我国弓形虫Chinese 1优势基因型感染对小鼠脑组织铁代谢影响

目的　探讨我国弓形虫Chinese 1优势基因型感染对宿主脑组织铁代谢及脑损伤的影响。方法　将20只C57BL/6（体质量15～17 g）小鼠随机分为对照组和感染组，每组10只。感染组每只小鼠腹腔注射4 000个弓形虫Chinese 1优势基因型TgCtwh3虫株速殖子，对照组小鼠注射等量无菌PBS，饲养6 d后处死小鼠并取其脑组织。采用电感耦合等离子体质谱法（inductively coupled plasma mass spectrometry, ICP⁃MS）检测小鼠脑组织铁元素水平；采用RNA芯片检测两组小鼠脑组织差异基因数目并对功能基因表达情况进行基因本体论（Gene Ontology, GO）功能富集；采用实时荧光定量PCR（fluorescent quantitative real⁃time PCR, qPCR）技术检测小鼠脑组织中弓形虫表面抗原1（Toxoplasma gondii surface antigen 1，TgSAG1）基因及部分锌铁调控蛋白（Zrt⁃ and Irt⁃like protein, ZIP）家族mRNA表达水平；采用光镜和电镜观察小鼠脑组织海马齿轮回（dentate gyrus, DG）超微结构；采用Western blotting检测谷胱甘肽过氧化物酶4（glutathione peroxidase 4, GPx4）蛋白表达水平；采用硫代巴比妥酸（TBA）法检测丙二醛（malondialdehyde, MDA）水平；采用免疫组化检测血管内皮生长因子（vascular endothelial growth factor, VEGF）蛋白表达光密度（optical density, OD）值。结果　光镜下可见感染组小鼠脑组织海马DG区细胞坏死，电镜下见感染组小鼠脑组织海马区出现胞质空泡化、核皱缩坏死、线粒体嵴断裂消融、自噬小体增加等超微结构变化。与对照组相比，感染组小鼠脑组织中铁元素水平上调[（32.92 ± 0.90） µg/g vs.（37.72 ± 1.10） µg/g；t = 3.397, P < 0.01]；RNA芯片检测感染组小鼠脑组织发现721个基因上调、276个基因下调，差异表达基因在金属离子结合能力上有明显富集。与对照组相比，感染组小鼠脑组织金属元素转运体ZIP2 mRNA表达水平上调（t = 8.659，P < 0.05）、GPx4表达下降[（1.046 ± 0.025） vs. （0.720 ± 0.101）；t = 3.129，P < 0.01]）、MDA水平升高[（4.37 ± 0.33） nmol/mgprot vs.（5.93 ± 0.54） nmol/mgprot；t = 2.451，P < 0.05）]、VEGF蛋白平均OD值上调[（0.348 3 ± 0.017 8） vs. （0.490 6 ± 0.010 5）；t = 6.641，P < 0.01]。结论　Chinese 1优势基因型弓形虫感染后，小鼠脑组织中铁元素蓄积、抗氧化能力下调、氧化应激水平升高，提示弓形虫感染可影响宿主脑组织铁代谢而导致脑损伤。     

广泛性焦虑障碍住院患者与健康对照者的认知功能比较研究

背景 广泛性焦虑障碍（GAD）是常见的慢性精神疾病，常伴有不同程度的认知功能损害，严重影响患者的生活质量及社会功能。 目的 比较GAD住院患者与健康对照者认知功能的差异。 方法 选取2018年8月至2020年1月在南方医科大学南方医院住院治疗的GAD患者为GAD组（n=30），同期通过广告在南方医科大学南方医院住院患者陪护人员中招募年龄、性别相匹配的健康志愿者为健康对照组（n=30）。使用汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）和Beck自杀意念量表中文版（BSI-CV）进行心理测评，采用精神运动警觉性任务（PVT）、Go/No-go联想任务、N-back任务分别评估认知功能的注意、抑制及工作记忆功能。比较两组一般情况、量表测评总分及认知功能差异，进一步采用多因素Logistic回归分析探究GAD住院患者和健康对照者的认知功能差异。 结果 GAD组HAMA、HAMD总分和最严重情况时BSI-CV总分及最严重情况时存在自杀意念者所占比例高于健康对照组（P<0.05）。N-back任务：GAD组1-back击中目标率（NBACK1a）、2-back击中目标率（NBACK2a）低于健康对照组，1-back击中目标的平均反应时（NBACK1b）长于健康对照组（P<0.05）。多因素Logistic回归分析结果显示，NBACK1a〔OR=0.946，95%CI（0.898，0.997），P=0.038〕、NBACK1b〔OR=1.007，95%CI（1.000，1.014），P=0.042〕是GAD的影响因素。 结论 与健康对照者相比，GAD住院患者的工作记忆较差，需要临床关注。     

