Oridonin ameliorates renal fibrosis in diabetic nephropathy by inhibiting the Wnt/ß-catenin signaling pathway.

Diabetic nephropathy (DN) is one of the most serious and frequent complications among diabetes patients and presently constitutes vast the cases of end-stage renal disease worldwide. Tubulointerstitial fibrosis is a crucial factor related to the occurrence and progression of DN. Oridonin (Ori) is a diterpenoid derived from rubescens that has diverse pharmacological properties. Our previous study showed that Ori can protect against DN by decreasing the inflammatory response. However, whether Ori can alleviate renal fibrosis in DN remains unknown. Here, we investigated the mechanism through which Ori affects the Wnt/ß-catenin signaling pathway in diabetic rats and human proximal tubular epithelial cells (HK-2) exposed to high glucose (HG) levels. Our results revealed that Ori treatment markedly decreased urinary protein excretion levels, improved renal function and alleviated renal fibrosis in diabetic rats. In vitro, HG treatment increased the migration of HK-2 cells while reducing their viability and proliferation rate, and treatment with Ori reversed these changes. Additionally, the knockdown of ß-catenin arrested cell migration and reduced the expression levels of Wnt/ß-catenin signaling-related molecules (Wnt4, p-GSK3ß and ß-catenin) and fibrosis-related molecules (α-smooth muscle actin, collagen I and fibronectin), and Ori treatment exerted an effect similar to that observed after the knockdown of ß-catenin. Furthermore, the combination of Ori treatment and ß-catenin downregulation exerted more pronounced biological effects than treatment alone. These findings may provide the first line of evidence showing that Ori alleviates fibrosis in DN by inhibiting the Wnt/ß-catenin signaling pathway and thereby reveal a novel therapeutic avenue for treating tubulointerstitial fibrosis.

Clean energy consumption, sleep duration, and the association of cancer: findings from the China health and retirement longitudinal study.

Objective: Studies of the association between clean energy consumption, sleep duration, and cancer are still extremely limited. We aim to investigate the individual or joint role of clean energy consumption, and sleep duration in cancer onset. Methods: We used data from the China Health and Retirement Longitudinal Study. Multivariable locally weighted regression (LOESS) models were first used to assess the individual association of daily sleep time with the risk to develop cancer. Multivariate logistic regression models were conducted on the individual and interaction effects of daily sleep time and cooking fuel. Results: We found that short sleep duration (≤6 hours) and non-clean energy consumption were respectively associated with an increased risk of cancer among older Chinese(p<0.05). We assessed daily sleep time in four quartiles, the adjusted odds ratios (AOR), and 95% confidence intervals (95% CI) for participants in the second (5.0 to <6.5 hours), third (6.5 to <8.0 hours), and fourth quartiles (≥8.0 hours) were 0.88 (95% CI: 0.65-1.20), 0.61 (95% CI: 0.40-0.91), and 0.53 (95% CI: 0.37-0.77), respectively. When we set the cutoff point(6.5 hours), participants who slept more than 6 hours had a 39% lower risk of cancer (AOR: 0.61, 95% CI: 0.46-0.79) compared with others. On the other hand, we conducted that exposure to clean fuel from cooking was negatively associated with cancer incidence (AOR: 0.73, 95% CI: 0.54, 0.97). Furthermore, the combination of longer sleep and cleaner fuels showed the lowest OR for cancer (AOR: 0.39, 95% CI: 0.24, 0.65). Conclusion: Our study showed that sleep duration and clean energy consumption were significantly associated with cancer in elderly Chinese people. In addition, the prevalence of cancer was higher among people who slept less than six hours and used non-clean energy sources. Paying greater attention to the effects of sleep duration and clean energy on the risk of cancer may yield practical implications for cancer prevention.

Delivery of WeChat-Based HIV Result e-Reports in Social Networks for Recruitment of High-Risk Population: Baseline Data From a Cluster Randomized Controlled Trial.

