肝紫斑病2例分析

病例1：男,67岁,以主诉腹胀、纳差1月余入院,无明显诱因,曾在当地医院按“肝硬化、胆囊炎”给予保肝治疗（具体用药不祥）,疗效不明显。自发病以来,偶有上腹部疼痛,无发热,无呕血、黑便,小便略黄,量正常。既往无肝炎、结核病史。2个月前曾因外伤致腰椎压缩性骨折,自行服用无准字号中药（活血化淤类，具体不祥）。查体见皮肤巩膜轻度黄染，腹部移动性浊音阳性，肝右肋下1cm，剑突下3cm，质软，无触痛，其他体格检查示未见异常。[第一段]     

Glisson蒂横断式肝切除术在临床中的应用研究

对2008年9月～2009年8月我院收治的24例采用Glisson蒂横断式行肝切除术的病例进行分析,观察手术时间、术中出血量、术后肝功能变化及并发症。所有病例均顺利行相应肝蒂结扎。平均手术时间为(140±25)min,术中出血量100～700mL,所有病例术中均未输血。术后无肝功能衰竭。所有患者均痊愈出院。Glisson蒂横断式肝切除术具有术中出血少、减轻术后肝功能损害,降低肿瘤肝内扩散等优点。     

现代肝脏外科的进展与思考

1888年德国外科医生Langenbuch成功实施了世界首例肝脏切除术,标志着现代肝脏外科的诞生。在百年发展历程中,肝脏外科历经盲目肝切除、规则性肝叶切除、不规则局部切除、解剖性肝段切除等发展阶段[1]。随着对肝脏解剖认识的深入,CT、MRI等影像学技术的发展,新的手术器械的应用,特别是活体     

巨大肝癌的外科手术治疗

目的探讨巨大肝癌外科治疗的可行性及手术要点。方法回顾性分析2008年7月至2010年5月间外科治疗的17例巨大肝癌手术及预后效果。结果手术切除率100%,围手术期病死率零。规则性切除4例,不规则性切除13例,平均手术时间（106±22）min（85～170 min）,平均术中失血（400±221）ml（100～1100 ml）,术后并发症11人,术后平均住院（15±4）d（11～21 d）,随访4～28个月,存活16例,死亡1例。结论巨大肝癌外科手术切除是可行的。手术的关键是术前做好认真评估和准备、制定切实可行的手术方案,术中避免大出血、保护好残余肝体积及功能,术后及时发现和处置并发症。     

Post-traumatic hepatic artery pseudo-aneurysm combined with subphrenic liver abscess treated with embolization

A 23-year-old man with post-traumatic hepatic artery pseudo-aneurysm and subphrenic liver abscess was admitted. He underwent coil embolization of hepatic artery pseudo-aneurysm. The pseudo-aneurysm was successfully obstructed and subphrenic liver abscess was controlled. Super-selective trans-catheter coil embolization may represent an effective treatment for hepatic artery pseudo-aneurysm combined with subphrenic liver abscess in the absence of other therapeutic alternatives.     

肝切除术122例分析

近6年来我院共施行各类肝叶切除122例现总结如下。临床资料一、一般资料:122例中男84例,女38例。年龄24～71岁。恶性病变71例:原发性肝细胞癌55例,肝胆管腺癌6例,肝内转移癌3例,胆囊癌累及肝脏6例,肝门胆管癌1例。其中合并肝硬化者53例,占肝细胞癌病人的95.63%。肿瘤直径>10cm者19例,     

肝再生增强因子在肝脏中的作用

肝再生增强因子（ALR）除了促进肝再生，保护肝损伤之外，可能在肝脏的器官形成和发育中也发挥着重要作用。介绍了ALR在肝脏中的生物学功能和机制研究的最新进展，并归纳总结了ALR在肝脏疾病的诊断和治疗中的应用。指出ALR可能通过线粒体途径调控肝细胞的凋亡，从而参与肝脏的修复和再生。未来ALR可能作为肝衰竭患者肝再生及预后评估的候选分子，并有望成为临床治疗严重肝病和肝衰竭的有效药物。     

肝星状细胞功能的研究进展

肝星状细胞(HSC)位于肝窦状隙的Disse腔,介于有窗孔(fenestrated)结构的肝窦内皮细胞和肝实质细胞之间[1].人们对HSC的来源还不清楚,最近有研究表明其分化自骨髓内的干细胞[2].     

