胰腺炎基础研究进展与展望

近年来,胰腺炎的病理生理机制研究取得了诸多实质性进展。其中,急性胰腺炎领域热点内容众多,如胰蛋白酶原异常激活、病理性钙超载、线粒体功能障碍、自噬、内质网应激、NF-κb激活、细胞程序性死亡等。慢性胰腺炎领域的研究则更多集中于胰腺星状细胞激活对慢性胰腺炎纤维化的影响,以此为主干,又可进一步研究自噬、外泌体等与胰腺星状细胞活化的关系。在胰腺炎的基础研究中,可以进行机制的深入发掘,而机制的发掘又为寻找疾病分子标记物、新药研发、治疗靶点选择等提供了源源不断的新思路。此外,免疫、肠道微生态等作为当前基础研究的热点领域,其在胰腺炎发生、发展中的作用值得进一步探索。     

术前预后营养指数对 584 例心脏手术后患者急性肾损伤的预测价值

目的评估术前预后营养指数(prognostic nutritional index,PNI)对择期体外循环(cardiopulmonary bypass,CPB)下非冠状动脉旁路移植(coronary artery bypass grafting,CABG)心脏手术后急性肾损伤(acute kidney injury,AKI)的预测价值。方法回顾性分析我院2019年5~9月584例行择期CPB下非CABG心脏手术患者资料,其中男268例(45.9%)、女316例(54.1%),平均年龄(52.1±11.6)岁。平均CPB时间(124.8±50.1)min、平均主动脉阻断时间(86.4±38.9)min。449例(76.9%)为单纯瓣膜手术。运用多因素逻辑回归建立AKI风险预测模型,通过受试者工作特征曲线下面积(AUC)与Hosmer-Lemeshow拟合优度检验明确术前PNI、克利夫兰临床评分(Cleveland Clinic Score,CCS)及预测模型对AKI的预测价值。净重新分类指数(net reclassification index,NRI)与AUC变化量用于明确术前PNI对CCS或AKI风险预测模型预测能力的改善情况。结果术前PNI不能有效预测CPB下非CABG心脏手术后AKI的发生(AUC=0.553,95%CI 0.489~0.617,P=0.095),且不能改善其它AKI预测模型的预测作用。本研究所构建的风险预测模型对AKI或严重AKI(2~3级)的发生均具有较高预测价值(AUC=0.741,95%CI 0.686~0.796,P<0.001),明显优于CCS(AUC=0.512,95%CI 0.449~0.576,P=0.703)。结论术前PNI不能有效预测择期CPB下非CABG心脏手术后AKI的发生,且对其它AKI预测模型无改善作用。     

Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury

BackgroundDamage to the renal microvasculature is a hallmark of renal ischemia-reperfusion injury (IRI)–mediated AKI. The miR-17∼92 miRNA cluster (encoding miR-17, -18a, -19a, -20a, -19b-1, and -92a-1) regulates angiogenesis in multiple settings, but no definitive role in renal endothelium during AKI pathogenesis has been established.MethodsAntibodies bound to magnetic beads were utilized to selectively enrich for renal endothelial cells from mice. Endothelial-specific miR-17∼92 knockout (miR-17∼92^endo−/−) mice were generated and given renal IRI. Mice were monitored for the development of AKI using serum chemistries and histology and for renal blood flow using magnetic resonance imaging (MRI) and laser Doppler imaging. Mice were treated with miRNA mimics during renal IRI, and therapeutic efficacies were evaluated.ResultsmiR-17, -18a, -20a, -19b, and pri–miR-17∼92 are dynamically regulated in renal endothelial cells after renal IRI. miR-17∼92^endo−/− exacerbates renal IRI in male and female mice. Specifically, miR-17∼92^endo−/− promotes renal tubular injury, reduces renal blood flow, promotes microvascular rarefaction, increases renal oxidative stress, and promotes macrophage infiltration to injured kidneys. The potent antiangiogenic factor thrombospondin 1 (TSP1) is highly expressed in renal endothelium in miR-17∼92^endo−/− after renal IRI and is a target of miR-18a and miR-19a/b. miR-17∼92 is critical in the angiogenic response after renal IRI, which treatment with miR-18a and miR-19b mimics can mitigate.ConclusionsThese data suggest that endothelial-derived miR-17∼92 stimulates a reparative response in damaged renal vasculature during renal IRI by regulating angiogenic pathways.     

