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.

Gastric ulcer （GU） is a high-incidence digestive system disease characterized pathologically by disruption of gastric mucosal integrity， with clinical features including a prolonged course and periodic recurrence. Modern medicine attributes its pathogenesis to the dynamic imbalance between aggressive and defensive factors，while traditional Chinese medicine （TCM） posits its development as closely linked to spleen deficiency. Current therapies combining acid suppressants and antibiotics face challenges such as high recurrence rates，poor mucosal healing，and adverse drug reactions. Long-term use may induce metabolic disturbances like hypergastrinemia and reduced intestinal microbiota diversity. Therefore，exploring safer and longer-lasting therapeutic strategies has become a critical focus. TCM has extensive clinical experience and unique advantages in GU prevention and treatment. Studies demonstrate that the classic formula Shenling Baizhu San exhibits therapeutic properties of "invigorating spleen and tonifying Qi to restore physiological balance and eliminating dampness and regulating middle energizer to unblock Qi movement"， enabling a holistic approach targeting both symptoms and root causes in GU with spleen deficiency as the core pathology by suppressing aggressive factors and strengthening defensive factors. Experimental research reveals its mechanisms involve enhancing the physicochemical barrier of the mucus layer，repairing epithelial barriers and microcirculation，modulating gastric acid secretion and gastrointestinal motility，and regulating microecological barriers and mucosal immunity. Clinical evidence confirms its synergistic effects in promoting ulcer healing，improving Helicobacter pylori eradication rates，and reducing recurrence risks. This review examined the etiology and pathogenesis of GU and systematically evaluated Shenling Baizhu San from three perspectives-clinical application，pharmacological effects， and experimental research-to provide insights for optimizing integrated traditional Chinese and Western medicine protocols and expanding its clinical applications.

Colorectal cancer is a common and malignant tumor in the digestive tract. Invasion and metastasis of cancer cells are key factors leading to the high mortality rate and postoperative recurrence of colorectal cancer. Chemotherapy is the main treatment method for preventing recurrence of this disease. However， there are many toxic side effects in clinical application， which seriously hinder the treatment process. Therefore， it is imperative to search for efficient and low-toxicity drugs. Traditional Chinese medicine （TCM） has a long history of treating colorectal cancer and offers advantages such as safety， effectiveness， multiple targets， multiple pathways and minimal toxic side effects， which have made it increasingly popular worldwide. According to TCM， the pathogenesis of colorectal cancer is rooted in both deficiency and excess. TCM formulas mainly focus on tonifying the body to address the invasion and metastasis of colorectal cancer， such as Jianpi compound， Jianpi Xiaoai decoction， and Bushen Jiedu Sanjie decoction. TCM monomers， such as emodin， berberine， and tanshinone， mainly focus on clearing heat and removing toxin， circulating blood and transforming stasis， and resolving swelling and dispersing nodules. Signaling pathways play a crucial role for analyzing invasion and metastasis， and research has shown that pathways such as Wnt/β-catenin， phosphatidylinositol-3 kinase/protein kinase （PI3K/Akt）， Janus kinase 2/signal transduction and transcription activating factor 3 （JAK2/STAT3）， nuclear factors-κB （NF-κB）， vascular endothelial growth factor （VEGF） play important roles in the invasion and metastasis of colorectal cancer. The invasion and metastasis of colorectal cancer can be inhibited via regulating the key proteins and related factors in these pathways. In this review， we searched various literature databases， such as PubMed， China National Knowledge Infrastructure （CNKI）， and VIP， using keywords such as "colorectal cancer"， "signaling pathway"， "invasion and metastasis"， and "traditional Chinese medicine"， to summarize and analyze the relevant pathways of TCM compounds and monomers against invasion and metastasis of colorectal cancer published in the past five years. The review aims to provide new insights and references for in-depth research on the therapy for invasion and metastasis of colorectal cancer and new drug development.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Objective:To Exploring the protective effect of hearing protectors worn by noise workers in the petrochemical industry and the factors affecting the protective effect of hearing protectors.Methods:From June 2021 to July 2023, 929 petrochemical workers were selected as the research subjects through cluster sampling. The noise exposure of workers and the usage of two types of hearing protectors were surveyed through questionnaire surveys and on-site occupational hygiene surveys. The protective effect of hearing protectors were evaluated by testing the PAR of workers. If the noise exposure value of workers minus the PAR value was less than 85 dB (A) , it was considered passed. Otherwise, it was considered not passed. The passing rate of the protective effect test of hearing protectors was analyzed through chi square test and the influencing factors for the effectiveness of workers hearing protectors in test were explored through single factor analysis and logistic regression models.Results:Among the research subjects, 80.5% of workers (748/929) had noise exposure levels greater than 85 dB (A) . The passing rate (80.9%) of the earmuff is greater than that of the earplug (52.6%) , and the median of PAR of the earmuff is 22 (16, 25) , which is greater than that of the earplug 15 (3, 22) dB dB, with a statistically significant difference ( P<0.001) . Univariate analysis and logistic regression models showed that length of service, exposure level to noise, and wearing comfort were the influencing factors of earplug protection effect ( P<0.05) , while wearing comfort was the influencing factor of earmuff protection effect ( P<0.05) . Conclusion:This study indicates that the protective effect of hearing protectors on workers in the petrochemical enterprise is poor, and the protective effect of earmuffs is greater than that of earplugs. Working experience, noise exposure level, and wearing comfort are the influencing factors of earplug protection effect, while wearing comfort is the influencing factor of earplug protection effect.

