Men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have heterogeneous symptoms and variable responses to treatment. We sought to identify clinical and treatment factors associated with pain improvement. Specifically, which presenting features and management strategies are associated with clinically meaningful reductions in pain among men with CP/CPPS? We performed a retrospective review of men evaluated for chronic pelvic or genitourinary pain by a single specialist from February 2023 to July 2025. Patients were included based on ICD codes for pelvic pain, genitourinary pain, or chronic prostatitis. Demographics, presenting symptoms, and initial and most recent visual analog scale (VAS) pain scores were collected. Intervention types were compared by analyzing VAS scores before and after receiving an intervention. 157 men were included, of which 103 had follow-up VAS data. The median follow up was 277 days and median symptom duration prior to presentation was 24 months. Diffuse pelvic pain was the most common phenotype (51.6%). The mean baseline and most recent VAS scores were 3.4 and 2.1, respectively. The greatest improvements were associated with penile block (- 3.8), spermatic cord block (- 2.6), and hydrodistension with cautery of ulcers (- 2.6). Cystoscopy was performed in 26.8% of patients. While often non-diagnostic (31%), cystoscopy frequently diagnosed inflammatory lesions (31%) and BPH (19%). Most patients with CP/CPPS experienced clinically meaningful pain reduction following subspecialist evaluation. Diffuse pain without clear triggers is common. Greater improvement with nerve blocks and treatment of Hunner's lesions supports a phenotype-driven approach. However, studies are needed to isolate and validate treatment effects.
Cirrhosis is a disease of impaired liver function and fibrosis caused by long-term liver damage. However, to date, no drugs have been approved to improve liver fibrosis. We report the results of a phase 2 study of S-005151 (generic name: Redasemtide), a partial peptide of High-Mobility Group Box 1 (HMGB1), in patients with chronic liver disease. This single-center, non-randomized, single-arm, open-label study was performed in Japan in patients with chronic liver disease (cohort A: 5 patients, cohort B: 5 patients) caused by HCV, HBV, MASH, or alcohol, with MR elastography of ≥ 4 kPa and Child-Pugh score up to 7 points. The primary endpoint was safety; secondary endpoints were efficacy against liver injury, function, and fibrosis. One adverse event (dysphonia) was observed in cohort A and one (fever) in cohort B, both of which were mild drug-related adverse events. S-005151 was well-tolerated. Regarding efficacy, there was a trend toward improvement post-treatment, with a decrease in transaminase and improvement in tissue inflammation scores in some cases; however, there was no significant improvement in hepatic dysfunction. Regarding liver fibrosis, there was a rapid and stable decrease in serum type IV collagen 7S levels, improvement in MR elastography findings, and an increase in platelet counts in some cases; 5 of 10 patients showed a trend toward improvement in liver fibrosis. S-005151 is well-tolerated in patients with chronic liver disease and may have therapeutic effects, in reducing liver damage and improving liver fibrosis. jRCT, jRCT 2031200232, Registered 4 December 2020 (https://jrct.mhlw.go.jp/latest-detail/jRCT2031200232).
Immune cells seed tissues in orchestrated waves beginning in utero. While the impact of prenatal environmental exposures is well-documented in neuroimmunology, the influence of maternal-fetal interactions on systemic immune development and its contribution to lifelong chronic inflammatory disease remains underappreciated. This narrative review synthesizes recent ontogeny data to demonstrate how diverse prenatal cues, ranging from maternal infection to microbial-derived metabolites, function as a "prenatal training ground" for the developing fetal immune system. These maternal signals interact with specific waves of hematopoiesis to shape long-lived tissue-resident immune cells. In many tissues, these prenatally programmed populations persist into adulthood, acting as lifelong immunological rheostats that dictate the type and intensity of local inflammatory responses. Furthermore, we critically evaluate the translational gaps in the field, highlighting fundamental species-specific differences in developmental timelines that necessitate careful alignment between preclinical animal models and human biology. We propose that many chronic immune conditions are not strictly adult-onset in their etiology, but rather adult-manifesting, making prenatal immune seeding a critical, yet overlooked, determinant of long-term health. Current interventions largely focus postnatally, but reorienting research and clinical focus toward prenatal factors provides new insights into the developmental origins of chronic inflammation and offers a novel therapeutic window to optimize the health trajectory of the next generation.
