Hypoxia and its induced vasculogenic mimicry (VM) formation, which both closely related with stem-like side population (SP) cells, are the main culprits leading to tumor invasion and metastasis. Sinomenine exhibits excellent anticancer activity in breast cancer, but whether and how it affects hypoxia-triggered VM formation in breast cancer SP cells remains unclear. In this study, breast cancer SP cells were sorted from MDA-MB-231 cells and cultured with sinomenine under hypoxic conditions. Sinomenine obviously repressed the migration and VM formation of breast cancer SP cells. Through downregulating SIAH2 and HIF-1α, sinomenine can inhibit epithelial-mesenchymal transition process of breast cancer SP cells. SIAH2 was identified as a target of miR-340-5p and was downregulated by it, and sinomenine can upregulate miR-340-5p. Hypoxia-induced downregulation of miR-340-5p and activation of SIAH2/HIF-1α pathway can be both counteracted by the sinomenine. Moreover, miR-340-5p inhibition and SIAH2 overexpression can partly counteract the anticancer effects of sinomenine. Taken together, sinomenine inhibits hypoxia-caused VM formation and metastasis of breast cancer SP cells by regulating the miR-340-5p/SIAH2 axis.

PURPOSE: The aim of this study was to demonstrate the joint fragment that mostly affects the outcome of the distal radius fracture surgically treated with a volar locking plate (VLP). METHODS: The outcomes of 69 patients with the distal radius fractures were evaluated at their final follow-up. The articular surface was divided into six specific fragments, and computed tomography (CT) was used to evaluate the degree of mismatch of each fragments. A plain radiograph was also obtained for evaluation of the distal radius alignment. Clinical outcomes were measured by using the Disabilities of the Arm, Shoulder and Hand (DASH) and Modified Mayo Wrist Score (MMWS). Univariate analyses were performed, with subsequent multiple logistic regression analyses. RESULTS: The mean follow-up period was 14.8 (range, 12 to 52) months. The group with a worse DASH score showed significantly greater mismatch in the volar and dorsal lunate facets, as well as the central depression of the distal radius (p = 0.042, 0.031, and 0.023, respectively). There was a significant positive correlation between the DASH score and degree of mismatch of the dorsal lunate facet and central depression of the distal radius (p = 0.040 and 0.011, respectively). Groups with worse MMWS showed significantly greater mismatch in the dorsal lunate facet (p = 0.025). There was a significant negative correlation between MMWS and abnormal ulnar variance and mismatch of the dorsal lunate facet and central depression of the distal radius (p = 0.041, 0.004, and 0.018, respectively). The result of multiple logistic regression analysis demonstrated that a mismatch of the dorsal lunate facet is a significant predictor for a worse MMWS (odds ratio = 3.072, p = 0.043). CONCLUSIONS: Articular surface mismatch of the dorsal lunate facet appears to mostly affect the surgical outcomes of the distal radius fractures using VLP. In cases where the dorsal lunate facet is heavily involved, surgeons should be cautious about its reduction and fixation.

BACKGROUND: Landoltia punctata can be used as renewable and sustainable biofuel feedstock because it can quickly accumulate high starch levels. ADP-glucose pyrophosphorylase (AGPase) catalyzes the first committed step during starch biosynthesis in higher plants. The heterotetrameric structure of plant AGPases comprises pairs of large subunits (LSs) and small subunits (SSs). Although several studies have reported on the high starch accumulation capacity of duckweed, no study has explored the underlying molecular accumulation mechanisms and their linkage with AGPase. Therefore, this study focused on characterizing the roles of different L. punctate AGPases. Methodology. Expression patterns of LpAGPs were determined through comparative transcriptome analyses, followed by coexpressing their coding sequences in Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana, and Nicotiana tabacum. RESULTS: Comparative transcriptome analyses showed that there are five AGPase subunits encoding cDNAs in L. punctata (LpAGPS1, LpAGPS2, LpAGPL1, LpAGPL2, and LpAGPL3). Nutrient starvation (distilled water treatment) significantly upregulated the expression of LpAGPS1, LpAGPL2, and LpAGPL3. Coexpression of LpAGPSs and LpAGPLs in Escherichia coli generated six heterotetramers, but only four (LpAGPS1/LpAGPL3, LpAGPS2/LpAGPL1, LpAGPS2/LpAGPL2, and LpAGPS2/LpAGPL3) exhibited AGPase activities and displayed a brownish coloration upon exposure to iodine staining. Yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays validated the interactions between LpAGPS1/LpAGPL2, LpAGPS1/LpAGPL3, LpAGPS2/LpAGPL1, LpAGPS2/LpAGPL2, and LpAGPS2/LpAGPL3. All the five LpAGPs were fusion-expressed with hGFP in Arabidopsis protoplasts, and their green fluorescence signals were uniformly localized in the chloroplast, indicating that they are plastid proteins. CONCLUSIONS: This study uncovered the cDNA sequences, structures, subunit interactions, expression patterns, and subcellular localization of AGPase. Collectively, these findings provide new insights into the molecular mechanism of fast starch accumulation in L. punctata.

Though paclitaxel (PTX) and doxorubicin (DOX) are amongst the most widely used and investigated drug pair for combination chemotherapy but surprisingly, not a single validated HPLC-UV method is available to analyze PTX and DOX simultaneously. So, herein a HPLC-UV method is developed and validated for the same, filling an indispensable gap in the literature. As these two moieties have characteristically different polarities, resolving them under the common chromatographic conditions is a challenging task. Herein, the principle of ion pair chromatography is utilized to resolve these two moieties on a C18 column employing an isocratic mobile phase comprised of acetonitrile and octane sulfonic acid buffer (67 : 37) and detected simultaneously at 231 nm using a UV detector only. The retention time is 4.4 and 7.2 min for PTX and DOX, respectively, with a total analysis time of less than 10 minutes, suitable for the formulation development and research, while LOQ is less than 0.066 μg/ml for both the drugs, suitable for the therapeutic drug monitoring at preclinical and clinical research setup. To substantiate the applicability of the developed method, a nanoformulation coloaded with PTX and DOX was designed and analyzed using the developed protocol. The method is also applied successfully to study the plasma kinetic profile of both the moieties simultaneously in Balb/c mice. Further, the method is validated as per the ICH guidelines fulfilling the unmet need of a validated analytical tool to simultaneously estimate PTX and DOX. Moreover, the results suggest that the principal of common ion chromatography demonstrated here can also be applied further for the simultaneous chromatographic separation of other polar and nonpolar moieties too. Consequently, the reported method surely will advance the toolset required for the precision-based combination chemotherapy.

This paper addresses the mixture symptom mention problem which appears in the structuring of Traditional Chinese Medicine (TCM). We accomplished this by disassembling mixture symptom mentions with entity relation extraction. Over 2,200 clinical notes were annotated to construct the training set. Then, an end-to-end joint learning model was established to extract the entity relations. A joint model leveraging a multihead mechanism was proposed to deal with the problem of relation overlapping. A pretrained transformer encoder was adopted to capture context information. Compared with the entity extraction pipeline, the constructed joint learning model was superior in recall, precision, and F1 measures, at 0.822, 0.825, and 0.818, respectively, 14% higher than the baseline model. The joint learning model could automatically extract features without any extra natural language processing tools. This is efficient in the disassembling of mixture symptom mentions. Furthermore, this superior performance at identifying overlapping relations could benefit the reassembling of separated symptom entities downstream.

PURPOSE: To examine the effects of fluid contamination on the reverse torque value (RTV) of abutment screws. 484 titanium fixtures were mounted into the stainless-steel holders. METHODS: 11 groups (44 specimens in each group) of implants were mounted in acrylic resin. Ten groups of fixture screw holes were contaminated with chlorhexidine, saliva, blood, fluoride, or combination groups, and one group served as a control without contamination. To simulate the oral environment, samples were subjected to thermal cycling and cyclic loading. RESULTS: The RTV means were less than the initial torque in both control and contamination groups. The maximum RTV mean was observed in the fluoride group (26.00 ± 1.02 Ncm). In other groups, this rate for control, blood, saliva, and chlorhexidine groups were 18.00 ± 1.78 Ncm, 22.12 ± 1.56 Ncm, 21.56 ± 1.43 Ncm, and 21.89 ± 1.02 Ncm, respectively. In combination groups, the maximum RTV mean was observed in the saliva+CHX group (23.89 ± 1.92 Ncm). In other combination groups, this rate for the blood+CHX, blood+saliva, saliva+fluoride, fluoride+CHX, and fluoride+blood groups were 22.56 ± 1.73 Ncm, 22.00 ± 1.54 Ncm, 20.11 ± 1.58 Ncm, 23.51 ± 1.19 Ncm, 21.02 ± 1.38 Ncm, and 20.11 ± 1.58 Ncm, respectively. The RTV was statistically significant (p < 0.05) for the contamination groups (except saliva) and combination groups compared to the control group. There is no statistically significant difference (p > 0.05) between the reverse torque value mean of the blood and saliva groups and between that of the fluoride and chlorhexidine groups. CONCLUSION: Implant-abutment specimens are suggested to be placed in a saliva environment and should be subjected to cyclic loading.

Copper oxide (CuO) nanoparticle- (NP-) decorated carbon NPs (CNPs) were produced as colloidal suspension through pulsed laser ablation technique in liquid (PLAL) medium. The antimicrobial activity of the produced NPs was tested against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), and anticancer activity was tested against breast cancer cell line, MCF-7, together with the biocompatibility assessment of these NPs. The X-ray diffraction (XRD) patterns of the obtained CNPs showed peaks at 26.58° and 43.78° (2θ) identical to (002) and (111) planes, respectively, of the carbon phases. It also displayed new peaks at 38.5° and 48.64° (2θ) after doping with CuO NPs. Transmission electron microscope (TEM) images revealed the crystalline nature with the spherical shape of the prepared CNPs with 5-40 nm diameter ranges. In addition, the NP effects on the bacterial cell walls and nucleic acid were confirmed using a scanning electron microscope (SEM) and microscopic fluorescence analysis. The NPs showed antibacterial activity through SEM examinations against the pathogenic microbial species, S. aureus and E. coli. In the cellular material release assay, the optical density of the bacterial cells, treated with NPs, displayed a significant increase with the time of exposure to NPs, and the cytotoxicity reached more than 80% of the level for the CNPs decorated with CuO NPs. The morphology of the MCF-7 cells treated with NPs decreased numbers, and the loss of contact with the surrounding cells was observed. These results confirmed that the CNPs decorated with CuO NPs have no observable side effects and can be safely used for therapeutic applications. It is also noteworthy that it is the first report of preparation of CuO NPs decorated with CNPs (CuO NPs-CNPs) by PLAL, and the produced NPs showed antimicrobial antiproliferative activities against breast cancer cell lines, MCF-7. The main advantage of the PLAL technique of synthesizing CuO NPs-CNPs provided a two-step, cost-effective, and eco-friendly method.

Ganoderma lucidum polysaccharides (GLP) have renal protection effect but there was no study on the diabetic nephropathy. This study was designed to investigate its effect and mechanism using a diabetic rat model induced by streptozotocin (50 mg/kg, i.p.). The diabetic rats were treated with GLP (300 mg/kg/day) for 10 weeks. The blood glucose, glycated hemoglobin, body weight, and the levels of blood creatinine, urea nitrogen, and urine protein were assessed. And renal pathologies were assessed by the tissue sections stained with hematoxylin-eosin, Masson's trichome, and periodic acid-Schiff. The expression of phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR), the autophagy proteins beclin-1, LC3-II, LC3-I, and P62; the apoptosis-related proteins caspase-3 and caspase-9; and the inflammation markers IL-6, IL-1β, and TNF-ɑ were assessed. Results showed that GLP alleviated the impairment of renal function by reducing urinary protein excretion and the blood creatinine level and ameliorated diabetic nephropathy. The expression of p-PI3K, p-Akt, and p-mTOR in the diabetic kidney were significantly reduced in the GLP treatment group compared to the without treatment group. GLP treatment activated the autophagy indicators of beclin-1 and the ratio of LC3-II/LC3-I but reduced p62 and also inhibited the expression of caspase-3, caspase-9 and IL-6, IL-1β, and TNF-ɑ. In conclusion, the effect of GLP amelioration diabetic nephropathy may be via the PI3k/Akt/mTOR signaling pathway by inhibition of the apoptosis and inflammation and activation of the autophagy process.

OBJECTIVE: Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein, which plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. However, little was known about the correlation between PTBP1 and glioma and its prognostic significance in glioma patients. Our aim was to investigate the expression, functional role, and prognostic value of PTBP1 in glioma. METHODS: We explored the expression of PTBP1 protein using immunohistochemistry in 150 adult malignant glioma tissues and 20 normal brain tissues and evaluated its association with clinicopathological parameters by chi-square test. Kaplan-Meier method was used to evaluate the prognostic effect of PTBP1 in glioma. Univariate/multivariate Cox analyses were used to identify independent prognostic factors. Transcriptional regulation network was constructed based on differentially expressed genes (DEGs) of PTBP1 from TCGA/CGGA database. GO and KEGG enrichment analyses were used to explore the function and pathways of DEGs. RESULTS: Out of the 150 malignant glioma tissues (60 LGG and 90 GBMs) and 20 normal brain tissues in our cohort, PTBP1 protein was high expressed in glioma tissues (79/150, 52.7%), but no expression was detected in normal brain tissues (0/20, 0%). The expression of PTBP1 was significantly higher in GBMs (P < 0.001). More than half of GBMs (62/90, 68.9%) were PTBP1 high expression. Chi-square test showed that the expression of PTBP1 was correlated with patient age, WHO grade, Ki-67 index, and IDH status. High expression of PTBP1 was significantly associated with poor prognosis in glioma, and it was an independent risk factor in glioma patients. Furthermore, we shed light on the underlying mechanism of PTBP1 by constructing a miR-218-TCF3-PTBP1 transcriptional network in glioma. CONCLUSION: PTBP1 was high expressed in glioma, and it significantly correlated with poor prognosis, suggesting a potential therapeutic target for glioma, particularly for GBM.

BACKGROUND: Gleditsiae Spina, widely used in traditional Chinese medicine, has a good curative effect on malignant tumors such as ovarian cancer, but the mechanism is not clear. So, we aimed to analyze the pharmacological mechanism of Gleditsiae Spina in the treatment of high-grade serous ovarian cancer (HGSC) based on network pharmacology and biological experiments. METHODS: The main active ingredients of Gleditsiae Spina were identified by high performance liquid chromatography (HPLC) and mass spectrometry (MS), and the active ingredients were performed by ADME screening. The component targets of Gleditsiae Spina were screened using the PharmMapper platform, and differentially expressed genes in normal and HGSC tissues were identified through the GEO database. Thereafter, the network of "active ingredient-targets" was constructed by cytoscape 3.7.2 software. The protein-protein interaction network was established by the BioGenet database to mine the potential protein function. Biological processes and pathways were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The binding ability of the core components of the Gleditsiae Spina and the core target of HGSC was verified by molecular docking and molecular dynamics simulation, and the therapeutic effect of Gleditsiae Spina was proved in vitro through cytotoxicity experiments. The effect of Gleditsiae Spina on the core pathway is obtained by western blotting. RESULTS: Gleditsiae Spina had cytotoxicity on HGSC based on network pharmacology and biological experiments. Luteolin, genistein, D-(+)-tryptophan, ursolic acid, and berberine are the identified core active ingredients of Gleditsiae Spina for regulating HGSC, with HPSE, PI3KCA, AKT1, and CTNNB1as the ideal targets. The prediction results were verified by molecular docking, molecular dynamic simulation, cell viability, and western blot analysis. CONCLUSION: Gleditsiae Spina mainly downregulates the expression of heparanase and β-catenin to affect the composition of tumor cytoplasmic matrix and can regulate the PI3K-AKT pathway, integrating multiple targets and multiple pathways to play a therapeutic role. It also provides a theoretical basis for the prevention of ovarian cancer and its treatment using traditional Chinese medicine in the future.

BACKGROUND: Tobacco use among adolescents has long-term adverse health consequences, especially during adulthood. Currently, little is known about tobacco use behaviour among adolescents in Comoros. Our study aims at estimating the prevalence and identifying key factors associated with tobacco use among adolescents in Comoros using the 2015 Comoros Global Youth Tobacco Survey data. METHODS: A national cross-sectional survey secondary data of 2,810 eligible school-going adolescents aged between 11 and 17 years was analysed. Complex sample logistic regression analyses were used to determine the correlates of current cigarette smoking and current use of noncigarette tobacco products. RESULTS: The overall prevalence of current cigarette smoking was 14.3% [males (18.5%) and females (9.9%)]. The prevalence of current use of noncigarette tobacco products was 5.8% [males (6.7%) and females (4.9%)]. Being male (AOR = 2.24; 95% CI:1.39-3.63), exposure to secondhand smoke inside (AOR =3.88; 95% CI:2.84-5.31) and outside (AOR =1.49; 95% CI: 1.08-2.03) their home, and exposure to tobacco industry promotion (AOR =2.90; 95% CI:2.21-3.80) were associated with current cigarette use among school-going adolescents. However, parental smoke (AOR = 1.20; 95% CI:0.78-1.87) and not exposed to antismoking education in schools (AOR = 0.97; 95% CI:0.76-1.22) were not associated with current cigarette use. On the other hand, being male (AOR = 1.24; 95% CI:0.82-1.86) was not associated with the current use of noncigarette tobacco products. Adolescents who were exposed to tobacco industry promotion (AOR = .2.58; 95% CI:1.54-4.32) and not exposed to antismoking education in school (AOR = 0.52; 95% CI:0.32-0.85) were more and less likely associated with noncigarette tobacco use. CONCLUSION: One in seven school-going adolescents smokes cigarettes, and approximately one in 20 school-going adolescents uses noncigarette tobacco products in Comoros. Exposure to secondhand smoke within and outside the home and exposure to tobacco industry promotion were associated with tobacco use in school-going adolescents in Comoros. Our findings suggest the need for adolescent-friendly gender-sensitive tobacco interventions, including strengthening existing tobacco control laws to prevent and reduce tobacco use among school-going adolescents in Comoros.

To study the SSR loci information and develop molecular markers, a total of 435,858 unigenes in transcriptome of Polygonatum sibiricum were used to explore SSR. The distribution frequency of SSR and the basic characteristics of repeat motifs were analyzed using MISA software, and SSR primers were designed by Primer 3.0 software and then validated by PCR. Moreover, the gene function analysis of SSR Unigene was obtained by Blast. The results showed that 112,728 SSR loci were found in the transcriptome of Polygonatum sibiricum, which distributed in 435,858 unigenes with a distribution frequency of 25.86%. Mo-nucleotide and Di-nucleotide repeat were the main types, accounted for 83.83% of all SSRs. The repeat motifs of A/T and AC/GT were the predominant repeat types of Mo-nucleotide and Di-nucleotide, respectively. A total of 113,305 pairs of SSR primers with the potential to produce polymorphism were designed for maker development. One hundred and fifty-four of the 500 randomly selected primers not only produced fragments with expected molecular size but also had high polymorphism, which could accurately separate the tested varieties. The gene function of unigenes containing SSR was mostly related to the molecular function of Polygonatum sibiricum. The SSR markers in transcriptome of Polygonatum sibiricum show rich type, strong specificity, and high potential of polymorphism, which will benefit the candidate gene mining and marker-assisted breeding. The developed markers can also provide technical methods for molecular identification of intraspecific species of Polygonatum Mill. and maker-assisted breeding of superior varieties of Polygonatum Mill.

BACKGROUND: Childhood overweight and obesity (OW/OB) is a worldwide public health problem, and its genetic risks remain unclear. OBJECTIVES: To investigate risks of OW/OB associated with genetic variances in SEC16B rs543874 and rs10913469, BDNF rs11030104 and rs6265, NT5C2 rs11191580, PTBP2 rs11165675, ADCY9 rs2531995, FAM120A rs7869969, KCNQ1 rs2237892, and C4orf33 rs2968990 in Chinese infants at 12-month old. METHODS: We conducted a case-control study with 734 infants included at delivery and followed up to 12-month old. The classification and regression tree analysis were used to generate the structure of the gene-gene interactions, while the unconditional multivariate logistic regression models were applied to analyze the single SNP, gene-gene interactions, and cumulative effects of the genotypes on OW/OB, adjusted for potential confounders. RESULTS: There were 219 (29.84%) OW/OB infants. Rs543874 G allele and rs11030104 AA genotype increased the risk of OW/OB in 12-month-old infants (P < 0.05). Those carrying both rs11030104 AA genotype and rs10913469 C allele had 4.3 times greater OW/OB than those carrying rs11030104 G allele, rs11191580 C allele, rs11165675 A allele, and rs543874 AA genotype. Meanwhile, the risk of OW/OB increased with the number of the risk genotypes individuals harbored. CONCLUSIONS: Rs543874, rs11030104, and rs11191580 were associated with OW/OB in 12-month-old Chinese infants, and the three SNPs together with rs10913469 and rs11165675 had a combined effect on OW/OB.

The aberrant expression of miRNA is strongly linked to numerous stages of triple-negative breast cancer (TNBC) progression, and it plays an indispensable role in the process from tumor onset and progress to invasion and metastasis. In this study, we first transfected miR-129-1-3p mimics and inhibitor into MDA-MB-231 TNBC cells, respectively. Then, we assessed the pathological role of miR-129-1-3p in MDA-MB-231 cells. The results showed that miR-129-1-3p were successfully inserted into MDA-MB-231 cells. Besides, miR-129-1-3p could distinctively repress the growth, migration along with infiltration of MDA-MB-231 cells, which might be related to the inhibition of GRIN2D expression. Our results indicate that miR-129-1-3p was illustrated to serve as a tumor repressor via targeting GRIN2D in TNBC cells and highlight that the restoration of miR-129-1-3p might be a new treatment target for TNBC.

AIM: This cross-sectional study is aimed at identifying normative ocular coherence tomography angiography (OCTA) values in a cohort of healthy adult Jordanian individuals and assessing the prevalence of different image artifacts and their impact on quantitative OCTA measurements. MATERIALS AND METHODS: One hundred and eighty-one eyes from 100 healthy participants were included in this study. All participants underwent a comprehensive ophthalmological examination including best corrected visual acuity, slit lamp examination, and dilated fundoscopy. Swept-source OCTA images were obtained and analyzed for all 181 eyes. We recorded vascularity measurements and analyzed the prevalence and effect of ten different artifacts on superficial and deep retinal and choriocapillaris layer images. RESULTS: Sixty-two percent of the participants were men (n = 62), and 38% (n = 38) were women. The age of participants ranged between 24 and 75 years (mean 50.5 ± 10.92). The mean central macular thickness was 237.71 (±22.905) μm, and the mean choroidal thickness was 257.73 (±77.027) μm. Artifacts were present in 46.4% of the acquired scans. Images with artifacts had higher mean age (p = 0.03), lower image quality (p < 0.001), higher central vascular density (p < 0.001), and lower inferior vascular density (p < 0.001) compared to artifact-free tomographs. Motion artifact was the most common type, which was present in 29 (16%) of images, followed by blink artifact 18 (9.9%), and Z offset 8 (4.4%). CONCLUSION: OCTA artifact detection and correction remains a challenging aspect of the diagnostic and follow-up process of patients with retinal pathologies. To our knowledge, this is the first study to examine the association between OCTA outputs and artifacts in healthy eyes. We report that in this cohort of normal individuals, images with artifacts had a significantly higher central vascular density (22.62 vs. 16.60) and a lower inferior vascular density (46.09 vs. 48.81). We also found that a significant increase in central vascular density is only present in images with Z offset artifact type (49.03). Motion artifact was the most common artifact seen in our series. However, we observed no alteration in quantitative parameters in images with motion artifacts.

PURPOSE: Accurately measuring an angle on a lower extremity X-ray is essential for the diagnosis and treatment of knee osteoarthritis (KOA). However, the angle is often affected by position, especially with flexion contracture and rotation. To date, there have been no quantitative analyses examining the relationship between lower extremity angle and patient position and no studies targeting patients with deformities. The aim of this study is to quantify the effect of position on angle measurements in lower extremity X-rays and to compare the effect in patients with different deformities. METHODS: Computed tomography (CT) data of 131 patients with knee pain were retrospectively analyzed. The subjects were categorized into the following groups: neutral (hip-knee-ankle angle (HKAA) between 175 and 185°), varus (HKAA less than 175°), valgus (HKAA more than 185°), and flexion (flexion contracture more than 10°). CT images were digitally reconstructed to anterior-posterior X-ray images using an average intensity projection algorithm. The process was then repeated while rotating the reconstruction plane from internal 9° to external 9°. In this manner, X-ray images were reconstructed in different rotational states. The following angles were measured from reconstructed X-ray images: HKAA, lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and femoral valgus angle (FVA). The measurements were then compared according to the degree of rotation. RESULTS: FVA significantly differed according to rotation in all groups (P < 0.001), with a difference of 1.3° (±0.4°). HKAA significantly changed only in the flexion contracture group (P < 0.001), which showed a difference of 1.0° (±0.7°). However, HKAA in the other groups, LDFA, and MPTA did not significantly differ depending on rotation. CONCLUSIONS: Radiographic measurement of FVA is subject to change according to rotation. HKAA significantly changed only in the flexion contracture group, so more care should be taken while obtaining X-rays of patients with flexion contracture.

OBJECTIVES: Abdominal aortic aneurysm (AAA), a disease with high mortality, is limited by the current diagnostic methods in the early screening. This study aimed to screen novel and significant biomarkers and construct a diagnostic model for AAA by using a novel machine learning method, i.e., an ensemble of the random forest (RF) algorithm and artificial neural network (ANN). METHODS AND RESULTS: Through a search of the Gene Expression Omnibus (GEO) database, two large-sample gene expression datasets (GSE57691 and GSE47472) were downloaded and preprocessed. Differentially expressed genes (DEGs) in GSE57691 were identified by R software, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Essential metabolic pathways related to positive regulation of cell death and NAD binding were found. Then, RF was used to identify key genes from the DEGs, and an AAA diagnostic model was established by ANN. A transcription factor (TF) regulatory network of key genes related to angiogenesis and endothelial migration was constructed. Finally, a validation dataset was used to validate the model and the area under the receiver operating characteristic curve (AUC) value was high. CONCLUSION: Potential AAA-associated gene biomarkers were identified by RF, and a novel early diagnostic model of AAA was established by ANN. The AUC indicated that the diagnostic model had a highly satisfactory diagnostic performance. In conclusion, this study will provide a promising theoretical basis for further clinical and experimental studies.

Despite increasing mortality rates from cardiovascular diseases (CVDs) in low- and middle-income countries, information on the estimation of 10-year CVD risk remains to be sparse. Therefore, this study was aimed at predicting the 10-year CVD risk among community dwellers in Malaysia and at identifying the association of distal (socioeconomic characteristics) and proximal (lifestyle practices) factors with 10-year CVD risk. We calculated the 10-year CVD risk score among 11,897 eligible respondents from the community health survey conducted by the South East Asia Community Observatory (SEACO) using the Framingham risk score (FRS). The findings indicate that 28% of respondents have a high chance of having CVD within the next ten years. After adjusting for the age of respondents, demographic and socioeconomic factors such as gender, ethnicity, marital status, education, income, and occupation had an association with the 10-year CVD risk. In addition, frequent eating out had an association with 10-year CVD risk, while physical activity was found to have no association with predicted CVD risk. CVD remained among the top five mortality causes in Malaysia. Health promotion strategies should emphasize the importance of having home-cooked meals as a healthy dietary behavior, to reduce the mortality rate among Malaysians due to CVDs.

MicroRNA (miRNA), a noncoding ribonucleic acid, is considered to be important for the progression of gene expression in plants and animals by rupture or translational repression of targeted mRNAs. Many types of miRNA regulate plant metabolism, growth, and response to biotic and abiotic factors. miRNA characterization helps to expose its function in regulating the process of post-transcriptional genetic regulation. There are a lot of factors associated with miRNA function, but the function of miRNA in the organic synthesis of by-products by natural products is not yet fully elucidated. The current review is aimed at observing and characterizing miRNAs and identifying those involved in the functioning of the biosynthesis of secondary metabolites in plants, with their use in controlled manipulation.

