肝纤维化定量诊断:有创还是无创?

准确量化评估肝纤维化程度对明确疾病诊断、治疗决策、监测疗效及判断预后均有重要参考价值。分析了有创及无创肝纤维化定量诊断方法的发展及应用现状。基于有创肝活组织检查的肝纤维化诊断方法已从描述性肝组织学评估发展到半定量分析,全量化客观测量肝纤维化技术可望改善传统半定量分析方法的观察者间误差、取样误差等不足;无创肝纤维化诊断方法则弥补了肝活组织检查的有创性、取样误差等不足,且对疾病远期结局有较好预测价值,但对肝纤维化动态变化的监测价值仍需要肝组织学分析的平行验证。由此认为,肝纤维化的无创评估方法尚不能完全替代肝组织学检查,但在明确诊断的患者中可减少肝活组织检查次数;无创诊断方法在肝纤维化动态监测的应用能力有待更多拓展与验证,而肝组织纤维化量化诊断方法也需要进一步验证其发现与疾病长期预后的关系。     

肝纤维化逆转的病理评估

肝纤维化是慢性肝脏疾病的共同病理结局,准确评估肝纤维化程度对明确疾病诊断、治疗决策、监测疗效及判断预后均有重要参考价值。目前已有多项临床研究证实,经过有效治疗肝纤维化/早期肝硬化是可以逆转的,如何正确评价肝纤维化逆转成为临床研究热点。肝活组织检查一直以来都是肝纤维化评价的金标准,因此其对纤维化逆转评价至关重要。从半定量、定量、定性评价3个方面回顾了现有肝纤维化病理分期标准在肝纤维化逆转中的临床应用进展,以提出更好的病理评价体系评估肝纤维化逆转。     

拉米夫定对慢性乙型肝炎伴重度肝纤维化患者的长期应用疗效——NUCB 4006十年随访研究

目的 评估拉米夫定(LAM)对慢性乙型肝炎伴重度肝纤维化患者长期治疗的临床和组织学结果.方法 39例重度肝纤维化(Ishak评分≥4分)的慢性乙型肝炎患者接受LAM治疗,最长达10年,评估随访期末患者疾病进展、肝组织学、病毒学以及生化学应答.数据分析采用配对t检验、Fisher确切概率法以及Willcoxon检验.结果 28例完成10年随访的患者中,5例出现疾病进展,占1 7.9%.16例患者在随访期末接受了第2次肝组织活检,与基线水平相比,肝组织学活动指数和纤维化评分均有明显好转(1.1±1.4比7.1±3.2,t=-0.82,P＜0.01;3.6±2.2比5.3±0.7,t=-2.89,P＜0.05).其中3例患者纤维比评分由基线时的5分改善为随访期末的0分.27例患者中,3例HBsAg消失,占11%,2例HBsAg血清学转换,占7%.23例HBeAg阳性患者至随访末,19例HBeAg消失,占83%,9例HBeAg血清学转换,占39%.在治疗期间,共有11例患者发生了病毒学突破或检测到LAM相关耐药变异,加用或换用其他核苷酸类似物,随访期末所有患者HBV DNA均＜1×103拷贝/mL.结论 LAM长期治疗能延缓慢性乙型肝炎伴重度肝纤维化患者的疾病进展,提高HBsAg及HBeAg的阴转率,持续维持HBV DNA于低水平,对某些患者能完全逆转肝纤维化,挽救治疗可减少LAM耐药变异对患者预后的影响.     

瞬时肝弹性测定在慢性乙型肝炎中的应用

在亚洲,慢性乙型肝炎病毒（HBV）感染是肝硬化与肝癌常见的病因。随抗病毒治疗进展,肝癌已成为一种潜在可预防的疾病,一项荟萃分析证实干扰素与核苷（酸）类似物能够减少慢性乙型肝炎中肝癌的发病风险,定期肝癌监测能够检查到早期和潜在可切除的肝癌,改善患者生存率。肝纤维化是炎症坏死的自然创面愈合过程,是导致肝硬化基本的致病过程。既往肝纤维化评估在很大程度上受阻于肝活检的局限性,引入瞬时肝弹性测定这一可靠及非侵入性肝纤维化检测方法,在病毒性肝炎难以研究的领域洒下了新的曙光。     

慢性乙型肝炎患者肝组织HBsAg、HBcAg表达及临床意义

目的：探讨慢性乙型肝炎患者肝组织中HBsAg、HBcAg表达与血清乙肝病毒载量及肝组织损伤程度之间的关系。方法：对90例慢性乙型肝炎患者进行肝组织活检，进行病理诊断及乙肝病毒HBsAg、HBcAg免疫组化染色．同时荧光定量检测血清HBVDNA含量，并分析其相关性。结果：血清HBVDNA定量、肝组织炎症程度及纤维化程度与肝组织HBsAg表达强度无相关性，而与肝组织HBcAg表达强度有明显的关联性；血清HBVDNA定量与肝组织炎症程度及纤维化间无明显的相关性。结论：在慢性乙型肝炎的免疫损伤过程中，HBcAg是靶抗原，血清HBV DNA结合肝组织病毒抗原的表达可作为抗病毒治疗的指标。     

