1.Morphological changes of sinusoidal endothelial cells in the patients with chronic hepatitis B
Jinghua HAO ; Jun SHI ; Wanhua REN
Chinese Journal of Infectious Diseases 2001;0(03):-
Objective To observe the morphological changes of sinusoidal endothelial cells(SECs) in the patients with chronic hepatitis B, and to study the relationship between the SECs changes and the development of hepatic microcirculation disorders. Methods The liver biopsy tissues from fifty three cases with hepatitis B were observed with light microscope and transmitted electronic microscope. Results The morphologies of SECs in patients with chronic hepatitis B changed significantly. The main manifestations included decreased sizes and reduced numbers of penestrate on SECs, basal membrane formation, cellular connection development between SECs, occurrence of WP bodies in SECs and the disappearance of SECs. The intimate contact occurred between SEC and lymphocyte or Kupffer cell. Conclusions The morphologies of SECs in patients with chronic hepatitis B develop significant change, which might be the initial step in the development of hepatic microcirculation disturbances.
2.Peripheral blood Th17 and CD4 + CD25+ regulatory T cell levels and their correlations in patients with primary hepatocellular carcinoma
Jie LI ; Wanhua REN ; Jun SHI ; Wei WU ; Zhi CHEN
Chinese Journal of Clinical Infectious Diseases 2012;5(5):257-260
Objective To investigate the peripheral blood Th17 and CD4 + CD25 + regulatory T cell levels and their correlations in patients with primary hepatocellular carcinoma (PHC).Methods Peripheral blood samples were collected from 30 PHC patients and 25 healthy controls in the First Affiliated Hospital of Zhejiang University from June 2008 to May 2009.Mononuclear cells were isolated and the Th17 and CD4 + CD25 + regulatory T cells were detected by flow cytometry and compared between patients and controls by t test.Spearman test was performed to analyze the correlation of Th17 with CD4 + CD25 +regulatory T cell concentrations.Results The levels of Th17 and CD4 + CD25 + regulatory T cells in peripheral blood in healthy controls were (2.10 ± 0.87) % and (7.10 ± 2.32) % ; while those in PHC patients were (3.38±1.68)% and (11.78±5.62)% (t=3.640 and 4.162,P<0.01).The level of Th17 cells was positively associated with that of CD4 + CD25 + regulatory T cells in PHC patients (r =0.821,P <0.01).Conclusion The levels of Th17 and CD4 + CD25 + regulatory T cells in peripheral blood are high in PHC patients and positively correlated with each other,which indicates that CD4 + CD25 + regulatory T cells may contribute to the disease progression and pathogenesis of carcinoma through inducing Th17 cells differentiation.
3.Efficacy of sequential add-on pegylated interferon α-2a in combination with adefovir dipivoxil in chronic hepatitis B patients with low serum HBeAg titer
Jianting FANG ; Yongjian JI ; Feifei LI ; Xizhen SUN ; Wanhua REN
Chinese Journal of Infectious Diseases 2013;31(10):608-612
Objective To investigate the efficacy of sequential add-on of pegylated interferon α-2a (PEGIFN-α-2a) for 48 weeks in chronic hepatitis B (CHB) patients with low serum hepatitis B e antigen (HBeAg) titer after long term adefovir dipivoxil (ADV) monotherapy.Methods This was a randomized,open and prospective clinical trial.Patients who had been treated with ADV for 72 to 144 weeks,with undetectable serum hepatitis B virus (HBV) DNA level,low HBeAg titer (5 S/CO< HBeAg<50 S/CO) and serum hepatitis B surface antigen (HBsAg) <5000 IU/mL were included.The patients were categorized into ADV monotherapy group and ADV plus PEGIFN-a-2a combination therapy group by random number table.Patients in ADV group continued ADV monotherapy and patients in combination therapy group added PEGIFN-α-2a to ADV for 48 weeks.After the treatment,efficacy of the two therapies were assessed by comparing the reduction of serum HBeAg reduction,HBeAg loss rate,HBeAg seroconversion rate,and reduction of intrahepatic HBV DNA and HBV covalently closed circular DNA (cccDNA).Pre-and post-treatment results were compared by paired samples t test.Comparison between groups was performed using indepedent samples t test.Comparison of rates between groups was performed using x2 test.Results The trial enrolled 55 CHB patients,and there were 27 patients in ADV monotherapy group,28 patients in combination therapy group.Baseline characteristics including age distribution,sex ratio,alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bilirubin (TBil),serum HBeAg and HBsAg,hepatic HBV DNA and HBV cccDNA were all comparable (all P>0.05).Twenty-five patients in ADV monotherapy group and 26 patients in combination therapy group completed 48 weeks treatment.HBeAg loss rates and seroconversion rates of combination therapy group were higher than those of ADV monotherapy group (x2 =5.38 and 4.69,respectively,both P<0.05).HBeAg titers of both groups were significantly lower than those of baseline (t=8.43 and 8.50,respectively,both P<0.05).The HBeAg titer of combination therapy group was lower than that of monotherapy group (t=5.60,P< 0.01).HBV DNA and HBV cccDNA in liver tissue of combination therapy group was (6.934±0.52) lg IU/mg and (5.63±0.54) lg IU/mg post-treatment,respectively,which were both lower than baseline (t=7.12.6.67,respectively,both P<0.01).HBV DNA in liver tissue of monotherapy group was (7.09=0.43) lg IU/mg post-treatment,which was lower than baseline (t=2.67,P=0.02).After treatment,HBV cccDNA in liver tissue of combination therapy group was lower than that of monotherapy group (t =2.87,P=0.00).Conclusions Compared with ADV monotherapy,sequential add-on of PEGIFN-a-2a in combination with ADV can achieve higher serum HBeAg loss rate and seroconversion rate and facilitate the clearance of hepatic HBV DNA and HBV cccDNA in CHB patients with low HBeAg titer after long-term ADV monotherapy.