Review of clinical characteristics,immune responses and regulatory mechanisms of hepatitis E-associated liver failure

Hepatitis E virus (HEV) is the most common cause of acute liver failure (LF) and one of the most common factors causing acute injury in acute-on-chronic LF (ACLF). When HEV-related LF occurs, a series of changes take place in both the intrahepatic environment and extrahepatic microenvironment. The changed types and distribution of immune cells (infiltrating macrophages and increased lymphocytes) in liver tissue, as well the increased proinflammatory cytokines and chemokines in the blood, indicate that the occurrence and progression of HEV-related LF are closely related to immune imbalance. The clinical features and immune reaction in the body during HEV-related acute LF (ALF) and ACLF are complicated. This review highlights recent progress in elucidating the clinical manifestations of HEV-associated ALF and ACLF and discusses the corresponding systemic immune changes and possible regulatory mechanisms.     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

早期卧位踏车训练对下肢重度烧伤患者的效果

目的探讨早期卧位踏车训练在下肢重度烧伤患者功能康复中的临床效果。方法2016年10月至2017年12月,下肢重度烧伤患者30例分为对照组和观察组,各15例。对照组采用常规综合康复,观察组此基础上增加早期卧位踏车训练。入院时和住院治疗6周后,采用焦虑自评量表(SAS)、抑郁自评量表(SDS)、疼痛数字评分法(NRS)、Berg平衡量表(BBS)和6分钟步行测试进行评定。结果治疗后,两组SAS、SDS、NRS评分均明显降低(t>3.636,P<0.01),观察组低于对照组(t>2.319,P<0.05);观察组BBS评分和6分钟步行距离高于对照组(t>2.541,P<0.05)。结论早期卧位踏车训练对下肢重度烧伤患者功能恢复有一定促进作用。     

Impact of Weight Loss During Chemotherapy in Chinese Patients with Unresectable Pancreatic Cancer

Background: Weight loss is frequently observed in pancreatic cancer patients. We aimed to study the prognostic impacts of weight loss early during chemotherapy.

Methods: A total of 72 patients of Chinese ethnicity with unresectable pancreatic cancer who underwent chemotherapy were reviewed. Critical weight loss (CWL) was defined as weight loss ≥ 5% within one month after treatment. The prognostic impact of weight loss and CWL were analyzed.

Results: 47 patients (65.3%) had weight loss after one month of treatment, with 14 (19.4%) suffering from CWL. Baseline characteristics were similar between patients with and without CWL. The median OS and Time-to-treatment-failure (TTF) of patients with CWL were shorter than those without CWL (OS: 4.8?months [CWL] versus [vs.] OS 7.1?months [No CWL]; TTF 1.6?months [CWL] vs. 3.2?months [No CWL]; both P?<?0.01). CWL was an independent adverse prognosticator for OS (Hazard Ratio [HR]?=?2.50; P?=?0.01) and TTF (HR = 2.71; P?<?0.01). Other independent prognosticators for OS were serum albumin <35?mg/dl and CA19-9?≥?1000?IU/ml, while CWL was the only independent prognosticator for TTF (HR 2.71 [95% CI 1.33–5.52]; P?<?0.01).

Conclusions: Development of CWL in early course of chemotherapy was associated with worse prognosis in Chinese patients with unresectable pancreatic cancers.     

Relationship Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Etiology of Acute Kidney Injury (AKI)

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since it was first recognized in December 2019, it has resulted in the ongoing worldwide pandemic. Although acute hypoxic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) are the main features of the disease, the involvement of other organs needs to be explored. There has been a growing concern regarding the association between acute kidney injury (AKI) and poor outcomes in SARS-CoV-2 patients. Based on current observational data, AKI is the 2^nd most common cause of morbidity and mortality behind ARDS in SARS-CoV-2 patients. Angiotensin-converting enzyme 2 (ACE2) receptor has been shown to be the cornerstone of SARS-CoV-2 infection and possibly plays a significant role in the occurrence of renal injury. The pathogenesis of AKI is likely multifactorial that involves not only direct viral invasion but also dysregulated immune response in the form of cytokine storm, ischemia to kidneys, hypercoagulable state, and rhabdomyolysis, among others. We performed a literature search of the Pubmed and Google Scholar database from 1996 to 2020 using the following keywords: severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019, angiotensin-converting enzyme 2 receptor, and acute kidney injury to find the most pertinent and highest-quality of evidence. Any cited references were reviewed to identify relevant literature. The purpose of this review is to discuss, explore, and summarize the relationship between AKI in SARS-CoV-2 patients, with a focus on its epidemiology, association with ACE2 receptors, and pathophysiology of AKI.