Background Renal allograft artery thrombosis (RAAT) is a severe vascular complication typically occurring within the first month post-transplantation and often resulting in graft loss. While most cases are attributable to surgical or technical factors, we report a rare case of late-onset RAAT secondary to acute antibody-mediated rejection (ABMR), further complicated by severe drug-induced neutropenia. Case presentation A 32-year-old female with end-stage renal disease underwent ABO-compatible living-donor kidney transplantation. The early post-transplant course was uneventful. On postoperative day 83, she presented with acute oliguria. Renal ultrasonography revealed absent allograft arterial flow, leading to a diagnosis of RAAT. Emergent thrombectomy successfully restored distal perfusion; however, renal function failed to recover, necessitating the resumption of renal replacement therapy. Upon admission for conversion to peritoneal dialysis(PD), severe neutropenia (absolute neutrophil count 0.55 × 10⁹/L) was identified, attributed primarily to mycophenolate mofetil. Donor-derived cell-free DNA (dd-cfDNA) was markedly elevated, indicating a high probability of active rejection. Given the unsalvageable graft and life-threatening neutropenia, allograft nephrectomy was performed. Histopathological examination confirmed acute ABMR with linear C4d positivity. Immunosuppression was subsequently discontinued, and the patient was successfully transitioned to PD with complete recovery of leukocyte counts. Conclusions This case illustrates that late-onset RAAT can serve as a catastrophic complication of acute ABMR. Furthermore, it highlights the clinical utility of dd-cfDNA as a non-invasive diagnostic adjunct when biopsy is contraindicated, and underscores the complex management dilemmas arising from concurrent graft failure and severe drug toxicity, which ultimately necessitate a multidisciplinary, patient-centered approach.

Psoriasis is an immune-mediated inflammatory skin disorder associated with systemic complications, including an elevated risk of chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). Managing psoriasis in patients undergoing peritoneal dialysis (PD) remains challenging, primarily due to contraindications to conventional systemic therapies and the limited evidence regarding biologic agents in this population. We report a case of severe psoriasis successfully treated with secukinumab in a 61-year-old man on PD. The patient was diagnosed with plaque psoriasis six years after dialysis initiation. Although initial symptoms improved with intensified dialysis and topical corticosteroids, the disease subsequently was exacerbated, presenting with extensive lesions and severe generalized pruritus that significantly impaired sleep quality. Secukinumab was initiated at 300 mg subcutaneously weekly for four weeks, followed by a maintenance dose of 300 mg every four weeks. At 12 months, the patient achieved complete clearance of psoriatic lesions with no adverse events or PD-related complications. This case highlights the paradoxical role of dialysis in psoriasis, which may either induce new-onset disease or ameliorate pre-existing lesions. Furthermore, it supports the efficacy and safety of secukinumab for severe psoriasis in PD patients. While IL-17A is implicated in dialysis-induced peritoneal damage, whether IL-17A inhibitors confer protective benefits on peritoneal membrane integrity in this population remains unknown and warrants dedicated investigation. Further studies are urgently needed to establish evidence-based guidelines for secukinumab use in PD patients.

