非酒精性脂肪性肝病客观化指标与中医辨证分型关系探讨

目的:探讨非酒精性脂肪性肝病(NAFLD)客观化指标与中医辨证分型的关系。方法:筛选NAFLD患者176例及健康对照组60例,观察记录两组人员中医证侯、肝功能、血脂、B超、CT肝脾比值结果,根据临床证候对`NAFLD患者进行中医辨证分为肝郁脾虚型、湿热内蕴型、痰瘀互结型、肝肾不足型4组,与对照组及各组间相互比较,分析辨证分型与客观化指标之间的关系。结果:NAFLD患者中医辨证分型以肝郁脾虚居多(29.54%)。各临床分型与对照组相比其客观化指标均有不同程度的异常。各组间比较ALT升高多集中在湿热内蕴型和痰瘀互结型,TG升高多为痰瘀互结型,LDL、TC升高多为肝肾不足型,CT肝脾比值降低以湿热内蕴型和痰瘀互结型为甚,B超呈重度改变多发于湿热内蕴型。结论:NAFLD患者客观化指标与中医辨证分型具有一定的内在关系。     

原发性肝癌不同血瘀证患者肝组织微小RNA表达差异的初步研究

目的对原发性肝癌中医辨证分型提供客观的量化标准。方法采用微小RNA（miRNA）芯片检测、实时定量PCR验证,对比观察原发性肝癌气虚血瘀证、肝郁血瘀证、肝胆湿热证及肝瘀痰结证患者（各3例,分别以证型命名组名）肝组织10种miRNA表达水平的差异;并与3例正常肝组织（正常组）进行比较。结果 miR-122-3p各证型组均明显高于正常组（P〈0.05）,气虚血瘀组明显高于其他各证型组（P〈0.05）;miR-30b-5p在肝胆湿热组明显低于其他各证型组（P〈0.05）,其他各证型组与正常组比较无显著性差异;miR-182-5p在气虚血瘀组、肝郁血瘀组和肝胆湿热组均明显高于正常组（P〈0.05）;miR-221-5p在肝胆湿热组和肝郁血瘀组明显低于其他各证型组及正常组（P〈0.05）,但这两组间无显著性差异;miR-221-3p在肝郁痰结组高于其他各证型组,但无统计学差异;miR-21-5p在气虚血瘀组、肝郁血瘀组和肝郁痰结组均高于肝胆湿热组和正常组,但无统计学差异。miR-222-3p、miR-214-3p、miR-491-3p、miR-422a各组间未见明显差异。结论原发性肝癌不同血瘀证患者肝组织miRNA水平存在显著性差异;本研究为原发性肝癌的中医辨证分型提供了客观的量化标准。     

Keratinocyte growth factor and beta-cell differentiation in human fetal pancreatic endocrine precursor cells

AIMS AND HYPOTHESIS: Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family with a high degree of specificity for epithelial cells in vitro and in vivo. Our aim was to study the effect of KGF on beta-cell growth and differentiation on islet-like cell clusters derived from human fetal pancreas. METHODS: We investigated the effects of KGF, in vitro, on beta-cell differentiation from undifferentiated pancreatic precursor cells and in vivo after transplantating human fetal pancreatic cells into athymic rats treated with KGF. RESULTS: Treatment of islet-like cell clusters with KGF in vitro did not change the number of insulin producing cells, as measured by the measurement of insulin content or DNA. The in vivo treatment of recipient rats with KGF increased the number of beta cells within the grafts 8 weeks after transplantation. At this time, glucose-stimulated insulin secretion was evaluated by glucose stimulation tests in rats bearing the transplants. Measurements of human C-peptide concentrations after glucose challenge showed that the newly differentiated beta cells in the KGF-treated group were functionally competent as opposed to the control group, where the graft failed to release insulin appropriately. CONCLUSION/INTERPRETATION: These findings suggest that in vivo, KGF is capable of inducing human fetal beta-cell expansion. The growth promoting effect of KGF on beta cells occurred mainly through the activation of ductal cell proliferation and their subsequent differentiation into beta cells.     

