利拉鲁肽治疗非酒精性脂肪性肝病合并2型糖尿病患者血脂、血管内皮功能和肝纤维化指标的变化*

目的 探讨应用利拉鲁肽治疗非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)患者血脂、血管内皮功能和血清肝纤维化指标的变化。方法 2014年1月～2018年12月我院收治的NAFLD合并T2DM患者90例,被随机分为对照组45例和观察组45例,分别给予二甲双胍或二甲双胍联合利拉鲁肽治疗12周。检测空腹血糖(FPG)、餐后 2 h 血糖(2hPPG)和糖化血红蛋白(HbA1c),使用高分辨超声诊断仪检测肱动脉内径变化,记录血管舒张内径达到最大值所需的时间(T₁)和舌下含化硝酸甘油后血管达最大内径所需的时间(T₂),计算肱动脉血流介导的内皮依赖性血管舒张功能(EDR)和硝酸甘油介导的内皮非依赖性血管舒张功能(END)。采用放射免疫分析法检测血清透明质酸(HA)、 层粘连蛋白(LN)、 IV型胶原(CIV)和 III型前胶原(PIIIP)。结果 在治疗结束时,观察组和对照组FPG分别为(7.3±1.9)mmol/L对(8.6±1.8)mmol/L,2hPPG分别为(9.8±2.3)mmol/L对(11.4±2.2)mmol/L,HbA1c水平分别为(7.2±1.0)%对(8.3±1.2)%,差异显著(P＜0.05);血清TC分别为(4.8±0.9)mmol/L对(5.6±1.2)mmol/L、TG分别为(1.5±0.4)mmol/L对(2.0±0.6)mmol/L、LDL-C分别为(2.0±0.6)mmol/L对(2.9±0.7)mmol/L和HDL-C分别为(1.6±0.3)mmol/L对(1.3±0.2)mmol/L,差异显著(P＜0.05);T₁分别为(56.1±6.5)s对(62.9±5.8)s,EDR分别为(7.8±1.0)%对(5.2±0.8)%和END分别为(21.3±2.9)%对(17.2±2.5)%,差异显著(P＜0.05);血清HA分别为(70.3±9.2)ng/ml对(85.9±10.3)ng/ml, CIV分别为(50.2±0.7)ng/ml对(67.3±0.9)ng/ml和PIIIP分别为(6.2±0.6)ng/ml对(8.3±0.5)ng/ml,差异显著(P＜0.05)。结论 应用利拉鲁肽治疗NAFLD合并2 型糖尿病患者能有效降低血糖,改善血管内皮功能,纠正脂代谢紊乱,对预防糖尿病患者大血管并发症可能有益。     

阿司匹林联合替格瑞洛或氯吡格雷对急性冠状动脉综合征患者高尿酸血症发生率影响的对比研究

目的 比较阿司匹林联合替格瑞洛或氯吡格雷对急性冠状动脉综合征(ACS)患者高尿酸血症发生率的影响.方法 选取2018年2~12月在中国医科大学盛京医院心内科住院的ACS患者476例.根据经皮冠状动脉介入治疗(PCI)术后患者应用抗血小板方案不同分为阿司匹林100 mg/d联合氯吡格雷75 mg/d组243例,阿司匹林100 mg/d联合替格瑞洛90 mg/bid组233例;以两组患者术前血尿酸值为基础对照,观察两组患者用药7天、1个月、3个月、6个月时的血尿酸水平及高尿酸血症发生率.结果 两组患者在性别、年龄等方面比较差异均无统计学意义(P>0.05).两组患者用药前血尿酸水平差异无统计学意义(P=0.238),用药1个月、3个月、6个月时,替格瑞洛组高尿酸血症发生率高于氯吡格雷组,差异有统计学意义(χ2值分别为7.623、20.367、14.018,P<0.05);多因素Logistic回归分析显示,在调整了混杂因素后,口服替格瑞洛与口服氯吡格雷对ACS患者高尿酸血症发生率影响仍有差异(β=-1.139,SE=0.249,Waldχ2=20.903,OR=0.320,95%CI 0.196~0.522);重复测量设计分析显示两组患者的血尿酸水平随着用药时间变化的趋势不同,用药组别与用药时间之间存在交互作用(F=6.201,P<0.05).结论 替格瑞洛组较氯吡格雷组对ACS患者血尿酸水平影响更大,导致高尿酸血症发生率更高,在用药3个月时血尿酸水平达高峰,需要临床医师重视血尿酸管理,建议患者至少要在用药1个月及3个月时复查血尿酸水平,便于及时调整用药与早期干预.     

