Causality of genetically determined serum metabolites on lower back pain or/and sciatica: a comprehensive Mendelian randomized study.

Background: There is an urgent need to confirm biomarkers reflecting the pathogenesis and targeted drugs of lower back pain or/and sciatica in clinical practice. This study aimed to conduct a two sample bidirectional Mendelian randomization (MR) analysis to explore the causal link between 486 serum metabolites and lower back pain or/and sciatica. Methods: All data come from two public shared databases of European ancestry and single nucleotide polymorphisms (SNPs) for lower back pain or/and sciatica acted as instrumental variables. The traditional inverse variance weighting (IVW) method, weighted-median method, MR-Egger methodand other methods were used to estimate causality. The horizontal pleiotropy, heterogeneities were also verified through the MR-Egger intercept test, Cochran's Q test, MR-PRESSO test and the leave-one-out sensitivity analysis. Reverse MR analysis was employed to evaluate the direct impact of metabolites on lower back pain or/and sciatica. Additionally, we conducted the colocalization analysis to reflect the causality deeply. Furthermore, metabolic pathway analysis was performed. Results: 28 metabolites (18 known metabolites, 1 identified metabolites and 9 unknown metabolites) relevant to the risk of sciatica or/and lower back pain after using genetic variants as probes at PIVW < 0.05 were identifed. Among them, 8 serum metabolites decreased risk of sciatica or/and lower back pain significantly (P < 0.05), and 14 serum metabolites increased risk of sciatica or/and lower back pain significantly (P < 0.05). No reverse causal association was found between 28 metabolites and sciatica or/and lower back pain. Colocalization analysis results showed that the associations between sciatica or/and lower back pain and the 28 identified metabolites were not due to shared causal variant sites. Moreover, pathway enrichment analysis identifed 11 signifcant metabolic pathways, which are mainly involved in the pathological mechanism of sciatica or/and lower back pain (P < 0.05). There was no horizontal pleiotropy or heterogeneity in the other analyses. Conclusion: Our analyses provided robust evidence of causal associations between blood metabolites on sciatica or/and lower back pain. However, the underlying mechanisms remain to be further investigated.

New evidence supports RYR3 as a candidate gene for developmental and epileptic encephalopathy.

Background: The ryanodine receptor 3 (RYR3) is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum and subsequent T-tubule depolarization. It is also expressed in the brain, and variants in the RYR3 gene can lead to congenital myopathy type 20 (MIM: #620310). Methods: We retrospectively analyzed the clinical characteristics and prognosis of a case of West syndrome, developmental and epileptic encephalopathy (DEE) caused by a missense variant in the RYR3 gene. We also reviewed and summarized the literature on epilepsy cases caused by RYR3 gene variants. Results: A 10-month-old female child with delayed psychomotor development and recurrent spasm-like seizures was diagnosed with infantile spasm syndrome and DEE. Treatment with various antiepileptic drugs resulted in initial improvement but ultimately failed to control the seizures. Whole-exome sequencing revealed a novel heterozygous variant c.10943C > T/p.T3648M in the RYR3 gene, and genome-wide sequencing ruled out other potentially pathogenic variants. Three previous reports have described RYR3 variants causing DEE, two of which were attributed to de novo heterozygous variants, and one was a compound heterozygote. Conclusion: The present case of DEE caused by a RYR3 heterozygous variant is consistent with previous rare cases of epilepsy caused by RYR3 gene variants in terms of pathogenesis and clinical features, but significantly different from congenital myopathy type 20. Our findings provide important evidence for the diagnosis of RYR3-related DEE, and we hypothesize that RYR3 gain-of-function variants resulting in "leaky" Ca2+ release channels may be a molecular genetic feature leading to DEE rather than myopathy.

Exploring the clinical complexity of cardio-facio-cutaneous syndrome: insights from a pediatric case series.

