Effect of hyaluronic acid on cytokines and immune cells change in patients of knee osteoarthritis.

PURPOSE: To evaluate the changes of cytokines and immune cells after Intra-articular hyaluronic acid(IAHA)injections in patients with knee osteoarthritis (KOA). PATIENTS AND METHODS: Sixteen patients were included in the study, with a total of 65 IAHA injections. The Numeric Rating Scale (NRS) and Lysholm scores were evaluated at each visit. The immune cells and 14 cytokines of synovial fluid were analyzed at each visit. The association between immune cells and cytokines were examined. RESULTS: IL-6 and IL-8 were the most common cytokines in the synovial fluid of KOA patients. The synovial fluid was orchestrated by macrophages (69%) and Lymphocytes (18%). Neutrophils were less to count of the total cell population (< 2%). The cytokines decreased significantly after the first injection and then tended to be stable. Lymphocytes increased a lot, while Macrophages decreased in the early stage, then increased after multiple injections. The proposition of M1 decreased in the early stage, then increased after multiple injections, while M2 increased consistently. M1 and M2 were positively associated with IL-6 and IL-8. CONCLUSION: The synovial fluid of KOA patients was orchestrated by macrophages (69%) and Lymphocytes (18%) and cytokines like IL-6 and IL-8. IAHA may play an anti-inflammatory functional role through the decreased production of IL-6 and IL-8 by macrophages through polarization. The results from this study partially revealed the effect of IAHA on cytokines and immune cells change in KOA patients, and therapies targeting pathogenic cytokines and immune cells might be used to attenuate the knee joint inflammation and release pain. TRIAL REGISTRATION: ChiCTR2100050133; date registered 17 August 2021.

Effect of alendronate sodium plus vitamin D3 tablets on knee joint structure and osteoarthritis pain: a multi-center, randomized, double-blind, placebo-controlled study protocol.

BACKGROUND: Osteoarthritis (OA) is a major cause of pain and disability worldwide. Despite the relatively high burden of the disease, the currently available non-surgical treatment options are directed towards symptomatic relief. Therefore, we propose the use of alendronate as a disease modifying agent to help slow and prevent OA. In addition, this study will utilize Whole-Organ Magnetic Resonance Imaging Score (WORMS) to evaluate the structural integrity of cartilage in the study population. High-quality evidence, limited to a few well-conducted randomized trials, highlights contradictory results on the effect of bisphosphonates on knee function and progression of OA. Therefore, a placebo-controlled, randomized trial is needed to evaluate the combined effect of alendronate and vit D on the structure of cartilage utilizing the WORMS score and its ability to treat knee pain in OA patients. METHODS: This multicenter, randomized, double-blinded, placebo-controlled study will evaluate the efficacy and safety of alendronate in early OA. Patients will undergo a 1:1 double-blinded randomization to receive a one-year course of either alendronate sodium vitamin D3 or placebo. The primary outcome is to compare WORMS score of knee joint at 6 and 12 months between both groups. Secondary endpoints will include WORMS score at 24 months, knee pain, radiographic progression of OA, severity of OA, quality of life, and serum inflammatory biomarkers at different assessment timepoints. To detect a 2.2% difference in cartilage loss between both groups with power of 80%, a sample size of 60 (30 per group) is proposed. DISCUSSION: This trial will give helpful and high-quality evidence regarding the potential therapeutic role of alendronate sodium vitamin D3, as compared to placebo, in the management of patients with knee OA regarding its role on cartilage loss, radiographic progression of OA, severity of OA, knee pain, quality of life, and inflammatory biomarkers. If proven effective, this intervention would be a great option for providing beneficial outcomes with a reduced cost in this patient population. TRIAL REGISTRATION: This trial was registered on clinicaltrials.gov (registration number: NCT04739592 ).

Integrated Bioinformatics Analysis of Hub Genes and Pathways Associated with a Compression Model of Spinal Cord Injury in Rats.

BACKGROUND Spinal cord injury (SCI) is a serious nervous system condition that can cause lifelong disability. The aim of this study was to identify potential molecular mechanisms and therapeutic targets for SCI. MATERIAL AND METHODS We constructed a weighted gene coexpression network and predicted which hub genes are involved in SCI. A compression model of SCI was established in 45 Sprague-Dawley rats, which were divided into 5 groups (n=9 per group): a sham operation group, and 1, 3, 5, and 7 days post-SCI groups. The spinal cord tissue on the injured site was harvested on 1, 3, 5, and 7 days after SCI and 3 days after surgery in the sham operation group. High-throughput sequencing was applied to investigate the expression profile of the mRNA in all samples. Differentially expressed genes were screened and included in weighted gene coexpression network analysis (WGCNA). Co-expressed modules and hub genes were identified by WGCNA. The biological functions of each module were investigated using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. RESULTS According to the RNA-seq data, a total of 1965 differentially expressed genes were screened, and WGCNA identified 10 coexpression modules and 5 hub genes. Module function analysis revealed that SCI was associated with immune response, cell division, neuron projection development, and collagen fibril organization. CONCLUSIONS Our study revealed dynamic changes in a variety of biological processes following SCI and identified 5 hub genes via WGCNA. These results provide insights into the molecular mechanisms and therapeutic targets of SCI.

