慢性乙型肝炎(CHB)是威胁人类健康的重大公共卫生问题,机体免疫应答不足是造成乙型肝炎病毒(HBV)持续感染、肝脏损伤加重及疾病迁延不愈的重要原因.从固有免疫、适应性免疫角度,综述中医药对CHB的免疫调节作用.中医药可以通过调节巨噬细胞吞噬功能、调节树突状细胞(DC)功能、提高自然杀伤细胞(NK)杀伤活性、改善辅助性T细胞失衡状态、增强T细胞亚群的免疫应答能力等途径调节CHB患者的免疫状态.

Background: Plasmacytoid dendritic cell (pDC) has been reported showing obvious maturation and deficient function in chronic hepatitis B (CHB) patients. One of the traditional Chinese medicine, Bushen Jianpi Recipe (BSJPR), has efficacy in suppressing HBV by improving immune system. In this study, we explained its mechanism on cellular level.Methods: We measured the contents of pDC maturation-related extracellular cytokines and intracellular signaling pathway proteins in HBV-infected or not infected PBMCs and pDCs to explore the cellular mechanism of BSJPR. There were six groups: a normal serum control group added with fetal bovine serum, a rat serum control group added with normal serum, two HBV virus groups added with normal serum and HBV with different concentrations, and two BSJPR groups added with drug-containing serum and HBV with different concentrations.Results: It was revealed that the effect of BSJPR on extracellular cytokines was vague, while intracellular toll-like receptor (TLR) /myeloid differentiation primary response 88 (MyD88) /TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathway proteins were induced by BSJPR.Conclusions: This study confirmed that BSJPR induces pDC to alleviate CHB via up-regulating intracellular TLR/MyD88/TRIF signaling pathway proteins rather than directly regulating extracellular cytokines.

目的:探讨慢性肝病患者食管胃底静脉曲张与血瘀证的相关性.方法:对210例慢性肝病患者进行常规胃镜检查,其中150例还接受窄波成像技术(NBI)放大内镜检查,观察血瘀证与非血瘀证组患者食管胃底静脉曲张及胃粘膜微血管变化,并应用Image-Pro Plus软件测定微血管的平均光密度值(MD).结果:①210例慢性肝病患者血瘀证者125例(59.52％),其中轻度血瘀证患者48例(22.86％)、中度血瘀证患者42例(20.00％)、重度血瘀证患者35例(16.67％);非血瘀证患者85例(40.48％).肝纤维化及肝硬化患者的血瘀证积分显著高于非血瘀证组,不同程度的血瘀证患者之间比较,差异有显著性意义.①210例患者中有53例伴有食管静脉曲张,33例出现红色征,16例出现胃底静脉曲张,30例患者胃底粘膜呈明显蛇皮征改变,28例患者出现斑疹,44例出现糜烂,门脉高压性胃病(PHG)轻型47例,PHG重型9例.③NBI胃镜下150例患者中52例胃粘膜下微血管出现内径增粗,78例患者微血管排列紊乱、42例患者微血管呈螺旋弯曲,46例患者血管内出现微血栓.血瘀证组患者微血管内径增粗发生率为43.86％、微血管排列紊乱发生率为60.53％、微血管螺旋弯曲发生率为32.46％,微血栓发生率为37.72％;非血瘀证组分别为5.56％、25.00％、13.89％、8.33％,两组比较,P＜0.05,差异有统计学意义,提示血瘀证患者胃粘膜微血管病变显著.轻、中、重度血瘀证组患者MD值为0.19±0.10、0.22±0.05、0.31±0.08;非血瘀证组MD则为0.15±0.04,组间比较,差异有显著性意义,P＜0.01.结论:慢性肝病患者随着病情加重,血瘀证程度随之加重,胃粘膜微血管形态异常如管径增粗,螺旋弯曲加重,提示胃粘膜微血管形态与血瘀证密切相关.

