Sodium tanshinone IIA sulfonate promotes spinal cord injury repair by inhibiting blood spinal cord barrier disruption in vitro and in vivo.

Spinal cord injury (SCI) leads to microvascular damage and the destruction of the blood spinal cord barrier (BSCB), which can progress into secondary injuries, such as apoptosis and necrosis of neurons and glia, culminating in permanent neurological deficits. BSCB restoration is the primary goal of SCI therapy, although very few drugs can repair damaged barrier structure and permeability. Sodium tanshinone IIA sulfonate (STS) is commonly used to treat cardiovascular disease. However, the therapeutic effects of STS on damaged BSCB during the early stage of SCI remain uncertain. Therefore, we exposed spinal cord microvascular endothelial cells to H2 O2 and treated them with different doses of STS. In addition to protecting the cells from H2 O2 -induced apoptosis, STS also reduced cellular permeability. In the in vivo model of SCI, STS reduced BSCB permeability, relieved tissue edema and hemorrhage, suppressed MMP activation and prevented the loss of tight junction and adherens junction proteins. Our findings indicate that STS treatment promotes SCI recovery, and should be investigated further as a drug candidate against traumatic SCI.

Tauroursodeoxycholic acid alleviates secondary injury in spinal cord injury mice by reducing oxidative stress, apoptosis, and inflammatory response.

BACKGROUND: Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid derivative, which has been demonstrated to have neuroprotective effects in different neurological disease models. However, the effect and underlying mechanism of TUDCA on spinal cord injury (SCI) have not been fully elucidated. This study aims to investigate the protective effects of TUDCA in the SCI mouse model and the related mechanism involved. METHODS: The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on axon degeneration induced by oxidative stress in vitro, the cortical neurons were treated with H2O2 with or without TUDCA added and immunostained with Tuj1. Mice were randomly divided into sham, SCI, and SCI+TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of the vertebra. TUDCA (200 mg/kg) or an equal volume of saline was intragastrically administrated daily post-injury for 14 days. RESULTS: We found that TUDCA attenuated axon degeneration induced by H2O2 treatment and protected primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis and promoted axon regeneration and remyelination in the lesion site of the spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated the recovery of limb function. CONCLUSIONS: TUDCA treatment can alleviate secondary injury and promote functional recovery by reducing oxidative stress, inflammatory response, and apoptosis induced by primary injury, and promote axon regeneration and remyelination, which could be used as a potential therapy for human SCI recovery.

Polydatin promotes the neuronal differentiation of bone marrow mesenchymal stem cells in vitro and in vivo: Involvement of Nrf2 signalling pathway.

Bone marrow mesenchymal stem cell (BMSC) transplantation represents a promising repair strategy following spinal cord injury (SCI), although the therapeutic effects are minimal due to their limited neural differentiation potential. Polydatin (PD), a key component of the Chinese herb Polygonum cuspidatum, exerts significant neuroprotective effects in various central nervous system disorders and protects BMSCs against oxidative injury. However, the effect of PD on the neuronal differentiation of BMSCs, and the underlying mechanisms remain inadequately understood. In this study, we induced neuronal differentiation of BMSCs in the presence of PD, and analysed the Nrf2 signalling and neuronal differentiation markers using routine molecular assays. We also established an in vivo model of SCI and assessed the locomotor function of the mice through hindlimb movements and electrophysiological measurements. Finally, tissue regeneration was evaluated by H&E staining, Nissl staining and transmission electron microscopy. PD (30 µmol/L) markedly facilitated BMSC differentiation into neuron-like cells by activating the Nrf2 pathway and increased the expression of neuronal markers in the transplanted BMSCs at the injured spinal cord sites. Furthermore, compared with either monotherapy, the combination of PD and BMSC transplantation promoted axonal rehabilitation, attenuated glial scar formation and promoted axonal generation across the glial scar, thereby enhancing recovery of hindlimb locomotor function. Taken together, PD augments the neuronal differentiation of BMSCs via Nrf2 activation and improves functional recovery, indicating a promising new therapeutic approach against SCI.

Mechanics and Biology Interact in Intervertebral Disc Degeneration: A Novel Composite Mouse Model.