BACKGROUND: Disclosure of infectious disease status to social network peers can facilitate reaching and early detection among high-risk populations. In this era of social media, globally, HIV/AIDS represents a high burden of infectious disease. Thus, delivery of an HIV result e-report via social media presents a new approach that has the potential to improve contact with and enrollment of the high-risk population in research studies and routine practice. OBJECTIVE: This study explores the effectiveness and associated factors of a recruitment strategy (ie, WeChat-based HIV e-report delivery in social networks) on the enrollment of men who have sex with men (MSM) for an HIV testing intervention study. METHODS: This was an enrollment result analysis of an ongoing cluster randomized controlled trial (RCT) aiming to promote HIV testing among MSM. Recruitment of potential participants was based on the unit of an egocentric social network, which includes 1 core member (an offline tested ego as the recruiter) and several network members (online alters as network associates). Alters' enrollment and alters' transformation to ego-recruiters (alter-ego) were measured as outcomes. Recruitment outcomes were compared between the exchangeable and regular e-report groups of the RCT. Associated factors of both outcomes were also investigated, including sociodemographic characteristics, health behaviors, social network characteristics, e-report types, and online delivery information. Binary outcomes were modeled using logistic models, with Firth correction for rare events. Qualitative interviews were conducted to understand facilitators and barriers in detail for alter-ego as the subsequent wave's recruiter. RESULTS: The e-report of 1157 egos who tested offline were delivered to 5165 alters in 3 recruitment waves; eventually, 1162 eligible alters enrolled in this RCT (response rate: 22.5%). In the exchangeable e-report group, 544 egos recruited 467 alters, of which 35 alters transformed to alter-egos (7.5%), whereas in the regular e-report group, 613 egos recruited 695 alters, of which 40 alters transformed to alter-egos (5.8%). Alters' enrollment at first wave was associated with a higher number of e-reports being forwarded by the egos. Alters' transformation to alter-egos for the subsequent wave was associated with the exchangeable e-report, higher income, being a Guangzhou resident, unprotected anal intercourse, preferring self-testing, and viewing senders' e-reports frequently. Qualitative interviews revealed that the lack of awareness of e-reports' function and inadequate access to e-reports at offline testing facilities were major barriers to alters' transformation to offline ego-recruiters. CONCLUSIONS: The delivery of e-report was feasible in MSM social network, and the success and sustainability of online recruitment depended on high levels of familiarity among MSM with the digital tool. The HIV e-report exchange mechanism might promote MSM to test HIV offline to get their own e-report for exchange in the community. The e-report provides an innovative recruitment method with great potential to trace direct contacts for infectious diseases studies.

Activation of AMPK-PGC-1α pathway ameliorates peritoneal dialysis related peritoneal fibrosis in mice by enhancing mitochondrial biogenesis.

BACKGROUND: The pathogenesis of peritoneal dialysis (PD)-related peritoneal fibrosis (PF) is not clearly understood, and current treatment options are limited. METHODS: In this study, the effect of PD-related PF on mitochondrial biogenesis was investigated, and the effect of activation of the adenosine monophosphate-activated protein kinase (AMPK)-PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) pathway on PF was evaluated in mice. RESULTS: In a mouse model of PD-related PF, AMPK-PGC-1α signaling (phospho-AMPK, PGC-1α, NRF-1, NRF-2 and TFAM expression) was downregulated, mitochondrial DNA (mtDNA) levels were reduced, and mitochondrial structure was damaged in the peritoneum. In addition, TdT-mediated dUTP nick-end labeling (TUNEL) staining showed typical apoptosis characteristics in peritoneal mesothelial cells (PMCs). Activation of the AMPK-PGC-1α pathway (PGC-1α overexpression or metformin, which is an agonist of AMPK) upregulated phospho-AMPK, PGC-1α, nuclear respiratory factors 1 (NRF-1) and 2 (NRF-2), and mitochondrial transcription factor A (TFAM) expression and mtDNA content, improved mitochondrial morphological manifestations, inhibited apoptosis of PMCs and alleviated PF. CONCLUSION: Our study may suggest that activation of the AMPK-PGC-1α pathway ameliorates PD-related PF by enhancing mitochondrial biogenesis.

