目的 观察半夏泻心汤含药血清对胃癌细胞来源外泌体诱导的腹膜间皮细胞纤维连接蛋白1(FN1)和层粘连蛋白γ1(LAMC1)表达及胃癌细胞与腹膜间皮细胞黏附、侵袭的影响,探讨其抑制胃癌腹膜转移的作用机制.方法 制备半夏泻心汤含药血清,提取人胃癌细胞NCI-N87外泌体,采用透射电镜观察及Western blot进行鉴定.将人腹膜间皮细胞HMrSV5分为正常对照组、模型组、5-氟尿嘧啶(5-FU)组和半夏泻心汤低、中、高剂量组,每组3个复孔,以NCI-N87细胞外泌体诱导HMrSV5细胞,并分别用10%含药血清培养,ELISA检测HMrSV5细胞上清液FN1和LAMC1含量,PCR检测HMrSV5细胞FN1和LAMC1 mRNA表达,荧光酶标仪检测NCI-N87细胞与HMrSV5细胞黏附情况,Transwell小室检测NCI-N87细胞向HMrSV5细胞侵袭情况.结果 透射电镜观察NCI-N87细胞外泌体呈椭圆或碟状囊泡结构,粒径介于40～80 nm,外泌体标志蛋白CD9、CD63高表达,钙网蛋白低表达.与正常对照组比较,模型组HMrSV5细胞上清液FN1和LAMC1含量明显增加,HMrSV5细胞FN1和LAMC1 mRNA表达明显升高,NCI-N87细胞和HMrSV5细胞黏附率明显升高,NCI-N87细胞向HMrSV5细胞侵袭数量明显增加(P＜0.01);与模型组比较,半夏泻心汤含药血清干预72 h后,HMrSV5细胞上清液FN1和LAMC1含量减少,HMrSV5细胞FN1和LAMC1 mRNA表达降低,NCI-N87细胞和HMrSV5细胞黏附率降低,NCI-N87细胞向HMrSV5细胞侵袭数量减少,其中半夏泻心汤中、高剂量组差异有统计学意义(P＜0.05,P＜0.01).结论 半夏泻心汤可降低胃癌细胞NCI-N87外泌体诱导的腹膜间皮细胞HMrSV5 FN1和LAMC1蛋白及mRNA表达,降低胃癌细胞与腹膜间皮细胞黏附和侵袭能力,可能是半夏泻心汤治疗胃癌腹膜转移的作用机制之一.

目的 探讨以脑电双频指数为目标导向的镇痛镇静策略在重症监护病房自发性脑出血患者早期血压管理中的应用.方法 将90例需要镇痛镇静治疗的成人自发性脑出血患者随机分为脑电双频指数镇静组(45例)和标准镇静组(45例).所有受试者均根据病情接受常规治疗,并持续泵入瑞芬太尼0.5～6.0 μg/(kg·h)-1镇痛.脑电双频指数镇静组通过适当使用镇静药物使脑电双频指数维持在65～85,标准镇静组Richmond躁动—镇静评分维持在0～2分,镇静药物均使用右美托咪定.2组受试者早期均按需使用乌拉地尔尽可能将收缩压降至110～140 mmHg,并持续维持.比较2组患者治疗过程中收缩压、舒张压、平均动脉压、血压变异率、脑电双频指数、脑组织氧合指数、非语言成人疼痛评估量表评分、机体反应水平分级评分、Richmond躁动—镇静评分量表评分、降压药物用量等的差异.结果 脑电双频指数镇静组收缩压变异率、平均动脉压变异率低于标准镇静组(P<0.05);脑组织氧合指数高于标准镇静组(P<0.01),脑电双频指数低于标准镇静组(P<0.01),降压药物用量低于标准镇静组(P<0.05),均差异有统计学意义.结论 以脑电双频指数为目标导向的镇痛镇静策略可以使自发性脑出血患者达到与主观镇痛镇静评分相同的镇痛镇静目标,并且血压波动更小,保证更高的脑组织供氧,减少降压药物的使用量.

