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:Spinal cord injury is a neurological disorder caused by traumatic or non-traumatic events,often leading to severe functional impairment below the injured segment.In recent years,neural stem cell transplantation has been considered to have significant therapeutic potential in regulating the inflammatory response after spinal cord injury,inhibiting excessive proliferation of glial scars,and promoting nerve regeneration. OBJECTIVE:To review and discuss the potential mechanism of action of acupuncture and neural stem cell transplantation therapy in inhibiting spinal cord injury-induced secondary injury,and to delve into the scientific basis for its treatment of spinal cord injury. METHODS:PubMed,Elsevier,WanFang,and CNKI databases were searched using"spinal cord injury,acupuncture,neural stem cells,SDF-1α/CXCR4 axis"as Chinese and English search terms.Totally 96 articles were finally included.The research findings of acupuncture combined with neural stem cells in the treatment of spinal cord injury were summarized and analyzed,and the mechanism of this combination therapy in the treatment of secondary injury after spinal cord injury was summarized. RESULTS AND CONCLUSION:(1)The stromal-derived factor 1α(SDF-1α)/chemokine receptor 4(CXCR4)axis plays a crucial role in neural stem cell transplantation for spinal cord injury.This signaling mechanism not only affects neural stem cell migration,proliferation,and differentiation,but is also a key factor in determining the efficiency of stem cell homing to the injury site.Therefore,the regulation of targeting this axis is of great significance in enhancing the therapeutic effect of spinal cord injury.(2)Acupuncture,as a traditional Chinese medicine therapy,shows unique advantages in the regulation of secondary injury in spinal cord injury.It can effectively reduce secondary injury after spinal cord injury by regulating inflammatory response,inhibiting apoptosis,improving microcirculation,reducing glial scar formation,and counteracting oxidative stress.(3)Acupuncture was also able to influence the expression and function of the SDF-1α/CXCR4 axis,thereby enhancing the homing and survival ability of neural stem cells and promoting nerve regeneration and functional recovery.(4)The therapy combining acupuncture and stem cell transplantation is an innovative treatment strategy for spinal cord injury and suitable for repairing neural circuits.It combines the wisdom of traditional Chinese medicine with the advantages of modern biotechnology,providing a new treatment option for spinal cord injury patients.However,this combination therapy is still in the research and exploration stage,and its long-term efficacy and safety need to be further verified.(5)Taken together,acupuncture and neural stem cell transplantation for the treatment of spinal cord injury has great potential for clinical application,but in-depth research and optimization of treatment options are still needed.In the future,we look forward to further revealing the efficacy mechanism and optimal indications of this therapy through more clinical trials and mechanism studies,so as to bring better hope of recovery and more efficient therapeutic effects to spinal cord injury patients.

BACKGROUND:Currently,spinal cord injury imposes a huge psychological and economic burden on patients and the National Health Service.The prevention,treatment,and rehabilitation of spinal cord injury have become an important topic in the field of medicine.Therefore,it is important to explore new effective therapeutic strategies based on an in-depth understanding of the underlying molecular mechanisms of spinal cord injury.OBJECTIVE:To review the research progress on the mechanism of action of mesenchymal stem cell-derived exosomes loaded with various miRNAs in improving the function of spinal cord injury,and based on the current status of clinical translation,to put forward a few thoughts and outlooks on their clinical use.METHODS:The first author searched CNKI and PubMed databases using"mesenchymal stem cells,exosomes,spinal cord injury,miRNA,pathophysiology,clinical translation,clinical trials,good manufacturing practice"as Chinese and English search terms.The types of literature included treatises and reviews,and the language types were English and Chinese.Finally,72 papers were screened and analyzed.RESULTS AND CONCLUSION:(1)This article outlines the biological properties of exosomes and the advantages that they can serve as good vectors for loading miRNAs.A variety of miRNAs mediated by mesenchymal stem cell-derived exosomes mainly promote the recovery of neuronal