[The predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure].

Objective: To determine the predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure. Methods: Patients with acute-on-chronic hepatitis B liver failure who were hospitalized in the Department of Hepatology of Qilu Hospital of Shandong University from January 2010 to July 2023 were retrospectively enrolled. According to the clinical outcomes of patients within 30 days of admission, they were divided into the survival group and the death group. The dynamic changes in NLR and initial values on day 3, 5, 8, and 12 in two groups were analyzed for the diagnostic value of 30-day prognosis in patients with acute-on-chronic hepatitis B liver failure. Logistic regression analysis and machine learning XGBoost algorithm were used to evaluate the risk factors influencing the prognosis of patients at 30 days. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of NLR and initial value change combined with MELD score on day 12 of admission in patients with chronic acute hepatitis B liver failure. Results: A total of 243 patients were enrolled in the study, including 145 patients in the survival group [115 males, 30 females, aged 25-74 (47±11)] and 98 patients in the death group [80 males, 18 females, aged 22-80 (49±13) ]. The median initial NLR of survival group and death group were 3.5 (2.1, 5.3) and 4.9 (2.9, 8.3), respectively, and the difference was statistically significant (P=0.003). The variation of NLR from the initial value on day 3, 5, 8, and 12 in the survival group [1.6 (0, 4.3), 1.9 (-0.2, 4.1), 2.0 (-0.1, 4.3) and 2.9 (0.3, 7.0), respectively] were lower than that in the death group [3.2 (0.9, 7.5), 5.1 (1.8, 7.6), 5.8 (2.0, 10.6) and 9.6 (3.5, 16.4), respectively] (all P<0.001). Logistic regression multivariate analysis showed that the changes in NLR on the 12th day and initial value (OR=1.07,95%CI:1.01-1.14, P=0.014), the changes in NLR on the 3rd day and initial value (OR=2.71, 95%CI: 1.32-5.55, P=0.007), the initial value of NLR (OR=1.18,95%CI:1.01-1.37,P=0.035) and fibrinogen (OR=0.21,95%CI:0.05-0.96,P=0.044) were related factors for death within 30 days. Machine learning XGBoost algorithm showed that the weight of the change between the NLR on the 12th day and the initial value was the highest. The area under the ROC curve of the combined MELD score was 0.812 (95%CI: 0.728-0.895), the specificity was 67.78%, and the sensitivity was 82.35%. Conclusion: Dynamic change of NLR combined with MELD score has high predictive value for the short-term prognosis of patients with acute-on-chronic hepatitis B liver failure.

[Efficacy and safety of Anlotinib in the treatment of advanced sarcoma].

Objective: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. The purpose of this study was to evaluate the efficacy and safety of anlotinib in the treatment of advanced sarcoma and to explore the relationship between adverse events (AEs) and efficacy. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and August 2021 were retrospectively analyzed. According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, the objective remission rate (ORR) and disease control rate (DCR) were calculated, and the progression free survival (PFS) and treatment-related AEs were recorded and analyzed. Survival analysis was conducted using the Kaplan-Meier survival rates were compared using the Log rank test. Results: Forty patients were treated for more than 1.5 months and received efficacy evaluation. The ORR and DCR after 3 months were 7.5%(3/40) and 80.0%(32/40), respectively. The overall ORR was 2.5%(1/40), the total DCR was 27.5%(11/40), and the median progression-free survival (m-PFS) was 6.70 months; The m-PFS of alveolar soft tissue sarcoma (ASPS) was 10.27 months, which was significantly longer than that of other subtypes of sarcoma (P=0.048). In addition, the DCR of ASPS and synovial sarcoma (SS) was significantly better than that of osteosarcoma (P<0.05). The most common AEs were elevated thyroid stimulating hormone (17.8%, 8/45), anemia (15.6%, 7/45), fatigue (11.1%, 5/45). Five patients developed grade 3 AEs after treatment; The PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (14.10 vs 6.00, P=0.024). Conclusions: The efficacy of anlotinib in the treatment of ASPS and SS is better than that of other subtypes. The PFS in the group with hand-foot syndrome was significantly longer than that of the group without hand-foot syndrome.

Change in smoking behaviour of people who suffer from respiratory disease.

