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Idiopathic scoliosis in children and adolescents refers to the development of unexplained scoliosis during childhood and adolescence. Chinese medicine rehabilitation is one of the effective methods to prevent its occurrence and improve clinical symptoms. In order to standardize the diagnosis and treatment of scoliosis in children and adolescents in China, to raise the attention to scoliosis in children and adolescents in society, and to ensure the standardization of Chinese medicine rehabilitation diagnosis and treatment, the expert group wrote this guideline based on the concept and method of evidence-based medicine, combined with evidence from expert discussion and clinical evaluation, and in accordance with the reporting rules of clinical treatment guidelines. This guideline covered and standardized the technical scope, normative references, terms and definitions (Cobb angle, idiopathic scoliosis, functional scoliosis, forward bending test, trunk rotation angle, weak link, core muscle strengthening, and Du-moxibustion), clinical diagnosis (clinical symptoms, clinical assessment, and imaging), TCM pattern differentiation, rehabilitation treatment [TCM rehabilitation treatment (oral administration of Chinese medicine, massage therapy, moxibustion, acupuncture therapy, acupotomy therapy, sling exercise training and traditional Chinese exercrises), modern rehabilitation therapy (physical agent modalities, exercise therapy, brace therapy and psychotherapy), prevention and management], and efficacy evaluation. This guideline can provide standardized diagnosis and treatment procedures for Chinese medicine practitioners and rehabilitation therapists in implementing Chinese medicine rehabilitation treatment of idiopathic scoliosis in children and adolescents in various rehabilitation institutions at all levels in China, the departments of rehabilitation or pediatrics in other Chinese medicine hospitals or general hospitals and provide a reliable evidence reference for clinical decision-making practice, with good clinical applicability, safety and effectiveness.

Background: The method of action of Bushen Formula (BSHXF) in the treatment of intervertebral disc degeneration (IVDD) was uncovered in this work using in vivo and in vitro tests. To clarify the mechanism of action of BSHXF, we validated the rat intervertebral disc degeneration model and the nucleus pulposus cell degeneration model.Methods: In an in vivo model of IVDD the study explores the impact of BSHXF on mitochondrial function, pro-inflammatory cytokines, pro-apoptotic factors, and matrix metalloproteinases. Additionally, it evaluates the induced degeneration of nucleus pulposus (NP) cells in an in vitro model stimulated by interleukin-1 β (IL-1β). The study measures the effects of BSHXF on both the inflammatory response and mitochondrial function.Results: The MRI results showed that BSHXF reduced intervertebral disc volume reduction and degradation of NP tissue. HE, SO-FG and immunofluorescence further confirmed the protective effect of BSHXF on degenerative intervertebral discs. BSHXF reduced the inflammatory levels of IL-6 IL-1β and TNF-α in degenerative intervertebral disc tissue. Meanwhile, JC-1, mPTP and ROS detection revealed that BSHXF can restore mitochondrial function by regulating the expression of antioxidant proteins, playing a protective role in NP cells. Finally, the WB results showed that BSHXF can alleviate IL-1β mediate the degeneration of NP cells. BSHXF can alleviate NP cell apoptosis by inhibiting the expression of bax, cleaved caspase-3, caspase-3, and cyt-c, and increasing the expression of Bcl-2.Conclusion: This study reveals that BSHXF inhibits the development of inflammatory factors, which may play a significant role in intervertebral disc degeneration. This implies that BSHXF is a suitable herbal medication for future research into inflammatory cytokine treatment. [ABSTRACT FROM AUTHOR]

