Melatonin attenuates postmyocardial infarction injury via increasing Tom70 expression

Mitochondrial dysfunction leads to reactive oxygen species (ROS) overload, exacerbating injury in myocardial infarction (MI). As a receptor for translocases in the outer mitochondrial membrane (Tom) complex, Tom70 has an unknown function in MI, including melatonin‐induced protection against MI injury. We delivered specific small interfering RNAs against Tom70 or lentivirus vectors carrying Tom70a sequences into the left ventricles of mice or to cultured neonatal murine ventricular myocytes (NMVMs). At 48 h post‐transfection, the left anterior descending coronary arteries of mice were permanently ligated, while the NMVMs underwent continuous hypoxia. At 24 h after ischemia/hypoxia, oxidative stress was assessed by dihydroethidium and lucigenin‐enhanced luminescence, mitochondrial damage by transmission electron microscopy and ATP content, and cell apoptosis by terminal deoxynucleotidyl transferase dUTP nick‐end labeling and caspase‐3 assay. At 4 weeks after ischemia, cardiac function and fibrosis were evaluated in mice by echocardiography and Masson's trichrome staining, respectively. Ischemic/hypoxic insult reduced Tom70 expression in cardiomyocytes. Tom70 downregulation aggravated post‐MI injury, with increased mitochondrial fragmentation and ROS overload. In contrast, Tom70 upregulation alleviated post‐MI injury, with improved mitochondrial integrity and decreased ROS production. PGC‐1α/Tom70 expression in ischemic myocardium was increased with melatonin alone, but not when combined with luzindole. Melatonin attenuated post‐MI injury in control but not in Tom70‐deficient mice. N‐acetylcysteine (NAC) reversed the adverse effects of Tom70 deficiency in mitochondria and cardiomyocytes, but at a much higher concentration than melatonin. Our findings showed that Tom70 is essential for melatonin‐induced protection against post‐MI injury, by breaking the cycle of mitochondrial impairment and ROS generation.     

分析三维重建及3D打印技术在腹部外科临床教学中的应用

目的分析在腹部外科的临床教学中应用三维重建技术与3D打印技术的临床效果。方法选择2016年1月—2017年12月我院接收的腹部外科实习生60例作为研究对象,2016年1—12月抽取30例设置为对照组,2017年1—12月抽取30例设置为观察组,对照组实习生采用常规临床教学方法学习腹部外科相关知识,观察组实习生则在常规临床教学基础上应用三维重建技术与3D打印技术。经带教后对比分析两组实习生的培训反馈结果以及理论知识考核、实践操作考核成绩。结果经带教后,观察组实习生对临床带教的学习兴趣、理论理解、知识点掌握、记忆效果以及操作技能均明显高于常规组,组间数据差异有统计学意义(P<0.05);经考核,其结果显示观察组实习生的理论知识成绩与实践操作成绩均明显高于常规组,组间差异有统计学意义(P<0.05)。结论在腹部外科实习生的临床教学中,除了常规教学方法之外,将三维重建技术与3D打印技术加入其中可获得良好的应用效果,能够显著提升实习生对临床教学的学习兴趣与记忆效果等,提升实习生理论知识成绩与实践操作能力,临床应用效果显著,值得推广。     

适合机械性取栓的急性栓塞性脑梗死动物模型的建立与评价

目的:建立并评价适合动脉内机械取栓的急性栓塞性脑梗死动物模型。方法:血流临时阻断凝血酶注入法制作急性栓塞性脑梗死模型,利用颅内动脉取栓装置行机械性取栓。应用数字减影血管造影(DSA)、磁共振弥散成像(DWI)、经颅多普勒及病理检查来评价模型建立的效果,比较模型建立前后表观弥散系数(ADC)、大脑中动脉流速(Vmca)变化情况。结果:DSA显示制模的成功率为83%。栓塞6 h DWI显示梗塞灶,24 h病理检查TTC染色可见梗死区。取栓后颈总动脉再通率为80%,栓塞前后、取栓前后Vmca的比较差异有统计学意义(P<0.05),取栓组与非治疗组6 h Vmca比较差异有统计学意义;取栓组ADC值呈上升趋势,非治疗组ADC值下降,两组24 h的比较差异有统计学意义(P<0.05)。结论:本研究所建立的模型稳定,重复性好,适用于颅内动脉取栓装置的实验研究和疗效评价。     

