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Hypoxia-mediated pancreatic beta cell death is one of the main causes of pancreatic beta celldeath, which leads to the loss of functional pancreatic beta cell mass and type 1 diabetes andtype 2 diabetes.However, the molecular mechanisms that control life and death of pancreatic beta cells remain poorly understood. Here we showed that mitochondrial fission was strongly induced in pancreatic beta cellsmainly due to an elevation of DRP1S616 phosphorylation through HIF-1αactivation and subsequent DRP1 mitochondrial translocation. Hypoxia-induced pancreatic beta cell death can be reversed by the inhibition of mitochondrial fission viaDRP1 knockdown. We further demonstrated that hypoxia-induced mitochondrial fission untightened the cristae formation, which subsequently triggers mitochondrial cytochrome c release and consequent caspase activation. Moreover, treatment with mitochondrial division inhibitor-1 (Mdivi-1), a specific inhibitor of DRP1-mediated mitochondrial fission, significantly suppressedbeta cell death in vitro, indicating a promising therapeutic strategy for treatment of diabetes.Taken together, our results reveal a crucial role for the DRP1-mediated mitochondrial fission in hypoxia-induced beta cell death, which provides a strong evidence for thisprocess as drug target indiabetestreatment. [ABSTRACT FROM AUTHOR]

The neutrophil to lymphocyte ratio (NLR), a simple marker of inflammation, has recently been showed to predict tumor recurrence in hepatocellular carcinoma (HCC) patients after hepatic resection or liver transplantation. However, whether it can be used to predict HCC development in cirrhotic patients remained unknown. The aim of this study was to evaluate the predictive value of the preoperative NLR for the development of HCC in cirrhotic patients who underwent splenectomy. A total of 230 HBV-associated cirrhotic patients who underwent splenectomy in our hospital from January 2000 to December 2012 were included in this study. Detailed clinical data included patients’ general characteristics, laboratory tests and imaging studies, surgical procedures and complications. Information on patients’ follow-up data was also obtained. We found that 38 (16.52%) patients developed HCC after splenectomy during the follow-up period. An elevated preoperative NLR was associated with increased risk of developing HCC in cirrhotic patients after splenectomy. The optimal cutoff value of NLR for HCC development was 2.27. In patients who developed HCC during the follow-up period, NLR scores showed no predictive value in overall survival after splenectomy. However, NLR scores appeared to have a much better predictive value in overall survival in patients who did not develop HCC. In conclusion, cirrhotic patients who underwent splenectomy remain at a relatively high risk of developing HCC, and an elevated preoperative NLR is associated with HCC development in cirrhotic patients who underwent splenectomy for hypersplenism. [ABSTRACT FROM AUTHOR]

Innovative human immunodeficiency virus (HIV) testing services will be needed to achieve the first 90 (90% of HIV-positive persons aware of their infection status) of the 90-90-90 target in China. Here, we describe an internet-based urine delivery testing service delivered through three pilot drugstores in Beijing that send specimens to a designated laboratory for HIV. From May 2016 to January 2017, we provided 500 HIV urine-testing service packs for display at the drugstores, and a total of 430 (86.0%) urine specimens were mailed back. All of the 430 urine specimens were of good quality and were tested. 70 urine specimens were HIV positive, showing a 16.3% (70/430) positivity rate. A total of 94.3% (66/70) of the HIV-positive participants obtained their test results through the internet, and 69.7% (46/66) of these participants received follow-up care. A total of 40 out of 46 (87.0%) participants agreed to have their results confirmed by a blood test, and 39 out of 40 (97.5%) participants were confirmed as HIV-1 positive, including two individuals that were previously diagnosed. Lastly, 28 out of 37 (75.7%) of the study participants were referred to the hospital and provided free antiviral treatment. Our data indicate that this innovative HIV testing service is effective and play an important role in HIV testing and surveillance. [ABSTRACT FROM AUTHOR]

