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.

ObjectiveTo characterize the changes of metabolites of Blumea balsamifera in the process of sweating by non-targeted metabolomics， and to investigate the influence of sweating processing on the constituents of B. balsamifera. MethodsUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） metabolomics was used to identify the metabolites in no sweating group（F1）， sweating 2 d group（F2） and sweating 4 d group（F3）， the differences of metabolites between the groups were compared by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and differential metabolites were screened according to the variable importance in the projection（VIP） value>1 and P<0.05， and the pathway enrichment of the differential metabolites was analyzed by Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsThe results of PCA and OPLS-DA showed a clear distinction between the three groups of samples， indicating significant differences in the compositions of the three groups of samples. A total of 433 differential metabolites were screened between the F1 and F2， with 154 up-regulated and 279 down-regulated， the significant up-regulated metabolites were tangeritin， 5-O-demethylnobiletin and so on， while the metabolites with significant down-regulation included alternariol， fortunellin， etc. A total of 379 differential metabolites were screened between the F2 and F3， with 150 up-regulated and 229 down-regulated， the significant up-regulated metabolites were isoimperatorin， helianyl octanoate and so on， and the significant down-regulated metabolites were hovenoside I， goyasaponin Ⅲ， etc. KEGG pathway enrichment analysis showed that tyrosine metabolism， isoquinoline alkaloid biosynthesis， phenylalanine， tyrosine and tryptophan biosynthesis， tryptophan metabolism， valine， leucine and isoleucine biosynthesis， pantothenate and coenzyme A biosynthesis may be the key pathways affecting metabolite differences of B. balsamifera after sweating treatment. ConclusionSweating can reduce the content of endophytic mycotoxins in B. balsamifera and has a great impact on the synthesis and metabolic pathways of total flavonoids and auxin. This study can provide a reference for the process research on the sweating conditions of B. balsamifera.

BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.

Objective:To investigate the effects of traditional Chinese curve-correcting and rotation-reducing spinal manipulation on biomechanical parameters and factors influencing herniated disc resorption in lumbar disc herniation(LDH).Methods:A retrospective analysis of 51 LDH patients treated between January 2022 and May 2024 was conducted.Lumbosacral parameters(vertebral rotation angle[α],disc angle[β],sacral slope[SS],lumbar lordosis[LL])were measured via MRI before treatment and at final follow-up.Disc resorption was assessed using Michigan State University(MSU)classification.Multivariate logistic regression identified factors associated with resorption.Results:Post-treatment α angle significantly decreased(3.02°→1.86°,P=0.002),while SS(28.4°→30.0°,P＜0.001)and LL angles(31.0°→35.12°,P＜0.001)increased;Disc resorption occurred in 56.86％(29/51)of patients.Longer disease course(OR=0.79,95％CI:0.69-0.91)and disc calcification(OR=0.03,95％CI:0.00-0.25)were independent inhibitors of resorption(P＜0.001).Conclusion:Spinal manipulation restores lumbosacral biomechanics by reducing vertebral rotation and increasing lumbar curvature,with higher resorption rates in patients with short duration(≤6 months),non-calcified discs,and MSU type 2-3 herniations.

The high incidence of peristoma moisture-related skin injury in patients with enterostomies seriously reduces patients′ quality of life. This paper reviewed the risk factors and risk prediction models for peristoma moisture-related skin injury, with the aim of providing an important basis for early identification and intervention in the high-risk group of peristoma moisture-related skin injury after clinical stoma surgery, and then providing a reference for the personalised health management of patients with intestinal stoma.

microRNA(miRNA),as a short non-coding RNA molecule,regulates bone-immune signal and stress response through transcription,translation as well as the combination of shear process,exerting the effect of promoting angiogenesis and repairing damage bone;type H vessels play a role in the cou-pling of angiogenesis and osteogenesis in the formation of new bone and promoting bone regeneration at the defect site.In re-cent years,miRNA regulates hypoxia inducible factor 1α(HIF-1 α)/vascular endothelial growth factor(VEGF),Notch,plate-let-derived growth factor-BB(PDGF-BB),Wnt/glycogen syn-thase kinase-3 β(GSK3 β)to affect the migration,recruitment,proliferation and differentiation of endothelial cells(ECs)and osteoblast(OB),promote the coupling of H-type vessels and os-teoblasts to improve bone homeostasis,and then prevent and treat bone metabolic diseases.This article explains the role of miRNA in regulating H-type vascular osteogenic coupling to provide tar-gets and pathways for improving bone homeostasis.In addition,the active ingredients of traditional Chinese medicine affect the differential expression of miRNA to promote H-type angiogenesis and provide strategies for clinical prevention and treatment of bone metabolic diseases.