Interpretable machine learning-derived nomogram model for early detection of diabetic retinopathy in type 2 diabetes mellitus: a widely targeted metabolomics study.

OBJECTIVE: Early identification of diabetic retinopathy (DR) is key to prioritizing therapy and preventing permanent blindness. This study aims to propose a machine learning model for DR early diagnosis using metabolomics and clinical indicators. METHODS: From 2017 to 2018, 950 participants were enrolled from two affiliated hospitals of Wenzhou Medical University and Anhui Medical University. A total of 69 matched blocks including healthy volunteers, type 2 diabetes, and DR patients were obtained from a propensity score matching-based metabolomics study. UPLC-ESI-MS/MS system was utilized for serum metabolic fingerprint data. CART decision trees (DT) were used to identify the potential biomarkers. Finally, the nomogram model was developed using the multivariable conditional logistic regression models. The calibration curve, Hosmer-Lemeshow test, receiver operating characteristic curve, and decision curve analysis were applied to evaluate the performance of this predictive model. RESULTS: The mean age of enrolled subjects was 56.7 years with a standard deviation of 9.2, and 61.4% were males. Based on the DT model, 2-pyrrolidone completely separated healthy controls from diabetic patients, and thiamine triphosphate (ThTP) might be a principal metabolite for DR detection. The developed nomogram model (including diabetes duration, systolic blood pressure and ThTP) shows an excellent quality of classification, with AUCs (95% CI) of 0.99 (0.97-1.00) and 0.99 (0.95-1.00) in training and testing sets, respectively. Furthermore, the predictive model also has a reasonable degree of calibration. CONCLUSIONS: The nomogram presents an accurate and favorable prediction for DR detection. Further research with larger study populations is needed to confirm our findings.

The Comparison of Various Types of Health Insurance in the Healthcare Utilization, Costs and Catastrophic Health Expenditures among Middle-Aged and Older Chinese Adults.

Rapid aging in China is increasing the number of older people who tend to require health services for their poor perceived health. Drawing on the China Health and Retirement Longitudinal Study (CHARLS) 2018 data, we used two-part model and binary logistic regression to compare various types of health insurance in the healthcare utilization, costs and catastrophic health expenditures (CHE) among the middle-aged and older adults in China. Compared with uninsured, all types of health insurance promoted hospital utilization rate (ranged from 8.6% to 12.2%) and reduced out-of-pocket (OOP) costs (ranged from 64.9% to 123.6%), but had no significant association with total costs. In contrast, the association of health insurance and outpatient care was less significant. When Urban Employee Medical Insurance (UEMI) as reference, other types of insurance did not show a significant difference. Health insurance could not reduce the risk of CHE. The equity in healthcare utilization improved and healthcare costs had been effectively controlled among the elderly, but health insurance did not protect against CHE risks. Policy efforts should further focus on optimizing healthcare resource allocation and inclining toward the lower socio-economic and poor-health groups.

Whole-blood magnesium and blood lipids are individually and jointly associated with an elevated likelihood of youngsters being overweight or obese: A matched case-control study using the propensity score.

OBJECTIVES: Youngsters who are overweight or obese (YOO) have become an important global health concern. Some micronutrients may be modifiable influential factors. This study aimed to investigate the individual and joint association of whole-blood magnesium (WBMg) and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in YOO. METHODS: This is a propensity score matching-based case-control study. YOO was defined depending on age- and sex-specific body mass index z-score, calculated with SAS macros (%group_standard and %WHO2007) from the World Health Organization website. WBMg, blood lipids, and covariates were carefully measured by trained technicians using a whole-blood, five-element, basic analyzer and atomic absorption spectrometer or automatic biochemical analyzer. Locally weighted scattered plot smoothing and multivariable conditional logistic regression models were applied to estimate the associations of WBMg and blood lipids in YOO. RESULTS: WBMg was positively associated with YOO. The adjusted likelihood of YOO significantly increased by 21% (odds ratio: 1.21; 95% confidence interval [CI], 1.10-1.33) with per-interquartile range elevation of WBMg. Compared with the 1st quartile, adjusted odds ratios among youngsters in the 2nd, 3rd, and 4th quartiles of WBMg were 1.11 (95% CI, 0.92-1.35), 1.29 (95% CI, 1.06-1.57), and 1.47 (95% CI, 1.18-1.83), respectively. Furthermore, the relationship between WBMg and YOO was moderated by lipid profiles. Compared with those having lower (< median) WBMg and TC, TG, LDL-C, or higher (≥ median) HDL-C, youngsters with both higher WBMg and TC, TG, LDL-C, or lower HDL-C had higher YOO odds, which averagely increased by 188%, 250%, 339%, and 369%, respectively. CONCLUSIONS: WBMg was an independent risk factor of YOO, and the associations were stronger among those with unhealthy blood lipids. Our findings can help to guide clinical and public health policies on the relevance of magnesium nutritional status.

