BACKGROUND: Bovine rotavirus (BRV) and bovine coronavirus (BCoV) are the most common viral agents in neonatal calf diarrhea and result in serious economic consequences. The aim of the study was to determine the epidemiology of those viruses in randomly selected dairy farms of Addis Ababa. METHODS: A cross-sectional study was conducted from November 2018 to April 2019 using a probability proportional to size (PPS) sampling technique. A total of 110 calves, less than 30 days of age, from 57 dairy herds were involved in the study. Associated factors of herds and calves were collected using semistructured interviews from farm owners and through physical observation of selected calves. Fecal samples were collected and analyzed using the sandwich ELISA method. Data generated from both semistructured interviews and laboratory investigation were analyzed using STATA_MP version 15. RESULTS: From the total 110 calves, 42 (38.18%) had diarrhea during the survey. The prevalence of bovine rotavirus and coronavirus was 3.64% (4/110) and 0.91% (1/110), respectively. Diarrhea, feeding colostrum timing, and sex of the neonatal calves had statistically significant association with bovine rotavirus infection (p < 0.05). All rotavirus-positive neonatal calves were identified in small scale dairy farms and in dairy farms that reported mortality though they lack statistically significant association. Only one coronavirus case was detected among the neonatal calves. The case was identified among small scale herds and in a herd with diarrheal cases. The sex of the coronavirus calf was female, diarrheic, and among 11-20 days old. CONCLUSION: The prevalence of rotavirus and coronavirus infections in neonatal calves was seldom in dairy farms of the study area. Rotavirus was more common than coronavirus, and further studies should be initiated on other (infectious and noninfectious) causes of neonatal calf diarrhea in the area.

Treponemal infections can be blood-borne with great public health consequences. This study is aimed at comparatively describing the five-year (2013-2017) regional epidemiology of treponemal infection using pregnant women in the sentinel survey and apparently healthy blood donors as a proxy for the general population at four sentinel sites in the Volta and Oti Regions of Ghana. We analyzed retrospective data from 17,744 prospective blood donors aged 18 to 58 years and 7,817 pregnant women in a sentinel survey with ages from 15 to 49 years at Hohoe, Ho, Tongu, and Krachi West sentinel sites in the Volta and Oti Regions. Laboratory data extracted include variables such as age, gender, date of blood donation, and Treponema pallidum chromatographic immunoassay results from the blood banks of the four study sites. The five-year treponemal infection rate among the pregnant women in the sentinel survey and prospective blood donors was 0.79% and 2.38%, respectively. Site-specific infection rate for population-based/sentinel survey was 4.6%/1.1%, 2.0%/0.5%, 1.3%/1.1, and 1.2%/0.3% for Hohoe, Ho, Krachi West, and Tongu, respectively. Significant gender disparity in Treponemal infection rate exists with a male preponderance. The regional infection rate in the sentinel survey is lower compared to the general population. Therefore, the use of pregnant women as a proxy for population estimates could underestimate the burden in the study jurisdiction.

OBJECTIVE: To evaluate the effect of the combination of calcium hydroxide (Ca(OH)2) and a novel electrolyzed superoxidized solution at neutral pH, known as OxOral® on Enterococcus faecalis growth in root canals. METHODS: Sixty human teeth were used, from which root canals were infected and randomly divided into the following treatment groups: saline solution, saline solution plus Ca(OH)2, OxOral®, and OxOral® plus Ca(OH)2. RESULTS: A permanent reduction in bacterial growth was observed at days 1, 6, 12, and 18 after OxOral® plus Ca(OH)2 treatment from 4.4 ± 0.074 log10 CFU/mL to 0.0 ± 0.001 log10 CFU/mL. In addition, alkaline conditions maintenance was observed from application time (pH = 12.2 ± 0.033) to 18 d posttreatment (pH = 12.6 ± 0.083). CONCLUSION: The combination of OxOral® and Ca(OH)2 provides an alkaline pH and inhibits E. faecalis growth into the root canals. Our study opens the possibility for further research on the use of OxOral® in endodontic therapy.

The investigation and study of the limbs, especially the human arm, have inspired a wide range of humanoid robots, such as movement and muscle redundancy, as a human motor system. One of the main issues related to musculoskeletal systems is the joint redundancy that causes no unique answer for each angle in return for an arm's end effector's arbitrary trajectory. As a result, there are many architectures like the torques applied to the joints. In this study, an iterative learning controller was applied to control the 3-link musculoskeletal system's motion with 6 muscles. In this controller, the robot's task space was assumed as the feedforward of the controller and muscle space as the controller feedback. In both task and muscle spaces, some noises cause the system to be unstable, so a forgetting factor was used to a convergence task space output in the neighborhood of the desired trajectories. The results show that the controller performance has improved gradually by iterating the learning steps, and the error rate has decreased so that the trajectory passed by the end effector has practically matched the desired trajectory after 1000 iterations.

Sophora viciifolia Hance is an edible plant used in traditional Chinese medicine. Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora viciifolia Hance. Here, we study the analgesic and anti-inflammatory effects, as well as the acute toxicity of sophocarpine from Sophora viciifolia Hance in mice. Sophocarpine (20, 40, and 80 mg/kgbw) significantly prolonged the delay period before a hot plate reaction occurred (all P < 0.05), and the delay before a tail-flick response was induced by a warm bath (P < 0.05; P < 0.01). Sophocarpine (40, 80 mg/kg) resulted in dose-dependent inhibition of the writhing reaction induced by acetic acid in mice (P < 0.05; P < 0.001, respectively). Sophocarpine (80 mg/kg) reduced the total duration of a formalin-induced pain response (P < 0.05). Sophocarpine prolonged the foot-licking latency of mice after the hot plate reaction, and this effect was antagonized by calcium chloride and enhanced by verapamil. Sophocarpine (20, 40, and 80 mg/kg) significantly inhibited xylene-induced ear edema (P < 0.01; P < 0.001; P < 0.001, respectively) and the penetration of acetic acid-induced dye into the peritoneal cavity (P < 0.01; P < 0.01; P < 0.001, respectively). It also reduced the levels of proinflammatory cytokine interleukin (IL)-1β, IL-6, and prostaglandin E2 (P < 0.05, P < 0.01, P < 0.001) and those of serum nitric oxide (P < 0.05). The results of this study suggest that sophocarpine possesses certain analgesic and anti-inflammatory activities, which may be related to calcium and inhibition of the secretion of inflammatory factors.

Autophagy plays an important role in cancer. Many studies have demonstrated that autophagy-related genes (ARGs) can act as a prognostic signature for some cancers, but little has been known in low-grade gliomas (LGG). In our study, we aimed to establish a prognostical model based on ARGs and find prognostic risk-related key genes in LGG. In the present study, a prognostic signature was constructed based on a total of 8 ARGs (MAPK8IP1, EEF2, GRID2, BIRC5, DLC1, NAMPT, GRID1, and TP73). It was revealed that the higher the risk score, the worse was the prognosis. Time-dependent ROC analysis showed that the risk score could precisely predict the prognosis of LGG patients. Additionally, four key genes (TGFβ2, SERPING1, SERPINE1, and TIMP1) were identified and found significantly associated with OS of LGG patients. Besides, they were also discovered to be strongly related to six types of immune cells which infiltrated in LGG tumor. Taken together, the present study demonstrated the promising potential of the ARG risk score formula as an independent factor for LGG prediction. It also provided the autophagy-related signature of prognosis and potential therapeutic targets for the treatment of LGG.

Recently, the translational application of noncoding RNAs is accelerated dramatically. In this regard, discovering therapeutic roles of microRNAs by developing synthetic RNA and vector-based RNA is attracting attention. Here, we studied the effect of BMP2 and miR-424 on the osteogenesis of Wharton's jelly-derived stem cells (WJSCs). For this purpose, human BMP2 and miR-424 DNA codes were cloned in the third generation of lentiviral vectors and then used for HEK-293T cell transfection. Lentiviral plasmids contained miR424, BMP-2, miR424-BMP2, green fluorescent protein (GFP) genes, and helper vectors. The recombinant lentiviral particles transduced the WJSCs, and the osteogenesis was evaluated by real-time PCR, Western blot, Alizarin Red staining, and alkaline phosphatase enzyme activity. According to the results, there was a significant increase in the expression of the BMP2 gene and secretion of Osteocalcin protein in the group of miR424-BMP2. Moreover, the amount of dye deposition in Alizarin Red staining and alkaline phosphatase activity was significantly higher in the mentioned group (p < 0.05). Thus, the current study results clarify the efficacy of gene therapy by miR424-BMP2 vectors for bone tissue engineering. These data could help guide the development of gene therapy-based protocols for bone tissue engineering.

Occupational exposure to the arylamines benzidine and β-naphthylamine increase bladder cancer risk up to 100-fold, making them some of the most powerful human carcinogens. We hypothesize that tumors arising in people with occupational exposures have different patterns of gene expression than histologically similar tumors from people without such exposures. In a case-case study, we compare gene expression in 22 formalin-fixed paraffin-embedded (FFPE) bladder tumors from men with high-level occupational exposure to arylamines to that in 26 FFPE bladder tumors from men without such exposure. Gene expression analysis was performed on the NanoString nCounter system using a PanCancer Progression Panel comprised of 740 cancer progression-related genes and a custom panel of 69 arylamine- and bladder cancer-related genes which were chosen from in vitro studies. Although fold differences were small, there was evidence of differential expression by exposure status for 17 genes from the Progression Panel and 4 genes from the custom panel. In total, 10 genes showed dose-response association at a p < 0.01, of which 4 genes (CD46, NR4A1, BAX, and YWHAZ) passed a false discovery rate (FDR) q value cutoff of 0.05 but were not significant after Bonferroni correction. Overall, we find limited evidence for differentially expressed genes in pathways related to DNA damage signaling and epithelial-to-mesenchymal transition (EMT).

BACKGROUND: A lot of effort is being done in the electronic medical record (EMR) system. However, it has not been implemented and used at the expected scale for maximal effectiveness. There is limited evidence on the factors affecting the utilization of EMR in this particular context, which are critical for targeted strategies. OBJECTIVE: To assess the magnitude and factors affecting the utilization of EMR among health professionals in eastern Ethiopia. METHODS: An institutional-based cross-sectional study was conducted among randomly selected 412 health professionals from Harari and Dire Dawa, eastern Ethiopia, using a pretested self-administered questionnaire. The tool was developed from previous literature, and a pilot survey was done before the actual study. Bivariable and multivariable binary logistic regression were done to assess the relationship between an independent variable with EMR use. Crude and an adjusted odds ratio with a 95% confidence interval were reported. A P value of less than 0.05 was used to declare a statistically significant association. RESULTS: A total of 412 health professionals with a mean age of 29 years (±6.4 years) were included. A total of 229 (55.6%) and 300 (72.8%) of them had good knowledge and attitude towards the EMR, while 279 (67.7%) used the service (54% used it on a daily basis). About 272 (66%) of the respondents reported that they prefer EMRs to paper-based systems. Health professionals with more than five years of experience had two times higher odds of using the service (AOR = 2.22; 95% CI; 1.12-4.42) than early-career workers. Health professionals trained in EMR would use the service more (AOR = 5.88; 95% CI; 2.93-11.88) compared to those who did not take the training. In addition, having good knowledge (AOR = 1.52; 95% CI; 0.92-1.5) and a good attitude towards the EMR system (AOR = 2.4; 95% CI; 1.35-4.31) showed to use EMR as compared to counterparts. CONCLUSIONS: The utilization of EMR was found to be optimal. Age, work experience, knowledge, attitude, and training of professionals were positively associated with the use of the service in their facility.

BACKGROUND: Grave's disease (GD) and Hashimoto's thyroiditis (HT) are autoimmune diseases of the thyroid gland in which genetic predisposition plays a major role in their development. Currently, the role of NLRP3 inflammasome and COX-2 has been documented in many autoimmune diseases. The purpose of the study is to delineate the impact of IL-1β (rs1143634), NLRP3 (rs3806265), and COX-2 (rs2745557) gene polymorphisms in the development of GD and HT. METHODS: A total of 256 newly diagnosed patients with autoimmune thyroid disease (135 patients with HT and 121 GD patients) as case groups and 145 controls were included in the study. RESULTS: Recessive and overdominant models showed a significant association between IL-1β rs1143634 SNP and HT development risk. The frequency of TT genotype and T allele of IL-1β rs1143634 SNP in the control group was significantly higher than the GD group. There was no significant association between NLRP3 rs3806265 polymorphism and HT and GD development. The frequency of GA genotype of COX-2 (rs2745557) in the control group was significantly higher than that in the HT group. There was no significant association between COX-2 rs2745557 genotypic and allelic distribution and GD development risk. The results revealed a significant relationship between some clinical features of HT and GD groups and SNPs studied. CONCLUSION: The results manifest the significant impact of IL-1β rs1143634 and COX-2 (rs2745557) SNPs and HT development and IL-1β rs1143634 SNP on GD occurrence risk. Furthermore, a significant relationship was observed between some clinical features of HT and GD groups and studied SNPs.

BACKGROUND: Aging is a process that biological changes accumulate with time and lead to increasing susceptibility to diseases like cancer. This study is aimed at establishing an aging-related prognostic signature in colon adenocarcinoma (COAD). METHODS: The transcriptome data and clinical variables of COAD patients were downloaded from TCGA database. The genes in GOBP_AGING gene set was used for prognostic evaluation by the univariate and multivariate Cox regression analyses. The model was presented by a nomogram and assessed by the Kaplan-Meier curves and calibration curves. The drug response and gene mutation were also performed to implicate the clinical significance. The GO and KEGG analyses were employed to unravel the potential functional mechanism. RESULTS: The Gene Set Enrichment Analysis result indicates that GOBP_AGING pathway is significantly enriched in COAD samples. Four aging-related genes are finally used to construct the aging-related prognostic signature: FOXM1, PTH1R, KL, and CGAS. The COAD patients with high risk score have much shorter overall survival in both train cohort and test cohort. The nomogram is then assembled to predict 1-year, 3-year, and 5-year survival. Patients with high risk score have elevated infiltrating B cell naïve and attenuated cisplatin sensitivity. The mutation landscape shows that the TTN, FAT4, ZFHX4, APC, and OBSCN gene mutation are different between high risk score patients and low risk score patients. The differentially expressed genes between patients with high score and low score are enriched in B cell receptor signaling pathway. CONCLUSION: We constructed an aging-related signature in COAD patients, which can predict oncological outcome and optimize therapeutic strategy.

BACKGROUND: Tetanus is a bacterial disease caused by the Clostridium tetani, which is a highly fatal, noncommunicable, and toxin-mediated disease. Globally, maternal and neonatal tetanus is a public health problem due to low maternal tetanus toxoid immunization. Ethiopia has the highest neonatal mortality and morbidity related to tetanus due to low tetanus toxoid immunization and the high number of home deliveries. The main objective of this systematic review and meta-analysis was to estimate the pooled coverage of at least two doses of tetanus toxoid immunization, and the pooled effect sizes of associated factors in Ethiopia. METHODS: Primary studies for this review were searched from the PubMed/MEDLINE online, ScienceDirect, Hinari, Google, and Google Scholar databases. Primary articles published from 2010 up to August 30, 2020, were included in this meta-analysis. Data were extracted in Microsoft Excel format and exported to STATA Version 14.0. A random-effects meta-analysis model was used to estimate the pooled coverage of two or more tetanus toxoid immunizations and its associated factors. Heterogeneity was evaluated by the I 2 test. Egger's weighted regression test was used to assess publication bias. RESULTS: We retrieved 212 records; of these, 199 articles were excluded for reasons. Finally, 14 studies were included in this meta-analysis. The pooled estimate of receiving at least two doses of tetanus toxoid immunization coverage in Ethiopia was 52.2% (95% CI: 42.47-61.93, I 2 = 98.4%). Antenatal care (OR = 7.8 (95% CI: 3.2, 19.2), I 2 = 96.3%), media exposure (OR = 8.3 (95% CI: 2.1, 33.3), I 2 = 98.1%), distance from the health facility (OR = 2.64 (95% CI: 1.1, 6.6), I 2 = 94.1%), educational status of women (OR = 4.7 (95% CI: 2.07, 9.56), I 2 = 94.2%), and educational status of husbands (OR = 2.995 (95% CI: 1.194, 7.512), I 2 = 92.5%) were factors significantly associated with receiving at least two doses of tetanus toxoid immunization coverage in Ethiopia. CONCLUSIONS: The coverage of tetanus toxoid immunization among childbearing women was low in Ethiopia. Strengthening maternal health service utilization (antinatal care and institutional delivery) to the nearest health facility even in health posts and empowering education for both women and their husbands is recommended to increase tetanus toxoid immunization coverage in Ethiopia.

There is not a described method to count the core label of c-Fos-positive neurons, avoiding false-positive and false-negative results. The aim of this manuscript is to provide guidelines for a secure and accurate method to calculate a threshold to select which core of c-Fos-positive neurons marked by immunofluorescence has to be scored. A background percentage was calculated by dividing the intensity value (0 to 255) of the core of c-Fos-positive neurons by its surrounding background from the 8-bit images obtained in a previous study. Using the background percentage from 20% up to 98%, raising 2% once for each score, as threshold to choose which core has to be counted, a script was written for the R program to count the number of the c-Fos-positive neurons and the comparison between control and experimental groups. The differences of the average number of the core counted c-Fos-positive neurons between control and experimental groups, at all thresholds studied, showed a rising value related to an increase of the background percentage threshold as well as a decrease of its p value related to an increase of the threshold of background percentage. For the smallest thresholds (high intensity of label), the differences between groups are suppressed (false negative). However, for the biggest thresholds (nonspecific label), these differences are always the same (false positive). Therefore, to avoid the false-negative and the false-positive values, it was chosen as the threshold of 62% the inflection point of the linear regression, which is equally different from the biggest and smallest values of the differences between groups.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). IPMNs are generally associated with high risk of developing malignancy and therefore need to be diagnosed and assessed accurately, once detected. Existing diagnostic methods are inadequate, and identification of efficient biomarker capable of detecting high-risk IPMNs is necessitated. Moreover, the mechanism of development of malignancy in IPMNs is also elusive. METHODS: Gene expression meta-analysis conducted using 12 low-risk IPMN and 23 high-risk IPMN tissue samples. We have also listed all the altered miRNAs and long noncoding RNAs (lncRNAs), identified their target genes, and performed pathway analysis. We further enlisted cyst fluid proteins detected to be altered in high-risk or malignant IPMNs and compared them with fraction of differentially expressed genes secreted into cyst fluid. RESULTS: Our meta-analysis identified 270 upregulated and 161 downregulated genes characteristically altered in high-risk IPMNs. We further identified 61 miRNAs and 14 lncRNAs and their target genes and key pathways contributing towards understanding of the gene regulation during the progression of the disease. Most importantly, we have detected 12 genes altered significantly both in cystic lesions and cyst fluid. CONCLUSION: Our study reports, for the first time, a meta-analysis identifying key changes in gene expression between low-risk and high-risk IPMNs and also explains the regulatory aspect through construction of a miRNA-lncRNA-mRNA interaction network. The 12-gene-signature could function as potential biomarker in cyst fluid for detection of IPMN with a high risk of developing malignancy.

This study is aimed at exploring the potential role of GSDMC in kidney renal clear cell carcinoma (KIRC). We analyzed the expression of GSDMC in 33 types of cancers in TCGA database. The results showed that the expression of GSDMC was upregulated in most cancers. We found a significant association between high expression of GSDMC and shortened patient overall survival, progression-free survival, and disease-specific survival. In vitro experiments have shown that the expression of GSDMC was significantly elevated in KIRC cell lines. Moreover, decreased expression of GSDMC was significantly associated with decreased cell proliferation. In summary, we believe that this study provides valuable data supporting future clinical treatment.

Colorectal cancer (CRC) is one of the most common malignancies of the digestive system. Recent studies have revealed the importance of RNA-binding proteins (RBPs) in tumorigenesis, but their role in CRC remains unclear. The present study systematically analyzed the relationships between RBPs and CRC using data from The Cancer Genome Atlas. We detected 483 differentially expressed RBPs and identified a series of pathways and processes using GO (Gene Ontology) analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Analyzing protein-protein interactions and modules identified the edges and modules of RBPs. Univariate and multivariate Cox regression analyses were then used to construct a prognostic model that included 13 RBPs. Survival analyses indicated that the overall survival (OS) was significantly lower for CRC patients in the high-risk group than for those in the low-risk group, and that high risk scores were associated with poor OS. Finally, we constructed a nomogram that included 13 RBPs for calculating the estimated survival probabilities of CRC patients at 1, 2, and 3 years. Calibration plots indicated good conformity between the predicted and observed outcomes. This study has revealed that the expression of RBPs differs between CRC and normal tissues. A prognostic model based on 13 RBP coding genes has been developed that can provide independent prognoses of CRC.

BACKGROUND AND AIMS: The prevalence, awareness, and treatment of hypertension, along with their sociodemographic, anthropometric, and lifestyle associations, were evaluated in a cross-sectional survey of childbearing age Tunisian women. Adherence to the Dietary Approaches to Stop Hypertension diet score was also assessed for hypertensive versus nonhypertensive women. METHODS AND RESULTS: A total of 1689 nonpregnant women, aged 20-49 years, were randomly sampled a regional (Greater Tunis), two-stage, stratified, cross-sectional cluster survey from March 2009 to January 2010. Data on medical history and sociodemographic characteristics were collected using a questionnaire. The average daily intake of energy and nutrients was computed using a specific Tunisian food composition database. The Dietary Approaches to Stop Hypertension diet score (0 to 10) was assessed by adding the individual scores (0 to 1) of ten nutrient components according to dietary guidelines. The overall prevalence of hypertension was 21.4%. Age, obesity, abdominal fat, parity, and family history were significantly associated with hypertension. The mean Dietary Approaches to Stop Hypertension accordance score was 4.93 for hypertensive women and 4.86 for nonhypertensive women (P = 0.0556). After adjustment for age, energy intake, and all nutritional covariates, no associations were observed between hypertension and Dietary Approaches to Stop Hypertension diet components. CONCLUSION: Though no clear-cut associations between hypertension and environmental or behavioral factors were identified in the study, the association with abdominal obesity and multiparity suggests that interventions aimed at lifestyle modifications to reduce these risk factors could be also useful in the prevention of hypertension.

BACKGROUND: Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model. METHODS: In vivo and in vitro experiments were carried out. LO2 cells were treated with thapsigargin (TG). In vivo, male BALB/c mice were treated with carbon tetrachloride (CCl4, 1 mL/kg) or tunicamycin (TM, 2 mg/kg). Then, the impact of ATF6 or RIP3 silencing on liver injury, hepatocyte necroptosis, and ER stress-related protein expression was examined. RESULTS: TG induced ER stress and necroptosis and ATF6 and RIP3 expression in LO2 cells. The knockdown of ATF6 significantly decreased RIP3 expression (p < 0.05) and increased ER stress and necroptosis. The downregulation of RIP3 significantly reduced necroptosis and ER stress (p < 0.05). Similar results were observed in CCl4 or the TM-induced mouse model. The knockdown of ATF6 significantly decreased CCl4-induced RIP3 expression and increased liver injury, necroptosis, and ER stress in mice livers (p < 0.05). In contrast, the downregulation of RIP3 significantly reduced liver injury, hepatocyte necroptosis, and ER stress. CONCLUSIONS: Hepatocyte ATF6 has multiple roles in acute liver injury. It reduces hepatocyte necroptosis via negative feedback regulation of ER stress. In addition, ATF6 can upregulate the expression of RIP3, which is not helpful to the recovery process. However, downregulating RIP3 reduces hepatocyte necroptosis by promoting the alleviation of ER stress. The findings suggest that RIP3 could be a plausible target for the treatment of liver injury.

