Objective The objective of the study was to explore whether Suanzaoren(Semen Ziziphi Spinosae,SZS)extract could improve insomnia by inhibiting the p38 mitogen-activated protein kinase(p38MAPK)/nuclear factor-κB(NF-κB)signaling pathway. Methods Forty SPF-grade Sprague-Dawley(SD)rats were included in the study,with 10 randomly selected rats serving as the control group.The remaining rats were injected intraperitoneally with p-chlorophenylalanine(PCPA)for 6 days to establish an insomnia model.After successful modeling,the rats were divided into the model group,SZS extract group(3.0 g/kg),and zopiclone group(1.25 g/kg).The rats in the SZS extract and zopiclone groups were administered with the corresponding drugs via gavage for 7 days,while the rats in the control and model groups received distilled water.Sleep latency and sleep duration were recorded,and behavioral changes were observed through elevated plus-maze and open field tests.The levels of oxidative stress markers and serum inflammatory factors were measured by enzyme-linked immunosorbent assay(ELISA).The expression levels of p38 MAPK,p-p38MAPK,p-NF-κBp65,and NF-κBp65 protein in the cerebral cortex were detected by Western blot.Neuronal structures in the cerebral cortex were observed under a transmission electron microscope. Results Compared with the control group,the model group exhibited abnormal appearances,significant body mass loss(p＜0.001),prolonged sleep latency and shortened sleep duration(p＜0.001).The SZS extract and zopiclone groups showed significant improvements in these parameters compared with the model group.Compared with the control group,the model group showed significant reduction in total movement distance(p＜0.001),fewer entries into the central zone(p＜0.01),and significant decrease in rearing frequency(p＜0.001);the levels of glutathione peroxidase(GSH-Px)and catalase(CAT)in the hippocampus were significantly reduced(p＜0.001);the serum levels of interleukin-1 β(IL-1β),tumor necrosis factor-α(TNF-α),and the expression levels of p-p38MAPK and p-NF-κBp65 in the cerebral cortex were significantly increased(p＜0.05).Compared with the model group,the SZS extract group showed significant increase in movement distance(p＜0.01)and rearing frequency(p＜0.001),significantly increased the GSH-Px and CAT levels(p＜0.001),and decreased the IL-1 β and TNF-α levels(p＜0.01);furthermore,the SZS extract group showed a significantly reduced p-p38MAPK and p-NF-κBp65 levels(p＜0.05).The SZS extract group showed significant improvement in the neuronal structure compared with the model group.

C1q/tumor necrosis factor-related protein-6 (CTRP6) has multiple protective effects against cardiovascular diseases. Myofibroblast differentiation plays a critical role in cardiac fibrosis under various cardiac pathological conditions. The aim of the present study was to determine the effects of CTRP6 on cardiac fibrosis, and to identify the possible mechanisms of action. Toward this end, we measured the expression of fibrotic markers, including collagen I, collagen III, CTGF, and TGFβ1, and assessed the effects of CTRP6 on cardiac fibroblast differentiation into myofibroblasts. CTRP6 inhibited the expression of the angiotensin II (Ang II)-induced myofibroblast markers α-SMA and SM22, and of profibrotic molecules, including collagen I, collagen III, CTGF, TGFβ1, MMP2, MMP9, and TIMP1. Furthermore, CTRP6 significantly attenuated the proliferation and migration of cardiac fibroblasts incubated with Ang II and activated the phosphorylation of AMP-activated protein kinase (AMPK). Incubation with an AMPK inhibitor reversed the subsequent inhibitory effects of CTRP6 on Ang II-induced myofibroblast differentiation. Therefore, CTRP6 suppresses cardiac fibrosis by inhibition of myofibroblast differentiation via AMPK pathway activation, suggesting CTRP6 as a target for the treatment of cardiac fibrosis.

