AIM:To investigate the expression levels of serum sirtuin 6(Sirt6)and nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2)in patients with primary glaucoma and their correlation with the severity of the disease. METHODS:This study is a cross-sectional study. Patients diagnosed with primary glaucoma at the hospital from August 2022 to June 2025 were enrolled and divided into mild-to-moderate and severe groups based on the mean deviation of visual field defects, along with healthy individuals as a control group. Clinical data were collected, and serum levels of Sirt6 and NOX2 were measured using enzyme-linked immunosorbent assay(ELISA). Correlations between serum Sirt6 and NOX2 levels and clinical parameters were analyzed. Multivariate Logistic regression was used to identify factors influencing disease severity, and the diagnostic efficacy of serum Sirt6 and NOX2 levels was evaluated using receiver operating characteristic(ROC)curves. RESULTS:A total of 120 patients with primary glaucoma(58 males, 62 females, mean age 60.08±8.19 y)and 100 controls(46 males, 56 females, mean age 60.23±8.67 y)were enrolled in this study. There were no statistically significant differences in sex or age between the two groups(both P>0.05). The intraocular pressure and serum NOX2 expression level in the primary glaucoma group were significantly higher than those in the control group, while the Sirt6 level was significantly lower than in the control group(all P<0.001). The AUC values of serum Sirt6 and NOX2 in the diagnosis of primary glaucoma were 0.733 and 0.770, respectively, with optimal cutoff values of 2.35 and 4.25 ng/mL, respectively. The AUC of the combined diagnosis of the two was 0.901, and its efficacy was obviously better than that of a single indicator(Zcombination-Sirt6=5.317, Zcombination-NOX2=4.720, P<0.001).The severe group had lower serum Sirt6 expression levels(P<0.05), and higher NOX2 expression levels(P<0.05)than the mild-to-moderate group. Serum Sirt6 expression levels were prominently negatively correlated with mean intraocular pressure(r=-0.354, P<0.05); NOX2 expression levels were prominently positively correlated with mean intraocular pressure(r=0.240, P<0.05). Multivariate Logistic regression analysis showed that a decrease in serum Sirt6 expression levels(OR=0.229, 95%CI: 0.090-0.581), an increase in serum NOX2 expression levels(OR=2.649, 95%CI: 1.658-4.232), an increase in mean intraocular pressure(OR=1.278, 95%CI: 1.118-1.462)which were risk factors for the progression to severe glaucoma. The AUC values of serums Sirt6 and NOX2 expression levels in diagnosing severe primary glaucoma were 0.794 and 0.800, respectively, the AUC, sensitivity, and specificity of the combined diagnosis of the two were 0.916, 80.00%, and 89.33%, respectively, and the combined diagnostic efficacy was better than that of a single indicator(Zcombination-Sirt6=2.627, P=0.009, Zcombination-NOX2=2.762, P=0.006). CONCLUSION:The decreased serum Sirt6 and increased NOX2 expression levels in patients with primary glaucoma are significantly correlated with disease severity, and the combined detection demonstrates good diagnostic value for primary glaucoma and its severity.

