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 application value of optimized mesenteric defect closure technique in laparoscopic-assisted right hemicolectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 26 patients who underwent laparo-scopic-assisted right hemicolectomy at Changzhi People′s Hospital Affiliated to Changzhi Medical College from May 2023 to June 2024 were collected. There were 11 males and 15 females, aged (65.7±1.8)years. All patients received optimized mesenteric defect closure using a combined extra-corporeal-laparoscopic suturing technique. Observation indicators: (1) surgical and intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. Results:(1) Surgical and intraoperative conditions. All 26 patients underwent laparoscopic-assisted right hemicolectomy with optimized mesenteric defect closure. The time of optimized mesenteric defect closure was 9.8(8.8,12.8)minutes, time of digestive tract reconstruction was 10.0(8.7,13.0)minutes, operation time was (164±4)minutes, volume of intraoperative blood loss was 50(50,100)mL. One of the 26 patients had intraoperative mesenteric hematoma, which required no specific intervention. The patient recovered uneventfully and was discharged from hospital. (2) Postoperative conditions. The visual analog scale pain score of 26 patients on postoperative day 1 and day 3 were 5(4,5) and 3(2,3), respectively. Time to postoperative first anal flatus and bowel movement were both 3(3, 4)days. Time to postoperative first intake of liquid diet was 2(2,3)days, duration of postoperative abdominal drainage was 4(3,5)days, and duration of postoperative hospital stay was 9(8,12)days. The number of lymph node dissected in 26 patients was 25(18,27) and the number of positive lymph node was 1(0,2). Cases in stage Ⅰ, stage Ⅱ and stage Ⅲ of tumor TNM staging were 5, 6, 15. (3) Follow-up. All 26 patients were followed up for 15(range, 6?20)months. Of the 26 patients, one case had incom-plete intestinal obstruction on postoperative day 25, which was diagnosed as adhesive intestinal obstruction based on imaging examination and classified as Clavien-Dindo grade Ⅱ. The patient recovered and was discharged after conservative treatment. None of the 26 patients had bleeding, infection of incision, anastomotic leakage, internal hernia, or delayed gastric emptying. There was no tumor recurrence, metastasis or death.Conclusion:The optimized mesenteric defect closure tech-nique in combined extracorporeal-laparoscopic suturing procedure can be used in laparoscopic-assisted right hemicolectomy.

Flap surgery is a complex surgical procedure that has become an effective method for the treatment of many diseases and traumas.Flap survival is closely related to a variety of factors including cellular autophagy,oxidative stress,inflammatory response,mesenchymal stem cells(MSCs)function,and vascular regeneration.Cellular autophagy maintains intracellular homeostasis and plays a key role in reducing oxidative stress and inflammation and promoting injury repair.Excessive oxidative stress and inflammatory responses pose a threat to flaps,affecting their survival and successful transplantation.Endothelial cells are involved in vascu-lar regeneration through proliferation,migration,and production of angiogenic factors,and vascular endothelial growth factor directly promotes blood vessel formation and maintains endothelial cell function.MSCs play an important role in promoting flap survival and tissue repair due to their unique biological properties and multiple mechanisms of action.The multiple roles played by cellular autophagy,oxidative stress,inflammatory response,MSCs function,and vascular regeneration in influencing postoperative flap survival are hereby elaborated.The aim is to provide a basis for the clinical application of regulating the above factors to improve postoperative flap survival,improve the success rate of flap surgery,reduce complications,and bring more hope for the recovery and quality of life of patients.

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 investigate the application value of optimized mesenteric defect closure technique in laparoscopic-assisted right hemicolectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 26 patients who underwent laparo-scopic-assisted right hemicolectomy at Changzhi People′s Hospital Affiliated to Changzhi Medical College from May 2023 to June 2024 were collected. There were 11 males and 15 females, aged (65.7±1.8)years. All patients received optimized mesenteric defect closure using a combined extra-corporeal-laparoscopic suturing technique. Observation indicators: (1) surgical and intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. Results:(1) Surgical and intraoperative conditions. All 26 patients underwent laparoscopic-assisted right hemicolectomy with optimized mesenteric defect closure. The time of optimized mesenteric defect closure was 9.8(8.8,12.8)minutes, time of digestive tract reconstruction was 10.0(8.7,13.0)minutes, operation time was (164±4)minutes, volume of intraoperative blood loss was 50(50,100)mL. One of the 26 patients had intraoperative mesenteric hematoma, which required no specific intervention. The patient recovered uneventfully and was discharged from hospital. (2) Postoperative conditions. The visual analog scale pain score of 26 patients on postoperative day 1 and day 3 were 5(4,5) and 3(2,3), respectively. Time to postoperative first anal flatus and bowel movement were both 3(3, 4)days. Time to postoperative first intake of liquid diet was 2(2,3)days, duration of postoperative abdominal drainage was 4(3,5)days, and duration of postoperative hospital stay was 9(8,12)days. The number of lymph node dissected in 26 patients was 25(18,27) and the number of positive lymph node was 1(0,2). Cases in stage Ⅰ, stage Ⅱ and stage Ⅲ of tumor TNM staging were 5, 6, 15. (3) Follow-up. All 26 patients were followed up for 15(range, 6?20)months. Of the 26 patients, one case had incom-plete intestinal obstruction on postoperative day 25, which was diagnosed as adhesive intestinal obstruction based on imaging examination and classified as Clavien-Dindo grade Ⅱ. The patient recovered and was discharged after conservative treatment. None of the 26 patients had bleeding, infection of incision, anastomotic leakage, internal hernia, or delayed gastric emptying. There was no tumor recurrence, metastasis or death.Conclusion:The optimized mesenteric defect closure tech-nique in combined extracorporeal-laparoscopic suturing procedure can be used in laparoscopic-assisted right hemicolectomy.