Plasma hemoglobin and the risk of death in HIV/AIDS patients treated with antiretroviral therapy.

BACKGROUND: Previous studies concerning the effect of plasma hemoglobin (HB) and other factors that may modify the risk of death in people living with HIV/AIDS (PLHIV) treated with antiretroviral therapy (ART) are limited. RESULTS: Higher HB was independently linked to a lower death risk in PLHIV, with a decrease of 29% (13%, 43%) per standard deviation (SD) increment after adjusting for CD4, VL and other potential factors [hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.57-0.87, P<0.001]. In addition, the addition of HB to the predictive model containing VL and CD4 significantly improved the C-index, by 0.69% (95% CI: 0.68%-0.71%), and net discrimination, by 0.5% (95% CI: 0.0%-1.6%, P=0.040), when predicting the death risk of PLHIV. CONCLUSIONS: A lower level of HB was an independent risk factor for HIV/AIDS-associated death in PLHIV. HB combined with VL and CD4 may be an appropriate predictive model of the death risk of PLHIV. MATERIALS AND METHODS: A propensity-score matching (PSM) approach was applied to select a total of 750 PLHIV (150 deceased and 600 living) from the AIDS prevention and control information system in the Wenzhou area from 2006 to 2018. Multivariable Cox proportional hazards regression models were formulated to estimate the effect of HB. The predictive performance improvement contributed by HB was evaluated using the C-index and net reclassification improvement.

Metabolomics-based multidimensional network biomarkers for diabetic retinopathy identification in patients with type 2 diabetes mellitus.

INTRODUCTION: Despite advances in diabetic retinopathy (DR) medications, early identification is vitally important for DR administration and remains a major challenge. This study aims to develop a novel system of multidimensional network biomarkers (MDNBs) based on a widely targeted metabolomics approach to detect DR among patients with type 2 diabetes mellitus (T2DM) efficiently. RESEARCH DESIGN AND METHODS: In this propensity score matching-based case-control study, we used ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry system for serum metabolites assessment of 69 pairs of patients with T2DM with DR (cases) and without DR (controls). Comprehensive analysis, including principal component analysis, orthogonal partial least squares discriminant analysis, generalized linear regression models and a 1000-times permutation test on metabolomics characteristics were conducted to detect candidate MDNBs depending on the discovery set. Receiver operating characteristic analysis was applied for the validation of capability and feasibility of MDNBs based on a separate validation set. RESULTS: We detected 613 features (318 in positive and 295 in negative ESI modes) in which 63 metabolites were highly relevant to the presence of DR. A panel of MDNBs containing linoleic acid, nicotinuric acid, ornithine and phenylacetylglutamine was determined based on the discovery set. Depending on the separate validation set, the area under the curve (95% CI), sensitivity and specificity of this MDNBs system were 0.92 (0.84 to 1.0), 96% and 78%, respectively. CONCLUSIONS: This study demonstrates that metabolomics-based MDNBs are associated with the presence of DR and capable of distinguishing DR from T2DM efficiently. Our data also provide new insights into the mechanisms of DR and the potential value for new treatment targets development. Additional studies are needed to confirm our findings.

The performance of noninvasive indexes of adults in identification of nonalcoholic fatty liver disease in children.

