Therapeutic mechanisms of modified Jiawei Juanbi decoction in early knee osteoarthritis: A multimodal analysis.

Modified Jiawei Juanbi decoction (MJD) is used for the treatment of early-stage knee osteoarthritis (KOA). Here, modified Jiawei Juanbi decoction (MJD) was employed for the treatment of early-stage knee osteoarthritis (KOA) and its mechanisms were assessed via metabonomics and network pharmacology. A total of 24 male Sprague-Dawley rats were randomly allocated into a normal control group, a model group, and an MJD group (n = 8 rats per group). Each rat group was further equally divided into two subgroups for investigation for either 14 or 28 days. A rat model of early-stage KOA was constructed and rats were treated with MJD. Effects were evaluated based on changes in knee circumference, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). We also analyzed histopathological changes in articular cartilage. High-resolution mass spectrometry was used to analyze the chemical profile of MJD, identifying 228 components. Using an LC-Q-TOF-MS metabonomics approach, 33 differential metabolites were identified. The relevant pathways significantly associated with MJD include arginine and proline metabolism, vitamin B6 metabolism, as well as the biosynthesis of phenylalanine, tyrosine and tryptophan. The system pharmacology paradigm revealed that MJD contains 1027 components and associates with 1637 genes, of which 862 disease genes are related to osteoarthritis. The construction of the MJD composition-target-KOA network revealed a total of 140 intersection genes. A total of 39 hub genes were identified via integration of betweenness centrality values greater than 100 using CytoHubba. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed several significantly affected signaling pathways including the HIF-1, AGE-RAGE (in diabetic complications), IL-17, rheumatoid arthritis and TNF pathways. Integrated-omics and network pharmacology approaches revealed a necessity for further detailed investigation focusing on two major targets, namely NOS2 and NOS3, along with their essential metabolite (arginine) and associated pathways (HIF-1 signaling and arginine and proline metabolism). Real-time PCR validated significantly greater downregulation of NOS2 and HIF-1ɑ in the MJD as compared to the model group. Molecular docking analysis further confirmed the binding of active MJD with key active components. Our findings elucidate the impact of MJD on relevant pathophysiological and metabolic networks relevant to KOA and assess the drug efficacy of MJD and its underlying mechanisms of action.

Cervical cord compression with lower limb sensory disturbance: three case reports and a literature review.

Lower limb sensory disturbance can be a false localizing sign of cervical spondylotic myelopathy. It may lead to delayed or missed diagnosis, resulting in an inappropriate management plan, especially in the presence of concurrent lumbar lesions. Three Asian patients with lower limb sensory disturbance were ineffectively treated in the lumbar region. Magnetic resonance imaging showed cervical disc herniation and cervical spinal cord compression. The patients underwent anterior cervical discectomy and interbody fusion using a stand-alone cervical interbody fusion cage. Postoperative imaging showed that the spinal cord compression was relieved. On the first postoperative day, the lower limb sensory disturbance was also relieved. The patients showed good recovery at the 3-month postoperative follow-up. These three cases of cervical cord compression with lower limb sensory disturbance were easily misdiagnosed as lumbar spondylosis. Anterior cervical discectomy and fusion had a good therapeutic effect. Therefore, the presence of lower limb sensory disturbance in a non-radicular classic pattern should always raise suspicion of a possible cord compression at a higher level.

Novel inflammatory markers in the blood of patients with knee synovitis.

OBJECTIVE: Synovitis is a joint disease that seriously affects patient quality of life, but there are currently no diagnostic markers. The albumin to fibrinogen ratio (AFR) and monocyte to lymphocyte ratio (MLR) are non-invasive and cost-effective markers for various systemic inflammatory diseases. However, these markers have not yet been investigated for synovitis. This cross-sectional study evaluated the predictive ability of AFR and MLR in patients with non-specific knee synovitis. METHODS: One hundred fifty-five patients with knee synovitis and 108 healthy control patients were enrolled. Patient characteristics, blood parameters, AFRs, and MLRs were assessed, and the diagnostic value of these factors was determined. RESULTS: Among 125 patients included, patients with synovitis had a lower AFR and higher MLR than control subjects. The diagnostic values of AFR and MLR were 0.86 and 0.84, respectively, and higher compared with other parameters by receiver operating characteristic curve assessments. Additionally, MLR was negatively correlated with AFR. Late-stage patients showed significantly lower AFRs and significantly higher MLRs than early-stage patients. Binary logistic regression analyses indicated that AFR was an independent predictor for synovitis severity. CONCLUSIONS: The AFR and MLR had high diagnostic value for knee synovitis. The AFR was an independent predictor for synovitis severity.