Tyrosinase and α-glucosidase enzymes are known as promising target candidates for inhibitors to control unwanted pigmentation and type II diabetics mellitus. Therefore, twenty extracts as enzyme inhibitors were prepared from edible spices: nutmeg, mace, star anise, fenugreek, and coriander aiming to explore their antioxidant, antibrowning, and antidiabetic potential. Results confirmed that all extracts showed potent antioxidant activity ranging from IC50 = 0.14 ± 0.03 to 3.69 ± 0.37 μg/mL. In addition, all extracts exhibited excellent antityrosinase (IC50 = 1.16 ± 0.06 to 71.32 ± 4.63 μg/mL) and anti-α-glucosidase (IC504.76 ± 0.71 to 42.57 ± 2.13 μg/mL) activities outperforming the corresponding standards, hydroquinone, and acarbose, respectively. Among all extracts, star anise ethyl acetate (Star anise ETAC) was found most potent inhibitor for both tyrosinase and α-glucosidase enzymes and was further studied to explore the mechanism of enzyme inhibition. Kinetic analysis revealed its irreversible but mixed-type tyrosinase inhibition with preferentially competitive mode of action. However, it binds reversibly with α-glucosidase through competitive mode of action. Further, star anise ETAC extract showed concentration dependent and posttreatment time-dependent antibrowning effect on potato slices and antidiabetic effect on diabetic rabbits in vivo proposing it promising candidate for tyrosinase-rooted antibrowning and α-glucosidase-associated diabetes management for future studies.

The study aimed to explore the antidepressant effect of Yinhuo Decoction and further to explore its underlying molecular mechanism acting on depressant. Here, high-performance liquid chromatography (HPLC) analysis was used to the composition analysis. Postmenopausal depression (PMD) model and corticosterone (CORT)-induced cell model were constructed. Adrenal coefficient and hematoxylin and eosin staining were applied to assess changes in the adrenal glands. MTT staining, Hoechst 33342 staining, and JC-1 fluorescence staining were used to detect the PC12 activity and apoptosis. CORT and oxidative stress indicators were measured using commercial kits. Western blot and immunohistochemical were used to detect the protein expression of GCR. In addition, genes related to SIRT1/PGC-1α pathway were also tested. In PMD model mice, Yinhuo Decoction evidently increased adrenal coefficient and relieved adrenal lesions. Meanwhile, we observed that Yinhuo Decoction reduced the CORT and GCR levels. In CORT-treated PC12 cells, Yinhuo Decoction remarkably reduced cytotoxicity and apoptosis. Besides, Yinhuo Decoction attenuated the oxidative stress response. Mechanically, we confirmed that Yinhuo Decoction reduced CORT-induced PC12 damage by regulating SIRT1/PGC-1α pathway. Thus, we concluded that Yinhuo Decoction antagonized CORT-induced injury in PC12 cells and improved depression in PMD mice. This provided a new direction for the treatment of depression.

PURPOSE: The article is aimed at improving the understanding of the sociocultural profile of adult orthodontic patients and their expectations. In particular, it addresses three main aspects: the motivation and needs that underpin the decision to start orthodontic treatment, how it influences the patients' daily life, and the different oral hygiene demands. MATERIALS AND METHODS: An online survey was completed by 276 patients undergoing orthodontic treatment with different techniques. The questions asked concerned gender, age, type of appliance, any previous orthodontic treatments, type of any previous retainers, reasons for therapy, satisfaction, pain, problems in eating, daily number of teeth brushings and flossings before and during the treatment, perception of cost, sensation of visibility of the appliance, and if they would recommend orthodontic treatment. RESULTS: A significant role within our sample is played by gender; 87.94% consisted of female patients out of which 72.57% wanted to improve their aesthetics, while only 54.84% of male patients cited the same reason. Invisible aligners were preferred by 67.70% of the patients due to them being considered the least painful, causing the fewest problems with eating, and the least visible. Metal braces were perceived as the less expensive treatment. Over a third of the patients (33.85%) had previously undergone orthodontic treatment, among them 54.05% wore a mobile retainer, 31.08% a fixed one, and 14.86% both. Daily tooth brushing and flossing increased during therapy with clear aligners by 48.94% and 126.39%, respectively. CONCLUSIONS: The greatest demand for orthodontic treatments comes from women, as they pay more attention to aesthetics, which makes the clear aligners the most common choice. The relapse after orthodontic treatment seems to cause a higher demand for retreatment, and oral hygiene habits significantly improve during orthodontic treatment, especially with the clear aligners.

OBJECTIVE: The current trial was designed to evaluate the effects of high-energy shockwave therapy on objective and subjective outcomes among participants with calcified rotator cuff tendinopathy. METHODS: This parallel-group, randomized trial consists of 42 patients affected by calcific tendinopathies divided into two groups of 21 participants. Patients having calcified tendinopathy aged between 30 and 65 years with type A or B calcification were selected in the trial after signing the written consent form. Participants in the ESWT+RPT group received eight sessions of shockwaves, while the RPT group was treated by routine physical therapy. About 2000 shockwaves of 0.32 mJ/mm2, 120 Hz per treatment, were given as 12 sessions for the first six weeks (2 sessions/week). Pain intensity and shoulder functional ability, ultrasonographic changes, and quality of life were assessed with the numeric pain rating scale (NPRS), Constant-Murley score (CMS), ultrasonography, and Western Ontario rotator cuff index (WORC). RESULTS: There were significant differences regarding NPRS and CMS between the two groups, at baseline and 6th and 12th weeks after intervention (p < 0.05). Within-group differences also showed statistically significant results after treatment (all p < 0.05). Significant results were seen in the WORC and ultrasonographic results pre- and posttreatment; more significant findings were found in the experimental group as compared to others. CONCLUSION: High-energy shockwave therapy has been proved to be effective and thus strongly recommended for the management of calcified rotator cuff tendinopathy, improving the pain, functionality, and quality of life of these participants and decreasing the size of calcified deposits. Shockwave therapy is proved to be superior to routine physiotherapy.

BACKGROUND: Type 2 diabetes is a major health concern worldwide. The present study is aimed at discovering effective biomarkers for an efficient diagnosis of type 2 diabetes. METHODS: Differentially expressed genes (DEGs) between type 2 diabetes patients and normal controls were identified by analyses of integrated microarray data obtained from the Gene Expression Omnibus database using the Limma package. Functional analysis of genes was performed using the R software package clusterProfiler. Analyses of protein-protein interaction (PPI) performed using Cytoscape with the CytoHubba plugin were used to determine the most sensitive diagnostic gene biomarkers for type 2 diabetes in our study. The support vector machine (SVM) classification model was used to validate the gene biomarkers used for the diagnosis of type 2 diabetes. RESULTS: GSE164416 dataset analysis revealed 499 genes that were differentially expressed between type 2 diabetes patients and normal controls, and these DEGs were found to be enriched in the regulation of the immune effector pathway, type 1 diabetes mellitus, and fatty acid degradation. PPI analysis data showed that five MCODE clusters could be considered as clinically significant modules and that 10 genes (IL1B, ITGB2, ITGAX, COL1A1, CSF1, CXCL12, SPP1, FN1, C3, and MMP2) were identified as "real" hub genes in the PPI network using algorithms such as Degree, MNC, and Closeness. The sensitivity and specificity of the SVM model for identifying patients with type 2 diabetes were 100%, with an area under the curve of 1 in the training as well as the validation dataset. CONCLUSION: Our results indicate that the SVM-based model developed by us can facilitate accurate diagnosis of type 2 diabetes.

BACKGROUND: Eucommiae Cortex is a Chinese herbal medicine with bone protective effects and treats osteoporosis. This study aimed to explore the pharmacological mechanisms of this complex mixture. METHODS: The active compounds and disease targets involved in the study were obtained from publicly available websites and databases. Core target genes were identified by protein-protein interaction (PPI) network and topology analysis and mapped to critical components by a "component-target" regulatory network. Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis and Gene Ontology (GO)analysis were performed to analyze the biological processes of target genes. Moreover, we carried out molecular docking, cell experiments, and quantitative real-time PCR to propel the research forward. RESULTS: Eucommiae Cortex contained 28 active ingredients and 85 potential targets for antiosteoporosis. PPI networks and topology analysis screened 17 core target genes. The therapeutic mechanism involves a series of biological reactions, including host-virus response, chemical stress, oxidative stress, and cell cycle control. The KEGG enrichment illustrated that the MAPK signaling pathway might play a significant role. The final experiment detected ten genes (EGF, AKT1, JUN, MAPK8, MAPK1, CASP3, FOS, VEGFA, EGFR, and MYC) and three compounds (quercetin, kaempferol, and beta- carotene) in the MAPK pathway. Firstly, the CCK-8 and ALP activity test results showed that three compounds could enhance the proliferation and differentiation of osteoblast-like MC3T3-E1 cells. Secondly, molecular docking confirmed the favorable binding potential. Subsequently, we observed that adding 1∗10-6 mol/L quercetin, 1∗10-5  mol/L kaempferol, and 1∗10-5  mol/L beta-carotene activated the ERK/JNK cascades and the heterodimer complex AP-1(Fos/Jun) in the MAPK pathway. CONCLUSION: MAPK pathway might provide an essential mechanism for the antiosteoporosis effect of Eucommiae Cortex. Eucommiae Cortex and its active ingredients have the potential to treat osteoporosis.

Clear evidence has shown that metal ions strongly connect and delicately tune the dynamic homeostasis in living bodies. They have been proved to be associated with protein structure, stability, regulation, and function. Even small changes in the concentration of metal ions can shift their effects from natural beneficial functions to harmful. This leads to degenerative diseases, malignant tumors, and cancers. Accurate characterizations and predictions of metalloproteins at the residue level promise informative clues to the investigation of intrinsic mechanisms of protein-metal ion interactions. Compared to biophysical or biochemical wet-lab technologies, computational methods provide open web interfaces of high-resolution databases and high-throughput predictors for efficient investigation of metal-binding residues. This review surveys and details 18 public databases of metal-protein binding. We collect a comprehensive set of 44 computation-based methods and classify them into four categories, namely, learning-, docking-, template-, and meta-based methods. We analyze the benchmark datasets, assessment criteria, feature construction, and algorithms. We also compare several methods on two benchmark testing datasets and include a discussion about currently publicly available predictive tools. Finally, we summarize the challenges and underlying limitations of the current studies and propose several prospective directions concerning the future development of the related databases and methods.

Turmeric rhizome (Curcuma longa L.) has been used without concern for safety as a culinary spice and traditional medicine under the ancient Ayurvedic medicinal system of India dating back nearly 4000 years. This preclinical safety evaluation was done to determine the safety of an oleoresin-based turmeric extract (CURCUGEN®). Guidelines from the Organization for Economic Co-operation and Development (OECD) directed the assessment of safety for the in vitro and in vivo application of CURCUGEN®. Safety of the herbal medicine was evaluated through the toxicological assessment of acute, oral, and 90-day repeated dosing, genotoxicity, and mutagenicity study. Genotoxicity tests included the in vitro bacterial reverse mutation test, chromosomal aberration test, and in vivo micronucleus test. The single dose of CURCUGEN® administered orally (gavage) to Sprague-Dawley (SD) rats resulted in a LD50 of >5000 mg/kg body weight. The subchronic assessment of CURCUGEN®, as administered to SD rats over 90 days resulted in a no observed adverse effect level (NOAEL) of 2000 mg/kg body weight/day. CURCUGEN® did not elicit any genotoxic or clastogenic effect in genotoxicity tests. The battery of safety studies carried out demonstrated that CURCUGEN® showed no evidence of general toxicity or genotoxicity.

OBJECTIVE: Hip fractures are quite common worldwide, especially among the elderly, and are associated with a high incidence of postoperative delirium, which worsens functional results and increases death. The causes of postoperative delirium in patients with hip fractures are unknown, and a separate pathobiology has been hypothesized. Substance P is a neuropeptide that has been linked to a number of immune-inflammatory and neurological conditions. The purpose of this study was to see if serum substance P levels could predict postoperative delirium in a group of hip fracture patients. METHODS: A total of 148 hip fracture patients were enrolled in the study, all of whom had no substantial pre-existing medical or cognitive issues. Demographic and regular laboratory data were gathered as a starting point. ELISA was used to examine substance P levels before and after surgery (after 1 day). Patients were then divided into two groups: "postoperative delirium" and "no postoperative delirium." Intergroup comparisons, study of delirium prevalence rates in postoperative serum substance P quartile categories, and binary logistic regression for postoperative delirium category as outcome were all done. RESULTS: Except for serum low-density lipoprotein (LDL) levels, there were no statistically significant variations in preoperative substance P levels or other baseline characteristics between the two groups. The "postoperative delirium" group had significantly higher postoperative substance P levels than the "no postoperative delirium" group (46.36.1 versus 31.94.7 pg/ml). There was a significant difference in postoperative delirium rates between the quartile categories of postoperative substance P, with the fourth quartile having the highest rate. Regression analysis revealed that postoperative substance P levels were related with a significantly increased OR (1.265, CI: 1.172-1.283) of postoperative delirium. CONCLUSION: In the current sample of hip fracture patients, a higher postoperative serum substance P level was linked to a higher risk of postoperative delirium. Further research into the utility of early postoperative serum substance P as a delirium indicator in hip fracture patients is needed.

There is growing interest in human adipose tissue-derived collagen as a replacement for animal origin or synthetic materials. Large amounts of adipose tissues around the kidney are being discarded after kidney surgery; thus, we planned to use this tissue as a potentially ideal source of human collagen. Optimization of the collagen extraction process can contribute to the quality, quantity, supply, and cost of collagen production. To extract highly purified and concentrated collagen from human perirenal adipose tissue, we developed a novel extraction process that is superior to the conventional methods in terms of extraction yield, in vitro cytocompatibility, and physicochemical aspects. The sequence of the process and optimized conditions are as follows: (1) destaining with 0.5% H2O2 for 1 h at 4°C, (2) noncollagenous proteins elimination with 1.5 M NaOH for 24 h at 4°C, (3) atelocollagen preparation with 1.0% pepsin for 48 h at 25°C, and (4) collagen hydrolysis with 1.0 M NaOH for 10 min at 60°C. The final product showed significantly increased hydroxyproline (355.26 ± 18.71 pg/mL) and glycine (22.752 μg/mL) content than the conventional acetic acid hydrolyzed collagen (164.13 ± 1.11 pg/mL and 0.947 μg/mL, respectively). The lyophilized collagen showed more specific peaks for amides A, B, I, II, and III on FT-IR analysis and showed a further native architecture of collagen fibrils in scanning electron microscope images. Therefore, the optimized process can be an effective protocol for extracting collagen from human perirenal adipose tissue.

OBJECTIVE: This study sought to evaluate the biocompatibility of Neomineral Trioxide Aggregate (Neo-MTA), MTA Repair High Plasticity (MTA-HP), and Mineral Trioxide Aggregate-Angelus white (MTA-Ang) in fibroblasts of human dental pulp. MATERIALS AND METHODS: Morphology was evaluated after 24 h of incubation. LIVE/DEAD assay and cell adhesion tests were performed at 24 h of treatment. Cell proliferation assays (MTSs) and Annexin V were performed at 48 h incubation with different treatments. The expression of Col-1 and TGF-β1 was tested by endpoint PCR at 5 days of treatment. RESULTS: Morphological changes were observed in all groups. Neo-MTA and MTA-Ang were associated with increased cell viability, and all materials induced apoptosis, with a higher percentage in the MTA-HP group than in the other groups. In the LIVE/DEAD assay, there was more damage to the cell membrane in the group of cells treated with MTA-HP than in the other groups. CONCLUSION: Neo-MTA and MTA-Ang presented similar biocompatibility, and both showed greater biocompatibility than MTA-HP. MTA-HP and MTA-Ang increased Col-1A gene expression, and Neo-MTA and MTA-Ang increased TGF-β1 gene expression in a similar way.

The release of untreated wastes from abattoirs into the environment and nearby water bodies poses a significant threat to public health. Such litters may contain pathogens, including antibiotic-resistant bacteria. This study investigated 80 samples collected from butchering tables, slaughter slabs, meat rinsing points, and abattoir wastes receiving water from two abattoirs (A and B). Total Enterobacteriaceae count (TEC) for each sample was determined, and Escherichia coli (E. coli), Salmonella spp., Shigella spp., and Staphylococcus aureus (S. aureus) were isolated and identified. Antimicrobial susceptibility testing was done on all bacterial isolates against nine locally used antibiotics. Overall, 118 bacterial isolates, comprising E. coli (42.5%), Salmonella spp. (27.5%), Shigella spp. (37.5%), and S. aureus (40.0%), were recovered. Of the 118 bacterial isolates, 104 (88.1%) were multidrug-resistant, including 58 (55.8%) from abattoir A and 46 (44.2%) from abattoir B; however, this difference was not statistically significant (p = 0.6837). Of the 32 S. aureus isolates, 29 (90.6%) were multidrug-resistant. All S. aureus were 100% sensitive to vancomycin, kanamycin, and amikacin. Similarly, 31 (91.2%) of the 34 E. coli isolates recovered in this study were multidrug-resistant. Salmonella spp. and Shigella spp. also showed high levels of multidrug resistance corresponding to 81.8% and 86.7%, respectively. All isolates of E. coli, Salmonella, and Shigella were 100% resistant to ampicillin and 100% sensitive to ciprofloxacin. Minimum and maximum mean values for TEC were 3.62-5.83 log CFU/mL for abattoir A and 4.08-5.56 log CFU/mL for abattoir B. The highest and lowest TEC counts were from slaughter slab and upstream water, respectively, in each abattoir. Our results indicate a predominance of multidrug-resistant bacteria in abattoir wastes and their receiving waters in the study sites. Hence, we recommend the treatment of abattoir wastes before disposal and improved hygiene and sanitation practices to enhance public health.

OBJECTIVE: To use habitat analysis (also termed habitat imaging) for classifying untreated breast cancer-enhanced magnetic resonance imaging (MRI) in women. Moreover, we intended to obtain clustering parameters to predict the BReast CAncer gene 1 (BRCA1) gene mutation and to determine the use of MRI as a noninvasive examination tool. METHODS: We obtained enhanced MRI data of patients with breast cancer before treatment and selected some sequences as the source of habitat imaging. We used the k-means clustering to classify these images. According to the formed subregions, we calculated several parameters to evaluate the clustering. We used immunohistochemistry to detect BRCA1 mutations. Moreover, we separately determined the ability of these parameters through independent modeling or multiple parameter joint modeling to predict these mutations. RESULTS: Of all extracted values, separation (SP) demonstrated the best prediction performance for a single parameter (area under the receiver operating characteristic curve (AUC), 0.647; 95% confidence interval (CI), 0.557-0.731). Simultaneously, models based on the Calinski-Harabasz Index and sum of square error performed better in the training (AUC, 0.903; 95% CI, 0.831-0.96) and verification (AUC, 0.845; 95% CI, 0.723-0.942) sets for multiparameter joint modeling. CONCLUSION: Based on the enhanced MRI of breast tumors and the subregions generated according to the habitat imaging theory, the parameters extracted to describe the clustering effect could reflect the BRCA1 status. Differences between clusters, including the general differences of cluster centers and clusters and the similarity of samples within clusters, were the embodiment of this mutation. We propose an algorithm to predict the BRCA1 mutation of a patient according to the enhanced MRI of the breast tumor.

OBJECTIVE: To prospectively study the application effect of traditional Chinese medicine (TCM) anticancer decoction with basic chemotherapy and nursing intervention on oral cancer patients after surgery and the effect on tumor markers and immune function. METHODS: Eighty-four postoperative oral cancer patients in our hospital from May 2017 to February 2019 were selected and divided into observation group (42 cases) and control group (42 cases). The control group was treated with basic chemotherapy combined with basic nursing care, and the observation group was treated with TCM anticancer decoction and comprehensive nursing intervention on the basis of the control group. The clinical efficacy, the occurrence of adverse reactions, the satisfaction of nursing care, and the two-year cumulative survival rate of the two groups were compared. The immune function, tumor marker level, VAS score, QoR40 score, and survival quality score of the two groups were compared before and after nursing care. RESULTS: The total clinical treatment efficiency of the observation group (88.10%) was significantly higher than that of the control group (69.05%), and the differences between the two groups in oral cleanliness, aspiration frequency, and oral comfort were statistically significant (P < 0.05). The differences in the occurrence of halitosis, oral fungal infection, leukopenia, gastrointestinal reaction, and fever in the observation group were statistically significant compared with the control group (P < 0.05). The nursing satisfaction rate in the observation group (95.24%) was significantly higher than that in the control group (78.57%). The two-year cumulative survival rate of the observation group (92.86%) was significantly higher than that of the control group (73.81%). After nursing care, CD4+, CD4+/CD8+, VAS scores, QoR40 scores, and quality of survival scores in both groups all increased, and CD8+, CD56+, CEA level, NSE level, and CA19-9 level all decreased (all P < 0.05). CONCLUSION: The clinical efficacy of TCM anticancer decoction with basic chemotherapy and nursing interventions in the treatment of postoperative oral cancer patients was remarkable, which could significantly improve patients' oral cleanliness and comfort, reduce the frequency of sputum aspiration, improve patients' immunity, reduce tumor marker levels, inhibit tumor activity, improve patients' nursing satisfaction, further improve patients' treatment compliance, reduce patients' pain level, improve patients' survival quality, and prolong patients' survival time with high safety. It could be used as a theoretical basis for subsequent clinical research.

The study of the metabolism of endogenous molecules is not only of great fundamental significance but also of high practical importance, since many molecules serve as drug targets and/or biomarkers for laboratory diagnostics of diseases. Thus, cardiac troponin molecules have long been used as the main biomarkers for confirmation of diagnosis of myocardial infarction, and with the introduction of high-sensitivity test methods, many of our ideas about metabolism of these cardiac markers have changed significantly. In clinical practice, there are opening new promising diagnostic capabilities of cardiac troponins, the understanding and justification of which are closely connected with the fundamental principles of the metabolism of these molecules. Our current knowledge about the metabolism of cardiac troponins is insufficient and extremely disconnected from various literary sources. Thus, many researchers do not sufficiently understand the potential importance of cardiac troponin metabolism in the laboratory diagnosis of myocardial infarction. The purpose of this comprehensive review is to systematize information about the metabolism of cardiac troponins and during the discussion to focus on the potential impact of cTns metabolism on the laboratory diagnosis of myocardial infarction. The format of this comprehensive review includes a sequential consideration and analysis of the stages of the metabolic pathway, starting from possible release mechanisms and ending with elimination mechanisms. This will allow doctors and researchers to understand the significant importance of cTns metabolism and its impact on the laboratory diagnosis of myocardial infarction.

Long-term arsenic (As) exposure can cause liver injury, hepatic cirrhosis, and cancer. Meanwhile, Dictyophora polysaccharides (DIP) have excellent antioxidation, anti-inflammation, and immune protection effects. There are currently few reports on the protection effects of DIP on As-induced hepatotoxicity and its pharmacological value. Therefore, this study was aimed at elucidating the protection of DIP on As-induced hepatotoxicity and exploring its preventive role in antifibrosis. In our study, the SD rat As poisoning model was established by the feeding method to explore the influence of As exposure on liver fibrosis. Then, DIP treatment was applied to the rats with As-induced liver fibrosis, and the changes of serum biochemical indexes and liver tissue pathology were observed. And the expression of fibrosis-related proteins TGF-β1, CTGF, and α-SMA levels was then determined to explore the DIP intervention function. The results demonstrated that through reduced pathological changes of hepatic and increased serum AST, ALT, TP, ALB, and A/G levels, DIP ameliorated liver fibrosis induced by As as reflected. And the administration of DIP decreased the concentration of HA, LN, PCIII, CIV, TBIL, and DBIL. In addition, the synthesis of TGF-β1 inhibited by DIP might regulate the expression of CTGF and decrease the proliferation of fibrinogen and fibroblasts, which reduced the synthesis of fibroblasts to transform into myofibroblasts. And a decrease of myofibroblasts downregulated the expression of α-SMA, which affected the synthesis and precipitation of ECM and alleviated the liver fibrosis caused by exposure to As. In conclusion, based on the pathological changes of liver tissue, serum biochemical indexes, and related protein expression, DIP can improve the As-induced liver fibrosis in rats and has strong medicinal value.

BACKGROUND: Increases in blood of amyloid beta-protein (Aβ) have been noted in patients with Alzheimer's dementia (AD). Recent studies have shown that blood amyloid beta-protein 1-42 (Aβ1-42) level is closely related to poststroke cognitive impairment (PSCI), which may be the influencing factor and even a predictor of PSCI. The aim of this systematic review was to synthesize the evidence for the association of cognitive impairment among PSCI. METHODS: PubMed (MEDLINE), EMBASE, Cochrane Library, the Cochrane Central Register of Controlled Trial (CENTRAL), CNKI, and WanFang data were searched. Case-control, cohort, and cross-sectional studies that evaluated the association between blood Aβ1-42 and PSCI were included irrespective of language and date of publication. The outcomes of this review consisted of (1) any dementia, (2) any cognitive impairment, and (3) any cognitive impairment no dementia, which were assessed at least 3 months (90 days) after stroke. Exposure of interest was blood Aβ1-42 level (including serum and plasma). RESULTS: Of 617 records retrieved, 8 studies (6 case-control and 2 cohort studies) involving 931 stroke patients were included for further analysis. 8 studies with 931 subjects explored the correlation between Aβ1-42 and PSCI. PSCI was reported in 457 patients, and the pooled SMD of amyloid beta-protein 1-42 was -0.96 (95% CI -1.10~-0.82, I 2 = 15%, P < 0.01). The results remained robust in sensitivity analysis adjusting for study quality, sample source, and cognitive scale score in analysis of studies, as well as in analysis adjusted for publication bias. CONCLUSIONS: Blood Aβ1-42 level was significantly negatively related to the risk for PSCI, and more prospective studies with large sample size are needed to define a precise threshold value of blood Aβ1-42 level to predict PSCI in the future. This study is registered with PROSPERO, registration number: CRD42021246165.

OBJECTIVE: This study aims to investigate the expression of neuronal transcription factor SOX11 in small-cell lung cancer (SCLC) and compare it with the expression of CD56 (nerve cell adhesion molecule), synaptophysin (Syn), chromogranin A (CgA), and thyroid transcription factor-1 (TTF-1) to explore the application value of SOX11 in the pathological diagnosis of SCLC. METHODS: Immunohistochemical methods were used to detect the expression of SOX11, TTF-1, CD56, Syn, and CgA in 120 lung tumor tissues, and experimental results were analyzed using SPSS23.0 statistical software. RESULTS: Immunohistochemical results showed that in the 120 lung tumor samples, SOX11 was highly expressed in SCLC and localized to the nucleus, with low or no expression in control carcinoid/lung neuroendocrine tumors, lung adenocarcinomas, and lung squamous cell carcinomas. Statistical analysis results revealed the following points. First, the expression of SOX11 was closely related to the tumor histological type. The expression of SOX11 in SCLC (positive rate of 63.33%) was significantly higher than that in carcinoid/neuroendocrine tumors (positive rate of 12.50%), lung adenocarcinoma (positive rate of 0%), and lung squamous cell carcinoma (positive rate of 0%). Second, immunohistochemical investigation of 60 SCLC cases revealed that the highest positive rates of CD56, TTF-1, and Syn, respectively, were 93.33 percent, 95 percent, and 86.67 percent. SOX11 also exhibited high sensitivity (0.633) and specificity (0.875) in SCLC. The positive rates of SOX11 and CgA were 63.33% and 50.00%, respectively. Statistical results revealed that the positive rate of CgA had no significant difference (P > 0.05). Lastly, the combined use of antibodies SOX11, CgA, CD56, Syn, and TTF-1 was more beneficial to improving the diagnosis rate of SCLC than the single use of one or two antibodies. CONCLUSION: The expression of SOX11 in different histological types of lung tumors differs considerably. SOX11 is highly expressed in SCLC. SOX11 can be used as a beneficial supplement to the combination of classical neuroendocrine markers and in combination with CgA, CD56, Syn, and TTF-1 to assist in the diagnosis of SCLC.

Bleomycin is a common antitumor agent used to treat many different types of malignancies; however, its main side effect is pulmonary fibrosis. The mechanism of bleomycin-induced pulmonary fibrosis (BIPF) has not been fully elucidated. Therefore, to further explore the molecular mechanisms of BIPF, we screened for microRNA (miRNA) and mRNA expression obtained from BIPF samples from the Gene Expression Omnibus database. Subsequently, we identified the differentially expressed miRNAs and genes that overlapped with the differentially expressed miRNAs target genes, predicted by using the miRWalk database selected as a candidate. The candidate genes were visualized based on Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses. A protein-protein interaction network was constructed. Hub differentially expressed genes were selected and corresponding miRNAs to construct a miRNA-mRNA regulation network. Then, we chose three key miRNAs to study their regulatory relationship in bleomycin-induced pulmonary fibrosis. Finally, mouse lung epithelial cells TC-1 and MLE-12 were treated with bleomycin with qPCR to validate the results of three important hub genes and all key miRNAs. And dual-luciferase report experiment was carried out to verify the interaction of mmu-miR-1946a and serpina3n. The results revealed that the imbalance of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a pivotal role in the occurrence and development of BIPF. In addition, Serpina3n and mmu-miR-1946a were proved interaction and may be involved in the regulation of the balance between MMP-9 and TIMP-1. The experimental results also verify the analysis. Our findings provide new insights into the key mediators and pathways related to the molecular mechanisms of BIPF.

