Objective To investigate the therapeutic effects of recombinant yeast hepatitis B virus(HBV)vaccine combined with interferon(IFN)α-1b and determine the rational dosage of HBV vaccine for the further clinical study with larger sample.Methods Two hundreds and sixteen patients with chronic hepatitis B(CHB)were enrolled in this randomized,multi-center,double-blinded and placebo-controlled clinical trial.All the subjects were not treated with antiviral drugs within 6 months and randomly divided into 90μg,60μg and placebo groups with a ratio of 1:1:1.All the patients were intramuscularly administrated with 90μg or 60μg recombinant HBV vaccine or placebo at week 0,2,6,10,14,18,22,respectively.Meanwhile,they were also treated with IFNα-1b 50μg,3 times a wcek for 24 weeks.All patients were followed up for 24 weeks after withdrawal of anti-HBV therapy.Serum HBV DNA level,HBeAg titer and liver function were monitored frequently.Interferon-γ secreting lymphoeytes were detected by Enzyme-linked immunospot(ELISPOT)in part of the patients.Results The serum HBV DNA levels were(6.03±1.79),(5.52±1.82)and(6.29±1.70)log10 copy/mL at week 24 of treatment in high dose,low dose and placebo groups,respectively (P=0.458).And the serum HBV DNA levels were(5.92±1.98),(5.49±1.99)and(6.16±1.76)log10 copy/mL at weck 24 after withdrawal of treatment,respectively(P=0.720).The rates of patients whose HBV DNA＜1×105 copy/mL in these three groups were 30.4%,39.4% and 20.8% at week 24 of treatment,respectively and there was significant difference between high dose group and low dose group(P=0.015).The rate of patients whose HBV DNA＜1×105 copy/mL at week 24 after withdrawal was highest in low dose group,but no significant differences before and after treatment in these three groups(P=0.257).The HBV DNA negative rates were 17.4%,25.4% and 6.9% in these three groups,respectively,which were significantly different(P=0.012).At week 24 of treatment and week 24 after withdrawal of treatment,the alanine aminotransferase normalization rate,HBeAg seroconversion rate were highest in low dose group,but no significant differences in these three groups.ELISPOT positive rates at week 24 of treatment and week 24 after withdrawal of treatment in high close and low dose groups were higher than that in placebo group(P＜0.05).The incidence of adverse events was similar and there was no drug related severe adverse events in each group.Conclusion Recombinant HBV vaccine maybe contribute to anti-HBV therapy and 60μg of dosage seems to be rational.

Objective:To explore the predictive value of serum microRNA (miR)-155-5p on prognosis in sepsis patients with acute liver injury.Methods:The clinical data of 103 sepsis patients with acute liver injury from March 2017 to March 2019 in Rongjun Hospital, Zhejiang Province, were retrospectively analyzed. Among them, 57 patients were improved (survival group) and 46 patients died in hospital (death group). The clinical data and serum miR-155-5p were compared between 2 groups, and the influencing factors of prognosis in sepsis patients with acute liver injury were analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the prognosis value of miR-155-5p.Results:The incidence of septic shock, age, procalcitonin (PCT), C-reactive protein (CRP), D-dimer, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), sequential organ failure score (SOFA) and miR-155-5p in death group were significantly higher than those in survival group: 95.65% (44/46) vs. 45.61% (26/57), (50.82 ± 10.52) years vs. (43.84 ± 7.32) years, (16.42 ± 4.97) μg/L vs. (7.20 ± 2.19) μg/L, (23.21 ± 8.59) mg/L vs. (16.73 ± 5.04) mg/L, (10.84 ± 3.17) mg/L vs. (4.16 ± 2.15) mg/L, (22.37 ± 3.16) scores vs. (16.72 ± 4.10) scores, (10.98 ± 3.74) scores vs. (6.84 ± 2.47) scores and 3.10 ± 0.97 vs. 2.25 ± 0.63, and there were statistical differences ( P<0.05). Multivariate Logistic regression analysis result showed that the APACHE Ⅱ, SOFA, PCT and miR-155-5p were the independent risk factors of prognosis in sepsis patients with acute liver injury ( OR=3.173, 2.732, 2.553 and 2.153; 95% CI 2.127 to 6.312, 2.018 to 6.056, 1.249 to 4.466 and 1.234 to 4.153; P<0.01 or <0.05). ROC curve analysis result showed that the cut-off value of miR-155-5p was 2.89, and the area under curve was 0.871 (95% CI 0.782 to 0.951), with a sensitivity of 86.1% and a specificity of 80.4%. Conclusions:Serum miR-155-5p is closely related to the clinical prognosis in sepsis patients with acute liver injury. It can be used as one of the potential prognostic indicators for patients, and is worthy of further clinical study and analysis.