BACKGROUND: Patient records' relevance is associated with a variety of needs and objectives. Substantiating the health of patients perpetually and allowing professionals in the medical field to assess both signs and symptoms that fall in a relatively wider temporal point of view and contributions that lead to enhanced diagnoses and treatment are all quintessential of patient records. The advancement of information technology systems has led to the anticipation that development will be put into digitization and electronic means of storing patient records in order to grease their handling. Cape Coast Teaching Hospital (CCTH) is piloting implementation of patient's electronic health record system. The introduction of the electronic health record system known as Lightwave Hospital Information Management System (LHIMS) was to provide a permanent solution to patients' continuity of care. User's acceptance of new information technology is seen to be one of the most challenging issues in information system. This study assesses healthcare providers' (HP') behavioural intention to use LHIMS to attend to clients in Cape Coast Teaching Hospital and other factors influencing it. METHODS: A nonexperimental cross-sectional study was used to obtain information from 84 HP recruited from the various departments and units in CCTH who use LHIMS to attend to clients. The sample size of 90, representing 8% of HP in CCTH, was randomly selected from the various departments and units. However, 84 (indicating 93.3% response rate) of the selected HP were available during the period of the research. RESULTS: Perceived ease of use (PEOU) of LHIMS had the strongest direct effect on perceived usefulness (PU), with a highly significant path coefficient of 0.75. PU had the greatest impact on attitude about HP' behavioural intention to use (BIU) LHIMS to attend to patients' healthcare delivery in CCTH (0.91). This relationship was highly significant at p < 0.001. PEOU did not have a significant direct effect on attitude about LHIMS use, as hypothesized in the original technology acceptance model. However, attitude towards use had a strong significant effect on HP' BIU of LHIMS, with a strong statistically significant path coefficient of 0.98 at p < 0.001. CONCLUSIONS: We conclude that attitude towards use have a significant influence on HP' behavioural intention to use LHIMS to attend to clients in Cape Coast Teaching Hospital.

Attenuating β amyloid- (Aβ-) induced microglial activation is considered to be effective in treating Alzheimer's disease (AD). Berberine (BBR) can reduce microglial activation in Aβ-treated microglial cells; the mechanism, however, is still illusive. Silencing of cytokine signaling factor 1 (SOCS1) is the primary regulator of many cytokines involved in immune reactions, whose upregulation can reverse the activation of microglial cells. Microglia could be activated into two different statuses, classic activated state (M1 state) and alternative activated state (M2 state), and M1 state is harmful, but M2 is beneficial. In the present study, N9 microglial cells were exposed to Aβ to imitate microglial activation in AD. And Western blot and immunocytochemistry were taken to observe inducible nitric oxide synthase (iNOS), Arginase-1 (Arg-1), and SOCS1 expressions, and the enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory and neurotrophic factor release. Compared with the normal cultured control cells, Aβ exposure markedly increased the level of microglial M1 state markers (P < 0.05), including iNOS protein expression, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 releases, and BBR administration upregulated SOSC1 expression and the level of microglial M2 state markers (P < 0.05), such as Arg-1 expression, brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF) releases, downregulating the SOCS1 expression by using siRNA, however, significantly reversed the BBR-induced effects on microglial M1 and M2 state markers and SOCS1 expression (P < 0.05). These findings indicated that BBR can inhibit Aβ-induced microglial activation via modulating the microglial M1/M2 activated state, and SOCS1 mediates the process.

PURPOSE: The femoral anterior bow is an important factor in matching a femoral implant to a femur. However, its morphology in the Chinese population has rarely been reported. In this study, a three-dimensional measurement approach was adopted to provide accurate data. The aim was to supply a reference for designing a long-stemmed femoral prosthesis that is more suitable for Chinese people. METHODS: Computed tomography data were collected from both lower limbs of 96 normal volunteers and reconstructed into a three-dimensional model using Mimics software. The parameters of the femoral anterior bow were measured using medical image analysis software. Statistical analysis was conducted using independent-samples and paired-samples t-tests with SPSS software. RESULTS: All the indexes showed significant sexual difference (P < 0.05). The minimum cross-sectional area of the femoral medullary cavity was larger in men (10.77 ± 1.53 mm) than in women (9.79 ± 1.27 mm). The distance from the position of the maximum curvature to the lower edge of the lesser trochanter was also larger in men (60.93 ± 5.81 mm) than in women (56.31 ± 2.80 mm). However, the curvature of the femoral medullary cavity centerline was larger in women (883.57 ± 249.74 mm) than in men (958.79 ± 266.61 mm). The femoral anterior bow morphological indexes of Chinese subjects were different from the published data for other populations. There were no significant differences between left and right femoral anterior bows in either sex (P > 0.05). CONCLUSION: The three-dimensional measurement approach adopted in this study is more convenient and accurate than previous conventional methods, with high repeatability. The morphological indexes of the femoral anterior bow in this research suggest that population characteristics should be taken into account. This study will provide references for the design of long-stemmed femoral prostheses in the Chinese population.

BACKGROUND: The development of factor VIII (FVIII) inhibitor in patients with hemophilia A (PWHA) is a great challenge for hemophilia care. Both genetic and environmental factors led to complications in PWHA. The development of inhibitory antibodies is usually induced by the immune response. Tumor necrosis factor α (TNF-α), one of the cytokines, might contribute to its polymorphism. In this study, we investigated the clinical factors, level of serum TNF-α, and polymorphism of c.-308G > A TNF - α gene in inhibitor development in severe PWHA. METHODS: A cross-sectional study was conducted among all PWHA in West Java province. The clinical parameters, FVIII, FVIII inhibitor, and serum TNF-α level were assessed. The genotyping of -380G > A TNF-α gene polymorphism was performed using polymerase chain reaction and Sanger sequencing. RESULTS: Among the 258 PWHA, 216 (83.7%) were identified as severe PWHA. The FVIII inhibitor was identified in 90/216 (41.6%) of severe PWHA, consisting of 45 high-titer inhibitors (HTI) and 45 low-titer inhibitors (LTI). There was a significant correlation between serum TNF-α level and the development of HTI (p = 0.043). The cutoff point of serum TNF-α level, which can be used to differentiate between HTI and LTI, was 11.45 pg/mL. The frequency of FVIII replacement therapy was significant only in HTI of severe PWHA regarding serum TNF-α level (p = 0.028). There is no correlation between polymorphisms of -380G > A TNF-α gene and inhibitor development (p = 0.645). CONCLUSIONS: The prevalence of FVIII inhibitor in severe PWHA in West Java, Indonesia, was 41.6%. The frequency of replacement therapy is a risk factor for inhibitor development. Serum TNF-α level might be used to differentiate between high and low inhibitor levels in severe hemophilia A, and this might support decision making regarding treatment options for inhibitor in severe hemophilia A.

BACKGROUND: This study is aimed at exploring the significance of the expression of miR-23a and miR-146a in patients with periodontitis and their correlations with inflammatory factors. METHODS: A total of 120 patients with chronic periodontitis admitted to the department of stomatology in Yantai Yuhuangding Hospital from August 2017 to December 2018 were enrolled as a study group, and 80 healthy volunteers in physical examination during the same period were enrolled as a control group. The expression of miR-23a, miR-146a, interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) in the saliva of people in the two groups was determined using the quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: The study group showed significantly higher relative expression of saliva miR-23a and miR-146a than the control group. The area under the curve (AUC) of saliva miR-23a and miR-146a for diagnosing periodontitis was 0.857 and 0.886, respectively. The expression of saliva miR-23a and miR-146a increased with the deterioration of periodontitis in the patients. After basic treatment, the study group showed significantly decreased expression of saliva miR-23a and miR-146a. Patients in the study group showed significantly higher levels of saliva IL-1β, IL-6, and IL-17 than those in the control group, and their saliva miR-23a and miR-146a were positively correlated with their saliva IL-1β, IL-6, and IL-17, respectively. CONCLUSION: Saliva miR-23a and miR-146a can be used as biomarkers for the diagnosis and assessment of periodontitis, and they may have regulatory relationships with IL-1β, IL-6, and IL-17.

AIM: The aim of our work was to determine the utility of DNM1 as a biomarker for the diagnosis and prognosis of colon cancer (CC). METHODS: DNM1 expression variations in CC vs. normal tissues were investigated using The Cancer Genome Atlas (TCGA) database. The association of DNM1 expression levels with the clinicopathological variables in CC prognosis was investigated using logistic regression analyses. Independent prognostic factors for CC were evaluated using univariate and multivariate Cox regression analyses. The correlation between DNM1 expression and immune cell infiltration was estimated using single-sample Gene Set Enrichment Analysis (ssGSEA). RESULTS: DNM1 expression in CC tissues was significantly higher than that in normal tissues. High DNM1 expression was significantly correlated with M stage, N stage, perineural invasion and lymphatic invasion and predicted poor prognosis. The univariate analysis highlighted that DNM1 was an independent CC risk factor. Results of ssGSEA showed that DNM1 was linked to several cancer-related pathways, including the neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, ECM-receptor interaction, dilated cardiomyopathy, and calcium signaling pathway. Moreover, DNM1 expression was positively correlated with the level of infiltration by Neutrophils, Tregs, NK cells, and Macrophages. CONCLUSION: DNM1 has a significant function and has diagnostic and prognostic potential for CC.

BACKGROUND: Intestinal parasites and Schistosoma mansoni infections adversely affect the health of humans in the world especially in sub-Saharan African countries including Ethiopia. Fishermen who spend most of their time in water bodies are supposed to be at high risk of schistosomiasis and other water-born parasites. However, the magnitude of these parasitic infections and their determinant factors are not well addressed. METHODS: A cross-sectional study was conducted at Lake Tana among 388 fishermen from March to May 2021. Questionnaire data was collected through face to face interview. Stool sample from each participant was processed by the Kato-Katz and spontaneous tube sedimentation techniques. Data were analyzed using SPSS version 26. RESULTS: One hundred sixty four (42.3%) and 88 (22.7%) participants were infected by intestinal parasites and Schistosoma mansoni, respectively. One hundred twenty two (31.4%) and 42 (10.8%) participants were infected by soil-transmitted helminths and intestinal protozoa, respectively. Attending only primary school (AOR = 2.02, p = 0.014) or being illiterate (AOR = 2.54, p = 0.004) and not washing hands before meal (AOR = 2.23, p = 0.007) were significantly associated with intestinal parasitic infections. Illiterate educational status (AOR = 2.37, p = 0.022), fishing by bargee (AOR = 2.43, p = 0.005), fishing ≥4 days per week (AOR = 2.27, p = 0.029), swimming habit (AOR = 3.03, p = 0.030), and participation in irrigation (AOR = 3.09, p ≤ 0.001) predispose fishermen to S. mansoni infection. CONCLUSION: Intestinal parasites and S. mansoni infections are highly prevalent among fishermen at Lake Tana basin. Low education level and frequent water contact predispose fishermen for intestinal parasites and S. mansoni. Therefore, health education to fishermen on intestinal parasites and S. mansoni infection and regular deworming should be advocated.

Brain tumor is a fatal disease, caused by the growth of abnormal cells in the brain tissues. Therefore, early and accurate detection of this disease can save patient's life. This paper proposes a novel framework for the detection of brain tumor using magnetic resonance (MR) images. The framework is based on the fully convolutional neural network (FCNN) and transfer learning techniques. The proposed framework has five stages which are preprocessing, skull stripping, CNN-based tumor segmentation, postprocessing, and transfer learning-based brain tumor binary classification. In preprocessing, the MR images are filtered to eliminate the noise and are improve the contrast. For segmentation of brain tumor images, the proposed CNN architecture is used, and for postprocessing, the global threshold technique is utilized to eliminate small nontumor regions that enhanced segmentation results. In classification, GoogleNet model is employed on three publicly available datasets. The experimental results depict that the proposed method is achieved average accuracies of 96.50%, 97.50%, and 98% for segmentation and 96.49%, 97.31%, and 98.79% for classification of brain tumor on BRATS2018, BRATS2019, and BRATS2020 datasets, respectively. The outcomes demonstrate that the proposed framework is effective and efficient that attained high performance on BRATS2020 dataset than the other two datasets. According to the experimentation results, the proposed framework outperforms other recent studies in the literature. In addition, this research will uphold doctors and clinicians for automatic diagnosis of brain tumor disease.

Polymeric materials from plants continue to be of interest to pharmaceutical scientists as potential binders in immediate release tablets due to availability, sustainability, and constant supply to feed local pharmaceutical industries. Paracetamol tablet formulations were utilized in investigating the potential binding characteristics of pectin harnessed from various okra genotypes (PC1-PC5) in Ghana. The pectin yields from the different genotypes ranged from 6.12 to 18.84%w/w. The pH of extracted pectin ranged from 6.39 to 6.92, and it had good swelling indices and a low moisture content. Pectin extracted from all genotypes were evaluated as binders (10, 15, and 20%w/v) and compared to tragacanth BP. All formulated tablets (F1-F18) passed the weight uniformity, drug content, hardness, and friability tests. Based on their crushing strength, tablets prepared with pectin from the various genotypes were relatively harder (P ≤ 0.05) than tablets prepared with tragacanth BP. Tablets prepared with pectins as binders at 10%w/v and 15%w/v passed the disintegration and dissolution tests with the exception of PC4 at 15%w/v. Incorporation of pectin from all genotypes (excluding PC5) as a binder at concentrations above 15%w/v (F13, F16, F14, and F15) produced tablets which failed the disintegration test and showed poor dissolution profiles. Thus, pectin from these genotypes can be industrially commodified as binders in immediate release tablets using varying concentrations.

BACKGROUND: Cilengitide is a selective α v β 3 and α v β 5 integrin inhibitor. We sought to investigate the effect of cilengitide on the neovascularization of abdominal aortic plaques in rabbits and explore its underlying antiangiogenic mechanism on human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: For the in vivo experiment, the abdominal aortic plaque model of rabbits was established and injected with different doses of cilengitide or saline for 14 consecutive days. Conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) were applied to measure the vascular structure and blood flow parameters. CD31 immunofluorescence staining was performed for examining neovascularization. Relative expressions of vascular endothelial growth factor (VEGF) and integrin of the plaque were determined. For in vitro experiments, HUVECs were tested for proliferation, migration, apoptosis, and tube formation in the presence of different doses of cilengitide. Relative expressions of VEGF, integrin, and Ras/ERK/AKT signaling pathways were determined for the exploration of underlying mechanism. RESULTS: CEUS showed modestly increased size and eccentricity index (EI) of plaques in the control group. Different degrees of reduced size and EI of plaques were observed in two cilengitide treatment groups. The expressions of VEGF and integrin in the plaque were inhibited after 14 days of cilengitide treatment. The neovascularization and apoptosis of the abdominal aorta were also significantly alleviated by cilengitide treatment. For in vitro experiments, cilengitide treatment was found to inhibit the proliferation, migration, and tube formation of HUVECs. However, cilengitide did not induce the apoptosis of HUVECs. A higher dose of cilengitide inhibited the mRNA expression of VEGF-A, β 3, and β 5, but not α V. Lastly, cilengitide treatment significantly inhibited the Ras/ERK/AKT pathway in the HUVECs. Conclusions. This study showed that cilengitide effectively inhibited the growth of plaque size by inhibiting the angiogenesis of the abdominal aortic plaques and blocking the VEGF-mediated angiogenic effect on HUVECs.

OBJECTIVE: To study the effects of dexmedetomidine in combination with ropivacaine in patients undergoing craniocerebral surgery and their efficiency on cognitive function and inflammatory response of patients. METHODS: 100 patients undergoing craniocerebral surgery in our hospital from November 2018 to September 2020 were randomly selected and divided into a control group and an experimental group by drawing lots, with 50 cases in each group. Patients in the control group received routine anesthesia, while those in the experimental group received 1 μg/kg of dexmedetomidine combined with 0.5% of ropivacaine for anesthesia to compare the anesthesia onset time, analgesic time, postoperative awake time, Social Disability Screening Schedule (SDSS) cognitive function score after waking, visual analogue scale (VAS) pain score, Ramsay sedation score, incidence of adverse reactions, postoperative inflammatory factor expression levels, and changes in heart rate, oxygen saturation, and blood pressure at T0, T1, T2, T3, and T4 between the two groups. RESULTS: The anesthesia onset time, SDSS cognitive function score after waking, VAS pain score, Ramsay sedation score, incidence of adverse reactions, and postoperative inflammatory factor expression levels in the experimental group were significantly lower than those in the control group (P < 0.05). The analgesic time and postoperative awake time in the experimental group were significantly longer than those in the control group, with statistical significance (P < 0.05). There were no statistically significant differences in the changes of heart rate, oxygen saturation, and blood pressure at T0, T1, T2, T3, and T4 between the two groups (P > 0.05). CONCLUSION: Dexmedetomidine combined with ropivacaine has high application value in craniocerebral surgery.

Studies have shown that COX-2 expression is upregulated in gastric cancer (GC) as well as in precancerous lesions and in Helicobacter pylori-induced inflammation, suggesting that cyclooxygenase-2 (COX-2) may play an important role in gastric carcinogenesis. We attempted to investigate the role of clarithromycin with tinidazole on Helicobacter pylori-related gastritis from the aspects of clinical effect and COX-2 expression. From January 2016 to January 2019, 130 patients with Helicobacter pylori-related chronic gastritis were collected and grouped into the observation group (OG) and the control group (CG). Altogether, 80 patients in the OG were treated with clarithromycin with tinidazole, while 50 patients in the CG were treated with amoxicillin with metronidazole. Clinical symptom improvement time, content of COX-2 and B cell lymphoma-2 (BCL-2), content of inflammatory factors interleukin-1 (IL-1), IL-4, and C-reactive protein (CRP), expression level of nutritional indicators serum albumin (ALB), realbumin (PA), and transferrin (TF), clearance of Helicobacter pylori, total effective rate, and incidence of adverse reactions were detected. Compared with the CG, the OG had shorter clinical symptom improvement time, lower COX-2 and Bcl-2, lower expression of inflammatory factors IL-1, IL-4, and CRP, higher expression of nutritional indicators ALB, TF, and PA, higher clearance rate of Helicobacter pylori, higher total effective rate, and lower incidence of adverse reactions. Clarithromycin combined with tinidazole can effectively improve the clinical effect of Helicobacter pylori-related gastritis and reduce the expression level of COX-2.

BACKGROUND: Anemia constitutes a major public health concern, which is associated with maternal and perinatal mortality. In low- and middle-income countries, the burden of anemia is profoundly high. Cameroon, as one of the low- and middle-income countries, has a disproportionate anemia burden. Factors associated with anemia prevalence are largely unknown in Cameroon. Hence, we determined the prevalence of anemia and its individual/household and community-level factors among adult women in Cameroon. METHODS: We derived data from the 2018 Cameroon Demographic and Health Survey for analysis in this study. Using the Stata version 14 software, univariate multilevel logistic regression analysis was used to select variables that had significant association with anemia at p < 0.05. Statistically significant variables were included in a multivariable multilevel logistic regression modelling to examine their associations with anemia. Results were reported using adjusted odds ratios (AOR) with their respective 95% confidence interval (CI). RESULTS: A total of 6,809 women aged 15-49 years were involved in this study with a mean age 30 ± 11.87 years. Approximately two-fifths of women were anemic. Of them, 0.8% were severely anemic, while 17.4% and 21.5% were moderately and mildly anemic, respectively. Current employment status (yes AOR = 0.77, 95% CI; 0.61-0.96) and parity (1-2 children AOR = 0.61, 95% CI; 0.44-0.86) were the main individual level factors associated with anemia, whereas region (Douala region AOR = 2.65, 95% CI; 1.61-4.36, North-West region AOR = 0.53, 95% CI; 0.28-0.99) was the community-level factor associated with anaemia. CONCLUSION: Empowerment of women through employment opportunities as well as focusing special attention in region where high prevalence of anemia could be crucial to decrease the burden of anemia and related maternal and perinatal mortality in the country.

PURPOSE: Recurrent miscarriage applies to pregnancy loss expulsion of the fetus within the first 24 weeks of pregnancy. This study is aimed at comparatively investigating the sera of women with RM with those who have no record of miscarriages to identify if there were any metabolite and metabolic pathway differences using 1H NMR spectroscopy. METHODS: Serum samples were collected from women with RM (n = 30) and those who had no records of RM (n = 30) to obtain metabolomics information. 1H NMR spectroscopy was carried out on the samples using Carr Purcell Meiboom Gill spin echo; also, Partial Least Squares Discriminant Analysis was performed in MATLAB software using the ProMetab program to obtain the classifying chemical shifts; the metabolites were identified by using the Human Metabolome Database (HMDB) in both the experimental and control groups. The pathway analysis option of the Metaboanalyst.ca website was used to identify the changed metabolic pathways. RESULTS: The results of the study revealed that 14 metabolites were different in the patients with RM. Moreover, the pathway analysis showed that taurine and hypotaurine metabolism along with phenylalanine, tyrosine, and tryptophan biosynthesis was significantly different in patients with RM. CONCLUSION: The present study proposes that any alteration in the above metabolic pathways might lead to metabolic dysfunctions which may result in a higher probability of RM.

INTRODUCTION: The function of the masticatory apparatus is complete when the dentition is intact with contact between the individual teeth and proper occlusion with the antagonists. For years, occlusal contacts have been studied to determine their exact location and describing various materials and methods for their registration such as paper foil, silk, and Shimstock foil. For years, occlusal contacts have been studied to determine their exact location and describe various materials and methods for their registration such as paper foil, silk, shim stock foil, the T-Scan system, and more recently the OccluSense system. The primary aim of the study was at evaluating which of the occlusal indicators is the most commonly used in practice, and the secondary aim was whether dentists are willing to use digital methods to examine occlusion. MATERIALS AND METHODS: The main primary information of the survey was collected by sending electronically anonymous questionnaires to 2014 dentists, randomly selected from all regions of the country. 228 questionnaires were filled in and returned. To achieve the goal of the study, the self-developed questionnaire was created and tested to survey the opinion about the use of occlusal indicators in dental practice. Each questionnaire contains questions about the sociodemographic and professional status of the people in the group and their opinion about the positives and negatives and the effectiveness of occlusal indicators. RESULTS: The obtained results confirm the statement that the most frequently used occlusal indicator in dental practice is the articulation paper. Articulation foil and silk are used less frequently than articulation paper. Of the listed quality indicators, Shimstock foil is rarely used in practice. Of the indicated quantitative indicators, the T-Scan system is more used than the OccluSense system. In the era of rapid technology development, the opinion and desire of dentists to increasingly want to introduce in their clinical practice quantitative methods are the digital diagnosis of occlusion. CONCLUSION: In any dental practice, if technically possible, digital methods would be used, giving more accurate and reliable data on the registered occlusal contacts.