A20 is a powerful suppressor for inflammatory response. This study aims to determine A20 level in patients with chronic hepatitis B (CHB), and analyze its association with the disease severity. The role of A20 in inflammatory response was further investigated in vivo and in vitro. Our results showed significantly higher A20 in both serum and liver tissues in CHB patients than in health controls. Serum A20 level was positively correlated with ALT, AST and TNF-α. To induce hepatitis with inflammation and liver injury, mice were injected intraperitoneally with D-galactosamine (D-GalN), resulting in rapid increase of A20 in serum and liver tissues. Consistently, HepG2 and Huh-7 cells exposed to Lipopolysaccharide (LPS) or D-GalN were promoted to express A20. Moreover, overexpression or knockdown of A20 inhibited or increased TNF-α secretion separately. A20 significantly reduced pro-inflammatory cytokines expression and down-regulated phospho-IκBα and phospho-p65 in both cells. In conclusion, elevated A20 expression is involved in the severity of CHB, suggesting A20 to be a possible serological biomarker for the disease prognosis. Additionally, the inflammatory response is attenuated by A20 through inhibiting NF-κB activity, which partially contributes to the hepato-protective function of this molecule. Thus, up-regulating A20 might be a potential strategy for preventing the progress of CHB.

目的 探讨清热解毒方对小鼠移植性肝癌抗肿瘤作用及趋化因子的影响.方法 建立小鼠CBRH-7919原位移植性肝癌模型,随机分为中药低、中、高剂量组和对照组,观察清热解毒方的抗肿瘤效应.采用趋化因子芯片筛选出不同剂量组间的差异基因(差异倍数至少为3),继而使用免疫组化及Western blotting方法对差异基因加以验证.结果 ①不同剂量清热解毒方均有不同程度的抗肿瘤作用(与对照组相比P≤0.01),组间比较显示高剂量组抑瘤作用更为明显(P≤0.01);②趋化因子芯片检测筛选出CXCL1、CXCL2、CXCL3、CXCR2及IL-1β为差异基因,其中中药干预组CXCL1、CXCL2、CXCL3及IL-1β基因表达下调,CXCR2基因上调,均以高剂量组最为明显(P≤0.05);③免疫组化和Western blotting方法分别在蛋白水平上验证了以上差异基因.结论 清热解毒方具有显著下调小鼠移植性肝癌模型中趋化因子CXCL1,CXCL2,CXCL3及IL-1β表达,上调趋化因子受体CXCR2的作用,其抗肿瘤作用的机制可能与此有关.

目的:观察补肾健脾方对HBeAg阳性原发性肝伴肝硬化癌患者免疫功能和生存质量影响.方法:采用前瞻性队列研究方法,将72例患者分为对照组36例,中药组36例.对照组以核苷类抗病毒药物及对症治疗为基础治疗,中药组在对照组治疗基础上加服补肾健脾方,比较两组患者免疫功能、瘤体近期疗效、生存质量,观察时间为12周.结果:观察结束时中药组脱落2例,对照组脱落4例;与对照组相比中药组患者CD3+、CD4+、NK细胞数量及IFN-γ水平显著升高(P＜0.05),CD4+CD25+细胞数量显著降低(P ＜0.05);KPS评分、总体健康状况,躯体、角色、情绪等功能及疲倦、失眠、便秘、腹泻等症状均明显好转(P＜0.05);实体瘤稳定率高于对照组(P＜0.05).结论:补肾健脾方可有效改善终末期肝癌患者生存质量、稳定瘤体大小,调节机体免疫平衡可能是其发挥疗效的作用机制之一.

