Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

Pneumoconiosis is a chronic interstitial lung disease caused by occupational exposure to mineral dust, characterized by persistent inflammation and progressive pulmonary fibrosis. Effective therapeutic options, however, remain limited. Recent multi-omics studies have revealed that glucose metabolic reprogramming, particularly the abnormal activation of glycolysis, plays a critical role in the pathogenesis of fibrotic diseases. This review summarized the key components involved in glycolytic reprogramming, including rate-limiting enzymes such as hexokinase, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase, as well as regulatory factors such as hypoxia-inducible factor-1α (HIF-1α) and AMP-activated protein kinase (AMPK). Their roles in metabolic regulation and fibrogenesis were elaborated. Special emphasis was placed on alveolar macrophages and fibroblasts, in which enhanced glycolysis and lactate accumulation drive inflammatory responses and collagen deposition, contributing to disease progression. Advances on pharmacological agents such as nintedanib, 2-deoxyglucose, quercetin, metformin, and resveratrol were reviewed, highlighting their antifibrotic potential through modulation of glycolytic enzymes or related signaling pathways. Additionally, the interactions between glycolysis and fatty acid metabolism, amino acid metabolism, and oxidative phosphorylation were discussed, underscoring the significance of multi-pathway coupling in pneumoconiosis. Metabolic abnormalities in pneumoconiosis result from multi-level interactions across cells, molecules, and tissues. Consequently, future therapeutic strategies should shift from single-target interventions toward coordinated regulation of multiple pathways, integrating tissue-targeted drug delivery, metabolism-based stratified interventions, and multi-target combination therapies to achieve precision and personalized treatment.

Objective To investigate the etiology and treatment of dysuria shortly after holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia (BPH), so as to improve the therapeutic efficacy. Methods A retrospective analysis was conducted on 1361 BPH patients who received HoLEP at our hospital during Mar. 2018 and Mar. 2025. All patients underwent ultrasound, computed tomography (CT), urethral probing or radiography, cystourethroscopy, and urodynamic testing. The causes, treatments and prognosis of dysuria after operation were summarized. Results ninety-eight patients (7.2%) experienced dysuria within 3 months after surgery, and all patients received initial urethral dilation. Among the 62 cases with urethral stricture, 28 were treated with urethral dilation (average of 8 sessions), 16 underwent external urethral incision, 8 underwent anterior urethroplasty, and 10 underwent transurethral plasma incision for urethral stricture. Of the 12 cases with residual prostate tissue, 5 underwent urethral plasma prostatectomy and 7 received medication. All of the 12 cases with bladder neck contracture underwent transurethral plasma incision of the bladder neck and local drug injection. Five cases with intravesical blood clots underwent urethral blood clot irrigation, 2 of which developed active bleeding and then underwent electrocoagulation. Four cases with detrusor dysfunction had catheters re-indwelled for one week followed by medication. Two cases with stone and one case with tissue fragment impacted in the urethra underwent urethral holmium lithotripsy and cystoscopic removal. All patients underwent reoperation successfully and experienced complete resolution or significant improvement of urinary difficulties. Conclusion A certain proportion of patients experience dysuria after HoLEP, with diverse etiologies. The combination of prevention and treatment can reduce the incidence of dysuria.

Objective To investigate the efficacy of Castor branching stent in treating Stanford type B aortic dissection(TBAD)involving aortic arch.Methods The clinical data of 18 patients with Stanford TBAD,who were treated with Castor branching stent at the Suining Municipal Central Hospital of China from January 2020 to January 2022,were retrospectively analyzed.Results The main bracket and branch bracket of Castor branching stent were successfully released in all the 18 patients with a surgical success rate of 100％,and no internal leakage occurred during operation.During the perioperative period,there were neither aorta-related deaths nor serious complications such as stroke,upper limb ischemia,internal leakage,or stent displacement.The patients were followed up for(14.7±8.3)months,no aorta-related death,stroke,upper limb ischemia,internal leakage,or stent displacement was observed,the blood flow of the left subclavian artery(LSA)was unobstructed,but there was thrombosis formation within the false lumen of the covered stent segment.Conclusion The Castor branching stent has the advantages of reasonable release mode,accurate positioning,effective isolation of the first rupture of Stanford TBAD and reconstruction of LSA,with no serious short-term complications.However,further follow-up observation is needed before its long-term efficacy can be clarified.

