Diabetic nephropathy (DN) is a prevalent and devastating complication of diabetes mellitus and is characterized by tubular atrophy, interstitial fibrosis, lipid metabolism dysregulation, and oxidative stress. Mesenchymal stem cell-derived exosomes (MSCs-Exo) have demonstrated promise in attenuating these DN-associated pathologies through multiple mechanisms. However, microRNAs (e.g., miR-21) encapsulated within MSCs-Exo may also have deleterious effects on DN through discrete molecular pathways, and the underlying mechanisms remain unclear. This study aimed to elucidate the role of the miR-21/p53 signaling axis in the MSC-Exo-mediated modulation of DN progression and to define the dual role of miR-21 in both therapeutic and pathogenic contexts. DN models were established in vitro using high-glucose–treated HK2 cells and in vivo using C57BL/KsJ db/db mice. The effects of MSCs-Exo, an miR-21 mimic, and the p53 activator C16 on cell proliferation, lipid metabolism, fibrosis, and oxidative stress were evaluated. The outcomes were quantified using transmission electron microscopy, qRT‒PCR, Western blotting, ROS fluorescence, hematoxylin and eosin (HE) staining, periodic acid–Schiff (PAS) staining, and Masson’s trichrome staining. MSCs-Exo significantly restored the proliferation of high-glucose–treated HK2 cells and concomitantly downregulated the expression of miR-21 and p53 and the dysregulation of lipid metabolism, oxidative stress, and fibrosis. In vivo, MSCs-Exo improved glycemic control, lipid profiles, and renal function in diabetic mice but also attenuated tubular atrophy and collagen deposition. However, miR-21–enriched MSCs-Exo markedly activated p53 signaling, exacerbating ferroptosis, lipid accumulation, and fibrosis. Further pharmacologic activation of p53 with C16 worsened these pathological changes, confirming the central role of p53 in miR-21-mediated pathogenic effects. The MSC-Exo/miR-21/p53 signaling axis plays a critical role in attenuating DN progression. Nonetheless, elevated miR-21 levels in MSCs-Exo activate the p53 pathway and drive ferroptosis, lipid accumulation, and fibrosis, thereby exerting pronounced pathogenic effects. Regulating miR-21 loading in MSCs-Exo may be a key strategy for optimizing their therapeutic efficacy in DN.

Background: Chronic kidney disease (CKD) is very common now and associates with high overall and cardio-vascular mortality. Numerous studies have reported that Heart rate variability (HRV) could also be used to detect cardiovascular autonomic dysfunction (CAD). We investigated the association of electrochemical skin conduc-tance (ESC) of EZSCAN results with HRV in non-dialysis CKD patients.Methods: In a cross-sectional study, we enrolled 248 prevalent non-dialysis CKD patients. Patients underwent a 24-h Holter (CB-2302-A, Bio Instrument, China). A time domain analysis of HRV was performed, and the following parameters were obtained: SDNN, SDANN, rMSSD, pNN50. EZSCAN device (Impeto Medical, Paris, France) measures ESC values of each participants. Mean global skin conductance computed as 0.5 * (reflecting (right + left hand)/2 + (right and left foot)/2). Log transforms data into a normal distribution for statistical analysis.Results: There were 142 males and 106 females included in the present study. Patients' age was 56.6 +/- 17.08 years. Logarithm(Log) (global ESC) was independently predicted by age (P<0.01), hypertension history, esti-mated Glomerular filtration rate (eGFR) and log SDNN (P<0.05). While log SDANN, rMSSD and pNN50 were not independent predictors for log (global ESC).Conclusion: Increased global ESC significantly associated with elevated HRV, specifically SDNN in non-dialysis CKD patients. This suggested that global ESC may appear to be an important predictor of CAD, and even could be used as a cardiovascular risk factor in non-dialysis CKD patients.

Background: Diabetic microvascular complications, including diabetic kidney disease (DKD), retinopathy (DR), and neuropathy (DN), were major causes of morbidity and mortality in diabetic patients worldwide. It has been suggested that urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were not the only indicators of renal function impairment in DKD and that they were also associated with diabetic peripheral neuropathy (DPN) which might affect nerve conduction velocity (NCV). As 30-40% of DPN patients had no subjective symptoms, while current perception threshold (CPT) could detect sensory nerve damage at an early stage. As a result, we aimed to investigate correlation between UACR, eGFR and CPT in DKD patients. Methods: A total of 273 DKD patients from the First Affiliated Hospital of Kunming Medical University from January 2018 to June 2020 were enrolled to complete the CPT test. CPT values of the bilateral median nerve and superficial and deep peroneal nerves at 2000 Hz, 250 Hz, and 5 Hz were collected. Results: In normoesthesia and hypaesthesia patients with DKD, MDRD-eGFR correlated negatively with TC (r =-0.135, P = 0.037), left superficial peroneal and deep peroneal nerve 2000 Hz CPT (r =-0.205, P = 0.001) and right superficial peroneal and deep peroneal nerve 2000 Hz CPT (r =-0.154, P = 0.017). Besides, left and right superficial peroneal and deep peroneal nerve 2000 Hz CPT correlated with CKD-EPI-eGFR and UACR. Multivariate logistic regression analysis found left superficial peroneal and deep peroneal nerve 2000 Hz CPT was independently associated with both MDRD-eGFR and CKD-EPI-eGFR. Conclusion: Decreased MDRD-eGFR and CKD-EPI-eGFR were expected to be a predictor of peripheral nerve injury in normoesthesia and hypaesthesia patients with DKD.

目的 探讨磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/生存素(Survivin)信号通路在腹膜间皮细胞上皮-间充质转分化(EMT)中的作用.方法 20只雄性SD大鼠随机分为模型组和对照组,模型组每天给予42.5 g/L葡萄糖腹膜透析液(100 mL/kg)腹腔注射建立大鼠腹膜间皮细胞EMT模型,对照组在相同条件下予等量的生理盐水腹腔注射.两组大鼠于4周末次腹膜透析后,留取腹膜组织,采用HE和Masson染色,观察腹膜组织形态学变化并测量腹膜组织厚度,采用实时定量PCR、Western印迹和免疫组化等方法检测腹膜组织p-AKT、AKT、Survivin的表达及EMT相关蛋白和mRNA的表达[紧密连接蛋白(ZO-1)、神经-钙黏素(N-cadherin)].结果 成功建立大鼠腹膜间皮细胞EMT模型,与对照组相比,模型组小鼠腹膜组织明显增厚,上皮细胞标志物ZO-1 mRNA及蛋白表达降低,间充质细胞标志物N-cadherin mRNA及蛋白表达升高,p-AKT、Survivin蛋白也明显升高(P<0.05),AKT蛋白表达无明显变化(P>0.05).结论 PI3K/AKT/Survivin信号通路参与腹膜间皮细胞EMT的发生与发展.

在经济全球化的背景下,培养留学生成为很多国家培养人才、实现国际间交流的重要方式.本文主要探讨国内现有的留学生教学方法及其在肾脏内科临床教学中的应用,探讨不同教学方式对课堂教学效果的影响,选择最有益于教学效果的教学方式,以实现MBBS项目的进步与发展.

Chronic kidney disease (CKD) is very common now and is associated with high overall and cardiovascular mortality. Numerous studies have reported that elevated heart rate (HR) is a risk factor for cardiovascular mortality. We investigated the link between serum endocan and circadian heart rate variability in non-dialysis stage 5 CKD patients.