OBJECTIVE: To analyse smoking behaviour in patients suffering from non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD) and pulmonary TB (PTB).METHODS: The study population comprised 421 inpatients newly diagnosed with NSCLC, COPD and PTB at the First Affiliated Hospital of Chongqing Medical University, Chongqing, China, and 362 healthy individuals (controls) recruited from September 2016 to March 2017. All participants were current smokers. After enrolment, the subjects were invited to participate in face-to-face interviews to complete the self-designed questionnaire. A follow-up survey was performed 2 years later.RESULTS: Two years after being diagnosed, patients with NSCLC, COPD and PTB had smoking cessation rates of respectively 76.8%, 62.8% and 63.7%. The cessation rate was only 10.2% in the control group (P < 0.01). The difficulty of smoking cessation after diagnosis in patients with the three diseases was significantly decreased (P < 0.01).CONCLUSION: The smoking cessation rate among participants suffering from NSCLC, COPD and PTB increased after diagnosis compared with that before diagnosis, and was significantly higher than the control group of healthy individuals.

Biological Characteristics and Molecular Mechanisms of Fludioxonil Resistance in Fusarium graminearum in China.

Fusarium graminearum is the primary causal agent of Fusarium head blight (FHB) of wheat. The phenylpyrrole fungicide fludioxonil is not currently registered for the management of FHB in China. The current study assessed the fludioxonil sensitivity of a total of 53 F. graminearum isolates collected from the six most important wheat-growing provinces of China during 2018 and 2019. The baseline fludioxonil sensitivity distribution indicated that all of the isolates were sensitive, exhibiting a unimodal cure with a mean effective concentration for 50% inhibition value of 0.13 ± 0.12 µg/ml (standard deviation). Five fludioxonil-resistant mutants were subsequently induced by exposure to fludioxonil under laboratory conditions. Ten successive rounds of subculture in the absence of the selection pressure indicated that the mutation was stably inherited. However, the fludioxonil-resistant mutants were found to have reduced pathogenicity, higher glycerol accumulation, and higher osmotic sensitivity than the parental wild-type isolates, indicating that there was a fitness cost associated with fludioxonil resistance. In addition, the study also found a positive cross resistance between fludioxonil, procymidone, and iprodione, but not with other fungicides such as boscalid, carbendazim, tebuconazole, and fluazinam. Sequence analysis of four candidate target genes (FgOs1, FgOs2, FgOs4, and FgOs5) revealed that the HBXT2R mutant contained two point mutations that resulted in amino acid changes at K223T and K415R in its FgOs1 protein, and one point mutation at residue 520 of its FgOs5 protein that resulted in a premature stop codon. Similarly, the three other mutants contained point mutations that resulted in changes at the K192R, K293R, and K411R residues of the FgOs5 protein but none in the FgOs2 and FgOs4 genes. However, it is important to point out that the FgOs2 and FgOs4 expression of all the fludioxonil-resistant mutants was significantly (P < 0.05) downregulated compared with the sensitive isolates (except for the SQ1-2 isolate). It was also found that one of the resistant mutants did not have changes in any of the sequenced target genes, indicating that an alternative mechanism could also lead to fludioxonil resistance.

[Pulmonary vascular remodeling is prior to the increase in pulmonary hypertension of chronic obstructive pulmonary disease].

Objective: To explore the remodeling of pulmonary arterioles in chronic obstructive pulmonary disease (COPD), and its effect on hemorheology of proximal pulmonary arteries, right ventricular structure and function , and the potential mechanisms. Method: A total of 34 patients undergoing surgical treatment for lung tumors admitted to the General Hospital of Ningxia Medical University were included in the study. According to the preoperative lung function, there were 15 patients with COPD complicated with lung tumor (COPD group) and 19 patients with normal pulmonary function with lung tumor (control group). All patients underwent cardiac nuclear magnetic resonance (CMR) before surgery, and the hemorheology of the proximal pulmonary arteries, right ventricular structure and function were obtained by CMR. The normal lung tissues distal to the tumor lesion were taken during the operation, and the morphological changes of the pulmonary arterioles were observed by hematoxylin-eosin staining and Weigert-van Gieson. Immunohistochemistry was used to detect the location and expression of α-smooth muscle actin(SMA) and proliferating cell nuclear antigen(PCNA) in pulmonary arterioles, and the expression of protein and mRNA of α-SMA in lung tissue was detected by Western-blotting and real-time quantitative PCR. Results: The results of CMR showed that mPAP was not statistically different between COPD group and control group (24.0±3.7 vs 22.8±1.6, P>0.05). The main pulmonary artery distensibility (mPAD%), right ventricular myocardial mass end-diastolic (RVMED), right ventricular myocardial mass end-systolic (RVMES), average negative flow(ANF) and regurgitant fraction(RF%) were statistically different between COPD group and control group (P<0.05). The wall thickness (WT), WT% and WA% were significantly higher in COPD group [(37±18) µm, (65±19)% and (55±23)%, respectively] than in control group [(19±3 )µm, (29±5)% and (40±7)%, respectively]. The number of pulmonary arterial smooth muscle cells per unit area and smooth muscle cell proliferation rate were significantly higher in COPD group than in the control group(P<0.01). The expression of α-SMA protein and mRNA in COPD group was higher than that in control group(P<0.05). WA% and WT% were correlated inversely with mPAD%, but positively with RVMES, RVMED and RF%. Conclusions: Pulmonary vascular remodeling and rheological changes, even right heart myocardial structural changes, were observed in COPD patients without pulmonary arterial hypertension. Pulmonary arteriolar remodeling can affect the main pulmonary arterial hemorheology in COPD patients and further affect the myocardial structure of right heart. Pulmonary arterial remodeling may be a new direction for the clinical treatment of COPD.

