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.

ObjectiveThe frequency difference limen (FDL) serves as a fundamental metric utilized for effectively quantifying the precise perceptual capabilities of the central auditory system. However, traditional measurement methods rely heavily on the active behavioral responses of subjects and are consequently highly susceptible to the negative influence of confounding subjective factors. Furthermore, existing research paradigms frequently employ uniform stimulus configurations that overlook critical individual perceptual differences. Based on brain-computer interface (BCI) technology, this comprehensive study aims to establish an objective and quantitative evaluation method for auditory frequency discrimination by systematically analyzing and decoding the specific neural responses elicited at the exact threshold state. MethodsWe designed a personalized rapid serial auditory presentation (RSAP) paradigm customized based on each individual’s precise FDL. A cohort of eleven healthy participants was recruited to evaluate the paradigm using pure-tone sequences at a baseline frequency of 4 000 Hz. This experimental paradigm simulates a realistic auditory perception environment through the continuous presentation of acoustic stimuli, thereby allowing for an in-depth investigation into the specific neural representations evoked by weak frequency deviations at the threshold state. Given that auditory stimulus-evoked response features exhibit complex and differentiated spatiotemporal distribution patterns across multiple frequency domains, this study further deeply integrates the cross-scale feature interaction module with the dynamic spatiotemporal attention allocation strategy, innovatively proposing the Multi-Scale Spatial-Temporal Dual Attention Network (MS-STAMNet). Specifically, the network constructs parallel processing branches with multiple receptive fields and introduces a dynamic adaptive weighting strategy to precisely localize core neural activity signals, further deeply integrating multi-scale information through cross-branch feature information interaction to achieve robust single-trial decoding of weak auditory evoked responses. ResultsThe comprehensive electrophysiological data analysis demonstrated that subtle auditory frequency deviation stimuli presented at the threshold level successfully elicited pronounced N2 and P3 event-related potential features, reflecting pre-attentive mismatch detection and subsequent cognitive evaluation, which were prominently distributed over the frontal, central, and temporal regions of the scalp. In the complex time-frequency domain, the extracted neural response characteristics exhibited distinct, statistically significant event-related synchronization within both the low-frequency δ and θ frequency bands, which was simultaneously accompanied by a widespread, prominent event-related desynchronization within the higher α band. A comparative analysis of model performance demonstrated that MS-STAMNet achieved an average unweighted average recall (UAR) of (69.67±6.12)% and area under the curve (AUC) of 0.761 8±0.07, significantly outperforming the established baseline models such as EEGNet and PLNet. Furthermore, a distinct dissociation phenomenon was verified between neural decoding and behavioral performance through regression analysis (R²=0.016, P=0.709), indicating that this model can effectively capture the implicit features of subtle frequency deviations, even when they fail to trigger explicit conscious responses. Additionally, attention weight visualization analysis further reveals the highly accurate focus of the network on key features concentrated over the bilateral temporal and fronto-parietal regions. ConclusionThis study systematically and comprehensively uncovers the multi-dimensional spatiotemporal evolutionary patterns of complex neural responses processing subtle acoustic variations under long-sequence threshold auditory stimulation. Concurrently, it verifies the efficacy and robustness of the proposed MS-STAMNet architecture in accurately deciphering weak, single-trial electroencephalogram signals amidst complex background noise. Ultimately, these neurophysiological and algorithmic findings lay a solid theoretical and methodological foundation for the objective and quantitative evaluation of individual auditory cognitive capabilities in clinical applications, transcending the fundamental limitations of traditional behavioral paradigms and providing robust technical support for future auditory research and related clinical assessments.

