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.

Objective: To evaluate the current situation of thermal environment in primary and secondary school classrooms during winter, and to analyze students thermal comfort needs, so as to provide a basis for improving classroom thermal environment. Methods: From December 16 to 26, 2024, a stratified cluster random sampling method was used to select 90 classrooms from 15 primary and secondary schools in centralized/air conditioned heating areas(Liaoning Province, Tianjin City, Shanghai City) and naturally ventilated areas(Anhui Province and Jiangxi Province)for on site environmental measurement. A questionnaire survey was conducted among 743 students. The differences between groups using the χ 2 test were compared. Based on actual measurement data, a predicted mean vote prepared percentage of dissatisfied (PMV-PPD) model for centralized/air conditioned classrooms and an adaptive model for naturally ventilated classrooms were established, and the thermal neutral temperature and comfort interval were calculated. Results: The average outdoor temperature during on site measurement was 4.00(0.20，7.00)℃. In classrooms with centralized or air conditioned heating systems, the measured average temperature was (19.33±2.59)℃, with a thermal comfort range of 20.35-25.35 ℃ and a thermal neutral temperature of 22.85 ℃. And 13.92% of students reported feeling cold, while 80.80% felt comfortable. In classrooms with natural ventilation, the measured average temperature was (12.26±1.83)℃, with a thermal neutral temperature of 19.67 ℃ and a thermal comfort range of 16.17-23.17 ℃. About 48.33% of students reported feeling cold, and 49.81 % felt comfortable.The results of univariate analysis showed that there were statistically significant differences in shoe thickness, temperature sensation, relative humidity sensation and wind speed sensation between centralized/air conditioned heating areas ( χ 2= 7.01 , 31.47, 13.57, 13.80,all P <0.05). There were also statistically significant differences in school stage for primary and secondary school students, body mass index, classroom location for seat, temperature sensation, relative humidity sensation and wind speed sensation between naturally ventilated areas ( χ 2=42.13, 11.13, 11.04, 60.39, 29.27, 38.46,all P <0.05). Conclusions There are differences in thermal environment and students subjective thermal comfort in primary and secondary schools under different ventilation modes in winter. The temperature standards for heated classrooms should be revised, and differentiated environmental regulation strategies should be adopted based on different ventilation methods to improve students health and comfort levels.

Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

ObjectiveTo investigate the ability of chimeric antigen receptor T-cell with programmed cell death-1 （PD-1） knockdown （si-PD-1 CAR-T） targeting folate receptor alpha （FRα） to eliminate hepatoma cells. MethodsThe bioinformatics database TCGA was used to analyze the expression level of FRα antigen in liver cancer tissue and normal liver tissue and the association between FRα expression and the survival of liver cancer patients. The mRNA encoding the CAR structure targeting FRα antigen and the small interfering RNA （siRNA） targeting the PD-1 gene were transduced into T cells using an electroporator to prepare FRα-CAR-T and si-PD-1-CAR-T cells. Flow cytometry was used to analyze the expression efficiency of FRα-CAR and the knockdown efficiency of PD-1. Hepatoma cell lines JHH-1 and Hep-G2 were cultured in vitro， and flow cytometry was used to analyze the expression of FRα on the surface of tumor cells. With FRα-CAR-T， si-PD-1 CAR-T， and mock vector-transduced T cells （Mock T） used as effector cells and with JHH-1 and Hep-G2 cells as target cells， CCK-8 assay was used to measure the killing efficiency of effector cells against target cells at different effector-to-target ratios （1∶1， 2.5∶1，5∶1，10∶1，20∶1）. ELISA was used to measure the secretion of interferon gamma （IFN-γ） and interleukin-2 （IL-2） in the supernatants from co-cultures of effector and target cells （10∶1）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while a one-way analysis of variance was used for comparison between multiple groups， and the SNK test was used for further comparison between two groups. The Kaplan-Meier method was used for comparison of survival differences. ResultsThe analysis of the TCGA database showed that there was a significant increase in the expression level of FOLR1 in liver cancer tissue， and liver cancer patients with high expression of FOLR1 had a significantly shorter overall survival than those with low expression （P=0.013）. After transduction of mRNA into T cells， the expression rate of FRα-CAR reached 89.8% in CAR-T and 84.7% in si-PD-1 CAR-T cells， and co-transfection with mRNA and siRNA could downregulate PD-1 in T cells and maintain a low expression state for at least 7 days. The expression rate of FRα antigen was 100% in JHH-1 cells， while it showed negative expression in Hep-G2 cells. CCK-8 assay showed that the killing efficiency of si-PD-1-CAR-T against JHH-1 cells was significantly higher than that against FRα-CAR-T cells （P<0.05）. ELISA showed that compared with Mock T cells， FRα-CAR-T cells co-cultured with JHH-1 cells showed significant increases in the secretion of IL-2 （1 032.50±135.90 pg/mL vs 50.26±7.87 pg/mL，P<0.001） and IFN-γ （1 430.56±184.20 pg/mL vs 89.05±11.26 pg/mL，P<0.001）， and in addition， the release levels of IFN-γ and IL-2 after co-culture of si-PD-1-CAR-T and JHH-1 cells were significantly higher than the release level of FRα-CAR-T （P<0.05）. ConclusionFRα is a potential target for liver cancer treatment， and PD-1 knockdown in T cells can significantly enhance the in vitro killing activity of FRα-CAR-T cells.

