目的 观察川芎嗪(Tetramethylpyrazine,TMP)对细菌脂多糖(LPS)诱导的脐静脉内皮细胞屏障损伤(HUVEC)的保护作用,并探索可能的作用机制.方法 将鉴定好的人脐带静脉内皮细胞根据加药处理因素不同,将实验分为空白对照组、LPS组,LPS+TMP组.对三组进行免疫荧光细胞骨架染色及细胞通透性实验、跨内皮电阻实验.应用Westernblot及qPCR方法进行mTOR表达量的定量分析.结果 免疫荧光细胞骨架染色表明与空白组相比,LPS组应力纤维明显增多、增粗.而应用TMP治疗后应力纤维变少、变细.跨内皮电阻实验表明,加药刺激前三组电阻值差无统计学意义(P＞0.05).加入药物刺激后,LPS组较空白组,电阻值明显降低,而TMP组较LPS组明显增加(P＜0.05).细胞通透性实验表明加药刺激后,LPS组较空白组,通透系数明显增加,而TMP组较LPS组明显降低(P＜0.05).Westernblot及qPCR方法表明LPS组较空白组mTOR表达量增加,而TMP治疗之后mTOR表达量较LPS组下降.结论 TMP可通过调控mTOR的表达量对LPS诱导的HUVEC内皮细胞屏障破坏起到保护作用.

急性肺损伤( acute lung injury,ALI)是一种毁灭性的呼吸系统疾病,导致内皮细胞障碍和细胞骨架改变,从而进展为肺水肿、呼吸衰竭及多器官功能障碍综合征 ( multiple organ dysfunction syndrome, MODS) ,最终导致死亡的发生[1].

急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是一种ICU 中常见的病死率较高的临床综合征,ARDS发生时,富含蛋白质的液体在肺泡中积聚,阻止肺部充满足够的空气,从而导致到达血液中的氧气减少,发生低氧血症[1 -2].急性肺损伤(acute lung injury,ALI )由严重的感染、外伤、休克、吸入有害气体及中毒等直接或间接因素引起的全身炎症反应综合征在肺部的表现,以肺泡及肺实质发生急性炎症为主要病理特征,其特点是发生低氧血症、非心源性肺水肿、肺顺应性降低和广泛的毛细血管渗漏[3].

目的:观察川芎嗪(tetramethylpyrazine,TMP)对脂多糖(lipopolysaccharide,LPS)诱导的人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)通透性变化和细胞骨架相关蛋白表达影响.方法:以体外培养的HUVECs为实验对象,将细胞随机分6组:正常对照组,LPS组(1μg/mL LPS),TMP低、中、高剂量防治组(60μg/mL TMP+1μg/mL LPS、120μg/mL TMP+1μg/mL LPS、240μg/mL TMP+1μg/mL LPS),纯TMP组(240μg/mL TMP).Transwell小室内建立内皮细胞通透性模型;细胞电压电阻仪测定各组细胞跨内皮细胞电阻值(TEER);FITC-葡聚糖法检测各组细胞通透性变化,Pull-Down实验拉下Rac1-GTPase活性蛋白,Western blotting检测各组细胞Rac1-GTPase、Rac1、LIMK1和p-LIMK1的蛋白表达.结果:3组不同浓度的TMP均可以抑制LPS诱导的内皮细胞TEER降低以及降低LPS导致的内皮细胞通透性的增加(P<0.05～P<0.01);Western blotting实验显示TMP可以有效抑制LPS诱导的HUVECs中的Rac1-GTPase、p-LIMK1、Rac1、LIMK1表达(P<0.05～P<0.01).结论:TMP可以有效抑制LPS诱导的HUVECs通透性升高,其机制可能与其下调Rac1/LIMK1信号通路中Rac1-GTPase活性蛋白、LIMK1磷酸化蛋白表达有关.

