1.Risk factors analysis of deep vein thrombosis in patients with hip fracture
Fang DONG ; Deqiang LIU ; Anli ZHU ; Mengpo FAN ; Zhizhen WANG
Chinese Journal of Primary Medicine and Pharmacy 2014;21(18):2733-2735
Objective To analyze the characteristics and risk factors of preoperative deep vein thrombosis in patients with hip fracture,and provide a theoretical basis for clinical treatment and intervention.Methods 470 patients with hip fracture were chosen as the objects of study.The clinical data of the patients were retrospectively analyzed,including age,gender,injury,combined with other systemic diseases,fracture type (whether old fractures),two D-dimer level.All the patients with deep venous thrombosis of lower extremity were divided into DVT group and nonDVT group.There were 83 cases in DVT group,387 cases in non-DVT group.The factors like aboves as independent variables,presence of deep vein thrombosis as dependent variable,,preoperative deep venous thrombosis of the characteristics and risk factors were analyzed.Results 83 patients had DVT,the incidence rate was 17.7%.There were significant difference in age (40/83 vs 268/387),combined with other system diseases (57/83 vs 283/387),prevention measures (58/83 vs 196/387),D-thrombosis two dimer level (16/83 vs 122/387) of the two groups (x2 =13.712,14.836,9.876,5.313,all P < 0.05).3 age ≥ 40 years,with other system diseases and injury,did not take to prevent the formation of thrombus measures were independent risk factors influencing the occurrence of DVT.Conclusion Age ≥40 years,combined with other system diseases and injury,don't take to prevent the formation of thrombus measures are independent risk factors influencing the occurrence of DVT.
2.Inhibitory effects of intervention of the TNFa/NF-kappaB signaling pathway activation on hepatoma cell proliferation.
Xing GU ; Min YAO ; Siye WANG ; Yun SHI ; Zhizhen DONG ; Liwei QIU ; Dengfu YAO
Chinese Journal of Hepatology 2014;22(6):434-439
OBJECTIVETo investigate the inhibitory effects of intervention of the tumor necrosis factor-alpha (TNFa)/nuclear factor-kappa B (NF-kappaB) signaling pathway activation on hepatoma cell proliferation and to explore its mechanism.
METHODSA rodent hepatoma model was established by feeding N-2-fluorenylacetamide (2-N-FAA) to male Sprague-Dawley rats. Human subjects with various liver diseases were enrolled in the study, and serum and peripheral blood nuclear cells were collected for analysis. HepG2 cells were cultured in vitro and treated with anti-TNFa (monoclonal antibody, mAb) to down-regulate its expression or transfected with siRNA targeting the p65 subunit of NF-kappaB to inhibit its activation. The liver cell line L02 was used as a control. Changes in protein and gene expression levels of NF-kappaB and TNFa were analyzed by Western blotting or enzyme-linked immunosorbent assay and real-time PCR, respectively. Changes in the cell cycle or apoptosis were evaluated by flow cytometry or Annexin-V/PI double-labeling assay, respectively.
RESULTSTNFa and NF-kappaB expression showed increasing trends during the malignant transformation of rat hepatocytes, and the differential expression patterns showed association with histopathological alterations in the hepatocytes. Following treatment with the TNFa mAb, the HepG2 cells showed a higher percentage of apoptotic cells than the untreated control cells (21.45% +/- 4.07% vs. 5.63% +/- 0.93%, q =10.07, P less than 0.01).There was a significant difference in the rate of cells in the G0/G1 phase in the p65-siRNA transfected cells (66.23% +/- 1.29% vs. untreated control cells: 59.00% +/- 1.02%, q =10.98, P less than 0.01). The decreased expression of TNFa and NF-kappaB in cell culture supernatants was positively correlated with the dose of treatment (r =0.89, P less than 0.01), with the most robust decreases being achieved with the highest concentrations ( P less than 0.01). NF-kappaB expression was significantly higher in the HepG2 cells than in the L02 cells, and transfection of p65-siRNA reduced the mRNA (93%) and protein (62%) levels and increased the cell apoptosis index (to 85%).
CONCLUSIONProliferation of hepatoma cells may be significantly inhibited by intervening in the activation of the TNFa/NF-kappaB signaling pathway, which promotes cell apoptosis and blocks cell cycling.
