直接抗病毒药物时代特殊人群HCV感染的管理和治疗

慢性丙型肝炎呈全球性流行,不同性别、年龄、种族、民族人群均易感染HCV。分别阐述了儿童丙型肝炎患者、合并肾损伤患者、肝移植患者、合并肝硬化患者、合并HIV感染者、急性丙型肝炎患者等不同特殊人群HCV感染的管理方法和个体化治疗方案。     

HCV基因异质性及其宿主基因多态性

丙型肝炎的进展、严重程度、治疗反应性差异不仅与病毒的遗传多样性有关,而且与宿主IL-28B、IP-10、ITPA基因多态性有关。分别介绍了HCV基因多态性和宿主基因单核苷酸多态性的分子流行病学、临床和治疗学方面的研究进展,提出迫切需要可靠的有关病毒及宿主的相关分子流行病学数据,以协助决策HCV筛检等公共卫生问题,降低丙型肝炎全球发病率和病死率。     

宿主 microRNAs 在 HCV 复制及搞 HCV 治疗中的作用

HCV 感染是导致慢性肝炎、肝硬化及肝细胞癌（HCC）的主要原因之一。微小 RNA（miRNAs）是一类非编码小分子 RNA,可参与人体多种生理、病理过程。简述了 miRNAs 调控 HCV 复制的机制,探讨了肝特异性 microRNA －122（miR －122）拮抗剂对丙型肝炎抗病毒治疗的作用。认为 miRNAs 对 HCV 的表达起着重要调节作用,有望成为治疗 HCV 感染的一种措施,但仍需进一步研究。     

HCV感染与动脉粥样硬化的关系

慢性感染和炎症反应与动脉粥样硬化的发生相关,而HCV感染是较为常见的感染性疾病。回顾了HCV感染与动脉粥样硬化相关疾病发生关系的最新进展,研究表明更多的证据支持HCV感染会增加冠心病、卒中、颈动脉粥样硬化的发生率以及因心血管事件的死亡风险。HCV感染是动脉粥样硬化的危险因素,虽然背后的机制尚需更多研究,但在丙型肝炎患者人群中应注意预防与控制动脉粥样硬化性疾病。     

老年HCV感染者抗病毒治疗研究进展

干扰素联合利巴韦林为目前公认的抗病毒治疗丙型肝炎的首选治疗方案,但在老年慢性丙型肝炎病人,由于在治疗过程中副反应多,故中断治疗或需要减少剂量的比例高,影响了抗病毒治疗的疗效。目前研究认为：老年HCV感染者进行抗病毒治疗非常必要,通过对治疗过程中干扰素和利巴韦林副作用的监测,可提高治疗的依从性,从而获得更高的持久病毒学应答率。     

无干扰素抗HCV方案的研究进展

当前,全球约有1.5亿慢性HCV感染者,其中20%会进展为肝硬化并最终死于终末期肝病和肝癌。干扰素(IFN)长期作为慢性丙型肝炎治疗的基石,在维持持续病毒学应答以及阻止病情进展方面有重要作用,但其疗效有限、不良反应多。近年来,直接抗病毒药物(DAAs)呈现出良好的疗效,在DAAs的基础上,介绍了无IFN抗HCV方案的最新研究进展,认为随着DAAs的出现,无IFN抗HCV方案发展迅速,前景较好。     

HCV母婴传播的分子机制及危险因素

HCV感染是一个全球性的健康问题,人群普遍易感,主要传播途径有血液传播、性传播、母婴传播。血液制品抗HCV筛查大大减少了HCV血液传播几率。直接抗病毒药物治疗丙型肝炎取得了突破性进展,HCV传播趋势得到明显遏制。但HCV感染具有隐匿性,丙型肝炎疫苗尚未研制成功,母婴传播缺乏有效的阻断措施,将成为HCV主要传染方式之一。降低HCV母婴传播率,对预防新生儿HCV感染及降低人群中丙型肝炎的感染率仍具有重要意义。近年来关于HCV母婴传播具体机制、危险因素的研究一直在进行,取得了不少成果,但仍有许多问题尚无统一认识。现就HCV母婴传播具体机制的国内外研究进展进行综述。     

