Berberine Blocks the Relapse of Clostridium difficile Infection in C57BL/6 Mice after Standard Vancomycin Treatment

Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI.     

Kallistatin Ameliorates Influenza Virus Pathogenesis by Inhibition of Kallikrein-Related Peptidase 1-Mediated Cleavage of Viral Hemagglutinin

Proteolytic cleavage of the hemagglutinin (HA) of influenza virus by host trypsin-like proteases is required for viral infectivity. Some serine proteases are capable of cleaving influenza virus HA, whereas some serine protease inhibitors (serpins) inhibit the HA cleavage in various cell types. Kallikrein-related peptidase 1 (KLK1, also known as tissue kallikrein) is a widely distributed serine protease. Kallistatin, a serpin synthesized mainly in the liver and rapidly secreted into the circulation, forms complexes with KLK1 and inhibits its activity. Here, we investigated the roles of KLK1 and kallistatin in influenza virus infection. We show that the levels of KLK1 increased, whereas those of kallistatin decreased, in the lungs of mice during influenza virus infection. KLK1 cleaved H1, H2, and H3 HA molecules and consequently enhanced viral production. In contrast, kallistatin inhibited KLK1-mediated HA cleavage and reduced viral production. Cells transduced with the kallistatin gene secreted kallistatin extracellularly, which rendered them more resistant to influenza virus infection. Furthermore, lentivirus-mediated kallistatin gene delivery protected mice against lethal influenza virus challenge by reducing the viral load, inflammation, and injury in the lung. Taking the data together, we determined that KLK1 and kallistatin contribute to the pathogenesis of influenza virus by affecting the cleavage of the HA peptide and inflammatory responses. This study provides a proof of principle for the potential therapeutic application of kallistatin or other KLK1 inhibitors for influenza. Since proteolytic activation also enhances the infectivity of some other viruses, kallistatin and other kallikrein inhibitors may be explored as antiviral agents against these viruses.     

心脏瓣膜置换同期行双极射频消融术治疗房颤的临床疗效

目的探讨心脏瓣膜置换同期行双极射频消融术(BRFA)治疗心房纤颤(AF)的临床疗效及安全性。方法回顾性分析2011年1月至2012年12月在瓣膜置换术同期行BRFA治疗的90例AF患者临床资料,患者在全身麻醉开胸直视体外循环下行瓣膜置换术及BRFA。术后随访患者心脏彩色超声、心电图等指标,分析比较其疗效。结果患者动脉阻断时间为65~120 min,平均(75.5±24.5)min,体外循环时间为45~200 min,平均(112.5±30.8)min;BRFA时间为13~28min,平均(21.5±7.5)min。随访结果表明91.11%患者术后3个月维持窦性心律,术后12个月左心房、左心室径线较术前明显减小,左心室射血分数较术前明显增高,差异有统计学意义(P0.05);同时房颤持续时间、术前左房径线及左室径线对手术成功有影响。结论心脏瓣膜置换术同期行BRFA治疗AF安全、简便且效果良好,值得临床推广应用。     

1294例女性高危型人乳头瘤病毒基因分型结果回顾性分析

目的了解北京地区妇科门诊就诊女性高危型人乳头瘤病毒(HPV)的感染及其基因亚型分布情况,为该市今后防治人乳头瘤病毒感染和宫颈癌提供参考依据。方法回顾性分析2013年1月至2014年5月该院妇科门诊就诊的1 294例女性宫颈拭子的13种高危型HPV基因分型检测结果,比较不同基因型的流行病学特点。采用SPSS17.0对数据进行统计学分析。结果 1 294例妇科门诊就诊女性中,以58型、16型和52型HPV最为常见,检出率分别为10.5%、9.2%和8.2%。各年龄段就诊女性中,30~40岁的HPV感染率最高(39.9%),其次为40~50岁、大于或等于60岁,差异无统计学意义(P0.05)。结论该地区妇科门诊就诊女性高危型HPV感染率较高,应加强HPV筛查力度,为今后HPV相关疾病的防治提供基础依据。     

高迁移率族蛋白B1靶向治疗的研究进展

高迁移率族蛋白B1 (HMGB1)为重要炎性因子,其为无菌性炎症与感染相关炎症反应的重要调节者,在感染、炎症及免疫反应中发挥重要作用.HMGB1表达水平可反映机体炎症及组织损伤的严重程度,且与相关疾病的预后密切相关.以HMGB1为治疗靶点,有望为感染、自身免疫性疾病、缺血再灌注损伤(IRI)、移植物抗宿主病(GVHD)等疾病的治疗提供潜在新策略.     

Alterations of gene profiles in Leydig-cell-regenerating adult rat testis after ethane dimethane sulfonate-treatment

Only occupying about 1%–5% of total testicular cells, the adult Leydig cell (ALC) is a unique endocrine cell that produces androgens. Rat Leydig cells regenerate after these cells in the testis are eliminated with ethane dimethane sulfonate (EDS). In this study, we have characterized Leydig cell regeneration and messenger ribonucleic acids (mRNA) profiles of EDS treated rat testes. Serum testosterone, testicular gene profiling and some steroidogenesis-related proteins were analyzed at 7, 21, 35 and 90 days after EDS treatment. Testicular testosterone levels declined to undetectable levels until 7 days after treatment and then started to recover. Seven days after treatment, 81 mRNAs were down-regulated greater than or equal to two-fold, with 48 becoming undetectable. These genes increased their expression 21 days and completely returned to normal levels 90 days after treatment. The undetectable genes include steroidogenic pathway proteins: steroidogenic acute regulatory protein, Scarb1, Cyp11a1, Cyp17a1, Hsd3b1, Cyp1b1 and Cyp2a1. Seven days after treatment, there were 89 mRNAs up-regulated two-fold or more including Pkib. These up-regulated mRNAs returned to normal 90 days after treatment. Cyp2a1 did not start to recover until 35 days after treatment, indicating that this gene is only expressed in ALCs not in the precursor cells. Quantitative polymerase chain reaction, western blotting and semi-quantitative immunohistochemical staining using tissue array confirmed the changes of several randomly picked genes and their proteins.