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: Type 2 diabetes mellitus (T2DM) is a complex, multifactorial disease with a significant global burden. Although genome-wide association studies (GWAS) have identified many T2DM-associated variants, most lie in non-coding regions, making it difficult to interpret their functional roles. Methods: We aimed to identify genetically regulated Cytosine–phosphate–Guanine (CpG) sites associated with T2DM by conducting a methylome-wide association study (MWAS), followed by Mendelian randomization (MR) and functional validation using human pancreatic cells and mouse models. MWAS was performed using summary statistics from large-scale GWAS and a DNA methylation (DNAm) prediction model to test associations between genetically predicted DNAm and T2DM. Results: We identified 111 CpG sites significantly associated with T2DM in Europeans, including 8 novel sites near genes not previously linked to T2DM. These findings were replicated in independent datasets. Many CpGs also showed associations with cardiometabolic traits, highlighting shared epigenetic mechanisms. Trans-ethnic MR analysis confirmed consistent effects for six CpGs in East Asians. Functional analysis revealed that several CpGs regulate gene expression in human pancreatic α- and β-cells. Among them, 2´-5´-oligoadenylate synthetase like (OASL) expression, regulated by a significant CpG, was differentially expressed in α-cells of T2DM cases compared to controls. Supporting evidence from mouse models suggests a role for OASL in glucose regulation. Conclusion Our study identifies novel genetically regulated CpG sites associated with T2DM risk and highlights OASL as a potential epigenetic regulator of glucose metabolism in α-cells. These findings provide mechanistic insights into the epigenetic architecture of T2DM and suggest potential targets for cross-ethnic biomarker development and therapeutic intervention.

Objective To analyze the influencing factors for postoperative anastomotic leak (AL) in carcinoma of the esophagus and gastroesophageal junction and construct a nomogram predictive model. Methods The patients who underwent radical esophagectomy at Jinling Hospital Affiliated to Nanjing University School of Medicine from January 2018 to June 2020 were included in this study. Relevant variables were screened using univariate and multivariate logistic regression analyses. A nomogram was then developed to predict the risk factors associated with postoperative AL. The predictive performance of the nomogram was validated using the receiver operating characteristic (ROC) curve. Results A total of 468 patients with carcinoma of the esophagus and gastroesophageal junction were included in the study, comprising 354 males and 114 females, with a mean age of (62.8±7.2) years. The tumors were predominantly located in the middle or lower esophagus, and 51 (10.90%) patients experienced postoperative AL. Univariate logistic regression analysis indicated that age, body mass index (BMI), tumor location, preoperative albumin levels, diabetes mellitus, anastomosis technique, anastomosis site, and C-reactive protein (CRP) levels were potentially associated with AL (P<0.05). Multivariate logistic regression analysis identified age, BMI, tumor location, diabetes mellitus, anastomosis technique, and CRP levels as independent risk factors for AL (P<0.05). A nomogram was developed based on the findings from the multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was 0.803, indicating a strong concordance between the actual observations and the predicted outcomes. Furthermore, decision curve analysis demonstrated that the newly established nomogram holds significant value for clinical decision-making. Conclusion The predictive model for postoperative AL in patients with carcinoma of the esophagus and gastroesophageal junction demonstrates strong predictive validity and is essential for guiding clinical monitoring, early detection, and preventive strategies.

Objective To investigate the prevalence of food intolerance among children in Zhuzhou area and its relationship with age,gender,systemic diseases,and food allergies,so as to provide a basis for the scientific adjustment of children's dietary structure.Methods A retrospective analysis was conducted on totally 1 592 children who underwent food intolerance and food allergen testing in the hospital,the positive rate and distri-bution of 14 kinds of food intolerance were assessed,and their correlation with various factors was analyzed.Results Among 14 kinds of food tested,milk and eggs had the highest positive rates of intolerance,at 82.22％and 55.78％,respectively.The majority of children were intolerant to 1 to 2 kinds of food,with a de-creasing trend in the number of children intolerant to multiple kinds of food.Among the 14 types of food,ex-cept for mushrooms and pork,there were statistically significant differences in the distribution of negative,mild,moderate,and severe intolerance in other foods(P＜0.05).Children tended to have moderate or even se-vere intolerance to milk and eggs,while they tended to have mild intolerance to other foods.There was no sta-tistically significant difference in the overall food intolerance rate between boys and girls(P=0.654),but the positive rate of tomato intolerance in girls was slightly higher than that in boys(P=0.043).Except for pork,there were statistically significant differences in the positive rates of intolerance to 14 different foods among different age groups(P＜0.05).The positive rates of intolerance to cod,mushrooms,and crabs increased with age,while the positive rates of intolerance to beef decreased with age.There was a statistically significant difference in the positive rate of milk intolerance between healthy children and children with skin allergies(P＜0.05).There was a statistically significant difference in the proportion of individuals who were tolerant and not allergic to milk compared to hose who were intolerant and allergic to milk(P＜0.05).There was a statistically significant difference in the proportion of individuals who were tolerant and not allergic to eggs compared to those who were intolerant and allergic to eggs(P＜0.05).Conclusion The positive rate of food intolerance among children in Zhuzhou area is relatively high,with milk and eggs being the main intolerant foods.There are differences in the positive rate of intolerance among different gender and age groups,and in-tolerance to milk and eggs is associated with food allergies to some extent.

