Intervertebral disc degeneration (IDD) is the most common and critical pathological basis for various spinal disorders. In this study, we investigated how plasminogen activator urokinase (PLAU) promotes IDD progression through the HIPPO pathway. Bioinformatics analysis showed that PLAU is a hub gene in IDD. Both in vitro and in vivo experiments confirmed that PLAU can promote the apoptosis of nucleus pulposus chondrocytes. PLAU activates the HIPPO signaling pathway by increasing the phosphorylation levels of mammalian ste20-like kinases 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), and yes associated protein (YAP), promoting chondrocyte apoptosis, which is one of the reasons for the accelerated progression of IDD. These findings provide new insights into the role of PLAU in IDD and highlight its potential as a therapeutic target for IDD.

Objective:Adolescent idiopathic scoliosis (AIS) can lead to right heart dysfunction. Inferior vena cava (IVC) diameter is an essential parameter of the right-heart function, but the relationship between scoliosis and the IVC diameter has not been established. This study aimed to investigate the correlation between the IVC diameter and the severity of AIS. Methods:This retrospective study examined the data from patients admitted to Peking Union Medical College Hospital between January 2000 and June 2014 with a diagnosis of AIS. A preoperative spine full-length standing X-ray was collected. The IVC diameter was measured during the expiration phase as a routine examination. Results:Among the 339 included patients, 269 had thoracic curves, and 311 had at least a thoracic or thoracolumbar curve. Significant correlations between the diameter of IVC and the coronal Cobb angle of main thoracic curves (r=0.142, P = .015) and thoracolumbar curves (r=0.580, P = .015) were observed. Regarding the possible confounding factors, the IVC diameter was also significantly correlated to body weight (r=0.327, P < .001) and body height (r=0.134, P = .014). In the partial correlation analysis correcting for body weight and height, the IVC inner diameter was correlated to the Cobb angle of the thoracic curve (r=0.172, P = .003) and the larger curve of either the thoracic or thoracolumbar curve (r=0.190, P = .001). Discussion:The result of this study implies that even in patients with mild scoliosis, there might already be underlying right heart function changes. Heart function should be taken into more consideration for AIS paitents. For patients with higher IVC diameters, a more throught cardiology assessment should be performed. Conclusion:The IVC diameter is positively correlated with the Cobb angle of thoracic curves or the larger one of thoracic or thoracolumbar curves in patients with AIS.

Degeneration of the intervertebral disc has been linked to lower back pain. To date, pathophysiological mechanisms of intervertebral disc degeneration (IDD) remain unclear; it is meaningful to find effective diagnostic biomarkers and new therapeutic strategies for IDD. This study aimed to reveal the molecular mechanism of IDD pathogenesis from the multidimensional transcriptomics perspective. Here, we acquired IDD bulk omics datasets (GSE67567 and GSE167199) including mRNA, microRNA expression profiles, and single-cell RNA sequencing (GSE199866) from the public Gene Expression Omnibus (GEO) database. Through principal component analysis and Venn analysis, we found different expression patterns in the IDD transcription level and identified 156 common DEGs in both bulk datasets. GO and KEGG functional analyses showed these dysregulators were mostly enriched in the collagen-containing extracellular matrix, cartilage development, chondrocyte differentiation, and immune response pathways. We also constructed a potentially dysregulated competing endogenous RNA (ceRNA) network between mRNAs and miRNAs related to IDD based on microRNA target information and co-expression analysis of RNA profiles and identified 36 ceRNA axes including ZFP36/miR-155-5p/FOS, BTG2/hsa-miR-185-5p/SOCS3, and COL9A2/hsa-miR-664a-5p/IBA57. Finally, in integrating bulk and single-cell transcriptome data analyses, a total of three marker genes, COL2A1, PAX1, and ZFP36L2, were identified. In conclusion, the key genes and the new ceRNA crosstalk we identified in intervertebral disc degeneration may provide new targets for the treatment of IDD.

