ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

Objective To explore the relationship between serum growth differentiation factor-15(GDF-15),chemerin,pentraxin 3(PTX3)levels and obesity,insulin resistance and inflammatory factors in patients with type 2 diabetes mellitus(T2DM),and to construct and evaluate the predictive efficacy.Methods A total of 231 T2DM patients admitted to the hospital from February 2020 to September 2022 were selected as T2DM group.Another 100 healthy subjects who came to the hospital for physical examination during the same period were selected as the control group.Serum GDF-15,chemerin and PTX3 levels of the two groups were detected and compared by enzyme-linked immunosorbent assay(ELISA).Clinical data of the two groups were collected and compared.Pearson correlation analysis and multiple linear regression were used to analyze the relationship between serum GDF-15,chemerin,PTX3 levels and obesity,insulin resistance and inflammation.Multivariate Logistic regression was used to evaluate the independent risk factors for T2DM development,and the com-bined prediction model of serum GDF-15,chemerin and PTX3 was constructed,and receiver operating charac-teristic(ROC)curve was plotted to evaluate its predictive efficacy for T2DM development.Results Compared with the control group,body mass index(BMI),waist-to-hip ratio(WHR),systolic blood pressure,total cho-lesterol,triglyceride,fasting blood glucose,fasting insulin(FINS),homeostasis model assessment of insulin re-sistance(HOMA-1R),interleukin(IL)-1β,IL-6,GDF-15,chemerin and PTX3 were all increased in T2DM group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis showed that se-rum GDF-15,chemerin and PTX3 levels were positively correlated with BMI,WHR,FINS,HOMA-IR,IL-1βand IL-6 in T2DM group(P＜0.05).Multiple linear regression analysis showed that BMI,FINS,HOMA-IR,IL-1β and IL-6 were positively correlated with serum GDF-15,chemerin and PTX3 levels(P＜0.05).Multiva-riate Logistic regression analysis showed that the increase of serum GDF-15,chemerin and PTX3 levels was an independent risk factor for T2DM development(P＜0.05).ROC curve analysis results showed that the com-bined prediction model of serum GDF-15,chemerin and PTX3 had better prediction efficiency,and its area un-der the curve,sensitivity,specificity and accuracy were higher than those applied alone.Conclusion The levels of GDF-15,chemerin and PTX3 in serum of T2DM patients are elevated,and their levels increase with the ex-acerbation of obesity,insulin resistance and inflammatory response in T2DM patients.The combined predic-tion model constructed in this study has good predictive efficacy and has high predictive value for the occur-rence of T2DM.

BACKGROUND:The distribution of the necrotic area plays an important role in hip preservation treatment.At present,there are few studies on whether the difference in the three-dimensional spatial distribution of osteonecrosis of the femoral head affects the clinical outcome of fibular support. OBJECTIVE:To explore the relationship between the spatial distribution and clinical outcome at the sites of osteonecrosis of the femoral head and fibular support using CT three-dimensional reconstruction so as to provide a basis for optimizing the applicable conditions of fibular support and improving the hip preservation effect of fibular support. METHODS:Eighty patients with osteonecrosis of the femoral head who were treated with fibular support for hip preservation from January 2010 to January 2021 were selected as the study subjects according to the inclusion criteria.They were followed up for at least 2 years.According to the clinical outcome,the patients were divided into the successful hip preservation group(n=55)and the failure hip preservation group(n=25).3D reconstruction was performed according to the preoperative and postoperative CT images of the patients.According to the three-column theory,the femoral head was divided into outer nine areas,middle nine areas and inner nine areas(L1-9,C1-9,and M1-9)to explore the spatial distribution of necrotic area of the femoral head and fibular support area and its relationship with clinical outcome. RESULTS AND CONCLUSION:(1)Before operation,the necrotic area of the femoral head was mainly distributed in L1,L2,L4,L5,C1,C2,C4,and C5(the upper and middle part of the anterior part of the outer ninth area and the middle part of the middle ninth area).After operation,the fibular support area was mainly distributed in L5,L6,C5,and C6(the middle and lower part of the outer ninth area and the middle and lower part of the middle ninth area).(2)There were significant differences in the distribution of osteonecrosis of the femoral head between the successful hip preservation group and the failure hip preservation group in L8(the posterior middle part of the outer ninth area),C3(the anterior lower part of the middle ninth area),C6(the lower middle part of the middle part of the inner ninth area)and M2(the anterior middle part of the inner ninth area)(P<0.05).There was a significant difference in the distribution of fibular support in L5 and L6(middle and lower part of outer nine)(P<0.05).Among them,the L8 region could be used as an independent predictor of hip preservation failure in fibular support surgery.The area under the curve of the L8 single factor prediction model was 0.698[95%CI(0.575,0.822)];the sensitivity was 76%,and the specificity was 63.6%.(3)It turns out,when the necrotic area involves L8,C3,C6,and M2,especially L8,the failure of fibular support may increase,and when the fibular support involves L5 and L6,the effect of hip preservation is often not ideal.