肝纤维化分期与舌下络脉积分的关系

目的：探讨肝组织纤维化分期与舌下络脉变化的关系。方法：观察118例慢性乙型肝炎（CHB）及HBV携带者的舌下络脉，并采用细针穿刺术，取肝组织进行病理分析，研究肝组织分期与舌下络脉的关系。结果：①在行肝活检的88例CHB患者中，有不同程度纤维化改变的占86．36％（76／88），而其中已有43．18％（38／88）的患者组织学可见假小叶形成，S。期仅有13．6％（12／88）；30例HBV携带者中，s。期有30％（9／30），肝组织学异常者占70％（21／30），其中肝硬化者13．33％（4／30）；②S0～S。各分期95％的可信限（CI）分别为9．81～12．29，11．26～13．41，12．11～14．71，14．53～16．90，17．43～19．52。积分〉14者，86％肝活检分期≥S：，积分〉17者，肝组织多可见假小叶形成。组间比较，S。与S1期差异无显著性意义。结论：舌下络脉积分与肝组织学分期成正相关，积分越高，纤维化程度越明显，在判断肝纤维化的病程、动态跟踪的过程中，观察舌下络脉的变化是个安全、简单、科学而又行之有效的方法。     

肝脏特异性基因miR-122与肝脏疾病研究进展

作为肝脏特异性基因miRNA之一的miR-122,其与肝脏生理及病理过程有密切联系。它不仅可促进肝细胞分化,还可调控脂类代谢。对肝脏疾病,miR-122可通过慢性丙型肝炎病毒（HCV）基因5＇-UTR结合序列相互作用来促进HCV病毒复制,反之,亦可通过miR-122-cylin G1/p53-HBV调控路径抑制慢性乙型肝炎病毒（HBV）表达及复制过程。另外,miR-122可抑制肝细胞增殖过程及其恶性转化。值得注意的是,用于HCV慢性感染治疗的首个miR-122靶向药物已研究中。随着miR-122调控慢性肝炎、肝癌作用机制及影响肝功能发挥的研究逐渐被人们所认知,在慢性感染性疾病及肿瘤治疗中,其已成为一个重要且有效治疗途径。     

Effect of bax,bcl—2 and bcl—xL on regulating apoptosis in tissues of normal liver and hepatocellular carcinoma

AIM: To investigate the expression of bax, bcl-2 and bcl-xL mRNA in the tissues of normal liver and hepatocellular carcinoma (HCC), and analyze the relationship between the expression of bax, bcl-2 and bcl-xL mRNA and clinical parameters of HCC patients. METHODS: The expression of bax, bcl-2 and bcl-xL mRNA of normal liver and HCC was measured by Northern blot. Statistical analyses were made by t test and correlation analysis. RESULTS: A very low mRNA level was indicated at bax, bcl-2 and bcl-xL in the HCC tissues in contrast to the tissues of normal liver by Northern blot analysis. The analyses of mRNA level revealed that HCC tissues exhibited a mean 7.6-fold decrease in bax, 4.2-fold in bcl-2 and 3.5-fold in bcl-xL in comparison with normal control tissues, respectively. Positive correlation was found between bax and bcl-xL (r=0.7061, P<0.01). There was no significance between the mRNA expression of these three genes and age, gender, tumor differentiation and tumor stage of HCC patients. CONCLUSION: The results are consistent with the fact that apoptosis rarely occurs in normal livers but increases in HCC, indicating that bcl-2 and bcl-xL may play a very important role in regulating the apoptosis of normal liver and HCC.     

