小细胞肺癌组织中lncRNA表达谱的差异

目的：观察长链非编码RNA（ lncRNA）在未发生转移的小细胞肺癌和发生转移的小细胞肺癌组织中表达的差异。方法：利用高通量lncRNA芯片技术分别检测3例未发生转移的小细胞肺癌组织和3例发生转移的小细胞肺癌组织中lncRNA表达谱的变异,经对原始数据进行预处理达到均一化后,筛选出差异表达的lncRNA,进行聚类分析。结果：将lncRNA表达在发生转移的小细胞肺癌组织中与未发生转移的小细胞肺癌组织中的变化倍数在2倍以上并有显著差异（ P＜0.05）的lncRNA,确定为差异性表达的lncRNA。其中在3例发生远处转移的患者肺癌组织中变化均在2倍以上的共842条,占所有lncRNA的12.1％。其中,2倍以上表达上调的共440条,2倍以上表达降低的共402条;5倍以上表达升高的共31条;5倍以上表达降低的共65条。结论：发生转移的小细胞肺癌组织与未发生转移的小细胞肺癌组织比较,lncRNA表达谱发生显著变化。提示差异性表达的lncRNAs参与了小细胞肺癌侵袭和转移的恶性表型。     

长链非编码RNA H19促进人胃癌MGC-803细胞增殖的实验研究

目的 探讨长链非编码RNA H19在胃癌组织及细胞株中的表达情况及其对人胃癌细胞增殖的影响。方法 采用实时定量PCR检测30例胃癌组织及其对应癌旁组织,以及胃癌细胞株MGC-803、SGC-7901和胃黏膜上皮正常GES-1细胞中H19的表达情况;分析胃癌组织H19表达与临床病理特征（年龄、性别、分化程度、肿瘤浸润深度、淋巴结转移及TNM分期）的关系。将胃癌MGC-803细胞分别转染H19特异性小干扰RNA（si-H19组）和阴性对照序列（si-NC组）,分别采用四甲基偶氮唑蓝法和克隆形成实验检测两组细胞的增殖情况。结果 与癌旁组织和黏膜上皮正常细胞相比较,胃癌组织和细胞株中H19的表达水平升高。胃癌组织中H19表达与年龄、性别、分化程度均无关（P＞0.05）,但与肿瘤浸润深度、淋巴结转移及TNM分期有关（P＜0.05）。si-H19组中H19表达水平低于si-NC组,且细胞活力和细胞克隆数均低于si-NC组,以上差异均有统计学意义（P＜0.05）。结论 胃癌组织及细胞株中H19呈高表达,下调H19表达能显著抑制胃癌细胞的增殖能力,H19可能参与了胃癌的发生、发展。     

Investigating the Relationship between Vitamin D and Persistent Symptoms Following SARS-CoV-2 Infection

The emergence of persistent symptoms following SARS-CoV-2 infection, known as long COVID, is providing a new challenge to healthcare systems. The cardinal features are fatigue and reduced exercise tolerance. Vitamin D is known to have pleotropic effects far beyond bone health and is associated with immune modulation and autoimmunity. We hypothesize that vitamin D levels are associated with persistent symptoms following COVID-19. Herein, we investigate the relationship between vitamin D and fatigue and reduced exercise tolerance, assessed by the Chalder Fatigue Score, six-minute walk test and modified Borg scale. Multivariable linear and logistic regression models were used to evaluate the relationships. A total of 149 patients were recruited at a median of 79 days after COVID-19 illness. The median vitamin D level was 62 nmol/L, with n = 36 (24%) having levels 30–49 nmol/L and n = 14 (9%) with levels <30 nmol/L. Fatigue was common, with n = 86 (58%) meeting the case definition. The median Borg score was 3, while the median distance covered for the walk test was 450 m. No relationship between vitamin D and the measures of ongoing ill-health assessed in the study was found following multivariable regression analysis. These results suggest that persistent fatigue and reduced exercise tolerance following COVID-19 are independent of vitamin D.     

Cognitive deficits in vasculitis of the nervous system: a cross-sectional study

Objectives: To identify the cognitive and functional deficits in a well-characterized group of patients with vasculitis of the nervous system.

Methods: Sixty-seven patients diagnosed with Central Nervous System (CNS) or Peripheral nervous System (PNS) vasculitis over a 14-year period were retrospectively identified. Data on clinical presentation, laboratory, radiographic and tissue biopsy investigations, and treatment were collated. Cognitive, functional and quality of life evaluation assessments were performed in 31 patients who agreed to participate and included Addenbrooke’s Cognitive Examination-revised (ACE-R), Nottingham Extended Activities of Daily Living (NEADL) and EQ-5D-3L quality of life questionnaires.

Results: CNS vasculitis patients exhibited cognitive impairment, with a mean ACE-R score of 74/100 (standard deviation (SD) 16). NEADL and EQ-5D-3L scores were in the impaired range at 41/66 (SD 21) and 57/81 (SD 22), respectively. Patients with just PNS vasculitis exhibited fewer cognitive deficits with ACE-R and NEADL scores of 87 (SD 8) and 46 (SD 16) respectively. EQ-5D-3L score was in the impaired range of 65 (SD 22).

Conclusions: Vasculitis of the nervous system and, in particular, CNS vasculitis causes cognitive impairment and deficits in functional ability. Such patients should be targeted for cognitive rehabilitation.     