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病毒水平和慢性乙型肝炎(简称“慢乙肝”)疾病的进展和远期预后直接相关,没有肝脏的炎症和坏死,肝纤维化、肝硬化和肝细胞癌的发生就会大大减少,因此,抑制HBV复制或清除HBV感染,即抗病毒是慢性乙型肝炎治疗的关键。目前,有关慢乙肝抗病毒治疗的指南和共识将慢乙肝分为HBeAg阳性     

基于病理和影像学的肝纤维化量化评估技术的临床应用

肝纤维化/肝硬化是慢性肝脏疾病的常见病理结局,准确评估肝纤维化程度对明确疾病诊断、治疗决策、监测疗效及判断预后均有重要参考价值。目前两类量化评估技术得到了较为广泛应用,一是基于肝穿刺病理的量化评估技术,为细化肝纤维化分期及评估肝纤维化进展和逆转提供了金标准;二是基于影像学的无创量化评估技术,因其可重复性而在肝纤维化的动态监测与临床转归预测中发挥重要作用。主要介绍了上述两类量化评估技术的发展及其临床应用,以期更好地指导临床实践。     

肝纤维化诊断及其严重程度评估

<正>肝纤维化是继发于各种慢性肝损害后的组织修复反应,其严重程度是肝硬化肝功能失代偿、肝细胞癌等远期预后的重要危险因素。1肝纤维化的病理学诊断及严重程度评估肝组织活检病理学检查一直以来被认为是肝纤维化诊断的“金标准”。从最初的主观描述性诊断到半定量评分以及客观全定量技术的应用,肝纤维化病理学诊断技术得以不断发展和完善。肝活检取     

α干扰素治疗慢性乙型肝炎肝纤维化血清标记与病理评价

目的评价干扰素α(IFN)的抗肝纤维化作用及其抗病毒疗效的关系。方法干扰素α治疗36例慢性乙型肝炎患者,对照组用常规方法治疗,治疗前后检测血清肝纤维化指标HA、PC-Ⅲ、Ⅳ-C、LN以及TGF-β1,B超引导下肝穿作组织学炎症活动度和纤维化程度的评分比较。结果IFN组治疗后HA、PC-Ⅲ、Ⅳ-C、LN和TGF-β1均较治疗前明显降低(P＜0.01),与对照组治疗后相比较,HA、PC-Ⅲ和TGF-β1明显降低(P＜0.05)。IFN组治疗后组织学炎症活动度评分为(9.3±3.2)分降至(6.2±2.1)分,肝纤维化程度评分由(7.5±2.2)分降至(5.1±1.8)分(P值均＜0.05)。结论肝纤维化程度的改善与毒抗病毒疗效密切相关,α干扰素对慢性乙型肝炎肝纤维化有较好疗效。     

乙型肝炎肝硬化的分期及治疗进展

肝硬化是慢性乙型肝炎疾病进展的重要阶段,明确肝硬化严重程度对评估预后至关重要,目前以肝硬化并发症为基础的临床分期应用广泛,而病理分期仍有待细化。治疗方面,2015年各肝病学会相继更新了慢性乙型肝炎诊疗指南,乙型肝炎肝硬化的抗病毒治疗较前更加积极。预后方面,有效的抗病毒治疗实现了早期肝硬化的逆转,降低了肝病相关终点事件的发生,但逆转的机制仍有待进一步探讨。     

青少年高血压的研究进展

随着人们生活和行为方式的改变,高血压发病明显呈年轻化趋势。在青少年时期识别高血压病高危人群有助于早期进行有效干预和治疗,降低未来高血压的发生率及其严重性。现试从青少年高血压的诊断、发病因素、特点、治疗策略等方面的研究进展作一综述。     

Morbidity in cardiovascular diseases in immigrants in Sweden

INTRODUCTION: Although immigration to Sweden has increased in the last few decades, the incidence rates of cardiovascular disease and coronary heart disease in immigrants are unknown. The aim of the present study is to estimate whether place of birth affects the incidence rates of cardiovascular disease and coronary heart disease. MATERIAL AND METHODS: The study was designed as a follow-up study on morbidity in cardiovascular disease and coronary heart disease between 1 January 1997 and 31 December 1998, including three and a half million persons with age range 35-64 years, of whom 550 000 were born abroad, from the database MigMed consisting of the whole Swedish population. Incidence rates and relative risks were estimated by indirect standardization and a proportional hazard model. RESULTS: The age-adjusted risk of coronary heart disease was higher in most foreign-born groups than in Swedes. For example, in nine of 12 male groups, the relative risks varied between 1.1 and 2.2, and in seven of 12 female groups, the relative risks varied between 1.4 and 2.5. When also adjusting for level of education and employment status, the risks were still high, but on a lower level. CONCLUSIONS: Foreign-born people possess an over-risk of cardiovascular or coronary heart disease(CVD/CHD) compared with Swedish-born persons, also when level of education and employment status are taken into account.     