Background. Low back pain (LBP) has the characteristics of chronic and persistence, which is a heavy social burden. Intervertebral disc degeneration (IVDD) is a major cause of LBP. The typical features of IVDD are extracellular matrix (ECM) degradation and nucleus pulposus cell (NP) apoptosis. Bushen Huoxue Formula (BSHXF) has good clinical effects on LBP. However, the mechanism of BSHXF affecting ECM and NP cells is still unclear. Aim of the Study. In this study, the impact of BSHXF on autophagy and apoptosis of NP cells was studied through the AMPK/SIRT1 pathway. Material and Methods. NP cells were extracted through the digestion of collagenase and trypsin, and the components of BSHXF were identified. Cell Counting Kit-8 was applied to detect the impact of BSHXF on NP cells. Mitochondrial function was detected using MitoTracker assay, ATP kit, and SOD kit. Autophagy and apoptosis were detected by RT-qPCR, western blotting, and flow cytometry. Results. BSHXF promoted NP cell survival in a concentration-dependent manner, and the elimination of rat serum did not increase cell proliferation; TNF-α accelerated ECM degradation, ROS accumulation, and NP cell apoptosis and decreased autophagic flux. BSHXF restored mitochondrial function and autophagic flux. In addition, AMPK/SIRT1 pathway activation was associated with IVDD. Conclusions. BSHXF regulates autophagy and enhances autophagic flux to suppress excessive ROS production and restore mitochondrial function in an AMPK/SIRT1-dependent manner. However, the protection of BSHXF on TNF-α-treated cells was eliminated by 3-MA. Furthermore, the protective impact of BSHXF on ECM degradation and apoptosis induced by TNF-α was restrained by an AMPK inhibitor. Therefore, maintaining the proper autophagy illustrates treatment strategy for IVDD. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a quite common disease in both China and the United States with a reported indidence of 0.13-0.23%. The incidence of fracture in AS patients is higher compared with the ordinary population. Thoracolumbar fractures are the most common type with some complications. Treatment is usually focused on restoration of spinal stability because of the unique character of the AS spine. Surgical treatment is the primary treatment method and percutaneous fixation could be a minimally invasive option for most patients. To observe the clinical effect of thoracolumbar fracture of AS treated with posterior percutaneous long-segment internal fixation in 21 patients. Forty-one patients were divided into (1) a percutaneous group (21) and (2) an open surgery group (20). Posterior long-segment internal fixation with rod and screws was randomized and performed either openly or percutaneously. General data of the two groups were compared before the surgery and other parameters were compared during and after the surgery. SPSS 20 was used for statistics and P<0.05 was considered significant differences. Forty-one patients were included in the study. Operating time, blood loss during surgery, misplacement of screws, bed rest time after operation and VAS were measured. Forty-one patients diagnosed with thoracolumbar fractures of AS were treated from Nov. 2014 to Nov. 2018. All patients were divided into a percutaneous group and an open surgery group by means of a random table. Twenty patients underwent open fixation with long-segment screws and 21 others treated with percutaneous long-segment internal fixation. Reduction was performed with positioning and manipulation before sterilization. Small incisions were made according to the preoperation plan and then screws were inserted under fluorscopy. The rod must be shaped beforehand and then put into position. Operating time, blood loss, misplacement of pedicle screws and length of bed rest after operation were recorded. Imaging examinations were performed to evaluate the bone union, spinal cord injury and spinal column balance during follow up. All patients, followed up for 6 to 48 months (mean time 21.7 months), showed bony union and no signs of loosening or broken rods or screws. During surgery, there were no displaced screws or nerve injuries. No infections were found during or after the surgery; all surgical wounds healed. Significant differences were found for operating time, blood loss during the operation and length of bed rest after surgery within the two groups (P <0.05). No significant difference was found on visual analog score (VAS) after operation and improvement of Cobb angle of spinal kyphosis (P >0.05). As a minimally invasive surgery, posterior percutaneous long-segment internal fixation can achieve results similar to traditional open surgery in relieving patients' pain and correcting spinal kyphosis with less operating time, less blood loss during operation and less traumatic impact. It could be considered the first choice or a comparatively ideal method for the treatment of thoracolumbar fractures of AS patients. 3D print technique could be used for helping reduction and shaping of the rod. percutaneous fixation system (Approved for this indication). [ABSTRACT FROM AUTHOR]