In pulmonary arterial hypertension (PAH), microRNAs (miRNAs) are related with dysfunction of pulmonary arterial endothelial cells. miR-1226-3p was found to be downregulated in the serum of PAH patients, while few studies have illustrated the regulation mechanism of miR-1226-3p on PAH. In this study, we aimed to systematically investigate the role of miR-1226-3p in PAH. Sprague-Dawley (SD) rats were treated with monocrotaline (MCT) to establish the PAH models. The right ventricular systolic pressure (RVSP), ratio of the right ventricle to the left ventricle with septum (RV/(LV+S) ratio), and nitric oxide (NO) content were used to reflect the symptom of the rats. The rat models were used to observe the regulation mechanism of miR-1226-3p on PAH, and dual-luciferase reporter assay was used to verify the binding effect of miR-1226-3p to Pfn1. Besides, the qRT-PCR and western blot were used to measure the expression levels of miR-1226-3p and some keys proteins such as eNOS and Pfn1, respectively. The results showed that the PAH models were established successfully. The RVSP levels and the RV/(LV+S) ratio of the PAH rats were higher than those indexes in normal rats, while the NO content showed the opposite trends. Besides, the decreased miR-1226-3p and eNOS were, respectively, found in the PAH rats and rPAECs, and overexpressed miR-1226-3p could reverse the disadvantages of the PAH rats including increased RVSP, high RV/(LV+S) ratio, and decreased NO content. Furthermore, miR-1226-3p could directly target the 3'-UTR of Profilin-1 (Pfn1). Overexpressed Pfn1 led to decreased eNOS, while miR-1226-3p could partly inhibit the expression of Pfn1 and increase the expression level of eNOS in rPAECs. In summary, this study suggests miR-1226-3p as a protector to increase eNOS, improve NO content in rPAECs of the PAH rats via targeting Pfn, and finally protect the rats from the injury induced by PAH.

BACKGROUND: Currently, immunotherapy is widely used for breast cancer (BC) patients, and tumor mutation burden (TMB) is regarded as a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in BC are not fully understood. METHODS: Comprehensive bioinformatic analyses were performed using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Survival curves were analyzed via Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used for prognosis analysis. Gene set enrichment analysis (GSEA) was performed to explore regulatory mechanisms and functions. The CIBERSORT algorithm was used to calculate the tumor-infiltrating immune cell fractions. RESULTS: We analyzed somatic mutation data of BC from TCGA and ICGC datasets and found that 19 frequently mutated genes were reported in both cohorts, namely, SPTA1, TTN, MUC17, MAP3K1, CDH1, FAT3, SYNE1, FLG, HMCN1, RYR2 (ryanodine receptor 2), GATA3, MUC4, PIK3CA, KMT2C, TP53, PTEN, ZFHX4, MUC16, and USH2A. Among them, we observed that RYR2 mutation was significantly associated with higher TMB and better clinical prognosis. Moreover, GSEA revealed that RYR2 mutation-enriched signaling pathways were related to immune-associated pathways. Furthermore, based on the CIBERSORT algorithm, we found that RYR2 mutation enhanced the antitumor immune response by enriching CD8+ T cells, activated memory CD4+ T cells, and M1 macrophages. CONCLUSION: RYR2 is frequently mutated in BC, and its mutation is related to increased TMB and promotes antitumor immunity; thus, RYR2 may serve as a valuable biomarker to predict the immune response.

Circular RNAs (circRNAs), a novel type of noncoding RNAs, have been demonstrated to behave as microRNA (miRNA) sponges to exert their effects during pathological processes of diseases. However, the roles of circRNAs have not been explored in necrotizing enterocolitis (NEC). This study sought to identify differentially expressed circRNAs and predict their potential biological functions in NEC. circRNA expression profiles in terminal ileum from newborn rats with NEC and normal controls were explored using next-generation sequencing. In the NEC group, 53 circRNAs were significantly differentially expressed, including 9 upregulated and 44 downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted, and circRNA-miRNA interaction networks were generated to predict the potential roles of circRNAs in NEC progression. Further investigation revealed that most circRNAs include miRNA binding sites and that some are implicated in NEC development. In conclusion, this study's findings demonstrate that differentially expressed circRNAs are involved in NEC development via their interactions with miRNAs, making them prospective targets for NEC diagnosis and treatment.

To evaluate the association between dentists' profile and health work management with the performance of primary care dental teams in the Brazilian National Health System, both nationally and regionally. Secondary data analysis from a Brazilian National Programme that evaluated 18,114 Brazilian dental teams, working in the public sector, between 2013 and 2014. Twenty-four independent variables taken from dentists' profile and dental team management characteristics were analysed to assess their influence on reported "dental team performance." An estimated score was generated from their performance on 20 dental procedures by an item response theory model. Multiple linear regression models were performed for each Brazilian geographical region, separately and for the whole of Brazil. p values ≤ 0.05 were considered significant. Two variables related to dentists' profile, "having graduate studies" (β = 0.151) and "undertaking continuing professional development training" (β = 0.101), were associated with enhanced dental team performance in all five Brazilian geographical regions and nationally. The dental team management variables of "having a flexible dental appointment list" (β = 0.218) and "monitoring oral health indicators" (β = 0.132) also contributed to improve team performance in each of the regions and nationally. Dentists' profile influenced the performance of dental teams from south region more than the other regions. The findings suggest that continuing professional development, including postgraduate education, and strategic management characteristics are important for primary dental care performance and should be reflected in health policy initiatives in support of quality care. Regional factors could be considered for health care management.

BACKGROUND: Orthodontists use mini-implants temporarily as an effective mode of skeletal anchorage devices. The placement of mini-implants can cause pain and discomfort to the patients. Patients often develop swelling, and the pain could interfere with their daily activities. Practitioners tend to prescribe antibiotics and pain medication for management. OBJECTIVES: The main objectives of this study are to evaluate the pain perception and discomfort due to mini-implant placement experienced by the patient and evaluate the interventions for pain management commonly practiced among orthodontists. MATERIALS AND METHODS: The study was designed as a questionnaire-based cross-sectional study. A total of 271 patients were assessed, for whom 625 mini-implants (ranging from 1.2 to 2 mm diameter and length 8-14 mm) were placed. Pain scores were assessed using the VAS and the "Faces" pain rating scale to collect data about discomfort in daily activity and function. Data was collected from 244 patients. A total of 155 orthodontists were questioned regarding the prescription of medications and the interventions for managing pain and adverse effects. RESULTS: Average pain score among female subjects was 16.71 and among men was 13.5. The highest pain scores were recorded for palatal mini-implants with an average score of 36.29 and the least for interradicular mini-implants with an average score of 9.02. Among the subjects, 47.9% of them took analgesics, and the most commonly prescribed analgesics were paracetamol (39%). Swelling at the site is where the mini-implants were placed, and ulceration due to implants were commonly dealt with the excision of the surrounding soft tissue, composite placement, and palliative care with oral analgesic gels. CONCLUSION: Female subjects had more mini-implants placed, and female subjects had also given more pain scores than their male counterparts. Palatal mini-implants caused the highest pain, followed by mini-implants placed at the infrazygomatic crest and the buccal shelf region. Palatal mini-implants caused maximum discomfort during speech and eating, followed by the mini-implant in the buccal shelf and the infrazygomatic crest region that also caused difficulty in yawning and laughing. Infiltration anesthesia was commonly given for the placement of interradicular implants and extra-alveolar mini-implants. Paracetamol was the most prescribed by the orthodontists, and more than half the doctors did not regularly prescribe antibiotics.

OBJECTIVE: In this paper, we retrospectively reviewed the difference in clinical effectiveness of shock wave therapy and electroacupuncture therapy on knee osteoarthritis. METHODS: A total of 128 treatment cases of knee osteoarthritis patients were extracted from the medical record system of Shenzhen Longhua District Central Hospital during the period from January 1, 2018, to January 30, 2020. The cases were divided into three groups for different treatments: shock wave group (n = 54), electroacupuncture group (n = 41), and control group (n = 33). The shock wave group was given shock wave therapy combined basis clinical treatment; meanwhile, the electroacupuncture group was given electroacupuncture on the basis of actual clinical treatment. The control group was given conventional topical nonsteroidal anti-inflammatory drugs (Voltaren). Osteoarthritis index scale, NRS scale, and WHOQOL-BREF were observed before treatment, after 2 weeks, and 4 weeks after treatment. RESULTS: This study found that the osteoarthritis index scale and NRS scale of the shock wave group and the electroacupuncture group were lower than those before treatment; it had significant difference (P < 0.001). In WHOQOL-BREF, the shock wave group and the electroacupuncture group improved significantly four weeks after treatment (P < 0.001), which was statistically different from the conventional group (P = 0.04). CONCLUSION: Physical and rehabilitation medicine treatment (shock wave therapy) and traditional medical treatment (electroacupuncture) have better clinical effects on knee osteoarthritis, compared with conventional treatment. Shock wave and electric acupuncture have no apparent adverse reaction, suggesting that the treatment is safe and effective.

Since the ancient Egyptians, people have always been worried about their physical appearance. Nowadays, for some cultures like Latin American, physical appearance depends on the context, and the concept of beauty is to have wider hips and more prominent buttocks. One way to achieve these goals is to inject foreign modelants that include some oils to modify certain body regions. Until today, the search continues to find a modelling agent that is nonteratogenic, noncarcinogenic, and not susceptible to infection and can stay at the spot where it was injected (not migration). This review is aimed at providing a brief, comprehensive assessment of the use of modeling agents and summarizes some key imaging features of filler-related complications. The topics of this review are historical data, epidemiology, classification of dermal fillers (xenografts, hyaluronic acid derivatives, autografts, homografts, synthetic materials), adverse reactions, imaging method used in the detection of injectable fillers, MRI patterns observed in complications of injectable fillers, and histological findings of immune response, treatment, and conclusions. We present several classifications of injectable fillers based on composition, degradation, and complications. Additionally, readers will find some representative cases of the most common locations of injectable fillers demonstrating their infiltrative MRI patterns.

BACKGROUND: There is no better treatment method towards paraquat-induced acute lung injury (ALI) at present. Ambroxol combined with methylprednisolone exhibits a significant improvement effect on ALI treatment, whereas their mechanism in ALI is still unclear. METHODS: 64 patients with ALI caused by paraquat poisoning brought to our hospital from January 2015 to January 2018 were selected. They were separated into a combined treatment group (CTG) and a routine treatment group (RTG) on the basis of different treatment methods. The survival of patients was observed after 7 days of treatment. Arterial blood gas, oxygen partial pressure (PaO2), partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), patient's spontaneous respiratory rate (RR), tidal volume (VT), and positive end-expiratory pressure (PEEP) were observed before and after treatment for 7 days. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were analyzed. The differences of indexes between the dead patients and the survivors were observed, and the potential predictive value of death was analyzed. RESULTS: After treatment, the indexes of patients were significantly improved in both groups compared with those before therapy. Further comparison showed that the improvement of PaO2, PaCO2, and PaO2/FiO2 in CTG was obviously higher than that in RTG (p < 0.05). The improvement of RR, PEEP, and VT in CTG was obviously higher than that in RTG (p < 0.05). The decreased degree of IL-6 and TNF-α in CTG was higher than that in RTG (p < 0.05). The 7-day mortality rate of 64 patients was 39.06%, and there was no obvious difference in the 7-day survival rate in both groups (p = 0.649). IL-6 and TNF-α were expected to be potential prediction indexes of paraquat-induced ALI. CONCLUSION: Ambroxol combined with methylprednisolone significantly improved the oxygen partial pressure and oxygenation index of patients with paraquat-induced ALI and inhibited the inflammatory response of patients.

BACKGROUND: Hepatic fibrosis is a severe liver disease that has threatened human health for a long time. In order to undergo timely and adequate therapy, it is important for patients to obtain an accurate diagnosis of fibrosis. Laboratory inspection methods have been efficient in distinguishing between advanced hepatic fibrosis stages (F3, F4), but the identification of early stages of fibrosis has not been achieved. The development of proteomics may provide us with a new direction to identify the stages of fibrosis. METHODS: We established serum proteomic maps for patients with hepatic fibrosis at different stages and identified differential expression of proteins between fibrosis stages through ultra-high-performance liquid chromatography tandem mass spectrometry proteomic analysis. RESULTS: From the proteomic profiles of the serum of patients with different stages of liver fibrosis, a total of 1,338 proteins were identified. Among three early fibrosis stages (control, F1, and F2), 55 differential proteins were identified, but no proteins simultaneously exhibited differential expression between control, F1, and F2. Differential proteins were detected in the comparison between different fibrosis stages. Significant differences were found between advanced fibrosis stages (F2-vs.-F3 and F3-vs.-F4) through a series of statistical analysis, including hierarchical clustering, Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction network analysis. The differential proteins identified by GO annotation were associated with biological processes (mainly platelet degranulation and cell adhesion), molecular functions, and cellular components. CONCLUSIONS: All potential biomarkers identified between the stages of fibrosis could be key points in determining the fibrosis staging. The differences between early stages may provide a useful reference in addressing the challenge of early fibrosis staging.

Prednisolone has been used frequently in the treatment of acute lymphoblastic leukemia. However, to overcome the challenges of the treatment, the development of additional therapies is of great importance. Small, non-protein-coding RNAs, namely, microRNAs (miRNAs), are critical epigenetic regulators with physiological and pathological importance. This study is aimed at determining the effects of miR-146a, miR-155, and miR-181a inhibition with their corresponding anti-miRs on both leukemic and healthy cells, individually and with prednisolone. Leukemic (SUP-B15) and healthy B-lymphocyte (NCI-BL 2171) cell lines were used in this study. A total of 12 experimental groups included individual and combinational silenced ALL-associated miRNAs (hsa-miR-155, hsa-miR-146a, and hsa-miR-181a) and their combination with prednisolone. Cytotoxicity, proliferation, cell cycle, and apoptosis analyses were performed by using WST-1, trypan blue, APC-BrdU, Annexin V, and JC-1 methods in each study group, respectively. To control the effectiveness of anti-miR transfection and prednisolone application, miRNA expression analysis was performed from all groups. Anti-miR application was effective on the viability, proliferation, cell cycle, and apoptosis of leukemia cells, and this effect was increased with prednisolone administration. In addition, this activity was found to be very low on healthy cells. In conclusion, anti-miR applications may have the potential for clinical use of adjuvant to or as an alternative to conventional therapies for childhood acute lymphoblastic leukemia.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease that causes joint destruction. The condition imposes a significant economic burden on patients and societies. The present study is aimed at evaluating the cost-effectiveness of Infliximab, Adalimumab, and Etanercept in treating rheumatoid arthritis in Iran. METHODS: This is a cost-effectiveness study of economic evaluation in which the Markov model was used. The study was carried out on 154 patients with rheumatoid arthritis in Fars province taking Infliximab, Adalimumab, and Etanercept. The patients were selected through sampling. In this study, the cost data were collected from a community perspective, and the outcomes were the mean reductions in DAS-28 and QALY. The cost data collection form and the EQ-5D questionnaire were also used to collect the required data. The results were presented in the form of an incremental cost-effectiveness ratio, and the sensitivity analysis was used to measure the robustness of the study results. The TreeAge Pro and Excel softwares were used to analyze the collected data. RESULTS: The results showed that the mean costs and the QALY rates in the Infliximab, Adalimumab, and Etanercept arms were $ 79,518.33 and 12.34, $ 91,695.59 and 13.25, and $ 87,440.92 and 11.79, respectively. The one-way sensitivity analysis confirmed the robustness of the results. In addition, the results of the probabilistic sensitivity analysis (PSA) indicated that on the cost-effectiveness acceptability curve, Infliximab was in the acceptance area and below the threshold in 77% of simulations. The scatter plot was in the mentioned area in 81% and 91% of simulations compared with Adalimumab and Etanercept, respectively, implying lower costs and higher effectiveness than the other two alternatives. Therefore, the strategy was more cost-effective. CONCLUSION: According to the results of this study, Infliximab was more cost-effective than the other two medications. Therefore, it is recommended that physicians use this medication as the priority in treating rheumatoid arthritis. It is also suggested that health policymakers consider the present study results in preparing treatment guidelines for RA.

A novel method for semiautomated assessment of directions of collagen fibers in soft tissues using histological image analysis is presented. It is based on multiple rotated images obtained via polarized light microscopy without any additional components, i.e., with just two polarizers being either perpendicular or nonperpendicular (rotated). This arrangement breaks the limitation of 90° periodicity of polarized light intensity and evaluates the in-plane fiber orientation over the whole 180° range accurately and quickly. After having verified the method, we used histological specimens of porcine Achilles tendon and aorta to validate the proposed algorithm and to lower the number of rotated images needed for evaluation. Our algorithm is capable to analyze 5·105 pixels in one micrograph in a few seconds and is thus a powerful and cheap tool promising a broad application in detection of collagen fiber distribution in soft tissues.

Diffuse large B-cell lymphoma (DLBC) is a kind of tumor with rapid progress and poor prognosis. Therefore, it is necessary to explore new biomarkers or therapeutic targets to assist in diagnosis or treatment. This study is aimed at screening hub genes by weighted gene coexpression network analysis (WGCNA) and exploring the significance of overall survival (OS) in DLBC patients. Statistical data using WGCNA to analyze mRNA expression in DLBC patients came from The Cancer Genome Atlas (TCGA) dataset. After analyzing with clinical information, the biological functions of hub genes were detected. Survival analysis, Cox regression detection, and correlation analysis of the hub genes were carried out. The potential function of the hub gene related to prognosis was predicted by gene set enrichment analysis (GSEA). The results showed that APOE, CTSD, LGALS2, and TMEM176B expression in normal tissues was significantly higher than that in cancer tissues (P < 0.01). Survival analysis showed that patients with high APOE and CTSD were associated with better OS (P < 0.01). APOE and CTSD genes were mainly enriched in the regulation of ROS and oxidative stress. The two hub genes related to the prognosis of DLBC were identified and verified based on WGCNA. Survival analysis showed that the overexpression of APOE and CTSD in DLBC might be beneficial to the prognosis. These findings identified vital pathways and genes that may become new therapeutic targets and contribute to prognostic indicators.

OBJECTIVES: Combining the advantages of static magnetic fields (SMF) and coculture systems, we investigated the effect of moderate-intensity SMF on the chondrogenesis and proliferation of mandibular bone marrow mesenchymal stem cells (MBMSCs) in the MBMSC/mandibular condylar chondrocyte (MCC) coculture system. The main aim of the present study was to provide an experimental basis for obtaining better cartilage tissue engineering seed cells for the effective repair of condylar cartilage defects in clinical practice. METHODS: MBMSCs and MCCs were isolated from SD (Sprague Dawley) rats. Flow cytometry, three-lineage differentiation, colony-forming assays, immunocytochemistry, and toluidine blue staining were used for the identification of MBMSCs and MCCs. MBMSCs and MCCs were seeded into the lower and upper Transwell chambers, respectively, at a ratio of 1 : 2, and exposed to a 280 mT SMF. MBMSCs were harvested after 3, 7, or 14 days for analysis. CCK-8 was used to detect cell proliferation, Alcian blue staining was utilized to evaluate glycosaminoglycan (GAG), and western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) detected protein and gene expression levels of SOX9, Col2A1 (Collagen Type II Alpha 1), and Aggrecan (ACAN). RESULTS: The proliferation of MBMSCs was significantly enhanced in the experimental group with MBMSCs cocultured with MCCs under SMF stimulation relative to controls (P < 0.05). GAG content was increased, and SOX9, Col2A1, and ACAN were also increased at the mRNA and protein levels (P < 0.05). CONCLUSIONS: Moderate-intensity SMF improved the chondrogenesis and proliferation of MBMSCs in the coculture system, and it might be a promising approach to repair condylar cartilage defects in the clinical setting.

PURPOSE: To assess the effect of platelet-rich plasma (PRP) on the healing response of the corneal epithelium in eyes undergoing phototherapeutic keratectomy (PTK). METHODS: We prospectively examined 20 eyes of 10 patients undergoing bilateral PTK for granular corneal dystrophy or band keratopathy. Patients were randomly assigned to start topical administration of PRP ophthalmic suspension (PRP group) or artificial tears (control group) 4 times daily for 2 weeks. Immediately, 1, and 2 days, and 1 week after PTK, we quantitatively measured the staining area of the corneal epithelium, using slit-lamp photography. We also determined the subjective symptoms and the satisfaction, using the visual analogue system (VAS). RESULTS: The staining area in the PRP group was significantly smaller than that in the control group on days 1 and 2 (Wilcoxon signed-rank test, p = 0.022 and p = 0.017, respectively), but not on day 7 (p = 0.317). The recovery rate of the corneal epithelium in the PRP group was significantly higher than that in the control group on days 1 and 2 (p = 0.022 and p = 0.017, respectively), but not on day 7 (p = 0.317). We found no significant differences in pain (p = 0.139), foreign body sensation (p = 0.108), epiphora (p = 1.000), or satisfaction (p = 0.295), between the two groups. Postoperative complications did not occur in any of the eyes in the study. CONCLUSIONS: The PRP treatment was effective for enhancing corneal epithelial recovery in the early postoperative period, without significant adverse events, in post-PTK-treated eyes, suggesting that it may hold promise as one of the treatment options for treating such postsurgical patients.

OBJECTIVE: Nephrotic syndrome (NS) is a common glomerular disease caused by a variety of causes and is the second most common kidney disease. Guizhi is the key drug of Wulingsan in the treatment of NS. However, the action mechanism remains unclear. In this study, network pharmacology and molecular docking were used to explore the underlying molecular mechanism of Guizhi in treating NS. METHODS: The active components and targets of Guizhi were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Hitpick, SEA, and Swiss Target Prediction database. The targets related to NS were obtained from the DisGeNET, GeneCards, and OMIM database, and the intersected targets were obtained by Venny2.1.0. Then, active component-target network was constructed using Cytoscape software. And the protein-protein interaction (PPI) network was drawn through the String database and Cytoscape software. Next, Gene Ontology (GO) and pathway enrichment analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. And overall network was constructed through Cytoscape. Finally, molecular docking was conducted using Autodock Vina. RESULTS: According to the screening criteria, a total of 8 active compounds and 317 potential targets of Guizhi were chosen. Through the online database, 2125 NS-related targets were identified, and 93 overlapping targets were obtained. In active component-target network, beta-sitosterol, sitosterol, cinnamaldehyde, and peroxyergosterol were the important active components. In PPI network, VEGFA, MAPK3, SRC, PTGS2, and MAPK8 were the core targets. GO and KEGG analyses showed that the main pathways of Guizhi in treating NS involved VEGF, Toll-like receptor, and MAPK signaling pathway. In molecular docking, the active compounds of Guizhi had good affinity with the core targets. CONCLUSIONS: In this study, we preliminarily predicted the main active components, targets, and signaling pathways of Guizhi to treat NS, which could provide new ideas for further research on the protective mechanism and clinical application of Guizhi against NS.

INTRODUCTION: The effect of surgical timing on vertebral refracture rate and mortality remains elusive after percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP), and we aim to assess the impact of surgical timing on vertebral refracture rate and mortality in patients undergoing percutaneous vertebroplasty. METHODS: We did a retrospective cohort study of patients who underwent PKP or PVP because of osteoporotic vertebral compression fracture (OVCF) between April 1, 2014 and March 31, 2016. The primary outcome measure was the incidence of vertebral refracture. Secondary outcomes included the mortality and chronic back pain. RESULTS: The rate of vertebral refracture was significantly lower in early surgical timing group than that in late surgical timing group (HR 2.415, 95% CI 1.318-4.427; P = 0.004). We found that the bone mineral density (BMD) was only the risk factor to increase the vertebral refracture rate after vertebroplasty (P = 0.001). In addition, there was similar mortality between the two groups (15.7% in early surgical timing group versus 10% in late surgical timing group). Male patients (27.3%, 12/44) had higher mortality compared to female patients (10.6%, 20/189), while the mortality was higher in patients with cerebral infarction (25%, 3/12) than those without cerebral infarction (12.1%, 17/140). CONCLUSIONS: Surgical timing significantly affects the vertebral refracture rate after PKP or PVP, which is also influenced by BMD. The mortality after the surgery is not affected by the surgical timing, but gender and cerebral infarction may be the risk factors of mortality.

