BACKGROUND:In China,the patient population with osteonecrosis is large,and there is an urgent need to find new preventive targets to develop more effective treatment strategies.Metabolomics studies have shown that there is an association between human metabolites and osteonecrosis,but the causal relationship between blood metabolites and osteonecrosis has not yet been clarified.OBJECTIVE:To investigate the causal relationship between blood metabolites and osteonecrosis through two-sample Mendelian randomization analysis.METHODS:The public data of 486 blood metabolites(exposure factors)and osteonecrosis(outcome factors)were collected.Data of 486 blood metabolites were derived from a genome-wide association estimate for blood metabolites published in Nature Genetics in 2014,which covered 7 824 European adults.The single nucleotide polymorphism data for osteonecrosis were obtained from the FinnGen public database R11 dataset,containing information on a total of 431 614 samples and 21 306 430 single nucleotide polymorphism loci,with 1 788 cases of osteonecrosis and 429 826 controls,with all participants being of European descent.Mendelian randomization analysis(inverse variance weighting method,MR-Egger method,and weighted median method)was performed by Rstudio software,and then the heterogeneity test,horizontal pleiotropy test and Steiger directionality test were performed to ensure the robustness and reliability of the results.RESULTS AND CONCLUSION:(1)Sixteen blood metabolites were identified as having a significant causal relationship with osteonecrosis(Pinverse variance weighting＜Pfalse discovery rate＜0.05).(2)Eight blood metabolites increased the risk of osteonecrosis(including four known metabolites and four unknown metabolites),specifically pantothenate,beta-hydroxyisovalerate,hippurate,salicyluric glucuronide,X-08766,X-11452,X-12776 and X-14662.(3)Eight blood metabolites could reduce the risk of osteonecrosis(six known metabolites and two unknown metabolites),including cortisol,1-palmitoylglycerol(1-monopalmitin),pyroglutamyl glycine,2-stearoylglycerophosphocholine,p-cresol sulfate,ergothioneine,X-06307,X-12092.(4)The above results suggest that there is a causal relationship between 16 blood metabolites and osteonecrosis,which is expected to be a potential target for intervention in the occurrence and treatment of osteonecrosis in the future.(5)Despite the lack of relevant data from large-scale Asian populations at present,this study provides important reference value for the field of osteonecrosis in China based on European population data.In the future,domestic medical workers may be able to achieve precise intervention for osteonecrosis by regulating metabolite levels.In addition,based on the results of this study,relevant researchers can further explore the mechanism of action of metabolites in the treatment of osteonecrosis with traditional Chinese medicine,which not only helps to deepen the understanding of traditional Chinese medical therapies but also promotes the progress of integrated traditional Chinese and Western medicine research,driving the development of personalized treatment plans that are more suitable for the characteristics of the Chinese population.

BACKGROUND:In China,the patient population with osteonecrosis is large,and there is an urgent need to find new preventive targets to develop more effective treatment strategies.Metabolomics studies have shown that there is an association between human metabolites and osteonecrosis,but the causal relationship between blood metabolites and osteonecrosis has not yet been clarified.OBJECTIVE:To investigate the causal relationship between blood metabolites and osteonecrosis through two-sample Mendelian randomization analysis.METHODS:The public data of 486 blood metabolites(exposure factors)and osteonecrosis(outcome factors)were collected.Data of 486 blood metabolites were derived from a genome-wide association estimate for blood metabolites published in Nature Genetics in 2014,which covered 7 824 European adults.The single nucleotide polymorphism data for osteonecrosis were obtained from the FinnGen public database R11 dataset,containing information on a total of 431 614 samples and 21 306 430 single nucleotide polymorphism loci,with 1 788 cases of osteonecrosis and 429 826 controls,with all participants being of European descent.Mendelian randomization analysis(inverse variance weighting method,MR-Egger method,and weighted median method)was performed by Rstudio software,and then the heterogeneity test,horizontal pleiotropy test and Steiger directionality test were performed to ensure the robustness and reliability of the results.RESULTS AND CONCLUSION:(1)Sixteen blood metabolites were identified as having a significant causal relationship with osteonecrosis(Pinverse variance weighting＜Pfalse discovery rate＜0.05).