腺病毒介导酸性成纤维生长因子对兔角膜内皮细胞感染及促增殖作用的实验研究

目的　观察复制缺陷型重组腺病毒载体介导酸性成纤维生长因子 (aFGF)对体外培养的兔角膜内皮细胞 (RCEC)的感染效率和促增殖作用。方法　 2 93A细胞扩增复制缺陷型重组腺病毒 ,选用细胞半数感染剂量 (TCID50 )法测定病毒滴度。体外培养RCEC ,用携带报告基因 (LacZ)的重组腺病毒 (Ad LacZ)感染RCEC ,二甲基甲酰胺 (X gal)染色估计瞬时感染效率 ,将含aFGF的重组腺病毒 (Ad aFGF)感染RCEC ,RT PCR、Westernblot分别检测aFGF转录及蛋白质表达情况 ,噻唑盐 (MTT)法检测转基因细胞增殖情况。结果　病毒滴度为 2× 10 8pfu/ml;重组腺病毒感染RCEC 2 4h后即可检测到外源基因表达 ,当感染倍数 (MOI)值等于 2 0时 ,Ad LacZ对RCEC的感染效率为 10 0 % ,感染Ad aFGF对RCEC增殖有促进作用 (F =2 17.10 7,P <0 .0 5 )。结论　复制缺陷型重组腺病毒载体介导的外源基因在RCEC中可有效表达 ,感染Ad aFGF对RCEC增殖具有促进作用。     

半规管开窗放置链霉素对正常和膜迷路积水耳的内耳功能和形态学影响

为探索临床应用氨基甙类药物治疗病的途径和可行性，对豚鼠正常耳和人工造成膜迷路积水耳行外半规管开窗放置硫酸链霉素后的内耳功能和形态进行观察。结果表明开窗放药后正常耳耳蜗电图（ＥＣｏｃｈＧ）动作电位（ＡＰ）阈值无变化，积水耳ＡＰ阈值升高，正常耳和积水耳冰水试验眼震消失。光镜下正常耳给药后三个半规管壶腹嵴和椭圆囊斑前庭上皮严重受损，耳蜗毛细胞正常；积水耳用药后前庭上皮受损更重，部分变性、萎缩，耳蜗底回及部分第二回毛细胞亦受损。揭示在膜迷路积水状态下对链霉素的耳毒敏感性增加。     

不明原因智力障碍/脑发育迟缓患儿染色体亚端粒重组突变的检测

目的联合应用多重连接依赖的探针扩增法和荧光原位杂交法检测染色体亚端粒重组,进行不明原因智力障碍／脑发育迟缓（mental retardation／developmental delay,MR／DD）的病因学研究。方法人选病例必须满足：①中一重度MR／DD;②无明确围产期异常病史;③无明确生后中毒、缺氧、中枢神经系统感染及头颅外伤等病史;④常规核型分析显示正常;⑤头颅影像及尿有机酸、氨基酸分析未提示典型遗传代谢性疾病或神经变性病;⑥男性患儿FMR1基因检测未提示脆性X综合征。并至少符合以下条件之一：①MR家族史阳性;②反复流产或围产期死亡家族史阳性;③体格发育异常;④面部畸形;⑤非面部畸形或发育异常。联合应用多重连接依赖的探针扩增法过筛和荧光原位杂交技术验证对患儿及父母标本进行染色体亚端粒重组检测。结果人组39例中发现4例阳性病例,重组分别为：①新发der（2）t（2;4）（pter;pter）,文献未见报道;②新发8pter缺失,国外曾有报道,但临床表型不同;③新发15q11．2缺失,属中间重组,结合患儿临床表型,Angelman综合征可能性大;④新发11qter缺失,文献未见报道。结论首次报道2种新重组,其新发出现提示致病性可能性大;染色体亚端粒重组是遗传性MR／DD的重要病因,临床表型差异大,对原因不明的常规染色体检查无异常的MR／DD患者均应进行检测,联合应用多重连接依赖的探针扩增法和荧光原位杂交法是相对经济的确诊手段。     

Emerging trends in sacubitril/valsartan research: A bibliometric analysis of the years 1995–2021