Background: Cardio-Facio-Cutaneous syndrome (CFCS) is a rare autosomal dominant genetic disorder primarily caused by BRAF gene mutations, posing diagnostic challenges due to its multifaceted clinical presentation. Objective: To elucidate the clinical characteristics of pediatric CFCS patients, expanding the phenotypic spectrum to enhance early diagnostic capabilities, while also presenting the relationship between genotye and corresponding phenotype severity. Methods: From January 2015 to March 2022, four children diagnosed with CFCS in Children's Hospital of Chongqing Medical University were included for analysis. Whole exome sequencing (WES) was conducted to identify the types and locations of possible gene mutations. Neurological development was assessed using electroencephalography (EEG), magnetic resonance imaging (MRI) and Gesell developmental evaluation. Results: All four CFCS patients exhibited de novo BRAF gene mutations, manifesting with cardiac malformations, distinctive facial features, skin and hair changes, and neurological abnormalities. WES revealed that the specific BRAF mutations were closely linked to their clinical severity. Three patients displayed milder symptoms (case 1-3, genotype I or II), demonstrating stability or slight improvement, whereas one patient (case 4, genotype III) suffered from a severe phenotype characterized by profound neurological and digestive system impairments, leading to a significantly reduced quality of life and a grim prognosis. Conclusion: In CFCS patients, severe developmental delay and seizures are predominant neurological features, possibly accompanied by continuous spike-and-wave during sleep (CSWS) and severe sleep disturbances. CFCS generally carries a poor prognosis, underscoring the importance of disease awareness and early genetic testing.

Clinical Characteristics of 118 Pediatric Patients With Acute Benign Myositis Associated With Influenza A Virus Infection.

OBJECTIVE: The objective of this study was to investigate the clinical and laboratory features of acute benign myositis associated with influenza A virus infection in children. METHODS: A retrospective analysis was performed on the clinical data of 118 children with acute benign myositis associated with influenza A virus infection who were admitted to the Children's Hospital of Chongqing Medical University during the epidemic period of influenza A from February 2023 to May 2023. RESULTS: (1) Most of the 118 children were preschool- or school-age. The most common symptom was sudden lower limb pain after fever, and bilateral calf myalgia was more common. The muscle enzyme spectrum ranged from 187.21 to 32191.00 µg/L (median: 3053 µg/L). Creatine kinase isoenzymes ranged from 5.15 to 749.7 µg/L (median 41.82 µg/L). Myoglobin ranged from 102.79 to 1200 µg/L (median 674.9 µg/L). (3) Examination: electromyography, muscle color Doppler ultrasound, radiograph and cardiac color Doppler ultrasound in Benign acute childhood myositis in children were rarely positive. (4) Treatment and prognosis: besides bed rest and a reduction of physical activity, oseltamivir treatment, drugs to improve energy metabolism, fluid replacement and alkalinization of symptomatic treatment. All children had a good prognosis without sequelae. CONCLUSIONS: This study summarized and analyzed the clinical characteristics of acute benign myositis associated with influenza A infection in children with the aim of allowing rapid and early diagnosis of the disease and reducing unnecessary diagnostic tests and treatments. Closely monitoring myalgia and the muscle enzyme spectrum is recommended to exclude other neuromuscular and metabolic diseases.

Compared to Fishmeal, Dietary Soybean Meal Improves the Reproductive Performance of Female Yellow Catfish (Pelteobagrus fulvidraco) Broodstock.

To investigate the effects of different dietary protein sources on the reproductive performance of female broodstock, yellow catfish (Pelteobagrus fulvidraco) were fed with three experimental diets using fishmeal (FM), soybean meal (SBM), and rapeseed meal (RSM) as main protein sources, respectively. Females (initial weight: 64.56 ± 0.45 g) were distributed into 9 net cages for feeding trial. Results indicated that 30% dietary SBM improved the reproductive performance for higher gonadosomatic index (GSI), relative fecundity, total egg production, egg diameter, and hatching rate. In addition, SBM and RSM diets resulted in higher estradiol (E2), vitellogenin (VTG), luteinizing hormones (LH), and lower follicle-stimulating hormone (FSH) and testosterone (T) in plasma (P < 0.05) of female broodstock. Dietary SBM and RSM also resulted in lower mesenteric fat index (MFI), plasma total cholesterol (TC), plasma total bilirubin (T-Bil) contents, and gonadal cortisol concentrations, while dietary SBM downregulated the transcription levels of steroidogenesis-related proteins by negative feedback (P < 0.05). The results demonstrated that dietary SBM and RSM could promote sex steroid hormone and VTG biosynthesis and showed hypocholesterolemic effects. Besides, 30% dietary SBM inclusion could improve the reproductive performance of female yellow catfish broodstock.