function by regulating the expression of nerve regeneration-associated proteins,repressing RAS homologous gene family member A,activating cyclophosphoadenosine effector-binding proteins,and signaling and transcriptional activation proteins 3,and regulating phosphoinositide and tensin homologue/programmed cell death factor 4 pathways.Inflammatory responses were improved by regulating endoplasmic reticulum-to-nucleus signaling 1,expression of interferon regulatory factor 5,Toll-like receptor 4/nuclear factor-kappa B pathway,and down-regulating related pro-inflammatory factors.Angiogenesis was promoted by inhibition of germination-associated domain 1-containing EVH1 and phosphatidylinositol 3-kinase regulatory subunit 2.(2)Further comparative analyses revealed that miR-216-5p,miR-145-5p,and miR-146b improved inflammatory responses by regulating related pathways.Combining these miRNAs may produce more significant effects;hypoxic preconditioning may be a preconditioning method to increase the efficacy of exosomal therapy.(3)There are currently no clinical trials applying mesenchymal stem cell-derived exosomes to spinal cord injury,which is related to the need to meet good manufacturing practices before they can be put into clinical use.Challenges such as the need for large-scale,high-volume cell production,the lack of an efficient and uniform method for isolating exosomes,and the need to pass a strict regulatory approval mechanism prior to clinical use have impeded the clinical entry.(4)miRNAs have great potential as exosomal contents of mesenchymal stem cells in the treatment of spinal cord injury,and their mechanism of action should be explored in depth as well as accelerated to the clinical trial stage in order to provide a new and effective method for the treatment of spinal cord injury.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Objective:To explore the mechanism by which the extract of Hedyotis diffusa Willd regulates TGF-β/Smad signaling transduction pathway and affects proliferation,invasion of renal cancer cells and expressions of Th1/Th2 cytokines in mice with renal cancer.Methods:Using mouse renal cancer Renca cells as the research object,after intervention with extracts of Hedyotis diffusa Willd,impact on migration ability of mouse renal cancer cells was detected at the cellular level using scratch assay;observing effect of CCK-8 experiment on proliferation ability of mouse renal cancer cells.A mouse kidney cancer model was established by subcutaneous inoculation under the right armpit,and effect of extract of Hedyotis diffusa Willd on proliferation and invasion of renal carcinoma in mice was studied.HE staining was used to observe histomorphology of transplanted tumor mass in mice;Western blot was used to detected expressions of TGF-β/Smad pathway protein TGF-β,Smad2 and p-Smad2 in mouse transplanted tumor tissue;levels of IL-2 and IL-10 in mouse serum were detected by ELISA to investigate whether the extract of Hedyotis diffusa Willd has an inhibitory effect on Th1/Th2 renal carcinoma immune shift.Results:CCK-8 experiment showed that the extract of Hedyotis diffusa Willd inhibited pro-liferation ability of mouse renal cancer Renca cells(P<0.05);scratch test results showed that extract of Hedyotis diffusa Willd effec-tively inhibited the healing ability of mouse renal cancer Renca cells(P<0.05);by constructing a mouse kidney cancer model,it was found that extract of Hedyotis diffusa Willd could inhibit the growth of transplanted tumor volume in mice(P<0.05);HE staining revealed that tumor cells in model group were dense,with numerous mitotic figures and minimal necrosis;whereas in Hedyotis diffusa Willd group and pathway inhibitor group,there was increased necrosis of cancer cells,accompanied by karyopyknosis or lysis;Western blot showed that compared with model group,expression of TGF-β and p-Smad2 in extract of Hedyotis diffusa Willd group and pathway inhibitor group were decreased(P<0.001);ELISA results showed that compared with model group,serum IL-2 expression increased in both Hedyotis diffusa Willd group and pathway inhibitor group(P<0.000 1).IL-10 expression decreased in Hedyotis diffusa Willd group(P<0.05)and pathway inhibitor group(P>0.05).Conclusion:Extract of Hedyotis diffusa Willd may inhibit protein expressions in TGF-β/Smads signaling pathway,further regulate the secretion of Th1/Th2 cytokines,thereby inhibiting proliferation and migration of mouse renal cancer cells both in vitro and in vivo.