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.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

OBJECTIVE To establish a method for simultaneous determination of plasma concentration of lamotrigine（LTG）， levetiracetam（LEV） and perampanel（PER） in children with epilepsy and apply this method in clinical practice. METHODS Plasma proteins were precipitated with acetonitrile. Using PER-D 5 as internal standard， ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method was adopted. The determination was performed on ACQUITY UPLC HSS T3 C 18 column with mobile phase consisted of 0.1% formic acid with 5 mmol/L ammonium acetate-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃， and sample size was 5 μL. The analysis time was 5 min. The electrospray ionization source and multiple reaction monitoring mode were used for positive ion scanning. The ion pairs used for quantitative analysis of LTG， LEV， PER and internal standard were m / z 255.9→144.9， m / z 171.1→126.1， m / z 350.1→219.0 and m / z 354.9→220.2， respectively. The steady-state trough concentrations of the aforementioned drugs in the plasma of 14 pediatric epilepsy patients receiving combination therapy were determined using the same UPLC-MS/MS method as above. RESULTS The linear ranges of LTG， LEV and PER were 0.15-24 μg/mL （ R 2 ＞0.993）， 0.312 5-50 μg/mL （ R 2 ＞0.997） and 6.25-1 000 ng/mL （ R 2 ＞0.997）， respectively. The lower limits of quantification were 0.15 μg/mL， 0.312 5 μg/mL and 6.25 ng/mL， respectively. RSDs of intraday and interday precision tests of the three drugs were no more than 9.83%， and the accuracies （relative errors） were between －9.33% and 13.72%（ n ＝6 or n ＝18）； the average extraction recovery rates were 86.4%-97.9%， and the average matrix effects were 86.9%-110.0% （ n ＝6）. The absolute values of the relative errors in the stability tests were all below 15%. The steady-state trough concentrations of LTG， LEV and PER were （5.64±4.03）μg/mL， （10.67±8.78）μg/mL and（450.20±251.27）ng/mL， respectively； the rates of achieving target trough concentrations were 71.4%， 37.5% and 84.6%， respectively. CONCLUSIONS The established UPLC-MS/MS method is specific， rapid and suitable for the plasma concentration monitoring in epileptic children receiving combination therapy.

ObjectiveTo construct an intelligent model for literature screening， retrieval， and data extraction with a systematic review of coronary heart disease syndromes as an example， so as to improve the efficiency of evidence-based Chinese medicine research. MethodsBased on China National Knowledge Infrastructure （CNKI）， VIP and Wanfang Data Resource System， the articles related to coronary heart disease syndrome research published from January 1， 2000 to December 31， 2023 were retrieved. Automated tools were used to batch retrieve paper metadata. Using text similarity algorithms， papers were merged， deduplicated， and subjected to preliminary screening based on titles and abstracts. Further screening was performed using object detection and image processing technologies on the full texts and statistical tables. Natural language processing （NLP） techniques and pre-trained models were applied to extract information. ResultsThe initial search retrieved 56 255 coronary heart disease syndrome-related articles. By artificial intelligence-assisted preliminary and secondary screening， the manual verification scope was narrowed to 1075 articles. Ultimately， 646 coronary heart disease syndrome related studies were included manually. With accuracy verification showing over 90% consistency in semantic recognition and element decomposition processes， we achieved data extraction and standardization processing for both basic literature information and 38 syndrome element statistics. ConclusionBy incorporating natural language processing， pre-trained models， artificial intelligence image processing and other technologies， this study enabled efficient retrieval， screening and standardized data extraction of Chinese medicine research literature.

Objective: To explore the isotemporal substitution effects among different intensities of physical activity within a 10 minute recess period on the mental health of junior high school students, aiming to provide evidence based references for targeted practical interventions. Methods: From May to November 2024, a total of 845 junior high school students from Tianjin,Taiyuan and L Liang in Shaanxi Province,Puyang in Henan Province,Xi an in Shaanxi Province,Quzhou in Zhejiang Province,and Chaoyang in Liaoning Province were selected by using a combination of stratified random sampling and convenience sampling. ActiGraph wGT3X-BT accelerometers was used to measure physical activity during a 10 minute recess period. Mental health status was assessed with the Depression Anxiety Stress Scale (DASS-21). An isotemporal substitution model was constructed in 1 minute increments to predict the effects of substituting different physical activity behaviors on students mental health. Results: During recess, sedentary behavior (SB) was predominant among junior high school students, with an average duration of [7.08(5.85,7.98)] minutes, while moderate to vigorous physical activity (MVPA) accounted for the shortest duration at [0.42(0.21,0.85)] minutes. There were statistically significant differences in MVPA,LPA and SB time between students of different genders and grades( Z/H =-9.08,-8.34,-9.51;84.87,126.82,135.27,all P <0.01). Isotemporal substitution analysis, adjusted for gender and age, showed that replacing 1 minute of SB with 1 minute of MVPA significantly improved anxiety levels ( β =-0.29, 95% CI =-0.53 to -0.04) and overall mental health ( β =-0.72, 95% CI =-1.39 to -0.04), with both results reaching statistical significance (both P <0.05). No significant effects were observed for other substitution patterns (both P >0.05). Conclusions Substituting SB with MVPA during a 10 minute recess period exerts a positive impact on the mental health of junior high school students. It is recommended to optimize the daily recess activity structure in schools to enhance students mental well being.