Objective·To investigate the salivary metabolic characteristics of periodontitis patients with chronic renal failure(CRF)and analyze the role of phosphorus metabolites in this pathological process.Methods·A total of 45 patients treated at the Department of Nephrology and the Department of Periodontology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine were enrolled,including 15 patients with both periodontitis and CRF in the CRF group,15 with only periodontitis in the periodontitis(CP)group,and 15 in the healthy control(HC)group.All participants underwent unstimulated saliva collection and periodontal clinical examination.Periodontal clinical parameters were recorded,and renal function indicators of patients in the CRF group were documented.Untargeted metabolomic analysis of saliva samples was performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Principal component analysis(PCA)was used to analyze inter-group differences and screen differential metabolites.Significantly differential metabolites were further analyzed for pathway enrichment using the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.One major differential metabolite was selected for in vitro experiments to verify its effect on osteogenic differentiation of mouse embryonic preosteoblasts MC3T3-E1.Results·Probing depth(PD),clinical attachment loss(CAL),and plaque index(PI)in the CRF group were significantly higher than those in the CP group(all P<0.05).In the CRF group,urea level(r=0.41)and creatinine level(r=0.61)were positively correlated with PD,and creatinine level was also positively correlated with CAL(r=0.53).Estimated glomerular filtration rate(eGFR)was negatively correlated with PD(r=-0.69)and CAL(r=-0.56),respectively.PCA results showed significant differences in metabolite profiles among the three groups,with phosphoric acid presenting remarkable differences.KEGG analysis revealed that the enriched differential metabolites were mainly involved in protein digestion and absorption,neuroactive ligand-receptor interaction,sphingolipid metabolism,necroptosis,choline metabolism in cancer,ovarian steroidogenesis,sphingolipid signaling,and mineral absorption.In vitro experiments confirmed that 4 mmol/L phosphate ions downregulated the mRNA and protein expression levels of Runt-related transcription factor 2(Runx2),alkaline phosphatase(Alp),and osteocalcin(Ocn)in MC3T3-E1 cells(all P<0.05),thereby inhibiting osteogenic differentiation.Conclusion·Periodontal tissue destruction is more severe in periodontitis patients complicated with CRF than those without CRF.Upregulated salivary phosphorus concentration may be one of the mechanisms by which chronic kidney disease aggravates periodontal tissue destruction.Excessively high phosphorus concentration can inhibit osteogenic differentiation.

Renal allograft artery thrombosis (RAAT) is a severe vascular complication that typically occurs within the first month after transplantation and frequently results in graft loss. Although most cases are attributed to surgical or technical factors, we report a rare case of late-onset RAAT secondary to acute antibody-mediated rejection (ABMR), further complicated by severe drug-induced neutropenia. A 32-year-old female with end-stage renal disease underwent an ABO-compatible living-donor kidney transplantation, with an uneventful early postoperative course. On postoperative day (POD) 83, she presented with acute oliguria. Doppler ultrasonography revealed absent allograft arterial flow, confirming RAAT. Emergent thrombolysis restored macrovascular patency; however, renal function failed to recover, necessitating a return to hemodialysis. During readmission for peritoneal dialysis (PD) catheter placement, she developed life-threatening neutropenia, attributed to drug-induced myelosuppression, predominantly from mycophenolate mofetil with possible additive effects of ganciclovir and trimethoprim-sulfamethoxazole. Concurrently, markedly elevated donor-derived cell-free DNA (dd-cfDNA) levels (plasma 1.36

Chronic kidney disease(CKD)is a major global public health issue that significantly impacts patients' health and quality of life.Chronic kidney disease-mineral and bone disorder(CKD-MBD),a common complication of CKD,not only leads to systemic bone metabolic abnormalities but also causes local changes such as a decrease in alveolar bone mass.Its pathological mechanisms involve multiple aspects,including calcium-phosphorus metabolism imbalance,uremic toxin damage,inflammation and oxidative stress,nutritional and metabolic disorders,as well as hormonal and growth factor dysregulation.Renal dysfunction leads to hyperphosphatemia,hypocalcemia,and secondary hyperparathyroidism,disrupting the dynamic balance between bone formation and resorption.The accumulation of uremic toxins and inflammatory cytokines induces oxidative stress,thereby suppressing osteoblast differentiation while promoting osteoclast activation.Moreover,metabolic disturbances,including vitamin D deficiency and protein-energy wasting,along with hormonal and growth factor dysregulation,impair alveolar bone homeostasis and exacerbate bone disorders.When patients with CKD undergo alveolar surgeries,such as tooth extraction and dental implant placement,they face risks of bleeding,infection,and poor wound healing.Therefore,targeted perioperative management is necessary,including multidisciplinary collaboration with nephrologists to comprehensively assess renal and coagulation functions,appropriate surgical timing,the use of minimally invasive techniques,and enhanced infection prevention.This article reviews the characteristics,mechanisms,and clinical risks of CKD-related alveolar bone changes,providing reference for related mechanism exploration and oral diagnosis and treatment.

