The mechanism and experimental verification of Ixeris sonchifolia promoting apoptosis of hepatocellular carcinoma based on network pharmacology: Ixeris sonchifolia Induces Hepatocellular Carcinoma Apoptosis via the PI3K/AKT Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. AIM OF THE STUDY: This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. MATERIALS AND METHODS: We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. RESULTS: A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. CONCLUSION: Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.

[Retracted] MicroRNA­505 is downregulated in human osteosarcoma and regulates cell proliferation, migration and invasion.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the control GAPDH western blotting bands shown in Fig. 4H on p. 496 were strikingly similar to data that were submitted for publication in advance of this article in different form by different authors at different research institutes [Liu F, Bai C and Guo Z: The prognostic value of osteopontin in limited­stage small cell lung cancer patients and its mechanism. Oncotarget 8: 70084­70096, 2017]. A further independent investigation conducted in the Editorial Office revealed that other western blotting data were likely to have been shared in common, comparing between the two articles. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to the submission of this article to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, it was admitted that the authors Feng Chang, Jian-Na Liu and Jun-Xin Lin did not initially provide their agreement to be authors on this paper; otherwise, the rest of the authors accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 491­500, 2018; DOI: 10.3892/or.2017.6142].

Recent advances in recurrent hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, accounting for 75%-85% of cases. Although treatments are given to cure early-stage HCC, up to 50%-70% of individuals may experience a relapse of the illness in the liver after 5 years. Research on the fundamental treatment modalities for recurrent HCC is moving significantly further. The precise selection of individuals for therapy strategies with established survival advantages is crucial to ensuring better outcomes. These strategies aim to minimize substantial morbidity, support good life quality, and enhance survival for patients with recurrent HCC. For individuals with recurring HCC after curative treatment, no approved therapeutic regimen is currently available. A recent study presented novel approaches, like immunotherapy and antiviral medication, to improve the prognosis of patients with recurring HCC with the apparent lack of data to guide the clinical treatment. The data supporting several neoadjuvant and adjuvant therapies for patients with recurring HCC are outlined in this review. We also discuss the potential for future clinical and translational investigations.

Clinical Evaluation of Metagenomic Next-Generation Sequencing Method for the Diagnosis of Suspected Ascitic Infection in Patients with Liver Cirrhosis in a Clinical Laboratory.

Metagenomic next-generation sequencing (mNGS), mostly carried out in independent clinical laboratories, has been increasingly applied in clinical pathogen diagnosis. We aimed to explore the feasibility of mNGS in clinical laboratories and analyze its potential in the diagnosis of infectious ascites. Two reference panels composed of 12 strains commonly appearing in peritonitis were constructed to evaluate the performance metrics based on in-house mNGS protocols. The mNGS clinical detection value was analyzed in 211 ascitic samples and compared with culture and composite standards. Finally, eight patients with cirrhosis were prospectively enrolled to verify the clinical value of mNGS in peritoneal infection diagnosis. The mNGS analytical performance showed that the assay had great linearity, specificity, stability, interference, and limits of detection of 33 to 828 CFU/mL. The sensitivity and specificity of mNGS for bacterial or fungal detection using culture standards were 84.2% and 82.0%, respectively. After adjustment using digital PCR and clinical judgment, the sensitivity and specificity increased to 87.2% and 90.1%, respectively. Compared with culture, mNGS detected a broad range of pathogens and more polymicrobial infections (49% versus 9%, P < 0.05). The pathogen results were obtained within 24 h using mNGS in eight prospective cases, which effectively guided antibiotics therapy. mNGS testing in clinical laboratories affiliated with a hospital has certain advantages. It has unique superiority in pathogens detection, particularly in patients with polymicrobial infections. However, considering spectrum characteristics and test cost, pertinent pathogen panels should be developed in clinical practice. IMPORTANCE This study established and evaluated a complete metagenomics next-generation sequencing assay to improve the diagnosis of suspected ascitic infection in a clinical laboratory affiliated with a hospital. The assay is superior to traditional culture testing and will aid in the early and accurate identification of pathogens, particularly in patients with polymicrobial infections. This assay is also essential for precision therapy and can reduce the incidence of drug resistance stemming from irrational use of antibiotics.