脓毒症（sepsis）在1991年初次被定义为感染所致的机体全身炎症反应综合征（SIRS）。2016年脓毒症国际共识更新至Sepsis 3.0，即由感染所致宿主免疫反应失调引起的威胁生命的器官功能障碍。在脓毒症免疫抑制阶段，程序性死亡受体1（programmed cell death protein-1，PD-1）与程序性死亡受体-配体1（programmed cell death 1 ligand 1，PD-L1）相结合能够抑制部分免疫细胞活化增殖从而达到负性调节免疫系统的作用。本综述主要围绕脓毒症中PD-1/PD-L1在T细胞、树突状细胞（DCs）、单核细胞、巨噬细胞等免疫细胞发挥免疫功能中的作用，以及对抗PD-1/PD-L1抗体疗法的应用前景进行阐述。

目的 探索形成性评价在病理生理学教学中的应用及效果.方法 于2017年9月—2020年1月在本校部分班级开展形成性评价教学,围绕课堂教学设计前中后三个测评环节,平时测评成绩和期末考试成绩按比例组成本课程综合成绩.选择本校两个年级卓越医师班进行教学对比研究,并在2017级临床本科和2018级护理本科开展教学效果调查.结果 授课教师根据测评结果可以及时发现教学问题并进行调整;实施形成性评价的实验班级综合分显著提高(P<0.05);调查结果反馈学生非常认可形成性评价教学模式.结论 开展形成性评价对提高病理生理学的教学效果具有积极意义.

目的:观察硫化氢(H2 S)对糖尿病大鼠空间学习记忆的影响,并探讨其机制.方法:雄性SD大鼠随机分为正常(CON)组、糖尿病(STZ)组、糖尿病+硫氢化钠(NaHS)组(SH组)和正常+NaHS(CH)组,每组8只.采用一次性腹腔注射链脲佐菌素的方法制备1型糖尿病大鼠模型.造模成功4周后,SH组和CH组大鼠每天腹腔注射NaHS溶液56μmol/kg.处理4周后,测定大鼠空腹血糖(FBG)和体质量(BW);利用Morris水迷宫测试各组大鼠的空间学习记忆能力(逃避潜伏期、正确象限停留时间和到达正确象限的潜伏期);HE染色观察海马组织病理结构改变;利用试剂盒检测海马组织总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)水平;实时荧光定量聚合酶链式反应检测海马组织核因子E2相关因子2(Nrf2)和血红素氧化酶1(HO-1)mRNA表达情况.结果:与CON组比较,CH组各项指标差异均无统计学意义(P>0.05);STZ组逃避潜伏期和到达正确象限的潜伏期延长,在正确象限停留时间缩短,大鼠海马组织病理结构损伤明显,FBG和MDA含量增加,BW、T-AOC、SOD、GSH-Px活性和Nrf2、HO-1 mRNA表达下降,差异均有统计学意义(P<0.01).与STZ组比较,除FBG外,SH组中以上各项指标均明显改善,差异均有统计学意义(P<0.05～P<0.01).结论:H2S可以改善糖尿病大鼠的认知功能障碍,其机制可能与抑制海马组织氧化应激损伤、上调Nrf2/HO-1通路的表达相关.

目的 观察脂多糖诱导小鼠内毒素血症发生时的心肌损伤情况,及丹参酮ⅡA(TⅡA)对心肌损伤有无预防保护作用,是否与RhoA/Rock(Rho激酶)通路激活有关.方法 雄性8～10周龄C57BL/6J小鼠40只,SPF级,体重(20±2)g,依据随机数字表法将小鼠随机分成空白对照组(CON组)、模型组(LPS组)、丹参酮预处理组(TL组)以及丹参酮组(T组)(n＝10).利用腹腔注射脂多糖(LPS)建立内毒素血症模型.TL组和T组,注射丹参酮10mg/(kg·d)共7d;CON组,LPS组生理盐水等体积注射7d.LPS组、TL组末次注射1h后,腹腔注射LPS(10mg/kg).LPS注射6h后,超声心动图测定小鼠心功能.12h后,心肌组织做HE染色,光镜下观察小鼠心肌形态结构的变化;酶联免疫吸附实验,检测心肌组织白介素-1β(IL-1β)的蛋白水平;蛋白质印迹法(Western blot)检测小鼠心肌组织RhoA和Rock1的蛋白含量.结果 超声心动图结果 表明,与CON组比,LPS组和TL组,心率(HR)、射血分数(EF)、短轴缩短率(FS)、每搏输出量(SV)和心输出量(CO)均下降(P<0.05),与LPS组相比,TL组HR、SV、EF、FS和CO均升高(P<0.05);HE染色显示,LPS组心肌组织横纹模糊,胞浆淡染,有炎细胞浸润,TL组未见心肌组织形态学明显改变;与CON组相比,LPS组心肌组织IL-1β、RhoA和Rock1蛋白含量均升高(P<0.05),与LPS组相比,TL组可以降低IL-1β、RhoA和Rock1蛋白含量(P<0.05).结论 内毒素血症引起的小鼠心肌损伤,在丹参酮ⅡA预处理下,可以降低炎性因子,减轻损伤,其作用可能与抑制RhoA/Rock(Rho激酶)通路激活有关.

