限制性输血与开放性输血对急性上消化道出血患者凝血功能、血液流变学及预后的影响

摘要 目的：探讨限制性输血与开放性输血对急性上消化道出血患者凝血功能、血液流变学及预后的影响。方法：选取2018年1月~2020年1月期间我院收治的急性上消化道出血患者80例,根据随机数字表法分为对照组（n=40）和研究组（n=40）,对照组患者输血方式采用开放性输血,研究组患者输血方式采用限制性输血,比较两组患者治疗24 h后、48 h后、72 h后的止血率。统计两组患者死亡率、疗效、再出血率和不良事件发生率。比较两组治疗前、治疗72 h后的Blatchford评分及凝血功能指标：凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）以及血液流变学指标：全血黏度、血浆黏度、红细胞比容。结果：研究组治疗24 h后的止血率高于对照组（P<0.05）;两组治疗48 h后、治疗72 h后的止血率组间比较差异无统计学意义（P>0.05）。两组治疗72 h后Blatchford评分均下降,且研究组低于对照组（P<0.05）。两组治疗72 h后PT、APTT均升高,且研究组高于对照组（P<0.05）。两组死亡率比较差异无统计学意义（P>0.05）;研究组不良事件总发生率、再出血率均低于对照组（P<0.05）。研究组治疗后的临床总有效率高于对照组（P<0.05）。两组治疗72 h后全血黏度、血浆黏度、红细胞比容均升高,且研究组高于对照组（P<0.05）。结论：与开放性输血相比,急性上消化道出血患者采用限制性输血,可迅速止血,有效防止患者凝血功能紊乱及血液流变学异常,同时还可减少不良事件总发生率、再出血率,可进一步改善患者预后。     

A Prognostic Model to Predict Recovery of COVID-19 Patients Based on Longitudinal Laboratory Findings

Virologica Sinica - The temporal change patterns of laboratory data may provide insightful clues into the whole course of COVID-19. This study aimed to evaluate longitudinal change patterns of key...     

过表达TRAF6对人急性髓系白血病细胞自噬活性的影响

该文旨在探讨过表达肿瘤坏死因子受体相关因子6(tumor necrosis factor receptorassociated factor 6,TRAF6)对人急性髓系白血病(acute myeloid leukemia,AML)细胞自噬活性的影响。利用基因表达数据库GEO分析TRAF6在AML患者白血病细胞中的mRNA表达水平。通过癌症基因组图谱TCGA分析TRAF6表达与AML患者临床预后的关系。将TRAF6重组质粒载体转染人AML细胞系(KG-1a和THP-1),采用自噬激活剂雷帕霉素(Rapamycin)和自噬相关抑制剂3-甲基腺嘌呤(3-methyladenine,3-MA)、巴弗洛霉素A1(bafilomycin A1,Baf-A1)分别处理AML细胞。荧光定量PCR、蛋白免疫印迹技术检测过表达TRAF6后白血病细胞自噬标志物(LC3和p62)mRNA和蛋白水平;免疫荧光方法检测LC3绿色荧光斑点结构(puncta);流式细胞术检测细胞凋亡率;CCK-8实验检测AML细胞的体外增殖能力。结果显示,AML患者白血病细胞高表达TRAF6(P<0.01);TRAF6高表达的白血病患者总体生存率和无事件生存率均较TRAF6低表达组显著降低(P=0.01)。TRAF6重组质粒转染能够显著增加两株AML细胞系中TRAF6的mRNA和蛋白水平(P<0.05)。Rapamycin处理能够激活AML细胞系自噬水平,过表达TRAF6后AML细胞LC3 mRNA和LC3II蛋白水平表达上调(P<0.05)、p62 mRNA和蛋白水平下调(P<0.05)以及LC3 puncta聚集增多。用Baf-A1处理以阻断过表达TRAF6的白血病细胞系中的自噬流后,LC3II蛋白表达水平显著提高(P<0.05)。3-MA处理过表达TRAF6的白血病细胞后,LC3II蛋白表达减少、p62蛋白表达增加(P<0.05)。此外,过表达TRAF6降低白血病细胞凋亡率和促进细胞的体外增殖(P<0.001),而过表达TRAF6后联合3-MA处理则可逆转TRAF6对白血病细胞的抗凋亡和促增殖作用(P<0.001)。以上研究结果提示,过表达TRAF6能够增强AML细胞的自噬活性,促进AML细胞的生长。     

Transient effect of single or repeated acute deoxynivalenol and zearalenone dietary challenge on fecal microbiota composition in female finishing pigs

