Comparative genomics analysis of Clostridium difficile epidemic strain DH/NAP11/106

Clostridium difficile PCR ribotype 106 (also identified as restriction endonuclease analysis [REA] group DH) recently emerged as the most common strain causing C. difficile infection (CDI) among US adults. We previously identified this strain predominating our pediatric cohort. Pediatric clinical CDI isolates previously characterized by REA underwent antibiotic resistance testing and whole genome sequencing. Of 134 isolates collected from children, 31 (23%) were REA group DH. We performed a comparative genomics analysis to identify DH-associated accessory genes. We identified five DH-associated genes that are associated with virulence in other bacterial species but not previously known to contribute to CDI. These genes are associated with intestinal mucosal adhesion (collagen-binding surface protein), sporulation (sporulation integral membrane protein YtvI), and protection from oxidative stress and foreign DNA (DNA phosphorothioation-dependent restriction proteins, sulfurtransferase, and DNA sulfur modification proteins). The association of these genes was validated in a cohort of 623 publicly available C. difficile sequences, 10 (1.6%) of which were monophyletic to REA group DH through in silico multilocus sequence typing and core genome phylogenetic analysis. Further investigation is required to determine the contribution of these genes to the emergence and virulence of this epidemic strain.     

Maternal exercise training attenuates endotoxin-induced sepsis in mice offspring

Regular exercise during pregnancy can prevent offspring from several diseases, such as cardiovascular diseases, obesity, and type II diabetes during adulthood. However, little information is available about whether maternal exercises during pregnancy protect the offspring from infectious diseases, such as sepsis and multiple organ dysfunction syndrome (MODS). This study aimed to investigate whether maternal exercise training protects the offspring from endotoxin-induced septic shock in mice. Female C57BL/6 mice performed voluntary wheel exercises during pregnancy. All dams and offspring were fed normal chow with sedentary activity during lactation and after weaning. At 10-week-old, mice were intraperitoneally injected a lethal (30 mg/kg) or nonlethal (15 mg/kg) dose of lipopolysaccharide (LPS), following which the survival of mice that were administered a lethal dose was monitored for 60 h. Plasma, lung, and liver samples were collected 18 h after the injection to evaluate the cytokine concentration or mRNA expression from those administered a nonlethal dose. Although maternal exercise training could not prevent lethality during an LPS-induced septic shock, it significantly inhibited the LPS-induced loss of body weight in female offspring. Regular maternal exercise significantly inhibited the mRNA expression of the LPS-induced inflammatory cytokines, such as interleukin-1β (IL-1β) and interferon-γ (IFN-γ), in the plasma and liver. Thus, maternal exercise inhibited the LPS-induced inflammatory response in female offspring, suggesting that regular exercise during pregnancy could be a potential candidate of the onset of sepsis and MODS in offspring.     

脓毒血症大鼠心肌II型磷脂酶A_2活性变化及其调控

观察了脓毒血症大鼠心肌ＩＩ型ＰＬＡ２ 活性、蛋白质含量及其ｍ ＲＮＡ 的变化。结果发现, 脓毒血症早期与晚期心肌ＩＩ型ＰＬＡ２ 活性较对照组分别降低２５ ．０ ％ （Ｐ ＜ ０ ．０５）及增高４７．６ ％ （Ｐ ＜ ０ ．０１）,ＩＩ型ＰＬＡ２ 蛋白质含量分别降低２７．０％ 及增高４８ ．０ ％（ 均Ｐ ＜ ０ ．０１）; 心肌ＩＩ型ＰＬＡ２ ｍ ＲＮＡ合成率与含量呈现类似的双相变化, 在脓毒血症早、晚期ｍＲＮＡ 合成率分别降低４５．０％ 和升高７０．０ ％ （均Ｐ ＜ ０ ．０１）,ｍＲＮＡ含量分别降低３４．１ ％ 和增加１５７ ．０％ （均Ｐ＜ ０ ．０１） 。脓毒血症早、晚期心脏ＩＩ型ＰＬＡ２ ｍ ＲＮＡ半衰期无显著变化（Ｐ ＞ ０．０５） 。实验结果表明大鼠脓毒血症发生过程中心肌ＩＩ型ＰＬＡ２ 活性呈现出先下降后升高的变化, 这一变化受其ｍＲＮＡ 转录水平的调节。     

小剂量糖皮质激素联合持续性血液净化治疗儿童严重脓毒症的效果及安全性研究

摘要 目的：分析小剂量糖皮质激素联合持续性血液净化治疗儿童严重脓毒症的效果及安全性。方法：选择自2021年1月至2023年1月接诊的102例儿童严重脓毒症患儿作为研究对象,随机分为对照组和观察组,各51例;对照组予以经典治疗方案,观察组在对照组的基础上,予以小剂量糖皮质激素联合持续性血液净化治疗;记录两组治疗后各项信息,比较两组治疗前后外周血乳酸、中心静脉血氧饱和度（ScvO₂）、血清炎症指标、PCIS评分、APACHE Ⅱ评分,观察主要并发症发生情况。结果：与对照组相比,观察组机械通气、低血压持续及入住ICU等时间较短,7 d内停升压药率较高（P＜0.05）;两组28 d病死率比较无差异（P＞0.05）;观察组治疗后乳酸、降钙素原（PCT）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）水平均较对照组低,ScvO₂水平较对照组高（P＜0.05）;观察组治疗后PCIS评分较对照组高,APACHE Ⅱ评分较对照组低（P＜0.05）;观察组主要并发症发生率低于对照组（P＜0.05）。结论：小剂量糖皮质激素联合持续性血液净化治疗有利于儿童严重脓毒症患儿病情转归,减少主要并发症发生,可能与阻断炎症反应有关,值得进一步研究应用。     

无创血流动力学监测指导严重脓毒症患者血管活性药物的应用

目的:探讨无创血流动力学监测技术在严重脓毒症患者液体复苏后指导血管活性药物使用的意义。方法:选择2014年6月至2016年6月我院急诊处收治的严重脓毒症患者56例为研究对象,分为观察组和对照组,每组各28例。对照组进行常规对症治疗,观察组在对照组治疗基础上使用无创血流动力学监测仪指导治疗。观察两组患者在治疗前及治疗后6 h血流动力学及微循环灌注指标、液体复苏6 h后液体平衡量及血管活性药物使用量,及在重症监护病房(EICU)的入住时间。结果:治疗后两组患者尿量均大于30 m L/h,提示复苏成功。两组患者治疗后血液动力学指标和微循环灌注指标较治疗前均明显好转(均P0.05);治疗后,两组间血液动力学指标和微循环灌注指标比较无明显差异(P0.05)。观察组液体复苏6 h后液体平衡量明显少于对照组(P0.05),观察组血管活性药物用量均明显高于对照组(P0.05),观察组患者在EICU病房住院时间明显短于对照组(P0.05)。结论:无创血流动力学监测对严重脓毒症患者的液体恢复管理和治疗过程具有指导意义,使血管活性药物得到有效利用,精确进行液体管理,减少盲目补液,缩短病程,减少患者的住院时间,经济高效,是指导治疗和评估治疗疗效的重要手段。