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In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Background Count time series (e.g., daily deaths) are a very common type of data in environmental health research. The series is generally autocorrelated, while the widely used generalized linear model is based on the assumption of independent outcomes. None of the existing methods for modelling parameter-driven count time series can obtain consistent and reliable standard error of parameter estimates, causing potential inflation of type I error rate. Methods We proposed a new maximum significant ρ correction (MSRC) method that utilizes information of significant autocorrelation coefficient ρ estimate within 5 orders by moment estimation. A Monte Carlo simulation was conducted to evaluate and compare the finite sample performance of the MSRC and classical unbiased correction (UB-corrected) method. We demonstrated a real-data analysis for assessing the effect of drunk driving regulations on the incidence of road traffic injuries (RTIs) using MSRC in Shenzhen, China. Moreover, there is no previous paper assessing the time-varying intervention effect and considering autocorrelation based on daily data of RTIs. Results Both methods had a small bias in the regression coefficients. The autocorrelation coefficient estimated by UB-corrected is slightly underestimated at high autocorrelation (≥ 0.6), leading to the inflation of the type I error rate. The new method well controlled the type I error rate when the sample size reached 340. Moreover, the power of MSRC increased with increasing sample size and effect size and decreasing nuisance parameters, and it approached UB-corrected when ρ was small (≤ 0.4), but became more reliable as autocorrelation increased further. The daily data of RTIs exhibited significant autocorrelation after controlling for potential confounding, and therefore the MSRC was preferable to the UB-corrected. The intervention contributed to a decrease in the incidence of RTIs by 8.34% (95% CI, -5.69–20.51%), 45.07% (95% CI, 25.86–59.30%) and 42.94% (95% CI, 9.56–64.00%) at 1, 3 and 5 years after the implementation of the intervention, respectively. Conclusions The proposed MSRC method provides a reliable and consistent approach for modelling parameter-driven time series with autocorrelated count data. It offers improved estimation compared to existing methods. The strict drunk driving regulations can reduce the risk of RTIs.

Background Evaluating recurrent events within a time-to-event analysis framework effectively utilizes all relevant information to address the clinical question of interest fully and has certain advantages in randomized controlled trials (RCTs). However, the Prentice, Williams, and Peterson (PWP) model disrupts the randomness of the risk set for subsequent recurrent events other than the first and consequently introduces bias in estimating effects. This study aimed to propose a weighted PWP model, evaluate its statistical performance, and assess the potential consequences of using common practices when each recurrence has different baseline hazard functions. Methods We proposed adjusting the estimate of treatment effect through a weighting strategy that constructed a virtual population balanced between groups in each risk set. A simulation study was carried out. The characteristic of the simulation data was the baseline hazard changed with the number of events. The proposed weighted PWP model was compared with current methods, including Cox for time-to-first-event, Poisson, negative binomial (NB), Andersen-Gill (AG), Lin-Wei-Yang-Ying (LWYY), and PWP models. Model performance was evaluated by bias, type I error rates, and statistical power. All models were applied to a real case from a randomization trial of Chemoprophylaxis treatment for Recurrent Stage I Bladder Tumors. Results The results showed that the proposed weighted PWP model performed best with the lowest bias and highest statistical power. However, other models, including the Cox for time-to-first-event, Poisson, NB, AG, LWYY, and PWP models, all showed different degrees of bias and inflated type I error rates or low statistical power in the case of the baseline hazard changed with the number of events. Covariate adjustment via outcome regression can lead to inflated type I error rates. When the number of recurrent events was restricted, all weighting strategies yielded stable and nearly consistent results. Conclusions Recurrent event data should be analyzed with caution. The proposed methods may be generalized to model recurrent events. Our findings serve as an important clarification of how to deal with collider bias in the PWP model in RCTs.