Peritoneal mesothelial cells (PMCs) are critical components of the peritoneum, and prolonged exposure to high glucose in peritoneal dialysis fluid can lead to structural and functional impairment of the peritoneal membrane. However, whether such cellular damage is caused by glucose itself or by the hyperosmotic environment remains controversial. To elucidate the mechanisms underlying high glucose-induced PMCs apoptosis, we obtain the first dynamic proteomic atlas of HMrSV5 cells under different concentration of glouse and mannitol stimulation. After excluding osmosis, 626 differentially expressed proteins are detected following high glucose stimulation. Notably, the up-regulated differentially expressed proteins are significantly enriched in the oxidative phosphorylation pathway, implicating mitochondrial dysfunction in the apoptotic process. Protein–protein interaction network analysis further reveals that NDUFV1, a core subunit of mitochondrial complex I, might be a key regulator. To validate clinical relevance, we perform a comparative proteomic analysis of peritoneal dialysis effluents from new and long-term peritoneal dialysis patients. The clinical proteomics data reveal a marked enrichment of oxidative phosphorylation in the early-stage of dialysis patients, coinciding with notably up-regulation of NDUFV1. Molecular biology experiments demonstrate that the up-regulation of NDUFV1 increases reactive oxygen species production, disrupted mitochondrial membrane potential, thereby promoting apoptosis. In summary, our findings indicate that glucose-based peritoneal dialysis primarily induces mitochondrial oxidative phosphorylation mediated apoptosis of PMCs through high glucose, with NDUFV1 serving as a critical mediator in this process. These results provide new insights into the prevention and treatment of peritoneal dialysis related peritoneal injury.

Introduction Periodontitis and chronic kidney disease (CKD) are inter-related conditions that can significantly impact patient health. This study aims to evaluate the efficacy of active non-surgical periodontal therapy (NSPT) combined with supportive periodontal care (SPC) in reducing tooth loss and improving masticatory function in patients with CKD and stage III periodontitis.Methods and analysis This randomised controlled trial will recruit 86 patients diagnosed with both stage III periodontitis and CKD. Participants will be randomly assigned at a 1:1 ratio to either an experimental group receiving active NSPT supplemented with SPC or a control group receiving oral hygiene instruction with scheduled periodontal monitoring. The intervention will last for 24 months, with assessments conducted at baseline and 3, 6, 12, 18 and 24 months. The primary outcome is the incidence of tooth loss due to periodontitis over the 2-year follow-up period. Secondary outcomes include the number of lost teeth, masticatory function, clinical periodontal parameters and oral health-related quality of life.Ethics and dissemination The study protocol and informed consent form were approved by the Institutional Ethics Committee of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SH9H-2022-T404-1). Findings will be disseminated to participants and published in peer-reviewed journals.Trial registration number ChiCTR2300068923.

BACKGROUND:Long-term peritoneal dialysis (PD) induces persistent inflammation and fibrosis of the peritoneal membrane (PM), altering the peritoneal solute transport rate (PSTR). We previously found elevated miR-503-5p levels in exosomes from PD effluent (PDE) in patients with high PSTR. As PSTR is strongly influenced by intraperitoneal inflammation, this study aimed to explore the relationship between miR-503-5p, inflammation, and peritoneal fibrosis and the underlying mechanisms. METHODS:Bioinformatics analyses were initially performed to identify the miR-503-5p target genes and determine the research subject. Real-time polymerase chain reaction (RT-PCR), miRNA RT-PCR, and western blotting were used to detect the expression levels of miR-503-5p and its targets in human MeT-5A mesothelial cells. A cell counting kit-8 assay was used to ascertain the impact of miR-503-5p on cellular proliferation, and cell cycle was evaluated using a FACScan flow cytometer. The miR-503-5p target genes were identified using mimic/inhibitor transfection and dual-luciferase reporter assays. The PDE exosomes (PDE-exos) labeled with PKH67 were used to observe their interactions with MeT-5A cells. RESULTS:Patients with PD who exhibited an increasing PSTR had notably elevated dialysate interleukin (IL)-6 concentrations, which demonstrated a positive correlation with the PSTR. The induction of lipopolysaccharides remarkably enhanced the expression of miR-503-5p and IL-6 in peritoneal mesothelial cells (PMCs). Overexpression of miR-503-5p induced cell cycle arrest in the G1/S phase and notably upregulated the expression of fibrotic indicators (alpha-smooth muscle actin and type I collagen) in PMCs. Cyclin D1 was a direct target of miR-503-5p and expressed in PMCs. Additionally, PKH67-labeled PDE-exos were internalized by PMCs. CONCLUSIONS:Patients with PD who had a high PSTR exhibited an elevated inflammatory state, and the presence of inflammatory factors stimulated the upregulation of miR-503-5p expression, which led to cell cycle arrest in PMCs and promoted peritoneal fibrosis development.