The aim of this study was to distinguish the characteristics of intervertebral disc degeneration (IVDD) originating from mechanics imbalance, biology disruption, and their communion, and to develop a composite IVDD model by ovariectomy combined with lumbar facetectomy for mimicking elderly IVDD with osteoporosis and lumbar spinal instability. Mice were randomly divided into four groups and subjected to sham surgery (CON), ovariectomy (OVX), facetectomy (mechanical instability, INS) or their combination (COM), respectively. Radiographical (n = 4) and histological changes (n = 8) of L4/5 spinal segments were analyzed. Tartrate-resistant acid phosphatase (TRAP) staining was conducted to detect osteoclasts, and expression of osterix (OSX), type I collagen (Col I), type II collagen (Col II) and vascular endothelial growth factor (VEGF) were evaluated by immunochemistry. OVX affected the body's metabolism but INS did not, as the body weight increased and uterus weight decreased in OVX and COM mice compared to CON and INS mice. OVX, INS, and COM caused IVDD in various degrees at 12 weeks after surgery. However, the major pathogeneses of OVX- and INS-induced IVDD were different, which focused on endplate (EP) remodeling and annulus fibrosus (AF) collapse, respectively. OVX induced osteopenia of vertebra. In contrast, INS promoted the stress-adaptive increase of subchondral bone trabeculae. The COM produced a reproducible severe IVDD model with characteristics of sparse vertebral trabeculae, cartilaginous EP ossification, subchondral bone sclerosis, fibrous matrix disorder, angiogenesis, disc stiffness, as well as space fusion. Additionally, all groups had elevated bone and cartilage turnover compared with CON group, as the quantity of trap + osteoclasts and the osteogenic OSX expression increased in these groups. Likewise, the VEGF expression levels were similar, accompanied by the altered matrix expression of disc, including the changed distribution and contents of Col II and Col I. The findings suggested that the composite mouse model to some extent could effectively mimic the interactions of biology and mechanics engaged in the onset and natural course of IVDD, which would be more compatible with the IVDD of elderly with vertebral osteoporosis and spinal instability and benefit to further clarify the complicated mechanobiological environment of elderly IVDD progression.

Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats.

BACKGROUND/AIMS: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats. METHODS: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1ß [IL-1ß], -IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism. RESULTS: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1ß, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway. CONCLUSION: TAN might have potential as a therapeutic agent for the treatment of RA.

Berberine inhibits the interleukin-1 beta-induced inflammatory response via MAPK downregulation in rat articular chondrocytes.

Osteoarthritis (OA) is one of the most chronic degenerative arthritic diseases, which gradually results in chondrocyte changes, articular cartilage degeneration, subchondral bone sclerosis, joint pain, swelling, and dysfunction. Berberine (BBR) has various confirmed biological activities, such as anti-inflammatory and antioxidant activities. However, the effect of BBR on the production of inflammation-associated proteins, including inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, metalloproteinases (MMPs), Collagen II, TNF-α, and IL-6 via the MAPK (mitogen-activated protein kinases) pathway in IL-1ß-stimulated rat chondrocytes, has not yet been studied. Thus, the purpose of this study was to evaluate whether BBR would decrease the production of inflammation-associated proteins through the MAPK signal pathway. Rat chondrocytes were cultured and pretreated with BBR at different concentrations (0, 25, 50, and 100 µM) and then stimulated with or without IL-1ß (10 ng/mL). The mRNA expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 was measured by real-time polymerase chain reaction (RT-PCR), and the protein expression of iNOS, COX-2, Collagen II, MMP-3,MMP-13, and MAPKs were measured by Western blotting. The results showed that the expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 increased in the IL-1ß-treated group and BBR showed an ability to inhibit the elevated expression under the pretreatment. Furthermore, the IL-1ß-induced downregulation of Collagen II could be ameliorated by BBR. Moreover, the expression of MAPKs was significantly decreased by BBR. These results demonstrated that BBR had the anti-catabolic and anti-inflammation abilities that were through the MAPKs in IL-1ß-induced rat chondrocytes. These findings may provide a novel therapeutic choice for treatment of OA using BBR.

Primary intraspinal dumbbell-shaped mesenchymal chondrosarcoma with massive calcifications: a case report and review of the literature.