Clinical evaluation of bacterial DNA using an improved droplet digital PCR for spontaneous bacterial peritonitis diagnosis.

Objective: Bacterial DNA (bactDNA) detection can be used to quickly identify pathogenic bacteria and has been studied on ascitic fluid. We aimed to retrospectively analyze the diagnostic value and applicational prospect of the bactDNA load in spontaneous bacterial peritonitis (SBP). Method: We extracted viable bactDNA from ascitic samples of 250 patients with decompensated cirrhosis collected from October 2019 to April 2021 and detected the bactDNA by droplet digital polymerase chain reaction (ddPCR). We used ascitic samples of a baseline cohort of 191 patients to establish diagnostic thresholds for SBP and analyze the patients' diagnostic performance based on ascites polymorphonuclear (PMN) and clinical manifestation. We performed bactDNA quantification analysis on 13 patients with a PMN less than 250 cells/mm3 but with clinical symptoms. The dynamic changes of the bactDNA load from eight patients (before, during, and after SBP) were analyzed. Results: After the removal of free DNA, the bactDNA detected by ddPCR was generally decreased (1.75 vs. 1.5 log copies/µl, P < 0.001). Compared with the traditional culture and PMN count in the SBP diagnosis, the bactDNA showed that the ddPCR sensitivity was 80.5%, specificity was 95.3%, positive predictive value was 82.5%, and negative predictive value was 94.7%, based on clinical composite criteria. In patients with a PMN less than 250 cells/mm3, the bactDNA load of 13 patients with symptoms was significantly higher than those without symptoms (2.7 vs. 1.7 log copies/µl, P < 0.001). The bactDNA in eight patients had SBP that decreased by 1.6 log copies/µl after 48 h of antibiotic treatment and by 1.0 log copies/µl after 3 days of continued treatment. Conclusion: BactDNA detection can be used to further enhance the diagnostic efficiency of SBP. Therefore, the application of ddPCR assay not only can be used to discriminate and quantify bacteria but also can be used in the clinical assessment for antibiotics treatment.

Immune responses and pathogenesis in persistently PCR-positive patients with SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 emerged in China in December 2019 and then rapidly spread worldwide. Why COVID-19 patients with the same clinical condition have different outcomes remains unclear. This study aimed to examine the differences in the phenotype and functions of major populations of immune cells between COVID-19 patients with same severity but different outcomes. Four common type adult inpatients with laboratory confirmed COVID-19 from Beijing YouAn Hospital, Capital Medical University were included in this study. The patients were divided into two groups based on whether or not COVID-19 polymerase chain reaction (PCR)-negative conversion occurred within 3 weeks. Peripheral blood samples were collected to compare the differences in the phenotype and functions of major populations of immune cells between the two groups of patients. The result shows that the proportions of CD3+ CD8+ CD38+ HLA-DR+ CD27- effector T killer cells generally declined, whereas that of CD3+ CD4+ CD8+ double-positive T cells (DPTs) increased in the persistently PCR-positive patients. In summary, considering the imbalance between effector T killer cells/CD3+CD4+CD8+ DPTs was a possible key factor for PCR-negative conversion in patients with COVID-19.

Dysregulation of the immune response affects the outcome of critical COVID-19 patients.