Immune thrombocytopenia (ITP) is characterized by reduced platelet production and platelet destruction. Despite the availability of numerous treatments, many patients develop treatment resistance, experience relapse, or suffer from persistent symptoms such as fatigue, highlighting the need for innovative immune-modulating techniques. This review highlights the chemical properties, clinical efficacy and safety evidence for rilzabrutinib. Bruton tyrosine kinase (BTK) is a promising therapeutic target in ITP as it is essential for B-cell receptor signaling, Fcγ receptor-mediated platelet clearance, and inflammatory amplification. Rilzabrutinib is a reversible, covalent oral BTK inhibitor developed to treat immune-mediated disorders. It targets several pathogenic immunological pathways. In the phase 2 LUNA 2 trial and the subsequent randomized, placebo-controlled, phase 3 LUNA 3 study, rilzabrutinib was clinically evaluated in patients with persistent or chronic ITP. The treatment resulted in durable platelet responses in extensively pretreated patients, decreased bleeding episodes, and led to significant improvements in patient-reported fatigue. The safety profile was generally good with adverse events considered mild to moderate. The approval of rilzabrutinib for persistent and chronic ITP represents an important addition to the therapeutic armamentarium for the disease. The drug's full potential will be further defined in future studies.
Multiple studies have consistently reported elevated oxidative stress and an impaired niacin skin flush response in patients with schizophrenia. This study aimed to compare differences in oxidative stress levels and the niacin skin flush response between patients stratified by the intensity of their response and healthy controls, and to analyze the correlations among oxidative stress markers, the niacin response, and clinical symptoms within the different response subgroups. A cross-sectional case-control design was employed. Fifty patients with chronic schizophrenia and 50 demographically matched healthy controls were enrolled. Plasma levels of malondialdehyde (MDA), total nitric oxide synthase (TNOS), and inducible nitric oxide synthase (iNOS) were measured in all participants, and the niacin skin flush response was assessed. Symptom severity in patients was rated using the Positive and Negative Syndrome Scale (PANSS). Based on the intensity of the niacin response, patients were further divided into high-response and low-response subgroups. Regression analysis was used to explore the associations among oxidative stress indicators, the niacin response, and clinical symptoms. MDA levels were significantly higher in the patient group than in the control group, whereas both TNOS and iNOS levels were significantly lower. The pattern of associations among oxidative stress markers, the niacin skin flush response, and clinical symptoms differed across response subgroups. These relationships may be influenced by factors such as sex, body mass index (BMI), age, and the dosage of antipsychotic medication. Patients with chronic schizophrenia exhibit abnormalities in oxidative stress and show individual variability in the niacin skin flush response. The intensity of the niacin response may be associated with factors such as sex, BMI, age, and medication, leading to significant differences in the relationships among variables across subgroups in regression analysis. The results suggest that oxidative stress may be involved in the pathophysiological processes of schizophrenia, and that niacin sensitivity may reflect the level of oxidative stress in the body and correlate with different clinical symptomatic profiles. No applicable.
Chronic respiratory diseases (CRDs) represent a substantial component of the global burden of disease, contributing significantly to morbidity, mortality, and healthcare expenditure worldwide. This review synthesizes current evidence on the epidemiology, determinants, and both population-level and individual impacts of four major respiratory health conditions: asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and smoking; the latter is both a disease in itself and a major contributor to respiratory and non-respiratory morbidity. Despite distinct pathophysiological mechanisms, these conditions share common risk factors, including environmental exposures and socioeconomic determinants, which contribute to diagnostic and management challenges. This review examines the burden of these conditions at both individual and population levels, explores current and future trends, and highlights the critical need for coordinated public health strategies, primary prevention, and global policy interventions to mitigate their growing impact. Considering the interconnections between human, animal, and environmental health, a unifying framework of planetary respiratory medicine and One Health may provide solutions to the CRD burden by promoting lung health across the life course.