OBJECTIVE:The Chinese version of Dietary Sodium Restriction Questionnaire (DSRQ) was adapted to evaluate its reliability and validity for measuring adherence to a sodium-restricted diet in peritoneal dialysis (PD) patients. METHODS:Specific items related to peritoneal dialysis were added to create a PD version of the DSRQ (PD-DSRQ), which was administered to 135 patients undergoing PD. Item analysis was performed using the critical ratio and homogeneity tests. The reliability of the questionnaire was determined by assessing the internal consistency. Content validity was evaluated using the expert evaluation method, and construct validity was assessed via exploratory and confirmatory factor analyses. RESULTS:The item analysis revealed correlation coefficients (R-values) ranging from 0.311 to 0.745 for each item, with statistically significant differences between the high and low subgroups for all items. The Cronbach's α coefficients for the overall PD-DSRQ and the attitude, subjective norm, and perceived behavioral control subscales were 0.805, 0.892, 0.794, and 0.889, respectively. The item-level content validity index ranged from 0.83 to 1.00, and the scale-level content validity index/universal agreement was 0.9894. Exploratory factor analysis identified a three-factor structure consistent with the original DSRQ, except for Question 18. The three factors had eigenvalues of 5.302, 4.179, and 1.290, which explained 64.32% of the variance. The average variance extracted for each dimension was 0.5777, 0.5654, and 0.5259, and the composite reliability values were 0.8864, 0.7956, and 0.8802, respectively, demonstrating good convergent and discriminant validity. CONCLUSION:The PD-DSRQ encompasses general information and three dimensions: attitude, subjective norms, and perceived behavioral control. The questionnaire demonstrated strong reliability and validity, making it a reliable tool for assessing adherence to sodium-restricted diets in patients undergoing PD.

The slow-developing neurological disorder Alzheimer's disease (AD) has no recognized etiology. A bioinformatics investigation verified copper metabolism indicators for AD development. GEO contributed AD-related datasets GSE1297 and GSE5281. Differential expression analysis and WGCNA confirmed biomarker candidate genes. Each immune cell type in AD and control samples was scored using single sample gene set enrichment analysis. Receiver Operating Characteristic (ROC) analysis, short Time-series Expression Miner (STEM) grouping, and expression analysis between control and AD samples discovered copper metabolism indicators that impacted AD progression. We test clinical samples and cellular function to ensure study correctness. Biomarker-targeting miRNAs and lncRNAs were predicted by starBase. Trust website anticipated biomarker-targeting transcription factors. In the end, Cytoscape constructed the TF/miRNA-mRNA and lncRNA-miRNA networks. The DGIdb database predicted biomarker-targeted drugs. We identified 57 differentially expressed copper metabolism-related genes (DE-CMRGs). Next, fourteen copper metabolism indicators impacting AD progression were identified: CCK, ATP6V1E1, SYT1, LDHA, PAM, HPRT1, SCG5, ATP6V1D, GOT1, NFKBIA, SPHK1, MITF, BRCA1, and CD38. A TF/miRNA-mRNA regulation network was then established with two miRNAs (hsa-miR-34a-5p and 34c-5p), six TFs (NFKB1, RELA, MYC, HIF1A, JUN, and SP1), and four biomarkers. The DGIdb database contained 171 drugs targeting ten copper metabolism-relevant biomarkers (BRCA1, MITF, NFKBIA, CD38, CCK2, HPRT1, SPHK1, LDHA, SCG5, and SYT1). Copper metabolism biomarkers CCK, ATP6V1E1, SYT1, LDHA, PAM, HPRT1, SCG5, ATP6V1D, GOT1, NFKBIA, SPHK1, MITF, BRCA1, and CD38 alter AD progression, laying the groundwork for disease pathophysiology and novel AD diagnostic and treatment.

