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.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

Clinical data of a patient with alveolar soft part sarcoma (ASPS) treated at Zhongshan Hospital, Fudan University were retrospectively analyzed. The patient was initially diagnosed with abdominal ASPS with multiple lung metastases. After 6 weeks of treatment with nivolumab and ipilimumab, the patient achieved stable disease (SD). In the 7th week, the treatment was changed to a combination of nivolumab (30 mg, d1, q3w), anlotinib (8 mg, d1-14, q3w) and ipilimumab (50 mg, d1, q6w). The patient remained SD at the 12th week. The patient then underwent iliac artery embolization and intensity-modulated radiation therapy for the lesion in the psoas major muscle, while continuing the combination treatment. By the 24th week, the evaluation showed partial remission (PR) of both primary tumor and lung metastases. The patient experienced mild adverse reactions during treatment.

Objective To explore the effects of Ginkgo biloba extract (GBE) on cardiac microvascular endothelial cells (CMECs) under oxygen and glucose deprivation/reperfusion (OGD/R) condition and its molecular mechanisms. Methods An OGD/R-induced injury model was established in CMECs. According to different intervention, CMECs were divided into four groups: normoxia blank control group (WT group), WT + GBE group, OGD/R group, and OGD/R + GBE group. Cell apoptosis was detected by flow cytometry technology in each group. The oxidative stress was examined by MitoSox staining. The migration abilities were measured by scratch assay. The expressions of PERK/eIF2α/CHOP, nuclear factor kappa B (NF-κB), and endothelial cell function markers were detected by Western blotting. Results Compared with the WT group, the endothelial cell apoptosis level in the OGD/R group significantly increased, with markedly aggravated cellular dysfunction. The expressions of p-NF-κB, vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were significantly upregulated (P＜0.05), and the activation of the CHOP signaling pathway was notably enhanced (P＜0.05). After intervention with GBE, endothelial cell apoptosis caused by OGD/R injury was significantly reduced, oxidative stress and inflammation levels were markedly downregulated, and the expression of p-NF-κB was considerably decreased (P＜0.05), while the CHOP signaling pathway was notably inhibited (P＜0.05). Furthermore, it was found that GBE could promote expression of SIRT6 to regulate the above molecules, thereby alleviating cardiac microvascular endothelial cell injury under OGD/R condition. On the contrary, when SIRT6 was knocked down, the protective effects were significantly reduced. Conclusions GBE improves endothelial cell dysfunction, endoplasmic reticulum stress, and endothelial cell apoptosis caused by OGD/R injury by promoting the expression of SIRT6 protein, thus regulating the NF-κB inflammatory pathway and CHOP signaling pathway.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

Surgical treatment is one of the key approaches for non-small cell lung cancer (NSCLC). Regular postoperative follow-up is crucial for early detection and timely management of tumor recurrence, metastasis, or second primary tumors. A scientifically sound and reasonable follow-up strategy not only extends patient survival but also significantly improves quality of life, thereby enhancing overall prognosis. This consensus aims to build upon the previous version by incorporating the latest clinical research advancements and refining postoperative follow-up protocols for early-stage NSCLC patients based on different treatment modalities. It provides a scientific and practical reference for clinicians involved in the postoperative follow-up management of NSCLC. By optimizing follow-up strategies, this consensus seeks to promote the standardization and normalization of lung cancer diagnosis and treatment in China, helping more patients receive high-quality care and long-term management. Additionally, the release of this consensus is expected to provide insights for related research and clinical practice both domestically and internationally, driving continuous development and innovation in the field of postoperative management for NSCLC.

