BACKGROUND & AIMS:The efficacy of radiofrequency ablation is constrained by incomplete tumor ablation, particularly in cases of excessive tumor volume, leading to elevated recurrence rates. Elucidating the genetic and microenvironmental alterations following incomplete ablation is essential for improving therapeutic outcomes. We aimed to identify the tumor-intrinsic molecular link between residual tumor cells and the immunosuppressive microenvironment that drives recurrence after radiofrequency ablation. METHODS:We retrospectively compared recurrence in hepatocellular carcinoma patients treated with radiofrequency ablation or liver resection and established complete and incomplete radiofrequency ablation mouse models. Transcriptomic dataset analysis (differentially expressed genes and weighted gene coexpression network analysis) combined with single-cell RNA sequencing was used to identify candidate genes linking incomplete ablation to regulatory T cell recruitment. Mechanistic roles were validated by Western blotting, reverse transcription quantitative polymerase chain reaction, flow cytometry, enzyme-linked immunosorbent assay, immunohistochemistry/immunofluorescence, and T-cell coculture assays, and the effect of p53-induced death domain protein 1 knockdown combined with anti-programmed cell death protein-1 therapy was assessed in vivo. RESULTS:Analysis of tumor recurrence post radiofrequency ablation revealed a significantly higher local recurrence rate in primary tumors exceeding 2 cm in size, indicating that incomplete ablation is a critical driver of local tumor regrowth. In preclinical animal models, incomplete radiofrequency ablation was associated with increased infiltration of regulatory T cells. Gene expression profiling identified marked upregulation of p53-induced death domain protein 1, which strongly correlated with regulatory T cell infiltration and unfavorable prognosis. Mechanistic studies demonstrated that p53-induced death domain protein 1 enhanced p53 expression via the caspase-2/murine double minute 2 axis, promoted transforming growth factor-β1 secretion, and drove T-cell differentiation into regulatory T cells. Silencing p53-induced death domain protein 1 in hepatocellular carcinoma cells reduced regulatory T cell infiltration and heightened sensitivity to immunotherapy. Strikingly, combining radiofrequency ablation with immunotherapy following p53-induced death domain protein 1 knockdown significantly enhanced treatment efficacy. CONCLUSIONS:These findings provide a robust theoretical and practical basis for integrating radiofrequency ablation with anti-programmed cell death protein-1-targeted therapy to mitigate recurrence and optimize clinical outcomes.

BACKGROUND:Conservative induction dose in methadone maintenance treatment (MMT) may lead to early dropout. Existing evidence mostly focuses on linear associations, leaving non-linear dose-response relationships and critical inflection points unexplored. METHODS:This retrospective cohort study analyzed 5083 first-time patients across 11 MMT clinics in Guangdong Province (2006-2021). The mean methadone dose in the first week defined the induction dose, and dropout within 30 days was the outcome. Restricted Cubic Spline (RCS) and threshold analysis explored non-linear and inflection points. RESULTS:After confounder adjustment, a significant negative association existed between dose and dropout (OR=0.900, 95% CI: 0.876-0.924), confirmed with weighting. A non-linear relationship was identified (Pnon-linear <0.001) with an inflection point at 40.71mg/day. Below this point, each 5mg/day dose increase reduced dropout risk by 17% (OR=0.83, 95% CI: 0.78-0.87). Above 40.71mg/day, the risk reduction was 6% (OR=0.94, 95% CI: 0.91-0.98). Sensitivity analysis (excluding 48 high doses) lowered the inflection point to 33.57mg/day. Subgroup analysis indicated interactions of the induction dose effect with both drug-use frequencies (P = 0.043) and the year entering MMT (P = 0.027). Those with higher drug frequency showed a smaller reduction in dropout risk after increasing the induction dose. CONCLUSION:The study identified a non-linear association between induction dose and early dropout, and there is a threshold effect inflection point. Based on current guidelines, there is a need to appropriately increase the starting dose of MMT, with further consideration of methadone safety and individual differences required in clinical practice.