Distal tibial tubercle osteotomy can lessen change in patellar height post medial opening wedge high tibial osteotomy? A systematic review and meta-analysis.

OBJECTIVE: Medial opening wedge high tibial osteotomy (MOWHTO) is a mainstream surgical method for treating early medial compartment knee osteoarthritis. Undesirable sequelae such as patella infera may happen following tuberosity osteotomy. We conducted this systematic review and meta-analysis to compare the change in patellar position after proximal tibial tubercle osteotomy (PTO) versus distal tibial tubercle osteotomy (DTO) intervention. METHODS: The 11 studies were acquired from PubMed, Medline, Embase and Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed by RevMan5.3. Mean differences, odds ratios and 95% confidence intervals were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Eleven observational studies were assessed. The methodological quality of the trials ranged from moderate to high. The pooled results of postoperative patellar height (Caton-Deschamps index and Blackburne-Peel index) and postoperative complications showed that the differences were statistically significant between PTO and DTO interventions. Patellar index ratios decreased significantly in the PTO groups, and 12 (9.2%) complications under DTO surgery and 2 (1.6%) complications under PTO surgery were reported. The differences of postoperative posterior tibial slope (angle) was not statistically significant, but postoperative posterior tibial slope of both groups increased. Sensitivity analysis proved the stability of the pooled results and the publication bias was not apparent. CONCLUSIONS: DTO in MOWHTO maintained the postoperative patellar height, and clinically, for patients with serious patellofemoral osteoarthritis, DTO can be preferred. Postoperative complications are easily preventable with caution. In view of the heterogeneity and small sample size, whether these conclusions are applicable should be further determined in future studies.

mRNA and long non-coding RNA expression profiles of rotator cuff tear patients reveal inflammatory features in long head of biceps tendon.

BACKGROUND: This study aimed to identify the differentially expressed mRNAs and lncRNAs in inflammatory long head of biceps tendon (LHBT) of rotator cuff tear (RCT) patients and further explore the function and potential targets of differentially expressed lncRNAs in biceps tendon pathology. METHODS: Human gene expression microarray was made between 3 inflammatory LHBT samples and 3 normal LHBT samples from RCT patients. GO analysis and KEGG pathway analysis were performed to annotate the function of differentially expressed mRNAs. The real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was admitted to verify their expression. LncRNA-mRNA co-expression network, cis-acting element, trans-acting element and transcription factor (TF) regulation analysis were constructed to predict the potential molecular regulatory mechanisms and targets for LHB tendinitis. RESULTS: 103 differentially expressed lncRNAs and mRNAs, of which 75 were up-regulated and 28 were down-regulated, were detected to be differentially expressed in LHBT. The expressions of 4 most differentially expressed lncRNAs (A2MP1, LOC100996671, COL6A4P, lnc-LRCH1-5) were confirmed by qRT-PCR. GO functional analysis indicated that related lncRNAs and mRNAs were involved in the biological processes of regulation of innate immune response, neutrophil chemotaxis, interleukin-1 cell response and others. KEGG pathway analysis indicated that related lncRNAs and mRNAs were involved in MAPK signaling pathway, NF-kappa B signaling pathway, cAMP signaling pathway and others. TF regulation analysis revealed that COL6A4P2, A2MP1 and LOC100996671 target NFKB2. CONCLUSIONS: LlncRNA-COL6A4P2, A2MP1 and LOC100996671 may regulate the inflammation of LHBT in RCT patients through NFKB2/NF-kappa B signaling pathway, and preliminarily revealed the pathological molecular mechanism of tendinitis of LHBT.

