Trends in nano-antimicrobial therapy for severe liver disease with infection / 临床肝胆病杂志

Severe liver disease with infection has always been a key and difficult point in clinical treatment. Through continuous exploration of nanomaterials, researchers have found that nanomaterials can achieve targeted antibacterial and immunomodulatory effects due to their special physicochemical properties. With reference to recent articles and advances, this article reviews the possible mechanisms of nano-therapies for severe liver disease with infection from the aspects of targeted antibacterial effect of nanomaterials without antibiotics, targeted antibacterial effect of nano-drug delivery systems, and targeted immunomodulatory therapy, so as to provide new treatment strategies for the prevention and treatment of severe liver disease with infection in clinical practice.

Pathogenic mechanism of liver injury caused by coronavirus disease 2019 and protective strategies for patients with viral hepatitis cirrhosis / 临床肝胆病杂志

Coronavirus disease 2019 (COVID-19) has spread to many countries in the world, and some patients show liver injury during the epidemic of COVID-19. In order to improve the awareness of COVID-19 among patients with viral hepatitis cirrhosis and strengthen patients’ self-protection and disease management, this article discusses the pathogenic mechanism of liver injury caused by COVID-19 and reasonable epidemic prevention, standardized medical treatment, and scientific medication for such patients and gives related recommendations, so as to ensure the routine management of viral hepatitis and reduce the risk of infection in such population.

Interventional effect of bicyclol on isoniazid-induced liver injury in rats and the expression of glucose-regulated protein 78, and growth arrest and DNA-damage-inducible gene 153 / 中华肝脏病杂志

Objective@#To investigate the interventional effect of bicyclol on isoniazid-induced liver injury in rats and the expression of endoplasmic reticulum stress (ERS) protein, glucose regulatory protein 78 (GRP78), and growth arrest and DNA-damage-inducible gene 153(CHOP).@*Methods@#Eighty Wistar rats were randomly divided into control group (8 rats) and model group (72 rats). After 10 days of intragastric administration of isoniazid, the model group rats were randomly divided into treatment group (A), natural recovery group (B), etiological persistence group (C) and etiological persistence plus treatment group (D). Sixteen rats from each group were sacrificed after 1 and 2 weeks of intervention with different methods. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Liver pathological morphology was observed. Apoptotic cells were detected by TUNEL assay. ERS protein expression was detected by Western blot. A t-test or randomized block analysis of variance, K-S test and Levene’s test were used to analyze the normality and homogeneity of variance. Kruskal-Wallis rank sum test was used for data that did not suit the conditions of t-test and variance analysis.@*Results@#ALT and AST were elevated in the model group, and liver pathological examination showed liver tissue damage. Apoptotic index was higher than control group (7.13% ± 1.55% vs. 0.75% ± 0.71%, Z = -3.411, P < 0.01), and the expression value of ERS protein in model group was significantly higher than control group (GRP78: 1.16 ± 0.30 vs. 0.23 ± 0.05, t = -6.008, P < 0.01; CHOP: 0.98±0.23 vs. 0.20 ± 0.10, t = -6.378, P < 0.01). Serum enzymes, apoptotic index and ERS protein expressions of rats were decreased after treatment with bicyclol, and the pathological damage was eased. Rats in natural recovery group recovered less than the treatment group.@*Conclusion@#Isoniazid-induced liver injury is associated to ERS-related excessive apoptosis and the therapeutic effect of bicyclol on drug-induced liver injury may minimize ERS-induced apoptosis.

Double plasma molecular adsorption combined with plasma exchange versus simple plasma exchange for the treatment of liver failure / 中国组织工程研究

