丙泊酚对未成年肥胖模型大鼠认知功能损害的机制

目的 研究丙泊酚对未成年肥胖大鼠认知功能的影响,并探讨其与海马组织中血红素加氧酶1（HO-1）、超氧化物歧化酶1（SOD1）蛋白及血浆中S100钙结合蛋白β（S100β）表达的关系。方法 取3周龄雄性SD大鼠140只,随机分为基础饲料组（n=40）和高脂饲料组（n=100）。基础饲料组予基础饲料喂养,高脂饲料组予高脂饲料喂养。喂养4周后,取高脂饲料组体质量≥基础饲料组平均体质量+1.4倍标准差的40只大鼠判定为肥胖建模成功。将基础饲料组大鼠随机分为正常脂肪乳组（NL组）、正常丙泊酚组（NP组）,将建模成功的肥胖大鼠随机分为肥胖脂肪乳组（OL组）、肥胖丙泊酚组（OP组）,每组均为20只。丙泊酚组腹腔注射丙泊酚100 mg/kg,脂肪乳组（对照）腹腔注射脂肪乳100 mg/kg,每天注射1次,连续7 d。停药后第1天,各组大鼠行Morris水迷宫实验评估大鼠空间学习记忆能力,ELISA检测大鼠血浆S100β含量,蛋白质印迹法检测海马组织中HO-1、SOD1蛋白表达,H-E染色观察海马CA1区神经元的变化。结果 与OL组比较,OP组第1～5天逃逸潜伏期均延长（P均<0.05）,第三象限停留时间缩短（P<0.05）,穿越平台次数减少（P<0.05）,血浆中S100β蛋白表达升高（P<0.05）,海马组织中HO-1和SOD1蛋白相对表达量均降低（P均<0.05）,海马CA1区神经元数量减少（P<0.01）。与NL组比较,NP组第1、2天逃逸潜伏期均延长（P均<0.05）,上述其余指标差异均无统计学意义（P均>0.05）。结论 丙泊酚通过下调未成年肥胖大鼠海马组织中抗氧化因子HO-1和SOD1的表达使大鼠S100β表达和氧化应激增加,从而导致其认知功能损害。     

间歇性低氧大鼠模型心肌氧化应激损伤变化及依达拉奉的干预作用

目的:通过建立间歇性低氧(IH)大鼠模型,探讨IH对大鼠心肌氧化应激损伤的影响及其可能作用机制,并进一步了解依达拉奉的干预作用,为临床阻塞性睡眠呼吸暂停低通气综合征及其相关心血管并发症的研究及防治提供新思路。方法:选取健康雄性Wistar大鼠80只,随机分为正常对照(NC)组、IH组、IH+依达拉奉组、IH+生理盐水(NS)组,每组20只。采用气体控制装置向密闭模拟舱中充入氮气、氧气及压缩空气的方法建立IH大鼠模型。造模4周后,检测大鼠血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)及心肌组织丙二醛(MDA)、超氧化物歧化酶(SOD)、羟自由基的含量;测定心肌细胞线粒体腺嘌呤核苷三磷酸(ATP)水平;光镜、透射电镜观察心肌形态学及超微结构改变;反转录-聚合酶链反应技术检测心肌组织Bcl-2、Bax、半胱氨酸蛋白酶3(Caspase-3) mRNA的表达情况。结果:(1)与NC组相比,IH组及IH+NS组LDH、CK、CK-MB、MDA、羟自由基含量明显增加,Bax、Caspase-3 mRNA表达明显升高( P值均<0.05);而SOD活力显著降低,ATP含量显著减少,Bcl-2 mRNA表达明显下降( P值均<0.05)。(2)光镜和透射电镜下,NC组心肌组织未见明显损伤,而IH组及IH+NS组心肌组织的形态学及超微结构均受损。(3)经依达拉奉干预后,血清LDH、CK、CK-MB及心肌组织MDA、羟自由基含量明显降低,Bax、Caspase-3 mRNA表达下降( P值均<0.05);SOD活力明显升高,ATP含量增加,Bcl-2 mRNA表达水平升高( P值均<0.05);且光镜及电镜下心肌组织损伤程度得到一定缓解。(4)心肌细胞Caspase-3 mRNA表达水平与CK( r=0.575)、CK-MB( r=0.460)、MDA( r=0.643)、羟自由基( r=0.454)、Bax mRNA( r=0.741)呈正相关,与ATP( r=-0.525)、Bcl-2 mRNA( r=-0.578)呈负相关。 结论:(1)IH可通过增加氧化物、降低抗氧化物及激活Bcl-2、Bax、Caspase-3引起大鼠心肌氧化应激损伤;(2)IH所致的心肌氧化应激损伤可能通过线粒体介导的细胞凋亡实现;(3)依达拉奉对IH所致的大鼠心肌损伤具有干预作用。     

