TLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model

Toll-like receptor 9 (TLR9) is highly expressed in B cells, and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on β-cell autoimmunity is not known. To fill this knowledge gap, we generated NOD mice with a B-cell–specific deficiency of TLR9 (TLR9^fl/fl/CD19-Cre+ NOD). The B-cell–specific deletion of TLR9 resulted in near-complete protection from T1D development. Diabetes protection was accompanied by an increased proportion of interleukin-10 (IL-10)–producing B cells. We also found that TLR9-deficient B cells were hyporesponsive to both innate and adaptive immune stimuli. This suggested that TLR9 in B cells modulates T1D susceptibility in NOD mice by changing the frequency and function of IL-10–producing B cells. Molecular analysis revealed a network of TLR9 with matrix metalloproteinases, tissue inhibitor of metalloproteinase-1, and CD40, all of which are interconnected with IL-10. Our study has highlighted an important connection of an innate immune molecule in B cells to the immunopathogenesis of T1D. Thus, targeting the TLR9 pathway, specifically in B cells, may provide a novel therapeutic strategy for T1D treatment.     

落花生根内生真菌Fusarium oxysporum LHS-P1-3中恩镰孢菌素类化合物及生物活性研究

目的 研究落花生根内生真菌Fusarium oxysporum LHS-P1-3的次级代谢产物及其生物活性。方法 使用硅胶色谱柱、高效液相色谱等对代谢粗提物进行分离纯化,采用质谱、核磁共振等方法测定化合物的结构,采用CCK-8法测试化合物的抗肿瘤细胞活性,使用表面等离子共振实验（surface plasmon resonance,SPR）研究化合物与胆固醇转运蛋白1（niemann-pick c1-like 1,NPC1L1）相互作用关系。结果 从落花生根内生真菌Fusarium oxysporum LHS-P1-3分离得到6个化合物,包括1个新化合物（1）与5个已知化合物：白僵菌素（2）、恩镰孢菌素I（3）、恩镰孢菌素MK1688（4）、恩镰孢菌素H（5）及恩镰孢菌素B（6）。化合物1～4对HepG2细胞和HeLa细胞的IC₅₀均小于10 μmol/L,化合物2～4则对HCT116细胞的IC₅₀小于10 μmol/L,SPR研究表明化合物2、4在20 μmol/L浓度下,可与NPC1L1蛋白相互作用。结论 化合物1为新的恩镰孢菌素类化合物,命名为恩镰孢菌素W。化合物1～5具有抗肿瘤活性,化合物2、4与NPC1L1蛋白存在相互作用,可能是NPC1L1蛋白的潜在抑制剂。     

中药抗药源性肝损伤评价模型及作用机制研究进展

肝脏是药物在机体内代谢的主要场所。药源性肝损伤（drug-induced liver injury,DILI）是药物过量或不当使用导致的机体不良反应之一。非甾体类抗炎药、抗菌药等均可能引起DILI。DILI发生机制主要与细胞色素P450酶、线粒体功能障碍、药物代谢反应、氧化应激、炎症反应等密切相关。中药可通过抑制氧化应激、炎症反应、减少细胞凋亡与影响细胞色素P450酶系统等发挥治疗肝损伤作用。通过对DILI发生机制、动物模型建立方法及中药干预机制等方面进行总结归纳,为DILI动物模型的合理选择及中药防治机制研究提供参考。     

Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/β-catenin pathway in the myocardium of mice after myocardial infarction

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/β-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.     

微创冠状动脉旁路移植术处理前降支病变的围术期结果

目的研究胸腔镜辅助下经左胸小切口微创直视下冠状动脉旁路移植术(minimally invasive direct coronary artery bypass grafting,MIDCAB)处理前降支病变的围术期结果及其安全性。方法回顾性分析2014年5月至2018年10月在我院接受MIDCAB 92例患者的临床资料,其中男72例(78.26%),年龄42~78(61.29±7.48)岁,女20例(21.74%),年龄30~80(61.30±12.26)岁。分析围术期并发症发生率、血制品使用情况、左心功能变化情况、呼吸机使用时间、住ICU时间及住院时间等指标。结果2例(2.17%)患者中转正中开胸手术,5例(5.43%)术中输入血液制品,2例(2.17%)二次开胸止血,4例(4.34%)术后低氧血症,1例(1.08%)再次气管插管。呼吸机使用时间3~227(22.35±35.39)h,住ICU时间16~777(78.85±108.62)h,术后住院时间2~36(8.86±6.05)d。住院死亡1例(1.08%)。结论MIDCAB处理前降支病变具有较好的围术期结果,尤其适用于孤立性前降支病变,可缩短术后呼吸机使用时间、减少血液制品使用、缩短住ICU时间及住院时间。     