4.Effect of Ginkgo biloba extract on cell proliferation and expression of TGF-1 and CTGF in rat hepatic stellate cells
Yuhua ZHU ; Chunqing ZHANG ; Hongwei XU ; Wanhua REN ; Xiaoxia L
Chinese Journal of Pathophysiology 2000;0(07):-
AIM:To investigate the effect of Ginkgo biloba extract(EGb761) on cell proliferation and expression of transforming growth factor ?1(TGF-?1) and connective tissue growth factor(CTGF) in rat hepatic stellate cells(HSC-T6).METHODS:HSC-T6 was cultured with EGb761 at concentration of 1,10,100 and 500 mg/L,and without EGb761 as blank control.MTT colorimetric assay was used for detecting the proliferation of HSCs and flow cytometry was used for observing the cell cycles of HSCs under different concentrations of EGb761.The expression of TGF-?1/CTGF mRNA and protein levels were determined by reverse transcription-polymerase chain reaction(RT-PCR) and Western blotting after 24 hours and 48 hours.RESULTS:EGb761 inhibited the proliferation of HSCs at the concentration of 10 mg/L,100 mg/L and 500 mg/L.G0/G1 stage was increased(P
5.Effects of parental anxiety and depression on the feelings and self-concept of children with leukemia
Hongmei WANG ; Yumei ZHANG ; Wei CHEN ; Wanhua REN ; Lijun CHEN ; Fei GAO ; Yunpeng DAI
Cancer Research and Clinic 2011;23(7):483-486
Objective To evaluate the anxiety and depression problems in children parents with leukemia, as well as the problems' influence to the psychosocial characteristics of leukemia children.Methods Twenty long-term survivors of childhood leukemia (group A), thirty children newly diagnosed as leukemia (group B) and fifty age-matched healthy controls (group C) completed the questionnaires allowing assessment of symptoms associated with anxiety, depression and self-concept. At the same time, the anxiety and depression in the parents of children with leukemia were also measured using SAS and SDS. Results The anxiety and depression scores of the parents in study group (48.56±9.23, 51.86±9.53) were much higher than that in normal population (37.23±12.59, 41.88±10.57) (P = 0.000, 0.000, respectively), the positive rate of anxiety and depression symptoms among group B was significantly higher than that among group A (60.0 % vs 25.0 %, 46.7 % vs 20.0 %; P <0.05, respectively). There was a significant positive relation between the depression and anxiety scores in the parents of children with leukemia(r =0.947, P =0.0000). Group A scored significantly higher on subscales of somatization/panic (6.11 ±4.36), generalized anxiety (5.72±4.56),social phobia (7.67±4.19) and the total scale (25.8±13.98) than group C (the score was 3.68±3.39, 2.54±2.99,4.24±2.88 and 15.9±10.52, respectively) (P<0.05, respectively), group B scored significantly higher on subscales of social phobia (6.03 ±2.16) than group C (4.24±2.88) (P =0.016). There was a significantly positive relation between the depression score in children with leukemia and the anxiety (r = 0.309, P = 0.029) & depression(r = 0.342, P = 0.015) scores in their parents. Group A scored significantly higher on the total score of self-concept(60.8±6.25) as well as the subscales of happiness(7.95±1.32) than group G (64.48±7.89 vs 8.64±1.19) (P =0.039, 0.026, respectively); and group B scored significantly higher on subscales of behavior (12.47±1.25), intelligence(10.80±2.12), physical appearance and attributes (8.40±2.66), anxiety (9.93±1.29) and the total scale (59.83±5.87) than group C (14.00±2.17, 12.60±2.96, 9.64±2.30, 11.38+2.18, 64.48±7.89) (P <0.05, respectively). There was a significantly positive relation between the score of gregarization subscale in leukemic children and the anxiety score in their parents (r = 0.337, P = 0.017). Conclusion The findings of our studies have suggested that the parents of children with leukemia are at risk for psychological difficulties, and which have a great influence on the psychological health of their children.