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.

Objective:To investigate the effects of traditional Chinese curve-correcting and rotation-reducing spinal manipulation on biomechanical parameters and factors influencing herniated disc resorption in lumbar disc herniation(LDH).Methods:A retrospective analysis of 51 LDH patients treated between January 2022 and May 2024 was conducted.Lumbosacral parameters(vertebral rotation angle[α],disc angle[β],sacral slope[SS],lumbar lordosis[LL])were measured via MRI before treatment and at final follow-up.Disc resorption was assessed using Michigan State University(MSU)classification.Multivariate logistic regression identified factors associated with resorption.Results:Post-treatment α angle significantly decreased(3.02°→1.86°,P=0.002),while SS(28.4°→30.0°,P＜0.001)and LL angles(31.0°→35.12°,P＜0.001)increased;Disc resorption occurred in 56.86％(29/51)of patients.Longer disease course(OR=0.79,95％CI:0.69-0.91)and disc calcification(OR=0.03,95％CI:0.00-0.25)were independent inhibitors of resorption(P＜0.001).Conclusion:Spinal manipulation restores lumbosacral biomechanics by reducing vertebral rotation and increasing lumbar curvature,with higher resorption rates in patients with short duration(≤6 months),non-calcified discs,and MSU type 2-3 herniations.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

BACKGROUND:Existing studies have preliminarily summarized the potential association between muscle activity of the affected lower limb and gait stability during walking in patients undergoing anterior cruciate ligament reconstruction.However,there are some issues such as incomplete observation of muscle categories,incomplete observation of walking action phases,and failure to consider synergistic effects among multiple muscle groups,which urgently require further improvement in this study.OBJECTIVE:To monitor muscle synergy information of the affected leg during walking in patients undergoing anterior cruciate ligament reconstruction and to analyze the association between muscle synergy information and gait stability.METHODS:Twenty-four male patients aged(21.66±4.09)years undergoing anterior cruciate ligament reconstruction,were recruited.Electromyographic and center of pressure data were collected from the affected lower limb during walking.A non-negative matrix decomposition algorithm was used to extract the number of muscle synergic elements from the affected leg,the time spent in peak activation of each muscle synergic element,and the muscle relative weight indexes.Correlation analysis was then performed with the center of pressure indexes.RESULTS AND CONCLUSION:Six types of muscle synergies were identified in the affected leg.The number of muscle synergic elements showed no significant correlation with the distance and speed of lateral displacement of the center of pressure.Regarding the peak activation time of muscle synergic elements,synergic element 3 in the dominant gait loading response period showed a significant negative correlation with the lateral displacement distance of the center of pressure(r=-0.413,P=0.045)and a significant negative correlation with the lateral displacement velocity of the center of pressure(r=-0.470,P=0.020).The activation time of the remaining types of muscle synergic elements was not significantly related with patient's gait stability indices.In terms of muscle relative weights,the rectus femoris muscle of synergistic element 1 in the dominant gait loading response period showed a significant negative correlation with the lateral displacement distance of the center of pressure(r=-0.592,P=0.005)and a significant negative correlation with the lateral displacement speed of the center of pressure(r=-0.529,P=0.014).Additionally,the relative weight of the biceps femoris muscle of synergistic element 3 in the dominant gait loading response period showed a significant negative correlation with the lateral displacement distance of the center of pressure(r=-0.428,P=0.037).To conclude,the central system in patients undergoing anterior cruciate ligament reconstruction regulates the synergistic muscle activity of the affected leg during walking to enhance gait stability in two primary ways:by prolonging the activation time of the muscle synergists during the dominant loading response period and enhancing the activation of the quadriceps muscle,in order to enhance the control of eccentric contractions of the knee joint during the landing of the affected leg and improve the stability of the knee joint;and by increasing the activation of the biceps femoris muscle during the loading response period,which increases the degree of knee flexion and enhances the lower limb's cushioning function during the landing of the affected leg.