目的 调查新型冠状病毒肺炎(COVID-19)疫情防控期间处于超负荷工作状态的新冠ICU护士的心理健康状况,并分析其影响因素,为护理人员在非常规工作状态下可能出现的心理健康问题的心理干预研究提供有力的数据支撑.方法 以兰州大学第一医院2020年2-3月COVID-19疫情防控期间连续28 d超负荷工作的13名新冠ICU护士作为研究对象,以问卷调查方式,采用症状自评量表(SCL)-90进行心理健康状况调查.结果 13名新冠ICU护士的SCL-90总分最高190分,最低104分,平均(143.15±30.89)分;SCL-90筛选阳性者7人,占53.85％;SCL-90的10个因子中,阳性人数排前三的因子为强迫、睡眠及饮食、焦虑.女护士SCL-90总分明显高于男护士,男、女比较差异有统计学意义(P＜0.05);Logistic回归分析结果显示,性别是影响新冠ICU护士SCL-90总分的影响因素(OR=1.204,95％CI:0.083～0.702).新冠ICU护士恐怖因子得分明显低于COVID-19疫情期间一般临床护士(P＜0.01),精神病性因子得分明显高于COVID-19疫情期间一般临床护士(P＜0.01);新冠ICU护士睡眠及饮食因子得分明显高于普通ICU护士(P＜0.05).结论 新冠ICU护士因高强度、超负荷工作更易发生心理健康异常状况,且女性多于男性,其表现以强迫症状、睡眠障碍、饮食行为异常及焦虑为主.

目的 观察半夏泻心汤及其不同拆方对抗生素诱导的菌群紊乱幼鼠结肠黏膜屏障的影响.方法 70只SPF级雄性Balb/c幼鼠随机抽取10只作为空白组,其余幼鼠予混合抗生素灌胃诱导肠道菌群紊乱,连续灌胃14 d,将造模幼鼠随机分为模型组、阳性对照组、全方组、辛开组、苦降组及甘补组,每组10只.阳性对照组予双歧杆菌四联活菌片溶液0.68 g/kg灌胃,全方组、辛开组、苦降组及甘补组分别予9.1、3.19、1.82、4.1 g/kg半夏泻心汤全方及相应拆方组药液灌胃,空白组、模型组灌胃等体积生理盐水,连续14 d.末次灌胃后收集幼鼠粪便,采用16S rDNA测序分析肠道菌群结构.腹腔注射脂多糖(10 mg/kg)诱导炎症反应,ELISA检测粪便清蛋白含量,HE染色观察结肠黏膜形态,Western blot检测结肠组织紧密连接蛋白ZO-1和Occludin表达.结果 与空白组比较,模型组幼鼠肠道菌群结构明显改变,结肠绒毛结构发育落后、隐窝不明显、腺体萎缩,粪便清蛋白含量明显增加(P<0.01),Occludin和ZO-1蛋白表达明显降低(P<0.01);与模型组比较,全方组和不同拆方组肠道菌群结构改善,有益菌丰度增加,有害菌丰度减少,结肠组织形态改善,粪便清蛋白含量降低,Occludin和ZO-1蛋白表达升高,总体以全方组较为显著(P<0.05,P<0.01).结论 半夏泻心汤及其不同拆方能调节抗生素诱导的菌群紊乱幼鼠肠道菌群结构,保护结肠黏膜屏障,其整体效应以半夏泻心汤全方较为明显.

Autophagy is a highly conserved intracellular catabolic process used to degrade cytoplasmic components. In recent years, it has attracted much attention because of its importance in the pathogenesis and targeted therapy of acute and chronic kidney disease. Autophagy plays an important role in maintaining renal homeostasis under physiological and pathological conditions. The study of conditional autophagy related gene knockout specific to various renal cells has gradually revealed the role of autophagy in renal diseases. Recent studies have found that autophagy deficiency may play a key role in different pathological states of the kidney. Activated autophagy shows cytoprotective function in both glomerulus and renal tubulointerstitium, suggesting that the up regulation of autophagy may become a potential therapeutic strategy. However, there is also contrary evidence that autophagy may be harmful, which poses a great challenge to the development of therapeutic strategies for up-regulated autophagy.

