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Objective To investigate the material basis and antitumor mechanism of Marsdenia tenacissima (MT) on hepatocellular carcinoma (HCC) by bioinformatics, network pharmacology and molecular docking technology. Methods Active ingredients of MT were collected by literature search and screened by Swiss ADME website, which targets were predicted by Swiss Target Prediction. The chip data of HCC (GSE147888) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes were screened by R software. HCC-related targets were collected from the Genecards and OMIM databases. The Venny online tool was used to obtain the intersection of the herbal medicine targets and the disease targets. Subsequently, drug-target network and protein–protein interaction (PPI) network were constructed by Cytoscape software and String platform. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by key genes. The expression of key genes in HCC and its effect on survival were analyzed by the GEPIA database. The Human Protein Atlas (HPA) was used to analyze the immunohistochemical expression of key genes in HCC. Finally, molecular docking was carried out to investigate interactions between the top five targets and their related active compounds. Results A total of 50 active components were screened and 12 common targets were identified related to MT and HCC. Scutellarein-4-Methylether, Tenasogenin, Sinapic Acid, Dresgenin and Kaempferol were considered as the critical components. JUN, MMP9 and PTGS2 were recognized as key therapeutic targets. The GO analyses demonstrated that key targets mainly involved in the process of gene silencing and inflammatory response. KEGG analysis suggested that key targets were enriched in TNF signaling pathway and IL-17 signaling pathway. Survival analysis by the GEPIA showed significant differences in the expression of ESR1, MMP1, MMP9, JUN, and PPARG between high and low risk groups. Immunohistochemical results showed that ESR1 and MMP9 were differentially expressed in normal and hepatocellular carcinoma tissues. The molecular docking results verified that the drug active ingredient could be stably bound to the target protein. Conclusion This study reflected the multi-component, multi-target and multi-pathway characteristics of the MT in the treatment of HCC, which could provide a scientific basis for the clinical application of MT in HCC.
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Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.
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Objective: To investigate the impact of portal hypertention with hypersplenism of different severity and splenectomy on prognosis of hepatocellular carcinoma (HCC). Methods: We retrospectively analyzed the clinical data of 403 patients with HCC who met the Milan criteria and received radical treatment in Tianjin Third Central Hospital from January 2008 to January 2018. Cox propor-tional risk regression analysis was performed for parameters such as platelet levels (PLT), albumin-bilirubin (ALBI) grade, aspartate ami-notransferase-to-platelet ratio index (APRI), and post-sinusoidal resistance (PSR). HCC patients with severe hypersplenism were as-signed into two groups according to treatment method: radical treatment for HCC alone and radical treatment for HCC plus splenecto-my. Clinical data were compared, and the two groups were evaluated using the Kaplan-Meier survival analysis method. Results: Univar-iate and multivariate analyses showed that PLT was an independent risk factor for overall survival (OS) and disease-free survival (DFS) in patients with HCC. OS curves differed significantly with different PLT among patients with HCC (P=0.013). Furthermore, parameters of portal hypertension in cirrhosis, such as PSR, APRI, and ALBI grade, were risk factors for HCC prognosis. The degree of portal hyper-tension and hypersplenism, liver function, and tumor-node-metastasis stage did not differ between the two groups (P>0.05). Survival analysis showed significantly longer OS in the radical treatment plus splenectomy group (P=0.025). Following were the 1-, 3-, and 5-year survival rates: radical treatment alone group 100% , 98.2% , and 68.5% and radical treatment plus splenectomy group. 97.1% , 79.4%, and 56.8%, respectively. DFS did not differ between the two groups (P=0.326). Conclusions: Clinical parameters, such as PLT, PSR, APRI, and ALBI grade, are important prognostic factors in HCC patients with portal hypertension and hypersplenism. Radical treat-ment for HCC plus splenectomy can improve OS in HCC patients within the Milan criteria with severe hypersplenism.
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DNA methylation is closely related to the genesis and development of pituitary adenoma. Studies have shown that high methylation in the promoter region of potassium voltage-gated chanel,shaker related subfamily,beta member 2,O-6-methylguanine-DNA methyltransferase,echinoderm microtubule associated protein like 2 ,ras homolog family member D ,homeobox B1 ,NNAT, and P16 inhibits the expression of these genes and regulates of the proliferation of pituitary adenoma. DNA methylation is also closely related to invasive pituitary adenoma. Therefore,further study on molecular mechanism of DNA methylation of pituitary adenoma will offer a new strategy for the diagnosis and treatment of pituitary adenoma.