Pyroptosis, the prototype of programmed cell death, is crucial to the development of multicellular organisms. Lung cancer is one of the most lethal cancers in the world. Because lung cancer progresses quickly, it is mostly found at an advanced stage, resulting in a very poor prognosis of lung cancer. At present, there is no treatment with good prognosis, but pyroptosis-based tumor therapy may be able to solve this problem. In the past few decades, it has been found that pyroptosis can affect the invasion, proliferation, and metastasis of tumor and apoptosis is an important system to resist cancer. Our study is aimed at constructing a prognostic model within pyroptosis-related genes. We developed a prognostic model by using TCGA and GEO database, and differentially expressed genes (DEGs) were identified. Five genes (NLRP1, NOD1, NLRC4, CASP9, and PLCG1) were identified to construct a prognostic model. According to the median risk score calculated by our formula, we divided patients into the high- and low-risk groups. Pyroptosis-related genes play important roles in tumor immunity and can be used to predict the prognosis of lung adenocarcinoma (LUAD).

The effects of ozone on hippocampal expression levels of brain-derived neurotrophic factor (BDNF) and c-fos protein (Fos) were evaluated in rats with chronic compression of dorsal root ganglia (CCD). Forty-eight adult female Sprague-Dawley rats were randomly divided into the following 4 groups (n = 12): sham operation (sham group), CCD group, CCD with 20 μg/ml of ozone (CCD + AO3 group), and CCD with 40 μg/ml of ozone (CCD + BO3 group). Except the sham group, unilateral L5 dorsal root ganglion (DRG) compression was performed on all other groups. On days 1, 2, and 4 after the operation, the CCD + AO3 and CCD + BO3 groups were injected with 100 μl of ozone with concentrations of 20 and 40 μg/ml, respectively. Thermal withdrawal latencies (TWLs) and mechanical withdrawal thresholds (MWTs) were measured at various time points before and after the operation. BDNF and Fos expressions were examined in the extracted hippocampi using immunohistochemistry. The TWLs and MWTs of CCD model rats that received ozone were lower with decreased BDNF and increased Fos expression levels, on day 21 after the operation, compared to those of the sham group (P < 0.05). The TWLs and MWTs of the CCD + AO3 and CCD + BO3 groups were higher with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD group (P < 0.05). The TWLs were longer and the MWTs were higher in the CCD + BO3 group at each time point with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD + AO3 group (P < 0.05). Our results revealed that ozone can relieve the neuropathic pain caused by the pathological neuralgia resulting from DRG compression in rats. The mechanism of action for ozone is likely associated with changes in BDNF and Fos expression levels in the hippocampus.

BACKGROUND: T-helper 17 (Th17) and CD4+CD25+ T-regulatory (Treg) cells play important roles in the pathogenesis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This study is aimed at investigating shifts in Treg/Th17 balance in the peripheral blood of HBV-ACLF patients at different disease stages. METHODS: Sixty HBV-ACLF patients, admitted to the First Hospital of Hunan University of Chinese Medicine, China, including early-stage (n = 20), middle-stage (n = 20), and late-stage patients (n = 20), were enrolled in the study. In addition, 20 patients with chronic hepatitis B and 20 healthy volunteers were also included in the study as controls. Flow cytometry, cytometric bead array, and quantitative real-time PCR protocols were used to evaluate the expression of Treg and Th17 cells as well as of related cytokines. RESULTS: The levels of Th17 cells and their effectors interleukin- (IL-) 17A, IL-23, and tumor necrosis factor-α increased with disease progression. Similarly, Treg cells and their effector cytokines transforming growth factor-β and IL-10 also increased. Although Treg and Th17 levels were positively correlated, the latter were always at higher numbers. Noteworthy, the Treg/Th17 ratio gradually decreased and was negatively correlated with ACLF severity. FoxP3 levels in the peripheral blood gradually decreased with ACLF progression, whereas ROR-γt gradually increased. Serum c-reactive protein, procalcitonin, and lipopolysaccharide were also upregulated with disease progression and positively correlated with Th17 abundance. Further, Th17, IL-17A, and IL-23 were independent risk factors for ACLF. A prognostic model for HBV-ACLF was established, with a correct prediction rate of 90.00% (54/60). CONCLUSION: Treg/Th17 imbalance occurs throughout the pathogenic course of HBV-ACLF, with an imbalance shift toward Th17. Hence, the Th17-mediated inflammatory response drives HBV-ACLF-associated inflammation and supports the pathological mechanisms of liver failure.

OBJECTIVE: In this study, we explored the influence of single nucleotide polymorphism (SNP) in the noncoding region of intercellular adhesion molecule 1 (ICAM1) gene on the occurrence and metastasis of primary hepatocellular carcinoma (PHC). METHODS: Sanger sequencing was used to analyze the genotypes of rs3093032, rs923366, and rs281437 locus in the 3'untranslated region (UTR) of the ICAM1 gene. The level of plasma ICAM1 was analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: After adjusting for risk factors such as BMI, smoking, drinking, family history of tumors, and hepatitis B virus test results, the CT genotype at rs3093032 of the ICAM1 gene (OR = 0.19, 95% CI: 0.08-0.44, P < 0.01), dominance model (OR = 0.23, 95% CI: 0.11-0.48, P < 0.01), and T allele (OR = 0.27, 95% CI: 0.14-0.53, P < 0.01) were related to the reduced risk of PHC susceptibility. rs923366 locus CT genotype (OR = 0.63, 95% CI: 0.44-0.90, P = 0.01), TT genotype (OR = 0.23, 95% CI: 0.10-0.53, P < 0.01), dominant model (OR = 0.55, 95% CI: 0.39-0.77, P < 0.01), recessive model (OR = 0.28, 95% CI: 0.12-0.62, P < 0.01), and T allele (OR = 0.55, 95% CI: 0.42-0.73, P < 0.01) were related to a reduction in the risk of PHC susceptibility. rs281437 locus CT genotype (OR = 2.08, 95% CI: 1.40-3.09, P < 0.01), TT genotype (OR = 5.20, 95% CI: 2.22-12.17, P < 0.01), dominant model (OR = 2.45, 95% CI: 1.69-3.54, P < 0.01), recessive model (OR = 4.32, 95% CI: 1.86-10.06, P < 0.01), and T allele (OR = 2.46, 95% CI: 1.79-3.38, P < 0.01) were significantly related to the increased risk of PHC susceptibility. SNPs at rs3093032, rs923366, and rs281437 of the ICAM1 gene were significantly correlated with TNM stage and tumor metastasis of PHC patients (P < 0.05). CONCLUSION: SNPs at rs3093032, rs923366, and rs281437 in the 3'UTR region of the ICAM1 gene are related to the occurrence and metastasis of PHC.

Postoperative cognitive dysfunction (POCD), as one of the common postoperative complications, mainly occurs after surgery and anesthesia, especially in the elderly. It refers to cognitive function changes such as decreased learning and memory ability and inability to concentrate. In severe cases, there could be personality changes and a decline in social behavior. At present, a great deal of research had been carried out on POCD, but its specific mechanism remains unclear. The release of peripheral inflammation-related factors, the degradation and destruction of the blood-brain barrier, the occurrence of central inflammation, and the neuronal apoptosis and synaptic loss could be promoted by neuroinflammation indicating that inflammatory mechanisms may play key roles in the occurrence of POCD.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seriously affected public health and social stability. The main route of the transmission is droplet transmission, where the oral cavity is the most important entry point to the body. Due to both the direct harmful effects of SARS-CoV-2 and disordered immune responses, some COVID-19 patients may progress to acute respiratory distress syndrome or even multiple organ failure. Genetic variants of SARS-CoV-2 have been emerging and circulating around the world. Currently, there is no internationally approved precise treatment for COVID-19. Mesenchymal stem cells (MSCs) can traffic and migrate towards the affected tissue, regulate both the innate and acquired immune systems, and participate in the process of healing. Here, we will discuss and investigate the mechanisms of immune disorder in COVID-19 and the therapeutic activity of MSCs, in particular human gingiva mesenchymal stem cells.

Background and Purpose. Postexposure onset of dietary restriction (DR) is expected to provide therapeutic nutritional approaches to reduce health risk from exposure to ionizing radiation (IR) due to such as manned space exploration, radiotherapy, or nuclear accidents as IR could alleviate radiocarcinogenesis in animal models. However, the underlying mechanisms remain largely unknown. This study is aimed at investigating the effect from postexposure onset of DR on genotoxicity and genomic instability (GI) induced by total body irradiation (TBI) in mice. Materials and Methods. Mice were exposed to 2.0 Gy of accelerated iron particles with an initial energy of 500 MeV/nucleon and a linear energy transfer (LET) value of about 200 keV/μm. After TBI, mice were either allowed to free access to a standard laboratory chow or treated under DR (25% cut in diet). Using micronucleus frequency (MNF) in bone marrow erythrocytes, induction of acute genotoxicity and GI in the hematopoietic system was, respectively, determined 1 and 2 months after TBI. Results and Conclusions. TBI alone caused a significant increase in MNF while DR alone did not markedly influence the MNF. DR induced a significant decrease in MNF compared to the treatment by TBI alone. Results demonstrated that postexposure onset of DR could relieve the elevated MNF induced by TBI with high-LET iron particles. These findings indicated that reduction in acute genotoxicity and late GI may be at least a part of the mechanisms underlying decreased radiocarcinogenesis by DR.

AIM: To evaluate the forensic application values of 19 autosomal short tandem repeat (STR) loci in canines. METHODS: The 19 STR loci in two canine groups (Pembroke Welsh Corgis, n = 200; Shiba Inus, n = 175) were analysed by the capillary electrophoresis platform. The allele frequencies and forensic parameters were calculated, and the genetic relationships between these two canine groups and a previously reported Labrador group were analysed. RESULTS: These two canine groups conformed to the Hardy-Weinberg equilibrium at all STRs except for locus VGL3438 in the Pembroke Welsh Corgi group, and there was no linkage disequilibrium among pairwise loci at the 19 STRs. All STRs were polymorphic in the Pembroke Welsh Corgi and Shiba Inu groups, of which the locus C38 had the highest polymorphism. And it was found that the genetic relationship between the Pembroke Welsh Corgi and Labrador groups were closer in the three canine groups (Pembroke Welsh Corgi, Shiba Inu and Labrador). CONCLUSION: The 19 STR loci had high genetic polymorphisms and forensic application values in Pembroke Welsh Corgi and Shiba Inu groups.

BACKGROUND: Cancer is primarily caused by smoking, alcohol, betel quit, a series of genetic alterations, and epigenetic abnormalities in signaling pathways, which result in a variety of phenotypes that favor the development of OSCC. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, accounting for 80-90% of all oral malignant neoplasms. Oral cancer is relatively common, and it is frequently curable when detected and treated early enough. The tumor-node-metastasis (TNM) staging system is used to determine patient prognosis; however, geographical inaccuracies frequently occur, affecting management. OBJECTIVE: To determine the additional relationship between factors discovered by searching for sociodemographic and metastasis factors, as well as treatment outcomes, which could help improve the prediction of the survival rate in cancer patients. Material and Methods. A total of 56 patients were recruited from the ambulatory clinic at the Hospital Universiti Sains Malaysia (USM). In this retrospective study, advanced computational statistical modeling techniques were used to evaluate data descriptions of several variables such as treatment, age, and distant metastasis. The R-Studio software and syntax were used to implement and test the hazard ratio. The statistics for each sample were calculated using a combination model that included methods such as bootstrap and multiple linear regression (MLR). RESULTS: The statistical strategy showed R demonstrates that regression modeling outperforms an R-squared. It demonstrated that when data is partitioned into a training and testing dataset, the hybrid model technique performs better at predicting the outcome. The variable validation was determined using the well-established bootstrap-integrated MLR technique. In this case, three variables are considered: age, treatment, and distant metastases. It is important to note that three things affect the hazard ratio: age (β 1: -0.006423; p < 2e - 16), treatment (β 2: -0.355389; p < 2e - 16), and distant metastasis (β 3: -0.355389; p < 2e - 16). There is a 0.003469102 MSE for the linear model in this scenario. CONCLUSION: In this study, a hybrid approach combining bootstrapping and multiple linear regression will be developed and extensively tested. The R syntax for this methodology was designed to ensure that the researcher completely understood the illustration. In this case, a hybrid model demonstrates how this critical conclusion enables us to better understand the utility and relative contribution of the hybrid method to the outcome. The statistical technique used in this study, R, demonstrates that regression modeling outperforms R-squared values of 0.9014 and 0.00882 for the predicted mean squared error, respectively. The conclusion of the study establishes the superiority of the hybrid model technique used in the study.

Cigarette smoke (CS) is the major cause of preventable death worldwide, and it can also cause damage to extrapulmonary organs, such as the liver, mainly due the generation of reactive oxygen species (ROS). The liver is an essential organ for human survival since it is mainly responsible for the body metabolism and among other things and it is the place where many endogenous and exogenous substances undergo biological transformation. Lycopene is a nonprovitamin A carotenoid found in red fruits and vegetables, and its role as a potent antioxidant is well known. In this study, we hypothesized that lycopene could protect mouse liver against long-term CS exposure. Thirty C57BL/6 mice were exposed to twelve cigarette smoke (12 cigarettes per day) for 60 days and pretreated with 25 mg/kg/day or 50 mg/kg/day of lycopene via orogastric gavage. After euthanasia, the hepatic tissue was collected for histopathological, antioxidant defense, oxidative stress, inflammatory, and collagen deposition analysis. Our analysis demonstrated that lycopene results in a suitable outcome to ameliorate the pathological changes, inflammatory and antioxidant profile in a mouse model of long-term CS exposure, and collagen accumulation in the hepatic extracellular matrix. This study demonstrates for the first time that supplementation of lycopene can be a possible pharmacological tool for the treatment of hepatic damage caused by exposure to long-term CS.

Habitual food intake and physical activity can affect chronic low-grade inflammation, which is common in the elderly, because of changes in the immune system and body composition. Thus, the present study proposes an evaluation of the influence of past eating habits on the effects of an intervention of resistance training plus dietary advice on the inflammatory profile of the elderly. We conducted an intervention study with 40 elderly people. The Revised Diet Quality Index (HEI-R) and the dietary total antioxidant capacity (dTAC) were calculated before the intervention based on a food frequency questionnaire validated to the elderly population. Participants were categorized according to the median of HEI-R and dTAC to assess the influence of the habitual diet quality on anthropometry and inflammatory markers (CRP, IL-8, CCL-2, and leptin) before and after the intervention. The 19-week intervention provided a long-term progressive resistance training associated with dietary advice focused on foods rich in compounds with anti-inflammatory and antioxidant properties. There was a greater reduction in weight, body mass index (BMI), and body fat (%) in the group with the lowest HEI-R and a greater reduction in the body fat (%) in the group with the lowest dTAC, indicating that the group that had a worse diet quality before the intervention responded better to it. The index HEI-R correlated negatively with Δweight and ΔBMI. dTAC correlated positively with Δmonocyte 1 chemotactic protein (CCL-2) and ΔC-reactive protein (CRP). In this scenario, elderly persons with bad habits can benefit from interventions to lifestyle change, while the better diet quality including dietary antioxidant sources can be useful to control weight and inflammatory biomarkers in this population.

PURPOSE: The aim of the present prospective study was to evaluate the effect of titanium mesh and concentrated growth factor (CGF) membranes in reconstructing severe labial bone defects during immediate implantation of anterior maxillary tooth. METHODS: Patients with severe defects presenting on the anterior labial bone plate of maxillary were enrolled in this study. During immediate implantation, the titanium mesh was used to maintain the space of bone graft, collagen membrane, and xenograft bone that were used to guide bone regeneration (GBR). Cone beam computed tomography (CBCT) was used to measure the height and the labial bone thickness around the implant at the time of the second stage surgery, 6 months, 1 year, and 2 years after restoration. The pink esthetic score (PES) was used to evaluate the esthetic outcomes after restoration. RESULTS: 18 patients were enrolled in this study. The survival rate of implants was 100%, and no complication was observed, except for 1 case of titanium mesh exposure which did not affect osteogenesis. In the second stage of surgery, the labial bone was completely reconstructed, and the top of the implant was covered with a small amount of new bone. The thickness of the labial bone was 3.01 mm (±0.23), 2.96 mm (±0.21), 2.93 mm (±0.19), and 2.92 mm (±0.16) at the time of the second stage surgery, 6 months, 1 year, and 2 years after restoration, respectively. The height of the marginal bone around implants was above the top of implant at the time of the second stage surgery and then reduced 0.72 mm (±0.07), 0.91 mm (±0.08), and 0.90 mm (±0.07) at the time point of 6 months, 1 year, and 2 years after restoration, respectively. The changes of bone thickness and height were statistically significant within one year, but stable after one year. The PES values showed the same tendency. CONCLUSIONS: With the limitation of the present prospective study, the combination of titanium mesh and CGF membrane could provide space maintenance for bone augmentation of alveolar bone defects and improve the bone regeneration in patients with severe labial bone defect when immediate implant of anterior maxillary.

Sex hormone dependence is associated with tumor progression and prognosis. Here, we explored the molecular basis of luminal A-like phenotype in sex hormone-dependent cancers. RNA-sequencing data from 8 cancer types were obtained from The Cancer Genome Atlas (TCGA). We investigated the enrichment function of differentially expressed genes (DEGs) in luminal A breast cancer (BRCA). Weighted coexpression network analysis (WGCNA) was used to identify gene modules associated with the luminal A-like phenotype, and we calculated the module's preservation in 8 cancer types. Module hub genes screened using least absolute shrinkage and selection operator (LASSO) were used to construct a gene signature model for the luminal A-like phenotype, and we assessed the model's relationship with prognosis, enriched pathways, and immune infiltration using bioinformatics approaches. Compared to other BRCA subtypes, the enrichment functions of upregulated genes in luminal A BRCA were related to hormone biological processes and receptor activity, and the downregulated genes were associated with the cell cycle and nuclear division. A gene module significantly associated with luminal A BRCA was shared by uterine corpus endometrial carcinoma (UCEC), leading to a similar phenotype. Fifteen hub genes were used to construct a gene signature model for the assessment of the luminal A-like phenotype, and the corrected C-statistics and Brier scores were 0.986 and 0.023, respectively. Calibration plots showed good performance, and decision curve analysis indicated a high net benefit of the model. The 15-gene signature model was associated with better overall survival in BRCA and UCEC and was characterized by downregulation of DNA replication, cell cycle and activated CD4 T cells. In conclusion, our study elucidated that BRCA and UCEC share a similar sex hormone-dependent phenotype and constructed a 15-gene signature model for use as a prognostic tool to quantify the probability of the phenotype.

BACKGROUND: Syncope is a common symptom in emergency department patients. Among various etiological factors, cardiac causes have the highest risk of mortality. The corrected QT interval is considered an independent predictor of mortality for many diseases. OBJECTIVES: Analyze QT interval analysis of patients presenting to the emergency department with syncope. METHODS: In this prospective observational study, patients who presented to the emergency department with syncope between January 1, 2018, and January 1, 2019 were included. RESULTS: The median age was 64 (49-78) years, and 58.8% of patients were male. The corrected QT interval (QTc) in patients with coronary artery disease and chronic obstructive pulmonary disease was longer than those without. There was no statistically significant association between hypertension, diabetes, stroke, thyroid disease, and prolonged QTc. Patients who did not survive had significantly prolonged QT intervals. According to ROC analysis, sensitivity of >440.5 ms QTc values in predicting mortality was 86% and specificity was 71% (AUC = 0.815; 95%CI = 0.71 - 0.91; p < 0.001). CONCLUSIONS: Patients admitted to emergency department with syncope and a prolonged QTc are associated with a higher mortality rate and thus can provide us with an important guide for the management of these patients.

Erratum for Biomed Res Int. 2021 Jul 14;2021:1738932.

OBJECTIVE: To analyze the effect of PFNA-II internal fixation on hip joint recovery and quality of life (QOL) in patients with lateral-wall dangerous type of intertrochanteric fracture. METHODS: One hundred and twelve patients with lateral-wall dangerous type of intertrochanteric fracture who underwent surgical treatment in our hospital from May 2017 to May 2019 were selected as the participants of the study. Based on the treatment method, all the enrolled patients were divided into two groups: proximal femoral nail antirotation (PFNA group; n = 59) who received closed reduction and minimally invasive PFNA internal fixation and dynamic hip screw group (DHS; n = 53) who received internal fixation. The clinical indicators, curative effect, hip function score, pain degree, postoperative QOL score, and complications were compared between the two groups. RESULTS: The operation time, intraoperative blood loss, postoperative drainage volume, and the incidence of postoperative complications in PFNA group were statistically lower than those in DHS group (P < 0.05). The curative effect in PFNA group was notably better than that in DHS group. There were no significant differences in scores of hip function, visual analogue scale (VAS), and QOL between the two groups before operation (P > 0.05). However, the hip function score and QOL score increased in both groups after surgery, and the increase was more significant in the PFNA group, while the VAS score decreased in both groups, and the decrease in PFNA group was more significant (P < 0.05). CONCLUSION: PFNA internal fixation for the treatment of lateral-wall dangerous type of intertrochanteric fracture has the advantages of short operation time, less intraoperative blood loss, effective improvement of hip joint function, and fewer postoperative complications, which is worthy of clinical application.

METHODS: Metabolomics was used to detect the secondary metabolites in SLBZP; the target protein was acquired by target fishing according to the compound's structure. The SymMap database was used to search herbal medicines for the target protein. The target gene of IBS gave rise to the common gene protein which is the potential target of SLBZP in IBS therapy. The interactions between target proteins were analyzed in a STRING database, the protein relationship network was analyzed using Cytoscape software, and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the core target gene group was carried out in a DAVID database in order to construct the "compound-traditional Chinese medicine/molecule-target-pathway" network. Molecular docking was used to verify the core protein and its related small molecular compounds. RESULT: There were 129 types of secondary metabolites in SLBZP. 80 target proteins of these metabolites were potential core targets for IBS treatment including acetylcholinesterase (AChE), arachidonate-5-lipoxygenase (ALOX5), B-cell lymphoma-2 (BCL2), recombinant cyclin D1 (CCND1), and catenin-β1 (CTNNB1), among others. Results from these targets indicated that the most enriched pathway was the tumor necrosis factor (TNF) signaling pathway (p < 0.001) and that the most abundant pathway was signal transduction. In the network nodes of the TNF signaling pathway, the Chinese medicines with the highest aggregation were Lablab semen album and Glycyrrhizae radix et rhizoma (degree = 11). The small molecules with the highest aggregation were oxypeucedanin and 3,5,6,7,8,3',4'-heptamethoxyflavone (degree = 4). Molecular docking results confirmed that daidzein 7-O-glucoside (daidzin) had the highest degree of binding to TNF proteins in the TNF signaling pathway. CONCLUSION: This study shows that SLBZP can treat IBS by influencing multiple targets and pathways, of which the TNF signaling pathway may be the most significant. This typifies the pharmacological characteristics of traditional Chinese medicine, i.e., multiple targets, numerous pathways, and specific therapeutic effects on diseases. SLBZP can therefore be used as a candidate drug for clinical IBS by intervening in human signal transduction.