Background:Sacubitril/valsartan has been approved for the treatment of heart failure (HF) patients with reduced ejection fraction; since then, it gradually became a new star drug in the therapy of HF. Nevertheless, the effectiveness of sacubitril/valsartan remains under investigation. Thus far, only a few bibliometric studies have systematically analyzed the application of sacubitril/valsartan.Methods:Publications on sacubitril/valsartan were retrieved from the Web of Science Core Collection on April 29, 2021. Data were analyzed using Microsoft Excel 2019 (Redmond, WA), VOS viewer (Redmond, WA), and Cite Space V (Drexel University, Philadelphia, PA).Results:A total of 1309 publications on sacubitril/valsartan published from 1995 to 2021 were retrieved. The number of publications regarding sacubitril/valsartan increased sharply in the last 6 years (2015–2021), and American scholars authored >40% of those publications. Most were published in the European Journal of Heart Failure, the United States was the bellwether with a solid academic reputation in this area. Solomon published the highest number of related articles and was the most frequently cited author. “Heart failure” was the leading research hotspot. The keywords, “inflammation,” “fibrosis,” and “oxidative stress” appeared most recently as research fronts.Conclusions:Research attention should be focused on clinical trial outcomes. Considering its effectiveness in HF, the mechanisms and further applications of sacubitril/valsartan may become research hotspots in the future and should be closely examined.     

关节镜下缝线固定治疗儿童胫骨髁间前棘骨折

目的探讨关节镜下应用缝线固定治疗儿童胫骨髁间前棘骨折的临床疗效。方法2003年5月～2006年7月,对11例胫骨髁间前棘骨折移位患儿,在关节镜下行骨折复位。以钢丝引导PDSⅡ缝线经骨隧道固定,术后石膏或支具外固定。术后随访采用IKDC和Lysholm评分标准评估疗效。结果全部病例均获随访,平均随访14个月(6～28个月),膝关节活动均正常,Lachman试验阴性;3～6个月,患儿均已恢复正常生活及部分体育锻炼;X线片显示骨折愈合。术后末次随访,KT-2000检查双膝松弛度相差0～4mm(平均1.5mm)。Lysholm评分术后末次随访93～100分,与术前56～79分比较,差异有统计学意义(P<0.01)。术后IKDC评分分级为A级(8例,占72.72%)和B级(3例,占27.28%)。结论儿童胫骨髁间前棘骨折经关节镜下骨折复位、缝线固定是一种创伤小、不损伤骺板、疗效可靠的治疗方法。     

三黄口服液治疗代谢综合征的疗效观察

目的:探讨三黄口服液对代谢综合征肥胖人群的临床疗效。方法:以20名健康志愿者为参照,将100名代谢综合征患者随机分为治疗组(60名)和安慰剂组(40名),分别予三黄口服液和安慰剂治疗12周,观察治疗前后患者心血管危险因素的变化。结果:与安慰剂组相比,治疗组(起效剂量为10 ml/人,黄连素浓度为0.16～0.22 mg/ml)除空腹血糖,甘油三酯在治疗前后无显著差异外,腰围、体质量指数、腰臀围比值、胰岛素抵抗指数,血清C反应蛋白水平、游离脂肪酸明显改善,差异有显著性(P<0.05);随着腰围的增大,男性的糖代谢异常、高血压病、血脂紊乱及代谢综合征的发生率均呈现增高趋势(P<0.01)。结论:三黄口服液可明显降低代谢综合征人群肥胖和胰岛素抵抗程度,并能改善炎症状态,减轻致心血管病的危险性。     

我国2005—2012年发表文献中药源性肝损伤诊断标准使用分析

目的:通过系统综述总结我国2005-2012年发表文献使用的药源性肝损伤(DILI)的诊断标准,了解我国DILI诊断标准的使用情况及其特点.方法:中国期刊全文专题数据库(CNKI)、中国生物医学文献数据库(CBM)、维普中文科技期刊数据库(VIP)、万方数据以关键词“药物性/药源性+肝损害/肝损伤/肝病/肝炎”对2005-2012年文献进行检索,使用Noteexpress软件对检索到的文献进行管理,排除不同数据库间重复的文献,按照纳入和排除标准,对文献进行筛选.用Excel2007建立文献摘录表,进行数据提取和分析.结果:有273篇文献纳入研究,包括199篇病例系列和74篇病例报告.199篇病例系列采用的DILI诊断标准不一,有15个不同的标准,采用最多的是我国通用标准、1997年Maria评分、以及以“病史、临床表现和相关检查等”作为诊断标准.199篇病例系列对这3种标准的使用并没有明显随时间变化的趋势.不同类别杂志的文献对DILI诊断标准的使用也没有明显的趋势.74篇病例报告均是根据病史、临床表现和相关检查等做出诊断.结论:药源性肝损伤(DILI)目前没有统一的标准,在DILI诊断标准的选择上应根据患者年龄、原患疾病、临床症状、各项相关检查等选择合适的诊断标准,尽量避免漏诊和误诊的发生.     

Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain

Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line‐derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex. Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased. Furthermore, normalizing GDNF expression with lentiviral vector constructs in the spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal glial activation, and pERK induction induced by tibia injection, but did not affect ongoing pain. Together these findings provide new evidence for the use of GDNF as a therapeutic treatment for bone cancer pain states.