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Humans , Adenoma , Genetics , DNA Methylation , Gene Expression Regulation, Neoplastic , Pituitary Neoplasms , Genetics , Promoter Regions, GeneticABSTRACT
Objective To investigate the value of Habib 4X in hepatic resection. Methods The clinical outcome of 21 patients with liver disease who received liver resection at the Tianjin Third Central Hospital from November 2009 to April 2010 were retrospectively evaluated. All the operations were carried out by using Habib 4X. Results All patients received hepatectomy, including right hepatectomy in three patients, left hepatectomy in one patient, multiple segmentectomy in nine patients, single segmentectomy in seven patients and partial liver resection in one patient. All tumors were reseeted completely. The mean operation time was (50±25) minutes and the mean blood loss was(129±117)ml. No patient was transferred to ICU. Three patients were complicated with bile leakage, one with lymphatic leakage and four with pleural effusion, and they were cured by non-surgical treatment. There were no patients with postoperative hemorrhage, incision infection or hepatic failure. No mortality was observed. The mean postoperative hospital stay was(19±14)days. Conclusions Radiofrequency energy was applied along the margins of the tumor to create zones of necrosis before resection with a scalpel, offering hepatobiliary surgeons an additional method for performing liver resections with minimal blood loss, low morbidity and mortality rates. As for malignant tumors, minor or major liver resection assisted by Habib 4X is safe, and it can reduce the chance of positive incisal margin.
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<p><b>OBJECTIVE</b>To establish a quantitative technique for assaying gene methylation in hepatocellular carcinoma (HCC) and evaluate its feasibility for clinical application.</p><p><b>METHODS</b>Following bisulfite modification and PCR amplification, the fragments of CDKN2A and ACTB were cloned into plasmids to generate calibration curves using SYBR Green quantitative PCR, and then these two genes were quantitatively analyzed in 41 cases of HCC specimen.</p><p><b>RESULTS</b>The amplification curve, dissociation curve, calibration curve and electrophoresis analysis showed that SYBR Green fluorescent quantitative PCR could assay 10(2)-10(8) copies/microL of recombinant plasmids with high specificity, high sensitivity and a wide detection range. The tests on 41 cases of HCC specimens further confirmed its feasibility for quantitative analysis of methylation.</p><p><b>CONCLUSION</b>SYBR Green fluorescent PCR is an easy, fast and high-throughout quantitative tool, and it can be used for methylation analysis in basic research or clinical assay.</p>
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Female , Humans , Male , Middle Aged , Actins , Genetics , Biopsy , Calibration , Carcinoma, Hepatocellular , Genetics , Pathology , DNA Methylation , Feasibility Studies , Fluorescence , Genes, p16 , Luminescent Measurements , Nucleic Acid Denaturation , Polymerase Chain Reaction , Methods , Sensitivity and Specificity , Transition TemperatureABSTRACT
<p><b>OBJECTIVE</b>To investigate the methylation frequencies of multiple tumor suppressor genes (TSGs) in hepatocellular carcinoma (HCC) and the clinical implication of aberrant DNA methylation in molecular carcinogenesis of HCC.</p><p><b>METHODS</b>Sixty samples of HCC and the paired adjacent liver tissue, 16 samples from post-hepatitis cirrhotic livers, 5 from livers with chronic hepatitis and 5 from normal livers were collected. Eight TSGs frequently silenced by hypermethylation of their promoters in various types of digestive tumors were selected, including APC, RASSF1A, p16, GSTP1, MGMT, DAPK, SOCS-1 and RIZ1. The status of promoter methylation in these 8 genes was investigated using methylation-specific polymerase chain reaction. The clinicopathological data of HCC were also analyzed in order to evaluate the clinical implication of aberrant methylation in HCC.</p><p><b>RESULTS</b>Methylation of the 8 TSGs was quite frequent in HCC, with a methylation rate of 95.0% in RASSF1A, 90.0% in APC, 73.3% in GSTP1, 65.0% in p16, 61.6% in RIZ1 and 60.0% in MGMT. Methylation of the 6 genes was more frequent in HCC than that in adjacent tissues (P < 0.05). The methylation rate of MGMT, GSTP1 and RIZ1 in the adjacent tissues was 41.6%, 40.0% and 25.0%, respectively, significantly higher than that in cirrhotic liver (P < 0.05). p16 methylation was more frequently observed in HCC in elderly patients. The frequency of MGMT methylation was tended to be higher in giant HCC than that in the other types of HCC. Patients with MGMT methylation in the tumor were found to have a shorter disease free survival.