BACKGROUND: Mesenchymal chondrosarcoma is a rare malignant tumor arising from bone or soft tissues. Instraspinal dumbbell-shaped mesenchymal chondrosarcoma is even rarer; however, it should not be neglected by clinicians. CASE PRESENTATION: A 26-year-old female was referred to our hospital with a 1.5-month history of sciatic pain and numbness in the left leg. Computed tomography and magnetic resonance imaging scans revealed an intraspinal dumbbell-shaped mass which had distinguishing features of neurogenic tumors, surprisingly, with massive calcifications, and no tumor metastasis was found. Then the patient underwent a total resection of the tumor, and during the operation, we found that the right nerve root of the fifth lumbar almost disappeared. The tumor was diagnosed as mesenchymal chondrosarcoma by histopathological examination after operation. Adjuvant therapies were not performed. However, recurrence of the tumor occurred 5 months later, and she underwent a total resection again combined with radiotherapy after second surgery. CONCLUSIONS: To the best of our knowledge, this case study presents the first report in literature about primary instraspinal dumbbell-shaped mesenchymal chondrosarcoma with massive calcifications, which may provide some evidence for clinical practice. As the clinical symptoms and radiographic findings of mesenchymal chondrosarcoma are usually not specific, clinicians should consider it as a possible case and diagnose it through careful histopathological examination. Sometimes, calcification could be seen in tumors, which may influence or reflect the growth of tumor and disease prognosis. Although prognosis in mesenchymal chondrosarcoma varies from person to person, generally, complete resection, adjuvant therapy, and regular examinations are recommended to perform for patients with mesenchymal chondrosarcoma.

Reliability and validity of the Chinese version of the Short Musculoskeletal Function Assessment questionnaire in patients with skeletal muscle injury of the upper or lower extremities.

BACKGROUND: The Short Musculoskeletal Function Assessment (SMFA) questionnaire is one of the most commonly used scales to evaluate functional status and quality of life (QOL) of patients with a broad range of musculoskeletal disorders. However, a Chinese version of the SMFA questionnaire for the psychometric properties of skeletal muscle injury patients in China is still lacking. The current study translated the SMFA into Chinese and assessed its reliability and validity among Chinese patients with skeletal muscle injury of the upper or lower extremities. METHODS: The original SMFA was translated from English into Chinese and culturally adapted according to cross-cultural adaptation guidelines. A multicenter cross-sectional study was conducted, comprising 339 skeletal muscle injury patients (aged 20-75 years) from 4 hospitals. The SMFA, the health survey short form (SF-36) along with a region-specific questionnaire (including the disabilities of the arm, shoulder, and hand questionnaire (DASH), the hip disability and osteoarthritis outcome score (HOOS), the knee injury and osteoarthritis outcome score (KOOS), and the foot function index (FFI)) were completed according to the region of injury. Reliability was estimated from the internal consistency using Cronbach's α and validity was assessed via convergent validity, known-groups comparison, and construct validity. RESULTS: Cronbach's α coefficient was over 0.75 for two subscales and four categories of the SMFA, suggesting that the internal consistency reliability of the SMFA was satisfactory. Known-groups comparison showed that the dysfunction index and the bother index of the SMFA discriminated well between patients who differed in age, gender, injury location, and operation status rather than in subgroups based on the body mass index (BMI). The convergent validity of the SMFA was good, as moderate to excellent correlations were found between the subscales of the SMFA and the four subscales of SF-36 (physical function, role-physical, bodily pain, and social functioning) and the region-specific questionnaires. The construct validity was proved by the presence of a six-factor structure that accounted for 66.85 % of the variance. CONCLUSION: The Chinese version of the SMFA questionnaire is a reliable and valid instrument to measure patient-reported impact of musculoskeletal injuries in the upper or lower extremities.

Dual Cannula Combined With Modified Shoelace Continuous Capsular Closure Technique in Hip Arthroscopic Surgery.

The Technical Note aims to present an arthroscopic capsular closure technique at the end of the hip arthroscopy. The technology employs a dual-channel approach and modified shoelace suture technique to continuously suture the hip capsule. Recent studies have indicated that routine intraoperative repair of the articular capsule at the end of the hip arthroscopy is advocated. However, the majority of the hip capsular closure techniques are relatively complex, time-consuming, and bring many complications, which has hindered their widespread use in clinical practice. Herein, we provide an arthroscopic capsular closure technique using the modified shoelace continuous suture in combination with a dual cannula for correcting hip instability during hip arthroscopic surgery of femoroacetabular impingement.

Chronic ACLD Knees with Early Developmental Cartilage Lesions Exhibited Increased Posterior Tibial Translation during Level Walking.

