Methylenetetrahydrofolate reductase genetic polymorphisms and esophageal squamous cell carcinoma susceptibility: A meta-analysis of case-control studies.

OBJECTIVES: Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk. METHODOLOGY: MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs). RESULTS: Nineteen studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. CONCLUSIONS: Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T.

Analysis of Pathogenic Bacterial Spectrum, Drug Resistance and Risk Factors for Mortality of Bloodstream Infection in Patients with Hematologic Diseases / 中国实验血液学杂志

OBJECTIVE@#To analyze the pathogenic bacterial spectrum, drug resistance, and risk factors associated with multidrug-resistant bacterial infection and mortality in patients with hematologic diseases complicated by bloodstream infections, so as to provide reference for rational drug use and improving prognosis.@*METHODS@#Positive blood culture specimens of patients with hematologic diseases in two Class A tertiary hospitals of Shanxi province from January 2019 to December 2021 were retrospectively analyzed. Pathogen distribution, drug resistance and outcomes of patients with bloodstream infection were investigated, then the multivariate logistic analysis was performed to analyze the risk factors of multidrug-resistant bacterial infection and factors affecting prognosis.@*RESULTS@#203 strains of pathogens were identified, mainly Gram-negative bacteria (GNB) (69.46%, 141/203), of which Escherichia coli (E.coli) had the highest incidence (41.13%, 58/141), followed by Klebsiella pneumoniae (20.57%, 29/141) and Pseudomonas aeruginosa (12.77%, 18/141). Extended-spectrum beta-lactamase (ESBL)-producing E.coli and Klebsiella pneumoniae were 46.55% (27/58) and 37.93% (11/29), respectively. Carbapenem-resistant Gram-negative bacteria accounted for 10.64% (15/141). And Gram-positive bacteria accounted for 27.59% (56/203), Staphylococcus epidermidis, Streptococcus pneumoniae, and Staphylococcus aureus were the most frequently isolated pathogen among Gram-positive bacteria (14.29%, 12.50% and 10.71%, respectively), of which methicillin-resistant Staphylococcus aureus accounted for 33.33% (2/6), coagulase-negative staphylococci accounted for 87.50% (7/8), without vancomycin- or linezolid-resistant strain. Additionally, fungi accounted for 2.95% (6/203), all of which were Candida. Multidrug-resistant Gram-negative bacteria (MDR-GNB) accounted for 53.90% (76/141). Duration of neutropenia >14 days was a risk factor for developing MDR-GNB infection. The 30-day all-cause mortality was 10.84%. Multivariate logistic regression analysis showed that the significant independent risk factors for mortality were age≥60 years (P <0.01, OR =5.85, 95% CI: 1.80-19.07) and use of vasopressor drugs (P <0.01, OR =5.89, 95% CI: 1.83-18.94).@*CONCLUSION@#The pathogenic bacteria of bloodstream infection in patients with hematological diseases are widely distributed, and the detection rate of multidrug-resistant bacteria is high. The clinicians should choose suitable antibiotics according to the results of bacterial culture and antibiotic susceptibility test.

Clinical Characteristics and Nomogram Model of Nosocomial Infection in Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model.@*METHODS@#The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established.@*RESULTS@#164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 μmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285).@*CONCLUSION@#Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.

Clinical Characteristics and Risk Factors for 30-Day Mortality in Patients with Hematologic Diseases Infected by Carbapenem-Resistant Organisms / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics of hospitalized patients with hematologic diseases complicated with carbapenem-resistant organisms (CRO) infection and analyze the risk factors of 30-day all-cause mortality.@*METHODS@#The clinical data and laboratory test data of 77 hospitalized patients with hematologic diseases complicated with CRO infection in department of hematology of the Third Hospital of Shanxi Medical University from January 2015 to December 2020 were retrospectively analysed, the risk factors of 30-day all-cause mortality after CRO infection were analyzed by multivariate logistic regression.@*RESULTS@#Among the total of 77 patients with hematologic diseases complicated with CRO infection, 29 died and 48 survived within 30 days of infection, with a case fatality rate of 37.66%. A total of 93 strains of CRO were isolated from these patients, of which Acinetobacter baumannii had the highest detection rate (25.81%, 24/93), followed by Pseudomonas aeruginosa (18.28%, 17/93). The lung was the most common site of CRO infection. The detected pathogens were highly resistant to carbapenems, and 64.52% (60/93) of the pathogens were resistant to imipenem with minimum inhibitory concentration (MIC)≥16 μg/ml. The results of the univariate analysis showed that albumin concentration <25 g/L (P =0.048), serum creatinine concentration≥120 μmol/L (P =0.023), age-adjusted Charlson comorbidity index (ACCI) (P =0.037) and primary treatments (supportive treatment, immunosuppressive therapy, chemotherapy, HSCT) (P =0.048) were significantly associated with 30-day all-cause mortality after infection. The results of multivariate logistic regression analysis showed that when CRO infection confirmed, albumin concentration <25 g/L (P =0.014, OR=6.171), serum creatinine concentration≥120 μmol/L (P =0.009, OR=10.867) were independent risk factors for 30-day mortality of patients with hematologic diseases complicated with CRO infection.@*CONCLUSION@#The mortality rate of CRO-infected patients with hematologic diseases is high. The detected pathogenic bacteria are highly resistant to imipenem. The albumin concentration <25 g/L and the serum creatinine concentration≥ 120 μmol/L at diagnosis of CRO infection were independent risk factors for 30-day mortality of the patients with hematologic diseases.