We aimed to investigate the predictive ability of serum levels of D-dimer (DD) in the first trimester for the occurrence of hypertensive disorders of pregnancy (HDP). In this retrospective, case-cohort study, we measured the levels of DD, plasma pregnancy-associated protein A (PAPP-A), and free β-subunit of human chorionic gonadotropin (free β-hCG) and analyzed fetal nuchal translucency (NT) in 150 healthy gravidas, 126 cases of gestational hypertension (GH), 53 cases of preeclampsia (PE), and 41 cases with severe preeclampsia (SPE). Likelihood ratio models and risk models were built using single markers (DD, PAPP-A, free β-hCG, and NT) and combinations of those markers. Analyses showed that the levels of DD multiple of the median (MoM) in the GH, PE, and SPE groups were all significantly higher than those in the control group, with significant differences between groups (χ 2 = 70.325, P < 0.001). The area under curve (AUCs) for DD in the GH, PE, and SPE groups was 0.699, 0.784, and 0.893, respectively; the positive likelihood ratio (+LR) was 1.534, 1.804, and 2.941, respectively; and the negative likelihood ratio (-LR) was 0.022, 0.081, and 0, respectively. When the cut-off values of DD for the GH, PE, and SPE groups were 0.725, 0.815, and 0.945 MoM, respectively, the corresponding sensitivities were 0.992, 0.962, and 1.000, respectively. As gestational hypertension progressed, the levels of DD tended to increase gradually. The maternal serum level of DD in the first trimester had correlative and diagnostic value for HDP. The sensitivity and specificity of maternal serum levels of DD level in the first trimester for different types of HDP were significantly different; the best sensitivity and specificity were detected in the SPE group. First trimester DD level, combined with other biochemical markers, may improve our ability to diagnose HDP.

Microcephaly (MCPH) is a developmental anomaly of the brain known by reduced cerebral cortex and underdeveloped intellectual disability without additional clinical symptoms. It is a genetically and clinically heterogenous disorder. Twenty-five genes (involved in spindle positioning, Wnt signaling, centriole biogenesis, DNA repair, microtubule dynamics, cell cycle checkpoints, and transcriptional regulation) causing MCPH have been identified so far. Pakistani population has contributed in the identification of many MCPH genes. WES of three large consanguineous families revealed three pathogenic variants of MCPH1, CENPJ, and CASK. One novel (c.1254delT) deletion variant of MCPH1 and one known (c.18delC) deletion variant of CENPJ were identified in family 1 and 2, respectively. In addition to this, we also identified a missense variant (c.1289G>A) of CASK in males individuals in family 3. Missense mutation in the CASK gene is frequent in the boys with intellectual disability and autistic traits which are the common features that are associated with FG Syndrome 4. The study reports novel and reported mutant alleles disrupting the working of genes vital for normal brain functioning. The findings of this study enhance our understanding about the genetic architecture of primary microcephaly in our local pedigrees and add to the allelic heterogeneity of 3 known MCPH genes. The data generated will help to develop specific strategies to reduce the high incidence rate of MCPH in Pakistani population.

Biofilm formation is easily found in patients suffered from ventilator-associated pneumonia (VAP) in neonatal intensive care unit (NICU) and makes the VAP infections not only harder to be treated but easier to relapse. In order to find some novel ways to inhibit biofilm formation, this study describe a previously unrecognized role for the human umbilical cord mesenchymal stem cells (hUCMSCs). In addition to multiple differentiation, hUCMSCs have the ability to prevent the biofilms formation in vitro by secreting antibacterial peptides (LL-37 and hBD-2). This occurred while P. aeruginosa PA27853 and hUCMSCs were cocultured, and the filtrated medium, which was the supernatant containing antibacterial peptides (5.9 ng/ml of LL-37, 1.77 ng/ml of hBD-2), and inhibited the growth of the bacterial biofilm on the surface of tracheal tube (2.5#, for preterm infant). Using microarrays, we were able to demonstrate that the antibacterial peptides from hUCMSC affected biofilm formation by downregulating the gene-encoded polysaccharide biosynthesis protein. In addition, in order to find out the most suitable concentration of hUCMSCs, P. aeruginosa was cocultured with eight-level concentrations of hUCMSCs, and we found that the concentration of LL-37 was positively correlated with the concentration of hUCMSCs. Meanwhile, the concentration of LL-37 became stable while the hUCMSC concentration reaches higher than 5 × 106 cells/ml. But the concentration of hBD-2 had no significant correlation with hUCMSCs. The collection of these stem cells is not only limited by ethics but also reduces host rejection. This makes it possible to use autologous hUCMSCs to treat neonatal VAP.

BACKGROUND: Endometriosis (EMs) is a benign chronic condition that tends to recur in women of childbearing age, with an incidence of approximately 10%. It is a multifactorial disease for which the pathogenesis is currently unclear. This study is aimed at investigating the expression and clinical significance of tRNA-derived small RNA (tsRNA), a novel noncoding small RNA with potential regulatory functions, in endometriosis. METHODS: The tRF/tiRNA expression profiles in endometrial tissues from three pairs of endometriosis patients and controls were detected by tRF&tiRNA PCR microarray technology and then verified by quantitative real-time polymerase chain reaction (qPCR). The target genes and target sites of TRF396, tiRNA-5030-GlnTTG-3, TRF308, and TRF320 were predicted by miRanda, and the network diagram of their interaction with miRNA was drawn. The impact of tRNA-derived fragments on the pathogenesis of endometriosis was analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: Two upregulated and 19 downregulated tRNA-derived fragments were identified. The qRT-PCR results of 2 upregulated and 2 downregulated RNA-derived fragments were consistent with the RNA Seq data. The OR2B4 gene related to TRF396, the DGAT1 gene related to tiRNA-5030-GlnTTG-3, the KLF16 gene of TRF308, and the RNF213 gene of TRF320 had significant correlations. Gene Ontology and pathway analysis showed that the target genes of TRF396 and tiRNA-5030-GlnTTG-3 were mainly involved in the intrinsic components of the membrane and the overall composition of the membrane in cell components; molecular functions mainly involve olfactory conduction and G protein-coupled receptor activity. In the biological process, it was mainly involved in the detection of sensory stimuli. The target genes of TRF308 and TRF320 were mainly involved in the intracellular part; molecular functions are mainly related to DNA binding transcription factor activity and protein binding and mainly related to biological regulation of biological processes. Pathway analysis showed that the RAP1 signaling pathway and the AXON GUIDANCE signaling pathway may participate in the progression of endometriosis. CONCLUSION: The differential expression of tRF/tiRNA in endometriosis may be related to the pathogenesis of endometriosis. Furthermore, tRF/tiRNA may be a biomarker for the diagnosis and treatment of EMs in the future.

INTRODUCTION: The mortality risk in children admitted to Pediatric Intensive Care Units (PICU) is usually estimated by means of validated scales, which only include objective data among their items. Human perceptions may also add relevant information to prognosticate the risk of death, and the tool to use this subjective data is fuzzy logic. The objective of our study was to develop a mathematical model to predict mortality risk based on the subjective perception of PICU staff and to evaluate its accuracy compared to validated scales. METHODS: A prospective observational study in two PICUs (one in Spain and another in Latvia) was performed. Children were consecutively included regardless of the cause of admission along a two-year period. A fuzzy set program was developed for the PICU staff to record the subjective assessment of the patients' mortality risk expressed through a short range and a long range, both between 0% and 100%. Pediatric Index of Mortality 2 (PIM2) and Therapeutic Intervention Scoring System 28 (TISS28) were also prospectively calculated for each patient. Subjective and objective predictions were compared using the logistic regression analysis. To assess the prognostication ability of the models a stratified B-random K-fold cross-validation was performed. RESULTS: Five hundred ninety-nine patients were included, 308 in Spain (293 survivors, 15 nonsurvivors) and 291 in Latvia (282 survivors, 9 nonsurvivors). The best logistic classification model for subjective information was the one based on MID (midpoint of the short range), whereas objective information was the one based on PIM2. Mortality estimation performance was 86.3% for PIM2, 92.6% for MID, and the combination of MID and PIM2 reached 96.4%. CONCLUSIONS: Subjective assessment was as useful as validated scales to estimate the risk of mortality. A hybrid model including fuzzy information and probabilistic scales (PIM2) seems to increase the accuracy of prognosticating mortality in PICU.

Although there is no doubt regarding the involvement of oxidative stress in the development of glioblastoma, many questions remained unanswered about signaling cascades that regulate the redox status. Given the importance of the substance P (SP)/neurokinin 1 receptor (NK1R) system in different cancers, it was of particular interest to evaluate whether the stimulation of this cascade in glioblastoma-derived U87 cells is associated with the induction of oxidative stress. Our results showed that SP-mediated activation of NK1R not only increased the intracellular levels of malondialdehyde (MDA) and reactive oxygen species (ROS) but also reduced the concentration of thiol in U87 cells. We also found that upon SP addition, there was a significant reduction in the cells' total antioxidant capacity (TAC), revealing that the SP/NK1R axis may be involved in the regulation of oxidative stress in glioblastoma cells. The significant role of SP/NK1R in triggering oxidative stress in glioblastoma has become more evident when we found that the abrogation of the axis using aprepitant reduced cell survival, probably through exerting antioxidant effects. The results showed that both MDA and ROS concentrations were significantly reduced in the presence of aprepitant, and the number of antioxidant components of the redox system increased. Overall, these findings suggest that aprepitant might exert its anticancer effect on U87 cells through shifting the balance of oxidant and antioxidant components of the redox system.

Cancer is one of the top causes of mortality, and it arises when cells in the body grow abnormally, like in the case of breast cancer. For people all around the world, it has now become a huge issue and a threat to their safety and wellbeing. Breast cancer is one of the major causes of death among females all over the globe, and it is particularly prevalent in the United States. It is possible to diagnose breast cancer using a variety of imaging modalities including mammography, computerized tomography (CT), magnetic resonance imaging (MRI), ultrasound, and biopsies, among others. To analyze the picture, a histopathology study (biopsy) is often performed, which assists in the diagnosis of breast cancer. The goal of this study is to develop improved strategies for various CAD phases that will play a critical role in minimizing the variability gap between and among observers. It created an automatic segmentation approach that is then followed by self-driven post-processing activities to successfully identify the Fourier Transform based Segmentation in the CAD system to improve its performance. When compared to existing techniques, the proposed segmentation technique has several advantages: spatial information is incorporated, there is no need to set any initial parameters beforehand, it is independent of magnification, it automatically determines the inputs for morphological operations to enhance segmented images so that pathologists can analyze the image with greater clarity, and it is fast. Extensive tests were conducted to determine the most effective feature extraction techniques and to investigate how textural, morphological, and graph characteristics impact the accuracy of categorization classification. In addition, a classification strategy for breast cancer detection has been developed that is based on weighted feature selection and uses an upgraded version of the Genetic Algorithm in conjunction with a Convolutional Neural Network Classifier. The practical application of the suggested improved segmentation and classification algorithms for the CAD framework may reduce the number of incorrect diagnoses and increase the accuracy of classification. So, it may serve as a second opinion tool for pathologists and aid in the early detection of diseases.

PURPOSE: This study is aimed at determining the impact of work-related low back pain (LBP) on functional performance and physical capabilities. METHODS: This cross-sectional study included women (n = 25, mean age, 38.12 ± 4.59) and men (n = 25, mean age, 37.20 ± 5.38) with a history of work-related mechanical chronic LBP who visited our university hospital's outpatient department. All participants were assessed for primary outcomes, including the severity of LBP on rest and on activity, functional performance, and physical capabilities using a numeric pain rating scale (NPRS), Roland-Morris disability questionnaire (RDQ), five-time sit-to-stand test (FTSST), and fifty-foot walk test (FFWT), respectively. Independent t-tests compared the scores of the outcomes between groups while Pearson's correlation coefficient identified the correlation between the outcomes' measures at a significance level of 0.05. RESULTS: With a response rate of 63.29%, a total of fifty participant's data were obtained for the analysis. A comparison between women and men groups highlighted a significant difference in the scores of the FTSST and FFWT; however, there were insignificant differences in the scores of the NPRS at rest, NPRS on activity, and RDQ. The bivariate correlation revealed a highly significant, positive, and moderate correlation between the scores of NPRS at rest and FTSST, NPRS on activity and FTSST, NPRS at rest and FFWT, NPRS on activity and FFWT, FTSST and RDQ, and FFWT and RDQ in the women group. Similarly, there was a significant, positive, and low correlation between the scores of FTSST and RDQ and FFWT and RDQ in the men group. CONCLUSION: Work-related chronic LBP affected the physical capabilities of women more than those of men. However, it equally affected the functional performance of all participants in the study. Furthermore, work-related chronic LBP affected the physical capabilities (FTSST and FFWT) and functional performance (RDQ) of women more than those of men.

Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord as hallmark features of the disease. It results from mutations in the integrin β2 subunit gene ITGB2, which encodes the integrin beta chain-2 protein CD18. In this study, we aimed to investigate the case of a five-month-old boy who presented with a clinical phenotype and flow cytometry results suggesting LAD1 disease. Sanger sequencing of all exons and intron boundaries of ITGB2 identified a novel in-frame deletion in exon 7 (ITGB2 c.844_846delAAC, p.Asn282del) in the patient. The p.Asn282del mutation was heterozygous in the child's parents, whereas it was absent in the 96 control individuals from North Africa. This variant was evaluated by two in silico mutation analysis tools, PROVEAN and MutationTaster, which predicted that the mutation was likely to be pathogenic. In addition, molecular modeling with the YASARA View software suggested that this novel mutation may affect the structure of integrin beta-2 and, subsequently, its interaction with integrin alpha-X. In summary, we report a novel pathogenic mutation p.Asn282del associated with LAD1 that expands the mutation diversity of ITGB2 and suggest the combination of flow cytometry and ITGB2 sequencing as a first-line diagnostic approach for LAD disease.

Fetal calf serum (FCS) is used for in vitro cell culture, as it provides the cells with various growth-promoting compounds. For applications in humans, FCS does not meet the required safety standards and should be replaced by an appropriate substitute. This study analyzed the suitability of using human platelet lysate (hPL) as a substitute for FCS in endothelial cell cultures for in vitro and in vivo tissue engineering applications. The focus was placed on standardized, commercially available hPLs (MultiPL'30, MultiPL'100), which are approved for applications in humans, and compared to laboratory-prepared hPLs (lp-hLP). Human umbilical vein endothelial cells (HUVEC) were cultured with FCS or with different hPLs. Cell morphology, proliferation, viability, apoptosis, and necrosis, as well as the organization of vascular structures, were assessed. No morphological changes were noticed when FCS was replaced by standardized hPLs in concentrations of 1-10%. In contrast, the use of lp-hLPs led to irregular cell shape and increased vacuolization of the cytoplasm. HUVEC proliferation and viability were not compromised by using media supplemented with standardized hPLs or pl-hPLs in concentrations of 1-10%, compared to cells grown in media supplemented with 20% FCS. The apoptosis rate using lp-hPLs was higher compared to the use of standardized hPLs. The necrosis rate tended to be lower when FCS was replaced by hPLs. HUVEC formed more pronounced capillary-like structures when the media were supplemented with hPLs instead of supplementation with FCS. Thus, compared to the use of FCS, the use of hPLs was beneficial for the growth and optimal expression of functional endothelial cell characteristics during in vitro experiments. Commercially available hPLs proved to be particularly suitable, as they led to reproducible results during in vitro experiments, while meeting the safety requirements for in vivo use.

BACKGROUND: Stroke is a cardiovascular disorder causing mortality globally and long-lasting harm worldwide. The disease occurs when the blood flow to the brain is either interrupted or blocked. This disruption leads to the increase in reactive oxygen species (ROS), especially superoxide free radicals, resulting in oxidative stress. The superoxide radicals are removed by superoxide dismutase (SOD), a key antioxidant enzyme. In this work, we investigated haematological indices and superoxide dismutase enzyme activity in Ghanaian patients with stroke and healthy control participants. MATERIALS AND METHODS: Thirty stroke patients attending a stroke clinic and thirty apparently healthy control participants were recruited into the study. Blood samples were collected to determine haematological indices and SOD enzyme activity in red blood cells. RESULTS: The stroke patients had significantly high blood parameters such as white blood cell (p < 0.001), neutrophil (p < 0.001), lymphocyte (p = 0.003), and eosinophil (p < 0.001) comparing with study participants without stroke, who were the control group in the study. Other blood parameters such as red blood cell, (p < 0.001), haemoglobin (p < 0.001), and haematocrit (p < 0.001) levels and mean cell haemoglobin concentration (p = 0.030), platelet (p = 0.010), and plateletcrit (p = 0.027) were high in stroke patients comparing with study control participants and statistically significant. Blood lymphocyte levels observed in stroke patients correlated negatively and significantly with SOD activity levels. SOD activity levels were significantly lower in stroke patients compared with the control group (p < 0.001). Low values of the antioxidant enzyme SOD activity levels, lymphocytes, and high values of plateletcrit were significant predictors of stroke. CONCLUSION: Haematological parameters such as WBC, lymphocyte, platelet levels, and red cell indices were significantly different in the stroke patients being studied. There was negative correlation between lymphocyte significantly with SOD activity and high oxidative stress in stroke patients compared with the control group. Lymphocytes and plateletcrit levels were also good predictors of the occurrence of stroke.

As the most common form of developmental malformation affecting the heart and endothoracic great vessels, congenital heart disease (CHD) confers substantial morbidity and mortality as well as socioeconomic burden on humans globally. Aggregating convincing evidence highlights the genetic origin of CHD, and damaging variations in over 100 genes have been implicated with CHD. Nevertheless, the genetic basis underpinning CHD remains largely elusive. In this study, via whole-exosome sequencing analysis of a four-generation family inflicted with autosomal-dominant CHD, a heterozygous SMAD1 variation, NM_005900.3: c.264C > A; p.(Tyr88∗), was detected and validated by Sanger sequencing analysis to be in cosegregation with CHD in the whole family. The truncating variation was not observed in 362 unrelated healthy volunteers employed as control persons. Dual-luciferase reporter gene assay in cultured COS7 cells demonstrated that Tyr88∗-mutant SMAD1 failed to transactivate the genes TBX20 and NKX2.5, two already well-established CHD-causative genes. Additionally, the variation nullified the synergistic transcriptional activation between SMAD1 and MYOCD, another recognized CHD-causative gene. These data indicate SMAD1 as a new gene responsible for CHD, which provides new insight into the genetic mechanism underlying CHD, suggesting certain significance for genetic risk assessment and precise antenatal prevention of the family members inflicted with CHD.

OBJECTIVE: To investigate the clinical value of ultrasound combined with electrophysiological examination in the diagnosis of early carpal tunnel syndrome, we aimed to provide a new EMG (electromyography) method for detecting early carpal tunnel syndrome by exploring the wrist back stretch position and electrophysiological examination. METHODS: For the 82-lateral wrist (case group) of 62 patients with clinical symptoms or confirmed carpal tunnel syndrome and 40 normal healthy patients, neuroelectrophysiological measurements were performed using a Keypoint6.0 EMG evoked potentiometer, measuring each group twice: conventional position (before compression) and dorsal wrist extension position. The measures for each measurement included DSL, DML, and CAMP. Measure sensory conduction first and then measure motor conduction. The measurements were analyzed in a comprehensive comparative analysis. Combined ultrasound examination, the positive rate of combined ultrasound examination and electrophysiological examination was compared, respectively. RESULTS: In the carpal tunnel syndrome (CTS) group, the anterior and posterior median nerve DSL was (4.27 ± 0.73) ms and (4.82 ± 0.65) ms, and SNAP was (13.32 ± 13.68) UV and (12.19 ± 11.04) UV; the median nerve (wrist-bunions) DML was (5.29 ± 1.26) ms and (5.54 ± 1.29) ms, and CMAP was (6.44 ± 2.40) mV and (6.21 ± 2.46) mV. Mid-median DSL and DM in the CTS group L were significantly longer than before compression; median nerve SNAP and CMAP were significantly reduced compared with before compression. CONCLUSION: Electrophysiological testing at the dorsal carpal extension position has high diagnostic value in the diagnosis of mild carpal tunnel syndrome. It helps to improve the diagnostic rate of early carpal tunnel syndrome, while providing a more accurate and effective EMG detection of early carpal tunnel syndrome, and combination examination of neuroelectrophysiology and ultrasound can improve the diagnosis rate of compression peripheral nerve diseases and clarify the site, nature, and scope of compression lesions, which is worthy of clinical application.

Fibroblasts of the gingiva play a key role in oral wound healing in diabetes. In this study, effects of astaxanthin (ASTX), a xanthophyll carotenoid, were tested on gingival fibroblasts in a wound healing assay in vitro. The aim of this study was to determine whether ASTX can recover delayed wound healing or not when oxidative stress is elevated by high glucose exposure. For this purpose, human gingival fibroblasts were incubated with or without ASTX following exposure to systemic doses of low glucose (LG) and high glucose (HG) in culture media (5- and 25-, 50 mM D-glucose in DMEM Ham's F12) following 24 hours of incubation. Levels of ROS (Reactive oxygen species) were determined for each experimental group by confocal microscopy. Cell proliferation and viability were assessed by an automated cell counter with trypan blue assay. Wound healing assay was designed in 60 mm petri dishes. Cells were exposed to 5-, 25-, and 50 mM glucose for 24 hours, and a straight line free of cells was created upon full confluency. 100 μM ASTX was added to the recovery group, simultaneously. Cells were monitored with JuLIⓇ-Br Cell History Recorder. ROS levels were significantly increased with increasing glucose levels, while cell proliferation and viability demonstrated a negative correlation with increasing oxidative stress. ROS levels significantly decreased in the 100 μM ASTX-treated group compared to the gingival fibroblasts treated with 50 mM HG medium-only, as well as growth rate and viability. Wound healing was delayed in a dose-dependent manner following high glucose exposure, while ASTX treatment recovered wounded area by 1.16-fold in the 50 mM HG group. Our results demonstrated that ASTX enhances gingival wound healing through its antioxidative properties following high glucose induced oxidative stress. Therefore, ASTX can be suggested as a promising candidate to maintain oral health in chronic wounds of the oral tissues related to diabetes.

Identifying Helicobacter pylori (H. pylori, Hp) infection in animals before and after artificial infection influences the subsequent experiment. We established effective and noninvasive detection methods, including the gastric fluid nested polymerase chain reaction (PCR) method and the 13C-urea breath test, which can detect Hp before modeling Hp infection in Mongolian gerbils. We designed a gas collection equipment for gerbils. Hp nested PCR was also performed on gastric fluid, gastric mucosa, duodenal contents, and faeces of gerbils challenged with Hp. Conventional Hp detection methods, including rapid urease assay and immunohistochemistry, were compared. Moreover, we assessed the natural infection of Hp in 135 gerbils that had never been exposed to Hp artificially from the major laboratory gerbil groups in China. In 10 Hp infected gerbils, the positive detection results were 100%, 100%, 90%, and 10% in gastric fluid, gastric mucosa, duodenal contents, and faeces with nested PCR, respectively. A rapid urease test performed on gastric mucosa showed that all animals were infected with Hp. Immunohistochemical detection and bacteria culture of gastric mucosa samples that were positive by the nested PCR method also confirmed the presence of Hp. 9% (3/35) and 6% (2/31) natural infection rates were found in conventional gerbil groups from the Capital Medical University and Zhejiang Laboratory Animal Center. In conclusion, we established two noninvasive Hp detection methods that can be performed before modelingHp infection, including the gastric fluid nested PCR method and the 13C-urea breath test.

BACKGROUND: Free light chains κ and λ (FLC κ, FLC λ) are of great significance in diagnostic and monitoring monoclonal gammopathy. Freelite and N-Latex methods are two common monitoring methods at present. But the two meanings are not completely equivalent, especially for patients with renal insufficiency. We analyzed the changes of serum and urine FLC in renal insufficiency patients without monoclonal gammopathy and the clinical significance of these changes. METHODS: This study is an observational study. Patients ≥ 18 years old, who met the diagnostic criteria of chronic kidney disease (CKD), excluding monoclonal gammopathy, were selected. Fasting serum and 24-hour urine were taken to detect serum FLC κ, serum FLC λ, SCr, serum β 2-microglobulin, urinary FLC κ, urinary FLC λ, urinary α 1-microglobulin, and urinary β 2-microglobulin. RESULTS: There was a good correlation between the two methods for determining serum/urinary FLC. No matter serum or urine, FLC showed a good correlation with renal function by the N-Latex method, but not by the Freelite method. Under the N-Latex method, FLC κ/λ remained stable, which was basically within the reference range of healthy people and was not affected by renal function. There was a good correlation between FLC detected by N-Latex and microglobulin in serum and urine. CONCLUSION: When the concentration of FLC is low, the N-Latex method is more recommended to monitor FLC. The FLC measured by the N-Latex method is more closely related to renal function. The ratio of FLC κ/λ determined by the N-Latex method remained stable within the recommended range.

Most patients with diabetes mellitus are asymptomatic, which leads to delayed and more complex treatment. At the same time, most individuals are routinely subjected to standard clinical laboratory examinations, which create large health datasets over a lifetime. Computer processing has been used to search for health anomalies and predict diseases using clinical examinations. This work studied machine learning models to support the screening of diabetes through routine laboratory tests using data from laboratory tests of 62,496 patients. The classification and regression models used were the K-nearest neighbor, support vector machines, Bayes naïve, random forest models, and artificial neural networks. Glycated hemoglobin, a test used for diabetes diagnosis, was used as the target. Regression models calculated glycated hemoglobin directly and were later classified. The performance of classification computer models has been studied under various subdataset partitions and combinations (e.g., healthy, prediabetic, and diabetes, as well as no healthy and no diabetes). The best single performance was achieved with the artificial neural network model when detecting prediabetes or diabetes. The artificial neural network classification model scored 78.1%, 78.7%, and 78.4% for sensitivity, precision, and F1 scores, respectively, when identifying no healthy group. Other models also had good results, depending on what is desired. Machine learning-based models can predict glycated hemoglobin values from routine laboratory tests and can be used as a screening tool to refer a patient for further testing.

Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is a natural herbal drug that has been widely used to treat many diseases. The antitumor effects of G. pentaphyllum were first described in the illustrated catalog of plants. Gypenosides are the major active components of G. pentaphyllum, and they have been widely reported to possess antitumor effects in prostate cancer, gastric cancer, hepatocellular carcinoma, colon cancer, lung cancer, and breast cancer. However, research on the use of gypenoside in the treatment of bladder cancer has not been conducted. In this study, we explored the potential molecular mechanisms of gypenosides in the treatment of bladder cancer using network pharmacology and experimental validation. First, we used a network pharmacology-based method to identify both the effective components of gypenosides and the molecular mechanism underlying their antibladder cancer effects. The results were further confirmed by molecular docking, CCK8 and colony formation assays, and cell cycle and cell apoptosis analyses. Additionally, a mouse xenograft model of bladder cancer was used to investigate the antitumor effect of gypenosides in vivo. We identified 10 bioactive ingredients and 163 gene targets of gypenosides. Network exploration suggested that VEGFA, STAT3, and PI3KCA may be candidate agents for the antibladder cancer effect of gypenosides. In addition, analysis of the Kyoto Encyclopedia of Genes and Genomes pathway revealed that the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway may play a crucial role in the mechanism of action of gypenosides against bladder cancer. Molecular docking revealed that gypenosides combine well with PI3K, AKT, and mTOR. As expected, gypenosides displayed apoptosis-inducing properties in bladder cancer cells by inactivating the PI3K/AKT/mTOR signaling pathway in vitro. Furthermore, gypenosides significantly (P < 0.05) inhibited the growth of bladder cancer cells in vivo. Mechanistically, gypenosides induced the apoptosis of bladder cancer cells via inactivation of the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Premature loss of deciduous teeth can lead to loss of space and have a negative effect on occlusion. The use of space maintainers can reduce the severity of problems such as crowding. However, the literature is controversial regarding the effects of early loss of primary first molars The aim of this study was to determine the factors affecting the need for unilateral space maintainer for the first deciduous molars in late mixed dentition. In this cross-sectional study, fifty children between 6 to 8 years who had lost a primary first molar unilaterally later than 6 months ago were randomly selected. Midline deviation, molar and canine relationships at both sides, facial growth pattern, and the amount of space loss were all assessed. Data were analyzed using SPSS version 25 via one-sample t-test, paired t-test, and linear regression (alpha = 0.05). METHODS: In this cross-sectional study, 47 children aged 8 to 10 years with early unilaterally loss of first primary molar in the past 6 months were randomly selected. First, the type of occlusion based on the angle molar relationship and the growth pattern of face based on the Hall and Farkas and midline were assessed. Anterior crowding was measured. SPSS 25 program and Chi-square, t-test, ANOVA, and linear regression were used to analyze the data. A significance level of 0.05 was considered. RESULTS: The results showed that the amount of space loss is 0.56 mm (maxilla = 0.54 and mandible = 0.58), which is not clinically significant, and there is no need for space maintainer. Increasing age (p = 0.021) and increasing the percentage ratio of facial pattern (p = 0.009) significantly reduced the space loss and increased the duration of tooth loss (p = 0.002), and molar relationship in the control side (p = 0.05) and increasing the canine to lateral distance (p = 0.016) significantly increased the space loss. Other factors such as crowding, midline deviation, and canine relationship on the control side did not have significant effects on space loss. CONCLUSION: Space loss due to extraction of the first primary molars in late mixed dentition was neither statistically nor clinically significant. However, in cases of severe crowding, the vertical growth pattern of the face, and molar relationship, further studies are needed, and follow-up of patients is recommended.