The combined use of unilateral pedicle screw and contralateral facet joint screw fixation in transforaminal lumbar interbody fusion.

PURPOSE: This paper is to evaluate the efficacy and safety of transforaminal lumbar interbody fusion (TLIF) using unilateral pedicle screws along with contralateral translaminar facet joint screw (UPS+TFS) fixation in comparison with the method using bilateral pedicle screws fixation (BPS) in degenerative lumbar diseases. METHODS: Forty patients with single-level lumbar diseases were divided into two groups randomly. One group was treated by TLIF with BPS fixation while the other group was treated by the new technique with UPS+TFS fixation. The preoperative and postoperative ODI, JOA, VAPS scores, mean operation time, mean operation blood loss, fusion rate and complications were collected for comparison under two surgical methods. In terms of complications, only two cases of superficial infection in the BPS group and one case of urinary tract infection in the other group was found. RESULTS: The mean operation time and blood loss was significantly less in UPS+TFS group than in BPS group. The preoperation and postoperative ODI, JOA and VAPS at the intervals of 6 weeks, 3, 6 months and 1 year between the BPS and UPS+TFS group showed no significant disparities. Only one patient in UPS+TFS group was not fused with pseudoarthrosis formation. CONCLUSIONS: The clinical efficacy and safety of TLIF with UPS+TFS fixation were comparable to BPS fixation; however, the soft tissue injury and the corresponding operation cost were reduced with unilateral pedicle screw plus translaminar facet screw fixation.

Neuroserpin upregulates in the early period of sustained spinal cord compression.

BACKGROUND: Neuroserpin (NSP) is a neuroprotective factor in the situation of ischemia of a brain, such as stroke. However, it has never been reported in the spinal cord, which is part of the central nervous system (CNS). METHODS: The expression of NSP was detected using Western blotting and neuron apoptosis detected by TUNEL staining following spinal cord ischemia caused by sustained compression in rats. RESULTS: The results showed that NSP was upregulated in the injury area of spinal cord, accompanied with the activation of micorglia and tissue plasminogen activator (tPA), which suggested that NSP also plays a neuroprotective role in spinal cord compression since neuronal apoptosis appears when NSP returns to normal levels or even lower. CONCLUSIONS: NSP upregulates in early periods of sustained spinal cord compression.

A new prediction model for patient satisfaction after total knee arthroplasty and the roles of different scoring systems: a retrospective cohort study.

BACKGROUND: Although total knee arthroplasty (TKA) is an efficacious treatment for end-stage osteoarthritis, ~20% of patients are dissatisfied with the results. We determined which factors contribute to patient satisfaction and compared the various scoring systems before and after surgery. METHODS: In this retrospective cohort study, 545 patients were enrolled and evaluated preoperatively and 1 year postoperatively. Patient demographics, as well as scores for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short Form (SF)-12, and 1989 Knee Society Clinical Rating System (1989 KSS), were recorded preoperatively and postoperatively. The possible predictors were introduced into a prediction model. Scores for overall satisfaction and the 2011 Knee Society Score (2011 KSS) were also assessed after TKA to identify the accuracy and agreement of the systems. RESULTS: There were 134 male patients and 411 female patients, with an overall prevalence of satisfaction of 83.7% 1 year after surgery. A history of surgery (p < 0.001) and the 1989 KSS and SF-12 were of the utmost importance in the prediction model, whereas the WOMAC score had a vital role postoperatively (change in WOMAC pain score, p < 0.001; change in WOMAC physical function score, p < 0.001; postoperative WOMAC pain score, p = 0.004). C-index of model was 0.898 > 0.70 (95% confidence interval (CI): 0.86-0.94). The Hosmer-Lemeshow test showed a p value of 0.586, and the AUC of external cohort was 0.953 (sensitivity=0.87, specificity=0.97). The agreement between the assessment of overall satisfaction and the 2011 KSS satisfaction assessment was general (Kappa=0.437 > 0.4, p < 0.001). CONCLUSION: A history of surgery, the preoperative 1989 KSS, and the preoperative SF-12 influenced patient satisfaction after primary TKA. We recommend the WOMAC (particularly the pain subscale score) to reflect overall patient satisfaction postoperatively.