目的:探讨血府逐瘀汤联合脑室-腹腔分流术治疗常压性脑积水的临床疗效.方法:选取2011年1月-2018年4月我院收治的脑积水患者60例,采用随机数字表法分为对照组和治疗组,各30例.其中对照组予以脑室-腹腔分流术治疗,治疗组在对照组的基础上联合血府逐瘀汤治疗.比较两组患者临床疗效、巴氏指数评分(BI)、格拉斯哥昏迷指数评分(GCS)、神经功能缺损评分(NIHSS)、中医症状积分及随访情况.结果:治疗组患者临床总有效率为97.44％,对照组患者临床总有效率为84.62％,差异具有统计学意义(P＜0.05);经治疗,与对照组相比,治疗组患者BI、GCS、NIHSS评分及中医证候积分改善情况更明显,差异具有统计学意义(P＜0.05);经治疗,与对照组相比,随访时治疗组患者脑积水程度更轻(P＜0.05).结论:血府逐瘀汤联合脑室-腹腔分流术的治疗方案显著优于单纯脑室-腹腔分流术的常规举措,有利于脑室水肿的吸收消退,可有效降低头痛程度、频率及其并发症的发生风险.血府逐瘀汤具有行气活血、祛瘀止痛的功效,在改善脑水肿患者临床相关评分及中医证候积分方面,取得满意效果,值得临床推广.