(2)Eight blood metabolites increased the risk of osteonecrosis(including four known metabolites and four unknown metabolites),specifically pantothenate,beta-hydroxyisovalerate,hippurate,salicyluric glucuronide,X-08766,X-11452,X-12776 and X-14662.(3)Eight blood metabolites could reduce the risk of osteonecrosis(six known metabolites and two unknown metabolites),including cortisol,1-palmitoylglycerol(1-monopalmitin),pyroglutamyl glycine,2-stearoylglycerophosphocholine,p-cresol sulfate,ergothioneine,X-06307,X-12092.(4)The above results suggest that there is a causal relationship between 16 blood metabolites and osteonecrosis,which is expected to be a potential target for intervention in the occurrence and treatment of osteonecrosis in the future.(5)Despite the lack of relevant data from large-scale Asian populations at present,this study provides important reference value for the field of osteonecrosis in China based on European population data.In the future,domestic medical workers may be able to achieve precise intervention for osteonecrosis by regulating metabolite levels.In addition,based on the results of this study,relevant researchers can further explore the mechanism of action of metabolites in the treatment of osteonecrosis with traditional Chinese medicine,which not only helps to deepen the understanding of traditional Chinese medical therapies but also promotes the progress of integrated traditional Chinese and Western medicine research,driving the development of personalized treatment plans that are more suitable for the characteristics of the Chinese population.

OBJECTIVE: To explore the effectiveness of the flexor digitorum longus (FDL) transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy in the treatment of stage ⅠAB progressive collapsing foot deformity (PCFD). METHODS: Between January 2019 and September 2023, 19 patients (19 feet) with stage ⅠAB PCFD were treated with FDL transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy. There were 11 males and 8 females, aged 18 to 60 years, with an average age of 45.5 years. Nine cases were on the left foot and 10 cases on the right foot. The disease duration was 9-21 months, with an average of 12.3 months. Postoperatively, the effectiveness was evaluated by visual analogue scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) score, and Tegner score. Based on X-ray films, the talonavicular coverage angle (TNCA), talus-first metatarsal angle (T1MT), Meary angle, and pitch angle were measured. The plantar pressure parameters of the foot were measured by the Footscan plantar pressure measurement system, including peak pressure and load of the forefoot, midfoot, and hind foot. The patients' satisfaction with the surgical outcome was evaluated. RESULTS: All 19 surgeries were successfully completed. One patient had poor incision healing after operation, while the incisions of the remaining patients healed by first intention. All patients were followed up 12-28 months (mean, 16.8 months). At last follow-up, the VAS score significantly decreased compared with that before operation, and the AOFAS score and Tegner score significantly increased ( P<0.05). Radiological measurements showed that the TNCA, T1MT, Meary angle, and Pitch angle all significantly improved compared with those before operation ( P<0.05). Plantar pressure tests indicated that the peak pressures of the forefoot and midfoot significantly reduced compared with those before operation ( P<0.05), while the peak pressure of the hind foot showed no significant change ( P>0.05). The forefoot load significantly increased and the midfoot load decreased compared with those before operation ( P<0.05), while the hind foot load showed no significant change ( P>0.05). The total satisfaction rate of patients with the surgical outcome (very satisfied+satisfied) reached 84.2% (16/19). CONCLUSION The FDL transfer combined with single-bundle spring ligament reconstruction and medial displacement calcaneal osteotomy can effectively correct the stage ⅠAB PCFD, improve the abnormal distribution of plantar pressure and load, alleviate foot pain symptoms, and improve foot movement function. The patient's satisfaction is high. However, the long-term effectiveness still needs to be further observed and clarified.
