INTRODUCTION:To assess the relationship between the rate of residual renal function (RRF) decline in the first year and all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients.METHODS:Incident PD patients were divided into two groups by the corresponding RRF decline value, when hazard ratio (HR) = 1 was found by the restricted cubic spline. The associations of rate of decline of RRF in the first year with mortality were evaluated.RESULTS:Of 497 PD patients, 122 patients died. After adjusting for confounding factors, patients in fast-decline group had a significant increase risk of all-cause and cardiovascular mortality (HR: 1.97 and 2.09, respectively). Each 0.1-mL/min/1.73 m2 /month decrease in RRF in the first year of PD was associated with a 19% and 20% higher risk of all-cause and cardiovascular mortality, respectively.CONCLUSIONS:Faster decline of RRF in the first year was independently associated with all-cause and cardiovascular mortality in PD patients.
ABSTRACT Purpose: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice. Methods: PCCL was orally administered at a dose of 20 mg·kg–1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg–1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1β levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2. Results: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression. Conclusions: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.
Diabetic nephropathy (DN), a vascular complication of diabetes mellitus, is the leading cause of death in diabetic patients. The contribution of aberrantly expressed circRNAs to diabetic nephropathy in vivo is poorly understood. Integrated comparative circRNA microarray profiling was used to examine the expression of circRNAs in diabetic kidney of db/db mice. We found that circRNA_010383 expression was markedly downregulated in diabetic kidneys, mesangial cells and tubular epithelial cells cultured in high-glucose conditions. circRNA_010383 colocalized with microRNA-135a (miR-135a) and inhibited miR-135a function by directly binding to miR-135a. In vitro, the knockdown of circRNA_010383 promoted the accumulation of extracellular matrix (ECM) proteins and downregulated the expression of transient receptor potential cation channel, subfamily C, member (TRPC1), which is a target protein of miR-135a. Furthermore, circRNA_010383 overexpression effectively inhibited the high-glucose-induced accumulation of ECM and increased TRPC1 levels in vitro More importantly, the kidney-target of circRNA_010383 overexpression inhibited proteinuria and renal fibrosis in db/db mice. Mechanistically, we identified that a loss of circRNA_010383 promoted proteinuria and renal fibrosis in DN by acting as a sponge for miRNA-135a. This study reveals that circRNA_010383 may be a novel therapeutic target for DN in the future.
目的 观察不同中医证型晚期肺鳞癌化疗疗效及其中医干预临床疗效.方法 入选经确诊的初治晚期肺鳞癌患者,设单纯化疗组(A组):气阴两虚型化疗组(A1组)、瘀阻肺络型化疗组(A2组);化疗联合中医干预组(B组):化疗联合补中益气汤合沙参麦冬汤治疗组(B1组);化疗联合血府逐瘀汤治疗(B2组);给予GP方案化疗.从治疗肿瘤效果、生存质量、药物毒性反应、中医症状评分4个方面评价临床疗效.结果 单纯化疗组比较:A2组较A1组有效率明显更高、不良反应发生率更低、中医临床评分明显更低(P<0.05).化疗联合中医干预组与单纯化疗组比较:与A组相比,B组生存质量提高率及提高稳定率明显高更高,不良反应发生率更低,中医症状评分明显更低(P<0.05).结论 瘀阻肺络型肺鳞癌患者对GP化疗方案的疗效明显好于气阴两虚型.中医经辨证论治干预,能显著提高患者生存质量、减少不良反应,改善症状.
Background Albumin-globulin ratio (AGR), a variable based on serum albumin and non-albumin proteins, has been demonstrated as a predictor of mortality in patients with malignant neoplasm. The aim of this study was to evaluate the prognostic value of AGR on peritoneal dialysis (PD) patients. Methods We retrospectively analyzed 602 incident PD patients from January 1st, 2008, to December 31st, 2017, at our center and followed them until December 31st, 2018. Kaplan-Meier curves and multivariate Cox regression models were applied to analyze the association between AGR and all-cause of mortality and cardiovascular mortality. Results The median follow-up time was 32.17 (interquartile range = 32.80) months. During follow-up, 131 (21.8%) patients died, including 57 patients (43.5%) who died due to cardiovascular diseases. Kaplan-Meier curves showed that patients with AGR > 1.26 had better rates of survival than those with AGR ≤ 1.25 ( p < 0.001). After adjusting for potential confounders, the lower AGR level was significantly associated with an increased all-cause and cardiovascular mortality [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.07–2.32, p = 0.022 and HR: 2.01, 95% CI: 1.10–3.69, p = 0.023 respectively]. Conclusions Patients with a low AGR level had an increased all-cause and cardiovascular mortality. AGR may be a useful index in identifying patients on PD at risk for CVD and all-cause of mortality.