Objective: To construct an index system of public health risk assessment for air pollution emergency, so as to provide a tool of evaluating the public health risks of air pollution emergency. Methods: Index system of public health risk assessment for air pollution emergency was established through literature review and group discussions. The index system was determined through two rounds of Delphi expert consultations involving specialists in environmental health, toxicology, epidemiology, health emergency response, and atmospheric monitoring. The effectiveness of the consultation was evaluated by positive coefficient, authority coefficient and coordination coefficient. The weights of index were determined using a combination weighting method of the expert scoring method and the entropy weight method. Results: Fifteen experts participated in the consultation, including 11 males and 4 females. There were 8 experts with a doctor degree, 6 experts with a master degree, 1 experts with a bachelor degree. A total of 11 experts with senior professional titles, and 4 experts with associate senior professional titles. The average work experience was (23.73±10.48) years. The expert positive coefficients for the two rounds of consultations were 83.33% and 100%, respectively. The expert authority coefficients were 0.794 and 0.811, respectively. The coefficients of variation for the importance, feasibility, and sensitivity scores of each index in the two rounds of comsultations were 0.097 to 0.352, 0.078 to 0.478, 0.115 to 0.388, and 0.049 to 0.133, 0.052 to 0.153, 0.049 to 0.178, respectively. The Kendall's coefficients of concordance were 0.237 and 0.440 (both with P<0.05) for the two rounds of consultations. The constructed assessment index system included "likelihood" "hazard" "vulnerability" "controllability" with comprehensive weights of 0.206 7, 0.059 6, 0.378 1, and 0.355 5, respectively. Among the 13 second indicators, "monitoring capability" had the highest comprehensive weight of 0.192 6. Among the 40 tertiary indicators, "real-time monitoring of atmospheric pollutants" "retrospective evaluation of early forecasting results" "types, quantities, and combined effects of atmospheric pollutants" "exposure modes of the population to atmospheric pollutants" had relatively high comprehensive weights of 0.089 5, 0.043 1, 0.041 1 and 0.040 3, respectively. Conclusion The constructed index system of public health risk assessment for air pollution emergency can be applied to the public health risk assessment for air pollution emergencies.