Testicular dysfunction is one of the serious secondary complications in diabetes. Lycium barbarum polysaccharide (LBP) has long been considered to possess a wide range of beneficial properties including antiaging, anticancer and reproductive-enhancing. Abnormal autophagy was reported to play a significant role in accelerating diabetic reproductive injury. However, the autophagy regulation mechanism of LBP on diabetic testicular dysfunction is incompletely understood. We investigate the protective effects of LBP on diabetic testicular dysfunction and its underlying mechanism with different approaches. Protective effects of LBP (40 mg/kg) on testicular functions were assessed through the use of sperm parameters, testosterone levels and hematoxylin and eosin staining. Antioxidant capacity and serum malondialdehyde levels were determined using assay kits. Immune intensity of Beclin-1 and LC3I in testes was detected by immunofluorescence staining. Western blot analysis was used to detect expressions of p-PI3K, Akt, p-Akt, Beclin-1, LC3I and LC3II proteins. Q-PCR was used to evaluate Beclin-1 and LC3I mRNA expressions in testis. Administration of LBP (40 mg/kg) considerably recovered testicular function, obviously improved testicular histopathologic structure and significantly increased antioxidant enzyme activities. Immunofluorescence staining showed that immune intensity of Beclin-1 and LC3I significantly decreased in the LBP 40 mg/kg group. The results of Q-PCR and western blot analysis showed that LBP 40 mg/kg significantly downregulated Beclin-1 and LC3I protein expressions upregulated p-PI3K and p-Akt protein expressions and decreased Beclin-1 and LC3I mRNA expressions compared with diabetic mice. In conclusion, inhibition of PI3K/Akt pathway-mediated testicular excessive autophagy may be a target for protective effects of LBP on diabetic testicular dysfunction.

The coronavirus disease 2019 (COVID-19) pandemic has imposed a substantial disease burden globally and has further exacerbated pre-existing health inequities. This study aimed to provide a comprehensive assessment of the burden and inequities associated with COVID-19 across diverse populations. Using data from the Global Burden of Disease 2021, we systematically analyzed deaths, incidence, disability-adjusted life years (DALYs), and years of life lost (YLLs) of COVID-19 stratified by sex, age, and region. The temporal trends pre- and post-2019 (i.e., 1990-2019 and 2019-2021) were measured using average annual percent change (AAPC). Additionally, the cross-country absolute and relative sociodemographic index (SDI)-related health inequities were assessed using the slope index and concentration index, respectively. The SDI is a composite development indicator that incorporates income, educational attainment, and fertility conditions. Trends in the global burden of all-cause mortality and DALYs exhibited significant declines (AAPC < 0) from 1990 to 2019 but underwent a marked reversal trend (AAPC > 0) following the COVID-19 pandemic. In 2021, COVID-19 resulted in 2.28 billion incident cases and 7.89 million deaths globally, with an age-standardized DALYs rate of 2,501 per 100,000 population. While incidence rates were relatively evenly distributed across populations, mortality was disproportionately higher among males and older adults. Substantial health inequities in the burden of COVID-19 were evident across 204 countries and territories, with absolute widening inequities notably in 2021 (e.g., the slope index of inequity for DALYs rose from 2,713 in 2020 to 4,044 in 2021). Greater inequities are disproportionately concentrated among males, middle-aged and older individuals, and regions with lower SDI levels. These findings highlight the substantial disease burden of COVID-19 and elucidate the multidimensional health inequities exacerbated by the pandemic, providing crucial evidence for targeted interventions to address inequities and strengthen resilience in future global health emergencies.

