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 understand the microclimate in primary and secondary school classrooms for the study period during the winter heating season, so as to provide a reference for the revision and improvement of relevant health standards. Methods: In December 2024, stratified random sampling was used to select 30 primary and secondary schools and 180 classrooms from the northern regions with centralized heating (Liaoning Province, Tianjin City) and the southern regions without centralized heating (Shanghai City, Anhui Province, and Jiangxi Province). Indoor temperature, relative humidity, wind speed, CO 2 and other indicators were measured on site. Variance analysis, t-test, Mann-Whitney U test and Kruskal-Wallis H test were used to analyze the differences in the microclimate of classrooms among regions and urban and rural differences. Results: The average temperature in the middle of the classrooms tested on site was (16.47±4.72)℃, and the variance analysis showed that the difference between the regions was statistically significant ( F=27.80, P <0.01). Among them, Tianjin had the highest average temperature of (20.43± 2.12 )℃, followed by Liaoning (19.03±2.23)℃, Shanghai (15.33±5.32)℃, Anhui (12.79±1.74)℃, and Jiangxi (11.69± 1.68 )℃. Horizontal temperature difference was 0.90 (0.50, 1.60)℃, the vertical temperature difference was 0.20 (0.10,0.60)℃, the average relative humidity was (44.39±16.16)%, the wind speed was 0.03(0.01,0.11)m/s, and the differences among different provinces and cities were statistically significant ( H/F =40.62, 82.69, 95.06, 55.28, all P <0.01). The average CO 2 volume concentration in urban areas of Tianjin, Liaoning, and Shanghai was 0.21(0.16,0.30)%, and there was no statistically significant difference ( H=4.65, P =0.10). There were grade differences in relative humidity ( F =3.71, 6.21) and CO 2 ( H =14.72, 12.92) in the north and the south (all P <0.05). In addition, the temperature, relative humidity, wind speed and CO 2 in the middle of the classroom were 42.8%, 67.8%, 100.0% and 22.2% respectively. Conclusions The temperature in the middle of the classroom in the non centralized heating area is lower than the standard, the relative humidity of classroom in the centralized heating area is lower than the standard，and the CO 2 in the classroom in winter is lower than the standard. It is recommended to install heating facilities in schools with low temperatures to increase the temperature and increase the frequency of ventilation in classrooms or adopt mechanical ventilation strategies to reduce CO 2 volume concentration.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Objective To explore the efficacy and safety of interventional embolism in the treatment of hemoptysis from non-bronchial arterial system.Methods We retrospectively analyzed clinical data of 23 cases of non-bronchial artery system derived hemoptysis from February 2017 to November 2024.The hemorrhagic blood vessels were only the non-bronchial artery system in 6 cases,and from the non-bronchial artery system and bronchial arteries in 17 cases.Sources of non-bronchial artery systems included 14 intercostal arteries,5 thyrocervical trunk,5 subscapular arteries,4 internal thoracic arteries,3 external thoracic arteries,5 diaphragmatic arteries,1 renal artery,and 1 left gastric artery.All the patients were treated with interventional embolism.Recurrence rate was followed up and postoperative complications were recorded.Results The immediate hemostasis rate after surgery was 95.7%(22/23).In one case,hemoptysis was relapsed within 24 h after the operation due to omission of diaphragmatic artery,and hemoptysis did not recurred after the secondary embolization.After surgery,there was 1 case of abdominal discomfort,2 cases of fever,and 2 cases of chest pain.The symptoms disappeared after conservative treatment.After the operation,the follow-up was 4-36 months(median,30 months).A total of 20 patients did not re-develop hemoptysis,while 3 had relapsed hemoptysis at 4 months,4 months,and 36 months after operation,respectively,with a recurrence rate of 13.0%(3/23).No serious complications occurred.Conclusion Interventional embolism is effective in the treatment of non-bronchial hemoptysis,which is safe and feasible.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