Septoria tritici blotch (STB) is a major disease problem of wheat worldwide. To optimize the introgression of resistance genes in elite genotypes throughout traditional or molecular breeding programs, a full understanding of the quantitative inheritance of resistance to Zymoseptoria tritici, plant height (PH), and thousand kernel weight (TKW) is needed. In this study, maternal and cytoplasmic effects of resistance to STB were investigated using P1 (susceptible, high-yielding line) and P2 (resistant, low-yielding line) durum wheat lines and their F1, RF1, F2, RF2, BC1, RBC1, BC2, and RBC2 progeny, assessed for resistance to STB during three growing seasons. Duncan mean's analysis revealed significant differences between generation means for STB, PH, and TKW. The two parents had an extreme pattern. The F1 and RF1 segregated close to their respective parents, suggesting the presence of cytoplasmic and maternal genetic effects for Z. tritici resistance, PH, and TKW. Separate generation mean's analysis confirmed the results of the Duncan test. A three-parameter model was found to be not adequate for all traits in all three growing years; while a digenic epistatic model with cytoplasmic or/and maternal effect was adequate for all cases. Narrow-sense heritability was in the range of 50-60%, 30-69%, and 28-31% for STB, PH, and TKW, respectively. For STB, high heritability and the presence of fixable epistatic effect is encouraging and could lead to creating varieties with the right female parent to exploit cytoplasmic and maternal effects in order to improve resistance to Z. tritici in durum wheat.

Several factors are involved in the emergence of antibiotic-resistant bacteria and pose a serious threat to public health safety. Among them, clustered regularly interspaced short palindromic repeat- (CRISPR-) Cas system, an adaptive immune system, is thought to be involved in the development of antibiotic resistance in bacteria. The current study was aimed at determining not only the presence of antibiotic resistance and CRISPR-Cas system but also their association with each other in Salmonella enteritidis isolated from the commercial poultry. A total of 139 samples were collected from poultry birds sold at the live bird markets of Lahore City, and both phenotypic and genotypic methods were used to determine antimicrobial resistance. The presence of the CRISPR-Cas system was determined by PCR, followed by sequencing. All isolates of S. enteritidis (100%) were resistant to nalidixic acid, whereas 95% of isolates were resistant to ampicillin. Five multidrug-resistant isolates (MDR) such as S. enteritidis isolate (S. E1, S. E2, S. E4, S. E5, and S. E8) were found in the present study. The CRISPR-Cas system was detected in all of these MDR isolates, and eight spacers were detected within the CRISPR array. In addition, an increased expression of CRISPR-related genes was observed in the standard strain and MDR S. enteritidis isolates. The association of the CRISPSR-Cas system with multiple drug resistance highlights the exogenous acquisition of genes by horizontal transfer. The information could be used further to combat antibiotic resistance in pathogens like Salmonella.

The study was an extension of our earlier work on antiinflammatory and anticancer properties of G. asiatica fruit. We aimed to develop a bioassay guided multistep purification technique for producing bioactive fractions of G. asiatica crude extracts. Dried fruit powder was sequentially fractionated with 100% dichloromethane, 100% methanol (MeOH), and 50% MeOH. Active extracts were subjected to liquid-liquid partitioning followed by subfractionation using RP-HPLC. Antioxidant, antiinflammatory, and anticancer activities of the fruit extracts, and their potent fractions were evaluated in vitro, while identification of compounds from the bioactive fractions was performed by ESI-MS/MS analysis. The amount of the identified compounds present was confirmed using external standards adopting a simple, accurate, and rapid analytical HPLC method. The results showed that 100% and 50% MeOH extracts possessed bioactivity; one of which (the 50% MeOH extract) displayed potent activity in all in vitro bioassays. MeOH extract (50%) derived fraction C and hydroalcoholic fraction 5 (GAHAF5) were observed to possess higher antioxidant, antiinflammatory, and in vitro anticancer activity. IC50 of GAHAF5 against MCF-7, HEp-2, and NCI-H522 cancer cells was recorded as 26.2, 51.4, and 63 μg/mL, respectively. ESI-MS/MS and HPLC analysis identified catechin, chlorogenic acid, caffeic acid, and morin as potential bioactive compounds in the GAHAF5 fraction with concentrations of 1230, 491, 957, and 130 μg/g, respectively. The findings indicated that G. asiatica bioactive fractions possessed antiinflammatory activity in vitro and were cytotoxic against breast cancer, lung cancer, and laryngeal cancer cell lines.

Histopathological images contain morphological markers of disease progression that have diagnostic and predictive values, with many computer-aided diagnosis systems using common deep learning methods that have been proposed to save time and labour. Even though deep learning methods are an end-to-end method, they perform exceptionally well given a large dataset and often show relatively inferior results for a small dataset. In contrast, traditional feature extraction methods have greater robustness and perform well with a small/medium dataset. Moreover, a texture representation-based global approach is commonly used to classify histological tissue images expect in explicit segmentation to extract the structure properties. Considering the scarcity of medical datasets and the usefulness of texture representation, we would like to integrate both the advantages of deep learning and traditional machine learning, i.e., texture representation. To accomplish this task, we proposed a classification model to detect renal cancer using a histopathology dataset by fusing the features from a deep learning model with the extracted texture feature descriptors. Here, five texture feature descriptors from three texture feature families were applied to complement Alex-Net for the extensive validation of the fusion between the deep features and texture features. The texture features are from (1) statistic feature family: histogram of gradient, gray-level cooccurrence matrix, and local binary pattern; (2) transform-based texture feature family: Gabor filters; and (3) model-based texture feature family: Markov random field. The final experimental results for classification outperformed both Alex-Net and a singular texture descriptor, showing the effectiveness of combining the deep features and texture features in renal cancer detection.

PURPOSE: The improvement of the long-term survival of patients receiving kidney transplantation remains challenging. Ischemia reperfusion injury (IRI) reduces long-term renal graft survival in the early posttransplantation phase. However, few studies have investigated the effects of IRI on the pathogenesis of chronic renal graft failure. Silent information regulator 1 (SIRT1) regulates antioxidative stress and inflammatory response and protects against IRI. This study is aimed at investigating the role of resveratrol (RSV), an SIRT1 activator, in preventing renal injury in a rat renal transplantation model. METHODS: A classical F334-to-LEW orthotopic renal transplantation rat model was established. The experiment group was treated with RSV from three days prior to kidney transplantation and the treatment lasted until the day of harvest. Uninephrectomized F344 and Lewis rats were used as controls. After 12 weeks, the effects of RSV were evaluated according to renal function, histopathology, immunohistochemistry, and western blotting. The activities of oxidative stress-related markers and proinflammatory cytokines were also assessed. RESULTS: RSV treatment significantly ameliorated renal function and histopathological lesions in kidney-transplanted rats and increased the levels of GSH, SOD, and CAT and decreased the levels of MDA and iNOS. Furthermore, RSV also inhibited the expression of proinflammatory cytokines/chemokines such as TNF-α, CD68, and IL-6 in kidney-transplanted rats. In addition, the transplant group displayed significantly lower level of SIRT1 and higher level of Ac-NF-κBp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF-κBp65. CONCLUSION: SIRT1 plays an important role in the pathogenesis of chronic renal allograft dysfunction. It is a potential therapeutic agent for ameliorating inflammation and oxidative stress-induced renal injury following kidney transplantation by activating the SIRT1/NF-κB signaling pathway.

METHOD: This study was conducted according to Arksey and O'Malley's framework. To investigate the evidence on the effects of Kinect-based rehabilitation, a search was executed in five databases (Web of Science, PubMed, Cochrane Library, Scopus, and IEEE) from 2010 to 2020. RESULTS: Thirty-three articles were finally selected by the inclusion criteria. Most of the studies had been conducted in the US (22%). In terms of the application of Kinect-based rehabilitation for stroke patients, most studies had focused on the rehabilitation of upper extremities (55%), followed by balance (27%). The majority of the studies had developed customized rehabilitation programs (36%) for the rehabilitation of stroke patients. Most of these studies had noted that the simultaneous use of Kinect-based rehabilitation and other physiotherapy methods has a more noticeable effect on performance improvement in patients. CONCLUSION: The simultaneous application of Kinect-based rehabilitation and other physiotherapy methods has a stronger effect on the performance improvement of stroke patients. Better effects can be achieved by designing Kinect-based rehabilitation programs tailored to the characteristics and abilities of stroke patients.

BACKGROUND: Obesity induced by excessive nutrients can cause fatty liver and metabolic dysfunction, which leads to hepatic dysfunction and local/systemic inflammatory responses. Previously, we analyzed the antioxidant, antilipotoxicity, and anti-inflammatory effects of protein hydrolysates in vitro. The aim of the present study is to investigate the antiobesity and hepatoprotective effects of protein hydrolysates derived from Protaectia brevitas (PHPB) in an obese mouse model. METHODS: For this in vivo study, 40 mice were included and divided into four groups: (1) normal diet group, (2) high-fat-diet (ctrl(-)) group, (3) high-fat-diet and silymarin-treated (ctrl(+)) group, and (4) high-fat-diet and PHPB-treated group. After 6 weeks of treatment, body weight and the amount of daily food intake were observed. Moreover, the major organs and blood of animals were collected for the analysis of serum chemistry, histopathological examination, and obesity- and inflammation-related gene expressions. RESULTS: The body weight and the amount of daily food intake significantly decreased in the PHPB-treated group compared with those in the ctrl(-) group. The levels of serum ALT, AST, ALP, creatinine, blood urea nitrogen, glucose, bilirubin, total cholesterol, TG, low-density lipoprotein, IL-6, TNF-α, and IGF-1 significantly reduced in the PHPB-treated group, whereas the serum free fatty acid, albumin, high-density lipoprotein, and adiponectin concentrations increased. In the analysis of weight of the liver, kidney, lungs, spleen, and fat tissues (from epididymal, perirenal, and mesentery tissues), the PHPB-treated group showed decreased values compared with the ctrl(-) group. In the histopathological analysis, the PHPB-treated group showed significantly reduced macrovesicular fatty change and inflammatory cell infiltration in the liver, and the size of the adipocyte in the epididymis also significantly decreased. The obesity- and inflammation-related gene (IL-6, TNF-α, IGF-1, leptin, AP2/FABP4, AMPK-α2, β3AR, and PPAR-γ) expressions in the liver and epididymal adipose tissue were reduced in the PHPB-treated group. CONCLUSIONS: Overall, the results of this study suggest that the protein hydrolysates that derived from Protaectia brevitas produce antiobesity and hepatoprotective effects via anti-inflammatory activities.

The human P-glycoprotein (P-gp) and the NorA transporter are the major culprits of multidrug resistance observed in various bacterial strains and cancer cell lines, by extruding drug molecules out of the targeted cells, leading to treatment failures in clinical settings. Inhibiting the activity of these efflux pumps has been a well-known strategy of drug design studies in this regard. In this manuscript, our earlier published machine learning models and homology structures of P-gp and NorA were utilized to screen a chemolibrary of 95 in-house chalcone derivatives, identifying two hit compounds, namely, F88 and F90, as potential modulators of both transporters, whose activity on Staphylococcus aureus strains overexpressing NorA and resistant to ciprofloxacin was subsequently confirmed. The findings of this study are expected to guide future research towards developing novel potent chalconic inhibitors of P-gp and/or NorA.

BACKGROUND: Intimate partner violence (IPV) against pregnant women is a recognized global public health problem affecting all spheres of women and unborn infants. In Ethiopia, although inconsistent, individual studies avail; there is a dearth of systematic reviews and meta-analysis about the prevalence and associated factors of intimate partner violence. Thus, the present study was aimed at determining the pooled prevalence of IPV and its determinant factors during pregnancy. METHODS: The report of meta-analysis follows the Preferred Reporting Items for Systematic Review and Meta-Analysis 20 guideline (PRISMA 20). Databases including PubMed/Medline, CINAHL, SCOPUS, HINARI (research4life), AJOL, IRIS, and AIM were searched. Heterogeneity test was assessed by the Cochrane chi-square (χ2) and quantified by I 2 statistics test. Publication bias was tested by funnel plots and Egger's test. Sensitivity test and subgroup analysis were also performed. Effect size was calculated by random effects model. RESULTS: A total of 26 studies, including data from 13, 912 participants, were included in the analysis. The prevalence of IPV ranged from 7% to 81% with overall estimated pooled prevalence of 37% (30% -44%, I 2 = 96.5%, p ≤ 0.001). Of this, the prevalence of physical, sexual, and psychological violence was 24% (95% CI; 19%-30%), 21% (95% CI; 16%-26%), and 27% (95% CI; 22%-32%), respectively. Factors such as lack of formal education, childhood violence, rural residency, low decision-making power, family history of violence, attitude, unplanned and unwanted pregnancy by women and partners, late initiation of antenatal care, partner alcohol, and khat use were associated with IPV. CONCLUSION: More than one-third of pregnant women experienced IPV. The most prevalent form of IPV was psychological violence followed by physical and sexual violence. The identified risk for IPV including victim, pregnancy, and perpetrator-related factors indicated the need of a holistic approach in the promotion, prevention, and treatment of IPV. The finding of this study suggests the need of strengthening women empowerments (capacity building) against traditional beliefs, attitudes, and practices. This study also suggests the need of evaluation and strengthening the collaborative work among different sectors such as policy-makers, service providers, administrative personnel, and community leaders, including the engagement of men partners.

[This retracts the article DOI: 10.1155/2013/318698.].

AIMS: Cryptococcosis is an invasive fungal disease that is associated with an increasing prevalence along with a very high fatality and is primarily caused by Cryptococcus. However, its mechanism to cause pathogenicity is not yet completely understood. In this study, we aim to screen the lncRNA markers in human monocytic (THP-1) cells infected by Cryptococcus neoformans (C. neoformans) through high-throughput sequencing technology and to explore its effects on biological functions. METHODS: We initially conducted an lncRNA microarray analysis of the THP-1 cells infected by C. neoformans and normal THP-1 cells. Based upon these data, RT-qPCR was used to verify the expressions of the selected lncRNAs and mRNAs. We then performed functional and pathway enrichment analyses. Lastly, target prediction was performed by using the lncRNA target tool which was based on the differentially expressed lncRNAs. RESULTS: We determined 81 upregulated and 96 downregulated lncRNAs using microarray. In addition, the profiling data showed 42 upregulated and 57 downregulated genes and discovered that neuroactive ligand-receptor interaction, tyrosine metabolism, and phenylalanine metabolism are extremely impaired in the regulation of C. neoformans infection. GO enrichment analysis of the 99 differentially expressed mRNAs exhibited that these modules showed different signaling pathways and biological mechanisms like protein binding and metal ion binding. Moreover, lncRNAs and mRNAs were analyzed for their coexpression relations. A qRT-PCR analysis confirmed that the expression of the top 10 differently expressed mRNA and lincRNA. The expressions of the lncRNAs after C. neoformans infection in THP-1 cells were detected by RNA-sequence, suggesting that microarray analysis could reveal lncRNAs having functional significance that might be linked with the progression of patients. CONCLUSION: The current study analyzed the differential lncRNAs and mRNAs in C. neoformans infection and predicted the corresponding pathways and their correlations that can offer new potential insights into the mechanistic basis of this condition.

EMs is a kind of benign disease with certain malignant behaviors. The adhesion, invasive growth, and angiogenesis of ectopic endometrial cells are the pathological basis of EMs occurrence, but its etiology and pathogenesis have not been completely illustrated yet. In our research, we aim to investigate the role of miR-363 in the pathogenesis of endometriosis. Real-time quantitative PCR was used to detect the expression of miR-363 before and after ESC/NSC transfection. CCK-8, flow cytometry, and transwell assay were used to detect the effect of the miR-363 expression on cell proliferation, apoptosis, and invasion. The effects of the miR-363 expression on the contents of Fas/APO-1 and ICAM-1 in cell culture supernatant were detected by ELISA. qRT-PCR and WB assay were used to detect the effects of the miR-363 expression on the mRNA and protein expression levels of ICAM-1, MMP-7, and VEGF in ESC. The increased expression of miR-363 could inhibit the proliferation and invasion of ESC, promote apoptosis, and inhibit the secretion of FAS/APO-1 and ICAM-1. The knockdown expression of miR-363 promoted proliferation and invasion of NSC, inhibited apoptosis, and promoted secretion of FAS/APO-1 and ICAM-1. VCAM-1, VEGF, and MMP-7 were detected in ESCs before transfection. The protein expression level was higher than that of NSCs. Compared with pretransfection, the protein levels of VCAM-1, VEGF, and MMP-7 in the M-363 group were significantly downregulated. The downregulated expression of miR-363 was associated with a stronger cell proliferation ability, a lower cell apoptosis rate, and a stronger ESC. Migration is associated with invasiveness, proliferation, angiogenesis, and immune escape. The low expression of miR-363 promotes endogenesis through posttranscriptional regulation of target genes VCAM-1, MMP-7, and VEGF. The differential expression of miR-363 between ESC and NSC may be an important factor in the many biological differences between ESC and NSC.

BACKGROUND: Invasive breast carcinoma (BRCA) is a common type of breast cancer with a high clinical incidence. Thus, it is significant to find effective biomarkers for BRCA diagnosis and treatment. Although some members of armadillo (ARM) repeat family of proteins are confirmed to be biomarkers in cancers, the role of armadillo repeat-containing 1 (ARMC1) in BRCA remains unknown. METHODS: We firstly analyzed the ARMC1 expression in normal breast tissues and BRCA samples and its association with overall survival by the public database. Next, the χ 2 test was used to evaluate the prognostic significance of ARMC1 expression in TCGA-BRCA patient samples. The ARMC1 mutations in BRCA were explored in the cBioportal database. Besides, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore the biological functions of ARMC1 in BRCA. Finally, immunohistochemistry and immunofluorescence staining were performed to validate the ARMC1 expression in BRCA. RESULTS: ARMC1 expression in tumor samples was significantly higher than that in normal tissues, and higher expression of ARMC1 was related to lower survival. Moreover, the tumor stage and histology of BRCA patients were associated with ARMC1 expression. ARMC1 genetic mutations occurred in 32% of BRCA patients, and the amplification and high expression of ARMC1 accounted for most of them. Furthermore, functional enrichment analysis suggested that ARMC1 might be involved in the cell cycle in BRCA. Ultimately, increased ARMC1 expression was found in clinical breast carcinoma tissues by our confirmatory experiments. CONCLUSIONS: ARMC1 may play a significant role in BRCA and act as a biomarker, which provides valuable clues for the treatment and diagnosis of BRCA.

Wireless sensor network (WSN) is made up of tiny sensor nodes. The application of WSN in diverse fields has seen a tremendous escalation in recent years. WSN applications are constrained by the limited set of computing resources possessed by the sensor nodes and the security aspects of data communication in the WSN. Many algorithms based on nature-inspired optimization (NIO) have been proposed in the past to optimize the issue of energy efficiency and security in WSN. In the proposed work, two opportunistic routing algorithms, i.e., intelligent opportunistic routing protocol (IOP) and trust-based secure intelligent opportunistic routing protocol (TBSIOP), are compared against two NIO algorithms developed for achieving energy efficiency and security in WSN for performance analysis. The performance is evaluated by simulating the algorithms on MATLAB and comparing the obtained results with existing ACO-based and PSO-based routing algorithms. It is observed that the TBSIOP outperforms the NIO-based algorithms in terms of energy efficiency, network lifetime, packet delivery ratio, end-to-end delay, and average risk level. All the parameters under consideration are recorded in the presence of a maximum of 50% malicious nodes for 25, 50, and 100 nodes' test cases. The increasing size of the network has a significant effect on the performance of TBSIOP, as the packet delivery ratio is close to 100%. Also, TBSIOP can easily avoid malicious nodes during the routing process as reflected from the results. This will improve the network lifetime of TBSIOP compared to other protocols. As far as the application of the work is concerned, it would be beneficial for smart healthcare services. It can also help in better communication during the sharing of data by providing energy-efficient services and keeping the network alive for a longer period.

The study was aimed at designing and characterizing the ondansetron hydrochloride (OND) bearing agarose (AG), and hydroxypropyl methyl cellulose (HPMC) mucoadhesive buccal films employing glycerol as a plasticizer. The buccal delivery of ondansetron hydrochloride was remarkably boosted by employing physical (iontophoresis) and chemical enhancement approaches (chemical penetration enhancers). To explore the influence of different formulation components, i.e., agarose, hydroxypropyl methyl cellulose (HPMC), and glycerol on various evaluating parameters, i.e., tensile strength, swelling index, ex vivo mucoadhesion time, and subsequently on in vitro drug release, a D-optimal design was opted. A buccal film bearing OND was mounted on bovine buccal mucosa for ex vivo permeation studies and impact of chemical and physical enhancement techniques on the permeation profile was also analysed. A linear release profile was revealed in in vitro drug release of OND over 60 minutes and outcomes ascertained the direct relationship between HPMC content and in vitro drug release and inverse relationship was depicted by AG content. The FTIR and DSC thermal analysis was executed to determine the physicochemical interactions and results exposed no chemical interactions between drug and polymers. The drug (OND) appeared as tiny crystals on smooth film surface during scanning electron microscopy (SEM) analysis. A notable enhancement in permeation flux, i.e., 761.02 μg/min of OND during ex vivo permeation studies was witnessed after the application of current (0.5-1 mA) without any time lag and with enhancement ratio of 3.107. A time lag of 15 minutes, 19 minutes, and 26 minutes with permeation flux of 475.34 μg/min, 399.35 μg/min, and 244.81 μg/min was observed after chemical enhancer pretreatment with propylene glycol, Tween 80, and passive, respectively. Rabbit was employed as the experimental animal for pharmacokinetic studies (in vivo) and cats for pharmacological activity (in vivo), and the results illustrated the enhanced bioavailablity (2.88 times) in the iontophoresis animal group when compared with the rabbits of control group. Likewise, a remarkable reduction in emesis events was recorded in cats of iontophoresis group. Conclusively, the histopathological examinations on excised buccal mucosa unveiled no severe necrotic or cytopathetic outcomes of current.

The aim of this study is to demonstrate the relationship between the proximal attachment of the coracobrachialis muscle and the short head of the biceps brachii and the distal attachment of the pectoralis minor. Their correlation with the bifurcated coracoid process (CP) will be also assessed. On the basis of these observations, a new classification of structures attached to the coracoid process is proposed. Classical anatomical dissection was performed on one hundred forty-five upper limbs. Three types of relationship between the coracobrachialis muscle and the short head of the biceps brachii were observed in the cadavers. In type I (occurring in 54%), the coracobrachialis and the short head of the biceps brachii created a common junction attached to a single CP. Type II was divided into two subtypes (a and b). Subtype IIa (frequency 10%) was represented by independent proximal attachments of the short head of the biceps brachii and the coracobrachialis muscles to the CP. In subtype IIb (frequency 5%), the coracobrachialis muscle was two-headed (the first head located under the second) and not connected to the short head of the biceps brachii; all heads were attached to a single CP. Type III (frequency 31%) was characterized by a two-headed coracobrachialis muscle, the first head originating from a bifurcated CP laterally to the short head of the biceps brachii and the second medially to this structure. Different variations connected with the mentioned structures could be problematic for surgeons during operations, so detailed knowledge of them could contribute to more efficient procedures.

NSCLC (non-small-cell lung cancer) is the deadliest cancer in the world. Artesunate is one of the most potent and rapidly acting antimalarial agents. Recently, emerging evidence has suggested the anticancer function of artesunate. In our work, we aimed to investigate the molecular mechanism of artesunate-induced growth inhibition in human lung adenocarcinoma cells and reported that the anticancer effects of artesunate is related to its ability in downregulating AKT/Survivin signaling in A549 cells. The effect of artesunate on the proliferation of A549 cells was determined by CCK-8 assay and colony formation assay; its effect on A549 cell apoptosis was evaluated by lactate dehydrogenase (LDH) release assay. The role of artesunate on the activation of AKT/Survivin signaling was analyzed by western blot and quantitative QPCR. Finally, we used two mouse tumor models to investigate the function of artesunate on the in vivo growth of lung cancer cells. Artesunate treatment caused significant growth inhibition and apoptosis in A549 cells. Mechanistically, artesunate downregulated the activation of AKT/Survivin signaling. In agreement, hyperactivation of AKT signaling restored artesunate-induced growth inhibition in A549 cells. In mouse lung cancer models, artesunate administration significantly reduced the growth of A549 cells and LLC cells in nude mice and immunocompetent mice, respectively. Our findings suggest that artesunate serves as a potential tumor suppressor in lung cancer and hopefully can provide new insight into the development of therapeutic strategies in the clinical lung cancer treatment.

BACKGROUND: Burnout is a public health problem that disproportionately affects nurses in sub-Saharan Africa because of the weak health systems that create an unconducive workplace environment. In Uganda, there is limited evidence on the burden of burnout among nurses in a manner that undermine advocacy and policy formulation. We aimed to assess the level of burnout and associated factors among nurses in northern Uganda. METHODS: This was a cross-sectional survey conducted among 375 randomly selected nurses from health facilities in northern Uganda. Data were collected using a self-administered questionnaire. Data analysis consisted of descriptive statistics and logistic regression at a 95% level of significance in SPSS version 25. RESULTS: Majority of the respondents were female 56.5% (n = 223). Nearly half, 49.1% (n = 194) of respondents had high levels of burnout, 36.2% (n = 143) reported average levels of burnout, and 14.7% (n = 58) reported low levels of burnout. Factors associated with burnout were age (AOR: 2.90; 95% CI: 1.28-6.58; p = 0.011), social support (AOR: 0.45; 95% CI: 0.22-0.94; p = 0.033), healthy eating (AOR: 0.06; 95% CI: 0.02-0.22; p < 0.001), workload (AOR: 0.31; 95% CI: 0.14-0.68; p = 0.004), and management responsibilities (AOR: 3.07; 95% CI: 1.54-6.12; p = 0.001). CONCLUSION: Half of the nurses in northern Uganda experienced high levels of burnout. The Ministry of Health should consider recruiting more nurses to reduce workload and adjust working hours to prevent workplace-related burnout among nurses in the country.

In the latest APG IV classification system, Amaryllidaceae is placed under the order of Asparagus and includes three subfamilies: Agapanthoideae, Allioideae, and Amaryllidoideae, which include many economically important crops. With the development of molecular phylogeny, research on the phylogenetic relationship of Amaryllidaceae has become more convenient. However, the current comparative analysis of Amaryllidaceae at the whole chloroplast genome level is still lacking. In this study, we sequenced 18 Allioideae plastomes and combined them with publicly available data (a total of 41 plastomes), including 21 Allioideae species, 1 Agapanthoideae species, 14 Amaryllidoideae species, and 5 Asparagaceae species. Comparative analyses were performed including basic characteristics of genome structure, codon usage, repeat elements, IR boundary, and genome divergence. Phylogenetic relationships were detected using single-copy genes (SCGs) and ribosomal internal transcribed spacer sequences (ITS), and the branch-site model was also employed to conduct the positive selection analysis. The results indicated that all Amaryllidaceae species showed a highly conserved typical tetrad structure. The GC content and five codon usage indexes in Allioideae species were lower than those in the other two subfamilies. Comparison analysis of Bayesian and ML phylogeny based on SCGs strongly supports the monophyly of three subfamilies and the sisterhood among them. Besides, positively selected genes (PSGs) were detected in each of the three subfamilies. Almost all genes with significant posterior probabilities for codon sites were associated with self-replication and photosynthesis. Our study investigated the three subfamilies of Amaryllidaceae at the whole chloroplast genome level and suggested the key role of selective pressure in the adaptation and evolution of Amaryllidaceae.