目的:探讨半夏泻心汤及其拆方对混合抗生素诱导的菌群紊乱幼鼠的治疗作用及可能的作用机制.方法:将70只雄性BALB/c幼鼠随机分为7组,分别为空白组、模型组、双歧杆菌四联活菌片组(西药组,0.68 g·kg-1)及半夏泻心汤全方组、辛开组、苦降组、甘补组(9.1、3.19、1.82、4.1 g·kg-1),每组10只.除空白组外,其余各组予混合抗生素灌胃诱导肠道菌群紊乱,14 d后西药组予双歧杆菌四联活菌片灌胃,全方组、辛开组、苦降组及甘补组分别予半夏泻心汤及不同配伍药组灌胃,空白组、模型组给予等体积生理盐水,1次/d,共14 d.连续给药14 d后无菌采集粪便样本用于16SrDNA测序分析肠道菌群,并经腹腔注射脂多糖(LPS,10 mg·kg-1)诱导炎性反应,苏木素-伊红(HE)染色观察结肠黏膜组织形态,甲苯胺蓝染色和免疫组织化学观察结肠黏膜巨噬细胞浸润,实时荧光定量聚合酶链式反应(Real-time PCR)检测白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)及白细胞介素-10(IL-10)mRNA的表达情况.结果:与空白组比较,模型组幼鼠肠道微生物结构显著改变(P＜0.01),结肠黏膜损伤明显,巨噬细胞浸润减少,炎性因子IL-1β、IL-6、IL-8、TNF-α及IL-10 mRNA表达水平均显著降低(P＜0.01).与模型组比较,西药组、半夏泻心汤及其拆方组均能增加菌群相对丰度和物种多样性,提高拟杆菌门、厚壁菌门等有益菌的比例(P＜0.01);同时西药组、半夏泻心汤及其拆方组均能改善结肠黏膜损伤(P＜0.05,P＜0.01),增加巨噬细胞浸润(P＜0.05,P＜0.01),升高IL-6、IL-8、TNF-α mRNA表达水平(P＜0.01);西药组、半夏泻心汤及苦降、甘补组升高IL-1βmRNA表达(P＜0.01);西药组、半夏泻心汤及辛开、甘补组IL-10mRNA表达升高(P＜0.05,P＜0.01).结论:半夏泻心汤及拆方组能调整抗生素暴露幼鼠肠道菌群,保护肠道菌群紊乱后结肠黏膜免疫屏障,以半夏泻心汤全方为最佳配伍.

目的 探讨床旁超声评估右心功能对机械通气患者撤机结果的预测价值.资料与方法纳入82例机械通气患者,采用T管模式进行自主呼吸试验(SBT),以拔管后自主呼吸时间超过48 h为撤机成功.在SBT开始10 min后或SBT失败前测量患者的右心室功能指标,包括三尖瓣环根部侧壁收缩期位移(TAPSE)、三尖瓣舒张早期血流峰速度和舒张晚期血流峰速度比值(E/A)、右心室舒张末期面积/左心室舒张末期面积比(RVarea/LVarea)以及呼气末下腔静脉内径(dIVC).比较撤机成功组(n=61)和撤机失败组(n=21)患者的右心功能指标,并评价各心功能指标对撤机结果的预测价值.结果 撤机失败组患者中心静脉压高于撤机成功组[(10.0±3.2)mmHg比(7.2±2.8)mmHg,P＜0.05];撤机成功组TAPSE高于撤机失败组[(24.70±6.96)mm比(13.33±6.42)mm,P＜0.01],E/A比值也高于撤机失败组(1.50±0.49比1.08±0.51,P＜0.01),而RVarea/LVarea和dIVC均低于撤机失败组(P均＜0.05).TAPSE和三尖瓣E/A预测撤机结果的受试者工作特征曲线下面积分别为0.88和0.76.结论 SBT前超声评估机械通气患者的右心功能可以预测其撤机结果,并可指导其液体管理.

目的 探讨目标导向性镇痛对重症加强治疗病房(ICU)无创正压通气(NPPV)患者的影响.方法 回顾性分析.纳入我院ICU收治的需NPPV的264例患者,其中经验性镇痛组118例,目标性镇痛组146例.经验性镇痛组常规给予镇痛镇静治疗,镇痛药物采用瑞芬太尼,镇静药物采用丙泊酚、咪达唑仑或右美托咪定,镇静深度维持Richmond躁动-镇静量表(RASS)评分＜1分;目标性镇痛组先用瑞芬太尼使重症监护疼痛观察工具评分＜2分,镇痛达标后再用镇静药物使RASS评分维持在＜1分.所有患者均利用ICU谵妄评估量表评估是否发生谵妄.分别观察两组患者NPPV停止时镇痛和镇静药物的用量、依从性(以开始通气后24h内的总通气时间为依据)、谵妄发生率、有创通气率、NPPV总时间和ICU住院时间.结果 两组患者的年龄、性别、APACHEⅡ评分,通气前的平均动脉压、心率、呼吸频率、SpO2、动脉血气值、NPPV原因比较,差异均无统计学意义.目标性镇痛组镇痛、镇静药物剂量均少于经验性镇痛组,其依从性高于经验性镇痛组[(12.6±5.8)h比(10.9±4.8)h],P＜0.05),而谵妄发生率和有创通气率均低于经验性镇痛组(分别为15.8％比25.4％和32.9％比44.9％,均P＜0.05).目标性镇痛组NPPV总时间较经验性镇痛组缩短[(28.6±8.8)h比(37.3±10.7)h,P＜0.05],但两组患者ICU住院时间比较,差异无统计学意义.结论 目标导向性镇痛可改善NPPV患者的依存性,减少镇静药物的使用,降低其谵妄发生率和有创通气率.