Methylation of SOX1 and VIM promoters in serum as potential biomarkers for hepatocellular carcinoma.

Aberrant methylation of tumor-related genes has been identified as a promising biomarker for hepatocellular carcinoma (HCC). This study aimed to investigate the diagnostic value of SRY (sex determining region Y)-box 1 (SOX1) and Vimentin (VIM) promoter methylation for HCC. The study included 360 subjects, 240 patients with HCC, 29 with liver cirrhosis (LC), 66 with chronic hepatitis B (CHB) and 25 healthy controls (HCs). The methylation status of SOX1 and VIM promoters in the serum was detected by methylation-specific polymerase chain reaction (MSP). The methylation frequencies of SOX1 and VIM promoters in HCC patients were significantly higher than those in LC (p<0.001 and p<0.001), CHB (p<0.001 and p<0.001) and HC (p<0.001 and p<0.001) subjects. Furthermore, hypermethylation of SOX1 and VIM promoters were found in patients with advanced TNM stage (III-IV) and larger tumor size (≥5 cm) compared with early stage (I-II) (p<0.001 and p=0.004) patients with smaller tumor size (<3 cm) (p=0.018 and p=0.001). Moreover, the VIM promoter methylation frequency was higher in patients with portal vein tumor thrombosis (PVTT) (p=0.006) and vascular invasion (p=0.003). In addition, the combination of α-fetoprotein (≥20 ng/ml) with SOX1 and VIM promoter methylation significantly improved their diagnostic value. In conclusions, aberrant methylation of SOX1 and VIM promoters may be potential biomarkers for noninvasive detection of HCC and HCC metastasis.

Long-term allopurinol use decreases the risk of prostate cancer in patients with gout: a population-based study.

BACKGROUND: Clinical observations indicated an increased risk of developing prostate cancer in gout patients. Chronic inflammation is postulated to be one crucial mechanism for prostate carcinogenesis. Allopurinol, a widely used antigout agent, possesses potent anti-inflammation capacity. We elucidated whether allopurinol decreases the risk of prostate cancer in gout patients. METHODS: We analyzed data retrieved from Taiwan National Health Insurance Database between January 2000 and December 2012. Patients diagnosed with gout during the study period with no history of prostate cancer and who had never used allopurinol were selected. Four allopurinol use cohorts (that is, allopurinol use (>365 days), allopurinol use (181-365 days), allopurinol use (91-180 days) and allopurinol use (31-90 days)) and one cohort without using allopurinol (that is, allopurinol use (No)) were included. The study end point was the diagnosis of new-onset prostate cancer. Multivariable Cox proportional hazards regression and propensity score-adjusted Cox regression models were used to estimate the association between the risk of prostate cancer and allopurinol treatment in gout patients after adjusting for potential confounders. RESULTS: A total of 25 770 gout patients (aged between 40 and 100 years) were included. Multivariable Cox regression analyses revealed that the risk of developing prostate cancer in the allopurinol use (>365 days) cohort was significantly lower than the allopurinol use (No) cohort (adjusted hazard ratio (HR)=0.64, 95% confidence interval (CI)=0.45-0.9, P=0.011). After propensity score adjustment, the trend remained the same (adjusted HR=0.66, 95% CI=0.46-0.93, P=0.019). CONCLUSIONS: Long-term (more than 1 year) allopurinol use may associate with a decreased risk of prostate cancer in gout patients.

