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BACKGROUND: Osteoarthritis (OA) is a debilitating joint disorder characterized by the progressive degeneration of articular cartilage. Although the role of ion channels in OA pathogenesis is increasingly recognized, diagnostic markers and targeted therapies remain limited. METHODS: In this study, we analyzed the GSE48556 dataset to identify differentially expressed ion channel-related genes (DEGs) in OA and normal controls. We employed machine learning algorithms, least absolute shrinkage and selection operator(LASSO), and support vector machine recursive feature elimination(SVM-RFE) to select potential diagnostic markers. Then the gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to explore the potential diagnostic markers' involvement in biological pathways. Finally, weighted gene co-expression network analysis (WGCNA) was used to identify key genes associated with OA. RESULTS: We identified a total of 47 DEGs, with the majority involved in transient receptor potential (TRP) pathways. Seven genes (CHRNA4, GABRE, HTR3B, KCNG2, KCNJ2, LRRC8C, and TRPM5) were identified as the best characteristic genes for distinguishing OA from healthy samples. We performed clustering analysis and identified two distinct subtypes of OA, C1, and C2, with differential gene expression and immune cell infiltration profiles. Then we identified three key genes (PPP1R3D, ZNF101, and LOC651309) associated with OA. We constructed a prediction model using these genes and validated it using the GSE46750 dataset, demonstrating reasonable accuracy and specificity. CONCLUSIONS: Our findings provide novel insights into the role of ion channel-related genes in OA pathogenesis and offer potential diagnostic markers and therapeutic targets for the treatment of OA.
As society ages, the incidence of knee osteoarthritis continues to rise, bringing with it a series of social impacts and medical pressure. Despite the increasing recognition of the role of ion channels in the pathogenesis of OA, diagnostic markers and targeted therapies remain limited.This study investigated the role of TRP as possible diagnostic tools for OA.Seven TRP-related genes were identified as the best traits to distinguish OA from healthy samples, and then we constructed and validated risk scores for three key genes (PPP1R3D, ZNF101, and LOC651309) relevant to OA ion channel gene modules.Our findings provide novel insights into the role of ion channel-related genes in OA pathogenesis and offer a reference for further clinical diagnosis.
Subject(s)
Biomarkers , Computational Biology , Ion Channels , Machine Learning , Osteoarthritis , Humans , Osteoarthritis/genetics , Osteoarthritis/diagnosis , Ion Channels/genetics , Computational Biology/methods , Biomarkers/metabolism , Gene Expression Profiling , Gene Regulatory Networks , Support Vector MachineABSTRACT
Objective:To investigate the feasibility and effects of modified sequential correction technique combined 3-columns osteotomy for severe kyphoscoliosis.Methods:A retrospective analysis was performed on 18 patients (7 males and 11 females) with severe kyphosis who received modified sequential correction technique combined 3-columns osteotomy in our hospital from June 2019 to April 2020. Preoperative, postoperative and final follow-up clinical and imaging outcomes were evaluated.Results:In this cohort, the average fixed segment was 11.2±3.8. The average operative duration was 401.9±68.9 min and the average intraoperative blood loss was 2 418.8±736.9 ml. The Cobb angle was improved significantly from 65.0°±16.4° pre-operatively to 41.6°±14.1° post-operatively. At final follow-up, it was 41.4°±14.3°, which was not significantly different from that after operation. Global kyphosis (GK) was 65.5°±20.8° pre-operatively and 28.1°±13.8° post-operatively with correction rate of 57.8%±17.8%. However, GK was 29.3°±14 .2° at postoperative 1 year , which was not significantly different from that after operation. There was no significant difference in C 7PL-CSVL ( F=0.449 , P=0.642) or SVA ( F=3.519, P=0.058) among the three time points. There was no alter of SEP and MEP observed during operation. Four patients had temporary lower limb numbness after operation, while the symptoms disappeared at 6 months after operation. There was no instrumental failure during the follow-up. Conclusion:Patients with severe kyphoscoliosis can obtain satisfied local correction by undergoing modified sequential correction technique combined 3-columns osteotomy without significant loss of correction at 1 year after operation. It can effectively avoid instability and dislocation of the osteotomy site and massive bleeding during the operation. As a simplified surgical procedure, it can reduce the difficulty of rod loading without prolonged operation duration. Further, this technique can ensure lower incidence of neurological complications and rod failure.