Neuroprotection is one of the core treatment strategies for brain injuries including traumatic brain injury (TBI). NR2B9c is a promising neuroprotective peptide but its clinical translation is limited because of poor brain penetrability. Exosomes are naturally occurring nanovesicles having therapeutic potential for TBI as well as an efficient drug delivery carrier to the brain. Here, we engineered exosomes with neuron targeting peptide rabies virus glycoprotein (RVG29) via bio-orthogonal click chemistry technique and loaded it with NR2B9c, developing RVG-ExoNR2B9c. RVG29 conjugated exosome had higher neuron targeting efficiency compared to naïve exosomes both in vivo and in vitro. RVG-ExoNR2B9c had great cytoprotective effect against oxygen glucose deprived Neuro2a cells. Intravenous administration of RVG-ExoNR2B9c significantly improved behavioral outcomes and reduced the lesion volume after TBI injury in a mice controlled cortical impact model. Due to their multifunctionality and significant efficacy, we anticipate that RVG-ExoNR2B9c have the potential to be translated both as therapeutic agent as well as cargo delivery system to the brain for the treatment of TBI.

OBJECTIVES:The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients. MATERIALS AND METHODS:Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro-CT. MC3T3-E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis-related factors were detected. RT-PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation. RESULTS:Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3-E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS. CONCLUSIONS:IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3-E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.

Objective·To survey the status quo of knowledge, attitude, belief and practice (KAP) of safe medication in the process of medication therapy management in dialysis patients, and analyze the related factors.Methods·This study was a cross-sectional study with the maintenance dialysis patients selected from the Department of Nephrology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from March 2019 to March 2021. The KAP scale for safe medication in patients with chronic kidney disease verified by reliability and validity tests was used to evaluate the status quo of safe medication, and their medication list and clinical characteristics were also investigated. The occurrence of medication-related problems (MRPs) was evaluated according to the Strand classification system. The related factors of KAP level of safe medication in the dialysis patients were analyzed by univariate analysis and multiple linear regression analysis.Results·A total of 187 maintenance dialysis patients were included, including 103 patients with maintenance hemodialysis (MHD) and 84 patients with continuous ambulatory peritoneal dialysis (CAPD). The mean age of them was (60.19±12.80) years, the mean dialysis duration was (44.31±36.90) months, and the mean numbers of comorbidities and medications were 6.37±2.17 and 7.48±2.66, respectively. In the dialysis patients, the mean score of KAP scale was (77.68±18.53) points. The mean scores of knowledge, attitude, and practice of safe medication were (24.96±8.92), (17.19±3.18), and (35.40±8.18) points, respectively. The univariate analysis results showed that there were significant differences of KAP scores for safe medication in the dialysis pattern, the educational level, the economic level and the occurrence of renal anemia in the maintenance dialysis patients (all P<0.05). In addition, the more comorbidities or medications for regulating calcium and phosphorus metabolism the patients had, or the more MRPs occurred, the lower KAP scores for safe medication the patients got (all P<0.05). Multiple linear regression results showed that the dialysis patients with CAPD (β=8.391, 95%CI 3.436‒13.347, P=0.001), with higher education (β=9.159, 95%CI 0.978‒17.339, P=0.028), with per capita monthly household income of over 6 000 yuan (β=8.309, 95%CI 1.891‒14.727, P=0.011), with less comorbidities (β=-1.582, 95%CI -2.783‒-0.382, P=0.010), and with less MRPs (β=-2.284, 95%CI -3.987‒-0.581, P=0.009) had higher KAP scores.Conclusion·The KAP level of safe medication in the patients with maintenance dialysis is low. The hemodialysis, low educational level, low economic level, high number of comorbidities, and high number of MRPs are risk factors for low level of KAP of safe medication in dialysis patients.