Objectives This study aimed to investigate the therapeutic effects of Suan Zao Ren(Semen Ziziphi Spinosae,SZS)extract on insomnia induced by p-chlorophenylalanine(PCPA)in rats and its influence on the thioredoxin-interacting protein(TXNIP)/nucleo-tide-binding domain Leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3)inflammasome pathway,and to preliminarily explore the mechanism by which SZS extract improves insomnia. Methods Fifty male Sprague-Dawley(SD)rats were used,with 8 rats in the blank group and 42 rats in the modeling group.The modeling group was induced by intraperitoneal injection of PCPA at a dose of 500 mg·kg-1 for six consecutive days,with daily cage exchange.After 6 days,40 successfully modeled rats were randomly divided into five groups:the model group(equal volume of distilled water),the positive group(0.75 mg·kg-1),and low-,medium-,and high-dose SZS extract groups(1.5,3,and 6 g·kg-1,respectively),with 8 rats in each group.Treatments were administered for seven consecutive days.Enzyme-linked immunosorbent assay was used to measure levels of 5-hydroxytryptamine(5-HT)and gamma-aminobutyric acid(GABA)in the rat cerebral cortex.The thiobarbituric acid(TBA)method was used to determine malon-dialdehyde(MDA)levels,and the hydroxylamine method was used to determine superoxide dismutase(SOD)levels.The 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)method was used to measure total antioxidant capacity(TAOC)in the cerebral cortex.Pathological changes in the cerebral cortex were observed,and Western blot was used to detect the protein expressions of TXNIP,NLRP3,apoptosis-associated speck-like protein containing a Caspase activation and recruitment domain(CARD),and cysteine-aspartate-specific protease 1(Caspase-1)in the cerebral cortex. Results Compared with the blank group,the model group showed a significantly prolonged sleep latency(p＜0.001)and a significantly shortened sleep duration(p＜0.001).There were no changes in serum MDA and SOD levels.MDA levels in the cerebral cortex were significantly increased(p＜0.001),while SOD and TAOC levels were significantly decreased(p＜0.001).The 5-HT level was increased(p＜0.05),and the GABA level was significantly decreased(p＜0.001).SZS extract improved these conditions to varying degrees.Light microscopy showed no significant changes in cortical neurons but transmission electron microscopy revealed intact mitochondrial structures in the blank group,while the model group showed swollen and unclear mitochondria with reduced organelles.After 7 days of treatment,these conditions improved in the SZS extract groups.Compared with the blank group,the expressions of the four proteins in the model group were increased,and the expressions of these proteins were decreased in the SZS extract groups compared with the model group. Conclusion SZS extract may exert an antioxidant effect to treat insomnia by down-regulating the expression of TXNIP/NLRP3 proteins and regulating oxidative stress levels in the cerebral cortex.

目的 观察强骨抗萎膏对尾吊大鼠骨细胞凋亡和内质网应激的影响,探讨强骨抗萎膏防治模拟失重状态下骨丢失的机制.方法 60 只SD大鼠分为对照组、模拟失重组、强骨抗萎膏组、阿仑膦酸钠组,骨疏康颗粒组,每组 12 只.采用尾部悬吊模拟失重状态,尾吊 28 d;对照组和模拟失重组给予每日等体积生理盐水灌胃,其它 3 组复制模型,分别每日给予中药强骨抗萎膏 2.4 g/kg,阿仑膦酸钠 0.007 g/kg,骨疏康颗粒 0.26 g/kg灌胃.持续给药 4 周后处死大鼠,TUNEL法检测骨细胞凋亡情况;Western blot法检测葡萄糖调节蛋白 78(GRP78)和线粒体融合蛋白 2(MFN2)表达,RT-PCR和Western blot检测骨组织中蛋白激酶R样内质网激酶(PERK),肌醇依赖性激酶 1α(IRE1α)、活化转录因子 6(ATF6)及C/EBP同源蛋白(CHOP)的基因和蛋白表达.结果 TUNEL结果显示模拟失重组骨细胞凋亡较对照组增加,强骨抗萎膏可抑制骨细胞凋亡.与对照组大鼠比较,模拟失重组PERK基因表达量明显增高(P＜0.05),强骨抗萎膏组较模拟失重组PERK基因表达量下降(P＜0.05);与对照组比较,模拟失重组的GRP78、PERK、CHOP和ATF6 蛋白含量明显增高(P＜0.05),MFN2 蛋白表达降低(P＜0.05),强骨抗萎膏组较模拟失重组GRP78、PERK、CHOP和ATF6 蛋白含量均明显降低(P＜0.05),MFN2 表达量升高.结论 强骨抗萎膏可以改善模拟失重大鼠骨细胞凋亡,通过抑制骨组织内质网应激相关因子GRP78、PERK、ATF6 和CHOP,上调MFN2 表达,从而改善失重条件下的骨丢失.