Was femoral nerve block effective for pain control of medial opening-wedge high tibial osteotomy?: A single blinded randomized controlled study.

BACKGROUND AND PURPOSE: Medial compartment femoro-tibial osteoarthritis (OA) is a common disease and opening-wedge high tibial osteotomy (OWHTO) is the common surgical procedure carried out for these patients. While most researchers are focusing on the surgical techniques during operation, the aim of this study is to evaluate the pain control effect of femoral nerve block (FNB) for OWHTO patients. METHODS: In this prospective, single-center, randomized controlled trial (RCT) study, 41 patients were operated on by OWHTO for OA during 2017 to 2018. Twenty of them (group A) accepted epidural anesthesia with FNB and 21 patients (group B) only had their single epidural anesthesia. All blocks were successful and all the 41 patients recruited were included in the analysis and there was no loss to follow-up or withdrawal. Systematic records of visual analog scores (VAS), quadriceps strength, mean number of times of patient-controlled intravenous analgesia (PCIA), using of additional opioids or nonsteroidal anti-inflammatory drugs (NSAIDs), and complications were done after hospitalization. The Student t test and Chi-Squared test was used and all P values ≤.05 were considered statistically significant. RESULTS: VAS scores at rest (3.48 ±â€Š1.0 vs 4.68 ±â€Š1.1) and on movemment (4.51 ±â€Š0.6 vs 4.97 ±â€Š0.8) decreased more in group A than group B with significance at follow-up of 12 hours. The quadriceps strength, consumption of additional opioids or NSAID injections and mean number of times that the patients pushed the PCIA button didnot differ significantly within each group. CONCLUSION: This RCT study shows that FNB in patients undergoing OWHTO for unicompartmental osteoarthritis of the knee could result in significant reduction in VAS scores at 12 hours postoperatively.Research registry, Researchregistry4792. Registered April 7, 2019 - Retrospectively registered, http://www.researchregistry.com.

Vitamin D3 protects articular cartilage by inhibiting the Wnt/ß-catenin signaling pathway.

Low expression levels of 25-hydroxyvitamin D (vitamin D3) in the blood have been reported to be associated with the progression of osteoarthritis; however, the mechanisms by which this occurs remain unclear. The present study aimed to determine the effects of vitamin D3 on chondrocytes. MTT assays were used to determine whether vitamin D3 affects chondrocytes viability. Primary chondrocytes were treated with control culture medium, vitamin D3, tumor necrosis factor (TNF)-α, TNF-α + PNU-74654 [Wingless-related integration site (Wnt)/ß-catenin signaling pathway inhibitor] or TNF-α + vitamin D3. Reverse transcription-quantitative PCR and western blotting were utilized to measure the gene and protein expression of collagen II, aggrecan, matrix metalloproteinase (MMP)-3 and MMP-13, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, Wnt-3a and nuclear ß-catenin. The results demonstrated that TNF-α reduced the expression levels of aggrecan and collagen II, and increased the expression levels of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5. Furthermore, vitamin D3 and PNU-74654 were observed to partially attenuate the effects induced by TNF-α. Moreover, similar findings were reported following co-treatment with vitamin D3 and TNF-α. Western blotting data revealed that TNF-α increased Wnt-3a and ß-catenin protein levels in chondrocytes, while Vitamin D3 and PNU-74654 decreased the expression levels of Wnt-3a and nuclear ß-catenin. In conclusion, the findings of the present study provided evidence to suggest that vitamin D3 may prevent articular cartilage degeneration and osteoarthritic disease progression by inhibiting the expression levels of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 through suppressing the Wnt/ß-catenin signaling pathway. These results suggested that vitamin D3 may be of therapeutic value for the prevention and treatment of osteoarthritis.

