and diversity.

High kernel elongation (HKE) is one of the high-quality characteristics in rice. The objectives of this study were to determine the effects of ageing treatments, gene actions, and inheritance pattern of kernel elongation on cooking quality in two populations of rice and determine the path of influence and contribution of other traits to kernel elongation in rice. Two rice populations derived from crosses between MR219 × Mahsuri Mutan and MR219 × Basmati 370 were used. The breeding materials included two F1 progenies from the two populations, and their respective parents were grown in four different batches at a week interval to synchronize the flowering between the female and male plants. Scaling tests and generation means analysis were carried out to determine ageing effects and estimate additive-dominance gene action and epistasis. The estimation of gene interaction was based on quantitative traits. Path coefficient analysis was done using SAS software version 9.4 to determine the path of influence (direct or indirect) of six quantitative traits on HKE. Results obtained showed that nonallelic gene interaction was observed in all traits. The results before ageing and after ageing showed significant differences in all traits, while the gene interaction changed after ageing. The HKE value improved after ageing, suggesting that ageing is an external factor that could influence gene expression. The epistasis effect for HKE obtained from the cross Mahsuri Mutan × MR219 showed duplicate epistasis while that obtained from a cross between Basmati 370 × MR219 showed complimentary epistasis. Besides, the heritability of HKE was higher in Basmati 370 × MR219 compared to that obtained in Mahsuri Mutan × MR219. The path analysis showed that the cooked grain length and length-width ratio positively significantly affected HKE. It was concluded that ageing treatment is an external factor that could improve the expression of HKE. The findings from this study would be useful to breeders in the selection and development of new specialty (HKE) rice varieties.

OBJECTIVE: Interleukin- (IL-) 34 is a new type of cytokine with neuroprotective effects discovered in recent years. However, the relationship between IL-34 and vascular dementia (VaD) has not yet been elucidated. The purpose of this study is to determine whether IL-34 is involved in cognitive impairment of VaD. METHODS: From January 2017 to December 2020, 84 VaD patients and 60 healthy controls who attended Qingpu Branch of Zhongshan Hospital were prospectively included in the study. Once included in the study, demographic features of all research subjects are collected. They include age, gender, education, white blood cells (WBC), neutrophil, lymphocyte, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC). Meanwhile, the Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function of participants. The serum IL-34 level was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: There was no significant difference between the demographic features of VaD patients and healthy controls (p > 0.05). However, the serum IL-34 levels of VaD patients and healthy controls are 27.6 ± 3.9 pg/ml and 41.8 ± 6.0 pg/ml, respectively, and there is a significant statistical difference between them (p < 0.001). The results of bivariate correlation analysis showed that serum IL-34 levels were significantly positively correlated with MoCA scores (r = 0.371, p = 0.023). Further regression analysis showed that IL-34 was still correlated with MoCA after adjusting for demographic features (β = 0.276, p = 0038). CONCLUSIONS: Serum IL-34 levels in VaD patients were significantly reduced, which may be an independent predictor of cognitive impairment in VaD patients.

The aim of the present work was to investigate the risk factors for gastric cancer- (GC-) associated thrombotic diseases in a Han Chinese population. A total of 333 patients diagnosed with GC, 68 with thrombotic diseases included in the case group and the remaining 265 in the control group, were enrolled. The relevant data for the participants, including general information (gender, age, smoking, and drinking), comorbidities (diabetes, hypertension, and anemia), tumor-related data (tumor site, histology, degree of differentiation, and clinical stage), and treatment-related data (surgery, chemotherapy, hormones, transfusion, and peripherally inserted central venous catheter (PICC)), were collected. Statistically significant factors derived from univariate analyses were then subjected to multivariate logistic regression analyses. The results demonstrate a statistically significant difference in age, diabetes, hypertension, histology, surgery, chemotherapy, and PICC (P < 0.05), compared with control. Age, diabetes, surgery, and PICC serve as independent risk factors for GC-associated thrombotic diseases (P < 0.05). The present work demonstrates that GC-associated thrombotic diseases are significantly associated with age, diabetes, surgery, and PICC, suggesting a potential target for early detection and preventive strategy for GC patients with thrombophilia.

Bioactive peptides attract growing concerns for their participation in multiple biological processes. Their roles in the pathogenesis of type 1 diabetes mellitus remain poorly understood. In this study, we used LC-MS/MS technology to compare the peptide profiling between pancreatic tissue of T1DM mice and pancreatic tissue of matched control groups. A total of 106 peptides were differentially expressed in T1DM pancreatic tissue, including 43 upregulated and 63 downregulated peptides. Most of the precursor proteins are insulin. Further bioinformatics analysis (GO and pathway analysis) indicated that the potential functions of these differential peptides were tightly related to regulation of endoplasmic reticulum stress. In conclusion, this study highlights new candidate peptides and provides a new perspective for exploring T1DM pathogenesis and clinical treatments.

The recent COVID-19 pandemic has impacted nearly the whole world due to its high morbidity and mortality rate. Thus, scientists around the globe are working to find potent drugs and designing an effective vaccine against COVID-19. Phytochemicals from medicinal plants are known to have a long history for the treatment of various pathogens and infections; thus, keeping this in mind, this study was performed to explore the potential of different phytochemicals as candidate inhibitors of the HR1 domain in SARS-CoV-2 spike protein by using computer-aided drug discovery methods. Initially, the pharmacological assessment was performed to study the drug-likeness properties of the phytochemicals for their safe human administration. Suitable compounds were subjected to molecular docking to screen strongly binding phytochemicals with HR1 while the stability of ligand binding was analyzed using molecular dynamics simulations. Quantum computation-based density functional theory (DFT) analysis was constituted to analyze the reactivity of these compounds with the receptor. Through analysis, 108 phytochemicals passed the pharmacological assessment and upon docking of these 108 phytochemicals, 36 were screened passing a threshold of -8.5 kcal/mol. After analyzing stability and reactivity, 5 phytochemicals, i.e., SilybinC, Isopomiferin, Lycopene, SilydianinB, and Silydianin are identified as novel and potent candidates for the inhibition of HR1 domain in SARS-CoV-2 spike protein. Based on these results, it is concluded that these compounds can play an important role in the design and development of a drug against COVID-19, after an exhaustive in vitro and in vivo examination of these compounds, in future.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication which may be caused by a perioperative nutrition problem. We aimed to study whether patients with high nutritional risk (NRS2002 score ≥ 5) might benefit from preoperative nutrition support regarding the risk of CR-POPF after open pancreaticoduodenectomy. METHODS: Consecutive patients undergoing open pancreaticoduodenectomy with complete record of NRS2002 at two Chinese institutions between 2013 and 2018 were analysed. CR-POPF was diagnosed following the 2016 ISGPS criteria. Nutrition support included oral nutrition supplement and enteral and parenteral nutrition. Clinical and economic outcomes were analysed. RESULTS: 522 cases were included. 135 cases (25.9%) were at high nutritional risk (NRS2002 score ≥ 5), among which 41 cases (30.4%) received preoperative nutrition support. The CR-POPF rate was significantly lower in the preoperative nutrition support group compared with the no nutrition support group (12.2% versus 28.7%, P = 0.038). Multivariate analysis showed that preoperative nutrition support was a protective factor for CR-POPF in patients at high risk [OR 0.339, 95% CI (0.115-0.965), P = 0.039]. Higher albumin and a larger diameter of the main pancreatic duct were found to be other protectors for CR-POPF. CONCLUSIONS: Patients with high nutritional risk (NRS2002 score ≥ 5) may profit from preoperative nutritional support manifested in the reduction of CR-POPF.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. Therefore, there is an urgent call for the investigation of novel biomarkers in HCC. In the present study, we identified 6 upregulated lncRNAs in HCC, including LINC01134, RHPN1-AS1, NRAV, CMB9-22P13.1, MKLN1-AS, and MAPKAPK5-AS1. Higher expression of these lncRNAs was correlated to a more advanced cancer stage and a poorer prognosis in HCC patients. Enrichment analysis revealed that these lncRNAs played a crucial role in HCC progression, possibly through a series of cancer-related biological processes, such as cell cycle, DNA replication, histone acetyltransferase complex, fatty acid oxidation, and lipid modification. Moreover, competing endogenous RNA (ceRNA) network analysis revealed that these lncRNAs could bind to certain miRNAs to promote HCC progression. Loss-of-function assays indicated that silencing of RHPN1-AS1 significantly suppressed HCC proliferation and migration. Though further validations are still needed, these identified lncRNAs could serve as valuable potential biomarkers for HCC prognosis.

Cisplatin is an efficacious anticancer agent, but its use is limited by ototoxicity and resultant irreversible sensorineural hearing loss. Cisplatin ototoxicity is associated with cochlear cell oxidative stress and mitochondrial damage. However, mitophagy is vital for maintaining mitochondrial quality and cellular metabolism. Accordingly, we investigated the role of mitophagy in regulating cisplatin-induced ototoxicity using the auditory cell line HEI-OC1. In this study, HEI-OC1 cells were treated with either cisplatin alone (10 μM, 0, 8, 16, and 24 h); cisplatin (10 μM, 24 h) post transfection with small-interfering (si)RNAs targeting mitophagy-associated mRNAs; cisplatin (10 μM, 24 h) succeeding pretreatment with the mitophagy suppressor, 3-methyladenine (3-MA; 5 or 10 mM, 6 h); or cisplatin (30 μM, 24 h) following pretreatment with the mitophagy promoter, carbonyl cyanide m-chlorophenylhydrazone (CCCP; 1 or 2 μM, 2 h). The viability of cells, expression of mitophagy marker, and mitochondrial functions were then assessed in these cells. Cell viability was determined by a water-soluble tetrazolium assay; expression of mitophagy-associated proteins PINK1, Parkin, BNIP3, FUNDC1, p62, and LC3B was analyzed by Western blotting, mitochondrial membrane potential by flow cytometry, intracellular ATP by spectrophotometry, and mitochondrial degradation by dual staining for mitochondria and autophagosomes or lysosomes. Our results showed that cisplatin gradually reduced the viable cell number over time, induced mitochondrial depolarization, decreased intracellular ATP concentration, and enhanced the expression of PINK1, Parkin, BNIP3, p62, and LC3B. In addition, Parkin and BNIP3 knockdown accelerated cisplatin-induced loss of cell viability, mitochondrial membrane potential, mitophagosome/lysosome formation, and reduction in intracellular ATP production. Pretreatment with 3-MA aggravated the cisplatin-induced cytotoxicity, while that with CCCP reversed this effect. Overall, our findings indicate that mitophagy protects HEI-OC1 cells against cisplatin-induced cell death. Consequently, we strongly believe that targeted promotion of mitophagy may confer protection against cisplatin-induced ototoxicity.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers for systemic inflammation condition. Although NLR has emerged as a risk factor for poor survival in end-stage renal disease (ESRD) patients, the relationship between PLR and mortality is still unknown. We aimed to explore the interaction of NLR and PLR in predicting mortality in hemodialysis (HD) patients. METHOD: We enrolled 360 HD patients for a 71-month follow-up. The endpoint was all-cause and cardiovascular (CV) mortality. Pearson correlation analysis was conducted to evaluate the relationship between factors and NLR or PLR. Kaplan-Meier curves and Cox proportional analysis were used to assess the prognostic value of NLR and PLR. RESULTS: NLR was positively correlated with neutrophil and negatively correlated with lymphocyte, hemoglobin, and serum albumin. PLR was positively correlated with neutrophil and platelet and negatively correlated with lymphocyte and hemoglobin. In multivariate Cox regression, a higher NLR level was independently associated with all-cause mortality (OR 2.011, 95% CI 1.082-3.74, p = 0.027), while a higher PLR level might predict CV mortality (OR 2.768, 95% CI 1.147-6.677, p = 0.023) in HD patients. CONCLUSION: NLR and PLR are cheap and reliable biomarkers for all-cause and CV mortality to predict survival in HD patients.