Objectives To identify multifactorial contributors to treatment-seeking delays among Chinese young and middle-aged stroke patients using socioecological model.Design Descriptive phenomenological interview study.Setting A tertiary hospital in China.Participants Twenty acute stroke patients with treatment-seeking delays and 16 family members were recruited for dyadic semistructured interviews.Primary and secondary outcome measures Barriers influencing treatment-seeking delays across individual, interpersonal and systemic levels. And how do interlevel interactions shape decision-making trajectories?Results Data analysis revealed 5 overarching themes encompassing 12 subthemes: (1) limited stroke-specific health literacy; (2) psychological barriers at symptom onset; (3) inadequate interpersonal support systems; (4) structural impediments to timely care; (5) decision-making dynamics across levels. Delay was characterised as a sequential cascade mediated by cognitive misattribution, emotional paralysis, relational dependency, institutional constraints and cross-level feedback loops. Two dominant pathways, silent progression and diverted seeking, were identified.Conclusion Treatment-seeking delay among young and middle-aged stroke patients arises through dynamic interactions across socioecological strata rather than isolated factors. Integrated interventions targeting public awareness, familial preparedness, workplace policies and healthcare accessibility are required to disrupt this cascade.

In women with prediabetes after prior gestational diabetes mellitus (GDM), whether intermittent metformin treatment as needed is as effective as continuous use in preventing type 2 diabetes mellitus (T2DM) is unknown. We aimed to test whether an intermittent metformin treatment is non-inferior to continuous metformin strategy for prevention of T2DM in women with prediabetes after GDM. A randomized, open-label, non-inferiority trial was conducted at three centers in China. Women aged 18–45 years with prior GDM and prediabetes at 4–12 weeks postpartum were randomly assigned to receive lifestyle intervention plus intermittent or continuous metformin treatment. In the continuous group, participants were initially treated with lifestyle intervention and metformin was initiated when lifestyle intervention alone failed to maintain euglycemia and continued without interruption throughout the trial. In the intermittent group, participants were initially treated with lifestyle intervention and metformin was added when they failed to maintain euglycemia and was discontinued if the glycemic status returned to normal. The primary outcome was the difference in incidences of newly diagnosed diabetes between the two groups during the 3-year follow-up, compared against a non-inferiority margin of 10-percentage-point by following the intention-to-treat principle. Secondary outcomes included the percentage of prediabetes remission, changes from baseline in body weight, body mass index, waist circumference, fasting plasma glucose, 2-h plasma glucose, and hemoglobin A1c. Among the 376 women randomized, 11.5

INTRODUCTION:There is an increasing concern on the risks of cardiovascular diseases in migrant workers in China. In the Zhoushan Archipelago, an urbanized area comprising 103 inhabited islands, migrant workers represent a growing population at risk of ischemic stroke, while the clinical characteristics of migrant workers with stroke remain understudied. This study aimed to identify the clinical characteristics of ischemic stroke in migrant workers compared with local residents in the Zhoushan Archipelago. METHODS:A total of 1,006 patients with ischemic stroke were included (452 migrant workers and 554 local residents). Clinical and radiological data were collected and compared between groups. Continuous and categorical variables were compared using t tests (or non-parametric tests) and chi-square tests, respectively. Binary logistic regression analyses were used to investigate differences between groups. Statistical significance was defined as p < 0.05. RESULTS:In these patients, compared with local residents, migrant workers had a higher body mass index but lower rates of diabetes and atrial fibrillation and lower levels of lymphocyte, uric acid, folate, and vitamin B12, with higher ratios of overweight and obese cases (p < 0.05 for all). There was no significant difference between the two groups in etiological classification of stroke. Regarding the ischemic regions, migrant workers showed a higher incidence of basal ganglia infarctions (p < 0.05). CONCLUSION:Ischemic stroke in migrant workers showed a distinct clinical profile compared with local residents, underscoring the need for targeted preventive healthcare interventions for migrant workers in an urbanized archipelago setting.

