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.     

空肠营养对重症急性胰腺炎的疗效观察

目的：探讨早期空肠营养对重症急性胰腺炎（SAP）的疗效。方法：118名重症急性胰腺炎患者随机分为EN组和TPN组．比较两组SAP病人住院时间、费用、感染率、并发症及死亡率等。结果：TPN组住院时间长,费用高,感染率、并发症及病死率高。差异具有显著性。结论：早期空肠营养支持可明显改善SAP病情,提高治疗效果。     

重症肺炎影响极低出生体重儿血小板及凝血功能的研究

目的:通过观察我院收治的极低出生体重新生儿肺炎的临床治疗,研究重症肺炎对该类疾病患儿的血小板及凝血功能的影响,探讨其临床研究价值.方法:将47例一般肺炎的极低出生体重新生儿设为对照组,45例重症肺炎的极低出生体重新生儿设为实验组,对比分析两组患儿的血小板参数的检测指标并行患儿凝血功能检查.结果:在血小板参数方面,实验组在MPV和PDW的数据较对照组高,而在PLT明显较低;在凝血功能方面,实验组在PT、APTT和TT等方面的数据较对照组高,而在FIB方面明显较低.结论:临床上对动态监测重症肺炎患儿血小板的变化情况,对判断该疾病患儿的预后具有积极的参考与预警意义,而对重症肺炎患儿出现凝血系统功能紊乱及时把握具体发病机制,对症进行凝血功能恢复治疗,值得临床进一步研究与探讨.     

贝伐单抗辅助的23G玻璃体切割术治疗严重增生性糖尿病视网膜病变的疗效观察

目的：2011年,我国糖尿病患者人数高达9240万。糖尿病视网膜病变（diabeticretinopathy,DR）作为糖尿病患者的常见并发症,在糖尿病人群中的患病率为37％,是导致成人获得性盲的最主要原因之一。严重增生性糖尿病视网膜病变以牵拉性视网膜脱离、玻璃体出血为特征,具有致盲率大,手术难度高等特点。针对与此,本文主要探讨术前注射贝伐单抗对23G玻璃体切割手术治疗严重增生性糖尿病视网膜病变患者效果的影响。方法：回顾性病例对照研究。共收集严重增生性糖尿病视网膜病变患者70例,药物辅助手术组（A组）21例,术前3—7天行玻璃体腔注射贝伐单抗（1．25mg／O．05mL）;单纯手术组（B组）49例,行23G玻璃体切割术。分析两组术前及术后视力、手术时间、医源性裂孔、电凝、术后出血的不同。结果：在术后3月,两组视力提高有统计学意义（P〈O．05）。A组平均手术时间为74分钟,而B组平均手术时间为85分钟（P〉0．05）。医源性裂孔在A组中有1例,而B组中有16例（P〈0．05）,在A组中有3例使用电凝,B组中有25例使用电凝（P〈0．05）。A组有1例出现术中及术后出血,B组为20例（P〈O．05）。结论：在这个回顾性研究中,我们发现对于严重增生性糖尿病视网膜病变的病人,术前玻璃体腔注射1．25mg／O．05ml贝伐单抗可以显著减少医源性裂孔的发生,减少术中电凝使用及术中术后出血的发生。     

不同剂量乌司他丁联合微量推注泵美罗培南对重症肺炎患者的疗效及血管生成素2的影响

摘要 目的：探讨与分析不同剂量乌司他丁联合微量推注泵美罗培南对重症肺炎患者的疗效及血管生成素-2的影响。方法：2019年1月到2022年2月选择在本院诊治的重症肺炎患者78例作为研究对象,将其分为研究组与对照组各39例,两组都给予美罗培南微量推注治疗,研究组与对照组分别给予高剂量与低剂量的乌司他丁治疗,连续应用7 d,观察患者的疗效及血清血管生成素2表达变化情况。结果：研究组的ICU住院时间、退热时间、炎症吸收时间与痰液颜色改变时间较对照组少（P<0.05）。研究组的治疗总有效率较对照组高（P<0.05）。两组治疗后的血清白细胞介素-6（IL-6）、白细胞介素-17（IL-17）含量明显低于治疗前(P<0.05),研究组治疗后的血清IL-6、IL-17含量也明显低于对照组（P<0.05）。两组治疗后的血清血管生成素-2含量低于治疗前,治疗后研究组血清血管生成素-2含量低于对照组（P<0.05）。结论：高剂量乌司他丁联合微量推注泵美罗培南在重症肺炎患者的应用能抑制血清血管生成素-2的表达,也可抑制血清IL-6、IL-17的表达,从而能提高治疗效果,促进改善患者的临床症状,有利于患者康复。     

