Clinical analysis of peritoneal dialysis in the treatment of rapidly progressive glomerulonephritis

Objective To observe the clinical characteristics and prognosis of patients with rapidly progressive glomerulonephritis (RPGN) caused by lupus nephritis, antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, or primary glomerulonephritis who were treated with peritoneal dialysis (PD) and then withdrew PD because of renal recovery. Methods Data of the above patients were retrospectively analyzed. The patients were diagnosed as RPGN and received PD therapy in Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University from February 2009 to August 2018. The patients were divided into early withdrawal group (PD time≤183 days, n=24) and late withdrawal group (PD time＞183 day, n=24). The differences of clinical characteristics between the two groups were compared. The cumulative incidence of adverse events in both groups was analyzed using Kaplan-Meier curves. Cox proportional hazards model was used to analyze the risk factors influencing the prognosis of patients. Results Forty-eight RPGN patients were included. The median time of maintaining PD was 178(76, 378) days. Compared with the late withdrawal group, the patients in early withdrawal group had lower levels of urine volume, serum albumin and parathyroid hormone, and lower rates of gross hematuria and hypertension at the beginning of PD, and received higher rates of methylprednisolone impulse, combined immunosuppressive agents, and hemodialysis or continuous renal replacement therapy (all P＜0.05). At the time of PD withdrawal, the levels of serum creatinine, serum calcium, serum albumin and parathyroid hormone in the early withdrawal group were significantly lower than those in the late withdrawal group (all P＜0.05). The Kaplan-Meier curves showed that there was no significant difference in the cumulative survival of patients in both groups (log-rank test χ2=3.485, P=0.062). Cox regression analysis revealed serum creatinine≥209 μmol/L at the time of PD withdrawal was an independent risk factor for poor prognosis (HR=5.253，95%CI 1.757-15.702, P=0.003). Conclusions PD can be used for RPGN patients caused by lupus nephritis, ANCA-associated vasculitis and primary nephritis. Serum creatinine≥209 μmol/L at the time of PD withdrawal is an independent risk factor for poor prognosis.     

四妙勇安汤方源探析

四妙勇安汤由金银花、玄参、当归、甘草4味药物组成,为《古代经典名方目录(第一批)》中100个经典名方之一。经溯源发现,四妙勇安汤源于《石室秘录》,后由《古今图书集成·医部全录》《验方新编》等书引用。从古代文献记载来看均有方无名,"四妙勇安汤"之名,最早见于1956年《中医治疗动脉栓塞性坏疽症的成效》,是由当时记者吕民报道河北省释迦宝山用"四妙勇安汤"治疗当地的动脉栓塞性坏疽时冠名。四妙勇安汤从方药组成与剂量上看,从《石室秘录》开始即是"金银花三两,当归二两,生甘草一两,玄参三两",历代版本《方剂学》确定四妙勇安汤金银花、玄参、当归、甘草的比例就是3∶3∶2∶1。而查阅文献,释迦宝山临证所用的四妙勇安汤由"玄参132 g,当归99 g,银花66 g,甘草33 g"组成,金银花、玄参、当归、甘草的比例变成2∶4∶3∶1。从治疗时间上看,原方记载的7日愈或是10日愈,而释迦宝山将其用到了三四个月,甚至五六个月。研究认为,古籍中的四妙勇安汤,应该是用于疾病的初期,尽早发现和治疗;而释迦宝山修改过的剂量,是广泛用于脱骨疽的中后期,甚至出现坏疽的严重病情所使用的,因此服药时间长,剂量大。且四妙勇安汤临证不仅限于治疗脱骨疽,也用于大头疮等,现代该方的使用已经大为拓展。相关研究已证实四妙勇安汤具有抗炎、稳定斑块、降脂、保护血管、改善血液流变学、抗凝、抑制血栓形成和促纤溶等作用,后续应开展君臣佐使辨析,对其临床应用范围重新进行界定。     

双球囊与缩宫素用于促宫颈成熟以及引产的效果比较

目的比较双球囊与缩宫素用于促宫颈成熟并引产的临床效果。方法选取于2017年7月—2018年7月在本院分娩的足月妊娠孕妇100例为研究对象,随机平均分为观察组和对照组各50例,观察组采用双球囊引产,对照组采用缩宫素进行引产,对比2组孕妇的总产程、宫颈成熟度、引产成功率和新生儿Apgar评分、并发症发生率等。结果观察组促宫颈成熟有效率(100%)、引产成功率(96%)均高于对照组(82%,74%),差异均有统计学意义(P<0.05),治疗后新生儿Apgar评分、并发症发生率差异均无统计学意义(P>0.05);宫颈Bishop评分观察组(9.12±1.42)高于对照组(7.92±1.56),观察组总产程(8.23±2.54)h,对照组(13.45±3.77)h,差异均有统计学意义(P<0.05)。结论双球囊用于妊娠引产效果显著,能明显促进宫颈成熟、缩短产程,保障分娩的顺利进行,安全可靠,值得在临床中推广。     

基于医院信息系统的乳腺癌临床特征及中西医用药特征分析

目的 解析真实世界中乳腺恶性肿瘤患者的人群特征、诊断特征、中西医用药特征，为乳腺癌的临床防治提供参考。方法 采集2002年2月至2015年5月全国60家三级甲等医 院信息系统（Hospital Information System，HIS）中，出院诊断为“乳腺癌”的患者用药信息，采用SAS9.3统计软件，对人口学信息、诊断信息、医嘱用药信息等进行描述性分析。结果 39798例乳腺癌患者，平均年龄（50.93者，平均年龄）岁；多以门诊入院，入院病情以“一般”为主;合并疾病主要为高血压，骨肿瘤，联用西药以抑制肿瘤细胞增殖、治疗并发症、缓解放化疗不良反应为主；中医辨证以痰瘀互结证，气阴两虚证，肝气淤滞证，脾气亏虚证型最为常见，临床清热解毒剂、益气扶正剂，活血化瘀剂应用较多。结论 乳腺癌中西医结合治疗，联用药物广泛，临床治疗基本符合临床指南。     

以医院登记为基础的20万例恶性肿瘤患者生存报告

背景与目的：恶性肿瘤是全球重大的公共健康问题，患者生存率是评价恶性肿瘤诊治水平的重要指标。通过描述以医院登记为基础的20万例恶性肿瘤患者的生存情况，以真实世界数据从一个侧面反映我国恶性肿瘤的治疗效果。方法：纳入2008年1月1日—2017年12月31日之间在复旦大学附属肿瘤医院确诊为恶性肿瘤并接受住院治疗的患者共计202 542例。通过患者复诊病史资料、电话随访及死因数据链接等方式收集生存随访信息，随访统计时间截至2019年11月30日。应用寿命表法估计各个病种1年、3年和5年总生存率（overall survival，OS），以性别、年龄组、首次治疗时间分层。采用Kaplan-Meier生存曲线绘制各病种的总体生存曲线。结果：患者总体的1年、3年、5年OS分别为89.8%、77.4%和71.0%；男性患者5年OS为58.8%，女性患者为78.7%。在常见的恶性肿瘤中，甲状腺癌患者的5年OS最高，为98.6%；胰腺癌患者最低，为11.4%。2013—2017年首次治疗的乳腺癌、肺癌和肾癌患者5年OS分别为90.0%、55.9%和80.7%，显著高于2008—2012年首次治疗患者，其他肿瘤未见显著上升。结论：大部分恶性肿瘤患者经规范诊治可以获得较为理想的预后，女性生存情况显著优于男性，乳腺癌和肺癌患者的生存改善可能归功于新的临床治疗和早诊手段。     

依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.