BACKGROUND:Bone has bioelectric effects.However,bone defects can lead to loss of endogenous bioelectricity in bone.The implantation of bone tissue engineering scaffolds with bioelectric effect into bone defects will replenish the missing electrical signals and accelerate the repair of bone defects. OBJECTIVE:To introduce the bioelectric effect of bone tissue and expound the repair effect of electrical stimulation on bone defects,summarize the research progress of bioelectric effect applied to bone tissue engineering,in order to provide new ideas for the research of bone tissue engineering. METHODS:Relevant articles were searched on CNKI,WanFang,PubMed,Web of Science and ScienceDirect databases,using"bioelectrical effect,bioelectrical materials,electrical stimulation,bone tissue engineering,bone scaffold,bone defect,bone repair,osteogenesis"as the English and Chinese search terms.Finally,87 articles were included for analysis. RESULTS AND CONCLUSION:(1)Bioelectrical effect combined with ex vivo electrical stimulation to design bone tissue engineering scaffolds is an ideal and feasible approach,and the main materials involved include metallic materials,graphene materials,natural bio-derived materials,and synthetic biomaterial.At present,the most widely used conductive material is graphene material,which benefits from its super conductivity,large specific surface area,good biocompatibility with cells and bones,and excellent mechanical properties.(2)Graphene materials are mainly introduced into the scaffold as modified materials to enhance the conductivity of the overall scaffold,while its large surface area and rich functional groups can promote the loading and release of bioactive substances.(3)However,there are still some major challenges to overcome for bioelectrically effective bone tissue engineering scaffolds:not only electrical conductivity but also the overall performance of the bracket needs to be considered;lack of uniform,standardized preparation of bioelectrically effective bone tissue engineering scaffolds;extracorporeal electrical stimulation intervention systems are not yet mature enough;lack of individualized guidance on stent selection to enable the selection and design of the most appropriate stent for patients with different pathologies.(4)When designing conductive scaffolds,researchers have to deeply consider the comprehensive effects of the scaffolds,such as biocompatibility,mechanical properties,and biodegradability.This combination of properties can be achieved by combining multiple materials.(5)Beyond that,clinical translation should be the ultimate consideration for conductive stent design.On the basis of evaluating the safe current threshold for electrical stimulation to act on the human body and facilitate the repair of bone defects,animal experiments as well as basic experiments are designed and then applied to the clinic to achieve the ultimate goal of applying bioelectrical effect bone tissue engineering scaffolds in the clinic.

OBJECTIVE To study the effect of different doses of aspirin on clinical efficacy in acute stage of Kawasaki’s disease, and to explore the optimal dose of aspirin. METHODS A total of 150 patients suffered from Kawasaki’s disease were randomly selected by hospital information system from March to May 2022 for retrospective analysis. According to different doses of aspirin, they were divided into three groups: high dose group(>50 mg·kg−1·d−1), medium dose group(30−50 mg·kg−1·d−1) and low dose group(<30 mg·kg−1·d−1). The antipyretic time, the incidence of non-response to intravenous human immunoglobulin, the improvement of laboratory indexes and prevalence of adverse drug reaction were compared among the three groups. RESULTS There was no significant difference in body temperature recovery among the three groups under different doses of aspirin. There was no significant difference in patients with non-response to intravenous human immunoglobulin among the three groups. Before treatment, there were no significant differences in white blood cell(WBC) count, blood platelet(PLT) count and C-reactive protein(CRP) concentration among the three groups. After treatment, the count of WBC, PLT and CRP in the three groups was significantly improved compared with that before treatment, and the difference was statistically significant(P<0.05). However, there was no significant difference in the above indexes among the three groups after treatment. There was a higher incidence of adverse reactions in children treated with medium or high dose aspirin. CONCLUSION Different doses of aspirin combined with intravenous human immunoglobulin have good therapeutic effect on Kawasaki’s disease, but considering the safety and economy of aspirin, low dose administration is recommended.