Macrocytic anemia is frequently associated with liver dysfunction; however, reliable biomarkers for predicting chronic liver disease (CLD) in this population remain limited. This longitudinal study included 693 individuals with macrocytic anemia from the China Health and Retirement Longitudinal Study (CHARLS). Individuals with a mean corpuscular volume (MCV) > 100 fL were defined as having macrocytic anemia. C-reactive protein-triglyceride-glucose index (CTI) was calculated by the formula of CTI = 0.412×Ln(CRP [mg/L]) + Ln(TG [mg/dL] × FPG [mg/dL])/2. Then, the association between CTI and CLD was assessed using three sequentially adjusted Cox regression models, along with restricted cubic splines and subgroup analyses. Model 1 was unadjusted; Model 2 adjusted for demographic characteristics including age, gender, marital status, education, and BMI; Model 3 further adjusted for smoking, drinking, sleep night, and socioeconomic status (SES) based on the Model 2. Key predictors were selected by Least Absolute Shrinkage and Selection Operator (LASSO) to construct a clinical nomogram. We found that a higher CTI was linked to a greater chance of developing liver disease, which remained robust after sequential adjustment for confounders. In Model 3, the hazard ratio (HR) for CTI was 1.607 (95% confidence interval [CI]: 1.085-2.381; P = 0.018). Restricted cubic spline analysis confirmed a linear positive relationship between CTI and CLD risk. This link was consistent across different ages, genders, and lifestyles. When we built a prediction tool using CTI and other factors like age and marital status, it showed a fair ability to estimate a person's risk. CTI may serve as a simple and potentially useful indicator to identify individuals with macrocytic anemia who are at a higher risk of chronic liver disease, helping guide earlier prevention efforts.
Although home-based exercise training programs are increasingly used to manage chronic ankle instability (CAI), recreational athletes' perceptions of such programs remain unclear. In this study, we explored the perceptions of recreational athletes with CAI toward a home-based exercise training program. A descriptive qualitative study was conducted using semi-structured interviews among recreational athletes with CAI, recruited via purposive and snowball sampling strategies. Participant eligibility was determined based on the inclusion criteria recommended by the International Ankle Consortium guidelines. Interviews were conducted online, audio-recorded, transcribed verbatim, and thematically analyzed using ATLAS.ti software. Trustworthiness was ensured through researcher triangulation and iterative coding. Twelve recreational athletes with CAI (7 males; mean [range] age 24.7 [20-36] years) from five sports (badminton [n = 4], football [n = 3], basketball [n = 3], yoga [n = 1], and running [n = 1]) were interviewed. Four overarching themes emerged: (1) perceived inadequacy of current self-management approaches, encompassing ad-hoc exercise routines and short-term symptom relief; (2) barriers and facilitators to adherence, including exercise execution competence, self-discipline, and performance-driven motivation; (3) essential design features for effective home programs, comprising strength and balance training, video-based instruction, professional feedback, minimal equipment, short sessions, and cross-sport applicability; and (4) athlete-centered indicators of success, defined as pain-free stability, confidence, and fear-free sports participation. Recreational athletes with CAI prefer a concise, low-equipment, video-guided home-based exercise training program emphasizing strength and balance, professional feedback, and multi-sport applicability. Success is defined by physical stability and restored confidence, informing the design of user-centered interventions to enhance adherence and recovery.