Receiving Human Immunodeficiency Virus Serostatus Disclosure from Male Sexual Partners and Related Factors among Men Who Have Sex with Men Aged 50 and Above / 中国医学科学院学报

Objective To investigate the rate and correlates of receiving human immunodeficiency virus(HIV) serostatus disclosure from their most recent male sexual partners among men who have sex with men(MSM) aged 50 and above. Methods With a geosocial networking application,we recruited participants through online convenience sampling to collect the demographic variables,behavioral information,receiving HIV serostatus disclosure,etc.Univariate and multivariate analyses were performed to interpret the associated factors of receiving HIV serostatus disclosure. Results Overall,38.4%(398/1037) of participants received HIV serostatus disclosure from their most recent male sexual partners.The multivariable analysis demonstrated that the following populations were less likely to receive HIV serostatus disclosure from their most recent male sexual partners:participants with junior high school degree or below(OR=0.660,95%CI=0.473-0.922, P=0.015) compared to those with senior high school degree or above;participants unemployed(OR=0.537,95%CI=0.322-0.896, P=0.017) and employed(OR=0.663,95%CI=0.466-0.944, P=0.022) compared to those retired;participants without knowledge about HIV or acquired immune deficiency syndrome(AIDS) compared to those with knowledge about HIV/AIDS(OR=0.636,95%CI=0.466-0.868, P=0.004);participants having ≥2 male sexual partners in the last year(OR=0.433,95%CI=0.320-0.586, P<0.001) compared to those having none or one male sexual partner;participants never been tested for HIV(OR=0.544,95%CI=0.403-0.734, P<0.001) compared to those ever been tested for HIV;participants ever been diagnosed to have sexually transmitted infection(STI)(OR=0.472,95%CI=0.349-0.637, P<0.001) compared to those never diagnosed to have STI;and participants with higher level of HIV stigma(OR=0.742,95%CI=0.604-0.912, P=0.005). Conclusions Our findings indicated that the MSM aged 50 and above had low possibility of receiving HIV serostatus disclosure from the most recent male sexual partners.Education,employment status,number of sexual partners,HIV/AIDS-related knowledge,HIV testing behaviors,STI infection history,and HIV stigma contributed to this result.

Averaging Strategy to Form the Imaging for Routine Reading of Insulinoma from Pancreatic Perfusion Dataset / 中国医学科学院学报

Objective To determine the appropriate averaging strategy for pancreatic perfusion datasets to create images for routine reading of insulinoma.Methods Thirty-nine patients undergoing pancreatic perfusion CT in Peking Union Medical College Hospital and diagnosed as insulinoma by pathology were enrolled in this retrospective study.The time-density curve of abdominal aorta calculated by software dynamic angio was used to decide the timings for averaging.Five strategies,by averaging 3,5,7,9 and 11 dynamic scans in perfusion,all including peak enhancement of the abdominal aorta,were investigated in the study.The image noise,pancreas signal-to-noise ratio(SNR),lesion contrast and lesion contrast-to-noise ratio(CNR)were recorded and compared.Besides,overall image quality and insulinoma depiction were also compared.ANOVA and Friedman's test were performed.Results The image noise decreased and the SNR of pancreas increased with the increase in averaging time points(all P0.99)and were higher than that of the first group(all P<0.05).There was no significant difference in overall image quality among the 5 groups(P=0.977).Conclusions Image averaged from 5 scans showed moderate image noise,pancreas SNR and relatively high lesion contrast and lesion CNR.Therefore,it is advised to be used in image averaging to detect insulinoma.