Humans ; Female ; Male ; Osteotomy/methods* ; Adult ; Middle Aged ; Calcaneus/surgery* ; Young Adult ; Adolescent ; Tendon Transfer/methods* ; Treatment Outcome ; Plastic Surgery Procedures/methods* ; Foot Deformities/surgery* ; Ligaments, Articular/surgery*

BACKGROUND:Hormonal osteonecrosis of the femoral head is strongly associated with aging,but the regulatory targets and mechanisms are still unclear.Through bioinformatics combined with machine learning analysis and experimental verification,the key genes of hormonal osteonecrosis of the femoral head mediated by cell senescence will be identified,which will provide new ideas for the prevention and treatment of hormonal osteonecrosis of the femoral head.OBJECTIVE:To screen and validate the senescence core genes of hormonal osteonecrosis of the femoral head using bioinformatics analysis to explore its mechanism of action.METHODS:The GSE123568 dataset was obtained from the GPL15207 platform of the GEO database,which contained the gene expression profiles of peripheral serum samples of 30 hormonal osteonecrosis of the femoral head patients and 10 healthy controls.Data on 279 cellular senescence-related genes were obtained from the CellAge database.Differential analysis and weighted correlation network analysis(WGCNA)were performed on hormonal osteonecrosis of the femoral head gene profiles,and both were intersected with senescence-related genes and then concatenated to obtain hormonal osteonecrosis of the femoral head senescence potential genes,and GO and KEGG analyses were performed.The machine learning method screened out the pivotal genes,constructed nomogram model,and performed consensus clustering and immune infiltration analysis.Finally,clinical femoral samples were collected for validation by qPCR and western blot assay.RESULTS AND CONCLUSION:(1)41 potential genes were obtained,which were mainly enriched in biological processes such as aging and oxidative stress response,as well as FoxO and tumor necrosis factor signaling pathways.(2)The pivotal genes catalase,connective tissue growth factor,forkhead box protein O3,insulin receptor substrate 2,and mitogen-activated protein kinase kinase 11 were obtained after machine learning identification,and the predictive ability of nomogram model was good.(3)The patients were classified into three groups,namely a,b and c,by the consensus clustering analysis.Catalase,forkhead box protein O3,insulin receptor substrate 2,and mitogen-activated protein kinase kinase 11 were differentially expressed among the three molecular subtypes(P＜0.05).Results of immune infiltration showed that the abundance of immune cells,such as activated CD4+T cells,activated CD8+T cells,and eosinophils,differed among the three molecular subclasses(P＜0.05).(4)The results of qPCR and western blot assay showed that the expression of catalase,connective tissue growth factor,forkhead box protein O3,and mitogen-activated protein kinase kinase 11 was lower in hormonal osteonecrosis of the femoral head group compared to the control group(P＜0.05),and the expression of insulin receptor substrate 2 was elevated(P＜0.05).(5)It is concluded that through in-depth analysis combined with bioinformatics and machine learning,and further experimental verification,five hormonal osteonecrosis of the femoral head age-related hub genes were finally identified.These genes are catalase,connective tissue growth factor,forkhead box o3,insulin receptor substrate 2,and serine/threonine kinase 11.These genes may provide potential molecular targets for the prevention and treatment of hormonal osteonecrosis of the femoral head in the future by regulating the cellular aging process.

Objective:To discuss the efficacy of temporomandibular joint disc anchoring(TMJDA)in the treatment of anterior disc displacement without reduction(ADDWoR)from clinical and imaging perspectives,in order to improve the clinicians'understanding of this surgical approach.Methods:Twenty-one ADDWoR patients who underwent TMJDA were retrospectively collected,involving a total of 25 temporomandibular joints(TMJs).The maximum mouth opening,visual analogue scale(VAS)score for pain,and Helkimo index were measured preoperatively,1 month postoperatively,and 6 months postoperatively in all the patients.Postoperative complications and satisfaction questionnaires were designed for the patients to self-evaluate the efficacy,and their magnetic resonance imaging(MRI)findings were assessed.Results:Compared with preoperative period,the maximum mouth opening at 1 month and 6 months postoperatively was significantly increased(P<0.05);compared with 1 month postoperatively,the maximum mouth opening at 6 months postoperatively was significantly increased(P<0.05).Compared with preoperative period,the VAS scores at 1 month and 6 months postoperatively were significantly decreased(P<0.05);compared with 1 month postoperatively,the VAS score at 6 months postoperatively was significantly decreased(P<0.05).Compared with preoperative period,the percentages of the patients with Di 0 and DiⅠ scores were significantly increased(P<0.05),while those with DiⅡand DiⅢ scores were significantly decreased(P<0.05),indicating significant improvement in TMJ function after surgery.Among the 21 ADDWoR patients,14(66.67%)were satisfied and 7(33.33%)were basically satisfied.Compared with preoperative period,the disc length was significantly increased postoperatively(P<0.01),while no significant difference was observed in condylar height(P>0.05);all displaced discs were repositioned postoperatively;among the 25 joints,23(92.00%)were evaluated as"excellent"and 2(8.00%)were evaluated as"good".No patients experienced postoperative facial nerve injury,local alopecia,surgical area depression,salivary fistula,or Frey syndrome;3 patients(3 joints)developed numbness in the preauricular area within 24 hours postoperatively,which resolved by the 6-month follow-up.Conclusion:TMJDA for the treatment of ADDWoR can stably reposition the disc,significantly improve mouth opening and pain levels,with a low incidence of postoperative complications.