BACKGROUND: MutS homolog 2 (MSH2), with the function of identifying mismatches and participating in DNA repair, is the "housekeeping gene" in the mismatch repair (MMR) system. MSH2 deficiency has been reported to enhance cancer susceptibility for the association of hereditary nonpolyposis colorectal cancer. However, the expression and prognostic significance of MSH2 have not been studied from the perspective of pan-cancer. METHODS: The GTEx database was used to analyze the expression of MSH2 in normal tissues. The TCGA database was used to analyze the differential expression of MSH2 in pan-cancers. The prognostic value of MSH2 in pan-cancer was assessed using Cox regression and Kaplan-Meier analysis. Spearman correlations were used to measure the relationship between the expression level of MSH2 in pan-cancer and the level of immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). RESULTS: MSH2 is highly expressed in most type of cancers and significantly correlated with prognosis. In COAD, KIRC, LIHC, and SKCM, the expression of MSH2 was significantly positively correlated with the abundance of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, macrophages, and neutrophils. In THCA, MSH2 expression correlated with CD8+T Cell showed a significant negative correlation. MSH2 had significantly negative correlations with stromal score and immune score in a variety of cancers and significantly correlated with TMB and MSI of a variety of tumors. CONCLUSIONS: MSH2 may play an important role in the occurrence, development, and immune infiltration of cancer. MSH2 can emerge as a potential biomarker for cancer diagnosis and prognosis.

OBJECTIVE: To evaluate whether a low-dose perioperative infusion of Dex reduces early POCD. DESIGN: This study was a double-blind, randomized, placebo-controlled trial that randomly assigned patients to Dex or saline placebo infused during surgery and patient-controlled intravenous analgesia (PCIA) infusion. Patients were assessed for postoperative cognitive decline. Interventions. Dex was infused at a loading dose of 0.5 μg/kg intravenously (15 min after entering the operation room) followed by a continuous infusion at a rate of 0.5 μg/kg/h until one-lung ventilation or artificial pneumothorax ended. Patients in the Dex group received regular PCIA pump with additional dose of Dex (200 μg). RESULTS: In total, 126 patients were randomized, and 102 patients were involved in the result analysis. The incidence of POCD was 36.54% (19/52) in the Dex group and 32.00% (16/50) in the normal saline (NS) group, with no statistic difference. No significant difference was observed between the two groups in terms of Telephone Interview for Cognitive Status-Modified (TICS-m) scores at different times. However, the TICS-m score at 7 days after surgery was significantly lower than that at 30 days in 102 patients (32.93 ± 0.42 vs. 33.92 ± 0.47, P = 0.03). The visual analogue scale scores in the Dex group were significantly lower than those in the NS group 1 day postoperation at rest and activity (2.00 [1.00-3.00] vs. 3.00 [2.00-4.00], P < 0.01; 4.00 [3.00-5.00] vs. 5.00 [4.00-6.00], P < 0.05, respectively). Patients receiving Dex or NS had no statistical difference in activities of daily living (ADLs) scores at 7 and 30 days after surgery, but the ADL score at 30 days after surgery showed a significant reduction compared with that at 7 days (P < 0.01). Patients in the Dex group had a shorter hospital length of stay (15.26 ± 3.77 vs. 17.69 ± 5.09, P = 0.02) and less expenses (52458.71 ± 10649.30 vs. 57269.03 ± 9269.98, P = 0.04) than those in the NS group. CONCLUSIONS: Low-dose Dex in the perioperative period did not reduce the incidence of early POCD in thoracic surgery. However, it relieved postoperative pain, decreased the hospitalization expenses, and shortened the length of stay.

BACKGROUND: Potential antibacterial substances, such as titanium dioxide (TiO2), are being extensively studied throughout the research world. A modified hydrothermal nanotitania extraction was shown to inhibit Staphylococcus aureus growth in the laboratory. However, the toxicity effect of the extract on rats is unknown. In this study, we observed the effects of a modified hydrothermal nanotitania extraction on the skin and behavior of Sprague-Dawley rats. METHODS: Sprague-Dawley (Rattus norvegicus) rats were used as the experimental animals. The skin around the dorsum of the tested animals was shaved and pasted with 0.1 mg and 0.5 mg of the nanotitania extraction. The color and condition of the pasted area and the behavior of the animals were observed. RESULTS: 0.1 mg nanotitania extraction application on the dorsum of the rat produced no skin color changes at day 1, day 3, day 5, or day 7 postapplication. There were no changes in their behavior up to day 7 with no skin rashes or skin scratches seen or fur changes. However, 0.5 mg of nanotitania extraction resulted in redness and less fur regrowth at day 7. CONCLUSIONS: A 0.1 mg modified nanotitania extraction was observed to have no effect on the skin of Sprague-Dawley rats.

OBJECTIVE: The aim of this study was at investigating the risk stratification and prognostic value of hypersensitive troponin T (hs-TnT) combined with matrix metalloproteinase 2 (MMP-2) in patients with acute coronary syndrome (ACS). METHODS: 80 patients with coronary syndrome admitted to our hospital from January 2019 to January 2020 and 40 healthy people (control group) in the same period were selected. According to different types of diseases, the patients were divided into an acute group (n = 40) and stable group (n = 40). Besides, they all were monitored by the hs-TnT value, serum MMP-2, and coronary angiography at admission and the comparative analysis was carried out. The patients in both groups were followed up for 30 days, and the incidence of adverse cardiovascular events in the patients during this period was recorded. RESULTS: Compared with those in the control group, the MMP-2 and hs-TnT levels in the acute group and the stable group were significantly higher and the MMP-2 and hs-TnT levels in the acute group were significantly higher than those in the stable group, with statistically significant differences (P < 0.05). The 30-day follow-up results showed that the incidence of adverse cardiovascular events in the acute group was significantly higher than that in the stable group, with statistically significant differences (P < 0.05). The hs-TnT and MMP-2 levels in the acute myocardial infarction (AMI) group were significantly higher than those in the unstable angina pectoris (UAP) group, with statistically significant differences (P < 0.01). The hs-TnT and MMP-2 levels in the non-single-vessel group were significantly higher than those in the single-vessel group, with statistically significant differences (P < 0.01). CONCLUSION: The hs-TnT and MMP-2 high expression levels are closely associated with myocardial injury, and they can effectively predict the severity of patients' disease. In addition, the hs-TnT and MMP-2 elevated levels can be considered as an important index to judge the short-term treatment efficacy and the risk stratification of early ACS, playing an important role in clinical treatment and rehabilitation in the later stage.

OBJECTIVES: This study screened for factors affecting coronavirus disease 2019 (COVID-19) incidence in type 1 diabetes mellitus (T1DM) patients, appraised vitamin D's efficacy in preventing COVID-19, and assessed the effects of clinical characteristics, glycemic status, vitamin D, and hydroxychloroquine administration on COVID-19's progression and severity in T1DM patients. METHODS: This retrospective research on 150 adults was conducted at Security Forces Hospital, Riyadh, KSA. Participants were allocated to three groups (50/group): control, T1DM, and T1DM with COVID-19. Participants' fasting blood glucose (FBG), glycated hemoglobin (HbA1c), complete blood count, vitamin D, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, lactate dehydrogenase (LDH), prothrombin time, activated partial thromboplastin time, D-dimer, liver and kidney function, and hydroxychloroquine treatment were retrieved and analyzed. RESULTS: The percentages of comorbidities and not taking hydroxychloroquine were significantly higher among T1DM patients with COVID-19 than patients with T1DM only. Mean vitamin D level was significantly lower in T1DM with COVID-19 patients than in the other two groups. Vitamin D showed a significant negative correlation with LDH, CRP, ESR, ferritin, and D-dimer, which was the most reliable predictor of COVID-19 severity in T1DM patients. CONCLUSION: Comorbidities and vitamin D deficiency are risk factors for COVID-19 in patients with T1DM. Patients who do not take hydroxychloroquine and have higher FBG and HbA1c levels are vulnerable to COVID-19. Vitamin D may be useful for preventing COVID-19 in T1DM patients. Comorbidities, higher FBG and HbA1c levels, not taking hydroxychloroquine, and vitamin D inadequacy elevate COVID-19 progression and severity in patients with T1DM.

There is a lack of information on the psychophysiological response of pilots under hypoxic conditions. The study of the physiological, psychological, cardiorespiratory, neurological, behavioural, sensory, and cognitive symptoms that may appear during training in hypobaric chambers is essential to optimize the training processes of aircrew members. Thus, the present study is aimed at analyzing the psychophysiological responses of aircrew members in an incremental hypoxia training protocol. Psychophysiological responses of 44 aircrew members (34 males and 10 females) in an incremental hypoxia training protocol (3 minutes at 0 meters, 8 minutes at 5,000 meters, and maximum time at 7500 meters) were measured. Results suggested that the incremental hypoxia training protocol did not affect cortical arousal and handgrip strength; however, it increased the sympathetic tone, perceived stress, perceived effort, and heart rate and decreased forced expiratory volume and blood oxygen saturation. Thus, we concluded that acute hypoxic hypobaric exposure leads to decreased parasympathetic tone, blood oxygen saturation, and maximal spirometry values, without negatively affecting handgrip strength and cortical arousal. This information will lead to find specific training systems that meet the real needs of aircrew.

BACKGROUND: Accurate and effective biomarkers for the prognosis of patients with hepatocellular carcinoma (HCC) are poorly identified. A network-based gene signature may serve as a valuable biomarker to improve the accuracy of risk discrimination in patients. METHODS: The expression levels of cancer hallmarks were determined by Cox regression analysis. Various bioinformatic methods, such as GSEA, WGCNA, and LASSO, and statistical approaches were applied to generate an MTORC1 signaling-related gene signature (MSRS). Moreover, a decision tree and nomogram were constructed to aid in the quantification of risk levels for each HCC patient. RESULTS: Active MTORC1 signaling was found to be the most vital predictor of overall survival in HCC patients in the training cohort. MSRS was established and proved to hold the capacity to stratify HCC patients with poor outcomes in two validated datasets. Analysis of the patient MSRS levels and patient survival data suggested that the MSRS can be a valuable risk factor in two validated datasets and the integrated cohort. Finally, we constructed a decision tree which allowed to distinguish subclasses of patients at high risk and a nomogram which could accurately predict the survival of individuals. CONCLUSIONS: The present study may contribute to the improvement of current prognostic systems for patients with HCC.

Tumor necrosis factor-α is a common cytokine that increases in inflammatory processes, slows the differentiation of bone formation, and induces osteodystrophy in the long-term inflammatory microenvironment. Our previous study confirmed that the Elongation protein 2 (ELP2) plays a significant role in osteogenesis and osteogenic differentiation, which is considered a drug discovery target in diseases related to bone formation and differentiation. In this study, we applied an in silico virtual screening method to select molecules that bind to the ELP2 protein from a chemical drug molecule library and obtained 95 candidates. Then, we included 11 candidates by observing the docking patterns and the noncovalent bonds. The binding affinity of the ELP2 protein with the candidate compounds was examined by SPR analysis, and 5 out of 11 compounds performed good binding affinity to the mouse ELP2 protein. After in vitro cell differentiation assay, candidates 2# and 5# were shown to reduce differentiation inhibition after tumor necrosis factor-α stimulation, allowing further optimization and development for potential clinical treatment of inflammation-mediated orthopedic diseases.

BACKGROUND: The liver is the primary organ for amino acid metabolism, and metabolic disorder of amino acids is common in liver disease. However, the characteristics of plasma amino acid profiles in patients with HBV-related cirrhosis and the impacts of late-evening snack (LES) on cirrhosis are unclear. OBJECTIVES: To investigate the characteristics of plasma amino acid profiles in patients with HBV-related chronic hepatitis, cirrhosis, and the effects of late-evening snacks on plasma amino acid profiles. METHODS: 86 patients with HBV-related cirrhosis and eighty patients with chronic hepatitis B were included in this study. The plasma amino acid profiles were measured by the amino acid analyzer. Patients were randomly divided into two groups, of which the liver cirrhosis group was to receive daily LES (n = 43) or non-LES (n = 43) for 6 months. Plasma amino acid profiles and biochemical parameters were measured in both groups at baseline and after 1, 3, and 6 months. RESULTS: Compared to healthy controls, the plasma concentration in the liver cirrhosis group of threonine, serine, glycine, glutamine, cysteine, tyrosine, phenylalanine, arginine, and methionine increased significantly (P < 0.05), while the ratio of branched chain amino acids (BCAA) to aromatic amino acids (AAA) decreased significantly (P < 0.05). A carbohydrate-predominant LES treatment resulted in a significant increase in BCAA/AAA and decrease in the level of ammonia and glutamine compared with baseline after 6 months of supplementation (P < 0.05). Patients with Child-Pugh B and C are more responsive to changes in amino acid profiles than those with Child-Pugh A. CONCLUSIONS: The application of an LES carbohydrate module for six months in liver cirrhosis patients was associated with increased BCAA/AAA and decreased level of ammonia. Patients with Child-Pugh B and C grades were the most beneficial population.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage (p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.

BACKGROUND: Nowadays, metabolic syndrome (MetS) has become a great public health crisis that threatens too many lives worldwide. Many previous studies have been investigated the association between MetS and anthropometric indices. This study is aimed at investigating the association between anthropometric indices with gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). We were using data from a large population-based cohort of seemingly healthy women and men. METHODS: A total of 7216 participants were included in this study. The serum levels of GGT, ALP, ALT, and AST with bioimpedance measures were obtained at the time of enrollment. Multiple regression analysis was performed to assess the relationship between anthropometric indices and serum levels of the aforementioned laboratory tests. RESULTS: Serum levels of GGT, ALP, ALT, and AST significantly correlated with body mass index (BMI). Only ALP had a significant association with visceral fat area (VFA). AST, ALT, and ALP levels had a positive correlation with 50 kHz whole-body phase. CONCLUSION: From the findings of this study, body mass index consistently appeared a good predictor of elevated hepatic enzymes and triglycerides. Thus, it can be helpful in clinical settings to identify patients at risk of nonalcoholic fatty liver disease, which is closely related to metabolic syndrome.

OBJECTIVE: In the recent time, endoradionuclide therapy for metastatic castration-resistant prostate carcinoma employing 177Lu-PSMA-617 has yielded encouraging results and several clinical trials with the agent are currently ongoing. Routine preparation of 177Lu-PSMA-617 patient doses can be made simpler and convenient, if the ingredients essential for radiolabeling are made available in a ready-to-use lyophilized form. METHODS: PSMA-617 freeze-dried kit was formulated and used for the preparation of 177Lu-PSMA-617 clinical dose with high radiochemical purity using low/medium specific activity 177Lu. Detailed radiochemical studies were performed to determine the maximum activity and volume of 177LuCl3, which can be added in the kit for the formulation of 177Lu-PSMA-617. Studies were also performed to determine the shelf life of the kit to ensure its long-term usage. Studies were performed in buffer as well as human serum medium to determine the stability of the 177Lu-PSMA-617 complex after storing in respective media up to 7 days postpreparation. About ten patient doses of 177Lu-PSMA-617 were administered, and posttherapy scans were acquired. RESULTS: The formulated freeze-dried kit of PSMA-617 could be radiolabeled with an average percentage radiochemical purity > 98.53 ± 0.38. The freeze-dried kit was found suitable for tolerating up to 0.5 mL of 177LuCl3 (in 0.01 N HCl) and specific activity of 555 MBq/μg (15 mCi/μg) for the preparation of the patient dose of 177Lu-PSMA-617. The 177Lu-PSMA-617 complex prepared using the freeze-dried kit of PSMA-617 was observed to maintain % radiochemical purity (RCP) of 96.74 ± 0.87 and 94.81 ± 2.66, respectively, even after storing up to 7 days in buffer and human serum, respectively. 177Lu-PSMA-617 prepared using the in-house formulated freeze-dried kit of PSMA-617 exhibited accumulation in metastatic lesions picked up in a pretherapy PET scan. Reduction in number as well as size of lesions was observed in posttherapy scans acquired after two months of administering the first therapeutic dose of 177Lu-PSMA-617. CONCLUSIONS: The freeze-dried kit of PSMA-617 could be used for the preparation of 177Lu-PSMA-617 with high radiochemical purity (>98%) in a reproducible manner. 177Lu-PSMA-617 prepared using the developed kit was successfully evaluated in patients suffering from metastatic prostate cancer.

Although more and more evidence supports CDC28 protein kinase subunit 1B (CKS1B) is involved significantly in the development of human cancers, most of the researches have focused on a single disease, and pan-cancer studies conducted from a holistic perspective of different tumor sources have not been reported yet. Here, for the first time, we investigated the potential oncogenic and prognostic role of CKS1B across 33 tumors based on public databases and further verified it in a small scale by RNA sequencing or quantitative real-time PCR. CKS1B was generally highly expressed in a majority of tumors and had a notable correlation with the prognosis of patients, but its prognostic significance in different tumors was not exactly the same. In addition, CKS1B expression was also closely related to the infiltration of cancer-associated fibroblasts in tumors such as breast invasive carcinoma, kidney chromophobe, lung adenocarcinoma, and tumor-infiltrating lymphocytes in tumors such as glioblastoma multiforme, bladder urothelial carcinoma, and brain lower grade glioma. Moreover, reduced CKS1B methylation was observed in certain tumors, for example, adrenocortical carcinoma. Cell cycle and kinase activity regulation and PI3K-Akt signaling pathway were found to be involved in the functional mechanism of CKS1B. In conclusion, our first pan-cancer analysis of CKS1B contributes to a better overall understanding of CKS1B and may provide a new target for future cancer therapy.

OBJECTIVE: We aimed to assess the effects of renal denervation (RDN) on systemic and pulmonary hemodynamics in a swine model of thromboxane A2- (TXA2-) induced pulmonary arterial hypertension (PAH). METHODS: The study protocol comprised two PAH inductions with a target mean pulmonary artery pressure (PAP) of 40 mmHg at baseline and following either the RDN or sham procedure. Ten Landrace pigs underwent the first PAH induction; then, nine animals were randomly allocated in 1 : 1 ratio to RDN or sham procedure; the second PAH induction was performed in eight animals (one animal died of pulmonary embolism during the first PAH induction, and one animal died after RDN). In the RDN group, ablation was performed in all available renal arteries, and balloon inflation within artery branches was performed in controls. An autopsy study of the renal arteries was performed. RESULTS: At baseline, the target mean PAP was achieved in all animals with 25.0 [20.1; 25.2] mcg of TXA2. The second PAH induction required the same mean TXA2 dose and infusion time. There was no statistically significant difference in the mean PAP at second PAH induction between the groups (39.0 ± 5.3 vs. 39.75 ± 0.5 mmHg, P > 0.05). In the RDN group, the second PAH induction resulted in a numerical but insignificant trend toward a decrease in the mean systemic blood pressure and systemic vascular resistance, when compared with the baseline induction (74 ± 18.7 vs. 90.25 ± 28.1 mmHg and 1995.3 ± 494.3 vs. 2433.7 ± 1176.7 dyn∗sec∗cm -5, P > 0.05, respectively). No difference in hemodynamic parameters was noted in the sham group between the first and second PAH induction. Autopsy demonstrated artery damage in both groups, but RDN resulted in more severe lesions. CONCLUSIONS: According to our results, RDN does not result in significant acute pulmonary or systemic hemodynamic changes in the TXA2-induced PAH model. The potential chronic effects of RDN on PAH require further research.

BACKGROUND: Adjuvant chemotherapy with CapeOX regimen is widely used in resected rectal cancer, which brings benefits to patients. But drug-related toxicities are severe during this process; thus, survival outcomes may potentially be affected. This study explored the efficacy of two Chinese herbal injections, Aidi injection (ADI) and Brucea javanica oil emulsion injection (BJOEI), as adjuvant drugs in CapeOX adjuvant chemotherapy on rectal cancer patients. METHODS: A total of 240 cases were enrolled in this retrospective study. 80 cases received CapeOX with ADI (the ADI group), 80 cases received CapeOX with BJOEI (the BJOEI group), and the rest 80 cases received CapeOX alone (the control group). After four cycles' chemotherapy, adverse reactions (ADRs) and quality of life (QOL) were analyzed. Then, patients received follow-up for at least one year, and the endpoint was disease-free survival (DFS). RESULTS: All patients completed at least four cycles' adjuvant chemotherapy. The incidence of leukopenia and thrombocytopenia was significantly lower in the ADI group; the incidence of nausea was significantly lower in the BJOEI group; the incidence of hand-foot syndrome was significantly lower in both the ADI group and BJOEI group. Significant difference was found in the control group regarding the Karnofsky Performance Status (KPS) scores prior and posttreatment. No difference was found among three groups regarding one-year DFS. CONCLUSION: As adjuvant drugs for rectal cancer during CapeOX chemotherapy, ADI shows advantages in decreasing leukopenia and thrombocytopenia, while BJOEI results better in remitting nausea. Both two CHIs had positive impacts on decreasing hand-foot syndrome and the maintenance of patients' QOL. It is worthy of further study and promotion for CHIs.

Oral carcinoma represents one of the most common malignancies worldwide. Oral squamous cell carcinomas (OSCCs) account over 90% of all oral malignant tumors and are characterized by high mortality in the advanced stages. Early diagnosis is often a challenge for its ambiguous appearance in early stages. Mucosal infection by the human papillomavirus (HPV) is responsible for a growing number of malignancies, particularly cervical cancer and oropharyngeal carcinomas. In addition, Candida albicans (C. albicans), which is the principal fungi involved in the oral cancer development, may induce carcinogenesis through several mechanisms, mainly promoting inflammation. Medical knowledge and research on adolescent/pediatric patients' management and prevention are in continuous evolution. Besides, microbiota can play an important role in maintaining oral health and therefore all human health. The aim of this review is to evaluate epidemiological and pathophysiological characteristics of the several biochemical pathways involved during HPV and C. albicans infections in pediatric dentistry.

OBJECTIVE: This study intends to analyze the data of fungemia in a large tertiary hospital from 2010 to 2019, and is aimed at understanding its epidemic characteristics and drug resistance. METHODS: The "Hospital Infection Real-Time Monitoring System" was used to retrieve the case information of patients who were hospitalized for more than 48 hours from 2010 to 2019. The questionnaire was designed to collect patients' basic information, infection situation, drug resistance, and other related information. Statistical software was used for analysis. RESULTS: The fungi detection rate was in the range of 0.19%~0.75% in ten years, the average rate was 0.29%, and the rate 0.2%~0.3% since 2013, which was lower than that from 2010 to 2012. Non-Candida albicans was the main fungus, accounting for 62.50%. The drug resistance of non-C. albicans was higher than that of C. albicans, among which C. glabrata had the highest resistance rate. Data analysis showed that the patients with more serious basic diseases, combined with infection of other sites, surgery, long hospital stay, combination of antibiotics, and invasive catheterization, were more likely to occur fungemia. CONCLUSION: We should pay more attention to the patients with high-risk factors of fungemia and focus on the drug resistance of non-C. albicans, choose the right antifungal drugs, so as to improve the level of diagnosis and treatment.