Spectrum-effect relationship between HPLC fingerprints and bioactive components of Radix Hedysari on increasing the peak bone mass of rat / 药物分析学报

The traditional Chinese medicine of Radix Hedysari plays an important role in invigorating gas for as-cending, benefiting blood for promoting production of fluid, and promoting circulation for removing obstruction in collaterals, which is consistent with the principle of treatment for osteoporosis. This study is designed to investigate the bioactive components on increasing peak bone mass (PBM) by exploring the spectrum-effect relationship between chromatography fingerprints and effect. Multiple indicators are selected to evaluate the pharmacological activity. In fingerprints, 21 common peaks are obtained, five of which are identified. Furthermore, gray relational analysis (GRA) is a quantitative method of gray system theory and is used to describe the correlation degree of common peaks and pharmacological activities with relational value. 21 components are then divided into three different regions, of which ononin and calycosin play an extremely significant role in increasing PBM. In addition, factor analysis and hierarchical cluster analysis (HCA) are used to screen the optimal producing area for Radix Hedysari. This provides a comprehensive and efficient method to improve the quality evaluation of Radix Hedysari, confirming the bioactive components for PBM-enhancement and further develop its medicinal value.

The Anti-antioxidant Role of Ginsenoside Rg1 Regulating Nrf2 on Focal Cerebral Ischemia Reperfusion SD Rats / 昆明医科大学学报

Objective To study antioxidant role and mechanism of Rg1 in rats with cerebral ischemia reperfusion injury (IRI).Methods One hundred and twenty healthy male rats were randomly divided into six groups: control group, sham operation group, model group, different concentration (30,60,90 mg/kg) of Rg1 treatment group.MCAO SD rats model was established by suture－occluded method;the Rg1 treatment groups were given Rg1 i.p. in advance, after 24 hours of reperfusion, neurobehavioral scores of all groups were examined by Longa’s standard;The expression of Nrf2 and HO－1 were analyzed by western blot;The content of SOD and MDA was detected by kit.Results The score of model group rats are significantly higher than control group,compared with the model group, the score of different concentration of Rg1 treatment group was decreased (P＜0.05) . The Nrf2 and HO－1 expression in model group was mildly higher than the control or sham group (P＜0.05) . Both of them in every Rg1 treatment group was higher than model group. Compared with control or sham group, SOD content was observably depressed but MDA content was dramatically increased in model group,interestingly,SOD content was enhanced, MDA content was attenuated in different concentration of Rg1 treatment group (P＜0.05). Conclusion Rg1 increases Nrf2 and HO－1 protein expression and SOD content, reduces MDA content,improves neurofunctional performance of rats after MCAO,and alleviates cerebral cerebral IRI.

Prevention and treatment of Hedysari Radix polysaccharide on carbon tetrachloride-induced hepatic fibrosis and bone loss / 中草药

Objective: To investigate the protective effect of Hedysari Radix polysaccharide (HRP) on liver fibrosis in mice and the correlation between the hepatic fibrosis and bone loss. Methods: The mice were sc injected with 40% carbon tetrachloride (CCl4) dissolved in olive oil solution (0.1 mL/kg, once every 5 days ), while given high-, mid-, and low-dose (20, 10, and 5 g crude drug/kg) HRP and colchicines (0.6 mg/kg) daily. Continuous 35 d later, the activity of alanine transarninase (ALT) and aspartate transferase (AST), contents of total protein (TP) and albumin (ALB) were investigated by related reagent kit, and then, calculated the albumin/globulin (A/G) ratio, liver and thymus indexes and liver histological of tissue pathology were determined. The serum level of acid phosphatase resistant to acid phosphatase (TRACP), alkaline phosphatase (ALP), Ca, P, and the bone level of hydroxyproline (Hyp) were investigated by related reagent kit to observe bone loss. Results: The model group compared with the Sham group, the levels of ALT, AST, and TP increase, showed obvious liver pathological damage, liver and thymus index increase, levels of TRACP, ALP, Ca, and P decrease, and Hyp increase. HRP could significantly improve the hepatic fibrosis and bone loss induced by CCl4 in mice. Conclusion: The liver fibrosis in mice could also cause bone loss and be the primary cause of bone loss in this experiment. The certain market value of this Chinese materia medica is developed for its significant effect and contact between hepatic fibrosis and bone loss is initially investigated, which lays the foundation to further discuss the mechanism of the above two.