Bcl-2 family of proteins in indolent B-cell non-Hodgkin's lymphoma: study of 116 cases

The bcl-2 family of proteins comprises both antagonists and agonists of apoptosis. We have investigated whether subsets of indolent B-cell non-Hodgkin's lymphoma (IB-NHL) differ in the expression of the bcl-2 family members; 116 cases of IB-NHL, composed of chronic lymphocytic leukemia (CLL, n = 48), follicular lymphoma (FL, n = 38), marginal zone B-cell lymphoma (MZBCL, n = 15), and mantle cell lymphoma (MCL, n = 15), were investigated for expression of bcl-2, bcl-X, mcl-1, bax, and bak proteins by immunohistochemistry. Expression of bcl-2 and bcl-X proteins was moderate/high among most IB-NHLs. Expression of mcl-1 was low/absent in most cases of CLL and MCL and low/moderate in most cases of FL and MZBCL. Most MCLs did not express bax protein. Bax expression was absent/low among most cases of CLL and low/moderate among most cases of FL and MZBCL. Expression of bak was moderate/low among most cases of CLL, MZBCL, and MCL but was absent/low among most cases of FL. The different subsets of IB-NHLs differ in their expression of mcl-1, bax, and bak proteins.     

Apoptosis and immaturity in acute myeloid leukemia

The primary cause of treatment failures in acute myeloid leukemia (AML) is the emergence of both resistant disease and early relapse. Among the most frequent agents of these phenomena are defects in the mitochondrial-mediated apoptotic pathway. This pathway is regulated by bcl-2 family of anti-apoptotic (bcl-2, bcl-xl, mcl-1) and pro-apoptotic proteins (bax, bad, bak). In particular, bcl-2 dimerizes with several members of bcl-2 family of proteins, altering the threshold of cell death. The flow cytometric quantitative measurement of bcl-2 and bax expression for the determination of bax/bcl-2 ratio provided crucial clinical information in AML: in our hands, lower bax/bcl-2 ratio conferred a very poor prognosis with decreased rates of complete remission (CR) and overall survival (OS). Moreover, striking correlations were found between lower bax/bcl-2 ratio and higher progenitor marker expression, such as CD34, CD117 and CD133 antigens, confirming the link between this apoptotic index and the maturation pathways. However, the capacity of bax/bcl-2 ratio to clearly identify patients with different prognosis with regard to CR and OS within the CD34+, CD117+ and CD133+ subgroups implies that other mechanisms, such as proliferation and/or cell cycle dysregulation may be involved to explain its clinical significance. Finally, small molecules that target both the receptor- and mitochondrial-mediated pathway of apoptosis are providing encouraging results in patients with relapsed and/or refractory disease (i.e. CDDOMe, bcl-2 antisense oligonucleotides, CEP-701, etc), confirming the key role of apoptotic mechanisms on the outcome of AML patients.     

Apoptosis and immaturity in acute myeloid leukemia

The primary cause of treatment failures in acute myeloid leukemia (AML) is the emergence of both resistant disease and early relapse. Among the most frequent agents of these phenomena are defects in the mitochondrial-mediated apoptotic pathway. This pathway is regulated by bcl-2 family of anti-apoptotic (bcl-2, bcl-xl, mcl-1) and pro-apoptotic proteins (bax, bad, bak). In particular, bcl-2 dimerizes with several members of bcl-2 family of proteins, altering the threshold of cell death. The flow cytometric quantitative measurement of bcl-2 and bax expression for the determination of bax/bcl-2 ratio provided crucial clinical information in AML: in our hands, lower bax/bcl-2 ratio conferred a very poor prognosis with decreased rates of complete remission (CR) and overall survival (OS). Moreover, striking correlations were found between lower bax/bcl-2 ratio and higher progenitor marker expression, such as CD34, CD117 and CD133 antigens, confirming the link between this apoptotic index and the maturation pathways. However, the capacity of bax/bcl-2 ratio to clearly identify patients with different prognosis with regard to CR and OS within the CD34+, CD117+ and CD133+ subgroups implies that other mechanisms, such as proliferation and/or cell cycle dysregulation may be involved to explain its clinical significance. Finally, small molecules that target both the receptor- and mitochondrial-mediated pathway of apoptosis are providing encouraging results in patients with relapsed and/or refractory disease (i.e. CDDOMe, bcl-2 antisense oligonucleotides, CEP-701, etc), confirming the key role of apoptotic mechanisms on the outcome of AML patients.     