Safety and efficacy of coblopasvir and sofosbuvir in patients with genotypes 1, 2, 3 and 6 HCV infections without or with compensated cirrhosis

A simple, pangenotypic and effective treatment regimen for patients with a broad range of chronic hepatitis C virus (HCV) infections remains an unmet medical need. We conducted a phase 2, randomized, open study involving untreated patients with chronic HCV genotypes 1, 2, 3, or 6 infections. Patients without cirrhosis were randomly assigned in a 1:2 ratio to receive capsules of the NS5A inhibitor coblopasvir at a dose of 30 or 60 mg plus tablets of the nucleotide polymerase inhibitor sofosbuvir (400 mg) once daily for 12 weeks. Patients with cirrhosis received 60 mg coblopasvir plus sofosbuvir for 12 weeks. The primary endpoint was the sustained virologic response at 12 weeks after the end of therapy (SVR12). Of the 110 patients who were enrolled in the study, 59 were male, 62.7% had HCV genotype 1, 24.5% had genotype 2, 6.4% had genotype 3, and 6.4% had genotype 6. The average age was 45.5 years. A total of 10.9% of patients had compensated cirrhosis. The rate of SVR12 was 98.2% in the intention‐to‐treat (ITT). One genotype 6 patient with cirrhosis experienced virologic relapse. One genotype 2 patient without cirrhosis failed to complete the follow‐up and quit the study. Serious adverse events (SAEs) were reported in 2 patients and were not related to coblopasvir and sofosbuvir. Most adverse events (AEs) did not require treatment. Coblopasvir plus sofosbuvir taken once daily for 12 weeks provided high rates of sustained virologic response (SVR) and had a good safety profile among patients with HCV genotypes 1, 2, 3, or 6 infections, including those with compensated cirrhosis.     

A large real‐world cohort study examining the effects of long‐term entecavir on hepatocellular carcinoma and HBsAg seroclearance

Real‐world studies examining reduction in risk of hepatocellular carcinoma (HCC) in patients receiving antivirals are limited by the small size of the studies, or by data insufficiency and heterogeneity with short follow‐up duration. We aimed to examine the real‐world long‐term outcome of patients receiving entecavir treatment on HCC incidence and HBsAg seroclearance. The incidence of HCC in 1225 entecavir‐treated patients between 2002 and 2015 was compared with the HCC incidence estimated using the REACH‐B, GAG‐HCC and CU‐HCC scores. Standardized incidence ratios (SIR) were calculated. The impact of entecavir treatment on HBsAg seroclearance was also explored. The median follow‐up of the cohort was 6.6 years, with 66 cases of HCC development. Using the REACH‐B model, the reduction of HCC risk was significant from year 6 onwards with SIR of 0.68 (95% CI 0.535‐0.866) at year 10. In subgroup patients without cirrhosis, consistent risk reduction was observed from the fifth year and the SIR reached 0.51 (95% CI 0.271‐0.704) by year 10. Benefit in cirrhotic patients was demonstrated when using the GAG‐HCC and CU‐HCC score, with the SIR at year 10 being 0.38 (95% CI 0.259‐0.544) and 0.46 (95% CI 0.314‐0.659), respectively. The cumulative rate of HBsAg seroclearance was 5.2%. HBsAg level at third year of treatment and baseline‐to‐3‐year percentage reduction was predictive of subsequent HBsAg seroclearance. In conclusion, long‐term entecavir therapy was associated with significant reduction in the risk of HCC in the real world. However, HBsAg seroclearance rate remained low. Additional therapy may be considered in patients with adverse predictive factors for subsequent HBsAg seroclearance.     

应用基于体素的形态学测量在不同程度OSAHS脑灰质密度变化的研究

目的应用基于体素的形态学测量(VBM)技术初步探讨不同程度的OSAHS对大脑微观结构的影响。 方法应用PHILIPS 3.0 T磁共振对通过脑MRI-VBM技术比较研究2016年1月至2017年12月我院确诊的轻、中、重度OSAHS患者的脑结构变化情况。 结果①本研究对55例确诊的OSAHS患者依据睡眠呼吸暂停低通气指数(AHI)将其分为轻、中、重度,各组间年龄、性别及海拔无明显差异(均P>0.05),轻度组平均血氧饱和度(MSpO₂)、最低氧饱和度(LSpO₂)均明显高于中度、重度组(P<0.05),重度OSAHS组AHI显著高于轻度、中度组(P＝0.000); ②中度OSAHS患者与轻度OSAHS患者VBM-MRI相比较,包括左侧杏仁核、左侧海马、左侧脑岛脑灰质体积减少;③重度OSAHS患者与轻度OSAHS患者VBM-MRI相比较,右侧海马旁回脑灰质体积减少;④重度OSAHS患者与中度OSAHS患者VBM-MRI相比较：包括左侧脑岛、左侧尾状核、左侧豆状壳核脑灰质体积增加;左侧丘脑、右侧丘脑脑灰质体积减少。 结论不同程度的OSAHS患者间歇缺氧下导致脑灰质有不同程度的变化,说明了OSAHS对患者的脑结构有着一定程度的影响。     