Determination of eight active components in Radix Hedysari by HPLC and its cluster analysis / 药学学报

An HPLC method was established for the determination of adenosine, γ-aminobutyric acid (GABA) and six flavonoids (calycosin-7-glucoside, ononin, calycosin, isoliquiritigenin, formononetin and medicarpin) in Radix Hedysari. The samples were extracted with methanol by refluxing for 4 h. The HPLCDAD was performed on a Diamonsil C18 column (250 mm×4.6 mm, 5 μm) with acetonitrile-water as the mobile phase. The column temperature was at 40℃ and the flow rate was 1.0 mL·min-1, while the temperature of drift tube was 110.5℃ and the nebulizing gas flow was 3.1 L·min-1 for the ELSD system. The results showed all the eight components had good linear relationships (r2=0.992 8-1.000 0) in the range of the test concentration. The RSD of precision, stability and repeatability were less than 2%. The average recovery rates were 96.78%-103.45%, and RSD were 0.29%-1.61%. The index component contents of Radix Hedysari form 24 different origins were determined and used as variable factors in clustering analysis. The results were classified into 2 groups basically in accordance with the regional cluster. And the consequence was in consistent with the results of principal component analysis. This HPLC method is simple, shows good sensitive and accurate, and provides the experimental basis for multi-index control of Radix Hedysari. Clustering analysis for Radix Hedysari quality control has a certain reliability and objectivity.

Efficacy of combination antiviral therapy following childbirth in pregnant HBV carriers receiving telbivudine for prevention of mother-to-child transmission / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of combination therapy with peg-IFNalpha and adefovir (CPIA) in women who were hepatfis B virus (HBV) carriers and had just given birth and received telbivudine (LdT) during pregnancy for prevention of mother-to-child transmission.</p><p><b>METHODS</b>One-hundred-and-fifty third trimester-pregnant women who were HBV carriers with highly-viremic were treated with LdT until time of birth. After delivery, those women with alanine aminotransferase (ALT) level exceeding two times the upper limit of normal and HBV DNA level that had decreased more than 31 gIU/mL or hepatitis B e antigen (HBeAg) titer that had decreased more than 50% were switched to CPIA for 96 weeks.</p><p><b>RESULTS</b>Following delivery, 45 of the women were switched to the CPIA treatment, of which 91.1% (41/45) achieved virological response, 55.6% (25/45) achieved HBeAg clearance or seroconversion, and 26.7% (12/45) achieved hepatitis B surface antigen (HBsAg) clearance or seroconversion.The immediate post-delivery (and pre-CPIA) levels of HBeAg and HBV DNA were negatively associated with HBeAg clearance. Ninety-eight of the total study participants stopped the LdT treatment and there were no cases of significant deterioration of liver function.</p><p><b>CONCLUSION</b>Pregnant women who are HBV carriers and receive LdT for protection against mother-to-child transmission, and who show significant ALT elevation and decreased HBeAg titer and/or reduced HBV DNA after delivery, may be good candidates for the CPIA therapy following delivery.</p>

Clinical features of antiviral therapy in 12 patients with hepatitis C virus-related cirrhosis after splenectomy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effects and influencing factors of common antiviral therapy (low-dose interferon plus ribavirin, IFN+RBV) in patients with hepatitis C virus (HCV)-decompensated cirrhosis following splenectomy.</p><p><b>METHODS</b>Twelve patients were treated post-surgery with low-dose IFN (300-500 MIU QOD) or pegylated (Peg)-IFN (50 mug/w) and RBV (0.6-0.9 g/d) for 72 weeks if carrying the lb genotype or 48 weeks if carrying the 2a genotype. All patients were followed-up for 24 weeks after treatment completion to determine the virological response (VR) rates, measured as rapid (R)VR, complete early (cE)VR, 24 hr (24)VR, and sustained (S)VR. Statistical comparisons were made using the t-test or rank sum test, and correlation analyses were made using the Chi-square test. Differences were considered significant at P less than 0.05.</p><p><b>RESULTS</b>All 12 patients completed the treatment course and follow-up. Three patients could not tolerate the Peg-IFN and were switched to IFN, and six patients developed hemolysis that required RBV dose adjustment. The VR rates were: 25.0%, RVR; 50.0%, cEVR; 16.7%, 24VR; 86.0%, SVR. Only one patient was a non-responder, and only one relapsed. Of the patients who achieved SVR, 100% had shown RVR, 83.3% showed cEVR, and 50.0% showed 24VR, suggesting that RVR and cEVR may effectively predict SVR.</p><p><b>CONCLUSION</b>Some HCV-decompensated cirrhosis patients may benefit from antiviral therapy following surgical resolution of hypersplenism. The occurrence of RVR and cEVR in these patients is positively correlated with achieving SVR. Physician-patient communication during early antiviral treatment and close clinical monitoring accompanied by psychological counseling throughout promotes success of the treatment approach.</p>