In the present study, we examined the synergetic effect of forskolin and mevastatin administration on lipid profile and lipid metabolism in omental adipose tissue in dyslipidemic rats. The study was conducted on forty male albino rats. The rats were randomly classified into four main groups of ten animals in each group as follows: group A, served as control nontreated; group B, rats that received Triton WR 1339 (500 mg/kg); group C, rats that received Triton WR 1339 with forskolin (100% FSK extract 0.5 mg/kg/day) for four weeks; and group D, dyslipidemic rats received both mevastatin and forskolin. At the end of the experimental period, blood and omental adipose tissue samples were collected, preserved, and used for biochemical determination of lipid profile and mRNA expression profile of adenylate cyclase (AC), hormone-sensitive lipase, respectively (HSL), and adenosine monophosphate-activated protein kinase (AMPK). The results showed a significant decline in the serum concentration of total cholesterol, LDL-cholesterol, and triglycerides, although there was a significant increase in serum levels of HDL-cholesterol and glycerol in rats received forskolin alone or with mevastatin when compared with control and dyslipidemic groups. The mRNA expression levels of AC, HSL, and AMPK were significantly increased in omental adipose tissue of rats received forskolin when compared with other groups. In conclusion, forskolin acts synergistically with mevastatin to lower lipid profile and improve lipid metabolism in dyslipidemic rats through upregulation of AMPK expression.

PURPOSE: To evaluate the prognostic role of prothrombin time (PT) and activated partial thromboplastin time (APTT) for newly diagnosed multiple myeloma (MM). METHODS: We retrospectively analyzed 354 patients with newly diagnosed MM who received primary treatment in our center. The propensity score matching technique was used to reduce the bias between groups. RESULTS: Among 354 patients, lengthened PT or APTT was observed in 154 (43.5%) patients and 200 (56.5%) patients had normal PT and APTT. Patients with lengthened PT or APTT had significantly shorter median overall survival (OS) (37.5 vs. 73.8 months, p < 0.001) and progression-free survival (PFS) (23.1 vs. 31.6 months, p = 0.001) than those with normal PT and APTT. Univariate Cox proportional hazards regression analyses showed that lengthened PT or APTT was associated with shorter OS (HR = 2.100, 95% CI: 1.525-2.893, p < 0.001). Lengthened PT or APTT was also a poor prognostic factor for OS (HR = 3.183, 95% CI: 1.803-5.617, p < 0.001) in multivariable analyses. The poor effect of lengthened PT or APTT on PFS was confirmed in univariate analysis (HR = 1.715, 95% CI: 1.244-2.365, p = 0.001), but it had no impact on PFS in multivariate analysis (p = 0.197). In the propensity score matching analysis, 154 patients, 77 in each group, were identified. Among 154 matched patients, the OS of patients with lengthened PT or APTT was shorter (38.4 vs. 51.0 months, p = 0.030), but PFS was similar (29.0 vs. 35.0 months, p = 0.248). CONCLUSION: These results demonstrated that lengthened PT or APTT was an independent poor prognostic factor for patients with newly diagnosed MM.

To investigate the mechanisms through which Yinchenhao decoction (YCHD) inhibits hepatocellular carcinoma (HCC), we analyzed YCHD ingredients absorbed into the bloodstream by using network pharmacology. We conducted a weighted gene coexpression network analysis on gene expression data collected from the Gene Expression Omnibus and The Cancer Genome Atlas databases to derive an HCC gene set; moreover, we used four online prediction system databases to predict the potential targets of YCHD ingredients absorbed into the bloodstream. We discovered that YCHD directly interfered with 17 HCC-related disease targets. Subsequent gene ontology enrichment analyses of these 17 disease targets revealed that YCHD exhibited effects through 17 biological processes, 7 molecular functions, and 9 cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated 14 pathways through which YCHD inhibits HCC. We observed similar trends in how the 17 small molecules interfered with the key target set. We surmised that YCHD inhibits HCC by regulating inflammatory and metabolic pathways. Network pharmacological analysis of YCHD ingredients absorbed into the bloodstream may provide new insights and serve as a new method for discovering the molecular mechanisms through which YCHD inhibits HCC.

BACKGROUND: Thymoma is a heterogeneous tumor originated from thymic epithelial cells. The molecular mechanism of thymoma remains unclear. METHODS: The expression profile, methylation, and mutation data of thymoma were obtained from TCGA database. The coexpression network was constructed using the variance of gene expression through WGCNA. Enrichment analysis using clusterProfiler R package and overall survival (OS) analysis by Kaplan-Meier method were carried out for the intersection of differential expression genes (DEGs) screened by limma R package and important module genes. PPI network was constructed based on STRING database for genes with significant impact on survival. The impact of key genes on the prognosis of thymoma was evaluated by ROC curve and Cox regression model. Finally, the immune cell infiltration, methylation modification, and gene mutation were calculated. RESULTS: We obtained eleven coexpression modules, and three of them were higher positively correlated with thymoma. DEGs in these three modules mainly involved in MAPK cascade and PPAR pathway. LIPE, MYH6, ACTG2, KLF4, SULT4A1, and TF were identified as key genes through the PPI network. AUC values of LIPE were the highest. Cox regression analysis showed that low expression of LIPE was a prognostic risk factor for thymoma. In addition, there was a high correlation between LIPE and T cells. Importantly, the expression of LIPE was modified by methylation. Among all the mutated genes, GTF2I had the highest mutation frequency. CONCLUSION: These results suggested that the molecular mechanism of thymoma may be related to immune inflammation. LIPE may be the key genes affecting prognosis of thymoma. Our findings will help to elucidate the pathogenesis and therapeutic targets of thymoma.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most prevalent metabolic disease during pregnancy, but the diagnosis is controversial and lagging partly due to the lack of useful biomarkers. CpG methylation is involved in the development of GDM. However, the specific CpG methylation sites serving as diagnostic biomarkers of GDM remain unclear. Here, we aimed to explore CpG signatures and establish the predicting model for the GDM diagnosis. METHODS: DNA methylation data of GSE88929 and GSE102177 were obtained from the GEO database, followed by the epigenome-wide association study (EWAS). GO and KEGG pathway analyses were performed by using the clusterProfiler package of R. The PPI network was constructed in the STRING database and Cytoscape software. The SVM model was established, in which the β-values of selected CpG sites were the predictor variable and the occurrence of GDM was the outcome variable. RESULTS: We identified 62 significant CpG methylation sites in the GDM samples compared with the control samples. GO and KEGG analyses based on the 62 CpG sites demonstrated that several essential cellular processes and signaling pathways were enriched in the system. A total of 12 hub genes related to the identified CpG sites were found in the PPI network. The SVM model based on the selected CpGs within the promoter region, including cg00922748, cg05216211, cg05376185, cg06617468, cg17097119, and cg22385669, was established, and the AUC values of the training set and testing set in the model were 0.8138 and 0.7576. The AUC value of the independent validation set of GSE102177 was 0.6667. CONCLUSION: We identified potential diagnostic CpG signatures by EWAS integrated with the SVM model. The SVM model based on the identified 6 CpG sites reliably predicted the GDM occurrence, contributing to the diagnosis of GDM. Our finding provides new insights into the cross-application of EWAS and machine learning in GDM investigation.

BACKGROUND: Anemia is a situation in which the number and size of red blood cells, or the concentration of hemoglobin, fall below established cut-off values. Low hemoglobin level during pregnancy favors the alteration of placental angiogenesis and resulted in restricting the availability of nutrients to the fetus and consequently causing fetal growth retardation and low weight at birth. This study is aimed at assessing the hemoglobin level and associated factors among pregnant women in rural communities of Jimma zone, Southwest Ethiopia. METHODS: A community-based cross-sectional study design was carried out among 367 pregnant women from June 1 to 30, 2020. Systematic random sampling was used to select study subjects. Hemoglobin level was measured by using HemoCue HB 301. An interviewer-administered structured questionnaire was used to collect the data. Descriptive statistics were used to describe the study subjects. A multivariable linear regression model was employed after the linearity, normality, multicollinearity, and homoscedasticity assumptions were checked. The unstandardized beta (β) coefficient along with a 95% confidence interval was computed to estimate the association between explanatory and dependant variables. Statistical significance was declared at P value < 0.05. RESULTS: The mean (± SD) hemoglobin level of the respondents was 12.66 (±1.44) g/dl. The overall magnitude of anemia (hemoglobin level < 11 g/dl) among pregnant women was found to be 85 [23.16%, (95% CI: 18.3%-27.5%)]. Meal frequency [β = 0.40, (95% CI: 0.12, 0.69), P = 0.005], interpregnancy interval [β = 0.08, (95% CI: 0.02, 0.15), P = 0.007], mid-upper arm circumference measurement [β = 0.13, (95% CI: 0.07, 0.20), P ≤ 0.001], own fruits/vegetable [β = 0.55, (95% CI: 0.79, 0.31), P ≤ 0.001], coffee consumption [β = -1.00, (95% CI: -1.31, -0.68), P ≤ 0.001], and having history of still birth [β = -0.63, (95% CI: -1.06, -0.20), P = 0.004] were significantly associated with the hemoglobin level of pregnant women. CONCLUSIONS: Anemia was identified to be a moderate public health problem in the study area. Therefore, nutritional counseling should focus on the necessity of at least one extra meal, promotion of fruits/vegetable consumption, and improving the nutritional status of the women during antenatal care follow-up. Moreover, early screening and management of women with a history of stillbirth for anemia are also essential.

The aim of this study is to investigate the targeting efficiency of FITC-SS31 to mitochondria in both normal and H2O2-induced oxidative damaged 661W cells, characterizing the properties of FITC-SS31 in the biological assays. The purity and molecular weight of FITC-SS31 were identified using HPLC and MS. MTT and LDH assays were used to evaluate the cytotoxicity and cell permeability. The binding ability of FITC-SS31 to cells was demonstrated by flow cytometry. The colocalization of FITC-SS31 and MitoTracker both in normal and oxidative cells was analyzed by a laser confocal microscope. We detected the DEGs between SS31+H2O2 and H2O2-alone-treated cells by RNA seq. GO and KEGG analyses were performed to predict the functional gene of SS31. The molecular weight of FITC-SS31 was 1142.2 with the 97.76% purity. The flow cytometry results showed that the MFI (mean fluorescence intensity) of FITC-SS31 in normal cells in the 4 h probe treatment group was higher than that in the 2 h and the 0 h group. The MFI in the 2 h probe treatment group was much higher than that in the 4 h and 0 h groups in damaged cells. The positive rate of 10 μM FITC-SS31 was higher than that of 1 μM and 5 μM. Fluorescein imaging analysis confirmed that FITC-SS31 was overlapped with MitoTracker. Through the analysis, DEGs were highly expressed in "localization, organelle, antioxidant activity, binding" functions and enriched in "AMPK signaling pathway, MAPK targets/nuclear events mediated by MAP kinase pathway and PI3K-Akt signaling pathway." It is speculated that SS31 exerts an antioxidant effect through one of these pathways. We hypothesized that SS31 could play a more efficient role in the pathological cells in the half-life period to avoid cell death due to oxidative damage. The functions of the DEGs in SS31+H2O2 and H2O2-alone samples are related to the localization and antioxidant activity of SS31. DEGs are mostly enriched in the AMPK signaling pathway, which needs further studies.

As of December 2020, since the beginning of the year 2020, the COVID-19 pandemic has claimed worldwide more than 1 million lives and has changed human life in unprecedented ways. Despite the fact that the pandemic is far from over, several countries managed at least temporarily to make their first-wave COVID-19 epidemics to subside to relatively low levels. Combining an epidemiological compartment model and a stability analysis as used in nonlinear physics and synergetics, it is shown how the first-wave epidemics in the state of New York and nationwide in the USA developed through three stages during the first half of the year 2020. These three stages are the outbreak stage, the linear stage, and the subsiding stage. Evidence is given that the COVID-19 outbreaks in these two regions were due to instabilities of the COVID-19 free states of the corresponding infection dynamical systems. It is shown that from stage 1 to stage 3, these instabilities were removed, presumably due to intervention measures, in the sense that the COVID-19 free states were stabilized in the months of May and June in both regions. In this context, stability parameters and key directions are identified that characterize the infection dynamics in the outbreak and subsiding stages. Importantly, it is shown that the directions in combination with the sign-switching of the stability parameters can explain the observed rise and decay of the epidemics in the state of New York and the USA. The nonlinear physics perspective provides a framework to obtain insights into the nature of the COVID-19 dynamics during outbreak and subsiding stages and allows to discuss possible impacts of intervention measures. For example, the directions can be used to determine how different populations (e.g., exposed versus symptomatic individuals) vary in size relative to each other during the course of an epidemic. Moreover, the timeline of the computationally obtained stages can be compared with the history of the implementation of intervention measures to discuss the effectivity of such measures.