OBJECTIVE To investigate the target blood pressure level of restrictive fluid resuscitation in patients with traumatic hemorrhagic shock. METHODS Sixty patients with traumatic hemorrhagic shock admitted to the First Affiliated Hospital of Bengbu Medical College from January 2016 to December 2018 were enrolled. All patients were resuscitated with sodium acetate ringer solution after admission. According to the difference of mean arterial pressure (MAP) target, the patients were divided into low MAP (60 mmHg ≤ MAP < 65 mmHg, 1 mmHg = 0.133 kPa), middle MAP (65 mmHg ≤ MAP < 70 mmHg) and high MAP (70 mmHg ≤ MAP < 75 mmHg) groups by random number table using the admission order with 20 patients in each group. Those who failed to reach the target MAP after 30-minute resuscitation were excluded and supplementary cases were deferred. The restrictive fluid resuscitation phase was divided into three phases: before fluid resuscitation, liquid resuscitation for 30 minutes and 60 minutes. The most suitable resuscitation blood pressure level was further speculated by monitoring the inflammatory markers and hemodynamics in different periods in each group of patients. Pearson correlation analysis was used to detect the correlation of variables. RESULTS Before fluid resuscitation, there was no significant difference in hemodynamics or expressions of serum cytokines among the three groups. Three groups of patients were resuscitated for 30 minutes to achieve the target blood pressure level and maintain 30 minutes. With the prolongation of fluid resuscitation time, the central venous pressure (CVP), cardiac output (CO) and cardiac index (CI) were increased slowly in the three groups, and reached a steady state at about 30 minutes after resuscitation, especially in the high MAP group and the middle MAP group. The expressions of serum inflammatory factors in the three groups were gradually increased with the prolongation of fluid resuscitation time. Compared with the low MAP group and the high MAP group, after 30 minutes of resuscitation the middle MAP group was superior to the other two groups in inhibiting the expressions of pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and promoting anti-inflammatory factors IL-10 [TNF-α mRNA (2-ΔΔCt): 0.21±0.13 vs. 0.69±0.34, 0.57±0.35; IL-6 mRNA (2-ΔΔCt): 0.35±0.31 vs. 0.72±0.39, 0.59±0.42; IL-10 mRNA (2-ΔΔCt): 1.25±0.81 vs. 0.61±0.46, 0.82±0.53; all P < 0.05], but there was no significant difference in promoting the expression of IL-4 mRNA among three groups. At 60 minutes of resuscitation, compared with the low MAP group and the high MAP group, the middle MAP group could significantly inhibit the expressions of TNF-α, IL-6 and promote IL-10 [TNF-α mRNA (2-ΔΔCt): 0.72±0.35 vs. 1.05±0.54, 1.03±0.49; IL-6 mRNA (2-ΔΔCt): 0.57±0.50 vs. 1.27±0.72, 1.01±0.64; IL-10 mRNA (2-ΔΔCt): 1.41±0.90 vs. 0.81±0.48, 0.94±0.61; all P < 0.05]. Compared with the high MAP group, the middle MAP group had significant differences in promoting the expression of IL-4 mRNA (2-ΔΔCt: 1.32±0.62 vs. 0.91±0.60, P < 0.05). There was no significant difference in serum cytokine expressions at different time points of resuscitation between the low MAP group and the high MAP group (all P > 0.05). Correlation analysis showed that there was a strong linear correlation between MAP and mRNA expressions of TNF-α, IL-6, IL-10 in the middle MAP group (r value was 0.766, 0.719, 0.692, respectively, all P < 0.01), but had no correlation with IL-4 (r = 0.361, P = 0.059). Fitting linear regression analysis showed an increase in 1 mmHg per MAP, the expression of TNF-α mRNA increased by 0.027 [95% confidence interval (95%CI) = 0.023-0.031, P < 0.001], IL-6 mRNA increased by 0.021 (95%CI = 0.017-0.024, P < 0.001), and IL-10 mRNA increased by 0.049 (95%CI = 0.041-0.058, P < 0.001). CONCLUSIONS When patients with traumatic hemorrhagic shock received restrict fluid resuscitation at MAP of 65-70 mmHg, the effect of reducing systemic inflammatory response and improving hemodynamics is better than the target MAP at 60-65 mmHg or 70-75 mmHg. It is suggested that 65-70 mmHg may be an ideal target MAP level for restrictive fluid resuscitation.

本研究通过虚拟教学软件的融合、透视、剖视、360度旋转的观察模式呈现剖宫产术前护理、手术过程及术中观察、术后护理等,直观了解剖宫产过程,充分利用AR交互式的实验过程进行临床实践仿真,学生可以自主练习操作,在虚拟环境中完成"准护士"的角色转换,无需教师陪伴,每次练习后进行相应的在线考核.学生在课前预习,让技能实训翻转课堂成为现实.基于AR技术构建虚拟教学情境突破了传统教学情境在时空、空间及师资力量等方面的限制,着眼于促进学生的观察、操作、互动等学习过程以达到培养护生岗位胜任力的目标.

结合国内外医学教育标准和我校的办学特色,我校打破传统医学教育模式,开设了"卓越人才培养实验班",突出"以学生为中心"的教学理念,基础医学院探索适合我校临床医学本科专业人才培养的医学基础课程教学模式.本文介绍了我校基础医学院在"卓越人才培养实验班"基础医学课程教学和考核的具体实施.

探索翻转课堂结合案例教学在病理生理学教学中的效果.选取口腔医学专业2012级学生(60人)作为对照组,2014级学生(60人)作为实验组,分别采用传统教学法和翻转课堂结合案例教学法,通过问卷调查和两组学生理论知识测试和病例讨论成绩比较教学效果.多数学生对翻转课堂结合案例教学法比较满意,实验组学生成绩高于对照组(P<0.05).翻转课堂案例教学法能够提高病理生理学的教学效果,促进学生综合能力的提升.