Opening-Wedge High Tibial Osteotomy Using Autograft versus Allograft: A Systematic Review and Meta-analysis.

Bone grafting is a good alternative for filling the inevitable void that is created following opening-wedge high tibial osteotomy (OWHTO). This systematic review and meta-analysis evaluated whether bone grafting is necessary for OWHTO and the successful outcomes of OWHTO using either autograft (AU) or allograft (AL). All analyzed studies were acquired from PubMed, Medline, Embase, CNKI, Google Scholar, and Cochrane Library. Data were independently extracted by two coauthors and were analyzed using RevMan5.3. Mean differences, odds ratios, and 95% confidence intervals were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess the risk of bias. In total, 10 studies were assessed including three randomized controlled trials and seven observational studies. The methodological quality of the trials ranged from low to high. The overall estimate demonstrated that the difference between OWHTO using AU and AL groups and OWHTO using no filling group was not statistically significant for the loss of correction, and complications, but OWHTO using no filling group statistically showed better knee society score. Pooled results of reoperations, lateral cortex breaches, complications, and clinical function assessments showed no significant difference between AU and AL materials. Using AL statistically reduced the operative time compared with using AU. OWHTO with or without bone graft does not affect postoperative complications. No loss of correction was observed due to the lack of bone grafting. In addition, OWHTO without bone graft performs better for postoperative clinical function assessment. Complications and clinical results of medial OWHTO were similar using AL and AU and neither reported a median loss of correction of following OWHTO. Compared with using AU, using AL avoids harvest site complications and reduces operative time. To sum up, OWHTO without any bone graft is recommended for medial unicompartmental osteoarthritis of the knee. Further large-sample, multicenter, high-quality, randomized controlled trials are warranted to verify the outcomes of this meta-analysis.

Comparison of arthroscopic suture-bridge technique and double-row technique for treating rotator cuff tears: A PRISMA meta-analysis.

BACKGROUND: Rotator cuff tear is a common shoulder disorder in the elderly. Either arthroscopic double-row (DR) or suture-bridge (SB) technique for rotator cuff tear patients is needed to choose. We conducted this systematic review and meta-analysis to compare the clinical outcomes of arthroscopic SB versus DR intervention. METHODS: The 7 studies were acquired from PubMed, Medline, Embase, CNKI, Google, and Cochrane Library. The data were extracted by 2 of the co-authors independently and were analyzed by RevMan5.3. Mean differences (MDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa scale were used to assess risk of bias. RESULTS: Seven studies including 1 randomized controlled trial and 6 observational studies were assessed. The methodological quality of the trials ranged from low to moderate. The pooled results of American Shoulder and Elbow Surgeons score, Constant score, visual analog scale score, and range of motion showed that the differences were not statistically significant between the 2 interventions. The difference of University of California at Los Angeles (UCLA) score was statistically significant between SB and DR intervention, and SB treatment was more effective (MD = -0.95, 95% CI = -1.70 to -0.20, P = .01). The difference of re-tear rate was statistically significant and SB treatment achieved better result than DR treatment (OR = 0.31, 95% CI = 0.15-0.64, P = .001). Sensitivity analysis proved the stability of the pooled results and the publication bias was not apparent. CONCLUSIONS: Both arthroscopic SB and DR interventions had benefits in rotator cuff tear. SB treatment was more effective in UCLA score and had lower re-tear rate than DR treatment. The arthroscopic SB technique is recommended as the optical choice for rotator cuff tear.

Is arthroscopic repair superior to biceps tenotomy and tenodesis for type II SLAP lesions? A meta-analysis of RCTs and observational studies.