Peripheral neuropathy (PN) is an incurable complication of multiple myeloma (MM) which adversely affects patients' quality of life. The important roles that Circular RNAs (circRNAs) play in tumor progression, and exosome-mediated intracellular communication has been recognized as a crucial factor in the pathogenesis of MM. However, the role of exosome-derived circRNAs (exo -circRNAs) in MM and MM-induced PN remains elusive. In this study, we aimed to investigate the correlation between serum exo-circRNAs and MM to preliminarily explore the role of exo-circRNAs in MM-related PN. A cohort of 25 MM patients and 5 healthy control (HC) individuals were enrolled in the study. High-throughput sequencing and qRT PCR validation of serum exo-circRNAs were used to generate the aberrantly expressed exo-circRNAs profiles. Bioinformatics analysis was done using GO, KEGG, miRanda, Targetscan and Metascape. Correlation analysis was conducted between chr2:2744228–2,744,407+ and clinical characteristics of PN. ROC curve, univariate and multivariate COX regression models were conducted to identify the prognostic potential of chr2:2744228–2,744,407+ in the MM-related PN. 265 upregulated circRNAs and 787 downregulated circRNAs, with at least a two-fold difference in expression level in MM patients vs HC, were screened. Bioinformatics analysis indicated that upregulated circRNAs had the potential to facilitate MM-related PN. Furthermore, PCR validated the abundant expression of chr2:2744228–2,744,407+ in the serum exosomes of 25 MM patients. Bioinformatics analysis indicated that chr2:2744228–2,744,407+ might induce MM related PN via the downstream miRNA and GRIN2B axis. Overexpressed chr2:2744228–2,744,407+ in the serum exosomes of MM patients might lead to the downregulation of hsa-miR-6829-3p, elevation of GRIN2B in the serum and PC12 cells, and inhibited cell viability. The correlation analysis indicated that the expression of chr 2:2744228–2,744,407+ was positively correlated with the clinical characteristics of PN. ROC curve, univariate and multivariate COX regression analysis identified that chr2:2744228–2,744,407+ is an independent prognostic factor in the MM related PN. We identified that the abnormal expression of the serum exo -circRNA was correlated with MM-related PN, implying that exo-circRNA has potential as a novel therapeutic target for MM related PN. • An abundant exo -circRNA profile was found in the serum of MM patients. • The upregulated exosomal chr2:2744228–2,744,407+ might have the potential to induce MM related PN via the ceRNA mechanism. • chr2:2744228–2,744,407+ was identified as the biomarker and independent prognostic indicator in MM related PN. [ABSTRACT FROM AUTHOR]

Osteoporosis is a common metabolic bone disease that results from the imbalance of homeostasis within the bone. Intra-bone homeostasis is dependent on a precise dynamic balance between bone resorption by osteoclasts and bone formation by mesenchymal lineage osteoblasts, which comprises a series of complex and highly standardized steps. Programmed cell death (PCD) (e.g., apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis) is a cell death process that involves a cascade of gene expression events with tight structures. These events play a certain role in regulating bone metabolism by determining the fate of bone cells. Moreover, existing research has suggested that natural products derived from a wide variety of dietary components and medicinal plants modulate the PCDs based on different mechanisms, which show great potential for the prevention and treatment of osteoporosis, thus revealing the emergence of more acceptable complementary and alternative drugs with lower costs, fewer side effects and more long-term application. Accordingly, this review summarizes the common types of PCDs in the field of osteoporosis. Moreover, from the perspective of targeting PCDs, this review also discussed the roles of currently reported natural products in the treatment of osteoporosis and the involved mechanisms. Based on this, this review provides more insights into new molecular mechanisms of osteoporosis and provides a reference for developing more natural anti-osteoporosis drugs in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