Abstract Objective The microinflammatory state can influence the occurrence of dialysis-related complications in dialysis patients. Chronic periodontitis (CP), in which plaque biofilm is considered to be the initiating factor, is a chronic infectious disease in the oral cavity. It is still uncertain whether CP affects the microinflammatory state in peritoneal dialysis (PD) and the occurrence of dialysis-related complications. The purpose of this study was to investigate the correlation between the periodontal index and clinical parameters in peritoneal dialysis patients with CP and dialysis-related complications, including peritoneal dialysis-associated peritonitis (PDAP) and cardiovascular and cerebrovascular events (CCEs). Methods This was a retrospective cohort study, and 76 patients undergoing PD were enrolled. Clinical parameters, the occurrence of PD-related complications and periodontitis-related indicators, including the gingival index (GI), plaque index (PLI), probing depth (PPD) and clinical attachment loss (CAL), were collected. Correlation analysis was used to explore the correlation between periodontal or clinical parameters and the occurrence of PD-related complications. Results All the patients had different degrees of periodontitis (mild 9.2%, moderate 72.4%, severe 18.4%); PPD was inversely related to serum albumin (r = − 0.235, p = 0.041); CAL has a positive correlation with serum C-reactive protein (rs = 0.242, p = 0.035); PLI was positively correlated with serum calcium (r = 0.314, p = 0.006). ANOVA, multivariate logistic regression analysis and Kaplan-Meier Survival curve suggested that CAL was a risk factor for the occurrence of PDAP. There was no correlation between periodontal parameters and CCEs or poor prognosis. Conclusion CP is universally present in PD patients, and the presentation of periodontitis influences the systemic inflammatory state in PD patients. CP is a risk factor for PDAP.

Disease-centered problem-based learning (PBL) integrated course inspires the thinking of medical students in the case scenario to stimulate students' motivation of active learning. In this paper, the study of diabetes cases was taken as an example. Through the design of PBL cases, the scenario was reconstructed and information was provided step by step, so as to induce the students to discuss and learn the related knowledge of glucose metabolism and understand the predisposing factors of diabetes. Furthermore, students' critical thinking could be inspired through the information of the misdiagnose and mistreatment to recognize the clinical presentation and inducement of diabetic ketoacidosis. This teaching model is conducive to the cultivation of medical students' questioning spirit and critical thinking, laying a foundation for the cultivation of innovative medical talents.

目的 探讨间充质干细胞来源外泌体(MSCs-Exo)对高糖致腹膜间皮损伤的影响.方法 将MET-5A细胞分成3组:正常对照组(不予处理)、高糖组(高糖处理)、共培养组(高糖和MSCs-Exo共培养),通过CCK-8法选用效果最明显的高糖浓度和MSCs-Exo浓度,各组分别处理24 h后收集细胞和上清液.CCK-8法测定各组细胞增殖活力,流式细胞技术检测细胞凋亡情况,qRT-PCR检测细胞因子IL-6、TNF-α的表达,ELISA检测培养上清液中IL-6的水平.结果 高糖组细胞的增殖能力明显低于正常对照组(P<0.001),细胞凋亡率、IL-6和TNF-α的表达显著高于正常对照组(P<0.001);与高糖组相比,共培养组细胞增殖能力提高(P<0.001),细胞凋亡率、IL-6和TNF-α 的表达则明显下调(P<0.05).结论 高糖对腹膜间皮细胞有明显的促凋亡和促炎作用,MSCs-Exo可以促进腹膜间皮细胞的增殖,抑制高糖刺激下细胞凋亡的发生和炎症因子的表达.

