[Analysis of clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues].

Objective: To explore the clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues. Methods: A retrospective analysis was performed according to different data types. An independent sample t-test, Mann-Whitney U test, chi-square test, or Fisher's exact probability method were used. Chronic hepatitis B patients followed up for four years were collected from the follow-up case database of the Department of Infectious Diseases of Zhongshan Third Hospital from January 2009 to December 2018 and were divided into two groups, A and B, with 87 and 145 cases respectively, according to the duration of HBeAg-negativity≤ 3 and persistent positivity >3 years. Statistical analysis was conducted on the age, gender, family history, baseline, follow-up visit duration, liver function, and other data among the two patient groups. Results: There were no statistically significant differences in gender, age, family history of liver cirrhosis, family history of liver cancer, liver cirrhosis condition before treatment, fatty liver disease combined condition before treatment, baseline HBsAg, anti-HBc, alanine aminotransferase, albumin, or total bilirubin between the two groups of patients (P > 0.05). HBV DNA and HBeAg were significantly higher in group B than those in group A at baseline, with P≤0.001. Aspartate aminotransferase and γ-glutamyl transferase were significantly higher in group A than those in group B at baseline. The proportion of family history of hepatitis B was significantly higher in group B (69.0%) than that in group A (50.6%) among the two groups of patients, and the difference was statistically significant (P = 0.005). The proportion of mothers with hepatitis B was significantly higher in group B (25.5%) than in group A (11.5%), P = 0.010. During the treatment process, the HBV DNA quantification was significantly higher in group B than that in group A at 0.5 and 1 years (P≤0.002). The proportion of HBV DNA <100IU/ml was also significantly different at six months and one year (χ(2)=30.327, P < 0.001 and χ(2)=11.779, P = 0.001). The HBsAg level was higher in group B than that of group A in the second and fourth years, P < 0.05. During the entire treatment process, the HBeAg level was significantly higher in group B than that in group A (P < 0.001). A total of seven cases developed liver cirrhosis or cancer during follow-up, including three cases in group A and four cases in group B (P > 0.05). Conclusion: HBeAg-positive patients with chronic hepatitis B have persistent HBeAg positivity when treated with long-term nucleos(t)ide analogues. Accordingly, a greater proportion of this kind of patient family and mothers have a remarkable history of hepatitis B and a reduced HBV DNA relapse rate in the early stages (within a year or less).

[Efficacy and safety of Kangbingdu granules in the treatment of influenza: a randomized, double-blind, double-dummy, positive-drug parallel control multicenter clinical trial].

Objective: To observe the efficacy and safety of Kangbingdu granules (KBD) in the treatment of influenza. Methods: A multicenter, randomized, double-blind, double-dummy, and positive-drug parallel control trial was conducted in 27 Grade ⅢA hospitals in China and the subjects were randomly assigned to the KBD test group or the oseltamivir phosphate capsule control group at a ratio of 1∶1. 200 subjects were planned to be enrolled in each group. The experimental group was given KBD (18g each time, 3 times a day) and oseltamivir phosphate simulator orally, while the control group was given oseltamivir phosphate capsule (75 mg each time, twice a day) and KBD simulator orally for 5 days. The primary efficacy indicators included the remission time of major clinical symptoms and the time of complete defervescence. The secondary efficacy indicators included dosage of acetaminophen, the change of traditional Chinese medicine (TCM) syndrome score and the remission time of other important clinical symptoms. The efficacy of KBD in the test group and Oseltamivir phosphate control group were compared. Adverse events or adverse reactions were observed at the same time to evaluate the safety of KBD Granules. Results: A total of 393 subjects from 27 Grade ⅢA hospitals in China were enrolled. The experimental group included 195 subjects and 191 subjects (97.95%) completed the trial, While the control group included 198 subjects and 195 subjects (98.48%) completed the trial. There was no significant difference in the shedding rate and rejection rate between the two groups (P>0.05). In the Full Analysis Set (FAS), the mean age of the experimental group was (34.9±14.4) years old, with 83 males (42.78%). The mean age of the control group was (33.3±13.5) years old, with 78 males (39.59%). There were no statistically significant differences between the two groups in demographic data, physical examination, viral pathogen detection, total score of TCM syndromes and scores of each symptom at baseline (P>0.05). In the FAS, the remission time M (Q1, Q3) of major clinical symptoms was 3.0 (3.0, 4.0) days in the experimental group and 3.0 (3.0, 4.0) days in the control group, and the difference was not statistically significant (P>0.05). The time M (Q1, Q3) of complete defervescence was 34.0 (20.3, 49.0) hours in the experimental group and 36.5 (19.6, 48.8) hours in the control group, and the difference was not statistically significant (P>0.05). KBD granules had the same effect as Oseltamivir phosphate capsule (P>0.05) in terms of acetaminophen dosage, TCM syndrome effect and disappearance rate of most important clinical symptoms. Meanwhile, the disappearance rate of dizziness and chest distress on day 3 in the KBD granules group was better than that of oseltamivir phosphate capsule (P<0.05). Conclusion: KBD granules have the same efficacy as Oseltamivir Phosphate capsule in the treatment of influenza and the drug safety is good.