Extracellular vesicles (EVs) are increasingly investigated across a wide range of diseases as potential biomarkers and therapeutic tools. To date, EVs have been isolated from diverse sources, including urine, blood, saliva, tissue, and cell cultures, with research focusing primarily on their protein and RNA cargo. Owing to their non-invasive accessibility, selective cargo loading, and molecular richness, biological fluid-derived EVs have been proposed as promising candidates for biomarker discovery. In addition, several studies have explored EVs for therapeutic purposes, either by direct administration to diseased cells or organisms, by engineering them to enhance their efficacy, or by targeting them to modulate pathological processes. In this systematic review, we synthesize current evidence on the diagnostic and therapeutic roles of EVs in CKD and related conditions, integrating findings across different EV sources, cargos, and disease models, and providing an integrated perspective on the role of EVs in chronic kidney disease-related research. By comparing molecular findings from diagnostic and therapeutic studies, we also identify key overlapping pathways and biological processes that may represent relevant mechanistic frameworks. Recognizing these convergent pathways can help unify data and guide future research toward mechanism-driven, and clinically translatable EV applications in nephrology.
Artificial intelligence (AI)-based screening tools show promise for early identification of chronic liver disease (CLD), yet their effectiveness in real-world settings may depend on clinician response to AI-generated recommendations. We performed a post hoc analysis of the intervention arm of the pragmatic, cluster-randomized DULCE trial, in which primary care clinicians received electrocardiogram-based machine learning (ECG-ML) alerts indicating elevated risk for CLD. Clinicians were categorized as high engagement (HE; top quartile) or low engagement (LE), and diagnostic yield was defined as the proportion of ECG-ML-positive cases with confirmed CLD. Among 110 clinicians receiving ≥1 alert (1385 ECG-ML-positive patients), overall engagement was 29.8%. HE was associated with higher detection of advanced CLD (OR 2.12, 95% CI 1.36-3.30; p = 0.001) and any CLD (OR 2.59, 95% CI 1.83-3.68; p < 0.001) compared with LE. Diagnostic yield was 10.6% versus 2.9% for advanced CLD and 22.3% versus 5.0% for any CLD in HE versus LE (OR 2.99, 95% CI 1.73-5.16; p < 0.001 and OR 3.74, 95% CI 2.44-5.75; p < 0.001, respectively). These findings suggest that the effectiveness of AI-based screening may depend not only on algorithm performance but also on clinician engagement with AI recommendations and highlight the importance of accounting for engagement when designing and interpreting AI-enabled clinical trials. ClinicalTrials.gov NCT05782283.
Air pollution exposure is increasingly recognized as a risk factor for chronic kidney disease (CKD), but the underlying mechanisms, especially the complex gene-environment interactions as reflected in genetic susceptibility, transcriptomic, and proteomic signatures, remain to be elucidated. We conducted a large-scale prospective cohort study including 330,002 UK Biobank participants with an average follow-up of 13.0 years. Annual average concentrations of PM2.5, PM2.5-10, PM10, NO2, and NOX were assessed. Cox proportional hazards models were applied to estimate CKD risk associated with long-term air pollution exposure. We further evaluated non-linear relationships using restricted cubic splines (RCS), potential mediators via mediation analyses, and CKD susceptibility through additive interaction analyses with baseline comorbidities and polygenic risk scores (PRS). Additionally, transcriptome-wide association study (TWAS) and proteome-wide two-step Mendelian randomization (MR) were integrated to explore potential molecular pathways. Higher exposures to PM2.5 (HR: 1.36, 95% CI: 1.22-1.51, per 5 µg/m³), PM2.5-10 (HR: 1.25, 95% CI: 1.07-1.46, per 5 µg/m³), PM10 (HR: 1.20, 95% CI: 1.06-1.36, per 10 µg/m³), and NOX (HR: 1.04, 95% CI: 1.02-1.07, per 20 µg/m³) were significantly associated with increased CKD risk, whereas NO2 showed no significant association (HR: 0.98, 95% CI: 0.95-1.00, per 10 µg/m³). RCS revealed non-linear relationships for PM2.5-10 and PM10. Mediation analyses indicated that incident hypertension and type 2 diabetes mellitus (T2DM) acted as potential mediators in these associations. Crucially, additive interaction analyses revealed that participants with pre-existing hypertension or type 1 diabetes mellitus (T1DM) were significantly more vulnerable to specific pollution-driven CKD. Compared to individuals with low genetic risk and low air pollution exposure, those with both high genetic risk and high exposure exhibited the highest CKD risk, demonstrating a clear gradient effect across categories. TWAS identified shared genes potentially linking air pollutants with CKD, including upregulated transcripts (STX2, PHOSPHO2, NECAB3) and downregulated transcripts (CDK3, MEIOB, NDUFAF1, CRIPAK). Furthermore, proteome-wide MR analyses identified ALDH3A1, F12, and SNCG as potential risk proteins, and GNLY and MEGF10 as protective proteins. This study provides comprehensive evidence that long-term air pollution exposure is associated with increased CKD risk and offers exploratory insights into the potential molecular pathways underlying this association, advocating the incorporation of renal health considerations into air quality control policies.
