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: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

BACKGROUND: Whether adherence to a healthy lifestyle is associated with a lower risk of developing pneumonia and a better long-term prognosis remains unclear. This study aimed to investigate associations of individual and combined lifestyle factors (LFs) with the incidence risk and long-term prognosis of pneumonia hospitalization. METHODS: Using data from the China Kadoorie Biobank study, we used the multistate models to investigate the role of five high-risk LFs, including smoking, excessive alcohol drinking, unhealthy dietary habits, physical inactivity, and unhealthy body shape, alone or in combination in the transitions from a generally healthy state at baseline to pneumonia hospitalization or cardiovascular disease (CVD, regarded as a reference outcome), and subsequently to mortality. RESULTS: Most of the five high-risk LFs were associated with increased risks of transitions from baseline to pneumonia and from pneumonia to death, but with different risk estimates. The greater the number of high-risk LFs, the higher the risk of developing pneumonia and long-term mortality risk after pneumonia, with the strength of associations comparable to that of LFs and CVD. Compared to participants with 0-1 high-risk LF, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for transitions from baseline to pneumonia and from pneumonia to death in those with five high-risk LFs were 1.43 (1.28-1.60) and 1.98 (1.61-2.42), respectively. Correspondingly, the respective HRs (95% CIs) for transitions from baseline to CVD and from CVD to death were 2.00 (1.89-2.11) and 1.44 (1.30-1.59), respectively. The risk estimates changed slightly when further adjusting for the presence of major chronic diseases. CONCLUSION In this Chinese population, unhealthy LFs were associated with an increased incidence and long-term mortality risk of pneumonia.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Life Style ; Pneumonia/etiology* ; Prognosis ; Risk Factors ; Smoking

Objective:To explore the optimal age cutoff for diagnosis and the prognosis of early-onset gastric cancer in young patients.Methods:Clinicopathological data of patients with gastric adenocarcinoma aged ≤45 years who had undergone radical gastrectomy in the Department of Gastric Surgery, Fudan University Shanghai Cancer Center from January 2013 to December 2018 were retrospectively collected. Patients with distant metastases, other malignant tumors, combined organ resection, gastric stump cancer, positive margin, and incomplete clinical or follow-up data were excluded. X-tile software analysis of the actual overall survival of the collected cases yielded an optimal cut-off of 32 years. Accordingly, the enrolled cases were divided into an early-onset young group (age ≤32 years) and young adult group (age >32 years). Clinicopathological characteristics, long-term survival, and postoperative recurrence were compared between the two groups. Univariate and multivariate analyses were performed using the Cox proportional hazards model to identify the factors affecting the prognosis of young patients with gastric cancer.Results:The study cohort comprised 462 patients, including 256 (55.4%) women, 419 (90.7%) with middle and lower gastric cancers, and 343 (74.2%) with poorly differentiated tumors. There were 101 patients in the early-onset young group and 361 in the young adult group. These groups did not differ significantly in terms of sex, body mass index, tumor location, tumor size, surgical procedure, neurovascular invasion, or tumor stage (all P>0.05). The proportion of patients with poorly differentiated tumors in the early-onset young group was significantly higher than that in the young adult group (89.1%[90/101] vs. 70.1%[253/361], χ 2=15.26, P<0.001). All study patients completed 5 years of follow-up, the median duration of which was 101 months (61-133 months). Death or tumor recurrence occurred in 151 patients (32.7%), in 118 of whom the sites of recurrence and metastasis could be identified, 38 in the early-onset young group and 80 in the young adult group. Fifty-five (46.6%) patients developed peritoneal metastases and 40 (33.9%) hematogenous metastases. In the early-onset young group, 20 patients developed peritoneal metastases, 11 hematogenous metastases, five distant lymph node metastases, and two local recurrence. In the young adult group, 35 patients developed peritoneal metastases, 29 hematogenous metastases, six local recurrences, and 10 distant lymph node metastases. The 5-year overall survival and disease-free survival rates were significantly higher in the young adult group than in the early-onset young group (73.7% vs. 57.4%, P=0.002 and 70.6% vs. 55.4%, P=0.004, respectively). Cox multivariate analysis showed that age >32 years (HR=0.63, 95%CI: 0.43-0.90, P=0.012) was an independent protective factor for overall survival, whereas later N stage (HR=1.67, 95%CI:1.09-2.57, P=0.018) was an independent risk factor for overall survival after surgery ( P<0.05). Age >32 years (HR=0.60, 95%CI: 0.41-0.86, P=0.006) was also an independent protective factor for disease-free survival, whereas later N stage was an independent risk factor (HR=1.69, 95%CI: 1.08-2.64, P=0.021). Conclusion:Young patients with early-onset gastric cancer aged ≤32 years have worse tumor differentiation and prognosis.

