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 examine the mechanistic of organochlorine-associated changes in lung function. METHODS: This study investigated 76 healthy older adults in Jinan, Shandong Province, over a five-month period. Personal exposure to organochlorines was quantified using wearable passive samplers, while inflammatory factors and thyroid hormones were analyzed from blood samples. Participants' lung function was evaluated. After stratifying participants according to their thyroid hormone levels, we analyzed the differential effects of organochlorine exposure on lung function and inflammatory factors across the low and high thyroid hormone groups. Mediation analysis was further conducted to elucidate the relationships among organochlorine exposures, inflammatory factors, and lung function. RESULTS: Bis (2-chloro-1-methylethyl) ether (BCIE), was negatively associated with forced vital capacity (FVC, -2.05%, 95% CI: -3.11% to -0.97%), and associated with changes in inflammatory factors such as interleukin (IL)-2, IL-7, IL-8, and IL-13 in the low thyroid hormone group. The mediation analysis indicated a mediating effect of IL-2 (15.63%, 95% CI: 0.91% to 44.64%) and IL-13 (13.94%, 95% CI: 0.52% to 41.07%) in the association between BCIE exposure and FVC. CONCLUSION Lung function and inflammatory factors exhibited an increased sensitivity to organochlorine exposure at lower thyroid hormone levels, with inflammatory factors potentially mediating the adverse effects of organochlorines on lung function.
Environmental Exposure ; Hydrocarbons, Chlorinated/metabolism* ; China ; Ethyl Ethers/metabolism* ; Environmental Monitoring ; Thyroid Hormones/blood* ; Lung/physiology* ; Inhalation Exposure/statistics & numerical data* ; Air Pollution/statistics & numerical data* ; Air Pollutants/metabolism* ; Humans ; Male ; Female ; Middle Aged ; Aged

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Objective:In accordance with the urban spatial structure and functional positioning outlined in the General Plan for the Overall Urban Development of Beijing(2016-2035),this study analyzed the allocation and equity of human resources in the Beijing Center for Disease Control and Prevention(CDC)system from 2019 to 2023,aiming to provide a reference for future planning.Methods:Based on the Plan,Beijing was divided into five structural regions.Descriptive statistical analysis,the Gini coefficient,and the Theil index were used to comprehensively evaluate the allocation and equity of regional human resources.Results:From 2019 to 2023,the total number of human resources in the Beijing CDC system showed a slow growth trend,with an overall shortage in staffing;however,the quality structure of personnel was relatively good.Equity among the structural regions gradually improved,as indicated by the annual decrease in both the Gini coefficient and the total Theil index.The contribution of inter-group differences to the total Theil index was greater than that of intra-group differences.Conclusions:There is a certain gap between the current human resource allocation in the Beijing CDC system and the requirements of non-capital function relocation and functional positioning of each structural region.It is recommended to align with urban planning,increase the number of personnel performing public health functions,and establish human resource allocation standards,plans,and working mechanisms that meet the development needs of each structural region,thereby better serving the functional positioning of the capital city and the health of its residents.