目的 观察肾气丸对糖尿病ZDF大鼠肾脏损伤的影响及对足细胞损伤的干预作用.方法 实验分为对照组[ZDF(fa/+),14只]、模型组[ZDF(fa/fa),20只]及肾气丸组[ZDF(fa/fa)+肾气丸,20只].对照及模型组大鼠每日灌服生理盐水(10 mL/kg),肾气丸组每天灌服肾气丸水煎液(8.12 g/kg).饲养期间,记录大鼠一般状态,定期称重并于12、16、20周龄测定空腹血糖.治疗4周后(16周龄)或治疗8周后(20周龄)处死大鼠,收集血清及24 h尿液.检测血清中总胆固醇(CHOL)、甘油三酯(TG)、血肌酐(CREA)、血尿酸(UA)、血尿素氮(BUN)及尿微量白蛋白的含量,取肾组织进行形态学观察,免疫荧光法检测足细胞标志物nephrin的表达水平.结果 与对照组比较,16周龄和20周龄模型组大鼠体重增长率明显下降(P<0.05),空腹血糖水平显著升高(P<0.05),血清总胆固醇、甘油三酯、肌酐、尿酸及尿微量白蛋白水平显著升高(P<0.05);肾脏形态学表现为肾小球毛细血管扩张,肾小球纤维化、硬化,系膜区增宽,肾小管上皮细胞空泡样改变及糖原沉积,肾小管萎缩,管腔内蛋白管型,间质胶原组织增多;超微结构显示肾小球基底膜增厚,足细胞线粒体肿胀,足突融合;模型组肾组织足细胞标志物nephrin表达减少;相较模型组,肾气丸治疗4或8周后,大鼠体重增长率明显上调(P<0.05),空腹血糖水平显著降低(P<0.05),血清甘油三酯、肌酐、尿酸及尿微量白蛋白水平显著减少(P<0.05),肾组织病理损伤减轻,nephrin表达增强.结论 肾气丸可减轻糖尿病大鼠肾脏病理损害,改善肾功能,维护足细胞结构和功能,发挥肾脏保护作用.

Background: ShenQiWan is commonly used in traditional Chinese medicine for the treatment of diabetic nephropathy, which is closely related to mitochondrial fusion and endoplasmic reticulum stress. This study aimed to investigate the intervention effect and molecular mechanisms of ShenQiWan on renal injury in KKAy mice.Methods: C57BL/6J mice (11 weeks old) were fed a regular diet upon arrival, while KKAy mice (11 weeks old) were fed a high-fat diet upon arrival. At 12 weeks of age, KKAy mice with random blood glucose ≥13.9 mmol/L were identified as diabetic mice and randomly divided into the model group (n = 30) and the treatment group (n = 30), while C57BL/6J mice of 12 weeks old (n = 30) served as the control group. The treatment group received daily aqueous decoction of ShenQiWan (13.5 g/kg), while the control group and model group received daily equal amounts of saline from 12 weeks old to 24 weeks old. The general status of mice was observed regularly, and fasting blood glucose and 24-hour urine microalbumin were measured. Ten mice were euthanized in each group at the age of 16, 20, and 24 weeks, serum samples were used for biochemical indexes and kidney tissues were used for morphological studies. GRP78, OPA1, MFN1, MFN2 mRNA and protein expression were detected by Real-time PCR, immunohistochemistry and Western blot.Results: The mice in the model group exhibited symptoms of lethargy, slow movement, obesity, polyuria and proteinuria. Morphological observation revealed pathological changes, including thickening of the glomerular basement membrane and interstitial fibrosis. After treatment with ShenQiWan, the fasting blood glucose level of KKAy mice was significantly reduced, urinary albuminuria was decreased, serum biochemical indexes were improved, renal tissue pathological changes were significantly alleviated. The results also showed a significant reduction in the expression of endoplasmic reticulum stress-related factor GRP78 and an increase in the expression of mitochondrial fusion-related factors OPA1, MFN1 and MFN2 after treatment with ShenQiWan.Conclusion: ShenQiWan can protect diabetic mice from renal damage by modulating mitochondrial fusion and alleviating endoplasmic reticulum stress, exerting its protective effects.

