BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

OBJECTIVE:Patients with osteoporotic vertebral compression fractures still have residual back pain after vertebral augmentation.The current research is characterized by limited sample size,complex confounding factors,and inconsistent research results.To gain a deeper understanding of this phenomenon,the aim of this study was to identify and evaluate the risk factors for residual back pain after surgery through a systematic review and meta-analysis.METHODS:A comprehensive search was conducted in CNKI,VIP,WanFang,CBMdisc,PubMed,The Cochrane Library,Embase,and Web of Science for case-control studies on residual back pain after vertebral body augmentation for osteoporotic vertebral compression fractures from database inception to July 2024.The search terms were a combination of subject terms and free terms.The basic information,patient characteristics,surgical-related indicators,and risk factors for surgical back pain of the included studies were extracted.After evaluating the bias risk of all included studies,a meta-analysis was conducted using Stata 14.0 software on the relevant indicators.RESULTS:(1)21 case-control studies with a total of 8 043 patients were included.Among them,965 patients developed back pain.The quality score of all 21 studies was ≥7.(2)The meta-analysis results showed that age(WMD=0.98,95％CI:0.40-1.56,P=0.010),bone mineral density(WMD=-0.28,95％CI:-0.34 to-0.21,P=0.000),the number of vertebral fractures(OR=3.50,95％CI:2.65-4.62,P=0.000),thoracolumbar fracture index(OR=3.65,95％CI:2.61-5.11,P=0.000),cement volume(OR=6.89,95％CI:2.62-18.17,P=0.000),and cement distribution(OR=2.38,95％CI:1.93-2.93,P=0.000)were risk factors for the development of back pain after vertebral body augmentation in patients with osteoporotic vertebral compression fractures.CONCLUSION:Current evidence indicates that age,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,bone cement injection volume,and the distribution of bone cement are risk factors for low back pain.Specifically,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,and non-uniform distribution of bone cement are identified as independent risk factors for low back pain.Patients exhibiting these high-risk factors require vigilant monitoring and prompt intervention to mitigate the occurrence of clinical low back pain,thereby enhancing patient outcomes and quality of life.

BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95％Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95％CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95％CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95％CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95％CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95％CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95％CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.

BACKGROUND:Neutrophil extracellular traps and activated platelets are involved in the invasion,metastasis,growth,and angiogenesis of lung cancer,and are closely related to the development and prognosis of lung cancer.OBJECTIVE:To review the mechanism of neutrophil extracellular traps and activated platelets in lung cancer and their application in diagnosis,prognosis,and treatment of lung cancer.METHODS:"Platelet activation,lung neoplasms,extracellular traps,treatment"for English search terms and"lung cancer,neutrophil-extracellular traps,platelet activation,P-selectin,treatment"for Chinese search terms were searched in PubMed and CNKI databases.After reading the title and abstract of the literature,according to the inclusion and exclusion criteria,63 articles with high relevance were finally included.RESULTS AND CONCLUSION:(1)Formation of neutrophil extracellular traps and platelet activation were induced by lung tumor.(2)Neutrophil extracellular traps and activated platelets jointly promote the proliferation,growth and metastasis of lung cancer.(3)Neutrophil extracellular traps can be used as a novel biomarker for the diagnosis,prognosis and progression of lung cancer.(4)Targeting neutrophil extracellular traps and activating platelets can be used as potential therapies for lung cancer.

