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.

Panvascular diseases are systemic diseases with atherosclerosis as the pathological core， involving multiple vascular beds and target organs throughout the body. Due to their wide range and complexity， the traditional single-discipline prevention and treatment model struggles to meet the needs of systematic management， while clinical diagnosis often remains one-sided and insufficient， leading to delayed treatment. Literature reviews show that panvascular diseases involve a wide range of lesion sites， numerous influencing factors， and are prone to endangering life and health. It is urgent to construct a comprehensive and whole-course prevention and treatment management system， with vascular health as the goal and patients as the core. First， early screening and risk assessment should be conducted for high-risk groups. In terms of treatment decisions for patients， multi-disciplinary collaboration is needed to establish a scientific and standardized prevention and treatment path. Second， it is important to attach great importance to a people-centered approach， enhance patients' familiarity with the disease through cognitive intervention， and shift from passive treatment to active health care. Thirdly， it is needed to leverage the advantages of modern science and technology， promote the deep integration of artificial intelligence innovations and modern medicine， and help traditional diagnosis and treatment plans evolve towards precision， intelligence， and personalization. This will open up new paths for the modernization of the whole-course management of pan-vascular diseases. Fourth， efforts should be made to continue to carry forward and innovate the characteristics of traditional Chinese medicine， adhere to equal emphasis on modern and traditional medicine， promote complementary advantages and coordinated development of Chinese and Western medicine， and form a unique Chinese model for the whole-course management of panvascular diseases. Fifth， through the reintegration and redistribution of government， medical insurance， and medical resources， comprehensive talents in the broad vascular disciplines should be cultivated and an efficient hierarchical management model established， providing reference and guidance for the whole-course management of comprehensive diseases in the future.

ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

ObjectiveTo investigate the effect of Sanet Vision Integrator (SVI)-based visuomotor integration training on the severity of neglect symptoms, upper limb motor function and activities of daily living (ADL) in patients with post-stroke unilateral spatial neglect (USN). MethodsFrom July, 2023 to September, 2025, 41 patients with post-stroke USN in Beijing Bo'ai Hospital were enrolled and randomly assigned to control group (n = 20) and experimental group (n = 21). Both groups received conventional rehabilitation and visual scanning training, while the experimental group received supplementary SVI-based visuomotor integration training, including saccadic, rotation and hand-eye coordination training, for eight weeks. They were assessed with Chinese Behavioral Inattention Test-Hong Kong version (CBIT-HK), Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI) before and after treatment. ResultsAfter treatment, all the scores significantly improved in both groups (|t| > 4.004, P < 0.001), and the total scores of CBIT-HK and the core visual search sub-items (star cancellation, line crossing and letter cancellation), FMA-UE and MBI were better in the experimental group than in the control group (t > 2.096, P < 0.05). ConclusionSVI-based visuomotor training can effectively alleviate the USN symptoms, broaden the span of visual attention, facilitate the functional recovery of the affected upper extremity, and improve ADL in patients after stroke.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

AIM:To explore the regulatory mecha-nism of pinoresinol diglucoside(PDG)on angiogen-esis during osteoporotic fracture healing in vivo and in vitro.METHODS:Fifty male C57BL/6J mice were randomly divided into five groups:normal group,model group,PDG 0.005,0.015 g/kg groups,and parathyroid hormone 1-34(PTH1-34)4×10-5 g/kg group.The osteoporotic fracture model of ovariec-tomized combined with femoral fracture was estab-lished,the PDG group was given intragastric admin-istration every other day and the PTH1-34 group was given subcutaneous injection of PTH1-34 every other day for 8 weeks.Micro-CT scanning,immunofluo-rescence and immunohistochemical staining were used to detect the related parameters and protein expressions.Human umbilical vein endothelial cells(HUVECs)were cultured,normal group,PDG 1,10,100 μmol/L groups and PTH1-341 ng/mL group were set up.CCK-8 assay,scratch experiment,tubule for-mation experiment,immunofluorescence and Western blot were used to detect the related pa-rameters and protein expressions.RESULTS:In vivo experiments found,compared with the normal con-trol group,a small amount of bone callus volume of fracture site were increased in the model control group,while BMD of non-callus site of femur,tra-becular bone fraction(BV/TV),trabecular thickness(Tb.Th)and trabecular number(Tb.N)were de-creased(P＜0.01),and trabecular separation(Tb.Sp)was increased(P＜0.01).The positive expression of vascular endothelial marker vascular endothelial markers(CD31)was decreased(P＜0.01).Compared with mice in the model control group,bone callus volume,index of BMD and BV/TV were increased in the PDG 0.005 g/kg group(P＜0.05),index of BMD,BV/TV,Tb.Th,Tb.N were increased,and index of Tb.Sp was decreased in the PDG 0.015 g/kg group(P＜0.05),the positive expression of CD31 was in-creased in the PDG administration groups(P＜0.01),the protein expressions of vascular endothelial growth factor(VEGF-A)(P＜0.01),Yes-associated protein 1(YAP1)(P＜0.01),PDZ-binding motif(TAZ)(P＜0.05)and TEA domain transcription factor 2(TEAD2)(P＜0.01)were increased in callus in the PDG 0.015 g/kg groups.Cell experiments found,compared with the normal control group,PDG groups promoted the proliferation,migration and tubule formation activity of HUVECs to varying de-grees(P＜0.05),at the same time,the expression of endothelial cadherin(E-cadherin)was decreased(P＜0.01),and VEGF-A,TEAD2,TAZ and YAP1 protein expression were increased(P＜0.05).CONCLUSION:PDG may accelerate osteoporotic fracture healing by promoting bone angiogenesis through regulat-ing Hippo signal pathway.