BACKGROUND: The aim of this study is to evaluate the performance of three existing prediction scores which are applicable to adults for identifying nonalcoholic fatty liver disease (NAFLD) in Chinese children. METHODS: We used data from routine check-up based medical records of 1845 children to validate the performance of three existing scoring systems including the hepatic steatosis index (HSI), Zhejiang University index (ZJU index), and triglyceride-glucose index (TyG index) in detection of NAFLD in children. Propensity score matching was applied to adjust for potential confounding effects in both training and validation cohorts. The area under the curve (AUC) of the receiver operating characteristic curve analysis was utilized to assess the performance of the three scoring systems. RESULTS: Children with NAFLD had higher scores of HSI, ZJU index, and TyG index when compared with the control group (children without NAFLD). Elevated HSI, ZJU index, and TyG index scores were significantly associated with the presence of pediatric NAFLD since adjusted odds ratio and 95% CI with per interquartile range elevation of the HSI, ZJU index, and TyG index were 32.81 (20.48, 52.55), 26.31 (16.97, 40.79), and 1.83 (1.57, 2.13), respectively. In terms of discrimination of NAFLD in children, the AUC of the HSI, ZJU index, and TyG index depending on the validation cohort were 0.964, 0.960, and 0.769, respectively. CONCLUSIONS: The HSI and ZJU index could be appropriate noninvasive biomarkers in distinguishing NAFLD in children from their controls with satisfied accuracy, which would emphasize the clinical and public health policy relevance of pediatric NAFLD. Our findings need to be confirmed by additional longitudinal studies.

Morphological changes in and quantitative analysis of macular retinal microvasculature by optical coherence tomography angiography in hypertensive retinopathy.

Hypertension is a serious global health problem. Hypertensive retinopathy is generally considered to be a predictor of vascular disease elsewhere in the human body. In the past few decades, a variety of grading systems have been proposed for hypertensive retinopathy. However, these grading systems have some limitations. This study utilized optical coherence tomography angiography (OCTA) to investigate the morphological changes and macular retinal microvasculature in depth among 100 patients with hypertensive retinopathy and 66 healthy participants. Five main pathological changes were discovered in hypertensive retinopathy, as follows: focal capillary sparsity, scattered microangioma, focal macular arch ring defects, focal capillary disorder, and focal capillary nonperfusion at the levels of the superficial and deep vascular networks. In addition, we have found that the number of various pathological changes shows an increasing trend as hypertensive retinopathy progresses and may be related to renal damage. Finally, deep vessel density tended to decrease with progressive stages of hypertensive retinopathy and could be the best indicator to predict the risk of hypertensive retinopathy. Our study, therefore, proposes 3 stages of hypertensive retinopathy without macular edema according to the pathophysiology found by OCTA: stage 1 (only focal capillary sparsity), taking the place of KWB grade I; stage 2 (focal capillary sparsity and scattered microangioma), taking the place of KWB grade II; and stage 3 (focal capillary sparsity, scattered microangioma, focal capillary disorder, and nonperfusion), taking the place of KWB grade III. Hence, OCTA may be a potentially useful tool for evaluating the pathophysiology and staging of hypertensive retinopathy. Further longitudinal prospective studies are needed to confirm our findings.

Association of n-6 PUFAs with the risk of diabetic retinopathy in diabetic patients.

Diabetic retinopathy (DR), the most common microvascular complication of diabetes and leading cause of visual impairment in adults worldwide, is suggested to be linked to abnormal lipid metabolism. The present study aims to comprehensively investigate the relationship between n-6 polyunsaturated fatty acids (PUFAs) and DR. This was a propensity score matching based case-control study, including 69 pairs of DR patients and type 2 diabetic patients without DR with mean age of 56.7 ± 9.2 years. Five n-6 PUFAs were determined by UPLC-ESI-MS/MS system. Principle component regression (PCR) and multiple conditional logistic regression models were used to investigate the association of DR risk with n-6 PUFAs depending on independent training and testing sets, respectively. According to locally weighted regression model, we observed obvious negative correlation between levels of five n-6 PUFAs (linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid and arachidonicacid) and DR. Based on multiple PCR model, we also observed significant negative association between the five n-6 PUFAs and DR with adjusted OR (95% CI) as 0.62 (0.43,0.87). When being evaluated depending on the testing set, the association was still existed, and PCR model had excellent classification performance, in which area under the curve (AUC) was 0.88 (95% CI: 0.78, 0.99). In addition, the model also had valid calibration with a non-significant Hosmer-Lemeshow Chi-square of 9.44 (P = 0.307) in the testing set. n-6 PUFAs were inversely associated with the presence of DR, and the principle component could be potential indicator in distinguishing DR from other T2D patients.

