BACKGROUND:Fracture healing is a very complex physiological process,which is influenced by many factors.In recent years,the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics,and the mechanical stress environment around the fracture end has an important role in regulating fracture healing.Among them,the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.OBJECTIVE:To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.METHODS:A search with the keywords of"compressive stress,fracture healing,cytokine,bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,tumor necrosis factor-α"in Chinese and English was conducted in the CNKI,WanFang,PubMed,and Web of Science.Initially 506 articles were retrieved,and 94 eligible articles that met the criteria were screened and finally summarized.RESULTS AND CONCLUSION:Current studies have found that compressive stress has different effects on different cytokines during fracture healing,which can be achieved mainly by influencing cell signaling,gene expression regulation,and modulation of cell behavior.Among them,compressive stress can be linked to cytokines such as bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,and tumor necrosis factor-α.This process involves cell proliferation,differentiation and migration,inflammatory response,and changes in the environmental and nutritional conditions of the fracture end,which are key factors affecting fracture healing.The whole paper summarizes the complexity of cytokine action mechanism,the mechanism of compressive stress on its regulation needs to be further carried out in-depth research,and the problems and limitations in the research are considered and future prospects.

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.

BACKGROUND:Fracture healing is a very complex physiological process,which is influenced by many factors.In recent years,the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics,and the mechanical stress environment around the fracture end has an important role in regulating fracture healing.Among them,the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.OBJECTIVE:To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.METHODS:A search with the keywords of"compressive stress,fracture healing,cytokine,bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,tumor necrosis factor-α"in Chinese and English was conducted in the CNKI,WanFang,PubMed,and Web of Science.Initially 506 articles were retrieved,and 94 eligible articles that met the criteria were screened and finally summarized.RESULTS AND CONCLUSION:Current studies have found that compressive stress has different effects on different cytokines during fracture healing,which can be achieved mainly by influencing cell signaling,gene expression regulation,and modulation of cell behavior.Among them,compressive stress can be linked to cytokines such as bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,and tumor necrosis factor-α.This process involves cell proliferation,differentiation and migration,inflammatory response,and changes in the environmental and nutritional conditions of the fracture end,which are key factors affecting fracture healing.The whole paper summarizes the complexity of cytokine action mechanism,the mechanism of compressive stress on its regulation needs to be further carried out in-depth research,and the problems and limitations in the research are considered and future prospects.

AIM:This study aimed to investigate the inhibitory effects and potential mechanisms of cyasterone(CYA)on inflammation and apoptosis of chondrocytes in knee osteoarthritis(KOA).METHODS:A rat model of KOA was established through anterior cruciate ligament transection(ACLT).Rats were randomly divided into 5 groups(n=6 in each group):normal control(NC),ACLT,ACLT+CYA(10 mg/kg),ACLT+CYA+SR9009(BMAL1 inhibitor),and ACLT+CYA+LY294002(PI3K inhibitor).Pathological changes in cartilage were evaluated using hematoxylin-eosin(HE)and safranin O/fast green staining,graded according to the Osteoarthritis Research Society International(OARSI)system.Immunohistochemistry was employed to measure the expression levels of BMAL1,phosphorylated phosphati-dylinositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-AKT)and phosphorylated nuclear factor-κB(p-NF-κB)in cartilage.An in vitro KOA model was created by stimulating rat chondrocytes with interleukin-1β(IL-1β).Cell vi-ability was assessed using the CCK-8 assay,while enzyme-linked immunosorbent assay(ELISA)was used to quantify pro-inflammatory cytokines(IL-6,IL-1β and TNF-α).Apoptosis was analyzed via flow cytometry,and the protein expression levels of BMAL1,PI3K,p-PI3K,AKT,p-AKT,NF-κB and p-NF-κB were evaluated using Western blot.RESULTS:In vivo,the rats in ACLT group exhibited significant chondrocyte degradation and lacunae formation compared with NC group,confirming the successful establishment of the KOA model.The rats in ACLT+CYA,ACLT+CYA+SR9009 and ACLT+CYA+LY294002 groups showed improved cartilage integrity compared with ACLT group,with reduced OARSI scores(P<0.05),increased BMAL1 expression(P<0.05),and decreased levels of p-PI3K,p-AKT and p-NF-κB(P<0.05).In vitro,the chondrocytes in IL-1β+CYA,IL-1β+CYA+SR9009 and IL-1β+CYA+LY294002 groups exhibited lower levels of IL-6,IL-1β and TNF-α(P<0.05),decreased apoptosis rates(P<0.01),increased BMAL1 protein ex-pression(P<0.05),and reduced p-PI3K/PI3K,p-AKT/AKT and p-NF-κB/NF-κB ratios(P<0.05),compared with IL-1β group.CONCLUSION:Cyasterone alleviates chondrocyte inflammation and apoptosis in KOA by activating BMAL1,which subsequently inhibits the phosphorylation of PI3K/AKT/NF-κB signaling pathway.