Objective: To explore the effect of different obesity indicators in predicting cardiovascular and cerebrovascular diseases (CVD) risk among patients with type 2 diabetes mellitus (T2DM), so as to provide the evidence for the early identification of CVD risk among T2DM patients. Methods: The patients with T2DM under community management in Qingpu District, Shanghai Municipality were selected as the study subjects in January 2025. Basic information such as gender, age, and blood glucose control status were collected through the Shanghai Chronic Disease Information Management System, while history of CVD were obtained from residents' electronic health records and the Shanghai Disease Control Information Platform. Obesity was assessed using body mass index (BMI), waist circumference (WC), BMI combined with WC, waist-to-height ratio (WHtR), and triglyceride (TG) combined with WC indicators. The association between obesity and CVD was analyzed using multivariable logistic regression models. The predictive effect of each obesity indicators for CVD was evaluated using the area under the receiver operating characteristic curve (AUC). Results: A total of 4 367 patients with T2DM were included, including 2 121 males (48.57%) and 2 246 females (51.43%). The average age was (68.71±8.05) years. The prevalence of CVD was 44.49%. Multivariable logistic regression analysis showed that after adjusting for age, education level, history of hypertension, duration of T2DM, use of glucose-lowering medications, renal function, and blood glucose control status, obese T2DM patients had a 389.4% increased risk of CVD compared to those with normal BMI; centrally obese T2DM patients had a 100.4% increased risk compared to those with normal WC; T2DM patients with isolated general obesity and compound obesity had 161.0% and 241.1% increased risks of CVD, respectively, compared to those with normal BMI and WC; centrally obese T2DM patients had a 100.4% increased risk compared to those with normal WHtR; T2DM patients with normal TG-high WC and high TG-high WC phenotypes had 83.1% and 68.8% increased risks of CVD, respectively, compared to those with normal TG and normal WC (all P<0.05). BMI had the highest AUC, at 0.714, with sensitivity and specificity of 0.675 and 0.642, respectively. This was followed by BMI combined with WC, which had an AUC of 0.707, with sensitivity and specificity of 0.635 and 0.679, respectively. Conclusions Obesity defined by BMI, WC, BMI combined with WC, WHtR, and TG combined with WC increases the risk of CVD among patients with T2DM. BMI and BMI combined with WC have better predictive effect in predicting CVD risk among patients with T2DM, and can be used as the primary obesity indicators for CVD risk screening.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

PURPOSE: Deep vein thrombosis (DVT) of the left and right lower extremities was treated in the same way, but the left and right extremities received different levels of attention. This study aimed to investigate the differences between the right and left lower extremity deep vein thrombosis (LEDVT). METHODS: Clinical characteristics of LEDVT patients from July 2020 to June 2022 were retrospectively analyzed to compare the incidence of LEDVT on different limbs, demographics, predisposing factors, and anatomical characteristics. The exclusion criteria were bilateral LEDVT and recurrent thrombosis. Measured data was analyzed using independent samples t-test or Mann-Whitney test. Count data were analyzed by Chi-square test. A p < 0.05 was considered a statistically significant difference. RESULTS: There were 478 patients included in this study and the ratio of left to right LEDVT on the left and right limbs was 3.16:1 (363:115). Left LEDVT predominantly affected female, with the major aged > 50 years (50 - 60 years: 16.80%; > 60 years: 57.30%). The primary predisposing factor was iliac vein compression syndrome, with iliofemoral thrombosis being the main type. Male patients with LEDVT on the right limb were predominant and the age of onset was usually ≤ 60 years (52.17%). The main predisposing factor was recent surgery or trauma (< 30 days) and femoropopliteal thrombosis was the main type. In more detail, the left iliac vein was compressed mainly in the proximal segment, and the right iliac vein was compressed mainly in the intermediate and distal segments. Recent surgery or trauma to the locomotor system and genitourinary system often induced LEDVT. CONCLUSION The incidence of LEDVT on the left is significantly higher than that on the right. LEDVT on different sides has different characteristics, which is crucial for prevention and diagnosis in the relevant population so there are also differences in treatment of the affected limbs.
Humans ; Venous Thrombosis/etiology* ; Male ; Female ; Middle Aged ; Lower Extremity/blood supply* ; Retrospective Studies ; Adult ; Aged ; Age Factors ; Sex Factors ; Risk Factors ; Acute Disease ; Incidence ; Aged, 80 and over ; Young Adult ; Adolescent

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.