The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. The present study aims to evaluate the role of age on treatments and outcome of HCC patients. 1530 patients firstly diagnosed with HCC were retrospectively included and classified as older (≥65 years, n = 318, 21%) and younger patients (<65 years, n = 1212, 79%). The two groups were compared with clinical characteristics, tumor burden, Barcelona Clinics Liver Cancer (BCLC) stage, treatments and long-term prognosis. Elderly patients were more HCV infected, had more diabetes, poorer performance status, and were less aggressively treated. The proportion of HCC within BCLC stage 0-A, B or C was similar between the two groups, but elderly patients were more presented with BCLC stage D. The overall survival of older patients was poorer compared to younger patients before and after propensity score matching. However, elderly patients were less often effectively treated with surgery and loco-regional therapies across different BCLC stages. After stratified by BCLC stages or treatments, older patients showed comparable long-term outcome to younger patients. Performance status, BCLC stages and effective treatments, rather than age, was independent factors determining prognosis in the whole cohort and only elderly patients by multivariate analysis. In conclusion, older could have comparable survival to younger patients within the same tumor stage or after similar treatments. Thus, equally active treatments should be encouraged to elderly patients. [ABSTRACT FROM AUTHOR]

Background: While studies have shown that cigarette smoking has negative implications on the long-term outcome following liver transplantation, its role in early complications is inconclusive. Methods: The clinical data of 162 consecutive adult patients who underwent elective liver transplantation from January, 2012 to March, 2016 were analyzed. Patients were defined as active smokers, ex-smokers, or non-smokers on the basis of documentation at the time of liver transplantation. The overall complications following liver transplantation were expressed as the comprehensive complication index (CCI). The specific complications such as the incidence of hepatic artery thrombosis, biliary complications, acute kidney injury were also assessed. A meta-analysis was carried out based on results from the present study and 11 published studies. Results: We found that cigarette smoking was not associated with higher CCI scores and smokers did not have a higher risk for developing hepatic artery thrombosis, biliary complications, acute kidney injury after liver transplantation. Meta-analysis confirmed the null association between cigarette smoking and an increased incidence of hepatic artery thrombosis or biliary complications in liver transplant recipients. However, the pooled results showed a significantly higher risk of cardiovascular diseases and de-novo malignancies in smokers following liver transplantation. Conclusion: There is not enough evidence supporting an association between cigarette smoking and early mortality and morbidity after liver transplantation. However, smokers should still be encouraged to quit before and after liver transplantation due to the long-term health benefits of smoking cessation. [ABSTRACT FROM AUTHOR]