Objective:To evaluate value of CT perfusion in evaluating the efficacy of different vascular reconstruction methods in the treatment of adult ischemic moyamoya disease.Methods:The clinical data of 80 adult patients with moyamoya disease with ischemic blood type who received revascularization in the Affiliated Hospital of Jining Medical University from February 2019 to February 2023 were retrospectively analyzed, including 43 patients who received superficial temporal arterio-middle cerebral artery anastomosis (direct group) and 37 patients who received brain-dural arterio-artery vascularization (indirect group). The improvement of clinical symptoms, Modified Rankin Scale (mRS) Score, collateral vessels and CTP parameters were compared between the two groups.Results:The improvement of clinical symptoms in the direct group was better than that in the indirect group ( P<0.05), and the significant remission rate was significantly higher than that in the indirect group [86.0%(37/43) vs 59.5%(22/37), χ 2=7.262, P=0.007]. The postoperative mRS score in the direct group was significantly lower than that before surgery [0(0, 1) vs 1(1, 2), Z=5.550, P<0.001]. The score of mRS After surgery in the indirect group was significantly lower than that before surgery [0(0, 1) vs 1(1, 2), Z=4.281, P<0.001], but there was no statistically significant difference between the two groups ( P>0.05). There was no significant difference in digital subtraction angiography (DSA) collateral vessel formation between the two groups ( P>0.05). The CTP parameters of the two groups before and after surgery were consistent between observers and within observers [intraclass correlation coefficient (ICC) range 0.88-0.94]. In the operation area, the relative cerebral blood flow (rCBF) after surgery was significantly increased, and the relative time to peak (rTTP) and relative mean transit time (rMTT) were significantly decreased in both groups, with statistical significance ( P<0.05). In the ipsilateral basal ganglia and frontal lobe, rCBF in the direct group was significantly increased, rTTP and rMTT were significantly decreased, and the differences were statistically significant (all P<0.05), while there were no statistically significant differences in parameters in the indirect group (all P>0.05). The changes of rCBF, rTTP and rMTT in the operative area in the direct group were better than those in the indirect group, and the changes of rCBF, rTTP and rCBF in the basal ganglia and frontal lobe were better than those in the indirect group, with statistical significance (all P<0.05), while there were no statistically significant differences in the remaining parameters (all P>0.05). Conclusions:CT perfusion is of great value in evaluating the difference of clinical symptom improvement in the treatment of adult ischemic moyamoya disease with different vascular reconstruction methods.

Objective:To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) complicated by fatigue.Methods:COPD patients enrolled in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of acute exacerbations in the past year, smoking status, biofuel exposure, occupational exposure, modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1)/forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, tuberculosis, cardiovascular disease, diabetes mellitus) were collected. Fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire, with a score ≤43 defined as fatigue. Patients were divided into fatigue and non-fatigue groups, and multivariate regression analysis was used to screen factors associated with fatigue in COPD patients. Results:A total of 597 COPD patients were included, of which 280(46.9%) had fatigue symptoms. Compared with non-fatigue patients, fatigue patients had lower FEV 1%pred, FEV 1/FVC, and body mass index (BMI), higher CAT and mMRC scores, and a higher proportion of occupational exposure, bronchiectasis, and treatment with long-acting β 2-agonists (LABA)/long-acting muscarinic antagonists (LAMA)/inhaled corticosteroids (ICS) (all P<0.05). Multivariate regression analysis showed that high CAT score ( OR=2.312, 95% CI: 1.366-3.911), high mMRC score ( OR=1.484, 95% CI: 1.053-2.091), occupational exposure ( OR=1.513, 95% CI: 1.082-2.116), comorbid bronchiectasis ( OR=2.452, 95% CI: 1.102-5.457), low BMI ( OR=0.935, 95% CI: 0.891-0.981), and high CAT-energy score ( OR=1.301, 95% CI: 1.149-1.473) were risk factors for fatigue in COPD patients. The CAT-energy score was highly correlated with the FACIT-F score ( r=0.260, P<0.001), and a CAT-energy score ≥2 could preliminarily screen COPD patients with fatigue. Conclusions:COPD patients with comorbid fatigue have a heavy symptom burden, are more likely to have a history of occupational exposure and bronchiectasis, and the CAT-energy score is of great reference value for screening COPD patients with fatigue.

