人类非嗜肝病毒所致肝炎患者临床特征的相关性分析

目的  探讨人类非嗜肝病毒所致肝炎的病因和临床特征。方法  对176例人类非嗜肝病毒性肝炎患者进行临床研究,用常规方法检测112例甲-戊型肝炎标志物,排除嗜肝病毒感染。检测单纯疱疹病毒（HSV）、EB病毒（EBV）、巨细胞病毒（CMV）、柯萨奇病毒（CoxV）等病毒的IgM、IgG型抗体和自身抗体（线粒体抗体和抗核抗体）,随访6个月,并将其临床症状体征、肝功能指标与同期急性病毒性肝炎比较。结果  非嗜肝病毒肝炎患者病原体以CMV感染最多（34.7%）,其次分别为EB病毒和轮状病毒感染（24.4%、9.6%）,非嗜肝病毒肝炎患者的乏力、纳差、厌油、恶心、肝肿大、皮肤黄染发生率较同期急性病毒性肝炎低,两者比较差异有统计学意义（P <0.01）,其脾肿大、淋巴结肿大的发生率较同期急性病毒性肝炎高,两者比较差异有统计学意义（P <0.01）;非嗜肝病毒肝炎患者肝功能的ALT、AST、TBIL值较同期的急性病毒性肝炎值低,两者比较差异有统计学意义（P <0.01）,清蛋白、凝血酶原时间值与急性病毒性肝炎比较,差异无统计学意义（P > 0.05）;非嗜肝病毒肝炎患者的单一感染的ALT、AST、TBIL较复合感染时间短,两者比较差异有统计学意义（P <0.01）。结论  巨细胞病毒、EB病毒等为非嗜肝病毒肝炎的常见病原体,临床表现为急性肝损伤,但较急性病毒性肝炎轻,单一感染较复合感染轻,预后较好。

     

人类免疫缺陷病毒,艾滋病病毒1型艾滋病患者CD4+T淋巴细胞水平与机会感染及病毒载量的相关性分析

目的  分析人类免疫缺陷病毒,艾滋病病毒-1（HIV-1）型艾滋病（AIDS）患者体内CD4+T淋巴细胞水平与艾滋病病毒载量及机会性感染的相关性。方法  通过Real-time PCR OBASAmpliPrep/COBAS TaqMan全自动病毒载量仪（Roche公司）和流式细胞仪（FACSCOUNT）绝对计数法对95例HIV-1型AIDS患者定量检测血浆中HIV-1 RNA和CD4+T淋巴细胞数。结果  低文化程度的35～50岁已婚男性农民是HIV-1型AIDS患者的多见人群,主要通过性传播途径感染;机会感染最常见部位是呼吸系统感染90例次（51.5％）;机会感染发病率最多的是细菌性肺炎48例次（27.4％）;根据CD4+T淋巴细胞计数分层水平分为5组,细菌性肺炎、卡氏肺孢子虫肺炎、肺结核、口腔念珠菌感染、隐球菌脑膜炎、感染性腹泻及单纯疱疹各自在5组间比较差异有统计学意义（P <0.05）,其余机会感染各自在5组间比较差异无统计学意义（P >0.05）;CD4+T细胞计数低于200个/μl时,机会感染发生例次率为97.7%;病毒量<103拷贝/ml的AIDS中,以CD4+T细胞数在200～399个/μl的个体较多（75%）,病毒量≥105拷贝/ml的AIDS中,CD4+T细胞数在<200个/μl的个体45例（73.8%）;CD4+T淋巴细胞值与病毒载量对数值呈负相关（r =-0.34,P <0.01）。结论  AIDS患者机会性感染的发生率高,随病毒载量上升CD4+T淋巴细胞数呈现不同程度的下降趋势,CD4+T细胞计数是AIDS患者发生机会性感染的独立危险因素,加强对患者CD4+T细胞计数观察是预测机会性感染的重要手段。

     

E2F1 is not essential for apoptosis induced by potassium deprivation in cerebellar granule neurons

Cerebellar granule neurons (CGNs) undergo apoptosis when deprived of depolarizing concentration of potassium. A key regulator of cell cycle, E2F1, was believed to play a role in CGN apoptosis induced by potassium deprivation. However, here we demonstrated that although E2F1 was upregulated in wild type CGNs following potassium deprivation, CGNs that derived from E2F1 knockout mice underwent apoptosis at a similar rate as the wild type. Analysis of the apoptotic neurons revealed no difference in the activation of caspase-3 in E2F1 null and wild type CGNs. Furthermore, knockdown of E2F1 expression by RNA interference failed to attenuate the apoptosis of CGNs induced by potassium deprivation. Taken together, our results suggested that E2F1 is not essential for apoptosis induced by potassium deprivation in CGNs.     