Multiple drug resistance TB (MDR-TB) has greatly jeopardized the effective control of tuberculosis in Africa. This study is aimed at determining the incidence and predictors of drug resistant-TB amongst bacteriologically diagnosed cases in the Littoral region of Cameroon. This was a descriptive cross-sectional survey conducted from January 2016 to December 2017. A total of 1665 participants were enrolled from 32 diagnostic and treatment centers (DTCs) in the Littoral region. Demographic, clinical, socioeconomic, and behavioral data were obtained using a pretested structured questionnaire. Drug susceptibility testing was performed using Gene Xpert MTB/RIF assay and line probe assay (LPA). Consent was obtained from participant/guidance. Data analysis was carried with SPSS version 21. Univariate and multiple logistic regression was performed at 5% significance level. The incidence of rifampicin and MDR-TB was 86 (5.2%) and 75 (4.5%), respectively. More (11.3%) cases of drug resistance were diagnosed in 2016 compared to 2017 (3.7%). Eleven (0.7%) were resistant to rifampicin only. A total of 19 (4.4%) cases of rifampicin resistance were detected from newly diagnosed cases and 67 (5.4%) from previously retreated cases. Pre-XDR-TB was detected in 2 (2.7%) of the MDR-TB cases amongst whom 1 (1.3%) was extensive drug resistance TB (XDR-TB). Age greater than 60 years old (OR = 4.98, p = 0.047), being married (OR = 1.91, p = 0.006), being currently incarcerated (OR = 1.74, p = 0.027), and having contact with known TB cases (OR = 1.88, p = 0.007) were associated to MDR-TB in a univariate analysis. This study highlights the declining rates of TB drug resistance in the region over the years probably due to the introduction of Gene Xpert that results in early detection of RR-TB. It also shows that age greater than 60 years, being married, and incarcerated are predictors of drug resistant-TB, while the year of patient enrolment and previous exposure to TB treatment were independent predictors of drug resistance in the Littoral region of Cameroon.

The function of glutamate ionotropic receptor NMDA type subunit 1 (GRIN1) in neurodegenerative diseases has been widely reported; however, its role in the occurrence of glioma remains less explored. We obtained clinical data and transcriptome data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Hub gene's expression differential analysis and survival analysis were conducted by browsing the Gene Expression Profiling Interactive Analysis (GEPIA) database, Human Protein Atlas database, and LOGpc database. We conducted a variation analysis of datasets obtained from GEO and TCGA and performed a weighted gene coexpression network analysis (WGCNA) using the R programming language (3.6.3). Kaplan-Meier (KM) analysis was used to calculate the prognostic value of GRIN1. Finally, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Using STRING, we constructed a protein-protein interaction (PPI) network. Cytoscape software, a prerequisite of visualizing core genes, was installed, and CytoHubba detected the 10 most tumor-related core genes. We identified 185 differentially expressed genes (DEGs). GO and KEGG enrichment analyses illustrated that the identified DEGs are imperative in different biological functions and ascertained the potential pathways in which the DEGs may be enriched. The overall survival calculated by KM analysis showed that patients with lower expression of GRIN1 had worse prognoses than patients with higher expression of GRIN1 (p = 0.004). The GEPIA and LOGpc databases were used to verify the expression difference of GRIN1 among GBM, LGG, and normal brain tissues. Ultimately, immunohistochemical assay results showed that GRIN1 was detected in normal tissue and not in the tumor specimens. Our results highlight a potential target for glioma treatment and will further our understanding of the molecular mechanisms underlying the treatment of glioma.

OBJECTIVE: To explore the role of conjoint fascial sheath (CFS) suspension in the treatment of severe ptosis. METHODS: A total of 110 patients with severe ptosis who were admitted to our hospital from May 2018 to December 2020 were included. Fifty-seven patients treated with frontalis suspension were assigned into group A, and the remaining 53 patients treated with CFS suspension were assigned into group B. The curative effect, ocular surface alterations, complications, and satisfaction in the two groups were compared. RESULTS: Patients in group B suffered from severe upper eyelid retraction and lid lag than those in group A, as well as more limited range of motion (ROM) (P < 0.05). The curative effect and patient satisfaction in group B were higher than those in group A (P < 0.05). Postsurgical complications in group B were fewer than those in group A (P < 0.05). CONCLUSION: CFS suspension is effective in the treatment of severe ptosis.

BACKGROUND: Cancer stem cells (CSCs) are responsible for tumorigenesis, chemoresistance, and metastasis. Chemoresistance is a major challenge in the management of lung cancer. Glutathione-sulphur-transferase-π (GST-π) plays an important role in the origin and development of various types of cancer by regulating the cellular redox balance. Recent investigations have demonstrated that GST-π is associated with the chemoresistance of lung CSCs (LCSCs). However, the mechanism of GST-π in lung cancer, particularly in LCSCs, remains unclear. The present study is aimed at exploring the potential role of GST-π in stemness and cisplatin (DDP) resistance of LCSCs. Materials and methods. In the present study, lung cancer cell spheres were established using the A549 cell line, which according to our previous research, was confirmed to exhibit characteristics of stem cells. Next, GST-π protein expression, apoptosis percentage, and intracellular reactive oxygen species (ROS) concentration in A549 adherent cells and A549 cell spheres were analyzed by western blotting and flow cytometry, respectively. Finally, DDP resistance, ROS concentration, and GST-π expression in LCSCs were analyzed following the interference with GST-π using DL-buthionine-(S,R)-sulphoximine and N-acetylcysteine. RESULTS: The results revealed that GST-π was highly expressed in A549 cell spheres compared with A549 adherent cells and was associated with a decreased intracellular ROS concentration (both P < 0.05). Regulating GST-π protein expression could alter DDP resistance of LCSCs by influencing ROS. CONCLUSION: These results suggested that GST-π may be important for LCSC drug resistance by downregulating ROS levels. These findings may contribute to the development of new adjuvant therapeutic strategies for lung cancer.

Juvenile dermatomyositis is a chronic and rare autoimmune disorder classified into the spectrum of idiopathic inflammatory myopathies. Although this entity is mainly characterized by the presence of pathognomonic cutaneous lesions and proximal muscle weakness, the clinical manifestation can be highly heterogeneous; thus, diagnosis might be challenging. Current treatment recommendations for juvenile dermatomyositis, based mainly upon case series, include the use of corticosteroids, immunomodulatory, and immunosuppressive agents. Recently, several specific autoantibodies have been shown to be associated with distinct clinical phenotypes of classic dermatomyositis. There is a need to further evaluate their relevance in the formation of various clinical features. Furthermore, while providing more personalized treatment strategies, one should consider diversity of autoantibody-related subgroups of juvenile dermatomyositis.

PURPOSE: Contradicting definitions of periprosthetic joint infection (PJI) are in use. Joint aspiration is performed before total hip arthroplasty (THA) revision. This study investigated the influence of PJI definition on PJI prevalence at THA revision. Test quality of prerevision aspiration was evaluated for the different PJI definitions. METHODS: 256 THA revisions were retrospectively classified to be infected or not infected. Classification was performed according to the 4 different definitions proposed by the Musculoskeletal Infection Society (MSIS), the Infectious Diseases Society of America (IDSA), the International Consensus Meeting (ICM), and the European Bone and Joint Infection Society (EBJIS). Only chronic PJIs were included. RESULTS: PJI prevalence at revision significantly correlated with the applied PJI definition (p = 0.01, Cramer's V = 0.093). PJI prevalence was 20.7% for the MSIS, 25.4% for the ICM, 28.1% for the IDSA, and 32.0% for the EBJIS definition. For synovial fluid white blood cell count, the best ROC-AUC for predicting PJI was 0.953 in combination with the MSIS definition. CONCLUSION: PJI definition significantly influences the rate of diagnosed PJIs at THA revision. Synovial fluid white blood cell count is a reliable means to rule out PJI. In cases with a borderline high synovial white blood cell count before THA revision as the only sign of chronic PJI, an extended diagnostic work-up should be considered.

BACKGROUND: Intervertebral disc is responsible for absorbing and transmitting mechanical compression. Under physiological conditions, the peripheral annulus fibrosus (AF) cells are subjected to different magnitudes of transverse mechanical stretch depending on the swelling of the central nucleus pulposus tissue. However, the biological behavior of AF cells under mechanical stretch is not well studied. OBJECTIVE: This study was performed to study the effects of mechanical tension on AF cell senescence and the potential signaling transduction pathway. METHODS: Rat AF cells were made to experience different magnitudes of mechanical stretch (2% elongation and 20% elongation for 4 hours every day at 1 Hz) in a 10-day experiment period. The inhibitor RKI-1447 of the Rho-associated coiled-coil-containing protein kinases (ROCK) was added along with culture medium to investigate its role. Cell proliferation, cell cycle, telomerase activity, and expression of senescence markers (p16 and p53) were analyzed. RESULTS: We found that 20% elongation significantly decreased cell proliferation, promoted G0/G1 cell cycle arrest, decreased telomerase activity, and upregulated mRNA/protein expression of p16 and p53. Moreover, the inhibitor RKI-1447 partly resisted effects of 20% elongation on these parameters of cell senescence. CONCLUSION: High mechanical stretch obviously induces AF cell senescence through the RhoA/ROCK pathway. This study provides us a deeper understanding on the AF cell's behavior under mechanical stretch.

OBJECTIVE: Rap1GAP is considered a tumor suppressor gene, but its regulatory mechanism in papillary thyroid cancer (PTC) has not been clearly elucidated. The aim of this study was to explore whether the regulation between Rap1GAP and sodium/iodine transporter (NIS) in tumorigenesis of PTC is mediated by TGF-β1. METHODS: Western blotting (WB) and quantitative reverse-transcription polymerase chain reaction were performed to analyze the relationships between TGF-β1 concentration and NIS expression. After transfecting BCPAP cells with siRNAs, the Rap1GAP interference model was successfully established. Then, the expression and nuclear localization of TGF-β1 and pathway-related proteins were detected. Flow cytometry was applied to analyze cell apoptosis and cycle. WB was performed to detect apoptotic-related proteins. Wound healing and transwell assays were used to measure cell migration and invasion. EDU was performed to detect cell proliferative activity. RESULTS: The results suggested that TGF-β1 could significantly inhibit the expression of NIS in both mRNA and protein levels. In BCPAP cells transfected with siRNA-Rap1GAP, the expression levels of TGF-β1, Foxp3, and p-Smad3 were significantly increased. By applying immunofluorescence assay, the nuclear localizations of TβR-1 and p-Smad3 were found to be activated. Moreover, anti-TGF-β1 can reverse the decrease in NIS expression caused by downregulation of Rap1GAP. Additionally, the knockdown of Rap1GAP could alter the cell apoptosis, cycle, migration, invasion, and proliferation of BCPAP. CONCLUSION: The downregulation of Rap1GAP expression can activate the TGF-β/Smad3 pathway to inhibit NIS expression and alter the tumor cell functions of PTC.

The hypothalamus plays a central role in the integrated regulation of feeding and energy homeostasis. The hypothalamic arcuate nucleus (ARC) contains a population of neurons that express orexigenic and anorexigenic factors and is thought to control feeding behavior via several neuronal circuits. In this study, a comparative proteomic analysis of low-fat control diet- (LFD-) and high-fat diet- (HFD-) induced hypothalamic ARC was performed to identify differentially expressed proteins (DEPs) related to changes in body weight. In the ARC in the hypothalamus, 6621 proteins (FDR < 0.01) were detected, and 178 proteins were categorized as DEPs (89 upregulated and 89 downregulated in the HFD group). Among the Gene Ontology molecular function terms associated with the DEPs, protein binding was the most significant. Fibroblast growth factor receptor substrate 2 (Frs2) and SHC adaptor protein 3 (Shc3) were related to protein binding and involved in the neurotrophin signaling pathway according to Kyoto Encyclopedia of Genes and Genomes analysis. Furthermore, high-precision quantitative proteomic analysis revealed that the protein profile of the ARC in mice with HFD-induced obesity differed from that in LFD mice, thereby offering insight into the molecular basis of feeding regulation and suggesting Frs2 and Shc3 as novel treatment targets for central anorexigenic signal induction.

Gastric cancer (GC), as an epidemic cancer worldwide, has more than 1 million new cases and an estimated 769,000 deaths worldwide in 2020, ranking fifth and fourth in global morbidity and mortality. In mammals, both miRNAs and transcription factors (TFs) play a partial role in gene expression regulation. The mRNA expression profile and miRNA expression profile of GEO database were screened by GEO2R for differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Then, DAVID annotated the functions of DEGs to understand the functions played in biological processes. The prediction of potential target genes of miRNA and key TFs of mRNA was performed by mipathDB V2.0 and CHEA3, respectively, and the gene list comparison was performed to look for overlapping genes coregulated by key TFs and DEMs. Finally, the obtained miRNAs, TF, and overlapping genes were used to construct the miRNA-mRNA-TF regulatory network, which was verified by RT-qPCR. 76 upregulated DEGs, 199 downregulated DEGs, and 3 upregulated miRNAs (miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p) were identified from the expression profiles of mRNA (GSE26899, GSE29998, GSE51575, and GSE13911) and miRNA (GSE93415), respectively. Through database prediction and gene list comparison, it was found that among the 199 downregulated DEGs, 61, 71, and 69 genes were the potential targets of miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p, respectively. 199 downregulated DEGs were used as the gene list for the prediction of key TFs, and the results showed that RFX6 ranked the highest. The potential target overlap genes of miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p were 4 genes (SH3GL2, ATP4B, CTSE, and SORBS2), 7 genes (SLC7A8, RNASE4, ESRRG, PGC, MUC6, Fam3B, and FMO5), and 6 genes (CHGA, PDK4, TMPRSS2, CLIC6, GPX3, and PSCA), respectively. Finally, we constructed a miRNA-mRNA-TF regulatory network based on the above 17 mRNAs, 3 miRNAs, and 1 TF and verified by RT-qPCR and western blot results that the expression of RFX6 was downregulated in GC tissues. These identified miRNAs, mRNAs, and TF have a certain reference value for further exploration of the regulatory mechanism of GC.

OBJECTIVE: Determining sensitivity to allergens is an essential step in diagnosing children with allergic diseases. Chronic cough has remained poorly understood with causative triggers. The purpose of our study was to shed light on the relationship between sensitization to aeroallergens and chronic cough. METHODS: This population-based study examined children (aged 7 years to 13 years) between June and July 2016. The 1,259 children, 72 of whom (5.7%) had a chronic cough, and 1,187 of whom (94.3%) did not (controls), completed the questionnaire, but 1,051 children completed skin prick tests (SPTs) with eight aeroallergens. RESULTS: There were positive SPT results to at least 1 allergen in 549 children (52.2%). Sensitization to house dust mite (HDM) was most common (chronic cough = 46.9%; controls = 47.2%), followed by pollen (chronic cough = 21.9%; controls = 16.5%) in both groups, but there was no difference in allergic profile and sensitization to aeroallergen (P > 0.05 for all comparisons). Multivariable analysis with adjustment for confounding indicated that children who were in sensitization to pollen had an increased risk of chronic cough (aOR = 2.387; 95% CI: 1.115 to 5.111; P = 0.025). Multivariable analysis with adjustment for confounding indicated that children who were exposed to current smoking (aOR = 4.442; 95% CI: 1.831 to 10.776; P = 0.001) and mold (aOR = 1.988; 95% CI: 1.168 to 3.383; P = 0.011) were associated with chronic cough. CONCLUSION: Sensitization to pollen should be considered as a potential contributing factor to the development of chronic cough in school-aged children.

OBJECTIVE: We investigated combined cognitive and exercise interventions in the literature and summarized their effectiveness in improving poststroke cognitive impairment (PSCI). Data Sources. Electronic databases and trial registries were searched from their inception until July 2020. Study Selection. Trials were collected with the following study inclusion criteria: (1) patients over 18 years of age who were diagnosed with PSCI; (2) combined cognitive-exercise interventions, regardless of the order of the two types of interventions or whether they were administered simultaneously; (3) any control group studied at the same time that was deemed acceptable, including no intervention/routine care, delayed intervention, sham intervention, and passive training; (4) the use of any validated cognitive neuropsychological test to evaluate cognitive function; and (5) clinically administered random trials with controls. Data Extraction. Five randomized controlled trials met the inclusion criteria. Two reviewers independently assessed the eligibility of the full texts and methodological quality of the included studies using the Cochrane risk of bias tool. Inconsistent results were resolved by additional discussion or decided by a third examiner, if necessary. Data Analysis. Meta-analysis demonstrated that the combined interventions had a significant effect on executive function and working memory [Stroop test (time), standardized mean difference (SMD) = 0.42, 95% confidence interval (CI): 0.80-0.04, p = 0.02; Trail Making Test, SMD = 0.49, 95% CI: 0.82-0.16, p = 0.004; Forward Digit Span Test, SMD = 0.91, 95% CI: 0.54-1.29, p ≤ 0.001]. While it was impossible to conduct a meta-analysis of global cognitive function and other cognitive domains, individual experiments demonstrated that the combined interventions played a significant role in global cognition, reasoning ability, logical thinking, and visual-spatial memory function. CONCLUSIONS: Our analyses demonstrated that the combined interventions had a significant effect on the improvement of PSCI, particularly in terms of executive function. However, the moderate risk of bias in the included trials and the small number of relevant studies indicated a need for more uniform diagnostic and evaluation criteria, and larger trials would provide stronger evidence to better understand the effectiveness of the combined interventions. This trial is registered with trial registration number INPLASY202160090.

INTRODUCTION: Oral health is considered as one of the essential components of the overall health of every individual. Maintaining oral health is a gradual process that requires commitment. Children who require special care such as hearing impairment experience difficulty in maintaining oral health primarily due to communication difficulties. This study is aimed at using different interventions to evaluate the improvement of oral hygiene in hearing impaired children. MATERIALS AND METHODS: Fifty-nine children were recruited in this study that were allocated randomly into each group with twenty children as follows: group 1: pictorial, group 2: video, and group 3: control. Mean plaque and gingival scores were noted before and after the use of different interventions. Oral hygiene was categorized as "excellent," "good," and "fair." Gingival health was categorized as "healthy," "mild gingivitis," and "moderate gingivitis." RESULTS: Thirty-four children (57.6%) were from 12-13 years of age bracket, and 25 (42.4%) belonged to 14-16 years of age. Regarding gender, there were 37 (62.7%) males and 22 (37.3%) females. About comparison of mean gingival and plaque scores before and after interventions in each group, a significant difference was found in group 1 (p < 0.001) and group 2 (p < 0.001), as compared to group 3 where the difference in scores was not significant (p > 0.05). CONCLUSION: Maintaining oral health requires the compliance of individuals to perform different methods of preventive dentistry, such as tooth brushing and use of dental floss. The use of different oral hygiene educational interventions such as pictorial and video methods have been proven and useful for hearing impaired children in improving oral health.

BACKGROUND: To know the clinical value of mammotome-assisted minimally invasive resection (MAMIR) in the treatment of patients with breast neoplasm, we performed a retrospective clinical study for the patients treated with the MAMIR and conventional open resection (COR). METHODS: Postoperative complications were compared between 40 patients treated with the MAMIR and 40 patients treated with the COR. The postoperative complications mainly included intraoperative blood loss, hospitalization days, operative time, surgical scar, and incidence of postoperative complications. RESULTS: We found that the amount of intraoperative blood loss, hospitalization days, operative time, surgical scar, and incidence of postoperative complications in the MAMIR group were significantly lower than those of patients in the COR group. CONCLUSION: Our results indicated that patients with breast neoplasm treated with the MAMIR had better outcomes, which reinforced the advantage of this approach.

Tissue engineering is biomedical engineering that uses suitable biochemical and physicochemical factors to assemble functional constructs that restore or improve damaged tissues. Recently, cell therapies as a subset of tissue engineering have been very promising in the treatment of ocular diseases. One of the most important biophysical factors to make this happen is noninvasive electrical stimulation (ES) to target ocular cells that may preserve vision in multiple retinal and optic nerve diseases. The science of cellular and biophysical interactions is very exciting in regenerative medicine now. Although the exact effect of ES on cells is unknown, multiple mechanisms are considered to underlie the effects of ES, including increased production of neurotrophic agents, improved cell migration, and inhibition of proinflammatory cytokines and cellular apoptosis. In this review, we highlighted the effects of ES on ocular cells, especially on the corneal, retinal, and optic nerve cells. Initially, we summarized the current literature on the in vitro and in vivo effects of ES on ocular cells and then we provided the clinical studies describing the effect of ES on ocular complications. For each area, we used some of the most impactful articles to show the important concepts and results that advanced the state of these interactions. We conclude with reflections on emerging new areas and perspectives for future development in this field.

The human skeleton of a young adult male with marked asymmetry of the bilateral upper extremities was excavated from the Mashiki-Azamabaru site (3000-2000 BCE) on the main island of Okinawa in the southwestern archipelago of Japan. The skeleton was buried alone in a corner of the cemetery. In this study, morphological and radiographic observations were made on this skeleton, and the pathogenesis of the bone growth disorder observed in the left upper limb was discussed. The maximum diameter of the midshaft of the humerus was 13.8 mm on the left and 21.2 mm on the right. The long bones comprising the left upper extremity lost the structure of the muscle attachments except for the deltoid tubercle of the humerus. The bone morphology of the right upper extremity and the bilateral lower extremities was maintained and was close to the mean value of females from the Ohtomo site in northwestern Kyushu, Japan, during the Yayoi period. It is assumed that the anomalous bone morphology confined to the left upper extremity was secondary to the prolonged loss of function of the muscles attached to left extremity bones. In this case, birth palsy, brachial plexus injury in childhood, and acute grey matter myelitis were diagnosed. It was suggested that this person had survived into young adulthood with severe paralysis of the left upper extremity due to injury or disease at an early age.

Traditional pathogenic diagnosis presents defects such as a low positivity rate, inability to identify uncultured microorganisms, and time-consuming nature. Clinical metagenomics next-generation sequencing can be used to detect any pathogen, compensating for the shortcomings of traditional pathogenic diagnosis. We report third-generation long-read sequencing results and second-generation short-read sequencing results for ascitic fluid from a patient with liver ascites and compared the two types of sequencing results with the results of traditional clinical microbial culture. The distribution of pathogenic microbial species revealed by the two types of sequencing results was quite different, and the third-generation sequencing results were consistent with the results of traditional microbial culture, which can effectively guide subsequent treatment. Short reads, the lack of amplification, and enrichment to amplify signals from trace pathogens, and host background noise may be the reasons for the high error in the second-generation short-read sequencing results. Therefore, we propose that long-read-based rRNA analysis technology is superior to the short-read shotgun-based metagenomics method in the identification of pathogenic bacteria.

Endothelial inflammation and vascular damage are essential risk factors contributing to hypertension. Suppressor of cytokine signaling 3 (SOCS3) is involved in the regulation of multiple inflammatory pathways. A large number of studies have shown that the anti-inflammatory effect of SOCS3 in hypertension, obesity, and allergic reactions has brought more insights into the inhibition of inflammation. Therefore, we selected a tagSNP of SOCS3 (rs8064821) to investigate whether they are contributing to the risk of hypertension in the Chinese population. In total, 532 patients with hypertension and 569 healthy controls were enrolled for two central of China. SOCS3 rs8064821 C>A polymorphism was genotyped using TaqMan assay. SOCS3 rs8064821 CA genotype was associated with an increased risk of hypertension (OR = 1.821, 95%CI = 1.276-2.600, P = 0.001). Rs8064821 A allele was associated with higher SOCS3 mRNA level in PBMCs from healthy donors. SOCS3 rs8064821 C>A polymorphism may contribute to the risk of hypertension in the Chinese population by regulating the expression of SOCS3.