AIM: To investigate the comorbidity status of myopia and depressive symptoms among middle school students, identify key influencing factors, and establish a prediction model, thereby providing empirical evidence for the comprehensive intervention of these two conditions.METHODS: Students from 3 middle schools in Feidong county were recruited between 2022 and 2024. Myopia was defined as uncorrected visual acuity ≤5.0 with spherical equivalent refraction <-0.50 diopters(D). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale(CES-D), with a score ≥16 indicating the presence of depressive symptoms. A database was established and data were entered using EpiData software. Pearson's Chi-square test and multivariate Logistic regression analysis were performed to identify influencing factors and screen variables with R statistical software(version 4.5.2). Finally, a Stacking ensemble prediction model was constructed using Python3.13 software. RESULTS: The study included 2 476 students, consisting of 1 380 males and 1 096 females. The overall detection rate of myopia-depressive symptom comorbidity among the studied students was 14.54%. Univariate analysis showed that variables were significantly associated with the comorbidity, including family structure, grade level, sugar-sweetened beverage intake, exercise frequency, school bullying, and parental physical or verbal abuse(all P<0.05). Multivariate Logistic regression analysis identified the following risk factors: higher grade levels(8th grade: OR=1.9143, 95%CI: 1.1096-3.3024; 9th grade: OR=1.7884, 95%CI: 1.0506-3.0444; 11th grade: OR=2.1847, 95%CI: 1.1980-3.9840; 12th grade: OR=3.4606, 95%CI: 1.8250-6.5621), daily consumption of sugar-sweetened beverages more than once(OR=3.1383, 95%CI: 1.7112-5.7560), low frequency of moderate-to-vigorous exercise on weekends and holidays(mostly achievable: OR=3.3115, 95%CI: 1.009-10.8685), alcohol consumption(OR=4.4021, 95%CI: 2.7383-7.0766), daily sedentary time exceeding 10 h(OR=1.8594, 95%CI: 1.2141-2.8476), lack of puberty education(OR=3.0098, 95%CI: 2.0659-4.3848), and exposure to parental physical or verbal abuse(OR=2.4050, 95%CI: 1.1484-5.0364). Protective factors included no experience of school bullying(OR=0.0055, 95%CI: 0.0002-0.1602), no history of severe injury(OR=0.3118, 95%CI: 0.1823-0.5332), outdoor activities during class breaks(OR=0.1672, 95%CI: 0.0752-0.3719), and moderate after-school homework duration(2-3 h per day: OR=0.4802, 95%CI: 0.2620-0.8801). The constructed Stacking prediction model demonstrated good discriminative ability, with an area under the receiver operating characteristic curve(AUC)of 0.855, a sensitivity of 81.5%, and a specificity of 74.0%. Key predictive factors included alcohol consumption status, location of recess activities, unhealthy lifestyle composite index(interaction term between sedentary duration and sugar-sweetened beverage intake frequency), academic stress index(interaction term between sedentary duration and homework duration), and after-school homework duration.CONCLUSION: The comorbidity of myopia and depression among middle school students is jointly influenced by multiple factors such as lifestyle, academic pressure, and family/campus environment. It is advocated to implement a three-level intervention system that includes restricting the sale of sugar-sweetened beverages, conducting psychological screening for sedentary students, and carrying out family-school-medical collaborative management of drinking behaviors. This model can be applied to school health screening and the early identification of high-risk groups in community adolescent health management. It is suitable for middle school students in regions with similar economic levels, but not applicable to students receiving special education or those with severe organic diseases.

[摘 要] 目的：探究重楼皂苷Ⅱ（PPⅡ）抑制甲状腺癌（TC）恶性生物学行为的分子机制。方法：常规培养甲状腺癌细胞TPC1，实验分为sh-NC、sh-可溶性半乳糖凝集素3（sh-LGALS3）、OE-NC、OE-LGALS3和 OE-LGALS3 + PPⅡ组，用转染试剂将应用质粒转染至各组TPC1细胞中。qPCR法检测TPC1细胞中LGALS3 mRNA的表达，WB法检测各组TPC1细胞中LGALS3、PI3K/AKT信号通路相关蛋白的表达，CCK-8法、Transwell实验、划痕愈合实验和流式细胞术分别检测各组TPC1细胞增殖、迁移和侵袭能力，以及细胞凋亡情况。结果：PPⅡ抑制TPC1细胞的增殖、迁移和侵袭，并诱导其凋亡（均P < 0.000 1）。数据库数据分析显示LGALS3在甲状腺癌组织中高表达（P < 0.001）且是PPⅡ的靶基因。LGALS1在TPC1细胞中呈高表达（P < 0.000 1），敲减LGALS3抑制TPC1细胞的恶性生物学行为，并促进其凋亡（均P < 0.000 1），PPⅡ通过抑制LGALS3 mRNA和蛋白的表达（P < 0.01或P < 0.001）从而抑制TPC1细胞的恶性生物学行为（P < 0.01或P < 0.000 1），PPⅡ抑制LGALS3表达抑制PI3K/AKT信号通路的激活水平（P <0.001或P <0.000 1），LGALS3通过PI3K/AKT信号通路促进TPC1细胞的恶性生物行为（P < 0.000 1）。结论：PPⅡ通过抑制TPC1细胞中LGALS3的表达，缓解PI3K/AKT信号通路的过度激活从而发挥抑癌作用。