6.Clinical features and outcomes in acute ischemic stroke patients with remote symptomatic intracranial hemorrhage after intravenous thrombolysis
Jinfang ZHOU ; Wanhua WANG ; Zhaoxi MA ; Yan ZHANG ; Jieming REN ; Hongzhou WANG ; Liyun LU ; Zhicheng BAO ; Yongjun CAO ; Qi FANG
International Journal of Cerebrovascular Diseases 2017;25(5):412-415
ObjectiveTo investigate clinical features and outcomes in acute ischemic stroke patients with remote symptomatic intracranial hemorrhage (sICHr) after intravenous thrombolysis.MethodsThe acute ischemic stroke patients with sICHr after intravenous thrombolysis therapy were enrolled retrospectively.The clinical data were collected and the related literature was analyzed and summarized.ResultsA total of 6 acute ischemic stroke patients with sICHr were enrolled, including 4 males.Three patients had a history of using antiplatelet agents, 2 with atrial fibrillation, 4 with hypertension, 3 with previous stroke history, 4 with smoking history, and 4 had sICHr at 2 h after intravenous thrombolysis.Of the 14 hemorrhagic foci (except in the infarct areas), 10 were in the cerebral cortex.Three patients died within 1 week, and 1 was in a persistent vegetative state.Conclusions SICHr after intravenous thrombolysis in patients with acute ischemic stroke is mainly located in the cerebral cortex.The outcomes in acute ischemic stroke patients with SICHr after intravenous thrombolysis are poor, and the mortality is high.
7.Clinical significance of cysteinyl leukotriene receptor expression in primary hepatocellular carcinoma.
Xizhen SUN ; Jie LI ; Wanhua REN ; Jianting FANG ; Yaru CHENG ; Yongjian JI
Chinese Journal of Hepatology 2015;23(12):944-949
OBJECTIVETo investigate expression of the cysteinyl leukotriene receptor (CysLT1R) in hepatocellular carcinoma (HCC) tissues and determine its clinical significance.
METHODSCancerous and paraneoplastic liver tissues were collected from 30 patients with HCC and from 12 patients with liver hemangioma patients (controls). Real-time PCR and immunohistochemistry were used to evaluate the expression of CysLT1R in these tissues and assess the relationship with clinical pathological features. T-test,?Fisher's exact test and Kaplan-Meier survival analysis were used for statistical analysis.
RESULTSThe expression of CysLT1R in adjacent liver tissues (100%) was higher than that in the HCC (43.33%, P = 0.000) and normal liver tissues (41.67%, P = 0.000). The level of CysLT1R mRNA was also higher in paraneoplastic liver tissues (0.0339+/-0.0221) than in the paired HCC tissues (0.0127+/-0.0116, t = 2.911, P = 0.008) and normal liver tissues (0.0154+/-0.0123, t = -2.310, P = 0.033). There was no difference between the levels in HCC and normal liver tissues (P more than 0.05). Higher level of CysLT1R mRNA, higher level of serum alpha-fetoprotein, and higher tumor stage (III-IV) were associated with poor prognosis (respectively 4.372, P = 0.037; 24.187, P = 0.000; 8.75, P = 0.003). However, no evident relationship between the expression of CysLT1R and other clinical features was observed. Conclusions Overexpression of CysLT1R may contribute to the occurrence and progression of HCC.
Carcinoma, Hepatocellular ; diagnosis ; metabolism ; Case-Control Studies ; Disease Progression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms ; diagnosis ; metabolism ; Neoplasm Staging ; Prognosis ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, Leukotriene ; metabolism ; alpha-Fetoproteins ; metabolism
8.Hepatic microcirculatory disturbances in patients with chronic hepatitis B.