Relationship between hepatitis B virus reverse transcriptase 181 mutation and S gene mutation in hepatitis B virus chronically infected patients.

This study aims to explore clinical significance of HBV rt181 mutation. Serum samples were collected from 226 CHB patients with no anti-viral treatment, and 72 patients with adefovir dipivoxil treatment over 1 year. HBV genes of reverse transcriptase regions were amplified by nested PCR. HBV DNA in pre-S/S regions sequences were determined by sequencing. Mutations in HBV were characterized by mutational analysis. Results indicated that resistant mutation was found in 16 samples (7.08%) with no anti-viral treatment. It showed higher prevalence in patients with adefovir dipivoxil treated samples 30/72(41.67%). Mutation sites of pre-existing and adefovir dipivoxil induced resistance were different (adefovir dipivoxil induced resistance mode is rtA181T/V, and pre-existing mode is the other). Resistance mutation was found just in genotype C patients. Among 25 containing rtA181T/V mutation patients, 7 rtA181T mutation cases with sW172L, 6 rtA181T mutation cases with sW172*, 12 rtA181Vmutation cases with sL173F. In conclusion, mutation sites of pre-existing and adefovir dipivoxil induced resistance were different. HBV genotype C is prone to occur resistance mutation than genotype B. rtA181T mutation was accompanied with not only sW172 * mutation, but also sW172L mutation, rtA181V mutation was accompanied with sL173F mutation or Pre-S2 initiation codon to termination mutation.

Plasma interleukin-10 predicts short-term mortality of acute-on-chronic hepatitis B liver failure.

BACKGROUND: Interleukin (IL)-10 is a pleiotropic cytokine with anti-inflammatory and immunosuppressive properties in liver failure. Biomarkers are urgently needed to predict prognosis of acute-on-chronic hepatitis B liver failure (ACHBLF). AIM: To investigate the potential diagnostic value of plasma IL-10 as a biomarker for predicting the mortality of ACHBLF. METHODS: This prospective study consisted of 115 newly diagnosed ACHBLF patients from May 2009 to October 2013 as a training cohort and 54 ACHBLF patients from November 2013 to March 2015 as a validating cohort. Plasma IL-10 level was measured using enzyme-linked immunosorbent assay. RESULTS: In the training cohort, the plasma IL-10 level of nonsurvivals [median (centile25; centile75): 12.38 (8.76; 15.52) pg/mL] was significantly higher than that in survivals [6.55 (5.43; 7.65) pg/mL, P < 0.001]. Plasma IL-10 (hazard ratio = 1.205, 95% confidence interval: 1.145-1.267, P < 0.001) was identified as an independent risk factor for mortality of ACHBLF patients. Furthermore, plasma IL-10 showed higher area under the curve of receiver operating characteristic (AUROC) than model for end-stage liver diseases (MELD) for predicting 1-month (0.887 vs. 0.779, P < 0.05), 2-month (0.878 vs. 0.779, P < 0.05) and 3-month (0.917 vs. 0.776, P < 0.001) mortality. However, we did not find significant differences in AUROC between IL-10 and IL-10 plus MELD for 1-, 2- and 3-month mortality. ACHBLF patients with plasma IL-10 > 9.6 pg/mL showed poor survival time than patients with plasma IL-10 ≤ 9.6 pg/mL at the end of 1 month in the training and validation cohorts. CONCLUSIONS: Plasma IL-10 performed better than MELD in predicting the prognosis of acute-on-chronic hepatitis B liver failure. Furthermore, plasma IL-10 > 9.6 pg/mL predicts a poor 1-month mortality.

Serum SOX11 promoter methylation is a novel biomarker for the diagnosis of Hepatitis B virus-related hepatocellular carcinoma.

