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 investigate the association between lifestyle and risk of heart disease and diabetes in the elderly population in Xi&#39;an City. Methods From January 2021 to January 2024, a staged cluster sampling method was used to investigate the lifestyle and the occurrence of heart disease and diabetes in elderly population aged 60 years and above in the communities of Xi&#39;an. Multivariate logistic regression was used to analyze the relationship between lifestyle and the risk of heart disease and diabetes. Results A total of 413 elderly people were investigated, of which 31.96% had heart disease, 27.12% had diabetes, and 10.90% had diabetes with heart disease. Multivariate logistic regression analysis revealed that age, BMI, family history, sweet food preference, smoking, and sitting and lying for a long time were risk factors for diabetes in the elderly population (P<0.05). Age, BMI, family history, history of diabetes, preference for salted products, smoking, drinking, and sitting and lying for a long time were risk factors for heart disease in the elderly population (P<0.05). Conclusion The incidence rates of heart disease and diabetes are high in the elderly population in Xi&#39;an City. The risk of diabetes is related to unhealthy lifestyles such as sweet food preference, smoking, and sitting and lying for a long time, while heart disease is related to unhealthy lifestyles such as preference for salted products, smoking, drinking, and sitting and lying for a long time.

Objective To analyze the trend of heart disease death and the life expectancy without cause of death in Qidong City, Jiangsu Province from 1990 to 2019, and to provide reference for the prevention and control of heart disease. Methods Data on heart disease deaths among residents in Qidong City from 1990 to 2019 were collected through the Qidong City Death Registration and Monitoring System. The crude mortality rate (CR) and Chinese age-standardized mortality rate (CASR), potential years of life loss (PYLL), average years of life loss (AYLL), potential life loss years rate (PYLLR), life expectancy, and life expectancy without cause of death were calculated, and the annual percentage change (APC) was used to analyze the trend of heart disease death. Using SAS9.2 software, the death trend prediction was conducted by the ARIMA model in time series analysis. Results From 1990 to 2019, 27,762 residents died of heart disease in Qidong City, with a CR of 81.20/100 000 and an APC of 3.734%. There were 12 358 deaths of heart disease in men, with a CR of 73.24/100 000 and an APC of 3.86%, while there were 15 404 deaths of heart disease in women, with a CR of 88.95/100 000 and an APC of 3.63%. CR showed an upward trend (all P < 0.001). The PYLL for heart disease was 66 192.00 person-years, the AYLL was 13.23 person-years, and the PYLLR was 2.16‰. The life expectancy loss from heart disease was gradually increasing: 0.89 years in 1990 to 1.85 years in 2019, with an APC of 0.405% (P<0.001, a statistically significant trend). The prediction results showed that in 2029, the life expectancy after heart disease would reach 88.17 years. Conclusion From 1990 to 2019, the crude mortality rate of heart disease in Qidong City has showed an increasing trend, leading to an increasing loss of life due to heart disease year by year. The mortality rate and life loss of heart disease in women are higher than those in men. Targeted intervention measures should be further adopted to reduce the mortality rate of heart disease among residents in Qidong.