Objective:To explore the optimal age cutoff for diagnosis and the prognosis of early-onset gastric cancer in young patients.Methods:Clinicopathological data of patients with gastric adenocarcinoma aged ≤45 years who had undergone radical gastrectomy in the Department of Gastric Surgery, Fudan University Shanghai Cancer Center from January 2013 to December 2018 were retrospectively collected. Patients with distant metastases, other malignant tumors, combined organ resection, gastric stump cancer, positive margin, and incomplete clinical or follow-up data were excluded. X-tile software analysis of the actual overall survival of the collected cases yielded an optimal cut-off of 32 years. Accordingly, the enrolled cases were divided into an early-onset young group (age ≤32 years) and young adult group (age >32 years). Clinicopathological characteristics, long-term survival, and postoperative recurrence were compared between the two groups. Univariate and multivariate analyses were performed using the Cox proportional hazards model to identify the factors affecting the prognosis of young patients with gastric cancer.Results:The study cohort comprised 462 patients, including 256 (55.4%) women, 419 (90.7%) with middle and lower gastric cancers, and 343 (74.2%) with poorly differentiated tumors. There were 101 patients in the early-onset young group and 361 in the young adult group. These groups did not differ significantly in terms of sex, body mass index, tumor location, tumor size, surgical procedure, neurovascular invasion, or tumor stage (all P>0.05). The proportion of patients with poorly differentiated tumors in the early-onset young group was significantly higher than that in the young adult group (89.1%[90/101] vs. 70.1%[253/361], χ 2=15.26, P<0.001). All study patients completed 5 years of follow-up, the median duration of which was 101 months (61-133 months). Death or tumor recurrence occurred in 151 patients (32.7%), in 118 of whom the sites of recurrence and metastasis could be identified, 38 in the early-onset young group and 80 in the young adult group. Fifty-five (46.6%) patients developed peritoneal metastases and 40 (33.9%) hematogenous metastases. In the early-onset young group, 20 patients developed peritoneal metastases, 11 hematogenous metastases, five distant lymph node metastases, and two local recurrence. In the young adult group, 35 patients developed peritoneal metastases, 29 hematogenous metastases, six local recurrences, and 10 distant lymph node metastases. The 5-year overall survival and disease-free survival rates were significantly higher in the young adult group than in the early-onset young group (73.7% vs. 57.4%, P=0.002 and 70.6% vs. 55.4%, P=0.004, respectively). Cox multivariate analysis showed that age >32 years (HR=0.63, 95%CI: 0.43-0.90, P=0.012) was an independent protective factor for overall survival, whereas later N stage (HR=1.67, 95%CI:1.09-2.57, P=0.018) was an independent risk factor for overall survival after surgery ( P<0.05). Age >32 years (HR=0.60, 95%CI: 0.41-0.86, P=0.006) was also an independent protective factor for disease-free survival, whereas later N stage was an independent risk factor (HR=1.69, 95%CI: 1.08-2.64, P=0.021). Conclusion:Young patients with early-onset gastric cancer aged ≤32 years have worse tumor differentiation and prognosis.

