Dent disease is a rare X-linked recessive renal tubular disease characterized by low molecular weight proteinuria，hypercalcemia and nephrocalcinosis. It is also a major cause of tubular proteinuria in children. According to different causative genes，Dent disease can be divided into three types：type 1 is caused by mutations in the CLCN5 gene，accounting for about 60%-70%；type 2 is caused by mutations in the OCRL gene，accounting for about 15%-20%；type 3 has a similar clinical phenotype but no known pathogenic gene mutations. CLCN5 encodes the voltage-dependent 2Cl -/1H +exchange channel CIC-5，which is involved in proximal renal tubule endocytosis. Its mutations can cause a variety of proximal tubular dysfunction symptoms，mainly including low molecular weight proteinuria. The use of gene detection technology has resulted in an increase in reports on Dent disease year after year. At present，the specific mechanism underlying Dent disease remains unknown. This article reviews the research progress of CLCN5，hoping to provide new insight for the mechanism research of CLCN5 and the specific treatment of Dent disease type 1.

Objective: To explore the relationship between coronary tortuosity and coronary microvascular disease (CMVD). Methods: Patients with typical angina symptoms and without serious coronary artery stenosis by coronary angiography were enrolled from June 2014 to December 2016, and CMVD was diagnosed by single photon emission tomography (SPECT). According to the SPECT results, patients were divided to the CMVD group and non-CMVD group. The baseline clinical characteristics, results of coronary angiography were compared between the two groups. The logistic analysis was used to analyze the relationship between coronary tortuosity and CMVD. Result: A total of 117 cases were enrolled, with 69 cases in the CMVD group and 48 cases in the non-CMVD group. No differences were found in gender distribution, age, hypertension, lipid abnormality, hyperuricemia and uses of statins between the two groups (all P>0.05). Incidence of diabetes (78.26%(54/69) vs. 35.42% (17/48) , P<0.05), hs-CRP ((4.29±2.15)mmol/L vs. (2.63±1.20)mmol/L, P<0.001), LDL-C ((2.98±0.96)mmol/L vs. (2.52±0.83)mmol/L, P=0.008) and homocysteine ((13.7±5.61)mmol/L vs. (11.5±4.38)mmol/L, P=0.025) levels were higher in the CMVD group than in the non-CMVD group. The data derived from echocardiographic examination were similar between the two groups. The Corrected TIMI frame counts were higher in the CMVD group than in non-CMVD group (LAD: 31.56±4.92 vs. 27.31±3.75, LCX: 29.47±4.18 vs. 26.62±3.19, RCA: 29.09±5.05 vs. 26.24±3.28, all P<0.001). The incidences of coronary atherosclerosis (76.81% (53/69) vs. 27.08% (13/48) , P<0.001) and coronary tortuosity ( (60.87% (42/69) vs. 33.33% (16/48) , P=0.035) were also higher in the CMVD group than in non-CMVD group. Logistic analysis found that coronary tortuosity (OR=6.111, 95%CI 2.707-13.794, P<0.001), diabetes (OR=6.565, 95%CI 2.883-14.948, P<0.001) and coronary atherosclerosis (OR=8.918, 95%CI 3.822-20.808, P<0.001) were independent risk factors of CMVD. Conclusion Coronary tortuosity, diabetes and coronary atherosclerosis are related to CMVD in this patient cohort.

Objective To explore the short and long term curative effects of percutaneous transhepatic cholangioscopic lithotomy (PTCSL) in the treatment of intrahepatic stone (IHS).Methods 38 IHS patients were enrolled,who were treated with PTCSL between January 2008 and July 2013.Results PTCSL was successfully completed in all the 38 IHS cases.Stone clearance rate was 84.2％ and the average episode of stone removal was (2.6 ± 0.9) times.Average diameter of percutaneous transhepatic fistula was (18.4 ± 0.6) F and the average time from percutaneous transhepatic puncture and fistulization to cholangioscopic lithotomy was (7.2 ± 0.7)d.The average operation time was (68 ± 20) min,intraoperative blood loss was (20 ± 13) ml,and hospitalization was (4 ± 2) days.The hepatolith recurrence rate in patients with stones completely removed was 37.5％ (12/32),and 1 case developed into biliary cirrhosis.Patients with calculi residual suffered from higher hepatolith recurrence rate of 83.8％ (5/6),with biliary cirrhosis found in 1 case.Conclusions PTCSL is safe and effective in treating primary IHS,which is indicated in multiple recurrent IHS especially in after biliary surgery patients.It has the advantages of minimally invasion,less bleeding,less postoperative pain,less complications,and fast postoperative recovery.