锌指蛋白 A20是具有独特生物学特征和生物学活性的一类具有锌指结构的蛋白，上世纪90年代美国病理学家 Dixit 在研究内皮细胞对 TNF 诱导应答的基因时发现使用 TNF、IL-1和 PLS 刺激内皮细胞时均能够高速表达一条特殊基因，这条基因的可读编码是一种新型的锌指蛋白，即锌指蛋白 A20（Zinc-finger protein A20，A20）［1］。锌指蛋白 A20作为炎症内源性调控的关键分子之一，参与机体内多种生理反应。本文从锌指蛋白 A20的生物学特征出发，阐述其生物活性及其可能的作用机制，并综述其在肝损伤中的研究进展。

目的：分析鲍曼不动杆菌感染的耐药情况并探讨应对措施。方法：对鲍曼不动杆菌感染296例临床及耐药性进行分析。结果：鲍曼不动杆菌感染率分别为0.48%和0.52%；感染主要分布在重症监护室(18.58%)、急诊科(18.24%)及呼吸内科(14.53%)。有182株(61.49%)来源于呼吸道标本(包括痰液及气管切开分泌物)；合并基础疾病≥3种97例,190例联合使用≥2种抗生素,119例抗生素使用时间≥2周。药敏结果显示鲍曼不动杆菌对美罗培南敏感率为86.49%；其次为亚胺培南/西司他丁,敏感率为86.15%；多重耐药及泛耐药发生率分别为30.74%(91/296)和10.81%(32/296)。结论：鲍曼不动杆菌的耐药性呈上升趋势,碳青霉烯类抗生素对鲍曼不动杆菌仍具有较好的抗菌活性。应警惕及避免鲍曼不动杆菌感染的危险因素。

介绍周荣耀主任医师补肾健脾为主辨治原发性肝癌的临床经验.认为“积之成也,正气不足,而后邪气踞之”中晚期肝癌患者多正气亏虚,以补肾健脾扶助正气为主的辩证论治,疗效显著.并附验案1则.

Objective To evaluate the clinical efficacy of ginger partition moxibustion on special points for the treatment of chronic gastritis.Methods Ninety cases were randomized into two groups: treatment group in which 45 cases were treated by ginger partition moxibustion on Zhongwan(RN12),Tianshu(ST25) and Zusanli(ST36) points,and control group in which 45 cases were treated by Rabeprazole and Weifuchun Tablet,with the course of 3 months.The clinical efficacy,clinical symptom scores,working time and recurrence were observed in the following 6 months.Results The overall effective rate was 95.6%in the treatment group and 84.4% in the control group,with a difference between the two groups(P0.05).The stomachache,abdominal destention and fullness,anorexia,acid regurgitation and loose stool were alleviated remarkably in treatment group,with significant differences between before and after treatment(P0.05,P0.01),there were significant differences in scores of stomachache,abdominal destention and fullness in control group(P0.05);after treatment,the anorexia,acid regurgitation and loose stool in treatment group were statistically different from controls(P0.05).There were significant differences in average working time and recurrence between the two groups(P0.05).Conclusion Ginger partition moxibustion on special points has positive effect on chronic gastritis,with rapid action and low recurrence rate.

Objective To evaluate the diagnostic value of anti-mitochondrial antibodies-M2 subtype, anti-gp210, anti-Sp100 by detecting in patients with primary biliary cirrhosis (PBC). Methods Serum samples were detected for AMA-M2, anti-gp210 and anti-Sp100 by immunoblotting assay in 2000 patients with cryptogenic hepatitis, and other 15 healthy individuals were taken as control group. Patients were diagnosed as PBC (129 cases, 6.45%), AIH (205 cases, 10.25%), AIH-PBC overlap syndrome (15 cases, 0.75%), fatty liver (514 cases, 25.70%), drug-induced hepatitis (379 cases, 18.96%), and other unexplained hepatitis (758 cases, 37.90%). Results The positive rates of these three antibodies were 97.67%(126/129), 41.86%(54/129), 27.91%(36/129), respectively. The simultaneous occurrence rate of anti-gp210 and anti-Sp100 was 9.30% (12/129).There were 12 cases with positive anti-gp210 and anti-Sp100 antibody, 3 of whom were diagnosed as PBC through liver puncture. In PBC group, patients with AMA-M2 antibody titer high than 1︰800 accounted for 62.80%(81/129), while the percents of patients with titers ranged from 1︰25 to 1︰100 and from 1︰100 to 1︰200 were 13.95%(18/129) and 30%(12/129), respectively. Conclusions AMA-M2 antibody is still the main marker for PBC diagnosis. The combined detection of AMA-M2 antibody, anti-gp210, anti-Sp100 in PBC have a higher value and play a good supporting role in screening other autoimmune liver diseases.