Background Diarrhea disease is a common intestinal infectious disease, and its incidence is affected by meteorological conditions. A better understanding of its epidemiological patterns and influencing factors, together with the construction of reliable prediction models, is of great significance for precise public health prevention and control. Objective To clarify the epidemic characteristics of adult diarrhea disease in Shanghai, analyze the associations of meteorological factors and a web search index with adult diarrhea disease, and develop and compare forecasting models to support precise regional prevention and control. Methods Weekly surveillance data of adult diarrhea disease cases from the Shanghai Comprehensive Surveillance Information System for Diarrhea Diseases, together with concurrent meteorological observation data and web search index (Baidu index) data from 2014 to 2019, were collected. A distributed lag non-linear model (DLNM) was adopted to analyze the associations of multiple meteorological factors and the web search index with the number of diarrhea disease cases. By integrating meteorological factors and web search index data, three types of forecasting models were developed, including autoregressive integrated moving average (ARIMA), Random Forest, and extreme gradient boosting (Xgboost), and their predictive performances were evaluated. Results Adult diarrhea disease in Shanghai exhibited seasonal variation, with an major incidence peak in summer and winter peaks in some years. The number of cases declined annually after 2015. Mean temperature was significantly associated with the risk of diarrhea disease, and both low and high temperature exposures were associated with increased risks. The highest risk was observed at 32.8°C (RR=2.04, 95%CI: 1.62, 2.55), while the strongest effect of low temperature was observed at 0.9 °C (RR=1.53, 95%CI: 1.25, 1.88). When relative humidity exceeded 69%, the risk of diarrhea disease increased with relative humidity, reaching a peak at 81% (RR=1.20, 95%CI: 1.07, 1.35). When weekly cumulative precipitation exceeded 16 mm, the risk also increased with increasing precipitation, reaching a maximum at 105 mm (RR=1.23, 95%CI: 1.07, 1.42). The web search index was positively associated with the risk of diarrhea disease. Model prediction indicated that both the Random Forest model and the Xgboost model adequately captured the overall trend in diarrhea disease cases, with R² values generally exceeding 0.7. Notably, the Xgboost model demonstrated greater accuracy in capturing peak intensities. Conclusion Meteorological factors are associated with adult diarrhea disease in Shanghai. The web search index may serve as an auxiliary indicator for diarrhea forecasting. Machine learning models, with advantages in integrating multisource data, may provide effective predictive tools for the prevention and control of diarrhea disease.

Objective: To investigate the association of sleep and circadian rhythm disruption indicators (including chronotype, sleep duration, and social jetlag) with co-occurring depressive and anxiety symptoms among primary and secondary school students, so as to provide a reference for promoting their mental health. Methods: In October 2023, a total of 15 944 primary and secondary school students were recruited from Nanjing, using a stratified cluster random sampling method. The Morning and Evening Questionnaire-5, Center for Epidemiological Studies Depression, and Generalized Anxiety Disorder-7 were used for the survey. Chi-square test was employed for intergroup comparisons, and Logistic regression model was applied to analyze the independent and joint effects of sleep related factors on comorbid symptoms of depressive and anxiety among primary and middle school students. Results: The prevalence of co-occurring depressive and anxiety symptoms among primary and secondary school students in Nanjing was 16.9%. After adjusting for covariates, Logistic regression analysis revealed significant independent associations between evening chronotype ( OR=6.55, 95%CI =5.59-7.68), insufficient sleep duration ( OR=3.05, 95%CI =2.60-3.59), and social jetlag ≥2 h ( OR= 2.09 , 95%CI =1.85-2.37) with comorbid symptoms of depressive and anxiety among students (all P <0.05). Concurrent of evening chronotype and insufficient sleep ( OR=7.54, 95%CI =3.55-16.01), as well as evening chronotype and social jetlag ≥2 h ( OR=4.18, 95%CI =3.01-5.81), were associated with an increased risk of co-occurring depressive and anxiety symptoms (both P < 0.05 ). In the female and high school student subgroups, the combination of evening chronotype and insufficient sleep or social jetlag ≥2 h showed stronger joint effects on co-occurring depressive and anxiety symptoms [ OR (95% CI )=8.46(3.25-22.04) and 15.90(3.66-69.08); 7.87(4.90-12.65) and 4.85(3.10-7.59), respectively; all P <0.05]. Conclusions Evening chronotype, insufficient sleep, and social jetlag≥2 h may serve as risk factors for comorbid symptoms of depressive and anxiety in school aged populations. Paying attention to the coexistence of multiple sleep related risk factors may help mitigate the occurrence of emotional disorders in this demographic.