Mucosal healing comprises a key goal of ulcerative colitis (UC) treatment. Anterior gradient protein 2 (AGR2) plays an important role in maintaining intestinal homeostasis in UC. However, the role of AGR2 in the repair of mucosal injury is not yet clear. This study is aimed at investigating the expression of AGR2 in the intestinal tissues of children with UC and its role in repairing mucosal injury. Forty UC patients who were hospitalized in the Pediatric Gastroenterology Ward of Shengjing Hospital affiliated with China Medical University between July 1, 2013, and May 31, 2020, and 20 children who had normal colonoscopy results during the same period (control group) made up the study sample. The disease activity of UC was evaluated based on the pediatric ulcerative colitis activity index, and the ulcerative colitis endoscopic index was evaluated according to the Rachmilewitz score. Immunohistochemical staining was employed to examine the differences in AGR2 expression in the intestinal mucosa between groups. The protective effect of AGR2 in a model of tumor necrosis factor-alpha- (TNF-α-) induced intestinal mucosal barrier injury and the underlying molecular mechanism were explored through in vitro experiments. The results showed that compared with the normal control group, UC patients in the remission or active period had significantly higher expression of AGR2 in the intestine. AGR2 expression was positively correlated with Ki67, an intestinal epithelial cell proliferation marker, but negatively correlated with the degree of endoscopic mucosal injury. In an in vitro model, AGR2 overexpression promoted cell proliferation and migration and inhibited TNF-α-induced intestinal epithelial barrier damage by activating yes-associated protein (YAP). Collectively, our study suggests that AGR2 might serve as a valuable biomarker to help assess the condition and mucosal healing status of UC patients. In vitro, AGR2 promoted the repair of intestinal mucosal barrier injury by activating YAP.

BACKGROUND: Intervertebral disc degeneration (IDD) disease is a global challenge because of its predominant pathogenic factor in triggering low back pain, whereas cartilaginous endplate degeneration (CEPD) is the main cause of IDD. Accumulating evidence have indicated that the differentially expressed microRNAs (DEMs) and differentially expressed genes (DEGs) have been determined to be involved in multiple biological processes to mediate CEPD progression. However, the differentially expressed circular RNAs (DECs) and their potential biofunctions in CEPD have not been identified. METHODS: GSE153761 dataset was analyzed using R software to predict DECs, DEMs, and DEGs. Pathway enrichment analysis of DEGs and host genes of DECs and protein-protein interaction network of DEGs were conducted to explore their potential biofunctions. Furthermore, we explore the potential relationship between DEGs and DECs. RESULTS: There were 74 DECs, 17 DEMs, and 68 DEGs upregulated whereas 50 DECs, 16 DEMs, and 67 DEGs downregulated in CEPD group. Pathway analysis unveiled that these RNAs might regulate CEPD via mediating inflammatory response, ECM metabolism, chondrocytes apoptosis, and chondrocytes growth. A total of 17 overlapping genes were predicted between the host genes of DEGs and DECs, such as SDC1 and MAOA. Moreover, 6 upregulated DECs, of which hsa_circ_0052830 was the most upregulated circRNA in CEPD, were derived from the host genes SDC1, whereas 8 downregulated DECs were derived from the host genes MAOA. CONCLUSION: This will provide novel clues for future experimental studies to elucidate the pathomechanism of CEPD and therapeutic targets for CEPD-related diseases.

BACKGROUND: Given the increasing prevalence of primary tooth caries in Iran and the importance of providing evidence- and theory-based family-centered prevention programs, the present study is aimed at determining the family-centered social cognitive factors preventing deciduous tooth caries among children using the intervention mapping protocol. METHODS: This cross-sectional study was performed on 240 Iranian mothers in Ilam who were randomly selected to participate in the study. The data were collected using a self-designed questionnaire including items on demographic information and social cognitive constructs (knowledge, attitude, perceived severity, perceived benefits, perceived barriers, practice guidance, perceived self-efficacy, behavior intention, subjective norms, and social norms). The questionnaire was completed by mothers, and the data were analyzed by performing one-way analysis of variance and linear regression. RESULTS: The results obtained from linear regression analysis showed that perceived self-efficacy (B = 0.295, p < 0.001), perceived barriers (B = 0.084, p < 0.028), practice guidance (B = 0.774, p < 0.001), and social norms (B = 0.137, p < 0.020) accounted for 71% of the behavioral intention variance and were the most important predictors for preventing primary tooth caries among children. CONCLUSION: The findings suggest that perceived self-efficacy, perceived barriers, practice guidance, and social norms are essential for developing family-centered programs to prevent primary tooth caries in children.

Imaging of the postoperative spine requires the identification of several critical points by the radiologist to be written in the medical report: condition of the underlying cortical and cancellous bone, intervertebral disc, and musculoskeletal tissues; location and integrity of surgical implants; evaluation of the success of decompression procedures; delineation of fusion status; and identification of complications. This article presents a pictorial narrative review of the most common findings observed in noninstrumented and instrumented postoperative spines. Complications in the noninstrumented spine were grouped in early (hematomas, pseudomeningocele, and postoperative spine infection) and late findings (arachnoiditis, radiculitis, recurrent disc herniation, spinal stenosis, and textiloma). Complications in the instrumented spine were also sorted in early (hardware fractures) and late findings (adjacent segment disease, hardware loosening, and implant migration). This review also includes a short description of the most used diagnostic techniques in postoperative spine imaging: plain radiography, ultrasound (US), computed tomography (CT), magnetic resonance (MR), and nuclear medicine. Imaging of the postoperative spine remained a challenging task in the early identification of complications and abnormal healing process. It is crucial to consider the advantages and disadvantages of the imaging modalities to choose those that provide more accurate spinal status information during the follow-up. Our review is directed to all health professionals dealing with the assessment and care of the postoperative spine.

People infected with chronic hepatitis B virus (HBV) might progress to acute-on-chronic liver failure (ACLF) with a high fatality rate. Long noncoding RNAs (lncRNAs) are involved in human diseases, but it is unknown whether lncRNAs are involved in the progression of chronic HBV infection to ACLF. Hence, this study is aimed at systemically identifying and characterizing the landscape and the molecular mechanism of lncRNAs in the pathogenesis of chronic HBV infection progress to ACLF. RNA sequencing (RNA-Seq) of peripheral blood samples from 5 ACLF and 5 HBV infection patients was performed. We detected 9733 lncRNAs, including 406 annotated lncRNAs and 9327 novel lncRNAs. A total of 407 lncRNAs were found to be significantly dysregulated in the patients with ACLF as compared with those in the chronic HBV infection patients. The flanking protein-coding genes of differentially expressed lncRNAs were enriched with pathways that might contribute to the pathogenesis of ACLF, such as the WNT signaling pathway. Furthermore, 9 selected differentially expressed lncRNAs validated by the qRT-PCR, showing that the expression patterns of these 9 lncRNAs were consistent with the RNA-Seq data. Four selected differentially expressed lncRNAs were also validated in another patient cohort comprising 80 patients with ACLF and 65 patients with chronic HBV infection. Aberrant lncRNAs might be used to develop novel diagnostic biomarkers or drug targets for ACLF.

The study is aimed at assessing whether the early surgical intervention improves survival in acute mesenteric ischemia with septic shock. A retrospective study design was applied to review the charts of patients admitted to the intensive care unit. The data were collected through a review of the full patient chart including physician and nursing notes, pathology reports, intraoperative findings, CT findings, and endoscopy. The diagnosis of AMI for each patient was determined through clinical presentation/endoscopic visualization/laboratory results/radiographic imaging, surgical exam (tissue or visual) and/or autopsy. Death and survival were evaluated between short and long-time-interval for septic shock groups using the chi-square test followed by calculating the P value. Total survival among the surgery group was 60 patients (95.24%) compared to 3 (4.76%) survival among patients who did not have surgery. The time from the onset of a shock to the time of surgical incision was calculated. The mean time to surgery was 17.7 hours. Total 65 patients (29.52%) had surgery between 4 and 12 hours from the onset of hypotension. Survivals among this group of patients were 41.7% (n = 25). The survival difference was statistically significant than died patients with respect to the time of surgical intervention (P = <0.001). Early removal of ischemic bowel in patients with AII-related surgery has improved survival.

BACKGROUND: Vitiligo is a disfiguring skin disease with profound psychosocial impacts, such as anxiety, but the reported effect sizes of associations vary. We aimed to conduct a meta-analysis to quantify the strength of association between anxiety and vitiligo and to estimate the prevalence of anxiety among individuals with vitiligo. METHODS: A systematic literature search was performed in five online databases (MEDLINE, Embase, Web of Science, Cochrane Library, and PsycINFO) from inception until March 20, 2020. All of the eligible studies were comprehensively reviewed, and all of the available data were analyzed according to our predefined criteria. RESULTS: Twenty-one studies involving 3259 patients in 11 countries were included in this meta-analysis. Compared with the healthy control group, patients with vitiligo often had concomitant anxiety (OR = 6.14 [95% CI: 3.35-11.24], I 2 = 30.1%). The pooled prevalence of anxiety in female patients was significantly higher than that in males (OR = 2.24 [95% CI: 1.31-3.84], I 2 = 0.0%). Subgroup analysis showed that the pooled prevalence of clinical anxiety disorder and anxiety symptoms was 12% (95% CI: 7%-16%, I 2 = 76.3%) and 34% (95% CI: 21%-46%, I 2 = 94.7%), respectively. No publication bias has been detected by Begg's funnel plot and Egger's test. CONCLUSION: Patients with vitiligo have high anxiety comorbidity, with female predominance. Dermatologists and psychiatrists should be vigilant to the presence of anxiety, apply appropriate interventions to reduce the psychological impacts in a timely manner, and thus promote recovery in vitiligo patients. However, due to some objective limitations (poor information about the OR and diversity in assessment tools among included studies), findings should be interpreted with caution.

BACKGROUND: The effects of different testicular sperm extraction methods on the embryonic development and clinical outcome of azoospermic men in intracytoplasmic sperm injection (ICSI) cycles have not been researched. Our goal was to evaluate the effect of different sperm retrieval methods used for patients with OA or NOA on the embryonic development and clinical outcomes during the ICSI cycles. METHODS: This was a retrospective cohort study. A total of 530 azoospermic patients who underwent 570 ICSI cycles met the study criteria. ICSI was performed using testicular sperm by TESA in 282 cycles (TESA group); ICSI with testicular sperm by mTESE was performed due to NOA in 90 cycles (mTESE group); ICSI with testicular sperm by MESA was performed in 198 cycles (MESA group). The embryonic development and clinical outcomes of the three groups were counted. RESULTS: The general characteristics of the three groups were comparable. Our findings showed that the three groups were matched in terms of infertility durations and age. The mean age and the mean BMI of the female partners were similar in the three groups. Also, our findings showed there were no significant differences in the three groups regarding day 3 of the menstrual cycle FSH and days of stimulation. The research results showed that the total dose of FSH and E2 on the HCG administration day was also not statistically different in the three groups. The number of oocytes retrieved had no significant differences in the three groups. However, the number of 2PNs per cycle and the number of cleavages per cycle were higher in the MESA group than in the other two groups; the TESA group and mTESE group were similar. The number of good quality D3 embryos and the number of good quality D5 embryos were significantly decreased in the mTESE group as compared to the other two groups. Good quality D3 embryos and the rate of good quality D5 embryos in the mTESE group were lower than those in the other two groups. Moreover, the clinical pregnancy rates of the TESA group (50.71%) and the MESA group (51.52%) were similar, but both were much higher than that of the mTESE group (32.22%). CONCLUSIONS: The mTESE provides a good clinical outcome for NOA patients with severe spermatogenic impairment, including the rate of good quality D3 embryos, the rate of good quality D5 embryos, and the clinical pregnancy rate. However, our data suggested that both the TESA and MESA groups had better embryonic development and clinical outcomes than the mTESE group.