Obesity is a risk factor of cardiovascular disease-related mortality and may be associated with changes in the autonomic nerve activity. Nurses working shifts and caring for patients are under great mental and physical pressure, and research has proven that these can negatively affect the body. The objective of this study was to examine the influence of obesity in nurses on their heart rate variability (HRV) and determine whether age or shift type moderates this influence. A questionnaire survey and HRV measurements were conducted on nurses at a hospital in Taiwan during a routine employee health checkup. HRV analysis was conducted using a noninvasive HRV monitor for five minutes. A total of 242 nurses with a mean age of 28.98 ± 6.56 years were enrolled in this study. An overly large waist circumference (WC) had a negative impact on high frequency (HF), low frequency (LF), and standard deviation of normal-to-normal interval (SDNN), while an overly high body mass index (BMI) had a negative impact on very low frequency (VLF) and SDNN. The interaction term "overly large WC × age" had a negative impact on HF (β = -0.21, p = 0.010) and LF (β = -0.18, p = 0.030), whereas the interaction term "overly high BMI×age" had a negative impact on HF (β = -0.27, p = 0.001), LF (β = -0.19, p = 0.023), and VLF (β = -0.17, p = 0.045). The interaction terms "overly large WC × shift type" and "overly high BMI × shift type" did not influence any HRV parameters. As age increased, so did the degree to which the HF and LF of nurses with an overly large WC were lower than normal, and so did the degree to which the HF, LF, and VLF of nurses with an overly high BMI were lower than normal.

Curcumin is a type of plant polyphenol extracted from Curcuma longa L. rhizome, which demonstrates antitumor activity in breast cancer cells in vitro. To investigate the combined effect and possible mechanism of curcumin and glucose-gold nanoparticles (Glu-GNPs), the radiosensitivity of breast carcinoma xenografts was assessed in nude mice. MDA-MB-231 cells labeled with firefly luciferase were inoculated into the mammary fatty pads of nude mice to establish a transplantation tumor model of human breast cancer. The tumor-bearing mice were treated with different drugs (curcumin, Glu-GNPs, and cisplatin) for 3 weeks prior to radiotherapy. The body weights and tumor volumes of the mice were measured in regular intervals. Tumor bioluminescence intensity was determined in real-time using an in vivo bioluminescence imaging system to monitor tumor growth. Transplanted tumor tissue samples were taken for hematoxylin and eosin (HE) staining, and the expression of VEGF, HSP90, HIF-1α, and MMP9 was evaluated via reverse transcription-quantitative PCR or immunohistochemistry. The results revealed that the breast tumor-bearing nude mouse model was successfully established, as evidenced by a stable expression of luciferase. Curcumin inhibited the growth of tumors without causing significant weight loss in mice. Furthermore, additive inhibition was demonstrated when curcumin was administered in combination with Glu-GNPs and irradiation. Tumor bioluminescence intensity was decreased in the model group following curcumin, Glu-GNPs, and irradiation treatment. HE staining demonstrated that transplanted tumors were malignant, with necrotic tissue exhibited centrally. It was concluded that curcumin administered in combination with Glu-GNPs and X-ray irradiation could reduce the protein expression of VEGF, HSP90, HIF-1α, and MMP9 in tumor tissue when compared with the model group. Curcumin and Glu-GNPs administered with X-ray irradiation significantly inhibited tumor growth and induced radiosensitivity, which may be associated with the inhibition of angiogenesis in tumor tissue.

PURPOSE: The acellular dermal matrix plays an important role in reinforcing thin mastectomy skin and repositioning the implant in prosthetic breast reconstruction. As the concept of prepectoral plane has become widespread, the role of the acellular dermal matrix has become increasingly important. However, evidences and standards for appropriate thickness and direction during placement remain insufficient. This study is aimed at testing the assumption that differences in the acellular dermal matrix thickness and orientation during placement may affect surgical outcomes including the incidence of postoperative complications. METHODS: This was a retrospective single-centered analysis of 43 patients (50 breasts) who underwent implant-based reconstruction with MegaDerm® (L&C Bio, Seoul, Korea) and 23 patients (23 breasts) who underwent implant-based reconstruction with DermACELL® (LifeNet Health, Virginia Beach, VA, USA), two types of human-derived acellular dermal matrix. All surgeries were performed by a single surgeon. Demographic variables, surgery-related factors, and complications were compared between a thick matrix group (1.5-2.3 mm) and a thin matrix group (1.0-1.5 mm). The same processes were performed in the nonreverse and reverse matrix insertion groups. RESULTS: Baseline demographics and surgery-related data were summarized according to matrix thickness and direction. There were no significant intergroup differences in the demographic variables such as history of smoking, radiation, or chemotherapy. The mean drain volume was significantly higher in the thick matrix group than that in the thin matrix group (p = 0.0445). However, there were no significant differences in overall complication rates by matrix thickness (p = 0.3139). Additionally, there were no significant differences in complications between the nonreverse and reverse matrix insertion groups (p = 0.538). CONCLUSION: Our findings suggest that patients with a thick acellular dermal matrix need a prolonged period for engraftment. However, the thickness did not directly affect the surgical outcomes between the thick and thin matrix groups. Likewise, the orientation in which the acellular dermal matrix was inserted did not affect the surgical outcomes including postoperative complications.

METHODS: The subjects included 13 PI patients from the Hubei Provincial Hospital of TCM, Hubei University of TCM, and Wuhan Traditional Chinese Medicine Hospital, and the corresponding noninsomniac spouses of the patients were selected as controls. TWBXG was continuously administered for 4 weeks. The feces of PI patients and their noninsomniac spouses before and after treatment with TWBXG were collected. The intestinal flora composition of each group was detected by metagenomic sequencing, and the efficacy of TWBXG was evaluated by the PSQI scale. RESULTS: Compared with the control group, the model group showed an increase in the abundance of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, and Blautia obeum, while those of Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii were decreased. Compared with pretreatment, the PSQI score was significantly reduced (P < 0.05), the abundance of Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii increased, and that of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, and Blautia obeum decreased after treatment. However, there was still a certain gap in the abundance of related flora in the treatment group compared with the control. CONCLUSION: PI is associated with disturbances in the intestinal flora and is mainly related to the disorders of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, Blautia obeum, Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii. TWBXG can effectively treat PI, and its effect may be achieved by regulating the disordered intestinal flora. Clinical Trials. The study was registered in the Chinese clinical trial registry and approved by the World Health Organization clinical trial registration platform (Effects of the modified Tianwang Buxin granule and modified Tianwang Buxin decoction pieces on insomnia: a randomized, controlled trial, ChiCTR-IPR-17011549).

Curcumin (CUR) has interesting properties to cure cancer. Cold atmospheric plasma (CAP) is also an emerging biomedical technique that has great potential for cancer treatment. Therefore, the combined effect of CAP and CUR on inducing cytotoxicity and apoptosis of melanoma cancer cells might be promising. Here, we investigated the combined effects of CAP and CUR on cytotoxicity and apoptosis in B16-F10 melanoma cancer cells compared to L929 normal cells using MTT method, acridine orange/ethidium bromide fluorescence microscopic assay, and Annexin V/PI flow cytometry. In addition, the activation of apoptosis pathways was evaluated using BCL2, BAX, and Caspase-3 (CASP3) gene expression and ratio of BAX to BCL2 (BAX/BCL2). Finally, in silico study was performed to suggest the molecular mechanism of this combination therapy on melanoma cancer. Results showed that although combination therapy with CUR and CAP has cytotoxic and apoptotic effects on cancer cells, it did not improve apoptosis rate in melanoma B16-F10 cancer cells compared to monotherapy with CAP or CUR. In addition, evaluation of gene expression in cancer cell line confirmed that CUR and CAP concomitant treatment did not enhance the expression of apoptotic genes. In silico analysis of docked model suggested that CUR blocks aquaporin- (AQP-) 1 channel and prevents penetration of CAP-induced ROS into the cells. In conclusion, combination therapy with CAP and CUR does not improve the anticancer effect of each alone.

INTRODUCTION: miR-199a has been reported as an oncogene of various cancers. However, the biological function and regulatory mechanism of miR-199a in keratinocytes of cholesteatoma are still unclear. METHODS: Detection by qRT-PCR was conducted on miR-199a's expression in both thirty pairs of cholesteatoma tissues and normal skins. For characterizing the function of miR-199a, this research adopted transwell assay, wound healing assay, and CCK8 assays. Under the support of qRT-PCR, efforts were made to investigate the relative expression of candidate target genes. Moreover, the evaluation of the targeting relationship between miR-199a and the candidate target gene was conducted with the dual-luciferase reporter assay. RESULTS: The upregulation of miR-199a was found in cholesteatoma tissues, which facilitated the proliferation, migration, and invasion of HaCaT cells, while its downregulation caused opposite results. CONCLUSIONS: The findings of the present research offer more insights into the molecular mechanism of cholesteatoma progression.

BACKGROUND: The National Science and Technology Development Agency (NSTDA) in Thailand researched and prototyped digital radiography systems under the brand name BodiiRay aiming for sustainable development and affordability of medical imaging technology. The image restoration and enhancement were implemented for the systems. PURPOSE: The image quality of the systems was evaluated using images from phantoms and from healthy volunteers. METHODS: The survey phantom images from BodiiRay and other two commercial systems using the exposure settings for the chest, the abdomen, and the extremity were evaluated by three experience observers in terms of the high-contrast image resolution, the low-contrast image detectability, and the grayscale differentiation. The volunteer images of the chests, the abdomens, and the extremities from BodiiRay were evaluated by three specialized radiologists based on visual grading on 5-point scaled questionnaires for the anatomy visibility, the image quality satisfaction, and the diagnosis confidence in using the images. RESULTS: BodiiRay phantom results were similar to those from the commercial systems. The overall performance averaged across the exposure settings showed that BodiiRay was slightly better than Fujifilm FDR Go in the low-contrast detectability (p = 0.033) and in the grayscale differentiation (p = 0.004). It was also slightly better than Siemens YSIO Max in the high-contrast resolution (p = 0.018). The images of chest, pelvis, and hand phantoms illustrated comparable visual quality. For volunteer images, the percentage of the images scored ≥4 ranged from 61% to 99%, 23% to 92%, and 96% to 99% for the chest, abdomen, and extremity images, respectively. The average score ranged from 3.63 to 4.46, 3.18 to 4.21, and 4.41 to 4.51 for the chest, abdomen, and extremity images, respectively. CONCLUSION: The phantom image results showed the comparability of these systems. The clinical evaluation showed BodiiRay images provided sufficient image qualities for digital radiography of these body parts.

PURPOSE: To examine choroidal neovascularization (CNV) characteristics in patients with exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), using swept-source optical coherence tomography angiography (SS-OCTA), and investigate agreement with OCT B-scan, fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) by two different examiners. METHODS: This is a retrospective multicentric study that involved patients with a history of AMD and PCV. Examiner A, who had access to OCTA, B-scan OCT, FFA, and ICGA imaging, had to differentiate between AMD and PCV, study the activity of AMD using Coscas' criteria (active vs. quiescent), and categorize PCV subtypes, while examiner B had only access to OCTA. Then, the diagnostic concordance was assessed between both examiners. RESULTS: A total of 27 patients (11 females (40.7%) and 16 males (59.3%), P = 0.231) were included in the analysis. Among those, 13 patients presented with neovascular AMD and 14 patients with PCV. There were 92.3% of correct answers regarding appropriate diagnosis and lesion characterization among AMD patients, against 61.5% of correct answers among PCV patients. The overall interrater reliability agreement between examiners, using Cohen's kappa coefficient (κ) was 0.70 (0.5082-0.8916). Disagreement was found with one active AMD misdiagnosed as inactive AMD, three inactive PCV misdiagnosed as inactive AMD, and one inactive PCV misdiagnosed as active AMD. CONCLUSION: SS-OCTA alone remains limited in some specific phenotypes of PCV, which suggests the ongoing role of B-scan OCT associated with FFA and ICGA in the diagnosis of these conditions.

OBJECTIVE: To assess the effectiveness and safety of extracorporeal shockwave therapy (ESWT) for the treatment of chronic low back pain (CLBP). METHODS: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement standard. We identified relevant studies by searching multiple electronic databases, trial registries, and websites up to April 30, 2021, and examining reference lists. We selected RCTs that compared ESWT, in unimodal or multimodal therapeutic approaches, with sham ESWT or other active therapies. Two investigators independently extracted data and assessed the risk of bias and quality of the evidence. The main outcomes were pain intensity and disability status, examined as standardized mean differences (SMD) with 95% confidence intervals (CI). The risk of bias was assessed by using Cochrane Back and Neck (CBN) Group risk of bias tool and Jadad score, and GRADE was applied to determine the confidence in effect estimates. Heterogeneity was explored using sensitivity analysis and meta-regression. RESULTS: Ten RCTs, including a total of 455 young to middle-aged individuals (29.2-55.8 years), were identified. Compared with control, the ESWT group showed lower pain intensity at month 1 (SMD = -0.81, 95% CI -1.21 to -0.42), as well as lower disability score at month 1 (SMD = -1.45, 95% CI -2.68 to -0.22) and at month 3 (SMD = -0.69, 95% CI -1.08 to -0.31). No serious shockwave-related adverse events were reported. CONCLUSION: The use of ESWT in CLBP patients results in significant and quantifiable reductions in pain and disability in the short term. However, further well-conducted RCTs are necessary for building high-quality evidence and promoting the application of ESWT in clinical practice.

OBJECTIVE: To explore the effect and related mechanism of LncRNA PVT1 on hypoxia-induced cardiomyocyte injury. METHODS: PVT1RNA and miR-214-3p levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell vitality and apoptosis were, respectively, evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry analysis. Starbase and Dual luciferase reporter (DLR) gene assay was employed to validate the interaction between miR-214-3p and PVT1. RESULTS: PVT1 was statistically upregulated, and miR-214-3p was statistically downregulated in hypoxia-induced H9c2 cells. The survival rate of H9c2 cells induced by hypoxia decreased statistically, while the apoptosis rate increased statistically (P < 0.05). PVT1 knockdown upregulated the hypoxia-induced H9c2 cell viability and inhibited apoptosis. DLR assay verified the targeting relationship between PVT1 and miR-214-3p. In addition, miR-214-3p inhibitors reversed the viability of H9c2 cells with PVT1 knockout and promoted apoptosis. CONCLUSION: Silencing PVT1 can enhance the hypoxia-induced H9c2 cell viability and inhibit apoptosis, providing a potential target for the treatment of cardiovascular diseases.

BACKGROUND: With the COVID-19 epidemic breakout in China, up to 25% of diagnosed cases are considered to be severe. To effectively predict the progression of COVID-19 via patients' clinical features at an early stage, the prevalence of these clinical factors and their relationships with severe illness were assessed. METHODS: In this study, electronic databases (PubMed, Embase, Web of Science, and Chinese database) were searched to obtain relevant studies, including information on severe patients. Publication bias analysis, sensitivity analysis, prevalence, sensitivity, specificity, likelihood ratio, diagnosis odds ratio calculation, and visualization graphics were achieved through software Review Manager 5.3, Stata 15, Meta-DiSc 1.4, and R. RESULTS: Data of 3.547 patients from 24 studies were included in this study. The results revealed that patients with chronic respiratory system diseases (pooled positive likelihood 6.07, 95% CI: 3.12-11.82), chronic renal disease (4.79, 2.04-11.25), cardiovascular disease (3.45, 2.19-5.44), and symptoms of the onset of chest tightness (3.8, 1.44-10.05), shortness of breath (3.18, 2.24-4.51), and diarrhea (2.04, 1.38-3.04) exhibited increased probability of progressing to severe illness. C-reactive protein, ratio of neutrophils to lymphocytes, and erythrocyte sedimentation rate increased a lot in severe patients compared to nonsevere. Yet, it was found that clinical features including fever, cough, and headache, as well as some comorbidities, have little warning value. CONCLUSIONS: The clinical features and laboratory examination could be used to estimate the process of infection in COVID-19 patients. The findings contribute to the more efficient prediction of serious illness for patients with COVID-19 to reduce mortality.

OBJECTIVES: To evaluate the utility of radiomics features in differentiating central lung cancers and atelectasis on contrast-enhanced computed tomography (CT) images. This study is retrospective. MATERIALS AND METHODS: In this study, 36 patients with central pulmonary cancer and atelectasis between July 2013 and June 2018 were identified. A total of 1,653 2D and 2,327 3D radiomics features were extracted from segmented lung cancers and atelectasis on contrast-enhanced CT. The refined features were investigated for usefulness in classifying lung cancer and atelectasis according to the information gain, and 10 models were trained based on these features. The classification model is trained and tested at the region level and pixel level, respectively. RESULTS: Among all the extracted features, 334 2D features and 1,507 3D features had an information gain (IG) greater than 0.1. The highest accuracy (AC) of the region classifiers was 0.9375. The best Dice score, Hausdorff distance, and voxel AC were 0.2076, 45.28, and 0.8675, respectively. CONCLUSIONS: Radiomics features derived from contrast-enhanced CT images can differentiate lung cancers and atelectasis at the regional and voxel levels.

lncRNA is a transcript that is more than 200 bp in length. Currently, evidence has shown that lncRNA is of great significance in cell activity, involved in epigenetics, gene transcription, chromatin regulation, etc. The existence of an intestinal mucosal mechanical barrier hinders the invasion of pathogenic bacteria and toxins, maintaining the stability of the intestinal environment. Serious destruction or dysfunction of the mechanical barrier often leads to intestinal diseases. This review first summarizes the ability of lncRNAs to regulate the intestinal mucosal mechanical barrier. We then discussed how lncRNAs participate in various intestinal diseases by regulating the intestinal mucosal mechanical barrier. Finally, we envision its potential as a new marker for diagnosing and treating intestinal inflammatory diseases.

BACKGROUND: Celiac disease (CeD) is an autoimmune intestinal disorder caused by gluten protein consumption in genetically predisposed individuals. As biopsy sampling is an invasive procedure, finding novel noninvasive serological markers for screening of at-risk CeD population is a priority. Metabolomics is helpful in monitoring metabolite changes in body fluids and tissues. In the present study, we evaluated serum metabolite levels of CeD patients relative to healthy controls with the aim of introducing new biomarkers for population screening. METHOD: We compared the serum metabolic profile of CeD patients (n = 42) and healthy controls (n = 22) using NMR spectroscopy and multivariate analysis. RESULT: 25 metabolites were identified by serum metabolic profiling. Levels of 3-hydroxyisobutyric acid and isobutyrate showed significant differences in CeD patients' samples compared with healthy controls (p < 0.05). According to pathway analysis, our data demonstrated that changes in nine metabolic pathways were significantly disrupted/affected in patients with CeD. These enriched pathways are involved in aminoacyl-tRNA biosynthesis; primary bile acid biosynthesis; nitrogen metabolism; glutamine and glutamate metabolism; valine, leucine, and isoleucine biosynthesis and degradation; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and arginine biosynthesis. CONCLUSION: In summary, our results demonstrated that changes in the serum level of 25 metabolites may be useful in distinguishing CeD patients from healthy controls, which have the potential to be considered candidate biomarkers of CeD.

Autoimmune disorder is a chronic immune imbalance which is developed through a series of pathways. The defect in B cells, T cells, and lack of self-tolerance has been greatly associated with the onset of many types of autoimmune complications including rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and chronic inflammatory demyelinating polyneuropathy. The SLE is an autoimmune disease with a common type of lupus that causes tissue and organ damage due to the wide spread of inflammation. In the current study, twenty anti-inflammatory peptides derived from plant and animal sources were docked as ligands or peptides counter to proinflammatory cytokines. Interferon gamma (IFN-γ), interleukin 3 (IL-3), and tumor necrosis factor alpha (TNF-α) were targeted in this study as these are involved in the pathogenesis of SLE in many clinical studies. Two docking approaches (i.e., protein-ligand docking and peptide-protein docking) were employed in this study using Molecular Operating Environment (MOE) software and HADDOCK web server, respectively. Amongst docked twenty peptides, the peptide DEDTQAMMPFR with S-score of -11.3018 and HADDOCK score of -10.3 ± 2.5 kcal/mol showed the best binding interactions and energy validation with active amino acids of IFN-γ protein in both docking approaches. Depending upon these results, this peptide could be used as a potential drug candidate to target IFN-γ, IL-3, and TNF-α proteins to control inflammatory events. Other peptides (i.e., QEPQESQQ and FRDEHKK) also revealed good binding affinity with IFN-γ with S-scores of -10.98 and -10.55, respectively. Similarly, the peptides KHDRGDEF, FRDEHKK, and QEPQESQQ showed best binding interactions with IL-3 with S-scores of -8.81, -8.64, and -8.17, respectively.

OBJECTIVE: This study is set out to explore the potential difference of miR in PD through GEO data and provide diagnostic indicators for clinical practice. METHODS: In this study, differential miR was screened through the Gene Expression Omnibus (GEO) database, 68 PD patients treated in our hospital from May 2017 to March 2018 were collected as the research group (RG), and 50 normal subjects who underwent physical examination in our hospital during the same period were collected as the control group (CG). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression and diagnostic value of miR-374a-5p in serum of patients. The potential target genes of miR-374a-5p were predicted, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology Consortium (GO) were carried out. RESULTS: GEO2R analysis revealed that 193 miRs are expressed differentially, of which 78 were highly expressed and 115 were poorly expressed. The miR-374a-5p expression in the serum of the RG was reduced markedly and had a diagnostic value. Targetscan and miRDB online websites were used to predict their target genes, with 415 common target genes. miR-374a-5p may participate in 27 functional pathways and 8 signal pathways. CONCLUSION: miR-335-5p has low expression in PD and is expected to be a potential diagnostic indicator.

The proposed method introduces algorithms for the preprocessing of normal, COVID-19, and pneumonia X-ray lung images which promote the accuracy of classification when compared with raw (unprocessed) X-ray lung images. Preprocessing of an image improves the quality of an image increasing the intersection over union scores in segmentation of lungs from the X-ray images. The authors have implemented an efficient preprocessing and classification technique for respiratory disease detection. In this proposed method, the histogram of oriented gradients (HOG) algorithm, Haar transform (Haar), and local binary pattern (LBP) algorithm were applied on lung X-ray images to extract the best features and segment the left lung and right lung. The segmentation of lungs from the X-ray can improve the accuracy of results in COVID-19 detection algorithms or any machine/deep learning techniques. The segmented lungs are validated over intersection over union scores to compare the algorithms. The preprocessed X-ray image results in better accuracy in classification for all three classes (normal/COVID-19/pneumonia) than unprocessed raw images. VGGNet, AlexNet, Resnet, and the proposed deep neural network were implemented for the classification of respiratory diseases. Among these architectures, the proposed deep neural network outperformed the other models with better classification accuracy.

