Cystic fibrosis: An update for clinicians. Part 2: Hepatobiliary and pancreatic manifestations

This paper, the second in the series, will build on the first and explore the importance of liver and pancreatic manifestations of cystic fibrosis (CF) and the effect on morbidity and mortality of this multifaceted genetic condition. It will also further develop the critical role of the gastroenterologist as part of the multidisciplinary group of clinicians and allied health staff in the effective management of patients with CF.     

Spatiotemporal Trend Analysis of Precipitation Extremes in Ho Chi Minh City,Vietnam During 1980-2017

In this study,the spatiotemporal variability of trends in extreme precipitation events in Ho Chi Minh City during the period 1980-2017 was analyzed based on sev...     

Computational estimation of potential inhibitors from known drugs against the main protease of SARS-CoV-2

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide recently, leading to global social and economic disruption. Although the emergently approved vaccine programs against SARS-CoV-2 have been rolled out globally, the number of COVID-19 daily cases and deaths has remained significantly high. Here, we attempt to computationally screen for possible medications for COVID-19 via rapidly estimating the highly potential inhibitors from an FDA-approved drug database against the main protease (Mpro) of SARS-CoV-2. The approach combined molecular docking and fast pulling of ligand (FPL) simulations that were demonstrated to be accurate and suitable for quick prediction of SARS-CoV-2 Mpro inhibitors. The results suggested that twenty-seven compounds were capable of strongly associating with SARS-CoV-2 Mpro. Among them, the seven top leads are daclatasvir, teniposide, etoposide, levoleucovorin, naldemedine, cabozantinib, and irinotecan. The potential application of these drugs in COVID-19 therapy has thus been discussed.

Approved drugs predicted to interact with critical residues in the substrate-binding site of SARS-CoV-2 Mpro can be promising inhibitors.     

Transvenous retrograde embolization of ruptured brain arteriovenous malformations: A case report and review of the literature

Hemorrhagic stroke due to ruptured brain arteriovenous malformations (AVMs) is a common cause in young stroke patients. When the ruptured AVMs are in deep location, the choice of endovascular intervention with the arterial approach to AVM embolization is routine but in many cases, it is not feasible due to the inability to access because of the small and tortuous arterial branch, however, the intravenous approach also results in high complete obliteration rates but also carries a higher risk of stroke than the intra-arterial route. We describe a 36-year-old female patient diagnosed with intracranial and intraventricular hemorrhage who underwent complete transvenous embolization of the ruptured AVMs, and achieved near-complete clinical recovery after 1 month with the modified Rankin scale 1.     

Impact of Infectious Disease after Lactococcus lactis Strain Plasma Intake in Vietnamese Schoolchildren: A Randomized,Placebo-Controlled,Double-Blind Study

Lactococcus lactis strain Plasma (LC-Plasma) is reported to have anti-viral effects via direct activation of plasmacytoid dendritic cells, which upregulate the production of type I and III interferons. A randomized, placebo-controlled, double-blind, parallel group study was designed for elementary schoolchildren, grades 1 to 3, in Vietnam. LC-Plasma or a control were administered to schoolchildren as a beverage (1.0 × 10¹¹ count LC-Plasma/day/person). The primary endpoint was to determine the efficacy of LC-Plasma in reducing the cumulative days absent from school due to upper respiratory disease (URID) and gastrointestinal disease (GID), and the secondary endpoint was to evaluate the potency of LC-Plasma on URID/GID symptoms and general well-being scores. LC-Plasma intake significantly reduced the cumulative days absent from school due to URID/GID (Odds ratio (OR) = 0.57, p = 0.004) and URID alone (OR = 0.56, p = 0.005); LC-Plasma also significantly reduced the number of cumulative fever positive days during the first 4 weeks of intervention (OR = 0.58, p = 0.001) and cumulative days with diarrhea during the last 4 weeks of the intervention period (OR = 0.78, p = 0.01). The number of positive general wellbeing days was significantly improved in the LC-Plasma group compared with the control throughout the intervention period (OR = 0.93, 0.93, p = 0.03, 0.04 in the first and last 4 weeks of the intervention, respectively). These data suggest that LC-Plasma seems to improve the health condition of elementary schoolchildren and reduces school absenteeism due to infectious disease, especially URID.     

Statins use and its impact in EGFR‐TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan

Statins have been shown to be a beneficial treatment as chemotherapy and target therapy for lung cancer. This study aimed to investigate the effectiveness of statins in combination with epidermal growth factor receptor‐tyrosine kinase inhibitor therapy for the resistance and mortality of lung cancer patients. A population‐based cohort study was conducted using the Taiwan Cancer Registry database. From January 1, 2007, to December 31, 2012, in total 792 non‐statins and 41 statins users who had undergone EGFR‐TKIs treatment were included in this study. All patients were monitored until the event of death or when changed to another therapy. Kaplan‐Meier estimators and Cox proportional hazards regression models were used to calculate overall survival. We found that the mortality was significantly lower in patients in the statins group compared with patients in the non‐statins group (4‐y cumulative mortality, 77.3%; 95% confidence interval (CI), 36.6%‐81.4% vs. 85.5%; 95% CI, 78.5%‐98%; P = .004). Statin use was associated with a reduced risk of death in patients the group who had tumor sizes <3 cm (hazard ratio [HR], 0.51, 95% CI, 0.29‐0.89) and for patients in the group who had CCI scores <3 (HR, 0.6; 95% CI, 0.41‐0.88; P = .009). In our study, statins were found to be associated with prolonged survival time in patients with lung cancer who were treated with EGFR‐TKIs and played a synergistic anticancer role.     

