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Abstract Background Activation of pericytes leads to renal interstitial fibrosis, but the regulatory mechanism of pericytes in the progression from AKI to CKD remains poorly understood. CD36 activation plays a role in the progression of CKD. However, the significance of CD36 during AKI-CKD, especially in pericyte, remains to be fully defined. Methods GEO and DISCO database were used to analyze the expression of CD36 in pericyte during AKI-CKD; IRI to conduct AKI-CKD mouse model; Hypoxia/Reoxygenation (H/R) to induce the cell model; RT-qPCR and Western blotting to detect gene expression; IP and confocal-IF to determine the core fucosylation (CF) level of CD36. Flow cytometry (AV/PI staining) to detect the cell apoptosis and JC-1 staining to react to the change of mitochondrial membrane potential. Results During AKI to CKD progression, CD36 expression in pericytes is higher and may be influenced by CF. Moreover, we confirmed the positive association of CD36 expression with pericyte-myofibroblast transition and the progression of AKI-CKD in an IRI mouse model and hypoxia/reoxygenation (H/R) pericytes. Notably, we discovered that FUT8 upregulates both CD36 expression and its CF level, contributing to the activation of the mitochondrial-dependent apoptosis signaling pathway in pericytes, ultimately leading to the progression of AKI-CKD. Conclusion These results further identify FUT8 and CD36 as potential targets for the treatment in the progression of AKI-CKD.

Abstract Background Peritoneal dialysis (PD) and conventional in‐center hemodialysis (HD) are treatment options for patients with end‐stage kidney disease (ESKD). However, their impact on all‐cause mortality is unclear. Methods We conducted a multicenter, open‐label, randomized, non‐inferiority trial to determine the effect of dialysis modality on mortality in patients with ESKD. Eligible patients were recruited from 30 sites across China and assigned to receive either PD or HD in a ratio of 1:1. The primary outcome was all‐cause mortality. Non‐inferiority was defined as the upper bound of the one‐sided 95% confidence interval (CI) for the hazard ratio (HR) being ≤1.25. Results A total of 414 patients with incident ESKD were randomly assigned to PD (n = 213) or HD (n = 201). During a median follow‐up of 1.7 years, 37 patients in the PD group and 31 in the HD group died, giving respective event rates per patient‐year of 0.061 and 0.071. The HR for mortality on PD in comparison with HD was 0.76 (95% CI 0.47–1.24) after adjustment for age, sex, and diabetes status, achieving the limit for non‐inferiority. There were more adverse events (p = 0.003), serious adverse events (p = 0.009), and adverse events leading to hospitalization (p = 0.003) in the PD group than in the HD group; however, there was no significant between‐group difference in adverse events leading to death or discontinuation of treatment. Conclusions PD was non‐inferior to conventional in‐center HD in terms of survival in patients with ESKD. Our findings underscore the need for shared decision‐making between physicians and patients regarding the selection of dialysis modality. Trial registration Registered at ClinicalTrials.gov (NCT01413074).

Abstract Under long-standing threat of seasonal influenza outbreaks, it remains imperative to understand the drivers of influenza dynamics which can guide mitigation measures. While the role of absolute humidity and temperature is extensively studied, the possibility of ambient ozone (O3) as an environmental driver of influenza has received scant attention. Here, using state-level data in the USA during 2010–2015, we examined such research hypothesis. For rigorous causal inference by evidence triangulation, we applied 3 distinct methods for data analysis: Convergent Cross Mapping from state-space reconstruction theory, Peter-Clark-momentary-conditional-independence plus as graphical modeling algorithms, and regression-based Generalised Linear Model. The negative impact of ambient O3 on influenza activity at 1-week lag is consistently demonstrated by those 3 methods. With O3 commonly known as air pollutant, the novel findings here on the inhibition effect of O3 on influenza activity warrant further investigations to inform environmental management and public health protection.