Objective To comprehensively evaluate the multidimensional impact of the"Tianjin Experience"of Chest Pain Center(CPC)development on in-hospital mortality,optimization of treatment workflows,and regional coordination of care for patients with acute myocardial infarction(AMI),with the aim of providing scientific evidence to further improve the model and enhance AMI treatment outcomes.Methods This study analyzed data from the"Cardiovascular and Cerebrovascular Acute Events Surveillance System"maintained by the Tianjin Center for Disease Control and Prevention from 2013 to 2024.A segmented regression model was applied to assess the long-term trends in in-hospital mortality from acute myocardial infarction(AMI),with a particular focus on evaluating the impact of the chest pain center program on treatment outcomes.Additionally,supplementary analyses were conducted using surveillance data from the Tianjin Chest Pain Center Quality Control Team between 2017 and 2024.To verify the effectiveness of treatment process optimization,temporal trends in key time-based process indicators were assessed,including Door-in-Door-out(DIDO)time at non-PCI hospitals,Door-to-Wire(D-to-W)time,and First Medical Contact to Wire(FMC-to-W)to wire time.Results According to the data from the Tianjin Center for Disease Control and Prevention,the average 28-day AMI mortality rate in the overall patient population was 9.85％.Between 01/2013 and 12/2014,the mortality rate showed a significant upward trend(P＜0.01),followed by a downward trend from 01/2015 to 12/2024,although the latter did not reach statistical significance(P＞0.05).From 2013 to 2024,a total of 27 633 AMI cases with complete clinical records were collected from Tianjin Chest Hospital,with an average 28-day mortality rate of 4.55％.The mortality rate exhibited a decreasing trend from 01/2013 to 12/2016,with an annual percent change(APC)of-7.56(P＜0.05).From 01/2017 to 12/2024,the trend stabilized,with an APC of 0.39(P＞0.05).Conclusions The development of the CPC system in Tianjin significantly reduced key treatment times and improved the overall efficiency of AMI management.While population-level AMI mortality rates began to decline after 2015,the rate of improvement has slowed,indicating a continued need for optimizing the regional coordinated care system to further enhance patient outcomes.

Aim To explore the mechanism of ligustil-ide(LIG)improving demyelination by inhibiting in-flammatory response in mice with distal middle cerebral artery occlusion(dMCAO)through AIM2/caspase-1 signal pathway.Methods Thirty C57BL/6N male mice were randomly divided into three groups:sham operation group(Sham group,n=10),model group(dMCAO group,n=10)and treatment group(LIG group,n=10).The dMCAO mouse model was estab-lished by electrocoagulation in dMCAO group and LIG group.The mice were scored by Longa after waking up,and the changes of cerebral blood flow were moni-tored by laser speckle blood flow imaging system after dMCAO.One hour after modeling,LIG(30 mg·kg-1·d-1)was injected intraperitoneally in LIG group,and the same amount of normal saline was injected in sham group and dMCAO group for one week until the end of the experiment.The mice in each group were stained with TTC,and the brain injury was observed pathologically.Fatigue turning bar test and open field test were used to evaluate the motor function and anxie-ty degree of mice,and then the brain tissues of mice were taken for black gold staining to compare the chan-ges of myelin sheath in each group.Immunofluores-cence staining was used to detect the average fluores-cence intensity of MBP,IBA1 and GFAP in CC,CPU and CX regions of mouse brains.ELISAwas used to de-tect the contents of TNF-α,IL-6,IL-1 β,IL-17A and BDNF in brain tissue proteins of mice.Western blot-ting was used to detect the protein expressions of AIM2,caspase-1 and ASC-in each group.Results Compared with the dMCAO group,the infarct area was reduced,the behavior was significantly improved and the demyelination was reduced in the LIG group.The expression of MBP protein in CC,CPU and CX regions increased(P＜0.05),the expression of IBA1 in CX decreased(P＜0.01),and the expression of GFAP in-creased in CC,CPU and CX regions(P＜0.01).The results of ELISA showed that the levels ofTNF-α(P＜0.01),IL-6(P＜0.01),IL-1β(P＜0.05)and IL-17A(P＜0.01)significantly decreased,while the ex-pression of BDNF increased(P＜0.05).The protein expression levels of AIM2,caspase-1 and ASC in mouse brain decreased after treatment(P＜0.01).Conclusion LIG has a protective effect on demyelina-tion in dMCAO mice,which may be related to the inhi-bition of AIM2/caspase-1 signaling pathway and in-flammation and to the promotion of BDNF secretion.