目的 探讨肾气丸对糖尿病ZDF大鼠肾损伤的干预作用及其作用机制是否为通过PERK通路降低ERS.方法 12周龄雄性ZDF(fa/fa)大鼠随机分为模型组与肾气丸组,同周龄雄性ZDF(fa/+)大鼠为对照组.肾气丸组每日灌服肾气丸水煎液(8.12 g/kg),对照组和模型组每日灌服等量生理盐水.定期观察大鼠一般状态并检测空腹血糖及24 h尿微量白蛋白.16周龄时取材,运用PAS、Masson、PAM-HE染色观察肾组织病理变化,检测肾组织GRP78、PERK、eIF2α、ATF4等因子表达水平.结果 模型组大鼠出现体重增长缓慢、体毛光泽度减弱、活动不积极等表现,肾气丸组较模型组相比大鼠体重稳定增长,体毛光亮,活动较正常.模型组大鼠空腹血糖和24 h尿微量白蛋白均显著高于对照组,肾气丸组较模型组明显降低(P<0.05).模型组肾小球毛细血管扩张,基膜不规则增厚,系膜区增宽,部分肾小球出现节段性硬化;可见肾小管萎缩,肾间质纤维组织增生.灌服肾气丸后,肾病理变化明显减轻.模型组GRP78、PERK和eIF2α的mRNA和蛋白表达均显著高于对照组,肾气丸组显著低于模型组(P<0.05);模型组和肾气丸组ATF4的mRNA表达无差异,但肾气丸组ATF4的蛋白明显低于模型组(P<0.05).结论 肾气丸可能通过影响内质网应激PERK通路减轻糖尿病ZDF大鼠的肾损伤.

目的 回顾性探究基于案例教学法(case-based learning,CBL)的半翻转课堂教学模式在病理生理学本科生线上教学中的应用.方法 选取北京中医药大学2017—2020年病理生理学授课学习的所有本科生,分为对照组(2017—2019年以传统课堂模式教学的本科生)和实验组(2020年基于CBL的半翻转课堂教学的本科生),教学完成后,针对学生的教学满意度等问卷调查、期末考试成绩以及教学督导专家意见进行总结.结果 与传统的教学模式相比,学生对基于CBL的半翻转课堂线上教学模式中教师的教学以及学生的学习效果评价较好[自主学习能力(3.96±0.93)分、满足个人学习要求(3.95±0.86)分、知识掌握情况(3.80±0.86)分];与其他线上平台相比,利用微信授课易被学生接受[(3.87±1.03)分];线上授课[实验组2020年成绩为85.0(81.0,89.0)分]的学生期末考试成绩较传统课堂教学模式[对照组:2017年、2018年、2019年成绩分别为75.0(66.5,83.5)分、73.0(67.0,80.0)分、76.0(67.5,84.5)分]明显提高(P<0.001);教学督导专家也有积极的评价.结论 基于CBL的半翻转课堂在病理生理学本科生线上教学效果好,学生满意度高,是一种值得尝试的教学模式.

在高等医学教育体系中,病理学实验侧重病变器官、组织的形态学观察.随着虚拟技术的发展,依靠虚拟技术建立的数字化教学平台在高校实验教学中的应用越来越广泛,并逐渐引入病理实验教学中.本研究阐述了病理实验教学模式的发展变化,通过调查问卷的形式,就学生对数字化教学平台的满意度、对教学模式的支持度进行了调查研究,旨在进一步促进病理实验教学模式的融合,激发学生兴趣,提高教学质量,加快教学改革.

与传统的线下课堂教学相比,线上教学给教师、学生及网络平台均带来了巨大挑战.本研究针对北京中医药大学2020年中医学实验班二年级120名本科生开展为期一学期的线上病理生理学教学,并从线上教学的挑战性、线上课堂的实施策略、教学问卷调查及学习成绩等方面总结了线上教学实践过程,形成了病理生理学线上教学的经验,为进一步提高医学课程的线上教学水平和医学生的人才培养质量提供参考借鉴.