PURPOSE: To investigate the influence on the adjacent segment degeneration (ASD) of short-segment lateral lumbar interbody fusion (LLIF) at 2 years postoperatively. METHODS: Ninety-seven consecutive patients who underwent one- or two-level LLIF were included from two institutions. We diagnosed radiographical adjacent segment degeneration with the appearance of adjacent spondylolisthesis (>3 mm) or deterioration of adjacent disk height (>3 mm) on plain radiographs or decrease of the intervertebral angle (>5 degrees). The differences between the two groups with and without radiographical ASD were investigated using univariate and multivariate analyses to determine the risk factors for ASD. The variables included extent of adjacent decompression, posterior fixation method (open method or percutaneous method), and facet violation on postoperative CT. RESULTS: In total, 19 patients (19.6%) were diagnosed as radiographical ASD 2 years after surgery. Univariate analysis showed that the ASD (+) group had a high frequency of adjacent decompression (21.1 vs. 3.8%, p = 0.035) compared with the ASD (-) group. There were no differences between the two groups in posterior fusion method (percutaneous method 42.1 vs. 57.7%, p = 0.221) or facet joint violation (15.8 vs. 14.1%, p = 0.860). The multivariate analysis found adjacent intervertebral decompression to be a risk factor for ASD 2 years after surgery (odds ratio: 9.95; 95% confidence interval: 1.2-82.1). CONCLUSIONS: Adjacent intervertebral decompression was considered to be a potential risk factor for the development of ASD after spinal fusion with LLIF.

Lung adenocarcinoma (LUAD) remains one of the leading causes of cancer-related deaths worldwide. This study is aimed at constructing a risk scoring model based on necroptosis-related miRNAs to predict prognosis of LUAD. Expression profile of miRNA in LUAD was downloaded from The Cancer Genome Atlas (TCGA) database. We screened the differentially expressed necroptosis-related miRNAs between LUAD patients and normal samples, thus constructed a seven miRNA-based risk stratification on the basis of the TGCA cohort. This risk stratification was prove to be effective in predicting the overall survival (OS) of patients with LUAD. Furthermore, we constructed a nomogram model based on the combination of risk characteristics and clinicopathological features, which was also prove to be accurate and efficient in predicting OS of LUAD patients. Functional enrichment analyses on the targeted genes of these miRNAs with prognostic value were carried out. Results indicated that these targeted genes were closely related to the development and metastasis of tumors. In summary, our research has developed a prognostic model based on the expression of miRNAs related to necroptosis. This model might be used to predict the prognosis of LUAD accurately, which might be helpful in improving treatment efficacy of LUAD.

BACKGROUND: The aim of the study was to compare the morphological distinctions of the posterior wall (PW) in different complex acetabular fractures using 3D software and fracture mapping technique and ultimately to provide for improved clinical treatment. METHODS: One hundred and fourteen patients with complex acetabular fracture associated with PW were recruited. All patients were divided into two groups according to the injury mechanism of the PW: Group A (both-column and PW) and Group B (including posterior column and PW; T shape and PW; and transverse and PW). Fracture mapping was generated on the intra- and extrasurface of a standard template. The radiological parameters including spatial displacement, articular surface area, articular range, marginal impaction, and multifragments of the two groups were compared. RESULTS: The spatial displacement, intra-/extra-articular surface area, and start and end point in Group A were 10.9 mm (IQR, 8.4-15.2), 8.2 ± 2.6 cm2, 17.9 ± 5.3 cm2, 0.8° (IQR, -6.0-16.2), and 107.5° (IQR, 97.2-116.9), respectively. The results in Group B were 30.4 mm (IQR, 16.8-48.7), 4.1 ± 2.0 cm2, 10.6 ± 4.4 cm2, 29.5° (IQR, 19.2-38.0), and 117.5° (IQR, 98.2-127.2), respectively. Marginal impaction was defined by Letournel et al. All the differences between two groups were significant (P < 0.05). The fracture map in Group A showed an "L"-shaped pattern and a "cusp" on the ilium, and the PW was located at 1/5 to 1/4 of the posterosuperior part of the acetabulum. The fracture maps in Group B were scattered and lacked consistency, and the PWs were confined to 1/10 to 1/8 of the posterior acetabulum. CONCLUSIONS: Quantitative measurements and fracture mapping represented the differences in morphological characteristics of PWs associated with complex acetabular fractures.

This study presents an automated algorithm that measures ocular deviation quantitatively using photographs of the nine cardinal points of gaze by means of deep learning (DL) and image processing techniques. Photographs were collected from patients with strabismus. The images were used as inputs for the DL segmentation models that segmented the sclerae and limbi. Subsequently, the images were registered for the mathematical algorithm. Two-dimensional sclera and limbus were modeled, and the corneal light reflex points of the primary gaze images were determined. Limbus recognition was performed to measure the pixel-wise distance between the corneal reflex point and limbus center. The segmentation models exhibited high performance, with 96.88% dice similarity coefficient (DSC) for the sclera segmentation and 95.71% DSC for the limbus segmentation. The mathematical algorithm was tested on two cranial nerve palsy patients to evaluate its ability to measure and compare ocular deviation in different directions. These results were consistent with the symptoms of such disorders. This algorithm successfully measured the distance of ocular deviation in patients with strabismus. With complementation in the dimension calculations, we expect that this algorithm can be used further in clinical settings to diagnose and measure strabismus at a low cost.

AIM: In this study, we aimed to investigate the efficacy of catheter directed thrombolysis (CDT) and peripheral intravenous thrombolysis (PIT) in the treatment of patients with acute pulmonary embolism (APE) and assess its effect on the prognosis of patients. METHODS: We recruited 74 patients with APE, who were assigned to CDT and PIT groups, according to the treatments received by them. The arterial partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (Pa CO2), pulmonary artery pressure (PAP), pulmonary artery obstruction index (PAOI), thrombus volume, pain score, and therapeutic benefits were compared between the two groups before and after treatment, and the factors affecting patient prognoses were also analyzed. RESULTS: Using the clinical data before treatment as the baseline, it was found that changes in indicators of plasma, thrombus volume, and pain scores were significantly better in the CDT group than in the PIT group after treatment. The total effective rate of CDT was higher than that of PIT in the treatment of APE. The mean follow-up time for both the CDT and PIT groups was 41.08 ± 9.12 months, and the total mortality rate was 14.8% and 31%, respectively. The logistic regression analysis revealed the significant impacts of previous incidences of pulmonary embolism (PE), concurrent deep vein thrombosis (DVT), and pulmonary arterial hypertension (PAH) on the occurrence and progression of APE, and these factors were subsequently identified as risk factors for APE using Kaplan-Meier survival analysis. Observations from PAE onset to the end of follow-up revealed that there was a difference in survival rates between the CDT and PIT groups. CONCLUSIONS: Taken together, CDT is an effective treatment strategy for APE and can provide effective symptomatic relief. In addition, the previous incidences of PE, concurrent DVT, and PAH are important risk factors that affect the survival rates of patients with APE.

Three-dimensional printing (3DP) has recently gained importance in the medical industry, especially in surgical specialties. It uses different techniques and materials based on patients' needs, which allows bioprofessionals to design and develop unique pieces using medical imaging provided by computed tomography (CT) and magnetic resonance imaging (MRI). Therefore, the Department of Biology and Medicine and the Department of Physics and Engineering, at the Bioastronautics and Space Mechatronics Research Group, have managed and supervised an international cooperation study, in order to present a general review of the innovative surgical applications, focused on anatomical systems, such as the nervous and craniofacial system, cardiovascular system, digestive system, genitourinary system, and musculoskeletal system. Finally, the integration with augmented, mixed, virtual reality is analyzed to show the advantages of personalized treatments, taking into account the improvements for preoperative, intraoperative planning, and medical training. Also, this article explores the creation of devices and tools for space surgery to get better outcomes under changing gravity conditions.

Eye temperature and intraocular pressure are two measurable parameters that can be monitored as a health index with aging. Deviations from the normal range of intraocular pressure and temperature lead to the formation of many diseases. This study has been carried out to evaluate the relations between the physiological and anatomical changes of the eye with aging using mathematical modeling. 2D computer-aided design of the human eye has been developed for two major groups: 21 to 30 years and 41 to 50 years. The computer simulation has been carried out to determine the effects of physiological changes of tear evaporation, fluid dynamics, blood flow, and metabolism of eye tissues with aging. The simulation has been carried out in the standing and the supine position of a human body. The rate of temperature change is - 0.0075 K per year in the standing position and - 0.007 K per year in the supine position because of the modeled anatomical and physiological effects. All the three simulation parameters of this study, the temperature of the human eye, the intraocular pressure, and the aqueous humor flow velocity, have been compared with the recent practical and simulation-based experiments to validate our results.

Biomedical named entity recognition (BioNER) from clinical texts is a fundamental task for clinical data analysis due to the availability of large volume of electronic medical record data, which are mostly in free text format, in real-world clinical settings. Clinical text data incorporates significant phenotypic medical entities (e.g., symptoms, diseases, and laboratory indexes), which could be used for profiling the clinical characteristics of patients in specific disease conditions (e.g., Coronavirus Disease 2019 (COVID-19)). However, general BioNER approaches mostly rely on coarse-grained annotations of phenotypic entities in benchmark text dataset. Owing to the numerous negation expressions of phenotypic entities (e.g., "no fever," "no cough," and "no hypertension") in clinical texts, this could not feed the subsequent data analysis process with well-prepared structured clinical data. In this paper, we developed Human-machine Cooperative Phenotypic Spectrum Annotation System (http://www.tcmai.org/login, HCPSAS) and constructed a fine-grained Chinese clinical corpus. Thereafter, we proposed a phenotypic named entity recognizer: Phenonizer, which utilized BERT to capture character-level global contextual representation, extracted local contextual features combined with bidirectional long short-term memory, and finally obtained the optimal label sequences through conditional random field. The results on COVID-19 dataset show that Phenonizer outperforms those methods based on Word2Vec with an F1-score of 0.896. By comparing character embeddings from different data, it is found that character embeddings trained by clinical corpora can improve F-score by 0.0103. In addition, we evaluated Phenonizer on two kinds of granular datasets and proved that fine-grained dataset can boost methods' F1-score slightly by about 0.005. Furthermore, the fine-grained dataset enables methods to distinguish between negated symptoms and presented symptoms. Finally, we tested the generalization performance of Phenonizer, achieving a superior F1-score of 0.8389. In summary, together with fine-grained annotated benchmark dataset, Phenonizer proposes a feasible approach to effectively extract symptom information from Chinese clinical texts with acceptable performance.

BACKGROUND: The global need for efficient and cost-effective use of healthcare resources in low-income countries has led to the introduction of lay health workers (LHWs) as a link of the community to healthcare services. As such, the LHWs perform a variety of tasks such as education, support for care delivery, and social support across all disease types. However, little is known about their ability to support dementia care and management in the community. PURPOSE: The goal of the pilot intervention was to evaluate the 5-day training intervention for LHWs in rural southwestern Uganda in community-based care and management of people with dementia, and implementation of the knowledge and skills gained. METHODS: This was a "pre" and "post" pilot intervention study which involved a qualitative assessment of LHWs' knowledge on community-based management and care for people with dementia. We focused on four core competency domains in the WHO dementia toolkit. The intervention included a five-day training of the LHWs on dementia care, eight weeks of implementation, and an evaluation of the experiences. Analysis focused on the needs assessment, early detection and management, community engagement, support for people with dementia; and evaluation of the eight weeks implementation. RESULTS: Before the training, the LHWs did not know much about what dementia-related support to provide in the community. Activities were limited to general support, including nutrition, and health education. After the training, LHWs had a basic understanding of dementia and began sensitizing the communities. They felt more comfortable working with people with dementia and reported a notable change in the attitude of family members. However, they reported challenges in differentiating the signs of early dementia from superstitious beliefs. CONCLUSION: With enhanced capacity, LHWs may be able to support community-based management for people with dementia. A larger study is needed to explore potential roles for LHWs and further assess effectiveness of the LHWs' skills.

The present study is aimed at evaluating the haematobiochemical and immune system alterations in rabbit's exposure to amoxicillin. Thirty-two healthy rabbits were randomly divided into four (n = 8) groups comprising of three experimental groups and one control group. After 7 days of the acclimatization period, the study animals were given different doses of amoxicillin orally (100, 150, and 200 mg/kg body weight) for 21 days. The hematological results revealed that red blood cells, hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration decreased significantly (P < 0.05) whereas white blood cells, neutrophils, and granulocyte exhibited a significantly increasing trend. Serum biochemical analysis showed a significantly increased concentration of HDL, LDL, serum globulin cholesterol, triglyceride, urea, uric acid, creatine, and calcium while plasma fibrinogen, blood sugar, albumin, and total protein were decreased significantly. Furthermore, liver function enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and bilirubin significantly increased. Antioxidant enzymes and oxidative stress parameters such as malondialdehyde concentrations (MDA) increased significantly while catalase, superoxide dismutase, reduced glutathione, and peroxidase reduced significantly in antibiotic amoxicillin-treated groups as compared to the untreated control group (P < 0.05). Microscopic histopathological examination showed negative structural changes in liver, kidney, and heart tissues due to karyorrhexis; a disorganized hepatic cord in the liver; increased Bowman's space, necrotic renal tubules, and degenerative glomerulus in the kidney; and necrotic cardiac cells and cytoplasmic vacuolization in the heart, in antibiotic amoxicillin-treated rabbit groups as compared to the control group. In conclusion, amoxicillin induced stress and physiological and immunological impairments due to the adverse effects on haematobiochemical parameters and histopathological and tissue protein changes in target animals.

Several genes on chromosome 1q21 region predict a high risk of multiple myeloma (MM); however, the underlying molecular pathology remains elusive. Overexpression, amplification, or activation of SET Domain Bifurcated 1 (SETDB1), which is located on 1q21, is closely associated with poor prognosis of many human solid malignancies. In our study, upregulation of SETDB1 might indicate an unfavorable prognosis of MM using bioinformatics analysis from GEO databases and MMRF-CoMMpass. Here, increased SETDB1 expression was observed in the plasma cells from newly diagnosed multiple myeloma patients compared to those from the normal controls. Meanwhile, SETDB1 overexpression was the result of increased copy numbers of SETDB1 gene. In MM patients, the Kaplan-Meier analysis was employed to demonstrate that increased SETDB1 expression was associated with shorter overall survival (OS) and event-free survival (EFS). Besides, we conducted multifactorial cox regression analysis to state that SETDB1 expression was an independent biomarker for OS and EFS. MM patients with higher SETDB1 expression showed higher levels of beta-2 microglobulin (β2M), lactate dehydrogenase (LDH), and bone marrow biopsy plasma cells (BMPC) and lower levels of haemoglobin (HGB). Functional enrichment analysis suggested that SETDB1 could promote cell cycle progression in myeloma. Finally, we observed that SETDB1 was distinctly correlated with tumor immunity in MM. SETDB1 expression in myeloma cells was positively correlated with CD56dim natural killer cells but negatively correlated with infiltrating levels of type17 T helper cells, effector memory CD8 T cells, activated dendritic cells, and natural killer T cells from whole bone marrow (WBM) biopsies. Taken together, these results indicated that SETDB1 could be used as a novel biomarker for predicting the prognosis of MM patients.

The most significant complication of parotid gland tumor surgery is facial weakness. This study compares the occurrence of transient facial palsy in patients with parotid gland tumors who underwent surgery without monitoring to those who underwent surgery with monitoring. The study's aim was to investigate facial nerve function in patients undergoing parotidectomy as well as the effect of intraoperative facial nerve monitoring and the effect of certain risk factors on the surgery and onset of postoperative facial palsy. This prospective study included 100 patients who underwent parotidectomy. The study cohort was divided into two groups. Group I included 50 patients who underwent surgery without neuromonitoring and group II included 50 patients who underwent surgery with neuromonitoring. The neurological assessment was conducted using the House-Brackmann scale. Preoperatively and one month postoperatively, electroneuronography (ENoG) and blink reflex tests were done. The analyses showed a significant reduction of the compound muscle action potential (CMAP) amplitude of the orbicularis oculi and orbicularis oris muscles and prolonged R1 and R2 blink reflex latencies 1 month after surgery. On neurological and electrophysiological studies, the rate of postoperative transient facial nerve dysfunction was significantly different between the groups. Significantly more patients, operated with use of facial nerve monitoring, presented postoperatively normal nerve function (i.e., House-Brackmann grade I) compared to those who underwent surgery without monitoring (78% and 26%, respectively; p < 0.001). Monitoring had a statistically significant impact on the prevalence of facial nerve conduction disorders in patients who underwent surgery, according to the blink reflex and ENoG studies. The duration of the surgical procedure was not affected by monitoring in any way. The clinical evaluation of facial nerve function (House-Brackmann scale) and some ENoG results 1 month after surgery were found to have a significant correlation. To summarize, using monitoring considerably reduced the negative impact of local factors and the prevalence of transient facial nerve palsy.

The development of innovative antifungal agents is essential. Some fungicidal agents are no longer effective due to resistance development, various side effects, and high toxicity. Therefore, the synthesis and development of some new antifungal agents are necessary. 1,2,4-Triazole is one of the most essential pharmacophore systems between five-membered heterocycles. The structure-activity relationship (SAR) of this nitrogen-containing heterocyclic compound showed potential antifungal activity. The 1,2,4-triazole core is present as the nucleus in a variety of antifungal drug categories. The most potent and broad activity of triazoles have confirmed them as pharmacologically significant moieties. The goal of this review is to highlight recent developments in the synthesis and SAR study of 1,2,4-triazole as a potential fungicidal compound. In this study, we provide the results of a biological activity evaluation using various structures and figures. Literature investigation showed that 1, 2, 4-triazole derivatives reveal the extensive span of antifungal activity. This review will assist researchers in the development of new potential antifungal drug candidates with high effectiveness and selectivity.

Exercise in the form of physical activity can provide neuroprotective benefits. The purpose of this study is to determine the effect of the task balance training program (TBT program) on the glial cell-derived neurotrophic factor levels, cognitive function, and postural balance in old people. The population of this study was the old people members of the Batara Hati Mulia Gowa Foundation who were willing to participate in the study (n = 66). The sample of this study was obtained through a random sampling technique to determine the treatment (n = 32) and control (n = 34) groups. Before and after implementing the TBT program, glial cell-derived neurotrophic factor (GDNF) level measurement and cognitive function and postural balance assessment were performed. Cognitive function was measured by using Montreal cognitive assessment (MoCA). Postural balance was measured in two ways by using the timed up and go (TUG) test and Tinetti performance-oriented mobility assessment (POMA). The treatment group showed significantly greater changes than the control group in GDNF levels (2.24 (±0.63) vs. 1.24 (±0.43), P = 0.001), cognitive function (24.66 (±3.42) vs. 19.18 (±2.67), P = 0.001), and postural balance (TUG [14.00 (±4.04) vs. 18.68 (±3.98)]; POMA [26.53 (±1.74) vs. 23.47 (±3.06)], P = 0.001) after training. The treatment group also showed a significant relationship between GDNF levels and cognitive function (r = 0.840, P = 0.001) and postural balance (TUG [r = 0.814, P = 0.001]; POMA [r = 0.630, P = 0.001]). The TBT program affects the levels of GDNF in old people. The TBT program involves cognitive function improvement and affects postural balance changes in old people.

In keratoconus, the cornea assumes a conical shape due to its thinning and protrusion. Early detection of keratoconus is vital in preventing vision loss or costly repairs. In corneal topography maps, curvature and steepness can be distinguished by the colour scales, with warm colours representing curved steep areas and cold colours representing flat areas. With the advent of machine learning algorithms like convolutional neural networks (CNN), the identification and classification of keratoconus from these topography maps have been made faster and more accurate. The classification and grading of keratoconus depend on the colour scales used. Artefacts and minimal variations in the corneal shape, in mild or developing keratoconus, are not represented clearly in the image gradients. Segmentation of the maps needs to be carried out for identifying the severity of the keratoconus as well as for identifying the changes in the severity. In this paper, we are considering the use of particle swarm optimisation and its modifications for segmenting the topography image. Pretrained CNN models are then trained with the dataset and tested. Results show that the performance of the system in terms of accuracy is 95.9% compared to 93%, 95.3%, and 84% available in the literature for a 3-class classification that involved mild keratoconus or forme fruste keratoconus.

OBJECTIVES: To develop and implement a "semi-presential" technology platform to support urgent and priority dental care for the elderly in the context of the COVID-19 pandemic among the Chilean population. METHODS: A dental mobile clinic was implemented along with the development of a technological platform designed to support emergency and priority dental procedures, including teleconsultation with specialists. Under strict biosafety protocols, dental care was provided in five Chilean regions between February and May 2021. Sociodemographic, medical, and dental data were recorded. RESULTS: A total of 135 patients over sixty years old, with a mean age of 72 years, were treated, 48 males and 87 females were attended between February and May 2021 in five different regions of Chile. 53.3% required immediate or urgent treatment, and 24.4% were derived to specialists from whom 60.6% needed immediate or urgent treatment. 74.3% of teleconsultations were derived to an oral pathology specialist. CONCLUSION: It was shown that a "semi-presential" technology platform implemented in a mobile dental clinic can help elderly people who are impeded to look for traditional dental assistance during a pandemic.

Kidney failure occurs whenever the kidney stops to operate properly and would be unable to cleanse or refine the bloodstream as it should. Chronic kidney disease (CKD) is a potentially fatal consequence. If this condition is diagnosed early, its progression can be delayed. There are various factors that increase the likelihood of developing kidney failure. As a consequence, in order to detect this potentially fatal condition early on, these risk factors must be checked on a regular basis before the individual's health deteriorates. Furthermore, it lowers the cost of therapy. The chronic kidney or renal disease will be recognized in this work utilizing fuzzy and adaptive neural fuzzy inference systems. The fundamental purpose of this initiative is to enhance the precision of medical diagnostics used to diagnose illnesses. Nephron functioning, glucose levels, systolic and diastolic blood pressure, maturity level, weight and height, and smoking are all elements to consider while developing a fuzzy and adaptable neural fuzzy inference system. The output variable describes a specific patient's stage of chronic renal disease based on input factors such as stage 1, stage 2, stage 3, stage 4, and stage 5. The outcome will show the present stage of a patient's kidney. As a result, these methods can assist specialists in determining the stage of chronic renal disease. MATLAB software is used to create the fuzzy and neural fuzzy inference systems.

OBJECTIVE: Dietary supplements (DS) may improve micronutrient deficiencies, but the unique eating habits and cultural customs of the Chinese Mongolian population affect their choice of DS. Therefore, this study adopted a cross-sectional method to explore the current status of DS use and to assess the influencing factors in the Mongolian population in Inner Mongolia, China. METHODS: We used a multistage random cluster sampling method to select 1,434 Mongolian people aged ≥ 18 years in Hohhot and Xilinhot, Inner Mongolia. Data regarding general patient characteristics and DS use through questionnaire surveys were obtained, and the blood plasma was collected for biochemical index detection. The binary logistic regression and decision tree algorithm were used to predict the factors influencing DS use among the Mongolian population. RESULTS: Among 1,434 participants that completed the baseline survey, the usage rate of DS was 18.83%, and more women than men used DS (P = 0.017). Higher use of DS was reported among individuals aged ≤ 34 years, but this difference is not statistically significant (P = 0.052). Usage rate was higher among those living in urban areas (P < 0.001), those with higher education (P < 0.001), those engaged in mental work (P < 0.001), and nonsmokers (P = 0.019). The biochemical test results showed that the proportion of people with abnormal total cholesterol levels using DS was lower (P = 0.003), but that of those with abnormal triglyceride levels using DS was higher (P = 0.001), compared with the proportion of those with normal levels in each case. The most commonly used supplement was calcium (58.15%). Education level was the main factor affecting DS intake. The results of the binary logistic regression model and decision tree model both showed that region, educational level, and abnormal triglyceride levels were significant factors influencing DS intake among Mongolians. CONCLUSION: Findings from this study indicate that DS intake is uncommon in the Mongolian population. In addition, sex, region, education level, and triglyceride levels may influence DS use.

INTRODUCTION: Testicular torsion is a surgical emergency that results in testicular ischemia as a result of rotation of the spermatic cord around itself. Oxidative damage occurs in the testis and distant organs with the overproduction of free radicals and overexpression of proinflammatory cytokines by reperfusion after surgery. In this study, we aimed to investigate the effects of cerium oxide (CeO2), an antioxidant nanoparticle, on lung and kidney tissues in testicular torsion/detorsion (T/D) in rats. MATERIALS AND METHODS: After ethics committee approval, 24 rats were equally (randomly) divided into 4 groups. Left inguinoscrotal incision was performed in the control (C) group. In group CeO2, 0.5 mg/kg CeO2 was given intraperitoneally 30 minutes before inguinoscrotal incision. In group T/D, unilateral testicular T/D was achieved by performing an inguinoscrotal incision and rotating the left testis 720° clockwise, remaining ischemic for 120 minutes, followed by 120 minutes of reperfusion. In group CeO2-T/D, 0.5 mg/kg CeO2 was given intraperitoneally 30 minutes before testicular T/D. At the end of the experiment, lung and kidney tissues were removed for histopathological and biochemical examinations. RESULTS: Glomerular vacuolization (GV), tubular dilatation (TD), tubular cell degeneration and necrosis (TCDN), leukocyte infiltration (LI), and tubular cell spillage (TCS) in renal tissue were significantly different between groups (p = 0.012, p = 0.049, p < 0.003, p = 0.046, and p = 0.049, respectively). GV and TCDN were significantly decreased in group CeO2-T/D compared to group T/D (p = 0.042 and p = 0.029, respectively). Lung tissue neutrophil infiltration, alveolar thickening, and total lung injury score (TLIS) were significantly different between groups (p = 0.006, p = 0.001, and p = 0.002, respectively). Neutrophil infiltration and TLIS were significantly decreased in group CeO2-T/D compared to group T/D (p = 0.013 and p = 0.033, respectively). Lung and kidney tissue oxidative stress parameters were significantly different between groups (p < 0.05). Renal tissue glutathione-s-transferase (GST), catalase (CAT), and paraoxonase (PON) activities were significantly higher, and malondialdehyde (MDA) levels were significantly lower in group CeO2-T/D than in group T/D (p = 0.049, p = 0.012, p < 0.001, and p = 0.004, respectively). GST and PON activities were higher, and MDA levels were lower in group CeO2-T/D than in group T/D in the lung tissue (p = 0.002, p < 0.001, and p = 0.008, respectively). Discussion. In our study, cerium oxide was shown to reduce histopathological and oxidative damage in the lung and kidney tissue in a rat testis torsion/detorsion model.

INTRODUCTION: Hepatitis B virus disease is a viral infection caused by the hepatitis B virus (HBV), which is a major public health problem worldwide. According to the World Health Organization (WHO) estimate, two billion people worldwide have serologic evidence of past or present HBV infection. The risk of infection is high among health professionals due to the risk of occupational contact with fluids of infected patients and the risk of needle stick injury. This study is aimed at assessing HBV vaccination coverage and reasons for possible defiance of the vaccine among healthcare workers in Bosaso, Somalia. Methodology. An institution-based cross-sectional study was conducted by using a quantitative approach to identify hepatitis B virus vaccination coverage and reasons for vaccine defiance in Bosaso from September 2020 to November 2020. Healthcare workers (HCWs) in Bosaso city both in public and private health facilities who accepted to participate in this study were interviewed by using a structured questionnaire, and SPSS was used to analyze the collected data. RESULTS: We found that only (16.4%) of HCWs were fully vaccinated. The main reasons for not taking the vaccine by the participants were the unavailability of the vaccine (42%), high vaccine cost (28.7%), lack of time (20.7%), and fear of vaccine side effects (7.5%). The majority (69.7%) of HCWs demonstrated good knowledge about HBV infection. The vaccination uptake was significantly higher among midwives (p = 0.02; OR = 1.21; 95%CI = 1.39 - 67.41) and individuals aged under 30 years (p = 0.03; OR = 8.6; 95%CI = 1.17-63.26). CONCLUSION: Our study revealed that vaccination coverage of HCWs in Bosaso was very low because of the unavailability of vaccines, high cost of the vaccine, lack of time, and fear of vaccine side effects. Therefore, the development and implementation of policies related to HBV vaccination are recommended.

[This retracts the article DOI: 10.1155/2014/360687.].