高血压专科3706例住院继发性高血压患者病因构成分析

目的分析2012-2016年河南省人民医院高血压科住院高血压患者9439例中继发性高血压患者3706例病因分类及构成比较,为高血压防治提供病因学参考。方法采用回顾性研究方法,分析9439例住院高血压患者中3706例继发性高血压患者年龄、性别构成及病因分类。结果9439例住院高血压患者中原发性高血压占60.74%(5733例),继发性高血压占39.26%(3706例)。在继发性高血压患者中,心理因素性高血压例数最多(1175例,31.70%),其次例数较多的是阻塞性睡眠呼吸暂停低通气综合征(779例,21.02%)、原发性醛固酮增多症(728例,19.64%)、肾血管性高血压(702例,18.94%)。与原发性高血压患者相比,心理因素性高血压、原发性醛固酮增多症、肾血管性高血压、甲状腺功能减退症、青光眼患者年龄较大,心理因素性高血压、内分泌性继发性高血压的女性患者较多(P<0.05)。与原发性高血压患者相比,继发性高血压患者的年龄[(50.2±15.0)比(46.6±15.2)岁]较大、男性患者比例[54.6%(2024/3706)比64.5%(3695/5733)]较小(均P<0.05)。继发性高血压和原发性高血压患者中女性的平均年龄高于男性(P<0.05)。结论2012-2016年高血压住院患者中继发性高血压占39.26%,高于国内外文献报道。住院的高血压患者心理因素性高血压比例居于首位,阻塞性睡眠呼吸暂停低通气综合征、原发性醛固酮增多症、肾血管性高血压的比例也较高。年龄较大的高血压患者中也筛查出不少继发性高血压。     

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy

Objective: To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2(ACE2) receptor and viral spike protein by virtual screening. Methods: The three-dimensional(3 D)-coordinate file of the receptor-binding domain(RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration(FDA)-approved drugs from Drug Bank and natural compounds from Traditional Chinese Medicine Systems Pharmacology(TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine(CM) herb sources were listed in this paper. Results: It was found that digitoxin, a cardiac glycoside in Drug Bank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen(莲花清瘟), a CM formula reportedly exerting activity against severe acute respiratory syndrome(SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score. Conclusions: A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-Co V-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.     

Clinical Experience in Treatment of Alzheimer''s Disease with Jiannao Yizhi Formula (健脑益智方) and Routine Western Medicine

Objective: To investigate the long-term therapeutic effects of the Chinese medicine Jiannao Yizhi Formula(健脑益智方, JYF) in the treatment of Alzheimer's disease(AD). Methods: Sixty mild-to-moderate AD participants were recruited and randomly allocated to the treatment(30 with JYF) and the control groups(30 with donepezil) for 6 months with the random numbers. The primary outcomes were scores of Alzheimer's Disease Rating Scale-Cognitive(ADAS-Cog) and Chinese Medicine Symptom Scale(CM-SS). The secondary outcomes were scores of Mini Mental State Examination(MMSE), Montreal Cognitive Assessment(MoCA), and Activities of Daily Living(ADL). Safety assessments were conducted at baseline and the 6 th month of treatment. Serum levels of acetylcholine(Ach), amyloid-β protein 42(Aβ_(42)), and the microtubule-associated protein tau(Tau) were also determined by enzyme-liked immunosorbent assay. Results: Fifty-one participants were included in the final analyses(JYF n=27; donepezil n=24). Compared with baseline, both JYF and donepezil increased the MoCA and MMSE scores and decreased the ADAS-Cog and CM-SS scores(P0.05 or P0.01). Both drugs increased the serum levels of Ach and decreased the serum levels of Aβ_(42) and Tau(all P0.05). There was no significant difference in these variables between the two groups, which showed that JYF was not inferior to donepezil. No obviously significant changes were observed in the ADL. No severe adverse events were observed in both groups. Conclusion: The effect and safety of JYF for the treatment of AD were not inferior to those of donepezil.     