AIM:To investigate the relationship between the level of monocyte chemoattractant protein-1(MCP-1)in the aqueous humor and macular microcirculation in patients with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS:A total of 327 patients(327 eyes)with RVO-ME treated in our hospital from July 2022 to July 2024 were selected as the research objects. According to the recurrence or not, they were divided into non-recurrence group(291 cases, 291 eyes)and recurrence group(36 cases, 36 eyes). The clinical data, macular microcirculation index and MCP-1 level were collected. Unordered multinomial Logistic regression was used to analyze the effect of MCP-1 on RVO-ME recurrence after excluding the influence of other factors. Cubic spline was used to analyze the dose-response relationship between macular microcirculation indexes and MCP-1 expression level and RVO-ME recurrence. Multiple linear regression was used to analyze the relationship between macular microcirculation parameters and MCP-1 expression level, and the difference of MCP-1 expression level in recurrence under different macular microcirculation parameters was analyzed. Bootstrap method was used to test the mediating effect of macular microcirculation indexes on MCP-1 expression level and RVO-ME recurrence.RESULTS: The course of ME, the incidence of vitreomacular traction(VMT), the incidence of fibrous membrane epiretinal membrane(ERM), best corrected visual acuity(BCVA), hyperreflective foci in the inner and outer retinal layers(HRF), the frequency and dose of anti-vascular endothelial growth factor(VEGF)injection in the recurrence group were significantly higher than those in the non-recurrence group(all P<0.05). The external limiting membrane(ELM)integrity and ellipsoid zone(EZ)integrity in the recurrence group were significantly worse than those in the non-recurrence group(all P<0.05). The central foveal thickness(CFT), central macular thickness(CMT), superficial capillary plexus(SCP)vascular density, deep capillary plexus(DCP)vascular density and MCP-1 in the recurrence group were higher than those in the non-recurrence group(all P<0.05), and the foveal avascular zone(FAZ)area was lower than that in the non-recurrence group(P<0.05). Logistic analysis showed that MCP-1 was a risk factor for RVO-ME recurrence before and after adjusting for confounding factors. There was a significant non-linear dose-response relationship between macular microcirculation indexes and MCP-1 expression and the risk of RVO-ME recurrence(non-linear test, all P<0.001). The vascular density of CFT, CMT, SCP and DCP was positively correlated with the expression level of MCP-1(all P<0.05), while the FAZ was negatively correlated with MCP-1 expression level(P<0.05). With the increase of vessel density in CFT, CMT, SCP and DCP, and the decrease of FAZ, the expression level of MCP-1 increased, and the risk of RVO-ME recurrence showed an upward trend. The proportion of MCP-1 in Q3(>28.47 pg/mL)group was the highest(P<0.05). Macular microcirculation parameters play a mediating effect between MCP-1 expression level and RVO-ME recurrence.CONCLUSION: The level of MCP-1 in aqueous humor is positively correlated with RVO-ME recurrence, and it is closely related to macular microcirculation. Macular microcirculation has a mediating effect between MCP-1 level and RVO-ME recurrence.

Objective To validate the efficacy of the prediction model for difficulty of peroral endoscopic myotomy (POEM) through an independent cohort. Methods A total of 617 patients with achalasia who underwent POEM at the Endoscopy Center of Zhongshan Hospital, Fudan University from January 2021 to December 2023 were included. The general data of patients were collected, and the predictive value of the prediction model for POEM difficulty in the validation cohort was estimated. The stratified analysis was undergone according to the difficulty risk scores. Results In 617 consecutive patients, technical difficulty was observed in 90 cases (14.6%). The predictive model demonstrated moderate discriminatory capacity with an area under the receiver operating characteristic curve (AUC) of 0.711 (95%CI 0.643-0.780). Patients were stratified into three risk categories according to the difficulty risk scores: low-risk (＜0.1), medium-risk (0.1-0.25), and high-risk (≥0.25). The corresponding technical difficulty rates were 7.3%, 16.9%, and 51.6%, respectively. Conclusion The prediction model for POEM difficulty built by our center shows good stability and discrimination, and has good clinical application value.