目的 探讨缺血性脑卒中和非脑卒中病人颈动脉内中膜厚度与狭窄程度的关系.方法 选取应急总医院收治的缺血性脑卒中病人300例作为缺血性卒中组,选取同期非脑卒中病人245例作为对照组,应用彩色多普勒超声检查评估内中膜厚度定量测量(QIMT)、血管硬度指数β值、血管扩张性系数(DC)、血管顺应性系数(CC)、附壁斑块及颈动脉狭窄程度.结果 缺血性卒中组QIMT和血管硬度指数β值高于对照组,DC、CC值低于对照组,差异有统计学意义(P<0.01);缺血性卒中组的附壁斑块及颈动脉狭窄率均高于对照组,且对照组大多数为轻度狭窄,而缺血性卒中组狭窄程度覆盖所有狭窄分级,且中重度狭窄比例更高.结论 颈动脉内中膜厚度及狭窄程度与缺血性脑卒中的发生发展有密切关系,早期进行彩色多普勒检测对提高脑卒中病人的诊治水平有重要临床意义.
目的 观察脂必泰胶囊治疗动脉粥样硬化性脑梗死恢复期的临床疗效.方法 将符合标准的84例动脉粥样硬化性脑梗死恢复期病人随机分为观察组与对照组,各42例.对照组予以阿司匹林、阿托伐他汀等治疗,观察组在对照组基础上加用脂必泰胶囊治疗,两组均治疗14d.观察并比较两组血脂水平、临床疗效、美国国立卫生研究院卒中量表(NIHSS)评分、治疗前后中医证候积分改善情况.结果 治疗前,两组血脂各项比较,差异无统计学意义(P>0.05);治疗后,两组总胆固醇、三酰甘油、低密度脂蛋白胆固醇水平与治疗前比较,差异有统计学意义(P<0.01),且观察组总胆固醇、三酰甘油、低密度脂蛋白胆固醇水平明显低于对照组(P<0.05或P<0.01),高密度脂蛋白胆固醇明显高于对照组(P<0.05).治疗前,两组NIHSS评分比较,差异无统计学意义(P>0.05);治疗后,两组NIHSS评分较治疗前降低,差异有统计学意义(P<0.01),且观察组低于对照组(P<0.05).治疗后,观察组总有效率高于对照组(78.13%与53.13%,x2=4.433,P=0.035).治疗前,两组中医证候积分比较,差异无统计学意义(P>0.05);治疗后,两组中医证候积分明显降低,差异有统计学意义(P<0.01),且观察组低于对照组(f =5.153,P=0.000).结论 脂必泰胶囊联合常规西药治疗动脉粥样硬化性脑梗死恢复期,可调节病人血脂,并改善中医症状.
Transforming growth factor (TGF)-β/Smad signalling plays a central role in the pathogenesis of peritoneal fibrosis related to peritoneal dialysis (PD). Parthenolide (PTL), a naturally occurring phytochemical, is isolated from the shoots of feverfew (Tanacetum parthenium) and displays analgesia, anti-inflammation and anticancer activities. In this study, we examined the therapeutic potential of PTL on PD-related peritoneal fibrosis induced by daily intraperitoneal injection of 4.25% dextrose-containing PD fluid (PDF) in vivo and TGF-β1-induced epithelial-mesenchymal transition (EMT) in vitro. PTL was administered daily before PDF injection or after 14 days of PDF injection. Both PTL treatments showed a protective effect on peritoneal fibrosis and prevented peritoneal dysfunction. Similarly, PTL suppressed the expression of fibrotic markers (fibronectin and collagen I) and restored the expression of the epithelial marker (E-cadherin) in TGF-β1-treated HMrSV5 cells. Furthermore, PTL inhibited TGF-β1-induced Smad2 and Smad3 phosphorylation and nuclear translocation but did not influence Smad1/5/9 phosphorylation or activate other downstream signalling pathways of TGF-β1, including AKT, extracellular signal-regulated kinase (ERK) or p38. In conclusion, PTL treatment may represent an effective and novel therapy for PD-associated peritoneal fibrosis by suppressing the TGF-β/Smad pathway.