老年急性冠脉综合征患者血清生长分化因子-15的表达及其临床意义

目的观察生长分化因子-15(GDF-15)在老年急性冠脉综合征(ACS)患者血清中的变化及其对近期预后的预测价值。方法选取老年ACS患者116例,分为急性心肌梗死(AMI)组46例,不稳定型心绞痛(UAP)组70例,同时设同期因胸痛、胸闷症状入院经冠脉造影排除冠心病的对照组40例。采集空腹外周血,采用酶联免疫法测定患者血清GDF-15浓度。对ACS患者随访6月,记录其心血管不良事件的发生情况。结果 AMI组GDF-15水平为(815.41±227.54)ng/L,显著高于UAP组[(735.06±144.94)ng/L,P0.05]与对照组[(641.97±143.90)ng/L,P0.01]。同时UAP组与对照组GDF-15水平比较差异也有统计学意义(P0.01)。发生心血管事件组GDF-15水平高于未发生心血管事件组(P0.01)。结论 GDF-15水平在老年ACS患者中明显升高,其升高程度与ACS的类型有关,GDF-15可作为判断老年ACS近期预后的指标。     

Carcinosarcoma of the liver with mesenchymal differentiation

We report an extremely rare case where a mesenchymal differentiation, especially embryonal sarcoma, was demonstrated in cholangiocarcinoma. At autopsy, a yellowish-white tumor （15 cm× 12 cm） was found in the right hepatic lobe, and there were several daughter nodules in both hepatic lobes. Histologically, most of the main tumor and all of the daughter nodules examined showed sarcomatous changes （spindle cells, pleomorphic ceils and hyalization）. Histologic examination of a part of the main tumor disclosed a focus of adenocarcinoma within the tumor. The frequent transitions between the adenocarcinomatous areas and the sarcomatous areas suggested that sarcomatous transformation occurred in the cholangiocarcinoma and then spread rapidly. Immunohistochemically, the adenocarcinomatous elements were positive for cytokeratin, carcinoembryonic antigen （CEA） and epithelial membrane antigen, and negative in the sarcomatous cells. Vimentin was positive only in the sarcomatous elements. The findings of the present case support the view that carcinosarcomas represent carcinomas that develop sarcomatous elements via metaplasia of the epithelial element.     

Melatonin promotes hepatic differentiation of human dental pulp stem cells: clinical implications for the prevention of liver fibrosis

Melatonin's effect on hepatic differentiation of stem cells remains unclear. The aim of this study was to investigate the action of melatonin on hepatic differentiation as well as its related signaling pathways of human dental pulp stem cells (hDPSCs) and to examine the therapeutic effects of a combination of melatonin and hDPSC transplantation on carbon tetrachloride (CCl₄)‐induced liver fibrosis in mice. In vitro hepatic differentiation was assessed by periodic acid‐Schiff (PAS) staining and mRNA expression for hepatocyte markers. Liver fibrosis model was established by injecting 0.5 mL/kg CCl₄ followed by treatment with melatonin (5 mg/kg, twice a week) and hDPSCs. In vivo therapeutic effects were evaluated by histopathology and by means of liver function tests including measurement of alanine transaminase (ALT), aspartate transaminase (AST), and ammonia levels. Melatonin promoted hepatic differentiation based on mRNA expression of differentiation markers and PAS‐stained glycogen‐laden cells. In addition, melatonin increased bone morphogenic protein (BMP)‐2 expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. Furthermore, melatonin activated p38, extracellular signal‐regulated kinase (ERK), and nuclear factor‐κB (NF‐κB) in hDPSCs. Melatonin‐induced hepatic differentiation was attenuated by inhibitors of BMP, p38, ERK, and NF‐κB. Compared to treatment of CCl₄‐injured mice with either melatonin or hDPSC transplantation alone, the combination of melatonin and hDPSC significantly suppressed liver fibrosis and restored ALT, AST, and ammonia levels. For the first time, this study demonstrates that melatonin promotes hepatic differentiation of hDPSCs by modulating the BMP, p38, ERK, and NF‐κB pathway. Combined treatment of grafted hDPSCs and melatonin could be a viable approach for the treatment of liver cirrhosis.     