Objective     To investigate the accuracy of 18F-FDG positron emission tomography/computed tomography (PET/CT) combined with CT three-dimensional reconstruction (CT-3D) in the differential diagnosis of benign and malignant pulmonary nodules. Methods     The clinical data of patients who underwent pulmonary nodule surgery in the Department of Thoracic Surgery, Northern Jiangsu People&#39;s Hospital from July 2020 to August 2021 were retrospectively analyzed. The preoperative 18F-FDG PET/CT and chest enhanced CT-3D and other imaging data were extracted. The parameters with diagnostic significance were screened by the area under the receiver operating characteristic (ROC) curve (AUC). Three prediction models, including PET/CT prediction model (MOD PET), CT-3D prediction model (MOD CT-3D), and PET/CT combined CT-3D prediction model (MOD combination), were established through binary logistic regression, and the diagnostic performance of the models were validated by ROC curve. Results     A total of 125 patients were enrolled, including 57 males and 68 females, with an average age of 61.16±8.57 years. There were 46 patients with benign nodules, and 79 patients with malignant nodules. A total of 2 PET/CT parameters and 5 CT-3D parameters were extracted. Two PET/CT parameters, SUVmax≥1.5 (AUC=0.688) and abnormal uptake of hilar/mediastinal lymph node metabolism (AUC=0.671), were included in the regression model. Among the CT-3D parameters, CT value histogram peaks (AUC=0.694) and CT-3D morphology (AUC=0.652) were included in the regression model. Finally, the AUC of the MOD PET was verified to be 0.738 [95%CI (0.651, 0.824)], the sensitivity was 74.7%, and the specificity was 60.9%; the AUC of the MOD CT-3D was 0.762 [95%CI (0.677, 0.848)], the sensitivity was 51.9%, and the specificity was 87.0%; the AUC of the MOD combination was 0.857 [95%CI (0.789, 0.925)], the sensitivity was 77.2%, the specificity was 82.6%, and the differences were statistically significant (P<0.001). Conclusion     18F-FDG PET/CT combined with CT-3D can improve the diagnostic performance of pulmonary nodules, and its specificity and sensitivity are better than those of single imaging diagnosis method. The combined prediction model is of great significance for the selection of surgical timing and surgical methods for pulmonary nodules, and provides a theoretical basis for the application of artificial intelligence in the pulmonary nodule diagnosis.

OBJECTIVE To explore the effect of single dose and multiple doses of silibinin on the in vivo pharmacokinetics of nevirapine in rats. METHODS Thirty male SD rats were randomly divided into blank control group, multiple administration of low-dose group(30 mg·kg−1) , multiple administration of high-dose group(100 mg·kg−1), single administration low-dose group(30 mg·kg−1) , and single administration high-dose group(100 mg·kg−1). Blood samples were collected to determine the concentration of nevirapine and its metabolites in rat plasma after an oral administration of 10 mg·kg−1 nevirapine. The kinetic parameters of nevirapine and its metabolites in each group were calculated by DAS and analyzed statistically. RESULTS Compared with the blank control group, multiple doses of 100 mg·kg−1·d−1 silibinin significantly increased the AUC of nevirapine by 61.78%, Cmax by 124.62% and decreased the clearance rate to 64.11%; multiple doses of 30 mg·kg−1·d−1 silibinin significantly increased the Cmax of nevirapine by 84.85%; a single dose of 100 mg·kg−1 or 30 mg·kg−1 silibinin significantly increased the Cmax of nevirapine by 65.19% and 32.12%, respectively. The metabolic ratio of 12-hydroxy-nervirapine was decreased by 31.5% by multiple doses of 100 mg·kg−1·d−1 silibinin where the pharmacokinetic parameters of 4-carboxyl-nervirapine remained unchanged. CONCLUSION Silibinin significantly affects the pharmacokinetics of nevirapine in rats. The drug-drug interaction should be considered when nevirapine and silibinin are concomitant.

Objective To understand the death status, mortality trend, cause of death and life loss of injury and poisoning among residents in Qidong City, Jiangsu Province from 1990 to 2019, and to provide a reference for formulating public health policies. Methods Data on injury and poisoning death of residents in Qidong City from 1990 to 2019 were collected through the death cause registration and monitoring system of Qidong City, Jiangsu Province. Indicators such as crude death rate (CR) and standardized death rate (CASR), average years of lost life (AYLL), and potential years of life lost rate (PYLLR) were calculated. Annual percentage change (APC) was used to analyze the trend of death from injury and poisoning. Results From 1990 to 2019, 18 163 residents in Qidong City, Jiangsu Province died of injuries and poisoning. The CR was 53.12/100 000 (APC=0.74%), and the CASR was 39.43/100 000 (APC=-1.86%). The male CR was 66.90 100 000 (APC=0.75%), and the male CASR was 52.42/100 000 (APC=-1.75%), while the female CR was 39.69/100 000 (APC=0.73%), and the female CASR was 26.63/100 000 (APC=-2.14%). Analysis of the standardized mortality rate showed a downward trend year by year (P<0.001). PYLL caused by injury and poisoning was 318 502.50 person-years (APC=-4.00%), AYLL was 26.02 years/person (APC=-3.26%) and the PYLLR was 10.39‰ (APC=-3.54%). The top five death causes of injury and poisoning are motor vehicle accidents, suicide, drowning, accidental falls and accidental poisoning, accounting for 87.17% of the total deaths from injuries and poisoning. Drowning was the leading cause of death for children aged from 0 to 14. Motor vehicle accidents were the leading cause of death for residents aged from 15 to 64, and accidental falls were the leading cause of death for residents over 65. Conclusion Injury and poisoning are one of the main causes of death among residents in Qidong City, Jiangsu Province. The distribution characteristics of injurie and poisoning deaths of different genders and ages are different. According to their distribution characteristics, targeted and specific measures should be taken to reduce mortality.