Early steroid withdrawal in HIV-infected kidney transplant recipients: Utilization and outcomes

Kidney transplant (KT) outcomes for HIV-infected (HIV+) persons are excellent, yet acute rejection (AR) is common and optimal immunosuppressive regimens remain unclear. Early steroid withdrawal (ESW) is associated with AR in other populations, but its utilization and impact are unknown in HIV+ KT. Using SRTR, we identified 1225 HIV+ KT recipients between January 1, 2000, and December 31, 2017, without AR, graft failure, or mortality during KT admission, and compared those with ESW with those with steroid continuation (SC). We quantified associations between ESW and AR using multivariable logistic regression and interval-censored survival analysis, as well as with graft failure and mortality using Cox regression, adjusting for donor, recipient, and immunologic factors. ESW utilization was 20.4%, with more zero HLA mismatch (8% vs 4%), living donors (26% vs 20%), and lymphodepleting induction (64% vs 46%) compared to the SC group. ESW utilization varied widely across 129 centers, with less use at high- versus moderate-volume centers (6% vs 21%, P < .001). AR was more common with ESW by 1 year (18.4% vs 12.3%; aOR: _1.081.61_2.41, P = .04) and over the study period (aHR: _1.021.39_1.90, P = .03), without difference in death-censored graft failure (aHR _0.600.91_1.36, P = .33) or mortality (aHR: _0.751.15_1.77, P = .45). To reduce AR after HIV+ KT, tailoring of ESW utilization is reasonable.     

Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients

Individualized posttransplant immunosuppression is hampered by suboptimal monitoring strategies. To validate the utility of urinary CXCL10/Cr immune monitoring in children, we conducted a multicenter prospective observational study in children <21 years with serial and biopsy-associated urine samples (n = 97). Biopsies (n = 240) were categorized as normal (NOR), rejection (>i1t1; REJ), indeterminate (IND), BKV infection, and leukocyturia (LEU). An independent pediatric cohort of 180 urines was used for external validation. Ninety-seven patients aged 11.4 ± 5.5 years showed elevated urinary CXCL10/Cr in REJ (3.1, IQR 1.1, 16.4; P < .001) and BKV nephropathy (median = 5.6, IQR 1.3, 26.9; P < .001) vs. NOR (0.8, IQR 0.4, 1.5). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66–0.86). Low (0.63) and high (4.08) CXCL10/Cr levels defined high sensitivity and specificity thresholds, respectively; validated against an independent sample set (AUC = 0.76, 95% CI 0.66–0.86). Serial urines anticipated REJ up to 4 weeks prior to biopsy and declined within 1 month following treatment. Elevated mean CXCL10/Cr was correlated with first-year eGFR decline (ρ = −0.37, P ≤ .001), particularly when persistently exceeding ≥4.08 (ratio = 0.81; P < .04). Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function for use in real-time clinical monitoring in children.     

不同方法治疗急性大脑中动脉M2段闭塞效果

目的对比常规治疗、经静脉溶栓和血管内治疗对急性大脑中动脉M2段(MCA-M2)闭塞的临床疗效。方法76例急性MCA-M2闭塞患者分别接受常规治疗(常规组,n=31)、静脉溶栓治疗(溶栓组,n=27)和血管内治疗(血管内组,n=18),比较3组疗效相关指标。结果治疗后24 h,血管内组美国国立卫生研究院卒中量表(NIHSS)评分较基线下降≥4分者占比(83.33%)显著高于常规组(48.15%,校正前及校正后P均<0.01)。随访90天,相比常规组,溶栓组和血管内组良好预后率均提高、死亡率均降低,非症状性颅内出血发病率增加(校正前P均<0.05);经年龄、基线NIHSS评分、发病至入院时间校正后差异均无统计学意义(P均>0.05)。溶栓组1例出现症状性颅内出血。血管内组血管再通率94.44%。结论对于MCA-M2闭塞性急性脑梗死患者,急诊血管内治疗安全、有效,可早期快速改善神经功能。     

血管紧张素转化酶2在冠状病毒感染所致肺损伤及其他肺部疾病中研究进展

血管紧张素转化酶2(ACE2)为拮抗血管紧张素转化酶-血管紧张素(ACE-AngⅡ)的关键调控分子。本文总结ACE2通过与新型冠状病毒(SARS-CoV-2)以及非典型性肺炎(SARS)病毒所携带的S蛋白结合,介导上述病毒进入宿主细胞进行复制并发挥细胞毒性作用,并探讨使用二甲双胍以及血管紧张素转化酶抑制剂/血管紧张素受体拮抗剂(ACEI/ARB)缓解SARS-CoV-2感染所致肺组织损伤的可能性。此外,就ACE2以及介导的AngⅡ水解产物Ang(1~7)在急性肺损伤(ALI)、肺纤维化和肺动脉高压中的研究进展进行综述。ACE2在新型冠状病毒肺炎(COIVD-19)的发病机制中发挥着重要作用,可成为设计、研发(COIVD-19)相关治疗药物的重要靶点。