This study investigates the static and fatigue behavior of porous and conventional anterior cervical cages. Porous structure titanium anterior cervical cages were manufactured using direct selective laser sintering technique. Four different types of cervical cages were designed and manufactured, among which three designs consist of porous structure (type 1, type 2, and type 3) and manufactured using metal 3D printing. Remaining one design (type 4) was manufactured using conventional machining and did not consist any porous structure. All types of manufactured cages were tested in compression under static and fatigue loading conditions as per ASTM F2077 standard. Static and fatigue subsidence testing was performed using ASTM F2267 standard. Static compression testing results of type 1 and type 4 cages reported higher yield load when compared to the type 2 and type 3 cages. Static subsidence testing results reported almost 11% less subsidence rate for additively manufactured cages than the conventional cages. Fatigue subsidence testing results showed that type 2 and type 3 cages can withstood approximately 21% higher number of cycles before subsidence as compare to the type 1 and type 4 cages. During fatigue testing, all the cages design survived 5 million cycles at the 3000 N loading. For 6000 N and 8000 N, loading rate type 2 and type 3 cages showed lower fatigue life when compared to other cages design. Since fatigue life of type 2 and type 3 cage designs were reported lower than other cages design, it is concluded that the performance of the additively manufactured porous cages can be significantly varied based upon the cage design features.

PURPOSE: Urinary tract infections (UTIs) are the most common infections among hospitalized patients. Cystoscopy is a minimally invasive procedure to check bladder disease, among the patients receiving procedure, approximately 10% of patients may experience UTI. In this study, a neural network model with high accuracy, sensitivity, and specificity was developed to predict the probability of UTIs caused by cystoscopic procedures. To reduce antibiotic overuse during cystoscopic procedures, the model can provide clinicians with a rapid assessment of whether patients require prophylactic antibiotics. MATERIALS AND METHODS: Patients who underwent cystoscopic procedures at China Medical University Beigang Hospital from 2016 to 2019 were retrospectively reviewed. A total of 1647 patients were enrolled, and 147 cases of urinary tract infection occurred. An artificial neural network (ANN) and logistic regression analysis were used to develop the prediction models, and the two models were compared. RESULTS: The logistic regression analysis model had an accuracy of 91%, sensitivity of 2%, and specificity of 99%, indicating that the logistic regression model predicted that most patients had a low risk of infection. The neural network model had a high accuracy of 85%, sensitivity of 80%, and specificity of 88%. CONCLUSIONS: Because the logistic regression model had low sensitivity and missed most cases of UTI, the logistic regression model is inappropriate for clinical application. The neural network model has superior predictive ability and can be considered a tool in clinical practice.

Antimicrobial resistance is the key threat to global health due to high morbidity and mortality. The alteration of bacterial proteins, enzymatic degradation, and change of membrane permeability towards antimicrobial agents are the key mechanisms of antimicrobial resistance. Based on the current condition, there is an urgent clinical need to develop new drugs to treat these bacterial infections. In the current study, the binding patterns of selected antimicrobial peptides (AMPs) with different multidrug-resistant bacterial strains have been analyzed. Among ten selected AMPs in this study, napin and snakin-1 exhibited the best scores and binding patterns. Napin exhibited strong interactions with penicillin-binding protein 1a of Acinetobacter baumannii (with a binding score of -158.7 kcal/mol and ten hydrogen bonds), with glucose-1-phosphate thymidylyltransferase of Mycobacterium tuberculosis H37Rv (with a binding score of -107.8 kcal/mol and twelve hydrogen bonds), and with streptomycin 3″-adenylyltransferase protein of Salmonella enterica (with a binding score of -84.2 kcal/mol and four hydrogen bonds). Similarly, snakin-1 showed strong interactions with oxygen-insensitive NADPH nitroreductase of Helicobacter pylori (with a binding score of -105.0 kcal/mol and thirteen hydrogen bonds) and with penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus (with a binding score of -103.8 kcal/mol and twenty-three hydrogen bonds). The docking results were further validated by molecular dynamics simulations. The results of this computational approach support the evidence of efficiency of these AMPs as potent inhibitors of these specific proteins of bacterial strains. However, further validations are required to fully evaluate the potential of selected AMPs as drug candidates against these resistant bacterial strains.

BACKGROUND: Minichromosome maintenance (MCM) genes are crucial for genomic DNA replication and are important biomarkers in tumor biology. In this study, we aimed to identify the diagnostic, therapeutic, and prognostic value of the MCM2-10 genes in patients with lung cancer. METHODS: We examined the expression levels, gene networks, and protein networks of lung cancer using data from the ONCOMINE, GeneMANIA, and STRING databases. We conducted a functional enrichment analysis of MCM2-10 using the clusterProfiler package using TCGA data. The correlation between the MCM2-10 expression and lung cancer prognosis was evaluated using Cox regression analysis. The influence of clinical variables on overall survival (OS) was evaluated using univariate and multivariate analyses. The TIMER database was used to evaluate the correlation between tumor infiltrating levels and lung cancer. Kaplan-Meier Plotter pan-cancer RNA sequencing was used to estimate the correlation between the MCM5 expression and OS in different immune cell subgroups in patients with lung adenocarcinoma (LUAD). Finally, the 1-, 3-, and 5-year predictions of LUAD were performed using nomogram and calibration analysis. RESULTS: The expression of MCM2, 3, 4, 5, 6, 7, 8, and 10 in lung cancer was higher than that for normal samples. The MCM5 expression was associated with poor OS in patients with LUAD, and prognosis was related to TNM stage, smoking status, and pathological stage. The MCM5 expression is correlated with immune invasion in LUAD and may affect prognosis due to immune infiltration. CONCLUSION: MCM5 may serve as a molecular biomarker for LUAD prognosis.

BACKGROUND: Serum chitinase-3-like protein 1 (CHI3L1) is a promising marker for diagnosing liver fibrosis. This meta-analysis was carried out to assess the diagnostic performance of serum CHI3L1 for the estimation of liver fibrosis. METHODS: Systematic searches were performed on PubMed, Embase, Web of Science, Scopus, the Cochrane Library, Google Scholar, Sinomed, the China National Knowledge Infrastructure (CNKI), the Chinese Medical Journal Database, and the Wanfang databases for available studies. The primary studies were screened strictly according to inclusion and exclusion criteria, and sensitivity, specificity, and other measures of accuracy of serum CHI3L1 for evaluating liver fibrosis were pooled with 95% confidence intervals. I 2 was calculated to assess heterogeneity, and sources of heterogeneity were explored by subgroup analysis. Deeks' test was used to assess for publication bias, and likelihood ratio was used to determine posttest probability. RESULTS: Our research integrated 11 articles, accounting for 1897 patients older than 18 years old. The pooled sensitivity and specificity for significant fibrosis, advanced fibrosis, and cirrhosis were 0.79 and 0.82 with an area under the receiver operating characteristic curve (AUC) of 0.85, 0.81 and 0.83 with an AUC of 0.91, and 0.72 and 0.74 with an AUC of 0.85, respectively. Random-effects models were used to assess for significant heterogeneity, and subgroup analysis showed that age and aetiology of included patients were likely sources of heterogeneity. No potential publication bias was found for serum CHI3L1 in the diagnosis of significant fibrosis, advanced fibrosis, or cirrhosis, and posttest probability was moderate. CONCLUSION: Measurement of serum CHI3L1 is a feasible diagnostic tool for liver fibrosis.

Due to challenges in early-stage detection, aggressive behavior, and poor response to systemic therapy, pancreatic cancer is one of the most fatal cancer types globally. The role of RNA-binding protein (RBP) transcription and translation of cancer cells has been well demonstrated, although their roles in pancreatic cancer is less well understood. In this study, we found that heterogeneous nuclear ribonucleoprotein C (hnRNPC), a RBP, is highly expressed in pancreatic ductal adenocarcinoma (PDAC) tissues and cells. In addition, we discovered that overexpression of hnRNPC in PDAC cells in vitro increased cell proliferation, migration, invasion, and metastasis. The presence of hnRNPC promoted tumorigenesis of pancreatic cells in metastatic in vivo models, which was also validated. In silico analyses revealed that hnRNPC is a strong positive regulator of IQ Motif Containing GTPase Activating Protein 3 (IQGAP3) activity. The experimental confirmation of this association revealed a direct interaction of IQGAP3 and hnRNPC to induce cell growth and invasion in PDAC cells by activating the epithelial-mesenchymal transition. In light of the findings that hnRNPC accelerates PDAC progression by interfering with IQGAP3, it appears that this technique for diagnosis and treatment of PDAC may have promise.

BACKGROUND: The purpose of this randomized trial is to compare the efficacy of weekly once regime of neutral sodium fluoride (NaF) oral rinse with that of acidulated phosphate (APF) formulated daily mouth rinse in the reduction of white spot lesions (WSLs) associated with fixed orthodontic appliance treatment. METHODS: The participants (n = 90) of this single-center, two-arm parallel study without a control group were randomly assigned with 1 : 1 distribution to each of the two groups after the bonding of brackets. Group A/test group 1 (n = 45) was given weekly rinse of neutral sodium fluoride (Colgate® PreviDent® Dental Rinse-0.2% NaF), and for group B/test group 2 (n = 45), an APF formulated daily oral rinse (Colgate® Ortho Defense@ PhosFlur® Rinse-0.044% w/v of NaF) was given for six months. The outcome was assessed by the International Caries Detection and Assessment System (ICDAS) index for scoring the demineralization, and for scoring gingivitis, Loe and Silness gingival index (GI) was utilized. Four different time points "T0"immediately before bonding procedures, "T1" after 4weeks, "T2" after 12 weeks, and "T3" after 24 weeks were taken to assess the ICDAS and GI scores. RESULTS: The mean ICDAS scores for group A (NaF) were 0.025, 0.051, 0.093, and 0.113 and for group B (APF) were 0.014, 0.022, 0.038, and 0.015 at different points of time. The GI scores for group A were 0.008, 0.22, 0.33, and 0.38 and for group B were 0.003, 0.136, 0.181, and 0.097 at different time points. There was a statistically significant difference (p < 0.05) for both groups in terms of reducing WSL and GI. CONCLUSION: APF formulated daily oral rinse-0.044% w/v of NaF-is more effective than the weekly once regimen of 0.2% NaF oral rinse to prevent white spot lesions.

The purpose of this study was to investigate the effect of image preprocessing on radiomic features estimation from computed tomography (CT) imaging of locally advanced rectal cancer (LARC). CT images of 20 patients with LARC were used to estimate 105 radiomic features of 7 classes (shape, first-order, GLCM, GLDM, GLRLM, GLSZM, and NGTDM). Radiomic features were estimated for 6 different isotropic resampling voxel sizes, using 10 interpolation algorithms (at fixed bin width) and 6 different bin widths (at fixed interpolation algorithm). The intraclass correlation coefficient (ICC) and the coefficient of variation (CV) were calculated to assess the variability in radiomic features estimation due to preprocessing. A repeated measures correlation analysis was performed to assess any linear correlation between radiomic feature estimate and resampling voxel size or bin width. Reproducibility of radiomic feature estimate, when assessed through ICC analysis, was nominally excellent (ICC > 0.9) for shape features, good (0.75 < ICC ≤ 0.9) or moderate (0.5 < ICC ≤ 0.75) for first-order features, and moderate or poor (0 ≤ ICC ≤ 0.5) for textural features. A number of radiomic features characterized by good or excellent reproducibility in terms of ICC showed however median CV values greater than 15%. For most textural features, a significant (p < 0.05) correlation between their estimate and resampling voxel size or bin width was found. In CT imaging of patients with LARC, the estimate of textural features, as well as of first-order features to a lesser extent, is appreciably biased by preprocessing. Accordingly, this should be taken into account when planning clinical or research studies, as well as when comparing results from different studies and performing multicenter studies.

BACKGROUND: The aim was to evaluate the association between the professional training of dentists and their outpatient production (OP) of clinical and collective/preventive procedures and the total number of procedures registered in a health information system. METHODS: It included all 19,947 primary dental care units participating in the Program for Improvement of Access and Quality of Primary Care (PMAQ-AB 2nd cycle) and the number of clinical procedures (CP), collective/preventive procedures (PP), and total procedures (TP) registered in the ambulatory information system between November 2013 and July 2014 for each participant oral health team. The outcome was being above the national median of procedures. The main variables related to training were the dentists specialising in family health, the level of training, and participation in permanent education. Effect estimates were calculated by multiple logistic regression. RESULTS: In the final model, controlled by contextual factor work process, family health specialists had higher chances (odds ratio (OR) = 1.13, 95% CI: 1.00; 1.27) of producing above the national median of CP than nonspecialists, OR = 1.06 (0.96; 1.18) for PP and OR = 1.17 (1.08; 1.27) for TP. Dentists taking permanent education had higher chances than those not taking it of producing above the national median for CP, PP, and TT, respectively, with OR = 1.40 (1.20; 1.62), OR = 1.24 (1.09; 1.40), and OR = 1.28 (1.18; 1.39). CONCLUSION: Training in family health performs more procedures in primary care settings than those without training. However, this OP is influenced by variables related to the municipality and the work process, especially for PP. If the highest production observed is a consequence of training, then public health managers can not only encourage training policies such as permanent education policies to expand the use of services.

Based on Freud's personality theory, 839 nurses from 5 public hospitals in Shandong Province were selected by the convenience sampling method. A cross-sectional survey was conducted to investigate the correlation among resilience, work-family conflict (WFC), and anxiety (SAS). The purpose of this study was to explore the relationship among resilience, WFC, and SAS of these nurses and to provide evidence with reducing WFC and SAS for the nurses. The results showed that the total score of resilience, WFC, and SAS was 58.00 ± 18.27, 53.46 ± 13.29, and 49.98 ± 14.73, respectively. There was 47.68% of the nurses that had anxiety, and 10.97% of the nurses had severe anxiety. There were significant differences in the score of SAS among the length of service, self-perceived health status, confidence in nursing professional development, WFC, and resilience (P < 0.05). This study draws the following conclusions: the proportion of anxiety is high, and the level of resilience is lower than the domestic norm. Length of service, self-perceived health status, confidence in nursing professional development, WFC, and resilience were the important influencing factors of anxiety. It is suggested that hospital managers should pay attention to the mental health of nurses, take active intervention measures according to the influencing factors of SAS, improve nurses' psychological resilience, reduce WFC and anxiety, improve nurses' mental health and well-being, and ensure nursing safety.

BACKGROUND: Recent protocols for posturographic assessment of postural control and balance have included head shake test conditions to challenge the vestibular contributions of postural control in an effort to increase the diagnostic accuracy of identifying individuals with impaired balance. However, evidence is limited regarding the test-retest reliability of such assessment protocols. PURPOSE: The purpose of this study was twofold: to determine the test-retest reliability of postural control assessment on the Biodex Biosway™, an accessible and field expedient tool for posturographic assessment, and to determine the test-retest reliability of the Head Shake Sensory Interaction and Balance Test (HS-SIB), an adaptation of the modified Clinical Test of Sensory Interaction and Balance (mCTSIB) which adds two head shake conditions to challenge the vestibular contributions to postural control. Study Design. This was a correlational time series cohort study completed in a biomechanics laboratory. METHODS: The sample consisted of nineteen healthy adults (10 females, 9 males). Sway Index, Equilibrium Score, and the area of the ellipse enclosing 95% of the anterior-posterior (AP) and medial-lateral (ML) center of gravity (COG) displacement (AREA95) are the 3 summary variables. Standard Error of Measurement (SEM) and Minimum Detectable Change (MDC) are also reported. RESULTS: Test-retest reliability was generally poor with limited exceptions. Moderate to good reliability was observed for the more challenging stance conditions (ICC range 0.58-0.81), including those with head shake. CONCLUSIONS: Field-expedient systems, such as the Biodex BioSway™, may offer reliable posturographic testing where gold-standard methods are not available. Clinicians should be aware that less demanding test conditions have limited reliability; however, test-retest reliability of this assessment tool is improved with more challenged stance conditions and the inclusion of a head shake task.

OBJECTIVE: Through a network pharmacology method, we screened the main active compounds of Citri Reticulatae Pericarpium (CRP), constructed a drug-ingredient-disease-target network, explored the molecular mechanism of its treatment of myocardial hypertrophy, and validated it by using molecular biology approach. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards were utilised to collect the effective component in CRP and the targets of CRP and myocardial hypertrophy. The STRING database constructed the protein interaction network. The drug-ingredient-disease-target network was outlined by the Cytoscape 3.9.0 software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Real-time PCR (RT-PCR) and Western blotting were utilised to determine the mRNA and protein level of the critical targets of CRP therapy for myocardial hypertrophy. RESULTS: We found that five practical components of CRP exerted therapeutic effects on myocardial hypertrophy by modulating 41 targets. Further analysis revealed that naringenin was the essential active compound in CRP that regulated myocardial hypertrophy. In addition, we showed that the active compounds of CRP might exert antihypertrophy effects via regulating essential target proteins such as AKT1-, MAPK3-, PPARA-, PPARG-, and ESR1-mediated signaling pathways such as cell proliferation, nuclear receptor activation, and oxidative stress. The molecular biology experiments demonstrated that naringenin inhibited the mRNA level of NPPA and NPPB induced by Ang II and regulated related targets such as AKT1, MAPK3, PPARA, PPARG, and ESR1. CONCLUSION: CRP could inhibit myocardial hypertrophy through multitarget and multiapproach.

PURPOSE: The aim of this study was to investigate the effect of reduced radiation doses on the image quality of cone-beam computed tomography scans and the suitability of such imaging for orthodontics, oral surgery, dental implantology, periodontology, and endodontology. MATERIALS AND METHODS: Cone-beam computed tomography scans of a live patient were performed using seven attenuation filters with increased thickness to decrease the effective radiation dose from 22.4 to 1.8 μSv, and the effects of different radiation doses on image quality were further analysed. Quantitative image quality was calculated using dedicated measures, such as signal and contrast-to-noise ratio and sharpness. A panel of five certified raters assessed the cone-beam computed tomography scans qualitatively. Nine anatomical structures relevant to dentistry were identified, and the overall acceptance was assessed. RESULTS: Linear reduction of the effective radiation dose had a nonlinear effect on image quality. A 5-fold reduction in the effective dose led to acceptable quantitative and qualitative image quality measures, and the identification rate of dental anatomical structures was 80% or greater. The use of less than 40% of the reference dose was unacceptable for all dental specialties. CONCLUSIONS: The ideal radiation dose for specific diagnostic requirements remains a patient-related and specialty-related decision that must be made on an individual basis. Based on the results of this study, it is possible to reduce exposure in selected patients, and at the same time obtain sufficient quality of images for clinical purposes.

BACKGROUND: Infectious bronchitis virus (IBV) is a highly contagious viral disease of chicken typically affecting the reproductive and respiratory tract and results in possible economic causes from its serious infectious and transmission characteristics. METHODS: A cross-sectional study was carried on serum samples of chickens selected from six (two commercial and four small holder) farms and two types of production (broiler and layer) to detect seroprevalence of IBV and its associated risk factors in Bishoftu and Holeta areas of central Ethiopia from June 2021 to September 2021. A total of 354 blood samples were collected and subjected to indirect ELISA test by IBV antibody test kit ((ProFLOK IBV), from ProFLOK Laboratories Inc., (USA)) to detect specific antibodies against IBV. RESULTS: Overall, 97.46% seroprevalence was identified. From 230 and 124 samples collected from commercial and smallholder poultry farms, 226 (98.26%) and 119 (95.98%) positive results were obtained, respectively. Among the production types of chickens, high seroprevalence (99.31%) was found in layer poultry, and lower seroprevalence (96.17%) was found in the case of broiler chicken. Significant association was observed among different associated risk factors particularly age, sex, breed, and production types of chickens. From the tested chickens, all age groups, species, and farm types have high seroprevalence of IBV. The prevalence of IBV was highly significant (p ≤ 0.01) in the study site. The risk factors indicated could have increased infection prevalence, pathogens' economic impact, and disease occurrence. CONCLUSION: IBD is complicating factor affecting poultry production systems in the area. Vaccine and biosecurity measures are recommended for the control of IBV. Furtherly, identification and characterization (by using RT-PCR) of persistent serotype of IBV circulating in the field are recommended.

OBJECTIVES: This study is aimed at investigating the anticancer activity of Fuzheng Jiedu decoction (FJD) alone or in combination with cisplatin in ovarian cancer (OC) models, as well as its underlying mechanisms of action. METHODS: The anticancer activities of FJD, cisplatin, and the combination of the PI3K inhibitor (LY294002, LY) or activator (IGF-1) were evaluated in OC cell lines in vitro and in a SKOV3 xenograft mouse model in vivo. The cell proliferation and invasion ability were measured using MTT, EdU, and transwell assays, respectively. The cell apoptosis was examined by flow cytometry and JC-1 assays. The expression levels of the Bcl-2 family and the PI3K/AKT/mTOR/NF-κB pathway-related proteins were analyzed by Western blot. RESULTS: The in vivo and in vitro studies showed that FJD administration could significantly inhibit cell proliferation and promote cell apoptosis in two OC cell lines SKOV3 and 3AO and partially decreased the tumor volumes and weights. In addition, FJD could significantly downregulate the protein levels of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, NF-κB, p38, and Bcl-2 and upregulate the Bax, Cyt-C, and cleaved caspase-3 in OC tumor tissues and cells. FJD cotreatment increased the efficacy of cisplatin, including inhibiting OC cell proliferation and invasion, promoting cell apoptosis, and inhibiting the PI3K/AKT/mTOR signaling pathway, while this enhancement was suppressed by IGF-1. Similarly, LY also enhanced the anticancer efficacy of cisplatin. CONCLUSIONS: This study indicated that FJD could improve the efficacy of cisplatin by inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. It is suggested that FJD may be a valuable adjuvant drug for the treatment of OC.

Allergic asthma is associated with T helper (Th) 2 cell-biased immune responses and characterized by the airway hyperresponsiveness (AHR). Studies have shown that the acupoint catgut-embedding therapy (ACE) has a therapeutic effect on allergic asthma. However, the relevant mechanism is poorly understood. In present study, female BALB/c mice were sensitized and challenged with ovalbumin (OVA) to establish a model of allergic asthma. AHR was evaluated by using airway resistance (R L ) and lung dynamic compliance (Cdyn). Airway inflammation and mucus hypersecretion were observed by HE and PAS staining. Inflammatory cells were counted, and related cytokines in bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA). Pulmonary group 2 innate lymphoid cell (ILC2s) proportions were analyzed by flow cytometry. The expression of nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) was detected by immunostaining. Our results showed that OVA induction resulted in a significant increase in R L , accompanied by a significant decrease in Cdyn. The levels of interleukin- (IL-) 4, IL-13, OVA-specific IgE in BALF, and the percentage of ILC2 in the lungs were markedly increased accompanied by a significant decreased in interferon-γ (IFN-γ). Furthermore, the expressions of p-NF-κB p65 and COX-2 in airways were significantly upregulated. After ACE treatment, the indicators above were significantly reversed. In conclusion, ACE treatment inhibited the secretion of Th2 cytokines and the proliferation of ILC2s in the lungs, thereby dampening the inflammatory activity in allergic asthma. The underlying mechanism might be related to the inhibition of NF-κB/COX-2 pathway.

Cancer is one of the primary causes of mortality globally, and the discovery of new anticancer drugs is the most important need in recent times. Natural products have been recognized as effective in fight against various diseases including cancer for over 50 years. Plants and microbes are the primary and potential sources of natural compounds to fight against cancer. Moreover, researches in the field of plant-based natural compounds have moved towards advanced and molecular level understandings from the last few decades, leading to the development of potent anticancer agents. Also, plants have been accepted as abundant and prosperous sources for the development of novel therapeutic agents for the management and prevention of different cancer types. The high toxicity of some cancer chemotherapy drugs, as well as their unfavorable side effects and drugs resistance, drives up the demand for natural compounds as new anticancer drugs. In this detailed evidence-based mechanistic review, facts and information about various medicinal plants, their bioactive compounds with their potent anticancer activities against different cancers have been gathered, with further approach to represent the molecular mechanism behind the anticancer activity of these plants. This review will be beneficial for investigators/scientists globally involved in the development of natural, safe, effective, and economical therapeutic agents/drugs against various cancers. This might be an important contribution in the field of drug discovery, where drugs can be used alone or in combination to increase the efficacy of newly synthesized drugs.

Innovations in digital manufacturing enabled the fabrication of implant-supported fixed dental prostheses (ISFDPs) in a wide variety of recently introduced materials. Computer-aided design and computer-aided manufacturing (CAD-CAM) milling allows the fabrication of ISFDPs with high accuracy by reducing the fabrication steps of large-span frameworks. The longevity of ISFDPs depends on the overall mechanical properties of the framework material including its fit, and the physical properties of the veneering material and its bond with the framework. This comprehensive review summarizes the recent information on millable CAD-CAM framework materials such as pre-sintered soft alloys, fiber-reinforced composite resins, PEEK, and PEKK in high-performance polymer family, and 4Y-TZP. Even though promising results have been obtained with the use of new generation millable CAD-CAM materials for ISFDPs, clinical studies are lacking and future research should focus on the overall performance of these millable materials in both static and dynamic conditions.

Structural variation (SV) is an important type of genome variation and confers susceptibility to human cancer diseases. Systematic analysis of SVs has become a crucial step for the exploration of mechanisms and precision diagnosis of cancers. The central point is how to accurately detect SV breakpoints by using next-generation sequencing (NGS) data. Due to the cooccurrence of multiple types of SVs in the human genome and the intrinsic complexity of SVs, the discrimination of SV breakpoint types is a challenging task. In this paper, we propose a convolutional neural network- (CNN-) based approach, called svBreak, for the detection and discrimination of common types of SV breakpoints. The principle of svBreak is that it extracts a set of SV-related features for each genome site from the sequencing reads aligned to the reference genome and establishes a data matrix where each row represents one site and each column represents one feature and then adopts a CNN model to analyze such data matrix for the prediction of SV breakpoints. The performance of the proposed approach is tested via simulation studies and application to a real sequencing sample. The experimental results demonstrate the merits of the proposed approach when compared with existing methods. Thus, svBreak can be expected to be a supplementary approach in the field of SV analysis in human tumor genomes.

Endoscopic techniques in spine surgery are rapidly evolving, with operations becoming progressively safer and less invasive. Lumbar interbody fusion (LIF) procedures comprise many spine procedures that have benefited from endoscopic assistance and minimally invasive approaches. Though considerable variation exists within endoscopic LIF, similar principles and techniques are common to all types. Nonetheless, innovations continually emerge, requiring trainees and experienced surgeons to maintain familiarity with the domain and its possibilities. We present two illustrative cases of endoscopic transforaminal lumbar interbody fusion with a comprehensive literature review of the different approaches to endoscopic LIF procedures.

Biomedical researchers and biologists often search a large amount of literature to find the relationship between biological entities, such as drug-drug and compound-protein. With the proliferation of medical literature and the development of deep learning, the automatic extraction of biological entity interaction relationships from literature has shown great potential. The fundamental scope of this research is that the approach described in this research uses technologies like dynamic word vectors and multichannel convolution to learn a larger variety of relational expression semantics, allowing it to detect more entity connections. The extraction of biological entity relationships is the foundation for achieving intelligent medical care, which may increase the effectiveness of intelligent medical question answering and enhance the development of precision healthcare. In the past, deep learning methods have achieved specific results, but there are the following problems: the model uses static word vectors, which cannot distinguish polysemy; the weight of words is not considered, and the extraction effect of long sentences is poor; the integration of various models can improve the sample imbalance problem, the model is more complex. The purpose of this work is to create a global approach for eliminating different physical entity links, such that the model can effectively extract the interpretation of the expression relationship without having to develop characteristics manually. To this end, a deep multichannel CNN model (MC-CNN) based on the residual structure is proposed, generating dynamic word vectors through BERT (Bidirectional Encoder Representation from Transformers) to improve the accuracy of lexical semantic representation and uses multihead attention to capture the dependencies of long sentences and by designing the Ranking loss function to replace the multimodel ensemble to reduce the impact of sample imbalance. Tested on multiple datasets, the results show that the proposed method has good performance.

OBJECTIVE: To study the effect of health education combined with personalized psychological nursing intervention on pregnancy outcome of pregnant women with gestational diabetes mellitus (GDM). METHODS: 170 patients with GDM admitted to Guangdong Women and Children Hospital from January 2018 to December 2018 were selected as study subjects and randomly divided into two groups. During the period from diagnosis of GDM to termination of pregnancy, both groups were given routine education and routine examination, and the intervention group adopted health education combined with personalized psychological nursing interventions during pregnancy. The pregnancy weight, blood glucose index, compliance, disease awareness, self-adjustment management ability, satisfaction, and pregnancy outcome were measured before and after the intervention. RESULTS: There were no statistically significant differences in pregnancy weight, fasting plasma glucose, and 2 h postprandial blood glucose between the two groups before intervention (P = 0.768, 0.605, and 0.762). After intervention, lower levels of the above indicators were obtained in the intervention group than in the control group (P < 0.001). The compliance and satisfaction with the intervention in the intervention group were significantly higher than those in the control group (P < 0.001). The intervention group had remarkably higher disease awareness rate and self-psychological adjustment and management ability than the control group (P < 0.001). Better pregnancy outcomes were observed in the intervention group compared with the control group (P < 0.001). CONCLUSION: For patients with GDM, health education combined with personalized psychological nursing on the basis of the conventional nursing can effectively control patients' condition and ensure a better pregnancy outcome, which merits widespread promotion.

