Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

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Bone marrow-derived mesenchymal stem cells repair severe acute pancreatitis by secreting miR-181a-5p to target PTEN/Akt/TGF-β1 signaling

BackgroundSevere acute pancreatitis (SAP) is associated with high morbidity and mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown obvious protective effect on SAP. However, little is known about the underlying mechanism. The objective of this study is to unravel the role and regulatory mechanism of miR-181a-5p in BMSCs-mediated pancreatic repair.MethodsBMSCs were isolated from Sprague-Dawley rats and characterized by flow cytometry and Oil Red O staining. Sodium taurocholate- and caerulein-induced models were used as SAP models in vivo and in vitro, respectively. Pancreatic injury were evaluated by H&E and histopathological analysis, as well as by measuring levels of amylase, lipase and cytokines. qRT-PCR and western blotting were performed to detect the level of miR-181a-5p and the protein levels of PTEN/Akt, respectively. ELISA was conducted to detect the levels of TNF-α, IL-1β, IL-6, angiopoietin, IL-4, IL-10 and TGF-β1. The apoptotic rate of AR42 J cells was quantitated by concurrent staining with Annexin-V-FITC and PI.ResultsBMSCs significantly attenuated pancreatic injury in SAP rats by reducing inflammatory infiltration and necrosis, and this effect was abolished by CXCR4 agonist AMD3100. ADM3100 exhibited more severe pancreatic injury and decreased miR-181a-5p levels in the pancreas and serum compared to SAP group. Overexpression of miR-181a-5p in BMSCs (BMSCs-miR-181a-5p) markedly potentiated the protective effect of BMSCs by reducing histological damage and levels of amylase and lipase. Moreover, BMSCs-miR-181a-5p dramatically reduced levels of angiopoietin, TNF-α, IL-1β and IL-6, but induced the levels of IL-4 and IL-10. In caerulein-treated AR42 J cells, co-culturing of BMSCs-miR-181a-5p alleviated caerulein-induced increase of amylase and lipase, and apoptosis via PTEN/Akt/TGF-β1 signaling.ConclusionBMSCs alleviate SAP and reduce inflammatory responses and apoptosis by secreting miR-181a-5p to target PTEN/Akt/TGF-β1 signaling. Hence, BMSCs-miR-181a-5p could serve as potential therapeutic target for SAP.     

Induction of apoptosis and c-myc in L1210 lymphocytic leukemia cells by adenosine

High concentrations of adenosine (Ado), when added to L1210 lymphocytic leukemia cells, resulted in apoptosis or programmed cell death. The apoptotic process was accompanied by distinct morphological changes including chromatin condensation and blebbing of plasma membranes. Extensive DNA fragmentation was correlated with Ado concentrations. Furthermore, apoptosis in these cells was preceded by an early but transient expression of c-myc proto-oncogene, and was not influenced by homocysteine thiolactone added to the cells. Since severe combined immunodeficiency (SCID) is associated with a deficiency of adenosine deaminase, leading to defects in both cellular and humoral immunity, Ado-induced apoptosis may thus be a contributing factor in the pathology of SCID.     

Factores de riesgo asociados a fallecimiento por la variante ómicron de COVID-19: análisis retrospectivo con personas mayores de Canarias

Background and aimsSince the beginning of the COVID-19 pandemic, the elderly population has had the highest rates of complications and mortality. This study aimed to determine the influence of different risk factors on deaths due to the Omicron variant in the Canary Islands.Materials and methodsA retrospective observational study of 16,998 cases of COVID-19 over 40 years of age was conducted in the Canary Islands between August 1, 2022, and January 31, 2023. We extracted sociodemographic data (age and sex) and clinical data (death, vaccination history, hospital admission, previous diseases, and treatments).ResultsAmong the deaths, there was a higher proportion of males aged over 70 years, with diabetes, cardiovascular, renal, respiratory, and systemic diseases, and nursing home residents. Significant differences were observed in the number of doses of the vaccine. The multiple regression model showed that male sex (OR [95% CI] = 1.92 [1.42–2.58]), age (70–79 years, 9.11 [4.27–19.43]; 80–89 years, 21.72 [10.40–45.36]; 90–99 years, 66.24 [31.03–141.38]; 100 years or older, 69.22 [12.97–369.33]), being unvaccinated (6.96, [4.01–12.08]), or having the last dose administered at least 12 months before the diagnosis (2.38, [1.48–3.81]) were significantly associated with mortality.ConclusionsMultiple factors may increase the risk of mortality due to COVID-19 in the elderly population. In our study, we found that only three predictors can effectively explain the variability: older age, male sex, and not being vaccinated or last vaccination date prior to one year.     