Recruiting participants for clinical trials in primary care settings remains challenging, not least for interventions targeting individuals with chronic obstructive pulmonary disease (COPD). Clinical outcomes and the effects of interventions receive considerable attention compared to factors influencing recruitment success. Identifying and addressing possible barriers and facilitators is essential for optimizing recruitment strategies and ensuring the feasibility of trials. This study aimed to assess uncertainties regarding recruitment for a digitally based Guided Self-Determination (GSD) follow-up program for people with COPD, prior to a fully powered cluster randomized controlled trial (cRCT), and to explore characteristics of primary care practices and patients willing to be included in the study. The intervention was a 9-month digitally based follow-up program performed with the GSD counseling method, conducted by nurses in primary care practices. Eligible primary care practices were invited to participate, and participants were recruited through their respective practices. The primary feasibility outcome was recruitment, assessed at both the practice (cluster) and patient (participants) level. Eligible participants were people between 35 and 80 years diagnosed with COPD. Baseline characteristics included demographic data, COPD Assessment Test, Dyspnea-12, WHO-5 Well-being Index, and Health Education Impact Questionnaire domains. Progression criteria Go, Amend, and Stop were applied to assess feasibility. Recruitment occurred from May to December 2024. Of 16 eligible practices, 12 (75%) responded, of which ten (83%) agreed to participate, corresponding to 63% of the eligible practices. A total of 64 participants with COPD were recruited, 28 in the intervention and 36 in the control clusters. The overall median recruitment rate was 6.5 participants per cluster, 7 in the intervention clusters and 6 in the control clusters. One of three progression criteria, cluster recruitment, met the target Go, while cluster sizes and participant recruitment met the amended criteria. Recruitment was deemed feasible. However, successful cluster-level recruitment does not necessarily ensure effective patient enrollment, highlighting the necessity for amendments before a fully powered cRCT. Future research should integrate qualitative data obtained from patients and primary care practitioners to enhance the understanding of recruitment strategies. ClinicalTrials.gov (NCT06401512). Registered 23 April 2024, https://clinicaltrials.gov/study/NCT06401512.