Objective To analyze the research distribution, classic literature, hotspots and frontiers of septic shock. Methods Studies that described septic shock published in the Chinese Biomedical Literature Database (CBM) from January 1, 1977 to December 31, 2017 were included. And the cooperation map between the provinces and core authors related to septic shock, the frequency of occurrence of research keywords, and cluster analysis were obtained by means of visual analysis software Ucinet 6. Results In recent years, the research on septic shock in China has shown an increasing trend year by year, but the research power was mainly concentrated in the relatively developed regions of the central and eastern regions such as Guangdong, Beijing and Jiangsu, while less researches in Inner Mongolia, Qinghai and Tibet that were relatively poor area. The core research team was mainly consisted of Professor Liu Dawei, Professor Du Bin who are located in Peking Union Medical College Hospital, and Professor Qiu Haibo in Zhongda Hospital Southeast University. For the research hotspots, the current research hotspots are confusing. Most studies focused on the treatment, nursing and prognosis of septic shock in recent years, but few studies focused on the pathogenic factors, testing methods, pathological processes and microcirculation of septic shock. And there were few collaborative studies between hospitals across provinces and cities. Conclusion There are more than 400 research articles on septic shock in the past decade, which are mainly concentrated in the hospitals of the central and eastern provinces with the Department of Critical Care Medicine and mainly focus on the treatment and prognosis of septic shock. In the future, researches on pathogenic factors and pathological processes should be strengthened, and cross-provincial and multidisciplinary research need to be formed. Key words: Septic shock; Research literature; Author; Author unit; Key words

目的 探讨膈肌浅快呼吸指数(diaphragm rapid shallow breathing index,D-RBSI)对机械通气慢性阻塞性肺疾病(简称慢阻肺)患者撤机结果的预测价值.方法 纳入2016年3月至2017年3月我院重症医学科收治的76例机械通气慢阻肺患者.患者通过撤机筛查后以持续气道正压通气模式进行自主呼吸试验(spontaneous breathing test,SBT),SBT开始后10 min或SBT失败时记录患者的呼吸频率(respiratory rate,RR)和潮气量,并利用床旁超声测量患者的膈肌活动度(diaphragmatic displacement,DD).以RR和DD的比值(RR/DD)计算D-RBSI,通过受试者工作特征(receiver operating characteristic,ROC)曲线分析D-RBSI对机械通气慢阻肺患者撤机结果的预测价值.结果 共有28例患者撤机失败.成功组和失败组患者的年龄和急性生理学和慢性健康状况评分系统Ⅱ评分无明显差异.成功组患者DD大于失败组[(22±6) mm比(13±5) mm,P＜0.001)],RBSI和D-RBSI均低于失败组[RBSI:(40±14)次/(min.L)比(52±20)次/(min.L),P=0.003;D-RBSI:(0.95±0.51)次/(min.mm)比(1.79±0.83)次/(min.mm),P＜0.001)].两组患者的RBSI和D-RBSI之间相关性良好(R2=0.778,P＜0.001).D-RBSI对患者撤机结果预测的ROC曲线下面积高于RBSI[(0.85比0.75,P＜0.001)],D-RBSI＞1.13次/(min.mm)预测撤机失败的敏感性为0.82,特异性为0.81.结论 超声监测机械通气慢阻肺患者SBT时D-RBSI可有效判断其撤机结果.