Intercellular communication via gap junctions in activated rat hepatic stellate cells

BACKGROUND AND AIMS: Gap junctional communication was studied in quiescent and activated hepatic stellate cells. METHODS: Connexin expression and intercellular dye transfer were studied in rat hepatic stellate cells in culture and in vivo. RESULTS: Protein expression of connexin 43 was up-regulated in activated hepatic stellate cells in vivo and in vitro and was mainly localized on the cell surface, whereas connexin 26 was found intracellularly. In contrast to hepatocytes, hepatic stellate cells do not express connexin 32. Confluent hepatic stellate cells in culture communicate via gap junctions, resulting in lucifer yellow transfer and propagation of intracellular calcium signals. Phorbol ester induces a protein kinase C-dependent hyperphosphorylation and degradation of connexin 43 and inhibits intercellular communication on a short-term time scale. At the long-term level, vitamin D(3) , lipopolysaccharide, thyroid hormone T(3), dexamethasone, platelet-derived growth factor, endothelin 1, and interleukin 1beta up-regulate connexin 43 protein and messenger RNA expression and enhance intercellular communication. Slight down-regulation of connexin 43 is observed in response to vitamin A. Connexin 43 induction by endothelin 1 is inhibited by both endothelin A and endothelin B receptor antagonists. In coculture systems, hepatic stellate cells communicate with each other, which is suggestive of a syncytial organization, but no communication was found between hepatic stellate cells and other liver cell types. As shown by immunohistochemistry and electron microscopy, gap junctions are formed between activated hepatic stellate cells in vivo. CONCLUSIONS: Gap junctional communication occurs between hepatic stellate cells, is enhanced after activation, and underlies complex regulation by cytokines, hormones, and vitamins.     

L-精氨酸对糖尿病大鼠心肌缺血再灌注损伤的影响

目的:观察糖尿病大鼠心肌缺血再灌注时血管紧张素Ⅱ、胰岛素样生长因子1、醛固酮、细胞间黏附分子1和自由基代谢的变化及L-精氨酸对其的影响。方法:实验于2005-02/2006-06在江苏大学医学院机能学实验室完成。①实验分组:腹腔注射链脲佐菌素制作糖尿病大鼠模型,30只大鼠造模成功。按随机数字表法分为3组(n=10):心肌缺血再灌注组:开胸结扎冠脉,造成心肌缺血,60min后放松再灌注60min;L-精氨酸治疗组:于手术前4周灌胃L-精氨酸250mg/(kg·d),然后重复心肌缺血再灌注组操作;假手术组:完成操作后只穿线不结扎,观察2h作为对照。实验结束时心室取血6mL,摘取心脏,留取左心室心肌组织。②实验评估:检测大鼠血浆血管紧张素Ⅱ、醛固酮和血清胰岛素样生长因子1含量及心肌细胞间黏附分子1蛋白表达。检测大鼠血清、心肌组织超氧化物歧化酶、谷胱甘肽-过氧化物酶活性、丙二醛含量及心肌线粒体Na ,K -ATP酶、Mg2 -ATP酶、Ca2 -ATP酶活性。结果:30只大鼠全部进入结果分析。①与假手术组相比,心肌缺血再灌注组血浆血管紧张素Ⅱ、醛固酮含量明显升高(P<0.05～0.01),血清胰岛素样生长因子1含量降低(P<0.05);L-精氨酸治疗4周后血浆血管紧张素Ⅱ、醛固酮含量低于心肌缺血再灌注组(P<0.05～0.01),血清胰岛素样生长因子1含量高于心肌缺血再灌注组(P<0.05)。②与假手术组相比,心肌缺血再灌注组血清、心肌丙二醛含量明显升高(P<0.05),血清、心肌超氧化物歧化酶和谷胱甘肽-过氧化物酶活性明显降低(P<0.05￣0.01);用L-精氨酸治疗4周后血清、心肌丙二醛含量低于心肌缺血再灌注组(P<0.05￣0.01),血清、心肌超氧化物歧化酶和谷胱甘肽-过氧化物酶活性高于心肌缺血再灌注组(P<0.05～0.01)。③与假手术组相比,心肌缺血再灌注组心肌线粒体Na ,K -ATP酶、Mg2 -ATP酶、Ca2 -ATP酶活性明显降低(P<0.05),心肌细胞间黏附分子1蛋白表达明显升高(P<0.01);用L-精氨酸治疗4周后心肌线粒体Na ,K -ATP酶、Mg2 -ATP酶、Ca2 -ATP酶活性明显高于心肌缺血再灌注组(P<0.05),心肌细胞间黏附分子1蛋白表达低于心肌缺血再灌注组(P<0.05)。结论:血管紧张素Ⅱ、醛固酮和胰岛素样生长因子1可能共同参与了糖尿病心肌缺血再灌注的发生,细胞间黏附分子1蛋白表达与糖尿病心肌损伤关系密切。L-精氨酸通过减少细胞间黏附分子1蛋白表达,起心肌保护作用。糖尿病心肌缺血再灌注时存在自由基代谢异常,补充L-精氨酸后,可通过提高超氧化物歧化酶、谷胱甘肽-过氧化物酶和ATP酶活性,降低丙二醛水平,减轻自由基损伤,改善心肌组织功能。