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Objective:To investigate the clinical and imaging outcomes of Lenke 5 idiopathic scoliosis posterior selective fusion with "Last Touching Vertebra-1" as the lower instrumented vertebra (LIV).Methods:A total of 103 patients with Lenke 5 idiopathic scoliosis who underwent posterior selective fusion orthopedic surgery from April 2009 to March 2020 were analyzed retrospectively. The LIV was the last touching vertebra (LTV) in 45 cases (LTV group) and the LTV-1 in 58 cases (LTV-1 group). The follow-up duration was more than 2 years. SRS- 22 questionnaire was used to evaluate the clinical effects at 2 years after operation. The anterior and lateral radiographs of the whole spine were measured preoperatively, postoperatively and at 2 years after operation to obtain all the following imaging parameters, including scoliosis Cobb angle, apical vertebral translation (AVT), coronal balance, LIV tilt, LIV lower intervertebral disc angle, LIV translation, LIV lower vertebral translation, LTV/LIV rotation degree, lumbar lordosis angle, pelvic incidence angle, sagittal balance. The complications were summarized and were analyzed for investigating potential risk factors.Results:At 2 years after operation, the correction rates of main Cobb in LTV group and the LTV-1 group were 60.2%±11.1% and 55.3%±14.1%, respectively. The coronal balance was 3.5±9.8 mm and 4.9±10.6 mm respectively. The sagittal balance was -15.5±18.1 mm and -19.6±22.6 mm respectively. There was no significant difference between the two groups ( t=2.305, P=0.085; t=-0.695, P=0.489; t=0.992, P=0.324). The incidence of proximal junction kyphosis in the two groups was 2.2% (1/45) and 8.6% (5/58), respectively. The incidence of significant loss of main Cobb correction and distal adding-on was 13.3% (6/45) and 25.9% (15/58) respectively without significant difference (χ 2=1.891, P=0.169; χ 2=2.451, P=0.117). Compared with non-complication patients (39 cases), 19 patients with complications in LTV-1 group had a greater degree of coronal balance to the convex side (23.9±9.5 mm vs. 14.6±11.5 mm, t=3.06, P=0.003), a greater LIV tilt (29.2°±3.7° vs. 25.3°± 5.3°, t=2.85, P=0.006), and a greater degree of LTV rotation (1.0(1, 1) vs. 0.6(0, 1), Z=-2.97, P=0.003). Logistic regression analysis showed that large preoperative LIV tilt and large preoperative coronal balance were the risk factors of complications during follow-up. Conclusion:The selection of LTV and LTV-1 as LIV in patients with Lenke 5 adolescent idiopathic scoliosis could obtain satisfied coronal, sagittal balance and low incidence of mechanical related complications during follow-up. For patients with preoperative coronal balance >17.0 mm or LIV tilt >25.3°, the risk of mechanical related complications might be higher than that when "LTV-1" was selected as LIV.