Background Extracellular vesicles (EVs) from peritoneal dialysis effluent (PDE), containing molecules such as proteins and microRNAs (miRNAs), may be potential biological markers to monitor peritoneal function or injury. Peritoneal inflammation is an important determinant of peritoneal solute transport rate (PSTR). Thus, the aim of this study is to determine whether the specific proteins capable of evaluating the PSTR could be found in PDE-EVs, and explore the underlying mechanism for the association between PSTR and peritoneal inflammation. Methods Sixty patients undergoing peritoneal dialysis (PD) were divided into two groups: high/high average transport (H/A) group (PET >0.65) and low/low average transport (L/A) group (PET <0.65). EVs derived from PDE (PDE-EVs) were isolated by ultracentrifugation. Proteomic analysis was performed to explore the differentially expressed proteins and identify the potential biomarkers in PDE-EVs from the two groups, and we focused on glycoprotein 96 (GP96) as it could be involved in the inflammatory process. The expression of GP96 in PDE-EVs and inflammatory cytokines was quantified by real-time PCR and enzyme-linked immunosorbent assay. The infiltration of macrophages and neutrophils into the peritoneum was detected using immunohistochemistry in a PD rat model. Results The expression of PDE-EVs-GP96 was significantly higher in the H/A group, and was positively correlated with the PSTR and the level of the inflammatory factor interleukin (IL)-6. GP96-enriched EVs enhanced the secretion of proinflammatory cytokines IL-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8 in macrophages, which was reversed by a pharmacological GP96-specific inhibitor (PU-WS13). The GP96 inhibitor also reduced local peritoneal inflammation by decreasing the infiltration of inflammatory cells and levels of proinflammatory cytokines (IL-6 and TNF-α) and chemokines (CCL2, CXCL1, and CXCL2) in a PD rat model. Conclusions PDE-EVs-GP96 is a new promising tool to evaluate the status of peritoneal inflammation and PSTR, and the mechanism may be related to affecting the inflammatory properties of macrophages.

Background: Ultrafiltration (UF) volume and peritoneal solute transport rate (PSTR) are common parameters used to evaluate the efficacy of peritoneal dialysis (PD) on individual patients. It is unclear whether the level of exosomal microRNA (miRNA) in peritoneal dialysis effluent (PDE) can predict UF or PSTR. This study was designed to investigate if there is a correlation between PDE exosomal miRNA (miR432-5p) levels and various UF volumes and PSTRs in PD patients. It also aimed to explore the underlying mechanism of water and dialytic sodium removal (DSR). Methods: The PSTR was quantified using the 4-hour (4 h) 3.86% dialysate to plasma creatinine ratio. The PDE exosomes (PDE-exo) were isolated by ultracentrifugation. An miRNA assay was used to identify the different miRNA in the PDE-exo of patients in a high (H; PSTR 0.65, n=5) and low (L; PSTR <0.65, n=5) group. We focused on miR-432-5p as bioinformatic analysis had shown that it could be involved in sodium transport. We used mimic/inhibitor transfection and dual luciferase reporter assay to verify the target genes of miR-432-5p. We used PKH-67 stained PDE-exo to observe their interaction with human MeT-5A mesothelial cells. Results: Our results showed that the PDE-exo-miR-432-5p level was higher in group H than in group L. The levels of PDE-exo-miR-432-5p were positively correlated with PSTR (r=0.391; P<0.05; n=40) and negatively correlated with the 4 h UF volume (r=-0.376; P<0.05; n=40) and 4 h DSR (r=-0.535; P<0.01; n=24). Epithelial sodium channel alpha subunit (alpha-ENaC) was revealed as a direct target gene of miR-432-5p and expressed on both human peritoneum and MeT-5A cells. Furthermore, we found the PKH67 labeled-PDEexo could be internalized into MeT-5A cells. Conclusions: A high PDE-exo-miR-432-5p level was associated with poor UF volume and DSR. It may be that PDE-exo-miR-432-5p affects DSR through downregulating alpha-ENaC expression.

目的:探讨Mini-CEX在肾病学科实习带教中的实践与效果评价.方法:以进入肾脏内科实习的2015级临床及口腔医学生为研究对象.利用Mini-CEX评估系统,以实习前后作自身对照,比较出科考成绩以及师生对教学满意度等情况.结果:与入科时比,实习医生出科前的Mini-CEX得分在自我介绍、询问病史等8个方面均有提高(P<0.001),带教老师对使用Mini-CEX的满意度显著升高(P<0.001),而对于应用Min-CEX来指导临床带教内容具有针对性方面,临床带教老师和实习医学生的满意度均高于90％.结论:在肾脏病学实习带教中,利用Mini-CEX来指导带教可以提高教学质量,并有助于改善教学满意度.