Objective:To assess chronic obstructive pulmonary disease (COPD)-related clinical competency, confidence, and management practices among general practitioners (GPs) in Pudong community health centers. Methods:A cross-sectional survey was conducted. Stratified random sampling across four regional strata yielded 457 valid responses (99.34% response rate). Results:While 56.02% of GPs managed 11-30 COPD patients monthly, 96.06% reported COPD constituted <30% of their caseload. Clinical engagement was suboptimal: 80.74% performed spirometry ≤10 times annually, and 45.73% referred cough/dyspnea patients directly to specialists. Significant competency gaps were identified in inhaled pharmacotherapy, classification, CAT/mMRC usage, spirometry interpretation, and inhaler instruction. Confidence in management was low (mean score: 2.85/5). Regression analysis revealed that proficiency correlated with standardized residency training, COPD-specific continuing medical education (CME) attendance, and physician age. Both competency and confidence levels correlated positively with the frequency of management practices. Conclusion:GPs in Pudong exhibit inadequate COPD knowledge depth, poor clinical application skills, and low decision-making confidence. These findings highlight the need for training programs integrating theoretical instruction with hands-on practice to support improvements in competency and promote standardized community-based COPD management.

Objective:Several modifiable healthy lifestyle factors have been demonstrated to exert an effect of blood pressure lowering. However, there remains limited evidence regarding the association between healthy lifestyle scores (HLS) and hypertension, particularly within the Chinese population. The present prospective cohort study was designed to systematically investigate the relationships between HLS, their long-term dynamic changes, and the incident risk of hypertension. Methods:A total of 3,743 participants aged ≥18 years who were free of hypertension at baseline were included in the study and followed up prospectively. The HLS was calculated based on the number of healthy lifestyle factors. The Cox proportional hazards regression model was employed to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) for evaluating the associations between HLS, their long-term changes, and the risk of incident hypertension. In addition, a quantile regression (QR) approach was applied to assess the associations of HLS with blood pressure levels. Results:During a median follow-up period of 6.46 years, 857 cases of hypertension were identified. The HLS was significantly associated with a reduced risk of hypertension, with a 14% risk reduction observed (HR: 0.86, 95% CI: 0.80-0.92). Compared with the low HLS group (0-3), the HRs (95% CIs) for incident hypertension were 0.80 (95% CI: 0.66-0.97), 0.78 (95% CI: 0.64-0.95), and 0.61 (95% CI: 0.49-0.75) for the HLS groups with 4, 5, and ≥6, respectively (P for trend <0.001). In comparison with participants maintaining a HLS of 0-3, those maintaining a HLS of 4 (HR: 0.60, 95% CI: 0.43-0.85), 5 (HR: 0.47, 95% CI: 0.32-0.69), and ≥6 (HR: 0.34, 95% CI: 0.23-0.51) exhibited a significantly lower risk of incident hypertension (P for trend <0.001). QR showed a significant negative association between HLS and blood pressure levels. Conclusion:As the HLS increased, the risk of hypertension showed a gradual downward trend. Furthermore, long-term maintenance of a high HLS was associated with a reduced risk of hypertension. Our findings provide additional evidence from China supporting the necessity of sustaining healthy lifestyles across the life course.

