Objective To systematically analyze the disease burden, long-term trends, and age-sex distribution of major valvular heart disease (VHD) subtypes—rheumatic heart disease (RHD), non-rheumatic valvular disease (NRVD), and non-rheumatic calcific aortic valve disease (CAVD)—in global, Chinese, and US populations from 1990 to 2021, providing evidence for public health strategies and clinical resource allocation. Methods Based on publicly available data from the Global Burden of Disease (GBD) Study 2021, we extracted incidence, mortality, and disability-adjusted life years (DALYs) for VHD from 1990 to 2021. Age-standardized rates (ASRs) were calculated using the GBD 2021 global standard population, and the estimated annual percentage change (EAPC) with its 95% uncertainty interval (UI) was computed for the period. Data from the Agency for Healthcare Research and Quality (AHRQ), the European Society of Cardiology (ESC)/Eurostat surveys, and Chinese national registries were used for trend triangulation and contextual background. Results From 1990 to 2021, the ASR and disease burden of RHD significantly decreased globally and in China (EAPC for DALYs in China: −4.8%, 95%UI: −5.0% to −4.6%). In contrast, the burden of NRVD and CAVD steadily increased in aging populations like those in China and the US, with a higher burden observed in older adults and males. In 2021, the incidence of NRVD and CAVD peaked in individuals aged ≥65 years, with rates being significantly higher in men than in women. RHD burden was concentrated in low socio-demographic index (SDI) regions, whereas NRVD/CAVD burden was strongly associated with high-SDI regions. Conclusion The global VHD epidemiological landscape is transitioning from an RHD-dominant to an NRVD/CAVD-dominant pattern. China faces a dual challenge of a residual RHD burden and a rapidly growing burden of degenerative valvular diseases. Developing tailored screening, prevention, and treatment strategies for different disease subtypes and populations is crucial.

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.

[Purpose]To investigate the choice of medical institutions for the first-treatment of can-cer patients after diagnosis and the factors influencing it,so as to provide a reference basis for the rational allocation of health resources and the promotion of hierarchical diagnosis and treatment of cancer.[Methods]A total of 1 140 common cancer patients from 1 provincial,3 municipal and 6 county-level medical institutions in Shandong Province were included in the study,and a ques-tionnaire survey was conducted on their basic personal information and the selection of medical institutions.Chi-square test and Fisher exact test were used to compare different groups,and mul-ti-classification unordered Logistic regression were used to explore the factors influencing the se-lection of cancer patients.[Results]1 077 valid questionnaires were collected.The selection rates of first-treatment institutions for cancer patients were county hospitals(29.90％),city hospitals(35.28％),and provincial hospitals(34.82％),and the high level of medical care was the main reason for the selection of first-treatment institutions for cancer patients.The results of multi-clas-sification unordered Logistic regression showed that when choosing municipal and county medical institutions as the first treatment institution compared to choosing a county medical institution for the first treatment as a reference,compared to patients with stage Ⅰ tumors,patients with tumor stages at stage Ⅲ(OR=1.789,95％CI:1.014～3.158)and stage Ⅳ(OR=2.005,95％CI:1.179～3.409)were more likely to choose municipal medical institutions;and patients with annual house-hold income of 10 000～＜50 000 CNY(OR=0.625,95％CI:0.414～0.943)were less likely to choose mu-nicipal medical institutions compared to those with an annual household income of＜10 000 CNY.When choosing provincial and county medical institutions as the first treatment institution com-pared to patients in stage Ⅲ(OR=2.885,95％C1:1.549～5.372)and stage Ⅳ(OR=3.104,95％CI:1.724～5.586)compared to patients with stage Ⅰ tumors when choosing a county medical institu-tion for the first treatment was used as a reference;married(OR=2.248,95％CI:1.127～4.484)patients were more likely to choose provincial healthcare organizations than unmarried/divorced/widowed patients;patients with a family history of cancer compared to patients without a family history of cancer(OR=1.650,95％CI:1.115～2.441)were more inclined to choose provincial healthcare institutions;compared with patients＜45 years old,patients over 60 years old(OR=0.483,95％CI:0.242～0.962)were less inclined to choose provincial hospitals;and compared with patients who were not aware of knowledge related to cancer,those who were aware of knowledge related to cancer(OR=0.613,95％CI:0.441～0.852)patients were less inclined to choose provin-cial hospitals.[Conclusion]Vigorously carrying out publicity on cancer prevention and treatment knowledge,improving the cancer prevention and treatment literacy of cancer patients.strengthen-ing vertical cooperation among medical institutions at all levels,improving the provincial-munici-pal-county cancer prevention and treatment network,and promoting the sinking of high-quality medical resources are important ways to improve the cancer prevention and treatment capacity of counties and promote the work of hierarchical medical system.