AIM:A strain was isolated and identified as the H3N8 subtype of the avian influenza virus from a sick chicken at a farm in Yangjiang,Guangdong Province,named A/chicken/Yangjiang/552/2023(abbreviated as YJ/552).The aim of this research is to determine its genetic evolution,biological properties and pathogenicity in hamsters.This study may provide a theoretical strategy for preventing and treating the H3N8 subtype avian influenza virus-induced epidemic.METHODS:A strain of H3N8 avian influenza virus from chickens was characterised by phylogenetic analy-sis,antigenic diversity,receptor-binding specificity,neuraminidase activity,replication,and transmission in hamsters and a systematic pathological analysis was conducted.RESULTS:This novel avian influenza virus was generated through complex recombination of Eurasian avian H3 genes,North American avian N8 genes and six internal genes of H9N2 sub-type AIV.The cleavage site of the outer protein,HA,was PEKQTR↓GLF,which is characteristic of the low pathogenic avian influenza virus.The HA gene of YJ/552 exhibited the highest nucleotide homology with A/China/ZMD-22-2/2022(H3N8)at 99.09%,while the NA gene showed the highest homology with A/chicken/Dongguan/879/2022(H3N8)at 99.01%.This strain preferentially binds to avian-type receptors and could bind to human-type receptors.This virus could effectively replicate in the trachea and lungs of inoculated and contact hamsters.CONCLUSION:YJ/552 is a recombi-nant H3N8 avian influenza virus replicated in the upper respiratory system and transmitted in hamsters.This study pro-vides data support for the early warning and prevention of H3 subtype avian influenza viruses.

Purpose To investigate the value of intratumoral and peritumoral radiomics features based on multi-parametric MRI for preoperative prediction of lymphovascular invasion(LVI)in clinical lymph node-negative(cN0)breast cancer.Materials and Methods This retrospective study included 280 patients with pathologically confirmed breast cancer who underwent preoperative MRI at Henan Provincial People's Hospital from January 2017 to May 2021.Patients were randomly divided into a training cohort and a testing cohort.After Z-score normalization,feature selection was performed using Select K Best and least absolute shrinkage and selection operator regression.Random forest algorithms were used to construct intratumoral,peritumoral,and combined intratumoral-peritumoral radiomics models for LVI prediction.Model performance and clinical utility were evaluated using the area under the receiver operating characteristic curve(AUC),calibration curves and decision curve analysis.Results High Ki-67 expression(≥20%),axillary lymph node metastasis and positive diffusion weighted imaging(DWI)margin sign were more common in the LVI-positive group(χ2=5.959,18.316,20.554,all P<0.05).In the testing cohort,the AUC values of the dynamic contrast-enhanced(DCE)-Intra and DCE-Com models for predicting LVI status were higher than those of the DWI sequence,whereas the AUC value of the DWI-Peri model was higher than that of the DCE sequence.The DWI-DCE-Com model achieved AUCs of 0.836 and 0.818 in the training and testing cohorts,respectively,which surpassed the predictive performance of single-sequence intratumoral-peritumoral radiomics models(DWI-Com,DCE-Com).Decision curve analysis showed that the DWI-DCE-Com model provided greater net clinical benefit across a reasonable range of threshold probabilities.Conclusion Radiomics models based on multiparametric MRI features from intratumoral and peritumoral regions can effectively predict LVI status in cN0 breast cancer,offering valuable support for preoperative individualized treatment decision-making.