[Estimating the basic reproduction number of COVID-19 in Wuhan, China].

Objective: The number of confirmed and suspected cases of the COVID-19 in Hubei province is still increasing. However, the estimations of the basic reproduction number of COVID-19 varied greatly across studies. The objectives of this study are 1) to estimate the basic reproduction number (R(0)) of COVID-19 reflecting the infectiousness of the virus and 2) to assess the effectiveness of a range of controlling intervention. Methods: The reported number of daily confirmed cases from January 17 to February 8, 2020 in Hubei province were collected and used for model fit. Four methods, the exponential growth (EG), maximum likelihood estimation (ML), sequential Bayesian method (SB) and time dependent reproduction numbers (TD), were applied to estimate the R(0). Results: Among the four methods, the EG method fitted the data best. The estimated R(0) was 3.49 (95%CI: 3.42-3.58) by using EG method. The R(0) was estimated to be 2.95 (95%CI: 2.86-3.03) after taking control measures. Conclusions: In the early stage of the epidemic, it is appropriate to estimate R(0) using the EG method. Meanwhile, timely and effective control measures were warranted to further reduce the spread of COVID-19.

[Prevention effectiveness of the "Internet Plus-based AIDS Comprehensive Prevention Service System" among MSM in Guangzhou: a dynamic model of infectious disease].

Objective: To evaluate the effect of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM in Guangzhou, during 2010-2017, using a dynamic compartmental model. Methods: A dynamic compartmental model was developed to describe the HIV situation among MSM in Guangzhou. This model was parameterized on data from published literature or surveillance programs from the Guangzhou CDC. The Matlab 7.0 software was used for coding and analysis on collected data. HIV prevalence was analyzed among MSM under the status quo data and estimated the impact by the "Internet Plus" AIDS prevention services project. Results: HIV prevalence would have increased to 22.75% in 2017, and the total number of new HIV infections would have been 11 038, from 2010 to 2017, using the data status quo. Under the Guangzhou "Internet Plus" AIDS prevention services project, the prevalence of HIV among MSM from 2010 to 2017 was estimated to be 8.44%, 9.68%, 10.65%, 11.34%, 11.73%, 11.83%, 11.71% and 11.43% in Guangzhou, which were similar to the surveillance data. The total number of new infections in the past 8 years under the "Internet Plus" scenario was estimated to be 4 009. The "Internet Plus" program would have prevented 7 029 (63.68%) new infections during 2010-2017 as compared to the number, status quo. Conclusions: The fitting result of dynamic compartmental model seemed more reasonable, which was applicable to predict HIV epidemic among MSM in Guangzhou, suggesting that the increase of HIV prevalence had been curbed since the "Internet Plus" project which was launched in 2010, and the "Interner Plus-based AIDS Comprehensive Prevention Service System" had achieved the purpose as planned, epidemiologically.

[Impact of the 90-90-90 goal and pre-exposure prophylaxis on HIV transmission and elimination in men who have sex with men in China: A mathematical modeling study].

Objective: To establish a dynamic compartmental model to predict the impact of HIV testing and treatment and pre-exposure prophylaxis (PrEP) on the annual incidence of HIV infection in men who have sex with men (MSM) in China from 2018 to 2037. Methods: A dynamic compartmental model was developed to describe the HIV epidemic in MSM in China. The model was parameterized using data from the literature available. We used MATLAB 7.0 software for data simulation and graphics rendering. We analyzed HIV transmission among MSM and estimated the impact of expanded HIV testing and treatment and PrEP on HIV elimination in MSM. Results: Under the current policy, the number of new HIV infections would reach 770 000, the infection rate would reach 11.1% and the incidence rate would reach 0.72/100 person years in MSM in the next 20 years. Under the 90%-90%-90% goal, 440 000 new infections (57.7%) would be reduced, the HIV infection rate would decline to 5.7% and the incidence rate would decline to 0.24/100 person years in the next 20 years, but it is still unlikely to achieve the goal of HIV elimination. With 100% PrEP compliance, the required PrEP coverage rates for achieving HIV elimination in the next 10, 15 and 20 years would be 65%, 32% and 19%, respectively. Conclusion: It is necessary to strengthen the comprehensive intervention in MSM, continue to expand HIV testing and treatment, and improve PrEP adherence and coverage to further control and eliminate the epidemic of HIV/AIDS in MSM.