目的:探讨黄芪甲苷联合葛根素对高糖诱导的H9c2细胞内质网应激及其凋亡相关因子的影响.方法:将对数生长期的H9c2细胞随机分为对照组、甘露醇对照组、高糖组、高糖+4-苯基丁酸(4-phenylbutyric acid,4-PBA)组、毒胡萝卜素(thapsigargin,TG)组、高糖+黄芪甲苷+葛根素组;CCK-8法检测H9c2细胞活力;Western blot检测凋亡相关蛋白B淋巴细胞瘤2(B-cell lymphoma-2,Bcl-2)和Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)表达.RT-qPCR及Western blot检测葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)、肌醇酶1α(inositol-re-quiring enzyme 1α,IRE1α)、调控X盒结合蛋白1(X-box binding protein 1,XBP1)、转录因子C/EBP同源蛋白(C/EBP homologous protein,CHOP)、p53上调凋亡调节因子(p53 up-regulate modulator of apoptosis,PUMA)mRNA和蛋白的表达.结果:与对照组相比,高糖组Bax/Bcl-2比值显著增加(P<0.01),高糖组和TG组GRP78、IRE1α、XBP1、CHOP和PUMA表达增加(P<0.05),4-PBA或黄芪甲苷联合葛根素均可降低高糖诱导的GRP78、IRE1α、XBP1、CHOP和PUMA的高表达和Bax/Bcl-2比值(P<0.05).结论:黄芪甲苷联合葛根素对高糖诱导的H9c2细胞内质网应激及凋亡相关因子有抑制作用.

针对“两张皮”“贴标签”等高校课程思政建设中存在的不足之处，从论述课程思政是加强高校思想政治工作的重要切入点，结合中医药院校病理学课程特色，深度挖掘课程中蕴含的思政元素，从爱国奉献、敬业奋斗、求真务实、实践创新等四个方面，构建课程思政的有效策略和方法。首先，明确病理学课程思政建设目标、科学设计病理学课程思政教学体系；其次，加强病理学课程思政建设的组织领导、提高教师的思想政治工作水平；最后，制定病理学课程的特色育人目标、建立第一课堂和第二课堂相联动的育人模式和建立体现三全育人标准的病理学课程考核评价体系。课

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease worldwide and is the main microvascular complication of diabetes. The increasing prevalence of diabetes has increased the need for effective treatment of DKD and identification of new therapeutic targets for better clinical management. Mitophagy is a highly conserved process that selectively removes damaged or unnecessary mitochondria via the autophagic machinery. Given the important role of mitophagy in the increased risk of DKD, especially with the recent surge in COVID-19-associated diabetic complications, in this review, we provide compelling evidence for maintaining homeostasis in the glomeruli and tubules and its underlying mechanisms, and offer new insights into potential therapeutic approaches for treatment of DKD.

随着中医药在全球地位的提升,中医院校的留学生数量也在增加.病理生理学是医学基础学科之一,是医学生必修课程,同时也是紧密联系基础与临床的桥梁学科之一.提高病理生理学教学质量是留学生基础教学的重要方面,将对其今后的临床工作有很大的帮助.课堂教学中,教师灵活运用包括思维导图、案例式教学、问题导入法等多种教学方法和手段,使抽象的病理生理学内容变得生动而具体,有助于提高中医院校留学生病理生理学的教学质量,提升教学效果.