Peritoneal fibrosis is a common complication of long-term peritoneal dialysis (PD) and the principal cause of ultrafiltration failure during PD. The initial and reversible step in PD-associated peritoneal fibrosis is the epithelial-mesenchymal transition (EMT). Although the mechanisms in the EMT have been the focus of many studies, only limited information is currently available concerning microRNA (miRNA) regulation in peritoneal fibrosis. In this study, we aimed to characterize the roles of microRNA-145 (miR-145) and fibroblast growth factor 10 (FGF10) in peritoneal fibrosis. After inducing EMT with transforming growth factor-?1 (TGF-?1) in vitro, we found that miR-145 is significantly up-regulated, whereas FGF10 is markedly down-regulated, suggesting a close link between miR-145 and FGF10 in peritoneal fibrosis, further confirmed in luciferase reporter experiments. Furthermore, in human peritoneal mesothelial cells (i.e. HMrSV5 cells), miR-145 mimics induced EMT, whereas miR-145 inhibition suppressed EMT, and we also observed that miR-145 suppressed FGF10 expression. In vivo, we found that the exogenous delivery of an miR-145 expression plasmid both blocked FGF10 and intensified the EMT, whereas miR-145 inhibition promoted the expression of FGF10 and reversed the EMT. In conclusion, miR-145 promotes the EMT during the development of peritoneal fibrosis by suppressing FGF10 activity, suggesting that miR-145 represents a potential therapeutic target for managing peritoneal fibrosis.
1 病例报告 患者男性,57岁.主因"双下肢无力、步态 不稳8年,加重半年"于2018-06-20以"周围神经病"收入院.8年前无明显诱因出现双下肢无力感,步态不稳,可步行约8000步,无头晕、头疼,无言语不清,有时伴双下肢麻木,症状持续存在.4年前于外院行肌电图检查结果显示广泛周围神经损害,右肥肠神经活检病理检查结果显示有髓神经纤维重度丢失,偶见有髓神经轴突变性形成的髓球样结构,重度周围神经病理改变.口服维生素B12治疗,效果欠佳,症状逐渐加重,走路距离逐渐缩短,曾数次摔倒,站立、坐下等动作需他人协助.近半年患者症状再次加重,步行50m较为费力.患者精神尚可,进主食少,大小便正常,近期无明显体重下降,近2天睡眠较以前增多.8年前曾行头颅CT检查结果提示脑梗死.吸烟40余年,约10支/d.饮酒40余年,每天约8两白酒.入院查体:意识清楚,语言流利,颈部、背部、双侧腹股沟区出现弥漫性对称性膨隆(图1),双上肢肌力5级,双下肢肌力4级,双下肢膝关节
Peritoneal fibrosis (PF) is a major cause of ultrafiltration failure in patients receiving long-term peritoneal dialysis (PD), and effective prevention and treatment strategies are urgently needed. The dimethylamino Michael adduct of a natural product-derived micheliolide (MCL), dimethylaminomicheliolide (DMAMCL), is a new lead compound with the advantages of high stability, low toxicity, and sustainable release of MCL. This study aimed to investigate the protective effect of DMAMCL against PD-related PF and the mechanisms involved. In this study, we found that DMAMCL significantly decreased PD-induced extracellular matrix (ECM) deposition in a mouse model of PD, and that delayed DMAMCL administration halted the progression of PF in an established PD model. In addition, rapamycin administration induced autophagy and significantly ameliorated PF. The protective effect of DMAMCL against PF was weakened when co-administered with DMAMCL and 3-methyladenine. Inducing autophagy by rapamycin decreased transforming growth factor-β1–induced ECM accumulation in vitro. MCL promoted autophagy and inhibited ECM deposition. The anti-fibrotic effect of MCL was eliminated when knocking down ATG7 by siRNA. Taken together, DMAMCL might prevent against PF through activating autophagy. The anti-fibrotic effect of DMAMCL may be a new candidate for the treatment in patients with PD-related PF.