Objective:To establish an early prediction Nomogram model for severe acute pancreatitis(SAP) complicated with acute renal injury (AKI), and evaluate the prediction efficiency of the model.Methods:The clinical data of 295 SAP patients hospitalized in Zhejiang Rongjun Hospital from July 2017 to June 2021 were retrospectively analyzed, and the patients were divided into AKI group ( n=61) and non-AKI group ( n=234) according to whether complicated with AKI. The common characters, clinical data and laboratory examination results were compared. The risk factors for SAP complicated with AKI was analyzed by multivariate logistic regression analysis, and a nomogram prediction model was established by R software. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate its prediction performance. Results:The acute physiology and chronic health assessment Ⅱ (APACHEⅡ) and Ranson score, the incidence of abdominal compartment syndrome (ACS) and systemic inflammatory response syndrome (SIRS), the cases of shock and mechanical ventilation, and the levels of blood lactic acid (BLA), blood creatinine (Scr), urea nitrogen (BUN), C-reactive protein (CRP), procalcitonin (PCT) and cystatin C(Cys C) in peripheral blood were significantly higher in AKI group than those in non-AKI group, while the levels of blood calcium were lower than those in non-AKI group, and the differences were statistically significant (all P value <0.05). Multivariate logistic regression analysis showed that APACHEⅡ score ( OR=1.185, 95% CI 1.074-1.308, P=0.001), Ranson score ( OR=12.668, 95% CI 5.102-31.456, P<0.001), Scr ( OR=1.028, 95% CI 1.002-1.054, P=0.034), PCT ( OR=4.298, 95% CI 1.379-13.395, P<0.001) and Cys C ( OR=38738.38, 95% CI 43.190-347459.41, P<0.001) were independent risk factors for SAP complicated AKI. Serum calcium ( OR=0.0001, 95% 0.000-0.048, P<0.001) was an independent protective factor for SAP complicated AKI. A Nomogram prediction model based on the six factors above were established, and its AUC, sensitivity and specificity to predict AKI were 0.987, 99.0% and 98.5% in the training set, and were 0.976, 98.6% and 94.2% in the validation set. Conclusions:This study successfully established an early prediction model with high predict value for SAP complicated with AKI, which can efficiently predict the risk of SAP with concurrent AKI.

Abstract OBJECTIVE To establish an environmental microbial identification information database for a high-risk production area of sterile formulations in pharmaceutical enterprises using various microbial identification techniques. METHODS For four consecutive quarters, microorganisms were collected from intermediates, pharmaceutical water, clean spaces, personnel and equipment surfaces, and identified using VITEK biochemical identification, MALDI-TOF MS protein identification, and 16S rRNA/ITS gene identification techniques. Combined with microbial morphology and source information analysis, a corresponding microbial identification information database was established. RESULTS A total of 89 bacterial and 5 fungal identification results were collected and related morphological analysis was conducted. Among the 94 collected strains, Gram-positive Cocci and Gram-positive Bacillus accounted for 60.6%, which was the common contaminating bacteria in clean areas; 46 strains of microorganisms were collected in the B-level environment, with Staphylococcus being the main dominant genus, accounting for 45.7%, followed by Bacillus(17.4%), Micrococcus(6.5%), and Yeast(4.3%), one strain of Burkholderia cepacia was also isolated in the B-level environment; 29 strains of microorganisms were collected from pharmaceutical water, mainly Gram-negative bacteria(58.6%). CONCLUSION This study establishes a microbial identification information database that integrates biochemical, protein, and gene identification results, and conduct relevant analysis to provide a basis for pharmaceutical enterprises to carry out risk control, strengthen the management of unacceptable microorganisms, and conduct microbial data deviation surveys and traceability analysis; enterprises can also use the identification results to establish an environmental microbial map, control and eliminate microbial pollution in a targeted manner, improve the level of sterility assurance, and ensure the quality and safety of drugs.