Mechanical stress has been viewed as one of the key risk factors in accelerating the intervertebral disc degeneration process. The goal of the present study was to employ a repeated strike loading bovine caudal disc system to elucidate the pathophysiological impacts of cumulative mechanical stress on the disc. The discs in the model groups were subjected to two different mechanical stresses: one strike loading or repeated strike loading. The following indices were analyzed: histological morphology, glycosaminoglycan release, disc height, cell viability, apoptosis-related protein expression, and catabolism-related gene expression. Both mechanical stress modes induced degenerative changes in the discs by day 11, such as clefts and delamination of the annulus fibrosus; they increased glycosaminoglycan release. Cell viability was significantly decreased and catabolic gene expression was significantly up-regulated in the degenerative loading group and repeated strike loading group by day 9. These alterations remained evident in the annulus fibrosus tissue of the repeated strike loading group on day 11. Our data suggests that the repeated strike loading model adopted in this study could lead to degenerative changes in the disc organ model. Annulus fibrosus cells displayed a more noticeable response to mechanical stress damage and a slower recovery process, suggesting that the annulus fibrosus serves as a pivotal factor in disc degeneration due to mechanical stress injuries. The study also indicates that due to the gradual self-repair of intervertebral disc cells after injury, it is necessary to apply repeated strike loading on the disc at specific intervals when researching the repair of chronic disc injuries.

Objective: This study aimed to develop and validate a new nomogram model that can predict new vertebral fractures after surgery for osteoporotic compression fractures to optimize surgical plans and reduce the incidence of new vertebral compression fractures., Methods: 420 patients with osteoporotic vertebral compression fractures were randomly sampled using a computer at a fixed ratio; 80% of the patients were assigned to the training set, while the remaining 20% were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression method was applied to screen the factors influencing refracture and construct a predictive model using multivariate logistic regression analysis., Results: The results of the multivariate logistic regression analysis showed a significant correlation between bone cement leakage, poor cement dispersion, the presence of fractures in the endplate, and refractures. The receiver operating characteristic curve (ROC) results showed that the area under the ROC curve (AUC) of the training set was 0.974 and the AUC of the validation set was 0.965, which proves that this prediction model has a good predictive ability. The brier score for the training set and validation set are 0.043 and 0.070, respectively, indicating that the model has high accuracy. Moreover, the calibration curve showed a good fit with minimal deviation, demonstrating the model's high discriminant ability and excellent fit. The decision curve indicated that the nomogram had positive predictive ability, indicating its potential as a practical clinical tool., Conclusion: Cement leakage, poor cement dispersion, and presence of fractures in the endplate are selected through LASSO and multivariate logistic regressions and included in the model development to establish a nomogram. This simple prediction model can support medical decision-making and maybe feasible for clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao, Zheng, Yao, Wang, Tan, Xin, Li and Chen.)

Background: Quinazolines are an important class of benzopyrimidine heterocyclic compounds with a promising antitumor activity that can be used for the design and development of osteosarcoma target compounds. Objective: To predict the compound activity of quinazoline compounds by constructing 2D- and 3D-QSAR models, and to design new compounds according to the main influencing factors of compound activity in the two models. Methods: First, heuristic method and GEP (gene expression programming) algorithm were used to construct linear and non-linear 2D-QSAR models. Then a 3D-QSAR model was constructed using CoMSIA method in SYBYL software package. Finally, new compounds were designed according to molecular descriptors of 2D-QSAR model and contour maps of 3D-QSAR model. Several compounds with optimal activity were used for docking experiments with osteosarcoma related targets (FGFR4). Results: The non-linear model constructed by GEP algorithm was more stable and predictive than the linear model constructed by heuristic method. A 3D-QSAR model with high Q 2 (0.63) and R 2 (0.987) values and low error values (0.05) was obtained in this study. The success of the model fully passed the external validation formula, proving that the model is very stable and has strong predictive power. 200 quinazoline derivatives were designed according to molecular descriptors and contour maps, and docking experiments were carried out for the most active compounds. Compound 19g.10 has the best compound activity with good target binding capability. Conclusion: To sum up, the two novel QSAR models constructed were very reliable. The combination of descriptors in 2D-QSAR with COMSIA contour maps provides new design ideas for future compound design in osteosarcoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lian, Sang, Li, Zhai and Bai.)