Background and Aims:Valeric acid activates the nuclear factor E2-related factor 2(Nrf2)pathway.Recent studies have demonstrated its potent antitumor activity in breast and oral cancers.However,its role in gastric cancer treatment remains unclear.This study aimed to investigate the effects of valeric acid on inflammatory responses and survival in a gastric cancer xenograft model in nude mice and to explore the potential underlying mechanisms to provide new insights for gastric cancer therapy.Methods:A xenograft model was established by subcutaneous injection of human gastric cancer MKN-45 cells into 80 Balb/c nude mice,which were then equally randomized into four groups:control and low-,medium-,and high-dose valeric acid groups(10,20,and 40 mg/kg,respectively).The mice received daily intraperitoneal injections of either saline or valeric acid for 30 days.Tumor growth was monitored during the treatment period.Twelve hours after the final administration,five mice from each group were sacrificed by cervical dislocation;blood was collected via eyeball removal,and tumors were excised and weighed.Histopathological changes in the tumors were observed by HE staining.Serum levels of macrophage inflammatory protein-2(MIP-2),interleukin-10(IL-10),and tumor necrosis factor α(TNF-α)were measured by ELISA.mRNA and protein expression levels of Nrf2 and its downstream molecules,quinone oxidoreductase-1(NQO-1)and heme oxygenase-1(HO-1),were assessed in tumor tissues using qRT-PCR and Western blot.The remaining 15 mice per group were monitored for survival analysis.Results:Compared with the control group,all valeric acid-treated groups showed a significant reduction in tumor volumes at all observation time points and final tumor weight(all P＜0.05),with a dose-dependent trend.HE staining revealed densely arranged tumor cells with high cell density in the control group,while various degrees of tumor necrosis and reduced cell density were observed in valeric acid-treated groups,most pronounced in the high-dose group.ELISA results showed that serum levels of MIP-2 and TNF-α were significantly decreased,while IL-10 levels were significantly increased in valeric acid-treated groups compared to controls(all P＜0.05),exhibiting dose dependence.qRT-PCR and Western blot analyses demonstrated that the mRNA and protein expression levels of Nrf2,HO-1,and NQO-1 in tumors were significantly elevated in the valeric acid groups compared with the control group(all P＜0.05),also showing dose dependence.Survival analysis indicated that the median survival times were 47 d(control),68 d(low dose),81 d(medium dose),and 90 d(high dose),with all valeric acid groups having significantly prolonged survival compared to the control group(all P＜0.05).Conclusion:Valeric acid effectively inhibits the growth of gastric cancer xenografts,attenuates systemic inflammatory responses,and prolongs the survival of nude mice,possibly through activation of the Nrf2 pathway and modulation of the tumor microenvironment.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Objectives:To compare the differences in three rat intervertebral disc degeneration(IDD)models constructed by needle injections of ethanol into the nucleus pulposus,annulus fibrosus,and endplate,respectively.Methods:45 6-week-old Sprague-Dawley rats were randomly divided into three groups using a random number table method,with 15 rats in each group.Three different needle injection of ethanol methods including nucleus pulposus injection(nucleus pulposus injection group),annulus fibrosus injection(annulus fibrosus injection group),and endplate injection(endplate injection group)were used to construct IDD models at the Co6/7 intervertebral disc in rats.At 1,2,3,and 4 weeks post-modeling,3 rats from each group were randomly selected using a random number table for X-ray examination to measure and calculate the disc height index(DHI)of the Co6/7 in rats.Subsequently,rats were euthanized under excessive anesthesia,and the Co6/7 intervertebral disc along with adjacent vertebral bodies were harvested for hematoxylin-eosin(HE)staining to observe degeneration,and the degeneration degree was histologically scored.Results:One rat in each of the nucleus pulposus injection group and annulus fibrosus injection group died unexpectedly due to anesthesia;In the endplate injection group,two rats died due to postoperative infection.At 1,2,3,and 4 weeks after modeling,3 rats were selected from each group of the remaining rats,and a total of 36 rats were included in the result analysis.The remaining rats were sacrificed by excessive anesthesia.One week after modeling,the Co6/7 DHI in each group was lower than that before modeling(Nucleus pulposus injection group:0.117±0.002 vs 0.134±0.005;Annulus fibrosus injection group:0.126±0.005 vs 0.133±0.005;Endplate injection group:0.127±0.002 vs 0.130±0.007,all P＜0.05),which gradually decreased over time.After modeling in each group,the annulus fibrosus broke,the arrangement of fibers gradually became disordered,the matrix and cells of the nucleus pulposus were gradually lost or even completely disappeared,the intervertebral discs gradually collapsed,and the intervertebral spaces gradually narrowed.The degeneration rate and degree of the nucleus pulposus injection group were faster and higher than those of the other two groups.Four weeks after modeling,the DHI of the nucleus pulposus injection group was 0.090±0.008,which was lower than that of the annulus fibrosus injection group(0.106±0.007,P＜0.05)and endplate injection group(0.109±0.000,P＜0.05);The histological score of the nucleus pulposus injection group was 10.00±0.82,which was higher than that of the annulus fibrosus injection group(9.00±1.41,P＜0.05)and endplate injection group(8.75±0.96,P＜0.05).Conclusions:The three needle injection of ethanol methods have their own unique characteristics for constructing IDD models.Nucleus pulposus injection induces the fastest and most severe degeneration,endplate injection leads to slower degeneration but is more in line with natural degeneration processes,and annulus fibrosus injection falls between the other two methods in terms of degeneration characteristics.