[This retracts the article DOI: 10.1155/2018/1096079.].

Mitochondrial DNA haplogroup classification is used to study maternal lineage of ancient human populations. The haplogrouping of ancient DNA is not easy because the DNA is usually found in small pieces in limited quantities. We have developed Haplotracker, a straightforward and efficient high-resolution haplogroup classification tool optimized specifically for ancient DNA samples. Haplotracker offers a user-friendly input interface for multiple mitochondrial DNA sequence fragments in a sample. It provides accurate haplogroup classification with full-length mitochondrial genome sequences and provides high-resolution haplogroup predictions for some fragmented control region sequences using a novel algorithm built on Phylotree mtDNA Build 17 (Phylotree) and our haplotype database (n = 118,869). Its performance for accuracy was demonstrated to be high through haplogroup classification using 8,216 Phylotree full-length and control region mitochondrial DNA sequences compared with HaploGrep 2, one of the most accurate current haplogroup classifiers. Haplotracker provides a novel haplogroup tracking solution for fragmented sequences to track subhaplogroups or verify the haplogroups efficiently. Using Haplotracker, we classified mitochondrial haplogroups to the final subhaplogroup level in nine ancient DNA samples extracted from human skeletal remains found in 2,000-year-old elite Xiongnu cemetery in Northeast Mongolia. Haplotracker can be freely accessed at https://haplotracker.cau.ac.kr.

Meiotic chromosomes endure rapid prophase movements that ease the formation of interhomologue recombination intermediates that drive synapsis, crossing over, and segregation process. To generate these fast moves, the meiotic telomere complex (MTC) enables telomere-inner nuclear membrane attachment during meiotic prophase I and transfers cytoskeletal signals via another complex: the LINC complex. Furthermore, disruption or mutations of any of the MTC genes (TERB1, TERB2, and MAJIN) alters telomere association with the nuclear envelope leading to impairment of homologous pairing and synapsis, a meiotic arrest, and consequently to male infertility. To decipher the effect of TERB1, TERB2, and MAJIN missense mutations on protein structure, stability, and function, different bioinformatic tools were used in this study including VEP, Mutabind2, Haddock, Prodigy, Ligplot, ConSurf, DUET and MusiteDeep. In total, thirty mutations were predicted to be deleterious using VEP web server: seventeen for TERB1, eleven for TERB2, and two for MAJIN. All these single nucleotide polymorphisms were further analyzed and only 11 SNPs (W8R, G25R, P649A, I624T, C618R, F607V, S604G, C592Y, C592R, G187W, and R53C) were found to be the most damaging by at least six software tools and exert deleterious effect on the TERB1, TERB2, and MAJIN protein structures and likely functions. They revealed high conservation, less stability, and having a role in posttranslational modifications. This in silico approach provides information to gain further insights about variants that might affect stability, change binding affinity, and edit protein-protein interactions to facilitate their identification and functional characterization associated with male infertility.

The epidemiological studies in Iran on HPV18 nucleotide changes are rare. This type of virus is prevalent in the Iranian population. Therefore, in the present study, we aimed to identify the genetic variability in HPV18 in the E6 region to evaluate the prevalence of lineage distribution and sublineages in a sample population in Iran. Overall, 60 HPV18 confirmed cases were investigated between 2019 and 2021. The specimens were collected, and molecular genotyping was done using the Linear Array HPV Genotyping Test. DNA extraction was performed by a viral DNA/RNA kit. The HPV E6 gene was amplified by using type-specific primers designed according to the HPV18 genome prototype sequence. The sequencing of the E6 region was successfully done on 43 samples which were then compared to the reference sequence. The most frequent sublineage of HPV18 in this study was A4 (69.7%), followed by A1 (18.6%) and A3 (11.6%). Neither A2 nor A5 sublineage was not detected in this study. The related nucleotide acid changes according to the main references were as follows: A3: T104C/T232G/T485C/C549A, A4: T104C/T485C/C549A. The predominance of A lineage with the high frequency of A4 sublineage was found in the present research. The importance of sublineages in susceptibility to a progressive form of infection requires to be more investigated among the different population.

BACKGROUND: Musculoskeletal disorders (MSDs) are affecting up to 95% of teachers and are considered a primary occupational health hazard leading to absenteeism, early retirement, and lower quality of life and teaching quality. AIM: The current study is aimed at exploring the prevalence and risk factors of MSDs among the schoolteachers in Hail, Saudi Arabia. METHODS: A cross-sectional study was conducted online among the teachers in Hail City using the Nordic Musculoskeletal Questionnaire. Teachers were randomly selected from randomly selected high schools. Teachers with at least 1 year experience were recruited for the study. Descriptive statistics, Cochran's Q test, and binominal regression were used to investigate the prevalence of MSDs among such teachers and to determine if the percentage of MSDs differed by anatomical region and risk factor (one hundred forty-five males and 106 females filled out the questionnaires). RESULTS: The prevalence of MSDs in the last 12 months was 93.63% (235 of 251 teachers). Interestingly, 91% of the affected participants (214 of 235 teachers) complained of MSDs in more than one anatomical region. The most affected site was the lower back (183 of 251 teachers, 72.91%), followed by the shoulders (168 of 251 teachers, 66.93%), and the least affected sites were the elbows (45 of 251 teachers, 17.93%). The females showed a higher prevalence of MSDs than the males. Only gender was a significant risk factor for shoulder and neck MSDs (p < 0.02). CONCLUSION: Overall, the findings of the current study suggest a high prevalence of MSDs among teachers, especially in the lower back and shoulders. The affected teachers should learn more about biomechanics and ergonomics and should engage in exercise to improve their health. Future studies should focus on identifying the biomechanical and ergonomic risk factors of MSDs and on designing MSD prevention programmes to reduce the burden of MSDs.

BACKGROUND: The aim of the current study was to evaluate and compare the influence of Dycal, Lime-Lite, TheraCal LC, Biodentine, resin-modified glass ionomer cement (RMGIC), and Activa BioActive as the pulp capping material on the shear bond strength of resin composite to dentin. METHODS: A total of 70 extracted caries-free molars were randomly assigned to seven groups. Six test groups were covered with various protective liners: Dycal, TheraCal LC, Lime-Lite, Activa BioActive, Biodentine, and RMGIC. The control group received no liner pretreatment. Each sample was bonded to resin composite using the total-etch Tetric N bond adhesive. The samples were then tested for shear bond strength using the universal testing machine at a cross-head speed of 1 mm/min until bond failure occurred. The data were analyzed using the one-way ANOVA test followed by the Tamhane post hoc test for pairwise comparisons of the groups. RESULTS: Independent of the type of the applied liner, all groups exhibited inferior SBS to dentin compared to the control group. TheraCal and RMGIC showed significantly higher shear bond strength than Biodentine and Dycal, which showed the lowest shear bond strength. Lime-Lite and Activa also had significantly lower SBS results than TheraCal. The mode of fracture was predominantly cohesive in Dycal, Biodentine, and TheraCal and adhesive in Activa. CONCLUSION: This present study concludes that the bond strength of resin composite to dentin can be affected differently using various types of liners.

Mandibular bone regeneration is still a big challenge in those diabetic patients with poorly controlled blood glucose. In this study, we prepared a novel glucose-sensitive controlled-release fiber scaffold (PVA-HTCC/PEO-rhBMP2-glucose oxidase (PHPB-G)), which contained the recombinant human bone morphogenetic protein 2 (rhBMP2) by coaxial cospinning and grafted with glucose oxidase (GOD). We presented evidence that PHPB-G could undergo a series of structural changes with the blood glucose and promoted bone regeneration in diabetic rat. PHPB-G expanded the voids in nanofibers when blood glucose levels elevated. More importantly, its slow-release rhBMP2 effectively promoted the healing of bone defects. These data suggested that the PHPB-G delivery system may provide a potential treatment strategy for patients with severe diabetic alveolar bone defects.

BACKGROUND: The Chinese patent drug Yinzhihuang granule (YZHG) is used to treat hepatitis B. This research is aimed at exploring the multicomponent synergistic mechanism of YZHG in the treatment of inflammation-cancer transformation of hepar and at providing new evidence and insights for its clinical application. METHODS: To retrieve the components and targets of Yinzhihuang granules. The differentially expressed genes (DEGs) of hepar inflammation-cancer transformation were obtained from TTD, PharmGKB, and GEO databases. Construct the compound-prediction target network and the key module network using Cytoscape 3.7.1. RESULTS: The results show that hepatitis B and hepatitis C shared a common target, MMP2. CDK1 and TOP2A may play an important role in the treatment with YZHG in hepatitis B inflammatory cancer transformation. KEGG pathway enrichment showed that key genes of modules 1, 2, and 4 were mainly enriched in the progesterone-mediated oocyte maturation signaling pathway and oocyte meiosis signaling pathway. CONCLUSION: The multicomponent, multitarget, and multichannel pharmacological benefits of YZHG in the therapy of inflammation-cancer transition of hepar are directly demonstrated by network pharmacology, providing a scientific basis for its mechanism.

We determined player-to-player distance, body-to-ball contact, and exercise intensity during three training modalities in various football populations. 213 participants were recruited, ranging from 9-year-old boys to young men and 11-year-old girls to middle-aged women. All groups were analysed with video-filming and GPS-based Polar Pro monitors during three types of football training for 20 min, i.e., COVID-19-modified training (CMT) with >2-metre player-to-player distance, small-sided games (SSG), and simulated match-play with normal rules (SMP), in randomised order. Time spent in a danger zone (1.5 m) per-percent-infected-player (DZ PPIP) ranged from 0.015 to 0.279% of playing time. DZ PPIP for SSG was higher (P < 0.05) than CMT and SMP. The average number of contacts (within 1.5 m) with a potentially infected player ranged from 12 to 73 contacts/hour. SSG had more (P < 0.05) contacts than CMT and SMP, with SMP having a higher (P < 0.05) number of contacts than CMT. Time/contact ranged from 0.87 to 3.00 seconds for the groups. No player-to-player and body-to-ball touches were registered for CMT. Total player-to-player contacts were 264% higher (P < 0.05) in SSG than SMP, ranging from 80 to 170 and 25 to 56 touches, respectively. In all groups, a greater total distance was covered during SMP compared to CMT (38-114%; P < 0.05). All groups performed more high-intensity running (33-54%; P < 0.05) and had higher heart rates during SMP compared to CMT. Different types of football training all appear to exert a minor COVID-19 infection risk; however, COVID-19-modified training may be safer than small-sided game training, but also match-play. In contrast, exercise intensity is lower during COVID-19-modified training than match-play.

OBJECTIVE: Multiple emulsions have the ability to incorporate both lipophilic and hydrophilic actives in the same preparation and facilitate permeation of active ingredients through skin. The current study was aimed at formulating niacinamide/ferulic acid-loaded stable multiple emulsion (MNF) and its in vitro/in vivo characterization as a cosmeceutical product. METHODS: Both the compounds were evaluated for their radical scavenging potential by the DPPH method and FTIR analysis. Then, placebo and active formulations were prepared using a double emulsification method and were investigated for stability testing (changes in color, odor, and liquefaction on centrifugation, pH, and globule size) for a period of three months. Afterwards, MNF was investigated for in vitro sun protection factor, rheological studies, entrapment efficiency, zeta potential, zeta size, and ex vivo permeation. Moreover, after ensuring the hypoallergenicity and safety, it was also checked for its cosmeceutical effects on human skin using noninvasive biophysical probes in comparison with placebo. RESULTS: Results demonstrated that MNF showed a non-Newtonian behavior rheologically and both MNF and placebo were stable at different storage conditions. Entrapment efficiency, zeta potential, and zeta size were 93.3%, -5.88 mV, and 0.173 μm, respectively. Moreover, melanin, sebum, and skin erythema were significantly reduced while skin elasticity and hydration were improved. CONCLUSION: It is evident that niacinamide and ferulic acid can be successfully incorporated in a stable multiple emulsion which has potent cosmeceutical effects on human skin.

BACKGROUND: Ankylosing spondylitis (AS) is a rheumatism that mainly affects the axial bones and joints. Xinfeng capsule (XFC) is a preparation with a remarkable clinical effect that is used in our hospital. And it has definite curative effect and less side effects in the treatment of AS. OBJECTIVE: Data mining and network pharmacology were used to analyze the efficacy of Chinese medicine Xinfeng capsule on treating the hypercoagulable state of ankylosing spondylitis and the underlying mechanism behind it. METHODS: Clinical data were collected and compiled from the Department of Rheumatology and Immunology of the First Affiliated Hospital of Anhui University of Chinese Medicine. Cluster analysis was used to investigate herbs that frequently used to treat AS, Apriori module was used to analyze the association rules between herbs and laboratory indexes, and the random walk model was used to reveal the therapeutic efficacy of XFC against AS. The TCMSP database was used to acquire the active components and targets of XFC, and the GeneCards and OMIM database were used to obtain the targets of AS. Afterward, an active ingredient-target network was established and core targets were screened for; overlapping targets were screened for the protein-protein interaction (PPI) network analysis, the Gene Ontology (GO) enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Molecular docking was adopted to investigate the interactions between main active components and core targets. RESULTS: Frequently used herbs could be divided into three groups, and according to the analysis of Apriori module, there is a strong correlation between XFC and the improvement of ESR and hs-CRP, and the results of the random walk model demonstrated that the effect of XFC on improving PLT, ESR, and hs-CRP was superior to the use of traditional Chinese medicine alone. In total, 103 active compounds of XFC and 59 overlapping targets were obtained. The PPI relationships were obtained through the STRING database, and 13 core targets were identified. 1786 GO enrichment results and 205 KEGG enrichment results were obtained, including NF-kappa B signaling pathway, TNF signaling pathway, and IL17 signaling pathway. The outcomes of molecular docking revealed a close relationship between the active compounds of XFC and core targets. CONCLUSION: This study demonstrated that XFC can effectively improve the hypercoagulable state and the inflammatory indices of AS patients through data mining, and it has a strong correlation with the clinical improvement of inflammation. The active compounds of formononetin, triptolide, quercetin, and kaempferol may be the key active components of XFC in regulating AS, possibly through inhibiting the activation of NF-kappa B signaling pathway to improve hypercoagulable state.

Development of large, clinically sized tissue constructs with efficient mass transport is a tremendous need in tissue engineering. One major challenge in large tissue-engineered constructs is to support homogeneous delivery of oxygen and nutrients throughout the tissue scaffold while eliminating induced hypoxic regions in depth. To address this goal, we introduced an especial channeled architecture on porous silk-based tissue scaffolds to improve supplying of oxygen to the cells in central regions of the scaffolds. Oxygen gradients were measured and evaluated in three scaffold prototypes, namely, one unchanneled and two channeled scaffolds with different channel diameters (500 μm and 1000 μm). The channels were introduced into the constructs using stainless-steel rods arranged uniformly in stainless-steel mold, a fabrication method that enables precise control over channel diameter and the distance between channels. During 2-week culture of G292 cells, the 1000 μm channeled scaffolds demonstrated higher oxygen concentration at the center compared to 500 μm channeled prototype; however, the oxygen concentration approached the same level around the last days of culture. Nevertheless, homogenous oxygen distribution throughout the 1000 μm channeled constructs and the consequence of higher cell proliferation at day 14 postseeding corroborate the efficient elimination of induced hypoxic regions; and therefore, it holds promise for clinically relevant sized scaffold especially in bone tissue engineering.

Segmental bony defects of the mandible constitute a complete loss of the regional part of the mandible. Although several types of customized three-dimension-printed mandible prostheses (CMPs) have been developed, this technique has yet to be widely used. We used CMP with a pressure-reducing device (PRD) to investigate its clinical applicability. First, we used the finite element analysis (FEA). We designed four models of CMP (P1 to P4), and the result showed that CMP with posterior PRD deployment (P4 group) had the maximum total deformation in the protrusion and right excursion positions, and in clenching and left excursion positions, posterior screws had the minimum von Mises stress. Second, the P4 CMP-PRD was produced using LaserCUSING from titanium alloy (Ti-6Al-4V). The fracture test result revealed that the maximum static pressure that could be withstood was 189 N, and a fatigue test was conducted for 5,000,000 cycles. Third, animal study was conducted on five male 4-month-old Lanyu pigs. Four animals completed the experiment. Two animals had CMP exposure in the oral cavity, but there was no significant inflammation, and one animal had a rear wing fracture. According to a CT scan, the lingual cortex of the mandible crawled along the CMP surface, and a bony front-to-back connection was noted in one animal. A histological examination indicated that CMP was significantly less reactive than control materials (p = 0.0170). Adequate PRD deployment in CMP may solve a challenge associated with CMP, thus promoting its use in clinical practice.

BACKGROUND: Laser speckle flowgraphy (LSFG) can be used to estimate optic nerve blood flow. This study used LSFG to evaluate optic nerve microcirculation in patients with thyroid eye disease (TED). METHODS: This was a retrospective review of patients with active TED who underwent LSFG between October 2020 and June 2021. The mean blur rate (MBR) for different severities of active TED was analyzed by one-way analysis of variance (ANOVA). RESULTS: A total of 30 patients (60 eyes) with a diagnosis of active TED who underwent LSFG were included. The mean age was 49 (range, 33-74) years. Mean best-corrected visual acuity was the worst in the group with sight-threatening active TED (0.29 ± 0.33 logarithm of the minimum angle of resolution, p = 0.01). The MBR-overall was the highest in the group with mild active TED (28.5 ± 2.7), followed by that in the moderate to severe (23.6 ± 3.2), and in the sight-threatening (20.2 ± 4.3) active TED groups (p < 0.001). The MBR-vessel was 57.1, 47.0, and 39.3 in the mild, moderate to severe, and sight-threatening active TED groups, respectively (p < 0.001). The MBR-tissue was 16.9, 14.4, and 12.0 in the mild, moderate to severe, and sight-threatening active TED groups, respectively (p < 0.001). CONCLUSIONS: This study demonstrates that optic nerve blood flow is lower with more severe active TED. In addition, LSFG is an effective, objective, and noninvasive method for evaluating the severity of TED.

OBJECTIVE: This study is aimed at evaluating the effect of Chinese traditional Wushu (CTW) on cancer-related fatigue (CRF), sleep quality, and upper limb dysfunction. Data Sources. We searched studies containing randomized controlled trials up to July 2021 in PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang database, and China Biological Medicine on this topic. METHODS: A randomized controlled trial of CTW on major outcome indicators such as CRF, sleep quality, and upper limb dysfunction of breast cancer survivors. Study screening, data extraction, and risk of bias assessment were performed independently by two reviewers. Meta-analysis was conducted with Stata 16.0 software. The quality of the evidence was assessed by the Cochrane Collaboration Risk of Bias (ROB2.0). RESULTS: Eighteen studies met the requirements for meta-analysis (n = 1331). We found that CTW has no obvious effect on improving breast cancer survivors' CRF (SMD = -0.733; P = 0.059; I 2 = 89.3%), but it can effectively improve their sleep quality (WMD = -2.266; P = 0.022; I 2 = 99.2%) and upper limb dysfunction (SMD = 1.262; P ≤ 0.001; I 2 = 88.5%). CONCLUSION: Although more studies on this topic are needed to prove the effectiveness of this method, the results of our review show that CTW is significantly helpful for better sleep and upper limb dysfunction. But the effects on CRF will need to be confirmed further. Implications for Cancer Survivors. In the future intervention process, to verify the effectiveness of CTW on improving CRF for breast cancer survivors, it would be suggested to pay close attention to breast cancer survivors' response to exercise, achieve regular follow-up, strictly conduct the intervention scheme on the premise of ensuring absolute security, and reduce the loss of intervention objects.

BACKGROUND: Inflammation is a frequent phenomenon in the pathogenesis of hepatic disorders leading to fibrosis and cirrhosis. Phytopharmaceuticals developed from traditional medicine can provide effective therapeutic alternatives to conventional medications. Datura stramonium (DS) has reported traditional uses in inflammatory diseases. In this study, we have tried to validate its potential as a source of anti-inflammatory agents. METHODS: Powdered leaf part of DS was extracted using ethyl acetate (EA) to provide the extract (DSL-EA). Lymphocyte and macrophage viability and acute toxicity assays established the safety profile, while nitric oxide (NO) scavenging assay estimated the in vitro anti-inflammatory potential. Noninvasive anti-inflammatory, antidepressant, and antinociceptive activities were monitored using BALB/c mice using low and high doses (150 and 250 mg/kg). Major inflammatory studies were performed on Sprague-Dawley male rats using CCl4-induced liver injury model. Disease induction was initiated by intraperitoneal injections of CCl4 (1 mL/kg of 30% CCl4 in olive oil). The rats were divided into six groups. The anti-inflammatory potential of DSL-EA in low and high doses (150 and 300 mg/kg, respectively) was assessed through hematological, biochemical, liver antioxidant defense, oxidative stress markers, and histological studies as well as the expression of Nrf2 and iNOS. RESULTS: DSL-EA exhibited prominent in vitro NO scavenging (IC50: 7.625 ± 0.51 μg/mL) and in vivo anti-inflammatory activity in paw and anal edema models. In CCl4 model, hematological investigations revealed vasotonic effects. Liver functionality was significantly (P < 0.001 - 0.05) improved in DSL-EA-treated rats. The activity level of endogenous antioxidant enzymes in liver tissues was improved in a manner identical to silymarin. The extract reduced the percent concentration of oxidative stress markers in liver tissues. Furthermore, DSL-EA displayed restorative effects on histological parameters (H and E and Masson's trichrome staining). Immunohistochemistry studies showed marked decline in Nrf2 expression, while overexpression of iNOS was also observed in disease control rats. The damage was distinctly reversed by the extract.

OBJECTIVE: To investigate synergic therapeutic effects of combined injection of intralesional mesenchymal stem cells derived from human umbilical cord blood (UCB-MSCs) and polydeoxyribonucleotide (PDRN) combined with microcurrent therapy (MIC) on full thickness rotator cuff tendon tear (FTRCTT) in rabbit models. METHODS: Thirty-two rabbit models were assigned to 4 different groups. FTRCTT in the supraspinatus tendon was created. After 6 weeks, 4 types of procedures (0.2 mL normal saline injection, group 1 (G1-NS); 0.2 mL SC injection, group 2 (G2-MSC); 0.2 mL SC and weekly four injections of 0.2 mL PDRN with sham MIC, group 3 (G3-MSC+PDRN+sham MIC); and 0.2 mL SC and weekly four injections of 0.2 mL PDRN with MIC for four weeks, group 4 (G4-MSC+PDRN+MIC)) were performed in FTRCTT. Gross morphologic and histological changes of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule (PECAM-1) and motion analysis were performed. RESULTS: There was a significant difference in gross morphologic changes between baseline and week 4 posttreatment in group 4 compared to the other three groups (p = 0.01). In groups 3 and 4, all parameters of histochemical and motion analysis have been found to be significantly greater than the ones in groups 1 and 2 (p < 0.05). In group 4, PCNA-, VEGF-, and PECAM-1-stained cells, as well as walking distance, were significantly greater than the ones in group 3 (p < 0.05). CONCLUSION: The treatment with UCB-MSCs and PDRN combined with MIC might be the most effective in rabbit models' traumatic FRTCTT.

BACKGROUND: Parkinson's disease (PD) is a neurological disorder that is marked by the deficit of neurons in the midbrain that changes motor and cognitive function. In the substantia nigra, the selective demise of dopamine-producing neurons was the main cause of this disease. The purpose of this research was to discover genes involved in PD development. METHODS: In this study, the microarray dataset (GSE22491) provided by GEO was used for further analysis. The Limma package under R software was used to examine and assess gene expression and identify DEGs. The DAVID online tool was used to accomplish GO enrichment analysis and KEGG pathway for DEGs. Furthermore, the PPI network of these DEGs was depicted using the STRING database and analyzed through the Cytoscape to identify hub genes. Support vector machine (SVM) classifier was subsequently employed to predict the accuracy of genes. RESULT: PPI network consisted of 264 nodes as well as 502 edges was generated using the DEGs recognized from the Limma package under the R software. Moreover, three genes were identified as hubs: GNB5, GNG11, and ELANE. By using 3-gene combination, SVM found that prediction accuracy of 88% can be achieved. CONCLUSION: According to the findings of the study, the 3 hub genes GNB5, GNG11, and ELANE may be used as PD detection biomarkers. Moreover, the results obtained from SVM with high accuracy can be considered as PD biomarkers in further investigations.

OBJECTIVES: We aimed to identify and classify the Internet of Things (IoT) technologies used for Alzheimer's disease (AD)/dementia as well as the healthcare aspects addressed by these technologies and the outcomes of the IoT interventions. Methodology. We searched PubMed/MEDLINE, IEEE Explore, Web of Science, OVID, Scopus, Embase, Cochrane, and Google Scholar. In total, 13,005 papers were reviewed, 36 of which were finally selected. All the reviews were independently carried out by two researchers. In the case of any disagreement, the problem was resolved by holding a meeting and exchanging views. Due to the diversity of the reviewed studies, narrative analysis was performed. RESULTS: Among the technologies used for the patients including radio frequency identification (RFID), near field communication (NFC), ZigBee, Bluetooth, global positioning system (GPS), sensors, and cameras, the sensors were employed in 36 studies, most of which were switch and vital sign monitoring sensors. The most common aspects of AD/dementia care monitored using these technologies were activities of daily living (ADLs) in 27 studies, followed by sleep patterns and disease diagnosis in 19 and 14 studies, respectively. Sleeping, medication, vital signs, agitation, memory, social interaction, apathy, movement, tracking, and fall were other aspects monitored by IoT. Then, their outcomes were reported. CONCLUSION: Using IoT for AD/dementia provides many opportunities for considering various aspects of this disease. Moreover, the ability to use various technologies for gathering patient-related data provides a comprehensive application for almost all aspects of the patients' care with high accuracy.

OBJECTIVE: This study was designed to determine the antioxidant activity of the extracts of beetroot by using beetroot energy drink and flavored milk (products). Material & Methods. This experimental trial was conducted at Jinnah University for Women, Pakistan, under the approval of local institutional review board number JUW/DFST/RCB010/2020. All the materials such as beetroot, carrot, cucumber, and lemon were obtained commercially from which two products were formulated: beetroot energy drink (sample1) and flavored milk (sample 2). These formulated products were evaluated for quality analysis (pH and brix), phytochemical screening using the Keller-Kiliani test, Salkowski's test, Alkaline reagent test, lead acetate test, ferric chloride test, protein test, quantitative test of phenol, antioxidant activity, sensory analysis, and shelf life study. The paired t-test was applied to detect significant differences between two samples. RESULTS: The phytochemical analysis revealed that cardiac glycosides, phytosterol, flavonoids, and terpenoids were found in both energy booster drink (EBD) and flavored milk (FM) except phenolic compounds that were found only in EBD. The antioxidant capacity of beetroot juice was far greater than FM. The statistical sensorial analysis of FM and EBD reported a significant mean difference between most of the groups with p < 0.0001. CONCLUSION: This study concludes that energy drinks having beetroot indicated higher antioxidant capacity than flavored milk. The nutraceutical products (energy booster drink and flavored milk) containing beetroot are enriched with optimum quantities of proteins and fats and low carbohydrates at a stable pH with an adequate total energy content.

OBJECTIVES: Papillary thyroid carcinoma (PTC) is the most common endocrine system malignant thyroid cancer, and patients with lymph node metastasis typically exhibit poor prognosis. MicroRNAs (miRNAs) can act as either oncogenes or tumor suppressors in PTC. This study was aimed at using PTC transcriptome data obtained from The Cancer Genome Atlas (TCGA) to identify differentially expressed, survival-related miRNAs and target genes. METHODS: We analyzed the TCGA datasets to identify differentially expressed mRNAs/miRNAs in 493 PTC patients with stage I_II group (stages I and II) versus stage III_IV group (stages III and IV) according to TNM staging. The Kaplan-Meier survival analysis, the Cox regression analysis, and the log-rank test were performed to investigate survival-related miRNAs. RESULTS: We identified 36 significantly differentially expressed miRNAs in the stage I_II group versus the stage III_IV group, in which 31 were upregulated and only 5 were downregulated (i.e., hsa-miR-891a-5p, hsa-miR-892a, hsa-miR-888-5p, hsa-miR-891b, and hsa-miR-892b). Additionally, five signature miRNAs (hsa-miR-206, hsa-miR-299-3p, hsa-miR-299-5p, hsa-miR-496, and hsa-miR-509-3-5p) were associated with the overall survival of PTC patients. We also found that LMX1B, whose expression was inversely correlated with hsa-miR-206 expression, was a putative target gene of hsa-miR-206 and LMX1B was likely to serve as a tumor suppressor in PTC. CONCLUSION: hsa-miR-206b might be involved in promoting TNM staging in PTC via targeting of LMX1B.