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis.Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness.Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated.Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

Background Residual kidney function (RKF) impacts patients’ survival rate and quality of life when undergoing peritoneal dialysis (PD). This meta-analysis was conducted to systematically identify risk and protective factors associated with RKF decline and loss.Methods We searched three English and one Chinese databases from inception to January 31, 2023, for cohort and cross-sectional studies exploring factors associated with RKF decline or loss. The random effects model was employed to aggregate risk estimates and 95% confidence intervals (CIs) from multivariate analysis. Sensitivity and subgroup analyses were performed to explore the heterogeneity among the studies.Results Twenty-seven studies comprising 13549 individuals and 14 factors were included in the meta-analysis. Based on the meta-analysis results, risk factors involving male gender (hazard ratio (HR) 1.689, 95%CI 1.385–2.061), greater body mass index (BMI) (odds ratio (OR) 1.081, 95% confidence interval (CI) 1.029–1.135), higher systolic blood pressure (SBP) (HR 1.014, 95%CI 1.005–1.024), diabetes mellitus (DM) (HRRKF loss 1.873, 95%CI 1.475–2.378), DM (ORRKF decline 1.906, 95%CI 1.262–2.879), peritonitis (relative ratio (RR) 2.291, 95%CI 1.633–3.213), proteinuria (OR 1.223, 95%CI 1.117–1.338), and elevated serum phosphorus (RR 2.655, 95%CI 1.679–4.201) significantly contributed to the risk of RKF decline and loss in PD patients. Conversely, older age (HR 0.968, 95%CI 0.956–0.981), higher serum albumin (OR 0.834, 95%CI 0.720–0.966), weekly Kt/V urea (HR 0.414, 95%CI 0.248–0.690), baseline urine volume (UV) (HR 0.791, 95%CI 0.639–0.979), baseline RKF (HR 0.795, 95%CI 0.739–0.857) exhibited protective effects. However, diuretics use, automatic peritoneal dialysis (APD) modality and baseline RKF did not significantly impact RKF decline.Conclusions Patients with male gender, greater BMI, higher SBP, DM, peritonitis, proteinuria, and elevated serum phosphorus might have a higher risk of RKF decline and loss. In contrast, older age, higher serum albumin, weekly Kt/V urea, baseline UV, and baseline RKF might protect against RKF deterioration.

AbstractBackground & Aims Complete blood count (CBC)-derived inflammatory markers are predictive biomarkers for the prognosis of many diseases. However, there was no study on patients with peritoneal dialysis-associated peritonitis (PDAP). We aimed to investigate the value of these markers in predicting treatment failure of acute peritonitis in chronic PD patients.Methods The records of 138 peritonitis episodes were reviewed and divided into treatment success or failure groups in a single center for 10 years. CBC-derived markers and other routine data were recorded before peritonitis treatment was initiated. Univariate and multivariate regression analyses and the receiver operating characteristic (ROC) curve about the predictors of treatment outcomes were performed.Results Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and derived NLR were significantly higher in the failure group. Univariate logistic regression results showed that NLR and PLR were risk factors of treatment outcomes. The backward stepwise multivariate logistic regression results demonstrated that NLR [adjusted odds ratio (aOR), 1.376; 95% confidence intervals (CI), 1.105–1.713; p = .004], PLR (aOR, 1.010; 95%CI, 1.004–1.017; p = .002) were risk factors, but hemoglobin-to-lymphocyte ratio (HLR) (aOR, 0.977; 95%CI, 0.963–0.991; p = .001), and SII (aOR, 0.999; 95%CI, 0.998–1.000; p = .040) were protective factors. A combination of age, PD vintage, Gram-positive peritonitis, staphylococcus aureus, culture-negative, NLR, PLR, HLR, and SII would improve prognostic performance. The area under this ROC curve was 0.85, higher than other factors.Conclusions NLR, PLR, HLR, and SII were associated with PDAP outcomes. Age, PD vintage, NLR, and PLR were significant risk factors in PDAP patients.

AbstractBackground National holidays are associated with high mortality in some diseases, but little is known about patients undergoing peritoneal dialysis (PD). The research aimed to investigate the impact of national holidays on the health outcomes of PD patients.Methods Over ten years, all episodes of unplanned hospitalization, death, and peritonitis in PD patients were collected in our center. Seven national holidays in China were chosen, and non-holiday days were selected as the control period. The effect of national holidays was observed by comparing the hospitalization, death, and peritonitis rates between holiday and non-holiday groups.Results There were 297 events in all holiday periods and 1247 in non-holiday periods. There is no significant difference in hospitalization rate between holiday and non-holiday groups (32.4% ± 6.4% vs. 29.2% ± 3.4%, p = 0.175). So is the death rate [6.3% (4.8–12.3%) vs.5.0% (4.2–8.9%), p = 0.324] and peritonitis rate [0.19 (0.13–0.53) vs. 0.22 (0.18–0.27), p = 0.445] between the two groups. Significant differences were observed in the distribution of peritonitis causes between the two groups (p = 0.017). The rate of secondary to other infections in the holiday group was significantly higher than in the non-holiday group (25.0 vs. 10.3%, p = 0.015).Conclusion Our study suggested no national holiday effect on health outcomes of PD patients based on ten-year data in our center.

