BACKGROUND:Knee osteoarthritis(KOA)is a common chronic inflammatory disease that causes damage to joint cartilage and surrounding tissues.Immune cells play an important role in the immune-inflammatory response in knee osteoarthritis,but the specific mechanisms involved are still not fully understood. OBJECTIVE:To evaluate the potential causal relationship between 731 immune cell phenotypes and the risk of knee osteoarthritis using Mendelian randomization. METHODS:Summary statistics of genome-wide association studies(GWAS)for 731 immune cell phenotypes(from GCST0001391 to GCST0002121)obtained from the GWAS catalog and GWAS data for knee osteoarthritis from the IEUGWAS database(ebi-a-GCST007090)were used.Inverse variance-weighted method,MR-Egger regression,weighted median method,weighted mode method,and simple mode method were employed to investigate the causal relationship between immune cells and knee osteoarthritis.Sensitivity analyses were conducted to assess the reliability of the Mendelian randomization results.Reverse Mendelian randomization analysis was also performed using the same methods. RESULTS AND CONCLUSION:The forward MR analysis indicated significant causal relationships(FDR<0.20)between knee osteoarthritis and four immune cell phenotypes,namely CD27 on CD24+CD27+in B cells(OR=1.026,P=0.000 26,Pfdr=0.18),CD33 on CD33dim HLA DR-in myeloid cells(OR=1.014,P=0.000 50,Pfdr=0.18),and CD45RA+CD28-CD8br%CD8br in Treg cells(OR=1.001,P=0.000 78,Pfdr=0.18),and PDL-1 on monocytes in mononuclear cells(OR=0.952,P=0.000 98,Pfdr=0.18).These immune cell phenotypes showed direct positive or negative causal associations with the risk of knee osteoarthritis.Reverse Mendelian randomization analysis revealed no significant causal relationships(FDR<0.20)between knee osteoarthritis as exposure and any of the 731 immune cell phenotypes.The results of sensitivity analysis show that the P-values of the Cochran's Q test and the MR-Egger regression method for bidirectional Mendelian randomization were both greater than 0.05,indicating that there is no significant heterogeneity and pleiotropy in the causal effect analysis between immune cell phenotypes and knee osteoarthritis.To conclude,there may be four potential causal relationships between immune cell phenotypes,such as CD27 on CD24+CD27+cells,CD33 on CD33dim HLA DR-cells,CD45RA+CD28-CD8br%CD8br cells,and PDL-1 on monocytes,and knee osteoarthritis.These findings provide valuable clues for studying the biological mechanisms of knee osteoarthritis and exploring early prevention and treatment strategies.They also offer new directions for the development of intervention drugs.

AIM:To investigate the impact of es-ketamine-mediated opioid-free anesthesia(OFA)on postoperative gastrointestinal function in patients undergoing laparoscopic distal gastrectomy for gas-tric cancer.METHODS:A total of 150 pa-tients,scheduled for elective laparoscopic distal gas-trectomy for gastric cancer and meeting the inclu-sion and exclusion criteria,were randomly assigned to either the OFA group or the opioid-based anes-thesia(OBA)group using a random number ta-ble,with 75 patients in each group.The OFA group was administered an anesthesia regimen pri-marily consisting of esketamine,while the OBA group received conventional opioid anesthesia,pri-marily consisting of sufentanil and remifentanil.The primary outcome measure was postoperative flatus time,defined as the interval from the end of sur-gery to the first passage of gas.RESULTS:The OFA group exhibited a shorter postoperative flatus time compared to the OBA group(P＜0.01).Intraopera-tive blood loss and norepinephrine consumption were significantly less in the OFA group compared to the OBA group(P＜0.05);the postoperative HADS-D score was better in the OFA group than in the OBA group,and both the OFA and OBA groups showed significantly lower postoperative HADS-A and HADS-D scores compared to their preoperative levels(P＜0.05);the incidence rate of abdominal distension was significantly lower in the OFA group compared to the OBA group(P＜0.05).CONCLUSION:The use of esketamine-mediated opioid-free anesthesia can expedite gastrointestinal function recovery,reduce hospital stay duration,and decrease postoperative adverse reactions in patients undergoing laparo-scopic distal gastrectomy for gastric cancer.