Objective To explore whether the locus coeruleus(LC)mediates the pain in mice with depressive-like behaviors and underlying mechanisms.Methods Male C57BL/6J mice were randomly divided into two groups,in-cluding control and chronic restraint stress(CRS)group.Novelty-suppressed feeding test,tail suspension test and forced swimming test were used to assess the formation of depressive-like behaviors and the establishment of CRS model.The mechanical pain threshold of mice was detected by Von Frey brush test.LC neuronal activity was de-tected by c-Fos immunofluorescence staining.Neuronal excitability in LC was detected using electrophysiology of i-solated brain slices.The influence on pain and depressive-like behaviors was identified by chemogenetics in LC.Results Compared with the Control group,CRS mice displayed significant depressive-like behavior after 3 weeks of CRS(CRS 3W),and the model was successful;CRS 3W mice showed a significant decrease in mechanical pain threshold and developed mechanical pain sensitivity.A lot of c-Fos+cells of LC was observed in CRS 3W mice,90％ of them were noradrenergic neurons.Compared with the Control group,the neuronal excitability of noradren-ergic neurons decreased in LC of CRS 3W mice.Compared with the Control group,chemogenetic activation of the LC noradrenergic neurons significantly reduced mechanical pain sensitization in CRS 3W mice.Conclusion The excitability of noradrenergic neurons in LC of CRS 3W mice decreases,and chemogenetic activation of noradrener-gic neurons in LC can relieve pain sensitization in CRS 3W mice.

Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective To investigate the relationship between appendicular skeletal muscle composition(muscle mass and muscle index)and glycosylated hemoglobin A1c(HbA1c)level in type 2 diabetes mellitus(T2DM)patients.Methods A total of 459 adult T2DM patients hospitalized in the Department of Endocrinology,Tangdu Hospital of Air Force Medical University from April 2021 to June 2022 were selected as the research objects.Bioelectrical impedance analysis was used to evaluate the body composition of the patients.The patients were divided into two groups according to HbA1c level:standard glycation group(HbA1c≤7.0%,n=145)and unqualified glycation group(HbA1c>7.0%,n=314).The two groups'general data,biochemical indexes,muscle content,fat content and other body composition were analyzed.Spearman correlation analysis and multiple logistic regression analysis were used to analyze the relationship between body composition and glycemic control in type 2 diabetic patients.Results The appendicular skeletal muscle mass and its index(ASMI)of the patients in the standard glycation group were better than those in the unqualified glycation group(P<0.05).However,there were no significant differences in gender,history of antidiabetic drugs and body fat(body fat content,limb fat content and visceral fat content)between the two groups(P>0.05).Spearman correlation analysis showed that appendicular skeletal muscle mass and its index were negatively correlated with HbA1c(r=-0.158,P=0.001;r=-0.187,P<0.001).Logistic regression analysis showed that upper limb skeletal muscle mass(OR=3.570,95%CI 2.293-5.559)and lower limb skeletal muscle mass(OR=1.297,95%CI 1.146-1.468)were independent protective factors for achieving glycation standard in HbA1c group.Conclusions The skeletal muscle mass of limbs is a protective factor for reaching the standard of HbA1c.With the increase of skeletal muscle mass of limbs,the level of HbA1c gradually decreases.Among them,the increase of upper limb muscle mass has a stronger correlation with reaching the standard of HbA1c.

Objective To explore the influential factors and predictive value of early femoral head collapse progression following allogeneic fibula grafting(AFG)surgery.Methods Clinical and radiological data of 68 patients(75 hips)with osteonecrosis of the femoral head(ONFH)who underwent AFG between January 2008 and December 2022 at the Orthopedics and Traumatology Department,Affiliated Hospital of Nanjing University of Chinese Medicine were retrospectively analyzed.Seventy-five hips were divided into stable(n=40)and progressive(n=35)groups based on the presence or absence of postoperative collapse progression.Age,gender,etiology,location of the lesion,Association Research Circulation Osseous(ARCO)stage,Japanese Committee of Osteonecrosis Investigation(JIC)classification,China-Japan Friendship Hospital(CJFH)classification,and Hounsfield units(HU)value of anterolateral sclerosis rim(ⅠSHU)were collected.Univariate and multivariate logistic regression analyses were used to identify the factors influencing early collapse progression after AFG.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of the identified factors influencing postoperative early collapse progression.Results Of the 75 hips,35(46.7%)had postoperative collapse progression.Univariate logistic regression analysis showed that age,ARCO stage,JIC classification,and ⅠSHU were in fluencing factors for early femoral head collapse progression after AFG(P<0.05).Multivariate logistic regression analysis showed that ARCO stage ⅢA and JIC classification C2 were independent risk factors for early femoral head collapse progression after AFG,while ⅠSHU was identified as an independent protective factor(P<0.05).The ROC curve analysis showed that the sensitivities of ARCO stage,JIC classification,ⅠSHU,and the combined predictive model were 0.850,0.725,0.800,and 0.775,the specificities were 0.486,0.657,0.743,and 0.914,and the area under the ROC curve(AUC)were 0.668,0.725,0.811,and 0.896,respectively.Conclusions ⅠSHU is associated with early collapse progression after AFG in patients with ONFH.ARCO stage ⅢA,JIC classification C2,and ⅠSHU are independent factors influencing postoperative early collapse progression and have a certain predictive value.