The microenvironment in the stomach is different from other digestive tracts, mainly because of the secretion of gastric acid and digestive enzymes, bile reflux, special mucus barrier, gastric peristalsis, and so on, which all contribute to the formation of antibacterial environment. Microecological disorders can lead to gastric immune disorders or lead to the decrease of dominant bacteria and the increase of the abundance and virulence of pathogenic microorganisms and then promote the occurrence of diseases. The body performs its immune function through innate and adaptive immunity and maintains microbial balance through the mechanism of immune homeostasis. Microecological imbalance can lead to the invasion of pathogenic microorganisms and damage mucosal barrier and immune system. The coexistence of gastric microorganisms (including viruses and fungi) may play a synergistic or antagonistic role in the pathogenesis of gastric diseases. Probiotics have the ability to compete with intestinal pathogens, increase the secretion of immunoglobulin A (IgA), stimulate the production of mucin, bacteriocin, and lactic acid, regulate the expression and secretion of cytokines, and regulate the growth of microbiota, which all have beneficial effects on the host microbial environment. At present, most studies focused on Helicobacter pylori, ignoring other stomach microbes and the overall stomach microecology. So, in this article, we reviewed advances in human gastric microecology, the relationship between gastric microecology and immunity or gastric diseases, and the treatment of probiotics in gastric diseases, in order to explore new area for further study of gastric microorganisms and treatment of gastric diseases.

BACKGROUND: The association between arterial stiffness and cardiovascular risk in CKD and ESRD patients is well established. However, the relationship between renal function estimation and properties of large arteries is unclear due to the four different methods used to quantify glomerular filtration. This study investigated the relationship between carotid-femoral pulse wave velocity (c-fPWV), as a measure of arterial stiffness, and accepted metrics of renal function. METHODS: This cross-sectional study was conducted in 431 health examination individuals in China, enrolled from January 2017 to June 2019. c-fPWV and blood pressure were measured, and blood samples were obtained for all participants. Four different methods were used to determine the estimated glomerular filtration rate (eGFR) as described by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations: (i) CKD-EPISCr formula based on SCr, (ii) CKD-EPICysC formula based on CysC, (iii) CKD-EPISCr/CysC formula based on Cr and CysC, and (iv) MDRD. RESULTS: Of all of the study participants (average age 53.1 ± 13.0 years, 68.1% male), 23.7% had diabetes mellitus and 66.6% had hypertension. The average eGFR values determined by the CKD-EPISCr, CKD-EPICysC, CKD-EPISCr/CysC, and MDRD equations were 91.9 ± 15.6, 86.8 ± 21.4, 89.6 ± 18.3, and 90.7 ± 16.6 ml/min/1.73m2, respectively. c-fPWV was significantly and negatively correlated with eGFR determined by CKD-EPISCr (r = -0.336, P < 0.001), CKD-EPICysC (r = -0.385, P < 0.001), CKD-EPISCr/CysC (r = -0.378, P < 0.001), and MDRD (r = -0.219, P < .001) equations. After adjusting for confounding factors, c-fPWV remained significantly and negatively correlated with eGFR determined by the CKD-EPICysC equation (β = -0.105, P = 0.042) and significantly and positively correlated with age (β = 0.349, P ≤ 0.01), systolic pressure (β = 0.276, P ≤ 0.01), and hypoglycemic drugs (β = 0.101, P = 0.019). CONCLUSION: In a health examination population in China, c-fPWV is negatively correlated with eGFR determined by four different equations; however, only the metric of eGFR determined by the equation for CKD-EPICysC showed an independent relation with c-fPWV.

While the world continues to grapple with the devastating effects of the SARS-nCoV-2 virus, different scientific groups, including researchers from different parts of the world, are trying to collaborate to discover solutions to prevent the spread of the COVID-19 virus permanently. Henceforth, the current study envisions the analysis of predictive models that employ machine learning techniques and mathematical modeling to mitigate the spread of COVID-19. A systematic literature review (SLR) has been conducted, wherein a search into different databases, viz., PubMed and IEEE Explore, fetched 1178 records initially. From an initial of 1178 records, only 50 articles were analyzed completely. Around (64%) of the studies employed data-driven mathematical models, whereas only (26%) used machine learning models. Hybrid and ARIMA models constituted about (5%) and (3%) of the selected articles. Various Quality Evaluation Metrics (QEM), including accuracy, precision, specificity, sensitivity, Brier-score, F1-score, RMSE, AUC, and prediction and validation cohort, were used to gauge the effectiveness of the studied models. The study also considered the impact of Pfizer-BioNTech (BNT162b2), AstraZeneca (ChAd0x1), and Moderna (mRNA-1273) on Beta (B.1.1.7) and Delta (B.1.617.2) viral variants and the impact of administering booster doses given the evolution of viral variants of the virus.

During the infection and treatment of the SARS-CoV-2 viral infection, age and comorbidities play a major role in the successful management of COVID-19. The nutritional status changes which occur in the body vary with the age and underlying conditions and has a vital role in the functioning of the immune system and cellular membrane integrity, thus minimizing the vulnerability to the infection. Considering the data already published by eminent researchers, a few micronutrients have shown outstanding results as supportive therapies in the treatment of viral infections. Micronutrient like zinc improves the membrane barrier integrity, has anti-inflammatory activity, and is involved in antibody production. Vitamin A supports the phagocytic activity of macrophages, while vitamin C reduces the worsening of respiratory tract infections by restoring the dysfunctional epithelial barrier of the lungs. Vitamin D, vitamin E, selenium, and omega-3 fatty acid metabolites play a major role in immunomodulation and in the inhibition of proinflammatory cytokine production. Magnesium is involved in the synthesis of antibodies, while copper, vitamin B12, and folate have significant effects on immune cells. A few researchers suggest that iron supplementation has reduced the risk of acquiring respiratory tract infections in children. As the age of the patient increases, the need for micronutrients increases, thus leading to an imbalanced nutritional status which in turn increases the risk and fatality of the infections. The use of micronutrients in modulating the inflammatory, immune responses, and the epithelial barrier integrity is explored during the treatment of viral infections for faster recovery.

Schistosomiasis is a neglected disease, as the World Health Organization classified it in the second category after malaria. World Health Organization approved praziquantel (PZQ) as the only chemotherapy to treat schistosomiasis. Over the years, some problems have arisen with PZQ, as it showed poor efficacy in the early stages of infection as well as the emergence of some resistance to it. In searching for new alternative drugs to treat schistosomiasis, the researchers intensified their efforts to find a new drug. The present study focuses on evaluating the effect of three plant extracts Artemisia annua, Nigella sativa, and Allium sativum at different doses of 31.25, 62.5, 125, 250, and, 500 μg/ml; in vitro study was accomplished on the Schistosoma mansoni adult worms. The results declared that the concentration of 500, 250, and 125 of Artemisia annua was more effective on adult worms, and the same concentrations of Nigella sativa and Allium sativum gave less effect on the adult worms than the previous plant. In vivo study was accomplished on the hamster's tissue after exposing it to doses of the plants' extracts with different concentrations; it showed the presence of calcifications and damage to the worm eggs in the liver and spleen, as well as reducing the size of granulomas. After conducting many confirmatory studies Artemisia annua extract can be used as an effective and safe treatment for Schistosoma disease.

The internal thickness of the carotid artery is the vertical distance between the intima of the carotid artery and the middle mold. Its normal thickness is less than 1 mm. It can be used to judge the degree of arteriosclerosis. Under normal circumstances, the change of the internal thickness of the carotid artery is caused by cardiovascular disease. The purpose of this article is to study the relationship between the thickness of the carotid artery and the metabolism of calcium and phosphorus, parathyroid hormone, microinflammatory state, and cardiovascular disease. This article uses ultrasound measurement to measure the IMT of ESRD patients and carotid arteries with normal renal function. The analysis includes blood pressure, blood phosphorus, blood calcium, blood creatinine, blood urea nitrogen, blood sugar, glycosylated hemoglobin, blood lipids, parathyroid hormone, and C reaction. The correlation between clinical indicators includes protein and carotid IMT in ESRD patients which can be used in designing a diagnostic plan for patients through correlation research. The results showed that the carotid artery IMT of ESRD nondialysis patients was 13% thicker than that of those with normal renal function, and it was significantly positively correlated with age, blood pressure, blood phosphorus, glycosylated hemoglobin, and C-reactive protein. The correlation ratio with calcium and phosphorus was about 0.1.

BACKGROUND: Ferroptosis plays a vital role in hepatocellular carcinoma (HCC). CISD1 is known to regulate ferroptosis negatively. However, the correlations of CISD1 to prognosis in HCC and its potential mechanism remain unclear. AIM: To investigate the expression level and prognostic value of CISD1 in HCC. METHODS: Gene expression and clinical data for 33 cancer types in TCGA were downloaded from the UCSC Xena platform. Pan-cancer analysis was performed to determine the expression profile and prognostic value of CISD1 in human cancers. GEO datasets and Human Protein Atlas (HPA) were used to verify the mRNA and protein expression levels. The influence of CISD1 on clinical prognosis in HCC was evaluated using a Kaplan-Meier plotter. The PPI network was constructed using the STRING database and Cytoscape. GO and KEGG pathways were constructed using the "clusterProfiler" R package with the FDR cutoff of 0.05. The methylation at the CISD1 promoter was detected using UALCAN and GEO datasets. The correlations between CISD1 and HCC immune infiltrates were investigated via TIMER. RESULTS: Pan-cancer analysis of TCGA data showed that CISD1 is differentially expressed in multiple tumors. Data of gene expression microarrays reveal that the mRNA expression of CISD1 is higher in HCC than that in normal tissue. The protein level of CISD1, validated by the Human Protein Atlas (HPA) database, was upregulated consistently with mRNA levels in HCC samples. High CISD1 expression was associated with better overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS) in LGG, but with poorer OS, DFS, DSS, and PFS in LIHC. Protein-protein interaction (PPI) analysis and GO/KEGG analysis showed that the PPI network and GO term of CISD1 were mainly associated with energy and iron metabolism. Promoter hypomethylation correlated with overexpression of CISD1. CISD1 expression was positively correlated with infiltrating levels of CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in HCC. CONCLUSIONS: These findings suggest that hypomethylation of the CISD1 promoter increases its expression in HCC. CISD1 is associated with prognosis and immune infiltrating levels of CD8+ T cells, macrophages, neutrophils, and DCs in HCC patients. These findings suggest that CISD1 can be used as a prognostic biomarker for determining prognosis in HCC.

Chronic obstructive pulmonary disease (COPD) is pulmonary emphysema characterized by blockage in the airflow resulting in the long-term breathing problem, hence a major cause of mortality worldwide. Excessive generation of free radicals and the development of chronic inflammation are the major two episodes underlying the pathogenesis of COPD. Currently used drugs targeting these episodes including anti-inflammatory, antioxidants, and corticosteroids are unsafe, require high doses, and pose serious side effects. Nanomaterial-conjugated drugs have shown promising therapeutic potential against different respiratory diseases as they are required in small quantities which lower overall treatment costs and can be effectively targeted to diseased tissue microenvironment hence having minimal side effects. Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) are safe as their breakdown products are easily metabolized in the body. Drugs loaded on the PLGA NPs have been shown to be promising agents as anticancer, antimicrobial, antioxidants, and anti-inflammatory. Surface modification of PLGA NPs can further improve their mechanical properties, drug loading potential, and pharmacological activities. In the present review, we have presented a brief insight into the pathophysiological mechanism underlying COPD and highlighted the role, potential, and current status of PLGA NPs loaded with drugs in the therapy of COPD.

Physiology of orofacial pain pathways embraces primary afferent neurons, pathologic changes in the trigeminal ganglion, brainstem nociceptive neurons, and higher brain function regulating orofacial nociception. The goal of this study was to investigate the nitroxidergic system alteration at brainstem level (spinal trigeminal nucleus), and the role of peripheral P2 purinergic receptors in an experimental mouse model of pediatric inflammatory orofacial pain, to increase knowledge and supply information concerning orofacial pain in children and adolescents, like pediatric dentists and pathologists, as well as oro-maxillo-facial surgeons, may be asked to participate in the treatment of these patients. The experimental animals were treated subcutaneously in the perioral region with pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a P2 receptor antagonist, 30 minutes before formalin injection. The pain-related behavior and the nitroxidergic system alterations in the spinal trigeminal nucleus using immunohistochemistry and western blotting analysis have been evaluated. The local administration of PPADS decreased the face-rubbing activity and the expression of both neuronal and inducible nitric oxide (NO) synthase isoforms in the spinal trigeminal nucleus. These results underline a relationship between orofacial inflammatory pain and nitroxidergic system in the spinal trigeminal nucleus and suggest a role of peripheral P2 receptors in trigeminal pain transmission influencing NO production at central level. In this way, orofacial pain physiology should be elucidated and applied to clinical practice in the future.

OBJECTIVE: To report a nationwide survey of the endoscopic spine surgeons across Thailand. Furthermore, the survey will be focused on the perspective of experience, learning curve, motivations, and obstacles at the beginning of their practices. MATERIALS AND METHODS: The online survey consisting of 16 items was distributed to spine surgeons who are performing endoscopic spine surgery in Thailand via the Google forms web-based questionnaire to investigate participants' demographics, backgrounds, experience in endoscopic spine surgery, motivations, obstacles, and future perspectives. The data was recorded from January 7, 2020 to January 21, 2022. Descriptive statistics were used for analysis. RESULTS: A total of 42 surveys were submitted by 6 neurosurgeons (14.3%) and 36 orthopedic surgeons (85.7%). From the surgeons' perspective, the average number of cases that should be performed until one feels confident, consistently good outcomes, and has minimal complications was 27.44 ± 32.46 cases. For surgeons who starting the endoscopic spine practice, at least 3 workshop participation is needed. Personal interest (39 selected responses) and trending marketing or business purpose (25 selected responses) were the primary motivators for endoscopic spine surgery implementation. Lack of support (18 selected responses) and afraid of complications (16 selected responses) were pertinent obstacles to endoscopic spine surgery implementation. CONCLUSIONS: The trend of endoscopic spine surgery has continued to grow in Thailand, shown by the rate of implementation of endoscopic spine surgery reported by Thai spine surgeons. The number of appropriate cases until one feels confident was around 28 cases. The primary motivator and obstacles were personal interest and lack of support.

OBJECTIVE: To analyze the potential risk factors that affect the development of urosepsis following uroscopic minimally invasive lithotripsy and to develop a nomogram that predicts the probability of postoperative urosepsis. METHODS: We retrospectively analyzed the clinical data from patients that underwent percutaneous nephrolithotripsy (PCNL) or ureteroscopic lithotripsy (URL) between January 2018 and December 2019. The enrolled patients were grouped twice according to systemic inflammatory response syndrome (SIRS) and quick sequential organ failure assessment (qSOFA). After univariate and multivariate logistic regression analyses, we identified the independent predictive factors affecting the development of postoperative SIRS and urosepsis, and built the nomograms. RESULTS: From January 2018 to December 2019, 1959 patients underwent PCNL or URL, of whom 236 patients were accorded with the inclusion criteria. Of all 236 patients, 64 (27.12%) patients developed postoperative SIRS, and 17 (7.20%) patients developed postoperative urosepsis. Multivariate logistic regression analysis showed that positive preoperative urine culture (PUC+) (OR = 2.331, P = 0.044), procalcitonin (PCT) (OR = 1.093, P = 0.037), C-reactive protein (CRP) (OR = 1.017, P < 0.001), and neutrophil ratio (NEUT%) (OR = 1.091, P = 0.004) of postoperative were independent predictors of SIRS, and PCT (OR = 1.017, P = 0.003) and CRP (OR = 1.080, P < 0.001) were independent predictors of urosepsis. Additionally, the nomograms demonstrated good accuracy in predicting SIRS and urosepsis with a C-index of 0.884 (95% CI: 0.835-0.934) and 0.941 (95% CI: 0.885-0.996), respectively. CONCLUSIONS: The nomograms achieved the prediction of SIRS and urosepsis after uroscopic minimally invasive lithotripsy. Using this model, the risk of SIRS or urosepsis for an individual patient can be determined, which facilitates early diagnosis and rational treatment.

BACKGROUND: Nurses are one of the population groups with the highest prevalence of musculoskeletal disorders (MSDs). Preventive measures in Vietnamese hospitals on the job have not been proposed to study their effectiveness due to barriers related to the lack of knowledge about MSDs by health care administrators and the lack of human resources with expertise in MSD management in hospitals. OBJECTIVES: This study is aimed at evaluating the effectiveness of basic interventions (education, physical exercise) to prevent MSDs among district hospital nurses in Vietnam. Material and Methods. A quasi-experimental study was carried out before/after over a period of one year among two groups of nurses, one receiving the intervention (n = 162) and the other the control group (n = 128). The intervention includes 3 components: training on MSDs, ergonomics training, and instructions for physical exercise. The pre- and postintervention assessment tools included the Modified Nordic, Quality of Life Enjoyment and Satisfaction Short-Form (Q-LES-Q-SF), and the Kessler Psychological Distress Questionnaire (K6). A generalized estimating equation analysis was performed to assess the difference between the two groups at two points in time (before and after the intervention) on some indicators (prevalence of MSDs in the last 12 months and 7 days, score for quality of life and psychological distress). RESULTS: There was a significant difference of the test on the prevalence of MSDs in the last 7 days between the 2 groups before and after the intervention with the p value = 0.016. This difference occurred in 4 anatomical sites: neck, shoulder/upper arm, wrists/hand, and lower back, with p values being 0.013, 0.011, 0.038, and 0.009, respectively. CONCLUSIONS: The intervention measures are probably effective in reducing the prevalence of MSDs at 4 anatomical sites in the last 7 days. More in-depth studies are needed with a combination of measures over a longer period of time to obtain stronger evidence of interventions.

Whole-genome sequencing (WGS) data of a bacterial strain IITK SM2 isolated from an aquifer located in the middle Indo-Gangetic plain is reported here, along with its physiological, morphological, biochemical, and redox-transformation characteristics in the presence of dissolved arsenic (As). The aquifer exhibits oxidizing conditions relative to As speciation. Analyses based on 16S rRNA and recN sequences indicate that IITK SM2 was clustered with C. youngae NCTC 13708T and C. pasteuri NCTC UMH17T. However, WGS analyses using the digital DNA-DNA hybridization and Rapid Annotations using Subsystems Technology suggest that IITK SM2 belongs to a strain of C. youngae. This strain can effectively reduce As(V) to As(III) but cannot oxidize As(III) to As(V). It exhibited high resistance to As(V) [32,000 mg L-1] and As(III) [1,100 mg L-1], along with certain other heavy metals typically found in contaminated groundwater. WGS analysis also indicates the presence of As-metabolizing genes such as arsC, arsB, arsA, arsD, arsR, and arsH in this strain. Although these genes have been identified in several As(V)-reducers, the clustering of these genes in the forms of arsACBADR, arsCBRH, and an independent arsC gene has not been observed in any other Citrobacter species or other selected As(V)-reducing strains of Enterobacteriaceae family. Moreover, there were differences in the number of genes corresponding to membrane transporters, virulence and defense, motility, protein metabolism, phages, prophages, and transposable elements in IITK SM2 when compared to other strains. This genomic dataset will facilitate subsequent molecular and biochemical analyses of strain IITK SM2 to identify the reasons for high arsenic resistance in Citrobacter youngae and understand its role in As mobilization in middle Indo-Gangetic plain aquifers.

Neuroendocrine neoplasms (NENs) constitute about 2% of all malignant neoplasms, and the angiogenesis process in these tumors is still of a great interest. Vasohibin-1 (VASH-1) is an angiogenesis inhibitor, while vascular endothelial growth factor A (VEGF-A) is one of the main factors promoting vascular formation. The subject of this study was to assess serum concentration of these factors in patients with diagnosed NEN and in control group. Methods. The study group consisted of 120 patients with diagnosed NENs, while the control group consisted of 69 healthy volunteers. The concentrations of VASH-1 and VEGF-A in serum were tested using the ELISA. We also analyzed the association of the concentration of these factors with demographic data (e.g., age and gender), body mass index (BMI), primary tumor location, histological grade, metastasis, clinical staging, selected biochemical parameters and markers of NENs, and information on smoking habits. Results. The mean concentration of VASH-1 was 218.8 ± 359.8 pg/ml in the study group and 973.1 ± 1239.4 pg/ml in the control group, that difference was statistically significant (p < 0.05). In the NEN group, the highest concentration of VASH-1 was in patients with pancreatic NENs in relation to NENs with different location of the primary tumor (p < 0.05). Negative correlation was found between the concentration of VASH-1 and serotonin (r S = -0.19, p < 0.05). No statistically significant differences were observed for VEGF-A (p = 0.658). Conclusions. Patients with NENs showed lower serum level of VASH-1 in comparison to healthy volunteers. The highest level of VASH-1 was observed in tumors localized in pancreas. This might reflect the relevant function of VASH-1 in NENs and requires further evaluation to further knowledge of angiogenesis in NENs. Furthermore, the serum concentration of VEGF-A showed no statistical differences and probably does not have diagnostic value in this group of patients.

AIM: To explore the association between the serum C1q/tumor necrosis factor-related protein 9 (CTRP9) and the formation of coronary collateral circulation in obstructive coronary artery disease (CAD). METHODS: A total of 206 patients who underwent coronary angiography at Beijing Anzhen Hospital and had epicardial arteries with at least 95% stenotic lesion were enrolled. Blood samples were taken after an overnight fasting before the coronary angiography. Serum CTRP9 level was measured using commercial enzyme linked immunosorbent assay (ELISA) kit. The development of coronary collateralization was determined according to the Rentrop classification system. Rentrop score 0-1 was graded as impaired or less-developed coronary collateralization (n = 54) while the Rentrop score 2-3 was defined as well-developed collateralization (n = 152). RESULTS: Serum CTRP9 level was significantly higher in well-developed collateralization and diabetes groups (P < 0.001). To further explore the association between the CTRP9 level and coronary collateralization, the enrolled participants were divided into 3 tertiles according to the serum CTRP9 level. The prevalence of impaired coronary collateralization decreased stepwise with the increasing CTRP9 tertiles (P for trend <0.001). Multivariate regression analysis showed that the serum CTRP9 is independently associated with well-developed collateralization, with an OR (95% CI) of 4.49 (1.75-11.55) and 8.98 (2.75-29.35) in the tertiles 2 and 3, respectively. The following subgroup and receiver-operating characteristic (ROC) analysis also indicated that the diagnostic value of serum CTRP9 level for detecting the formation of collateralization persisted only in nondiabetic participants. Lastly, adding the serum CTRP9 into the baseline model could increase the diagnostic value of established model consisting of relevant factor for the discrimination of well-developed collateralization only in the nondiabetic group (P = 0.046). CONCLUSIONS: Serum CTRP9 reflects well-developed coronary collateralization in nondiabetic patients with obstructive CAD, and CTRP9 level ≥ 1.217 indicated a greater chance to forming well-developed coronary collaterals.

Antibiotic resistance is one of the significant problems globally; there is an increase in resistance with introducing every new class of antibiotics. Further, this has become one of the reasons for arising of new resistance mechanisms in Acinetobacter baumannii. In this study, we have screened natural compounds as a possible inhibitor against the NDM-1 β-lactamase enzyme from A. baumannii using a combination of in silico methods and in vitro evaluation. The database of natural compounds was screened against NDM-1 protein, using Glide docking, followed by QM-polarised ligand docking (QPLD). When the screened hits were validated in vitro, withaferin A and mangiferin had good IC50 values in reducing the activity of NDM-1 enzymes, and their fractional inhibitory concentration index (FICI) was ascertained in combination with imipenem. The withaferin A and mangiferin-NDM-1 docking complexes were analyzed for structural stability by molecular dynamic simulation analysis using GROMACS for 100 ns. The molecular properties of the natural compounds were then calculated using density functional theory (DFT). Withaferin A and mangiferin showed promising inhibitory activity and can be a natural compound candidate inhibitor synergistically used along with carbapenems against NDM-1 producing A. baumannii.

Met proto-oncogene (MET) amplification and tyrosine-protein kinase Met (c-Met) overexpression confer gefitinib resistance in non-small cell lung cancer (NSCLC). The natural product Licochalcone A (Lico A) exhibits a broad range of inhibitory effects against various tumors. However, the effects of Lico A on c-Met signaling and gefitinib resistance in NSCLC remain unclear. In the present study, Lico A efficiently overcame gefitinib-acquired resistance in NSCLC cells by suppressing c-Met signaling. Lico A decreased cell viability and colony formation dose-dependently and impaired in vivo tumorigenesis of gefitinib-resistant HCC827 and PC-9 cells. Furthermore, Lico A induced intrinsic apoptosis and upregulated the protein expression levels of cleaved poly (ADP-ribose) polymerase and cleaved caspase 3. Lico A promoted the interaction between c-Met and E3 ligase c-Casitas B-lineage lymphoma (Cbl), which enhanced c-Cbl-mediated c-Met ubiquitination and degradation. Depletion of c-Cbl compromised Lico A-induced c-Met ubiquitination and its inhibitory efficacy in gefitinib-resistant NSCLC cells. Taken together, the results suggest that Lico A is a promising antitumor agent that might be used to overcome c-Met overexpression-mediated gefitinib resistance in NSCLC cells.

OBJECTIVE: To explore whether Stromal Interaction Molecule-1 (STIM1) participates in the phenotypic transformation of NRK-52E cells under high-calcium microenvironment. MATERIALS AND METHODS: NRK-52E cells were treated with high concentration of calcium. The viability and apoptosis of cells were detected by CCK-8 (cell counting kit-8) and flow cytometry, respectively. The expression changes of phenotypic marker proteins (E-cadherin and OPN) and calcium channel proteins (STIMl and Orai1) in high-calcium environment were detected by western blotting and real-time quantitative polymerase chain reaction. The expression of STIMl protein in NRK-52E cells was upregulated and downregulated by plasmid-STIM1 and plasmid-shRNA-STIMl, respectively. The expressions of phenotypic marker proteins after upregulation or downregulation of STIMl were detected again. Besides, the intracellular calcium concentrations of NRK-52E cells in different treatments were detected by flow cytometry. RESULTS: High-calcium microenvironment can promote the phenotypic transformation and the adhesion of calcium salts in NRK-52E cells and simultaneously suppress the expression of STIMl protein in NRK-52E cells. Downregulation of STIMl protein could also promote the phenotype transformation, while both the gene silence of matrix gla protein (MGP) and overexpression of STIMl showed reverse results. CONCLUSION: STIMl protein plays an important role in promoting phenotypic transformation of NRK-52E cells in high-calcium microenvironment.

OBJECTIVE: The purpose of this study was to compare the perioperative complications and clinical efficacy of patients with cervical spondylosis with spinal cord compression (CSWSCC) with or without MRI T2WIHS (T2-weighted image high signal) by means of propensity matching score grouping. METHODS: We analyzed a single-center data of 913 surgical patients with CSWSCC by propensity matching score in this study, of which 326 patients had preoperative cervical MRI T2WIHS. The patient's general condition and perioperative indicators were collected. The MRI T2WIHS and normal groups were paired 1 : 1 to eliminate selection bias by propensity matching score. Finally, a total of 312 pairs were matched successfully. The results of perioperative complications and other outcome variables were compared between the two groups by Cox function analysis. RESULTS: The postoperative blood loss, operation time, blood transfusion volume, systemic complications, local complications, volume of drainage, abnormal use of antibiotic, length of hospital stay, and JOA (Japanese Orthopaedic Association) improvement rate were analyzed. As the only complication with significant statistical difference, the incidence of IRI (ischemia-reperfusion injury) in patients with MRI T2WIHS was significantly higher. The length of hospital stay was more significantly increased in patients with MRI T2WIHS; on the contrary, the JOA improvement rate decreased significantly. CONCLUSION: This study confirmed that there was no significant difference in the incidence of perioperative complications in CSWSCC patients with or without MRI T2WIHS, except for the IRI. Moreover, the JOA improvement rate of patients without MRI T2WIHS was significantly better, with the length of hospital stay reduced.