Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective To identify and analyze risk factors for acute renal failure (ARF) following lung transplantation and to develop a predictive model. Methods Data for this study were obtained from the United Network for Organ Sharing (UNOS) database, encompassing patients who underwent unilateral or bilateral lung transplantation between 2015 and 2022. We analyzed both preoperative and postoperative clinical characteristics of the patients. A combined approach utilizing random forest and least absolute shrinkage and selection operator (LASSO) regression was employed to identify key factors associated with the incidence of ARF post-transplantation, based on which a nomogram model was developed. The predictive performance of the constructed model was evaluated in both training and validation sets, using receiver operating characteristic (ROC) curves and area under the curve (AUC) metrics to verify and compare model effectiveness. Results A total of 15 110 lung transplantation patients were included in the study, consisting of6 041 males and 9 069 females, with a median age of 62.00 years (interquartile range: 54.00 to 67.00). The analysis revealed statistically significant differences between postoperative renal dialysis and non-dialysis patients regarding preoperative lung diagnosis, estimated glomerular filtration rate (eGFR), mechanical ventilation, preoperative ICU treatment, extracorporeal membrane oxygenation (ECMO) support, infections occurring within two weeks prior to transplantation, Karnofsky Performance Status (KPS) score, waitlist duration, double-lung transplantation, and ischemia time (P<0.05). Five key variables associated with ARF after lung transplantation were identified through random forest and LASSO regression: recipients’ eGFR, preoperative ICU treatment, ECMO support, bilateral lung transplantation, and ischemia time. A nomogram model was subsequently established. Model evaluation demonstrated that the constructed predictive model achieved high accuracy in both training and validation sets, with favorable AUC values, confirming its validity and reliability. Conclusion This study identifies common risk factors for ARF following lung transplantation and introduces an effective predictive model with potential clinical applications.

A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) represent a diverse family of secreted metalloproteinases, comprising 19 distinct members categorized into five groups based on their substrate specificity: proteoglycanases, procollagen N-peptidases, von Willebrand factor-cleaving protease, cartilage oligomeric matrix proteases and other proteases. Among these, ADAMTS proteoglycanases predominantly target hyalectans, pivotal components in extracellular matrix (ECM) remodeling and inflammation. Dysfunction of ADAMTS proteoglycanases disrupts the structure and function of hyalectans, thereby perturbing ECM homeostasis, resulting in reproduction disorders, including abnormal follicular development, ovulation dysfunction, impaired implantation, placentation and preterm labor. Hence, investigation of the role of ADAMTS proteoglycanases offers valuable insights into the molecular mechanisms underlying the physiological or pathological processes within the female reproductive system, thereby paving the way for innovative strategies in predicting, preventing and treating reproductive system diseases. This review summarizes the recent research advances in the structure and regulation of ADAMTS proteoglycanases and their role in female reproductive system.
Humans ; Female ; ADAMTS Proteins/physiology* ; ADAM Proteins/physiology* ; Pregnancy ; Animals ; Genitalia, Female/enzymology* ; Extracellular Matrix/metabolism*

Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

AIM To explore the relieving effect of Er Miao Wan on atopic dermatitis in mice.METHODS In vivo experiment:BALB/c mice were randomly divided into normal group,model group,dexamethasone group(2 mg/kg)and high,medium and low dose groups of Er Miao Wan(4.68,2.34 and 1.17 g/kg).The mouse model of atopic dermatitis was established by repeatedly smearing DNCB solution,and the model was given orally for 21 days.The skin lesion condition on the back of mice,ear swelling degree,and the weight difference between ear lobes were observed and recorded.HE staining was used to observe the histopathological changes in the skin lesion tissues of mice.Toluidine blue(TB)staining was used to observe the infiltration of mast cells in skin lesions.The expression of macrophage marker F4/80 in skin lesions was detected by IHC.The serum levels of TSLP,IL-4,IL-5 and total IgE were detected by ELISA.In vitro experiment:RAW264.7 cells in logarithmic growth period were given 400,200 and 100 μg/mL Er Miao Wan for intervention.Cell proliferation was detected by CCK-8 method.NO level in cell supernatant was detected by Griess method.TNF-α,IL-1 β and IL-6 levels in cell supernatant were detected by ELISA method.The expressions of proteins related to the MAPK/NF-κB signaling pathway in cells was detected by Western blot.RESULTS In vivo experiment:Compared with the model group,the scores of back skin lesions,the swelling degree of right ear and the weight difference between left and right ear pieces in the high-dose group of Er Miao Wan decreased(P＜0.05,P＜0.01),the thickness of skin lesions decreased,the infiltration of mast cells and macrophages decreased(P＜0.05,P＜0.01),and the inflammatory factors TSLP,IL-4,IL-5 and total IgE levels in serum decreased(P＜0.05,P＜0.01),and the expression of F4/80 in the skin lesions decreased(P＜0.01).In vitro experiment:Compared with the model group,the levels of NO,TNF-α,IL-1 β and IL-6 in Er Miao Wan 400 and 200 μg/mL groups decreased(P＜0.05,P＜0.01),and the phosphorylation levels of P38,JNK and P65 proteins decreased(P＜0.05,P＜0.01).CONCLUSION Er Miao Wan can alleviate skin lesion inflammation in DNCB-induced atopic dermatitis mice,and its mechanism may be related to inhibiting the activation of MAPK/NF-κB signaling pathway of macrophage,reducing macrophage infiltration and reducing Th2 cytokines.

Aim To investigate the effects of m6A demethylase ALKBH5 on cardiomyocytes pyroptosis in mice with myocardial infarction(MI).Methods The MI model of left anterior descending coronary artery ligation surgery was established by knocking down ALKBH5 using adeno-associated virus,and the hypox-ia model of mouse cardiomyocytes(HL-1)was estab-lished by knocking down small interfering RNA.The effects of ALKBH5 on the pyroptosis of MI mice and hypoxic HL-1 cells were observed.Subsequently,mechanism studies were conducted at the cellular lev-el,and the binding of ALKBH5 and IGF2BP2 to NL-RP3 mRNA was detected through RNA pull down and RNA immunoprecipitation(RIP)experiments.The MeRIP-qPCR method was used to determine the effects of ALKBH5 on the mRNA m6A level of NLRP3.Acti-nomycin D for RNA stability experiments were conduc-ted to detect the effects of ALKBH5 and IGF2BP2 on the stability of NLRP3 mRNA.Results Knocking down ALKBH5 in vivo and in vitro both inhibited NL-RP3 inflammasome activation and alleviated pyroptosis in MI mice and hypoxic HL-1 cells.Mechanistically,the results showed that NLRP3 mRNA could bind to ALKBH5 protein in HL-1 cells;knocking down ALK-BH5 could increase the m6A level of NLRP3 and re-duce the stability of NLRP3 mRNA;subsequently,it was confirmed that NLRP3 mRNA and IGF2BP2 pro-tein bound to each other;knocking down IGF2BP2 in-creased the mRNA stability of NLRP3.The Rescue ex-periment showed that knocking down IGF2BP2 re-versed the decrease in NLRP3 mRNA expression caused by knocking down ALKBH5.Conclusions ALKBH5 mediated m6A modification of NLRP3 pro-motes cardiomyocytes pyroptosis in mice with myocardi-al infarction.

Liver cirrhosis is a common chronic progressive liver disease， and such patients often have coagulation disorders， which may lead to thrombotic and hemorrhagic events. While traditional anticoagulant therapies have various limitations， the emergence of novel oral anticoagulants （NOAC） provides new options for anticoagulation treatment in patients with liver cirrhosis. This article comprehensively reviews the application of NOAC in patients with liver cirrhosis， discusses their advantages and potential risks， analyzes their pharmacokinetic and pharmacodynamic characteristics， and evaluates their efficacy and safety in the prevention and treatment of cirrhosis-associated thrombosis based on clinical evidence， in order to provide a reference for clinical decision-making.