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Objective:To investigate the correlations between cosmetic and radiographic parameters in patients with congenital scoliosis (CS) with vertebral segmentation failureand the clinical implication of cosmetic parameters.Methods:A total of 27 CS patients were retrospectively reviewed. Anteroposterior and lateral radiographs of the entire spine was taken. Simultaneously, photos were taken from the back in natural standing position and standing forward bending position. Seven cosmetic parameters were measured on the photographs: shoulder area index 1 (SAI1), shoulder area index 2 (SAI2), lumbar area index (LAI), shoulder angle (α 1), axilla angle (α 2), right and left waist angle difference (RLWAD) and hump index. Also, seven radiographic parameterswere measured on the radiographs: radiographic shoulder height difference (RSHD), T 1 tilt, first rib angle (FRA), clavicle angle (CA), clavicle-rib cage intersection (CRCI), clavicle chest cage angle difference (CCAD) and Cobb's angle. The correlation between cosmetic parameters and radiographic parameters was analyzed by Pearson correlation coefficient. Results:Of the 27 patients, 4 were males and 23 were females, with a mean of age 14.0±2.6 years (range 11-18 years). The apical vertebra ranged from T 5 to T 11. LAI was significantly correlatedwith CCAD, but correlation coefficient was only -0.44. The range of correlation coefficientsbetween SAI1 and all radiographic parameters was -0.17 to 0.53, and the range of correlation coefficients between SAI2 and all radiographic parameters was -0.16 to 0.53. However, all correlation coefficients were less than 0.56. Conclusion:Radiographic parameters cannot reflect cosmetic appearances of CS patients with vertebral segmentation failures accurately. More attention should be paid to cosmetic parameters in the evaluation of patients' appearances.
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Objective:To analyze the natural history and outcomes of major neurological complications in spinal deformity correction surgery and to determine the risk factors for no neurological recovery.Methods:All of 7 851 patients with spinal deformity who underwent deformity correction from January 2000 to December 2017 were reviewed. Major neurological complication featured by complete or incomplete paralysis of single or both lower extremities was identified in 59 patients, including 28 males and 31 females with an average age of 25.0±16.3 (range 6 to 71 years old). Among these cases, 6 were adolescent idiopathic scoliosis, 22 were congenital scoliosis, 10 were neuromuscular scoliosis, 5 were neurofibromatosis type 1, and 16 were other types. 5 patients had complete paraplegia of the lower limbs, 17 patients had incomplete paralysis of the lower limbs, and 37 patients had incomplete paraplegia of unilateral lower limb. Treatment included implant removal, debridement of hematoma, loosening the fixation and decompression by laminectomy for mechanical injury, as well as transfusion and press agent for ischemic injury. The neurological function was determined by the American Spinal Injury Association (ASIA) grading system.Fisher exact test and univariate logistics regression were used to determine the association between clinical, surgical parameters and no recovery of neurological function. For the identified factors with P value<0.10, multiple logistics regression was used to determine the independent risk factor for no recovery. Results:The incidence of major neurological complications was 0.75%(59/7851). At final follow-up, 42 patients (71.2%) had complete recovery and 10 patients (16.9%) had partial recovery, and 44 cases (74.6%) had recovery within 6 months. There were 7 cases had no recovery, including 3 with type I neurofibromatosis(ASIA: 1 grade A, 2 grade C), 1 with Scheuermann's disease (ASIA: grade C), 1 with arthrogryposis multiplex congenital (ASIA: grade B), 1 with poliomyelitis related scoliosis (ASIA:grade C), and 1 with idiopathic scoliosis (ASIA: grade A). Fisher test showed the distribution of etiology was statistically different between recovery and no recovery groups. Univariate logistics regression showed diagnosis as NF-1 ( OR=18.750, P=0.005), Cobb angle of the main curve >90° ( OR=4.444, P=0.073), preoperative deficit ( OR=5.750, P=0.046) and complete neurological injury ( OR=6.533, P=0.067) were potential risk factors for no recovery. Multivariate logistics regression showed that diagnosis with NF-I ( OR=35.477, P=0.005) was the risk factor for no recovery. Conclusion:For patients who underwent deformity correction that develops major neurological complications after surgery, 88.1% of patients were able to recover during follow-up, and 71.2% of patients achieved complete recovery. The first 3-6 month is the time window for neurological recovery. Patients with type I neurofibromatosis is the risk factor for no recovery.