Background: Postmenopausal women are one of the most vulnerable groups to osteoporosis. Romosozumab is a newly monoclonal drug that inhibits the activity of sclerostin. Since it has been on the market for only 3 years, there is a lack of systematic analysis on postmenopausal women and the efficacy is not clear. In this study, we compared randomized controlled trials to assess the effects of blosozumab versus placebo in perimenopausal and postmenopausal women., Methods: This meta-analysis has been registered in the PROSPERO registry (number CRD42020145839). The PubMed, Cochrane Library, ClinicalKey, and Embase databases were searched from inception date to July 01, 2021. We used the keywords "osteoporosis", "decreased bone mass", and "blosozumab" to retrieve studies on the relationship between blosozumab and osteoporosis in each database. The inclusion criteria were: (I) randomized controlled trials (RCTs) comparing the treatment of osteoporosis with blosozumab and a placebo or without treatment, (II) studies on postmenopausal women aged over 50 years, and (III) studies providing bone mineral density data. The quality of all randomized controlled trials included in this study was independently assessed by two researchers according to the Cochrane risk manual and was divided into high, medium and low quality. The main results analyzed were bone mineral density (BMD) and T-score. Our results mainly include BMD and procollagen type I N-terminal propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC)., Results: Three RCTs with 105 patients were selected from 157 retrieved articles. Due to high heterogeneity [BMD: Tau2=2.79; Chi2=11.70, degrees of freedom (df) =1 (P=0.0006); I2=91%], we could not perform statistical analysis of BMD. The results of BMD were then evaluated systematically. Three RCT studies were included in the evaluation. Compared with that of the placebo, blosozumab increased levels of the BMD biomarker osteocalcin [mean deviation (MD) 12.55; 95% confidence interval (CI), 8.18, 16.91; P<0.00001]. None of the 3 RCTs presented a risk of bias during the meta-analysis., Conclusions: The results suggested that blosozumab could be used as a target drug to improve BMD in postmenopausal women. This will provide a reference for the clinical treatment of postmenopausal women with osteoporosis.

Background: Similar pathogenesis makes Corona Virus Disease 2019 (COVID-19) associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and gouty arthritis (GA), and it is possible to introduce common drugs for the treatment of RA, AS and GA into the treatment of COVID-19. That is, "homotherapy for heteropathy", especially cytokine inhibitors. But little is known about the specific link between the diseases. In addition, "new use of old drugs" is an important short-term strategy for the treatment of COVID-19. Cepharanthine (CEP), a monomer component of traditional Chinese medicine (TCM), is mainly used in the treatment of leukopenia and has recently been proved to have a good therapeutic effect on COVID-19, but its specific molecular mechanism has not been clearly explained. The purpose of this work is to explore the common targets and signaling pathways among COVID-19, RA, AS, and GA by means of network pharmacology (NP), and to infer the potential mechanism of CEP in the treatment of COVID-19. Methods: Firstly, SwissTargetPrediction was used to predict the targets of CEP, and the pathogenic targets of COVID-19, RA, AS and GA were searched in GeneCards, OMIM, TTD, PharmGKB database and literature, respectively. Then, the protein interaction network of CEP and COVID-19 cross targets and the common targets of COVID-19, RA, AS and GA was constructed. Cytosscape 3.7.2 software was used to construct CEP-common targets-signaling pathways-COVID-19 network, module function analysis, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG). Finally, the molecular docking of hub targets and CEP was carried out by AutoDock software. Results: The results showed that the common targets of the four diseases were tumor necrosis factor (TNF), interleukin (IL)-6 and IL-1β, and involved Coronavirus disease, IL-17 signaling pathway and TNF signaling pathway. CEP has a good binding force with AKT Serine/Threonine Kinase 1 (AKT1), phosphatidylinositol 3-kinase (PIK3) CA, PIK3CD and Angiotensin-converting enzyme 2 (ACE2), and plays a role in the treatment of COVID-19 by regulating PI3K-Akt signaling pathway, Relaxin signaling pathway, VEGF signaling pathway and HIF-1 signaling pathway. Conclusion: Therefore, this study not only confirmed the potential mechanism of CEP in the treatment of COVID-19 at the molecular level, but also found that TNF and IL-17 inhibitors, which are commonly used in the treatment of RA, AS and GA, may also affect the treatment of COVID-19, which provides new clues and theoretical basis for the rapid discovery of effective therapeutic drugs for COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Ye, Jia, Li, Wei and Li.)