抗HCV小分子化合物的研究

目前抗HCV治疗的标准疗法是聚乙二醇干扰素(PEG-IFN)联合利巴韦林(RBV),但仍有部分患者不能达到治愈。近年来,靶向针对HCV生活周期中病毒蛋白的小分子化合物的研究得到了迅速发展,小分子化合物联合PEG-IFN、RBV三联治疗可以提高持续病毒学应答率。而对于不能应用/耐受干扰素治疗的慢性丙型肝炎患者,各类小分子化合物之间的联合抗病毒治疗也可取得较好的疗效。因此,认为小分子化合物给今后慢性丙型肝炎治疗带来新的希望。     

受HCV感染的围产期妇女其孩子HCV感染检测和确诊的失败

正【据《Clin Infect Dis》2016年4月报道】题:受HCV感染的围产期妇女其孩子HCV感染检测和确诊的失败(作者Kuncio DE等)HCV的垂直传播是儿科HCV感染的主要途径,HCV感染的母亲生育的孩子大约有5%可发展成慢性感染,基于这种风险建议进行孕妇和幼儿的丙型肝炎检测。该项研究评估了美国高丙型肝炎负担城市——费城,HCV阳性母亲其孩子的丙型肝炎检测     

TTV HCV重叠感染时TTV无明显致肝损伤作用

我们采用套式PCR方法回顾性研究了一组接受干扰素治疗的慢性丙型肝炎患者的TTV感染状况,对TTV重叠感染时丙型肝炎肝组织病变及干扰素治疗状况进行分析。研究结果对评价TTV致病性具有一定意义。 1 材料和方法 1.1材料病例及治疗:29例慢性丙型肝炎患者,均为肝功能持续异常超过6mo,血清抗HCV及HCV RNA阳性,乙型肝炎标志阴性。男16例,女13例,平均年龄34.6岁。采用α-2a干扰素300万u,或组合干扰素(CIFN)9μg或15μg,3次·d~(-1)cc,共24wk(5例用药12wk),停药后随访24wk以上。疗效判断标准为,ALT应答:ALT恢复正常;病毒应答:HCV RNA定性检测     

Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice

AIM:To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet(HFD).METHODS: Male swiss mice(6-wk old) were fed a highfat diet(HFD; 60% kcal from fat) or AIN-93(control diet; 15% kcal from fat) for 12 wk and received pentoxifylline intraperitoneally(100 mg/kg per day) for the last 14 d. Glucose homeostasis was evaluated by measurements of basal glucose blood levels and insulin tolerance test two days before the end of the protocol. Final body weight was assessed. Epididymal adipose tissue was collected and weighted for adiposity evaluation. Liver and adipose tissue biopsies were homogenized in solubilization buffer and cytokines were measured in supernatant by enzyme immunoassay or multiplex kit, respectively. Hepatic histopathologic analyses were performed in sections of paraformaldehyde-fixed, paraffin-embedded liver specimens stained with hematoxylin-eosin by an independent pathologist. Steatosis(macrovesicular and microvesicular), ballooning degeneration and inflammation were histopathologically determined. Triglycerides measurements were performed after lipid extraction in liver tissue. RESULTS: Pentoxifylline treatment reduced microsteatosis and tumor necrosis factor(TNF)-α in liver(156.3 ± 17.2 and 62.6 ± 7.6 pg/mL of TNF-α for non-treated and treated obese mice, respectively; P 0.05). Serum aspartate aminotransferase levels were also reduced(23.2 ± 6.9 and 12.1 ± 1.6 U/L for nontreated and treated obese mice, respectively; P 0.05) but had no effect on glucose homeostasis. In obese adipose tissue, pentoxifylline reduced TNF-α(106.1 ± 17.6 and 51.1 ± 9.6 pg/mL for non-treated and treated obese mice, respectively; P 0.05) and interleukin-6(340.8 ± 51.3 and 166.6 ± 22.5 pg/mL for non-treated and treated obese mice, respectively; P 0.05) levels; however, leptin(8.1 ± 0.7 and 23.1 ± 2.9 ng/mL for non-treated and treated lean mice, respectively; P 0.05) and plasminogen activator inhibitor-1(600.2 ± 32.3 and 1508.6 ± 210.4 pg/mL for non-treated and treated lean mice, respectively; P 0.05) levels increased in lean adipose tissue. TNF-α level in the liver of lean mice also increased(29.6 ± 6.6 and 75.4 ± 12.6 pg/mL for non-treated and treated lean mice, respectively; P 0.05) while triglycerides presented a tendency to reduction.CONCLUSION: Pentoxifylline was beneficial in obese mice improving liver and adipose tissue inflammation. Unexpectedly, pentoxifylline increased pro-inflammatory markers in the liver and adipose tissue of lean mice.     