AIM:To investigate the impact of es-ketamine-mediated opioid-free anesthesia(OFA)on postoperative gastrointestinal function in patients undergoing laparoscopic distal gastrectomy for gas-tric cancer.METHODS:A total of 150 pa-tients,scheduled for elective laparoscopic distal gas-trectomy for gastric cancer and meeting the inclu-sion and exclusion criteria,were randomly assigned to either the OFA group or the opioid-based anes-thesia(OBA)group using a random number ta-ble,with 75 patients in each group.The OFA group was administered an anesthesia regimen pri-marily consisting of esketamine,while the OBA group received conventional opioid anesthesia,pri-marily consisting of sufentanil and remifentanil.The primary outcome measure was postoperative flatus time,defined as the interval from the end of sur-gery to the first passage of gas.RESULTS:The OFA group exhibited a shorter postoperative flatus time compared to the OBA group(P＜0.01).Intraopera-tive blood loss and norepinephrine consumption were significantly less in the OFA group compared to the OBA group(P＜0.05);the postoperative HADS-D score was better in the OFA group than in the OBA group,and both the OFA and OBA groups showed significantly lower postoperative HADS-A and HADS-D scores compared to their preoperative levels(P＜0.05);the incidence rate of abdominal distension was significantly lower in the OFA group compared to the OBA group(P＜0.05).CONCLUSION:The use of esketamine-mediated opioid-free anesthesia can expedite gastrointestinal function recovery,reduce hospital stay duration,and decrease postoperative adverse reactions in patients undergoing laparo-scopic distal gastrectomy for gastric cancer.

Objective:To analyze the clinical efficacy of arthroscopic transverse release of the iliotibial band through peritrochanteric space for the treatment of external snapping hip.Methods:A total of 30 patients (12 males and 18 females) with bilateral external snapping hip underwent arthroscopic transverse release of the iliotibial band through peritrochanteric space in Department of Sports Medicine, Senior Department of Orthopaedics, the Fourth Medical Center, Chinese PLA General Hospital were retrospectively analyzed from May 2021 and June 2022. The average age was 32.5±8.2 years (range, 17-51 years). At the same time, 30 patients who underwent arthroscopic external release of the iliotibial band through the external surface of the iliotibial band (external iliotibial band group) were selected as control group, including 13 males and 17 females, aged 29.5±6.8 years (range, 11-45 years). The visual analogue scale (VAS), modified Harris hip score (mHHS), and gluteal muscle contracture disability scale (GDS) were compared between the two groups at preoperative, 6 months postoperative, and final follow-up.Results:All patients successfully completed the operation and were followed up for 17.5±3.3 months (range, 12-25 months). The VAS scores of the two groups at the last follow-up were lower than those before operation ( P<0.05). The mHHS scores before operation, 6 months after operation and at the last follow-up in the peritrochanteric space group were 76.5 (67.0, 85.5), 98.5 (94.8, 100.0) and 100.0 (97.0, 100.0), respectively, and those in the external iliotibial band group were 80.5 (70.0, 86.0), 100.0 (96.0, 100.0) and 100.0 (99.5, 100.0). The differences in mHHS scores between the two groups were statistically significant for intragroup comparisons ( P<0.05); of these, 6 months postoperatively and at the last follow-up were greater than preoperatively, with statistically significant differences ( P<0.05); the differences at 6 months postoperatively and at the last follow-up were not statistically significant ( P>0.05). There was no significant difference in mHHS scores between groups at different time points ( P>0.05). The GDS before operation, at 6 months after operation and at the last follow-up were 47.0 (35.8, 64.5), 90.0 (81.0, 94.0) and 93.5 (89.8, 98.0) in the peritrochanteric space group, and 51.0 (38.0, 64.5), 50.0 (81.0, 94.0) and 93.5 (89.8, 98.0) in the external iliotibial band group, respectively. The differences in GDS between the two groups were statistically significant for intragroup comparisons ( P< 0.05); of these, 6 months postoperatively and at the last follow-up were greater than preoperatively, with statistically significant differences ( P<0.05); the differences at 6 months postoperatively and at the last follow-up were not statistically significant ( P>0.05). There was no significant difference in GDS between groups at different time points ( P>0.05). Conclusion:Arthroscopic transverse release of the iliotibial band through peritrochanteric space for the treatment of external snapping hip can effectively reduce hip pain and improve hip function, with satisfactory clinical results, and can be used as an alternative treatment to transverse release through the external surface of the iliotibial band.