Critical cases of coronavirus disease 2019 (COVID-19) are associated with a high risk of mortality. It remains unclear why patients with the same critical condition have different outcomes. We aimed to explore relevant factors that may affect the prognosis of critical COVID-19 patients. Six critical COVID-19 inpatients were included in our study. The six patients were divided into two groups based on whether they had a good or poor prognosis. We collected peripheral blood samples at admission and the time point of exacerbation to compare differences in the phenotypes and functions of major populations of immune cells between the groups. On admission, compared to patients with poor prognoses, those with good prognoses had significantly higher counts of monocytes (P < .05), macrophages (P < .05), higher frequency of CD3+ CD4+ CD45RO+ CXCR3+ subsets (P < .05), higher frequency of CD14+ CD11C+ HLA-DR+ subset of dendritic cells (P < .05), and a lower count of neutrophils (P < .05). At the time point of exacerbation, the proportions of naïve CD4+ T cells (P < .05), Tregs, and Th2 cells in the poor prognosis group were relatively higher than those in the good prognosis group, and CD4+ memory T cells were relatively lower (P < .05). According to our results, the poor prognosis group showed a worse immune response than the good prognosis group at the time of admission and at exacerbation. Dysregulation of the immune response affects the outcome of critical COVID-19 patients.

Progress and prospects of biomarkers in primary liver cancer (Review).

Tumor biomarkers are important in the early screening, diagnosis, therapeutic evaluation, recurrence and prognosis prediction of tumors. Primary liver cancer is one of the most common malignant tumors; it has high incidence and mortality rates and seriously endangers human health. The main pathological types of primary liver cancer include hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined HCC­cholangiocarcinoma (cHCC­CC). In the present review, a systematic outline of the current biomarkers of primary liver cancer is presented, from conventional blood biomarkers, histochemical biomarkers and potential biomarkers to resistance­associated biomarkers. The important relationships are deeply elucidated between biomarkers and diagnosis, prognosis, clinicopathological features and resistance, as well as their clinical significance, in patients with the three main types of primary liver cancer. Moreover, a summary of several important biomarker signaling pathways is provided, which is helpful for studying the biological mechanism of liver cancer. The purpose of this review is to provide help for clinical or medical researchers in the early diagnosis, differential diagnosis, prognosis and treatment of HCC.

Humanized mouse model: a review on preclinical applications for cancer immunotherapy.

Due to the refractory and partial sensitive treatments to malignant cancers, immunotherapy has increasingly become a hotspot in effective anti-tumor research. However, at present, existing animal models could not accurately describe the interaction between human tissue and tumor cells for preclinical trials. Furthermore, it is a tough obstacle to reconstitute the immune system and microenvironment in a mouse model identical to humans due to species differences. In the establishment of the humanized mouse model, the co-transplantation of human immunocytes with/without tissues and tumor cells is the key breakthrough to solve this problem. The compelling progress has been investigated in the preclinical drug test for diverse tumor types. This review mainly summarized the development of immunodeficient mice, and the construction and practicability of the humanized mouse model. Furthermore, the investigators also highlight the pros and cons, and recent progress in immunotherapy research for advanced utility of human cancer diseases.

Protective Effect of Ganshuang Granules () on Liver Cirrhosis by Suppressing Regulatory T Cells in Mouse Model.

OBJECTIVE: To investigate the potential antifibrotic mechanisms of Chinese medicine Ganshuang Granules (, GSG) and to provide clinical therapeutic evidence of its effects. METHODS: A cirrhotic mouse model was established by intraperitoneally injecting a mixture of CCl4 (40%) and oil (60%) at 0.2 mL per 100 g of body weight twice a week for 12 weeks. After 12-week modeling, GSG was intragastric administrated to the mice for 2 weeks, and the mice were divided into low-, medium- and high-dose groups at doses of 1, 2 and 4 g/(kg·day), respectively. Liver morphology changes were observed using Masson's trichrome staining and B-ultrasound. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hyaluronic acid (HA) in serum were detected using an automatic biochemistry analyzer. The expressions of desmin, smooth muscle actin (SMA) and Foxp3 in liver were detected by immunoflfluorescence. The regulatory T cell (Treg) frequency was determined through flflow cytometry analysis. Collagen-I, SMA, IL-6, tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and transforming growth factor ß1 (TGF-ß1) expression levels were measured using quantitative polymerase chain reaction (qPCR). RESULTS: Masson's staining result showed fewer pseudolobule structures and fibrous connective tissue in the GSG-treatment groups than in the spontaneous recovery group. Ultrasonography showed that GSG treatment reduced the number of punctate hyperechoic lesions in mice cirrhotic livers. The serum ALT, AST, HA levels were significantly ameliorated by GSG treatment (ALT: F=8.104, P=0.000; AST: F=7.078, P=0.002; and HA: F=7.621, P=0.001). The expression levels of collagen-I and SMA in the cirrhotic livers were also attenuated by GSG treatment (collagen-I: F=3.938, P=0.011; SMA: F=4.115, P=0.009). Tregs, which were elevated in the fibrotic livers, were suppressed by GSG treatment (F=8.268, P=0.001). The expressions of IL-6, TNF-α and IL-1ß increased, and TGF-ß levels decreased in the cirrhotic livers after GSG treatment (IL-6: F=5.457, P=0.004; TNF-α: F=6.023, P=0.002; IL-1ß: F=6.658, P=0.001; and TGF-ß1: F=11.239, P=0.000). CONCLUSIONS: GSG promoted the resolution/regression of cirrhosis and restored liver functions in part by suppressing Treg cell differentiation, which may be mediated by hepatic stellate cells.

