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 survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

Background: To investigate directional deviations between pilot holes and final pedicle screw trajectories in freehand placement and analyze risk factors for misplacement. While pedicle screws are widely used in thoracolumbosacral surgery, directional deviations between pilot holes and final screw trajectories remain understudied as potential risk factors for misplacement. Methods: Thirty-three patients undergoing posterior fixation were prospectively enrolled. Inertial measurement units (IMUs) tracked the spatial positions of pedicle finders and screwdrivers via custom software. Surgeons (n = 6) were stratified into senior, middle, and junior groups. Analyzed variables included the use of tapping, surgeon experience, spinal deformity status, screw tip morphology, and surgical parameters. Results: Among 198 implanted screws (6.00 ± 2.88/patient), all exhibited trajectory deviations (8.12° ± 3.47°). Tapping significantly reduced deviations (7.23° ± 3.23° vs. 8.87° ± 3.31°, p < 0.01). Senior surgeons achieved smaller deviations (7.34° ± 3.33°) than the middle group (8.60° ± 3.51°, p = 0.039) and junior group (8.68° ± 3.49°, p = 0.022). Multivariate analysis confirmed tapping (p = 0.001) and senior experience (p = 0.023) as protective factors. No significant associations emerged for spinal deformity (8.43° ± 3.73° vs. 7.97° ± 3.35°, p = 0.377), screw tip type (cylindrical, 8.43° ± 3.26° vs. tapered, 8.07 ± 3.51°; p = 0.637), obesity, or surgical position parameters. Conclusions Freehand pedicle screw placement consistently produces trajectory deviations from pilot holes, and surgeon experience and tapping are modifiable protective factors. The IMU-based tracking system enables quantitative surgical motion analysis, suggesting its utility for training optimization and technique standardization.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

This study aimed to systematically construct a transitional curriculum for newly recruited surgical residents and to evaluate its preliminary application outcomes through pre and postimplementation assessments, so as to provide practical references for the design and dissemination of such curricula.

Objective To propose a framework for risk assessment and stepwise management of pulmonary nodules based on existing guidelines and key studies, and to clarify the boundaries for triage, workup escalation, and referral in different detection scenarios. Methods A problem-oriented evidence synthesis approach was used, prioritizing Chinese expert consensus, Fleischner Society Guidelines, British Thoracic Society (BTS) Guidelines, and Lung-RADS. This was supplemented by studies on risk models, imaging measurements, liquid biopsy, tissue sampling, and surgical treatments. This paper is not presented as a formal consensus or a validated clinical pathway. Results A three-tiered framework consisting of basic non-invasive assessment, advanced assessment, and invasive diagnosis was established. It specified the applicable populations, boundaries for the use of risk models, imaging review, management of conflicting results, evaluation of histopathological consistency, and post-intervention follow-up. Liquid biopsy, genetic testing, and artificial intelligence were defined as investigational or adjunctive tools. Conclusion This framework can serve as a preliminary reference for multidisciplinary teams in developing local protocols. It cannot replace applicable guidelines, pathological diagnosis, shared decision-making with patients, or real-world validation.