1背景 在医学领域,随着高通量测序等生物技术的发展,人们越来越认识到在人体体表和肠腔器官拥有丰富的微生物群落一微生物组,参与人体免疫调节、食物消化、维生素合成等一系列生命活动.而众多疾病的发病机制涉及到微生物群落的组成和行为的改变,如胃肠道炎症性疾病、AIDS相关的机会性感染、呼吸系统疾病、某些肿瘤等.人体微生物组拥有数量惊人的微生物数量(人体细胞数量10倍之多)及基因数量(人体基因的100多倍).目前,微生物组与临床疾病研究主要集中在炎症性肠病、糖尿病、过敏性疾病等.随着非培养生物分子生物技术等发展,人们认识到健康的肺部并非无菌,而呼吸道的微生物组群与多种呼吸道疾病有着特殊的关联.

目的 探讨脂多糖(Lipopolysaccharides,LPS)对人外周血中性粒细胞(neutrophil或polymorphonuclear neutrophil,PMN)吞噬结核分枝杆菌(Mycobacterium tuberculosis,M.tb)功能的影响及Toll样受体4(Toll-like receptor 4,TLR4)在其中发挥的作用.方法 取健康成人外周血PMN加入M.tb,抗酸染色、显微镜观察PMN吞噬M.tb情况;PMN与异硫氰酸荧光素(FITC)标记M.tb孵育5～20 min,流式细胞仪检测PMN吞噬率;不同浓度LPS作用PMN,流式细胞术检测PMN吞噬率;应用TLR4单克隆抗体后,流式细胞术检测LPS作用PMN的吞噬率变化.结果 PMN与M.tb作用,经抗酸染色,显微镜油镜观察到中性粒细胞内吞噬有大量粉红色索状M.tb.利用FITC标记M.tb,流式细胞术检测M.tb的标记率在95％.PMN与FITC标记M.tb 37℃水浴作用,利用流式细胞仪检测PMN吞噬率随孵育时间延长而增加.LPS预处理人PMN后,发现PMN 5 min吞噬百分率随LPS浓度增加而增高(P<0.05).TLR4单克隆抗体作用PMN,再与LPS作用后,PMN吞噬率较未加TLR4单克隆抗体作用有所降低(P<0.05).结论 LPS可通过TLR4增强PMN吞噬结核分枝杆菌功能.

Community‐acquired pneumonia (CAP) ,as a common severe infectious disease ,persistently poses threats to human health .The balance of inflammatory cytokines is closely associated with clinical outcomes of CAP ,glucocorticoids(GCs) therapy can not only regulate the immune response ,but also compensate the deficien‐cy of endogenous cortisol ,hence it can be used as one of common adjuvant therapies for CAP ,however ,the effica‐cy and safety remain to be determined .This article briefly describes inflammatory mechanisms of CAP and anti‐in‐flammatory effects of GCs ,introduces the value and safety of GCs in adjuvant treatment of CAP ,summarizes the application schemes for treatment of CAP ,and proposes that the use of medium and low dose of GCs in a short pe‐riod may benefit some of the CAP patients ,however ,more large‐scale clinical researches need to be carried out to verify and explore the indications for treatment of CAP with GCs and put forward the reasonable treatment regi‐mens .

Objective:To observe the effects of fasudil on the human umbilical vein endothelial cells(HUVECs) injury induced by lipopolysaccharide(LPS),explore its mechanism of action.Methods:HUVECs were obtained from human umbilical vein,digested with 0.1% type Ⅰ collagenase,and cultivated and passaged in endothelial cell culture medium.The cell morphology was observed under the inverted microscope,and the cells were identified using immunohistochemistry.HUVECs were randomly divided into the control group(cultured with endothelial cell medium),LPS group(cultured with 0.1 μg/mL LPS) and fasudil group(cultured with 3.275 μg/mL fasudil and 0.1 μg/mL LPS).The protein and mRNA levels of RhoA,ROCK2 and p-ERM were detected using Western blot and quantitative real-time PCR,respectively.Results:The primary cells could adhere to the plate after 24 hours of inoculation,and arranged as paving stone on the third day.The HUVECs identified using the immunohistochemistry staining of Ⅷ factor.related antigen.The protein and mRNA levels of RhoA,ROCK2 and p-ERM in LPS group were significantly higher than those in control group(P<0.01).The protein and mRNA levels of ROCK2 and p-ERM in fasudil group were lower than those in LPS group(P<0.01),the differences of the protein and mRNA levels of RhoA between fasudil group and LPS group were not statistically significant(P>0.05).Conclusions:The Rho/ROCK/ERM signaling pathway plays an important role in the cytoskeletal damage in HUVECs induced by LPS.Fasudil can inhibit the LPS-induced cytoskeletal rearrangement injury,the mechanism of which may be related to inhibiting the Rho/ROCK signaling pathway activation.

