Mitochondrial DNA haplogroup associated with sperm motility in the Han population

In this study, we aimed to determine whether the main mitochondrial DNA （mtDNA） haplogroups of the Han people have an impact on spermatozoa motility, We recruited 312 men who were consecutively admitted to two affiliated hospitals of College of Medicine, Zhejiang University from May 2011 to April 2012 as part of fertility investigations. Semen and whole blood samples were collected from the men. We determined the mtDNA haplogroups by analysing the sequences of mtDNA hypervariable segment I and testing diagnostic polymorphisms in the mtDNA coding region with DNA probes, No significant differences were found in the clinical characteristics of the mtDNA haplogroup R and non-R （P〉0.05）. Our results suggest that mtDNA haplogroup R is a strong independent predictor of sperm motility in the Han population, conferring a 2.97-fold （95% confidence interval： 1.74-4.48, P〈0.001） decreased chance of asthenozoospermia compared with those without haplogroup R.     

体外受精和胚胎移植后妊娠合并急性粟粒性肺结核的临床特点

目的总结体外受精和胚胎移植（IVF-ET）后妊娠发生急性粟粒性肺结核的临床特点。方法回顾性分析2001年1月至2005年12月在浙江大学医学院附属妇产科医院生殖中心接受IVF-ET后妊娠并发粟粒性肺结核的6例临床资料。结果IVF-ET后妊娠并发粟粒性肺结核患者的临床表现多不典型，以发热为主要表现，呼吸道症状隐匿。胸部影像学表现以粟粒性结节和浸润性改变为主。平均于移植后53．2d发病，1例人工流产终止妊娠，其余5例均在发病后2～4周内发生自然流产。结论发热为急性粟粒性肺结核的主要临床表现，IVF-ET后妊娠发生粟粒性肺结核的妊娠结局差，对抗炎治疗无效的发热患者应警惕肺结核，尽早行结核病的相关检查。     

血管活性药物对感染性休克患者肾脏灌注的影响

目的:观察血管活性药物多巴胺、多巴胺加间羟胺、去氧肾上腺素加多巴酚丁胺对感染性休克患者肾脏灌注的影响.方法:63例感染性休克患者经过积极的液体复苏以后,随机分成3组,分别应用多巴胺、多巴胺加间羟胺、去氧肾上腺素加多巴酚丁胺,观察尿量、肌酐清除率(Ccr)、钠排泄分数(FeNa)的变化.结果:多巴胺组和去氧肾上腺素加多巴酚丁胺组尿量明显多于基础值时(P＜0.05);Ccr去氧肾上腺素加多巴酚丁胺组明显高于基础值时和其他各组(P＜0.05);FeNa去氧肾上腺素加多巴酚丁胺组明显低于基础值时和其他各组(P＜0.05),多巴胺组与基础值时比较,显著增高(P＜0.05).结论:使用去氧肾上腺素加多巴酚丁胺能改善肾脏灌注,显著增加Ccr;多巴胺能增加尿量和FeNa,但改善肾脏灌注作用不确切;多巴胺加间羟胺不能改善肾灌注.     

正交试验优选防感颗粒的提取工艺

目的确立防感颗粒的最佳提取工艺。方法应用正交试验和HPLC,以防感颗粒中R,S-告依春、白花前胡甲素、苦杏仁苷及甘草苷4种活性成分含量为指标,采用多指标综合评分法,确定防感颗粒的提取工艺。结果防感颗粒最佳提取工艺为:药材加8倍量水,煎煮3次,每次1.5 h,乙醇浓度为60%。结论优选出的工艺稳定可靠,可用于防感颗粒的提取。     

药物性肝损伤与免疫性肝损伤肝组织中lncRNA表达谱的差异分析

目的:研究长链非编码RNA(lncRNA)在药物性肝损伤及免疫性肝损伤中表达谱的变化,并分析二者的差异。方法:利用lncRNA芯片技术分别检测对乙酰氨基酚诱导的小鼠药物性肝损伤及刀豆蛋白A诱导的小鼠免疫性肝损伤肝组织的lncRNA表达谱,通过对原始数据进行预处理达到均一化后,筛选出差异表达lncRNA并进行分析。结果:与正常肝脏组织比较,变化1.5倍以上并且差异有统计学意义(P0.05)的lncRNA被认为是差异表达的lncRNA;药物性肝损伤肝组织中变化1.5倍以上的共68条,其中升高1.5倍以上的共21条,降低1.5倍以上的共47条;免疫性肝损伤肝组织中变化1.5倍以上的共60条,其中升高1.5倍以上的共17条,降低1.5倍以上的共43条。所有的lncRNA中有8条lncRNA同时在2种肝损伤肝组织中上调,在药物性肝损伤肝组织上调的lncRNA中占38%,在免疫性肝损伤肝组织中占47%;有28条lncRNA同时在2种肝损伤肝组织中下调,在药物性肝损伤肝组织下调的lncRNA中占59%,在免疫性肝损伤肝组织中占65%。结论:与正常肝脏组织比较,药物性肝损伤肝组织和免疫性肝损伤肝组织中lncRNA表达谱均发生明显变化,且2种不同肝损伤肝组织比较,lncRNA表达谱也存在差异,提示2种肝损伤肝组织中这些同时上、下调的lncRNA可能参与了2种肝损伤之间相似或是相同的病理生理过程,而那些表达不同的lncRNA可能参与相对特异的肝损伤机制的发生。     