Maintenance therapy is key in prolonging remission and improving quality of life for hormone receptor-positive (HR + ), HER-2 negative (HER2-) metastatic breast cancer (MBC), but optimal strategies remain debated. This multicenter, open-label, randomized phase 3 trial conducted across 22 hospitals in mainland China (ClinicalTrials.gov, NCT04263298; Chinadrugtrials.org.cn, ChiCTR-IIR-17014036) compared the efficacy and safety of fulvestrant versus capecitabine as maintenance therapy in HR + /HER2- MBC patients after achieving objective response or disease control following first-line chemotherapy. The primary end point was investigator-assessed progression-free survival (PFS). A total of 210 patients underwent randomization, with 105 assigned to each group. As of the data cutoff date on March 1, 2025, the median follow-up was 33.6 months (range 1.5-81.1). Median PFS favored fulvestrant compared with capecitabine (17.3 months [95% CI 12.7-23.3] vs. 9.0 months [95% CI 7.5-14.3]; hazard ratio 0.63, 95% CI 0.47-0.99; p = 0.003). Overall survival data were not yet mature. Grade ≥3 adverse events (AEs) occurred in three patients (2.9%) in the fulvestrant group and 11 (10.5%) in the capecitabine group. Treatment discontinuation due to AEs occurred in 0% and 7.6% of patients, respectively. Fulvestrant maintenance therapy significantly improves PFS compared to capecitabine in HR + /HER2- MBC patients achieving objective response or disease control following first-line chemotherapy, with a favorable safety profile.

BACKGROUND:Females with healthy lifestyles have a lower risk of preterm birth (PTB). However, the association between paternal healthy lifestyle and PTB risk is not well investigated. OBJECTIVES:This study aimed to evaluate the association between an overall paternal healthy lifestyle and risk of PTB in their offspring. METHODS:The population-based, retrospective cohort included 810,475 couples who participated in the National Free Preconception Checkups Project in Guangdong Province, China, and successfully had a singleton livebirth between 1 January, 2014 and 1 November 1, 2019. A combination of paternal healthy lifestyle was measured: no smoking, no drinking, and healthy body mass index (18.5-23.9 kg/m2). Associations between healthy lifestyle factors and PTB risk were estimated by modified Poisson regression models with inverse probability of treatment weighting. RESULTS:After accounting for key maternal risk factors such as maternal age, parity, and maternal healthy lifestyle, risk ratios of infants experiencing PTB for couples where the male partner had a healthy lifestyle score of 1, 2, and 3 compared with a healthy lifestyle score of 0 were 0.94 (95% confidence interval: 0.90, 0.99), 0.94 (0.90, 0.98), and 0.90 (0.86, 0.94), respectively (Ptrend < 0.001). However, the association between paternal healthy lifestyle and PTB was only statistically significant among the subset of males evaluated for lifestyle factors >90 d before pregnancy. When shifting these 3 paternal unfavorable lifestyle factors, population attributable risk estimation suggests that 2.37% (1.90%, 4.65%) of PTB cases might be prevented. We did not find statistically significant additive interaction of paternal and maternal healthy lifestyles on risk of PTB (relative excess risk due to interaction: -0.04; -0.09, 0.01). CONCLUSIONS:Paternal healthy lifestyle was independently associated with a lower risk of PTB in their offspring. These findings highlight the importance of including lifestyle modifications among males to improve pregnancy outcomes.

Lipid homeostasis and vascular endothelial function are fundamental to cardiovascular health. This review systematically outlines the regulatory mechanisms that maintain the dynamic balance between the endothelium and systemic lipid metabolism, emphasizing the endothelium as an active regulator. The endothelium influences lipid metabolism in multiple organs by regulating vascular tone, angiogenesis, barrier integrity, and inflammatory response. Studies have demonstrated that genetic ablation of endothelial-specific genes disrupts lipid metabolism in key metabolic organs, including the liver, adipose tissue, and skeletal muscle. This impairment of endothelial function may result in obesity, insulin resistance, hyperlipidemia, and MASLD/MASH. The specific mechanisms linking endothelial dysfunction to systemic lipid metabolism are highlighted. This review clarifies the progression of systemic lipid metabolism disorders driven by an imbalance in the “endothelial-lipid metabolism homeostasis axis”. Potential therapeutic strategies targeting this axis for lipid-metabolism disorders and related cardiovascular diseases are also discussed.