Quercetin protects against chronic prostatitis in rat model through NF-κB and MAPK signaling pathways.

BACKGROUND: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common disease of urology, of which the pathogenesis and therapy remain to be further elucidated. Quercetin has been reported to improve the symptoms of CP/CPPS patients. We aimed to verify the therapeutic effect of quercetin on CP/CPPS and identify the mechanism responsible for it. METHODS: A novel CP/CPPS model induced with Complete Freund Adjuvant in Sprague Dawley rats was established and the prostates and blood specimens were harvested for further measurement after oral administration of quercetin for 4 weeks. RESULTS: Increased prostate index and infiltration of lymphocytes, up-regulated expression of IL-1ß, IL-2, IL-6, IL-17A, MCP1, and TNFα, decreased T-SOD, CAT, GSH-PX, and increased MDA, enhanced phosphorylation of NF-κB, P38, ERK1/2, and SAPK/JNK were detected in CP/CPPS rat model. Quercetin was identified to ameliorate the histo-pathologic changes, decrease the expression of pro-inflammatory cytokines IL-1ß, IL-2, IL-6, IL-17A, MCP1, and TNFα, improve anti-oxidant capacity, and suppress the phosphorylation of NF-κB and MAPKs. CONCLUSIONS: Quercetin has specific protective effect on CP/CPPS, which is mediated by anti-inflammation, anti-oxidation, and at least partly through NF-κB and MAPK signaling pathways.

MicroRNA-505 is downregulated in human osteosarcoma and regulates cell proliferation, migration and invasion.

Recent studies have demonstrated that microRNAs (miRNAs/miRs) are involved in osteosarcoma tumorigenesis, progression, invasion and metastasis. For example, miR-505 plays important roles in human carcinogenesis; however, its exact function in osteosarcoma remains unclear. MicroRNA profiles of osteosarcoma and normal tissues were obtained by miRNA microarray assays, which were validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Then, high-mobility group box 1 (HMGB1) expression was evaluated by qRT-PCR and western blot analysis. The correlation between miR-505 and HMGB1 was analyzed by Pearson correlation. In vitro, the biological functions of miR-505 were examined by wound healing, MTT and Transwell assays and western blot analysis in MG63 cells transfected with miRNA mimics or empty vector. Luciferase assay was utilized to assess whether HMGB1 is a target of miR-505. miRNA microarrays revealed 26 aberrant miRNAs in osteosarcoma tissues; miR-505 showed the most pronounced decrease (P<0.01), which was significantly associated with TNM stage and metastasis status (P<0.05). In addition, HMGB1 was highly expressed in osteosarcoma tissues (P<0.01), with a significantly negative correlation with miR-505 (r=-0.6679, P<0.001). Furthermore, miR-505 inhibited proliferation, migration and invasion abilities of MG63 cells (P<0.01). Moreover, luciferase activity of the HMGB1-3'-UTR plasmid was suppressed following miR-505 binding (P<0.01). Finally, HMGB1 overexpression partly reversed the effects of miR-505 on MG63 cells. In conclusion, miR-505 levels are decreased in osteosarcoma tissues, and reduced miR-505 expression is significantly associated with poorer clinical prognosis in patients with osteosarcomas. miR-505 inhibits osteosarcoma cell proliferation, migration and invasion by regulating HMGB1.