Promoter methylation of tumor suppressor gene SOX11 has been reported to contribute to the diagnosis and prognosis of various cancerous diseases, including gastric cancer, hematopoietic malignancies and nasopharyngeal carcinoma. However, there is no data on the diagnostic potential of serum SOX11 promoter methylation in hepatocellular carcinoma (HCC). This study was therefore aimed to investigate the potential role of serum SOX11 promoter methylation as a noninvasive biomarker in the diagnosis of patients with hepatitis B virus (HBV) associated HCC. A total of 205 subjects were retrospectively included, which consisted of 111 HCC patients, 66 chronic hepatitis B (CHB) and 28 healthy controls (HCs). Methylation of SOX11 promoter was determined by methylation-specific polymerase chain reaction. The methylation frequency of serum SOX11 promoter in HCC patients (69.4%, 77/111) was significantly higher than that in CHB patients (13.6%, 9/66; χ2 = 51.467, P<0.001) and HCs (10.7%, 3/28; χ2 = 31.489, P<0.001). There was significant difference of serum SOX11 promoter methylation in HCC patients with vascular invasion (49/58) and those without vascular invasion (28/53; χ2 = 13.058, P<0.001). Furthermore, the sensitivity of 69% was identified for SOX11 methylation in discriminating HCC from CHB, which was significant higher than the sensitivity of 57% for serum alpha-fetoprotein (AFP) (P<0.05). Notably, SOX11 promoter methylation plus AFP showed a sensitivity of 85% in discriminating HCC from CHB. These results suggested that serum SOX11 promoter methylation might serve as a useful and noninvasive biomarker for the diagnosis of HCC.

Low-level laser therapy alleviates mechanical and cold allodynia induced by oxaliplatin administration in rats.

PURPOSE: Cold and mechanical allodynia caused by oxaliplatin-induced acute peripheral neuropathy frequently occur after drug infusion. Low-level laser therapy (LLLT) has been used to improve pain symptoms associated with various conditions and may have potential as a therapy for oxaliplatin-induced allodynia. The purpose of the present study was to investigate the antiallodynic effect of LLLT in an oxaliplatin-treated animal model by assessing sensory behavioral responses, levels of nerve growth factor (NGF), and transient receptor potential M8 (TRPM8) in dorsal root ganglia (DRG) neurons, as well as substance P (SP) in the spinal dorsal horn. METHODS: Adult male Sprague-Dawley rats each received a total of four doses of oxaliplatin (4 mg/kg, i.p.), injected at 3-day intervals. Following oxaliplatin administration, LLLT (7.5 J/cm(2)) was applied for 12 consecutive days to the skin surface directly above sites where the sciatic nerve is distributed. Behavioral assessments were then performed, followed by immunoassays for NGF, TRPM8, and SP proteins. RESULTS: LLLT relieved both cold and mechanical allodynia induced by oxaliplatin in rats. Oxaliplatin-related increases in protein levels of NGF and TRPM8 in DRG and SP in the dorsal horn were also reduced after LLLT. CONCLUSION: The findings of this study support LLLT as a potential treatment for oxaliplatin-induced neuropathy. Moreover, our findings suggest that SP, TRPM8, and NGF proteins in the superficial dorsal horn and DRG may be involved in an antiallodynic effect for LLLT.

Up-regulation of A20 gene expression in peripheral blood mononuclear cells is associated with acute-on-chronic hepatitis B liver failure.

Aberrant immunity contributes to the pathogenesis of acute-on-chronic hepatitis B liver failure (ACHBLF), and A20 is a newly identified negative regulatory molecule of the immune response. However, no data have been reported for the role of A20 in ACHBLF. This study aimed to investigate A20 mRNA expression in ACHBLF and to determine the potential of A20 as a biomarker for the prognosis of ACHBLF. Quantitative real-time polymerase chain reaction (qPCR) was used to measure the mRNA expression of A20 in peripheral blood mononuclear cells (PBMCs) from 137 ACHBLF patients, 105 chronic hepatitis B (CHB) and 35 healthy controls (HCs). A secondary cohort with 37 ACHBLF patients was set up as validation data set. The plasma levels of interleukin (IL)-1ß, IL-6 and IL-10 were determined using enzyme-linked immunosorbent assay (ELISA). Receiver-operating characteristic (ROC) curves were used to determine the predictive value of A20 for the prognosis of ACHBLF patients. A20 mRNA expression in ACHBLF was significantly higher compared with CHB and HCs. In ACHBLF patients, A20 mRNA was closely associated with total bilirubin, albumin, international normalized ratio, prothrombin time activity and model for end-stage liver disease. Furthermore, A20 mRNA was significantly correlated with IL-6 and IL-10. An optimal cut-off value of 12.32 for A20 mRNA had significant power in discriminating survival or death in ACHBLF patients. In conclusion, our results suggest that the up-regulation of the A20 gene might contribute to the severity of ACHBLF and A20 mRNA level might be a potential predictor for the prognosis of ACHBLF.