手术室量化评估策略对肺癌手术患者应激的影响

肺癌为近年来发病率与病死率增长最快的恶性肿瘤之一,因其早期症状不明显,患者临床确诊通常已至中晚期,而肺癌晚期预后差难以治疗,因此肺癌严重威胁人民健康[1-7]。肺癌常用的治疗方案是手术治疗,特别是近年来胸腔镜手术方法的成熟,其创伤小、并发症少的特点进一步提高了肺癌患者手术的成功率与生存率[8-9]。     

慢性阻塞性肺疾病合并高血压的临床特征及危险因素分析

目的观察慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)合并高血压的临床特征,同时分析其相关的危险因素。 方法收集陆军军医大学新桥医院2016年1月至2018年12月住院的COPD合并高血压患者122例,观察COPD合并高血压的临床特征,同时以单纯COPD患者40例为对照组,应用多因素Logistic回归分析COPD合并高血压的危险因素。 结果122例COPD合并高血压患者中,29.41%合并冠心病、22.99%合并肾疾病和糖尿病、21.39%合并肺心病、14.97%合并脑梗死、4.28%合并心绞痛、4.28%合并心肌梗死、9.63%合并其他心血管疾病。合并冠心病、心肌梗死、其他心血管疾病患者平均年龄显著高于COPD合并高血压患者对照组(P<0.05);合并肺心病患者病程显著长于对照组(P<0.05);合并冠心病、糖尿病、脑梗死、心绞痛、心肌梗死患者每年急性加重次数显著多余对照组(P<0.05);合并心绞痛和其他心血管疾病患者住院时间显著长于对照组(P<0.05)。多因素Logistic回归分析显示年龄(>80岁)、吸烟支数(>700支/年)、饮酒史、CRP(>50 mg/L)、BNP(>100 ng/L)、高血糖是COPD患者合并高血压的危险因素。 结论COPD合并高血压易引起其他相关性疾病而加重病情,及早关注其危险因素可提高患者预后。     

严重脓毒症/脓毒症休克患者预后的高危因素

目的分析严重脓毒症/脓毒症休克患者的临床资料、致病菌分布及生化指标情况,探讨影响危重脓毒症患者预后的高危因素。 方法选择我院2004年12月至2014年12月收治的1 013例严重脓毒症/脓毒症休克患者作为研究对象,记录患者一般资料、生理学和慢性健康状况评分Ⅱ(APACHE Ⅱ)、感染部位及致病菌、生化指标等,根据预后情况分为存活组562例和死亡组451例,采用logistic回归分析影响患者预后的独立危险因素。 结果死亡组患者与存活组相比,年龄(59.62±11.21 vs. 46.32±9.46)岁、APACHE Ⅱ评分(25.26±8.75 vs. 13.67±6.57)、脓毒症休克所占比率(54.99% vs. 27.22%)均明显增加(P<0.05),存活组患者的血清白蛋白与血小板计数水平明显高于死亡组患者(P<0.05),降钙素原与血乳酸水平明显低于死亡组患者,差异均具有统计学意义(P<0.05)。2组患者呼吸系统感染比例(35.05% vs. 36.59%)与G^-菌感染比例(46.44% vs. 63.64%)最高,患者年龄、APACHEⅡ评分、血乳酸、降钙素原与危重脓毒症患者的预后呈负相关关系(r＝-0.359、-0.876、-0.582、-0.821,P<0.05),血清白蛋白与危重脓毒症患者的预后呈正相关关系(r＝0.637,P<0.05)。年龄+APACHEⅡ+血乳酸+血降钙素原+血清白蛋白联合检测对严重脓毒症/脓毒症休克患者死亡具有更高的预测价值(AUC＝0.981)。 结论年龄、APACHEⅡ评分、血乳酸、降钙素原及血清白蛋白是影响严重脓毒症/脓毒症休克患者预后的独立危险因素,对早期预测和有效改善严重脓毒症/脓毒症休克患者预后具有具有重要的临床。