Mechanism of action of ferroptosis in cholangiocarcinoma / 临床肝胆病杂志

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.

Clinical significance of cysteinyl leukotriene receptor expression in primary hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate expression of the cysteinyl leukotriene receptor (CysLT1R) in hepatocellular carcinoma (HCC) tissues and determine its clinical significance.</p><p><b>METHODS</b>Cancerous 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.</p><p><b>RESULTS</b>The 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.</p>

Efficacy of sequential add-on pegylated interferon α-2a in combination with adefovir dipivoxil in chronic hepatitis B patients with low serum HBeAg titer / 中华传染病杂志

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.

Peripheral blood Th17 and CD4 + CD25+ regulatory T cell levels and their correlations in patients with primary hepatocellular carcinoma / 中华临床感染病杂志

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.

Effects of parental anxiety and depression on the feelings and self-concept of children with leukemia / 肿瘤研究与临床

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.

Hepatic microcirculatory disturbances in patients with chronic hepatitis B / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To document morphological changes in hepatic microcirculation in liver tissue with hepatitis B and the pathogenesis of hepatic microcirculatory disturbances.</p><p><b>METHODS</b>Liver tissue samples were obtained from patients with hepatitis B by liver biopsy. These samples were examined with a light microscope and transmission electron microscope.</p><p><b>RESULTS</b>Hepatic 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.</p><p><b>CONCLUSIONS</b>Hepatic 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.</p>

Morphological changes of sinusoidal endothelial cells in the patients with chronic hepatitis B / 中华传染病杂志

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.

Effect of Ginkgo biloba extract on cell proliferation and expression of TGF-1 and CTGF in rat hepatic stellate cells / 中国病理生理杂志

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