OBJECTIVE: To explore the serological and molecular genetic characteristics of a family with subtype B(A)06. METHODS: A neonatal hyperbilirubinemia patient who was treated at Henan Children's Hospital on June 15, 2023 due to "yellowing of the skin and gradual aggravation", and was found to have inconsistent ABO forward and reverse typing through blood type testing, was selected as the research subject. Six milliliters of peripheral blood were collected from the newborn and her family members (grandfather, grandmother, father, mother and aunt) respectively. ABO blood group identification was performed by the blood group serological method. Human genomic DNA was extracted using the nucleic acid extraction or purification reagent BT-01. ABO gene exons 2 to 7 were amplified by PCR. The PCR-specific products that were successfully amplified were sequenced by Sanger method. Taking ABO*A1.01 as the reference sequence, the ABO gene sequences of the newborn and her family members were analyzed to determine the ABO genotype. The procedures followed in this study were approved by the Ethics Committee of Henan Children's Hospital (Ethics No.: 2022-K-L036). RESULTS: The serological results of ABO blood group showed that the newborn, her grandfather, father and aunt were all incompatible with the forward and reverse typing. The blood group phenotype of the newborn was AwB or B(A), the blood group phenotype of the grandfather was A2B or B(A), the blood group phenotype of the father and aunt were A2B, and the blood group phenotype of the grandmother and mother were both O. The screening test results of hemolytic disease of the newborn showed that the free test detected IgG anti-A1 antibody, while the elution test, direct antiglobulin test and antibody screening results were all negative. The Sanger sequencing results showed that the newborn had variations of c.261delG, c.297A>G, c.526C>G, c.657C>T, c.703G>A, c.796C>A and c.930G>A. Her grandfather had variations of c.297A>G, C.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C and c.930G>A. Her grandmother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T and c.829G>A. Her father and aunt had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.526C>G, c.646T>A, c.657C>T, c.681G>A, c.703G>A, c.771C>T, c.796C>A, c.829G>A and c.930G>A. Her mother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T, and c.829G>A.The genotype of the newborn was ABO*BA.06/ABO*O.01.01, her grandfather was ABO*BA.06/ABO*B.01, her grandmother was ABO*O.01.02/ABO*O.01.02, her father and aunt were ABO*BA.06/ABO*O.01.02, and her mother was ABO*O.01.01/ABO*O.01.02. The ABO*BA.06 allele of the newborn, grandfather, father and aunt was caused by the c.803C>G variation in exon 7 based on the ABO*B.01 allele. The ABO*BA.06 allele can be stably inherited in this family. CONCLUSION The blood type of neonatal patients with B(A)06 subtype can be accurately determined by gene sequencing technology. If the forward typing is ≤ 3+ agglutination intensity in newborn ABO blood group identification, the reason should be carefully analyzed, and the molecular biology technology and family gene sequencing results should be used to jointly determine if necessary.
Humans ; ABO Blood-Group System/genetics* ; Female ; Pedigree ; Male ; Infant, Newborn ; Asian People/genetics* ; Genotype ; China ; Blood Grouping and Crossmatching ; Hyperbilirubinemia, Neonatal/blood* ; East Asian People

Icodextrin peritoneal dialysis solution may produce cytotoxic α-dicarbonyl degradation products during heat sterilization, which must be monitored and controlled. The study established an o-phenylenediamine (OPD) derivatization HPLC-MS/MS method for the detection of these degradation products, enabling qualitative and quantitative analysis of α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution. The results indicated that the main α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution are 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 4-deoxyglucosone (4-DG), and 3,4-dideoxyglucosone-3-ene (3,4-DGE), along with two monocarbonyl degradation products, furfural and 5-hydroxymethylfurfural. The quantitative method for 3-DG, 3-DGal, 3,4-DGE and their structural analog, glucosone, was validated. 3-DG, 3-DGal, and glucosone exhibited good linear relationships within the range of 5-150 ng/mL, while 3,4-DGE showed good linearity in the range of 1-150 ng/mL. The spiked recovery rates for all compounds were between 86.8% and 100.0%. The detection limits for glucosone, 3-DG, and 3-DGal were approximately 2.4 ng/mL, and approximately 0.5 ng/mL for 3,4-DGE. The method established in this study can accurately determine α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution, providing an important basis for the quality control.