Ex vivo expanding hematopoietic stem cells by intracellular delivery of Cdx4 fusion proteins

Hematopoietic stem cells transplantation has been wildly used in clinical settings and has shown exciting results in treating a wide variety of diseases. However, the relative small number of hematopoietic stem cells in bone marrow, even lower in peripheral or umbilical cord blood limits its clinical utility. There are several protocols, which have been developed to expand hematopoietic stem cells to reach clinical goal. With the recent insights into the mechanisms of hematopoietic stem cells self-renewal, we postulate that Cdx4, which is coded by one of the caudal related homeobox genes and regulates the expression of hox genes, could fuse with protein transduction domains, thereby get the ability to cross cellular membrane. And the recombinant fusion proteins could be used in expanding hematopoietic stem cells. Meanwhile, Cdx4 fusion proteins would be more efficient than other methods that had been developed for it can up-regulate a cocktail of hox genes, which has been proved to be capable of amplifying hematopoietic stem cells. It would provide us an alternative protocol to amplify hematopoietic stem cells if the hypothesis proved to be practical.     

Heroin impairs map-picture-following and memory tasks dependent on gender and orientation of the tasks

Male and female heroin-dependent patients (HDPs) matched with "normal" people were tested on 4 topographical orientation tasks: schematic map-following, map-memory, schematic picture-following, and picture-memory tasks. The results showed that, in general, female HDPs demonstrated greater performance deficits in map-following and map-picture-memory tasks than did other participants. In the map-picture-following tasks, participants showed a preference for turning right versus turning left, reflected by lower correct scores and longer latencies in completing left-oriented tasks. In contrast, no difference in orientation preference was found for participants in memory tasks, except for female HDPs. Asymmetric dopamine receptor distribution in the brain, sex steroidal hormone, brain areas related to motor functioning and working memory, and gender-dependent lateralization may be involved in the different effects of heroin and rightward bias between men and women.     

Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice

The fiber specificity of skeletal muscle abnormalities in chronic heart failure (CHF) has not been defined. We show here that transgenic mice (8 weeks old) with cardiac-specific overexpression of calsequestrin developed CHF (50.9% decrease in fractional shortening and 56.4% increase in lung weight, P<0.001), cachexia (37.8% decrease in body weight, P<0.001), and exercise intolerance (69.3% decrease in running distance to exhaustion, P<0.001) without a significant change in muscle fiber-type composition. Slow oxidative soleus muscle maintained muscle mass, whereas fast glycolytic tibialis anterior and plantaris muscles underwent atrophy (11.6 and 13.3%, respectively; P<0.05). In plantaris muscle, glycolytic type IId/x and IIb, but not oxidative type I and IIa, fibers displayed significant decreases in cross-sectional area (20.3%, P<0.05). Fast glycolytic white vastus lateralis muscle showed sarcomere degeneration and decreased cytochrome c oxidase IV (39.5%, P<0.01) and peroxisome proliferator-activated receptor gamma co-activator 1alpha protein expression (30.3%, P<0.01) along with a dramatic induction of the MAFbx/Atrogin-1 mRNA. These findings suggest that exercise intolerance can occur in CHF without fiber type switching in skeletal muscle and that oxidative phenotype renders myofibers resistant to pathological insults induced by CHF.     

Deletion of integrin-linked kinase from skeletal muscles of mice resembles muscular dystrophy due to alpha 7 beta 1-integrin deficiency

Integrin-linked kinase (Ilk) is a serine/threonine kinase and an adaptor protein that links integrins to the actin cytoskeleton and to a number of signaling pathways involved in integrin action. We hypothesized that Ilk may act as an important effector of integrins in skeletal muscle, where these receptors provide a critical link between the sarcolemma and the extracellular matrix. Using the cre/lox system, we deleted Ilk from skeletal muscles of mice. The resulting mutants developed a progressive muscular dystrophy with multiple degenerating and regenerating muscle fibers, increased central nuclei, and endomysial fibrosis. These defects were widespread but were most severe near myofascial junctions where Ilk mutants showed displacement of focal adhesion-related proteins, including vinculin, paxillin, focal adhesion kinase, dystrophin, and the alpha 7 beta 1D-integrin subunits. Distal ends of mutant muscle fibers appeared irregular, and there was restructuring of the actin cytoskeleton. These findings resemble those seen in humans and mice lacking the alpha 7-integrin subunit and suggest that Ilk may act as a cytoplasmic effector of alpha 7 beta1-integrin in the pathogenesis of these deficiencies.     

Relationship between patient copayments in Medicare Part D and vaccination claim status for herpes zoster and tetanus-diphtheria-acellular pertussis

Objective: To assess the relationship between copay amount and vaccination claim submission status for tetanus-diphtheria-acellular pertussis (Tdap) and herpes zoster (GSK study identifier: HO-14-14319).

Methods: Retrospective analyses were performed using vaccination administrative claims data in patients aged ≥65 years with ≥1 claim for Tdap or zoster vaccines between 2012 and 2014. To avoid confounding by other financial responsibility, analyses were conducted among patients in the copayment phase of insurance. The impact of patient copay amount on vaccination claim status (“canceled” vs. “paid”) was evaluated by logistic regression separately for Tdap and zoster, adjusting for patient and provider characteristics.