姜黄素对实验性肝纤维化大鼠肝脏bax和bcl-2表达的影响

[目的]探讨姜黄素(curcumin,CUR)对大鼠肝纤维化的防治作用及对肝组织bax和bcl-2蛋白及基因表达的影响.[方法]建立CCl4致大鼠实验性肝纤维化模型.用免疫组化法比较正常组、模型组以及CUR组的bcl2、bax蛋白的表达,用RT-PCR法比较各组肝组织bcb-2、bax mRNA的表达.[结果]CUR组肝组织炎症和纤维化程度较模型组显著减轻.bax蛋白主要表达在肝细胞质,而纤维间隔及汇管区呈低表达;beb-2主要表达在纤维间隔及汇管区.bax及bcl-2在模型组及CUR组表达均高于正常组(P<0.01),CUR组均较模型组降低(P<0.01).bax及bcI-2 mRNA在模型组及CUR组表达比正常组增高(P<0.01,<0.05),CUR组均较模型组降低(P<0.05).[结论]CUR可能通过降低肝细胞表达bax、减少肝细胞凋亡而减轻肝脏损伤,通过降低bcl-2表达、诱导肝星状细胞凋亡发挥减轻肝纤维化的作用,防治大鼠肝纤维化.     

Immunohistochemical expression of bcl-2, bcl-xL, bax, p53 proteins in gastric adenoma and adenocarcinoma]

BACKGROUND/AIMS: The aim of this study was to investigate the immunohistochemical expression of bcl-2, bcl-xL, bax, and p53 proteins according to the pathological parameters such as grade of dysplasia, histological type, depth of invasion, lymph node metastasis, and TNM stage in the gastric adenoma and gastric adenocarcinoma. METHODS: Immunohistochemical staining using monoclonal bcl-2, bcl-xL, bax, p53 antibodies were performed on paraffin embedded specimens from forty-one gastric adenomas and 100 gastric adenocarcinomas. RESULTS: The expression rate of bcl-2 was higher in adenomas (34.2%), especially in high grade dysplasia (52.4%), than adenocarcinomas (2.0%). The expression rate of bcl-xL was higher in adenocarcinomas (55.0%) than adenomas (22%). The expression rate of the bax was higher in adenocarcinomas (58.0%) than adenomas (14.6%). In the adenocarcinoma, the bax expression was significantly related with the depth of invasion, lymph node metastasis, and TNM stage. The expression rate of p53 was higher in adenocarcinomas (64.0%) than adenomas (14.6%). CONCLUSIONS: Bcl-2 protein would be related with the development of gastric adenoma, especially with high grade dysplasia. Bcl-xL and p53 proteins would be involved in the development of relatively early stage of gastric adenocarcinoma but not in tumor progression. Bax protein would be involved in the development of gastric adenocarcinoma and related with depth of invasion, lymph node metastasis, and TNM stage.     

Dynamic expression of apoptosis-related genes during development of laboratory hepatocellular carcinoma and its relation to apoptosis

AIM: To explore the expression of p53, bcl-2, bax, survivin and the cell apoptosis during the development of tree shrew hepatocellular carcinoma (HCC), the relationship between expression of these genes, its impact on HCC development, and its relation to cell apoptosis. METHODS: Tree shrew HCC was induced with aflatoxin B1 (AFB1), and regular biopsy of liver tissues was carried out and the biopsy tissues were collected during cancer inducement. Liver biopsy tissue and HCC tissue were collected from 35 pre-cancerous experimental animals at wk 30 and 60 and at the 30th-, 60th-, and 90th-wk. Liver biopsy tissues were collected from 13 blank control animals at wk 30, 60, and 90. Expression of p53, bcl-2, bax, and survivin at each stage was examined by immunohistochemistry method. Apoptotic cells were detected in situ by the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) technique. RESULTS: The apoptosis rate of normal hepatic cells was extremely low, whereas it increased during the formation of HCC. Expression of the apoptosis-related genes p53, bd-2, bax, and survivin during the formation of HCC presented an increasing tendency. Expression of p53 did not noticeably relate to that of bcl-2, bax, and survivin, whereas expression of bcl-2 and bax was closely related. In HCC, p53 did not present a distinct relation to cell apoptosis, whereas its high level expression was probably related to liver cell proliferation. Survivin negatively correlated apoptosis index, and its overexpression could inhibit cell apoptosis. CONCLUSION: Apoptosis-related genes p53, bcl-2, bax, and survivin are all related to the occurrence of HCC. The anti-apoptosis effect of bcl-2 is influenced by bax, and ratio bcl/bax reflects more correctly the extent of cell apoptosis.     