凝血-纤溶失衡与子痫前期的关系及对产后大出血的预测价值研究

摘要 目的：分析凝血-纤溶失衡与子痫前期的关系及对产后大出血的预测价值。方法：选择我院自2018年1月至2021年12月接诊的160例子痫前期孕妇作为观察组,另选同期的160例健康妊娠孕妇作为对照组;以凝血酶-抗凝血酶复合物（TAT）/纤溶酶-α2纤溶酶抑制物复合物（PIC）比值评价凝血-纤溶失衡程度,使用Pearson相关性分析TAT/PIC比值与分娩孕周、分娩出血量的关系,通过AUC评价TAT/PIC比值对产后大出血的预测效能。结果：观察组血浆TAT水平高于对照组,PIC水平低于对照组,TAT/PIC比值大于对照组（P<0.05）;经Pearson相关性分析,子痫前期孕妇TAT/PIC比值与分娩出血量呈正相关,与出生体重呈负相关（P<0.05）;产后大出血组血浆TAT水平高于非产后大出血组,PIC水平低于非产后大出血组,TAT/PIC比值大于非产后大出血组（P<0.05）;经ROC曲线分析,TAT/PIC比值预测子痫前期孕妇产后大出血的AUC为0.910,大于TAT的0.665和PIC的0.650（P<0.05）。结论：子痫前期的发生可能与凝血-纤溶失衡有关,而TAT/PIC比值与分娩出血量及出生体重的关系密切,预测产后大出血的效能较好,值得临床予以重视应用。     

颅内压参数联合血清caveolin-1、AQP-4对高血压脑出血患者术后预后不良的预测价值

摘要 目的：探讨颅内压参数联合血清小窝蛋白-1（caveolin-1）、水通道蛋白4（AQP-4）对高血压脑出血（HICH）患者术后预后不良的预测价值。方法：选择2020年1月至2022年1月河北省胸科医院收治的106例HICH患者,术后随访3个月,根据格拉斯哥预后（GOS）评分将患者分为预后良好组（55例）,预后不良组（51例）。术后监测颅内压参数[压力反应指数（PRx）、平均颅内压波幅（MWA）、20 mmHg阈值下颅内压剂量（Dicp20）],检测血清caveolin-1、AQP-4水平。多因素Logistic回归分析HICH患者术后预后不良的因素。受试者工作特征曲线（ROC）分析颅内压参数联合血清caveolin-1、AQP-4预测HICH患者术后预后不良的价值。结果：预后不良组PRx、MWA、Dicp20以及血清caveolin-1、AQP-4水平高于预后良好组（P＜0.05）。低术前格拉斯哥昏迷评分（GCS）评分、高PRx、高Dicp20、高caveolin-1、高AQP-4是HICH患者术后预后不良的危险因素（P＜0.05）。联合PRx、Dicp20、caveolin-1和AQP-4预测HICH患者术后3个月预后不良的的曲线下面积为0.823,大于PRx、Dicp20、caveolin-1和AQP-4单独预测。结论：高PRx、Dicp20、caveolin-1、AQP4是HICH患者术后预后不良的危险因素,联合颅内压参数PRx、Dicp20及血清caveolin-1、AQP4预测HICH患者术后预后不良具有较高的价值。     

重症肺炎患者病原菌分布、临床结局分析及血清尿素氮与肌酐比值、尿素氮与白蛋白比值联合检测的临床意义

摘要 目的：分析重症肺炎（SP）患者病原菌分布和临床结局并探讨血清尿素氮与肌酐比值（UCR）、尿素氮与白蛋白比值（UAR）联合检测的临床意义。方法：选取2019年8月～2022年8月三六三医院收治的107例SP患者,根据临床结局分为死亡组和存活组。分析SP患者病原菌分布情况。采用单因素和多因素Logistic回归分析SP患者临床结局的影响因素,采用受试者工作特征（ROC）曲线分析血清UCR、UAR水平对SP患者临床结局的评估价值。结果：107例SP患者痰液标本中培养出122株病原菌,其中革兰阴性菌75株（61.48%）,革兰阳性菌39株（31.97%）,真菌8株（6.56%）。107例SP患者院内死亡率为40.19%（43/107）。多因素Logistic回归分析显示,年龄增加、肺外并发症≥2个和UCR、UAR升高为SP患者临床结局不良的独立危险因素,氧合指数增加为其独立保护因素（P＜0.05）。ROC曲线分析显示,血清UCR、UAR联合评估SP患者临床结局的曲线下面积（AUC）大于各指标单独评估。结论：SP患者病原菌分布以革兰阴性菌为主,血清UCR、UAR升高为SP患者临床结局不良的独立危险因素,可能成为SP患者临床结局的辅助评估指标,且二者联合评估SP患者临床结局的价值较高。