There will be some different outcomes after HBV infection:(1) acute self-limited hepatitis B;(2) chronic hepatitis;(3) chronic HBV carriers or HBsAg carriers;(4) occult chronic hepatitis B;(5) cirrhosis caused by chronic hepatitis B;(6) severe hepatitis.And(2)(3)(4)(5) could be called chronic HBV infection.Chronic hepatitis B is a long process which is positively correlated with cirrhosis and hepatocellular carcinoma.It is very important to cure chronic hepatitis B and prevent the occurrence of cirrhosis and hepatocellular carcinoma.Recently,lots of research achievements on the pathogenetic mechanism of chronic hepatitis B were reported,which mainly were related to viral load,genotype and state of the host immune.This article summarizes recent developments on pathogenetic mechanism of chronic hepatitis B.

Objective To investigate the presence of AMA-M2 antibodies in 1039 patients with cryptogenic hepatitis.Methods M2 antibodies were tested by ELISA.Results M2 antibodies were detected in 81(7.9%)of the 1039 patients;Of the 81 cases,57 were female and 24 were male,and the mean age was 53.0 ± 14.8 year old,and 78 patients were diagnosed as PBC;The most common symptoms were fatigue(74.4%,58/78),jaundice(61.5%,48/78)and skin itching(37.2%,29/78);Besides,39(50.0%) patients were with ANA positive,and 14(18.0%) with anti-SSA/Ro positive.Conclusion On the diagnosis of the disease,the detection of serum antimitochondrial autoantibodies(AMA) is an important indicator.The detection of AMA-M2 is important for early diagnosis of patients with PBC.

To evaluate the correlation of T cell subsets,serum immunoglobulin and complement levels with different kinds of syndromes of ZhongYi of post hepatitis liver cirrhosis,84 patients have been diagnosed as four kinds of syndrome of Zhong Yi including 40 patients with syndrome of accumulated dampness-heat(group①),20 patients with syndrome of blockade of dampness due to qistagnation(group②),12 patients with syndrome of Yin deficiency of liver and kidney(group③),11 patients with syndrome of Yang deficiency of spleen and kidney(group④).T-lymphocyte subsets(by flowcytometry) and serum immunoglobulin levels were measured for all the patients.Compared with control group,the IgA、IgG levels were increased significantly in all group(P0.05,P0.01).CD8+ T cells and NK amounts were decreased(P0.05)in group①.CD8+T cells were decreased significantly(P0.01),and CD4+ T cells were decreased(P0.05)in group②.CD4+/CD8+ ratio was significantly increased in group ② than in any other groups.The different kinds of syndrome of ZhongYi were related to status of immunity,and the syndrome of ZhongYi changed with the status of immunity.CD4+,CD8+,CD4+/CD8+ ratio,immunoglobulin levels determinations may help to define syndrome of ZhongYi and used to clinical diagnosis and treatment.

OBJECTIVE:To investigate the correlation between ER-a in the liver and cytokines of T lymphocytes subsets and serum signatures in PBC patients.METHODS:The research is performed with cross-sectional study. 80 PBC women patients without treatment were enrolled in PBC group, 10 healthy women as baseline-matched in healthy-control group, and 20 patients with non-autoimmune liver disease in non-PBC control group. The expression of IL-6, IL-8, IL-22, TNFa, IFNgamma, AMA-M2, Sp100 and gp210 were analyzed in Peripheral Blood using ELISA in all groups, and ER-a of patients were performed on tissues from liver biopsies in PBC group and non-PBC control group with immunohistochemistry. Spearman correlation test were performed on the indices to identified the association of all Parameters. numerical data were compared with Wilcoxon rank-sum test.RESULTS:Compared with healthy-control group, expression of serum cytokines are significantly higher in PBC and non-PBC groups (P less than 0.01), while no significant difference were observed between PBC and non-PBC groups. The positive rate of ER-a in PBC patients liver tissues in PBC group is higher than that in non-PBC group (Z=4.82, P less than 0.01). Expression of ER-a is positively correlated with positive rates of AMA-M2 antibody, Sp100 and gP210 of tissues of PBC patients ( r=0.898, 0.819, 0.814, P less than 0.01). ER-a is positive correlated with the expression of cytokines, among which the coefficient of correlation of IL-22, TNFa, IFNgamma is more than 0.7 (r=0.71, 0.89, 0.82, P less than 0.01), AMA-M2, Sp100, gp210 is negative in serum of non-PBC control group. No obviously correlations were indicated between the expression of ER-a and cytokines.CONCLUSION:A high level of expression of cytokines in the serum might be one of the factors of etiopathogenesis of PBC.

