Double deficiency of cathepsin B and L in the mouse pancreas alters trypsin activity without affecting acute pancreatitis severity

BackgroundPremature intracellular trypsinogen activation has long been considered a key initiator of acute pancreatitis (AP). Cathepsin B (CTSB) activates trypsinogen, while cathepsin L (CTSL) inactivates trypsin(ogen), and both proteins play a role in the onset of AP.MethodsAP was induced by 7 hourly intraperitoneal injections of cerulein (50 μg/kg) in wild-type and pancreas-specific conditional Ctsb knockout (Ctsb^Δpan), Ctsl knockout (Ctsl^Δpan), and Ctsb;Ctsl double-knockout (Ctsb^Δpan;Ctsl^Δpan) mice. Pancreatic samples were collected and analyzed by histology, immunohistochemistry, real-time PCR, and immunoblots. Trypsin activity was measured in pancreatic homogenates. Peripheral blood was collected, and serum amylase activity was measured.ResultsDouble deletion of Ctsb and Cstl did not affect pancreatic development or mouse growth. After 7 times cerulein injections, double Ctsb and Ctsl deficiency in mouse pancreases increased trypsin activity to the same extent as that in Ctsl-deficient mice, while Ctsb deficiency decreased trypsin activity but did not affect the severity of AP. Ctsb^Δpan;Ctsl^Δpan mice had comparable serum amylase activity and histopathological changes and displayed similar levels of proinflammatory cytokines, apoptosis, and autophagy activity compared with wild-type, Ctsb^Δpan, and Ctsl^Δpan mice.ConclusionDouble deletion of Ctsb and Ctsl in the mouse pancreas altered intrapancreatic trypsin activity but did not affect disease severity and inflammatory response after cerulein-induced AP.     

‘I believe high blood pressure can kill me:’ using the PEN-3 Cultural Model to understand patients’ perceptions of an intervention to control hypertension in Ghana

Objectives: Currently in Ghana, there is an on-going task-shifting strategy in which nurses are trained in hypertension management. While this study will provide useful information on the viability of this approach, it is not clear how patients in the intervention perceive hypertension, the task-shifting strategy, and its effects on blood pressure management. The objective of this paper is to examine patients’ perceptions of hypertension and hypertension management in the context of an on-going task-shifting intervention to manage blood pressure control in Ghana.

Design: Forty-two patients participating in the Task Shifting Strategy for Hypertension program (23 males, 19 females, and mean age 61. 7 years) completed in-depth, qualitative interviews. Interviews were transcribed, and key words and phrases were extracted and coded using the PEN-3 Cultural Model as a guide through open and axial coding techniques, thus allowing rich exploration of the data.

Results: Emergent themes included patients’ perceptions of hypertension, which encompassed misperceptions of hypertension and blood pressure control. Additional themes included enablers and barriers to hypertension management, and how the intervention nurtured lifestyle change associated with blood pressure control. Primary enabling factors included the supportive nature of TASSH nurses, while notable barriers were financial constraints and difficulty accessing medication. Nurturing factors included the motivational interviewing and patient counseling which instilled confidence in the patients that they could make lasting behavior changes.

Conclusions: This study offers a unique perspective of blood pressure control by examining how patients view an on-going task-shifting initiative for hypertension management. The results of this study shed light on factors that can help and hinder individuals in low-resource settings with long-term blood pressure management.     

The Health Belief Model in predicting healthcare workers' intention for influenza vaccine uptake in Jordan

BackgroundTheories of health behavior change are being inadequately adopted to understand the reasons behind low influenza vaccination rates among healthcare workers (HCWs). The Theory of Planned Behavior (TPB) is being used to predict intention-behavior relationship while the Health Belief Model (HBM) is being employed to predict actual behavior. The purpose of this study was to test a conceptual model based on the HBM’s constructs to predict Jordanian HCWs’ intentions for influenza vaccine uptake as an alternative to the TPB.MethodA cross-sectional questionnaire-based study was conducted in 2016 in a tertiary teaching hospital in Amman-Jordan including a convenience sample of 477 HCWs with direct patient contact. The study instrument was tested for validity and reliability. A conceptual regression model was proposed incorporating the constructs of the primary HBM with some modifications in the threat construct as well as an additional variable about explicit past vaccination behavior (in the past year and/or any previous history of influenza vaccine uptake).ResultsAlmost all the constructs of the HBM demonstrated significant differences between participants intending and those who did not intend to vaccinate against influenza. After adjusting for the confounding variables in the final conceptual regression model, past vaccination behavior (OR= 4.50, 95%Confidence Interval 3.38–6.00, P< 0.0005) and the perceived benefit scale (OR= 1.19, 95% Confidence Interval 1.11–1.28, P< 0.0005) were the only significant predictors of intentions to vaccinate against influenza in the next season.ConclusionTaking into consideration the altruistic beliefs of HCWs and their explicit past vaccination history augments the utility of the original HBM tool in predicting HCWs’ intentions to vaccinate against influenza in a way that is consistent with the predictive ability of the Theory of Planned Behavior.     