C·肉毒杀鼠素(冻干剂)应用研究

目的为研究C·肉毒杀鼠索对杀灭达乌尔黄鼠(简称黄鼠)的大面积应用情况和对家畜、家禽的毒害作用,进行了C·肉毒杀鼠素的应用研究.方法大面积投毒采用ES-2药饵撒播机[1],间隔约80m进行条投.羊、鸡采用直接灌胃.结果大面积应用的灭鼠率为83.72%.对羊、鸡最高剂量分别为500万MLD、150万MLD,均未出现中毒现象.结论 C·肉毒杀鼠素是较为理想的草原大面积杀灭黄鼠的理想、首选药物.     

高龄老年高血压的临床研究进展

随着社会老龄化进程的加快,80岁以上高龄老人的绝对数量以及占总人口的比例均在增加,如何提高高龄老年高血压的防治水平备受关注。现试从高龄老年高血压的临床特点、治疗策略等方面的临床研究进展作一综述。     

中国老年性耳聋的研究与干预进展

老年性耳聋已成为影响我国老年人生活质量的最主要的慢性病之一。助听器是目前帮助听力损失的老年人克服交流障碍的主要手段。在我国,数字助听器已逐渐取代模拟助听器并且体现出了更好的效果。但是老年听力损失患者中使用助听器的比例仍然很小。人工耳蜗植入也已被应用在老年患者中。我国针对老年人的听力康复服务还有较长的路要走。     

Sex Differences in Ethanol-induced Dopamine Release in Nucleus Accumbens and in Ethanol Consumption in Rats

In vivo microdialysis was used to examine changes in nucleus accumbens and striatal dopamine, dihydrophenylacetic acid (DO-PAC), and homovanillic acid (HVA) following acute administration of ethanol (0.0, 0.25, 0.5, 1.0, or 2.0 g/kg) in male and female Long-Evans rats. Following dialysis, rats were trained to bar-press for oral ethanol reinforcement. In nucleus accumbens, females showed significant increases in extracellular dopamine following 0.25 or 0.5 g/ kg ethanol, but did not show significant increases over baseline at the higher doses. Males showed slight increases in dopamine at the lower doses and decreased dopamine at 2.0 g/kg. In striatum, both sexes showed increased dopamine at the lower doses and decreased dopamine at 2.0 g/kg. There were slight increases in nucleus accumbens DOPAC and HVA at some doses in both sexes, but no changes in striatal metabolite levels. In addition to showing increased responsiveness to ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol than males during behavioral testing. The pattern of both greater ethanol-induced nucleus accumbens dopamine release and greater ethanol consumption in females supports the hypothesis that ethanol reward is mediated, at least in part, by the mesolimbic dopamine system.     

Epstein-Barr virus in malignancies in renal transplant recipients in Japan

A role for Epstein-Barr virus (EBV) in the development of malignancies including lymphomas, and carcinoma of the stomach, nasopharynx, thymus and salivary gland is suggested. It is indicated that EBV evokes polyclonal-B-cell-proliferative diseases in immunocompromised hosts, such as transplant patients, which results in monoclonal malignant lymphomas. The suppression of immune functions in these patients is thought to lead to incomplete elimination of the cells expressing EBV latent infection genes. To examine the etiological role of EBV in the development of malignancies following renal transplant in Japan, 42 malignancies in 1744 cases of renal transplant were studied for the presence and type of EBV. The polymerase chain reaction revealed that 5 malignancies were positive for EBV, all type A: 2 of 2 cases of non-Hodgkin's lymphoma (NHL), 2 of 8 cases of gastric adenocarcinoma of the common type, and 1 of 2 cases of gastric plasmacytoma. In situ hybridization revealed positive signals in the nucleus of tumor cells in 2 cases of NHL and 1 of plasmacytoma. Positive signals were found in the small lymphoid cells but not in the tumor cells in 2 cases of gastric carcinoma. On the basis of these findings, a role for EBV in the development of malignancies in renal transplant patients is unlikely except for lymphoid neoplasias.Abbreviations PCB polymerase chain reaction - EBV Epstein-Barr virus - NHL non-Hodgkin's lymphoma     

糖尿病大鼠心室肌细胞钾通道的改变

目的研究糖尿病大鼠心室肌细胞钾通道的改变及增加葡萄糖代谢对其的作用。方法取体重150～200g的雄性SpragueDawley大鼠,腹腔注射链脲菌素(STZ)建立糖尿病模型,采用酶解法获得单个心室肌细胞,应用膜片钳全细胞记录技术记录钾电流。结果糖尿病大鼠心室肌细胞瞬间外向性钾流(Ito)密度较对照组显著降低[ 60mV时,分别为(15.90±1.19)pA/pF(n=25)和(28.55±0.97)pA/pF(n=12),P<0.001];分别用100nmol/L胰岛素及1.5mmol/L二氯乙酸在体外预处理心室肌细胞4～5h和3～4h使Ito密度恢复至对照组水平[ 60mV时,分别为(29.40±0.38)pA/pF(n=20)和(27.35±0.97)pA/pF(n=12)]。结论糖尿病大鼠心室肌细胞钾通道功能发生改变,增加葡萄糖代谢可逆转这一改变,提示葡萄糖代谢与Ito功能间存在一定关系。