1.Research progress in medical treatment of primary biliary cirrhosis
Journal of Clinical Hepatology 2014;31(5):462-465
Primary biliary cirrhosis (PBC)is an autoimmune disease.Ursodeoxycholic acid (UDCA)is the only safe and effective drug for the treatment of PBC,as proved by randomized controlled clinical trials,so it is advocated as first-line therapy.Alternative therapies are urgently needed for patients with poor response to UDCA.In addition to the efficacy of UDCA,the classification of alternative and adjuvant therapies for UDCA nonresponders and the latest research progress in these therapies are reviewed;the efficacy of existing drugs and treat-ment prospects are evaluated,but more long-term clinical studies are needed to confirm the efficacy of immunosuppressants such as budes-onide and etanercept and other drugs.A number of novel molecular therapies for PBC are also undergoing clinical trials.There is currently no consensus on the medical treatment for patients with poor response to UDCA.Although studies have shown that some drugs can improve liver function and liver biochemistries,there is no definitive evidence that they improve long-term outcome.
2.Survey on medical interns’clinical practice
Ying WU ; Junkai WANG ; Dingkang YAO ; Liang ZHU
Chinese Journal of Medical Education Research 2003;0(02):-
To improve the quality of clinical practice education,questionnaires were distributed to the medical interns. Corresponding responses were proposed based on humanities quality,quality of clinical practice and its factors,views on after-department examination and training for clinical skill. The result shows most of students realized the importance of clinical practice. After reformation for clinical education,after-department examination could efficiently improve interns’ability to resolve practical problems. Management of teachers,development of students’clinical thinking and ability of communication between doctor and patient should be enhanced .
3.Clinical analysis of 22 patients with primary biliary cirrhosis.
Dingkang YAO ; Weifen XIE ; Lei WANG
Chinese Journal of Hepatology 2002;10(5):344-345
OBJECTIVETo improve the diagnosis and management of primary biliary cirrhosis (PBC).
METHODSClinical data of 22 cases of PBC were reviewed including the clinical manifestation, laboratory test, and the response to therapy.
RESULTSThere were 20 female patients with an average of 50 years old in total of 22 PBC patients. The major symptoms were pruritus, fatigue, anorexia, and abdominal discomfort. The major signs included jaundice, hepatomegaly, splenmegaly, and ascites. Very high levels of serum alkaline phosphatase (ALP) and serum gamma glutamyl transpeptidase (GGT), hyperbilirubinemia and hypergammaglobulinemia were also detected in most of the patients. The aminotransferase level was only slightly elevated but the AST/ALT ratio was reversed. It took 8 months (ranging from 2 months to 5 years) to confirm the diagnosis after the clinical manifestation onset. Ursodeoxycholic acid could decrease the serum levels of ALP and bilirubin in 80% of the patients (12/15) and improve the symptom of pruritus and fatigue in 72.7% of the patients (11/15).
CONCLUSIONSPBC mainly affects middle-aged women and the main clinical manifestations are hepatosplenomegaly, jaundice, pruritus, and fatigue. Liver function test typically reveal a cholestatic pattern accompanied by hypergammagloblinemia and a positive antimitochondrial antibody (AMA) including M2 subtype (AMA-M2). Ursodeoxycholic acid could improve the abnormal liver function tests and clinical features in PBC patients
Alkaline Phosphatase ; Bilirubin ; Cholestasis ; Female ; Hepatomegaly ; Humans ; Liver Cirrhosis, Biliary ; metabolism ; physiopathology ; Liver Function Tests ; Male ; Middle Aged ; Ursodeoxycholic Acid
4.Potential Serum Markers for Monitoring the Progression of Hepatitis B Virus-Associated Chronic Hepatic Lesions to Liver Cirrhosis.
Cheng WU ; Lijie LIU ; Peng ZHAO ; Dan TANG ; Dingkang YAO ; Liang ZHU ; Zhiqiang WANG
Gut and Liver 2015;9(5):665-671
BACKGROUND/AIMS: To screen for serum protein/peptide biomarkers of hepatitis B virus (HBV)-associated chronic hepatic lesions in an attempt to profile the progression of HBV-associated chronic hepatic lesions using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) techniques. METHODS: Using SELDI-TOF MS, serum protein/peptide profiles on the CM10 ProteinChip arrays were obtained from a training group including 26 HBV-associated hepatocellular carcinoma patients with liver cirrhosis (LC), 30 HBV-associated LC patients, 85 patients at different stages of liver fibrosis, and 30 asymptomatic HBV carriers. The most valuable SELDI peak for predicting the progression to LC in HBV-infected patients was identified. RESULTS: A SELDI peak of M/Z 5805 with value for predicting LC in HBV-infected patients was found and was identified as a peptide of the C-terminal fraction of the fibrinogen alpha-chain precursor, isoform 1. CONCLUSIONS: The peptide of the C-terminal fraction of the fibrinogen alpha-chain precursor, isoform 1 with M/Z 5805, may be a serological biomarker for progression to LC in HBV-infected patients.
Adult
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Aged
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Biomarkers/*blood
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Carcinoma, Hepatocellular/*virology
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Disease Progression
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Female
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Hepatitis B virus
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Hepatitis B, Chronic/*blood/complications
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Humans
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Liver Cirrhosis/*blood/pathology/virology
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Liver Neoplasms/*virology
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Male
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Middle Aged
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Protein Array Analysis
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Young Adult
5.Dynamic expression of tenascin in rat liver during liver fibrogenesis induced by CCl(4).
Dingkang YAO ; Shi LI ; Xiantao KONG ; Tingjun YE ; Jiangao FAN ; Lan ZHONG ; Guoliang WANG ; Liyan TIAN ; Wensen WU ; Mingsheng LI
Chinese Journal of Hepatology 2002;10(1):40-42
OBJECTIVETo study the expression of tenascin in normal and fibrotic rat liver.
METHODSLiver fibrosis induced in rat with CCl(4) were divided into three stages: the stage of hepatic injury (4 weeks), early stage of hepatic fibrosis (8 weeks) and later stage of hepatic fibrosis (12 weeks). Tenascin expression in liver tissue was observed by immunohistochemical method and in situ hybridization using digoxigenin-labelled DNA probe.
RESULTSIn normal rat liver there was a weak staining for tenascin. In both liver injury stage and early stage of hepatic fibrosis, both mRNA signal and immunostaining for tenascin were significantly increased as compared to that in normal liver. In later stage of hepatic fibrosis, mRNA signal and immunostaining for tenascin were decreased compared with that in early stage of hepatic fibrosis. The cellular source of tenascin in liver mainly restricted in mesenchymal cells.
CONCLUSIONSTenascin is a component of the extracellular matrix of liver tissue. Plays a role in early matrix organization during liver fibrogenesis.
Animals ; Carbon Tetrachloride ; Disease Models, Animal ; Extracellular Matrix Proteins ; biosynthesis ; genetics ; Image Processing, Computer-Assisted ; Immunohistochemistry ; In Situ Hybridization ; Liver Cirrhosis ; chemically induced ; metabolism ; Male ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Tenascin ; biosynthesis ; genetics
6.Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner.
Cancan ZHENG ; Xiaomei YU ; Yiyao LIANG ; Yidong ZHU ; Yan HE ; Long LIAO ; Dingkang WANG ; Yanming YANG ; Xingfeng YIN ; Ang LI ; Qingyu HE ; Bin LI
Acta Pharmaceutica Sinica B 2022;12(3):1271-1287
As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.