Heart Failure in South America

Continued assessment of temporal trends in mortality and epidemiology of specific heart failure in South America is needed to provide a scientific basis for rational allocation of the limited health care resources, and strategies to reduce risk and predict the future burden of heart failure. The epidemiology of heart failure in South America was reviewed. Heart failure is the main cause of hospitalization based on available data from approximately 50% of the South American population. The main etiologies of heart failure are ischemic, idiopathic dilated cardiomyopathy, valvular, hypertensive and chagasic etiologies. In endemic areas, Chagas heart disease may be responsible by 41% of the HF cases. Also, heart failure presents high mortality especially in patients with Chagas etiology. Heart failure and etiologies associated with heart failure may be responsible for 6.3% of causes of deaths. Rheumatic fever is the leading cause of valvular heart disease. However, a tendency to reduction of HF mortality due to Chagas heart disease from 1985 to 2006, and reduction in mortality due to HF from 1999 to 2005 were observed in selected states in Brazil. The findings have important public health implications because the allocation of health care resources, and strategies to reduce risk of heart failure should also consider the control of neglected Chagas disease and rheumatic fever in South American countries.     

岳阳市城区小学生血吸虫病防治健康教育现状调查

目的 调查湖南省岳阳市城区小学生血吸虫病防治知识、行为现状及健康教育需求情况,为制定科学有效的小学生血吸虫病健康教育方案提供参考依据。方法 采用分层整群抽样方法,抽取岳阳市城区洞庭湖湖畔学校和中心城区学校各2所,每所再从五、六年级分别抽取2个班的学生,通过调查问卷了解小学生血吸虫病相关知识、预防行为及健康教育需求,并进行统计分析。结果 共调查湖畔小学353人、中心城区小学363人,两组学校小学生年龄、性别、年级构成差异无统计学意义(t=-0.494,χ_性别²=1.615,χ_年级²=2.152;P均>0.05)。学生血吸虫病防治知识总知晓率为42.60%(305/716),其中,湖畔学校小学生血防知识知晓率(52.97%)高于中心城区(32.51%),差异有统计学意义(χ²=30.661,P<0.05);学生行为正确率为76.68%(549/716),血防知识知晓组行为正确率(81.31%)高于不知晓组(71.24%),差异有统计学意义(χ²=6...     

Antioxidant therapies in COPD

Oxidative stress is an important feature in the pathogenesis of COPD. Targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to be beneficial in the treatment of COPD. Antioxidant agents such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn), dietary polyphenols (curcumin, resveratrol, green tea, catechins/quercetin), erdosteine, and carbocysteine lysine salt, all have been reported to control nuclear factor-kappaB (NF-κ B) activation, regulation of glutathione biosynthesis genes, chromatin remodeling, and hence inflammatory gene expression. Specific spin traps such as α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo. Since a variety of oxidants, free radicals, and aldehydes are implicated in the pathogenesis of COPD, it is possible that therapeutic administration of multiple antioxidants will be effective in the treatment of COPD. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in COPD are discussed.     

Rising incidence of oesophageal adenocarcinoma in men in Australia

Adenocarcinomas of the oesophagus and of the gastric cardia have been reported to be increasing in incidence in many countries, while the incidence of squamous cell carcinoma of the oesophagus is stable and non-cardia gastric cancers are decreasing in incidence. Age-standardized incidence rates for the years 1982–93 for oesophageal adenocarcinoma and non-adenocarcinoma, and gastric cardia and non-cardia cancers were calculated based on state cancer registry incidence data. Time trends in the age-standardized rates were assessed using linear regression. A consistent increasing trend in the incidence of oesophageal adenocarcinoma in men was seen in all states of Australia and was statistically significant in all states except South Australia. There were no consistent nationwide trends in the incidence of oesophageal adenocarcinoma in women, although a trend towards an increase in the incidence of this cancer reached statistical significance ( P < 0.05) in three states (New South Wales, Victoria, Queensland). There were no important trends in the incidence of oesophageal non-adenocarcinoma in either men or women. There were no consistent nationwide changes in the incidence of gastric cardia cancer in either men or women, although this cancer was significantly increasing in Tasmania in both men and women. The incidence of cancer of the stomach not arising at the gastric cardia was significantly decreasing in men in all states and was also decreasing in women in all states, although in women this decrease was statistically significant only in New South Wales, Victoria and Western Australia. There has been a dramatic increase in the incidence of oesophageal adenocarcinoma in men in Australia. The incidence of this cancer in men is now approximately equal with that of non-adenocarcinoma of the oesophagus. The incidence of non-cardia stomach cancer continues to fall.     