BACKGROUND: Double plasma molecular adsorption system cannot only specifically absorb bilirubin and bile acids, but also eliminate toxins, inflammatory transmitters and cytokines in the body. In the absence of plasma or in the case of plasma deficiency, it can effectively remove harmful substances, prevent multiple organ failure and fight for time for the liver regeneration and recovery of liver function, which is suitable for liver failure caused by various reasons. OBJECTIVE: To compare the validity and safety of double plasma molecular adsorption system combined with plasma exchange and simple plasma exchange in the treatment of liver failure. METHODS: Sixty patients with liver failure admitted to the Guizhou Provincial People's Hospital from October 2014 to October 2017 were included and randomized into two groups (n=30/group) . Plasmapheresis was used in plasma exchange group, and the volume of plasma exchanged was 2 500-3 000 mL. The combination treatment group was treated by double plasma molecular adsorption system combined with plasma exchange, and the volume of plasma exchanged was 1 000-1 500 mL. In the two groups, the clinical effects and liver function were evaluated after three treatment sessions, and adverse reactions were observed during the artificial liver treatment. RESULTS AND CONCLUSION: After treatment, the levels of serum total bilirubin and alanine aminotransferase were significantly lower than those before treatment, and the prothrombin activity was significantly higher than that before treatment (P < 0.05) . However, the serum albumin level showed no significant difference in the combination treatment group before and after treatment. Compared with the plasma exchange group, the post-treatment levels of serum total bilirubin, alanine aminotransferase and serum albumin were significantly lower in the combination treatment group, and the prothrombin activity was significantly higher (P < 0.05) . (2) The total effective rate of the combination treatment group (83％) was significantly higher than that of the plasma exchange group (63％) (P < 0.05) . (3) During the artificial liver treatment, there was one case of rash, one case of chills and one case of hypotension in the combination group, while no adverse reaction occurred in the plasma exchange group. (4) To conclude, either double plasma molecular adsorption combined with plasma exchange or simple plasma exchange can markedly improve the liver function of patients with liver failure, and produce few adverse reactions. However, the combination of double plasma molecular adsorption and plasma exchange has an advantageous therapeutic effect and can reduce plasma consumption.

Suberoylanilide hydroxamic acid induces apoptosis of rat hepatic stellate cells in vitro / 中国病理生理杂志

AIM:To study the effects of suberoylanilide hydroxamic acid (SAHA) on the apoptosis of hepatic stellate cells (HSCs) and expression of associated proteins, and to investigate the mechanisms of SAHA to induce apoptosis.METHODS:The rat HSCs were isolated by OptiPrep gradient centrifugation method.The effect of SAHA on HSC proliferation was detected by real-time cell analyzer.The morphological changes of HSCs treated with SAHA at different concentrations were observed under inverted microscope.The apoptotic rates of HSCs were analyzed by flow cytometry with Annexin V-FITC/PI staining and fluorescence microscopy.The protein expression of α-smooth muscle actin (α-SMA), collagen I, tissue inhibitor of metalloproteinase 1 (TIMP1), glucose-regulated protein 78 (GRP78) and histone deacetylase 6 (HDAC6) was detected by Western blotting.The interaction of GRP78 with HDAC6 in the HSCs was determined by co-immunoprecipitation.RESULTS:HSCs were successfully isolated and cultured for 14 d, during which the HSCs changed gradually from rest state to active state.SAHA significantly inhibited the proliferation of HSCs in a time-and dose-dependent manner (P<0.05).The results of Western blotting showed that the protein expression levels of α-SMA, TIMP1, collagen-I and HDAC6 were significantly decreased (P<0.05), while GRP78 was significantly increased (P<0.05).Compared with activated HSCs, GRP78 and total acetyl-lysine protein were significantly increased in the co-immunoprecipitated HSCs treated with SAHA, while HDAC6 protein was significantly decreased, indicting that GRP78 formed a complex with HDAC6.CONCLUSION:The anti-hepatic fibrosis effect of SAHA may be related to down-regulation of HDAC6 and up-regulation of acetylated GRP78, thus inducing endoplasmic reticulum stress of HSCs and promoting the apoptosis of HSCs.

Effects of suberoylanilide hydroxamic acidon proliferation and apoptosis of human hepatic stellate cells / 基础医学与临床

Objective To determine the effects of histone deacetylase inhibitor suberoylanilide hydroxamic acid(SAHA) on the cell proliferation and apoptosis of the human hepatic stellate cell line LX-2.The possible underlying mechanisms were also investigated.Methods The LX-2 cells were treated with SAHA in vitro.The morphology of LX-2 cells in different concentrations groups was observed by inverted microscope;the proliferation of LX-2 cells was measured by MTT assay;the Annexin V-FITC and PI staining was used to detect the apoptosis of LX-2 cells by flow cytometry and fluorescence microscope;the expression of α-SMA,collagen Ⅰ,acH3K9,acH3K14 and acH3K18 were detected by Western blot.Results The morphology change of LX-2 cells showed that SAHA inhibited the proliferation rate of LX-2 cells and in a dose dependent manner(P<0.05).The LX-2 cells were sensitive to SAHA along with time increasing,and in a time-dependent manner(P<0.05).Western blot showed that the expression levels of α-SMA and collagen-Ⅰ were significantly lower(P<0.05),on the contrary,the acetylation levels of acH3K9,acH3K14 and acH3K18 were significantly higher (P<0.05).Conclusions The increased acetylation of the histone acH3K9,acH3K14,acH3K18 and the lower expressed α-SMA and collagen-Ⅰ in LX-2 cells may be one of the mechanisms of SAHA.