Obesity is a public health problem characterized by increased body weight due to abnormal adipose tissue expansion. Bioactive compound consumption from the diet or intake of dietary supplements is one of the possible ways to control obesity. Natural products with adipogenesis-regulating potential act as obesity treatments. We evaluated the synergistic antiangiogenesis, antiadipogenic and antilipogenic efficacy of standardized rebaudioside A, sativoside, and theasaponin E1 formulations (RASE1) in vitro in human umbilical vein endothelial cells (HUVECs), 3T3-L1 preadipocytes respectively, and in vivo using a high-fat and carbohydrate diet-induced obesity mouse model. Orlistat was used as a positive control, while untreated cells and animals were normal controls (NCs). Adipose tissue, liver, and blood were analyzed after dissection. Extracted stevia compounds and green tea seed saponin E1 exhibited pronounced antiobesity effects when combined. RASE1 inhibited HUVEC proliferation and tube formation by suppressing VEGFR2, NF-κB, PIK3, and-catenin beta-1 expression levels. RASE1 inhibited 3T3-L1 adipocyte differentiation and lipid accumulation by downregulating adipogenesis- and lipogenesis-promoting genes. RASE1 oral administration reduced mouse body and body fat pad weight and blood cholesterol, TG, ALT, AST, glucose, insulin, and adipokine levels. RASE1 suppressed adipogenic and lipid metabolism gene expression in mouse adipose and liver tissues and enhanced AMP-activated protein kinase levels in liver and adipose tissues and in serum adiponectin. RASE1 suppressed the NF-κB pathway and proinflammatory cytokines IL-10, IL-6, and TNF-α levels in mice which involve inflammation and progression of obesity. The overall results indicate RASE1 is a potential therapeutic formulation and functional food for treating or preventing obesity and inflammation.

PURPOSE: The previous lab and clinical studies of the correlation between the ultraviolet B and age-related cataract (ARC) did not reach in the universal agreement, especially in different morphological types of ARC. It is important to systemically summarize those previous data of epidemiological studies, which might penetrate the relevance between three morphological types of ARC, cortical, nuclear, and posterior capsular (PSC), with sunlight exposure. METHODS: PubMed, Web of Science, CNKI, Embase, and Cochrane were searched online. Data were extracted and recalculated, and quality check was performed by hand. Review Manager was used to perform the fixed effects meta-analysis on ARC and its morphological types. The highest exposed dose group was defined as the exposed group, and the lowest dose group as the control group as possible. RESULTS: Finally, the number of analyzed studies was 31: 20 for ARC and twelve, eleven, and nine for the morphological types cortical, nuclear, and PSC, respectively. The pooled OR for ARC was 1.15 (range 1.00~43.78, 95% CI 1.09 to 1.21). The cortical cataract revealed a slightly higher risk, and pooled OR was 1.03 (range 0.67~2.91, 95% CI 1.02 to 1.03). But the pooled OR for nuclear and PSC were 1.00 (range 0.50~5.35, 95% CI 1.00 to 1.00) and 0.99 (range 0.57~1.87, 95% CI 0.95 to 1.01), respectively. CONCLUSIONS: The systemic analysis of epidemiological articles reported till now reveals a significantly increased risk of ARC for those exposed with more sunlight, especially the morphological type of cortical cataract.

OBJECTIVE: This study was designed to explore the clinical efficacy of methotrexate combined with iguratimod on patients with rheumatoid arthritis (RA) and its influence on the expression levels of HOTAIR in serum. METHODS: A total of 268 RA patients were selected as research objects, 145 patients received methotrexate alone were used as a control group (CG), 123 patients received methotrexate combined with iguratimod were taken as a research group (RG), and serum of 60 healthy people undergoing physical examination was selected as a healthy control group (HCG). The therapeutic value of two therapeutic methods for RA was compared, and the HOTAIR expression in serum was detected by qRT-PCR. RESULTS: Compared with methotrexate used alone, the joint use of methotrexate and iguratimod could provide better clinical efficacy for RA patients and would not increase the incidence of adverse events. HOTAIR was highly expressed in the serum of RA patients, and its expression decreased after treatment. CONCLUSION: Combination therapy of methotrexate and iguratimod is a safe and effective way to treat RA patients, which can be popularized clinically.

PURPOSE: Wear and increased surface roughness are among the reasons for failure of posterior composite restorations. Considering the widespread use of bulk-fill composites in the posterior region, information about their wear resistance is imperative. The aim of this study was to compare the wear and surface roughness of four bulk-fill composite resins with a conventional composite. METHODS: Thirty composite discs (4 mm × 10 mm) were fabricated from EverX Posterior (GC), X-tra fil (Voco), Filtek Bulk-Fill Posterior (3M, USA), SonicFill 2 (Kerr), and Z250 (3M) composites. The baseline weight and surface roughness of specimens were measured. For the assessment of the attrition wear, the specimens were placed in a chewing simulator (Mechatronik). pH cycling was performed to erode the composite discs. They were then placed in a tooth brushing simulator machine (Dorsa) for abrasion wear. Finally, the weight and surface roughness of the specimens were measured. Data were compared using one-way ANOVA (alpha ≤ 0.05). RESULTS: One-way ANOVA showed that the mean weight changes were significant after attrition, abrasion, and erosion (P = 0.019), but changes in surface roughness were not significant (P ≥ 0.05). The results of Tukey's test showed no significant difference between the bulk-fill composites and Z250 regarding weight loss (P ≥ 0.05), but the weight loss of X-tra fil was significantly greater than that of EverX (P = 0.007) and Filtek Bulk-Fill (P = 0.005). CONCLUSIONS: Considering the limitations of this study, it appears that the wear and surface roughness of bulk-fill composites are within the acceptable range and are not different from those of a conventional composite.

Surgical procedures can generate significant preoperative anxiety (POA) in as much as 70% of the paediatric population. The role of hydroxyzine and distractive techniques such as clowns in the management of anxiety is controversial. Our main objective was to evaluate the effect of hydroxyzine on the control of POA. The secondary objective was to assess the potential additive effect of hydroxyzine and distracting techniques. We performed a randomized double-blind, controlled clinical trial in children aged 2-16 years undergoing outpatient surgery (n = 165). Subjects were randomized to hydroxyzine (group 1) or placebo (group 2). For the secondary objective, two further groups were made by allocation by chance to hydroxyzine plus accompaniment with clowns (group 3) and placebo plus clowns (group 4). All patients were accompanied by their parents as the standard procedure. POA was determined by a modified Yale scale of POA (m-YPAS). Compliance of children during induction of anesthesia (Induction Compliance Checklist (ICC)) was also assessed. No differences (p = 0.788) were found in POA control at the time of induction measured by m-YPAS (group 1: 39.2 ± 27.9; group 2: 37.0 ± 26.1; group 3: 34.7 ± 25.5; group 4: 32.4 ± 20.5). No differences were found in the level of ICC between the different treatment arms (group 1: 1.8 ± 3.4; group 2: 1.5 ± 3.0; group 3: 1.2 ± 2.4; group 4: 1.5 ± 2.7). The combination of all treatments (group 3) was the only effective strategy to contain the progression of anxiety. In conclusion, hydroxyzine was not effective to control POA in children. The combination of hydroxyzine and clowns avoided the progression of POA in our patients. This trial is registered with ClinicalTrials.gov identifier: NCT03324828 (registered 21 September 2017, subject recruitment started on 12th January 2018).

BACKGROUND: Collecting duct renal cell carcinoma (CDRCC) is a rare type of renal cancer characterized by a poor prognosis. The aim of this work was to develop a nomogram predicting the overall survival (OS) and cancer-specific survival (CSS) for patients with CDRCC. METHODS: A total of 324 eligible patients diagnosed with CDRCC from 2004 to 2015 were identified using the data from the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier curve was used to estimate the 1-, 3-, and 5-year OS and CSS of these patients. Univariate and multivariate Cox regression models were performed to identify the independent risk factors associated with OS and CSS. The nomogram was developed based on these factors and evaluated by the concordance index (C-index) and calibration curves using the bootstrap resample method. The predictive accuracy of the nomogram was also compared with the manual of the American Joint Committee on Cancer (AJCC). RESULTS: The estimated 1-, -3, and 5-year OS and CSS rates in the analytic cohorts were 56.4% and 60%, 32.5% and 37.3%, and 28.7% and 33.6%, respectively. The multivariate model revealed that age, tumor size, tumor grade, N stage, M stage, surgical type, and chemotherapy were independent predicted factors for OS, while tumor size, tumor grade, N stage, M stage, surgical type, and chemotherapy were independently linked to CSS. A nomogram was developed using these factors with relatively good discrimination and calibration. The C-index for OS and CSS was 0.764 (95% CI: 0.735~0.793) and 0.783 (95% CI: 0.754~0.812), which was superior to the AJCC stage (C-index: 0.685 (95% CI: 0.654~0.716) and 0.703 (95% CI: 0.672~0.734)). Patients were divided into low-risk, intermediate-risk, and high-risk groups according to the total points calculated by the nomogram. Patients in the low-risk group (97 mo and not reached) experienced significantly long median OS and CSS compared to the intermediate-risk (17 mo and 18 mo) and high-risk groups (5 mo for both). The calibration curves showed a good agreement between the predicted and actual probability related to OS and CSS. CONCLUSION: CDRCC has an aggressively biologic behavior with relatively poor prognosis. A survival prediction nomogram making an individualized evaluation of OS and CSS in patients with CDRCC was presented, potentially helping urologists to make a better risk stratification.

Treatment of knee osteoarthritis (OA) remains a challenging concern. Preclinical studies provided accumulating evidence on resveratrol efficacy in ameliorating degenerative articular damage. The present study was conducted to evaluate the effects of resveratrol as monotherapy on the serum level of type II collagen (Coll 2-1) and aggrecan in patients with knee osteoarthritis. The study was an open-labeled noncontrolled clinical trial. Resveratrol 500 mg/day in a single oral dose was given to the patients with knee osteoarthritis for 90 days. The serum levels of Coll-2-1, aggrecan, and biomarkers of inflammation were measured pre- and posttreatment. Hematological profiles and both hepatic and renal function markers were investigated at the baseline and at the end of the treatment for evaluating the tolerability and safety of resveratrol. Visual Analog Scale (VAS) for pain and Knee injury and Osteoarthritis Outcome Score (KOOS) for disease activity were clinically assessed monthly. Administration of 500 mg resveratrol for three months led to a nonsignificant decrease in the serum level of Coll 2-1 while a significant increase in aggrecan serum level. Resveratrol significantly improves pain score measured by VAS and KOOS after 30 days. Improvements in patients' activity and functional status were also evident at day 30 and kept on for three months which was reflected by KOOS subscale scores and with a significant improvement in all KOOS areas. In conclusion, oral administration of resveratrol as a monotherapy provides a remarkable improvement in the clinical status of the patients but has no significant effect on serum levels of Coll 2-1.

BACKGROUND: Loss to follow-up (LTFU) from antiretroviral therapy (ART) reduces treatment benefits and leads to treatment failure. Hence, this study was aimed at determining the incidence of loss to follow-up and predictors among HIV-infected adults who began first-line antiretroviral therapy at Arba Minch General Hospital. METHODS: We carried out an institutional-based retrospective cohort study, and data were collected from the charts of 508 patients who were selected using a simple random sampling technique. All the data management and statistical analyses were conducted using STATA version 14. Cumulative survival probability was estimated and presented in the life table, and the Kaplan-Meir survival curves were compared using the log-rank test. The Cox proportional hazard model was used to identify the independent predictors. RESULTS: We followed 508 patients for 871.9 person-years. A total of 46 (9.1%) experienced loss to follow-up, yielding an overall incidence rate of 5.3 (95% CI: 3.9-7.1) per 100 person-years. The cumulative survival probability was 90%, 88%, 86%, and 86% at the end of one, two, three, and four years, respectively. The predictors identified were age less than 35 years (adjusted hazard ratio (aHR = 1.96; 95% CI: 1.92-4.00)), rural residence (aHR = 1.98; 95% CI: 1.02-3.83), baseline body weight greater than 60 kilograms (aHR = 2.19; 95% CI: 1.11-4.37), a fair level of adherence (aHR = 11.5; 95% CI: 2.10-61.10), and a poor level of adherence (aHR = 12.03; 95% CI: 5.4-26.7). CONCLUSIONS: In this study, the incidence rate of loss to follow-up was low. Younger adults below the age of 35 years, living in rural areas, with a baseline weight greater than 60 kilograms, which had a fair and poor adherence level were more likely to be lost from treatment. Therefore, health professionals working in ART clinics and potential stakeholders in HIV/AIDS care and treatment should consider adult patients with these characteristics to prevent LTFU.

BACKGROUND: Intervertebral disc degeneration (IVDD) is the most significant cause of low back pain, the sixth-largest disease burden globally, and the leading cause of disability. This study is aimed at investigating the molecular biological mechanism of Danggui-Sini formula (DSF) mediated IVDD treatment. METHODS: A potential gene set for DSF treatment of IVDD was identified through TCMSP, UniProt, and five disease gene databases. A protein interaction network of common targets between DSF and IVDD was established by using the STRING database. GO and KEGG enrichment analyses were performed using the R platform to discover the potential mechanism. Moreover, AutoDock Vina was used to verify molecular docking and calculate the binding energy. RESULTS: A total of 119 active ingredients and 136 common genes were identified, including 10 core genes (AKT1, IL6, ALB, TNF, VEGFA, TP53, MAPK3, CASP3, JUN, and EGF). Enrichment analysis results showed that the therapeutic targets of DSF for diseases mainly focused on the AGE-RAGE signaling pathway involved in diabetic complications, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, apoptosis, cellular senescence, PI3K-Akt signaling pathway, and FoxO signaling pathway. These biological processes are induced mainly in response to oxidative stress and reactive oxygen species and the regulation of apoptotic signaling pathways. Molecular docking showed that there was a stable affinity between the core genes and the key components. CONCLUSIONS: The combination of network pharmacology and molecular docking provides a practical way to analyze the molecular biological mechanism of DSF-mediated IVDD treatment, which confirms the "multicomponent, multitarget and multipathway" characteristics of DSF and provides an essential theoretical basis for clinical practice.

Cell-based tissue engineering (TE) has been proposed to improve treatment outcomes in end-stage bladder disease, but TE approaches with 2D smooth muscle cell (SMC) culture have so far been unsuccessful. Here, we report the development of primary bladder-derived 3D SMC spheroids that outperform 2D SMC cultures in differentiation, maturation, and extracellular matrix (ECM) production. Bladder SMC spheroids were compared with 2D cultures using live-dead staining, qRT-PCR, immunofluorescence, and immunoblotting to investigate culture conditions, contractile phenotype, and ECM deposition. The SMC spheroids were viable for up to 14 days and differentiated rather than proliferating. Spheroids predominantly expressed the late myogenic differentiation marker MyH11, whereas 2D SMC expressed more of the general SMC differentiation marker α-SMA and less MyH11. Furthermore, the expression of bladder wall-specific ECM proteins in SMC spheroids was markedly higher. This first establishment and analysis of primary bladder SMC spheroids are particularly promising for TE because differentiated SMCs and ECM deposition are a prerequisite to building a functional bladder wall substitute. We were able to confirm that SMC spheroids are promising building blocks for studying detrusor regeneration in detail and may provide improved function and regenerative potential, contributing to taking bladder TE a significant step forward.

BACKGROUND: Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). METHODS: We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. RESULTS: We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed (P < 0.05) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) (P < 0.05, respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control (P < 0.05, respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. CONCLUSION: In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.

Mistletoes are considered to be the potential medicinal herbs due to their rich traditional uses. Loranthus globosus is a Bangladeshi mango mistletoe that has been reported as folk medicine for various ailments and diseases. In an attempt to explore its effectiveness in Alzheimer's disease (AD), we investigated the antioxidant and acetylcholinesterase inhibitory activity of L. globosus. We report that the crude methanol extract (CME) of the plant contains a good amount of polyphenolics and possesses antioxidant and cholinesterase inhibitory activity. Fractionation of CME with solvents of varying polarity revealed the highest activity and polyphenolic content in the ethylacetate fraction (EAF). Correlation analysis revealed a significant (P < 0.05) association of polyphenolics with the antioxidant and cholinesterase inhibitory properties. Using column chromatography with diaion resin, the polyphenolics (EAF-PP) were isolated from the EAF that displayed the potent antioxidant and cholinesterase inhibitory activities. Kinetic analysis showed that EAF-PP exhibited a competitive type of inhibition. A total of thirty-six compounds including catechin and its different derivatives were identified in the EAF-PP by LC/MS analysis. Bioactivity-guided separation approach afforded the isolation of the two major active compounds catechin and catechin dimer from the EAF-PP. Hence, EAF-PP represents a potential source of antioxidants and cholinesterase inhibitors, which can be used in the management of AD.

OBJECTIVE: Natural killer (NK) cell-deficient mice are useful models in biomedical research. NOD/SCID mice have been used as a model of this type in research. However, the actual status of NK cells in NOD/SCID mice and CB17/SCID mice in comparison with that in BALB/c mice has not been sufficiently evaluated. METHODS: Splenocytes from naïve or poly(I:C)-treated mice were isolated for phenotyping and analysis of cytotoxicity-related molecules and inhibitory receptors; for cytotoxicity assay, purified NK cells were also used. RESULTS: The proportion of splenic NK cells did not differ significantly between NOD/SCID and CB17/SCID mice. The perforin levels in NK cells were similar between the poly(I:C)-treated CB17/SCID and NOD/SCID mice, while the granzyme B and NKG2A/C/E levels in NK cells from NOD/SCID mice were significantly lower than those from CB17/SCID mice. Moreover, the NKG2D and Ly49A levels in NK cells from NOD/SCID mice were higher than those from CB17/SCID. The splenocytes from CB17/SCID mice showed higher cytotoxicity than those from NOD/SCID mice, while the cytotoxicity of purified NK cells basically did not differ between the two strains. After in vitro stimulation with cytokines, the splenocytes from CB17/SCID mice showed higher IFN-γ production than those from NOD/SCID mice; however, NK cells did not. CONCLUSION: There was no significant difference in the proportion of splenic NK cells between CB17/SCID and NOD/SCID mice, and the function of NK cells was only partially compromised in NOD/SCID mice. Caution should be taken when considering the use of NOD/SCID mice as an NK-deficient model.

The use of both a video laryngoscope and a video intubation stylet, compared with the use of a direct laryngoscope, is not only easier to learn but also associated with a higher success rate in performing endotracheal intubation for novice users. However, data comparing the two video devices used by novice personnel are rarely found in literature. Nondelayed intubation is an important condition to determine the prognosis in critically ill patients; hence, exploring intubation performance in various situations is of clinical significance. This study is aimed at comparing a video stylet and a video laryngoscope for intubation in an airway manikin with normal airway and cervical spine immobilization scenarios by novice personnel. We compared the performance of intubation by novices between the Aram Video Stylet and the McGrath® MAC video laryngoscope in an airway manikin. Thirty medical doctors with minimal experience of endotracheal intubation attempted intubation on a manikin five times with each device in each setting (normal airway and cervical spine immobilization scenarios). The order of use of the devices in each scenario was randomized for each participant. In the normal airway scenario, the Aram stylet showed a significantly higher rate of successful intubation than the McGrath® (98.7% vs. 92.0%; odds ratio (95% CI): 6.4 (1.4-29.3); p = 0.006). The intubation time was shorter using the Aram Stylet than that using the McGrath® video laryngoscope (p < 0.001). In the cervical immobilization scenario, successful endotracheal intubation was also more frequent using the Aram stylet than with the McGrath® (96.0% vs. 87.3%; odds ratio (95% CI): 3.5 (1.3-9.0); p = 0.007). The Aram Stylet intubation time was shorter (p < 0.001). In novice personnel, endotracheal intubation appears to be more successful and faster using the Aram Video Stylet than the McGrath® MAC video laryngoscope.

Age-related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation-induced RPE cell death has long been considered a contributor to the onset of AMD. Here, we applied a retinal degeneration (RD) rat model induced by blue light-emitting diode (LED) and a cell model constructed by H2O2 stimulus to mimic the prooxidant environment of the retina. We detected that the expression of miR-27a was upregulated and the expression of FOXO1 was downregulated in both models. So, we furtherly investigated the role of miR-27a-FOXO1 axis in RPE in protesting against oxidants. Lentivirus-mediated RNA was injected intravitreally into rats to modulate the miR-27a-FOXO1 axis. Retinal function and histopathological changes were evaluated by electroretinography (ERG) analysis and hematoxylin and eosin (H&E) staining, respectively. Massive photoreceptor and RPE cell death were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The damage to the retina was aggravated in the FOXO1 gene-knockdown and miR-27a-overexpression groups after exposure to LED but was alleviated in the FOXO1 gene-overexpression or miR-27a-knockdown groups. Dual luciferase assay was used to detect the binding site of miR-27a and FOXO1. Upregulated miR-27a inhibited the expression of FOXO1 by directly binding to the FOXO1 mRNA 3'UTR and decreased the autophagy activity of ARPE-19 cells, resulting in the accumulation of reactive oxygen species (ROS) and decrease of cell viability. The results suggest that miR-27a is a negative regulator of FOXO1. Also, our data emphasize the prominent role of miR-27a/FOXO1 axis in modulating ROS accumulation and cell death in RPE cell model under oxidative stress and influencing the retinal function in the LED-induced RD rat model.

Amides derived from ferulic acid have a wide spectrum of pharmacological activities, including antitumor and antifungal activity. In the present study, a series of ten amides were obtained by coupling reactions using the reagents (benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate (PyBOP) and N,N'-dicyclohexylcarbodiimide (DCC). All the compounds were identified on the basis of their IR, 1H- and 13C-NMR, HRMS data, and with yields ranging from 43.17% to 91.37%. The compounds were subjected to cytotoxic tests by the alamar blue technique and antifungal screening by the broth microdilution method to determine the minimum inhibitory concentration (MIC). The amides 10 and 11 displayed the best result in both biological evaluations, and compound 10 was the most potent and selective in HL-60 cancer cells, with no cytotoxicity on healthy cells. This amide had antifungal activity in all strains and had the lowest MIC against Candida albicans and Candida tropicalis. The possible mechanism of antifungal action occurs via the fungal cell wall. Molecular modeling suggested that compounds 10 and 11 interact with the enzymes GWT1 and GSC1, which are essential for the development of C. albicans. The findings of the present study demonstrated that compounds 10 and 11 may be used as a platform in drug development in the future.

The purpose of this study was to investigate the relationship between body compositions and bone mineral density (BMD) and the effect of composition substitution among Chinese children and adolescents without the influence of multicollinearity. A dual-energy X-ray absorptiometry scan was used to determine the amount of truncal fat (TF), nontruncal fat (NTF), fat-free mass (FFM), and BMD. The compositional data analysis and the compositional proportional substitution analysis were conducted to determine the effect of each part of body compositions on BMD and its substitution effects. Four hundred sixty-six (466) (boys: 51.9%) participants completed this cross-sectional study. For girls, in the overweight group, the relationship between TF and the BMD was positive (β = 2.943e - 01, p = 0.006) while the NTF showed the opposite trend (β = -2.358e - 01, p = 0.009). When 4% NTF or FFM was substituted by TF, the BMD increased by about 0.1 and 0.05 units (p < 0.05), respectively. For boys, the association between FFM and BMD was statistically positive (β = 4.091e - 02, p = 0.0001). There was a positive correlation between TF and BMD (β = 7.963e - 02, p = 0.036). But with the increase of BMI, this correlation shifted in the opposite direction. In conclusion, compared to TF and NTF, FFM had a better protective effect on BMD, especially for boys. The risk of NTF accumulation on BMD was greater than that of TF accumulation. Compared with girls, boys were more sensitive to the amount of TF.