Furochromones are specific bioactive secondary metabolites of many Apiaceae plants. Their biosynthesis remains largely unexplored. In this work, we dissect the complete biosynthetic pathway of major furochromones in the medicinal plant Saposhnikovia divaricata by characterizing prenyltransferase, peucenin cyclase, methyltransferase, hydroxylase, and glycosyltransferases. De novo biosynthesis of prim- O -glucosylcimifugin and 5- O -methylvisamminoside is realized in Nicotiana benthamiana leaves. Through comparative genomic and transcriptomic analyses, we further find that proximal duplication and high expression of a pentaketide chromone synthase gene SdPCS , together with the presence of a lineage-specific peucenin cyclase gene SdPC , lead to the predominant accumulation of furochromones in the roots of S. divaricata among surveyed Apiaceae plants. This study paves the way for metabolic engineering production of furochromones, and sheds light into evolutionary mechanisms of furochromone biosynthesis among Apiaceae plants. The complete biosynthetic pathway of Prim- O -Glucosylcimifugin and 5- O -Methylvisamminoside in Saposhnikovia divaricata is resolved and their de novo biosynthesis is reconstructed in Nicotiana benthamiana leaves. The evolutionary mechanisms of furochromone biosynthesis among Apiaceae plants is further analyzed.

Background Socioeconomic status and lifestyle conferred an impact on the incidence or first re-admission of chronic obstructive pulmonary disease (COPD), but the impact on recurrent re-admissions for COPD remains unclear. We aimed to simultaneously study their impacts on first hospital admission and re-admissions for COPD in a large prospective cohort study. Methods We included 439,463 participants without COPD at baseline from the UK Biobank and identified subsequent COPD-related admissions through linkage with national hospital databases, defined by International Classification of Diseases codes (ICD-9: 491, 492, 496; ICD-10: J40–J44). We adopted the Prentice, Williams and Peterson calendar time model to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of first admission and re-admissions for COPD associated with socioeconomic status and lifestyle factors (e.g., smoking, healthy diet, and physical activity). Subgroup analyses were further conducted by age, gender, and ethnicity. Results During a median follow-up of 13.7 years, 13,291 (3.02%) participants were hospitalized for COPD, among whom 6,980 (52.52%) were re-admitted with a median number of two hospital re-admissions per person. The risk of COPD re-admissions is elevated with the increasing number of cumulative admissions. Higher Townsend deprivation index, smoking, unhealthy diet, and lower physical activity were associated with a significantly increased risk of both first admission and re-admissions. The HRs of first admission and re-admissions were 1.08 (95%CI, 1.07–1.08) and 1.01 (95%CI, 1.01–1.02) per unit increase in Townsend deprivation index, respectively. Compared with non-smokers, both current smokers and ex-smokers had higher risks of first admission and re-admissions. Moderate- and vigorous-intensity physical activity was associated with decreased risks of admissions. Moreover, these associations were significantly modified by age, gender, and ethnicity. Conclusions Socioeconomic status and lifestyle factors are independent modifiable factors of first admission and multiple re-admissions for COPD. The findings provide important evidence to guide the management of patients with COPD to prevent or delay hospital admission for exacerbations.

Background China has introduced a series of stricter policies to criminalize drunk driving and increase penalties since May 2011. However, there is no previous study examining the time-varying impacts of drunk driving regulations on road traffic fatalities based on daily data. Methods We collected 6536 individual data of road traffic deaths (RTDs) in Guangzhou from 2008 to 2018. The quasi-Poisson regression models with an inclusion of the intervention variable and the interaction of intervention variable and a function of time were used to quantify the time-varying effects of these regulations. Results During the 11-year study period, the number of population and motor vehicles showed a steady upward trend. However, the population- and motor vehicles- standardized RTDs rose steadily before May 2011, the criminalizing drunk driving intervention was implemented and gradually declined after that. The new drunk driving intervention were associated with an average risk reduction of RTDs (ER = -9.01, 95% eCI: − 10.05% to − 7.62%) during the 7.7 years after May 2011. On average, 75.82 (95% eCI, 54.06 to 92.04) RTDs per 1 million population annually were prevented due to the drunk driving intervention. Conclusion These findings would provide important implications for the development of integrated intervention measures in China and other countries attempting to reduce traffic fatalities by stricter regulations on drunk driving.