Objective:To evaluate the relationship between postoperative changes in femoral head coverage (FHC) after S 2-Alar-Iliac (S 2AI) screw fixation and the development of sagittal imbalance during follow-up in patients with adult spinal deformity (ASD), providing insights for clinical assessment and treatment strategies. Methods:A consecutive cohort of 98 ASD patients who underwent S2AI fixation between September 2019 and September 2021 was retrospectively analyzed. Patients were divided into two groups based on changes in femoral head coverage (ΔFHC): the FHC-C group (upper quartile ΔFHC, 25 cases) and the FHC-NC group (lower quartile ΔFHC, 24 cases). Additionally, patients were classified into proximal junctional kyphosis (PJK) and non-PJK groups based on their clinical outcomes at the last follow-up. Standing full-spine anteroposterior and lateral X-rays were taken preoperatively, postoperatively, and at the two-year follow-up to measure and document the following spinal parameters: Cobb angle, proximal lumbar lordosis (PLL), distal lumbar lordosis (DLL), lumbar lordosis (LL), lordosis distribution index (LDI), sagittal vertical axis (SVA), coronal balance distance (CBD), thoracic kyphosis (TK), T 1 pelvic angle (T 1PA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL, and proximal junctional angle (PJA). Parameters related to hip joint coverage included: femoral head coverage (FHC), lateral center-edge angle (LCE angle), acetabular index (AI), Sharp angle, and extrusion index (EI). Comparisons of radiographic indicators between the two groups were performed at preoperative, postoperative, and final follow-up assessments. The visual analogue scale (VAS) was used to evaluate the hip pain and back pain. Results:At final follow-up, the incidence of PJK was significantly higher in the FHC-NC group [37.5% (9/24)] compared to the FHC-C group [16.0% (4/25)] (χ 2=3.952, P=0.042). Moreover, the increase in sagittal vertical axis (ΔSVA) was significantly greater in the FHC-NC group (35.9±44.7 mm vs. 14.6±31.8 mm, t=2.216, P=0.031). Patients with PJK had significantly higher preoperative T 1PA (36.8°±10.8° vs. 31.9°±18.4°, t=2.150, P=0.034) and lower immediate postoperative ΔFHC (1.7%±1.5% vs. 3.3%±2.5%, t=2.987, P=0.004), as well as lower changes in lateral center-edge angle during follow-up (0.3°±3.0° vs. 1.1°±8.9°, t=2.334, P=0.022). Pearson correlation analysis revealed significant negative correlations between postoperative ΔFHC and both ΔSVA ( r=-0.374, P=0.008) and proximal junctional angle changes (ΔPJA, r=-0.429, P=0.006). Additionally, increases in VAS leg pain scores correlated negatively with immediate postoperative FHC ( r=-0.314, P=0.025) and ΔFHC ( r=-0.298, P=0.031). Logistic regression indicated that immediate postoperative ΔFHC was a protective factor against PJK [ OR=0.722, 95% CI (0.541, 0.963), P=0.009), with a ROC-determined optimal ΔFHC cut-off of 3.90% (AUC=0.723, Youden index=0.847). Conclusions:Postoperative evaluation of femoral head coverage is clinically important for ASD patients undergoing S2AI screw fixation. A pre-to-post ΔFHC below 3.90% may indicate reduced hip compensation capacity, increasing risks for hip pain, sagittal imbalance progression, and PJK postoperatively.

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.

Objective:To evaluate the effect of continuous theta burst stimulation (cTBS) on postoperative cognitive dysfunction (POCD) in mice and its association with the excitability of parvalbumin (PV) neurons in the medial prefrontal cortex (mPFC).Methods:Twenty-four specific pathogen-free healthy male C57BL/6 mice, aged 8 weeks, weighing 18-24 g, in which adeno-associated virus (AAV) for labeling PV neurons was injected into the mPFC using stereotaxic surgery, were used in this study. Three weeks later, the mice were divided into 3 groups ( n=8 each) using a random number table method: control group (group C), POCD group (group P) and cTBS group. Group C received no treatment. A mouse model of POCD was established by performing tibial fracture surgery under sevoflurane anesthesia and the mice received sham stimulation from postoperative day 0 to day 4 in group P. Group cTBS underwent POCD model establishment and received cTBS stimulation from postoperative day 0 to day 4. Cognitive function was assessed using contextual fear conditioning, Y-maze and novel object recognition tests on postoperative day 5. The spontaneous firing frequency of PV neurons in the mPFC was then measured using ex vivo patch-clamp electrophysiology. Results:The results of contextual fear conditioning test showed that compared to group C, the percentage of freezing time was significantly increased in group P ( P<0.05); compared to group P, the percentage of freezing time was significantly decreased in group cTBS ( P<0.05). The results of Y-maze test showed that compared to group C, the alternation accuracy was significantly decreased in group P ( P<0.05); compared to group P, the alternation accuracy was significantly increased in group cTBS ( P<0.05). The results of novel object recognition test showed that compared to group C, the percentage of time spent exploring the novel object was significantly decreased in group P ( P<0.05); compared to group P, this percentage of time spent exploring the novel object was significantly increased in group cTBS ( P<0.05). The results of ex vivo patch-clamp electrophysiology showed that compared to group C, the spontaneous firing frequency of PV neurons in the mPFC was significantly decreased in group P ( P<0.05); compared to group P, the spontaneous firing frequency of PV neurons in the mPFC was significantly increased in group cTBS ( P<0.05). Conclusions:cTBS can ameliorate POCD in mice, and the mechanism is related to the restoration of excitability of PV neurons in the mPFC.