Objective To study and analyze the trend of diabetes death and the impact of life expectancy in Qidong City, Jiangsu Province from 1990 to 2019, and to provide a basis for formulating health policies. Methods Based on the surveillance data of deaths from all causes in Qidong City and the population data over the years from 1990 to 2019, the residents' diabetes mortality and temporal trends were analyzed. Joinpoint4.7.0.0 software was used to calculate relevant indicators including crude mortality (CR), age-standardized rates by China population (CASR), annual percentage change (APC), potential years of life lost (PYLL), and potential years of life lost rate (PYLLR). Results The CR of diabetes in Qidong City from 1990 to 2019 was 15.12/100 000, with a rate of 12.72/100 000 in males and a rate of 17.45/100 000 in females. The total CASR was 7.58/100 000, including 6.47/100 000 for males and 8.59/100 000 for females. Trend analysis showed that the APC of CR and CASR was 9.31% and 5.26% in males, and 8.12% and 4.40% in females, respectively. The APC of CR and CASR in the 45-64 years old group was 2.59% and 4.85%, respectively. The APC of CR and CASR in the 65 years old and above group was 7.20% and 9.79%, respectively. There were statistically significant differences except for the 15-44 years old group. The life expectancy of residents in Qidong City rose from 73.95 years in 1990 to 82.91 years in 2019 (APC=0.38, P<0.001), and life expectancy without diabetes rose from 74.01 years in 1990 to 83.39 years in 2019 (APC=0.39, P<0.001). Conclusion In the past 30 years, the diabetes mortality and life loss of residents in Qidong City have been increasing year by year and the trend is obvious. Women's diabetes mortality and life loss are higher than those in men. The level and increase rate of diabetes mortality in the high age group are higher than those in the low age group. It is necessary to carry out key intervention for the corresponding population.

Objective To analyze the epidemiological characteristics of hepatitis E virus, and to provide scientific reference for the development of prevention and control strategies for hepatitis E. Methods Descriptive analysis and clustering analysis were used for data analysis. Results From 2004 to 2019, 32,224 cases of hepatitis E were reported in Hubei Province, with an average annual incidence rate of 3.47/100,000, showing an overall upward trend. The incidence of hepatitis E was higher in winter and spring, with a peak occurring during January to May. The incidence of the male to female ratio was 2.5:1. The number of reported cases between 40-69 years old accounted for 68.25% of the total cases. Farmers, household chores, unemployed and retired personnel accounted for 72.68% of the total cases. Wuhan, Xiaogan, Jingmen, Yichang and Enshi were the top five cities for average annual incidence. Conclusion The incidence of hepatitis E in Hubei Province is generally on the rise, with obvious characteristics of time, population, and space distribution. It is necessary to strengthen education and monitoring of susceptible population to reduce the harm of hepatitis E to the health of the population.