Objectives:To assess the situation of retained cardiac implantable electronic device(CIED)leads after cardiac transplantation,the associated factors,and their impact on long-term prognosis.Methods:A retrospective analysis was conducted on 1 096 patients who underwent cardiac transplantation at Fuwai Hospital of the Chinese Academy of Medical Sciences from January 1,2005 to January 1,2022.Among them,204 patients(18.6%)received CIED therapy before cardiac transplantation.Two physicians independently reviewed the pre-and post-transplant chest X-rays to determine the presence of retained CIED leads.Logistic multivariate regression analysis was used to assess factors associated with retained CIED leads,and Kaplan-Meier survival curves were plotted to analyze the impact of retained CIED leads on long-term prognosis.Results:Among the 204 patients who received CIED therapy before cardiac transplantation,the highest proportion were those treated with implantable cardioverter defibrillator(ICD)and cardiac resynchronization therapy-defibrillator(CRT-D),accounting for 47.5%(97/204)and 40.7%(83/204),respectively.The mean duration from CIED implantation to cardiac transplantation was(45.1±40.0)months,and 38 patients(18.6%)had retained CIED leads after cardiac transplantation.The results of the logistic multivariate regression analysis showed that the duration from CIED implantation to cardiac transplantation was the only factor associated with retained CIED leads after cardiac transplantation(OR=1.020,95%CI:1.011-1.030,P=0.000).Cumulative all-cause survival rates among patients without CIED implantation(n=892),those without retained CIED leads(n=166),and those with retained CIED leads(n=38)were 88.5%,93.3%and 84.2%,respectively.Kaplan-Meier survival curve analysis showed no significant difference in cumulative all-cause survival among the three groups(log-rank P=0.643).Conclusions:In patients who received CIED implantation before cardiac transplantation,18.6%had retained leads after surgery.The duration from CIED implantation to cardiac transplantation is the only factor associated with lead retained after cardiac transplantation,but retained leads does not affect the outcome post heart transplantation.

Objective To investigate the potential mechanisms of anti-dizziness drugs in treating motion sickness.Methods Literature mining was utilized to obtain commonly used drugs for the treatment of dizziness.Corresponding targets for motion sickness were identified using databases such as GeneCards and literature,while the Herb database was used to obtain targets corresponding to drugs.Venn diagrams were employed to find the intersection of drug treatment targets,and the DAVID database was used for KEGG and GO analysis to determine the pathways corresponding to these targets.Sankey diagram tools were used to obtain the number of significant pathways corresponding to each target,thereby identifying core targets.The TCMSP database and literature were used to acquire the effective chemical components corresponding to each drug,and core components were determined based on the number of corresponding drugs.The intersection with core targets was taken to identify corresponding targets.The HPA database,along with single-cell transcriptomics and spatial transcriptomics,was used to determine the distribution of corresponding targets in brain neurons.Finally,AutoDock was used to determine the docking status between core effective components and core targets.Results A literature database was used to obtain 13 high-frequency drugs for treating dizziness,with 379 corresponding targets after deduplication.Databases and literature provided 1198 high-credibility targets corresponding to motion sickness,with 89 intersection targets between drugs and diseases.GO enrichment analysis yielded 1237 significant entries,including positive regulation of miRNA transcription,and KEGG enrichment analysis identified 51 neural function-related signaling pathways,such as the neuroactive ligand-receptor interaction pathway and the glutamatergic synapse pathway.Sankey diagrams identified 18 core genes,including MAPK3,AKT1,MAPK1,PRKCA,and INSR;drug component analysis determined beta-sitosterol as the core component,which can form good molecular docking with MAPK14,Bcl-2,and PRKCA.Conclusion Anti-dizziness drugs possess the potential to treat motion sickness and may exert neuroprotective effects through neural function-related pathways such as the neuroactive ligand-receptor interaction pathway and the glutamatergic synapse pathway.beta-sitosterol,as a core natural compound,can interact with proteins related to neural function and warrants further research and exploration.

Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.