Background: Chronic spinal pain is one of the most leading causes of disability among adults worldwide and is associated with significant health care use. The effect of acupuncture on chronic spinal pain seems controversial based on evidence-based perspective. Thus, we performed a protocol for systematic review and meta-analysis to evaluate the effectiveness of acupuncture for treatment of chronic spinal pain. Methods: This systematic review has been registered in PROSPERO (CRD42019120665), which will be conducted in accordance with preferred reporting items for systematic review and meta-analysis protocols 2015 statement. We will search 7 electronic databases to identify relevant studies from inception to November, 2022, which includes PubMed, MEDLINE, Embase, Cochrane Clinical Trials Database, Web of Science, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database. Cochrane “bias risk” tool is used to assess the bias risk of the quality of the included literature. RevMan V.5.3 software will be used to analyze all data. Results: A synthesis of current evidence of acupuncture for treating chronic spinal pain will be provided in this protocol. Conclusion: This review will provide directions and recommendations for future research and clinical practices of acupuncture for treating chronic spinal pain.

OBJECTIVES:Guillain-Barré syndrome (GBS) results from autoimmune attack on the peripheral nerves, causing sensory, motor and autonomic abnormalities. Emerging evidence suggests that there might be an association between COVID-19 and GBS. Nevertheless, the underlying pathophysiological mechanism remains unclear.MATERIALS AND METHODS:We performed bioinformatic analyses to delineate the potential genetic crosstalk between COVID-19 and GBS.RESULTS:COVID-19 and GBS were associated with a similar subset of immune/inflammation regulatory genes, including TNF, CSF2, IL2RA, IL1B, IL4, IL6 and IL10. Protein-protein interaction network analysis revealed that the combined gene set showed an increased connectivity as compared to COVID-19 or GBS alone, particularly the potentiated interactions with CD86, IL23A, IL27, ISG20, PTGS2, HLA-DRB1, HLA-DQB1 and ITGAM, and these genes are related to Th17 cell differentiation. Transcriptome analysis of peripheral blood mononuclear cells from patients with COVID-19 and GBS further demonstrated the activation of interleukin-17 signalling in both conditions.CONCLUSIONS:Augmented Th17 cell differentiation and cytokine response was identified in both COVID-19 and GBS. PBMC transcriptome analysis also suggested the pivotal involvement of Th17 signalling pathway. In conclusion, our data suggested aberrant Th17 cell differentiation as a possible mechanism by which COVID-19 can increase the risk of GBS.

Recently, during the pandemic infection of the novel SARS-CoV-2, some cases of Miller Fisher syndrome (MFS) have been reported. We want to summarize the main features of patients with MFS and COVID-19. A PubMed search was performed on 8 October to identify references reporting cases with MFS associated with COVID-19 from the first report of COVID-19 to 8 October 2020 using the following keywords: "Miller Fisher syndrome" AND "COVID-19" OR "SARS-CoV-2". A systematic review from the first report of coronavirus disease 2019 (COVID-19) to 8 October 2020 revealed 7 cases with Miller Fisher syndrome (MFS) associated with COVID-19. The 7 cases came from 5 countries but most of these patients were from Europe (85.7%), especially Spain. There are 5 cases of MFS diagnosed after the laboratory confirmation of SARS-CoV-2 infection. The mean onset time of MFS-associated neurological symptoms was 14.75 days after the diagnosis of COVID-19. However, the two remaining cases presented initially with MFS-associated neurological symptoms followed by the diagnosis of COVID-19. The most common symptoms of COVID-19-associated MFS were perioral paresthesias (57.1%), ataxia (57.1%), blurred vision (42.9), ophthalmoplegia (42.9), and generalized areflexia (42.9). However, more cohort and case-control studies are required to establish the epidemiological linkage.