目的 探讨温肾降压方加味联合硝苯地平控释片治疗老年高血压患者的效果及对血管内皮功能的影响.方法 将2016年1月至2017年12月因高血压于本院就诊的80例患者纳入研究并据随机数字表法进行分组.对照组40例采用硝苯地平控释片治疗,观察组40例联合温阳降浊汤加味,12周后比较临床疗效.结果 治疗后观察组收缩压、舒张压低于对照组,差异具有统计学意义(P<0.05);治疗后观察组内皮素(ET-1)、一氧化氮(NO)低于对照组(P<0.05);观察组总有效率为95.00%(38/40),高于对照组的77.50%(31/40)(P<0.05).结论 老年高血压患者采用温肾降压方加味联合硝苯地平控释片治疗效果显著,可有效降低血压水平,调节血管内皮功能,值得推广.
肝豆状核变性(HLD )又称威尔逊病(WD) ,是一种常染色体隐性遗传病,致病基因定位于染色体 13q14.3 的ATP7B ,该基因突变导致 P型铜转运 ATP酶功能减弱或丧失,导致血清铜蓝蛋白合成减少和胆道排铜障碍,铜离子在肝脏、脑、角膜、肾脏等部位沉积,引起进行性加重的锥体外系症状、精神症状、肝硬化、肾功能损害及角膜色素环(K-F环)[1] .妊娠期间发病患者罕见,容易延误诊断.现报道一例孕期发病伴A T P7B基因双突变的病例.
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Rationale: The incidence exercise-induced rhabdomyolysis is increasing in the healthy general population. Rhabdomyolysis can lead to the life-threatening systemic complications of acute kidney injury (AKI), compartment syndrome, and disseminated intravascular coagulopathy. Patient concerns: A 21-year-old man had bilateral lower limb pain and soreness, dark brown urine after lower exremity training. Laboratory results showed that creatinine kinase (CK) and myoglobin (Mb) increased to 140,500IU/L and 8632mg/L respectively, with elevated liver enzymes, Scr, and proteinuria. Diagnoses: Exercise-induced rhabdomyolysis with AKI. Interventions: The patient was hospitalized and treated with vigorous hydration and sodium bicarbonate for 6 days. Outcomes: After 6 days of treatment, the patient had a significant decrease in the CK and Mb levels. His renal function returned to normal. His laboratory tests had completely normalized during 2-week follow-up. Lessons: Exercise-induced rhabdomyolysis can cause serious complications such as AKI. Delayed diagnosis can be critical, so timely manner should be taken to achieve a favorable prognosis.
OBJECTIVES The association between mean platelet volume/platelet count ratio (MPV/PC) and mortality has been demonstrated in various populations but not in peritoneal dialysis (PD) patients. This study investigated the association between MPV/PC and all-cause and cardiovascular mortality in PD patients. MATERIALS AND METHODS In this single-center retrospective cohort study, 338 patients who underwent incident PD from January 2006 to June 2014 and had baseline MPV/PC were enrolled and followed until June 30, 2015. RESULTS The mean patient age was 50.5 ± 14.9 years (58.2% men, 22.8% diabetic). During a median follow-up of 25 (IQR 17 - 39) months, 58 patients died; 30 deaths were due to cardiovascular disease. The patients were stratified into two groups according to the PC, MPV, and MPV/PC quartiles. The all-cause and cardiovascular mortality were compared between both groups. MPV and MPV/PC and all-cause and cardiovascular mortality were significantly associated, even after adjusting for age, gender, Davies score, hemoglobin, albumin, and usage of platelet inhibitors. Only the association between baseline MPV/PC and all-cause and cardiovascular mortality was similar when we examined PC, MPV, and MPV/PC without stratification. In the multivariable adjusted model, each 0.01 increase in MPV/PC was associated with an adjusted hazard ratio (AHR) of 0.67 (95% CI, 0.51 - 0.89) for all-cause mortality and an AHR of 0.63 (95% CI, 0.42 - 0.96) for cardiovascular mortality. CONCLUSION MPV/PC may be a more reliable and accurate risk factor compared to MPV or PC alone. .
The prognostic nutritional index (PNI), a variable based on serum albumin concentration and total lymphocyte count in peripheral blood, is reported as a predictor of mortality in a variety of malignant tumor population. This study is aimed to evaluate whether PNI has prognostic value in patients on peritoneal dialysis (PD).
