Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

Diabetic sarcopenia (DS) is a common but often ignored skeletal muscle complication in individuals with diabetes mellitus. It is characterized by progressive loss of skeletal muscle mass, reduced muscle strength, and impaired physical performance, which may further increase the risk of falls, disabilities, metabolic disorders, and adverse clinical outcomes. Traditionally, DS has been attributed mainly to hyperglycemia, insulin resistance, aging-related muscle decline, and chronic complications of diabetes. However, increasing evidence suggests that lipid metabolic disturbance and pathological lipid metabolic reprogramming are not merely secondary consequences of diabetes, but may actively participate in the initiation and progression of DS. Under diabetic conditions, impaired fatty acid uptake, transport, oxidation, and storage disrupt skeletal muscle metabolic homeostasis, leading to ectopic lipid deposition and accumulation of lipotoxic intermediates. These lipid-derived metabolites can aggravate insulin resistance, impair mitochondrial energy production, enhance oxidative stress, activate chronic low-grade inflammation, and disturb protein synthesis and degradation balance, thereby accelerating skeletal muscle atrophy and functional decline. Lipid metabolic dysregulation may also interact with multiple pathological processes involved in DS, including mitochondrial dysfunction, inflammatory signaling, oxidative damage, impaired autophagy, and gut microbiota imbalance. These mechanisms do not occur independently; instead, they form a complex bidirectional vicious cycle with diabetes-related metabolic disorders. Specifically, mitochondrial dysfunction reduces fatty acid oxidative capacity, which further promotes lipid accumulation and lipotoxicity. Inflammatory activation can impair insulin signaling and muscle protein metabolism, while lipid overload may in turn amplify inflammatory responses. Similarly, gut microbiota dysbiosis and altered microbial metabolites may influence systemic inflammation, lipid metabolism, and skeletal muscle homeostasis. Therefore, lipid metabolic reprogramming provides an important mechanistic perspective for understanding the progression of DS from metabolic disturbance to structural and functional muscle impairment. Exercise intervention is an effective and clinically feasible non-pharmacological strategy for the prevention and management of DS. Both aerobic exercise and resistance training have been shown to improve insulin sensitivity, enhance fatty acid oxidation, increase mitochondrial biogenesis, reduce ectopic lipid deposition, and attenuate lipotoxic metabolite accumulation. These adaptations not only improved glucose and lipid metabolism, but also increased the preservation of muscle mass, muscle strength, and physical function. Moreover, combined exercise strategies may provide complementary benefits by integrating the metabolic advantages of aerobic exercise with the anabolic and functional effects of resistance training. Based on analyses of publicly available datasets and literature evidences, this review systematically summarizes the role of lipid metabolic disorders in the pathogenesis of DS, with particular attention to the molecular mechanisms linking lipid dysregulation to insulin resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota disturbance. Furthermore, this review discusses the potential mechanisms by which exercise intervention improves DS through the regulation of lipid metabolic reprogramming, and outlines exercise prescription strategies in terms of modality, intensity, frequency, and duration. Understanding the interaction between lipid metabolism and skeletal muscle dysfunction may provide new theoretical evidence for early identification, mechanistic research, and precision exercise therapy in DS. Overall, targeting pathological lipid metabolic reprogramming through exercise intervention represents a promising and clinically actionable approach for improving muscle health and prognosis in individuals with DS.

Surface enhanced Raman scattering(SERS)is an important technique for detecting pesticide residues.However,many pesticides have small Raman scattering cross sections and low affinity for gold/silver enhancement substrates,resulting in low sensitivity for direct SERS detection.Indirect methods typically require complex surface modifications and have poor universality.Here,a dual functional composite Au@MnO2 combined with acetylcholinesterase(AChE)was proposed for SERS biosensing of pesticides.The Au@MnO2 with oxidase-like activity could oxidize 3,3′,5,5′-tetramethylbenzidine(TMB)into oxTMB with a large Raman scattering cross section,producing strong SERS signal using Au@MnO2 itself as enhancement substrate.In the presence of AChE,acetylthiocholine(ATCh)was catalytically hydrolyzed to produce thiocholine(TCh),and its reducibility could induce the decomposition of MnO2.Consequently,oxidase-like activity of Au@MnO2 was declined,less oxTMB was produced,and gold nanoparticles(AuNPs)detached from the MnO2 layer,resulting in a weakened SERS response.Organophosphorus pesticides(OPs),as inhibitors of AChE,prevented the production of TCh,thereby blocking the decomposition of MnO2 and leading to the recovery of Raman signals.Under optimized conditions,the Raman signal switching strategy was successfully used for detection of three OPs,i.e.,fenthion,chlorpyrifos,and methyl parathion,with detection limits of 4×10-11 mol/L,2×10-9 mol/L,and 3×10-9 mol/L,respectively.In actual spinach sample testing,the spiked recoveries of the three OPs ranged from 86.5%to 110.6%.This study provided a new strategy for detecting pesticide residues using SERS.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