OBJECTIVE: Early articular cartilage lesion (CL) is a vital sign in the onset of posttraumatic knee osteoarthritis (PTOA) in patients with anterior cruciate ligament deficiency (ACLD). Researchers have suggested that altered kinematics could accelerate CLs and, therefore, lead to the onset of PTOA. However, little is known about whether specific knee kinematics exist that lead to early CL in chronic ACLD knees. Level walking is the most frequent and relevant in vivo activity, which greatly impacts knee health. We hypothesized that the knee kinematics during level walking in chronic ACLD knees with early tibiofemoral CL would significantly differ from those of chronic ACLD knees without early tibiofemoral CL. METHODS: Thirty patients with a chronic ACLD history, including 18 subjects with CLs and 12 subjects without CLs, and 35 healthy control subjects were recruited for the study from July 2020 to August 2022. The knee kinematic data during level walking were collected using a three-dimensional motion analysis system. The kinematic differences between groups were compared using statistical parametric mapping with one dimension for One-Way ANOVA. The cartilage statuses of the ACLD knees were assessed via MRI examination. The CLs distribution of subjects was evaluated using a modified Noyes scale and analyzed by chi-square tests. RESULTS: ACLD knees with CLs had significantly greater posterior tibial translation (7.7-8.0mm, 12%-18% gait cycle GC, p = 0.014) compared to ACLD knees without CLs during level walking. ACLD knees with CLs had greater posterior tibial translation (4.6-5.5mm, 0%-23% GC, p < 0.001; 5.8-8.0mm, 86%-100% GC, p < 0.001) than healthy controls during level walking. In the group of ACLD knees with CLs, CL is mainly located in the back of the tibia plateau and front of load bearing area of the medial femoral condyle (p < 0.05). CONCLUSION: Chronic anterior cruciate ligament deficient knees with cartilage lesions have increased posterior tibial translation compared to anterior cruciate ligament deficient knees without cartilage lesions and healthy subjects. The posterior tibial translation may play an important role in knee cartilage degeneration in ACLD knees. The increased posterior tibial translation and cartilage lesion characteristics may improve our understanding of the role of knee kinematics in cartilage degeneration and could be a helpful potential reference for anterior cruciate ligament deficient therapy, such as physical training to improve abnormal kinematic behavior.

Injectable, Electroconductive, Free Radical Scavenging Silk Fibroin/Black Phosphorus/Glycyrrhizic Acid Nanocomposite Hydrogel for Enhancing Spinal Cord Repair.

Spinal cord injury (SCI) often leads to a severe permanent disability. A poor inflammatory microenvironment and nerve electric signal conduction block are the main reasons for difficulty in spinal cord nerve regeneration. In this study, black phosphorus (BP) and glycyrrhizic acid (GA) are integrated into methacrylate-modified silk fibroin (SF) to construct a bifunctional injectable hydrogel (SF/BP/GA) with appropriate conductivity and the ability to inhibit inflammation to promote neuronal regeneration after SCI. This work discovers that the SF/BP/GA hydrogel can reduce the oxidative damage mediated by oxygen free radicals, promote the polarization of macrophages toward the anti-inflammatory M2 phenotype, reduce the expression of inflammatory factors, and improve the inflammatory microenvironment. Moreover, it induces neural stem cell (NSC) differentiation and neurosphere formation, restores signal conduction at the SCI site in vivo, and ameliorates motor function in mice with spinal cord hemisection, revealing a significant neural repair effect. An injectable, electroconductive, free-radical-scavenging hydrogel is a promising therapeutic strategy for SCI repair.

Transplantation of Wnt5a-modified Bone Marrow Mesenchymal Stem Cells Promotes Recovery After Spinal Cord Injury via the PI3K/AKT Pathway.

