OBJECTIVETo investigate the inhibitory activities of norcantharidin (NCTD), a demethylated analogue of cantharidin, on Hep3B cells (a human hepatoma cell line) with deficiency of p53.

METHODSThe survival rate of the Hep3B cells after treating with NCTD was measured by MTT assay. Cell cycle of treated cells was analyzed by flow cytometry, and DNA fragmentation was observed by electrophoresis. The influence of inhibitors for various caspases and anti-death receptors antibodies on the NCTD-induced apoptosis in the cells was determined.

RESULTSNCTD treatment resulted in growth inhibition of Hep3B cells in a dose- and time-dependent manner. Cell cycle analysis of the cells after treatment with NCTD for 48 h shows that NCTD induced G(2)M phase arrest occurs at low concentration ([Symbol: see text] 25 μmol/L) but G(0)G(1) phase arrest at high concentration (50 μmol/L). The addition of both caspase-3 and caspase-10 inhibitors completely inhibited DNA fragmentation. Addition of anti-TRAIL/DR5 antibody significantly inhibited DNA fragmentation.

CONCLUSIONNCTD may inhibit the proliferation of Hep3B cells by arresting cell cycle at G(2)M or G(0)G(1) phase, and induce cells apoptosis via TRAIL/DR5 signal transduction through activation of caspase-3 and caspase-10 by a p53-independent pathway.

Antibodies, Neoplasm ; pharmacology ; Antibodies, Neutralizing ; pharmacology ; Apoptosis ; drug effects ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Caspase 10 ; metabolism ; Caspase 3 ; metabolism ; Caspase Inhibitors ; pharmacology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Fragmentation ; drug effects ; Humans ; Immunohistochemistry ; Liver Neoplasms ; enzymology ; pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Signal Transduction ; drug effects ; TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

BACKGROUNDThe public vaccination program of hepatitis B virus (HBV) was launched during 1984 in Taiwan, China. However, the long-lasting protective efficacy of HBV vaccination among adolescents older than 15 years of age was seldom recorded.

METHODSA seroepidemiological survey was conducted among 4575 first-year university students in Taiwan, China during 2000 to 2003, including the serological data of HBV by testing HBV surface antigen (HBsAg), surface antibody (anti-HBs), HBV core antibody (anti-HBc) and demographic information.

RESULTSHBsAg carrier rate among male university students born before the initiation of the HBV vaccination program decreased from 12.8% to 4.8% among those born after the vaccination program (P < 0.001, chi(2) test for linear trend). Similarly, HBsAg carrier rate among female university students born before the initiation of the HBV vaccination program decreased from 8.1% to 2.7% among those born after the vaccination program (P < 0.001, chi(2) test for linear trend). Both male and female students in eastern Taiwan had the highest HBsAg carrier rate compared with the other places. Using multiple logistic regression analysis, compared with students born after July 1984, the adjusted OR of HBsAg carrier rate decreased from 3.10 for students born before June 1981 to 1.56 for students born from July 1983 to June 1984 (95% CI 1.96 - 4.91, P < 0.001; 95% CI 1.06 - 2.28, P = 0.024; respectively).

CONCLUSIONSPublic vaccination provides long-lasting protection again HBV infection among the university students in Taiwan, China older than 18 years of age. There is a geographic variation of HBV infection among young adults in Taiwan, China.

Adolescent ; Adult ; Carrier State ; epidemiology ; Female ; Hepatitis B ; epidemiology ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; immunology ; Humans ; Male ; Mass Vaccination ; Taiwan ; epidemiology ; Time Factors

Most haemoglobin (Hb) variants are clinically silent. However, some Hb variants may interfere with the measurement of haemoglobin A1c (HbA1c), resulting in spurious values depending on the assays used. We herein report the case of a 53-year-old Taiwanese man with type 2 diabetes mellitus, who presented with an abnormal HbA1c peak on ion-exchange chromatography. Additional investigations, including intensified self-monitored blood glucose tests, an alternative HbA1c assay, and a glycaemic indicator based on a different method, revealed that the HbA1c values were falsely elevated. Subsequent DNA analysis confirmed that the patient was heterozygous for the insertion of an isoleucine residue at codons 117/118 of the a1-globin gene, Hb Phnom Penh. Clinical laboratorians should be aware of the interfering factors in their HbA1c analysis. Cautious inspection of the chromatogram may provide a valuable clue to the presence of an Hb variant.
Chromatography, High Pressure Liquid ; Chromatography, Ion Exchange ; Diabetes Complications ; blood ; Diabetes Mellitus, Type 2 ; blood ; complications ; Dyslipidemias ; blood ; complications ; Hemoglobins, Abnormal ; analysis ; Humans ; Hypertension ; blood ; complications ; Hypoglycemia ; blood ; Male ; Middle Aged ; Reproducibility of Results ; Sequence Analysis, DNA ; Taiwan

Adult ; Bone Neoplasms ; diagnosis ; pathology ; Chondrosarcoma ; diagnosis ; pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Mediastinal Neoplasms ; diagnosis ; pathology ; Neurilemmoma ; diagnosis ; pathology ; Peripheral Nervous System Neoplasms ; diagnosis ; pathology ; Phrenic Nerve ; Ribs ; Tomography, X-Ray Computed

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.