BACKGROUND:Collagen combined with microneedling therapy has gradually become an important means of improving skin photoaging.OBJECTIVE:To summarize and explore the main mechanism and clinical application status of collagen combined with microneedle therapy.METHODS:PubMed,China National Knowledge Infrastructure,and ScienceDirect databases were searched for Chinese and English literature published before August 2024.Chinese and English search terms were"ultraviolet radiation,photoaging,collagen,microneedling,clinical applications."Finally,74 articles were included for summary.RESULTS AND CONCLUSION:Collagen treats skin photoaging through mechanisms such as inhibiting matrix metalloproteinase expression,retaining skin moisture,and reducing melanin formation.Microneedles can better promote the penetration of collagen into deep layers of the skin,breaking down the skin's barrier and increasing the absorption rate.Collagen combined with microneedles has various beneficial effects for treating skin photoaging,such as whitening,anti-wrinkle,improving skin elasticity,shrinking pores,and repairing skin barriers.It also has the advantages of easy operation,significant effects,and high safety.Currently,the research on collagen combined with microneedling therapy is still in its early stages,and achieving clinical application may become a key research direction in the future.The clinical application of collagen combined with microneedles for the treatment of photoaging still faces many challenges,such as exploring the optimal mechanical structure and materials of microneedles,selecting appropriate microneedle types,and insufficient clinical evidence that collagen combined with microneedles can further delay the treatment of skin photoaging.

BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.

BACKGROUND:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.

OBJECTIVE:To evaluate the efficacy and safety of different immunosorbent columns in the treatment of rheumatoid arthritis through a network meta-analysis,and provide evidence-based basis for clinical diagnosis and treatment.METHODS:By computer,the databases of VIP,WanFang,CNKI,PubMed,CBM,CochraneLibrary,and Web of Science were searched for published cohort studies of immunosorbent column for the treatment of rheumatoid arthritis,with a time limit until August 2024.The quality of the included randomized controlled trials was assessed using the Cochrane5.4 manual.The quality of retrospective cohort studies were evaluated via the Newcastle-Ottawa Scale(NOS).Bayesian network meta-analysis was performed using R4.1.1 software.RESULTS:A total of 13 studies were included,with a total sample size of 891 cases,and 4 immunosorbent columns were included.The results of the network meta-analysis showed that the top three orders that reduce C-reactive protein level:HA280 adsorption column+conventional Western medicine＞PH-350 adsorption column+conventional Western medicine＞A protein adsorption column;the top three orders that reduce erythrocyte sedimentation rates:leukocyte adsorption column＞HA280 adsorption column+conventional Western medicine＞PH-350 adsorption column+conventional western medicine;the top three orders that reduce swollen joint count:leukocyte adsorption column＞A protein adsorption column+conventional western medicine＞PH-350 type adsorption column+conventional Western medicine;the top three orders that reduce tenderness joint counts:leukocyte adsorption column＞A protein adsorption column+conventional western medicine＞PH-350 adsorption column+conventional Western medicine;the top three orders that reduce patients' disease activity evaluation:PH-350 adsorption column+conventional western medicine＞leukocyte adsorption column＞A protein adsorption column;the top three orders that reduce visual analogue scale scores:PH-350 adsorption column+conventional Western medicine＞A protein adsorption column＞leukocyte adsorption column;the top three orders that reduce physician's disease activity assessment:PH-350 adsorption column+conventional Western medicine＞leukocyte adsorption column＞conventional Western medicine.CONCLUSION:Based on the 13 articles,in terms of reducing C-reactive protein level,HA280 adsorption column and conventional Western medicine are the preferred choice.In terms of reducing erythrocyte sedimentation rate,swollen joint count,and tender joint count,leukocyte adsorption column is the preferred choice.In terms of reducing patient's disease activity evaluation,physician's disease activity evaluation and visual analogue scale scores,PH-350 adsorption column and conventional Western medicine are the first choice.Different immunosorbent columns can be reasonably and accurately selected according to the patient's specific conditions.

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.