American Indian/Alaska Native (AI/AN) individuals were disproportionately affected by the COVID-19 pandemic. We aimed to evaluate whether the presence of chronic health conditions (CHC) impacted COVID-19 testing and vaccination for AI/AN people in Oklahoma. We pooled survey data that included adult AI/AN participants weighted using the 2022 American Community Survey. We used modified Poisson regression to estimate prevalence proportion ratios (PPR) and 95% confidence intervals (CI) accounting for weighting, multiple imputation, and confounders to determine whether access to COVID-19 testing and vaccine uptake differed by CHC status. Among the 1,139 participants, 62.6% reported being diagnosed with a CHC. The majority reported being tested for COVID-19 (80.6%) and that testing access was easy (81.7%). We observed no association between CHCs and being tested (Adjusted PPR: 1.08, 95% CI: 0.97, 1.19) or testing access (Adjusted PPR: 1.08, 95% CI: 0.95, 1.21). Over half (57%) of participants received a COVID-19 vaccine. Among unvaccinated individuals, 9.7% reported they were likely to get a vaccine. While we observed no association between CHCs and vaccine status (Adjusted PPR: 1.08, 95% CI: 0.90, 1.27), unvaccinated individuals with a CHC reported they were more likely to get a vaccine compared to individuals with no CHC (Adjusted PPR: 1.81, 95% CI: 1.01, 2.62). The AI/AN population is at higher risk of developing CHC, which increases the risk for severe COVID-19. Thus, evaluating barriers to accessing testing and vaccines is important to improve outcomes. This analysis is important in supporting programs for seasonal epidemics and future pandemics. NCT04870307, NCT05236270.
Tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF) are considered efficacious and safe nucleoside/nucleotide analogs (NAs) for patients with chronic hepatitis B (CHB). However, real-world data on TMF for CHB patients with low-level viremia (LLV) remain scarce. This study investigated the real-world effectiveness and safety of TMF combined with entecavir (ETV) in the treatment of CHB patients with LLV, and compared the efficacy and safety of TMF combined with ETV and tenofovir alafenamide (TAF) combined with ETV in the treatment of CHB patients with LLV. This retrospective real-world study included CHB patients with LLV who received treatment with either TMF combined with ETV or TAF combined with ETV. After the 48-week follow-up, this study evaluated the differences between the two groups in terms of virological response rate (VR rate), ALT normalization rate, HBsAg and HBeAg seroclearance rate, liver fibrosis assessment, and safety endpoints (renal function and blood lipids). A total of 258 patients were enrolled: 123 in the experimental group (TMF combined with ETV) and 135 in the control group (TAF combined with ETV). The levels of HBV DNA and AST in both groups were significantly lower than the baseline levels after 48-week treatment period (P < 0.05). The VR rate at week 48 was 79.67% in the experimental group, while that in the control group was 72.59%, and there was no statistically significant difference between the two groups (P = 0.184). With respect to the ALT normalization rate, HBsAg seroclearance rate, HBeAg seroclearance rate and liver transient elastography (TE) results, no statistically significant differences were detected between the two groups (P > 0.05). Similarly, for the safety endpoints, including serum creatinine (Cr), glomerular filtration rate (eGFR), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels, none of these indicators significantly differed between the two groups. TMF combined with ETV was found to be effective in CHB patients with LLV and appeared to have a favorable safety profile within the limitations of the available data. It exhibits robust antiviral activity and can improve the liver function of patients.
IntroductionThis research sought to understand the relationship of the neutrophil percentage-to-albumin ratio (NPAR) and mortality from cardiovascular (CVD) and all causes in populations with CKD.Methods7,553 CKD patients were included and grouped into quartiles based on NPAR. Kaplan-Meier curves were utilized for survival analysis, while a multivariate Cox proportional hazards model calculated the risk ratio of NPAR on CVD and all-cause mortality. The potential linear connection of NPAR with CVD/all-cause mortality was analyzed through restricted cubic spline (RCS) analysis, and receiver operating characteristic (ROC) analysis was used to assess predictive performance. Subgroup analysis was executed with stratification according to demographic characteristics.ResultsThe Kaplan-Meier curve indicated that a higher NPAR was linked to a greater risk of CVD/all-cause mortality (p < 0.0001). In fully adjusted models, a one-unit rise in NPAR correlated with a 185% rise in the likelihood of dying from CVD diseased (HR = 2.85, 95% CI 2.26-3.47) and a 154% rise in the likelihood of dying from any cause (HR = 2.54, 95% CI 2.22-2.91). A non-linear link for NPAR and CVD/all-cause mortality was validated through RCS analysis, with a P value <0.001. ROC analysis showed that NPAR had modest discriminative ability for predicting all-cause mortality (AUC = 0.601), with an optimal cutoff value of 1.48. Across different subgroups, NPAR reliably predicted CVD and all-cause mortality in CKD patients.ConclusionElevated NPAR were linked with a higher likelihood of CVD mortality and all-cause mortality in patients with CKD and could serve as an effective prognostic biomarker.
