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.

ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Objective:To investigate the efficacy and safety of transurethral water vapor thermal therapy(WVTT)using the Rezūm system for benign prostatic hyperplasia(BPH)in the real world.Methods:A total of 181 patients with BPH were recruited from the Second Affiliated Hospital of Nanjing Medical University from August 2022 to December 2023,of whom 173 patients were treated with WVTT using the Rezūm system,while 8 patients were treated with WVTT combined with TURP.They were followed up at 1,3,and 6 months postoperatively to assess changes in the IPSS,QoL,Qmax,IIEF-5,and the occurrence of any complications.Results:All 181 surgeries in this group were successfully completed.The operation time of the Rezūm system was(4.6±1.4)mi-nutes.The postoperative indwelling catheterization time was(8.0±2.1)days.With a follow-up of at least 6 months,there was a significant decrease in PV,IPSS and QoL,and a remarkable increase had been found in Qmax as well(P＜0.05).There was no sig-nificant difference in IIEF-5 before and after the operation(P＞0.05).In this groups of patients,postoperative complications mainly included 95 cases(52.5％)of gross hematuria,6 cases(3.3％)of retrograde ejaculation,5 cases(2.8％)of urethral stricture,4 cases(2.2％)of prostatitis,and 10 cases(5.5％)of urinary tract infection.Four cases(2.2％)underwent surgical retreatment for BPH after surgery.Conclusion:In the real world,the use of Rezūm thermal steam ablation system for the treatment of BPH has sat-isfactory short-term effect,short surgical time,and significant improvement in IPSS,QoL,Qmax,which does not adversely affect sexu-al function.

Objective To determine the knee joint cartilage thickness using different methods and explore the feasibility of mathematical statistical models of dataset for the prediction of cartilage thickness.Methods A total of 304 patients diagnosed as knee osteoarthritis(OA)combined with varus deformity and undergoing unilateral total knee arthroplasty at the Second Affiliated Hospital of Army Medical University from March 2023 to March 2024 were selected for the study.All patients had complete preoperative and postoperative clinical data.The healthy cartilage at four anatomical sites of patients,including the distal femur lateral condyle,lateral tibial plateau,posterior medial femoral condyle,and posterior lateral femoral condyle were selected,and the knee joint cartilage thickness was determined based on preoperative MRI analysis,robotic navigation system tracing,tissue section of surgical specimen and digital vernier caliper.The baseline indicators of demographics,disease and imaging ffor patients were collected to construct a dataset,and four models of linear regression analysis,principal component analysis,Least Absolute Shrinkage and Selection Operator(LASSO)regression analysis,and K-nearest neighbors(KNN)analysis were established for predicting the accuracy,determination coefficient(R2)and root mean square error(RMSE),and the regression equation for predicting cartilage thickness was established.Results The knee joint cartilage thicknesses determined by preoperative MRI analysis,robotic navigation system tracing,tissue section of surgical specimen had no statistically significant difference with that by digital vernier caliper(P>0.05).The predictive efficiencies of models of linear regression analysis,principal component analysis,and LASSO regression analysis for the knee joint cartilage thickness all failed to meet the expectations(R2<0.3,RMSE>0.03).The predictive effect of KNN model on the cartilage thickness of the distal femur lateral condyle and lateral tibial plateau was not ideal(R2=0.23,RMSE=0.29),while it had potential predictive value(accuracy=0.21,accuracy=0.15).Conclusion The prediction model of knee joint cartilage thickness based on individual parameters has certain scientificity,and the feasibility of KNN model is relatively high.However,due to insufficient sample size and unclear individual parameter weight,the efficiencies of the four established prediction models are not ideal,which fails to provide definite prediction equations.Therefore,the construction scheme of the prediction model still needs to be further optimized.