Objective:To investigate the the differential expression of EIF5A2 in intrahepatic cholangiocarcinoma cell lines RBE,HCCC9810,and HUCCT1,and its effects on HCCC9810 cell migration and invasion,epithelial mesenchymal transition,and PI3K/AKT signaling pathway.Methods:The differential expression of EIF5A2 in RBE,HCCC9810,and HUCCT1 cell lines was detected using WB method.The HCCC9810 cell line,with the highest expression of EIF5A2,was selected for this experiment.The expression of EIF5A2 in HCCC9810 cell line was silenced by transient transfection of small interfering RNA.The best silencing effect of small interfering RNA was screened by WB.Scratch assay and Tran-swell migration invasion assay were used to detect the effect of silencing EIF5A2 on the migration and invasion ability of HCCC9810 cells.WB was used to detect the effect of silencing EIF5A2 on PI3K/AKT signaling pathway and epithelial mesenchymal transition in HCCC9810 cells.Results:The WB results showed that EIF5A2 had the highest expression in the HCCC9810 cell line,and siRNA1 had the best silencing effect on EIF5A2 in the HCCC9810 cell line.Scratch assay and Transwell migration invasion assay results showed that silencing EIF5A2 in the HCCC9810 cell line resulted in a decrease in cell invasion and metastasis ability(P＜0.05).At the same time,the expression of p-PI3K and p-AKT in the PI3K/AKT signaling pathway was significantly decreased(P＜0.05),while the epithelial cell marker E-cadherin expression increased(P＜0.05)and the stromal cell marker N-cadherin expression decreased(P＜0.05).Conclusion:EIF5A2 may promote epi-thelial mesenchymal transition and enhance the migration and invasion ability of intrahepatic cholangiocarcinoma cells through the PI3K/AKT signaling pathway.

Obsessive-compulsive disorder (OCD) is characterized by recurrent episodes of intrusive thinking and/or behavior, persistent and variable symptoms, and chronic recurrence. It is clearly recommended in the OCD treatment guidelines that psychotherapy can effectively improve clinical symptoms and play an important role in maintaining long-term efficacy. However, previous research and clinical practice paid little attention to the application of psychological interventions in OCD.Currently, there is insufficient understanding of psychotherapy for OCD, especially the proven first-line exposure and response prevention therapy (ERP), cognitive-behavioral therapy, and Morita therapy.Due to limited resources, they have not received effective intervention. Therefore, this article reviews the relevant research on psychological therapy intervention for OCD in recent years, summarizes the intervention effects of different psychological therapy methods on OCD and further elaborates on possible therapeutic mechanisms.Based on this, combined with the existing research, this article clarifies the effect of various behavioral psychological interventions and their combined treatment, and explores group and online forms of psychological intervention in order to increase the accessibility of psychotherapy for OCD patients.

Objective Focusing on the problems of unbalanced nursing education resources and insufficient training,it discusses the path of nursing echelon training and nursing education resources optimization in secondary hospitals.Methods Based on nursing questionnaire,interview data and platform logs from 4 secondary hospitals in Hainan Province,Latent Dirichlet Allocation topic modeling,sentiment analysis and Social Network Analysis were used.Identify the core problems of educational resources and training system and propose optimization schemes.Results Topic modeling revealed that insufficient educational resources and information silos were major obstacles to shared platform development.Similarity analysis result showed high consistency in feedback regarding disconnected training content and single training models.Sentiment analysis result indicated that 50％of negative feedback focused on inadequate evaluation and incentive mechanisms.Social Network Analysis validated the significant role of multi-node collaboration in optimizing resource flows.Conclusion Building shared platforms,implementing differentiated training systems,and developing localized nursing faculty are critical pathways to achieving homogenized nursing education,providing valuable references for optimizing regional nursing education.

Blood from a case of group B epidemic cerebrospinal meningitis identified in February 2024 in Ganzhou City,Jiangxi Province,and throat swabs from close contacts were collected for isolation and culture.The isolates were subjected to serogrouping,drug sensitivity testing,and whole genome sequencing and analysis,to provide a basis for epidemiological inves-tigation and clinical drug use.One strain of Neisseria meningitidis was isolated from the blood of the case and denoted group B.The MLST type was ST-7962,with no clonal group attribution.The phylogenetic tree showed that it was genetically close to the 1977 Shanghai carrier isolate(id-52231).Drug sensitivity results indicated that the strain was sensitive to 8 drugs:azithro-mycin,cefotaxime,minocycline,ceftriaxone,chloramphenicol,meropenem,rifampicin,and benzylpenicillin;resistant to cot-rimoxazole,levofloxacin,and ciprofloxacin;and showed an intermediate response to penicillin.This report describes the first case of ST-7962 group B meningoencephalitis found in Jiangxi Province.Monitoring of Neisseria meningitidis carriage,drug re-sistance,and molecular characteristics of strains in the healthy population in this region should be strengthened,to provide la-boratory support for the clinical use of medications,traceability,and control of the pathogen underlying meningoencephalitis infection.