Objective:To explore the application value of machine learning prediction model for neural invasion in gallbladder cancer based on enhanced computed tomography (CT) and clinical characteristics.Methods:The retrospective cohort study was conducted. The clinical and imaging data of 502 patients with gallbladder cancer who were admitted to The First Affiliated Hospital of Xinxiang Medical University from January 2010 to June 2024 were collected. There were 171 males and 331 females, aged 65(range, 35?91)years. All patients underwent preoperative abdominal enhanced CT and radical resection. The 502 patients were randomly divided into a training set of 351 cases and a test set of 151 cases at a 7:3 ratio. The training set was used to construct prediction model, and the test set was used to validate prediction model. Observation indicators: (1)neural invasion in gallbladder cancer and influencing factor analysis; (2) construction and validation of machine learning prediction models for neural invasion in gallbladder cancer. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Logistic regression model was performed for univariate and multivariate analyses. Independent influencing factors were incor-porated to construct machine learning models using the standard library modules based on Python 3.9. Receiver operating characteristic (ROC) curves were plotted, and the accuracy, sensitivity, specificity, area under the curve (AUC), precision, F1 score, positive predictive value, negative predic-tive value, and Kappa value were calculated to evaluate the predictive performance of the models. The Delong test was used to assess the differences in AUC among different models in the test set. The Hosmer-Lemeshow test and Brier score were used to evaluate the calibration of the models. Results:(1) Neural invasion in gallbladder cancer and influencing factor analysis. Of the 502 patients with gallbladder cancer, 131 cases had neural invasion, and 371 cases had no neural invasion. Results of multivariate analysis showed that total bilirubin, carcinoembryonic antigen, CA199, CA125, neutrophil-lymphocyte ratio, liver invasion detected by CT, vascular invasion detected by CT, hilar or retroperi-toneal lymph node metastasis detected by CT, and tumor stages T3 and T4 were independent influencing factors for neural invasion in patients with gallbladder cancer [ odds ratios=3.747, 2.395, 3.917, 3.596, 2.805, 2.377, 3.523, 2.774, 5.080, 6.809, 95% confidence interval ( CI) as 1.890?7.430, 1.154?4.971, 2.054?7.472, 1.807?7.155, 1.506?5.225, 1.241?4.553, 1.666?7.449, 1.483?5.189, 2.050?12.589, 2.552?18.168, P<0.05]. (2) Construction and validation of machine learning predic-tion models for neural invasion in gallbladder cancer. Based on the independent influencing factors, seven machine learning models were constructed, including logistic regression, K-nearest neighbors, support vector machine, random forest, decision tree, back-propagation neural network, and gradient boosting machine. The ROC curves of seven machine learning models in the test set were plotted, and the AUC were 0.900(95% CI as 0.851?0.948), 0.741(95% CI as 0.646?0.829), 0.836(95% CI as 0.762?0.895), 0.782(95% CI as 0.701?0.855), 0.839(95% CI as 0.770?0.901), 0.817(95% CI as 0.738?0.887), 0.843(95% CI as 0.770?0.909), respectively. Results of Delong test showed that the logistic regression model had the highest AUC. The sensitivity and specificity of the logistic regression model were 0.868 and 0.805 respectively, indicating the best balance. Results of Hosmer-Lemeshow test showed that the logistic regression model had a good goodness-of-fit ( χ2=5.320, P>0.05). The Brier score of the logistic regression model was relatively low, as 0.168, which verified its calibration advantage. Conclusion:Total bilirubin, carcinoembryonic antigen, CA199, CA125, neutrophil-to-lymphocyte ratio, liver invasion detected by enhanced CT, vascular invasion detected by enhanced CT, hilar or retroperitoneal lymph node metastasis detected by enhanced CT, and tumor stages T3 and T4 are independent influencing factors for nerve invasion in patients with gallbladder cancer. Seven machine learning models are constructed based on enhanced CT and clinical characteristics to predict neural invasion in gallbladder cancer, of which the logistic regression model demonstrates good predictive performance.