AIM To investigate the effect of Fuzheng Hefu Zhiyang Formula(FZHFZY)on psoriasis-like skin lesions and immune regulation in mice.METHODS In the in vivo experiment,30 BALB/c mice were randomly divided into the blank group,the model group,the dexamethasone group(1.5 g/kg of compound dexamethasone acetate cream),and the low-dose(2.5 g/kg)and high-dose(5 g/kg)FZHFZY groups,with six mice in each group.The experiment groups were treated with respective FZHFZY and dexamethasone,and the other groups were given normal saline for 10 consecutive days,during which psoriatic skin lesions were induced with imiquimod cream for 7 consecutive days.The mice had their area and severity of psoriasis assessed by PASI score;their histological changes of skin lesions.observed with Hematoxylin-eosin(HE)staining;their F4/80 ratio of skin lesions observed with immunohistochemical(IHC)staining;their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected by Western blot;and their mRNA expressions of tumor necrosis factor-α(TNF-α),IL-17,IL-23 and IL-1β detected by RT-qPCR.In the in vitro research,the cultured RAW264.7 cells were divided into the blank group,the LPS group,and the FZHFZY groups(1 200,600,300,150 μg/mL).The cells had their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected with Western blot;and their mRNA expressions of IL-6,TNF-α,IL-23 and IL-8 detected by RT-qPCR.RESULTS The in vivo experiment showed that compared to the model group,the FZHFZY groups demonstrated decreased PASI score(P＜0.01);improved epidermal thickening and parakeratosis of skin lesions as revealed by HE staining result and increased expression of F4/80 in IHC staining sections;decreased protein expression ratios of p-P38/P38,p-ERK/Erk and p-P65/P65 in skin(P＜0.05,P＜0.01);and reduced mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β in the skin(P＜0.01).FZHFZY(0～2 400 μg/mL)showed no significant cytotoxicity towards RAW264.7 cells in vitro(P＞0.05).Compared to those of the LPS group,the cells exposed to FZHFZ at concentrations of 1 200 and 600 μg/mL demonstrated decreased protein expression ratios of p-P38/P38,p-ERK/Erk,and p-P65/P65(P＜0.05,P＜0.01);and significantly decreased mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β(P＜0.01).CONCLUSION FZHFZY alleviates imiquimod-induced psoriatic lesions in mice and suppresses inflammatory response in LPS-stimulated RAW264.7 cells by inhibiting P38/Erk/NF-κB signaling pathway.

Objective:To investigate the clinical, pathological, and molecular biological characteristics of gastric hepatoid adenocarcinoma (HAS) in order to provide reference for clinical treatment.Methods:Thirty-two patients diagnosed with hepatoid adenocarcinoma after radical gastrectomy for gastric cancer at Shanxi Cancer Hospital were included from January 2019 to December 2021. Immunohistochemistry, in situ hybridization, and next-generation sequencing (NGS) methods were used to analyze immune markers and molecular characteristics in the pathological tissues from 32 patients with HAS. Cox regression analysis and Kaplan-Meier method were used to analyze the prognostic factors of overall survival and disease-free survival.Results:Among the 32 patients with HAS, 26 were male, 6 were female; aged 28-77 years, with an median age 62.0 (53.8, 67.2) years. Fifteen cases of HAS were located in the cardia, 10 cases in the antrum, and 7 cases in the body of the stomach. The maximum diameter of the mass was 3-10 cm, and mainly ulcerative in gross. The immunohistochemistry and in situ hybridization results showed that the positive rates of AFP, SALLA4, and Glypican-3 were 68.8% (22/32), 68.8% (22/32), 78.1% (25/32), respectively; Seven patients had microsatellite status of dMMR. Two cases of HER2 gene amplification and 2 cases of EB virus positivity. The NGS results showed that HAS was often accompanied by multiple gene mutations, with 23 cases having ≥ 2 gene mutations and 6 cases having ≥10 gene mutations. The TP53 gene had the highest mutation frequency; 4 cases had genetic structural variations; 28 cases had copy number variation. In addition, there were 7 cases of MSI-H and 9 cases of TMB-H. Follow-up results showed that 12 cases died, 9 cases developed metastasis, and the shortest survival time was 5 months.Conclusions:Gastric HAS is a type of tumor with high invasiveness and poor prognosis. The combined detection of AFP, SALLA4 and Glypican-3 can improve the diagnostic rate of tumors. dMMR/MSI-H and TMB-H patients in HAS are significantly higher than those in ordinary gastric cancer, and the high frequency mutation genes in HAS are often accompanied by multiple potential therapeutic targets. Immunotherapy combined with chemotherapy and targeted therapy are expected to become the treatment direction of HAS.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.