BackgroundNephrotic syndrome that is resistant to steroid therapy is termed refractory nephrotic syndrome (RNS), a condition that is associated with an increased risk of end-stage renal disease. Immunosuppressants are used to treat RNS; however, prolonged use may lead to significant adverse effects. Mizoribine (MZR) is a novel agent used in long-term immunosuppressive therapy, which has few adverse effects, but data on its long-term use in patients with RNS are unavailable. ObjectiveWe propose a trial to examine the efficacy and safety of MZR compared with cyclophosphamide (CYC) in Chinese adult patients with RNS. MethodsThis is a multicenter, randomized, controlled interventional study with a screening phase (1 week) and a treatment phase (52 weeks). This study has been reviewed and approved by the Medical Ethics Committees of all 34 medical centers that are participating. Patients with RNS consent to participation, and are enrolled and randomized to an MZR group or a CYC group (1:1 ratio), with each group receiving tapering doses of oral corticosteroids. Participants are assessed for adverse effects, and laboratory results are collected at 8 visits during the treatment phase (weeks 4, 8, 12, 16, 20, 32, 44, and 52 [exit visit]). Participants are able to withdraw voluntarily, and investigators are required to remove patients when there are safety concerns or deviations from the protocol. ResultsThe study started in November 2014 and was completed in March 2019. A total of 239 participants from 34 hospitals in China have been enrolled. Data analysis has been completed. The results are being finalized by the Center for Drug Evaluation. ConclusionsThis study examines the safety and efficacy of MZR as a long-term treatment approach for Chinese adults with RNS. It is the longest lasting and largest randomized controlled trial to examine MZR in Chinese patients. The results can help determine whether RNS should be considered as an additional indication for MZR treatment in China. Trial RegistrationClinicalTrials.gov NCT02257697; https://clinicaltrials.gov/ct2/show/NCT02257697 International Registered Report Identifier (IRRID)RR1-10.2196/46101

Osteoporosis, one of the most serious and common complications of diabetes, has affected the quality of life of a large number of people in recent years. Although there are many studies on the mechanism of diabetic osteoporosis, the information is still limited and there is no consensus. Recently, researchers have proven that osteoporosis induced by diabetes mellitus may be connected to an abnormal iron metabolism and ferroptosis inside cells under high glucose situations. However, there are no comprehensive reviews reported. Understanding these mechanisms has important implications for the development and treatment of diabetic osteoporosis. Therefore, this review elaborates on the changes in bones under high glucose conditions, the consequences of an elevated glucose microenvironment on the associated cells, the impact of high glucose conditions on the iron metabolism of the associated cells, and the signaling pathways of the cells that may contribute to diabetic bone loss in the presence of an abnormal iron metabolism. Lastly, we also elucidate and discuss the therapeutic targets of diabetic bone loss with relevant medications which provides some inspiration for its cure.

Introduction Hyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes. The efficacy and negative effects of currently existing treatment options have made HK management questionable. Sodium zirconium cyclosilicate (SZC), a novel highly selective potassium binder, is approved for the treatment of HK. The present study will be aimed to assess the safety, effectiveness and treatment patterns of SZC in Chinese patients with HK in a real-world clinical setting as it is required by China’s drug review and approval process.Methods and analysis This is a multicentre, prospective cohort study which plans to enrol 1000 patients taking SZC or willing to take SZC from approximately 40 sites in China. Patients ≥18 years of age at the time of signing the written informed consent and with documented serum potassium levels ≥5.0 mmol/L within 1 year before study enrolment day will be included. Eligible patients will receive SZC treatment and will be followed up for 6 months from enrolment day. The primary objective will be to evaluate the safety of SZC for the management of HK in Chinese patients in terms of adverse events (AEs), serious AEs as well as discontinuation of SZC. The secondary objectives will include understanding the SZC dosage information in terms of its effectiveness and treatment patterns under real-world clinical practice and assessing effectiveness of SZC during the observational period.Ethics and dissemination This study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (approval number: YJ-JG-YW-2020). All the participating sites have received the ethics approval. Results will be disseminated through national and international presentations and peer-reviewed publications.Trial registration number NCT05271266.