Expression and clinical significance of astrocyte elevated gene-1, β-catenin, and cyclin D1 in hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo investigate the expression and clinical significance of astrocyte elevated gene-1 (AEG-1), β-catenin, and cyclin D1 in hepatocellular carcinoma (HCC) tissues. MethodsA total of 40 HCC samples and 40 samples of corresponding para-carcinoma tissues from the patients with pathologically confirmed HCC who underwent surgery in The People′s Hospital of Guizhou from July 2013 to December 2014 were randomly selected, and 8 samples of normal liver tissues were selected as controls. The immunohistochemistry SP was used to measure the protein expression of AEG-1, β-catenin, and cyclin D1 in HCC tissues, corresponding para-carcinoma tissues, and normal liver tissues, and the correlation between their expression and HCC clinicopathological characteristics was analyzed. The chi-square test or Fisher′s exact test was used for comparison of categorical data between groups, and the Spearman rank correlation was used to analyze the correlation of AEG-1 with β-catenin, and cyclin D1 in HCC. ResultsHCC tissues and para-carcinoma tissues showed significantly higher protein expression of AEG-1, β-catenin, and cyclin D1 than normal liver tissues (χ2=7.840, 4.274, 8.817, 4.274, 9.919, and 4.850, P=0.005, 0.039, 0.003, 0.039, 0.002, and 0.028). The positive expression of AEG-1, β-catenin, and cyclin D1 showed no significant differences across the patients with different sexes, ages, HBsAg status, or tumor sizes (all P＞0.05), but showed significant differences across the patients with different degrees of pathological differentiation, TNM stages for liver cancer, and metastases (all P＜0.05). The correlation analysis showed that the protein expression of AEG-1 was positively correlated with that of β-catenin and cyclin D1 (r=0.420 and 0.741, both P＜0.01). ConclusionAEG-1, β-catenin, and cyclin D1 may play vital roles in the development and progression of HCC. AEG-1 may up-regulate the expression and activity of cyclin D1 and β-catenin and thus promote the development and metastasis of HCC. A combined measurement of AEG-1, β-catenin, and cyclin D1 can be used as an important parameter for HCC gene therapy and prognostic evaluation.

Levels of histone modifications in activated primarily cultured rat hepatic stellate cells / 中国病理生理杂志

AIM:To investigate the changes of histone modifications during the activation of primarily cultured rat hepatic stellate cells ( HSCs) and the relationship between histone modification patterns andα-smooth muscle actin (α-SMA) expression, and to explore the roles of histone modifications in the activation of HSCs.METHODS:The rat HSCs were isolated by in situ perfusion of collagenase combined with density gradient centrifugation, cultured in vitro and identi-fied by immunofluorescence staining.The morphological features of the cells were observed under inverted microscope.The changes of desmin and α-SMA during the activation of HSCs were detected by immunofluorescence staining and Western blotting.The levels of histone 3 lysine 4 dimethylation (H3K4me2), histone 3 lysine 9 dimethylation (H3K9me2), his-tone 3 lysine 9 acetylation (acH3K9) and histone 4 lysine 12 acetylation (acH4K12) in quiescent HSCs and activated HSCs were determined by Western blotting.RESULTS: The morphology of HSCs shifted from a quiescent phenotype to highly activated myofibroblast during the culture.Immunofluorescence staining and Western blotting showed that the expres-sion levels of α-SMA and desmin were increased over time and reached maximum at 15 d.According to the results of cell morphology and immunofluorescence staining, the cells cultured for 24 h and 15 d were quiescent and activated HSCs, re-spectively.Compared with quiescent HSCs, there were higher H3K4me2 and lower H3K9me2, acH3K9 and acH4K12 modification levels in activated HSCs ( P<0.01 ) .CONCLUSION: Histone modifications show anomalous expression during the activation of primarily cultured rat HSCs.Histone modifications may contribute to the transdifferentiation of HSCs and the development of hepatic fibrosis.