Background: Clinical data regarding the influence of diabetes mellitus (DM) on the outcomes of patients undergoing hepatectomy are conflicting. To determine the impact of DM on the clinical outcomes of patients undergoing hepatectomy, we systematically reviewed published studies and carried out a meta-analysis. Methods: A systematic literature search of Pubmed, Sciencedirect, Web of Science, and Chinese Biomedical Database was conducted from their inception through February 2, 2016. The combined relative risk (RR) or hazard ratio (HR) with 95% confidence intervals (95% CI) was calculated. Results: A total of 16 observational studies with 15710 subjects were eligible for meta-analysis. The pooled results showed that DM significantly increased the risk of overall postoperative complications (RR 1.34; 95% CI 1.19–1.51; P<0.001), DM-associated complications (RR 1.8; 95% CI 1.29–2.53; P<0.001), liver failure (RR 2.21; 95% CI 1.3–3.76; P = 0.028) and post-operative infections (RR 1.59; 95% CI 1.01–2.5; P = 0.045). In addition, DM was also found to be significantly associated with unfavorable overall survival and disease free survival after liver resection. The pooled HR was 1.63 (95% CI 1.33–1.99; P<0.001) for overall survival and 1.55 (95% CI 1.07–2.25; P = 0.019) for disease free survival. Conclusion: DM is associated with poor outcomes in patients undergoing hepatectomy. DM should be taken into account cautiously in the management of patients undergoing hepatectomy. Further prospective studies are warranted to explore effective interventions to improve the poor outcomes of diabetic patients undergoing hepatectomy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the quality of life (QOL) of overweight and obese middle or high school students and identify relevant factors influencing their QOL scores. Methods: 716 students were recruited from 6 middle or high schools in Hangzhou, China. The Chinese version of the Youth Quality of Life Instrument–Weight Module (YQOL-W) was self administered. The YQOL-W scores were compared among different BMI groups, gender, educational status, annual household income, parental education and recruitment community using t test or one-way analysis of variance. The independent association of these variables with QOL among overweight and obese students was examined using multivariable linear regression modeling. Results: Overweight and obese students reported lower total scores, self, social and environment scores than their normal weight peers (all P<0.001). The QOL of overweight and obese middle and high school students was associated with BMI value, gender, educational status, parental education, and recruitment community. Girls had lower total scores, self, social and environment domain scores than boys (all P<0.001); high school students had lower total and three domain scores than middle school students (all P<0.05). Students whose fathers had higher education reported higher total scores, self and social scores than students with less educated fathers (all P<0.05). Students whose mothers had higher education reported higher environment scores than students with less educated mothers (P = 0.01). Students from migrant communities reported significantly lower total scores, self and social scores than those from rural communities (all P<0.05), but comparable scores with those from urban communities (P>0.05). Students from migrant communities reported comparable environment scores with those from rural and urban communities (P>0.05). Conclusions: Overweight and obesity have negative effects on students’ quality of life. Therefore weight specific QOL could be included in weight reduction interventions as a relevant outcome. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the performance of physical examination (PE) skills during our diagnostic medicine course and analyze the characteristics of the data collected to provide information for practical guidance to improve the quality of teaching. Seventy-two fourth-year medical students were enrolled in the study. All received an assessment of PE skills after receiving a 17-week formal training course and systematic teaching. Their performance was evaluated and recorded in detail using a checklist, which included 5 aspects of PE skills: examination techniques, communication and care skills, content items, appropriateness of examination sequence, and time taken. Error frequency and type were designated as the assessment parameters in the survey. The results showed that the distribution and the percentage in examination errors between male and female students and among the different body parts examined were significantly different (p<0.001). The average error frequency per student in females (0.875) was lower than in males (1.375) although the difference was not statistically significant (p = 0.167). The average error frequency per student in cardiac (1.267) and pulmonary (1.389) examinations was higher than in abdominal (0.867) and head, neck and nervous system examinations (0.917). Female students had a lower average error frequency than males in cardiac examinations (p = 0.041). Additionally, error in examination techniques was the highest type of error among the 5 aspects of PE skills irrespective of participant gender and assessment content (p<0.001). These data suggest that PE skills in cardiac and pulmonary examinations and examination techniques may be included in the main focus of improving the teaching of diagnostics in these medical students. [ABSTRACT FROM AUTHOR]

Background: Childhood obesity is a growing public health concern in China. It not only compromises physical health, but also has negative impacts on psychosocial well-being. As obesity rates increase, finding out what the perceptions of Chinese youth are regarding their weight is important for intervention planning and evaluation. However, there is a paucity of available obesity-specific instruments for children and adolescents in China and youth weight-specific quality of life (QOL) has been little reported. This study aimed to evaluate the measurement properties of the Chinese version of the Youth Quality of Life Instrument – Weight Module (YQOL-W). Methods: The Chinese version of the YQOL-W was administered to 840 youth aged 11–18 from nine schools. Measurement properties including measurement model, reliability, validity and burden were evaluated. Results: Confirmatory factor analysis showed that a three-factor model had acceptable model fit. The instrument had robust internal consistency reliability with Cronbach's α ranging from 0.84 to 0.96 and acceptable test-retest reliability with the intraclass correlation coefficients (ICCs) all higher than 0.7. The standard error of measurement (SEM) values for the Self, Social and Environment factors and total score were 10.352, 9.526, 12.086 and 8.425, respectively. The small real differences (SRDs) for the Self, Social and Environment factors and total score were 28.675, 26.387, 33.478, and 23.337, respectively. The Pearson's correlation coefficients between the YQOL-W and the PedsQL4.0 General Core Scales were stronger between comparable dimensions than those between less comparable dimensions, demonstrating convergent and discriminant evidence of construct validity. Significant differences were found in subscale and total scores across weight status, age and genders (P<0.01), supporting the known-groups validity of the instrument. Conclusion: The Chinese version of the YQOL-W has acceptable measurement properties and can be used to assess the weight-specific QOL of children and adolescents in China. [ABSTRACT FROM AUTHOR]