BACKGROUND: West Africa has witnessed the unprecedented outbreak of Ebola virus disease (EVD). The Ebola virus (EBOV) can cause Ebola hemorrhagic fever, which is documented as the most deadly viral hemorrhagic fever in the world. RT-PCR had been suggested to be employed in the detection of Ebola virus; however, this method has high requirements for laboratory equipment and takes a long time to determine Ebola infection. Although Xpert Ebola is a fast and simple instrument for the detection of Ebola virus, its effect is still unclear. This study is aimed at evaluating the accuracy of Xpert Ebola in diagnosing Ebola virus infection. METHODS: Using the keywords "Xpert" and "Ebola virus", relevant studies were retrieved from the database of PubMed, Embase, Web of Science, and Cochrane. RT-PCR was employed as a reference standard to evaluate whether the study is eligible to be included in the meta-analysis. Data from these included studies were extracted by two independent assessors and were then analyzed by the Meta-DiSc 1.4 software to produce the heterogeneity of sensitivity (SEN), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) of the study. The results of pooled analysis were plotted, together with the summary receiver operating characteristic (SROC) curve plotted by calculating the area under the curve (AUC). Generated pooled summary estimates (95% CIs) were calculated for the evaluation of the overall accuracy of this study. RESULTS: Five fourfold tables were made from the four studies that were included in the meta-analysis. The pooled sensitivity of Xpert Ebola was 0.98 (95% confidence interval (CI) (0.95, 0.99)), and the pooled specificity was 0.98 (95% CI (0.97, 0.99)). The pooled values of positive likelihood ratio was 53.91 (95% CI (12.82, 226.79)), with negative likelihood ratio being 0.04 (95% CI (0.02, 0.08)) and diagnostic odds ratio being 2649.45 (95% CI (629.61, 11149.02)). The AUC was 0.9961. CONCLUSIONS: Compared with RT-PCR, Xpert Ebola has high sensitivity and specificity. Therefore, it is a valued alternative method for the clinical diagnosis of Ebola virus infection. However, the Xpert Ebola test is a qualitative test that does not provide quantitative testing of EBOV concentration. Whether it can completely replace other methods or not calls for further evidences.

BACKGROUND: Diabetes mellitus is a clinical syndrome caused by genetic and environmental factors. Growing evidence suggests that exposure to environmental endocrine disruptors and activation of NLRP3 inflammasome signaling play a vital role in diabetes. However, it is unclear how PCB118, a common environmental endocrine disruptor, contributes to the incidence of diabetes, and its specific mechanism of action is unknown. In this study, we explored whether ROS-induced NLRP3 inflammasome priming and activation were related to PCB118 exposure in mouse islet β-TC-6 cells and the mechanisms of diabetes. METHODS: Mouse islet β-TC-6 cells were cultured with PCB118 as a stimulating factor and ROS inhibitor N-acetyl cysteine (NAC) as an intervention. Cellular toxicity due to PCB118 was detected using the Cell Counting Kit-8; ROS was measured using DCFH-DA; the expressions of NLRP3, procaspase-1, caspase-1, pro-IL-1β, and IL-1β protein were detected by western blot; and IL-6, IL-18, and C-C chemokine ligand 2 (CCL-2) were measured by ELISA. RESULTS: PCB118 caused significant toxicity to the cells when the stimulation concentration was equal to or greater than 80 nmol/L at 72 hours (p < 0.05) and increased the levels of ROS, NLRP3, caspase-1, IL-1β, IL-6, IL-18, and CCL-2 (p < 0.05); the expressions of procaspase-1 and pro-IL-1β were downregulated in a dose-dependent manner after PCB118 exposure (p < 0.05), which was prevented by pretreatment with NAC (p < 0.05). CONCLUSIONS: PCB118 can activate NLRP3 inflammasome signaling in islet beta cells via the oxidative stress pathway and cause inflammation in islet beta cells. It suggests that environmental endocrine disruptors play an important role in the inflammation of islet beta cells and may contribute to the development of diabetes through NLRP3 inflammatory signaling.

OBJECTIVE: This study is aimed at analyzing different points of force application during miniscrew supported en masse retraction of the anterior maxillary teeth to identify the best line of action of force in lingual orthodontic treatment. MATERIALS AND METHODS: Three-dimensional (3D) finite element models were created to stimulate en masse retraction with different heights and positions of the miniscrew and lever arm to change the force application points; a 150 g retraction force was applied from the miniscrew to the lever arms, and the initial tooth displacements were analyzed. RESULTS: Lingual crown tipping and occlusal crown extrusion were seen at all heights and positions of the miniscrew and lever arm, but when the miniscrew height was at 8 mm and the power arm was located between the lateral incisors and canines, these tipping patterns were less than those obtained with a 4.5 mm high miniscrew and a lever arm located distal to the canines. CONCLUSION: All miniscrew heights and lever arm positions showed initial lingual crown tipping and labial root tipping with occlusal crown extrusion. However, the 8 mm miniscrew height and the lever arm located between the lateral incisor and canine showed fewer amounts of these tipping patterns than a 4.5 mm miniscrew height and lever arm located distal to the canines. Therefore, this could be the preferred point of force application during en masse retraction in lingual treatment with additional torque control methods.

OBJECTIVES: To establish a novel animal model of intervertebral disc degeneration (IVDD) in rats and to investigate the effect of 17β-estradiol (E2) intervention in this model. METHODS: This study was divided into two parts: animal model (four groups: Sham, ovariectomy (OVX), Puncture, and OVX+Puncture; three-time points: 4, 8, and 12 weeks; three female rats/group/time point) and drug intervention (Sham, OVX+Puncture+corn oil, and OVX+Puncture+E2; three female rats/group). The rats were analyzed by micromagnetic resonance imaging (MRI), hematoxylin and eosin (HE) staining, and safranin-O staining. RESULTS: MRI and histological scores significantly differed among the four groups at the three-time points (all P < 0.05). IVDD progressed with time in the OVX, Puncture, and OVX+Puncture groups (all P < 0.05). The changes were the most obvious in the OVX+Puncture group. In the E2 intervention part, the Veh group had the worst MRI signals and histological scores (P < 0.05). The MRI scores in the E2 group were less obvious compared to the Sham group (P > 0.05). Also, the histological scores were significantly different between the Sham and E2 groups (P < 0.05). CONCLUSIONS: The combination of ovariectomy and needle puncture can synergically induce IVDD in rat coccygeal discs. Estrogen treatment can effectively ameliorate IVDD progression in the newly established IVDD models.

BACKGROUND: To investigate the chronic photodamage induced by the low-intensity blue light of phones, we carried out a clinical pilot study and established an animal model by irradiating SD rats with a homemade illuminator. METHODS: Clinical investigation: A total of 25 clinical medical workers in our hospital were selected and divided into a control group and an observation group according to the daily video terminal use time. Multifocal electrophysiological system (Mf-ERG) was used for retinal functional examination. Animal experiment: A total of sixty SD rats were randomly divided into a control group (n = 6) and an experimental group (n = 54). The experimental rats were divided into nine groups, which were exposed to the blue light illuminator of the simulated cell phone array for different time. The visual electrophysiology of the rats was tested, and changes in structure were observed by H&E staining and transmission electron microscopy. RESULTS: In clinical investigation, macular centers near the concave area retinal photoreceptor cells have reduced amplitude. In animal experiments, the amplitude of photoreceptor cells decreased, the peak time was delayed, and the amplitudes were lower in the experimental groups. H&E staining and transmission electron microscope showed retinal tissue structure and functional damage in experimental groups. CONCLUSIONS: Long-term exposure to low-illuminance blue light can cause retinal tissue structure and functional damage, and the chronic damage due to low-illuminance light warrants attention. The clinical registration number is 2018-KY-KS-LHL.

PURPOSE: To study postoperative Health-Related Quality of Life (HRQOL) after instrumented fusion for fresh subaxial cervical trauma and the effect of spinal cord injury (SCI). METHODS: From a total of 65 patients, 17 (26%) patients suffered on admission from SCI. Twenty-five patients underwent anterior, 25 posterior, and 15 circumferential cervical surgery for a single cervical injury. Sagittal roentgenographic parameters were measured in 65 age-matched asymptomatic controls and in patients on admission, eight months postoperatively and at final follow-up (lower C2-C7 curvature, cervical sagittal vertical axis (cSVA), spinocranial angle (SCA), T1-slope, neck tilt (NT), thorax inlet angle (TIA), cervical tilt (CT), cranial tilt (CrT), and occiput-C2 angle (C0-C2)). In the last evaluation, SCI patients were compared with their counterparts without SCI using national validated HRQOL instruments (SF-36 and neck disability index (NDI)). RESULTS: Fusion included an average of 3 vertebrae (range 2-4 vertebrae). All 65 patients were followed for an average of 5.5 years, (range 3-7 years) postoperatively. In the last evaluation, 10 (15.4%) patients with incomplete SCI improved postoperatively at 1-2 grades. At the last observation, patients with SCI showed poorer HRQOL scores than their counterparts without SCI. In particular, each SF-36 domain score was correlated with SCA, T1-slope, cSVA, and CT. At baseline, patients showed higher NT, CrT, and C0-C2 angle than controls. Eight months postoperatively, cSVA, NT, TIA, and cranial tilt (CrT) were increased in patients. In the last observation, there was difference in the sagittal roentgenographic parameters between patients with SCI compared to those without SCI. Patients aged ≥55 years had postoperatively increased cSVA, NT, and CrT compared to their younger counterparts. CONCLUSION: At the final observation, HRQOL scores were lower in patients with SCI than in their non-SCI counterparts, obviously because of the associated neurologic impairment. SF-36 scores correlated with several sagittal roentgenographic parameters. These correlations should be taken in consideration by spine surgeons when performing cervical spine surgery for fresh cervical spine injuries.

OBJECTIVE: The aim of the study was to investigate molecular mechanisms underlying the role of miR-126-5p in cisplatin (DDP) sensitivity of non-small-cell lung cancer (NSCLC). METHODS: The expression of miR-126-5p and ADAM9 in NSCLC cancer tissues and adjacent tissues, cisplatin-sensitive and drug-resistant NSCLC patient tissues, human normal lung epithelial cells (BESA-2B), human lung adenocarcinoma cell lines A549 and H1560, and cisplatin-resistant mutant cell lines A549/DDP and H1560/DDP was detected by qRT-PCR. After overexpression of miR-126-5p or ADAM9 in A549/DDP and H1560/DDP, MTT and clone formation were used to detect the cell proliferation ability of each treatment group. Flow cytometry was used to detect changes in cell apoptosis. The protein expression of ADAM9 and key molecules of PTEN/PI3K/Akt pathways in cells was measured by western blot. RESULTS: Compared with NSCLC adjacent tissues and NSCLC cisplatin-sensitive tissues, miR-126-5p expression was downregulated in NSCLC tissues and cisplatin-resistant NSCLC tissues and ADAM9 was upregulated. qRT-PCR further detected that miR-126-5p was downregulated in A549, H1560, and their cisplatin-resistant strains A549/DDP and H1560/DDP, while ADAM9 was upregulated. Moreover, overexpression of miR-126-5p inhibited A549/DDP and H1560/DDP cell proliferation and promoted cell apoptosis. The results of dual luciferase showed that miR-126-5p targeted and negatively regulated ADAM9. We also found that overexpression of ADAM9 could reverse the effects of miR-126-5p on NSCLC cell proliferation, apoptosis, and cisplatin sensitivity, and this effect may be achieved by inhibiting the activity of the PTEN/PI3K/Akt signaling pathway. CONCLUSION: Our data indicated that miR-126-5p may negatively regulate ADAM9 to promote the sensitivity of clinical DDP treatment of NSCLC and be a potential therapeutic target for NSCLC treatment.

BACKGROUND: The combination of screw fixation and cage can provide stability in lumbar interbody fusion (LIF), which is an important technique to treat lumbar degeneration diseases. As the narrow surface cage is developed in oblique lateral lumbar interbody fusion (OL-LIF), screw fixation should be improved at the same time. We used the finite element (FE) method to investigate the biomechanics response by three different ways of screw fixation in OL-LIF. METHODS: Using a validated FE model, OL-LIF with 3 different screw fixations was simulated, including percutaneous transverterbral screw (PTVS) fixation, percutaneous cortical bone trajectory screw (PCBTS) fixation, and percutaneous transpedical screw (PPS) fixation. Range of motion (ROM), vertebral body displacement, cage displacement, cage stress, cortical bone stress, and screw stress were compared. RESULTS: ROM in FE models significantly decreased by 84-89% in flexion, 91-93% in extension, 78-89% in right and left lateral bending, and 73-82% in right and left axial rotation compared to the original model. The maximum displacement of the vertebral body and the cage in six motions except for the extension of model PTVS was the smallest among models. Meanwhile, the model PTVS had the higher stress of screw-rods system and also the lowest stress of cage. In all moments, the maximum stresses of the cages were lower than their yield stress. CONCLUSIONS: Three screw fixations can highly restrict the surgical functional spinal unit (FSU). PTVS provided the better stability than the other two screw fixations. It may be a good choice for OL-LIF.