Background: Major Depressive Disorder represents a prevalent and critical mental health issue that highlights the pressing need for innovative therapeutic solutions. Recent research has identified dysfunction within the glutamate system as a crucial element influencing both the onset and management of depressive symptoms. Although TAK-653 is a new positive allosteric modulator of AMPA receptors, its effects have not been rigorously examined in models of depression in primates. Methods: To assess its potential antidepressant properties, a chronic unpredictable mild stress protocol was implemented over 12 weeks to create a monkey model of depression, followed by a two-week treatment period with TAK-653. Results: Behavioral evaluations showed that following stress exposure, the monkeys exhibited reduced motivation for food, increased huddling, diminished movement, and a tendency to remain at the lower levels of their enclosure. They also displayed heightened anxiety in response to external stimuli. Plasma analyses indicated higher levels of cortisol, IL-6, and IL-8 in the stressed monkeys compared to baseline readings, confirming the efficacy of the stress-inducing protocol. Post-treatment with TAK-653 resulted in significant improvements, such as enhanced motivation for food, less huddling behavior, greater activity, and a move towards the upper areas of the enclosure. Additionally, the plasma analysis revealed a marked decrease in cortisol and IL-6 levels, along with an increased expression of BDNF. Conclusions: These findings indicate that TAK-653 effectively alleviates depression-like behaviors in nonhuman primate models, thereby paving the way for a promising new strategy in the treatment of depression.

Importance Previous studies have demonstrated the advantages of short-term histopathological outcomes and complications associated with transanal total mesorectal excision (TME) compared with laparoscopic TME. However, the long-term oncological outcomes of transanal TME remain ambiguous. This study aims to compare 3-year disease-free survival of transanal TME with laparoscopic TME. Objective To evaluate 3-year disease-free survival between transanal TME and laparoscopic TME in patients with rectal cancer. Design, Setting, and Participants This randomized, open-label, noninferiority, phase 3 clinical trial was performed in 16 different centers in China. Between April 2016 and June 2021, a total of 1115 patients with clinical stage I to III mid-low rectal cancer were enrolled. The last date of participant follow-up was in June 2024. Interventions Participants were randomly assigned in a 1:1 ratio before their surgical procedure to undergo either transanal TME (n = 558) or laparoscopic TME (n = 557). Main Outcomes and Measures The primary end point was 3-year disease-free survival, with a noninferiority margin of -10% for the comparison between transanal TME and laparoscopic TME. Secondary outcomes included 3-year overall survival and 3-year local recurrence. Results In the primary analysis set, the median patient age was 60 years. A total of 692 male and 397 female patients were included in the analysis. Three-year disease-free survival was 82.1% (97.5% CI, 78.4%-85.8%) for the transanal TME group and 79.4% (97.5% CI, 75.6%-83.4%) for the laparoscopic TME group, with a difference of 2.7% (97.5% CI, -3.0% to 8.1%). The lower tail of a 2-tailed 97.5% CI for the group difference in 3-year disease-free survival was above the noninferiority margin of -10 percentage points. Furthermore, the 3-year local recurrence was 3.6% (95% CI, 2.0%-5.1%) for transanal TME and 4.4% (95% CI, 2.6%-6.1%) for laparoscopic TME. Three-year overall survival was 92.6% (95% CI, 90.4%-94.8%) for transanal TME and 90.7% (95% CI, 88.3%-93.2%) for laparoscopic TME. Conclusions and Relevance In patients with mid-low rectal cancer, 3-year disease-free survival for transanal TME was noninferior to that of laparoscopic TME.