T-bet与Thl/Th2在乙型肝炎中的作用机制

T-bet是T-box家族的一种重要转录因子,在CD4+T细胞Thl型的分化中起重要作用,并抑制Th2细胞因子合成,可使完全分化的Th2逆转为Th1。目前已证实多种疾病的发生、发展和预后涉及Thl/Th2分化失衡。而T-bet对Thl/Th2分化调控作用在疾病中的作用机制有助于解释疾病的发展机制,为疾病的治疗提供依据。文中就T-bet在乙型肝炎中的作用机制作一综述。     

疗养院体检服务质量评价系统的实践

本文详细介绍了疗养院体检服务质量评价系统的设计目的 、设计方法和主要实现功能.该系统的应用,使体检人员的意见得到及时反馈,有助于管理者对各科室及员工的服务水准和存在问题进行判断总结,从而促进了疗养院体检服务质量水平的进一步提高.     

引导性反馈在内科模拟教学中的应用分析

目的探讨引导性反馈在内科模拟教学中的应用价值。方法此次研究所纳入的内科实习生均自2017年1月—2019年1月份进入本院,抽选量为80例。以随机数字表法完成分组,将应用常规内科模拟教学的40例内科实习生设立为参照组,将联合引导性反馈的40例患者设立为观察组。两组均由同组教师进行授课教学,教学后进行考核。经考核成绩分析和发放教学满意度问卷,比对两组实习生的教学情况。结果观察组的操作技巧、人文关怀、应急能力、理论知识分值更高,与参照组差异有统计学意义(P<0.05)。观察组的教学满意度更高,与参照组差异有统计学意义(P<0.05)。结论在内科模拟教学中开展引导性反馈,可强化学生对学习的反思,使学生教学积极性得到提高,有效提高学生教学成绩,改善教学质量。     

First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric,gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis

First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.     

不同剂量普奈洛尔治疗婴儿血管瘤的疗效评价

目的：探讨不同剂量普奈洛尔治疗婴儿混合型和深层血管瘤的临床效果，为血管瘤的治疗提供理论和实验依据。方法：将入选的62例混合型和深层血管瘤患儿随机分为普奈洛尔低剂量组和高剂量组，每组31例，分别采用1.5和3.0 mg.kg-1?d-1普奈洛尔口服，每日3次，疗程6个月，动态观察血管瘤的体积变化及不良事件发生率。结果：根据Achauer 疗效判定标准进行疗效比较，普奈洛尔低剂量组患儿总有效率为80.65%（其中Ⅰ级 6例，Ⅱ级 9例，Ⅲ级 11例，Ⅳ级5例)，普奈洛尔高剂量组患儿总有效率为93.55%(其中Ⅰ级 2例，Ⅱ级4例，Ⅲ级 10例，Ⅳ级15例)，普奈洛尔高剂量组疗效优于低剂量组(P<0.01)。不同部位和不同类型血管瘤疗效比较差异均无统计学意义(P>0.05)。2组患儿不良事件发生率比较差异无统计学意义(P>0.05)。 结论：普奈洛尔3.0 mg?kg-1?d-1口服治疗婴儿混合型和深层血管瘤疗效明显增加，但不良反应未见增加。建议临床治疗婴儿血管瘤时，可提高普奈洛尔的剂量，以提高治疗效果。     

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses

Background and aimsObservational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults.Methods and resultsThe China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]).ConclusionsThis study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.