Screening for Elderly Patients Admitted to the Emergency Department Requiring Specialized Geriatric Care

Background

There is a need for a brief geriatric assessment (BGA) tool to screen elderly patients admitted to the Emergency Department (ED) for their risk of a long hospital stay.

Objective

To examine whether a BGA administered to elderly patients admitted to the ED may predict the risk of a long hospital stay in the geriatric acute care unit.

Methods

This study had a prospective cohort study design, enrolling 424 elderly patients (mean age 84.0 ± 6.5 years, 31.6% male) who were evaluated in the ED using a BGA composed of the following items: age, gender, number of medications taken daily, history of falls during the past 6 months, Mini-Mental State Examination (MMSE) score, and non-use of home-help services (i.e., living alone without using any formal or informal home services or social help). The length of stay (LOS) was calculated in days. Patients were separated into three groups based on LOS: low (<8 days), intermediate (8–13 days), and high (>13 days).

Results

The prevalence of male gender was higher among patients with the longest LOS compared to those with intermediate LOS (p = 0.002). There were more patients with a history of falls in the high LOS group compared to the intermediate LOS group (p = 0.001) and the low LOS group (p < 0.001). The classification tree showed that male patients with an MMSE score <20 who fell with age under 85 years formed the end node with the greatest relative risk (RR) of a long hospital stay (RR = 14.3 with p < 0.001).

Conclusions

The combination of a history of falls, male gender, cognitive impairment, and age under 85 years identified elderly ED patients at high risk of a long hospital stay.     

Pharmacological separation of early afterdepolarizations from arrhythmogenic substrate in DeltaKPQ Scn5a murine hearts modelling human long QT 3 syndrome

Aim: To perform an empirical, pharmacological, separation of early afterdepolarizations (EADs) and transmural gradients of repolarization in arrhythmogenesis in a genetically modified mouse heart modelling human long QT syndrome (LQT) 3. Methods: Left ventricular endocardial and epicardial monophasic action potentials and arrhythmogenic tendency were compared in isolated wild type (WT) and Scn5a+/Δ hearts perfused with 0.1 and 1 μm propranolol and paced from the right ventricular epicardium. Results: All spontaneously beating bradycardic Scn5a+/Δ hearts displayed EADs, triggered beats and ventricular tachycardia (VT; n = 7), events never seen in WT hearts (n = 5). Perfusion with 0.1 and 1 μm propranolol suppressed all EADs, triggered beats and episodes of VT. In contrast, triggering of VT persisted following programmed electrical stimulation in 6 of 12 (50%), one of eight (12.5%), but six of eight (75%) Scn5a+/Δ hearts perfused with 0, 0.1 and 1 μm propranolol respectively in parallel with corresponding alterations in repolarization gradients, reflected in action potential duration (ΔAPD₉₀) values. Thus 0.1 μm propranolol reduced epicardial but not endocardial APD₉₀ from 54.7 ± 1.6 to 44.0 ± 2.0 ms, restoring ΔAPD₉₀ from ?3.8 ± 1.6 to 3.5 ± 2.5 ms (all n = 5), close to WT values. However, 1 μm propranolol increased epicardial APD₉₀ to 72.5 ± 1.2 ms and decreased endocardial APD₉₀ from 50.9 ± 1.0 to 24.5 ± 0.3 ms, increasing ΔAPD₉₀ to ?48.0 ± 1.2 ms. Conclusion: These findings empirically implicate EADs in potentially initiating spontaneous arrhythmogenic phenomena and transmural repolarization gradients in the re‐entrant substrate that would sustain such activity when provoked by extrasystolic activity in murine hearts modelling human LQT3 syndrome.     

醋酸精氨酸的毒理学试验研究

目的通过急性毒性实验和长期毒性实验,观察醋酸精氨酸对动物的毒性反应.方法急性实验选用KM小鼠80只,随机分成4组,每组20只,两个组分别从尾静脉注射0.5g/ml醋酸精氨酸和盐酸精氨酸25ml/kg体重;另两个组分别一次灌胃0.8g/ml的醋酸精氨酸和盐酸精氨酸40ml/kg体重,观察7d.长期毒性实验选用Wistar大鼠60只,分高、低剂量及正常对照组3个组.杂种狗6只,分高剂量组和正常对照组,高剂量组大鼠以20.0g·kg-1·d-1、狗12.0g·kg-1·d-1,低剂量大鼠组2.0g·kg-1·d-1 ,观察4周.结果小鼠急性试验(静脉和灌胃)所用剂量远大于拟用临床剂量的(0.4g·kg-1·d)80倍以上;长期毒性试验采用小鼠50倍于临床拟用剂量(20g/kg/d),狗30倍于临床拟用剂量(12.0g/kg/d),未发现明显的中毒反应,也未发现主要靶器官的损害.结论通过急性和长期毒性实验,证明大剂量或长时间使用醋酸精氨酸对机体无明显毒副作用.     

外泌体非编码RNA在非小细胞肺癌获得性耐药中的研究进展

非小细胞肺癌(non-small cell lung cancer,NSCLC)是肺癌中最常见的类型,对化疗及靶向药物的获得性耐药严重影响NSCLC患者的生存期,NSCLC获得性耐药机制复杂,确切机制仍不清楚.肿瘤来源或与肿瘤相关的外泌体是参与调控NSCLC获得性耐药的重要机制,可以通过传递核酸、蛋白质等赋予敏感细胞耐...