软骨利胶囊对骨关节炎小鼠股四头肌收缩蛋RmRNA表达的影响

背景:骨关节炎的病理改变涉及多种关节构成组织,其中骨骼肌的地位日渐引起研究者关注.目的:通过观察骨关节炎C57小鼠骨骼肌收缩蛋白α-肌动蛋白与肌球蛋白重链基因表达状况,探讨柔肝中药软骨制剂利胶囊对收缩蛋白基因表达的影响.设计、时间及地点:随机对照动物实验,于2004-09/2007-01在上海市中医药研究院骨伤科研究所完成.材料:选取7周龄清洁级C57小鼠18只,雌雄各半,体质量(20±5)g.软骨利胶囊(柔肝中药制剂),由上海中医药大学中药标准化中心提供.方法:18只C57小鼠按随机数字表随机分为正常组、模型组、软骨利组,每组6只.除正常组外,对小鼠进行运动负荷训练造模.软骨利组给予0.2 mL软骨利溶液(约含2 mg软骨利)灌胃5周,正常对照组和模型组给予0.2 mL生理盐水灌胃5周.主要观察指标:应用反转录-聚合酶链反应检测股四头肌肌α-actin、肌球蛋白重链4种亚型(Ⅰ,Ⅱa,Ⅱd/x,ITb)mRNh表达水平.结果:与空白组比较,模型组α-actin mRNA显著低表达(P<0.05),肌球蛋白重链Ⅱa,肌球蛋白重链Ⅱd/x mRNA低表达(P<0.05).与模型组比较,软骨利干预组α-actin与多种肌球蛋白重链亚型mRNA表达水平上调(P<0.05).结论:柔肝中药制剂软骨利能够促进骨骼肌收缩蛋白基因表达,提示其可改善骨关节炎动物骨骼肌肌力.     

Ets-1 mRNA、Ets-1及VEGF在膀胱移行细胞癌中的表达及意义

【目的】研究Eta-1 mRNA、Eta-1及血管内皮生长因子（vascular endothelial growth factor,VEGF）在膀胱移行细胞癌（BTCC）中的表达及意义。【方法】用原位杂交和免疫组化方法分别检测40例BTCC组织和12例正常膀胱黏膜组织中Ets—1 mRNA、Ets-1及VEGF的表达;分析Eta-1 mRNA、Ets-1表达与BTCC临床病理特征间的关系;研究BTCC中VEGF表达与Ets-1 mRNA、Ets-1表达的相关性。【结果】①Ets—1 mRNA、Ets-1在BTCC中高度表达,其表达阳性率分别为87．5％（35／40）和82．5％（33／40）（P〈0．01）,且随BTCC临床分期及病理分级的升高而增加,肿瘤复发组高于无复发组,肿瘤转移组高于无转移组（P〈0．05）。②VEGF在BTCC中阳性表达率为72．5％（29／40）,而对照组无一例阳性表达（P〈0．01）。在BTCC中Eta-1 mRNA、Ets-1表达与VEGF表达均呈正相关（相关系数Rs分别为0．707和0．797,P值均〈0．01）。【结论】①Ets-1 mRNA、Ets-1在BTCC中高度表达,并随BTCC分期分级升高而增加;Ets-1 mRNA、Ets-1蛋白与BTCC转移及复发密切相关。②BTCC中Eta-1 mRNA及Ets-1与VEGF表达均呈正相关,VEGF可诱导Ets-1表达。     

Rapid generation of sequence variation during primary HIV-1 infection.

OBJECTIVE: HIV-1 undergoes extensive genetic variation in infected individuals. The extent of genetic variation has been examined in patients with AIDS, but little is known regarding the appearance of HIV-1 genetic variation immediately following infection during the primary phase of HIV-1 infection prior to seroconversion. DESIGN: We examined HIV-1 genetic variation during this early phase of HIV-1 infection by polymerase chain reaction (PCR) and nucleotide sequence analysis of the V4 by polymerase chain reaction (PCR) and nucleotide sequence analysis of the V4 variable region and the CD4-binding domain. RESULTS: Our results demonstrate that extensive sequence variation is seen early after infection, although a predominant HIV-1 species is maintained. CONCLUSIONS: The type of variants that occur are dynamic, changing over time, and the mutations seen are consistent with those expected from random occurrence, unlike the pattern of variation previously reported during later stages of disease.     

Combined bromocriptine and growth hormone (GH) treatment in GH-deficient children with macroprolactinoma in situ.

