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.

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: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.

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

Objective:To explore the effect of systematic diagnosis and treatment model based on new classification on primary hypospadias.Methods:The data of 689 patients with primary hypospadias admitted to Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from March 2010 to June 2021 were retrospectively analyzed. Of all, 349 cases from March 2010 to June 2016 were treated with traditional treatment methods, and 340 cases from July 2016 to June 2021 were treated with systematic diagnosis and treatment model based on new hypospadias classification. Traditional treatment group of patients according to the European Society of Urology (EAU) guide classification, were divided into the distal-anterior type (located on the glans or distal shaft of the penis), intermediate-middle type (penile) and proximal-posterior type (penoscrotal, scrotal, perineal). For distal type, tubularized incised plate (TIP) or dorsal inlay urethroplasty (Inlay) was performed. Patients with intermediate-middle type underwent Inlay, and patients with proximal-posterior type underwent Bracka staging. In the systematic diagnosis and treatment group, hypospadias was reclassified into distal type (located on the glan or in the first third of the shaft of the penis), junctional type (the back two-thirds of the shaft of the penis and the base of the penis), and proximal type (scrotum or perineum). For distal type, TIP or Inlay was used. Patients with junctional type were treated with urethroplasty with union free graft and local flap method (Montage). Patients with proximal type were treated with Montage or Bracka staging. Patients with testicular volume <0.8 ml and glans width <1.0 cm were treated with human chorionic gonadotropin (HCG) before surgery. There were 349 patients in the traditional group, with an average age of (18.58±7.59) months. There were 157 cases of distal-anterior type, 47 cases of intermediate-middle type and 145 cases of proximal-posterior type. There were 181 cases with penile curvature < 30° and 168 cases with penile curvature ≥30°. There were 340 cases in the systematic diagnosis and treatment group, with an average age of (18.94±6.05) months. According to EAU classification, 160 cases were distal-anterior type, 42 cases were intermediate-middle type and 138 cases were proximal-posterior type. There were 197 cases with penile curvature < 30° and 143 cases with penile curvature ≥30°. There was no significant difference in the above indicators between the two groups ( P>0.05). The surgical methods, incidence of postoperative complications and the time of hospital stay between the two groups compared. The changes in penis size and testis volume before and after the use of hormones in the systematic treatment group were compared. Results:In the traditional group, 139 patients underwent TIP, 65 patients underwent Inlay, and 145 patients underwent Bracka staging. In the systematic diagnosis and treatment group, 187 cases were reclassified as distal type (153 cases underwent TIP and 34 cases underwent Inlay). Of the 69 cases of junctional type, 10 cases underwent Inlay, and 59 cases underwent Montage. Of the 84 cases of proximal type, 77 cases underwent Montage, and 7 cases underwent Bracka staging. There was significant difference between the two groups ( P<0.01). In the traditional group, there were 31 cases of urinary fistula (8.9%), 43 cases of urethral stricture (12.3%), 21 cases of urethral diverticulum (6.1%), 45 cases of penile recurvature (12.9%), and the total incidence of complications was 40.1% (140/349). There were 19 cases of urinary fistula (5.6%), 28 cases of urethral stricture (8.2%), 15 cases of urethral diverticulum (4.4%) and 24 cases of penile recurvature (7.1%) in the systematic diagnosis and treatment group. The total incidence of complications was 25.3%(86/340). There were statistically significant differences in the incidence of the above complications between the two groups ( P<0.05). There was a significant difference in the duration of hospital stay between the traditional group and the systematic diagnosis and treatment group [(4.3±1.2) d vs. (1.5±0.5) d, P=0.01]. The width of glans penis after HCG treatment was (1.35±0.14) cm, which was significantly higher than that before HCG treatment [(0.96±0.24) cm, P=0.03]. The length of penis [(2.55±0.19) cm vs. (2.29±0.16) cm] and the volume of testis [(0.76±0.24) ml vs. (0.64±0.15) ml] were not significantly different from those before treatment ( P>0.05). Conclusions:The new classification has clarified the choice of surgical methods, avoiding the amplification of surgical indications. The systematic diagnosis and treatment model based on new classification has significantly improved the treatment effect of hypospadias and effectively reduced postoperative complications. It provides an optional diagnosis and treatment model for hypospadias.

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.