Objective To evaluate the clinical efficacy of tendon-regulating and bone-setting manipulation combined with subtalar joint arthroereisis in the treatment of adolescent flexible flatfoot.Methods A retrospective analysis was conducted on the clinical data of 86 children with flexible flatfoot treated at Dongguan Hospital of Guangzhou University of Chinese Medicine(Dongguan Traditional Chinese Medicine Hospital)between December 2022 and February 2024.Based on pre-treatment physician-patient communication,the children were divided into an trial group(44 cases)and a control group(42 cases).The control group received subtalar joint arthroereisis alone,while the trial group received additional tendon-regulating and bone-setting manipulation just once one day before surgery and once weekly postoperatively for one month,with a follow-up period of no less than 6 months.The Visual Analogue Scale(VAS)pain score,American Orthopaedic Foot & Ankle Society(AOFAS)ankle-hindfoot score,Tegner activity score,radiographic parameters,and static plantar pressure parameters of the two groups were observed before and after surgery.Results(1)Regarding clinical data,all surgeries were successfully completed in both groups.There were no statistically significant differences in perioperative general data,including operative time,hospital stays,and complication rates(P＞0.05).All children were followed up for no less than 6 months.The results showed that at the final follow-up,the VAS pain score,AOFAS ankle-hindfoot score,and Tegner activity score were significantly improved in both groups compared to preoperative values(P＜0.05),and the improvement in the trial group was significantly greater than that in the control group(P＜0.05 or P＜0.01).(2)Regarding radiographic parameters,at the final follow-up,the talonavicular coverage angle(TNCA),talus-first metatarsal angle(T1MT),talus-second metatarsal angle(T2MT)on weight-bearing anteroposterior radiographs,and the Meary angle between the talus and the first metatarsal as well as calcaneal Pitch angle(Pitch angle)on weight-bearing lateral radiographs were significantly improved in both groups compared to preoperative values(P＜0.05).The improvement in Meary angle,T1MT angle,and T2MT angle in the trial group was significantly greater than that in the control group(P＜0.01).However,there were no statistically significant differences in TNCA and Pitch angle between the two groups at the final follow-up(P＞0.05).(3)Regarding plantar pressure testing,at the 1-month postoperative follow-up,the forefoot load increased significantly in both groups compared to preoperative values(P＜0.05),while the midfoot load significantly decreased(P＜0.05).The increase in forefoot load and decrease in midfoot load in the trial group were significantly greater than those in the control group(P＜0.05 or P＜0.01).However,there were no statistically significant differences in hindfoot load between preoperative and postoperative values or between the two groups at the 1-month follow-up(P＞0.05).Conclusion For adolescent flexible flatfoot,tendon-regulating and bone-setting manipulation combined with subtalar joint arthroereisis can effectively restore the arch,improve foot mechanical imbalance,thereby correcting flatfoot deformity and enhancing joint motor function.