非编码 RNA GlmY 对伤寒沙门菌生物膜形成的影响

目的: 探究非编码 RNA GlmY 对伤寒沙门菌生物膜形成的影响及其分子机制。方法: 用自杀质粒pGMB151介导的同源重组方法,制备 glmY 缺陷株;用96孔微量板结晶紫染色法检测各菌株生物膜形成情况;通过qRT PCR分析glmY 缺陷株及野生株中生物膜形成相关基因的mRNA表达水平。结果： 成功制备glmY缺陷株;细菌生物膜形成实验表明,与野生株相比,glmY缺陷株生物膜形成能力明显下降;qRT PCR分析结果显示,GlmY缺失后卷曲菌毛合成相关基因csgD和csgA的mRNA表达水平明显下调。结论： 伤寒沙门菌非编码 RNA GlmY可通过上调csgD和csgA的表达促进卷曲菌毛合成,进而促进生物膜的形成。     

胰腺癌根治术患者外周血CTCs水平与病理参数及预后的相关性

【摘要】目的 探讨胰腺癌根治术患者外周血循环肿瘤细胞（CTCs）水平与病理参数及预后的相关性。方法 选择2017年3月~2018年3月于我院行胰腺癌根治术的患者98例,选择同时期于我院体检的35例健康志愿者为对照组。采集外周血75 mL,用免疫磁珠负性富集和免疫荧光原位杂交技术检测CTCs水平。分析胰腺癌患者外周血CTCs水平与病理特征的相关性,用Kaplan Meier生存分析比较外周血CTCs阳性、阴性患者的生存时间,影响预后的多因素分析采取COX风险比例模型。结果 胰腺癌患者外周血中CTCs的阳性检出率为6327%（62/98）,检测数量0～27个,平均201个/ mL,对照组未检出CTCs阳性;Logistic回归分析结果显示,淋巴结转移、侵犯被膜是外周血CTCs阳性的独立危险因素（P＜005）;Kaplan Meier生存分析结果显示,CTCs阳性患者1年生存率为16133%,中位生存时间为245 d,CTCs阴性患者1年生存率为4722%,中位生存时间为352 d,两组比较差异有统计学意义（P=00004）;COX回归分析结果显示,CTCs阳性、淋巴结转移是导致预后不佳的独立危险因素（P＜005）。结论 胰腺癌患者外周血中CTCs检出率较高,其水平与淋巴结转移等病理特征相关,对预后也有一定的预测作用,检测外周血CTCs对胰腺癌的治疗有具指导意义。     

COL7A1基因复合杂合变异所致的隐性营养不良型大疱性表皮松解症家系的遗传学分析

目的对1个隐性营养不良型大疱性表皮松解症家系进行基因检测及产前诊断。方法利用PCR-Sanger测序技术检测患者COL7A1基因的全部外显子及其侧翼区的潜在变异,之后进行家系验证及产前基因诊断。结果Sanger测序显示患者COL7A1基因存在c.7289delC(p.Pro2430Glnfs*36)及c.7474C>T(p.Arg2492*)复合杂合变异,分别遗传自其母亲和父亲,在100名健康对照中未检测到上述变异。产前诊断胎儿COL7A1基因c.7289位置未见变异,c.7474位置存在C>T杂合变异,判断为携带者。结论明确了1例隐性营养不良型大疱性表皮松解症家系COL7A1基因的致病性变异,并成功进行了产前诊断。     

3D打印技术辅助肱骨髁间骨折治疗

肱骨髁间骨折因在目前局限的手术方式下很难达到最理想的效果而成为现阶段最难治疗的骨折之一。本研究将3D打印技术用于肱骨髁间骨折辅助治疗。53例肱骨髁间骨折患者被分为3D打印组及常规组两组,由同一小组骨科医生进行手术治疗。通过对术中、术后随访,3D打印组与常规组相比手术时间明显缩短;术中失血量明显减少;骨折愈合时间无显著差异;术后未发现严重并发症,并发症发生率也相对较低。