Objective To explore the correlation between chronic diseases and the risk of benign prostatic hyperplasia(BPH)in middle-aged and older Chinese man.Methods Data from the 2013 China Health and Retirement Longitudinal Study(CHARLS)were used,including 4 509 male participants aged 45 years and older.Chronic diseases and BPH diagnoses were obtained through a questionnaire survey.Logistic regression analysis was performed to identify independent risk factors for BPH.Restricted cubic splines(RCS)were used to explore the nonlinear relationship between variables and BPH prevalence,while stratified analyses were conducted to assess the differential impact of chronic diseases on BPH prevalence in different subgroups.Results Compared to patients without BPH,those with BPH had a significantly higher prevalence of comorbid chronic diseases,including hypertension,diabetes,chronic respiratory diseases,chronic heart disease,stroke,chronic kidney disease,chronic digestive diseases,arthritis or rheumatism,depression,and memory-related disorders.Multivariable Logistic regression analysis indicated that factors such as the 10-item Center for Epidemiological Studies Depression Scale(CESD-10)scores(OR=1.043,95% CI:1.022-1.063,P<0.001),chronic respiratory disease(OR=1.518,95% CI:1.143-1.998,P=0.003),chronic heart disease(OR=1.515,95% CI:1.143-1.998,P=0.003),chronic kidney disease(OR=2.384,95% CI:1.799-3.137,P<0.001),and chronic digestive disease(OR=1.427,95% CI:1.129-1.796,P=0.003)were independently associated with the occurrence of BPH.RCS analysis demonstrated no non-linear association between age,BMI,and CESD-10 scores and BPH.Stratified analysis revealed that the influence of these chronic conditions on BPH remained constantly stable across different subgroups.Conclusion BPH is commonly comorbid with various chronic diseases.Future treatment strategies for BPH should consider the shared pathological mechanisms between BPH and these chronic conditions,with a focus on integrated interventions targeting common pathways.

Objective To investigate the peripheral blood cytokine levels in patients with acute myocardial infarction(AMI),and to analyze its correlation with Killip classification,N-terminal brain natriuretic peptide precursor(NT-proBNP),cardiac troponin I(cTnI),creatine kinase isoenzymes(CK-MB),and to provide a theoretical basis for assessing the severity and prognosis of the disease.Methods A total of 312 patients with AMI admitted to Minhang Hospital,Fudan University from Jul 2021 to Oct 2023 were enrolled as the case group,and 201 patients with unstable angina pectoris were selected as the control group.General clinical data of the subjects were collected,and the concentrations of cytokines(IL-5,IFN-α,IFN-γ,IL-10,IL-12p70,IL-17,IL-1β,IL-2,IL-4,IL-6,IL-8,and TNF-α)in peripheral blood were detected by multiplex bead-based flow cytometry.NT-proBNP,cTnI and CK-MB were measured by chemiluminescence methods.The levels of cytokines between the two groups were compared,and their correlations with Killip classification,NT-proBNP,cTnI and CK-MB were analyzed.The predictive efficacy of cytokines for AMI was evaluated by receiver operating characteristic(ROC)curves.Results There were no significant differences in baseline data between the AMI group and the control group(P>0.05),with the exception of age.The levels of IL-6,IL-8 and TNF-α in the AMI group were higher than those in the control group(all P<0.01).The correlation analyses showed that IL-6 was positively correlated with Killip classification,NT-proBNP,cTnI and CK-MB(all P<0.01).ROC analyses showed that IL-6 levels had good predictive efficacy for AMI(AUC=0.882 9,P<0.01).Conclusion The expression of IL-6 was significantly increased in patients with AMI,and it was positively correlated with Killip classification,NT-proBNP,cTnI and CK-MB,suggesting that IL-6 may serve as a potential biomarker for assessing the severity of AMI.

Objective:In accordance with the urban spatial structure and functional positioning outlined in the General Plan for the Overall Urban Development of Beijing(2016-2035),this study analyzed the allocation and equity of human resources in the Beijing Center for Disease Control and Prevention(CDC)system from 2019 to 2023,aiming to provide a reference for future planning.Methods:Based on the Plan,Beijing was divided into five structural regions.Descriptive statistical analysis,the Gini coefficient,and the Theil index were used to comprehensively evaluate the allocation and equity of regional human resources.Results:From 2019 to 2023,the total number of human resources in the Beijing CDC system showed a slow growth trend,with an overall shortage in staffing;however,the quality structure of personnel was relatively good.Equity among the structural regions gradually improved,as indicated by the annual decrease in both the Gini coefficient and the total Theil index.The contribution of inter-group differences to the total Theil index was greater than that of intra-group differences.Conclusions:There is a certain gap between the current human resource allocation in the Beijing CDC system and the requirements of non-capital function relocation and functional positioning of each structural region.It is recommended to align with urban planning,increase the number of personnel performing public health functions,and establish human resource allocation standards,plans,and working mechanisms that meet the development needs of each structural region,thereby better serving the functional positioning of the capital city and the health of its residents.

