Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000，respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.

Objective To investigate the relationship between the comorbidity of dyslipidemia, hypertension and diabetes and lifestyle of adult residents in Hebei Province in 2018, and to provide reference for the development of chronic diseases prevention measures. Methods Using data from the surveillance of chronic diseases and their risk factors among adults in Hebei in 2018, 7 711 permanent residents aged ≥18 years were selected as the research subjects. Multivariate logistic regression analysis was used to analyze the relationship between the comorbidity of dyslipidemia, hypertension, and diabetes and lifestyle in adult residents. Results A total of 7 711 subjects aged ≥18 years were included in 2018. The comorbidity rates of hypertension and dyslipidemia, diabetes and dyslipidemia, and hypertension and diabetes were 16.88%, 7.91%, and 8.13%, respectively. The comorbidity rate of hypertension, diabetes, and dyslipidemia was 22.65%. These comorbidity rates increased with age and BMI. Multivariate logistic regression results showed that male, age, overweight/obesity, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep problems were risk factors for the comorbidity of the "three highs". Conclusion The prevalence of the "three highs" comorbidities is relatively high in Hebei Province, and there are multiple common risk factors. Maintaining a healthy lifestyle and implementing comprehensive prevention and control measures are the key to improving the health level of residents.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

The functional realization of proteins and other biological macromolecules depends on conformational dynamics and allosteric regulation, and elucidating their molecular mechanisms is an important foundation for understanding life processes. Molecular dynamics simulations are a powerful tool for investigating conformational evolution at the atomic level. However, traditional methods are limited by simulation timescales and high free-energy barriers, making it difficult to effectively capture rare conformations and their transition pathways. As a result, the development of enhanced sampling techniques has become key to overcoming this bottleneck. As a classical enhanced sampling technique, metadynamics suffers from several shortcomings, including strong dependence on collective variables and significant errors caused by bias potential accumulation. This article reviews three major improvement strategies. The first combines stochastic resetting with metadynamics, using trajectory-resetting mechanisms to improve sampling efficiency while avoiding the difficulty of optimizing collective variables. The second, SinkMeta, employs a “sinking” bias effect to enable efficient exploration of specific regions and paths. The third, OPES-based hybrid methods, improve the stability of free-energy estimation by optimizing the target distribution or the way the bias is constructed. These methods provide new ideas for characterizing free-energy landscapes and studying conformational transitions in complex biological systems, while also promoting the continued development of enhanced sampling methodologies.

Objective To analyze the prevalence of hyperuricemia (HUA) among adults in Hebei Province and its influencing factors related to comorbidities with ^“three highs^”, and to provide a theoretical basis for the prevention and control of HUA and multi-disease co-management. Methods Data were derived from the 2018 China Chronic Disease and Risk Factors Surveillance program conducted in Hebei Province. A multi-stage stratified cluster random sampling method was used to select permanent residents aged ≥18 years. All statistical analyses were adjusted for complex weighting. Design-based logistic regression was employed to analyze factors influencing HUA prevalence, and ordinal logistic regression was used to analyze the influencing factors of HUA patients and their comorbidity with ^“three highs^”. Results The prevalence of HUA among adults in Hebei Province was 10.42%, with males showing higher rates than females (P<0.05). The highest prevalence of HUA was observed in the 18-39 age group, followed by a declining trend, and a resurgence in those aged ≥70 (P<0.05). Among HUA patients with comorbidities, isolated HUA, 1 comorbidity, 2 comorbidities, and 3 comorbidities accounted for 13.94%, 33.33%, 39.17%, and 13.56%, respectively. HUA combined with hypertension and dyslipidemia represented the highest proportion (31.07%). Analysis of the influencing factors of HUA revealed that higher education levels, obesity, central obesity, and dyslipidemia increased the risk of HUA (P<0.05). Ordinal logistic regression analysis of HUA combined with three highs showed that HUA patients aged ≥50 years, overweight individuals, and those with chronic kidney disease had a higher number of patients with three highs (P<0.05). Conclusion HUA exhibits insidious onset, and it is recommended to include uric acid testing in routine physical examinations. Targeted prevention measures, such as early uric acid testing and health education, should be implemented by Hebei authorities for populations with higher education levels, obesity, central obesity, and dyslipidemia to reduce HUA incidence. Additionally, health education and regular medical check-ups are recommended for overweight HUA patients and those with chronic kidney disease to prevent comorbidities and alleviate disease burden.