Alternative splicing isoform of T cell factor 4K suppresses the proliferation and metastasis of non-small cell lung cancer cells.

The Wnt pathway has been implicated in the initiation, progression, and metastasis of lung cancer. T cell factor 4, a member of TCF/LEF family, acts as a transcriptional factor for Wnt pathways in lung cancer. Increasing amounts of evidence have shown that TCF-4 has multiple alternative splicing isoforms with transactivation or transrepression activity toward the Wnt pathway. Here, we found the presence of multiple TCF-4 isoforms in lung cancer cell lines and in normal bronchial epithelial cells. TCF-4K isoform expression was significantly decreased in lung cancer cells compared with normal bronchial epithelial cells and was identified as a transcriptional suppressor of the Wnt pathway in non-small cell lung carcinoma (NSCLC). Overexpression of TCF-4K significantly inhibited the proliferation and migration of NSCLC cells. Collectively, our data indicate that TCF-4K functions as a tumor suppressor in NSCLC by down-regulating the Wnt pathway.

Aberrant GSTP1 promoter methylation predicts short-term prognosis in acute-on-chronic hepatitis B liver failure.

BACKGROUND: Glutathione-S-transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute-on-chronic hepatitis B liver failure (ACHBLF). AIM: To evaluate the methylation level of GSTP1 promoter in acute-on-chronic hepatitis B liver failure and determine its predictive value for prognosis. METHODS: One hundred and five patients with acute-on-chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained. RESULTS: GSTP1 methylation levels were significantly higher in patients with acute-on-chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83-59.05%) than those with CHB (median 1.25%, interquartile range 0.48-2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67-1.27%; P < 0.01). In acute-on-chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = -0.24, P = 0.01) and model for end-stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1- or 2-month mortality of acute-on-chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cut-off points showed significantly poorer survival than those below (P < 0.05). CONCLUSIONS: Aberrant GSTP1 promoter methylation exists in acute-on-chronic hepatitis B liver failure and shows high predictive value for short-term mortality. It might serve as a potential prognostic marker for acute-on-chronic hepatitis B liver failure.

Methylation of suppressor of cytokine signalling 1 gene promoter is associated with acute-on-chronic hepatitis B liver failure.

Suppressor of cytokine signalling 1 (SOCS1) was demonstrated to play an important negative role in fulminant hepatitis and might be involved in acute-on-chronic hepatitis B liver failure (ACHBLF). This study was therefore to identify the potential role of SOCS1 and its promoter methylation pattern in ACHBLF patients. Sixty ACHBLF patients, 60 chronic hepatitis B (CHB) patients and 30 healthy controls were investigated in this study. We found that expression of SOCS1 mRNA in CHB and ACHBLF patients was significantly higher than that in healthy controls. The serum level of IL-6, IFN-γ and TNF-α was significantly higher in ACHBLF than CHB. Increased serum level of IL-6, IFN-γ and TNF-α was correlated with total bilirubin, ALT, PTA and MELD scores in ACHBLF. The degree of methylation of the SOCS1 in ACHBLF patients (35.0%, 21/60) was significantly higher than that in CHB patients (16.7%, 10/60). Furthermore, methylated group showed lower level of SOCS1, and higher MELD scores and mortality rate when compared with unmethylated group of ACHBLF. These results suggested that SOCS1 might contribute to immune-related liver damage in ACHBLF, and its aberrant methylation may be a key event for the prognosis of ACHBLF.

Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 predicts prognosis of acute-on-chronic hepatitis B liver failure.