Objective: To investigate the effect of Wuzi Yanzong Pills(WYP) containing serum on the vitality and related apoptotic proteins of IEC-6 cell treated by paclitaxel(PTX).Methods: Male SD rats were randomly divided into experiment group treated by 6 g·kg;·d; of WYP,and the control group treated by equivalent vehicle.The containing serum was prepared after 7-day treatment.The IEC-6 cells were randomly divided into the control group treated by 5%,10%,20% of normal rats serum,model group treated by normal rats serum plus PTX,and the experiment group treated by PTX plus 5%,10%,20% of WYP rats serum.The IC50 of PTX was detected using MTS.The proliferative rates of IEC-6 cells treated by different concentrations of PTX containing serum was determined by MTS assay.The DNA damage was detected with TUNEL method.The related apoptotic proteins including Bcl-2,Bax,Bcl-2/Bax,Cytc,and Caspase-3 were detected by Western blot.Results: PTX induced the apoptosis of IEC-6 cells.WYP had protective effects on the maintenance of cell shape and vitality.The experiment group showed a less apoptosis of TUNEL,decreases in the Bax,Cytc and cl-caspase-3 protein expressions and increases in the protein expressions of Bcl-2 and Bcl-2/Bax(P<0.01) when compared with the model group.Conclusion: WYP can reduce the apoptosis injury of IEC-6 cells induced by PTX by regulating the expression of Bcl-2/Bax.
Objective To investigate the effect of nervonic acid( NA) on IEC-6 cell induced by paclitaxel( PTX),including mechanism and vitality. Methods IEC-6 cell treated with PTX to detective PTX IC50. IEC-6 cells’ relative proliferative rates of NA in different levels( 5 μmol/L,10 μmol/L,20 μmol/L) were detected by MTS assay,the expression levels of A-FABP,p38,Bcl-2,Bax,Bcl-2/Bax,Cyt C and cl-Caspase-3 were detected by Western blotting,and apoptotic cells of IEC-6 were detected by TUNEL. Results PTX could encourage normal cells apoptosis. NA was characterized with biological functions such as maintenance of cell shape and vitality. TUNEL showed that PTX could promote cells apoptosis,and NA had a protective effect on IEC-6 apoptosis induced by PTX. The expressions of A-FABP,p-p38,Bax,Cyt C,cl-Caspase-3 were reduced and Bcl-2,Bcl-2/Bax expression were increased in NA group compared with PTX group( P < 0. 01). There was no significant difference of p38 in two groups( P > 0. 05).Conclusion NA can reduce paclitaxel-induced apoptosis of IEC-6 cells by regulating p38 pathway and Bcl-2/Bax.
Objective To investigate the protect effects of nervonic acid(NA) on paclitaxel(PTX) treated PC-12 cells, and observe the cell viability, the expressions of A-FABP, NF200, Bcl-2, Bax, Cyt C, cleaved caspase-3, and the Bcl-2/Bax expression ratio. Method The PC-12 cells were treated with PTX, and the IC50 was measured by method of MTS. Then, MTS method was used to detect the relative proliferation rate of different concentrations(5μmol·L;, 10μmol·L;, 20μmol·L;) of NA on PC-12 cells after treated with PTX(IC50) intervention. Detect the DNA fragmentation by method of TUNEL. The expression of related proteins was detected by Western blotting. Results PTX promote PC-12 cells apoptosis. NA has a role in maintaining cell morphology and maintaining cell viability. The TUNEL method showed that the green fluorescence in nervonic acid group was significantly less than that in the paclitaxel group. Compared with the expression in paclitaxel group, the expression of a-FABP, p-p38, Cyt C and cl-caspase3 were down-regulated in nervonic acid group(P<0.01), the NF200 and Bcl-2 were up-regulated(P<0.01), the ratio of Bcl-2/Bax was increased(P<0.01), and p38, Bax have no change(P>0.05).Conclusion NA can reduce the PTX-induced injury on PC 12 cells. The mechanism may be related to the up-regulation of NF-200, Bcl-2, Bcl-2/Bax expression and down-regulation of a-FABP, p-p38, Cyt C and cl-Caspase3 expression.