Clinical Features of Maintenance Hemodialysis Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.

BACKGROUND AND OBJECTIVES: Previous reports on the outbreak of coronavirus disease 2019 were on the basis of data from the general population. Our study aimed to investigate the clinical features of patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective, single-center study, we included 49 hospitalized patients on maintenance hemodialysis and 52 hospitalized patients without kidney failure (controls) with confirmed coronavirus disease 2019 at Tongren Hospital of Wuhan University from January 30, 2020 to March 10, 2020. Demographic, clinical, laboratory, and radiologic characteristics and treatment and outcomes data were analyzed. The final date of follow-up was March 19, 2020. RESULTS: The median age of 101 patients was 62 years (interquartile range, 49-72). All patients were local residents of Wuhan. In terms of common symptoms, there were differences between patients on hemodialysis and controls (fatigue [59% versus 83%], dry cough [49% versus 71%], and fever [47% versus 90%]). Lymphocyte counts were decreased (0.8×109/L [patients on hemodialysis] versus 0.9×109/L [controls], P=0.02). Comparing patients on hemodialysis with controls, creatine kinase-muscle and brain type, myoglobin, hypersensitive troponin I, B-type natriuretic peptide, and procalcitonin were increased, and the percentage of abnormalities in bilateral lung was higher in computed tomographic scan (82% versus 69%, P=0.15) and unilateral lung was lower (10% versus 27%, P=0.03). Common complications including shock, acute respiratory distress syndrome, arrhythmia, and acute cardiac injury in patients on hemodialysis were significantly higher. Compared with controls, more patients on hemodialysis received noninvasive ventilation (25% versus 6%, P=0.008). As of March 19, 2020, three patients on hemodialysis (6%) were transferred to the intensive care unit and received invasive ventilation. Seven patients on hemodialysis (14%) had died. CONCLUSIONS: The main symptoms of coronavirus disease 2019 pneumonia, including fever and cough, were less common in patients on hemodialysis. Patients on hemodialysis with coronavirus disease 2019 were at higher risk of death.

The association of tryptophan and phenylalanine are associated with arsenic-induced skin lesions in a Chinese population chronically exposed to arsenic via drinking water: a case-control study.

OBJECTIVES: We investigated the association of specific serum amino acids (AAs) with the odds of arsenic-induced skin lesions (AISL) and their ability to distinguish patients with AISL from people chronically exposed to arsenic. DESIGN: Case-control study. SETTING: Three arsenic-exposed villages in Wuyuan County, Hetao Plain, Inner Mongolia, China were evaluated. PARTICIPANTS: Among the 450 residents aged 18-79 years, who were chronically exposed to arsenic via drinking water, 56 were diagnosed as having AISL (defined as cases). Another 56 participants without AISL, matched by gender and age (±1 year) from the same population, were examined as controls. MAIN OUTCOME MEASURES AND METHODS: AA levels were determined by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics analysis. Potential confounding variables were identified via a standardised questionnaire and clinical examination. Multivariable conditional logistic regression model and receiver operating characteristic curve analyses were performed to investigate the relationship between specific AAs and AISL. RESULTS: Tryptophan and phenylalanine levels were negatively associated with AISL (p<0.05). Compared with that in the first quartile, the adjusted OR of AISL in the second, third and fourth quartiles were decreased by 44%, 88% and 79% for tryptophan and 30%, 80% and 80% for phenylalanine, respectively. The combination of these two higher-level AAs showed the lowest OR for AISL (OR=0.08; 95% CI 0.02 to 0.25; p<0.001). Furthermore, both AAs showed a moderate ability to distinguish patients with AISL from the control, with the area under the curve (AUC; 95% CI) as 0.67 (0.57 to 0.77) for tryptophan and 0.70 (0.60 to 0.80) for phenylalanine (p<0.05). The combined pattern with AUC (95% CI) was 0.72 (0.62 to 0.81), showing a sensitivity of 76.79% and specificity of 58.93% (p<0.001). CONCLUSIONS: Specific AAs may be linked to AISL and play important roles in early AISL identification. TRIAL REGISTRATION NUMBER: NCT02235948.