Experience with PRL-secreting macroadenomas in the pediatric and adolescent population is limited. Although use of synthetic GH after treatment of central nervous system tumors in children without active disease is accepted practice, reports of GH use in patients with central nervous system tumors in situ are rare. Furthermore, the effect of GH on tumor growth is not known. We report GH treatment (10 and 11.5 months), concomitant with bromocriptine (BC; dopamine agonist) therapy in two children, a 15.5-yr-old male and a 15.5-yr-old female, with PRL-secreting macroadenomas in situ. Surgical resection was deemed undesirable because of the risk of major morbidity due to the large size of the tumors and the close proximity to major vessels. Both patients were GH deficient and had heights below the fifth percentile coupled with arrested pubertal progress. During BC therapy, a decrease in tumor size and a reduction in serum PRL levels occurred in both patients, which continued after the addition of GH treatment. Neither patient experienced changes in visual acuity during combined treatment, and both experienced marked improvement in growth velocity. We conclude that in children with PRL-secreting tumors and GH deficiency in whom surgery is not advised, combined treatment with BC and GH appears to be safe and efficacious. To our knowledge, these patients represent the first report of the combined therapeutic use of BC and GH as the primary mode of treatment in children with prolactinoma in situ with documented GH deficiency.     

Impact of mitral regurgitation in patients with acute heart failure: insights from the RELAX-AHF-2 trial

Aims

The impact of mitral regurgitation (MR) in patients hospitalized for acute heart failure (AHF) is not well established. We assessed the role of MR in patients enrolled in the Relaxin in Acute Heart Failure 2 (RELAX-AHF-2) trial.

Methods and results

Patients enrolled in RELAX-AHF-2 with available data regarding MR status were included in this analysis. Baseline characteristics, in-hospital data, and clinical outcomes through 180-day follow-up were evaluated. The impact of moderate/severe MR was assessed. Among 6420 AHF patients with known MR status, 1810 patients (28.2%) had moderate/severe MR. Compared to patients with no/mild MR, those with moderate/severe MR were more likely to have history of heart failure (HF), prior HF hospitalization, more comorbidities, symptoms/signs of HF, lower left ventricular ejection fraction and higher N-terminal pro-B-type natriuretic peptide levels. Moderate/severe MR was associated with longer length of hospital stay, higher rates of residual dyspnoea, increased jugular venous pressure through the index hospitalization and a higher unadjusted risk of the composite of cardiovascular (CV) death or rehospitalization for HF/renal failure (RF) through 180 days (crude hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.03–1.27, p = 0.01). The association between moderate/severe MR and poorer outcomes was not maintained in a multivariable model including several covariates of interest (adjusted HR 1.03, 95% CI 0.91–1.17, p = 0.65). Similar findings were observed for HF/RF rehospitalization alone.

Conclusions

In patients with AHF, moderate/severe MR was associated with a worse clinical profile but did not have an independent prognostic impact on clinical outcomes.     

Epstein-barr virus-related gastric adenocarcinoma: an early secondary cancer post hemopoietic stem cell transplantation

BACKGROUND & AIMS: Epstein-Barr virus (EBV) infection has been associated with some cases of gastric cancer. METHODS: We studied a case of early onset gastric adenocarcinoma after nonmyeloablative hematopoietic stem cell transplantation for myeloma in a 56-year-old man. RESULTS: The development of gastric adenocarcinoma was preceded by severe graft-versus-host disease (GVHD) necessitating strong immunosuppression, which resulted in an intense reactivation of EBV infection. Three sequential gastric biopsy examinations performed at 100, 130, and 150 days after hematopoietic stem cell transplantation showed gastritis, dysplasia, and adenocarcinoma, respectively. There was no evidence of Helicobacter pylori infection. Quantitative polymerase chain reaction for circulating EBV showed a surge of EBV DNA peaking at the time of gastritis, followed by a gradual decrease afterward with adequate control of GVHD and tailing of immunosuppression. In situ hybridization for EBV-encoded early small RNA showed absence of EBV in the gastritis specimen, but the presence of EBV in the dysplastic and carcinoma specimens. Aberrant promoter methylation of E-cadherin was observed only in the carcinoma specimens, showing that infection with EBV preceded E-cadherin methylation. CONCLUSIONS: Mucosal damage caused by GVHD, immunosuppression, and EBV reactivation combined to lead to EBV infection of the gastric cells and initiation of carcinogenesis, suggesting this case to be a genuine EBV-related opportunistic malignancy post-transplantation. An interesting proposition is that this case also might reflect a compacted timeline of events in EBV-related gastric cancers developing in immunocompetent patients.     