Abstract To investigate the relationships between LncRNA NNT-AS1, CRP, PCT and their interactions and the refractory mycoplasma pneumoniae pneumonia (RMPP) in children. Serum levels of LncRNA NNT-AS1 of RMPP and non-RMPP (NRMPP) patients were detected by real-time PCR, and were analyzed together with serum c-reactive protein (CRP) and procalcitonin (PCT). Correlations between LncRNA NNT-AS1 and CRP and PCT were analyzed by Pearson correlation test. The ROC curve was used to analyze the potential of LncRNA NNT-AS1, CRP and PCT as biomarkers for predicting RMPP. Logistic regression crossover model and the Excel compiled by Andersson et al. were used to analyze the interactions among the biomarkers. We found that LncRNA NNT-AS1, CRP and PCT were all highly expressed in patients with RMPP. LncRNA NNT-AS1 could positively correlate with the expressions of CRP and PCT, and jointly promote the occurrence of RMPP. The combined diagnosis of LncRNA NNT-AS1, CRP and PCT could predict the occurrence of RMPP.

Objective Peritoneal fibrosis (PF) ultimately causes ultrafiltration failure and peritoneal dialysis (PD) termination, but there are few effective therapies for it. Core fucosylation, which is catalyzed by α1,6-fucosyltransferase (Fut8) in mammals, may play a crucial role in PF development. This study aims to assess the effects of inhibiting core fucosylation of epidermal growth factor (EGF) receptor on PF rats. Methods PF rats (established by 4.25% glucose dialysate) were treated with either an adenovirus-Fut8 short hairpin RNA (Fut8shRNA) or adenovirus-control. Masson’s staining and net ultrafiltration were performed at week six. Fut8 level and core fucosylation of EGF receptor and collagen I in the peritoneal membrane were assessed, and EGF signaling was detected, including signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) and their phosphorylation. Monocyte chemoattractant protein-1 (MCP-1) in peritoneal effluent was examined. Results Fut8 was upregulated in PF rats but decreased after Fut8shRNA treatment. EGF and EGF receptor expression was upregulated in PF rats, while core fucosylation of EGF receptor decreased after Fut8shRNA treatment. Masson’s staining results showed an increase in peritoneal thickness in PF rats but a decrease after Fut8shRNA treatment. Fut8shRNA treatment increased net ultrafiltration, reduced the expression of collagen I and MCP-1 compared to PF rats. Fut8shRNA treatment suppressed phosphorylation of STAT3 and NF-κB in the peritoneal membrane of PF rats. Conclusions Fut8shRNA treatment ameliorated the fibrotic changes in PF rats. A potential mechanism may be that Fut8shRNA treatment inactivated EGF signaling pathway by suppressing the phosphorylation of STAT3 and NF-κB.

Background: Hemodialysis is the main approach for renal replacement therapy in patients with end-stage renal disease (ESRD) in China. The timing of dialysis initiation is one of the key factors influencing patient survival and prognosis. Over the past decade, the relationship between the timing of dialysis initiation and mortality has remained unclear in patients with ESRD in China. Methods: Patients who commenced maintenance hemodialysis from 2009 to 2014 from 24 hemodialysis centers in Mainland China were enrolled in the study (n = 1,674). Patients were divided into 2 groups based on the year they started hemodialysis (patients who started hemodialysis from 2009 to 2011, and patients who started hemodialysis from 2012 to 2014). Analysis of the yearly change in the estimated glomerular filtration rate (eGFR) at the initiation of dialysis was performed for the 2 groups. Meanwhile, the patients were divided into 3 groups based on their eGFR at the initiation of dialysis (8 mL/min/1.73 m2). For these 3 groups, the relationship between the eGFR at the start of dialysis and mortality were analyzed. Results: The average eGFRs were 5.68 and 5.94 mL/min/1.73 m2 for 2009–2011 and 2012–2014, respectively. Compared with the 2009–2011 group, the proportion of patients with diabetes in 2012–2014 increased from 26.7 to 37.7%. The prognosis of patients with different eGFRs at the start of dialysis was analyzed using Kaplan-Meier survival curves. After adjusting for confounding factors through a Cox regression model, no significant difference was demonstrated among the 3 groups (8 mL/min/1.73 m2 [p = 0.403]). Conclusion: In Mainland China, the eGFR at the start of dialysis did not change significantly over time from 2008 to 2014 and had no association with the mortality of patients with ESRD.

