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 discuss the effect of royal jelly acid(10-HDA)on the proliferation and migration of the human colon cancer SW620 cells based on the network pharmacology,and to clarify its related molecular mechanism.Methods:The active ingredients such as 10-HDA and their corresponding targets were retrieved by using the keyword"royal jelly"from the Traditiomal Chinese Medicine Systems Pharmacology(TMSCP)Database and the Traditiomal Chinese Medicine Integrated Database(TCMID);the small molecule targets were predicted by the Swiss Target Prediction Database.The GeneCards Database and the Online Mendelian Inheritance in Man(OMIM)Database were used to obtain the targets with the keyword"Colon Cancer";the protein-protein interaction(PPI)network was constructed by using the String Database and Cytoscape 3.8.0 Software to screen the core targets;the Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were analyzed by Metascape Database;the specific ingredient 10-HDA was screened for the in vitro activity experiments.The human colon cancer SW620 cells with good growth status were divided into control group and different doses(1,5,10,15,and 20 mmol·L-1)of 10-HDA groups.The viabilities of the cells in various groups were detected by MTT method and the survival rates of the cells were calculated.The SW620 cells were divided into control group,low dose(5 mmol·L-1)of 10-HDA group,middle dose(10 mmol·L-1)of 10-HDA group,and high dose(15 mmol·L-1)of 10-HDA group;Hoechst33342 staining method was used to observe the morphology of the cells in various groups;cell scratch test was used to detect the scratch healing rates of the cells in various groups;flow cytometry was used to detect the percentages of the cells at different cell cycles in various groups;biochemical method was used to detect the activities of total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)in the cells in various groups;Western blotting method was used to detect the expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cysteine-containing aspartate proteolytic enzyme-3(Caspase-3),cysteine-containing aspartate proteolytic enzyme-9(Caspase-9),glycogen synthase kinase 3β(GSK3β),β-catenin,and cyclin D1 proteins in the cells in various groups.Results:Six active ingredients of royal jelly were screened out by the TCMSP Database,and 28 core targets of 10-HDA in the treatment of colon cancer were obtained.The GO function enrichment analysis mainly included the signaling pathways such as cell proliferation and apoptosis.The KEGG signaling pathway enrichment analysis included the cell cycle,prostate cancer,cell senescence,and p53 signaling pathways;the GSK3β/β-catenin signaling pathway was closely related to the cell cycle.Compared with control group,the viabilities of the cells in 5,10,15,and 20 mmol·L-110-HDA groups were decreased in a dose-dependent manner(P<0.05 or P<0.01),the numbers of apoptotic cells in different doses of 10-HDA groups were significantly increased,and the scratch healing rates of the cells were significantly decreased(P<0.05 or P<0.01);the percentages of the cells at S phase in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),the activities of T-AOC and SOD in the cells in different doses of 10-HDA groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the expression level of Bcl-2 protein in the cells in low dose of 10-HDA group was significantly decreased(P<0.01),and the expression level of GSK3β protein was significantly increased(P<0.05);compared with control group,the expression levels of Bax,Caspase-3,Caspase-9,and GSK3β proteins in the cells in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),and the expression levels of Bcl-2,β-catenin,and CyclinD1 proteins were significantly decreased(P<0.01).Conclusion:10-HDA can significantly inhibit the proliferation and migration of the colon cancer cells and promote the apoptosis and oxidation levels of the colon cancer cells,and its mechanism may be related to the activation of the GSK3β/β-catenin signaling pathway.

Objective: To evaluate the effects of application of vancomycin in the early stage of patients with extremely severe burn, in order to provide reference to drug for anti-infection treatment in the early stage of patients with extremely severe burn. Methods: Data of 15 patients of Kunshan explosion on August 2nd, 2014, admitted to the Department of Intensive Care in our hospital were retrospectively analyzed. The clinical efficacy of continuously intravenous dripping of vancomycin (combined with imipenem) in the early stage of burns (before and on post burn day 14) was analyzed. (1) The steady state plasma concentration of vancomycin was monitored respectively 30 min before the third, sixth, and tenth medication with direct chemiluminescent imaging method. (2) The distribution of Gram-positive bacteria of patients during hospitalization and their drug resistance to 14 antibiotics commonly used in clinic were analyzed. (3) Serum level of procalcitonin (PCT), white blood cell count, percentage of neutrophils before and after treatment, and efficacy grade of anti-infection treatment in the early stage of burns were analyzed. (4) Serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine before and after treatment, and the adverse effects during medication were analyzed. The WHONET 5.5 statistical software was used to analyze the distribution of Gram-positive bacteria in all the pathogens, and the status of drug resistance of Gram-positive bacteria to 14 antibiotics. Data were processed with Wilcoxon rank sum test. Results: (1) Twenty-nine times of steady state plasma concentration monitoring were performed in the patients in total, with the steady state plasma concentration of vancomycin from 4.3 to 42.1 μg/mL. In the monitoring before third, sixth, and tenth medication, the percentages of result reaching the standard were respectively 1, 3/14, and 2/7. (2) A total of 79 Gram-positive bacteria were isolated, including 49 (62.03%) strains of Staphylococcus aureus, 9 (11.39%) strains of Staphylococcus haemolyticus, 7 (8.86%) strains of Staphylococcus epidermidis, 12 (15.19%) strains of Enterococcus faecium, and 2 (2.53%) strains of Enterococcus faecalis. The above-mentioned Staphylococcus strains were with high drug resistance to antibiotics including penicillins, erythromycin, ciprofloxacin, and low drug resistance to linezolid, teicoplanin, and nitrofurantoin. The above-mentioned Enterococcus strains were with high drug resistance to antibiotics including erythromycin, ciprofloxacin, gentamicin, and low drug resistance to linezolid and teicoplanin. The above-mentioned Staphylococcus strains were all sensitive to vancomycin. Two strains of vancomycin-resistant Enterococcus were detected in the above-mentioned Enterococcus strains. (3) Serum level of PCT, white blood cell count, percentage of neutrophils of patients were (8.1±7.5) ng/mL, (24±10)×10⁹/L, and 0.898±0.029 before treatment, which were significantly higher than (3.0±2.8) ng/mL, (12±5)×10⁹/L, and 0.867±0.016 after treatment (with Z values respectively -2.103, -3.237, and -3.068, P<0.05 or P<0.01). After the early treatment, excellence, progess, and invalid results were achieved in 7, 5, and 3 patients, with the effective percentage of 4/5 in clinic. (4) There were no statistically significant differences in serum levels of AST, ALT, and creatinine of patients between before and after treatment (with Z values respectively-0.057, -1.508, and -1.363, P values above 0.05). Only one patient had liver and renal dysfunction during treatment. Conclusions The positive and reasonable use of vancomycin can remove most of the Gram-positive bacteria, and control the development of sepsis combined with imipenem in the early stage of patients with extremely severe burn. However, the dose of vancomycin should be individualized and the steady state plasma concentration should be monitored to maintain the blood concentration within the safe and effective range, so as to improve the rational use of vancomycin.