Cannabis withdrawal in cannabis use disorder (CUD) increase the risk of relapse and lacks effective treatments. The endocannabinoid enzyme fatty acid amide hydrolase (FAAH) may influence cannabis use and withdrawal, but the relationship between FAAH levels and withdrawal symptoms remains unclear. This study aims to investigate changes in FAAH levels during short-term abstinence from cannabis and their relationship with withdrawal symptoms. FAAH levels were measured in whole-brain regions of interest using positron emission tomography (PET) with the FAAH-specific probe [11C]CURB. An irreversible two-tissue compartment model determined [11C]CURB binding. Participants with CUD were scanned once after overnight abstinence (T1) and ~3-7 days after monitored last use (T2). FAAH polymorphism (rs324420) was determined from blood samples, and mood, cognition, withdrawal symptoms, and craving were assessed. In a sample of 14 participants (N = 17 prior to attrition) who completed both scans, FAAH binding in whole-brain increased between T1 and T2 (n = 14; %ΔFAAH = 10%; p = 0.003), with the largest change in the ventral striatum (11%, p = 0.026). Increases in FAAH (%ΔFAAH whole-brain) were significantly associated with longer cannabis abstinence, greater baseline depression severity, and tendency to act without thinking (p < 0.001). Short-term cannabis abstinence is associated with increases in brain FAAH levels. These changes are linked to traits and symptoms associated with relapse vulnerability, including negative mood and impulsivity. These preliminary findings suggest that FAAH may play a key role in the neurobiological response to short-term abstinence and could represent a potential target for interventions.
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To analyze the epidemiological characteristics and dynamic trends of people living with HIV (PLWH) in Huangshi between 2004 and 2024, thereby providing a scientific basis for the optimization of regional HIV prevention and control strategies. Surveillance data of PLWH from Huangshi during the period 2004-2024 were collected. Descriptive epidemiology methods were employed to examine the temporal distribution, demographic features (including age, sex, marital status), transmission routes, clinical manifestations, and mortality patterns. A Cochrane-Armitage trend test was utilized to assess changes in gender composition, while SPSS 27 was leveraged to establish a time-series model based on exponential smoothing techniques to forecast future mortality counts. The number of PLWH in Huangshi exhibited a marked increase post-2009, peaking in 2015, followed by a significant decline from 2020 onward. Key structural shifts were observed: (1) among reported cases, the 51-80 age group accounted for the highest proportion (representing the age composition within the infected population, rather than age-specific incidence in the general population). Male cases showed a pronounced upward trend, whereas female cases demonstrated a gradual decrease. (2) Sexual transmission constituted the predominant mode, accounting for 95.02% of cases, with heterosexual transmission highly concentrated among males aged 51-70 years. (3) The primary opportunistic infections were persistent fever and Pneumocystis pneumonia. Post-2013, mortality rates escalated significantly, yet over one-third of deaths were attributed to causes unrelated to HIV, with cardiovascular diseases and malignancies ranking as major contributors, reflecting a shift toward chronic comorbidity management. (4) Time-series modeling predicted a gradual decline in the estimated number of HIV-related deaths for the years 2025-2028. HIV transmission in Huangshi has evolved into a stage characterized by sexual transmission as the primary route, with a notable increase in the disease burden among older adults and males. The focus is now transitioning from HIV-related mortality to the management of chronic comorbidities. Future HIV prevention efforts in the city should adopt comprehensive strategies, including targeted interventions and enhanced surveillance for males-particularly older males-strengthened treatment and prevention measures, and integrated approaches to chronic disease management to address the evolving epidemiological landscape.