The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: The use of mechanical circulatory support in lung transplantation

ObjectiveThe use of mechanical circulatory support (MCS) in lung transplantation has been steadily increasing over the prior decade, with evolving strategies for incorporating support in the preoperative, intraoperative, and postoperative settings. There is significant practice variability in the use of these techniques, however, and relatively limited data to help establish institutional protocols. The objective of the AATS Clinical Practice Standards Committee (CPSC) expert panel was to review the existing literature and establish recommendations about the use of MCS before, during, and after lung transplantation.MethodsThe AATS CPSC assembled an expert panel of 16 lung transplantation physicians who developed a consensus document of recommendations. The panel was broken into subgroups focused on preoperative, intraoperative, and postoperative support, and each subgroup performed a focused literature review. These subgroups formulated recommendation statements for each subtopic, which were evaluated by the entire group. The statements were then developed via discussion among the panel and refined until consensus was achieved on each statement.ResultsThe expert panel achieved consensus on 36 recommendations for how and when to use MCS in lung transplantation. These recommendations included the use of veno-venous extracorporeal membrane oxygenation (ECMO) as a bridging strategy in the preoperative setting, a preference for central veno-arterial ECMO over traditional cardiopulmonary bypass during the transplantation procedure, and the benefit of supporting selected patients with MCS postoperatively.ConclusionsAchieving optimal results in lung transplantation requires the use of a wide range of strategies. MCS provides an important mechanism for helping these critically ill patients through the peritransplantation period. Despite the complex nature of the decision making process in the treatment of these patients, the expert panel was able to achieve consensus on 36 recommendations. These recommendations should provide guidance for professionals involved in the care of end-stage lung disease patients considered for transplantation.     

New approaches to moderate CRISPR-Cas9 activity: Addressing issues of cellular uptake and endosomal escape

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Prediction and validation of hematopoietic stem and progenitor cell off-target editing in transplanted rhesus macaques

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地鳖纤溶蛋白口服时间/pH依赖结肠靶向微囊的开发及评价＊

地鳖中的纤溶活性蛋白是从地鳖中提取的具有抗栓及抗肿瘤作用的有效成分，其口服易被上消化道酶分解从而限制了应用。采用恒流泵滴制法开发地鳖纤溶活性蛋白时间/pH依赖口服结肠靶向微囊（EnpolypHaga fibrinolytic protein oral colon targeting microcapsules， CTM-EFP）。采用单因素实验和正交实验相结合的方法寻找到包封率为60.17 % ± 2.72 %、载药量为15.50 % ± 0.44 % 的最佳配方。扫描电子显微镜（SEM）显示微囊呈球形、表面光滑，在人工肠液中24 h的累积释放度为99.53 % ± 0.69 %，在人工胃液中24 h累积释放度为7.43 ± 1.04 %，通过时间/pH依赖达到结肠靶向作用。CTM-EFP在人工肠液中的体外释放曲线符合Korsmeyer方程，提示地鳖纤溶活性蛋白（EnpolypHaga fibrinolytic protein， EFP）是通过扩散和侵蚀机制结合释放的。CTM-EFP为EFP的口服给药提供了一种新的剂型，为EFP应用于临床提供参考。     

原发性肺鳞癌中EGFR和ALK基因突变的临床研究北大核心

目的:探讨赣南地区原发性肺鳞癌患者EGFR和ALK基因突变的特点,科学指导此类患者优选靶向用药。方法:入组73例原发性肺鳞癌病例,采用ARMS-PNA技术检测EGFR基因第18、19、20、21外显子突变,应用不平衡法检测其中60例病例的ALK融合基因,回顾性分析EGFR和ALK基因突变患者的临床病理特征。结果:EGFR基因突变8例,阳性率为10.96%(8/73),4例为L858R突变,3例为19del突变,1例为G719X突变。女性患者突变率(66.67%,2/3)明显高于男性患者(8.57%,6/70)(P=0.030),EGFR基因突变在高龄(≥60岁)、进展期(N_(1-3)、Ⅲ+Ⅳ期)患者中相对较高,但差异无统计学意义(P>0.05)。EGFR基因突变与吸烟史、T分期以及肿瘤分布位置均无相关性(P>0.05);ALK融合基因表达2例,阳性率3.33%(2/60),与患者性别、年龄、吸烟史、TNM分期及肿瘤分布类型等各临床病理特征均无相关性(P>0.05);未发现EGFR和ALK基因共存突变病例。结论:赣南地区原发性肺鳞癌患者EGFR和ALK基因突变率相对不高,EGFR基因突变以L858R和19del突变为主,且好发于女性患者,可能是患者病情进展的预测因子之一。     

Correlation analysis of intestinal flora and pathological process of type 2 diabetes mellitus

ObjectiveTo observe the relationship between the different stages of type 2 diabetes mellitus (T2DM) and the intestinal flora and verify its underlying mechanism.MethodsT2DM rats were generated by high-fat diet (HFD) combined with intraperitoneal streptozotocin (STZ) injection. The rats were divided into four groups: the control group (fed with normal feed for 1 month), the HFD group (fed with HFD for 1 month), the T2DM group (HFD combined with STZ and blood glucose ≥11.1 mM), and the unformed T2DM model (Un-mod) group (HFD combined with STZ and blood glucose <11.1 mM). Feces were collected, and bacterial communities in the fecal samples were analyzed by 16S rRNA gene sequencing. The content of short-chain fatty acids (SCFAs) in feces was measured by gas chromatography. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of G protein-coupled receptor 41 (GPR41) and GPR43.ResultsAt different stages of T2DM, the intestinal flora and SCFAs content of rats were significantly decreased (all P < .05). Our results indicated that g__Prevotella had a significant negative correlation, and g__Ruminococcus_torques_group and g__lachnoclastic had a significant positive correlation with blood glucose. The content of SCFAs, in particular acetate and butyrate, in rat feces of different stages of T2DM were significantly reduced, as well as GPR41 and GPR43 expression. The results in the Un-mod group were similar to the T2DM group, and the expression of GPR41 and GPR43 proteins were significantly higher than those in the T2DM group (both P < .001).ConclusionThe intestinal flora–SCFAs–GPR41/GPR43 network may be important in the development of T2DM. Decreasing blood glucose levels by regulating the intestinal flora may become a new therapeutic strategy for T2DM, which has very important clinical and social values.     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.