The electrochemical behavior and thermodynamic properties of Ln(III) (Ln = Eu, Sm, Dy, Nd) were studied in 1-butyl-3-methylimidazolium bromide ionic liquid (BmimBr) at a glassy carbon (GC) electrode in the range of 293–338 K. The electrode reaction of Eu(III) was found to be quasi-reversible by the cyclic voltammetry, the reactions of the other three lanthanide ions were regarded as irreversible systems. An increase of the current intensity was obtained with the temperature increase. At 293 K, the cathodic peak potentials of −0.893 V (Eu(III)), −0.596 V (Sm(III)), −0.637 V (Dy(III)) and −0.641 V (Nd(III)) were found, respectively, to be assigned to the reduction of Ln(III) to Ln(II). The diffusion coefficients (Do), the transfer coefficients (α) of Ln(III) (Ln = Eu, Sm, Dy, Nd) and the charge transfer rate constants (ks) of Eu(III) were estimated. The apparent standard potential (E0*) and the thermodynamic properties of the reduction of Eu(III) to Eu(II) were also investigated. [ABSTRACT FROM AUTHOR]

Background: Serum lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) has been widely used for HCC diagnosis and follow-up surveillance as tumor serologic marker. However, the prognostic value of high pre-treatment serum AFP-L3% in patients with hepatocellular carcinoma (HCC) remains controversial. We therefore conduct a meta-analysis to assess the relationship between high pre-treatment serum AFP-L3% and clinical outcome of HCC. Methods: Eligible studies were identified through systematic literature searches. A meta-analysis of fifteen studies (4,465 patients) was carried out to evaluate the association between high pre-treatment serum AFP-L3% and overall survival (OS) and disease-free survival (DFS) in HCC patients. Sensitivity and subgroup analyses were also conducted in this meta-analysis. Results: Our analysis results showed that high pre-treatment serum AFP-L3% implied poor OS (HR: 1.65, 95%CI: 1.45–1.89 p<0.00001) and DFS (HR: 1.80, 95% CI: 1.49–2.17 p<0.00001) of HCC. Subgroup analysis revealed that there was association between pre-treatment serum AFP-L3% and endpoint (OS and DFS) in low AFP concentration HCC patients (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 2.53, 95% CI: 1.09–5.89, p = 0.03, respectively). Conclusion: The current evidence suggests that high pre-treatment serum AFP-L3% levels indicated a poor prognosis for patients with HCC and AFP-L3% may have significant prognostic value in HCC patients with low AFP concentration. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cigarette smoking is a potential risk factor for hepatocellular carcinoma (HCC) initiation, partially through interaction with hepatitis B virus (HBV). We examined the hypothesis that cigarette smoking might be associated with HBV-related HCC recurrence and patient survival after curative surgery. Patients and Methods: Data of 302 patients with HBV infection who had undergone curative resection for HCC were prospectively collected from 2008 to 2011. Smoking status and smoking quantity (pack-years, PY) were asked at admission. Factors affecting recurrence-free survival (RFS) were examined. RFS and liver-specific mortality (LSM) stratified by risk factors were compared with log-rank test. Results: 109 were current smokers. Current smokers were not different from non-smokers in tumor burden and surgical procedure. Univariate and multivariate analysis identified that heavy smoking (PY ≥20) was the most significant factor associated with HBV-related HCC recurrence after curative surgical resection (p = 0.001), followed by anti-HBV treatment (p<0.01), current smoking (p = 0.028), surgical margin <1 cm (p = 0.048) and blood transfusion >600 ml (p = 0.028). The median RFS in non-smokers, ex-smokers and current smokers was 34 months, 24 months and 26 months, respectively (p = 0.033). Current smokers had significantly worse RFS rate and increased 5-year cumulative LSM than non-smokers (p = 0.024, and p<0.001, respectively). Heavy smokers had significantly worse RFS than non- and light smokers (0