Objective To evaluate the efficacy and safety of a combination therapy regimen comprising stereotactic body radiation therapy (SBRT) combined with liposomal irinotecan, camrelizumab, and anti-angiogenic therapy (CAP) in patients with advanced bone and soft tissue sarcomas. Methods This study is a prospective subgroup analysis of the multicenter, open-label, single-arm phase Ⅱ CAP trial (NCT04569916), which enrolled 60 patients with advanced solid tumors who had progressed after standard therapy between November 2020 and February 2023, including 11 patients with advanced bone and soft tissue sarcomas. All patients received sequential liposomal irinotecan within 48 hours after stereotactic body radiotherapy (SBRT), followed by maintenance therapy with camrelizumab and an anti-angiogenic agent until disease progression or intolerable toxicity. The primary efficacy endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results In the bone and soft tissue sarcoma subgroup (n=11), three patients achieved partial response (PR), five had stable disease (SD), and three experienced disease progression (PD). ORR was 27.3%, and DCR was 72.7%. mPFS was 5.8 months (95%CI: 2.2-10.3), and mOS not reached. Regarding safety, adverse reactions primarily included bone marrow suppression, fatigue, and gastrointestinal reactions, indicating overall manageable toxicity. Conclusion As a subgroup analysis of the CAP study, this research suggests that radiotherapy combined with liposomal irinotecan, camrelizumab, and anti-angiogenic therapy demonstrates certain efficacy in advanced bone and soft tissue sarcomas that have failed multiple lines of treatment, with overall manageable adverse reactions. Future studies should expand the sample size.

ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology（GO） enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software， and the protein-protein interaction （PPI） network for key targets was depicted. Finally， the hub gene was determined through topological analysis. Auto Dock， PyMOL， and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments， a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin（HE） staining， uric acid test， enzyme linked immunosorbent assay（ELISA）， Western blot， and real-time polymerase chain reaction（Real-time PCR）， the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values， 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response， astrocyte activation， regulation of interleukin （IL）-8 production， nuclear receptor activity， and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway， advanced glycosylation end/receptor of advanced glycation endproducts（AGE/RAGE） signaling pathway， anti-inflammatory， and other pathways. PPI network indicated that albumin（ALB）， peroxisome proliferator-activated receptor-γ （PPAR-γ）， IL-6， IL-1β， and C-reactive protein（CRP） were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene （β-carotene）. Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose （7.76 g·kg^-1·d^-1）， medium-dose （15.53 g·kg^-1·d^-1）， and high-dose （31.05 g·kg^-1·d^-1） groups of Buyang Huanwu Tongfeng decoction had different degrees of remission， and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration， as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced， followed by the medium-dose and low-dose groups， and the expression of ALB， PPAR-γ， IL-6， IL-1β， and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB， PPAR-γ， IL-6， IL-1β， and CRP， inhibiting the PPAR-γ/nuclear transcription factor （NF）-κB pathway， and reducing AGEs/RAGE-mediated inflammation， Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.

BACKGROUND:Extracellular vesicles are secreted into the extracellular milieu by a wide range of cell types,including tumor cells,under different physiological and pathophysiological conditions,where a wide range of biological signals and cell-to-cell signaling exists.Tumor-derived extracellular vesicles may exacerbate cancer progression,survival,invasion,and promote angiogenesis. OBJECTIVE:To review the research progress of extracellular vesicles in the diagnosis and treatment of oral squamous cell carcinoma. METHODS:Literature search was performed by the first author in PubMed,WanFang,CNKI and other databases with the keywords"EVs,oral squamous cell carcinoma,diagnosis and treatment,biopsy,tissue engineering"in Chinese and English.Finally,63 articles were included for analysis. RESULTS AND CONCLUSION:(1)In oral squamous carcinoma saliva biopsies,extracellular vesicles play a crucial role in the progression of oral squamous cell carcinoma by acting as an information transfer tool between tumor cells and the surrounding microenvironment,carrying a wide range of biomolecules including soluble proteins,lipids,DNA,and RNA.These tiny vesicles not only play a key role in tumor growth and spread,but also provide important information about the biological properties of the tumor.(2)Saliva biopsy,as a non-invasive diagnostic method,can open up new possibilities for early diagnosis and targeted treatment of oral squamous cell carcinoma by analyzing the extracellular vesicles therein.(3)It has been found that bioactive molecules,such as microRNAs(miRNAs)and specific proteins,contained within extracellular vesicles can serve as biomarkers for oral squamous carcinoma and improve the accuracy of early diagnosis.Specific proteins in extracellular vesicles such as EHD2,CAVIN1,PF4V1,and CXCL7 show potential as novel predictive biomarkers.(4)In addition,this paper highlights the potential application of extracellular vesicles in the treatment of oral squamous carcinoma.Through engineering modifications,extracellular vesicles can serve as a new generation of nanoscale drug delivery systems to enhance the efficiency and specificity of targeted tumor therapy.(5)Future studies will further explore the effect and mechanism of extracellular vesicles in oral squamous cell carcinoma,which is expected to improve patients'survival and quality of life.

