自发性高血压大鼠永久性脑缺血模型建立的研究

目的在比较自发性高血压大鼠(SHR)与同龄无高血压Wistar大鼠永久性大脑中动脉阻塞(pMCAO)后脑缺血损伤情况并初步分析其可能机制。方法雄性SHR和Wistar大鼠各30只分别随机分为:pMCAO模型6 h组、假手术6 h组、pMCAO模型24 h组、假手术24 h组和正常组(均n=6)。采用线栓法制作pMCAO模型,术后6、24 h对大鼠进行神经功能学评分后处死,制作脑冠状切片。术后6 h处死大鼠脑部切片行尼氏染色后在组织学层面上观察神经元损伤情况;术后24 h处死大鼠脑部切片行尼氏染色后计算脑梗死体积和水肿程度百分比。正常组脑部切片经苏木精-伊红染色后计算脑部小血管壁/腔比。结果术后6和24 h,不同品系大鼠神经功能学评分差异无统计学意义(P0.05);术后6 h尼氏染色示SHR神经元损伤重于Wistar大鼠。术后24 h SHR脑梗死体积百分比[(28.05±2.38)%]大于Wistar大鼠[(25.23±1.33)%],差异有统计学意义(P0.05)。两品系大鼠之间脑水肿程度差异无显著性。脑部小血管壁/腔比SHR[(11.46±3.74)%]较Wistar大鼠[(8.73±1.73)%]增大(P0.05)。结论 pMCAO术后SHR的脑缺血损伤程度重于Wistar大鼠,可能与高血压引起的脑侧支循环血管壁增厚、僵硬,自我调节能力降低有关。     

Characterization of membrane occupation and recognition nexus repeat containing 3, meiosis expressed gene 1 binding partner,in mouse male germ cells

Mammalian spermatogenesis is a well-organized process of cell development and differentiation. Meiosis expressed gene 1 (MEIG1) plays an essential role in the regulation of spermiogenesis. To explore potential mechanisms of MEIG1''s action, a yeast two-hybrid screen was conducted, and several potential binding partners were identified; one of them was membrane occupation and recognition nexus repeat containing 3 (MORN3). MORN3 mRNA is only abundant in mouse testis. In the testis, Morn3 mRNA is highly expressed in the spermiogenesis stage. Specific anti-MORN3 polyclonal antibody was generated against N-terminus of the full-length MORN3 protein, and MORN3 expression and localization was examined in vitro and in vivo. In transfected Chinese hamster ovary cells, the antibody specifically crossed-reacted the full-length MORN3 protein, and immunofluorescence staining revealed that MORN3 was localized throughout the cytoplasm. Among multiple mouse tissues, about 25 kDa protein, was identified only in the testis. The protein was highly expressed after day 20 of birth. Immunofluorescence staining on mixed testicular cells isolated from adult wild-type mice demonstrated that MORN3 was expressed in the acrosome in germ cells throughout spermiogenesis. The protein was also present in the manchette of elongating spermatids. The total MORN3 expression and acrosome localization were not changed in the Meig 1-deficient mice. However, its expression in manchette was dramatically reduced in the mutant mice. Our studies suggest that MORN3 is another regulator for spermatogenesis, probably together with MEIG1.     

非高密度脂蛋白胆固醇水平与冠心病患者冠状动脉病变Gensini评分的相关性研究

目的 探讨非高密度脂蛋白胆固醇水平(non-HDL-C)与冠心病(CHD)患者冠状动脉病变Gensini评分的关系及临床意义。方法 对225例疑诊或既往临床诊断CHD患者予以冠状动脉造影(CAG),将造影阴性的39例作为对照组(HC组),造影阳性的186例患者诊断为CHD,结合临床特点分为心绞痛组(AP组)122例和心肌梗死组(AMI组)64例。采用Gensini评分对冠状动脉病变程度评分,测定患者全套血脂水平,探讨non-HDL-C及相关脂质成分与冠状动脉病变程度Gensini评分的相关性;同时对他汀类药物强化降脂达标,低密度脂蛋白胆固醇(LDL-C)<1.80 mmol/L的AP组患者进行non-HDL-C与冠状动脉病变程度Gensini评分的亚组分析。结果 AMI组non-HDL-C水平高于AP组及HC组,AP组non-HDL-C水平高于HC组,差异均有统计学意义(P<0.05);CHD患者non-HDL-C水平与Gensini评分呈正相关(r=0.562,P<0.05);LDL-C控制达标的AP组患者,高non-HDL-C组(≥2.60 mmol/L)比低non-HDL-C组(<2.60 mmol/L)Gensini评分明显升高,差异均有统计学意义(P<0.05)。结论 non-HDL-C与冠状动脉病变程度密切相关,non-HDL-C在评估LDL-C控制达标患者的冠状动脉病变程度及再发心血管事件风险上有一定价值,可作为LDL-C达标后心血管残余风险新的观察指标。     

Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation

Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose‐dependent manner. The observed apoptosis was accompanied by the melatonin‐induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4‐specific siRNA effectively attenuated the melatonin‐induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin‐induced apoptosis. Moreover, constitutively active Ca²⁺/calmodulin‐dependent protein kinase II alpha (CaMKIIα) abrogated the melatonin‐induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl‐2 promoter, leading to a reduction of bcl‐2 expression, whereas constitutively active CaMKIIα(T286D) or HDAC4‐specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin‐induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKIIα.     

抗信号识别颗粒抗体阳性肌病伴心脏损害1例

1临床资料患者,男,43岁,因"四肢近端肌肉无力9个月,加剧1周"于2013年9月22日入院。患者于9个月前无明显诱因下出现四肢肌肉无力,以近端肌力减退为主,主要表现为上楼梯费力,提重物困难,易疲劳,尚可参加工作,无发热、皮疹、肌痛、感觉异常等,无明显晨轻暮重的波动现象,上述症状逐渐加重,劳动耐量和日常生活能力进行性下     

肌少症对老年肝癌术后恢复及预后的影响

目的:肌少症对老年肝癌术后恢复及预后的影响。方法:选取2015年1月至2017年12月收治的114例老年肝癌，根据有无合并肌少症，分为肌少症组（n=35）和非肌少症组（n=79）。比较两组患者的术后恢复及生存情况。结果:肌少症组总并发症发生率、住院时间和30 d再入院率均高于对照组，差异均有统计学意义（P＜0.05）。肌少症组中位生存时间为25.9个月，1年、2年、3年累积总生存率为74.3%、51.1%、24.5%，而非肌少症组中位生存时间为35.7个月，1年、2年、3年累积总生存率为87.3%、75.6%、49.4%，差异有统计学意义（P=0.004）。单因素分析结果显示，老年肝癌术后预后与Charlson合并症指数（CCI）、肌少症、巴塞罗那分期（BCLC）、甲胎蛋白、肿瘤大小、肿瘤个数、肿瘤分化程度、微血管侵犯（MVI）相关（P＜0.05）。Cox多因素分析结果显示，CCI、肌少症、BCLC分期、肿瘤个数、MVI是老年肝癌术后预后的独立危险因素（P＜0.05）。结论:肌少症会增加老年肝癌患者术后并发症发生率，延长住院时间，影响术后恢复，同时也会降低总生存率。