BACKGROUND: The aim of this study was to systematically evaluate the relationship between the expression of m6A RNA methylation regulators and prognosis in HCC. METHODS: We compared the expression of m6A methylation modulators and PD-L1 between HCC and normal in TCGA database. HCC samples were divided into two subtypes by consensus clustering of data from m6A RNA methylation regulators. The differences in PD-L1, immune infiltration, and prognosis between the two subtypes were further compared. The LASSO regression was used to build a risk score for m6A modulators. In addition, we identified miRNAs that regulate m6A regulators. RESULTS: We found that fourteen m6A regulatory genes were significantly differentially expressed between HCC and normal. HCC samples were divided into two clusters. Of these, there are higher PD-L1 expression and poorer overall survival (OS) in cluster 1. There was a significant difference in immune cell infiltration between cluster 1 and cluster 2. Through the LASSO model, we obtained 12 m6A methylation regulators to construct a prognostic risk score. Compared with patients with a high-risk score, patients with a low-risk score had upregulated PD-L1 expression and worse prognosis. There was a significant correlation between risk score and tumor-infiltrating immune cells. Finally, we found that miR-142 may be the important regulator for m6A RNA methylation in HCC. CONCLUSION: Our results suggest that m6A RNA methylation modulators may affect the prognosis through PD-L1 and immune cell infiltration in HCC patients. In addition, the two clusters may be beneficial for prognostic stratification and improving immunotherapeutic efficacy.

BACKGROUND: Abnormal lipid metabolism is closely associated with the invasiveness and metastasis of cancer. Fatty acid-binding proteins (FABPs) play essential roles in lipid metabolism, and miRNAs can affect lipid metabolism by targeting FABPs. However, the exact mechanism is unknown. METHODS: FABP1 expression in HCC tissues was analyzed by immunochemistry with tissue microarrays. The lipid content was detected by Oil Red O staining, and the interaction between FABP1 and free fatty acid (FFA) was studied by a labeling and tracking method. miRNA arrays were used to detect the expression of miRNAs in IL-6-stimulated HCC cells. miR-603 expression was verified by qPCR. The proteins were checked by Western blot analysis. Gain and loss function evaluation was assessed by lentivirus and miRNA mimic transfection in Huh-7 cells, while reactive oxygen species (ROS) were detected by fluorescence. RESULTS: FABP1 expression was significantly decreased in approximately 90% (81/90) of HCC patients. FABP1 expression in adjacent tissues was closely associated with overall survival. Meanwhile, lipid was abundant in the adjacent tissues, yet significantly reduced in HCC tissues. FABP1 and FFA can promote each other for being uptaken by Huh-7 cells. FABP1 overexpression induced apoptosis and inhibited the proliferation, migration, invasion, and metastasis of Huh-7 cells. IL-6 treatment affected the expression of miRNAs, and miR-603 was overexpressed in HCC tissues. Also, miR-603 overexpression promoted the proliferation, migration, invasion, and metastasis of Huh-7 cells. Bioinformatic analysis predicted that miR-603 targets the 3'-UTR region of FABP1. However, miR-603 overexpression inhibited the expression of the FABP1 but increased the CPT1A, PPAR-α, and SREBP1 expressions. FABP1 overexpression reduced ROS in HCC cells, while miR-603 can reverse these effects. CONCLUSION: Our results indicate that in the pathogenesis of HCC, IL-6 induces miR-603 expression, which subsequently inhibits FABP1 expression, promotes the lipid metabolism- and synthesis-related proteins, and finally increases the cellular oxidative stress level and leads to the metastasis of HCC.

Temporomandibular disorders (TMD) have been traditionally associated with psychosocial factors; however, occupational stress as a factor related to TMD has not been adequately assessed in the literature. The aim was to investigate the association between stress at work and TMD on adult paid workers. An electronic search included PubMed, Scopus, Web of Science, Embase, and LILACS databases. Manual searches in the included articles' reference and gray literature were performed. There were no restrictions regarding language or publication period. The inclusion criteria comprised observational studies with paid workers of any category, of both sexes, above 18 years old, assessing occupational stress/stress or distress and TMD as diagnosis or isolated signs and symptoms. Methodological quality was evaluated using Joanna Briggs tools. We narratively assessed the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We collected 12 studies. 50% reported a positive association between stress and TMD diagnostic across various job categories. On the other hand, TMJ sounds (a TMD sign) and work stress were associated only in a musicians' population. However, the shortage of eligible articles and the methodological limitations provided a very low certainty of the evidence; only 4 of the studies used validated tools for both stress and TMD (2 reporting positive association). The association between stress and TMD is inconclusive by the available data. In the future, we expect more robust epidemiologic studies addressing these relevant aspects.

Osteosarcoma is the most common type of bone malignancy, and the pathogenesis has not been entirely elucidated yet. An important deimination modification enzyme PADI4 (peptidylarginine deiminase 4) has attracted much attention in recent years for its important function in several kinds of human tumors. However, the role of PADI4 on osteosarcoma tumorigenesis remains largely unrevealed. Here, we first assessed the effect of PADI4 on osteosarcoma proliferation by the CCK8 method and colony formation assay. Ectopically expressing PADI4 positively regulates the colony formation capacity of both U2OS and Saos-2 cells. Furthermore, we explored the related mechanism and showed that PADI4 could stimulate Wnt/β-catenin and MEK/ERK signaling in both U2OS and Saos-2 cells. Then, we detected expression of PADI4 in human tissues of osteosarcoma and revealed that differential expression of PADI4 was associated with tumorigenesis of osteosarcoma. Last, we performed the in vivo experiment in nude mice and results also showed PADI4 could affect the tumor growth. In conclusion, this work revealed that PADI4 could upregulate the proliferation of osteosarcoma, mainly via the Wnt/β-catenin and MEK/ERK signaling pathway. This study gives us new insight into the regulation mechanism of osteosarcoma proliferation and highlights PADI4 as a promising target for osteosarcoma diagnosis and treatment.

In sub-Saharan Africa (SSA), every 1 in 12 children under five dies every year compared with 1 in 147 children in the high-income regions. Studies have shown an association between birth intervals and pregnancy outcomes such as low birth weight, preterm birth, and intrauterine growth restriction. In this study, we examined the association between birth interval and under-five mortality in eight countries in West Africa. A secondary analysis of the Demographic and Health Survey (DHS) data from eight West African countries was carried out. The sample size for this study comprised 52,877 childbearing women (15-49 years). A bivariate logistic regression analysis was carried out and the results were presented as crude odds ratio (cOR) and adjusted odds ratios (aOR) at 95% confidence interval (CI). Birth interval had a statistically significant independent association with under-five mortality, with children born to mothers who had >2 years birth interval less likely to die before their fifth birthday compared to mothers with ≤2 years birth interval [cOR = 0.56; CI = 0.51 - 0.62], and this persisted after controlling for the covariates [aOR = 0.55; CI = 0.50 - 0.61]. The country-specific results showed that children born to mothers who had >2 years birth interval were less likely to die before the age of five compared to mothers with ≤2 years birth interval in all the eight countries. In terms of the covariates, wealth quintile, mother's age, mother's age at first birth, partner's age, employment status, current pregnancy intention, sex of child, size of child at birth, birth order, type of birth, and contraceptive use also had associations with under-five mortality. We conclude that shorter birth intervals are associated with higher under-five mortality. Other maternal and child characteristics also have associations with under-five mortality. Reproductive health interventions aimed at reducing under-five mortality should focus on lengthening birth intervals. Such interventions should be implemented, taking into consideration the characteristics of women and their children.

Renal interstitial fibrosis (RIF) is the main pathological manifestation of end-stage renal disease. Recent studies have shown that endoplasmic reticulum (ER) stress is involved in the pathogenesis and development of RIF. Traditional Chinese medicine (TCM), as an effective treatment for kidney diseases, can improve kidney damage by affecting the apoptotic signaling pathway mediated by ER stress. This article reviews the apoptotic pathways mediated by ER stress, including the three major signaling pathways of unfolded protein response, the main functions of the transcription factor C/EBP homologous protein. We also present current research on TCM treatment of RIF, focusing on medicines that regulate ER stress. A new understanding of using TCM to treat kidney disease by regulating ER stress will promote clinical application of Chinese medicine and discovery of new drugs for the treatment of RIF.

BACKGROUND: Pancreatic cancer is one of the most malignant tumors of the digestive system, and its treatment has rarely progressed for the last two decades. Studies on m6A regulators for the past few years have seemingly provided a novel approach for malignant tumor therapy. m6A-related factors may be potential biomarkers and therapeutic targets. This research is focused on the gene characteristics and clinical values of m6A regulators in predicting prognosis in pancreatic cancer. METHODS: In our study, we obtained gene expression profiles with copy number variation (CNV) data and clinical characteristic data of 186 patients with pancreatic cancer from The Cancer Genome Atlas (TCGA) portal. Then, we determined the alteration of m6a regulators and their correlation with clinicopathological features using the log-rank tests, Cox regression model, and chi-square test. Additionally, we validated the prognostic value of m6A regulators in the International Cancer Genome Consortium (ICGC). RESULTS: The results suggested that pancreatic cancer patients with ALKBH5 CNV were associated with worse overall survival and disease-free survival than those with diploid genes. Additionally, upregulation of the writer gene ALKBH5 had a positive correlation with the activation of AKT pathways in the TCGA database. CONCLUSION: Our study not only demonstrated genetic characteristic changes of m6A-related genes in pancreatic cancer and found a strong relationship between the changes of ALKBH5 and poor prognosis but also provided a novel therapeutic target for pancreatic cancer therapy.

INTRODUCTION: We aimed to develop and validate a nomogram for predicting the overall survival of patients with limb chondrosarcomas. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program database was used to identify patients diagnosed with chondrosarcomas, from which data was extracted from 18 registries in the United States between 1973 and 2016. A total of 813 patients were selected from the database. Univariate and multivariate analyses were performed using Cox proportional hazards regression models on the training group to identify independent prognostic factors and construct a nomogram to predict the 3- and 5-year survival probability of patients with limb chondrosarcomas. The predictive values were compared using concordance indexes (C-indexes) and calibration plots. RESULTS: All 813 patients were randomly divided into a training group (n = 572) and a validation group (n = 241). After univariate and multivariate Cox regression, a nomogram was constructed based on a new model containing the predictive variables of age, site, grade, tumor size, histology, stage, and use of surgery, radiotherapy, or chemotherapy. The prediction model provided excellent C-indexes (0.86 and 0.77 in the training and validation groups, respectively). The good discrimination and calibration of the nomograms were demonstrated for both the training and validation groups. CONCLUSIONS: The nomograms precisely and individually predict the overall survival of patients with limb chondrosarcomas and could assist personalized prognostic evaluation and individualized clinical decision-making.

BACKGROUND: The prevention of type 2 diabetes (T2D) and its associated complications has become a major priority of global public health. In addition, there is growing evidence that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of diabetes. Therefore, the purpose of this study was to develop and validate a nomogram based on independent predictors to better assess the 8-year risk of T2D in Japanese patients with NAFLD. METHODS: This is a historical cohort study from a collection of databases that included 2741 Japanese participants with NAFLD without T2D at baseline. All participants were randomized to a training cohort (n = 2058) and a validation cohort (n = 683). The data of the training cohort were analyzed using the least absolute shrinkage and selection operator method to screen the suitable and effective risk factors for Japanese patients with NAFLD. A cox regression analysis was applied to build a nomogram incorporating the selected features. The C-index, receiver operating characteristic curve (ROC), calibration plot, decision curve analysis, and Kaplan-Meier analysis were used to validate the discrimination, calibration, and clinical usefulness of the model. The results were reevaluated by internal validation in the validation cohort. RESULTS: We developed a simple nomogram that predicts the risk of T2D for Japanese patients with NAFLD by using the parameters of smoking status, waist circumference, hemoglobin A1c, and fasting blood glucose. For the prediction model, the C-index of training cohort and validation cohort was 0.839 (95% confidence interval (CI), 0.804-0.874) and 0.822 (95% CI, 0.777-0.868), respectively. The pooled area under the ROC of 8-year T2D risk in the training cohort and validation cohort was 0.811 and 0.805, respectively. The calibration curve indicated a good agreement between the probability predicted by the nomogram and the actual probability. The decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: We developed and validated a nomogram for the 8-year risk of incident T2D among Japanese patients with NAFLD. Our nomogram can effectively predict the 8-year incidence of T2D in Japanese patients with NAFLD and helps to identify people at high risk of T2D early, thus contributing to effective prevention programs for T2D.

