Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

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.

Virus-like particles(VLPs)are hollow nanoparticles composed of one or several virus structural proteins,which have a morphological structure similar to natural viruses but do not contain any genetic material.Due to the excellent innate immunogenicity and safety of VLPs,they are often used in the development of tumor vaccines.In addition,compared with traditional drug delivery vectors,VLPs have better biocompatibility and strong targeting ability,making them highly valued in the delivery of anti-tumor drugs.In recent years,the efficient delivery of gene editing tools using VLPs has provided new possibilities for tumor treatment.VLPs can inhibit tumor growth and spread through various mechanisms,such as activating immune responses to suppress tumor growth,stimulating the body's immune system,promoting the expression of tumor associated antigens,and enhancing the body's ability to recognize and clear tumor cells.These studies not only broaden the application scope of VLPs in the field of anti-tumor therapy,but also provide a broader prospect for future research and application.This article reviewed the research progress of VLPs derived from different viruses in preventive or therapeutic vaccines and drug delivery carriers,and explored new development strategies.

Objective To understand the challenges faced by elderly patients with multiple chronic conditions in community settings during the process of disease management,and to provide a basis for developing intervention strategies for managing comorbidities in the elderly.Methods A phenomenological research approach was adopted,using purposive sampling.From July to October 2024,16 elderly patients with multiple chronic conditions from 5 community service centers in Shenzhen were selected as study participants.Semi-structured in-depth interviews were conducted,and the interview data were analyzed using Colaizzi's seven-step method.Results Totally 4 themes and 8 sub-themes were extracted,including the disorder of multi-source health information structure and environment(insufficient systematic integration of health guidance,uneven quality of knowledge under multiple information channels),the exhaustion of self-management efficacy among chronic disease patients(the coexistence of multiple diseases aggravates the burden of physical and mental symptoms;negative emotions weaken the efficacy of active management),the absence of an integrated management mechanism for multiple diseases(repeated medical visits lead to poor treatment experience;multiple medications pose potential health risks),and the lack of in-depth and dynamic social support practices(formal operation of community support systems,family support facing the dilemma of filial piety and control).Conclusion Elderly patients with multiple chronic conditions in community settings face numerous challenges in disease management.Current chronic disease management in China primarily focuses on single diseases.It is recommended that healthcare professionals shift their perspective,improve the identification,assessment,nursing,and treatment of comorbidities in the elderly,and provide integrated chronic disease management approaches.This would enable a"one-stop"solution to the management challenges of multimorbidity in elderly patients,thereby enhancing their quality of life.