The G-protein-coupled bile acid receptor Gpbar1 (TGR5) has been demonstrated to be able to negatively regulate hepatic inflammatory response. In this study, we aimed to determine the methylation status of TGR5 promoter in patients with acute-on-chronic hepatitis B liver failure (ACHBLF) and its predictive value for prognosis. We enrolled 76 consecutive ACHBLF patients, 80 chronic hepatitis B (CHB) patients and 30 healthy controls (HCs). Methylation status of TGR5 promoter in peripheral mononuclear cell (PBMC) was detected by methylation-specific polymerase chain reaction (MSP). The mRNA level of TGR5 was determined by quantitative real-time polymerase chain reaction (RT-qPCR). We found that the frequency of TGR5 promoter methylation was significantly higher in ACHBLF (35/76, 46.05%) than CHB patients (5/80, 6.25%; χ(2) = 32.38, P < 0.01) and HCs (1/30, 3.33%; χ(2) = 17.50, P < 0.01). TGR5 mRNA level was significantly lower (Z = -9.12, P < 0.01) in participants with aberrant methylation than those without. TGR5 methylation showed a sensitivity of 46.05% (35/76), specificity of 93.75% (75/80), positive predictive value (PPV) of 87.5% (35/40) and negative predictive value (NPV) of 64.66% (75/116) in discriminating ACHBLF from CHB patients. ACHBLF patients with methylated TGR5 showed significantly poor survival than those without (P < 0.01). When used to predict 3-month mortality of ACHBLF, TGR5 methylation [area under the receiver operating characteristic curve (AUC) = 0.75] performed significantly better than model for end-stage liver diseases (MELD) score (AUC = 0.65; P < 0.05). Therefore, our study demonstrated that aberrant TGR5 promoter methylation occurred in ACHBLF and might be a potential prognostic marker for the disease.

Anesthetic practice for Caesarean section and factors influencing anesthesiologists' choice of anesthesia: a population-based study.

BACKGROUND: We examined the change in anesthetic practice for Caesarean section (CS) during the past decade and determined factors influencing anethesiologists' decisions. METHODS: The cases were identified from data retrieved from Longitudinal Health Insurance Database released by the Taiwan National Health Research Institute in 2008. Trend analysis was performed using logistic regression models. The decision tree analysis was performed using the chi-squared automatic interaction detector method and multivariable logistic regression analysis was performed to identify predictors of general anesthesia. RESULTS: A total of 25,606 women undergoing CS were studied. Logistic regression analyses revealed an upward trend of spinal anesthesia from 2000 to 2008 [57.8-67.5%, adjusted odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.05-1.07, P < 0.001] and a decreasing trend across time for both general and epidural anesthesia (5.5-3.9% and 36.7-28.6%; both OR < 1, both P < 0.001). Patterns of change in anesthetic practice across time for emergency and non-emergency CS were similar (all P < 0.05). Our data further demonstrated that early or threatened labor, a history of preeclampsia, antepartum hemorrhage, emergency CS, and previous CS were important predictors that influenced the anesthesiologists' choice of general anesthesia versus neuraxial anesthesia for women undergoing CS. CONCLUSIONS: Spinal anesthesia was the most common mode of anesthesia for CS deliveries in Taiwan during the past decade. Early or threatened labor, antepartum hemorrhage, emergency CS, previous CS, and preeclampsia are significant determinants of general anesthesia in CS deliveries.

Exportin 4 gene expression and DNA promoter methylation status in chronic hepatitis B virus infection.

Exportin 4 (XPO4) is a novel identified candidate tumour-suppressor gene involved in the pathogenesis of hepatocellular carcinoma (HCC). This study was aimed to determine the clinical features of XPO4 mRNA expression and promoter methylation status in peripheral blood mononuclear cells (PBMCs) of patients with chronic hepatitis B virus (HBV) infection. PBMCs were isolated from 44 HCC, 38 liver cirrhosis (LC), 34 chronic hepatitis B (CHB) patients and 17 healthy controls (HCs). The mRNA level and promoter methylation status of XPO4 were determined by quantitative real-time RT-PCR and methylation-specific PCR, respectively. XPO4 mRNA level of HCC patients was significantly lower compared with LC and CHB patients as well as HCs (all P < 0.01, respectively), and significant differences of the XPO4 mRNA level were found in LC and CHB group than in HCs (LC vs HCs, P < 0.01; CHB vs HCs, P < 0.05). Methylation rate of XPO4 promoter was significantly increased in patients with HCC than in patients with CHB and HCs (both P < 0.05). DNA methylation pattern was responsible for the suppression of XPO4 transcription in the progression of HBV infection (P = 0.000). Furthermore, AFP level was significantly higher in HCC patients with XPO4 methylation than in those without methylation ((8702 ± 15635) µm vs (1052 ± 5370) µm, P < 0.05). In conclusion, transcription of XPO4 gene was gradually decreased and methylation rate of XPO4 promoter was increased with the progression of HBV infection. Methylation status of XPO4 in PBMCs tended to be a noninvasive biomarker to predict HCC and the progression of HBV infection.