乙型肝炎肝硬化患者中医证型与超声影像学特征的关系

目的:探讨乙型肝炎肝硬化患者中医证型与肝脾大小及门静脉血流动力学的关系。方法:用彩超仪检测150例不同中医证型肝硬化(分为6型)患者的肝右叶最大斜径、前后径,肝左叶上下径、前后径,门静脉及脾静脉内径、血流速度,脾脏大小等超声指标,进行对比分析。结果:肝硬化血瘀证患者与肝气郁结证、湿热内蕴证、肝肾阴虚证患者相比,肝左叶上下径的差异有显著性意义(P<0.05);肝硬化湿热内蕴证患者与血瘀证患者相比,脾脏厚度差异有显著性意义(P<0.05);肝硬化湿热内蕴证患者与肝肾阴虚证、脾肾阳虚证、血瘀证患者相比,门静脉主干内径差异有显著性意义(P<0.05);肝硬化血瘀证患者与肝气郁结证患者相比,门静脉血流流速差异有显著性意义(P<0.01);脾静脉内径、血流流速各型之间比较差异无显著性意义。结论:超声检查对肝硬化中医辨证分型有一定指导意义,随着证型的发展,肝脾大小及门静脉血流动力学有相应改变。     

小儿慢性胃炎辨证分型与内镜象及幽门螺杆菌感染的相关性研究

[目的]探讨小儿慢性胃炎中医证型与胃黏膜改变及幽门螺杆菌感染之间的内在关系.[方法]将符合入选条件的404例慢性胃炎患儿中医辨证分型后进行胃镜检查及尿素13C-呼气试验(13 C-UBT)检查,并登记造表,进行统计学处理.[结果]肝胃不和型胃炎主要表现为胃黏膜充血和微小结节形成,脾胃湿热型胃炎表现以黏膜斑和黏膜糜烂为主,胃络瘀血型胃炎则以胃黏膜出现出血斑点为主,脾胃虚弱型胃炎以胃黏膜水肿为主,胃阴不足型胃炎以胃黏膜花斑为主.13 C-UBT阳性率实证高于虚证,与证型无相关性;13C-UBT值实证高于虚证,尤以肝胃不和型和脾胃湿热型为最高.[结论]小儿慢性胃炎中医辨证分型与胃黏膜改变及幽门螺杆菌感染之间存在实质性联系,为辨证施治提供了理论基础.     

生长分化因子15对急性冠状动脉综合征患者中期预后的预测价值

目的评估生长分化因子15(GDF-15)对急性冠状动脉综合征(ACS)患者中期预后的预测价值。方法连续入选95例急性冠状动脉综合征患者,采用酶联免疫吸附双抗体夹心法(ELISA)测定血浆GDF-15浓度,根据GDF-15中位数分为低浓度组和高浓度组,对出院患者进行定期随访,分别计算并比较2组患者的中期生存率以及主要不良心脏事件(MACE)发生率。生存率评估采用生存分析法。使用受试者工作特征(ROC)曲线分析GDF-15浓度对ACS患者的中期预后的预测价值。结果 ACS患者GDF-15浓度为921.56±462.20 ng/L,共随访患者95例,平均随访时间33.76±6.29月,死亡4例。生存分析提示GDF-15高浓度组患者的生存率低于GDF-15低浓度组(P=0.039)。GDF-15评估ACS患者中期生存的ROC曲线下面积(AUC)为0.853(SE=0.074,P=0.017,95%CI0.708~0.998),而GDF-15在预测ACS患者中期发生MACE的ROC曲线下面积为0.805(SE=0.068,P=0.000,95%CI 0.672~0.938)。结论 GDF-15可反映ACS患者的中期预后,作为一个有潜力的新标志物,能更好地帮助ACS患者进行危险分层及评估预后。     