Objective:To predict mechanical complications (MC) following spinal deformity surgery for adult spine deformity (ASD) using machine learning models, identify key risk factors, and develop a visualizable tool for individualized risk assessment.Methods:Clinical and radiological data from 525 patients with ASD who underwent surgery in our hospital between January 2017 and December 2021 were collected. Patients were randomly assigned to a training set (70%) and a test set (30%) for model development. The cohort included 88 males and 437 females, with a mean age of 42.2±18.1 years. Variables included demographic data, comorbidities, local and systemic radiological parameters, paraspinal muscle fat infiltration (FI), and vertebral bone quality (VBQ) scores. Multiple machine learning algorithms: Random Forest (RF), Gaussian Naive Bayes (GNB), Light GBM, Support Vector Machine (SVM), XGBoost (XGB), and Logistic Regression (LR) were trained and evaluated. Model performance was compared using the receiver operating characteristic curve (ROC) and precision-recall curve (PRC). SHAP (Shapley Additive Explanations) was used to rank risk factors, while LIME (Local Interpretable Model-Agnostic Explanations) was applied to visualize MC risk in individual cases.Results:Of the 525 patients, 135 (25.7%) developed postoperative MC. Among these, 80 (59.3%) experienced proximal junction kyphosis or failure (PJK/PJF), 7 (5.2%) had distal junction kyphosis or failure (DJK/DJF), 28 (20.7%) sustained rod fractures, and 29 (21.5%) showed significant loss of correction. In the validation cohort, the RF model achieved the highest area under the curve (AUC=0.80), followed by GNB (0.77), XGB (0.76), LR (0.74), LightGBM (0.73), and SVM (0.66). The RF model also demonstrated the best PRC value (0.58), highest sensitivity (0.65), and lowest Brier score (0.20). GNB, Light GBM, and LR models achieved the highest accuracy (0.78 each), while LightGBM exhibited the highest specificity (0.93). SHAP analysis identified higher preoperative VBQ scores, larger T 1 pelvic angle (TPA), and higher paraspinal muscle FI as the main risk factors for MC. Based on the RF model, a LIME-based tool was successfully constructed for individualized MC risk estimation. Conclusion:The RF model demonstrated the best overall predictive performance for MC. A machine learning-based prediction model has the potential to provide valuable guidance for surgical decision-making in ASD patients.

Aim To investigate the effect of hydrogen sulfide on macrophage calcification and its underlying mo-lecular mechanisms.Methods Oil red O staining was used to observe intracellular lipid accumulation,and von Kossa staining and atomic absorption spectroscopy were used for morphological and quantitative analysis of calcium deposition and intracellular calcium content in a mononuclear macrophage calcification model.Western blot and RT-PCR were used to detect the mRNA and protein expression of osteopontin(OPN)at different doses and treatment times of hydrogen sulfide.At the same time,Western blot was used to detect the expression changes of early growth response factor 1(EGR1),endo-plasmic reticulum stress-related markers C/EBP homologous protein(CHOP)and glucose-regulated protein 78(GRP78).Reactive oxygen species levels were evaluated by fluorescence probe staining,and the effect of hydrogen sulfide on macro-phage calcification was evaluated by combining von Kossa staining and calcium ion fluorescence probe staining.The mo-lecular mechanisms of hydrogen sulfide affecting macrophage calcification were explored by interfering with EGR1 expression and using endoplasmic reticulum stress inhibitor 4-phenylbutyric acid(4-PBA).Results Compared with oxidized low density lipoprotein(ox-LDL)group,β-glycerophosphate(β-GP)+40 g/L ox-LDL group showed a significant increase in intracellular lipid accumulation,while hydrogen sulfide significantly inhibited macrophage calcification in a con-centration-and time-dependent manner.Compared with the β-GP+ox LDL group,the most significant effect was observed after incubation with 100 μmol/L NaHS for 4 days.The hydrogen sulfide group showed a 66％decrease in intracellular calcium content(P＜0.01),a 71％decrease in intercellular calcium deposition(P＜0.01),and a 50％and 48％decrease in OPN mRNA and protein expression,respectively(P＜0.05).Hydrogen sulfide treatment upregulated the ex-pression of EGR1 by 21％,while downregulating the expression of CHOP and GRP78 by 58％and 59％,respectively(P＜0.01).The endoplasmic reticulum stress inhibitor 4-PBA could downregulate OPN expression by 73％(P＜0.01),while interfering with EGR1 expression completely counteracts the inhibitory effect of hydrogen sulfide on OPN expression and calcium deposition(P＜0.01).Conclusion Hydrogen sulfide significantly inhibits macrophage calcification by upregulating EGR1 expression and suppressing endoplasmic reticulum stress.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.