Identification of Diagnostic Biomarkers of Osteoarthritis Based on Multi-Chip Integrated Analysis and Machine Learning.

The pathogenesis of osteoarthritis (OA) is still unclear. It is therefore important to identify relevant diagnostic marker genes for OA. We performed an integrated analysis with multiple microarray data cohorts to identify potential transcriptome markers of OA development. Further, to identify OA diagnostic markers, we established gene regulatory networks based on the protein-protein interaction network involved in these differentially expressed genes (DEGs). Using support vector machine (SVM) pattern recognition, a diagnostic model for OA prediction and prevention was established. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that 190 DEGs were mainly enriched in pathways like the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, mitogen-activated protein kinase signaling pathway, nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, and osteoclast differentiation. Eight hub genes (POSTN, MMP2, CTSG, ELANE, COL3A1, MPO, COL1A1, and COL1A2) were considered potential diagnostic biomarkers for OA, the area under curve (AUC) was >0.95, which showed high accuracy. The sensitivity and specificity of the SVM model of OA based on these eight genes reached 100% in multiple external verification cohorts. Our research provides a theoretical basis for OA diagnosis for clinicians.

Pedicle Screw with Cement Augmentation in Unilateral Transforaminal Lumbar Interbody Fusion: A 2-Year Follow-Up Study.

OBJECTIVE: To evaluate safety and efficacy of pedicle screw with polymethyl methacrylate (PMMA) augmentation in unilateral transforaminal lumbar interbody fusion (uTLIF) in osteoporotic patients. METHODS: We randomly divided 50 osteoporotic patients with degenerative lumbar diseases diagnosed between February 2014 and November 2015 into 2 groups. One group underwent standard uTLIF, and the other group underwent uTLIF with PMMA augmentation. All patients were scheduled to attend a series of regular follow-up evaluations. Oswestry Disability Index, Japanese Orthopaedic Association score, visual analog scale score, lumbar lordotic angle, segmental lordotic angle, and disc space height (DSH) at each follow-up were collected and analyzed. RESULTS: The 2-year follow-up was completed by 24 patients in the uTLIF group and 23 patients in the PMMA group. Oswestry Disability Index, Japanese Orthopaedic Association score, and visual analog scale score showed significant improvements after surgery in both groups, with no significant difference between groups. DSH in the uTLIF group was 8.7 ± 2.3 mm and in the PMMA group was 10.7 ± 1.6 mm. Fusion rate in the uTLIF group was 19/24 and in the PMMA group was 21/23. DSH and fusion rate in the PMMA group were higher than those in the uTLIF group. No severe complications were observed after PMMA injection. CONCLUSIONS: Pedicle screw with PMMA augmentation can increase fixation stability and reduce DSH loss in uTLIF. Moreover, PMMA in the vertebral body did not impede the interbody fusion ability in uTLIF.

Biomechanical evaluation of different surgical procedures in single-level transforaminal lumbar interbody fusion in vitro.

BACKGROUNDS: A variety of improved surgical methods were adopted in the transforaminal lumbar interbody fusion. A mechanical stability provides an ideal environment for the formation of a fusion mass and is the basis of their good outcomes. The object of this study is to evaluate the initial similarities and differences of four commonly-used posterior surgical procedures biomechanically. METHODS: Biomechanical testing was performed at L3-4 motion segment in 6 fresh-frozen human cadaveric lumbar spines (L2-L5), including the following sequentially tested configurations: 1) intact motion segment; 2) bilateral pedicle screw fixation; 3) unilateral pedicle screw fixation; 4) unilateral pedicle screw plus contralateral translaminar facet joint screw fixation according to the Magerl technique; and 5) bilateral pedicle screw fixation with bilateral facetectomies. The range of motion, neutral zone and stiffness of each method and intact segment were collected and compared. FINDINGS: All of four methods reduce the range of motion significantly in flexion and extension and lateral bending but not in axial torsion compared with the native segment. There is no significant difference among four procedures about the range of motion in all loading modes. All of methods increase the stiffness of segmental motion compared with intact segment in all loading modes, but only bilateral pedicle screw fixation showed significant increases in stiffness in flexion and extension(p=0.02) and lateral bending(p=0.023). The stiffness offered by instrumented constructs in different methods showed no significant difference in all loading modes. INTERPRETATION: The stiffness offered by four different posterior fixations in single segmental transforaminal lumbar interbody fusion is not significantly different.