Objective To analyze the epidemiological characteristics of acute respiratory infections(ARIs)during the autumn-winter season in Beijing,providing evidence for the prevention,control,diagnosis,and treatment of ARIs.Methods A convenience sampling method was employed,enrolling patients who visited Peking Union Medical College Hospital(PUMCH)between September 2023 and February 2024 due to ARIs.Na-sopharyngeal swabs were collected,and real-time fluorescence quantitative PCR was used to detect six common respiratory pathogens[influenza A virus(FluA),influenza B virus(FluB),human rhinovirus(HRV),Myco-plasma pneumoniae(MP),respiratory syncytial virus(RSV),and adenovirus(ADV)],as well as SARS-CoV-2 infection.The distribution patterns of pathogen infections were analyzed.Results A total of 5556 eligible patients were included.The overall positivity rate for the six common respiratory pathogens was 63.7％,with sin-gle-pathogen positivity at 54.0％,dual-pathogen positivity at 8.9％,and triple or more pathogen positivity at 0.7％.The predominant pathogens detected were FluA(16.1％)and RSV(15.7％),followed by ADV(11.1％),MP(11.1％),HRV(10.0％),and FluB(10.0％).No significant difference in overall pathogen positivity was observed between genders.However,significant differences were found between autumn and winter(x2=34.617,P＜0.001)and among pediatric,young/middle-aged,and elderly patients(x2=422.38,P＜0.001).Specifically,MP(x2=8.647,P=0.003),FluA(x2=131.932,P＜0.001),and HRV(x2=174.199,P＜0.001)exhibited significantly higher positivity rates in autumn than in winter,whereas FluB was more prevalent in winter(x2=287.894,P＜0.001).In pediatric patients,MP,RSV,HRV,and ADV positivity rates were significantly higher than in young/middle-aged and elderly patients(all P＜0.001),whereas FluB was more common in young/middle-aged patients(both P＜0.001).The positivity rates of the six common respiratory pathogens significantly declined during the SARS-CoV-2 epidemic period,exhibiting an asynchronous seasonal pattern.Conclusions The prevalence of respiratory pathogens in Beijing is associated with age and season.Tar-geted preventive measures should be implemented in different seasons and for key populations.

Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Background Exposure to volatile organic compounds (VOCs) has been observed in both living and working environments. Volatile organic compounds metabolites (VOCMs) in urine can be used to assess the exposure to VOCs and potentially cause adverse effects on human body. Objective To quantitatively evaluate urinary VOCMs and their associations with renal function damage, and further trace the characteristics of potential environmental exposure to provide scientific evidence for effective prevention measures. Methods The study included a total of 6028 samples from four cross-sectional studies in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018, with exposure and health outcomes matched. Generalized linear models were employed to assess the associations of urinary VOCMs (urinary creatinine adjusted) with urinary protein levels and estimated glomerular filtration rate (eGFR), with coviriables including gender, age, body mass index, education, smoking, alcohol consumption, exercise frequency, diabetes, and hypertension. Weighted quantile sum (WQS) approach was utilized to analyze the effects of mixed exposure and to rank the contribution of individual VOCMs. The associations between VOCMs and associated living environments and occupational exposure characteristics were further investigated. Results Among the enrolled study participants (n=6028), a total of 11 urinary VOCMs were measured, with 10 metabolites having a positive rate of over 80% (84.59%-99.99%). There were 604 individuals (10.0%) having urinary protein abnormalities and 2831 individuals (47.0%) with eGFR reduced. Through a single and a multiple generalized linear model, 5 VOCMs exhibited statistically significant associations with urinary protein abnormalities and/or reduced eGFR levels (P<0.05): N-acetyl-S-(N-methylaminocarbonyl)-L-cysteine (AMC), N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEM), N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHB), 2-hydroxy-2-phenylacetic acid (MAD), and N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine (MB3). The WQS index indicated a significantly positive association between VOCMs and urinary protein abnormalities, and DHB contributed the most. The analysis on the potential sources of VOCs exposure showed that those who worked as a private entrepreneur or an employee (vs. government employees), rent houses (vs. owned real estate), had less number of rooms in the residence, fueled cars at self-service gas stations, and inhaled paint fumes in the past 48 h associated with higher VOCMs (P < 0.05) and DHB contributed the most. Conclusion Multiple VOCMs in urine are associated with significantly kidney function injuries. The mixture exposure to VOCMs is significantly associated with higher risks of urinary protein abnormalities. Occupational category, housing ownership, ways to fuel a car, and inhalation of paint odors are closely related with VOCMs levels.