Copper chelation by trientine dihydrochloride inhibits liver RFA-induced inflammatory responses in vivo.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. Radiofrequency ablation (RFA) is currently performed widely for managing HCC. RFA treatment causes damage around the ablation. Trientine dihydrochloride has been used to reduce the copper in liver. METHODS: The rats were treated with trientine dihydrochloride for 5 days before liver RFA. Liver function, copper concentration, inflammation biomarkers and MDA, SOD were analyzed after RFA treatment for 2 h, 2 and 5 days. RESULTS: The results indicated that trientine dihydrochloride reduced the copper in plasma and liver tissue significantly. And trientine dihydrochloride significantly inhibited RFA-induced inflammatory gene expression in liver. Similar inhibitory effects of trientine dihydrochloride were observed on ROS-induced malondialdehyde production in liver tissues. CONCLUSION: These results suggest that pre-treatment with the selective copper chelator trientine dihydrochloride can inhibit inflammatory response effectively during and after liver RFA in vivo. Chelation of copper to a lower level before liver RFA may be a novel strategy to prevent or ameliorate inflammatory responses in liver induced by RFA and to protect the parenchyma tissues in liver during and after RFA in HCC patients.

ESC reverses epithelial mesenchymal transition induced by transforming growth factor-ß via inhibition of Smad signal pathway in HepG2 liver cancer cells.

BACKGROUND: Epithelial mesenchymal transition (EMT) mediated by TGF-ß pays an important role in malignant tumor acquired abilities of migration and invasion. Our previous study showed that the extract of Stellera chamaejasme L. (ESC) was against proliferation of a variety of tumor cells, but there were no studies in the effects of ESC on EMT in tumor cells. In this study, TGF-ß was adopted to induce EMT in HepG2 cells and the influence of ESC on EMT was observed. METHODS: MTT assay was used to observe the cell viability. Wound healing assay and transwell assay were used to observe the migration and invasion activities. Western blot and immunofluorescence methods were used to observe the expression of proteins. RESULTS: We found that HepG2 cells induced by TGF-ß showed mesenchymal morphology, down-regulation of epithelial marker E-cadherin and up-regulation of mesenchymal marker Vimentin, indicating that TGF-ß could mediate epithelial mesenchymal induction in HepG2 cells. ESC could reverse the mesenchymal morphology and regulate expressions of marker proteins in HepG2 induced by TGF-ß and significantly inhibit TGF-ß induced HepG2 cell migration and invasion. We further found that ESC could also significantly depress Smad2 phosphorylation and nuclear translocation, and ESC had coordination with SB432542, a specific inhibitor of TßRI kinases. CONCLUSIONS: These results suggested that the ESC could reverse epithelial mesenchymal transition induced by TGF-ß via inhibition Smad2 signaling pathway.

Autophagy in anti-apoptotic effect of augmenter of liver regeneration in HepG2 cells.