Efficacy and safety of peginterferon alfa-2a (40 kd) plus adefovir for 96 weeks in HBeAg-negative chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of an extended course (96-week) of combination treatment with peginterferon alfa-2a (Peg-IFNa-2a; 40 kd] plus adefovir (ADV) for treating chronic hepatitis B (CHB) in Chinese patients with negativity for hepatitis B e antigen (HBeAg).</p><p><b>METHODS</b>A total of 25 consecutive patients with HBeAg-negative CHB were administered Peg-IFNa-2a (135-180 mug/week) plus ADV (10 mg/day) for 96 weeks. All patients were followed-up for 24 weeks after treatment completion. Levels of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HbsAg) were measured by fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescent microparticle immunoassay, respectively, at 12-week intervals throughout the treatment course and at the end-of-follow-up (week 120). Patients underwent serological analysis at 3-6 month intervals during treatment and follow-up to evaluate occurrence of adverse events; serological parameters included blood count, markers of liver, kidney and thyroid function, and levels of autoantibodies and creatine kinase.</p><p><b>RESULTS</b>For all patients, the 96-week course of Peg-IFNa-2a plus ADV reduced the level of HBV DNA below the detection threshold (less than 500 copies/ml by FQ-PCR). The overall rate of HBsAg seroconversion was 12% (3/25) at week 48, 28% (7/25) at week 96, and 32% (8/25) at week 120. The occurrences of adverse events were similar at week 48 and week 96.</p><p><b>CONCLUSION</b>The extended-course Peg-IFNa-2a plus ADV combination therapy achieved a 100% virological response and better rates of HBsAg seroconversion than 48 weeks of therapy, without a decrease in safety.</p>

Changes in lymphocyte surface expression of CD8 and CD38 molecules in peripheral blood of inactive HBsAg carriers following pegylated interferon a-2a therapy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects of pegylated interferon a-2a (Peg-INFa-2a) treatment on expression of CD8 and CD38 surface molecules on lymphocytes from peripheral blood of inactive hepatitis B surface antigen (HBsAg) carriers.</p><p><b>METHODS</b>Forty-four patients with hepatitis B virus (HBV) chronic infection (CHB) received a 48-week course of Peg-INFa-2a treatment, with 30 administered 135 mug/week and 14 administered 180 mug/week. Every 12 weeks of treatment, the subjects were assessed for HBsAg titer, presence of anti-hepatitis B e (HBe) antibody, serum alanine amino transaminase (ALT) levels, and lymphocyte surface expression of CD8 and CD38 molecules. Patients were classified as responders and non-responders according to standard parameters. Dynamic differences between the two groups over time were assessed by multivariate repeated measures ANOVA with Greenhouse-Geisser correction and differences at single time points were assessed by univariate ANOVA. Linear regression analysis was performed to evaluate the relationship of two variables.</p><p><b>RESULTS</b>The responders showed a significantly higher increase in ALT at week 12 (60.75+/-24.95 U/L vs. non-responders: 37.03+/-18.45 U/L; t = 2.905, P less than 0.01) and significantly higher proportion of CD8+CD38+ cells at week 24 (71.20+/-11.70% vs. non-responders: 56.79+/-7.72%; F = 23.941, P less than 0.01). The decline in level of HBsAg at week 24 was positively correlated with the increase in ALT level at week 12 (r = 0.386, P less than 0.01) and with expression levels of CD8 and CD38 molecules on lymphocytes at week 24 (r = 0.397, P less than 0.01).</p><p><b>CONCLUSION</b>Lower baseline levels of HBsAg correlated to better Peg-INFa-2a-related HBsAg clearance. Increased expression of CD8 and CD38 on lymphocytes is suggestive of intensive cellular immunity in CHB patients and may be related to HBV-induced hepatocyte damage and may promote the HBsAg clearance.</p>