Adult ; Aged ; Animals ; Apoptosis ; Carcinoma, Hepatocellular ; pathology ; Cell Proliferation ; Female ; Hep G2 Cells ; Hepatocytes ; metabolism ; Humans ; Liver Neoplasms ; pathology ; Male ; Middle Aged ; NF-kappa B ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Transfection ; Tumor Necrosis Factor-alpha ; metabolism
3.Exploring the Mechanism and Experimental Verification of Alhagi Sparsifolia Shap.in Treating Sepsis Based on Network Pharmacology
Zhizhen ZOU ; Xiling DENG ; Yunlai WANG ; Jie ZHANG ; Jiangtao DONG ; Xiaoling LIU ; Su LIANG ; Ju WANG ; Hui ZHANG ; Jiangdong WU ; Le ZHANG ; Fang WU ; Wanjiang ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(9):3024-3036
Objective Network pharmacology and molecular docking and molecular dynamics techniques were used to investigate the mechanism of action of Alhagi sparsifolia Shap.in the treatment of sepsis and to perform animal experimental verification.Methods First,we screened the effective ingredients and their action targets of Alhagi sparsifolia Shap.,meanwhile,screened relevant action targets for the treatment of sepsis,constructed a protein interaction(PPI)network,and performed topology analysis to draw a TCM disease target network diagram.Second,Kyoto Encyclopedia of genes and genomes enrichment analysis was performed for core targets in the network diagram,along with gene ontology functional enrichment analysis.This was followed by molecular docking and molecular dynamics simulation experiment validation of the core targets.Finally,mice were used for the verification of animal experiments.Results Thirty active components of Alhagi sparsifolia Shap.were screened out,and the top 5 ranked by degree value were quercetin,(-)-epigallocatechin,(-)-Epigallocatechin Gallate,genistein,kaempferol and epigallocatechin with 196 action targets;2144 disease-related targets for sepsis,105 targets for Alhagi sparsifolia Shap.-sepsis intersection,and the core targets were TNF,IL-6,AKT1,VEGFA,CASP3,IL-1β Et al.PI3K-Akt,TNF,HIF-1,AGE-RAGE,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert therapeutic effects on sepsis.Molecular docking results showed that camelina flavanoids bound equally well to each key target,among which the conformations with the lowest binding energy were(-)-Epigallocatechin Gallate-IL-6 and quercetin-IL-6.Molecular dynamics simulations were performed on the two pairs of complexes,and the results indicated that the stable binding could be achieved through a combination of electrostatic,van der Waals potential,and hydrogen bonding interactions.Animal experiments confirmed that Alhagi sparsifolia Shap.could inhibit the activation of PI3K/Akt signaling pathway,decrease the protein expression of Caspase-3,VEGF and reduced peripheral blood inflammatory factors secretion of TNF-α、IL-1βand IL-6,alleviating inflammatory injury in tissues and organs.Conclusion The therapeutic effect of Alhagi sparsifolia Shap.on sepsis is achieved through multi biological processes,multi targets,and multi pathways.It provides a certain theoretical basis for the clinical application of camel spines as well as sepsis treatment.
4. Clinical application of high mobility group box nuclear protein 1 subcomponent in the progression of liver cancer
Zhizhen DONG ; Min YAO ; Wenjie ZHENG ; Dengfu YAO
Chinese Journal of Hepatology 2018;26(11):869-872
The biological functions of high-mobility group (HMG) proteins include regulation of DNA replication, transcription, recombination and repair. According to molecular weight, sequence alignment and DNA structural characteristics, HMG proteins are subdivided into three superfamilies (HMGA, HMGB and HMGN). Recently, HMGB family members (HMGB1, HMGB2, HMGB3, and HMGB4) found to interact with hepatitis B or C virus. Therefore, activation of relevant signaling molecules to regulate transcription of genes related to hepatocellular carcinoma as a mediator of inflammation promoting HCC progression has attracted considerable attentions. This article focuses on the clinical application of the expression of HMGB family members in the process of HCC progression.