BACKGROUND:Rapid developments in the field of bioinformatics have provided new methods for the diagnosis of osteoarthritis.Artificial neural networks have powerful data computing and classification capabilities,which have shown better performance in disease diagnosis. OBJECTIVE:To establish a new diagnostic predictive model of osteoarthritis based on artificial neural network and to verify the diagnostic value of the model in osteoarthritis with an external dataset. METHODS:The eligible osteoarthritis-related data sets were downloaded through GEO database search and divided into Train group and Test group.The gene expression matrix of the Train group was analyzed to screen the differentially expressed genes.GO and KEGG enrichment analyses were performed on the differentially expressed genes.Through Lasso regression model,support vector machine model and random forest tree model,the key genes of osteoarthritis were further identified from the differentially expressed genes.The R software"Neuralnet"package was then used to construct the osteoarthritis diagnosis model based on artificial neural network,and the model performance was evaluated by the five-fold cross-validation.Two independent data sets in the Test group were used to verify their diagnostic results. RESULTS AND CONCLUSION:A total of 90 differentially expressed genes related to osteoarthritis were obtained by differential analysis,of which 33 were down-regulated and 57 were up-regulated.GO enrichment analysis showed that the differentially expressed genes were mainly involved in the following biological processes,including leukocyte-mediated immunity,leukocyte migration in bone marrow and chemokine production.KEGG enrichment analysis showed that these genes were mainly enriched in rheumatoid arthritis,interleukin-17 signaling pathway and osteoclast differentiation pathway.Five key genes for the diagnosis of osteoarthritis,HMGB2,GADD45A,SLC19A2,TPPP3 and FOLR2,were identified by three machine learning methods.The artificial neural network model of five key genes in the Train group showed that the accuracy was 96.36%and the area under the curve was 0.997.The five-fold cross validation of the neural network model showed that the average area under the curve was greater than 0.9 and the model was of robustness.Two independent data sets in the Test group showed its area under the curve was 0.814 and 0.788 respectively.Therefore,the establishment of an artificial neural network model for the diagnosis of osteoarthritis has a certain diagnostic value.

BACKGROUND:Rheumatoid arthritis is a chronic systemic autoimmune disease.It is important to study the immunological changes involved in it for diagnosis and treatment. OBJECTIVE:To identify immune-related biomarkers associated with rheumatoid arthritis utilizing bioinformatics techniques and examine alterations in immune cell infiltration as well as the relationship between immune cells and biomarkers. METHODS:Differential expression analysis was used to identify the immune-related genes that were up-regulated in rheumatoid arthritis based on the GEO and Immport databases.Kyoto encyclopedia of genes and genomes(KEGG)and gene ontology(GO)enrichment analyses were used to investigate the possible function of these elevated genes.The immunological characteristic genes associated with rheumatoid arthritis were screened using least absolute shrinkage and selection operator(Lasso)and support vector machine recursive feature elimination(SVM-RFE).Independent datasets were used for difference validation,and the diagnostic performance was evaluated by plotting receiver operating characteristic curves for feature genes.Immune cell infiltration was used to analyze the differential profile of immune cells in rheumatoid arthritis and the correlation between the characterized genes and immune cells.In order to ascertain the causal relationship between monocytes and rheumatoid arthritis in immune cells,Mendelian randomization analysis was ultimately employed. RESULTS AND CONCLUSION:There were 39 upregulated differentially expressed genes in rheumatoid arthritis.The genes were primarily enriched in chemotaxis,cytokine activity,and immune receptor activity,according to GO enrichment analysis,while kEGG enrichment analysis revealed that the genes were considerably enriched in the tumor necrosis factor signaling pathway and peripheral leukocyte migration.Lasso and SVM-RFE identified five feature genes:CXCL13,SDC1,IGLC1,PLXNC1,and SLC29A3.Independent dataset validation of the feature genes found them to be similarly highly expressed in rheumatoid arthritis samples,with area under the curve values greater than 0.8 for all five feature genes in both datasets.Immune cell infiltration indicated that most immune cells,including natural killer cells and monocytes,exhibited increased levels of infiltration in rheumatoid arthritis samples.The correlation analysis revealed a significant positive correlation between memory B cells and immature B cells and these five feature genes.Correlation analysis showed that the five feature genes were positively correlated with memory B cells and immature B cells.The inverse variance weighting method revealed that monocytes were associated with the risk of developing rheumatoid arthritis.