Objective:To assess the availability of a TCM quality of life(QOL) scale for CHB(Beta) created by our study team in a randomized controlled clinical trials.Methods:The study included 90 the damp-heat syndrome and 90 liver stagnation and spleen deficiency syndrome patients with CHB.All participants were randomized into two group,treatment group and control group.To compare the sensitivity of QOL scale with chronic liver disease questionnaire(CLDQ).Results:①CLDQ and TCM QOL scale for the respective correlation matrix result revealed a positive correlation among all items for both scales.No correlation was found among items for both scales on two two correlation matrix.②the responsibility of TCM QOL scale for CHB(Beta):There were statistically significant differences pre-and post-treatment in calibrated scale of all dimension items from TCM QOL scale in both groups(P all <0.01).In the control group,statistically significant differences pre-and 3 months post-treatment were only found in emotion subscale(P all <0.01),while the remaing dimension items and total score similar pre-and post-treatment(P>0.05).Also,statistically significant differences pre-and 6 months post-treatment could be found in calibrated scale of all dimension items from TCM QOL scale(P all <0.01).Conclusion:①The created TCM QOL scale is in an identified but relatively loose correlation to CLDQ scale due to its own specificity.②The created TCM QOL scale(Beta) has a better responsibility and sensitivity in the evaluation of QOL in patients with CHB,which could be an effective utilized in the evaluation system on the efficacy of TCM treatment in QOL of CHB.

Objective:To observe the the clinical efficacy with acupuncture point plaster therapy combining traditional Chinese medicine for treating liver depression and spleen deficiency type of patients with non-alcoholic steatohepatitis(NASH) and to evaluate quality of life of patients.Methods:Seventy-two patients with NASH were randomized into 2 groups.Combined treatment group with the acu-point plaster therapy and Chinese medicine treatment for 12 weeks;control group based on drug treatment for 12 weeks.Symptoms and signs such as body mass index,biochemical,imaging targets and changes in quality of life scale were observed before and after treatment.Results:After 12 weeks of treatment,the treatment group NASH clinical main symptoms and signs,including flank pain,weakness,bitter taste in the mouth were significantly improved;body mass index decreased significantly,down from 26.04 ± 2.03 to 23.62 ± 2.05,compared with the treatment,the difference was statistically significant(P0.05);serum biochemical parameters ALT,γ-GT,TC,TG than those before treatment significantly decreased,the difference was significant(P0.01 or P0.05);control group ALT,TG significantly decreased compared with before treatment,the difference was significant(P0.05).Ultrasound improvement rate in treatment group was 61.11%,control group 38.89%,difference between groups was significantly(P0.05);physiological function,bodily pain,vitality and mental health were significantly increased compared with control group and the difference was statistically significant(P0.05).Acu-point plaster therapy and Chinese medicine treatment could improve patient quality of life.Conclusion:The acu-point plaster therapy combined with traditional Chinese treatment of NASH is clinical efficacy,and can improve patient quality of life,safety,and is worth promoting in treatment programs.