Objective To explore the correlation between chronic diseases and the risk of benign prostatic hyperplasia(BPH)in middle-aged and older Chinese man.Methods Data from the 2013 China Health and Retirement Longitudinal Study(CHARLS)were used,including 4 509 male participants aged 45 years and older.Chronic diseases and BPH diagnoses were obtained through a questionnaire survey.Logistic regression analysis was performed to identify independent risk factors for BPH.Restricted cubic splines(RCS)were used to explore the nonlinear relationship between variables and BPH prevalence,while stratified analyses were conducted to assess the differential impact of chronic diseases on BPH prevalence in different subgroups.Results Compared to patients without BPH,those with BPH had a significantly higher prevalence of comorbid chronic diseases,including hypertension,diabetes,chronic respiratory diseases,chronic heart disease,stroke,chronic kidney disease,chronic digestive diseases,arthritis or rheumatism,depression,and memory-related disorders.Multivariable Logistic regression analysis indicated that factors such as the 10-item Center for Epidemiological Studies Depression Scale(CESD-10)scores(OR=1.043,95% CI:1.022-1.063,P<0.001),chronic respiratory disease(OR=1.518,95% CI:1.143-1.998,P=0.003),chronic heart disease(OR=1.515,95% CI:1.143-1.998,P=0.003),chronic kidney disease(OR=2.384,95% CI:1.799-3.137,P<0.001),and chronic digestive disease(OR=1.427,95% CI:1.129-1.796,P=0.003)were independently associated with the occurrence of BPH.RCS analysis demonstrated no non-linear association between age,BMI,and CESD-10 scores and BPH.Stratified analysis revealed that the influence of these chronic conditions on BPH remained constantly stable across different subgroups.Conclusion BPH is commonly comorbid with various chronic diseases.Future treatment strategies for BPH should consider the shared pathological mechanisms between BPH and these chronic conditions,with a focus on integrated interventions targeting common pathways.

Objective To investigate the peripheral blood cytokine levels in patients with acute myocardial infarction(AMI),and to analyze its correlation with Killip classification,N-terminal brain natriuretic peptide precursor(NT-proBNP),cardiac troponin I(cTnI),creatine kinase isoenzymes(CK-MB),and to provide a theoretical basis for assessing the severity and prognosis of the disease.Methods A total of 312 patients with AMI admitted to Minhang Hospital,Fudan University from Jul 2021 to Oct 2023 were enrolled as the case group,and 201 patients with unstable angina pectoris were selected as the control group.General clinical data of the subjects were collected,and the concentrations of cytokines(IL-5,IFN-α,IFN-γ,IL-10,IL-12p70,IL-17,IL-1β,IL-2,IL-4,IL-6,IL-8,and TNF-α)in peripheral blood were detected by multiplex bead-based flow cytometry.NT-proBNP,cTnI and CK-MB were measured by chemiluminescence methods.The levels of cytokines between the two groups were compared,and their correlations with Killip classification,NT-proBNP,cTnI and CK-MB were analyzed.The predictive efficacy of cytokines for AMI was evaluated by receiver operating characteristic(ROC)curves.Results There were no significant differences in baseline data between the AMI group and the control group(P>0.05),with the exception of age.The levels of IL-6,IL-8 and TNF-α in the AMI group were higher than those in the control group(all P<0.01).The correlation analyses showed that IL-6 was positively correlated with Killip classification,NT-proBNP,cTnI and CK-MB(all P<0.01).ROC analyses showed that IL-6 levels had good predictive efficacy for AMI(AUC=0.882 9,P<0.01).Conclusion The expression of IL-6 was significantly increased in patients with AMI,and it was positively correlated with Killip classification,NT-proBNP,cTnI and CK-MB,suggesting that IL-6 may serve as a potential biomarker for assessing the severity of AMI.