OBJECTIVE: To investigate the effects of Huayu Tongluo (transforming stasis and unblocking collaterals) moxibustion on cognitive function and insulin resistance in patients with type 2 diabetes mellitus (T2DM) and cognitive decline. METHODS: Ninety patients with T2DM and cognitive decline were randomly divided into a moxibustion group (n=45, 3 cases dropped out, 2 cases were eliminated) and a waiting moxibustion group (n=45, 2 cases dropped out). Both groups received routine hypoglycemic treatment for 12 weeks. The moxibustion group additionally received Huayu Tongluo moxibustion at Baihui (GV20), Shenting (GV24), and Dazhui (GV14). Pressing moxibustion was applied to Baihui (GV20) for 20 min, while suspended moxibustion was applied to Shenting (GV24) and Dazhui (GV14) for 20 min each. Treatments of moxibustion were administered every other day (three times per week) for 12 weeks. All patients were followed up for 12 weeks, during which their original hypoglycemic medication regimen was maintained. Before treatment, after 12 weeks of treatment, and at the 12-week follow-up, the scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), Addenbrooke's cognitive examination Ⅲ (ACE-Ⅲ), symbol digit modalities test (SDMT), and Athens insomnia scale (AIS) and the insulin resistance index (HOMA-IR) were observed in the two groups. RESULTS: Compared with before treatment, the MoCA scores, MMSE scores, ACE-Ⅲ subscale scores (attention, memory, language fluency, language, visuospatial ability) and total scores, and SDMT scores were increased (P<0.01), while the AIS scores were decreased (P<0.05) in the moxibustion group after treatment and at follow-up. Compared with before treatment, the MMSE score, ACE-Ⅲ subscale scores (memory, attention) and total score after treatment, as well as the ACE-Ⅲ subscale scores (language, memory, attention) and total score, and SDMT score at follow-up were increased (P<0.05, P<0.01) in the waiting moxibustion group. Compared with before treatment, HOMA-IR was decreased in both groups after treatment and at follow-up (P<0.01). At follow-up, ACE-Ⅲ subscale scores (attention, memory), and the total score in the moxibustion group were lower than those after treatment (P<0.05, P<0.01), and the ACE-Ⅲ language subscale score, total ACE-Ⅲ score, and SDMT score in the waiting moxibustion group were higher than those after treatment (P<0.01, P<0.05). After treatment and at follow-up, compared with the waiting moxibustion group, the moxibustion group had higher MoCA scores, MMSE scores, SDMT scores, ACE-Ⅲ subscale scores (attention, memory, language fluency) and total scores (P<0.05, P<0.01), and lower HOMA-IR (P<0.05). CONCLUSION Huayu Tongluo moxibustion can effectively improve cognitive function in patients with T2DM and cognitive decline. This improvement may be associated with the reduction in insulin resistance.
Humans ; Insulin Resistance ; Diabetes Mellitus, Type 2/complications* ; Male ; Female ; Moxibustion ; Middle Aged ; Aged ; Cognition ; Acupuncture Points ; Adult ; Cognitive Dysfunction/therapy*

Objective:To construct a Logistic regression model based on the energy spectral computed tomography(CT)parameters and clinical parameters characteristics,and to evaluate its diagnostic efficacy in the benign and malignant pulmonary ground glass nodules(GGN).Methods:162 GGN patients who were admitted to our hospital from April 2022 to March 2024 were selected,they were divided into benign group and malignant group according to pathological results.The difference of CT parameters[water content in normal scan period,water content in arterial period,slope of energy spectral curve in normal scan period and k value in arterial period]and clinical data between the two groups was compared.Multivariate Logistic regression model was used to analyze the independent influencing factors of malignant GGN.Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of the model for malignant GGN.Results:Water content in normal scan period in malignant group was significantly higher than that in benign group(P＜0.05).k value in normal scan period in the malignant group was significantly higher than that in the benign group(P＜0.05).Water content in arterial period in malignant group was higher than that in benign group(P＜0.05).k value in arterial period in the malignant group was higher than in benign group(P＜0.05).There were significant differences in smoking history,family history of tumor and chronic obstructive pulmonary disease(COPD)between benign group and malignant group(P＜0.05).Multivariate Logistic regression model analysis showed that,water content in normal scan period,k value in normal scan period,k value in arterial period,water content in arterial period,smoking history and family history of tumor were independent influencing factors of malignant nodule in GGN patients(P＜0.05).Based on the results of multi-factor Logistic regression analysis,the Logistic regression prediction model was constructed:logit(P)=ln(P/l-P)=0.015× water content in arterial period+1.214× smoking history+1.506× family history of tumor+0.013× water content in normal scan period 0.553× k value in normal scan period+0.202 × k value in arterial period.ROC curve results showed that the area under the curve(AUC)of the combined prediction model was 0.852,which was significantly higher than 0.654,0.607,0.628,0.759,0.707,0.682 of water content in normal scan period,k value in normal scan period,k value in arterial period,water content in arterial period,smoking history and family history of tumor.Conclusion:The Logistic regression model constructed based on the characteristics of energy spectral CT parameters and clinical parameters characteristics has good diagnostic efficacy for benign and malignant GGN.