鼠巨细胞病毒感染C57BL/6小鼠急性肝炎动物模型的建立与鉴定

目的：建立鼠巨细胞病毒（MCMV）感染C57BL/6小鼠急性肝炎模型并对其感染特点进行分析及鉴定。方法：将24 只C57BL/6小鼠随机分为阴性对照组（n =12）及病毒感染组（n =12），病毒感染组腹腔注射1.0×106 PFU（200 μL）MCMV悬液，阴性对照组注射等体积小鼠胚胎成纤维细胞（MEF）悬液。于感染后第3天和第7天取外周血分离血清检测谷丙转氨酶（ALT）及谷草转氨酶（AST）。同时进行肝组织病毒分离、组织病理学及MCMV IE和M55基因、细胞因子白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子α（TNF-α）的检测。结果：病毒感染组肝组织匀浆病毒分离均为阳性，肝炎发生率为100%。在感染后第3天即发生肝炎病理改变，病毒感染组血清ALT及AST较阴性对照组明显升高（P ＜0.01）；病毒感染组肝脏HE染色第3天可见局灶性炎性细胞浸润及肝脏点灶状坏死，持续至第7天，Ishak评分较阴性对照组明显升高（P ＜0.01）；在感染后第3天病毒感染组肝组织内可检测到MCMV IE及M55基因，且在感染后第7天仍可测得IE基因；感染后第3天及第7天病毒感染组炎性细胞因子IL-6、TNF-α及IL-1β mRNA表达水平明显升高（P ＜0.05）。 结论：成功建立MCMV感染C57BL/6小鼠急性动物肝炎模型，其感染表现主要集中在急性感染前期。     

从武汉抗疫看中医药文化认同与新的医学模式

从武汉抗疫中医药的投入使用情况,反思现代临床和国人所呈现出的中医药文化认同和就医习惯,探索其历史文化根源及社会因素与医学发展的内在关联。回顾历史,中医屡次临危受命,不负重托,如今大疫当前,中医药再次发挥了重要作用。故新时代探讨如何遵循中医药发展规律,传承精华、守正创新,坚持中医药原创优势,形成中医药学科优势整体化呈现的新模式医学,对提升全社会的中医药认知度具有重要意义。     

中华传统文化视角下疾病终末期患者尊严模型解析

目的:解析加拿大Chochinov疾病终末期患者尊严模型在中华文化情境下的适用性,并基于此对模型进行调适。方法:采用内容分析法,按照选定分析范围、抽取样本、确定分析单位和分析框架、资料分析四步完成。首先检索中、英文数据库中以中华文化背景下临终尊严为主题的文献,然后以尊严模型为框架对文献内容进行编码、归纳和分析。结果:尊严模型包含的多数主题符合我国临终患者的认知,如身体功能、医疗不确定性、死亡焦虑、隐私界限、照护要旨、他人负担、后事担忧等。但也出现了矛盾的主题,如忍受痛苦、自主性等,以及新的主题,包括家庭支持、病耻感和财务担忧。结论:加拿大版疾病终末期患者尊严模型并不完全符合中国文化,调适后的尊严模型更具我国文化特色,但仍需实证研究对模型进行验证。     

NRP-1单克隆抗体对乳腺癌裸鼠移植瘤生长的影响

 目的 探讨NRP-1单克隆抗体（NRP-1 MAb）的特异性，以及不同剂量的NRP-1 MAb治疗乳腺癌裸鼠移植瘤的疗效。方法 Western blot和共聚焦免疫荧光法检测NRP-1 MAb是否识别MCF7细胞上NRP-1蛋白。将MCF7细胞接种于BALB/c裸鼠皮下建立乳腺癌细胞移植瘤模型，并进行瘤组织传代。传代的肿瘤体积生长至300~500 mm3时，随机分为对照组、NRP-1 MAb低剂量组、中剂量组和高剂量组，每组6只，给药7次。观察荷瘤裸鼠一般状况，测量瘤体大小及裸鼠体重。实验结束时剥离瘤体称重，提取组织蛋白，Western blot检测组织中VEGF蛋白和NRP-1蛋白的表达量。结果 NRP-1MAb成功识别MCF7细胞上的NRP-1蛋白；NRP-1 MAb能够有效抑制MCF7细胞裸鼠移植瘤的生长，低剂量组（1 mg/kg）抑瘤率为47.01%，中剂量组（5 mg/kg）抑瘤率为65.70%，高剂量组（10 mg/kg）抑瘤率为69.19%。。结论 NRP-1 MAb能够识别并有效结合MCF7细胞膜上的NRP-1蛋白，且可抑制MCF7细胞移植瘤的生长，NRP-1 MAb抑制移植瘤的增长可能与下调NRP-1和VEGF表达有关。