Objective:To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) complicated by anorexia.Methods:This cross-sectional study included patients registered in the RealDTC study from May 2023 to December 2023. Demographic data, COPD Assessment Test (CAT) score, modified Medical Research Council (mMRC) dyspnea questionnaire score, Clinical COPD Questionnaire (CCQ) score, forced expiratory volume in one second (FEV 1), forced expiratory volume in the first second predicted of percentage (FEV 1%pred), FEV 1/forced vital capacity (FVC), Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade, GOLD group, number of acute exacerbations and hospitalizations in the past year, and score of the Functional Assessment of Anorexia Cachexia Therapy-Anorexia/Cachexia Subscale-12 (FAACT-A/CS-12) were collected. Patients with a FAACT-A/CS-12 score ≤30 were diagnosed as having anorexia. Multivariate logistic regression analysis was used to evaluate the influencing factors of anorexia in COPD patients. Results:A total of 617 COPD patients were included, of whom 109(17.7%) had anorexia. Compared with non-anorexia patients, COPD patients with anorexia had higher age, CAT, mMRC and CCQ scores, and more acute exacerbations and hospitalizations in the past year, while body mass index, FEV 1, FEV 1%pred and FEV 1/FVC were lower (all P<0.05). The proportions of patients with primary education or below, GOLD 3-4 grade and GOLD E group were higher in COPD patients with anorexia (all P<0.05). Logistic regression analysis showed that a CAT score of 10-<20 [odds ratio ( OR)=4.017, 95% confidence interval ( CI): 1.673-59.645], a CAT score of 20-<30 ( OR=9.686, 95% CI: 3.777-24.842), a CAT score of ≥30 ( OR=78.286, 95% CI: 7.654-800.689) and ≥1 hospitalization in the past year ( OR=2.050, 95% CI: 1.292-3.254) were independent risk factors for anorexia in COPD patients (all P<0.05). Conclusions:COPD patients with anorexia have poor lung function, high symptom burden and high risk of acute exacerbation. Clinicians should pay attention to the management of COPD patients with anorexia and take corresponding intervention measures.

Objective:To analyze the clinical characteristics of frailty in elderly patients with chronic obstructive pulmonary disease (COPD).Methods:COPD patients aged ≥65 years registered in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of exacerbations in the past year, exposure to risk factors (smoking, biomass fuel exposure, occupational exposure), modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, pulmonary tuberculosis, cardiovascular disease, diabetes mellitus) were collected. According to Fried′s frailty phenotype, patients meeting any 3 of the 5 criteria were defined as frail and divided into a frailty group and a non-frailty group. Multivariate regression analysis was used to screen the related factors of frailty in elderly COPD patients, and the receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) of related factors for frailty assessment. Results:A total of 496 elderly COPD patients were included, of which 144(29.0%) had comorbid frailty. The frailty group had lower mass body index (BMI), FEV 1%pred, and FEV 1/FVC, higher mMRC and CAT scores, more exacerbations and hospitalizations in the past year (all P<0.001), and higher proportions of patients with junior high school education or below, Global Initiative for Chronic Obstructive Lung Disease (GOLD) group E, and GOLD grades 3 and 4 (all P<0.05). Multivariate regression analysis showed that low education level ( OR=2.117, 95% CI: 1.119-4.003), low BMI ( OR=0.927, 95% CI: 0.867-0.991), GOLD grade 4 ( OR=4.251, 95% CI: 1.477-12.235), high CAT score ( OR=1.174, 95% CI: 1.127-1.224), and high mMRC score ( OR=4.578, 95% CI: 3.364-6.231) were independent risk factors for frailty in elderly COPD patients (all P<0.05). The ROC curve showed that CAT score (AUC=0.78) and mMRC score (AUC=0.81) had the highest AUC for assessing frailty in elderly COPD patients. Conclusions:Elderly COPD patients with frailty have lower BMI, worse lung function, and more severe symptom burden. The results provide clinical reference for the management of frail elderly COPD patients.