Objective:To investigate the impact of bedside ultrasound-guided hyperthermic intraperitoneal chemotherapy (HIPEC) after laparoscopic gastric cancer surgery on the prognosis of patients with only positive peritoneal lavage cytology (CY+) and no other distant metastases.Methods:The clinicopathological data of 49 patients with only positive peritoneal lavage cytology who underwent laparoscopic gastrectomy and D2 lymph node dissection from December 2017 to December 2022 were retrospectively analyzed. The patients were divided into the HIPEC group (27 cases) and the non-HIPEC group (22 cases) based on whether they received postoperative bedside ultrasound-guided HIPEC. The patterns of postoperative recurrence and metastasis and the 3-year survival rates were compared between the two groups. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to determine the prognostic factors.Results:There was no statistically significant difference in all baseline clinicopathological data between the two groups ( P>0.05); the median follow-up time for all patients was 31 months (ranging from 13 to 73 months), and the overall recurrence rate for all patients was 55.1% (27/49). Among them, 12 cases (24.5%) had peritoneal metastasis, 7 cases (14.3%) had hematogenous recurrence, 5 cases (10.2%) had distant lymph node metastasis, and 3 cases (6.1%) had local recurrence. The overall recurrence rates of patients in the HIPEC group and the non-HIPEC group were 51.8% (14/27) and 59.1% (13/22), respectively. There was no statistically significant difference (χ 2=0.26, P=0.612). The peritoneal metastasis rate of patients in the HIPEC group was 18.5% (5/27), which was lower than that of the non-HIPEC group at 31.8% (7/22). However, there was no statistically significant difference (χ 2=1.16, P=0.282). The proportions of local recurrence, hematogenous metastasis, and distant lymph node metastasis were comparable between the two groups (all P>0.05). The cumulative 3-year recurrence rates of the two groups were similar (70.7% vs. 71.3%, P=0.266). In the HIPEC group, the 3-year overall survival rate was 61.1%, which was significantly higher than that of the non-HIPEC group (31.5%). The difference was statistically significant ( P=0.014). The disease-free progression survival rates of the two groups were 29.3% and 28.7% respectively, and there was no statistically significant difference between them ( P=0.266). Cox multivariate analysis showed that no postoperative HIPEC (HR=5.21, 95%CI:1.90-14.31, P=0.001), poor tumor differentiation (HR=3.78, 95%CI:1.07-13.26, P=0.038), and later N stage (HR=6.18, 95%CI:1.39-7.59, P=0.017) were independent risk factors for the overall survival rate after surgery ( P<0.05). Later N stage (HR=3.67, 95%CI:1.07-12.55, P=0.038) was an independent risk factor for the disease-free progression survival rate after surgery ( P<0.05). Conclusion:Bedside ultrasound-guided HIPEC after laparoscopic gastrectomy and D2 lymph node dissection can improve the overall survival of CY+ gastric cancer patients.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To explore the prospective association between physical activity level and mor-tality risk in Chinese adults with chronic obstructive pulmonary disease(COPD).Methods:Based on the China Kadoorie Biobank(CKB)who had COPD at the baseline survey,this study employed the Cox proportional hazards regression model to estimate the prospective associations between the overall physical activity,different intensities(low-level,moderate-to-vigorous-level),and types(occupational,non-occupational)of physical activity level and the risks of all-cause and cause-specific mortality,such as vascular diseases,cancer,and respiratory diseases.Based on the quintiles of physical activity level,par-ticipants were divided into five groups(Q1-Q5),with the lowest quintile group(Q1)as the reference group.Hazard ratio(HR)and 95％confidence interval(95％CI)were calculated for the remaining.In our study,we also performed sensitivity and subgroup analyses,including age,gender,self-rated health status,severity of COPD,etc.Results:Among 33 588 COPD patients at the baseline survey,8 314(22.2％)deaths were documented during an average follow-up of(11.1±3.1)years.Negative linear associations between the overall physical activity level and mortality risk from all-cause,vascular,and respiratory diseases were observed(P trend for linear correlation being＜0.001,0.002,＜0.001).Compared with the lowest quintile group of total physical activity(Q1),the hazard ratios(HR)and 95％confidence intervals(CI)for all-cause mortality,vascular disease mortality,and respiratory disease mortality in the highest quintile group(Q5)were 0.77(0.70,0.85),0.77(0.65,0.91),and 0.58(0.48,0.71),respectively.The low-level and moderate-to-vigorous-level physical activity were nega-tively associated with all-cause mortality in the COPD patients(P trend for linear correlation:0.002,＜0.001,respectively).Compared with the lowest quintile group of low-intensity and moderate-to-vigorous intensity physical activity(Q1),the HRs(95％CI)for all-cause mortality in the highest quintile group(Q5)were 0.89(0.82,0.97)and 0.79(0.72,0.87),respectively.The occupational and non-occupational physical activity were also found to have a linear inverse association with all-cause mortality risk among the COPD patients(P trend＜0.001 and 0.015,respectively).Compared with the lowest quintile group of occupational and non-occupational physical activity(Q1),the HR(95％CI)for all-cause mortality in the highest quintile group(Q5)were 0.69(0.61,0.78)and 0.91(0.84,0.98),respectively.The associations between overall physical activity and all-cause mortality risk were stronger for patients aged 60 and above,female,and who reported poor health status(P for interaction:0.028,0.012,0.010).The protective effect of total physical activity was also applicable to the COPD patients of varying severity.Conclusion:Physical activity could reduce the mortality risk in a dose-response relationship among COPD patients,regardless of its intensity and type,especially among indi-viduals aged 60 and above,females,and those with poor self-report health status.

Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0％,males for 68.0％,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5％,males for 60.8％,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95％CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95％CI:-0.05 to-0.01;β=-0.07,95％CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95％CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.