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Objective:To investigate the clinical outcomes and complication of posterior surgery for Scheuermann kyphosis fusing to different distal fusion levels.Methods:From January 2012 to December 2017, a consecutive cohort of 34 patients who were treated with posterior spinal instrumented correction and satisfied the inclusion criteria were retrospectively reviewed, including 29 males and 5 females, aged 17.1±4.3 years (range, 12-30 years). All of the patients had a minimum follow-up of 2 years. According to the distal fusion level, patients were divided into 2 groups. Group sagittal stable vertebra (SSV) (22 cases) included patients whose lowest instrumented vertebra (LIV) was SSV; Group SSV-1 (12 cases) included patients who had a LIV one level above the SSV. Radiographic parameters including global kyphosis (GK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were measured in the standing radiographs before and after operation and at the latest follow up. Intraoperative and postoperative complications were recorded. The Scoliosis Research Society-22 questionnaire (SRS-22) were conducted at pre-operation and the final follow up to evaluate the clinical outcomes. The sagittal radiographic parameters and the incidence of distal junctional kyphosis (DJK) were compared between the two groups.Results:There were no significant differences in terms of age, sex, radiographic measurements and scores of SRS-22 between two groups preoperatively ( P>0.05). The correction rates of GK in the SSV group and the SSV-1 group were 42.8%±7.6% and 43.2%±8.4% ( t=0.151, P=0.881) respectively. While the correction rates loss were 1.2%±5.2% and 3.9%±7.2% ( t=0.767, P=0.449) at the latest follow up. No significant difference was observed in terms of other radiographic parameters ( P>0.05). During the postoperative follow up period, 3 patients (16.7%) in SSV group and 2 patients (13.6%) in SSV-1 group developed DJK. The incidence of DJK did not show any significant difference between two groups ( χ2=0.057, P=0.812). At the final follow-up, the function scores of SRS-22 in SSV-1 group (4.1±0.6) was significantly higher than SSV group (3.7±0.5) ( t=2.300, P=0.028) and there was no significant difference in the rest of the domain ( P>0.05). Conclusion:Compared with stopping at SSV, fusion to SSV-1 could achieve comparable curve correction with the preservation of more lumbar motility. Moreover, it would not increase the risk of DJK. As a result, we recommend selecting SSV-1 as the ideal LIV for SK patients.
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Objective:To establish age- and gender-based normative values of sagittal spinal-pelvic alignment in Chinese adult population, and to investigate influence of age, gender and ethnicity on sagittal spinal-pelvic alignment in Chinese normal adults.Methods:A total of 786 asymptomatic Chinese adult volunteers aged between 20 and 89 years were prospectively recruited from different spine centers. The inclusion criteria were: 1) age between 20 to 89 years old; and 2) Oswestry disability index (ODI) scored lower than 20. The exclusion criteria were: 1) previous history of spinal, pelvic or lower limb pathologies that could affect the spine; 2) presence of recent and/or regular back pain; 3) previous surgeries on spine, pelvic and/or lower limb; and 4) pregnancy. Demographic characteristics of these subjects including age, gender, body weight and height were recorded. During the enrollment of volunteers, 16 groups were defined based on the age (20 s, 30 s, 40 s, 50 s, 60 s, 70 s and 80 s) and gender. Whole body biplanar standing EOS X-ray radiographs were acquired to evaluate the sagittal alignment. Spinal-pelvic parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (T 5-T 12, TK), lumbar lordosis (L 1-S 1, LL), lower lumbar lordosis (L 4-S 1, LLL), global tilt (GT), T1 pelvic angle (TPA) and sagittal vertical axis (SVA) were measured. Values of PI-LL and lordosis distribution index (LLL/LL, LDI) were calculated. Radiographic measurements of 100 subjects were randomly selected to determine the intra- and inter-observer reliabilities using inter- and intra-class correlation coefficients (ICC). The spinal-pelvic parameters were compared among volunteers between different age and gender groups. The comparison was also made among various ethnic population. Results:The mean value was 23.7±7.1 kg/m 2 for BMI and 6.9%±2.5% (range, 0-18%) for ODI score. Each sagittal spinal-pelvic parameter was presented with mean