Objective To prepare in-house coagulation factor Ⅷ(F Ⅷ)inhibitor-positive control material and evaluate its perform-ance.Methods Frozen plasma samples from hemophilia A patients with positive factor Ⅷ inhibitors were pooled,and diluted with Owren's Veronal Buffer(OVB)to 1 BU/mL of the inhibitor concentration in the mixture,then aliquoted and freeze-stored.The homo-geneity and stability of the in-house quality control material were verified,and its suitability was further assessed through intra-laborato-ry reproducibility among different technologists and inter-laboratory comparisons.Results Twenty-one aliquots were randomly tested for homogeneity assessment,yielding an average of 1.05 BU/mL(range 0.9-1.15 BU/mL),with a standard deviation(SD)of 0.083 and coefficient of variation(CV)of 7.90％.The freshly prepared inhibitor-positive control samples contained a concentration of 1.03 BU/mL.After storage at-80℃ for 24 hours,1 week,1 month,2 months,3 months,4 months,5 months,6 months,7 months,8 months,and 9 months,thawed the samples showed relative deviations of 9％,0％,10％,9％,14％,15％,6％,0％,-10％,-5％,and 2％,respectively.The intra-laboratory CV value from different technologists at this center was 7.28％,and the inter-labora-tory CV across different centers was 18.75％.Conclusion The prepared in-house positive control material of Factor Ⅷ inhibitor ex-hibited adequate uniformity and stability.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Objective:To investigate the influencing factors and prognosis of early recurrence after gastrectomy for gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 2 078 patients who underwent gastrectomy for gastric cancer at six medical centers across China, including Fudan University Shanghai Cancer Center et al, between January 2012 and June 2023 were collected. There were 1 449 males and 629 females, aged (59±11) years. Patients were classified as early recurrence and late recurrence based on the time of post-operative recurrence. Observation indicators: (1) comparison of clinicopathological characteristics between gastric cancer patients with different recurrence types; (2) recurrence and metastasis of tumor; (3) survival of patients after postoperative recurrence of gastric cancer; (4) analysis of influencing factors for early recurrence after gastrectomy for gastric cancer. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the rank sum test. Multivariate analysis was conducted using the Logistic regression model. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. Results:(1) Comparison of clinicopathological characteristics between gastric cancer patients with different recurrence types. Among the 2 078 patients, 1 452 cases had early recurrence and 626 cases had late recurrence. There were significant differences in preoperative carcinoembryonic antigen, preoperative CA19-9, preoperative CA72-4, preoperative albumin, tumor diameter, neoadjuvant therapy, R 0 resection, combined organ resection, scope of gastric resection, nerve and vessel infiltration, degree of tumor differentiation, pathological N staging, pathological TNM staging between early and late recurrence patients ( P<0.05). (2) Recurrence and metastasis of tumor. Among the 2 078 patients, 200 cases had local recurrence, 1 213 cases had hematogenous metastases, 392 cases had distant lymph node metastases, and 731 cases had peritoneal metastases. Among the 1 452 early recurrence patients, 142 cases had local recurrence, 834 cases had hematogenous metastases, 289 cases had distant lymph node metastases, and 507 cases had peritoneal metastases. Among the 626 late recurrence patients, 58 cases had local recurrence, 379 cases had hematogenous metastases, 103 cases had distant lymph node metastases, and 224 cases had peritoneal metastases. One patient may have multiple forms of recurrence and metastasis. There was no significant difference in the above indica-tors between early and late recurrence patients ( χ2=0.13, 1.74, 3.40, 0.14, P>0.05). (3) Survival of patients after postoperative recurrence of gastric cancer. All 2 078 patients were followed up until death after recurrence, with a follow-up time of 31(range, 9?147)months. The 1-, 2-, 3-, and 5-year overall survival rates after recurrence were 33.5%, 17.2%, 10.1%, and 3.3% in early recurrence patients, versus 44.2%, 21.6%, 12.8%, and 5.8% in late recurrence patients, respectively, showing a significant difference in overall survival after recurrence between the two groups ( hazard ratio=0.84, 95% confidence interval as 0.76?0.92, P<0.05). (4) Analysis of influencing factors for early recurrence after gastrectomy for gastric cancer. Results of multivariate analysis showed that combined organ resection, total gastrectomy, pathological TNM staging as stage Ⅲ were independent risk factors for early recurrence after gastrectomy for gastric cancer ( odds ratio=1.31, 1.32, 1.34, 95% confidence interval as 1.01?1.70, 1.06?1.65, 1.05?1.71, P<0.05) and normal preoperative tumor markers, neoadjuvant therapy, R 0 resection were independent protective factors for early recurrence ( odds ratio=0.61, 0.50, 0.38, 95% confidence interval as 0.49?0.76, 0.35?0.72, 0.25?0.58, P<0.05). Conclusions:Compared with patients with late recurrence after gastric cancer surgery, patients with early recurrence have a poor prognosis, in which liver metastases is more common. Combine organ resection, total gastrectomy, pathological TNM staging as stage Ⅲ are independent risk factors for early recurrence, and normal preoperative tumor markers, neoadjuvant therapy, R 0 resection are independent protective factors for early recurrence after gastrectomy for gastric cancer.