完全右半肝-左半肝劈离式肝移植的临床应用:附四例报告

目的探讨完全右半肝-左半肝劈离式肝移植在成人-成人或成人-大体重儿童中的临床应用。方法回顾2019年1月至12月间首都医科大学附属北京友谊医院完成的4例完全右半肝-左半肝劈离式肝移植的供受者临床资料,分析劈离式肝移植的手术方式、冷缺血时间、手术时间、术中输血量,观察患者术后并发症及相关预后。结果4例完全右半肝-左半肝劈离式肝移植的受者包括3例成人和1例大体重儿童(45 kg),年龄范围14~48岁,体重范围45~61 kg,终末期肝病模型评分分别为21、12、41和30分。移植物质量与受者体质量比为0.85%~1.35%。冷缺血时间457~650 min,手术时长460~575 min。4例患者移植术后早期肝功能恢复顺利,均未出现小肝综合征。随访至术后6个月,其中1例出现胆道吻合口漏,经内镜逆行胰胆管造影术治疗后治愈;1例出现胆道狭窄,经皮肝穿刺胆道引流术治疗后反复胆道感染;1例术后6个月死于肺部感染。结论在严格病例选择的情况下,可以开展完全右半肝-左半肝劈离式肝移植。     

腘窝直接皮动脉穿支蒂螺旋桨皮瓣转位修复腘窝软组织缺损

目的探讨腘窝直接皮动脉穿支蒂螺旋桨皮瓣转位修复腘窝软组织缺损的临床效果。方法采用回顾性病例系列研究分析2013年6月至2019年6月,上海交通大学医学院附属新华医院(崇明)收治的9例腘窝软组织缺损患者临床资料,男6例,女3例,年龄25~73岁,平均49.6岁,腘窝缺损创面为6.5 cm×3.5 cm~17.0 cm×8.5 cm。根据解剖学基础,结合腘窝缺损创面的位置、大小、形状,设计并切取腘窝直接皮动脉穿支蒂螺旋桨皮瓣转位修复腘窝缺损创面,皮瓣面积最大为18.0 cm×10.0 cm,最小为7.5 cm×4.5 cm。根据皮瓣成活、感染控制、弹性色泽、外观形态、供区瘢痕、皮肤感觉、膝关节活动功能、患者认可度等情况,对患者术后疗效进行综合评价。结果 9例皮瓣术后全部顺利成活,供、受区伤口一期愈合,其中2例皮瓣远端发生皮缘坏死,给予换药处理后完全愈合。术后均获6~60个月随访,平均33个月,皮瓣成活优良,形态满意,色泽、弹性、质地与周围正常皮肤接近,供区瘢痕较小。疗效评价:满意8例,一般1例,无不满意。膝关节功能优7例,良1例,可1例。皮瓣肿胀评级,早期:Ⅰ度6例,Ⅱ度2例,Ⅲ度1例,Ⅳ度0例;后期:Ⅰ度8例,Ⅱ度1例,Ⅲ度0例,Ⅳ度0例。结论腘窝直接皮动脉穿支蒂螺旋桨皮瓣移位修复腘窝缺损创面方法简便、安全可靠、损伤较小,易于推广,是修复腘窝皮肤软组织缺损的理想方法之一。     

Knotless All-Inside Arthroscopic Modified Broström Procedure for Lateral Ankle Instability

One reported complication of the arthroscopic modified Broström operation is pain caused by the suture anchoring knot. We hypothesized that a knotless technique could reduce such pain. Therefore, in this study we evaluated the clinical and radiological outcomes after knotless all-inside arthroscopic modified Broström operation for lateral ankle instability. From July 2017 to November 2017, 28 patients were treated. Clinical and radiological features were evaluated preoperatively and 3, 6, and 12 months postoperatively using the American Orthopaedic Foot & Ankle Society ankle-hindfoot scale score, visual analogue scale score for pain, anterior talar drawer test, and talar tilt angle. The mean age of the 28 patients (14 men, 14 women) was 41.71 ± 17.19 years. Three (10.7%) complications, but no knot-associated pain, occurred. The clinical and radiological outcomes were significantly improved 12 months postoperatively compared with preoperative outcomes (all p < .05). Knotless all-inside arthroscopic modified Broström operation for lateral ankle instability avoided knot-associated pain and improved not only patient satisfaction but also clinical and radiological outcomes.     

ASO Visual Abstract: Development and Validation of Web-Based Nomograms for Predicting Cause-Specific Mortality in Surgically Resected Nonmetastatic Invasive Breast Cancer: A Population-Based Study

Annals of Surgical Oncology -