OBJECTIVE: Labral repair and biceps tenotomy and tenodesis are routine operations for type II superior labrum anterior posterior (SLAP) lesion of the shoulder, but evidence of their superiority is lacking. We conducted this systematic review and meta-analysis to compare the clinical outcomes of arthroscopic repair versus biceps tenotomy and tenodesis intervention. METHODS: The eight studies were acquired from PubMed, Medline, Embase, CNKI, and Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed by RevMan 5.3. Mean differences (MDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Eight studies including two randomized controlled trials (RCTs) and six observational studies were assessed. The methodological quality of the trials ranged from low to moderate. The pooled results of UCLA score, SST score, and complications showed that the differences were not statistically significant between the two interventions. The difference of ASES score and satisfaction rate was statistically significant between arthroscopic repair and biceps tenotomy and tenodesis intervention, and arthroscopic biceps tenotomy and tenodesis treatment was more effective. Sensitivity analysis proved the stability of the pooled results, and there were too less included articles to verify the publication bias. CONCLUSIONS: Both arthroscopic repair and biceps tenotomy and tenodesis interventions had benefits in type II SLAP lesions. Arthroscopic biceps tenotomy and tenodesis treatment provides better clinical outcome in ASES score and satisfaction rate and comparable complications compared with arthroscopic repair treatment. In view of the heterogeneity and confounding factors, whether these conclusions are applicable should be further determined in future studies.

Bioinformatics analysis of differentially expressed genes in rotator cuff tear patients using microarray data.

BACKGROUND: Rotator cuff tear (RCT) is a common shoulder disorder in the elderly. Muscle atrophy, denervation and fatty infiltration exert secondary injuries on torn rotator cuff muscles. It has been reported that satellite cells (SCs) play roles in pathogenic process and regenerative capacity of human RCT via regulating of target genes. This study aims to complement the differentially expressed genes (DEGs) of SCs that regulated between the torn supraspinatus (SSP) samples and intact subscapularis (SSC) samples, identify their functions and molecular pathways. METHODS: The gene expression profile GSE93661 was downloaded and bioinformatics analysis was made. RESULTS: Five hundred fifty one DEGs totally were identified. Among them, 272 DEGs were overexpressed, and the remaining 279 DEGs were underexpressed. Gene ontology (GO) and pathway enrichment analysis of target genes were performed. We furthermore identified some relevant core genes using gene-gene interaction network analysis such as GNG13, GCG, NOTCH1, BCL2, NMUR2, PMCH, FFAR1, AVPR2, GNA14, and KALRN, that may contribute to the understanding of the molecular mechanisms of secondary injuries in RCT. We also discovered that GNG13/calcium signaling pathway is highly correlated with the denervation atrophy pathological process of RCT. CONCLUSION: These genes and pathways provide a new perspective for revealing the underlying pathological mechanisms and therapy strategy of RCT.

Exploring the key genes and pathways of side population cells in human osteosarcoma using gene expression array analysis.

BACKGROUND: Human osteosarcoma (OS) is one of the most common primary bone sarcoma, because of early metastasis and few treatment strategies. It has been reported that the tumorigenicity and self-renewal capacity of side population (SP) cells play roles in human OS via regulating of target genes. This study aims to complement the differentially expressed genes (DEGs) that regulated between the SP cells and the non-SP cells from primary human OS and identify their functions and molecular pathways associated with OS. METHODS: The gene expression profile GSE63390 was downloaded, and bioinformatics analysis was made. RESULTS: One hundred forty-one DEGs totally were identified. Among them, 72 DEGs (51.06%) were overexpressed, and the remaining 69 DEGs (48.94%) were underexpressed. Gene ontology (GO) and pathway enrichment analysis of target genes were performed. We furthermore identified some relevant core genes using gene-gene interaction network analysis such as EIF4E, FAU, HSPD1, IL-6, and KISS1, which may have a relationship with the development process of OS. We also discovered that EIF4E/mTOR signaling pathway could be a potential research target for therapy and tumorigenesis of OS. CONCLUSION: This analysis provides a comprehensive understanding of the roles of DEGs coming from SP cells in the development of OS. However, these predictions need further experimental validation in future studies.

Short-term Follow-up of Antibiotic-loaded Articulating Cement Spacers in Two-stage Revision of Infected Total Knee Arthroplasty: A Case Series.