Mycotoxins are a major contaminant of pig feed and have negative effects on health and performance. The present study investigated the impact of single or repeated acute challenges with a diet naturally contaminated with deoxynivalenol (DON) and zearalenone (ZEN) on growth performances of finishing pigs and their fecal microbiota composition. A total of 160 pigs (castrated males and females) in two successive batches were randomly divided into four experimental groups of 40 pigs each. The control group received a control finisher diet from 99 to 154 days of age. Challenged groups were subjected to a 7-day acute challenge by being fed a DON- and ZEN-contaminated diet (3.02 mg DON/kg feed and 0.76 mg ZEN/kg feed) at 113 days (group DC), 134 days (group CD) or both 113 and 134 days (group DD). Microbiota composition was analyzed via 16S rRNA sequencing from fecal samples collected from the 80 females at 99, 119, 140 and 154 days. Challenged pigs (i.e. groups DC, CD and DD) reduced their average daily feed intake by 25% and 27% (P < 0.001) and feed efficiency by 34% and 28% (P < 0.05) during the first and second mycotoxin exposure, respectively. Microbiota composition was affected by mycotoxin exposure (P = 0.07 during the first exposure and P = 0.01 during the second exposure). At the family level, mycotoxin exposure significantly (P < 0.05) decreased the relative abundances of Ruminococcaceae, Streptococcaceae and Veillonellaceae and increased that of Erysipelotrichaceae at both 119 and 140 days of age. After the 7-day DON/ZEN challenge, the relative abundance of 6 to 148 operational taxonomic units (OTUs) differed among the treatment groups. However, none of these OTUs changed in all treatment groups. Using 27 functional pathways, pigs exposed to DON/ZEN challenges could be distinguished from control pigs using sparse partial least squares discriminant analysis, with a 15% misclassification rate. Regarding the functionality of these predictors, two pathways were involved in detoxifying mycotoxins: drug metabolism and xenobiotic metabolism by cytochrome P450. In challenged pigs, microbiota composition returned to the initial state within 3 weeks after the end of a single or repeated DON/ZEN challenge, highlighting the resilience of the gut microbiome. The feeding and growth performances of the pigs during challenge periods were significantly correlated with biological pathways related to health problems and modifications in host metabolism. To conclude, short-term DON/ZEN challenges resulted in transient modifications in the composition and functions of fecal microbiota.     

HIF‐1α forms regulatory loop with YAP to coordinate hypoxia‐induced adriamycin resistance in acute myeloid leukemia cells

Despite the improvement in acute myeloid leukemia (AML) treatments, most patients had a poor prognosis and suffered from chemoresistance and disease relapse. Therefore, there is an urgent need for elucidation of mechanism(s) underlying drug resistance in AML. In the present study, we found that AML cells showed less susceptibility to adriamycin (ADR) in the presence of hypoxia, while inhibition of hypoxia‐inducible factor 1α (HIF‐1α) by CdCl₂ can make AML cells re‐susceptibile to ADR even under hypoxia. Moreover, HIF‐1α is overexpressed and plays an important role in ADR‐resistance maintenance in resistant AML cells. We further found hypoxia or induction of HIF‐1α can significantly upregulate yes‐associated protein (YAP) expression in AML cells, and resistant cells express a high level of YAP. Finally, we found that YAP may not only enhance HIF‐1α stability but also promote HIF‐1α's activity on the target gene pyruvate kinase M2. In conclusion, our data indicate that HIF‐1α or YAP may represent a therapeutic target for overcoming resistance toward adriamycin‐based chemotherapy in AML.     

Expression Analyses of MicroRNAs in Hamster Lung Tissues Infected by SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5°C, cough, dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.     

甲状腺素对动脉瘤性蛛网膜下腔出血大鼠脑缺氧诱导因子-1α表达的影响及其机制*

目的:探讨甲状腺素(T4)对动脉瘤性蛛网膜下腔出血后大鼠脑缺氧诱导因子-1α(HIF-1α)表达的调节及其机制。方法:72只雄性成年SD大鼠随机分为以下4组:蛛网膜下腔出血模型组(SAH)(n=18)、蛛网膜下腔出血+甲状腺素组(SAH+T4)(n=18)、蛛网膜下腔出血+溶剂组(SAH+溶剂组)(n=18)、假手术组(n=18)。颈内动脉穿刺法建立蛛网膜下腔出血的模型,术后行颅脑CT平扫,建模后立即开始给药,按3 μg/100 g腹腔注射,每隔24 h一次,连续3 d,SAH+T4组予甲状腺素干预,SAH+溶剂组予等体积溶剂干预,均在建模后72 h处死;各组6只大鼠经多聚甲醛灌注处死后石蜡包埋切片行免疫组化染色检测HIF-1α及p-Akt蛋白、6只用TUNEL法检测凋亡,6只用干湿重法做脑水肿含量检测。结果:建模成功后SAH组及SAH+T4组、SAH+溶剂组大鼠的脑组织肿胀明显,蛛网膜下腔可见暗红色血凝块。SAH组神经行为学评分、脑含水量、凋亡率、HIF-1α蛋白、p-Akt蛋白均较假手术组明显增高(P＜0.05);SAH+T4组神经行为学评分、HIF-1α蛋白、p-Akt蛋白均较SAH组明显增高,其脑含水量、凋亡均较SAH组明显减少(P＜0.05)。结论:使用T4替代治疗可以上调动脉瘤性蛛网膜下腔出血后大鼠脑HIF-1α蛋白表达水平,可能是通过激活三磷酸肌醇激酶／蛋白激酶B(PI3K/Akt)信号通路,使凋亡率减小,最终大鼠行为学得以改善,对大鼠脑产生保护作用。