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Objective To explore the mechanism of Lidan Huatan Huoxue Decoction improving cognitive impairment caused by obesity based on metabolomics.Methods Twenty-four 6-week-old male SD rats were randomly divided into a normal group fed with regular diet(Con,n=6)and a modeling group fed with high-fat and high-sugar diet(n=18).Rats with a body mass that is 20%higher than the standard body mass of their age-matched peers fed with ordinary diet were considered to have a successful obese model established.The presence of cognitive impairment was assessed by Morris water maze and Barnes maze tests.After the obese-induced cognitive impairment(OICI)model was established,the modeling rats were randomly divided into a model group(Model,n=6),a donepezil group(Donepezil,n=6),and a Lidan Huatan Huoxue Decoction group(LHH,n=6).Drugs were administered to the donepezil and LHH groups by gastric intubation.The donepezil group was administered with a dose of 0.45 mg·(kg·d)-1,while the LHH group was administered with a dose of 25 g·(kg·d)-1.The normal and model groups were given the same volume of normal saline by gastric intubation for 8 weeks.Before the rats were sacrificed,water maze and Barnes maze experiments were conducted to assess cognitive function.After sacrifice,specimens were collected for biochemical and histological examination of liver tissue and brain tissue.Non-targeted metabolomic analysis using liquid chromatography-mass spectrometry(LC-MS)was performed on feces,serum,and brain tissue to analyze changes in differential metabolites in rats.Results Compared with the model group,the intervention of Donepezil and LHH effectively improved the learning and memory ability of OICI rats(P<0.05 or P<0.01),inhibited the overactivation of hippocampal microglia,and increased the number of hippocampal synaptic proteins.LHH improved metabolic-related indicators in OICI rats(P<0.05 or P<0.01).Metabolomic analysis showed significant differences in metabolites in feces,serum,and brain tissue between the model group and the normal group.The main affected pathways in fecal metabolites included steroid biosynthesis,caffeine metabolism,lysosome,vitamin B6 metabolism,phenylalanine,tyrosine,and tryptophan biosynthesis.The main affected pathways in serum metabolites included central carbon metabolism in cancer,pentose phosphate pathway,mineral absorption,protein digestion and absorption,and aminoacyl-tRNA biosynthesis.The main affected pathways in brain tissue metabolites included glycerophospholipid metabolism,β-alanine metabolism,propionic acid metabolism,niacin and nicotinamide metabolism,and caffeine metabolism.After LHH intervention,fecal metabolites showed the most significant changes,mainly involving vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Conclusion LHH can improve cognitive impairment in obese rats mainly by regulating fecal metabolites.The main pathways involved include vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Among them,vitamin B6 metabolism and vitamin digestion and absorption may be the most important pathways.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective To investigate the clinical efficacy of the traditional Chinese medicine(TCM)throat opening and brightening method in treating unilateral vocal cord paralysis(UVCP).Methods Sixty patients with UVCP were prospectively collected and randomly assigned to two groups:the Chinese herbal medicine group(trea-ted with Buyang Huanwu Decoction,n=30)and the throat opening and brightening method group(treated with TCM throat opening and brightening method,n=30).The clinical studies that had utilized injection laryngoplasty for the treatment of UVCP(historical control group).Evaluation indicators included the voice handicap index-10(VHI-10),GRBAS-G,objective acoustic measurements of voice(vocal intensity,F0,shimmer,jitter,HNR),and aerodynamic measurements(maximum phonation time,MPT).Results Before treatment,no significant differences were observed between the two groups in all the evaluation indicators(P＞0.05).Post-treatment,the throat open-ing and brightening method group demonstrated significant improvements in VHI-10,GRBAS-G,shimmer,jitter,HNR,and MPT compared to pre-treatment values(P＜0.01),and these improvements were superior to those in the Chinese herbal medicine group.Pre-treatment VHI-10,GRBAS-G,and shimmer scores in the throat opening and brightening method group were significantly higher than those in the historical literature group(P＜0.01).Af-ter treatment,no significant differences were noted in any assessed parameters between the two groups(P＞0.05).Conclusion The TCM throat opening and brightening method significantly enhances phonatory function and quality of life in patients with UVCP,showing comparable efficacy to injection laryngoplasty.