Spectrum of variants in a large Chinese Gitelman syndrome cohort.

Gitelman syndrome (GS) is caused by SLC12A3 biallelic variants. A previous study showed that large rearrangements (LRGs) of SLC12A3 accounted for the low sensitivity of genetic testing. However, a systematic screening for LRGs in Chinese GS patients is lacking. Massively parallel sequencing (MPS) and multiplex ligation-dependent probe amplification (MLPA) were performed to sequence the genomic DNA of patients with clinically diagnosed GS. Of 165 index cases, MPS identified 151 cases with two or more affected alleles and 14 cases with one variant allele. LRGs were detected by MLPA in 20 out of 27 cases, including 15 cases with suspected LRGs by MPS. Among these 20 cases with LRGs, the results of MPS and MLPA were identical in only 8 cases. Additional LRGs in 6 cases were detected by MLPA alone. In 6 cases, E4_E6del was identified by MPS, while E4_E5del and Intron6del were identified by MLPA. Among the 102 distinct variants, 30 are novel. LRGs were found in 20 cases (12.1%). LRGs were found in 12.1% of our Chinese GS patients cohort. We show that MPS and MLPA are two complementary techniques with the ability to improve the diagnostic yield of GS.

Flipped classroom combined with case-based learning is an effective teaching modality in nephrology clerkship.

BACKGROUND: The flipped classroom (FC) is recognized as an effective teaching approaches by emphasizing on the development of high-order abilities; however, the implementation of FC has not been well explored in nephrology education. The present study aims to investigate the efficacy of FC in teaching nephrology via comparing with the traditional lecture-based teaching (LBT). METHODS: Sixty-two medical clerkship students at Zhejiang University School of Medicine were equally allocated into either LBT or FC group demographically matched. The glomerular diseases module was chosen for the teaching content. Students from the FC group were required to study the pre-class materials in annotated PPT format in advance. In the class, case-based learning (CBL) was employed, students encountered the related clinical cases and participated in the face-to -face discussion. Students from the LBT group attended a didactic lecture during the class. Quiz and questionnaires were performed to assess the efficacy of FC versus LBT. RESULTS: Participants from the FC group performed better in the quiz than those from the LBT group with higher total scores (78.06 ± 2.515 vs. 65.16 ± 3.209, mean ± SEM), particularly the scores of the case analysis-related questions (35.81 ± 1.657 vs. 27.42 ± 1.910, mean ± SEM). In the survey, more students considered FC beneficial to comprehension, critical thinking, patient management and team work as compared with LBT. Meanwhile, more participants agreed increased in-class pressure in FC than in LBT. CONCLUSIONS: This study shows the positive impact of FC combined with CBL approach on nephrology education and provides an alternative pre-class and in-class format for the FC implementation.

Curcumin attenuates cyclosporine A­induced renal fibrosis by inhibiting hypermethylation of the klotho promoter.

Chronic kidney disease is increasingly considered to be a worldwide public health problem and usually leads to renal fibrosis. In the present study, curcumin, a polyphenol pigment extracted from turmeric, was demonstrated to exert protective effects on renal fibrosis via the suppression of transforming growth factor­ß (TGF­ß) downstream signaling, such as plasminogen activator inhibitor­1 (PAI­1), α­smooth muscle actin (α­SMA) and collagen I (Col I) downregulation. The present findings demonstrate that curcumin exerted a protective effect on cyclosporine A­induced renal fibrosis via a klotho (KL)­dependent mechanism, which inhibits the TGF­ß signaling pathway. Further research indicated that curcumin induced KL expression in HK­2 tubular epithelial cells by inhibiting CpG hypermethylation in the KL promoter, which mediates the loss of expression in cells. Methylation­specific polymerase chain reaction (PCR) combined with bisulfite sequencing identified numerous key CpG sites, such as 249, 240 and 236, whose methylation statuses are important for KL expression. A PCR reporter assay was utilized to further confirm these findings. In addition, the effects of curcumin on the regulation of DNA methyltransferase 1 (Dnmt1) expression were evaluated, and the data suggest that curcumin inhibits Dnmt1 expression and restricts CpG hypermethylation. Thus, the current study reveals that curcumin attenuated renal fibrosis by suppressing CpG methylation in the KL promoter, thus inducing KL expression, which inhibited TGF­ß signaling, which may provide a novel therapeutic approach for the treatment of renal fibrosis.

Moxibustion Therapy at CV4 Prevents Postoperative Dysuria after Procedure for Prolapse and Hemorrhoids.

Objective. To explore the intervention methods of the patients with dysuria after performing the procedure for prolapse and hemorrhoids (PPH). Methods. 100 cases with hemorrhoids were randomly divided into experimental and control groups. The control group received routine nursing care. As comparison, the experimental group, on the basis of conventional care, was treated with moxa roll moxibustion 1 hour after the operation for 30 minutes. The autonomous urination within 1 h, 2 h, 4 h, 6 h, and 8 h after operation and the catheterization rate 8 h after operation of two groups of patients were observed. Results. The median time of autonomous urination of control group (8 h) was significantly greater than that of the experimental group (6 h) (P < 0.001). Cox regression analysis showed that the moxibustion therapy was positively correlated with automatic micturition in the patients after PPH. The probability of automatic micturition in the experimental group was 2.032 times that in the control group (RR = 2.032, 95% CI: 1.278~3.230). The catheterization rate of control group (38%) was significantly higher than that of the experimental group (10%) (P < 0.001). Conclusion. The Guanyuan acupoint moxibustion can prevent dysuria after PPH and reduce the urethral catheterization.