OBJECTIVE:To explore the feasibility of Chinese medical syndrome identification in patients with post-hepatitis cirrhosis (PHC) by soft independent modeling of class analogy (SIMCA).METHODS:After variants were normalized, SIMCA was used to analyze clinical symptoms, physical signs, and biological parameters in 268 PHC patients, and the obtained distance of SIMCA was used to identify the syndromes of PHC. Some incorrect reasons were then tested by Mann-Whitney test.RESULTS:The recognition rates of 5 Chinese medical syndromes (Gan depression and Pi deficiency syndrome, Gan-Shen yin-deficiency syndrome, Pi-Shen yang-deficiency syndrome, inner accumulation of dampness-heat syndrome, and stasis-heat accumulation syndrome) were 72.9% in the nearest class, and 17.91% in the sub-near class, as well as the total recognition rate was 90.3%. The highest recognition rate (95.24%) presented in the recognition on Gan-Shen yin-deficiency syndrome. Among some vital symptom variants of nearest class, significant difference could be found between identified and un-identified syndromes (P < 0.05).CONCLUSION:Identification of Chinese medical syndromes by SIMCA has rather higher goodness-of-fit with clinical practice, to set up a SIMCA depended syndrome identifying system could offer a useful reference for Chinese medical syndrome identification.

OBJECTIVE:To study the action mechanism of Qinggan Huoxue Recipe (QGHXR) and its disassembled recipes for treatment of alcoholic liver fibrosis (ALF) by observing their regulation on the expressions of matrix metalloproteinases (MMPs) and type 1 tissue inhibitor of metalloproteinase (TIMP-1).METHODS:130 male SD rats were randomly divided into the blank control group (n=10), the CCI4 group (n=10), and the modeling group (n=110). Rats in the modeling group were intervened by complex factors dominated as alcohol. Eight weeks later they were randomly divided into 4 subgroups, i.e., the model group (n=25), the QGHXR group (n= 15), the Qinggan Recipe (QGR) group (n=15), and the Huoxue Recipe (HXR) group (n=15). Eight model rats were selected for pathological analysis to monitor the development of the modeling at the 4th, 8th, and 10th week of the experiment. The rest rats died during the modeling. Corresponding medicines were given to these treatment groups (at the dose of 4.75 g/kg, 1.50 g/kg, and 3.25 g/kg). All rats were killed at the end of the 12th week. The protein and mRNA expressions of MMP-2, MMP-9, and TIMP-1 were detected using Western blotting, fluorescent quantitative polymerase chain reaction, and immunofluorescence method.RESULTS:Compared with the blank control group, the expressions of MMP-2, MMP-9, and TIMP-1 significantly increased in the model group (1.81 +/- 0.28 versus 0.53 +/- 0.04, 1.60 +/- 0.16 versus 0.45 +/- 0.05, 1.20 +/- 0.02 versus 0.35 +/- 0.07, P < 0.01). Compared with the model group, QGHXR and its disassembled recipes all could decrease the protein and mRNA expressions of TIMP-1 (0. 56 +/- 0.05, 0.67 +/- 0.02, 0.70 +/- 0.02 versus 1.20 +/- 0.02, P < 0.05), increase the expressions of MMP-2 and MMP-9 (4.18 +/- 0.53, 2.70 +/- 0.40, 2.38 +/- 0.22 versus 1.81 +/- 0.28, 3.31 +/- 0.06, 2.56 +/- 0.20, 1.87 +/- 0.05 versus 1.60 +/- 0.16, P < 0.05, P < 0.01). QGHXR was superior to its disassembled recipes (P < 0.05, P < 0.01).CONCLUSION:The action mechanisms of QGHXR and its disassembled recipes might possibly be correlated with regulating MMPs.

The midnight-noon ebb-flow is based on the concept of holism which is called the adaptation of human body to natural environment.The acupuncture of Midnight-noon ebb-flow selects acupoints according to the theory that is in different time,the qi and blood disembogue the different meridians.It is the peak of the chronomedicine of traditional Chinese medicine.It combines the factor of time,spare with Biological Rhythm.The chronobiology which studies the biological Rhythm proves the objectivity of chronomedicine of TCM in terms of science.