Objective:To investigate the expression characteristics of Zeste enhancer of Zeste homolog 2 (EZH2) in breast cancer tissue and its influence on tumor progression and prognosis.Methods:Transcriptome data of breast cancer tissue and normal breast tissue adjacent to cancer as well as clinical data of patients were obtained from the cancer genome atlas (TCGA) database, gene expression comprehensive database and European genome phenotype archives database, and the difference of EZH2 expression was analyzed using TIMER 2.0 platform. The survival information of breast cancer patients was obtained from the Kaplan Meier Plotter database, and the overall survival time, relapse free survival time and distant metastasis free survival time of breast cancer patients with low EZH2 expression and high EZH2 expression were compared. Select 14 nude mice were selected and randomly divided into si-EZH2 group and control group, with 7 mice in each group.MCF7 culture suspensions transfected with EZH2 knockdown plasmid and control plasmid were inoculated for corresponding group. The body mass and tumor volume of two groups of nude mice inoculated with MCF7 cells were compared at different times. On the 28th day, the nude mice were euthanized and the tumors were dissected to compare the tumor mass of the two groups of nude mice. The normally distributed quantitative data was represented by xˉ ± s. Two independent sample t-tests were used for comparison between two groups, repeated measures ANOVA was used for comparison of body mass and tumor volume between two groups of nude mice at different times, and Bonferroni test was used for pairwise comparison. The comparison of survival rates was conducted using log rank test. Results:A total of 1085 breast cancer tissues and 291 normal adjacent breast tissues were included in the TCGA database. EZH2 expression in breast cancer tissues was higher than that in normal adjacent breast tissues ( P<0.05). In the Kaplan Meier Plotter database, the total survival time, relapse free survival time, and distant metastasis free survival time of breast cancer patients in the EZH2 overexpression group were shorter than those in the EZH2 low expression group ( P=0.013, <0.001, <0.001). After 7 days of inoculation with MCF7 culture suspension, significant subcutaneous tumors were observed on the left back of both groups of nude mice. On the first day, there were no statistically significant difference in body mass between the two groups of nude mice ( P>0.05); On day 7, 13, 19, 25, and 28, the body mass and tumor volume of both groups of nude mice gradually increased (nude mouse body mass: within group F=29.31, P<0.001, between groups F=234.32, P<0.001, Finteraction=16.83, P<0.001; Tumor volume: within group F=34.00, P<0.001, between groups F=193.17, P<0.001, Finteraction=35.61, P<0.001). And the body mass of the siEZH2 group nude mice was higher than that of control group (all P<0.05). On days 19, 25, and 28, tumor the volume of the siEZH2 group nude mice was smaller than that of control group (all P<0.05). On the 28th day, the mass of tumors dissected in the siEZH2 group of nude mice was lower than that in the control group [(0.30±0.07) g vs. (0.61±0.14) g, t=5.16, P<0.001]。 Conclusions:EZH2 is highly expressed in breast cancer tissues and is significantly associated with poor prognosis. Knockdown of EZH2 can significantly inhibit the proliferation and tumor formation of breast cancer cells.

Objective: To analyze the potential categories and influencing factors of the compliance trajectory of orthokeratology lenses (OK lens) in myopic children and adolescents, so as to provide a basis for dynamic and accurate intervention of OK lens compliance in myopic children and adolescents. Methods: From January to June 2024, 310 myopic children and adolescents wearing OK lens were selected as research subjects from the Ophthalmology Medical Center of Cangzhou Central Hospital using a convenient sampling method. Data were collected at four time points: when the glasses were first fitted (T0), 2 weeks after fitting (T1), 1 month later (T2), 3 months later (T3), and 6 months later (T4). The data collection methods included general information questionnaires, compliance surveys for OK lens wearers, the Behavior Rating Inventory of Executive Function-Self-report Version (BRIEF-SR), family support scales, and a self-made questionnaire on myopia control attitudes. A growth mixed model was used to identify the trajectory categories of compliance with OK lens wearing among myopic children and adolescents, and multiple Logistic regression analysis was employed to examine the influencing factors. Results: The compliance with OK lens among myopic children and adolescents were roughly divided into four developmental trajectories: C1 exemplary adherent (58 cases, 18.71%), C2 gradual progressor (130 cases, 41.94%), C3 fluctuating (85 cases, 27.42%), and C4 stubborn low follower (37 cases, 11.94%). Multivariate Logistic regression analysis showed that, with C1 group as the reference, age (C3, OR = 0.74 ), parental education level (C4, OR =0.67), executive function (C2, OR =0.69; C4, OR =0.44), family support (C3, OR =0.75) and myopia control attitude (C2, OR =0.39) were all influencing factors for the compliance trajectory of OK lens; with C2 group as the reference, age (C3, OR = 0.55 ), parental education level (C3, OR =0.34; C4, OR =0.64), executive function (C3, OR =0.77), and family support (C4, OR =0.58) were all influencing factors for the compliance trajectory of OK lens; with C3 group as the reference, age (C4, OR = 0.68 ), and myopia control attitude (C4, OR =0.44) were both influencing factors for the compliance trajectory of OK lens ( P <0.05). Conclusions The compliance of wearing OK lens in children and adolescents with myopia can be roughly divided into four trajectories, and there is group heterogeneity. Dynamic and precise compliance intervention strategies should be given based on different trajectories and influencing factors.