OBJECTIVE:A great deal of evidence indicates that regular exercise can improve the health status of elderly individuals,including reducing overall and abdominal fat levels,increasing muscle mass and bone mineral density of the limbs,thereby preventing or delaying the onset of sarcopenia and its comorbidities.This study aims to determine the most reliable type,duration,and intensity of exercise interventions through meta-analysis to prevent,delay,and alleviate sarcopenia and its comorbidities in elderly individuals.METHODS:Randomized controlled trials examining the effects of exercise interventions on elderly individuals with sarcopenia and its comorbidities were searched in the PubMed,Embase,Web of Science,Cochrane Library,CNKI,and WanFang databases.The Cochrane Risk of Bias Tool was used to assess the quality of the included studies,and RevMan 5.3 software was employed for meta-analysis.Subgroup analyses were conducted to explore the effects of different exercise intervention protocols on various outcome measures.In addition,Stata 16.0 software was used to perform sensitivity analysis to assess the stability of the results,and funnel plots and Egger's test were employed to evaluate publication bias,ensuring the comprehensiveness and reliability of the results.RESULTS:(1)Sixteen studies involving 861 patients with sarcopenia and its comorbidities were included.(2)The meta-analysis results indicated that,compared with the control group,exercise significantly improved grip strength,knee muscle strength,appendicular skeletal muscle mass,skeletal muscle index,Timed Up and Go test results,gait speed,and insulin-like growth factor 1 levels(P＜0.05).However,the effect of exercise intervention on the sit-to-stand test was not significantly improved(P＞0.05).(3)Based on the results of subgroup analysis,it is recommended that elderly patients with sarcopenia and its comorbidities engage in exercise at least three times per week,with each session lasting no more than 30 minutes or exceeding 45 minutes,for at least 12 weeks.The exercise protocol should be flexibly adjusted according to the patient's health status and individual needs.CONCLUSION:Exercise interventions significantly improve muscle mass,muscle strength,physical function,and insulin-like growth factor 1 levels in elderly individuals with sarcopenia and its comorbidities,thereby enhancing their quality of life.However,further research is needed to validate these findings and optimize specific intervention protocols.

BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

OBJECTIVE:Patients with osteoporotic vertebral compression fractures still have residual back pain after vertebral augmentation.The current research is characterized by limited sample size,complex confounding factors,and inconsistent research results.To gain a deeper understanding of this phenomenon,the aim of this study was to identify and evaluate the risk factors for residual back pain after surgery through a systematic review and meta-analysis.METHODS:A comprehensive search was conducted in CNKI,VIP,WanFang,CBMdisc,PubMed,The Cochrane Library,Embase,and Web of Science for case-control studies on residual back pain after vertebral body augmentation for osteoporotic vertebral compression fractures from database inception to July 2024.The search terms were a combination of subject terms and free terms.The basic information,patient characteristics,surgical-related indicators,and risk factors for surgical back pain of the included studies were extracted.After evaluating the bias risk of all included studies,a meta-analysis was conducted using Stata 14.0 software on the relevant indicators.RESULTS:(1)21 case-control studies with a total of 8 043 patients were included.Among them,965 patients developed back pain.The quality score of all 21 studies was ≥7.(2)The meta-analysis results showed that age(WMD=0.98,95％CI:0.40-1.56,P=0.010),bone mineral density(WMD=-0.28,95％CI:-0.34 to-0.21,P=0.000),the number of vertebral fractures(OR=3.50,95％CI:2.65-4.62,P=0.000),thoracolumbar fracture index(OR=3.65,95％CI:2.61-5.11,P=0.000),cement volume(OR=6.89,95％CI:2.62-18.17,P=0.000),and cement distribution(OR=2.38,95％CI:1.93-2.93,P=0.000)were risk factors for the development of back pain after vertebral body augmentation in patients with osteoporotic vertebral compression fractures.CONCLUSION:Current evidence indicates that age,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,bone cement injection volume,and the distribution of bone cement are risk factors for low back pain.Specifically,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,and non-uniform distribution of bone cement are identified as independent risk factors for low back pain.Patients exhibiting these high-risk factors require vigilant monitoring and prompt intervention to mitigate the occurrence of clinical low back pain,thereby enhancing patient outcomes and quality of life.