Objective:The aim of this study was to explore the molecular mechanisms of sulforaphane in the treatment of autism spectrum disorders (ASD), identify metabolomic biomarkers associated with efficacy and construct efficacy prediction models.Methods:Forty children with ASD who were treated in Second Xiangya Hospital of Central South University and Guangzhou Huiai Hospital were recruited from August 2016 to May 2019. The patients were randomly allocated into sulforaphane treatment group ( n=26) and placebo group ( n=14). The OSU Autism Rating Scale-DSM-Ⅳ (OARS-4) was used to assess the change in clinical symptoms of children with ASD at baseline, week 4, week 8 and week 12 of treatment. A generalized linear mixed model was used to compare the differences in OARS-4 scale scores between groups and time. Plasma samples were collected from patients before and after treatment for untargeted metabolomic detection using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Differential metabolites were screened using ANOVA-component analysis, and metabolic pathway analysis was performed. Then, spearman correlation analysis was performed to find differential metabolites significantly associated with the efficacy of sulforaphane treatment, and finally Fisher′s discriminant analysis was used to screen for efficacy predictors. Result:After 12 weeks of treatment, the clinical symptoms improvement was significantly better in the sulforaphane group than in the placebo group ( F=14.11, P<0.001). There were differences in a total of 201 metabolites between the two groups, which were mainly significantly enriched in glycerophospholipid metabolism and primary bile acid biosynthesis pathways. Spearman′s correlation analysis showed that taurine, phosphatidylserine and lysophosphatidylserine were significantly positively associated with symptom changes in patients with ASD ( r=0.643, 0.401, 0.414, P<0.05 or 0.001), while lysophosphatidylethanolamine, sphingomyelin and triglyceride metabolites were significantly negatively associated with symptom changes ( r=-0.481--0.392, all P<0.05). Among them, sphingomyelin (d35∶1) and taurine entered the Fisher′s discriminant analysis model, which the accuracy of efficacy prediction was 84.6%(22/26). Conclusions:The molecular mechanism of sulforaphane in improving ASD related clinical symptoms may be related to cell membrane phospholipid metabolism. Sphingomyelin (d35∶1) and taurine may be possible predictors on the efficacy of sulforaphane in the treatment of ASD.

Objective:The aim of this study was to explore the molecular mechanisms of sulforaphane in the treatment of autism spectrum disorders (ASD), identify metabolomic biomarkers associated with efficacy and construct efficacy prediction models.Methods:Forty children with ASD who were treated in Second Xiangya Hospital of Central South University and Guangzhou Huiai Hospital were recruited from August 2016 to May 2019. The patients were randomly allocated into sulforaphane treatment group ( n=26) and placebo group ( n=14). The OSU Autism Rating Scale-DSM-Ⅳ (OARS-4) was used to assess the change in clinical symptoms of children with ASD at baseline, week 4, week 8 and week 12 of treatment. A generalized linear mixed model was used to compare the differences in OARS-4 scale scores between groups and time. Plasma samples were collected from patients before and after treatment for untargeted metabolomic detection using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Differential metabolites were screened using ANOVA-component analysis, and metabolic pathway analysis was performed. Then, spearman correlation analysis was performed to find differential metabolites significantly associated with the efficacy of sulforaphane treatment, and finally Fisher′s discriminant analysis was used to screen for efficacy predictors. Result:After 12 weeks of treatment, the clinical symptoms improvement was significantly better in the sulforaphane group than in the placebo group ( F=14.11, P<0.001). There were differences in a total of 201 metabolites between the two groups, which were mainly significantly enriched in glycerophospholipid metabolism and primary bile acid biosynthesis pathways. Spearman′s correlation analysis showed that taurine, phosphatidylserine and lysophosphatidylserine were significantly positively associated with symptom changes in patients with ASD ( r=0.643, 0.401, 0.414, P<0.05 or 0.001), while lysophosphatidylethanolamine, sphingomyelin and triglyceride metabolites were significantly negatively associated with symptom changes ( r=-0.481--0.392, all P<0.05). Among them, sphingomyelin (d35∶1) and taurine entered the Fisher′s discriminant analysis model, which the accuracy of efficacy prediction was 84.6%(22/26). Conclusions:The molecular mechanism of sulforaphane in improving ASD related clinical symptoms may be related to cell membrane phospholipid metabolism. Sphingomyelin (d35∶1) and taurine may be possible predictors on the efficacy of sulforaphane in the treatment of ASD.