[Abstract] Objective: To investigate the effect and mechanism of miR-449b-5p on the proliferation of ovarian cancer cells. Methods: Cancer tissue and corresponding para-cancerous tissue specimens from 20 patients who underwent surgery in the Department of Obstetrics and Gynecology of Sichuan Provincial People&#39;s Hospital from June 2018 to June 2020 were collected for this study; in addition, normal ovarian epithelial cell line (HOSEpiC) and six human cervical cancer cell lines (SKOV3, ES-2, OVCAR-3, HO8910, CaOV-3 and A2780) were also selected. mRNA expressions of miR-449b-5p and CCNE2 in ovarian cancer tissues and cells were detected by qPCR. The plasmids miR-NC, miR-499b-5p mimic, miR-499b-5p inhibitor and pc-CCNE2 were transfected into SKOV3 cells separately or in combination. Cell growth and cell cycle were measured by the CCK-8 method and Flow cytometry, the expression of CCNE2 protein was detected by WB assay, respectively. The targeting relationship between miR-449b-5p and CCNE2 was verified by Dual luciferase reporter assay. miR-499b-5p transfected SKOV3 cells were injected subcutaneously in nude mice to construct xenograft model, and the tumor volume was measured weekly. Nude mice were sacrificed at day 42. The weight of the subcutaneous tumors was weighed by an electronic balance, and the expressions of CCNE2 and Ki67 were detected by immunohistochemistry. Results: Compared with normal ovarian tissues and epithelial cell line HOSEpiC, miR-499b expression was significantly downregulated in human cervical cancer tissues and cell lines SKOV3, ES-2, OVCAR-3, HO8910, CaOV-3 and A2780 (P<0.01). Compared with the Control group, the proliferation of SKOV3 cells in the miR-499b mimic group was significantly reduced (P<0.01) and the cell proportion in G0/G1 phase was significantly increased ( P<0.01); while the proliferation of SKOV3 cells in the miR-499b inhibitor group was significantly increased (P<0.01) and the cell proportion in G0/G1 phase was significantly reduced (P<0.01). Over-expression of miR-499b-5p significantly inhibited the luciferase activity of wild type CCNE2 plasmid (P<0.01) but had no effect on the luciferase activity of the mutant CCNE2 plasmid. Compared with the miR-499b mimic group, the growth of SKOV3 cells in the miR-499b mimic+pc-CCNE2 group was significantly increased (P<0.01) and the cell proportion in G0/G1 phase was significantly reduced (P<0.01). Compared with the miR-NC group, the tumor volume and weight of nude mice in the miR-499b mimic group were significantly reduced (all P<0.01), and the proportion of CCNE2 and Ki67 positive cells was significantly decreased (P<0.01). Conclusion: miR-449b-5p inhibits the growth and cell cycle progression of ovarian cancer cells by targeting Cyclin E2.

Given the opposing effects of Akt and AMP-activated protein kinase (AMPK) on metabolic homeostasis, this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic steatosis. Akt2–Ampkα2 double knockout (DKO) mice were placed on high fat diet for 5 months. Glucose metabolism, energy homeostasis, cardiac function, lipid accumulation, and hepatic steatosis were examined. DKO mice were lean without anthropometric defects. High fat intake led to adiposity and decreased respiratory exchange ratio (RER) in wild-type (WT) mice, which were ablated in DKO but not Akt2−/− and Ampkα2−/− mice. High fat intake increased blood and hepatic triglycerides and cholesterol, promoted hepatic steatosis and injury in WT mice. These effects were eliminated in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet promoted fat accumulation, and enlarged adipocyte size, the effect was negated in DKO mice. Fat intake elevated fatty acid synthase (FAS), carbohydrate-responsive element-binding protein (CHREBP), sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor-α (PPARα), PPARγ, stearoyl-CoA desaturase 1 (SCD-1), phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase), and diglyceride O-acyltransferase 1 (DGAT1), the effect was absent in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet dampened mitophagy, promoted inflammation and phosphorylation of forkhead box protein O1 (FoxO1) and AMPKα1 (Ser485), the effects were eradicated by DKO. Deletion of Parkin effectively nullified DKO-induced metabolic benefits against high fat intake. Liver samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B (LC3B), Pink1, Parkin, as well as enhanced phosphorylation of Akt, AMPK (Ser485), and FoxO1, which were consolidated by RNA sequencing (RNAseq) and mass spectrometry analyses from rodent and human livers. These data suggest that concurrent deletion of Akt2 and AMPKα2 offers resilience to fat diet-induced obesity and hepatic steatosis, possibly through preservation of Parkin-mediated mitophagy and lipid metabolism.