OBJECTIVE: Infection of total knee arthroplasty (TKA) is a rare but devastating complication. Two-stage revision is an effective treatment for late infected TKA. This study aimed to assess the short-term results of two-stage revision using articulating antibiotic-loaded spacers. METHODS: Twenty-five patients (10 men and 15 women) were diagnosed with late infections after TKA and treated with two-stage revision from April 2006 to August 2010; 19 of these patients had TKA for osteoarthritis and 6 for rheumatoid arthritis. Median age was 64.9 (range, 56-83) years. In the first-stage surgery, the prosthesis and all bone cement was removed. After thorough debridement, bone cement with vancomycin and tobramycin was put into a die cavity and made into temporary femoral and tibial spacers, respectively. In the cases of good knee range of motion, the temporary spacers were affixed to the bone surface using the same antibiotic bone cement. In the second surgery, gentamycin Refobacin Bone Cement with vancomycin was used to fix the prosthesis. After two-stage revision, patients were followed up clinically and radiologically at 1, 3, and 6 months, and then annually. Knee Society Score (KSS), knee function score, knee pain score, and knee range of motion (ROM) were assessed. RESULTS: Among the group, all spacers were easily removed, and bone defect degree showed no obvious change compared with pre-implant, 24 (96%) patients had been debrided once, and 1 patient had been debrided twice before reimplant prosthesis. Mean follow-up was 64.2 (range, 52-89) months. There was no infection recurrence at final follow-up. Compared with preoperative data, the KSS (66 [59, 71], 83 [80, 88] vs 46 [43, 57], P < 0.01), knee function score (43 [42, 49], 78 [73, 82] vs 32 [25, 37], P < 0.01), knee pain score (34 [33, 37], 42 [40, 45] vs 18 [16, 23], P < 0.01), and knee ROM (92° [86°, 96°], 94° [90°, 98°] vs 78° [67°, 86°], P < 0.01) were all improved during follow-up and at final visit. Three patients experienced complications in the interval period: one case had knee dislocation, one had knee instability, and one had a chip in the femoral component of the spacer. CONCLUSION: Using articulating antibiotic-loaded spacers showed benefits for treating infected TKA in selected patients. No infection recurrence was observed during follow-up.

Increased synovial fluid visfatin is positively linked to cartilage degradation biomarkers in osteoarthritis.

The aim of this study is to investigate visfatin levels in both synovial fluid (SF) and plasma of patients with primary knee osteoarthritis (OA) and its relationship with biomarkers of cartilage degradation in SF. Thirty OA patients, 12 SF control, and 12 plasma control subjects were enrolled in this study. Visfatin levels in both SF and plasma were measured using enzyme-linked immunosorbent assay (ELISA). Degradation biomarkers of collagen II and aggrecan in SF were also measured. The radiographic grading of OA in the knee was performed by the Kellgren-Lawrence (KL) criteria. Compared to controls, OA patients had higher SF visfatin concentration (8.95 ± 2.5 vs. 4.48 ± 2.49 ng/ml, P < 0.001). SF visfatin levels in KL grade 4 were significantly elevated compared with those of KL grade 3 (10.57 ± 2.49 vs. 7.54 ± 1.5 ng/ml, P = 0.001). SF visfatin positively correlated with degradation biomarker of collagen II, CTX-II (r = 0.497, P = 0.005), and degradation biomarker of aggrecan, AGG1 (r = 0.451, P = 0.012) and AGG2 (r = 0.434, P = 0.017). These findings suggest that SF visfatin might involved in cartilage matrix degradation.

TNFα-mediated apoptosis in human osteoarthritic chondrocytes sensitized by PI3K-NF-κB inhibitor, not mTOR inhibitor.