Clinical significance of anti-endothelial cell antibody in allogeneic hematopoietic stem cell transplantation recipients with graft-versus-host disease

Anti-endothelial cell antibody (AECA) is well known to reflect endothelial injury. Graft-versus-host disease (GVHD), a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), is also closely associated with endothelial injury. We hypothesized that AECA may be associated with GVHD. To investigate the clinical significance of AECA in allo-HSCT recipients with GVHD, we detected AECA by cyto-enzyme-linked immunosorbent assay (cyto-ELISA) in allo-HSCT recipients with acute and/or chronic GVHD (aGVHD and cGVHD). Incidences of anti-HMEC-1 AECA (anti-HMEC) and anti-EA.hy926 AECA (anti-EAHY) were significantly higher in patients with grade II–IV than grade 0–I aGVHD (P = 0.049, P = 0.011, respectively). There was no difference in the incidence of AECA between patients with and without cGVHD. Patients with anti-EAHY positive in the early stage post-transplant demonstrated a higher incidence of cGVHD (P = 0.044). In patients with grade 0–I aGVHD, AECA-positive patients had higher overall survival and disease-free survival (P < 0.05), and tended to have lower incidences of relapse and transplant-related mortality. Our data suggest that AECA plays an important role in the pathogenesis of GVHD.     

Rickettsial infection in five remote Orang Ulu villages in upper Rejang River, Sarawak, Malaysia.

People in 5 Orang Ulu villages in Sarawak, Malaysia were tested for rickettsial infection by Weil-Felix reaction and by indirect immunoperoxidase reaction. Of those surveyed 9.6% were positive for typhus. Of the positives, 3.8% were positive for tick typhus (7/11), scrub typhus (4/11) or endemic typhus (1/11). The incidence of typhus was higher among semi-nomadic Penans compared with the settled Kayans.     

三维超声对耻骨直肠肌变化所致老年性排便障碍的研究

目的探讨三维超声对老年便秘与耻骨直肠肌之间的相关性。 方法回顾收集2015年1月至2017年9月在山东大学附属千佛山医院肛肠科门诊就诊及住院的老年性便秘患者资料43例（观察组）及43例健康志愿者资料（对照组）,分别在静息期、力排期和缩肛期行盆底三维超声检查并对三维重建声像图进行分析,测量两组耻骨直肠肌后角大小及肛门截石3、6、9点位耻骨直肠肌的厚度。 结果观察组与对照组耻骨直肠肌后角在静息期［（83.556±2.110）°,（83.804±2.485）°］、缩肛期［（86.836±1.453）°,（86.557±1.375）°］比较差异均无统计学意义（t=-0.499,-0.915;P均>0.05）;在力排期［（79.905±2.381）°,（89.214±1.916）°］比较差异有统计学意义（t=-19.985,P<0.05）;在静息期与力排期耻骨直肠肌后角的差值为［（3.275±1.236）°,（-6.569±1.209）°］,两组比较差异有统计学意义（t=-37.147,P<0.05）。观察组与对照组截石3、6、9点位耻骨直肠肌厚度在静息期［（3.274±0.134）mm,（3.307±0.101）mm;（3.476±0.127）mm,（3.461±0.141）mm;（3.281±0.103）mm,（3.327±0.121）mm］、缩肛期［（3.282±0.154）mm,（3.376±0.113）mm;（3.982±0.214）mm,（4.117±0.173）mm;（3.275±0.134）mm,（3.327±0.119）mm］,两组比较差异无统计学意义（t=-0.407,0.519,-1.901,-1.168,-3.214,-1.898,P均>0.05）;在力排期［（3.731±0.129）mm,（3.216±0.087）mm;（4.271±0.169）mm,（3.596±0.134）mm;（3.724±0.112）mm,（3.221±0.089）mm］差异有统计学意义（t=20.924,20.517,23.073,P均<0.05）;观察组和对照组在静息期与力排期截石3、6、9点位耻骨直肠肌厚度的差值［（-0.426±0.091）mm,（-0.217±0.089）mm;（-0.589±0.137）mm,（-0.289±0.109）mm;（-0.431±0.111）mm,（-0.247±0.091）mm］,差异均有统计学意义（t=-10.773,-11.236,-2.659;P均<0.05）。 结论老年排便障碍患者的耻骨直肠肌后角在力排期较健康志愿者小,肛门截石3、6、9点位耻骨直肠肌厚度较健康志愿者厚,并且静息期与力排期差值越大,便秘程度越严重。     

The Nrf2 pathway is required for intracellular replication of Toxoplasma gondii in activated macrophages

Reactive oxygen species (ROS) produced by oxidases and nonenzymatic sources are important for host defence against intracellular pathogens. In this study, we knocked out the Nrf2 gene in RAW264.7 cells using the CRISPR/Cas9 system and investigated the antioxidant effects of the Nrf2 pathway in the cells stimulated by IFN‐γ and TNF‐α. The results indicated that the Nrf2 signalling pathway is necessary for maintaining redox homeostasis in activated RAW264.7 cells. Inactivation of Nrf2 impaired parasite growth. We also found that p62 contributes to Nrf2‐mediated pathways involved in T gondii infection. These findings suggest that the Nrf2/Keap1 pathway may be targeted to prevent and treat toxoplasmosis.