AIM: To investigate the role of autophagy in the anti-apoptotic effect of augmenter of liver regeneration (ALR). METHODS: Autophagy was induced through serum deprivation. An ALR-expressing plasmid was transfected into HepG2 cells, and autophagic flux was determined using fluorescence microscopy, electron microscopy, Western blot and quantitative polymerase chain reaction (qPCR) assays. After ALR-expressing plasmid transfection, an autophagy inhibitor [3-methyladenine (3-MA)] was added to HepG2 cells, and apoptosis was observed using fluorescence microscopy and flow cytometry. RESULTS: Autophagy was activated in HepG2 cells, peaking at 24 h after serum deprivation. Microtubule-associated protein light chain three-II levels were higher in HepG2 cells treated with ALR than in control cells, fluorescence microscopy, electron microscopy and qPCR studies showed the similar trend, and p62 levels showed the opposite trend, which indicated that ALR may play an important role in increasing autophagy flux. The numbers of apoptotic cells were substantially higher in HepG2 cells treated with both ALR and 3-MA than in cells treated with ALR alone. Therefore, the protective effect of ALR was significantly attenuated or abolished when autophagy was inhibited, indicating that the anti-apoptotic effect of ALR may be related to autophagy. CONCLUSION: ALR protects cells from apoptosis partly through increased autophagy in HepG2 cells and may be valuable as a new therapeutic treatment for liver disease.

Association of alcohol consumption and components of metabolic syndrome among people in rural China.

BACKGROUND: Accumulative evidence in the literature suggests alcohol consumption is a protective factor of the metabolic syndrome (MS). However, few studies investigated the relationship between alcohol consumption and components of MS. We examined association of several types of alcoholic beverage with components of MS among people in rural China. METHODS: In the Nantong Metabolic Syndrome Study (NMSS), a cross-sectional study, a total of 20,502 participants, including 13,505 women and 6,997 men aged 18-74 years, were recruited between 2007 and 2008 in Nantong, China. Socio-economic status, dietary intake, physical exercise, alcoholic beverage consumption, and smoking status information were obtained, and triglycerides (TG), high-density lipoprtein cholesterol (HDL-c), blood pressure (BP) and blood glucose level were examined for all participants. Logistic regression model and the restricted cubic spline approach were used to analyze the associations between alcoholic beverage consumption and MS components. RESULTS: The MS prevalence was 21.1% in the whole population, which was significantly low among drinkers (20.6%), compared with non-drinkers (23.6%) in women, and was comparable in men (16.4% versus 17.1%). High HDL-c level was observed among drinkers, compared with non-drinkers in both men and women. Low TG level and Systolic BP (SBP) were found only among rice wine drinkers in women, and high waist circumference, high TG and BP were found among beer and liquor drinkers in men. Furthermore, we found that the highest quartile of rice wine drink in women may decrease 24% risk of high TG, 30% risk of low HDL-c and 43% risk of high glucose among MS components cases respectively, compared with non-drinkers (p for trend <0.01 for those three components). While compared non-drinkers among men, the highest quartile of liquor drink may increase 32% risk of high SBP, 55% risk of high Diastolic BP (DBP) and 34% risk of abdominal obesity among MS components cases respectively, but decrease 45% risk of low HDL-c (p for trend <0.05 for those four components). CONCLUSION: Our data suggested that all alcoholic beverages increased HDL-c level. Rice wine decreased both TG level and blood glucose in women only and it could be one of healthy alcoholic beverages in MS prevention in Chinese women. While excessive liquor consumption increased BP and waist circumference level and it may lead to hypertension and central obesity in Chinese men.

Antiviral drug resistance increases hepatocellular carcinoma: a prospective decompensated cirrhosis cohort study.

AIM: To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients. METHODS: Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort. With two years of follow-up, 198 patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed. RESULTS: Among the antiviral treatment patients, 162 had a complete virological response (CVR), and 36 were drug-resistant (DR). The two-year cumulative incidence of hepatocellular carcinoma (HCC) in the DR patients (30.6%) was significantly higher than that in both the CVR patients (4.3%) and the control group (10.3%) (P < 0.001). Among the DR patients in particular, the incidence of HCC was 55.6% (5/9) in those who failed rescue therapy, which was extremely high. The rtA181T mutation was closely associated with rescue therapy failure (P = 0.006). The Child-Pugh scores of the CVR group were significantly decreased compared with the baseline (8.9 ± 2.3 vs 6.0 ± 1.3, P = 0.043). CONCLUSION: This study showed that antiviral drug resistance increased the risk of HCC in decompensated hepatitis B-related cirrhotic patients, especially in those who failed rescue therapy.