Objective:To compare the abilities of different neural networks to generate pseudo-computed tomography (CT) images from magnetic resonance imaging (MRI) images and to explore the feasibility of pseudo-CT for clinical radiotherapy planning.Methods:A total of 29 brain cancer patients with planning CT and diagnostic MRI were selected. 23 of these patients were used for training neural networks and 6 for testing pseudo-CT images. Cycle-consistent generative adversarial network (cycleGAN), contrastive learning for unpaired image-to-image translation (CUT), and improved network denseCUT proposed in this study were applied to generate pseudo-CT images from MRI images. The pseudo-CT images were imported into a clinical treatment planning system to verify the feasibility of applying this method to radiotherapy planning.Results:The comparison between the generated pseudo-CT images and real CT images showed that the mean absolute errors were (72.0±6.9), (72.5±8.0), and (64.6±7.3) HU for the cycleGAN, CUT, and denseCUT, respectively. Meanwhile, the structure similarity indices were 0.91±0.01, 0.91±0.01, and 0.93±0.01, respectively. The peak signal-to-noise ratios were (28.5±0.7), (28.5±0.7), and (29.5±0.7) dB, respectively. The 2%/2 mm γ passing rates were 98.05%, 97.92%, and 98.31% for the cycleGAN, CUT, and denseCUT, respectively.Conclusions:DenseCUT can generate more accurate pseudo-CT images and the pseudo-CT can meet the demand for the dose calculation of IMRT plan.

Objective:To investigate the regulation effect of miR-125b in the gastric cancer cell growth mediated by apoptosis related protein (Fas)/apoptosis related protein ligand (FasL) signal.Methods:Gastric cancer SGC-7901 cells were cultured in vitro. MiR-125b inhibitor sequence, NC sequence and transfection reagent were transfected into SGC-7901 cells and divided into three groups: miR-125b inhibited group, NC group and control group. The expression of miR-125b in transfected cells was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), and cell proliferation was detected by cell counting kit-8 (CCK-8) method. The colony formation was detected by plate cell clone formation assay. Cell apoptosis and cycle were detected by flow cytometry. The protein expression of Fas and FasL was detected by Western blot. The targeted regulation of Fas by miR-125b was detected by luciferase activity assay. Results:The expression level of miR-125 and the number of cell colony in miR-125b inhibited group was significantly lower than those in control group and NC group, and the inhibition rate of cell proliferation and apoptosis rate were significantly higher than that in control group and NC group (all P<0.05). The DNA content in G 1 phase in miR-125b inhibited group was significantly higher than that in control group and NC group, and the DNA content in S phase in miR-125b inhibited group was significantly lower than that in control group and NC group (all P<0.05). The expression of Fas and FasL protein in miR-125b inhibited group was significantly higher than that in control group and NC group (all P<0.05). The target site of miR-125b was found in 3′-UTR of Fas mRNA, and compared with the NC+ Fas 3′UTR-Wt group, the activity of luciferase in the miR-125b inhibited group+ Fas 3′-UTR-Wt group decreased significantly ( P<0.05). Conclusions:Inhibition of miR-125b expression can activate Fas/FasL signal and inhibit SGC-7901 cell proliferation, induce G 1 phase arrest of cell cycle and promote apoptosis.

Objective:To investigate the effects of piperine on experimental colon carcinogenesis induced by 1, 2-dimethylhydrazine (DMH)/sodium dextran sulfate (DSS) and its mechanism.Methods:36 mice were divided into control group, model group and piperine group, 12 mice in each group. The control group was given normal saline by gavage; The model group and piperine group were given 3.6 mg/(kg·d) of normal saline and piperine respectively after establishing the experimental colon cancer model induced by DMH/DSS. Tumor load and volume were observed. Hematoxylin and eosin (HE) staining was used to observe the histological change of colon in mice. RAS/PI3K/AKT related pathway protein expression was detected by Western blot.Results:The body weight gain, protein expression levels of cleaved poly-ADP ribose polymerase (PARP), cleaved caspase-3 in model group were significantly lower than those in the control group (all P<0.05). The protein expression levels of Bcl-2, Bax, pan-Ras, p-MEK, p-ERK, PI3K, p-AKT, NF-κBP65, c-Myc and cyclin D1 in model group were significantly higher than those in the control group (all P<0.05). The body weight gain, protein expression levels of cleaved PARP and cleaved caspase-3 in piperine group were significantly higher than those in model group (all P<0.05). The protein expression levels of Bcl-2, Bax, pan-Ras, p-MEK, p-ERK, PI3K, p-AKT, NF-κBP65, c-Myc and cyclin D1 in piperine group were significantly lower than those in model group (all P<0.05). Conclusions:Piperine can inhibit the occurrence of experimental colon cancer induced by DMH/DSS, which may involve multiple components of RAS/PI3K/AKT signal axis.