BACKGROUND:Changes in skeletal muscle mass have been indicated in studies addressing the effects of low-frequency pulsed magnetic fields on the structure and morphology of the skeletal muscle,but no relevant studies have been conducted on the morphologic changes that occur after chronic exposure to the low-frequency pulsed magnetic field. OBJECTIVE:To observe the effects of chronic exposure to low-frequency pulsed magnetic fields on the maximal voluntary contraction and morphologic indicators of the quadriceps muscle of the leg,thereby providing a reference of muscle morphologic changes for the use of this technique as a strategy for muscle function improvement. METHODS:Seventy healthy subjects were recruited and randomly divided into a test group that received magnetic field stimulation and a control group that underwent sham treatment,with 35 subjects in each group,and the total duration of the trial was 4 weeks.The test group underwent low-frequency pulsed magnetic stimulation for 15 minutes every 48 hours,while the control group underwent sham treatment,with the same intervention interval and duration as the test group.After 4 weeks of intervention,changes in the maximum voluntary contraction value of the quadriceps muscle in different groups were observed,and B-mode ultrasonography was utilized as a means of assessment to observe changes in muscle thickness,muscle cross-sectional area,and pinnation angle indexes. RESULTS AND CONCLUSION:After 4 weeks of chronic exposure to low-frequency pulsed magnetic fields,68 subjects completed the test.The maximum voluntary contraction value of the quadriceps muscle in the test group increased significantly(P=0.000),and the increment was significantly higher than that of the control group(P=0.008).Three indexes related to muscle morphology in the test group were significantly higher than the pre-test values(P=0.000),while in the control group,muscle thickness showed a significant reduction(P=0.020),there was no significant change in the pinnation angle,but a significant increase in the cross-sectional area(P=0.000).Intergroup comparisons revealed that the three indicators related to muscle morphology,including muscle thickness(P=0.012),pinnation angle(P=0.003),and cross-sectional area(P=0.049),were significantly higher in the test group than in the control group.The above data confirmed that the maximum voluntary contraction of the quadriceps muscle was significantly increased in healthy adults after 4 weeks of chronic exposure to the low-frequency pulsed magnetic field,and significant increases in the three muscle morphometric indices of muscle thickness,cross-sectional area,and pinnation angle were observed in the test group,providing a basis of muscle tissue morphology for the use of this technique as an exercise alternative and medical treatment strategy for muscle improvement.

OBJECTIVE To investigate the potential mechanism of berberine improving diabetes mellitus type 2 （T2DM） combined with metabolic-associated fatty liver disease （MAFLD） by regulating ceramide. METHODS Thirty-two db/db mice with blood glucose levels＞11.1 mmol/L （T2DM model） were divided into four groups： model group， berberine low- and high-dose groups [100， 200 mg/（kg·d）] and metformin group [300 mg/（kg·d）]， with 8 mice in each group. Additionally， 8 wt/wt mice were selected as the normal control group. Mice in each group were administered the corresponding drug solution or water by gavage once daily for a continuous period of 6 weeks. During the experiment， the body weight of the mice was monitored， and the differences in final body weight were analyzed. After the last administration， the body shape of the mice in each group was observed， and their fasting blood glucose （FBG） and the lipid indicators [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] were measured. Fasting serum insulin （FINS） levels were also measured， and the insulin resistance index HOMA-IR） and insulin sensitivity index （ISI） were calculated. Liver weight， liver index and serum liver function indicators [alanine transaminase （ALT）， aspartate transaminase（AST）] were assessed， and hepatic histopathological changes were observed. Additionally， the expression of fatty acid synthesis-related proteins [sterol regulatory element-binding protein 1 （SREBP1）， fatty acid synthase （FASN）， acetyl-CoA carboxylase 1 （ACC1）] in liver tissue was examined. Serum samples from the normal control group， model group， and berberine high-dose group were collected for non-targeted lipidomics analysis and validation. RESULTS Compared with the model group， the pathological changes， including disordered liver tissue cell arrangement and lipid vacuoles， were significantly improved in the berberine low- and high-dose groups. The significant decreases or down-regulations were observed in body weight in the last week， as well as FBG， TC， TG， and LDL-C levels， HOMA-IR （except for the berberine low-dose group）， liver weight， liver index， AST and ALT levels， and protein expressions of SREBP1， FASN and ACC1. Additionally， HDL-C levels， FINS （except for the berberine high-dose group）， and ISI （except for the berberine low-dose group） were significantly increased （P＜0.05）. A total of 21 potential differential metabolites， including multiple types of ceramides， were identified； these metabolites were primarily enriched in sphingolipid metabolism and glycerophospholipid metabolism pathways. Verification experiments confirmed that high-dose berberine significantly reduced the serum content of ceramide in model mice （P＜0.05）. CONCLUSIONS Berberine reduces insulin resistance， improves liver damage and lipid accumulation in the T2DM combined with MAFLD mice， and these effects may be related to the reduction of ceramide content.