[Research of the relationship of ubiquinone and beclin-1 and liver mitochondria].

OBJECTIVE: To study whether CO-Q10 can protect liver injury caused by acute on chronic liver failure (ACLF) by autophagy. METHODS: Rats were separated into three groups: control group, acute on chronic liver failure (ACLF) and intervenient group, liver tissues were observed by optical microscopy and electron microscopy. The levels of Beclin-1 expression were determined by real-time PCR. And Western Blot. RESULTS: Areas of necrosis detected in intervenient group were alleviated than in ACLF significantly. Most mitochondrias had been degradated in ACLF group while alive in intervenient group. Real-time PCR and Western Blot revealed level of beclin-1 in ACLF was lower than control and intervenient group. CONCLUSION: Intervenient group may ameliorate rat liver injury by promoting autophagy.

[Inhibition of glycogen synthase kinase 3b activity regulates Toll-like receptor 4-mediated liver inflammation].

OBJECTIVE: To determine the mechanism underlying the therapeutic activities of glycogen synthase kinase 3b (GSK3b) against hepatic ischemia-reperfusion (H-IR) injury by investigating the inhibitive effects of GSK3b on inflammation mediated by Toll-like receptor 4 (TLR4). METHODS: C57BL/6 male mice were subjected to 90 min of warm liver cephalad lobe ischemia, followed by reperfusion for various lengths of time. The mice were divided into three groups: the H-IR untreated model (control group), and the H-IR inflammation-induced models that received an intraperitoneal injection of purified lipopolysaccharide (LPS) endotoxin alone (inflammation group) or with pretreatment of the SB216763 GSK3b-specific inhibitor (intervention group). To create a parallel isolated cell system for detailed investigations of macrophages, marrow-derived stem cells were isolated from femurs of the H-IR control group of mice and used to derive primary macrophages. The cells were then divided into the same three groups as the whole mouse system: control, LPS-induced inflammation model, and inflammation model with SB216763 intervention. Differential expressions of inflammation-related proteins and genes were detected by Western blotting and real-time quantitative PCR, respectively. RESULTS: The phosphorylation levels of ERK, JNK and p38 MAPK were induced in liver at 1 h after reperfusion, but then steadily decreased and returned to baseline levels by 4 h after reperfusion. In addition, the phosphorylation levels of ERK and JNK were induced in macrophages at 15 min after LPS stimulation, while the phosphorylation level of p38 MAPK was induced at 1 h; SB216763 pretreatment suppressed the LPS-stimulated ERK, JNK and p38 phosphorylation in macrophages. In the mouse model, GSK3b activity was found to promote the gene expression of anti-inflammatory cytokine IL-10 (control: 0.21 ± 0.08, inflammation: 0.83 ± 0.21, intervention: 1.76 ± 0.67; F = 3.16, P = 0.027) but to significantly inhibit the gene expression of pro-inflammatory cytokines IL-12 (control: 0.11 ± 0.05, inflammation: 0.85 ± 0.11, intervention: 0.43 ± 0.10; F = 2.67, P = 0.038), TNF-a, (control: 0.052 ± 0.012, inflammation: 8.11 ± 0.98, intervention: 3.9 ± 0.82; F = 4.13, P = 0.016), IL-6 (control: 0.22 ± 0.08, inflammation: 6.37 ± 0.81, intervention: 2.11 ± 0.63; F = 3.21, P = 0.024), and IL-1b (control: 0.12 ± 0.07, inflammation: 2.51 ± 0.62, and intervention: 1.28 ± 0.33; F = 2.22, P = 0.030). CONCLUSION: Inhibition of GSK3b selectively regulates the expression of anti-inflammatory and pro-inflammatory cytokines in liver Kupffer cells (liver macrophages). This process may be one of the mechanisms underlying the ability of GSK3b to ameliorate hepatic ischemia-reperfusion injury, possibly because inhibition of pro-inflammatory cytokines may indirectly mediate liver cell apoptosis.