The present study aimed to investigate the expression of glucose-regulated protein 78 (GRP78) in osteosarcoma cells, and analyze the differences in expression between tumor and normal tissues, pre- and post-chemotherapy patients and metastatic and non-metastatic tumors. According to these results, the associations between the expression of GRP78 and tumor growth, metastasis and chemotherapeutics could be determined. Between 2007 and 2012, 60 patients who had been diagnosed with osteosarcoma were selected for the present study. Of these patients, 20 presented with non-metastatic tumors and 40 with metastatic tumors, and 20 had been treated without chemotherapy and 40 with chemotherapy. In addition, 60 specimens obtained from adjacent normal tissues were collected for the control groups. Immunofluorescence staining was used to examine the expression of GRP78 in the different tissues. The total RNA and protein were extracted from crushed tissues and used in the reverse transcription polymerase chain reaction and western blot analysis. GRP78 was primarily located in the intracavity of the endoplasmic reticulum. The expression level of GRP78 in the tumor tissue was higher than that in the normal tissue surrounding the tumor (P<0.01). In addition, the level was higher in the metastatic tumors compared with the non-metastatic tumors (P<0.05), and in the non-chemotherapy-treated patients compared with the chemotherapy-treated patients (P<0.01). The expression level of GRP78 mRNA in the tumor tissue was higher than that in the normal tissue (P<0.01). Furthermore, the level was higher in the metastasis group than in the non-metastasis group (P<0.05), and in the non-chemotherapy group than in the chemotherapy group (P<0.01). The expression level of GRP78 protein was higher in the tumor tissue compared with the normal tissue (P<0.01), in the metastasis group compared with the non-metastasis group (P<0.05), and in the non-chemotherapy group compared with the chemotherapy group (P<0.01). In conclusion, the present study detected the expression of GRP78 in patients with osteosarcoma and revealed a higher expression level in the tumor tissues compared with the normal tissues around the tumor, in the metastasis group compared with the non-metastasis group and in the non-chemotherapy-treated group compared with the chemotherapy-treated group.

Wear debris associated periprosthetic osteolysis represents a major pathological process associated with the aseptic loosening of joint prostheses. Naringin is a major flavonoid identified in grapefruit. Studies have shown that naringin possesses many pharmacological properties including effects on bone metabolism. The current study evaluated the influence of naringin on wear debris induced osteoclastic bone resorption both in vitro and in vivo. The osteoclast precursor cell line RAW 264.7 was cultured and stimulated with polymethylmethacrylate (PMMA) particles followed by treatment with naringin at several doses. Tartrate resistant acid phosphatase (TRAP), calcium release, and gene expression profiles of TRAP, cathepsin K, and receptor activator of nuclear factor-kappa B were sequentially evaluated. PMMA challenged murine air pouch and the load bearing tibia titanium pin-implantation mouse models were used to evaluate the effects of naringin in controlling PMMA induced bone resorption. Histological analyses and biomechanical pullout tests were performed following the animal experimentation. The in vitro data clearly demonstrated the inhibitory effects of naringin in PMMA induced osteoclastogenesis. The naringin dose of 10 μg/mL exhibited the most significant influence on the suppression of TRAP activities. Naringin treatment also markedly decreased calcium release in the stimulated cell culture medium. The short-term air pouch mouse study revealed that local injection of naringin ameliorated the PMMA induced inflammatory tissue response and subsequent bone resorption. The long-term tibia pin-implantation mouse model study suggested that daily oral gavage of naringin at 300 mg/kg dosage for 30 days significantly alleviated the periprosthetic bone resorption. A significant increase of periprosthetic bone volume and regaining of the pin stability were found in naringin treated mice. Overall, this study suggests that naringin may serve as a potential therapeutic agent to treat wear debris associated osteolysis.