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.

BACKGROUND: Owing to the high prevalence of antibiotic resistance in Helicobacter pylori ( H. pylori ) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs . esomeprazole for H. pylori eradication in a patient population in China. METHODS: This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori , evaluated using a 13 C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%. RESULTS: The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P  = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P  = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles. CONCLUSION: Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China. TRIAL REGISTRATION ClinicalTrials.gov , NCT04198363.
Humans ; Esomeprazole/therapeutic use* ; Double-Blind Method ; Helicobacter Infections/drug therapy* ; Male ; Female ; Middle Aged ; Helicobacter pylori/pathogenicity* ; Pyrroles/therapeutic use* ; Sulfonamides/therapeutic use* ; Adult ; Clarithromycin/therapeutic use* ; Amoxicillin/therapeutic use* ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Pyrrolidines/therapeutic use* ; Drug Therapy, Combination ; Proton Pump Inhibitors/therapeutic use*

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.

Objectives:This study aimed to compare the disease-free survival(DFS)and cervical lymph node metastasis risk in lip squamous cell carinoma(LSCC)patients between microwave thermochemotherapy and traditional surgical resection.Methods:A retrospective analysis was conducted on 106 eligible LSCC patients treated between January 2010 and January 2022.Patients were divided into the microwave thermochemotherapy group(n=37)and the surgery-alone group(n=69).Survival curves were generated using the Kaplan-Meier method,with DFS differences evaluated by Log-Rank test.Cox proportional hazards models and logistic re-gression were employed to screen prognostic factors and assess variables associated with cervical lymph node metastasis,respective-ly.Statistical analyses were performed using SPSS 26.0.Results:By September 2024,the objective response rate in the microwave thermochemotherapy group reached 94.59％(35/37).Survival analysis revealed no statistically significant difference in DFS be-tween the two groups(P=0.300).Multivariate logistic regression demonstrated that treatment modality was associated with cervical lymph node metastasis risk(P=0.022).The microwave thermochemotherapy group exhibiting a trend toward lower cervical lymph node metastasis rates compared to the surgery group.Conclusion:This study suggests that microwave thermochemotherapy achieves disease control efficacy comparable to surgical resection in early-stage LSCC patients and may reduce the likelihood of regional lymph node metastasis.

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.

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 investigate the effect of interaction between body mass index (BMI) and gender on the survival of advanced gastric cancer after immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 317 patients with advanced gastric cancer who were admitted to the Nanfang Hospital, Southern Medical University from November 2019 to October 2023 were collected. There were 205 males and 112 females, aged 56 (range, 21-79)years. All 317 patients were divided into three groups based on BMI of patients, including 58 cases with BMI <18.5 kg/m2 were classified as the low body mass group, 183 cases with BMI 18.5-24.0 kg/m2 were classified as the normal body mass group, and 76 cases with BMI >24.0 kg/m2 were classified as the overweight or obese group. Patients included in the study were treated with a programmed death-ligand 1 (PD-L1) based immunotherapy regimen for 3 cycles based on their specific conditions, and further decision was made whether to undergo radical surgery or continue comprehensive treatment after evaluating the efficacy. Observation indicators: (1) clinicopathological characteristics of patients; (2) follow-up and mortality status; (3) analysis of factors affecting survival of patients with advanced gastric cancer after immunotherapy. Comparison of measurement data with normal distribution among groups was conducted using the ANOVA. Comparison of measurement data with skewed distribution among groups was conducted using the Kruskal-Wallis H test. Comparison of count data among groups was conducted using the chi-square test. The Cox proportional hazard model was used for univariate and multivariate analyses. Nonlinear trend was analyzed using the restricted cubic spline (RCS) curve, and trend and correction graphs were created using the rcssci package (v1.0). Results:(1) Clinicopathological characteristics of patients. There was no significant difference in gender, age, Borrmann classification, Lauren classification, combined positive score of PD-L1, expression of human epidermal growth factor receptor 2, Epstein-Barr virus infection, carcino-embryonic antigen, CA19-9, CA72-4, alpha-fetoprotein, conversion surgery among the 3 groups of patients ( P>0.05), and there was a significant difference in mismatch repair combined with micro-satellite stability among the 3 groups of patients ( P<0.05). (2) Follow-up and mortality status. Of the 317 patients, 316 cases completed follow-up and 1 case in the overweight or obese group was lost to follow-up. The follow-up time of the 316 cases was 13.8(range, 0.9-48.2)months. During the follow-up, the number of death in the low body mass group, normal body mass group and overweight or obese group were 27, 70 and 31, respectively. (3) Analysis of factors affecting survival of patients with advanced gastric cancer after immunotherapy. Results of multivariate analysis showed that gender and BMI were independent factors affecting survival of patients with advanced gastric cancer after immunotherapy ( hazard ratio=0.066, 0.922, 95% confidence interval as 0.005-0.846, 0.855-0.994, P<0.05). Results of further analysis showed that the interaction between BMI and gender was an independent factor affecting survival of patients with advanced gastric cancer after immuno-therapy ( hazard ratio=1.152, 95% confidence interval as 1.024-1.296, P<0.05). Results of Cox regre-ssion analysis based on different gender showed that took patients of the normal body mass group as a reference, the male patients of the low body mass group had a significantly increased risk of death, showing a significant statistically difference ( hazard ratio=1.809, 95% confidence interval as 1.037-3.155, P<0.05). Results of RCS curve analysis showed that there was a non-linear correlation between BMI and survival of patients with advanced gastric cancer after immunotherapy ( P<0.05). Results of corrected RCS curve analysis using the rcssci package showed that there was a U-shaped relationship between BMI and survival of patients with advanced gastric cancer after immuno-therapy ( P<0.05), with the optimal cut-off value of BMI as 22.2 kg/m 2. Results of RCS curve analysis based on different gender showed that there was a U-shaped relationship between BMI and survival of male patients with advanced gastric cancer after immunotherapy ( P<0.05), with the optimal cut-off value of BMI as 22.7 kg/m 2. Conclusions:Gender, BMI and the interaction between BMI and gender are independent factors affecting survival of patients with advanced gastric cancer after immuno-therapy. There is a U-shaped relationship between BMI and survival of patients, with the optimal cut-off value of BMI as 22.2 kg/m 2, and there is a U-shaped relationship between BMI and survival of male patients, with the optimal cut-off value of BMI as 22.7 kg/m 2.