Development and validation of a prognostic nomogram for HIV/AIDS patients who underwent antiretroviral therapy: Data from a China population-based cohort.

BACKGROUND: Accurate forecast of the death risk is crucial to the administration of people living with HIV/AIDS (PLHIV). We aimed to establish and validate an effective prognosis nomogram in PLHIV receiving antiretroviral therapy (ART). METHODS: All the data were obtained from 2006 to 2018 in the Wenzhou area from China AIDS prevention and control information system. Factors included in the nomogram were determined by univariate and multiple Cox proportional hazard analysis based on the training set. The receiver operating characteristic (ROC) and calibration curves were used to assess its predictive accuracy and discriminative ability. Its clinical utility was also evaluated using decision curve analysis (DCA), X-tile analysis and Kaplan-Meier curve, respectively in an independent validation set. FINDINGS: Independent prognostic factors including haemoglobin, viral load and CD4+ T-cell count were determined and contained in the nomogram. Good agreement between the prediction by nomogram and actual observation could be detected in the calibration curve for mortality, especially in the first year. In the training cohort, AUC (95% CI) and C-index (95% CI) were 0.93 (0.90, 0.96) and 0.90 (0.85, 0.96), respectively. In the validation set, the nomogram still revealed excellent discriminations [AUC (95% CI): 0.95 (0.91, 1.00)] and good calibration [C-index (95% CI): 0.92 (0.82-1.00)]. Moreover, DCA also demonstrated that the nomogram was clinical beneficial. Additionally, participants could be classified into three distinct (low, middle and high) risk groups by the nomogram. INTERPRETATION: The nomogram presents accurate and favourable prognostic prediction for PLHIV who underwent ART. FUNDING: This work was supported by Zhejiang Basic Public Welfare Research Project (LGF19H260011), Wenzhou Basic Public Welfare Research Project (Y20180201), the Initial Scientific Research Fund (KYQD170301), the Major Project of the Eye Hospital Wenzhou the Major Project of the Eye Hospital Wenzhou Medical University (YNZD201602). Part of this work was also funded by National Natural Science Foundation of China (81670777) and Science and Technology Innovation Activity Plan and New Talents Plan for College Students in Zhejiang Province (2019R413073). The funders had no roles in study design, data collection, data analysis, interpretation and writing of the report.

Comprehensive analysis of the metabolomic characteristics on the health lesions induced by chronic arsenic exposure: A metabolomics study.

Early detection of the health lesions induced by chronic arsenic exposure (HLICAE) are crucial to prevent permanent arsenic-induced damage. If HLICAE can be identified in time, appropriate preventive and therapeutic measures may be provided without various avoidable lesions. The present study aims to assess the probability of HLICAE early recognition with metabolomics. Applying a case-control study, 94 participants with HLICAE (cases) and other 94 subjects without HLICAE (controls) were matched with gender and age (±1 year), coming from a previous chronic arsenic exposure cohort. Serum metabolomic profiles were assessed by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and analyzed with univariate and multivariate statistics. A total of 210 and 364 features were detected in positive and negative ion modes (ESI+/ESI-), respectively. The altered metabolic pathways included lipid and amino acid metabolisms. 28 metabolomics-based biomarkers were significantly associated with HLICAE and provided areas under the curve (AUC, 95% confidence interval) of 0.898 (0.836, 0.960) and 0.908 (0.855, 0.960) in the discovery phase, 78.6% and 86.4% of positive predictive values in the validation phase, in distinguishing HLICAE from controls in ESI+/ESI-, respectively. This study provides novel insights on mechanisms of health effects probably induced by chronic arsenic exposure, and these biomarkers may be applied in HLICAE early detection.