Spinal cord injury (SCI) is a severe neurological condition that can lead to paralysis or even death. This study explored the potential benefits of bone marrow mesenchymal stem cell (BMSC) transplantation for repairing SCI. BMSCs also differentiate into astrocytes within damaged spinal cord tissues hindering the cell transplantation efficacy, therefore it is crucial to enhance their neuronal differentiation rate to facilitate spinal cord repair. Wnt5a, an upstream protein in the non-classical Wnt signaling pathway, has been implicated in stem cell migration, differentiation, and neurite formation but its role in the neuronal differentiation of BMSCs remains unclear. Thus, this study investigated the role and underlying mechanisms of Wnt5a in promoting neuronal differentiation of BMSCs both in vivo and in vitro. Wnt5a enhanced neuronal differentiation of BMSCs in vitro while reducing astrocyte differentiation. Additionally, high-throughput RNA sequencing revealed a correlation between Wnt5a and phosphoinositide 3-kinase (PI3K)/protein kinase B(AKT) signaling, which was confirmed by the use of the PI3K inhibitor LY294002 to reverse the effects of Wnt5a on BMSC neuronal differentiation. Furthermore, transplantation of Wnt5a-modified BMSCs into SCI rats effectively improved the histomorphology (Hematoxylin and eosin [H&E], Nissl and Luxol Fast Blue [LFB] staining), motor function scores (Footprint test and Basso-Beattie-Bresnahan [BBB]scores)and promoted neuron production, axonal formation, and remodeling of myelin sheaths (microtubule associated protein-2 [MAP-2], growth-associated protein 43 [GAP43], myelin basic protein [MBP]), while reducing astrocyte production (glial fibrillary acidic protein [GFAP]). Therefore, targeting the Wnt5a/PI3K/AKT pathway could enhance BMSC transplantation for SCI treatment.

Capsule closure has better hip function than non-closure in hip arthroscopy for femoracetabular impingement: A systematic review and meta-analysis.

Background: The impact of capsular closure vs non-closure in hip arthroscopy for femoracetabular impingement (FAI) was assessed by a meta-analysis. Methods: With the most recent search update occurring in August 2022, relevant studies were found by searching the Pubmed and EMBASE databases. A collection of studies was made that conducted hip arthroscopy for FAI. Review Manager 5.3 was used to carry out the meta-analysis. The dichotomous and continuous factors were compared using the odds ratios (OR) and mean differences (MD). A fixed-effect or random-effect model was chosen, depending on the degree of heterogeneity (I2). Forest plots were used to assess the results. A significance level of P < 0.05 was applied to the statistical analysis. Results: Ultimately, 15 studies were incorporated into the meta-analysis. The surgery time was longer for the capsular closure group (CC group) compared to the non-closure (NC group) group. (P < 0.001, SMD = 8.59, 95%CI [7.40, 9.77], I2 = 32 %). Following hip arthroscopy, the CC group's mHHS was superior to that of the NC group (P = 0.001, MD = 2.05, 95%CI [0.83, 3.27], I2 = 42 %), HOS-ADL (P < 0.001, MD = 4.29, 95%CI [3.08, 5.50], I2 = 0 %). The capsular closure group had a reduced rate of postoperative complications (P = 0.001, OR = 0.21, 95%CI [0.08, 0.54], I2 = 0 %) and conversion to THA (P = 0.01, OR = 0.42, 95%CI [0.21, 0.83], I2 = 0 %) following hip arthroscopy than the non-closure group. The revision rate, VAS, and postoperative HOS-SSS did not significantly differ between these two groups (P＞0.05). Conclusion: The current meta-analysis found that the closed group had a lower complication rate and considerably greater mHHS and HOS-ADL following surgery compared to the non-closed capsule group. Whether this is related to the continuous progress of biomechanical and clinical research techniques deserves our attention. Level of evidence: Level IV, systematic review of Level I through Level III studies.

Transplantation of MiR-28-5p-Modified BMSCs Promotes Functional Recovery After Spinal Cord Injury.

Traumatic spinal cord injury (TSCI) is a prevalent central nervous system condition that imposes a significant burden on both families and society, affecting more than 2 million people worldwide. Recently, there has been increasing interest in bone marrow mesenchymal stem cell (BMSC) transplantation as a promising treatment for spinal cord injury (SCI) due to their accessibility and low immunogenicity. However, the mere transplantation of BMSCs has limited capacity to directly participate in the repair of host spinal cord nerve function. MiR-28-5p, identified as a key differentially expressed miRNA in spinal cord ischemia-reperfusion injury, exhibits differential expression and regulation in various neurological diseases. Nevertheless, its involvement in this process and its specific regulatory mechanisms in SCI remain unclear. Therefore, this study aimed to investigate the potential mechanisms through which miR-28-5p promotes the neuronal differentiation of BMSCs both in vivo and in vitro. Our results indicate that miR-28-5p may directly target Notch1, thereby facilitating the neuronal differentiation of BMSCs in vitro. Furthermore, the transplantation of lentivirus-mediated miR-28-5p-overexpressed BMSCs into SCI rats effectively improved footprint tests and Basso, Beattie, and Bresnahan (BBB) scores, ameliorated histological morphology (hematoxylin-eosin [HE] and Nissl staining), promoted axonal regeneration (MAP2 and growth-associated protein 43 [GAP43]), and facilitated axonal remyelination (myelin basic protein [MBP]). These findings may suggest that miR-28-5p-modified BMSCs could serve as a therapeutic target to enhance the behavioral and neurological recovery of SCI rats.