Recurrent disseminated intravascular coagulation and fulminant intra hepatic thrombosis in a patient with the anti-phospholipid syndrome

We describe a patient with the lupus anti-coagulant who had recurrent episodes, over a 2 year period, of a severe and disseminated intravascular coagulopathy. This patient also had positive serological assays for syphilis and anti-cardiolipin antibodies. Associated with the coagulopathy were co-expressed episodes of liver disease, ultimately terminating in fulminant liver failure. At autopsy the features were characteristic of the Budd-Chiari syndrome. This is the first report to document how consumptive coagulopathy may present as a dominant feature of the anti-phospholipid syndrome. It also clearly describes an immune mediated thrombotic mechanism as a cause of hepatic veno-occlusive disorders. Furthermore, this case highlights the varied clinical spectrum of the anti-phospholipid syndrome and suggests that a high index of suspicion is required to ensure its diagnosis.     

人胎肝干细胞的体外培养及诱导分化

为体外分离培养和诱导分化人胎肝干细胞 ,从原代分离培养人胎肝干细胞集落 ,免疫细胞化学鉴定细胞集落分子标志物的表达 ;在体外特定细胞因子作用下诱导干细胞定向分化为成熟肝脏细胞 ,对其生物学特性进行初步鉴定。结果 ,从人胎肝组织中成功分离表达AFP、Albumin、Cytokeratin等标志物的胎肝干细胞集落 ,在体外特定细胞因子作用下肝干细胞可定向分化为成熟肝脏细胞。因此人胎肝中同样存在具有干细胞特性的原始细胞 ,体外可定向分化为成熟肝细胞。人胎肝干细胞的分离培养对于生物型人工肝的制备及其深入研究奠定了良好的基础     

Japanese case of Budd-Chiari syndrome due to hepatic vein thrombosis successfully treated with liver transplantation

A 22‐year‐old Japanese woman was found to have severe esophageal varices and then suffered from hepatic encephalopathy. She was diagnosed with Budd‐Chiari syndrome (BCS) due to hepatic vein (HV) thrombosis accompanied by portal vein thrombosis without inferior vena cava (IVC) obstruction. Latent myeloproliferative neoplasm (MPN) lacking the JAK2‐V617F mutation was considered to be the underlying disease. Liver transplantation was strikingly effective for treating the clinical symptoms attributable to portal hypertension. Although thrombosis of the internal jugular vein occurred due to thrombocythemia, which manifested after transplantation despite anticoagulation therapy with warfarin, the thrombus immediately disappeared with the addition of aspirin. Neither thrombosis nor BCS has recurred in more than 4 years since the amelioration of the last thrombotic event, and post‐transplant immunosuppression with tacrolimus has not accelerated the progression of MPN. In Japan, IVC obstruction, which was a predominant type of BCS, is suggested to have decreased in incidence with recent improvements in hygiene. The precise diagnosis of BCS and causative underlying diseases should be made with attention to the current trend of the disease spectrum, which fluctuates with environmental sanitation levels. Because the stepwise strategy, including liver transplantation, has been proven effective for patients with pure HV obstruction in Western countries, this strategy should also be validated for utilization in Japan and in developing countries where HV obstruction potentially predominates.     