Jinghua HAO ; Jun SHI ; Wanhua REN ; Guoqing HAN ; Juren ZHU ; Shuyun WANG ; Yingbo XIE
Chinese Medical Journal 2002;115(1):65-68
OBJECTIVETo document morphological changes in hepatic microcirculation in liver tissue with hepatitis B and the pathogenesis of hepatic microcirculatory disturbances.
METHODSLiver tissue samples were obtained from patients with hepatitis B by liver biopsy. These samples were examined with a light microscope and transmission electron microscope.
RESULTSHepatic microcirculatory disturbances existed in patients with hepatitis B, including those with normal liver function, manifested by red blood cell aggregation in sinusoids seen under light microscope and sinusoidal capillarization seen under electron microscope. Weibel-Palade bodies in sinusoidal endothelial cells were seen in 26 out of 53 cases. Intimate contacts were found between lymphocyte/Kupffer cells and sinusoidal endothelial cells.
CONCLUSIONSHepatic microcirculatory disturbances exist in patients with hepatitis B. The appearance of Weibel-Palade bodies in sinusoidal endothelial cells may be a key step in the development of hepatic microcirculatory disturbances.
Adolescent ; Adult ; Aged ; Female ; Hepatitis B, Chronic ; pathology ; physiopathology ; Humans ; Liver ; blood supply ; pathology ; ultrastructure ; Liver Circulation ; Male ; Microcirculation ; pathology ; ultrastructure ; Microscopy, Electron ; Middle Aged
9.Clinical study on intervention of spleen-restoring decoction integrating with dormancy hygiene education on subhealthy insomnia of deficiency of both heart and spleen pattern.
Ren YE ; Zhengzhong YUAN ; Chunxiu DAI ; Wei LI ; Xiuhua SONG ; Zhiqing CHENG ; Wanhua HU ; Yan LIN ; Xiaoyun WANG ; Shuchen SUN ; Jincai HE
China Journal of Chinese Materia Medica 2011;36(16):2285-2289
OBJECTIVETo appraise the clinical efficacy, safety and compliance of the intervention of spleen-restoring decoction combined with dormancy hygiene education and the intervention of spleen-restoring decoction alone on sub-healthy insomnia of deficiency of both the heart and spleen pattern.
METHODStudy design took multi-centers, blind and randomized control trial, 107 participants with sub-healthy insomnia of deficiency of both the heart and spleen pattern were assigned to A group (52 cases) which was treated with the intervention of spleen-restoring decoction combined with dormancy hygiene education and B group (55 cases) which was treated with the intervention of spleen-restoring decoction single, compared by efficacy, PSQI score, CGI score, WHOQOL-BREF score and security.
RESULTThe efficacy of two group was 79.58%. There was no significant different between them. The PSQI scores before treatment was (11.80 +/- 2.08) and which afer treatment was (6.78 +/- 2.84) of A group. The PSQI scores before treatment was (11.61 +/- 2.00) and which afer treatment was (6.73 +/- 2.27) of B group. There was significant difference in PSQI scores both A group and B group after treatment (P < 0.01); the results of CGI score and WHOQOL-BREF score before and after measurement showed the same as PSQI. There were no significant difference between two groups in all scores after treatment and there was no interaction between time pots and treatment factors . Withdrawal reaction analysis: comparing CGI after withdraw 2 weeks and at the end of treatment course, there was no significant difference between two groups. The same result was in comparison among groups.
CONCLUSIONBoth the intervention of spleen-restoring decoction integrating with dormancy hygiene education and spleen-restoring decoction had obvious clinical efficacy on treating subhealthy insomnia of deficiency of both the heart and spleen pattern, and had high compliance and safety. The intervention of spleen-restoring decoction integrating with dormancy hygiene education showed no better clinical efficacy than spleen-restoring decoction did.
Adult ; Female ; Health Education ; Humans ; Hygiene ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Sleep Initiation and Maintenance Disorders ; drug therapy ; physiopathology ; Splenic Diseases ; drug therapy
10.Mechanism of action of ferroptosis in cholangiocarcinoma
Mingyu YANG ; Zhen YANG ; Wanhua REN
Journal of Clinical Hepatology 2022;38(4):951-955
The incidence and mortality rates of cholangiocarcinoma (CCA) are increasing constantly, and it is of great importance to explore new therapeutic targets. Ferroptosis, a unique pattern of cell death caused by iron-dependent cellular oxidative injury, is closely associated with iron metabolism and oxidative stress imbalance in cancer and has become a research hotspot in the field of tumor. This article introduces the mechanism of ferroptosis and the research advances in ferroptosis involved in the development and progression of CCA, and it is pointed out that the regulatory mechanism of ferroptosis has an important clinical value in the malignant progression of CCA.