Dynamic expression of apoptosis-related genes during development of laboratory hepatocellular carcinoma and its relation to apoptosis

AIM:To explore the expression of p53,bcl-2,bax,survivin and the cell apoptosis during the development of tree shrew hepatocellular carcinoma(HCC),the relationship between expression of these genes,its impact on HCC development,and its relation to cell apoptosis.METHONS:Tree shrew HCC was induced with aflatoxin B1(AFB1),and regular biopsy of liver tissues was carried out and the biopsy tissues were collected during cancer inducement.Liver biopsy tisue and HCC tissue were collected from 35pre-cancerous experimental animats at wk 30 and 60 and at the 30th_,60th_,and 90th-wk,Liver biopsy tissues were collected from 13 blank control animals at wk 30,60,and 90.Expression of p53,bcl-2,bax,and survivin at each stage was examined by immunohistochemistry method.Apoptotic cells were detected in situ by the terminal deoxynucleotidyl transferase-mediated nick end labeling(tunel)technique.RESULTS:The apoptosis rate of normal hepatic cells was extremely low,whereas it increased during the formation of HCC.Expression of the apoptosis-related genes p53,bd-2,bax,and suvivin during the formation of HCC presented an increasing tendency.Expression of p53 did not noticeably relate to that of bcl-2,bax,and survivin,whereas expression of bcl-2 and bax was closely related.In HCC,p53 did not present a distinct relation to cell apoptosis,whereas its high level expression was probably related to liver cell proliferation.Survivin negetively correlated apoptosis index,and its overexpression could inhibit cell apoptosis.CONCLUSION:Apoptosis-related genes p53,bcl-2,bax,and survivin are all related to the occurrence of HCC.The anti-apoptosis effect of bcl-2 is influenced by bax,and ratio bcl/bax reflects more correctly the extent of cell apoptosis.     

Cytosolic heat shock protein 60, apoptosis,and myocardial injury

BACKGROUND: Heat shock proteins (HSPs) are well known for their ability to "protect" the structure and function of native macromolecules, particularly as they traffic across membranes. Considering the role of key mitochondrial proteins in apoptosis and the known antiapoptotic effects of HSP27 and HSP72, we postulated that HSP60, primarily a mitochondrial protein, also exerts an antiapoptotic effect. Methods and Results- To test this hypothesis, we used an antisense phosphorothioate oligonucleotide to effect a 50% reduction in the levels of HSP60 in cardiac myocytes, a cell type that has abundant mitochondria. The induced decrease in HSP60 precipitated apoptosis, as manifested by the release of cytochrome c, activation of caspase 3, and induction of DNA fragmentation. Antisense treatment was associated with an increase in bax and a decrease in bcl-2 secondary to increased synthesis of bax and degradation of bcl-2. A control oligonucleotide had no effect on these measurements. We further demonstrated that cytosolic HSP60 forms a macromolecular complex with bax and bak in vitro suggesting that complex formation with HSP60 may block the ability of bax and bak to effect apoptosis in vivo. Lastly, we show that as cytosolic (nonmitochondrial) HSP60 decreases, a small unbound fraction of bax appears and that the amount of bax associated with the mitochondria and cell membranes increases. CONCLUSIONS: These results support a key antiapoptotic role for cytosolic HSP60. To our knowledge, this is the first report suggesting that interactions of HSP60 with bax and/or bak regulate apoptosis.