Background: Hypertension is prevalent in chronic kidney disease (CKD), but the control of hypertension is suboptimal. We reported the prevalence and characteristics of resistant and undertreated hypertension based on a nationwide survey aiming to improve blood pressure (BP) control. Methods: Resistant hypertension (RH) was defined as BP above the target (

Background/Aims: Risk factor studies for acute kidney injury (AKI) in China are lacking, especially those regarding non-traditional risk factors, such as laboratory indicators. Methods: All adult patients admitted to 38 tertiary and 22 secondary hospitals in China in any one month between July and December 2014 were surveyed. AKI patients were screened according to the Kidney Disease: Improving Global Outcomes’ definition of AKI. Logistic regression was used to analyze the risk factors for AKI, and Cox regression was used to analyze the risk of in-hospital mortality for AKI patients; additionally, a propensity score analysis was used to reconfirm the risk factors among laboratory indicators for mortality. Results: The morbidity of AKI was 0.97%. Independent risk factors for AKI were advancing age, male gender, hypertension, and chronic kidney disease. All-cause mortality was 16.5%. The predictors of mortality in AKI patients were advancing age, tumor, higher uric acid level and increases in Acute Physiologic Assessment and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. The hazard ratio (HR) for mortality with uric acid levels > 9.1 mg/dl compared with ≤ 5.2 mg/dl was 1.78 (95% CI: 1.23 to 2.58) for the AKI patients as a group, and was 1.73 (95% CI: 1.24 to 2.42) for a propensity score-matched set. Conclusion: In addition to traditional risk factors, uric acid level is an independent predictor of all-cause mortality after AKI.

Introduction Starting dialysis early or late both result in a low quality of life and a poor prognosis in patients undergoing haemodialysis. However, there remains no consensus on the optimal timing of dialysis initiation, mainly because of a lack of suitable methods to assess variations in dialysis initiation time. We have established a novel equation named DIFE (Dialysis Initiation based on Fuzzy-mathematics Equation) through a retrospective, multicentre clinical cohort study in China to determine the most suitable timing of dialysis initiation. The predictors of the DIFE include nine biochemical markers and clinical variables that together influence dialysis initiation. To externally validate the clinical accuracy of DIFE, we designed the assessment of DIFE (ADIFE) study as a prospective, open-label, multicentre, randomised controlled trial to assess the clinical outcomes among patients who initiate dialysis in an optimal start dialysis group and a late-start dialysis group, based on DIFE.Methods and analysis A total of 388 enrolled patients with end-stage renal disease will be randomised 1:1 to the optimal start dialysis group, with a DIFE value between 30 and 35, or the late-start dialysis group, with a DIFE value less than 30, using the Randomization and Trial Supply Management system. Participants will be assessed for changes in signs and symptoms, dialysis mode and parameters, biochemical and inflammatory markers, Subjective Global Assessment, Kidney Disease Quality of Life Short Form, Cognitive Assessment, medical costs, adverse events and concomitant medication at baseline, predialysis visiting stage and postdialysis visiting stage, every 12–24 weeks. The following data will be recorded on standardised online electronic case report forms. The primary endpoint is 3-year all-cause mortality. The secondary endpoints include non-fatal cerebrocardiovascular events, annual hospitalisation rate, quality of life, medical costs and haemodialysis related complications.Ethics and dissemination Ethical approval was obtained from the Ethics Committee of the First Affiliated Hospital of Dalian Medical University China (registration no: YJ-KY-2017–119) and the ethics committees of all participating centres. The final results of the ADIFE trial will be presented to the study sponsor, clinical researchers and the patient and public involvement reference group. Findings will be disseminated through peer-reviewed journals, Clinical Practice Guidelines and at scientific meetings.Trial registration number ClinicalTrial.gov. Registry (NCT03385902); pre-results.

Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.