Gentiopicroside (GPS), a main active secoiridoid glucoside derived from the roots of perennial herbs in the Gentianaceae family, has antispasmodic and relaxant effects. However, the vasorelaxant effects of GPS on aortic rings and the molecular mechanisms involved in these effects are not yet clear. Therefore, we investigated whether GPS inhibits phenylephrine- (PE-) or KCl-induced contractions in isolated rat thoracic aortic rings. The present study found that GPS produced a dose-dependent relaxation in aortic rings precontracted with PE or KCl and significantly reduced CaCl2-, narciclasine- (Rho-kinase activator-), and phorbol-12,13-diacetate- (PKC activator-) induced vasocontractions. Pretreatment with NG-Nitroarginine methyl ester hydrochloride (L-NAME, NOS inhibitor), methylene blue (sGC inhibitor), indomethacin (COX inhibitor), 4-aminopyridine (KV channel inhibitor), and glibenclamide (KATP channel inhibitor) had no influence on the vasorelaxant effect of GPS, while BaCl2 (Kir channel inhibitor), tetraethylammonium chloride (KCa channel inhibitor), ruthenium red (RYR inhibitor), and heparin (IP3R inhibitor) significantly reduced GPS-induced vasorelaxation. Moreover, GPS pretreatment remarkably inhibited the influx of Ca2+ in vascular smooth muscle cells stimulated using KCl or PE-containing CaCl2 solution. Western blot analysis confirmed that GPS treatment inhibited PE-induced increases in the protein levels of p-Akt, p-myosin light chain (MLC), and p-myosin-binding subunit of myosin phosphatase 1 (MYPT1) in the aortic rings. Additionally, the vasorelaxation activity of GPS was attenuated upon pretreatment with LY294002 (PI3K/Akt inhibitor), Y27632 (Rho-kinase inhibitor), and verapamil (L-type Ca2+ channel inhibitor). These findings demonstrate that GPS exhibits endothelium-independent vasorelaxant effects through inhibition of voltage-dependent, receptor-operated, and inositol triphosphate receptor (IP3R)/ryanodine receptor- (RYR-) mediated Ca2+ channels as well as the PI3K/Akt/Rho-kinase signaling pathway.

Dentoalveolar surgery is probably the major risk factor for MRONJ and for other complications following a tooth extraction, especially in patients affected by systemic diseases. The aim of this retrospective study is to evaluate whether a PRF plug inserted in the post extraction socket can prevent the onset of MRONJ. The patients were divided into two groups according to the surgical protocol that included the insertion or not of the PRF following the extraction and all the anamnestic, and clinical data were analyzed. In the control group, 5 patients developed MRONJ (19.23%) while in the study group, any case of MRONJ was reported. In the control group, patients who developed MRONJ had a CTX with less than 100 pg/mL (5 high-risk patients, Spearman's rank r = .547, p < .001). The use of platelet concentrates in patients with high risk of MRONJ is a user-friendly technique with an excellent cost-benefit ratio in oral surgery.

The incidence of nonalcoholic steatohepatitis (NASH) is increasing worldwide. Activation of Kupffer cells (KCs) is central to the development of diet-induced NASH. We investigated whether a combination of two active chemical components, geniposide and chlorogenic acid (GC), at a specific ratio (67 : 1), ameliorates diet-induced NASH and the underlying mechanisms involved. C57BL/6J mice exposed to a high-fat and high-cholesterol (HFHC) diet containing cholesterol, choline, and high-sugar drinking water, as well as RAW264.7 cells stimulated with lipopolysaccharide (LPS) were studied. The combination exerted a therapeutic effect on HFHC-induced NASH in mice. Simultaneously, GC was found to reduce the expression of cytokines secreted by hepatic macrophages, including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6, monocyte chemotactic protein 1 (MCP-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, GC reduced the number of KCs expressing F4/80. Furthermore, TNF-α, inducible nitric oxide synthase (INOS), IL-1β, and IL-6 mRNA and TNF-α protein expression levels were suppressed upon GC treatment in RAW264.7 cells. Our findings suggest that GC has a strong anti-inflammatory effect in NASH, and this effect can be attributed to the suppression of KC activity in the liver.

OBJECTIVE: Percutaneous tumor ablation is usually performed using computed tomography (CT) or ultrasound (US) guidance, although reliable visualization of the target tumor could be challenging. Magnetic resonance- (MR-) guided ablation provides more reliable visualization of the target tumors and allows multiplanar imaging of the treatment process, making it the modality of choice, in particular if lesions are small. METHODS: From March 2016 to January 2018, 32 patients scheduled for percutaneous treatment of T1 RCC underwent MR-guided MWA. Complications were classified according to the Clavien grade. Kaplan-Meier survival estimates were calculated to evaluate progression-free survival (PFS). RESULTS: Technical success was achieved in all lesions. The mean energy and procedure duration were 61.6 ± 8.7 kJ and 118.2 ± 26.7 min, respectively. The glomerular filtration rate (GFR) dropped rapidly after 1 month of treatment and slowly recovered within three months (P < 0.05). Postoperative pain and fever were the most common adverse events after treatment. Perirenal hematoma, thermal injury of the psoas muscle, and abdominal distension were common complications after MWA, and the incidence rates were 9.4% (3/32), 6.3% (2/32), and 6.3% (2/32), respectively. According to the Clavien grade classification, serious complications include hydrothorax, bowel injury, and renal failure, all of which have a probability of 3.1%. Of note, the three serious complications occurred in one patient. The 1-, 2-, and 3-year PFS rates were 96.9%, 93.8%, and 83.9%, respectively. The mean PFS rates were 33.972 months (95% CI: 33.045, 35.900). CONCLUSION: Microwave ablation is feasible under MR guidance and provides effective treatment of RCC in one session.

BACKGROUND: Hospital-acquired infections have remained a serious cause of mortality, morbidity, and extended hospitalization. Bacterial contamination of inanimate surfaces of the hospital environment and equipment is considered a major contributing factor to the development of several nosocomial infections worldwide. The hospital environment and many devices are an important reservoir of many clinically important bacterial agents including multidrug-resistant pathogens. Therefore, this systematic review and meta-analysis are aimed at investigating bacterial pathogens and their antimicrobial resistance patterns of inanimate surfaces and equipment in Ethiopia. METHODS: An exhaustive literature search was carried out using the major electronic databases including PubMed, Web of Science, MEDLINE, EMBASE, CINAHL, Google Scholar, Cochrane Library, Scopus, and Wiley online library to identify potentially relevant studies without date restriction. Original articles which address the research question were identified, screened, and included using the PRISMA flow diagram. Data extraction was prepared in Microsoft Excel, and data quality was assessed by using 9-point Joanna Briggs Institute critical appraisal tools. Then, data were exported to STATA 16.0 software for analyses of pooled estimation of outcome measures. Estimation of outcome measures at a 95% confidence interval was performed using DerSimonian-Laird's random-effects model. Finally, results were presented via text, figures, and tables. RESULTS: A total of 18 studies with 3058 bacterial isolates recovered from 3423 swab specimens were included for systematic review and meta-analysis. The pooled prevalence of bacterial contamination of inanimate surfaces and equipment was found 70% (95% CI: 59, 82). Among the Gram-negative bacterial species, the prevalence of ampicillin-resistant K. pneumoniae was the highest 80% (95% CI: 78, 92) followed by Citrobacter species 78% (95% CI: 57, 83). CONCLUSION: This study has shown a high prevalence of bacterial contamination of inanimate surfaces and equipment in Ethiopia.

PURPOSE: To compare the efficacy and safety of zip-type skin closure device (SCD) and staple in total knee arthroplasty (TKA). METHODS: Potential academic articles were identified from PubMed, Springer, ScienceDirect, and Cochrane Library from the inception of electronic databases to July 2020. The statistical analyses were performed with RevMan 5.1. RESULTS: One randomized controlled trial (RCT) and 5 non-RCTs met the inclusion criteria. Present meta-analysis reveals that SCD is associated with lower wound pain score, scar score, and readmission compared with a staple. No significant differences are identified in terms of wound total complications, dehiscence, blisters, and infection. CONCLUSIONS: Comparing with a staple, zip-type SCD is a less painful skin closure method with fewer medical cost undergoing TKA.

AIM: Investigation of the influences HCN2 and HCN4 has on bone marrow mesenchymal stromal cells (BMSCs) on cardiomyocyte differentiation. METHODS: Miniature adult pigs were used for bone marrow extraction and isolation of BMSCs. The identification of these BMSCs was done by using flow cytometry for the detection of expressed surface antigens CD45, CD11B, CD44, and CD90. Using HCN2 and HCN4 genes cotransfected into BMSCs as group HCN2+HCN4 while myocardial induction solution was used to induced BMSC differentiation in the BMSC induction group. Myocardial marker proteins α-actin and cTnT were detected by immunofluorescence staining, while α-actin, cTnT, and Desmin myocardial marker proteins expressed were detected by Western blot. The whole-cell patch-clamp technique was used to identify and detect cellular HCN2 channels, HCN4 channel current activation curve, and the inhibitory effect of CsCl on heterologous expression currents. RESULTS: Flow cytometry results showed that CD45 and CD11B were expressed negatively while CD90 and CD44 were positive. Post HCN2 and HCN4 gene transfection, immunofluorescence staining, and Western blot showed significantly increased HCN2, HCN4, α-actin, and cTnT expressed in group HCN2+HCN4 were, which could be compared to the expression levels in the BMSC-induced group. The HCN2+HCN4 group was able to document cell membrane channel ion currents that were similar to If properties. CONCLUSION: HCN2 and HCN4 overexpression can considerably enhance the MSC ability to differentiate into cardiomyocytes in vitro and restore the ionic current.

In order to explore the changes of intestinal flora and serum levels of relevant substances in patients with gastric cancer before and after surgery with carbon nanoparticle laparoscopy, a total of 180 patients with early distal gastric cancer who adopted laparoscopic radical gastrectomy for distal gastric cancer in the general surgery department of TCM Hospital of Shi Jia Zhuang City from January 2018 to January 2020 were selected and randomly divided into two groups: traditional laparoscopic operation (control group) and carbon nanoparticle laparoscopic operation (experimental group) were adopted for treatment for the two groups, respectively. Postoperative evaluation included the difference between the two groups in the operative time, the efficiency of intraoperative lymph node dissection, and the number of lymph node detection. The adverse reactions, changes of intestinal flora before and after surgery in the two groups, and the serum levels of epidermal growth factor receptor (EGFR), interleukin-32 (IL-32), and gastrin 17 were evaluated. In the experimental group, the success rate of carbon nanoparticle tracer black staining reached 100%, and the operation time of the experimental group was significantly shorter than that of the control group (P < 0.05). The lymph node detection rate of the experimental group was higher than that of the control group (P < 0.05), but there was no significant difference in the lymph node metastasis rate between the two groups (P > 0.05). The sentinel lymph node sensitivity of the experimental group reached 92.3%, and the specificity, accuracy, and positive and negative prediction rates reached 100%; the experimental group patients were with an obviously higher incidence of level I-II gastrointestinal reaction (P < 0.05). Postoperative increases in Bifidobacteria and Lactobacillus were observed in both groups, while decreases in Enterococcus and Escherichia coli were observed in both groups (P < 0.05). Moreover, the degree of increase and decrease in the experimental group was greater than that in the control group (P < 0.05). The serum levels of EGFR, IL-32, and gastrin 17 in the two groups were significantly lower than those in the control group on 3 d, 7 d, and 15 d after surgery (P < 0.05). In the radical gastrectomy for distal gastric cancer, carbon nanoparticle laparoscopy was not only helpful for the localization of small tumors but also for the thorough dissection of lymph nodes after the surgery, and the postoperative adverse reactions of carbon nanoparticle laparoscopy were also less, which was of great significance for the improvement of intestinal flora and the reduction of serum levels of EGFR, IL-32, and gastrin 17 in gastric cancer patients.

Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes-associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes-associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5-1.0 mmol/L). The HPLC results showed that AG-Gnp fairly hampers the formation of glycation adducts. Moreover, the in vivo studies revealed AG-Gnp mediated inhibition in the production of total-AGEs and -N ε -(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG-Gnp-treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs.

OBJECTIVE: To determine the accuracy of 16S rRNA polymerase chain reaction (PCR) for the diagnosis of neonatal sepsis through a systematic review and meta-analysis. METHODS: Studies involving 16S rRNA PCR tests for the diagnosis of neonatal sepsis were searched in the PubMed, Medline, Embase, and Cochrane Library databases. The methodological quality of the identified studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), and the sensitivity, the specificity, the positive likelihood ratio (PLR), the negative likelihood ratio (NLR), the diagnostic odds ratio (DOR), and the area under the curve (AUC) of operator characteristic (SROC) curves were determined. Heterogeneity between studies was analyzed by metaregression. Stata 14.0 and Meta-disc 1.4 software were used for the analyses. RESULTS: This meta-analysis included 19 related studies. The analysis found a sensitivity of 0.98 (95% CI: 0.85-1), specificity of 0.94 (95% CI: 0.87-0.97), PLR of 16.0 (95% CI: 7.6-33.9), NLR of 0.02 (95% CI: 0.00-0.18), DOR of 674 (95% CI: 89-5100), and AUC of 0.99 (95% CI: 0.97-0.99). Metaregression analysis identified Asian countries, arterial blood in blood samples, and sample size > 200 as the main sources of heterogeneity. This meta-analysis did not uncover publication bias. Sensitivity analysis showed that the study was robust. Fagan's nomogram results showed clinical usability. CONCLUSIONS: The results from this meta-analysis indicate that 16S rRNA PCR testing is effective for the rapid diagnosis of neonatal sepsis.

The study was aimed at investigating the effect of zoledronic acid on vascular morphometry in jawbones and long bones on a rat model. Twenty-four skeletal mature Sprague-Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla and a bone defect creation on the femur. After the surgical procedures, ZA or saline treatment was continued until sacrifice at week 2, week 4, and week 8 postoperatively. Vascular perfusion with MICROFIL was performed on all the animals. Micro-CT analysis demonstrated a tendency of decreased vessel density and vessel number in ZA-treated groups but no statistical difference. In conclusion, the neovessel formation is suppressed but not significantly by ZA treatment, indicating that angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.

BACKGROUND: Although deworming pregnant women is one of the strategies to reduce parasites (roundworms and hookworms) causing anemia and related perinatal and maternal complications, utilization of deworming medication among pregnant women in Cameroon is suboptimal. Comprehensive assessment of individual, household (including women's autonomy), and community-level factors associated with utilization of deworming medication has not been done so far. Therefore, we investigated the individual/household and community-level factors associated with deworming among pregnant married women in Cameroon. METHODS: Our study was limited to pregnant women because they have a greater risk due to increased chances of anemia. We used data from the 2018/19 Cameroon Demographic and Health Survey. Analysis on 5,013 pregnant married women was carried out using multilevel logistic regression. Odds ratios with a 95% confidence interval (CI) were reported. RESULTS: Our findings showed that about 29.8% of pregnant married women received deworming medications. The individual/household level predictors of deworming medications utilization identified in this study were women's educational level, wealth quintile, and skilled antenatal care. Distance to health facility and region were identified as community-level predictors of deworming medications utilization. Higher odds of receiving deworming medication occurred among educated and wealthier pregnant married women as well as among pregnant married women who had skilled antenatal care or lived in the south region, whereas lower odds were observed among pregnant married women living in the north region. CONCLUSION: Access to education and economic empowerment of pregnant married women in remote areas and the north region should be the primary focus of the Cameroon government to enhance deworming coverage in the country.

Human bodies encompass very important symbiotic and mutualistic relationships with tiny creatures known as microbiota. Trillions of these tiny creatures including protozoa, viruses, bacteria, and fungi are present in and on our bodies. They play important roles in various physiological mechanisms of our bodies. In return, our bodies provide them with the habitat and food necessary for their survival. In this review, we comprehend the gut microbial species present in various regions of the gut. We can get benefits from microbiota only if they are present in appropriate concentrations, as if their concentration is altered, it will lead to dysbiosis of microbiota which further contributes to various health ailments. The composition, diversity, and functionality of gut microbiota do not remain static throughout life as they keep on changing over time. In this review, we also reviewed the various biotic and abiotic factors influencing the quantity and quality of these microbiota. These factors serve a significant role in shaping the gut microbiota population.

BACKGROUND: We sought to determine the prognostic value of prothrombin time-international normalized ratio to albumin ratio (PTAR) in patients with hepatitis B virus-associated decompensated cirrhosis (HBV-DeCi). METHODS: The study enrolled 166 HBV-DeCi patients. Multivariate regression analysis was performed to identify predictors associated with mortality. RESULTS: Among the 166 HBV-DeCi patients, 27 (16.3%) had died by 30 days after admission. PTAR was markedly increased in nonsurvivors compared with survivors, and had a significant positive correlation with disease severity. Multivariate analysis identified PTAR as an effective independent predictor for mortality in HBV-DeCi patients. CONCLUSIONS: High PTAR was associated with poor outcomes and can act as a novel prognostic predictor for mortality in HBV-DeCi patients.

METHODS: A five-year hospital-based retrospective study was carried out among 8605 blood donors comprising 8517 males and 88 females using data on blood donors from Saboba Assemblies of God Hospital located in the Saboba District in the Northern Region of Ghana from 2013 to 2017. Blood bank records on HBV and HCV potential blood donors who visited the hospital to donate blood were retrieved. Donor demographic details, i.e., age and gender, were also recovered. Donors who were registered to the hospital but were not residents of the Northern Region were excluded from the study. Donors with incomplete records were also excluded from the study. The data was managed using Microsoft Excel spreadsheet 2016 and analysed using GraphPad Prism statistical software. RESULTS: The overall prevalence of asymptomatic viral hepatitis B and C infections in the general adult population was 9.59% (95% CI: 9.00-10.20) and 12.71% (95% CI: 12.00-13.40), respectively, with an HBV/HCV coinfection rate of 2.23% (95% CI: 1.90-2.60). The number of donors generally declined with advancement in years from 2038 (23.68%) since 2013 to as low as 1169 (13.59%) in 2016, except for 2017 where a sharp increase of 1926 (22.38%) was observed. The first and second highest proportions of donors fell within the age categories of 20-29 (51.53% (4434)) and 30-39 (32.90% (2831)) respectively. The seroprevalence rate of HBV, HCV, and HBV/HCV coinfection rates were generally higher among the female group than those observed among the male category. The year-to-year variation in HBV, HCV, and HBV/HCV infections was statistically significant. The highest year-to-year HBV seropositivity rate was 11.48% in the year 2013, while that for HCV and HBV/HCV coinfection was 16.24% and 5.85%, respectively, both documented in the year 2014. HBV and HBV/HCV coinfection rates were highest among donors aged <20 years old, while HCV seroprevalence was highest among donors aged 50-59 years old. Significantly higher odds of HBV/HCV coinfection (OR = 5.2; 95% CI:3.3-8.1) was observed in the 2014 compared to the year 2013. Donors aged <20years were at higher risks of HBV and HBV/HCV coinfection rates compared to the other age groups. CONCLUSION: The seroprevalence of HBV and HCV among donors in the Saboba District of the Northern Region of Ghana is endemic. The HBV/HCV coinfection rate also raises serious concern owing to its high prevalence rate among the younger age. Intensive public health education coupled with mobile screening and mass vaccination of seronegative individuals is advised so as to help curb further spread of the infection and in effect help safeguard the health status of potential donors in the district.

BACKGROUND: Each year, not less than three million women are circumcised, and more hundred million females have already been circumcised. In many African societies, the practice of female genital mutilation (FGM) is a serious cultural practice. Aim: This current study is aimed at identifying the socioeconomic predictors of female genital mutilation in Ghana. METHODS: The design adopted for this study was a descriptive cross-sectional survey relying on data from the Ghana Multiple Indicator Cluster Survey (MICS) 2017/18. SPSS software was used for data analysis. Chi-square and binary logistic regression were used for associations. RESULTS: Overall FGM prevalence, this study recorded was 11.7%. The region with the highest (50.5%) prevalence was the Upper West Region. Area of residence predicted rural (AOR = 2.30, 95%C.I. = 1.75-3.00) Upper West/western Region (AOR = 1.84, 95%C.I. = 1.23-2.75). In terms of ethnicity, the tribes that predicted FGM when compared with the Akan tribe were Guan (AOR = 8.91, 95%C.I. = 3.53-22.51), Gruma (AOR = 6.45, 95%C.I. = 2.91-14.31), Mole-Dagbani (AOR = 38.10, 95%C.I. = 21.20-68.49), Grusi (AOR = 45.30, 95%C.I. = 24.47 - 83.49), Mande (AOR = 68.58, 95%C.I. = 30.85 - 152.42), and other tribes (AOR = 29.33, 95%C.I. = 16.11-53.39). Women in the richest/poorest wealth index quintile (AOR = 1.80, 95%C.I. = 1.19-2.72). CONCLUSION: The study prevalence of FGM is still high in the northern part of Ghana, and the predicted factors were residence region, ethnicity, educational level, and economic status.

Intervertebral disc degeneration (IVDD) is a degenerative and chronic spinal disorder often associated with the older population. Oxidative stress is a major pathogenic factor of aging that results in the apoptosis of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) degradation. Quercetin (QUE), a naturally occurring flavonoid with antioxidant and anti-inflammatory properties, has been studied in research on degenerative diseases. However, the potential effects and mechanisms of action of QUE on IVDD remain unclear. In this study, the effects of QUE on antiapoptosis and ECM metabolism were firstly investigated in TBHP-treated NPCs. Meanwhile, the autophagy inhibitor, 3-MA, and p38 MAPK inhibitor, SB203580, were used in subsequent TBHP-induced NPC experiments to determine whether QUE exerted its protective effects through autophagy and the p38 MAPK/mTOR signaling pathway. Finally, the therapeutic effects of QUE were confirmed in vivo using a rat tail needle puncture-induced model of IVDD. We found that QUE treatment significantly alleviated oxidative stress-decreased cell viability and intracellular ROS levels in NPCs treated with TBHP. Furthermore, treatment with QUE led to a decrease in apoptosis as measured by decreased Bax and increased Bcl-2 expression and PE/7-AAD flow cytometry analysis. QUE also promoted ECM stability as measured by increased collagen II and aggrecan and decreased MMP13 levels. Our results also showed that QUE promoted the expression of autophagy markers beclin-1, LC3-II/I, and decreased p62. Inhibition of autophagy by inhibitor 3-MA may partially reverse the protective effect of QUE on apoptosis and ECM degeneration, indicating that autophagy was involved in the protective effect of QUE in NPCs. Further study confirmed that QUE partially inhibited the p38 MAPK signaling pathway and inhibition of p38 MAPK by SB203580 activated autophagy, indicating that QUE protected NPCs against apoptosis and prevented ECM degeneration via the p38 MAPK-autophagy pathway. Finally, using a rat tail puncture-induced model of IVDD, we confirmed that QUE had a protective effect against IVDD. Our results suggest that QUE could prevent IVDD by modulating p38 MAPK-mediated autophagy and, therefore, is a potential therapeutic strategy in the treatment of IVDD.

This study was for verifying that transfecting colon cancer cells (CCCs) with lncRNA NEAT1 packed with siRNA chitosan nanoparticles (CNPs) can suppress lncRNA NEAT1 and biological behaviors of the cells. siRNA targeting lncRNA NEAT1 expression vector was constructed and then transfected into CCCs after being packed with CNPs. Subsequently, the impact of the transfection on biological behaviors of the cells was evaluated. As a result, with high expression in CCCs, NEAT1 was negatively bound up with miR-377-3p in cases with colon cancer (CC), and dual luciferase reporter assay confirmed the potential binding region. Additionally, after downregulating NEAT1 in CCCs, transfection of NEAT1 siRNA packed with CNPs brought a great inhibition on cell proliferation and a promotion on apoptosis, and inhibiting miR-377-3p was able to offset the role of silencing NEAT1 in CCCs. Therefore, in our opinion, NEAT1 siRNA packed with CNPs can hinder the growth and metastasis of CCCs by knocking down NEAT1 in CC, and its mechanism may be achieved by targeting miR-377-3p, which offers a novel direction for treating CC.