Analysis of a randomized, double-blind, double-dummy, controlled, multicenter study confirmed the similar therapeutic efficacies of entecavir maleate and entecavir for treatment of HBeAg-positive chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of entecavir maleate (ETV) versus ETV in Chinese patients with hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB).</p><p><b>METHODS</b>The patient population of this previously published randomized, double-blind, double-dummy, controlled, multicenter study was expanded by patients in the 0.5 mg/day ETV maleate group (total n = 110) and patients in the 0.5 mg/day ETV group (total n = 108). At treatment weeks 12, 24 and 48, hepatitis B virus (HBV) DNA levels were measured by the Roche Cobas Ampliprep/Cobas Taqman PCR assay. Adverse events (AE) were recorded.</p><p><b>RESULTS</b>As in the original analysis, the two treatment groups showed similar characteristics at baseline. In addition, the results for the all therapeutic effects showed identical trends to the results obtained in the original analysis, including the statistically similar effects of ETV and ETV maleate treatment-induced decreases in mean HBV DNA level at weeks 12, 24, and 48 (ETV: by 4.28, 5.00, and 5.53 log10 IU/ml vs. ETV maleate: by 4.46, 4.99, and 5.51 log10 IU/ml, respectively; all vs. baseline P more than 0.05), achievement of undetectable levels of serum HBV DNA ( less than 20 IU/ml) at week 48 (ETV: 38.18% vs. ETV maleate: 35.19%; P more than 0.05), HBeAg loss rates at week 48 (ETV: 10.91% vs. ETV maleate: 12.96%; P more than 0.05), HBeAg seroconversion rates at week 48 (ETV: 7.77% vs. ETV maleate: 10.38%; P more than 0.05), normalization of alanine aminotransferase at week 48 (ETV: 75.47% vs. ETV maleate: 82.86%; P more than 0.05), and overall incidence of AE (ETV: 18.02% vs. ETV maleate: 17.43%; P more than 0.05).</p><p><b>CONCLUSION</b>Performing analysis of the therapeutic efficacies of entecavir maleate versus entecavir with a larger study population confirmed our original findings of similar efficacy and safety profiles for these two drugs in patients with HBeAg-positive CHB.</p>

Analysis of thyroid dysfunction and influencing factors in chronic hepatitis C patients treated with peg-IFNa-2a and ribavirin / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the frequency of thyroid dysfunction and determine its influencing factors in chronic hepatitis C (CHC) patients treated with pegylated-interferon alpha (peg-IFNa)-2a and ribavirin (RBV) combination therapy.</p><p><b>METHODS</b>A total of 194 CHC patients were treated with peg-IFNa-2a and RBV for 48 weeks. Development of thyroid dysfunction was recorded. Clinical and biological factors from pre-treatment (baseline) to post-treatment were statistically analyzed to determine correlation with thyroid dysfunction in this patient population.</p><p><b>RESULTS</b>Fifty-two (26.80%) of 194 peg-IFNa-2a/RBV-treated patients developed thyroid dysfunction. Dysfunction severity ranged from hyperthyroidism (n = 1, 0.52%) and hypothyroidism (n = 10, 5.15%) to subclinical hyperthyroidism (n = 4, 2.06%) and subclinical hypothyroidism (n = 37, 19.07%). The dysfunction rate was significantly higher after peg-IFNa-2a/RBV treatment (26.80% vs. 12.37% at baseline, x2 = 12.829, P less than 0.05, odds ratio (OR) = 0.386, 95% confidence interval (CI): 0.226-0.657), in females (33.00% vs. 20.21% in males, P less than 0.05, 95% CI: 1.016-3.040), and in thyroid auto-antibody positive patients (64.29% vs. 23.89% in negative patients, P less than 0.05, 95% CI: 1.681-36.183). Early virological response did not have any significant effect on dysfunction rate (23.00% vs. 30.85% no early virological response, x2 = 1.522, P more than 0.05) nor did end of treatment response (27.19% vs. 26.25% no response at end of treatment, x2 = 0.021, P more than 0.05). Patients who developed thyroid dysfunction had higher interleukin (IL)-6 at baseline (i.e. before peg-IFNa-2a/RBV treatment) (27.08+/-14.90 vs. 11.65+/-5.46 in patients who maintained normal thyroid function, t = 3.127, P less than 0.05, 95% CI: 5.28-25.58). IL-6 levels were not significantly different between the two groups at 24 weeks (6.30+/-2.47 vs. 6.81+/-2.80, t = 0.352, P more than 0.05). IL-6 levels before and after 48 weeks of treatment in normal thyroid function patients were 27.08+/-14.90 and 6.30+/-2.47, t = 3.632, P less than 0.05, and in thyroid dysfunction patients were 11.65+/-5.46 and 6.81+/-2.80, t = 1.997, P more than 0.05.</p><p><b>CONCLUSION</b>Peg-IFNa-2a/RBV combination therapy may cause thyroid dysfunction, especially hypothyroidism, in CHC patients. Female sex and thyroid auto-antibody positivity may put CHC patients at higher risk of developing thyroid dysfunction during peg-IFNa-2a/RBV therapy. Elevated IL-6 may be a predictive marker of peg-IFNa-2a/RBV-induced thyroid dysfunction.</p>