Objective To explore the expression change of intestinal epithelial tight junction (IJ)protein claudin-1 in mice with fulminant hepatic failure (FHF).Methods FHF was induced with a method that combined intraperitoneal injection of lipopolysaccharide (LPS,10 mg/kg) and D-galactosamine (GalN,800 mg/kg).Control saline (2 ml/kg,ip),LPS (10 mg/kg,ip) and GaIN (800 mg/kg,ip) were also detected.The effect of administration of anti-tumor necrosis factor alpha (TNF-α) IgG antibody (anti-TNF-α IgG,100 μg/per) on the level of TNF-α was assessed before administration of D-galactosamine/lipopolysaccharide.At the 2nd h,6th h,9th h,12th h,24th h after injection in FHF group,the 9th h after injection in control groups and 9th h after injection in anti-TNF-α IgG group,the mice were killed for the collection of large intestine specimens.Claudin-1 was analyzed with immunohistochemistry,Western blotting,and real-time quantitative PCR.Results Tight junction protein claudin-1 was localized along the apical region of the lateral plasma membrane representing the region of tight junctions in surface and crypt epithelial cells.Weakly distributed density of claudin-1 in intestinal mucosa was found in mice with FHF from the 9th h after injection.Compared to saline group,Western blotting analysis demonstrated markedly reduced claudin-1 expression in mice with FHF at the 6th h and 9th h after injection (6th h:0.8600±0.0208 vs 1.0,P ＜0.05; 9th h:0.6633 ±0.0328 vs 1.0,P ＜0.01).Furthermore,the expression of claudin-1 mRNA was markedly reduced at the 6th h,9th h,and 12th h after injection in mice with FHF (6th h:0.3067 ±0.1291 vs 1.0,P ＜0.05; 9th h:0.2233 ±0.1155 vs 1.0,P ＜0.01 ; 12th h:0.5275 ±0.1222 vs 1.0,P ＜0.05).Compared to saline group,no significant difference in claudin-1 expression was found with prophylactic treatment with anti-TNF-α-IgG antibody in mice with FHF at the 9th h after injection (protein:0.9533 ±0.0186 vs 1.0,P ＞0.05; mRNA:0.85 ±0.1437 vs 1.0,P ＞0.05).Conclusions The expression of tight junction protein claudin-1 was reduced at both protein and mRNA levels in intestinal epithelial cells that were induced by TNF-α in mice model of FHF.

Objective To evaluate the relationship between apoE gene polymorphisms and gallstone. Methods We included all the published studies on the association between apoE gene polymorphisms and gall-stone. A meta-analysis was employed to summarize all these studies, calculate the pooled OR and its 95% confidence interval (95% CI) , and test the overall effects. The Egger's publication bias analysis and sensitivity analysis were carried out to evaluate the reliability and stability of the meta-analysis. Results Eleven association studies between the apoE gene polymorphisms and gallstone fulfilled our inclusion criteria. There were 1248 patients with gallstones and 1660 controls. Remarkable heterogeneities were discovered in the allele ε4 and genotype E3/E4 of apoE between gallstone and control subjects in these studies (P<0. 05). Their ORs and 95%CIs were 1.32 (1.01, 1. 71), 1. 60 (1. 04, 2. 46), respectively (P<0. 05). The results of sensitivity analysis and publication bias analysis showed the reliability and stability of this meta-analysis. Conclusion apoE gene polymorphisms are associated with gallstone. Those with the alleleε4 or genotype E3 /E4 had a higher risk of suffering from gallstone.