Results: A total of 81,027 (39.2% with canceled claims) and 346,417 patients (56.8% with canceled claims) were included in the Tdap and zoster analyses, respectively. Mean (standard deviation) copay for canceled vs. paid claims was $37.2 (18.4) vs. $31.1 (20.1) for Tdap and $64.9 (36.9) vs. $53.5 (38.8) for zoster. The adjusted odds ratios (ORs) for a canceled Tdap vaccine claim, compared with Objective: To assess the relationship between copay amount and vaccination claim submission status for tetanus-diphtheria-acellular pertussis (Tdap) and herpes zoster (GSK study identifier: HO-14-14319).

Methods: Retrospective analyses were performed using vaccination administrative claims data in patients aged ≥65 years with ≥1 claim for Tdap or zoster vaccines between 2012 and 2014. To avoid confounding by other financial responsibility, analyses were conducted among patients in the copayment phase of insurance. The impact of patient copay amount on vaccination claim status (“canceled” vs. “paid”) was evaluated by logistic regression separately for Tdap and zoster, adjusting for patient and provider characteristics.

Results: A total of 81,027 (39.2% with canceled claims) and 346,417 patients (56.8% with canceled claims) were included in the Tdap and zoster analyses, respectively. Mean (standard deviation) copay for canceled vs. paid claims was $37.2 (18.4) vs. $31.1 (20.1) for Tdap and $64.9 (36.9) vs. $53.5 (38.8) for zoster. The adjusted odds ratios (ORs) for a canceled Tdap vaccine claim, compared with $0 copay, were 1.19 ($1–25 copay), 1.76 ($26–50 copay), 2.42 ($51–75 copay) and 2.40 ($76–100 copay), all p?<?.001. The adjusted ORs for a canceled zoster vaccine claim, compared with $0 copay, were 1.02 ($1–25), 1.39 ($26–50), 1.66 ($51–75), 2.07 ($76–100) and 2.71 (>$100), all p?<?.001 except for $1–25 (p?=?.172).

Conclusions: High patient copay is a barrier to Tdap and zoster vaccinations in Medicare Part D patients. Providing vaccines at low or no copay may improve vaccination rates in these adults.

GSK study identifier: HO-14-14319.     

临床分离沙门菌的耐药性及超广谱β-内酰胺酶类耐药基因

目的研究北京地区2012—2015年沙门菌临床分离株的血清型分布、耐药状况及超广谱β-内酰胺酶(ESBLs)耐药基因特征。方法采用最小抑菌浓度法测定北京市肠道门诊分离的677株沙门菌株对16种抗菌药物的耐药情况,采用聚合酶链反应(PCR)方法对244株β-内酰胺酶类耐药菌株进行耐药基因检测。结果677株沙门菌分为68种血清型,其中肠炎沙门菌、鼠伤寒沙门菌和山夫登堡沙门菌位居前3位。沙门菌对氨苄西林和阿莫西林/克拉维酸的耐药率分别为42.54%、40.77%,至少耐3种以上抗菌药物的菌株占57.16%。244株对氨苄西林和阿莫西林/克拉维酸耐药的沙门菌,携带至少一种ESBLs基因的菌株174株(71.31%),146株bla_(TEM-1)型,30株bla_(OXA-1)型,18株bla_(CTX-M)型(其中7株bla_(CTX-M-15),6株bla_(CTX-M-55)和5株bla_(CTX-M-14));20株同时携带2种耐药基因。结论该地区沙门菌携带ESBLs耐药基因水平较高,以bla_(TEM-1)为主,同时伴有bla_(OXA-1)和3种bla_(CTX-M)基因亚型,呈现基因多样性。     

1 251例重复人工流产术后落实不同避孕方法的效果评价

目的：评价重复人工流产术后即时落实不同避孕方法的效果。方法：1 251例重复人工流产者接受流产后服务（PAC）,自愿选择并即时落实避孕方法,随访不同避孕方法的使用情况及不良反应等。结果：所有重复流产者接受PAC后均即时落实避孕措施,其中复方口服避孕药（COC）组随访12个月续用率达31.2%;宫内节育系统（IUS）组随访12个月有3例因有生育要求取出,其余均坚持使用,另外有19例、13例和17例分别于随访3、6、12个月自COC组转入;宫内节育器（IUD）组随访12个月有1例异位妊娠,6例因有生育要求取出,其余均坚持使用,另外有23例、31例和19例分别于随访3、6、12个月自COC组转入。随访中发现部分人群有阴道点滴出血、经量减少、经量增多、闭经、节育环下移和腰酸不适等不良反应,给予处理并充分解释后均继续坚持使用。结论：科学有效的PAC能有效避免重复流产,保护女性生殖健康。