STUDY QUESTION:Is paternal age associated with neonatal outcomes? SUMMARY ANSWER:Paternal age is independently associated with preterm birth (PTB) and caesarean section. WHAT IS KNOWN ALREADY:Advanced maternal age has long been recognized as a major risk factor for adverse neonatal outcomes. However, the association between paternal age and neonatal outcomes are not well established, yet it is biologically plausible that an increasing number of genetic and epigenetic sperm abnormalities in older males may contribute to adverse neonatal outcomes. STUDY DESIGN SIZE DURATION:This population-based cohort study was based on the National Free Preconception Checkups Project between 1 January 2014 and 31 December 2019 in Guangdong Province, China. Paternal age at the maternal last menstrual period was measured. The main outcomes included caesarean section, PTB, small for gestational age (SGA) and perinatal infant death (PID). PARTICIPANTS/MATERIALS SETTING METHODS:A total of 783 988 mother-neonate-father trios were included in this study. A modified Poisson regression model was employed to estimate relative risk (RR) and 95% CI and logistic regression models were used to analyse the relative importance of predictors. We used restricted cubic splines to flexibly model the non-linear dose-response association between paternal age and neonatal outcomes. We also assessed additive interactions between paternal and maternal age on neonatal outcomes. MAIN RESULTS AND THE ROLE OF CHANCE:Neonates born to fathers aged 35-44 years had higher risks of caesarean section (RR: 1.07; 95% CI: 1.06-1.09) and PTB (RR: 1.15; 95% CI: 1.10-1.19) compared with neonates of fathers aged 25-34 years, after adjustment for confounders. The increased risks of PTB associated with paternal age appeared to be 'dose' dependent, with a J-shaped association curve (P for non-linearity<0.001). The relative importance of paternal age in predicting PTB and caesarean section was similar to, or even higher than, that of maternal age. The combined effects of advanced maternal and paternal age appeared to be less than additive joint effects (relative excess risk due to interaction<0). The association of paternal age with SGA or PID was not statistically significant (P > 0.05). LIMITATIONS REASONS FOR CAUTION:As with all observational studies, residual confounding could not be ruled out. Only couples who planned to conceive were included. WIDER IMPLICATIONS OF THE FINDINGS:In this population-based cohort study, paternal age was independently associated with caesarean section and PTB. These findings may be clinically useful in preconception counselling on parental age-related pregnancy risks. Our findings emphasize the need to further investigate the public health implications of increasing paternal age. STUDY FUNDING/COMPETING INTERESTS:This study was supported by the Guangdong Province Medical Research Funding (No. B2023416). No competing interests are reported. TRIAL REGISTRATION NUMBER:N/A.

Parkinson's disease (PD) is a devastating neurodegenerative disorder with growing prevalence worldwide and, as yet, no effective treatment. Drug repurposing is invaluable for detecting novel PD therapeutics. Here, we compiled gene expression data from 1231 healthy human brain samples and 357 samples across tissues, ethnicities, brain regions, Braak stages, and disease status. By integrating them with multiple-source genomic data, we found a PD-associated gene co-expression module, and its alignment with the CMAP database successfully identified drug candidates. Among these, meclofenoxate hydrochloride (MH) and sodium phenylbutyrate (SP) are indicated to be able to prevent mitochondrial destruction, reduce lipid peroxidation, and protect dopamine synthesis. MH was validated to prevent neuronal death and synaptic damage, improve motor function, and reduce anhedonic and depressive-like behaviors of PD mice. The interaction of MH with a PD-related protein, sigma1, was confirmed experimentally. Thus, our findings support that MH potentially ameliorates PD by interacting with sigma1.

BackgroundAtherosclerosis (AS) is the main cause of macrovascular disease. Previous studies have found sex differences in the prevalence of type 2 diabetes mellitus (T2DM) and its associated macrovascular disease outcomes. However, the relationship between sex differences, T2DM, and AS is not fully understood. This study attempts to explore possible associations between sex, treatment, and the burden of intracranial atherosclerosis (ICAS) in patients with T2DM who have experienced an acute ischemic cerebrovascular disease.MethodsWe focused on patients with T2DM with acute ischemic stroke or transient ischemic attack due to intracranial atherosclerotic stenosis. ICAS was assessed by 3T cardiovascular magnetic resonance vascular wall imaging. Plaque counts of the total, proximal, and distal intracranial arteries were used to assess plaque burden. Patients with a history of T2DM and currently taking hypoglycemic drugs were defined as being treated. Poisson regression models or negative binomial regression models were used to analyze the interaction between sex and treatment in relation to plaque burden.ResultsA total of 495 plaques were detected in 120 patients (75 male; mean age, 60.77 ± 11.01 years), including 311 proximal and 184 distal plaques. The intracranial culprit plaque was located proximal to the artery in both male (85.3%) and female (88.9%) patients. The adjusted total and proximal intracranial plaque burdens were 1.261 times (95% confidence interval [CI], 1.050–1.515, P=0.013) and 1.322 times (95%CI, 1.055–1.682, P=0.016) higher in male than in female patients. The risk ratio for proximal plaque burden in untreated male versus female patients was 0.966 (95%CI, 0.704–1.769). However, the proximal plaque risk ratio for treated male versus female patients was 1.530 (95%CI, 1.076–2.174). The interaction of sex and treatment significantly affected the proximal plaque burden.ConclusionMale patients with T2DM and acute cerebrovascular disease have a significantly higher adjusted risk of total and proximal intracranial plaque burden compared to female patients. Female patients undergoing antidiabetic treatment have a significantly reduced risk of proximal plaque to males. Considering that culprit plaques tend to accumulate in the proximal arteries, understanding how to reduce the burden of proximal plaques may help reduce the risk of adverse cerebrovascular events.