Anterior cervical surgery to treat diffuse idiopathic skeletal hypertrophic combined with cervical disc herniation: A case report.

RATIONALE: Diffuse idiopathic skeletal hyperostosis (DISH) is a skeletal disease characterized by calcification of anterolateral ligaments of the spine and the rest of the body. DISH combined with disc herniation induces complex symptoms and is more difficult to treat. Here, we describe a complicated case of a patient diagnosed with DISH as well as cervical disc herniation that was successfully treated using anterior cervical surgery. PATIENTS CONCERN: A 69-year-old Asian male experienced dysphagia and weakness in his left limbs. He also experienced a stiff neck and right slant over a 6-month period. DIAGNOSIS: An X-ray revealed calcification of the C4-7 vertebral front edge and a narrowed intervertebral space between C5/6. Coronal and sagittal computerized tomography (CT) and magnetic resonance imaging (MRI) both showed compression of the spinal cord at the cervical 5/6. Esophagography revealed that osteophytes in the anterior margin of vertebral body (C4-C7) oppressed the esophagus. INTERVENTIONS: An operation focused on anterior cervical C5/6 disc fusion and anterior vertebral C4-7 osteophyte removal was performed. OUTCOMES: After the operation, X-ray and CT showed that most osteophytes were removed and spinal cord compression was relieved. One day following the operation, both dysphagia and numbness in limbs were improved. Strong recovery was observed at the three-month follow-up exam. LESSONS: This complex DISH combined with disc herniation case is rarely observed in patients. Anterior cervical disc fusion and anterior vertebral osteophyte removal were effective treatment measures. This case study provides insight into treating cases presented with cervical spine complications associated with DISH combined with other ailments.

Association between cytokines and exosomes in synovial fluid of individuals with knee osteoarthritis.

Background: Cytokines in synovial fluid (SF) play a crucial role in knee osteoarthritis (KOA). Exosomes are nanovesicles that are abundant in SF and carry a large quantity of signaling molecules. The purpose of this study was to evaluate the cytokine profiles of SF-derived exosomes and try to explore its biological function.Methods: Twenty-four KOA patients who were scheduled for their first intra-articular injection or knee replacement surgery were enrolled and divided into the KL1-2 group and the KL3-4 group according to the Kellgren and Lawrence (KL) classification. SF was collected from the patient's knee for the isolation of exosomes. A multiplex cytokine assay was performed to detect the 21 cytokines in the exosomes. The SF derived-exosomes were exposed to PBMCs and chondrocytes to assess their immunomodulatory potential.Results: Exosomes were successfully extracted from the SF, with an average diameter of 92 nm. Most cytokines were detectable in the SF-derived exosomes. Twelve inflammatory cytokines and eight chemokines were elevated in the exosomes of the KL3-4 group compared to that of the KL1-2 group (p < .05). A higher number of PBMCs were chemo attracted and the proliferation of chondrocytes was restrained by the SF-derived exosomes from the KL3-4 group in comparison with the KL1-2 group (p < .05).Conclusion: Our data indicated that most cytokines in SF are not only in a free form but also associated with and enriched in exosomes. Exosomes from end-stage KOA patients have a higher level of cytokines, especially chemokines, in comparison with the cytokine profiles of the soluble SF. SF-derived exosomes recruit inflammatory cells and inhibit cartilage proliferation, thus promoting joint degeneration. These data provide a new perspective for understanding the changes in the inner environment of KOA.

Five years of follow-up of immediate quadriparesis caused by a large calcified mass in the ligamentum flavum: A case report.