Efficacy of low-dose interferon therapy for treating chronic hepatitis C patients who cannot tolerate standard treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic efficacy of interferon (IFN) therapy and risk of long-term administration for chronic hepatitis C (CHC) patients who cannot tolerate the standard treatment.</p><p><b>METHODS</b>Forty-six CHC patients who had proven intolerant to standard treatments were treated with low-dose IFN (non-pegylated IFN: 60 to 300MIU QOD, or pegylated IFN: 50 to 90 mug/w) plus ribavirin (RBV; 0.6g to 0.9 g/d) for 72 weeks.</p><p><b>RESULTS</b>Forty-three (93.5%) of the patients were able to tolerate the long-term treatment with low-dose IFN plus RBV. Only three patients experienced severe side effects (low white blood cell and platelet counts) that required treatment withdrawal. The virology response rates over treatment time were: rapid virologic response (RVR): 10.9%; early virus response (EVR): 30.4%; 24 week virologic response: 45.7%; and, 48 week virologic response: 47.8%. B-sonographic imaging revealed that three patients experienced improved liver morphology through the treatment course. The patients who achieved RVR, EVR, or 24 weeks virologic response also attained higher 48 week virologic response. The 24 week virologic response had the strongest predictive value of good prognosis.</p><p><b>CONCLUSIONS</b>Our study demonstrated that long-term treatment with low-dose interferon plus ribavirin is effective for patients who are otherwise intolerant to standard treatment. In these patients, low-dose IFN plus RBV can obtain a high virologic response rate at 48 week. Furthermore, the 24 week virologic response is sufficiently predictive of treatment success. As with any treatment regimen, it is important for healthcare workers to monitor the disease status and potential side effects throughout the course of therapy.</p>

The clinical significance of PreS1Ag and anti-PreS1 in patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the positive ratio and clinical significance of PreS1Ag and anti-PreS1 in patients with chronic hepatitis B.</p><p><b>METHODS</b>428 patients with chronic HBV infection were collected, these patients were divided into e antigen-positive CHB group, e antigen-negative CHB group, inactive HBsAg carrier group and HBsAg serum conversion group. The difference of positive ratio of PreS1Ag and anti-PreS1 among all groups or between every two groups were analyzed; The relationship of PreS1Ag and anti-PreS1 with HBV M and HBV DNA were also analyzed. SPSS13.0 software was used for statistical treatment. Fourfold table chi-square test or matched-pairs chi-square test was used for enumeration data, and independent sampler t test or rank-sum test was used for measurement data.</p><p><b>RESULTS</b>The differences of PreS1Ag among four groups were statistically significant (X2=141.7, P<0.05). The positive ratio of PreS1Ag in e antigen-positive CHB group was 95.7%, followed by 82.8% in e antigen-negative CHB group, 13.2% in inactive HBsAg carrier group and 2.2% in HBsAg serum conversion group. The difference of positive ratio of anti-PreS1 between HBsAg seroconversion group and HBsAg positive group was statistically significant (X2=6.919, P<0.05), which indicated that anti-PreS1 had good correlation with HBsAg seroconversion. The average absorbance ratio of PreS1Ag in high viral replication group (179.30) was higher than that in low viral replication group (133.87), statistical significance appeared (Z=-3.86, P<0.05). Though the difference of absorbance ratio of anti-PreS1 between two groups had no statistical significance (P>0.05), descent trend was apparent with virus replication level ascending. We analyzed the concordance of anti-HBs and anti-PreS1 by matched-pairs chi-square test, result showed no statistical significance of detection rate between them, X2=0.262, P>0.05. Serum PreS1Ag, HBeAg or HBcAg in liver tissue in reflecting hepatitis B replication had correlation with HBV DNA (X2=33.840, 24.159, 4.854 in order, P<0.05). Correlation coefficient between PreS1Ag and HBV DNA was higher (r=0.628) than that between HBeAg and HBV DNA (r=0.563).</p><p><b>CONCLUSION</b>PreS1Ag was more sensitive than HBeAg in diagnosing viral replication in patients with chronic hepatitis B. Anti-PreS1 as protective antibody may be involved in clearance of hepatitis B, positive result indicated recovery of chronic hepatitis B.</p>