Histamine antagonists in the treatment of shock hyperglycemia in the rat

The present study was undertaken to determine the effect of exogenous histamine and histamine blockers on blood glucose and hepatic glycogen in the rat. Forty-one nonfasted male Sprague-Dawley rats that had been anesthetized with intraperitoneal injections of urethane were injected intravenously (femoral) with histamine (10 mg/kg) five minutes after pretreatment with Ringer's solution (control), diphenhydramine (1 mg/kg) (H-1 blocker); metiamide (1 mg/kg) (H-2 blocker); or a combination of these blockers. Mean arterial pressure (carotid), blood glucose, and hepatic glycogen were measured. Within 30 minutes, histamine evoked a significant increase in blood glucose, and a decrease in hepatic glycogen, and a reduction in blood pressure. However, rats treated with the H-2 blocker metiamide or with a combination of H-1 and H-2 blockers did not show as significant a hypotensive response as rats treated with the H-1 blocker diphenhydramine alone. The hyperglycemic-glycogenolytic response to histamine was modified by diphenhydramine as well as by a combination of blockers, but not by metiamide alone. These results suggest that a) the hypotension did not initiate the hyperglycemic and glycogenolytic response; b) the H-2 blocker metiamide has little effect on the hyperglycemic response to exogenous histamine; and c) the H-1 blocker diphenhydramine may have antihyperglycemic properties.     

Ethnic variation in the annual rates of adult inflammatory bowel disease in hospitalized patients in Vancouver, British Columbia

BACKGROUND:

There is currently little available information regarding the impact of ethnicity on the clinical features of inflammatory bowel disease (IBD). Migrating populations and changing demographics in Vancouver, British Columbia (BC) provide a unique opportunity to examine the role of ethnicity in the prevalence, expression and complications of IBD.

OBJECTIVES:

To determine the demographics of IBD and its subtypes leading to hospitalization in the adult population of BC.

METHODS:

A one-year retrospective study was performed for all patients who presented acutely with IBD to Vancouver General Hospital from January 1, 2006 to December 31, 2006. Data regarding sex, age, ethnicity, IBD type and extent of disease, complications and management strategies were collected. Clinical data were confirmed by pathology and radiology reports.

RESULTS:

There were 186 cases of IBD comprising Crohn’s disease (CD) 56%, ulcerative colitis (UC) 43% and indeterminate colitis (1%) 1%. The annual rate of IBD cases warranting hospitalization in Caucasians was 12.9 per 100,000 persons (7.9 per 100,000 persons for CD and 5.0 per 100,000 persons for UC). This was in contrast to the annual rate of IBD in South Asians at 7.7 per 100,000 persons (1.0 per 100,000 persons for CD and 6.8 per 100,000 persons for UC) and in Pacific Asians at 2.1 per 100,000 persons (1.3 per 100,000 persons for CD, 0.8 per 100,000 persons for UC). The male to female ratio was higher in South Asians and Pacific Asians than in Caucasians. The extent of disease was significantly different across racial groups, as was the rate of complications.

CONCLUSIONS:

These early results suggest that there are ethnic disparities in the annual rates of IBD warranting hospitalization in the adult population of BC. There was a significantly higher rate of CD in the Caucasian population than in South Asian and Pacific Asian populations. The South Asian population had a higher rate of UC, with an increased rate of complications and male predominance. Interestingly, the rate of CD and UC was lowest in the Pacific Asian population. These racial differences – which were statistically significant – suggest a role for ethnodiversity and environmental changes in the prevalence of IBD in Vancouver.