Humans ; Acetabulum ; Consensus ; Developmental Dysplasia of the Hip/therapy* ; Hip Joint ; Treatment Outcome ; China

Objective:To compare the short-term efficacy of hip arthroscopic surgery assisted by platelet-rich plasma (PRP) and hip arthroscopy alone in the treatment of femoroacetabular impingement (FAI).Methods:A retrospective cohort study was performed on the clinical data of 133 FAI patients admitted to Fourth Medical Center of PLA General Hospital from January 2019 to January 2021. The patients included 86 males and 47 females, aged 19-71 years [(39.1±12.6)years]. A total of 67 patients were treated with hip arthroscopy alone (hip arthroscopy group), and 66 patients were treated with PRP after hip arthroscopy under ultrasound guidance (hip arthroscopy+PRP group). The two groups were compared before, at 12 months after surgery and at the last follow-up regarding the following items: Visual Analogue Scale (VAS), Modified Harris Hip Score, International Hip Outcome Tool-12 (iHOT-12), and Hip Outcome Score Activities of Daily Living Scale (HOS-ADL). The incidence rate of complications after surgery was compared between the two groups.Results:A total of 108 patients were followed up for 24-36 months [(28.5±3.8)months], while 25 patients were lost to follow-up because of withdrawal of consent, wrong telephone number, etc, including 11 patients (16.4%) in the hip arthroscopy group and 14 patients (21.2%) in the hip arthroscopy+PRP group. The values of VAS in the hip arthroscopy group before, at 12 months after surgery and at the last follow-up were 5.00(5.00, 7.00)points, 3.00(2.00, 3.75)points, and 1.00(0.00, 2.00)points, respectively; the values of Modified Harris Hip Score were 49.00(39.00, 57.00)points, 76.00(69.25, 82.00)points, and 86.00(82.00, 88.00)points, respectively; the values of iHOT-12 were 0.45(0.28, 0.58)points, 0.69(0.58, 0.80)points, and 0.81(0.70, 0.92)points, respectively; the values of HOS-ADL were 0.52(0.42, 0.68)points, 0.87(0.75, 0.93)points, and 0.93(0.86, 0.99)points, respectively. The scores of VAS in the hip arthroscopy + PRP group before, at 12 months after surgery and at the last follow-up were 6.00(5.00, 7.00)points, 3.00(2.00, 3.75)points, and 1.00(0.00, 2.00)points, respectively; the values of Modified Harris Hip Score were 46.50(37.00, 56.75)points, 78.00(72.00, 84.00)points, and 84.50(82.00, 88.00)points, respectively; the values of iHOT-12 were 0.42(0.26, 0.51)points, 0.66(0.58, 0.74)points, and 0.81(0.68, 0.88)points, respectively; the values of HOS-ADL were 0.54(0.38, 0.65)points, 0.87(0.72, 0.96)points, and 0.94(0.86, 1.00)points, respectively. In both groups, VAS, Modified Harris Hip Score, iHOT-12, and HOS-ADL were significantly improved at 12 months after surgery and at the last follow-up compared with those before surgery, and were further improved at the last follow-up compared with those at 12 months after surgery (all P<0.01). There were no significant differences in VAS, Modified Harris Hip Score, iHOT-12 and HOS-ADL between the two groups before, at 12 months after surgery and at the last follow-up (all P>0.05). There was no significant difference in the incidence rates of postoperative hip pain and clicking between the two groups (both P>0.05). Conclusion:Hip arthroscopy can considerably improve short-term hip symptoms and function in FAI patients, but the use of PRP treatment after hip arthroscopy cannot further improve its short-term efficacy in FAI patients.