Objective:To investigate the effect of blood lipids and statins use on the outcome of acute ischemic stroke (AIS) patients with cerebral microbleeds (CMBs).Methods:Consecutive AIS patients with CMBs hospitalized at the First People's Hospital of Taicang, Jiangsu Province from July 2023 to June 2024 were included retrospectively. At 3 months after onset, the modified Rankin Scale was used for outcome assessment. 0-2 was defined as good outcome and >2 was defined as poor outcome. Multivariate logistic regression analysis was used to identify independent influencing factors for poor outcome. Results:A total of 110 AIS patients with CMBs were enrolled, including 72 males (65.5%), aged 68.04±3.12 years. Thirty patients (27.3%) had poor outcome. Univariate analysis showed that age, baseline National Institutes of Health Stroke Scale (NIHSS) score, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and the proportion of patients with hypertension and diabetes in poor outcome group were significantly higher than those in good outcome group, while baseline high-density lipoprotein cholesterol and the proportion of patients using statins before onset were significantly lower than those in good outcome group ( P<0.05). Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.309, 95% confidence interval [ CI] 1.007-1.702; P=0.044), the baseline NIHSS score ( OR 1.541, 95% CI 1.143-2.078; P=0.005) and high triglycerides ( OR 5.150, 95% CI 2.150-8.717; P=0.023) were the independent risk factors for poor outcome, while high high-density lipoprotein cholesterol ( OR 0.001, 95% CI 0.001-0.034; P<0.001) and statins use ( OR 0.231, 95% CI 0.046-0.558; P=0.019) were the independent protective factors for good outcome. Conclusions:Blood lipid and statins use are independent influencing factors for the outcome of AIS patients with CMBs. The use of statins before onset is associated with a lower risk of poor outcome in AIS patients with CMBs.

Objective:To explore the relationship between the expression levels of succinate receptor 1 (SUCNR1) and Y-box binding protein 1 (YBX1) in colorectal cancer tissues of patients with colorectal cancer liver metastases (CRLM) and their clinicopathological characteristics and prognosis.Methods:One hundred and five CRLM patients who underwent surgical treatment in Suzhou Kowloon Hospital of Shanghai Jiao Tong University School of Medicine from January 2016 to May 2020 were taken as the study subjects. The high expression rates of SUCNR1 and YBX1 in cancer tissues and adjacent tissues were compared. Clinicopathological characteristics and prognosis of patients with high and low SUCNR1 and YBX1 expression were compared. Univariate and multivariate Cox proportional risk regression models were applied to analyze prognostic influencing factors.Results:SUCNR1 staining was mainly located on the cell membrane in colorectal cancer tissues, and positive staining showed yellow or brownish yellow; YBX1 was mainly located in the cytoplasm of colorectal cancer tissues, and positive staining showed yellow or brownish yellow. The high expression rate of SUCNR1 in cancer tissues (74.29%, 78/105) of CRLM patients was obviously higher than that in adjacent tissues (27.62%, 29/105), and the high expression rate of YBX1 in cancer tissues (84.76%, 89/105) was obviously higher than that in adjacent tissues (32.38%, 34/105), with statistically significant differences ( χ2=45.75, P<0.001; χ2=59.36, P<0.001). There were statistically significant differences in histological grade ( χ2=7.43, P=0.006) and the time from colorectal cancer diagnosis to liver metastasis ( χ2=9.19, P=0.002) between patients with high and low expression of SUCNR1; there was a statistically significant difference in time from colorectal cancer diagnosis to liver metastasis ( χ2=13.08, P<0.001) between patients with high and low expression of YBX1. The 3-year overall survival (OS) rates of patients with high and low expression of SUCNR1 were 52.56% and 77.78%, respectively, with a statistically significant difference ( χ2=6.10, P=0.014) ; the 3-year OS rates of patients with high and low expression of YBX1 were 53.93% and 87.50%, respectively, with a statistically significant difference ( χ2=6.02, P=0.014). Univariate analysis showed that, histological grade ( HR=4.69, 95% CI: 1.14-19.36, P=0.033), time from colorectal cancer diagnosis to liver metastasis ( HR=4.05, 95% CI: 1.02-16.62, P=0.048), cancer tissues SUCNR1 ( HR=5.12, 95% CI: 1.17-22.34, P=0.030), and YBX1 expression ( HR=6.29, 95% CI: 1.55-25.47, P=0.010) were all influencing factors for OS in CRLM patients. Multivariate analysis showed that, histological grade ( HR=4.16, 95% CI: 1.12-15.54, P=0.034), time from colorectal cancer diagnosis to liver metastasis ( HR=5.59, 95% CI: 1.25-24.99, P=0.024), expression of SUCNR1 in cancer tissues ( HR=3.68, 95% CI: 1.28-10.54, P=0.015), and expression of YBX1 in cancer tissues ( HR=3.42, 95% CI: 1.56-7.52, P=0.002) were all independent influencing factors for OS in CRLM patients. Conclusions:The high expression rates of SUCNR1 and YBX1 in cancer tissues of CRLM patients are higher than those in adjacent tissues. Patients with high and low SUCNR1 expression have differences in tumor histological grade, time from colorectal cancer diagnosis to liver metastasis, patients with high and low YBX1 expression has a difference in time from colorectal cancer diagnosis to liver metastasis. The 3-year OS rates of patients with low expression of SUCNR1 and YBX1 are higher than those of patients with high expression. The histological grade, the time from colorectal cancer diagnosis to liver metastasis, and the expression of SUCNR1 and YBX1 in cancer tissues are all independent influencing factors for OS in CRLM patients.