The effect of high glucose-based peritoneal dialysis fluids on thioredoxin-interacting protein expression in human peritoneal mesothelial cells.

BACKGROUND: It has been demonstrated that thioredoxin-interacting protein (TXNIP) interacted with NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and participated in the NLRP3 inflammasome activation. Our previous study has demonstrated that in human peritoneal mesothelial cells (HPMCs), exposure to high glucose-based peritoneal dialysis (PD) solutions induced mitochondrial reactive oxygen species (ROS) production, activation of NLRP3 inflammasome and IL-1ß expression. This study aimed to investigate the effect of high glucose-based PD fluids on the TXNIP expression and the underlying mechanisms by which TXNIP-NLRP3 interaction mediates the inflammatory injury to HPMCs in high glucose-based PD fluids conditions. METHODS: TXNIP gene and protein expression was detected by real-time polymerase chain reaction (RT-PCR) and immunoblot. Immunoprecipitation was used to evaluate the interaction between TRX1 and TXNIP, TXNIP and NLRP3. ROS production and IL-1ß expression was examined by flow cytometry and immunoblot and enzyme-linked immunosorbent assay (ELISA) respectively. RESULTS: It was identified that high glucose-based PD solutions enhance the level of TXNIP gene and protein in cultured HPMCs and a rat-based PD model. We also found that ROS generation induced by high glucose-based PD solutions disrupts the TRX1-TXNIP association, while promoting the binding of TXNIP to NLRP3 in HPMCs. Furthermore, the application of a ROS inhibitor (APDC) to HPMCs blocked the high glucose-based PD solution-induced TXNIP-NLRP3 binding, in addition to ROS production and IL-1ß expression. CONCLUSION: The results of the present study revealed a novel mechanism underlying high glucose-containing PD-mediated peritoneal inflammatory injury, supporting the attenuation of ROS generation as a potential therapeutic strategy to alleviate such pathology.

Association between the HLA-DQA1 rs2187668 polymorphism and risk of idiopathic membranous nephropathy: A PRISMA-compliant meta-analysis.

OBJECTIVE: Numerous studies have evaluated the association between the rs2187668 polymorphism in the human leucocyte antigen (HLA) complex class II HLA-DQ a-chain 1 (HLA-DQA1) gene and idiopathic membranous nephropathy (iMN) risk, which provided new insight into potential new targets for the treatment of iMN. However, this relationship remains inconclusive. Our aim was to evaluate the relationship between this polymorphism and iMN susceptibility by performing a meta-analysis. METHODS: Articles were identified in the PubMed, Google Scholar, EMBASE, Cochran Library databases. Meta-analyses were performed for rs2187668 allele frequency, genotypes, and the association with iMN susceptibility. Subgroup analyses, publication bias and sensitivity analyses were also conducted. RESULTS: 11 eligible studies (3209 cases and 7358 controls) from 7 articles were included. Statistical analyses were carried out using Stata 12.0, combining data from all the relevant studies. The pooled odds ratios (ORs) regarding the association between the HLA-DQA1 rs2187668 polymorphism and iMN risk were statistically significant [A vs G: OR = 3.34, 95% confidence interval (CI) = 2.70-4.13; AA vs GA + GG: OR = 8.69, 95% CI = 6.64-11.36; GG vs GA + AA: OR = 0.25, 95% CI = 0.19-0.33;AA vs GG: OR = 12.61, 95% CI = 8.02-19.81; GA vs GG: OR = 3.45, 95% CI = 2.79-4.25]. CONCLUSIONS: Our pooled analysis showed a significant association between rs2187668-(A) allele and iMN susceptibility, and the intervention of this mutation might bring new therapeutic strategy for iMN. However, further studies should be performed to confirm this finding.