value and standard deviationbased on age and gender. The ICCs of radiographic measurements ranged from 0.89 to 0.95, suggesting good to excellent intra- and inter-observer reliabilities. Significant differences were observed between males and females in multiple sagittal parameters (all P values <0.05). Compared to the male subjects, significantly higher values of PI (41.4° for male vs. 45.0° for female, P<0.001), PT (10.7° for male vs. 13.9° for female, P<0.001), PI-LL (-0.5° for male vs. 1.8° for female, P<0.001), and GT (10.9° for male vs. 13.5° for female, P<0.001) were documented in female subjects. Males had significantly higher values of LLL (28.6° for male vs. 26.6° for female, P<0.001) and LDI (0.68 for male vs. 0.63 for female, P<0.001). PI-LL, SVA, GT and TPA increased with aging from Group 40 s to Group 80 s, while LL, LLL and LDI decreased gradually, and TK decreased slowly with aging. Comparison of sagittal spinal-pelvic parameters between different ethnic subjects showed that Chinese adult population presented lower PI, SS, TK and LL as compared with American population; lower PI, SS and LL as compared with Japanese population. But the variation trend with aging tended to be consistent among different ethnic populations. Conclusion:Age- and gender-based normative values of sagittal spinal-pelvic alignment were established in asymptomatic Chinese adult population. Sagittal spinal-pelvic alignment varies with age and gender, and presented different compensation mechanism among different ethnic populations. Therefore, to achieve balanced sagittal alignment, age, gender and ethnicity should be take intoconsideration when planning spine correction surgery.
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Objective:To evaluate the clinical outcomes and complications of second sacral alar-iliac (S 2AI) technique utilized in adult patients with neuromuscular scoliosis, and to evaluate the impact on patients' quality of life. Methods:All of 11 patients (6 males and 5 females) applying S 2AI technique from January 2014 to December 2016 were retrospectively reviewed. The average age of the patients was 39.6±12.7 years. Among them, 8 cases were poliomyelitis, 2 cases were spinal muscular atrophy and 1 case was muscular dystrophy. All of 11 patients underwent posterior spinal fusion and utilized S 2AI screws for pelvic fixation. All patients were taken anteroposterior and lateral radiographs of the entire spine. Cobb's angle, spinal pelvic obliquity (SPO), regional kyphosis (RK), sagittal vertical axis (SVA) were recorded at pre-operation, post-operation and last follow-up. The Scoliosis Research Society (SRS)-22 questionnaires and Oswestry disability index (ODI) were utilized to evaluate the patient-reported outcomes. All complications were also recorded. Repeated measurement analysis of variance, t-test or non-parametric test was used to analyzed the data, respectively. Results:The average follow-up period was 62.4±10.8 months. The pre-operative Cobb angle was 98.0°±24.0°, and the post-operative Cobb angle was 60.7°±20.8°, of which difference was significant ( Z=3.015, P=0.003). The correction rate of Cobb angles was 57.2%±17.7%. 1-year after operation, the Cobb angle was 62.8°±23.6°, no loss of correction was found ( Z=0.294, P=0.797). And at last follow-up, the Cobb angle was 61.6°±21.7°, the correction maintained well ( Z=0.603, P=0.594). The pre-operative, post-operative, 1-year post-operative and last follow-up spinal pelvic obliquity were 37.0°±11.8°, 21.5°±11.6°, 23.2°±10.1° and 21.1°±8.6°. The significant improvement was obtained ( Z=2.934, P=0.003) and no loss of correction was found ( Z=0.690, P=0.519; Z=0.000, P=1.000). The pre-operative, post-operative, 1-year post-operative and last follow-up regional kyphosis were 46.8°±23.6°, 18.6°±10.6°, 18.9°±11.4° and 19.5°±9.8°. The significant improvement was obtained postoperatively ( Z=4.364, P<0.001) and remained stable at the last follow-up ( Z=0.074, P=0.945; Z=0.271, P=0.838). When compared the pre- and post-operative sagittal vertical axis, no significant difference was detected. In these patients, one patient had rod breakage and underwent revision, one patient suffered deep infection, and recovered by debridement surgery, one patient suffered from severe pain in the lower back and relieved with conservative treatment. Conclusion:The S 2AI technique utilized in patients with neuromuscular scoliosis could obtain satisfying clinical outcomes and provides safe, durable fixation with low rates of complications.