Objective To explore the influencing factors for chronic hepatitis C (CHC) with thyroid dysfunction (TD) in untreated Chinese patients and provide evidence for clinical individualized treatment. Methods One thousand and twelve untreated CHC patients were collected nationwide in China. Thyroid function and associated influencing factors (region, age, gender, and hepatitis C virus (HCV) RNA replication level) in the patients were investigated. The relationships between the influencing factors and CHC with TD were analyzed. Between-group comparison of categorical data was performed by χ2 test and Fisher′s exact test. Results There were geographical differences between different types of CHC with TD. Across different regions, the incidence of TD was highest in north and northwest China, i.e., 28.3% and 26.5%, respectively. Subclinical hypothyroidism was the most common type of TD, accounting for 58.8% of the total TD cases. Middle-aged patients were most common among the cases of CHC with TD (44.0%), who had a significantly higher incidence of hypothyroidism than other age groups (χ2=10.10、6.17, P=0.001、0.013). Females with CHC had a significantly higher incidence of TD than male patients (58.9% vs. 41.1%, χ2=13.1, P=0.00). Although a high HCV RNA replication level was most common in Chinese patients with CHC, this factor had little influence on TD. Conclusion In China, CHC with TD is influenced by geographic distribution, gender, and age, but less associated with HCV RNA replication level.

A growing body of literature highlights the cross-talk between tumor cells and the surrounding peritumoral stroma as a key modulator in the development, invasion, and metastasis of hepatocellular carcinoma (HCC). Hepatic stellate cells (HSC), an important component in the microenvironment of HCC, play an important role in the development and progression of “inflammation-fibrosis/cirrhosis-tumor”. The origin and activation of HSC, as well as the effects of HSC and their cytokines on the immune response in the proliferation, metastasis, and invasion of HCC, are reviewed. It is thought that HSC are not only a “hotbed” for tumor growth, but also help resist the tumor tracing and elimination mechanism of the immune system. Therefore, it is worth developing treatments targeting the tumor microenvironment when the single anti-cancer therapy is ineffective.

Objective To evaluate the mental disorders in mice with thioacetamide (TAA)-induced acute hepatic encephalopathy (AHE). Methods Thirty male Kunming mice were equally and randomly divided into two groups (treatment group and control group).Mice in the treatment group received an intraperitoneal injection of TAA (200 mg·kg -1 ·d -1 for 3 days,up to 600 mg·kg -1 ),as compared with the same volume of physiological saline in the control group.Neurological function score,light/dark box,open field,and elevated plus -maze test were used to determine behavioral parameters at 24 h after the model was established.Serum ammonia,aspartate amino transferase (AST),al-anine aminotransferase (ALT),and total bilirubin (TBil)were measured at 24 h post determination of behavioral parameters.Comparison be-tween two groups was made by independent -samples t test.Results In the light/dark box test,the treatment group had significantly reduced residence time in the light box and number of shuttles between two boxes (t =-4.006,P <0.01;t =-2.656,P <0.05);in the open field test,the treatment group had significantly reduced central distance,central time,and number of vertical movements (t =-3.639,P <0.05;t =-2.294,P <0.05;t =-2.282,P <0.05),as well as increased grooming time (t =5.992,P <0.01);meanwhile,the number of open-arm entries and residence time in the open arm for the treatment group were also reduced in the elevated plus -maze test,as compared with the control group (t =-3.584,P <0.05;t =-3.992,P <0.05).However,the total distance in the open field test showed no significant difference between the two groups (t =-0.96,P >0.05).Moreover,compared with the control group,the treatment group had significant-ly higher levels of serum ammonia (t =-3.168,P <0.05),ALT (t =4.316,P <0.05),AST (t =-2.581,P <0.05),and TBil (t =-9.127,P <0.01).Conclusion Mice with AHE induced by an intraperitoneal injection of low -dose TAA have anxiety -related behav-iors;the anxiety -related behaviors are not associated with reduced locomotor activities.

目的：提高腹膜恶性间皮瘤( peritoneal malignant mesothelioma, PMM)的诊断水平。方法回顾性分析1例PMM的临床资料。结果本例以进行性腹胀为主诉,入院发现腹水,腹水检查提示性质介于渗出液和漏出液之间,多次腹水脱落细胞学检查未见恶性细胞,血清肿瘤标志物轻度异常,结合正电子发射型计算机断层扫描检查提示结核性腹膜炎,建议行腹腔镜探查,患者拒绝遂予诊断性抗结核治疗后出院。1个月后症状加重,腹水增多,经腹腔镜探查并大网膜活检病理证实为PMM,确诊后1月余因多脏器功能衰竭死亡。结论对不明原因腹水,尤其伴网膜弥漫性肿胀者应考虑PMM的可能；腹水脱落细胞学检查阴性时,应考虑腹腔镜下大网膜活检病理检查,以及早诊断。