BACKGROUND: Heparin-induced thrombocytopenia is an immune response mediated by anti-PF4/heparin antibody, which is clinically characterized by thrombocytopenia and thromboembolic events. In this study, a prospective and multi-center clinical investigation 1) determined the positive rate of anti-PF4/heparin antibody in maintenance hemodialysis patients in China, 2) identified the related risk factors, and 3) further explored the effect of the anti-PF4/heparin antibody on bleeding, thromboembolic events, and risk of death in the patients. METHODS: The serum anti-PF4/heparin antibody was measured in 661 patients from nine hemodialysis centers, detected by IgG-specific ELISA and followed by confirmation with excess heparin. Risk factors of these patients were analyzed. Based on a two-year follow-up, the association between the anti-PF4/heparin antibody and bleeding, thromboembolic events, and risk of death in the patients was investigated. RESULTS: 1) The positivity rate of the anti-PF4/heparin antibody in maintenance hemodialysis patients was 5.6%. With diabetes as an independent risk factor, the positivity rate of the anti-PF4/heparin antibody decreased in the patients undergoing weekly dialyses ≥3 times. 2) The positivity rate of the anti-PF4/heparin antibody was not related to the occurrence of clinical thromboembolic events and was not a risk factor for death within two years in maintenance hemodialysis patients. 3) Negativity for the anti-PF4/heparin antibody combined with a reduction of the platelet count or combined with the administration of antiplatelet drugs yielded a significant increase in bleeding events. However, the composite determination of the anti-PF4/heparin antibody and thrombocytopenia, as well as the administration of antiplatelet drugs, was not predictive for the risk of thromboembolic events in the maintenance hemodialysis patients. CONCLUSIONS: A single detection of the anti-PF4/heparin antibody did not predict the occurrence of clinical bleeding, thromboembolic events, or risk of death in the maintenance hemodialysis patients.

BACKGROUND: Mesothelial cell injury plays an important role in peritoneal fibrosis. Present clinical therapies aimed at alleviating peritoneal fibrosis have been largely inadequate. Mesenchymal stem cells (MSCs) are efficient for repairing injuries and reducing fibrosis. This study was designed to investigate the effects of MSCs on injured mesothelial cells and peritoneal fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: Rat bone marrow-derived MSCs (5 × 10(6)) were injected into Sprague-Dawley (SD) rats via tail vein 24 h after peritoneal scraping. Distinct reductions in adhesion formation; infiltration of neutrophils, macrophage cells; number of fibroblasts; and level of transforming growth factor (TGF)-β1 were found in MSCs-treated rats. The proliferation and repair of peritoneal mesothelial cells in MSCs-treated rats were stimulated. Mechanically injured mesothelial cells co-cultured with MSCs in transwells showed distinct increases in migration and proliferation. In vivo imaging showed that MSCs injected intravenously mainly accumulated in the lungs which persisted for at least seven days. No apparent MSCs were observed in the injured peritoneum even when MSCs were injected intraperitoneally. The injection of serum-starved MSCs-conditioned medium (CM) intravenously reduced adhesions similar to MSCs. Antibody based protein array of MSCs-CM showed that the releasing of TNFα-stimulating gene (TSG)-6 increased most dramatically. Promotion of mesothelial cell repair and reduction of peritoneal adhesion were produced by the administration of recombinant mouse (rm) TSG-6, and were weakened by TSG-6-RNA interfering. CONCLUSIONS/SIGNIFICANCE: Collectively, these results indicate that MSCs may attenuate peritoneal injury by repairing mesothelial cells, reducing inflammation and fibrosis. Rather than the engraftment, the secretion of TSG-6 by MSCs makes a major contribution to the therapeutic benefits of MSCs.

Background: Monthly intravenous cyclophosphamide (IVCY) is a widely accepted induction therapy for lupus nephritis (LN) because this regimen balances the time needed for renal remission with the risk of adverse events. However, IVCY is associated with numerous severe toxicities. Mizoribine (MZR) was originally used as an antibiotic against Candida albicans, but researchers found it had strong immunosuppressive activity in various animal models. Previous clinical trials also examined the efficacy of MZR as an immunosuppressant, and it has been used for treatment of LN in Japan since 1990. We will conduct a phase 3 study in China to evaluate the efficacy and safety of oral MZR in comparison with standard IVCY in patients with LN. Methods: This study will be a multi-center, randomized, controlled, open-label clinical trial that consists of a screening period (seven days) followed by a treatment period (52 weeks). After screening, all eligible subjects will be randomized to an MZR or IVCY group in a 1:1 ratio. Then, subjects will initially receive methylprednisolone pulse therapy (0.5 g/day) for three days, followed by the study drug (MZR or CY) with oral corticosteroid therapy from visit two (day four). The efficacy and safety of oral MZR in comparison with standard IVCY will be determined. Discussion: This paper describes the protocol of a multi-center, open-label, randomized controlled trial that compares the efficacy and safety of MZR with IVCY for treatment of LN. The results may help determine whether LN should be considered an indication for this drug in China. Trial registration: ClinicalTrials.gov register, NCT02256150. Registered 2014-10-01. The protocol version number is 1.3 (2016-08-30).