A case-control study on the risk factors of hepatocellular carcinoma in Guizhou Province / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine the risk factor of HCC in Guizhou.</p><p><b>METHODS</b>A group case-control study design was conducted between 762 cases and 798 controls in Guizhou province. The main related-factors were analyzed with unconditional logistic regression model and evaluated by odds ratio (OR) and 95% confidence interval (95% CI).</p><p><b>RESULTS</b>There are significant differences between cases and controls in regarding to cigarette smoking 210 (27.6%),non-alcoholic fatty liver disease 336 (44.1%), alcoholic liver disease 245 (32.2%), family history of HCC 141 (16.5%), alcohol consumption 300 (39.4%), HBV infection 436 (57.2%), pickled food 290 (38.1%), and economic status 5 years ago 420 (55.1%) in cases,and cigarette smoking 116 (14.5%),non-alcoholic fatty liver disease 160 (20.1%), alcoholic liver disease 101 (12.7%), family history of HCC 40 (5.0%), alcohol consumption 180 (22.6%), HBV infection 82 (10.3%), pickled food 225 (28.2%), and economic status 5 years ago 647 (81.1%) in controls, with OR of each variable was 3.520, 2.464, 4.330, 2.219, 2.451, 19.245, 6.212, 0.174 respectively, P less than 0.01.</p><p><b>CONCLUSION</b>HBV infection and pickled food were the most common risks for HCC in Guizhou. Alcohol consumption excessively and cigarette smoking may increase the risk too.</p>

Diagnostic value of dilated intercellular space for non-erosive reflux disease / 中华消化内镜杂志

Objective To explore the diagnostic value of dilated intercellular space detected by light microscope for non-erosive reflux disease (NERD) and erosive esophagitis (RE). Methods A total of 104 subjects were divided into normal control group (n = 20), NERD group (n = 30) and RE group (n = 54).Biopsies were taken at 2-3 cm above the dentate line and were examined by light microscope to calculate the intercellular space and compared between different groups. Results The mean values of intercellular space in RE ( 1.40 ±0. 17 μm) and NERD ( 1.11 ± 0. 14 μm) were significantly higher than that in control group (0.66±0. 18 μm, x2 = 154. 170, P =0.000). But no significant difference was noted between RE and NERD groups ( t = 0. 044, P = 0. 834). The cut-off value of mean intercellular space with light microscope was 0. 89 μm, with sensitivity and specificity at 95.2% and 95.0%, respectively. Conclusion Dilated intercellular space under light microscope can be a sensitive, specific and objective indicator of NERD.

Changes of apoptosis and cell cycle of HSC in rat hepatic fibrosis by treatment with traditional Chinese medicine prescription (Dan-Shao-Hua-Xian ) / 中国病理生理杂志

AIM: To investigate the effect of a Chinese medicime, Dan-Shao-Hua-Xian capsule, on liver fibrosis induced by CCl_4 by observation of apoptosis and cell cycle variation in the liver cells. METHODS: Animal models were produced through eight-week treatment of the rats with CCl_4, alcohol and diet of high fat/low proteins, and then administration of Dan-Shao-Hua-Xian to the rats (1 g/kg) via stomach-tube-pouring for eight weeks was performed. Liver index, serum hyaluronic acid (HA) and glutamate pyruvate transaminase (ALT) were measured and hydroxyproline (Hyp) content in urine were determined. The extent of the liver fibrosis was observed under light microscope and apoptosis and cell cycle were also examined by cytometry between the two groups. RESULTS: Compared to the liver fibrosis group, the liver index, serum HA, ALT in the treatment group decreased, the development of liver fibrosis delayed, the urine Hyp and the number of apoptosed cells and the ratio of G_0/G_1 cells increased, as well as the S phase cells decreased, yet unable to return to normal. All those changes detected were statistically significant. CONCLUSIONS: The Dan-Shao-Hua-Xian is effective in treating the CCl_4-induced liver fibrosis in rats partly by virtue of inhibition of the growth of hepatic stellate cells and induction of apoptosis.