ObjectiveThis paper aims to observe the protective effect of Huamoyan granules on knee osteoarthritis （KOA） and explore whether its protective effect is oriented toward an anti-inflammatory direction by regulation of macrophage polarization， which can effectively inhibit the progression of pathological inflammatory response， reduce the release of inflammatory pain mediators， and downregulate the protein expression level of transient receptor potential vanilloid 1 （TRPV1）， so as to provide experimental evidence for its clinical application and investigate its action mechanism. MethodsAfter adaptive feeding， Sprague-Dawley （SD） rats were randomly divided into six groups： sham group， model group， celecoxib group， and high， medium， and low-dose synovitis granule groups （9.6， 4.8， 2.4 g·kg^-1）. The administration dose of celecoxib capsules was 20 mg·kg^-1. There were 10 rats in the sham group and 12 rats in the model group and each administration group. A KOA animal model was established by means of intra-articular injection of sodium iodoacetate into the knee joint. From the 10^th day of the experiment， each administration group was given intragastric administration at a dose of 10 mL·kg^-1 for 4 weeks. General conditions of rats in each group were assessed daily. The pressure pain threshold （PPT） to mechanical stimulation and joint diameter were recorded. X-ray examination was performed on the right knee joints of rats for imaging analysis. Enzyme linked immunosorbent assay （ELISA） was performed to detect the tumor necrosis factor-α （TNF-α）， serum interleukin-1β （IL-1β）， and other pro-inflammatory cytokines in rat serum samples， as well as the expression levels of neurogenic inflammatory mediators such as nerve growth factor （NGF） and calcitonin gene-related peptide （CGRP）. Histopathological changes in the knee joint synovial tissues were examined by hematoxylineosin （HE） staining. Safranin O-fast green staining was performed to observe and evaluate the degree of knee cartilage lesions. Western blot was employed to quantitatively analyze TRPV1， p38 mitogen-activated protein kinase （p38 MAPK）， and phosphorylated （p）-p38 MAPK in rat knee synovial tissues. Immunofluorescence （IF） was used to measure and assess M1/M2 macrophage polarization. ResultsCompared with those in the sham group， the circumference and joint diameter of the right knee were markedly enlarged in the model group （P<0.01）， while PPTs of rats showed a significant reduction （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in rats' serum were significantly elevated （P<0.01）， and the synovial Krenn score was increased （P<0.01）. The Mankin score of cartilage tissue was increased （P<0.01）， and the protein expressions of TRPV1 and p-p38 MAPK/p38 MAPK were significantly upregulated （P<0.01）. The experimental intervention significantly reduced the proportion of pro-inflammatory M1 macrophages in the total macrophage population （P<0.01）， and the percentage of M2 macrophages was decreased （P<0.01）. The M1/M2 macrophage ratio was significantly elevated （P<0.01）. Knee joint diameters of all dose groups of Huamoyan granules and the celecoxib group were reduced （P<0.01） compared with those of the model group， and the PPT recovery speeds in the high and medium-dose groups of Huamoyan granules were more obvious （P<0.05）. The contents of IL-1β， CGRP， and NGF in the rats' serum in all administration groups were significantly reduced （P<0.05， P<0.01）， and the content of TNF-α in rats' serum was significantly reduced （P<0.01）. All dose groups of Huamoyan granules demonstrated significant reductions in both synovial Krenn score （P<0.05， P<0.01） and protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in rats' synovial tissues （P<0.01）. The percentage of M1 macrophages in the synovial tissues of the celecoxib group and all dose groups of Huamoyan granules was decreased （P<0.01）. The percentage of M2 macrophages was increased （P<0.05）， and the M1/M2 ratio was decreased （P<0.01）. ConclusionHuamoyan granules can alleviate the inflammatory response of KOA， reduce the release of inflammatory pain mediators， and downregulate TRPV1 protein expression by regulating macrophage polarization. Its mechanism may be related to the TRPV1/p38 MAPK signaling pathway， thereby achieving the effect of improving peripheral pain hypersensitivity in KOA.