5. Molecular markers for the monitoring of malignant transformation of hepatocytes and early diagnosis of liver cancer
Yan YANG ; Min YAO ; Miao FANG ; Wenjie ZHENG ; Zhizhen DONG ; Dengfu YAO
Chinese Journal of Hepatology 2017;25(5):325-328
The monitoring of malignant transformation of hepatocytes or early diagnosis of primary hepatocellular carcinoma (PHC) remains a challenge in the medical world. Routine examinations including serum alpha-fetoprotein level and ultrasound examination have a limited value in the diagnosis of small hepatocellular carcinoma; however, the effective treatment of PHC depends on its early diagnosis. In recent years, molecular markers including important signaling molecules in PHC-related pathways, carcinoembryonic proteins, and non-coding RNA help with the monitoring of malignant transformation of hepatocytes or early diagnosis of liver cancer. This article reviews the valuable molecular markers in the monitoring of malignant transformation of hepatocytes or early diagnosis of liver cancer.
6. Dynamic expression of carnitine palmitoyltransferase II in the mitochondrial inner membrane during hepatocyte malignant transformation induced by lipid accumulation
Juanjuan GU ; Min YAO ; Yin CAI ; Miao FANG ; Li WANG ; Wenjie ZHENG ; Dengbing YAO ; Zhizhen DONG ; Dengfu YAO
Chinese Journal of Hepatology 2017;25(4):279-284
Objective:
To investigate the dynamic expression of hepatic carnitine palmitoyltransferase-II (CPT-II) in the mitochondrial inner membrane during hepatocyte malignant transformation induced by lipid accumulation.
Methods:
Male Sprague-Dawley rats were divided randomly into control, fatty liver, and induced cancer groups, which were fed with normal, high-fat (HF), and HF containing 2-fluorenylacetamide (0.05%, 2-FAA) diets, respectively, for 14 weeks. One rat from each group was sacrificed every two weeks and the blood and liver samples were collected. Liver morphological changes were evaluated with hematoxylin and eosin staining, and the liver tissue samples were divided into control, fatty liver, degeneration, precancerous, and cancerous groups accordingly. Hepatic lipids were dyed by the oil red O method. The CPT-II expression was measured by immunohistochemistry and compared with the specific CPT-II concentration (ng/mg liver protein, ng/mg P) among different groups. Serum levels of circulating total cholesterol (Tch), triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were quantitatively analyzed.
Results:
Massive lipid accumulation hepatocytes was seen in rats on HF and HF containing 2-FAA diets. The lipid levels in the control group were significantly lower than those in the fatty liver (
7. Abnormal expression of Wnt3a and inhibiting role of its molecular-targeted intervening in hepatocellular carcinoma
Wenli SAI ; Min YAO ; Wenjie ZHENG ; Mengna WU ; Jianying SUN ; Liuhong PAN ; Zhizhen DONG ; Dengfu YAO
Chinese Journal of Hepatology 2019;27(11):866-871
Objective:
To investigate the Wnt3a expression in tissues of HCC and its gene knockout on effects of HepG2 cell proliferation or xenograft tumor growth.
Methods:
Hepatic Wnt3a expressions in 87 HCC and their matched surrounding tissues were observed by tissue microarray and immunohistochemistry for analyzing its clinicopathological characteristics; Wnt3a-knockout HepG2 cell lines were established by Crispr/cas9-sgRNA system and genomic cleavage efficiency was verified at gene level by surveyor assay. The relative proteins were confirmed by Western blotting; Cell Counting Kit-8 assay was used to examine cell proliferation after knocking-out Wnt3a successfully, and the nude mice HepG2 cell xenograft tumors delete that the relationship between Wnt3a and HCC growth.
Results:
The positive Wnt3a with brown staining particles was mainly distributed in cytosol and membrane of hepatocytes. The incidence of hepatic Wnt3a expression in cancerous tissues (95.4%) was significantly higher (
8. Advances in basic and clinical research on hepatocellular carcinoma in 2016
Zhizhen DONG ; Xiaodong ZHU ; Zhao LI ; Yuge MAO ; Yuelong CHAI ; Dengfu YAO ; Huichuan SUN ; Jiye ZHU ; Kuansheng MA
Chinese Journal of Hepatology 2017;25(2):85-93
Hepatocellular carcinoma (HCC) is still one of common malignant cancers worldwide, with increasing incidence and mortality rates. Early diagnosis and effective treatment for HCC remain to be explored. This article introduces the research advances in the early specific diagnosis and effective therapies for HCC in 2016, such as molecular markers in the specific diagnosis and targeted therapy for HCC, main therapeutic regimens, robot-assisted liver resection, and no-touch radiofrequency ablation.