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.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective To screen the core genes related to colon cancer in order to provide a new research direction for molecular di-agnosis,targeted therapy and prognosis evaluation of colon cancer.Methods Colon cancer differentially expressed genes(DEGs)were screened out from the gene expression database(GEO),and functional annotation and pathway enrichment analysis of DEGs were per-formed by gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis in Metascape database.The network of protein interactions(PPI)was built utilizing the String database and Cytoscape software to identify the core genes.Survival analysis of se-lected core genes was performed using Kaplan-Meier plotter database,and expression level of core genes was verified using GEPIA2database.Metascape data was used to conduct KEGG pathway enrichment analysis on the selected core genes,and the signal pathway of core gene enrichment was identified.COL1A1 in the core gene was selected for immunohistochemical verification.Results A total of 468 DEGs were identified,including 162 UDEGs and 306 DDEGs.In the two datasets,there were 194 overlapping genes,of which 54 were up-regulated and 140 were down-regulated.With the help of CytoHubba plugin,the top 10gene nodes in the score were selected and identified as the possible core genes of colon cancer(COL1A1,MMP3,COL1A2,COL11A1,THBS2,BGN,MMP1,COL10A1,SPP1,INHBA).The prognosis and expression levels of these 10genes were analyzed,and the expression levels of the 10 core genes were different in colon cancer tissues and normal colon tissues.All of the 10 core genes were correlated with colon cancer prognosis except MMP1,among which MMP3 was positively correlated and the other 8genes were negatively correlated.KEGG analysis showed that core genes were mainly concentrated in three signaling pathways:cytoskeleton,extracellular matrix(ECM)receptor interaction and pro-tein digestion and absorption in muscle cells.Immunohistochemistry analysis revealed a marked increase in the expression level of COL1A1 within the tumor tissue compared to that in paracancer tissue.Conclusion The core genes COL1A1,MMP3,COL1A2,COL11A1,THBS2,BGN,MMP1,COL10A1,SPP1 and INHBA selected by bioinformation analysis may be involved in the occurrence and development of colon cancer,and may be related to the prognosis of patients with colon cancer.It is anticipated that it will serve as a clinically significant biomarker and a therapeutic target for colon cancer.

Objectives:To compare the differences in three rat intervertebral disc degeneration(IDD)models constructed by needle injections of ethanol into the nucleus pulposus,annulus fibrosus,and endplate,respectively.Methods:45 6-week-old Sprague-Dawley rats were randomly divided into three groups using a random number table method,with 15 rats in each group.Three different needle injection of ethanol methods including nucleus pulposus injection(nucleus pulposus injection group),annulus fibrosus injection(annulus fibrosus injection group),and endplate injection(endplate injection group)were used to construct IDD models at the Co6/7 intervertebral disc in rats.At 1,2,3,and 4 weeks post-modeling,3 rats from each group were randomly selected using a random number table for X-ray examination to measure and calculate the disc height index(DHI)of the Co6/7 in rats.Subsequently,rats were euthanized under excessive anesthesia,and the Co6/7 intervertebral disc along with adjacent vertebral bodies were harvested for hematoxylin-eosin(HE)staining to observe degeneration,and the degeneration degree was histologically scored.Results:One rat in each of the nucleus pulposus injection group and annulus fibrosus injection group died unexpectedly due to anesthesia;In the endplate injection group,two rats died due to postoperative infection.At 1,2,3,and 4 weeks after modeling,3 rats were selected from each group of the remaining rats,and a total of 36 rats were included in the result analysis.The remaining rats were sacrificed by excessive anesthesia.One week after modeling,the Co6/7 DHI in each group was lower than that before modeling(Nucleus pulposus injection group:0.117±0.002 vs 0.134±0.005;Annulus fibrosus injection group:0.126±0.005 vs 0.133±0.005;Endplate injection group:0.127±0.002 vs 0.130±0.007,all P＜0.05),which gradually decreased over time.After modeling in each group,the annulus fibrosus broke,the arrangement of fibers gradually became disordered,the matrix and cells of the nucleus pulposus were gradually lost or even completely disappeared,the intervertebral discs gradually collapsed,and the intervertebral spaces gradually narrowed.The degeneration rate and degree of the nucleus pulposus injection group were faster and higher than those of the other two groups.Four weeks after modeling,the DHI of the nucleus pulposus injection group was 0.090±0.008,which was lower than that of the annulus fibrosus injection group(0.106±0.007,P＜0.05)and endplate injection group(0.109±0.000,P＜0.05);The histological score of the nucleus pulposus injection group was 10.00±0.82,which was higher than that of the annulus fibrosus injection group(9.00±1.41,P＜0.05)and endplate injection group(8.75±0.96,P＜0.05).Conclusions:The three needle injection of ethanol methods have their own unique characteristics for constructing IDD models.Nucleus pulposus injection induces the fastest and most severe degeneration,endplate injection leads to slower degeneration but is more in line with natural degeneration processes,and annulus fibrosus injection falls between the other two methods in terms of degeneration characteristics.