Computational investigations of hERG channel blockers: New insights and current predictive models

Identification of potential human Ether-a-go-go Related-Gene (hERG) potassium channel blockers is an essential part of the drug development and drug safety process in pharmaceutical industries or academic drug discovery centers, as they may lead to drug-induced QT prolongation, arrhythmia and Torsade de Pointes. Recent reports also suggest starting to address such issues at the hit selection stage.In order to prioritize molecules during the early drug discovery phase and to reduce the risk of drug attrition due to cardiotoxicity during pre-clinical and clinical stages, computational approaches have been developed to predict the potential hERG blockage of new drug candidates.In this review, we will describe the current in silico methods developed and applied to predict and to understand the mechanism of actions of hERG blockers, including ligand-based and structure-based approaches. We then discuss ongoing research on other ion channels and hERG polymorphism susceptible to be involved in LQTS and how systemic approaches can help in the drug safety decision.     

Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review

BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease(IBD)patients,complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.AIM To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.METHODS We searched PubMed/MEDLINE,Embase,and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.RESULTS A total of 23 articles with 30 clinical studies and 1939 IBD patients were included.The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6μg/mL in IBD.Blood concentration of infliximab reaching 5.0-12.7μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease.Blood concentration of adalimumab reaching 7.2-16.2μg/mL or more could predict mucosal healing in IBD.The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8μg/mL in perianal fistulizing Crohn's disease.Blood concentration of vedolizumab surpassing 25.0μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9μg/mL.CONCLUSION Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies,whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.     

The critical role of therapeutic plasma exchange in ABO-incompatible liver transplantation

BackgroundThe shortage of donor liver restricts liver transplantation (LT). Nowadays, donor liver with ABO blood group incompatibility between donor and recipient has become an option to expand the source of donor liver. Although it is now possible to perform ABO-incompatible (ABO-I) LT, antibody-mediated rejection (AMR) has been recognized as the primary cause of desperate outcomes after ABO-I LT. Anti-A/B antibody is the trigger of immune response to ABO-I LT graft injury. Therapeutic plasma exchange (TPE) can quickly reduce the titer of plasma antibodies and effectively inhibit humoral immunity.Data sourcesWe searched PubMed and CNKI databases using search terms “therapeutic plasma exchange”, “ABO-incompatible liver transplantation”, “ABO-I LT”, “liver transplantation”, “LT”, “antibody-mediated rejection”, and “AMR”. Additional publications were identified by a manual search of references from key articles. The relevant publications published before September 30, 2020 were included in this review.ResultsDifferent centers have made different attempts on whether to use TPE, when to use TPE and how often to use TPE. However, the control standard of lectin revision level is always controversial, the target titer varies significantly from center to center, and the standard target titer has not yet been established. TPE has several schemes to reduce antibody titers, but there is a lack of clinical trials that provide standardized procedures.ConclusionsTPE is essential for ABO-I LT. Hence, further research and clinical trials should be conducted to determine the best regimen for TPE to remove ABO antibodies and prevent AMR.     

乳腺纤维囊性病性激素周期节律的变化

测定133例乳腺纤维囊性病(FCD)和17例正常人卵泡期、排卵期、黄体期、月经前期血和尿雌二醇(E_2)和孕酮(P)。根据性激素分泌类型不同分为5型:A型54例,E_2和P分泌峰提前出现,P分泌时相延长,E_2在排卵期分泌显著降低;B型16例,P分泌正常。但排卵期E_2浓变显著降低;C型16例,排卯期E_2分泌降低,黄体期出现P分泌峰,但其分泌延迟至月经前期,同时伴有E_2浓度增加;D型41例,虽然排卵期E_2和黄体期P分泌正常,但E_2和P分泌延迟消失,在月经前期均未能回复到正常;E型6例,没有P分泌,血尿E_2含量在月经周期中均处于低水平。对各型FCD患者与正常人血、尿E_2平均数进行比较,表明FCD的共同特点是卵泡期和月经前期血清E_2浓度增加和排卵期E_2浓度降低。