To investigate apoptosis of osteoarthritic (OA) chondrocytes stimulated with different inhibitors targeting tumor necrosis factor-alpha (TNFα) pathway, we isolated first passage chondrocytes from OA patients and then treated them with the inhibitors in combination with TNFα, and then collected the stimulated chondrocytes for Western blotting. Chondrocytes from OA patients expressed cleaved caspase-3 and PARP, suggesting apoptotic background. We here, validated that 10 ng/ml of TNFα couldn't induce more chondrocytes apoptosis. PI3K inhibitor LY294002 or NF-κB inhibitor CAPE, but not mTOR inhibitor rapamycin and MEK1/2 inhibitor U0126 in combination with TNFα could facilitate apoptosis. CAPE-induced more apoptosis could be explained by c-FLIP downregulation more than cIAP1 upregulation. And, we showed the first time that PI3K-NF-κB pathway, but not mTOR pathway could prevent chondrocytes apoptosis induced by a pro-apoptotic factor TNFα and call for attention while trying to inhibit NF-κB as a therapeutic target.

[Primary culture and adipogenic process of pre-adipocytes from infrapatellar fat pad of osteoarthritic patients].

OBJECTIVE: To investigate the primary culture and adipogenic process of pre-adipocytes from infrapatellar fat pad of osteoarthritic patients. METHODS: The pre-adipocytes were isolated by enzymatic digestion. The morphological changes of cultured cells were observed and the growth curve was drawn by CCK-8 method. During the adipogenic process, the intracytoplasmic lipid of differentiated cells was determined by oil red O staining. And the adiponectin levels in the culture supernatants were measured by ELISA (enzyme-linked immunosorbent assay). RESULTS: The primary cultured fibroblast-like cells were spindle-shaped. In the process of adipogenesis, the intracytoplasmic lipid droplets were observed at Day 3 and over 80% of the cells differentiated into adipocytes at Day 21. With the increasing number of adipocytes, the adiponectin levels in the culture supernatant elevated and peaked at Week 3. The differentiated cells were proven to be adipocytes functioning actively. CONCLUSION: The primary culture and adipogenic process of pre-adipocytes in infrapatellar fat pad of osteoarthritic patients has been successfully established. Thus it may provide an ideal model for the study of endocrine function of infrapatellar fat pad and understanding its role in the pathogenesis of osteoarthritis.

Overexpression of BMI-1 promotes cell growth and resistance to cisplatin treatment in osteosarcoma.

BACKGROUND: BMI-1 is a member of the polycomb group of genes (PcGs), and it has been implicated in the development and progression of several malignancies, but its role in osteosarcoma remains to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we found that BMI-1 was overexpressed in different types of osteosarcomas. Downregulation of BMI-1 by lentivirus mediated RNA interference (RNAi) significantly impaired cell viability and colony formation in vitro and tumorigenesis in vivo of osteosarcoma cells. BMI-1 knockdown sensitized cells to cisplatin-induced apoptosis through inhibition of PI3K/AKT pathway. Moreover, BMI-1-depletion-induced phenotype could be rescued by forced expression of BMI-1 wobble mutant which is resistant to inhibition by the small interfering RNA (siRNA). CONCLUSIONS/SIGNIFICANCE: These findings suggest a crucial role for BMI-1 in osteosarcoma pathogenesis.

Synovial fluid level of adiponectin correlated with levels of aggrecan degradation markers in osteoarthritis.

The objective of this study was to investigate adiponectin levels in both plasma and synovial fluid of female patients with knee osteoarthritis (OA) and to analyze the correlation between adiponectin and degradation markers of cartilage matrix in synovial fluid. Thirty female patients with knee OA were enrolled in this study. Levels of adiponectin and degradation markers of cartilage matrix were measured using enzyme-linked immunosorbent assay. Adiponectin level in synovial fluid was significantly lower with respect to paired plasma level (0.93 ± 0.64 vs. 7.50 ± 3.29 µg/ml, P < 0.001). Correlation analysis showed that synovial fluid adiponectin significantly correlated with degradation markers of aggrecan, AGG1 (r = 0.441, P = 0.015) and AGG2 (r = 0.445, P = 0.014), but not significantly correlated with degradation marker of collagen II, CTX-II. These findings suggest that adiponectin might involve in the regulation of the degradation of cartilage matrix in OA.