Objective To analyze the clinical features of chronic obstructive pulmonary disease (COPD) patients with heart failure (HF) in Nanjing and explore the influencing factors. Methods A total of 773 COPD inpatients were selected from January 2021 to January 2024 in Nanjing Combined Hospital of Traditional Chinese and Western Medicine, Nanjing Qixia District Hospital, Nanjing Lishui District People's Hospital, Nanjing Pukou District Hospital of Traditional Chinese Medicine and Nanjing First Hospital., and were divided into 2 groups according to the presence or absence of combined HF. The general data and medical records of the two groups were compared, the clinical characteristics of COPD patients with HF were summarized, and the influencing factors of COPD patients with HF were analyzed by multivariate logistic regression. Results Among the 242 patients (31.31%) with COPD had HF, chronic paroxysmal dyspnea was the most common first symptom, 169 patients (69.83%) had left heart failure, 63 patients (30.17%) were diagnosed as right heart failure or global heart failure , 17 patients (7.02%) had myocardial infarction. Multivariate logistic regression analysis showed that the risk of HF was 1.678 times and 1.691times higher in COPD groups ≥ 50 years old and male COPD groups than in < 50 years old and female groups, respectively; the risk of HF was 1.491 times higher in COPD groups engaged in physical work than in physical work groups; the risk of HF was 1.447 times and 1.580 times higher in COPD groups with hypertension and coronary heart disease than in COPD groups without hypertension and coronary heart disease, respectively; the risk of HF was 1.859 times higher in COPD groups smoking>400 vial/year than in COPD groups≤400 vial/ year; the risk of HF was 1.757 times higher in COPD groups with acute exacerbation frequency≥2 times/year than in COPD groups<2 times/year; the above differences were statistically significant (P<0.05). Conclusion Attention should be paid to elderly, male and heavy physical work group of COPD patients. Active treatment of hypertension and coronary heart disease, effective tobacco control and reduction of the frequency of acute exacerbation are effective ways to reduce the risk of HF in COPD patients in Nanjing.

Objective To investigate the impact of enterovirus 71(EV71)on skeletal muscle injury and explore its mechanism in relation to the caspase-1/interleukin(IL)-1 β signaling pathway in EV71-induced skeletal muscle damage.Methods One-day-old BALB/c suckling mice were divided randomly into three groups:normal control(NC)(n=60),EV71 infection model(n=60),and caspase-1 inhibitor(EV71+VX765)(n=15)groups.The NC and EV71 model groups were further subdivided into four subgroups(5,7,10,and 14 days)(n=5 mice per group).An EV71-infected model was established by intraperitoneal injection of 25 × 103 μL/kg EV71 viral solution for 3 consecutive days.Mice in the caspase-1 inhibitor group received VX765(20 mg/kg)intraperitoneally 6 hours post-viral inoculation,continued daily for 10 days until sample collection.Mice in the NC group received an equivalent volume of saline containing 5％dimethylsulfoxide and 10％PEG300,followed by 2％cell maintenance solution after 6 hours.Post-modeling body weight and clinical disease scores were recorded.Pathological skeletal muscle damage was observed by hematoxylin-eosin(HE)staining,and expression levels of EV71 VP-1(viral capsid protein),pro-caspase-1,cleaved-caspase-1,IL-1 β,α-smooth muscle actin(SMA),and Collagen Ⅰ were detected by Western blot and immunofluorescence.Results Compared with the NC group at the same time points,mice in the EV71 model group exhibited reduced body weight,elevated disease scores,and skeletal muscle pathology characterized by inflammatory cell infiltration,myofiber dissolution,and decreased cross-sectional area(HE staining).Western blot showed significantly increased levels of EV71 VP-1,IL-1β,α-SMA,and Collagen Ⅰ in skeletal muscle homogenate from EV71 mice at 5,7,and 10 days post-infection(P＜0.001).In contrast,mice in the VX765 group showed improved body weight,reduced clinical scores(P＜0.01),and significant downregulation of EV71 VP-1(P＜0.01),pro-caspase-1,cleaved-caspase-1,IL-1β,and Collagen Ⅰ compared with the EV71 model group(P＜0.01).These findings were confirmed by immunofluorescence,indicating that inhibition of caspase-1 alleviated EV71-induced skeletal muscle injury.Conclusions EV71 may induce skeletal muscle injury by activating the caspase-1/IL-1β signaling pathway.