Objective:To explore the effects of tetramethylpyrazine( TMP) on the levels of RhoA,Rho associated coiled coil forming protein kinase 2(ROCK2),myosin light chain(MLC) phosphorylation and ezrin-radxin-moesin(ERM) phosphorylation in the injury of human umbilical vein endothelial cells ( HUVECs ) induced by lipopolysaccharide ( LPS ) . Methods:The HUVECs were cultured in vitro,and divided into the control group,LPS group and TMP groups(0. 5,1. 0,1. 5 mg/mL). The mRNA levels of RhoA,ROCK2 and p-EZR in endothelial cells were detected by real-time fluorescence quantitative PCR,and the protein levels of RhoA,ROCK2,p-MLC and p-ERM were examined using western blotting. Results:Compared with the control group, the protein levels of RhoA, ROCK2, p-MLC and p-ERM,and the mRNA levels of RhoA,ROCK2 and p-Ezr in LPS group significantly increased(P<0. 01). The differences of the protein and mRNA levels of RhoA between LPS group and 3 TMP groups were not statistically significant(P>0. 05). Compared with the LPS group,the protein levels of ROCK2,p-MLC and p-ERM,and the mRNA levels of ROCK2 and p-Ezr decreased significantly in 3 TMP groups(P<0. 01). The differences of the expression of ROCK2,p-MLC and p-ERM within 3 TMP groups were statistically significant(P <0. 05 to P < 0. 01). Conclusions:TMP may protect the HUVECs against LPS-induced injury by inhibiting the expressions of ROCK2, p-MLC and p-ERM in Rho/ROCK signaling pathways, and reducing the injury of LPS on endothelial cell skeleton.

Objective To investigate whether ligustrazine can reduce endotoxemia and inhibit the increase of lipopolysaccharide (LPS)-induced vascular permeability by suppressing Rho/ROCK signaling pathway in guinea pigs. Methods Eighteen of white male healthy guinea pigs were divided into three groups randomly and pretreated with intravenous injection of ligustrazine(3 or 6 mg/kg) or saline. 30 min later, LPS (100, 300, 1 000 μg/0.1 mL/site) and saline (0.1 mL/site) were administered intracutaneously at the dorsum of guinea pigs. Vascular permeability was determined by leakage area and absorbance of 610 nm (OD610) of Evans Blue dye after intracutaneous injection of LPS (100-1 000 μg/site). Results Dye leakage in the skin began to increase at 5 min, and revealed significant increase 2 h after LPS injection. Significant differences in the dye leakage area(F = 5.77, P < 0.05) and the OD610 (F = 7.736, P < 0.05) induced by 100, 300 and 1,000 ug/site of LPS administration were demonstrated between the control and ligustrazine groups (3 or 6 mg/kg). Conclusion Ligustrazine has protective effect on the hypermeability of endothelial cells induced by lipopolysaccharide, and inhibition of Rho/ROCK signaling pathway is a possible mechanism.

目的：对“翻转课堂”教学模式在医学机能实验学教学中的应用及应用效果进行评价。方法选择2014级临床医学一系1、2班作为研究对象,其中1班为实验组,采用“翻转课堂”的教学模式进行机能实验学教学,2班为对照组,采用传统的教学模式进行教学。课程结束后对两组学生采用相同的理论考试、技能操作考核,同时对实验组学生进行问卷调查评价教学效果。结果与对照组相比,实验组的理论考试成绩和技能操作成绩均较高,两组差异具有统计学意义( P<0.001)；问卷调查结果显示实验组的学生对“翻转课堂”教学效果5个项目评价为满意和比较满意均达93％以上。结论“翻转课堂”的教学模式对医学机能实验学的教学效果有较大的提高,是适应新形势下教学要求的可行的教学模式,应用优势显著。