Objective To explore the expression of serum Linc02381 in patients with colorectal cancer(CRC)and its diagnostic value.Methods The relative expression levels of serum Linc02381 in CRC patients,patients with benign colorectal diseases and healthy individuals undergoing physical examination were detected by real-time fluorescence quantitative PCR.The relationship between the expression of serum Linc02381 in CRC patients and clinicopathological characteristics was analyzed.The levels of serum carcinoembryonic anti-gen(CEA),carbohydrate antigen 19-9,cytokeratin 19 fragment antigen 21-1(CYFRA21-1)and carbohydrate antigen 72-4 were detected by chemiluminescent immunoassay.The receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic value of serum Linc02381 and commonly used clinical tumor mark-ers for CRC.Results The relative expression level of serum Linc02381 in CRC group was compared with those in benign colorectal diseases group and healthy control group,and the difference was statistically signifi-cant(P<0.05).The relative expression levels of serum Linc02381 in CRC patients before and after the opera-tion were 2.918(2.173,3.811)and 1.809(1.495,2.014),respectively,and the difference was statistically significant(P<0.05).There was a statistically significant difference in histological stage between patients with high expression of serum Linc02381 and those with low expression of serum Linc02381(P<0.05).The results of the ROC curve showed that the area under the curve of the combined diagnosis of CRC by Linc02381,CEA and CYFRA21-1 could reach 0.905.Conclusion The combined application of serum Linc02381 with commonly used clinical such as CEA and CYFRA21-1 can improve the diagnostic value of CRC patients.

Objective·To detect the expression level of Fas-associated protein with death domain(FADD)in head and neck squamous cell carcinoma(HNSCC)and to explore the molecular mechanisms by which FADD promotes the proliferation of HNSCC cells.Methods·The GEPIA 2 database was utilized to analyze the expression level of FADD in tumor tissues and to evaluate its association with prognosis.Immunohistochemistry staining(IHC)was performed on HNSCC tissues to investigate the changes in FADD expression levels in normal,dysplastic,and tumor tissues.Stable FADD-knockdown Fadu and HSC3 cell lines were constructed and validated using Western blotting and quantitative real-time PCR(qRT-PCR).The regulatory effect of FADD on the proliferation of HNSCC cells was explored using the LiveCyte live-cell tracking system,colony formation assay,and cell viability assay.Proteins interacting with FADD were identified by co-immunoprecipitation mass spectrometry(Co-IP/MS),and further mechanistic studies were conducted using CRISPR/Cas9 technology,LiveCyte live-cell tracking system,and Western blotting.Results·Analysis of the GEPIA2 database indicated that FADD was significantly overexpressed in head and neck cancer and was associated with poor prognosis.IHC staining showed that FADD expression levels progressively increased from normal to dysplastic to tumor tissues in HNSCC patients.Knockdown of FADD in HNSCC cells resulted in significantly reduced proliferation and colony formation compared to the control group.Co-IP/MS results showed that FADD interacted with the CUX1 protein,and FADD knockdown led to increased CUX1 expression.Moreover,CUX1 knockdown significantly promoted HNSCC cell proliferation and reversed the anti-proliferative phenotype caused by FADD knockdown.Conclusion·FADD plays a significant pro-carcinogenic role in HNSCC and is associated with poor prognosis.FADD can further regulate tumor cell proliferation by interacting with CUX1 and suppressing its expression level.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

Objective·To detect the expression level of Fas-associated protein with death domain(FADD)in head and neck squamous cell carcinoma(HNSCC)and to explore the molecular mechanisms by which FADD promotes the proliferation of HNSCC cells.Methods·The GEPIA 2 database was utilized to analyze the expression level of FADD in tumor tissues and to evaluate its association with prognosis.Immunohistochemistry staining(IHC)was performed on HNSCC tissues to investigate the changes in FADD expression levels in normal,dysplastic,and tumor tissues.Stable FADD-knockdown Fadu and HSC3 cell lines were constructed and validated using Western blotting and quantitative real-time PCR(qRT-PCR).The regulatory effect of FADD on the proliferation of HNSCC cells was explored using the LiveCyte live-cell tracking system,colony formation assay,and cell viability assay.Proteins interacting with FADD were identified by co-immunoprecipitation mass spectrometry(Co-IP/MS),and further mechanistic studies were conducted using CRISPR/Cas9 technology,LiveCyte live-cell tracking system,and Western blotting.Results·Analysis of the GEPIA2 database indicated that FADD was significantly overexpressed in head and neck cancer and was associated with poor prognosis.IHC staining showed that FADD expression levels progressively increased from normal to dysplastic to tumor tissues in HNSCC patients.Knockdown of FADD in HNSCC cells resulted in significantly reduced proliferation and colony formation compared to the control group.Co-IP/MS results showed that FADD interacted with the CUX1 protein,and FADD knockdown led to increased CUX1 expression.Moreover,CUX1 knockdown significantly promoted HNSCC cell proliferation and reversed the anti-proliferative phenotype caused by FADD knockdown.Conclusion·FADD plays a significant pro-carcinogenic role in HNSCC and is associated with poor prognosis.FADD can further regulate tumor cell proliferation by interacting with CUX1 and suppressing its expression level.