Objective:To explore the expression level of Porphyromonas gingivalis, downstream of tyrosine kinase 3 (DOK3) and tumor-associated macrophage (TAM) in the tumor immunomicroenvironment of oral squamous cell carcinoma (OSCC) and the correlation with clinicopathological characteristics and prognosis of patients.Methods:A retrospective case-control study was conducted. The clinical data of 200 OSCC patients with Porphyromonas gingivalis-positive confirmed by 16S rDNA sequencing technology in the First Affiliated Hospital, Xinjiang Medical University between June 2008 and June 2020 were collected. The tumor tissues and the corresponding adjacent normal mucosal tissues of 6 OSCC patients (including 3 cases with Porphyromonas gingivalis -positive and 3 cases with Porphyromonas gingivalis-negative) were selected for high-throughput sequencing to screen differentially co-expressed genes. Immunohistochemistry method was used to detect the expressions of Porphyromonas gingivalis, DOK3, and CD206 (a TAM marker). The median H score of OSCC tissues was used as the threshold to categorize the expression level of Porphyromonas gingivalis, DOK3 and CD206 into low-expression (H score < threshold) and high-expression (H score ≥ threshold) groups. The overall survival (OS) analysis was conducted by using the Kaplan-Meier method, and the log-rank test was employed.Results:The high-throughput sequencing results revealed that DOK3 is a differentially co-expressed gene among normal oral mucosa, Porphyromonas gingivalis-positive, and Porphyromonas gingivalis-negative OSCC. In 200 patients with Porphyromonas gingivalis-positive OSCC, 139 exhibited high expression of Porphyromonas gingivalis (H score ≥ 7 points), while 61 showed low expression (H score < 7 points). There were statistically significant differences in the expression levels of Porphyromonas gingivalis in patients with different survival status, pathological T stage, pathological N stage, clinical stage, tumor diameter, degree of tumor differentiation and recurrence (all P < 0.05). Among the 139 OSCC patients with high expression of Porphyromonas gingivalis, 92 cases showed high expression of DOK3 (H score ≥ 6 points) and 47 showed low expression (H score < 6 points); 78 cases exhibited high expression of CD206 (H score ≥ 6 points), while 61 showed low expression (H score < 6 points). There were statistically significant differences in the DOK3 expression level in the high expression of Porphyromonas gingivalis OSCC patients with different age, survival status, pathological T stage, pathological N stage, and recurrence (all P < 0.05). There were statistically significant differences in the CD206 expression level in the high expression of Porphyromonas gingivalis OSCC patients with different pathological T stage, clinical stage, and degree of tumor differentiation (all P < 0.05). The expression of Porphyromonas gingivalis was positively correlated with the expressions of DOK3 and CD206 (both P < 0.01). At the last follow-up on April 6th, 2024, the median follow-up time was 45 months (3 to 106 month range). The median OS time of the 200 patients was 2 429 d, and the 3-year OS rate was 63.9%. The OS of OSCC patients with high expressions of Porphyromonas gingivalis, DOK3, and CD206 was worse than that in those with low expressions (all P < 0.05). Conclusions:The high expression levels of Porphyromonas gingivalis, DOK3, and TAM are associated with a poor prognosis of OSCC patients, suggesting their potential as key biomarkers for prognostic evaluation.

Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.