INTRODUCTION: Calcification of ligamentum flavum (CLF) is an important cause of spinal stenosis and spinal cord compression. CLF does not usually induce immediate quadriparesis. Here we describe a rare case of immediate quadriparesis due to a large calcified mass containing liquids in the ligamentum flavum, which was easily confused with gout crystals. PATIENT CONCERNS: A 74-year-old Asian male felt progressive bilateral arm and leg weakness. On the fourth day, acute quadriparesis occurred. DIAGNOSIS: Coronal and sagittal computerized tomography (CT) and magnetic resonance imaging (MRI) showed a large circular mass in the left posterior part of the cervical 3/4 spinal canal, protruding into the canal, and occupying one-half of the spinal canal. INTERVENTIONS: Emergency laminectomy was performed at C3/4 level. The huge cyst was excised and 1 ml of white viscous liquid flowed out. OUTCOMES: After operation, CT and MRI showed a full laminectomy of C3/4 and complete decompression of the cervical spinal cord. Hematoxylin-eosin (HE) staining showed that large amounts of calcium was deposited around cystic tissues. Five-year follow-up after laminectomy showed good recovery. CONCLUSION: This case of immediate quadriparesis, caused by a large calcified mass containing fluid, is very rare. It should be at the earliest stage of calcification. Laminectomy is an effective treatment. This calcification was deceptive and was easily confused with gout crystals. It can help to understand the exact pathophysiology of CLF.

The predictive role of monocyte-to-lymphocyte ratio in osteoporosis patient.

Osteoporosis is a chronic, progressive disease in which early diagnosis is very important. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have been reported as new predictors in inflammatory and immune diseases including osteoporosis. No studies have reported the relationship between monocyte-to-lymphocyte ratio (MLR) and osteoporosis patients.To investigated the ability of MLR to predict osteoporosis.Three hundred sixteen osteoporosis patients and 111 healthy control subjects were enrolled. Patients' laboratory and clinical characteristics were recorded. MLR, NLR, and PLR levels were calculated. The differences were compared and the diagnostic values of MLR were analyzed.There were 76 male and 105 female patients included, with a mean age of 56.57 ±â€Š9.95 years. The levels of MLR, NLR, and PLR in osteoporosis patients were all higher than those in healthy control subjects. The area under the curve of MLR was higher than those of NLR and PLR. Multivariate linear regression analysis showed that T-score was affected by age and MLR. MLR was positively correlated with C-reactive protein, erythrocyte sedimentation rate, red blood cell distribution width, age, sex, and inversely with hemoglobin. MLR and PLR levels were significantly higher in osteoporosis patients than in osteopenia patients (P < .05).The present study shows that MLR had a higher diagnostic value for osteoporosis. MLR may be a reliable, inexpensive, and novel potential predictor of osteoporosis.

[Internal fixation combined with bone grafting through the injured pedicle for the treatment of thoracolumbar burst fractures via a paraspinal intermuscular approach under MAST Quadrant retractor].

OBJECTIVE: To study clinical effects of short-segment fixation and injured vertebra bone grafting through injured pedicle for the treatment of thoracolumbar burst fractures under MAST Quadrant retractor via a paraspinal muscle approach. METHODS: The data of 42 patients with thoracolumbar burst fractures treated from June 2009 to September 2012 were reviewed. There were 19 males and 23 females, with an average age of (55.2±11.9) years old. The mean injury time was (5.8±4.3) days. Fracture segments included T10 in 3 cases, T11 in 6 cases, T12 in 13 cases, L1 in 9 cases, L2 in 7 cases, and L3 in 4 cases. According to Denis classification, 9 patients were type A, 21 patients were type B, 5 patiens were type C, 5 patients were type D, and 2 patients were type E. All the patients were treated with short-segment pedicle screw-rod system fixation under MAST Quadrant via the paraspinal muscle approach. The operative time, blood loss, complications and the height of vertebra, kyphosis Cobb angle, VAS scores, JOA scores were measured before and after treatment. RESULTS: After treatment, the vertebral height and kyphosis Cobb angle were restored. Compared with preoperative results, postoperative vertebral height and kyphosis Cobb angle, VAS scores and JOA scores were all improved. But there was no statistically significance in vertebral height, kyphosis Cobb angle between postoperative at 1 week and 1 year. CONCLUSION: Internal fixation combined with injured vertebra bone grafting through the injured pedicle for the treatment of thoracolumbar burst fractures via the paraspinal intermuscular approach under MAST Quadrant is a safe, minimally invasive, effective and satisfactory method.