Influencing factors of death in patients with MDR-TB based on Bayesian Cox regression model / 中南大学学报(医学版)

Objective:Multidrug-resistant tuberculosis(MDR-TB)has a high mortality and is always one of the major challenges in global TB prevention and control.Analyzing the factors that may impact the adverse outcomes of MDR-TB patients is helpful for improving the systematic management and optimizing the treatment strategies for MDR-TB patients.For follow-up data,the Cox proportional hazards regression model is an important multifactor analysis method.However,the method has significant limitations in its application,such as the fact that it is difficult to deal with the impacts of small sample sizes and other practical issues on the model.Therefore,Bayesian and conventional Cox regression models were both used in this study to analyze the influencing factors of death in MDR-TB patients during the anti-TB therapy,and compare the differences between these 2 methods in their application. Methods:Data were obtained from 388 MDR-TB patients treated at Lanzhou Pulmonary Hospital from November 1,2017 to March 31,2021.Survival analysis was employed to analyze the death of MDR-TB patients during the therapy and its influencing factors.Conventional and Bayesian Cox regression models were established to estimate the hazard ratios(HR)and their 95% confidence interval(95% CI)for the factors affecting the death of MDR-TB patients.The reliability of parameter estimation in these 2 models was assessed by comparing the parameter standard deviation and 95% CI of each variable.The smaller parameter standard deviation and narrower 95% CI range indicated the more reliable parameter estimation. Results:The median survival time(1st quartile,3rd quartile)of the 388 MDR-TB patients included in the study was 10.18(4.26,18.13)months,with the longest survival time of 31.90 months.Among these patients,a total of 12 individuals died of MDR-TB and the mortality was 3.1%.The median survival time(1st quartile,3rd quartile)for the deceased patients was 4.78(2.63,6.93)months.The majority of deceased patients,accounting for 50%,experienced death within the first 5 months of anti-TB therapy,with the last mortality case occurring within the 13th month of therapy.The results of the conventional Cox regression model showed that the risk of death in MDR-TB patients with comorbidities was approximately 6.96 times higher than that of patients without complications(HR=6.96,95% CI 2.00 to 24.24,P=0.002)and patients who received regular follow-up had a decrease in the risk of death by approximately 81% compared to those who did not receive regular follow-up(HR=0.19,95% CI 0.05 to 0.77,P=0.020).In the results of Bayesian Cox regression model,the iterative history plot and Blue/Green/Red(BGR)plot for each parameter showed the good model convergence,and parameter estimation indicated that the risk of death in patients with a positive first sputum culture was lower than that of patients with a negative first sputum culture(HR=0.33,95% CI 0.08 to 0.87).Additionally,compared to patients without complications,those with comorbidities had an approximately 6.80-fold increase in the risk of death(HR=7.80,95% CI 1.90 to 21.91).Patients who received regular follow-up had a 90% reduction in the risk of death compared to those who did not receive regular follow-up(HR=0.10,95% CI 0.01 to 0.30).The comparison between these 2 models showed that the parameter standard deviations and corresponding 95% CI ranges of other variables in the Bayesian Cox model were significantly smaller than those in the conventional model,except for parameter standard deviations of receiving regular follow-up(Bayesian model was 0.77;conventional model was 0.72)and pulmonary cavities(Bayesian model was 0.73;conventional model was 0.73). Conclusion:The first year of anti-TB therapy is a high-risk period for mortality in MDR-TB patients.Complications are the main risk factors of death in MDR-TB patients,while patients who received regular follow-up and had positive first sputum culture presented a lower risk of death.For data with a small sample size and low incidence of outcome,the Bayesian Cox regression model provides more reliable parameter estimation than the conventional Cox model.

Influencing Factors of HIV/ AIDS Death Based on Bayesian Cox Proportional Hazard Regression Model / 中山大学学报(医学科学版)

ObjectiveTo understand the composition of related characteristics of HIV/AIDS cases in Lanzhou and analyze the influencing factors of AIDS-related deaths. MethodsThe information of HIV/AIDS cases reported in Lanzhou from 2011 to 2019 was collected， the method of survival was used analysis and Bayesian Cox Proportional Hazard Regression Model was constructed to analyze the related factors of death. ResultsA total of 2 312 HIV/AIDS patients were selected in this study， including 45 AIDS-related deaths. The results of multivariate regression showed that the older the patients were， the higher the risk of death was； the risk of death of AIDS patients at the time of diagnosis was 13.91 times higher than that of HIV-infected patients； Patients who received CD4 testing had a lower risk of death than those who did not； The risk of death was 0.22 times higher among those who received antiretroviral therapy than those who did not receive antiretroviral therapy. ConclusionsAge at diagnosis， course of disease， antiviral therapy were the influencing factors of AIDS-related death in HIV/AIDS patients in Lanzhou. Therefore， it is necessary to strengthen health education for AIDS-related groups， advocate early detection， early diagnosis， and early treatment， expand the coverage of AIDS testing and treatment， prolong the survival time of AIDS patients.

Advances in ubiquitin-like protein ISG15-mediated anti-viral response / 病毒学报

ISG15 is a 15kD ubiquitin-like protein (UBL) induced by interferon (IFN). ISG15 can be covalently attached to proteins, which is called ISGylation process. ISGylation system contains ISG15, UBE1L, UBCH8 and HERC5 proteins, which are all essential for ISGylation. ISG15 and ISGylation system have been found to have anti-viral effects. A better understanding of how ISG15 mediates the anti-viral activity will provide insights for new anti-viral drugs development and new therapeutic strategies. The mechanisms underlying the ISG15 mediated anti-viral response have been explored extensively in recent years. This minireview summarized the research advances of how ISG15 mediated the anti-viral effects against different kinds of viruses.

Function of tumor suppressor p53 and its role in antiviral immunity / 病毒学报

Tumor suppressor p53, known as 'the guardian of the genome', has the ability to prevent the emergence of transformed cells by the induction of cell cycle arrest and apoptosis. Otherwise, there were researches about the function of p53, such as NDA repair, regulating metabolism and maternal reproduction in recent years. Furthermore, there was a new function for p53 in antiviral apoptosis mentioned in the research, Integration of interferon-alpha/beta signaling to p53 responses in tumour suppression and antiviral defense. In order to define the antiviral function of p53, many target genes has been defined, such as IRF9, IRF5, ISG15 and TLR3. All of these implied there must be a complex mechanism for role of p53 in antiviral innate immunity, adaptive immunity and inflammation.