Introduction:The increasing utilization of antiretroviral (ART) medications by people living with HIV(PLWH) poses a potential risk to the efficacy of standardized ART management protocols in resource-limited settings, particularly as it may accelerate the emergence of transmitted drug resistance (TDR). Our research aimed to elucidate the prevalence, risk factors, geographical variations, and transmission patterns of TDR to inform and enhance ART management strategies. Methods:The study covered newly diagnosed PLWH in Sichuan from July 2022 to June 2023. We conducted sequencing - based resistance profiling and then analyzed TDR via the Stanford HIV Drug Resistance Database and logistic regression to identify associated factors via SPSS. ArcGIS and spatial statistics were used to create LISA maps showing the TDR distribution. HIV-TRACE's Tamura Nei 93 model was used to assess genetic clustering, and QGIS was used to analyze TDR intensity within and between cities. Results:This study found that the prevalence of TDR in Sichuan had reached a moderate level, with a resistance rate of 10.91%. Resistance varied by drug class: 8.08% for NNRTIs, 1.34% for NRTIs, and 2.22% for PIs. Regions like LS, DY, SN, and LZ had higher TDR rates. Within NNRTIs, efavirenz (EFV) and nevirapine (NVP) resistance rates were 6.26% and 6.50%, respectively. Furthermore, risk factors for TDR included age under 15, HIV-1 subtypes, and residing in areas with high ART failure rates. In addition, spatial analysis showed significant clustering of TDR, especially for PIs and NNRTIs, with hotspots identified in certain regions. Among 1,486 drug-resistant PLWH, 52.76% formed resistance-linked networks, comprising 181 molecular clusters. Key resistance mutations included K103N, E138A, V179D, Y181C, and Q58E. The transmission intensity of TDR varied across regions, highlighting complex spatial dynamics. Discussion:The prevalence of TDR in Sichuan had reached moderate epidemic levels, with certain cities already experiencing high epidemic rates. It is urgent that we urgently expand targeted genotypic drug resistance detection and implement interventions to improve medication adherence.

OBJECTIVES:Global countries often apply containment policies (CPs) to combat infectious disease surges. Whether countries with longer cumulative duration of CPs are associated with slower long-term epidemic progression necessitates a thorough evaluation. METHODS:We collected CP and COVID-19 data of 185 territories during 2020-2022, with a total of 23 CPs. Using the target trial emulation and cloning-censoring-weighting approaches, we assessed the effectiveness of CPs with different cumulative durations in delaying countries from reaching the 1% and 10% cumulative infection incidence end points (i.e. 10,000 and 100,000 COVID-19 cases per million population, respectively) over a 3-year observation period. RESULTS:For reaching the 1% cumulative infection incidence, recommending closing workplaces and limiting gatherings to 10 people, each presented that a longer cumulative duration of those CPs is associated with a lower proportion of countries achieving this end point throughout 2020-2022. For reaching the 10% cumulative infection incidence, mandatory bans on public events and domestic movements, closing public transports, and screening and quarantining inbound tourists, each showed similar associations. Notably, long-lasting border bans upon high-risk regions are associated with a higher proportion of countries reaching the 10% cumulative infection incidence. CONCLUSIONS:From the long-term perspective, we highlight CPs that warrant extending the duration to achieve slower epidemic progression. By contrast, our findings demonstrate the limited effectiveness of the ban on regions in slowing the long-term epidemic progression.