[Objective] : To systematically evaluate the overall efficacy of external application of traditional Chinese medicine (EA-TCM) in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain (CIBP). [Methods] : We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems. It included four Chinese databases [Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure (CNKI), Wanfang Database, and China Science and Technology Journal Database (VIP) ], six English databases (Scopus, Embase, Web of Science, PubMed, Cochrane Library, and OpenGrey), and two registration systems (Chinese Clinical Trial Registry and ClinicalTrials.gov). The timeframe for the literature search extended from the inception of each database to December 31, 2023. Meta-analysis was performed using RevMan (v5.4.1), and the outcome indicators (pain relief rate, analgesic duration, quality of life, pain intensity, breakthrough pain frequency, and adverse reactions) were graded using GRADE profiler (v3.6). [Results] : According to the established inclusion and exclusion criteria, a total of 43 studies was deemed eligible, involving 3 142 participants with CIBP. The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone, the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate [risk ratio (RR) = 1.32, 95% confidence interval (CI): 1.24 to 1.41, P < 0.000 01], analgesic duration [mean difference (MD) = 1.33, 95% CI: 0.97 to 1.69, P < 0.000 01], and quality of life (MD = 5.66, 95% CI: 4.88 to 6.44, P < 0.000 01). Furthermore, the combined therapy significantly reduced pain intensity (MD = – 1.00, 95% CI: – 1.19 to – 0.80, P < 0.000 01), breakthrough pain frequency (MD = – 0.43, 95% CI: – 0.51 to – 0.36, P < 0.000 01), and adverse reactions (RR = 0.60, 95% CI: 0.53 to 0.68, P < 0.000 01) in CIBP patients. Based on the GRADE assessment, the level of evidence varied from low to moderate. [Conclusion] EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life. Additionally, the EA-TCM can effectively reduce the incidence of adverse reactions associated with three-step analgesic therapy.

Objective To explore the risk factors for postoperative respiratory failure (RF) in patients with esophageal cancer, construct a predictive model based on the least absolute shrinkage and selection operator (LASSO)-logistic regression, and visualize the constructed model. Methods A retrospective analysis was conducted on patients with esophageal cancer who underwent surgical treatment in the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center Gansu Hospital from 2020 to 2023. Patients were divided into a RF group and a non-RF (NRF) group according to whether RF occurred after surgery. Clinical data of the two groups were collected, and LASSO-logistic regression was used to optimize feature selection and construct the predictive model. The model was internally validated by repeated sampling 1000 times based on the Bootstrap method. Results A total of 217 patients were included, among which 24 were in the RF group, including 22 males and 2 females, with an average age of (63.33±9.10) years; 193 were in the NRF group, including 161 males and 32 females, with an average age of (62.14±8.44) years. LASSO-logistic regression analysis showed that the percentage of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) to predicted value (FEV1/FVC%pred) [OR=0.944, 95%CI (0.897, 0.993), P=0.026], postoperative anastomotic fistula [OR=4.106, 95%CI (1.457, 11.575), P=0.008], and postoperative lung infection [OR=3.776, 95%CI (1.373, 10.388), P=0.010] were risk factors for postoperative RF in patients with esophageal cancer. Based on the above risk factors, a predictive model was constructed, with an area under the receiver operating characteristic curve of 0.819 [95%CI (0.737, 0.901)]. The Hosmer-Lemeshow test for the calibration curve showed that the model had good goodness of fit (P=0.527). The decision curve showed that the model had good clinical net benefit when the threshold probability was between 5% and 50%. Conclusion FEV1/FVC%pred, postoperative anastomotic fistula, and postoperative lung infection are risk factors for postoperative RF in patients with esophageal cancer. The predictive model constructed based on LASSO-logistic regression analysis is expected to help medical staff screen high-risk patients for early individualized intervention.