BACKGROUND:Hormonal osteonecrosis of the femoral head is strongly associated with aging,but the regulatory targets and mechanisms are still unclear.Through bioinformatics combined with machine learning analysis and experimental verification,the key genes of hormonal osteonecrosis of the femoral head mediated by cell senescence will be identified,which will provide new ideas for the prevention and treatment of hormonal osteonecrosis of the femoral head.OBJECTIVE:To screen and validate the senescence core genes of hormonal osteonecrosis of the femoral head using bioinformatics analysis to explore its mechanism of action.METHODS:The GSE123568 dataset was obtained from the GPL15207 platform of the GEO database,which contained the gene expression profiles of peripheral serum samples of 30 hormonal osteonecrosis of the femoral head patients and 10 healthy controls.Data on 279 cellular senescence-related genes were obtained from the CellAge database.Differential analysis and weighted correlation network analysis(WGCNA)were performed on hormonal osteonecrosis of the femoral head gene profiles,and both were intersected with senescence-related genes and then concatenated to obtain hormonal osteonecrosis of the femoral head senescence potential genes,and GO and KEGG analyses were performed.The machine learning method screened out the pivotal genes,constructed nomogram model,and performed consensus clustering and immune infiltration analysis.Finally,clinical femoral samples were collected for validation by qPCR and western blot assay.RESULTS AND CONCLUSION:(1)41 potential genes were obtained,which were mainly enriched in biological processes such as aging and oxidative stress response,as well as FoxO and tumor necrosis factor signaling pathways.(2)The pivotal genes catalase,connective tissue growth factor,forkhead box protein O3,insulin receptor substrate 2,and mitogen-activated protein kinase kinase 11 were obtained after machine learning identification,and the predictive ability of nomogram model was good.(3)The patients were classified into three groups,namely a,b and c,by the consensus clustering analysis.Catalase,forkhead box protein O3,insulin receptor substrate 2,and mitogen-activated protein kinase kinase 11 were differentially expressed among the three molecular subtypes(P＜0.05).Results of immune infiltration showed that the abundance of immune cells,such as activated CD4+T cells,activated CD8+T cells,and eosinophils,differed among the three molecular subclasses(P＜0.05).(4)The results of qPCR and western blot assay showed that the expression of catalase,connective tissue growth factor,forkhead box protein O3,and mitogen-activated protein kinase kinase 11 was lower in hormonal osteonecrosis of the femoral head group compared to the control group(P＜0.05),and the expression of insulin receptor substrate 2 was elevated(P＜0.05).(5)It is concluded that through in-depth analysis combined with bioinformatics and machine learning,and further experimental verification,five hormonal osteonecrosis of the femoral head age-related hub genes were finally identified.These genes are catalase,connective tissue growth factor,forkhead box o3,insulin receptor substrate 2,and serine/threonine kinase 11.These genes may provide potential molecular targets for the prevention and treatment of hormonal osteonecrosis of the femoral head in the future by regulating the cellular aging process.

Objective:To select the differential prognostic lactic acid metabolism-related genes(LRGs)of the head and neck squamous cell carcinoma(HNSCC)to construct the LRGs prognostic model of HNSCC,and to clarify the potential mechanism.Methods:The HNSCC gene expression and clinical data were obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)Databases,the LRGs were identified through GeneCards Database,and R software was used to screen out the LRGs of HNSCC;univariate Cox regression analysis was used to identify prognosis-related genes;two different subtypes were identified based on the prognostis-related LRGs;Kaplan-Meier(K-M)curve analysis was used to compare the prognosis of the patients between two groups;CIBERSORT algorithm was used to perform the immuno-correlation analysis between two groups;multivariate Cox regression analysis and LASSO regression analysis were used to construct the prognostic model;receiver operating characteristic curve(ROC)and K-M survival curve were used to assess the relationship between LRGs and survival and prognosis of the HNSCC patients.The prognostic model was validated by GSE27020,GSE41613,and GSE65858 datasets.The experiment were grouped based on risk score,and immune-related analysis and tumor score analysis were performed.Results:The TCGA Database differential analysis results showed that 1 196 LRGs were identified from HNSCC samples;univariate Cox regression analysis selected 27 differentially expressed genes(DEGs)associated with the prognosis of the HNSCC patients.Two different LRGs subtypes(Group 1 and Group 2)were identified according to the prognosis-related genes.The K-M survival curves results showed that the overall survival(OS)of the patients in Group 2 was significantly higher than that in Group 1,and the immune cell expression amount of the patients in Group 2 was also higher than that in group 1.The multivariate Cox regression and LASSO regression analysis results screened out 9 LRGs,including hypoxanthine phosphoribosyltransferase 1(HPRT1),amyloid precursor protein(APP),glycogen phosphorylase L(PYGL),urokinase-type plasminogen activator(PLAU),cannabinoid receptor 2(CNR2),stanniocalcin 2(STC2),nucleotide binding oligomerization domain-like receptor protein 1(NLRP1),integrin-linked kinase(ILK),and forkhead box B1(FOXB1);the prognostic model was constructed.The K-M and ROC curve results indicated that the expression levels of above 9 genes were associated with the survival and prognosis of the HNSCC patients,providing good 1-year,2-year,and 3-year survival prediction effect,and the area under ROC curve(AUC)values were all greater than 0.650.Furthermore,the predictive ability of the prognosis model was validated in GSE27020,GSE41613,and GSE65858 datasets.The patients classified based on the risk scores had distinguishable immune statuses.Conclusion:The differentially expressed LRGs of HNSCC screened by bioinformatics methods are related to the survival and prognosis of the HNSCC patients;the prognostic model constructed by 9 LRGs can predict the survival status and treatment response of the HNSCC patients.