全身炎症反应与肝肾综合征关系的研究

目的分析肝衰竭患者并发肝肾综合征(HRS)与全身炎症反应(SIRS)的关系。方法在137例肝衰竭患者中,合并HRS68例,单纯肝衰竭69例。收集两组患者Child-Pugh分级、终末期肝病模型(MELD)和SIRS评分。结果 HRS患者SIRS评分为0.70±0.86分,高于对照组0.36±0.54分(P<0.05),白细胞计数为8.96±4.45×109/L,显著高于对照组(5.79±2.40×109/L,P<0.05);HRS患者总胆红素和凝血酶原时间分别为404.5μmol/L和21.7±8.8s,高于对照组(259.0μmol/L和17.6±9.6s,P<0.05),而钠和氯分别为132.6±6.0mmol/L和92.2±9.1mmol/L,显著低于对照组(137.2±3.8mmol/L和99.5±9.3mmol/L,P<0.05)。结论 SIRS与肝衰竭患者并发HRS关系密切。     

Projected focal nodular hyperplasia of the liver with pronounced atypical ductular reaction resembling ductal plate and expressing KIT

A 26‐year‐old woman was found to have a left abdominal tumor in the space among the hepatic left lobe, stomach and spleen. A laparoscopic examination revealed that the tumor was a projected liver tumor, and resection of the tumor was performed. Grossly, the tumor was not encapsulated and measured 4 cm × 4 cm × 5 cm. Microscopically, the tumor was composed of mature hepatocytes, fibrous septae, abnormal vessels and ductular reaction (DR). A pathological diagnosis of projected focal nodular hyperplasia (FNH) was made. Characteristically, the cells of the DR showed atypical features such as small cells and hyperchromatic nuclei. The DR assumed the features of ductal plate‐like structures and immunohistochemically expressed KIT, suggesting that the cells of DR are stem cells and that when the stem cells proliferate they take a form of ductal plate‐like structures, similar to fetal bile duct development. Immunohistochemically, the cells of DR were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK7, CK8, CK18, CK19, carcinoembryonic antigen (CEA), CA19‐9, Ki‐67 (labeling = 3%) and KIT, but negative for CK20, p53, TTF‐1, CDX2, MUC1, MUC2, MUC5AC and MUC6. The hepatocytes were positive for CK CAM5.2, CK8, CK18 and Ki‐67 (labeling = 4%), but negative for CK AE1/3, CK7, CK19, CK20, CEA, CA19‐9, p53, KIT, TTF‐1, CDX2, MUC1, MUC2, MUC5AC and MUC6. In conclusion, the author reported a projected FNH. The DR of the FNH showed atypical features such as small cells and hyperchromatic nuclei. The DR assumed features of ductal plate‐like structures. KIT was positive in the DR in the FNH, suggesting that the cells of DR are liver stem cells, and proliferation of these cells take features of ductal plate‐like structures, similar to embryonic biliary development. MUC apomucins are negative in the DR.     

58例肝癌患者手术前后中医复合证证候特点初步研究

目的:通过观察原发性肝癌患者手术前后中医复合证证候分布与转变情况,初步揭示肝癌患者手术前后的中医复合证证候变化特点,为手术后肝癌的辨证论治提供科学依据.方法:参照《中药新药临床研究指导原则》建立肝癌中医复合证证候定性和量化诊断标准,采用自身前后对照的方法,对58例肝癌手术患者手术前后中医复合证证候特点进行初步研究.结果:中医复合证证候分布及变化情况:肝癌患者手术前肝血瘀阻证、湿热内蕴证所占比例较高,分别为22.1％、20.9％;肝癌患者手术后以湿热内蕴证、脾气虚弱证所占比例较高,分别为21.8％、21.0％;手术后肝血瘀阻证减少,脾气虚弱证增多,两者手术前后差异有统计学意义(P＜0.05);其余各证手术前后差异无统计学意义(P＞0.05).中医复合证证候量化评分结果:肝癌患者手术前量化评分最高的两个证候是:湿热内蕴证22.66分、脾气虚弱证17.75分;手术后量化评分最高的两个证候是:脾气虚弱证24.98分、湿热内蕴证23.31分:手术后肝血瘀阻证减少,脾气虚弱证增多,两者手术前后差异有统计学意义(P＜0.05);其余各证手术前后差异无统计学意义(P＞0.05).结论:肝癌患者手术前后均呈现肝血瘀阻证和脾气虚弱证的症状,因此需重视活血化瘀、健脾益气,但术后肝血瘀阻证有所减少,脾气虚弱证增多,应该对活血化瘀和健脾益气力度有所调整,肝癌术后中医辨证论治应更重视健脾益气.肝癌患者手术前后湿热内蕴证均较多,手术前后变化无差异,故肝癌患者手术前后均应重视清热利湿.     