OBJECTIVE:To examine whether more stringent border controls (BCs), including quarantine, ban on regions, and total border closure, are associated with slower initial-stage epidemic progression compared to screening. METHODS:Using real-world BCs and COVID-19 epidemic data from 174 countries and regions from 1 January to 31 July 2020, we compared the effectiveness of different stringency BCs in slowing countries from reaching the first infection peak. To account for the immortal time bias due to staggered BC adoptions across countries, the target-trial-emulation and cloning-censoring-weighting approaches were applied. Kaplan-Meier model with inverse probability censoring weights (IPCW) was used to obtain effectiveness estimates for each BC. Country-specific timing and methods of implementing diagnostic testing were not included in the IPCW calculation model due to data unavailability. BC adoption timing was investigated as a potential mechanism for BCs' effectiveness. RESULTS:Compared with countries adopting basic border screening, those adopting more stringent BCs were not associated with a reduced risk of reaching the first infection peak, including the most stringent total border closure (Hazard Ratio [HR]: 1.07, 95% CI: 0.88-1.30). Countries adopting those stringent BCs experienced significant delays than those adopting screening potentially elucidating the mechanism. Further analysis revealed that BC adoption timing, regardless of stringency, was independently associated with the risk of the first infection peak attainment. CONCLUSIONS:More stringent BCs in response to pandemics did not necessarily lead to slower initial-stage epidemic progression if adoptions were delayed. These findings highlight the importance of considering both timing and stringency-rather than focusing on stringency alone-when adopting BCs against future emerging infectious disease surges.

Background:Anxiety symptoms are common among university students in China, posing challenges to mental health. Physical activity may reduce anxiety, but the mechanisms are not fully understood. This study examines how smartphone addiction acts as a mediator and sleep quality as a moderator in the relationship between physical activity and anxiety, aiming to offer theoretical insights and practical strategies for mental health interventions. Methods:This cross-sectional study was conducted in September 2023 at Guangxi University. A stratified sampling method was used to approach 719 students from diverse physical education classes to distribute questionnaires, and 527 valid questionnaires were returned. Validated instruments included the International Physical Activity Questionnaire-Short Form (IPAQ-SF), Smartphone Addiction Scale-Short Version (SAS-SV), Pittsburgh Sleep Quality Index (PSQI), and Self-Rating Anxiety Scale (SAS). Data analysis involved standardization, descriptive statistics, Pearson correlation, normality testing, mediation and moderation analyses, and Bootstrap validation. Results:(1) Physical activity was negatively correlated with smartphone addiction (r = -0.13, p < 0.01). (2) Smartphone addiction was positively correlated with poor sleep quality (r = 0.40, p < 0.01) and anxiety (r = 0.43, p < 0.01). (3) Poor sleep quality and anxiety were significantly correlated (r = 0.57, p < 0.01). (4) A masking effect occurred as the non-significant positive direct effect (β = 0.062) was nearly canceled out by the mediation of smartphone addiction (β = -0.058), inducing total effect near-zero. (5) Sleep quality significantly influenced the link between smartphone addiction and anxiety, especially in those with poorer sleep, where the impact of smartphone addiction on anxiety was stronger (β = 0.061, p = 0.036). Conclusion:This study revealed a more complex relationship between physical activity and anxiety than initially hypothesized. Our findings further revealed the relationship between physical activity and university students' anxiety, and considered the mediating role of smartphone addiction between the two, as well as the moderating role of sleep quality in the relationship between mobile phone addiction and university students' anxiety.