Objectives:This study aimed to compare the disease-free survival(DFS)and cervical lymph node metastasis risk in lip squamous cell carinoma(LSCC)patients between microwave thermochemotherapy and traditional surgical resection.Methods:A retrospective analysis was conducted on 106 eligible LSCC patients treated between January 2010 and January 2022.Patients were divided into the microwave thermochemotherapy group(n=37)and the surgery-alone group(n=69).Survival curves were generated using the Kaplan-Meier method,with DFS differences evaluated by Log-Rank test.Cox proportional hazards models and logistic re-gression were employed to screen prognostic factors and assess variables associated with cervical lymph node metastasis,respective-ly.Statistical analyses were performed using SPSS 26.0.Results:By September 2024,the objective response rate in the microwave thermochemotherapy group reached 94.59％(35/37).Survival analysis revealed no statistically significant difference in DFS be-tween the two groups(P=0.300).Multivariate logistic regression demonstrated that treatment modality was associated with cervical lymph node metastasis risk(P=0.022).The microwave thermochemotherapy group exhibiting a trend toward lower cervical lymph node metastasis rates compared to the surgery group.Conclusion:This study suggests that microwave thermochemotherapy achieves disease control efficacy comparable to surgical resection in early-stage LSCC patients and may reduce the likelihood of regional lymph node metastasis.

OBJECTIVE To explore the clinical efficacy and safety of Huangkui capsule combined with cyclophosphamide and prednisone in the treatment of immunoglobulin A(IgA)nephropathy with renal insufficiency.METHODS A total of 117 patients with IgA nephropathy and renal insufficiency who were hospitalized in the department of nephrology of the Second Affiliated Hospital of Dalian Medical University from February 2021 to March 2024 were divided into prednisone group(n=38),cyclophosphamide group(n=39)and Huangkui group(n=40)according to the random number table method.On the basis of standardized basic treatment,the three groups were treated with prednisone,prednisone+cyclophosphamide,and prednisone+cyclophosphamide+Huangkui capsule,respectively,with a course of 6 months.The clinical efficacy,renal function indexes,immunoglobulin levels,inflammatory factor levels before and after treatment,and the incidence of adverse reactions during treatment were compared among the three groups.RESULTS Finally,107 patients completed the study(35 in prednisone group,37 in cyclophosphamide group,and 35 in Huangkui group).After 6 months of treatment,there was a statistically significant difference in the total effective rate among the three groups(P=0.028),and the total effective rate of the Huangkui group was significantly higher than that of the prednisone group(P=0.023).In terms of renal function,the levels of blood urea nitrogen(BUN),serum creatinine(Scr),and urinary microalbumin(Umalb)in the three groups after treatment were significantly lower than those before treatment,while the estimated glomerular filtration rate(eGFR)was significantly higher than that before treatment(P＜0.05).Among them,the Huangkui group was superior to the other two groups in reducing BUN level(P＜0.05),and both the Huangkui group and cyclophosphamide group were superior to the prednisone group in improving Scr,Umalb and eGFR(P＜0.05).In terms of immunology,both the Huangkui group and cyclophosphamide group were superior to the prednisone group in increasing IgG level and decreasing IgA and IgM levels(P＜0.05).In terms of inflammatory factors,the Huangkui group was superior to the prednisone group and cyclophosphamide group in reducing tumor necrosis factor-α level(P＜0.05),and superior to the prednisone group in reducing interleukin-6 level(P＜0.05).There was no statistically significant difference in the total incidence of adverse reactions among the three groups(P＞0.05).CONCLUSIONS Huangkui capsule combined with cyclophosphamide and prednisone has a good therapeutic effect on IgA nephropathy with renal insufficiency.It can further improve patients'renal function and immune function,regulate inflammatory status,and has good safety.