血管性痴呆诊断、辨证及疗效评定标准(研究用)

血管性痴呆 (Va D)是由缺血性或出血性中风或缺血缺氧性脑损害导致的以认知损害为特征的一个综合征。为了适应我国痴呆领域临床研究的需要 ,中国中医药学会内科延缓衰老专业委员会痴呆工作小组完成了血管性痴呆诊断、辨证及疗效评定标准 (研究用 )的研究 (简称《Va D标准 (研究版 )》)。与我国现行的其他标准相比 ,本标准强调 :(1 )血管性痴呆的诊断必具痴呆、脑血管病和上述两种损害之间的因果关系 ;(2 )痴呆程度 (可疑、轻、中、重 )的确定采用临床痴呆评定表 (CDR) ;(3)痴呆中抑郁症评定量表 (CSDD) >8分与抑郁症鉴别 ,Hachinski缺血量表≥ 7分 ,除外阿尔茨海默病 ;(4)中医辨证采用 SDSVD量表 (肾精亏虚、痰浊阻窍、瘀血阻络、肝阳上亢、热毒内蕴、腑滞浊留、气血两虚 ) ;(5)疗效判定分为显效、有效、无效和恶化 ,并循证评价认知、行为、日常生活能力、总体印象和中医证候的疗效。本标准可作为临床研究中病例选择和疗效评定的指南 ,期待着试用和验证 ,并进一步修订和完善。     

Lack of therapeutic effects of gabexate mesilate on the hepatic encephalopathy in rats with acute and chronic hepatic failure

Background and Aim: Inflammation plays a pivotal role in liver injury. Gabexate mesilate (GM, a protease inhibitor) inhibits inflammation by blocking various serine proteases. This study examined the effects of GM on hepatic encephalopathy in rats with acute and chronic liver failure. Methods: Acute and chronic liver failure (cirrhosis) were induced by intraperitoneal TAA administration (350 mg/kg/day for 3 days) and common bile duct ligation, respectively, in male Sprague‐Dawley rats. Rats were randomized to receive either GM (50 mg/10 mL/kg) or saline intraperitoneally for 5 days. Severity of encephalopathy was assessed by the Opto‐Varimex animal activity meter and hemodynamic parameters, mean arterial pressure and portal pressure, were measured (only in chronic liver failure rats). Plasma levels of liver biochemistry, ammonia, nitrate/nitrite, interleukins (IL) and tumor necrosis factor (TNF)‐α were determined. Results: In rats with acute liver failure, GM treatment significantly decreased the plasma levels of alanine aminotransferase (P = 0.02), but no significant difference of motor activity, plasma levels of ammonia, IL‐1β, IL‐6, IL‐10 and TNF‐α or survival was found. In chronic liver failure rats, GM significantly lowered the plasma TNF‐α levels (P = 0.04). However, there was no significant difference of motor activity, other biochemical tests or survival found. GM‐treated chronic liver failure rats had higher portal pressure (P = 0.04) but similar mean arterial pressure in comparison with saline‐treated rats. Conclusions: Chronic GM treatment does not have a major effect on hepatic encephalopathy in rats with TAA‐induced acute liver failure and rats with chronic liver failure induced by common bile duct ligation.