</p><p><b>CONCLUSION</b>Different frequency of methylation in hepatocellular carcinomas, adjacent liver tissues and cirrhotic livers implies that epigenetic alteration in the hepatocellular carcinogenesis may be a gradually progressive process. Methylation status of MGMT, GSTP1 and RIZ1 may be promising in risk assessment of hepatocellular carcinoma and in early diagnosis. Furthermore, MGMT methylation might be also used as a potential prognostic biomarker for hepatocellular carcinoma patients.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Base Sequence , Carcinoma, Hepatocellular , Genetics , Metabolism , DNA Methylation , DNA Modification Methylases , Genetics , Metabolism , DNA Repair Enzymes , Genetics , Metabolism , DNA, Neoplasm , Genetics , DNA-Binding Proteins , Genetics , Metabolism , Disease-Free Survival , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Glutathione S-Transferase pi , Genetics , Metabolism , Hepatitis B, Chronic , Genetics , Metabolism , Histone-Lysine N-Methyltransferase , Liver , Metabolism , Liver Cirrhosis , Genetics , Metabolism , Liver Neoplasms , Genetics , Metabolism , Molecular Sequence Data , Neoplasm Recurrence, Local , Nuclear Proteins , Genetics , Metabolism , Transcription Factors , Genetics , Metabolism , Tumor Suppressor Proteins , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To study the effect of Qinggan Huoxue recipe (QGHXR) in treating alcoholic liver disease (ALD).</p><p><b>METHODS</b>By adopting the multi-centered, randomized and controlled method, the patients were divided in to the QGHXR group (60 patients) treated orally by QGHXR, the XCHG group (30 patients) treated orally by Xiaochaihu granule and the control group (30 patients) treated orally by conventional therapy such as glucurolactone, vitamin C. The changes in symptoms, signs, liver function, blood lipid, liver fibrosis markers, cytokines, lipid superoxidation parameters and B-untrasonographic figure after treatment of the two groups were observed.</p><p><b>RESULTS</b>The total therapeutic efficacy of QGHXR, improvements in anorexia, nausea, vomiting and jaundice as well as effect in reducing blood levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and triglyceride (TG) were superior in the QGHXR group to those in the other two groups (P < 0.01), and the effect in decreasing gamma-glutamyl transferase (GGT) and very low-density lipoprotein (VLDL) in the QGHXR group was more significant than that in the control group (P < 0.01). QGHXR also showed effects in lowering levels of liver fibrosis markers and cytokines, alleviating the anti-lipid superoxidation damage in liver, and could markedly improve the degree of fatty liver.</p><p><b>CONCLUSION</b>QGHXR shows obvious therapeutic effect in treating ALD, the mechanism could possibly be related with its effects in antagonizing lipid superoxidation, stabilizing hepatic cell membrane, adjusting the lipid metabolic disturbance of liver, regulating immune function, anti-liver fibrosis and promoting the intrahepatic metabolism of alcohol.</p>
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Drugs, Chinese Herbal , Therapeutic Uses , Fatty Liver, Alcoholic , Drug Therapy , Liver Cirrhosis, Alcoholic , Drug Therapy , Liver Diseases, Alcoholic , Drug Therapy , PhytotherapyABSTRACT
Objective To study the immune protective effects of liver graft on intestinal graft in simultaneous liver/small bowel transplantation. Method Rat models(Wistar to SD) of liver/small bowel transplantation(LSBTx),single liver transplantation(LTx)and single small bowel transplantation(SBTx) were established respectively. Twelve recipients from each group were used to determine survival time. Six recipients from each group were sacrificed for liver and/or small bowel biopsy at posttransplantation day 5,7 and 14,respectively. Rejections were detected by histopathology and mRNA expression of IL-2,IL-4,perforin and granzyme B in grafts by semi-quantitative reverse transcript PCR. Result The survival time of LSBTx recipients was (27.83?4.47) d,much longer than SBTx recipients (11.58?3.26) d,but was similar to LTx recipients (28.92?2.39) d. Allograft rejections of intestinal graft in LSBTx group were milder than that in STBx group,accompanied by down-regulated mRNA expression of perforin and granzyme B. Conclusion Simultaneous liver/small bowel transplantation in rats provides immune protection on intestinal graft.