Background: Quercetin is the most abundant flavonoid in fruit and vegetables and is believed to attenuate cardiovascular disease. We hypothesized that quercetin inhibits cardiac hypertrophy by blocking AP-1 (c-fos, c-jun) and activating PPAR-γ signaling pathways. Methodology/Principal Findings: The aim of this study was to identify the mechanism underlying quercetin-mediated attenuation of cardiac hypertrophy. Quercetin therapy reduced blood pressure and markedly reduced the ratio of left ventricular to body weight (LVW/BW) (P<0.05, vs. spontaneously hypertensive rats (SHRs)). In vitro, quercetin also significantly attenuated Ang II-induced H9C2 cells hypertrophy, as indicated by its concentration dependent inhibitory effects on [3H]leucine incorporation into H9C2 cells (64% reduction) and by the reduced hypertrophic surface area in H9C2 cells compared with the Ang II group (P<0.01, vs. Ang II group). Concurrently, we found that PPAR-γ activity was significantly increased in the quercetin-treated group both in vivo and in vitro when analyzed using immunofluorescent or immunohistochemical assays (P<0.05, vs. SHRs or P<0.01, vs. the Ang II group). Conversely, in vivo, AP-1 (c-fos, s-jun) activation was suppressed in the quercetin-treated group, as was the downstream hypertrophy gene, including mRNA levels of ANP and BNP (P<0.05, vs. SHRs). Additionally, both western blotting and real time-PCR demonstrated that PPAR-γ protein and mRNA were increased in the myocardium and AP-1 protein and mRNA were significantly decreased in the quercetin-treated group (P<0.05, vs. SHRs). Furthermore, western blotting and real time-PCR analyses also showed that transfection with PPAR-γ siRNA significantly increased AP-1 signaling and reversed the effects of quercetin inhibition on mRNA expression levels of genes such as ANP and BNP in hypertrophic H9C2 cells. Conclusions: Our data indicate that quercetin may inhibit cardiac hypertrophy by enhancing PPAR-γ expression and by suppressing the AP-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Xenotransplantation is a promising approach to circumventing the current organ shortage. However, T-cell-dependent anti-xenoresponses are a major challenge to successful xenografts. Given the advantages of the use of CTLA4-Ig in the survival of allografts, the purpose of the study was to investigate the therapeutic potential of CTLA4-IgG4 modified immature dendritic cells (imDCs) in the prevention of islets xenograft rejection. Methods: CTLA4-IgG4 was constructed by the fusion of the extracellular regions of porcine CTLA4 to human the hIgG4 Fc region. The imDCs were induced and cultured from porcine peripheral blood mononuclear cells (PBMC). The CTLA4-IgG4 modified imDCs were delivered via the portal vein to the liver of diabetic mice (insulin-dependent diabetes mellitus) before islet xenografting, and mCTLA4-Ig was administered intravenously after xenotransplantation. Results: The xenograft survival of mice receiving unmodified imDCs was approximately 30 days. However, following administration of CTLA4-IgG4 modified imDCs before grafting and mCTLA4-Ig after grafting, xenografts survived for more than 100 days. Flow cytometric analysis showed that the CD4+CD25+Foxp3+ Treg population was increased in spleens. The efficacy of donor CTLA4-IgG4 modified imDCs correlated partially with the amplification of Tregs. Conclusions: These results confirm that selective inhibition of the direct and indirect pathways of T-cell activation by donor CTLA4-IgG4 modified imDCs and receptor CTLA4-Ig is a highly effective strategy to promote survival of xenografts. [ABSTRACT FROM AUTHOR]