Relationship between liver pathology and clinical characters in HBV carriers / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To study the relationship between liver pathology and clinical characters of chronic HBV carriers.</p><p><b>METHODS</b>Analyze the age, sex, grade of liver inflammation and stage of liver fibrosis among patients with chronic HBV carriers (n = 58) and non-active HBsAg carriers (n = 32), and compare the grade of liver inflammation and stage of liver fibrosis in different groups according to age, ALT levels and with/without HBeAg. The data was processed by using t test or Chi-square test for statistical analysis, respectively.</p><p><b>RESULTS</b>(1) No differences existed in gender composition ratio between chronic HBV carriers and non-active HBsAg carriers. However, the ages of non-active HBsAg carriers group (35.2+/-7.6) were much older than that of the HBV carriers group (24.7+/-4.8) (t = 2.576, P = 0.017). (2) The stage of liver fibrosis in non-active HBsAg carriers group was more aggravated than that of the chronic HBV carriers group (Chi-square = 23.231, P less than 0.01), whereas no significant differences existed between these 2 groups (Chi-square = 0.058, P = 0.972). (3) As to the grade of liver inflammation and the stage of liver fibrosis, significant differences existed between the groups with higher level of serum ALT (20-40 U/L) and lower level ( is less than or equal to 20 U/L) (Chi-square = 7.827, P = 0.008; Chi-square = 14.303, P = 0.001), and similar results also existed between elder group (more than 40) and younger group (is less than or equal to 40) (Chi-square = 10.949, P = 0.001; Chi-square = 21.271, P less than 0.01); (4) Among the chronic HBV carriers, significant differences existed in grade of liver inflammation between groups with HBeAg positive and negative patients (Chi-square = 10.275, P = 0.002), and the latter was more aggravated; however, there was no difference in stage of liver fibrosis between them (Chi-square test = 3.457, P = 0.178).</p><p><b>CONCLUSION</b>Liver histopathology can be recommended to guide the clinical diagnosis and treatment, especially for the chronic HBV carriers, with elder age, ALT close to normal and HBeAg negative.</p>

The dendritic cell subsets function and the cytokines levels in plasma change in different period in patients with HBV infection / 中华肝脏病杂志

<p><b>OBJECTIVE</b>We studied the function of dendritic cells subsets and the cytokines levels in plasma in patients with different periods of returning (immune tolerance, hepatitis active and non-replicating period) and aimed to explore the possible reasons for HBV chronic infection.</p><p><b>METHODS</b>Thirty HBV infected patients in different stages of infection were enrolled and divided into three groups: the immune tolerance group (10 cases), the hepatitis active group (10 cases), and the non-replicating group (10 cases). Ten healthy people were enrolled and served as controls. Blood from the patients and controls were collected and the dendritic cells subsets function (The cytokine levels in different groups) were analyzed using statistical method.</p><p><b>RESULTS</b>The total IL-12 output and single nucleus IL-12 output of the total HBV infected patients were lower than that of the healthy control group (P value less than 0.01). The total IFNa output and single nucleus IFNa output of the total HBV infected patients had no significant difference between the total HBV infected patients and the healthy controls (P value more than 0.05). The total IL-12 output of the healthy control group was higher than that in others 3 groups of the HBV infected patients. (Z = -3.039, -2.967 ,-2.949, P value less than 0.01) and the single nucleus IL-12 output of the healthy control group was also higher than that in others 3 groups of the HBV infected patients. (Z =-3.027, -2.671 , -2.863, P value less than 0.01) . The total IFNa output and the single nucleus IFNa output of the healthy control group was higher than that in the hepatitis active group of HBV infected patients (Z = -3.016, -3.176, P value less than 0.01). While the plasma IFNa cytokine levels in the 3 HBV infection groups were higher than in the healthy control group (Z = -2.967, -2.896, -3.054, P value less than 0.01).</p><p><b>CONCLUSION</b>Difference existed between the function of dendritic cells subsets and the IFNa levels in different returning periods of HBV infected patients. The function of dendritic cells subsets has no significant difference in HBV patients with different periods of returning. The flawed function of dendritic cells subsets and the abnormal IFNa level may be one of the reasons for chronic HBV infection.</p>