Component analysis of Chinese medicine and advances in fuming-washing therapy for knee osteoarthritis via unsupervised data mining methods.

OBJECTIVE: To analyze the component law of Chinese medicines in fuming-washing therapy for knee osteoarthritis (KOA), and develop new fuming-washing prescriptions for KOA through unsupervised data mining methods. METHODS: Chinese medicine recipes for fuming-washing therapy for KOA were collected and recorded in a database. The correlation coefficient among herbs, core combinations of herbs, and new prescriptions were analyzed using modified mutual information, complex system entropy cluster, and unsupervised hierarchical clustering, respectively. RESULTS: Based on analysis of 345 Chinese medicine recipes for fuming-washing therapy, 68 herbs occurred frequently, 33 herb pairs occurred frequently, and 12 core combinations were found. Five new fuming-washing recipes for KOA were developed. CONCLUSION: Chinese medicines for fuming-washing therapy of KOA mainly consist of wind-dampness-dispelling and cold-dispersing herbs, blood-activating and stasis-resolving herbs, and wind-dampness-dispelling and heat-clearing herbs. The treatment of fuming-washing therapy for KOA also includes dispelling wind-dampness and dispersing cold, activating blood and resolving stasis, and dispelling wind-dampness and clearing heat. Zhenzhutougucao (Herba Speranskiae Tuberculatae), Honghua (Flos Carthami), Niuxi (Radix Achyranthis Bidentatae), Shenjincao (Herba Lycopodii Japonici), Weilingxian (Radix et Rhizoma Clematidis Chinensis), Chuanwu (Radix Aconiti), Haitongpi (Cortex Erythrinae Variegatae), Ruxiang (Olibanum), Danggui (Radix Angelicae Sinensis), Caowu (Radix Aconiti Kusnezoffii), Moyao (Myrrha), and Aiye (Folium Artemisiae Argyi) are the main herbs used in the fuming-washing treatment for KOA.

Obacunone targets macrophage migration inhibitory factor (MIF) to impede osteoclastogenesis and alleviate ovariectomy-induced bone loss.

INTRODUCTION: Osteoporosis is the most common bone disorder where the hyperactive osteoclasts represent the leading role during the pathogenesis. Targeting hyperactive osteoclasts is currently the primary therapeutic strategy. However, concerns about the long-term efficacy and side effects of current frontline treatments persist. Alternative therapeutic agents are still needed. OBJECTIVES: Obacunone (OB) is a small molecule with a broad spectrum of biological activities, particularly antioxidant and anti-inflammatory effects. This study aims to examine OB's therapeutic potential on osteoporosis and explore the rudimentary mechanisms. METHODS: Osteoclast formation and osteoclastic resorption assays were carried out to examine OB's inhibitory effects in vitro, followed by the in-vivo studies of OB's therapeutic effects on ovariectomy-induced osteoporotic preclinical model. To further study the underlying mechanisms, mRNA sequencing and analysis were used to investigate the changes of downstream pathways. The molecular targets of OB were predicted, and in-silico docking analysis was performed. Ligand-target binding was verified by surface plasmon resonance (SPR) assay and Western Blotting assay. RESULTS: The results indicated that OB suppressed the formation of osteoclast and its resorptive function in vitro. Mechanistically, OB interacts with macrophage migration inhibitory factor (MIF) which attenuates receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced signaling pathways, including reactive oxygen species (ROS), NF-κB pathway, and mitogen-activated protein kinases (MAPKs). These effects eventually caused the diminished expression level of the master transcriptional factor of osteoclastogenesis, nuclear factor of activated T cells 1 (NFATc1), and its downstream osteoclast-specific proteins. Furthermore, our data revealed that OB alleviated estrogen deficiency-induced osteoporosis by targeting MIF and thus inhibiting hyperactive osteoclasts in vivo. CONCLUSION: These results together implicated that OB may represent as a therapeutic candidate for bone disorders caused by osteoclasts, such as osteoporosis.