BACKGROUND: Cholecystectomy is one of the most common surgical procedures performed worldwide. The objective of this large, population-based cohort study is to explore the risk factors of pneumonia after cholecystectomy in Taiwan. METHODS: From the Taiwanese National Health Insurance Research Database, we selected all patients who underwent cholecystectomy by using ICD-9-codes, from January 1, 1998, to December 31, 2016. The patients were separated into two groups based on the presence or absence of postoperative pneumonia. Basic information, comorbidities, and postoperative complications were evaluated using a t-test or chi-square test. There were 6056 patients in the pneumonia group and 24224 patients in the control group. These two groups were shown in a ratio of 1 : 4 and were matched by age and sex. The log-rank test was used to examine differences in postoperative mortality between patients with and without pneumonia. Preoperative risk factors were analyzed using logistic regression analysis, after adjusting for age and sex. RESULTS: The final dataset included 282184 cholecystectomy patients. Of these patients, 6056 (2.15%) had postoperative new-onset pneumonia. The patient-related risk factors for pneumonia after cholecystectomy in the order of relevance were chronic obstructive pulmonary disease, congestive heart failure, cerebrovascular disease, diabetes mellitus, surgical type, hemodialysis, coronary artery disease, and liver cirrhosis. Compared to patients without postcholecystectomy pneumonia, those with postcholecystectomy pneumonia had higher rates of mortality (within first month, 1.72% vs. 2.28%, P < 0.005) and admission to intensive care unit (15.02% vs. 41.80%, P < 0.0001) and longer hospital stays (10.71 vs. 18.55 days, P < 0.0001). CONCLUSION: Our results show that postcholecystectomy associated with pneumonia had higher rates of morbidity and mortality in this clinical population. Early identification and possible management of risk factors for pneumonia could improve outcomes of cholecystectomy and lower the risk for patient comorbidities after surgery.

Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of SLC12A3 encoding thiazide-sensitive Na-Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, resulting in phenotypes such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. In this study, two GS families with proteinuria or Hashimoto's thyroiditis were analyzed for genetic-phenotypic association. Sanger sequencing revealed that two probands carried SLC12A3 compound heterozygous mutations, and proband A carried two pathogenic mutations: missense mutation Arg83Gln, splicing mutation, or frameshift mutation NC_000016.10:g.56872655_56872667 (gcggacatttttg>accgaaaatttt) in exon 8. Proband B carries two missense mutations: novel Asp839Val and Arg904Gln. Both probands manifested hypokalemia, hypomagnesemia, hypocalcinuria, metabolic alkalosis, and RAAS activation; in addition, the proband A exhibited decreased urinary chloride, phosphorus, and increased magnesium ions excretion, complicated with Hashimoto's Thyroiditis, while the proband B exhibited enhanced urine sodium excretion and proteinuria. The older sister of proband B with GS also had Hashimoto's thyroiditis. Electron microscopy revealed swelling and vacuolar degeneration of glomerular epithelial cells, diffuse proliferation of mesangial cells and matrix, accompanied by a small amount of low-density electron-dense deposition, and segmental fusion of epithelial cell foot processes in proband B. Light microscopy showed mild mesangial hyperplasia in the focal segment of the glomerulus, hyperplasia, and hypertrophy of juxtaglomerular apparatus cells, mild renal tubulointerstitial lesions, and one glomerular sclerosis. So, long-term hypokalemia of GS can cause kidney damage and may also be susceptible to thyroid disease.

BACKGROUND: Dyslipidemia is one of the leading causes of cardiovascular complications in diabetes mellitus (DM) patients. Though it is a major public health problem in Ethiopia, there is no a nation-wide study to determine dyslipidemia among DM patients yet. Therefore, this systematic review and meta-analysis intended to estimate the prevalence of hypertriglyceridemia and other plasma lipid abnormalities among people living with DM in Ethiopia. METHODS: We systematically searched PubMed, Google Scholar, African Journals Online, Hinari, and direct Google. Studies conducted until May 9, 2020, that reports the prevalence of dyslipidemia among people living with DM were included. The DerSimonian and Laird random-effects model was used to determine the pooled prevalence of lipid profile abnormalities. Heterogeneity was checked using the I 2 statistic, whereas publication bias was tested by funnel plot and Egger's test. Besides, subgroup and sensitivity analyses were performed. RESULTS: We used 18 primary studies, including 4961 participants living with DM, which met the eligibility criteria for the meta-analysis of hypertriglyceridemia. The estimate of hypertriglyceridemia (≥150 mg/dl) was 48.15% (95% CI: 38.15-58.15, I 2 = 98.4%) after performing the main meta-analysis using the random-effects model. The subgroup analysis showed a higher pooled estimate of hypertriglyceridemia among T2DM (57.80% (95% CI: 50.50-65.10), I 2 = 92.5%), studies that used probability sampling technique (59.09% (95% CI: 43.58-74.59), I 2 = 98.6%, p < 0.001), and studies from primary data sources (51.43% (95% CI: 40.72-62.13), I 2 = 98.0%, p < 0.001). Moreover, the estimated pooled prevalence of the total plasma cholesterol (TC ≥ 200 mg/dl) was 34.08% (95% CI: 28.41-39.75, I 2 = 92.4%), LDL - C ≥ 100 mg/dl was 41.13% (95% CI: 27.15-55.11, I2 = 98.8%), and HDL ≤ 40 mg/dl for men and ≤ 50 mg/dl for women was 44.36% (95% CI: 31.82-56.90, I 2 = 98.8%). CONCLUSIONS: The pooled prevalence of hypertriglyceridemia and other lipid abnormalities among DM patients was relatively high in Ethiopia. It strongly suggests the need to give maximal attention to the adherence of DM management to reduce the circulatory lipid profile abnormalities and subsequent complications. Prospero Registration. CRD42020182291.

BACKGROUND: The right to prefer mode of delivery is a crucial component of compassionate and respectful care that fosters both maternal and neonatal well-being as the failure to respect the mother's interest increases to the risk of maternal depression and posttraumatic stress. Thus, the aim of the study was to assess delivery mode preference and associated factors among pregnant women. METHODS AND MATERIALS: The study was conducted in two hospitals and two health centers. We used a cross-sectional study design incorporating 398 pregnant mothers attending an antenatal care follow-up from February to May 2018. The study excluded pregnant mothers with any previous uterine surgery including caesarean delivery from participation due to their restricted chance to prefer their mode of delivery. Data were collected by using a pretested questionnaire. Data were entered to EpiData Manager version 3.1 and exported to Statistical Package for the Social Sciences version 22 for analysis. Besides, the analysis included both the bivariate and multivariable analyses to check the association between dependent and independent variables. Finally, level of statistical significance was declared at P value < 0.05. RESULT: The participant's level of response was 100% (398). The age of the mothers ranges from 15 to 45 years old. The delivery mode preference of the caesarean section (C/S) and spontaneous vertex delivery (SVD) was 115 (28.9%) and 283 (71.1%), respectively. The study revealed that planned 47 pregnancy [AOR, 1.76; CI: 0.89-3.47], young age [AOR, 12.9; CI: 0.23-7.1], and primigravida [AOR, 1.24; CI: 0.29-5.2] were among the variables associated with maternal preference of caesarean section. Conclusion and Recommendation. Nearly one-third of the mothers preferred caesarean delivery as their mode of delivery due to fear of labor pain and repeated vaginal examination by the care providers. This is particularly seen in women who had received higher education level, claim their pregnancy as planned, their choice of delivery at hospital, young aged, pregnant for the first time, and those who had visited antenatal care repeatedly. This implies that policy makers and stakeholders should exert due emphasis to ongoing desire of caesarean delivery as the procedure is not without risk, if it is done without indication. For researchers, we recommend to investigate the preference of mode of delivery in a much broader aspect.

OBJECTIVE: To investigate the correlation of periodontal parameters and bite force in different stages of periodontitis after phase I periodontal therapy. METHODS: Periodontal clinical parameters such as mobility, attachment loss, gingival recession, and percentage of bone remaining were recorded at the mandibular first molar region after phase I therapy in subjects categorized according to the stage of periodontitis. Corresponding bite force was recorded at the first mandibular molar region using a bite force device after phase I therapy. ANOVA test was used to assess the significant difference among different groups. Pearson correlation coefficient was used to assess the correlation between measured variables. RESULTS: The ANOVA test represents that there is no statistical significant difference between the bite force in stage I, stage II, and stage III type of periodontitis. A strong positive correlation was found (r = 0.537) between bite force and percentage of remaining alveolar bone support whereas negative correlation was observed in measured parameters such as mobility (r = -0.0181), attachment loss (r = -0.608), and gingival recession (r = -0.435). CONCLUSION: Among all periodontal clinical parameters, the percentage of remaining alveolar bone is the strong predictor of bite force and mobility; attachment loss and gingival recession cannot predict the bite force in the first molar region. Bite force is variable in different stages of periodontitis.

PURPOSE: To investigate and compare the lens phosphoproteomes in patients with highly myopic cataract (HMC) or age-related cataract (ARC). METHODS: In this study, we undertook a comparative phosphoproteome analysis of the lenses from patients with HMC or ARC. Intact lenses from ARC and HMC patients were separated into the cortex and nucleus. After protein digestion, the phosphopeptides were quantitatively analyzed with TiO2 enrichment and liquid chromatography-mass spectrometry. The potential functions of different phosphopeptides were assessed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: In total, 522 phosphorylation sites in 164 phosphoproteins were identified. The number of phosphorylation sites was significantly higher in the cortex than in the nucleus, in both ARC and HMC lenses. The differentially phosphorylated peptides in the lens cortex and nucleus in HMC eyes were significantly involved in the glutathione metabolism pathway. The KEGG pathway enrichment analysis indicated that the differences in phosphosignaling mediators between the ARC and HMC lenses were associated with glycolysis and the level of phosphorylated phosphoglycerate kinase 1 was lower in HMC lenses than in ARC lenses. CONCLUSIONS: We provide an overview of the differential phosphoproteomes of HMC and ARC lenses that can be used to clarify the molecular mechanisms underlying their different phenotypes.

Cytochrome (CYP) enzymes catalyze the metabolic reactions of endogenous and exogenous compounds. The superfamily of enzymes is found across many organisms, regardless of type, except for plants. Information was gathered about CYP2D enzymes through protein sequences of humans and other organisms. The secondary structure was predicted using the SOPMA. The structural and functional study of human CYP2D was conducted using ProtParam, SOPMA, Predotar 1.03, SignalP, TMHMM 2.0, and ExPASy. Most animals shared five central motifs according to motif analysis results. The tertiary structure of human CYP2D, as well as other animal species, was predicted by Phyre2. Human CYP2D proteins are heavily conserved across organisms, according to the findings. This indicates that they are descended from a single ancestor. They calculate the ratio of alpha-helices to extended strands to beta sheets to random coils. Most of the enzymes are alpha-helix, but small amounts of the random coil were also found. The data were obtained to provide us with a better understanding of mammalian proteins' functions and evolutionary relationships.

PURPOSE: The purpose of the current meta-analysis was to evaluate whether multidisciplinary team improved overall survival of colorectal cancer. METHODS: PubMed, EMBASE, and Cochrane Library database were searched from inception to October 25, 2020. The hazard ratio (HR) and 95% confidence (CI) of overall survival (OS) were calculated. RESULTS: A total of 11 studies with 30814 patients were included in this meta-analysis. After pooling the HRs, the MDT group was associated with better OS compared with the non-MDT group (HR = 0.81, 95% CI 0.69-0.94, p = 0.005). In subgroup analysis of stage IV colorectal cancer, the MDT group was associated with better OS as well (HR = 0.73, 95% CI 0.59-0.90, p = 0.004). However, in terms of postoperative mortality, no significant difference was found between MDT and non-MDT groups (OR = 0.84, 95% CI 0.44-1.61, p = 0.60). CONCLUSION: MDT could improve OS of colorectal cancer patients.