目的:探讨超低频电磁场处理水(频谱水)及红外频谱照射(频谱外照)对糖尿病大鼠体重、血糖及肾损伤的干预作用.方法:90只大鼠随机分为5组,每组18只,即正常对照组、模型组(2％STZ 50mg/kg体重腹腔注射,随机血糖≥16.7mmol/L)、频谱水组(STZ+饮用频谱水)、外照组(STZ+频谱外照)、盐酸二甲双胍对照组(STZ+盐酸二甲双胍).正常对照组与模型组每日灌胃生理盐水,其余各组分别灌胃或进行相应药物治疗.观察大鼠一般状态,每两周测定体重、空腹血糖,饲养8周后取所需组织检测血清中尿素、肌酐、尿酸、24h尿微量白蛋白等指标并观察肾脏病理学改变.结果:糖尿病大鼠进行饮用频谱水或红外频谱照射在一定程度上可以降低糖尿病大鼠模型血清肌酐和尿酸水平,但是不能有效降低24h尿微量白蛋白,并且可以减轻糖尿病大鼠模型的肾小管上皮细胞变性,维持肾小管上皮细胞线粒体与粗面内质网结构.结论:饮用频谱水及频谱外照治疗对糖尿病模型大鼠干预8周后,可减轻大鼠肾小管上皮细胞线粒体、内质网损伤,缓解肾组织病变,降低血清肌酐、尿酸水平,从而起到保护肾脏的作用.

为培养新时代德才兼备的医学人才,加强学生思想政治教育至关重要,从而提升学生思想道德水平.结合现阶段医学生的学习情况和思想政治教育的特点,将课程思政内容融入病理学课程教学中.通过激发爱国情怀、学习适应损伤、追踪科技新知、寻找科学真相、启发思辨意识,渗透创新思维、浸润科学态度和洞悉国情民生等八项举措,将思想政治元素与理论知识完美结合,从而提升学生的知识储备、责任意识和服务能力,真正实现教书与育人相统一.课程思政融入病理学的教学实践,提升了学生的学习兴趣、责任意识和服务能力,取得了较好的教学效果.

针对解剖学、组织学与胚胎学和病理学的实验附属于各自的理论课,在不同的学期授课,各门实验课之间缺乏关联,造成知识的割裂的现状,梳理现有形态学实验课程,在教材编写、课程设立、教学手段方面进行了改革探索.尝试建立以人体系统、器官为主线,以疾病为中心,从正常器官结构到异常器官结构,从整体器官形态观察到镜下微细结构的实验模式.希望不断深入形态学实验教学改革,一方面有利于学生对关联知识的融会贯通,另一方面培养学生的临床意识.

目的 探讨黄芪注射液联合葛根素注射液通过缓解内质网应激(ERS)、抑制心肌细胞凋亡,改善2型糖尿病(T2DM)动物KKAy小鼠心脏损害,防治糖尿病心肌病的机制.方法 11周龄的KKAy糖尿病模型小鼠按血糖随机分为模型组和黄芪葛根组(黄芪注射液3 mL/kg联合葛根素注射液1.3 mL/kg进行治疗),同周龄雄性C57 BL/6 J小鼠作为正常对照组,适应性饲养1周后,于12周龄开始实验干预,在20、24和28周龄分批处理小鼠.电镜观察心肌形态改变,RT-PCR及West-ern Blot检测心脏组织葡萄糖调节蛋白78(GRP78)、C/EBP同源蛋白(C/EBP homologous Protein,CHOP)、p53凋亡上调基因(p53 up-regulate modulator of apoptosis,PUMA)基因和蛋白的表达.结果 透射电镜显示,模型组小鼠心肌细胞细胞核、内质网和线粒体肿胀,黄芪葛根组较模型组情况显著改善;RT-PCR和Western Blot结果显示,与正常组相比,3个周龄段模型组GRP78的基因和蛋白表达水平均明显升高,黄芪葛根组GRP78的基因和蛋白表达较模型组均显著下降,差异具有统计学意义(P<0.05).CHOP和PUMA的基因和蛋白表达,3个周龄段模型组较正常组均增加(P<0.05),24、28周龄黄芪葛根组较模型组均下降((P<0.05).结论 黄芪注射液与葛根素注射液联用对糖尿病小鼠心肌细胞超微结构具有保护作用,可缓解内质网应激,抑制心肌细胞凋亡,这可能是其防治糖尿病心肌病的机制之一.

形态学是医学生必修的基础课程,实验教学又是理论课程的实践,因此坚持形态学实验的发展和改革一直是高校教育的重点.随着科技发展,数字化技术融入实验教学平台中来,教学环境有了很大改善.文章对显微互动系统及数字化教学平台在形态学实验教学中的应用做了简要叙述,就传统教学模式和数字化教学模式进行对比分析,加强实验室的管理维护,让数字化技术更好地为教学服务.