This study explored the effects and underlying mechanism of Raf kinase inhibitory protein(RKIP)on apoptosis in mast cells sensitized by Echinococcus granulosus cyst fluid.Bone marrow-derived mast cells(BMMCs)were isolated and cultured from RKIP knockout(KO)and wild-type(WT)C57BL/6 mice.Cells were divided into control and sensitized groups.The sensitized group was incubated for 24 h in RPMI1640 medium containing 10%serum from mice infected with E.granulosus,then activated for 3 h or 6 h with E.granulosus cyst fluid.The control group was incubated for 24 h in RPMI1640 medium,and then received an equal vol-ume of PBS.Cells and supernatants were collected for analysis.Flow cytometry was used to detect the expression of CD117 and FcεRⅠα on BMMCs.The levels of β-hexosaminidase,IL-4,and TNF-α in the supernatant were quantified with ELISA.Western blot analy-sis was used to assess expression changes in RKIP,apoptosis-related proteins,and pathway proteins in BMMC before and after sensi-tization.Flow cytometry analysis revealed that after 4 weeks of induction,the CD117 and FcεRⅠα double-positivity rates on both WT and KO BMMC exceeded 90%.ELISA indicated that the E.granulosus cyst fluid resulted in significantly greater β-hexosaminidase re-lease(F=16.88,P<0.05),and levels of IL-4(F=16.51,P<0.05)and TNF-α(F=9.78,P<0.05)in the KO sensitized group than the WT sensitized group.With respect to the WT control group,the WT sensitized group showed significantly down-regulated pro-tein expression levels of RKIP(F=8.20,P<0.05)and Bcl-2(F=101.40,P<0.01)after 3 h,but significantly up-regulated levels of p-PI3K(F=8.04,P<0.05),p-Akt(F=32.52,P<0.01),p-P65(F=13.29,P<0.05),and cleaved-caspase-3(F=46.34,P<0.01).With respect to the WT sensitized group,the KO sensitized group showed significantly up-regulated protein expression of p-PI3K(F=8.45,P<0.05),p-Akt(F=8.58,P<0.05),p-P65(F=11.02,P<0.05),and Bcl-2(F=84.50,P<0.001)after 3 h,but significantly down-regulated expression of cleaved-caspase-3(F=15.66,P<0.05).In conclusion,RKIP may inhibit the PI3K/Akt/NF-κB pathway,thereby inducing apoptosis in mast cells sensitized by E.granulosus cyst fluid.This process may help ease aller-gic reactions caused by mast cells in echinococcosis,thus offering a promising new approach for preventing and treating such reactions.

Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter，single-arm，retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients，47 were male（79.7%）and 12 were female（20.3%），with a median age of 63.0（56.0，68.0）years and a body mass index of（24.7 ± 3.0）kg/m 2. Surgical procedures included 32 radical prostatectomies，24 partial nephrectomies，one radical nephrectomy，one adrenalectomy，and one ureteral reconstruction. The perioperative indicators，pathological results and postoperative complications were analyzed. The network monitoring data were collected，and the perioperative data of patients，remote system monitoring data and costs were compared between the two communication modes of optical transport network（OTN）and cloud-connect network（CCN）. Results:All 59 remote surgeries were successfully completed，with a mean operative time of（138.0 ± 54.0）minutes，median intraoperative blood loss of 50.0（30.0，100.0）ml and a postoperative hospital stay of 5.0（4.0，6.0）days. No cases required reoperation，Clavien-Dindo grade ≥3 complications，or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing：the shortest latency time（Hefei-Hangzhou，450 km）was（16.59 ± 0.80）ms，while the longest（Harbin-Hangzhou，2 200 km）latency time was（53.31 ± 0.31）ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time［（130.7 ± 70.5）minutes vs.（142.1 ± 42.9）minutes， P = 0.442］，postoperative hospitalization［6.0（4.0，8.0）d vs. 5.0（4.0，6.0）d， P = 0.581］，or readmission rates（0 vs. 0）. However，CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode，with its cost-effectiveness，excellent usability，and multi-point interconnection flexibility，is currently the preferred communication model for telesurgical applications.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.