金银花提取物对重症急性胰腺炎肺损伤大鼠的保护作用及机制研究

摘要 目的：探讨金银花提取物对重症急性胰腺炎肺损伤大鼠的保护作用及其分子机制。方法：选择60只大鼠并将其分为假手术组、模型组、金银花低剂量组、金银花中剂量组和金银花高剂量组。比较各组的肺组织和胰腺组织病理评分。采用全自动血气分析仪检测各组大鼠血氧分压、二氧化碳分压和氧合指数。采用酶联免疫吸附法检测各组炎症因子[白细胞介素（IL）-1、IL-6和肿瘤坏死因子-α（TNF-α）]水平。免疫印迹法检测各组肺组织中NF-κB通路相关蛋白（p-p65、p-IκBα、p65和IκBα蛋白）水平。结果：与假手术组相比,模型组肺组织和胰腺组织病理评分以及二氧化碳分压明显升高（P<0.05）。与模型组相比,金银花各剂量组肺组织和胰腺组织病理评分以及二氧化碳分压明显下降,并且呈剂量依赖性（P<0.05）。与假手术组相比,模型组血氧分压和氧合指数明显下降（P<0.05）。与模型组相比,金银花各剂量组血氧分压和氧合指数明显升高,并且呈剂量依赖性（P<0.05）。与假手术组相比,模型组IL-1、IL-6和TNF-α水平以及p-p65和p-IκBα蛋白水平明显升高（P<0.05）。与模型组相比,金银花各剂量组IL-1、IL-6和TNF-α水平以及p-p65和p-IκBα蛋白水平明显下降,并且呈剂量依赖性（P<0.05）。结论：金银花提取物对大鼠重症急性胰腺炎肺损伤具有一定保护作用,能够升高血氧分压和氧合指数并降低二氧化碳分压,并且其保护作用可能是通过抑制NF-κB通路介导的促炎症因子IL-1、IL-6和TNF-α的产生,缓解炎症性肺损伤。     

In silico epitope-based vaccine design against influenza a neuraminidase protein: Computational analysis established on B- and T-cell epitope predictions

ObjectiveInfluenza A virus belongs to the most studied virus and its mutant initiates epidemic and pandemics outbreaks. Inoculation is the significant foundation to diminish the risk of infection. To prevent an incidence of influenza from the transmission, various practical approaches require more advancement and progress. More efforts and research must take in front to enhance vaccine efficacy.MethodsThe present research emphasizes the development and expansion of a universal vaccine for the influenza virus. Research focuses on vaccine design with high efficacy. In this study, numerous computational approaches were used, covering a wide range of elements and ideas in bioinformatics methodology. Various B and T-cell epitopic peptides derived from the Neuraminidase protein N1 are recognized by these approaches. With the implementation of numerous obtained databases and bioinformatics tools, the different immune framework methods of the conserved sequences of N1 neuraminidase were analyzed. NCBI databases were employed to retrieve amino acid sequences. The antigenic nature of the neuraminidase sequence was achieved by the VaxiJen server and Kolaskar and Tongaonkar method. After screening of various B and T cell epitopes, one efficient peptide each from B cell epitope and T cell epitopes was assessed for their antigenic determinant vaccine efficacy. Identical two B cell epitopes were recognized from the N1 protein when analyzed using B-cell epitope prediction servers. The detailed examination of amino acid sequences for interpretation of B and T cell epitopes was achieved with the help of the ABCPred and Immune Epitope Database.ResultsComputational immunology via immunoinformatic study exhibited RPNDKTG as having its high conservancy efficiency and demonstrated as a good antigenic, accessible surface hydrophilic B-cell epitope. Among T cell epitope analysis, YVNISNTNF was selected for being a conserved epitope. T cell epitope was also analyzed for its allergenicity and cytotoxicity evaluation. YVNISNTNF epitope was found to be a non-allergen and not toxic for cells as well. This T-cell epitope with maximum world populace coverages was scrutinized for its association with the HLA-DRB1*0401 molecule. Results from docking simulation analyses showed YVNISNTNF having lower binding energy, the radius of gyration (Rg), RMSD values, and RMSE values which make the protein structure more stable and increase its ability to become an epitopic peptide for influenza virus vaccination.ConclusionsWe propose that this epitope analysis may be successfully used as a measurement tool for the robustness of an antigen–antibody reaction between mutant strains in the annual design of the influenza vaccine.     

骨水泥强化椎弓根螺钉联合椎间融合复位治疗老年重度腰椎滑脱的临床研究

摘要 目的：观察椎间融合复位联合骨水泥强化椎弓根螺钉治疗老年重度腰椎滑脱的临床效果。方法：回顾性分析我院于2016年3月~2019年3月期间收治的老年重度腰椎滑脱患者92例,根据治疗方案的不同可将患者分为A组（n=44）和B组（n=48）,A组给予椎弓根螺钉联合椎间融合复位治疗,B组给予骨水泥强化椎弓根螺钉联合椎间融合复位治疗,对比两组视觉疼痛模拟评分（VAS）、Oswestry功能障碍指数（ODI）及日本骨科协会（JOA）腰腿痛评分、临床指标、滑脱距离、滑脱率、椎间隙高度、椎间融合率、椎间孔高度、并发症及螺钉松动情况。结果：术后12个月,两组VAS、ODI、JOA评分均下降,且B组低于A组（P<0.05）。两组术中出血量对比组间无统计学差异（P>0.05）,B组手术时间长于A组,住院时间短于A组,椎间融合率高于A组（P<0.05）。术后12个月,两组滑脱距离、滑脱率均下降,且B组小于A组（P<0.05）。术后12个月,两组椎间隙高度、椎间孔高度均升高,且B组高于A组（P<0.05）。两组并发症发生率组间对比无差异（P>0.05）。结论：老年重度腰椎滑脱患者椎间融合复位联合骨水泥强化椎弓根螺钉治疗,虽一定程度上延长了手术时间,但可促进临床症状,改善椎间高度及腰椎滑脱程度,缩短住院时间,且不增加并发症发生率。