OBJECTIVE To explore the distribution of pathogens isolated from the cervical cancer(CC)patients with postoperative urinary catheter-associated urinary tract infection(UTI)and analyze the predictive values of se-rum high mobility group protein B1(HMGB1),Toll-like receptor 4(TLR4)and nuclear factor kappa B(NF-κB).METHODS Totally 116 patients with CC who underwent radical resection in the First Affiliated Hospital of Henan University of Science and Technology from Jan.2021 to Jan.2024 were enrolled in the study and were divided into the infection group with 31 cases and the non-infection group with 85 cases according to the status of complication with UTI after urinary catheterization.The midstream urine specimens were collected by aseptic method,the pathogens were isolated and identified.The serum HMGB1 level was detected by means of enzyme-linked immu-nosorbent assay,the relative expression levels of peripheral blood TLR4 and NF-κB proteins were detected by Western blot.The efficiencies of serum HMGB1,TLR4 and NF-κB in prediction of postoperative urinary catheter-associated UTI in the CC patients were analyzed by means of receiver operating characteristic(ROC)curves.RESULTS Totally 49 strains of pathogens were isolated from 31 CC patients with postoperative urinary catheter-associated UTI,and the patients who had infection of single species were dominant.Gram-negative bacteria were the most common pathogens,accounting for 61.22％.There were significant differences in the age,complication with diabetes mellitus,duration of urinary catheter indwelling,postoperative uroschesis and previous history of UTI between the infection group and the non-infection group(P＜0.05);there were significant differences in the levels of serum HMGB1,TLR4 and NF-κB between the two groups(P＜0.05).The area under the curve(AUC)of the joint detection of serum HMGB1,TLR4 and NF-κB was 0.906 in prediction of the postoperative urinary catheter-associated UTI in the CC patients,with the sensitivity 83.87％;the predictive efficiencies of the joint de-tection of the indexes were better than those of the single detection(P＜0.05).CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the CC patients with postoperative urinary catheter-asso-ciated UTI.The joint detection of the serum HMGB1,TLR4 and NF-κB has the highest value in prediction of postoperative urinary catheter-associated UTI in the CC patients.

Objective:To evaluate the safety and feasibility of radical hepatectomy after conversion therapy in patients with initially unresectable advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 72 patients with initially unresectable advanced HCC admitted to the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University and the Department of Hepatobi-liary and Pancreatic Surgery, Henan Provincial People's Hospital from January 2020 to July 2024 were retrospectively collected, including 61 males and 11 females, aged (58.4±9.1) years. The clinicopathological data of the patients, such as tumor characteristics, conversion treatment regimens, perioperative data, and follow-up situations were analyzed to evaluate the therapeutic effect and safety.Results:Among the patients, there were five cases of China liver cancer staging Ⅰb, six cases of Ⅱa, 22 cases of Ⅱb, 32 cases of Ⅲa and sevene cases of Ⅲb. There were 53 patients scored as Child-Pugh A and 19 as Child-Pugh B. Conversion treatment fashion included immunotherapy combined with targeted therapy and immunotherapy plus targeted therapy combined with hepatic arterial chemoembolization or hepatic arteryinfusion chemotherapy. Liver resection after conversion therapy was as follows: 16 cases of right hemihepatectomy, 20 cases of left hemihepatectomy, 11 cases of mesohepatectomy, seven cases of right posterior hepatectomy, 1 case of caudate lobectomy, 17 cases of local resection. Postoperative pathology showed that there were 17 cases of pathologic complete response and 55 cases of pathologic partial response. One patient died of liver failure after surgery, while the rest had no major complications. The postoperative hospital stay was (13.1±5.1) d. The follow-up time was 21.5(10.2, 32.1) months. The multivariate Cox analysis demonstrated that pathologic partial response and adjuvant therapy duration shorter than 5 cycles were identified as independent risk factors-affecting both recurrence-free survival and overall survival in patients with HCC undergoing sequential surgery after conversion therapy (all P<0.05). Conclusion:Sequential surgical resection provides survival benefits for patients with initially unresectable and advanced HCC after conversion therapy, which is a safe and effective therapeutic strategy.