Corrigendum: Inhibitory effects of Rhaponticin on osteoclast formation and resorption by targeting RANKL-induced NFATc1 and ROS activity.

[This corrects the article DOI: 10.3389/fphar.2021.645140.].

Biomechanical analysis of sacroiliac joint motion following oblique-pulling manipulation with or without pubic symphysis injury.

Background: Oblique-pulling manipulation has been widely applied in treating sacroiliac joint (SIJ) dysfunction. However, little is known about the biomechanical mechanism of the manipulation. This study aims to analyze the SIJ motion under oblique-pulling manipulation, in comparison with compression and traction loads. Methods/Study Design: A total of six specimens of embalmed human pelvis cadavers were dissected to expose the SIJ and surrounding ligaments. Through a servo-hydraulic testing system, biomechanical tests were performed on the stable pelvis and the unstable pelvis with pubic symphysis injury (PSI). A three-dimensional (3D) photogrammetry system was employed to determine the separation and nutation in three tests: axial compression (test A), axial traction (test B), and oblique-pulling manipulation (test C). Results: After applying the testing loads, the range of nutation was no more than 0.3° (without PSI) and 0.5°(with PSI), separately. Except for test B, a greater nutation was found with PSI (p < 0.05). Under both conditions, nutation following test A was significantly greater than that of other tests (p < 0.05). SIJ narrowed in test A and separated in tests B and C, where the range of motion did not exceed 0.1 mm (without PSI) or 0.3 mm (with PSI) separately. Under both conditions, the separation of SIJ in test C was not as apparent as the narrowness of SIJ in test A (p < 0.05). Compared to SIJ, a more significant increasing displacement was found at the site of the iliolumbar ligament (p < 0.05). Nevertheless, when the force was withdrawn in all tests, the range of nutation and separation of SIJ nearly decreased to the origin. Conclusion: Pubic symphysis is essential to restrict SIJ motion, and the oblique-pulling manipulation could cause a weak nutation and separation of SIJ. However, the resulting SIJ motion might be neutralized by regular standing and weight-bearing load. Also, the effect on SIJ seems to disappear at the end of manipulation. Therefore, the stretching and loosening of surrounding ligaments need to be paid more attention to.

Pain Management of Hallux Valgus Surgery Is Achieved by Cocktail Therapy.

Background: Hallux valgus is a relatively common forefoot disease in clinical practice. The aim of our study was to assess the role of local cocktail drugs and postoperative pain after hallux valgus surgery. Methods: A retrospective case-control study was conducted to analyze 75 moderate to severe hallux valgus patients from June 1, 2018 to December 1, 2019. All patients were divided into cocktail and control groups according to whether the cocktail therapy was used or not after the operation. The anesthesiologist did not provide analgesic treatment other than nerve block anesthesia and intravenous anesthesia, such as analgesic pumps. The operative region of the cocktail group received a mixture of 10 ml of 0.75% ropivacaine, 10 ml of flurbiprofen axetil injection, and 1 ml of compound betamethasone injection, whereas the control group received nothing in the surgical spot. We recorded patients' VAS scores preoperatively and at 6, 24 hours postoperatively; the length of hospital stay and the number of hospitalization expenses; the scores of Kolcaba comfort level; and the scores of Pittsburgh sleep quality. Result: There was no significant difference in age or sex between the two groups. The VAS scores at 6 and 24 hours postoperatively were significantly lower in the cocktail group. The average length of hospital stay was 8.24 days in the control group and 3.73 days in the cocktail group. The average total hospitalization cost of the control group was ¥28285.16, and that of the cocktail group was ¥22366.31. In expenses of total hospitalization costs, the cocktail group was lower than the control group. Kolcaba's comfort various scores and the total score of the cocktail group were higher than the control group. The total score of PSQI and all dimensions in the experimental group were lower than those in the control group. Conclusion: We found a significant difference in the results of postoperative pain management except for age, sex, and hospitalization expenses. After hallux valgus surgery, inject cocktail drugs around the first metatarsophalangeal joint did reduce postoperative pain level. Level of Evidence. Level III, case-control study.