ObjectiveTo compare the difference in adverse reactions after oxaliplatin-containing chemotherapy between colorectal cancer patients with or without spleen-kidney yang deficiency syndrome. MethodsA retrospective study was conducted using the electronic medical records of Beijing Hospital of Traditional Chinese Medicine， Capital Medical University. A total of 483 colorectal cancer patients from January 1， 2009 to December 31， 2022 were selected. Patients were divided into two groups based on their syndrome types， that was spleen-kidney yang deficiency syndrome （SKYDS） group （130 cases） and non-SKYDS group （353 cases）. The incidence of adverse reactions including gastrointestinal reactions， liver damage， bone marrow suppression， and peripheral neurotoxicity after completing 2， 4， 6， and more than 6 cycles of chemotherapy was compared between the two groups. Univariate and multivariate logistic regression analyses were used to analyze the associations of age， gender， alcohol history， primary tumor location， tumor differentiation， tumor staging， chemotherapy courses， and syndrome types with the occurrence of gastrointestinal adverse reactions， liver function damage， bone marrow suppression and peripheral neurotoxicity in colorectal cancer patients who have completed 2， 4， 6 and more than 6 cycles of oxaliplatin-containing chemotherapy. ResultsThere were significant differences in the occurrence of gastrointestinal reactions after completing 2， 4， 6 and more than 6 cycles of chemotherapy between the two groups （P＜0.01）， with much more severe conditions in SKYDS group than non-SKYDS group （P＜0.01）. There was no significant difference in liver function damage and bone marrow suppression between groups （P＞0.05）. There were statistically significant differences in the occurrence of peripheral neurotoxicity after completion of 2 cycles （P=0.044）， 4 cycles （P=0.002） and more than 6 cycles （P＜0.001） of chemothe-rapy， with higher rate in SKYDS group than the non-SKYDS group （P＜0.05）. Univariate analysis showed that female， patients with stage Ⅲ tumors and patients having completed ≥ 6 cycles of chemotherapy had a higher incidence of bone marrow suppression （P＜0.05）， and patients with SKYDS had a higher incidence of gastrointestinal reactions （P＜0.001）. Patients with a history of drinking， stage Ⅳ cancer， and ≥6 cycles of chemotherapy had a higher incidence of liver function injury （P＜0.05）. Patients with stage Ⅲ cancer， ≥6 cycles of chemotherapy， and SKYDS had a higher incidence of peripheral neurotoxicity （P＜0.05）. Multivariate analysis showed that the risk factor for bone marrow suppression was chemotherapy ≥6 cycles （P=0.001）， and SKYDS was the risk factor for gastrointestinal reaction （P＜0.001）. The risk factor for liver function damage was tumor stage Ⅳ （P=0.001） and SKYDS （P=0.039）. All variables had no significant correlation with the occurrence of peripheral neurotoxicity. ConclusionFor colorectal cancer patients， being diagnosed with SKYDS is a risk factor for developing gastrointestinal adverse reactions and peripheral neurotoxicity following chemotherapy with an oxaliplatin-based regimen.