Objective To investigate the postoperative efficacy of laparoscopic hiatal hernia repair(LHHR)combined with Toupet or Dor fundoplication for the treatment of esophageal hiatal hernia(HH).Methods A retrospective analysis was conducted on the case data of HH patients who underwent LHHR combined with Toupet(Toupet group,n=53)and Dor(Dor group,n=53)fundoplication between December 2018 and December 2022 in Department of General Surgery of Gansu Provincial Hospital.Intraoperative and postoperative recovery outcomes of both groups were observed.We analyzed and compared the incidence of dysphagia and gastroesophageal reflux disease questionnaire(GERD-Q)scores at preoperative and postoperative intervals of 1 month,6 months,and 1 year.The incidence of postoperative complications and the 1-year recurrence rate were compared between the two groups.Additionally,factors influencing postoperative dysphagia within the first month were examined.Results The differences between the two groups in operation time,intraoperative bleeding,postoperative ventilation time,postoperative extubation time and hospitalization time were not statistically significant(P>0.05).There was no significant difference in the incidence of immediate postoperative dysphagia in two groups(P>0.05).Furthermore,the differences between the two groups in the incidence of postoperative complications,such as bloating,abdominal pain and diarrhea,were not statistically significant(P>0.05).The incidence of dysphagia in Toupet group was higher than that in Dor group at 1 month postoperatively,and the difference was statistically significant(P=0.017);but the difference in the incidence of dysphagia between the two groups at 6 months and 1 year postoperatively was not statistically significant(P=0.767,1.000).The results of binary logistic regression analysis showed that both surgical procedure(OR=2.613,95%CI 1.141-5.983,P=0.023)and esophageal contractile reserve function(OR=2.921,95%CI 1.203-7.095,P=0.018)were independent risk factors for the incidence of dysphagia in patients with HH at 1 month after surgery.Compared with the preoperative period,the GERD-Q symptom scores were lower in both groups at 1 month,6 months,and 1 year postoperatively,and the difference was statistically significant(P<0.05);but there was no statistically significant difference between the groups at the same time point(Fintergroup=0.334,P=0.565).The difference between the two groups in 1-year postoperative recurrence rates was not statistically significant(P>0.05).Conclusions LHHR combined with Toupet or Dor fundoplication are both safe and effective surgical procedures for the treatment of HH,with excellent reflux control,fewer complications and lower recurrence rates,but Toupet fundoplication is more likely to have postoperative short-term dysphagia than Dor fundoplication.

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

This article reports a first case of combined infection with severe fever with thrombocytopenia syndrome(SFTS)and scrub typhus in Dalian City.The patient was admitted to the hospital due to recurrent fever for 7 days and loss of consciousness for 1 day.Pathogen metagenomic sequencing(mNGS),SFTSV quantitative PCR,and enzyme-linked immunosorbent assay(ELISA)IgM tests were performed,showing positive results for Orientia tsutsugamushi and SFTSV nucleic acids.Based on clinical manifestations and epidemiological history,the patient was diagnosed with combined infections.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.