Objective:Burn-induced gut dysfunction plays an important role in the development of sepsis and multiple organ dysfunction. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) is critical in paracelluar barrier functions via regulating vascular endothelial growth factor (VEGF) and myosin light chain kinase (MLCK) expression. Previous studies have also demonstrated that histone deacetylase inhibitors (HDACIs) can repress HIF-1α. This study aims to examine whether valproic acid (VPA), a HDACI, protects against burn-induced gut barrier dysfunction via repressing HIF-1α-dependent upregulation of VEGF and MLCK expression. Methods:Rats were subjected to third degree 55% TBSA burns and treated with/ without VPA (300mg/kg). Intestinal barrier dysfunction was evaluated by permeability of intestinal mucosa to fluorescein isothiocyanate (FITC)-dextran and histologic evaluation. Histone acetylation, tight junction protein zonula occludens 1 (ZO-1), VEGF, MLCK and HIF-1α were measured. In addition, CaCO2 cells were transfected with siRNA directed against HIF-1α and were stimulated with CoCl2 (1mM) for 24 hours with/without VPA (2mM) followed by analysis of HIF-1α, MLCK, VEGF and ZO-1. Results:Burn insults resulted in a significant increase in intestinal permeability and mucosal damage, accompanied by a significant reduction in histone acetylation, ZO-1, upregulation of VEGF, MLCK expression, and an increase in HIF-1α accumulation. VPA significantly attenuated the increase in intestinal permeability, mucosa damage, histone deacetylation and changes in ZO-1 expression. VPA also attenuated the increased VEGF, MLCK and HIF-1α protein levels. VPA reduced HIF-1α, MLCK and VEGF production and prevented ZO-1 loss in CoCl2-stimulated Caco-2 cells. Moreover, transfection of siRNA directed against HIF-1α led to inhibition of MLCK and VEGF production, accompanied by upregulation of ZO-1. Conclusions:These results indicate that VPA can protect against burn-induced gut barrier dysfunction. These protective effects may be due to its inhibitory action on HIF-1α, leading to a reduction in intestinal VEGF and MLCK expression and minimizing ZO-1 degradation. [ABSTRACT FROM AUTHOR]

Background and Aims:Installing the transjugular intrahepatic portosystemic shunt for portal hypertension is relatively safe, but complications are still high. To explore a new method of portacaval shunt, the magnetic compression technique was introduced into the shunting procedure. Methods:A portal-inferior vena cava shunt was performed on 6 male mongrel dogs by two hemocompatible Nd-Fe-B permanent magnets, parent and daughter. The parent magnet was applied to the inferior vena cava guided by a catheter through the femoral vein. The daughter magnet was moved to the anastomosis position on the portal vein with a balloon catheter through the splenic vein. After the daughter magnet reached the target position, the two magnets acted to compress the vessel wall and hold it in place. Five to 7 days later, under X-ray guidance, the magnets were detached from the vessel wall with a rosch-uchida transjugular liver access set. One month later, histological analysis and portal venography were performed. Results:5-7 days after the first surgery, a mild intimal hyperplasia in the portal vein and the inferior vena cava, and continuity of the vascular adventitia from the portal vein to the inferior vena cava as observed. During the second surgery, the contrast media could be observed flowing from the portal vein into the inferior vena cava. Portal venography revealed that the portosystemic shunt was still present one month after the second surgery. Conclusions:Magnamosis via a device of novel design was successfully used to establish a portacaval shunt in dogs. [ABSTRACT FROM AUTHOR]

Background: We have observed at our clinical work that acute lung injury (ALI) often occurs in patients transplanted with donor livers persevered for long time. So, we conducted this study to investigate the influence of cold preservation time (CPT) of donor liver on ALI induced by liver transplantation (LT), and further study the role of nuclear factor-κB (NF-κB) in the process., Methods: Wistar rats were used as donors and recipients to establish orthotopic rat liver transplantation models. Donor livers were preserved at 4°C for different lengths of time. The effect of NF-κB inhibitor, ammonium pyrrolidinedithiocarbamate (PDTC), on ALI was detected. All samples were harvested after 3 h reperfusion. The severity of liver injury was evaluated first. The expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in liver tissue and liver outflow serum were measured respectively. The severity indexes of ALI, the activity of NF-κB and inhibitor-κBα (I-κBα) in lung/liver were measured accordingly., Results: With the prolonged liver CPT, the liver damage associated indexes and ALI-related indexes all increased significantly. TNF-α and IL-1β in liver outflow serum increased accordingly, and the activity of NF-κB in liver/lung increased correspondingly. All these ALI-associated indexes could be partially reversed by the use of PDTC., Conclusions: Extended CPT aggravates the damage of donor liver and induces the expressions of TNF-α and IL-1β in liver. These inflammatory factors migrate to lung via liver outflow blood and activate NF-κB in lung, inducing ALI finally. NF-κB may play a critical role in LT-related ALI. Patients with or at risk of ALI may benefit from acute anti-inflammatory treatment with PDTC.