Abstract Background Total knee arthroplasty (TKA) is an effective and also mature surgical interventions that improves life quality and provides pain relief. Accurate bone cuts are important to prevent TKA malalignment and it requires cautious preoperative plan and precise bone resection. Recently, robotic-assisted TKA techniques have been used to improve the accuracy of bone resection and implantation. However, the system described above suits for only one prosthesis type. Methods Five types (MicroPort_CS, Smith& Nephew_GII, Johnson&Johnson_PFC_PS, kingnow _VLQX_PS and Akmedical_A3GT_PS) implants were included in our study and three Sawbones models were used for each implant. Procedures were performed by experienced joint replacement surgeons using HURWA robotic-assisted TKA system. Results our study indicated that the bone resection error of HURWA robotic-assisted system was below 0.5 mm (with SDs below 0.3 mm), and all of the bone resection angles were below 0.5° (with SDs below 0.3°). The bone resection angles and levels deviation of different brand prosthesis types were below 0.5 mm (with SDs below 0.3 mm) and below 0.5° (with SDs below 0.3°) respectively. Conclusion It suggested that our system may be suitable for different prosthesis types.

Patients with spinal muscular atrophy (SMA) are susceptible to the respiratory infections and might be at a heightened risk of poor clinical outcomes upon contracting coronavirus disease 2019 (COVID-19). In the face of the COVID-19 pandemic, the potential associations of SMA with the susceptibility to and prognostication of COVID-19 need to be clarified. We documented an SMA case who contracted COVID-19 but only developed mild-to-moderate clinical and radiological manifestations of pneumonia, which were relieved by a combined antiviral and supportive treatment. We then reviewed a cohort of patients with SMA who had been living in the Hubei province since November 2019, among which the only 1 out of 56 was diagnosed with COVID-19 (1.79%, 1/56). Bioinformatic analysis was carried out to delineate the potential genetic crosstalk between SMN1 (mutation of which leads to SMA) and COVID-19/lung injury-associated pathways. Protein-protein interaction analysis by STRING suggested that loss-of-function of SMN1 might modulate COVID-19 pathogenesis through CFTR, CXCL8, TNF and ACE. Expression quantitative trait loci analysis also revealed a link between SMN1 and ACE2, despite low-confidence protein-protein interactions as suggested by STRING. This bioinformatic analysis could give hint on why SMA might not necessarily lead to poor outcomes in patients with COVID-19.

Osteosarcoma is the most common primary bone malignancy and is a neoplasm thought to be derived from the bone-forming mesenchymal stem cells. Aberrant activation of oncogenes and inactivation of tumour suppressor genes by somatic mutations and epigenetic mechanisms play a pivotal pathogenic role in osteosarcoma. Aside from alterations in these protein-coding genes, it has now been realized that dysregulation of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and the recently discovered circular RNAs (circRNAs), is crucial to the initiation and progression of osteosarcoma. CircRNAs are single-stranded RNAs that form covalently closed loops and function as an important regulatory element of the genome through multiple machineries. Recently, an increasing number of studies suggested that circRNAs also played critical roles in osteosarcoma. This review summarizes recent development and progression in circRNA transcriptome analysis and their functions in the modulation of osteosarcoma progression.

Spinal cord injury (SCI) may lead to persistent locomotor dysfunction and somatosensory disorders, which adversely affect the quality of life of patients and cause a significant economic burden to the society. The efficacies of current therapeutic interventions are still far from satisfaction as the secondary damages resulting from the complex and progressive molecular alterations after SCI are not properly addressed. Recent studies revealed that long non‐coding RNAs (lncRNAs) are abundant in the brain and might play critical roles in several nervous system disorders. At the cellular level, lncRNAs have been shown to regulate the expression of protein‐coding RNAs and hence participate in neuronal death, demyelination and glia activation. Notably, SCI is characterized by these biological processes, suggesting that lncRNAs could be novel modulators in the pathogenesis of SCI. This review describes recent progresses in the lncRNA transcriptome analyses and their molecular functions in regulating SCI progression.

BACKGROUND: Growing rod techniques have been demonstrated to be a valuable treatment in early-onset scoliosis; however, repeated surgeries and general anesthesia cannot be avoided. METHODS: This study included 12 immature swine that were randomly assigned to receive either a novel growing rod system (experimental group) or a traditional growing rod system (control group). Lengthening was undertaken at 4-week intervals, for a total observation period of 12 weeks. Radiography, computed tomography, and motion analysis of the spine were conducted to evaluate rod extension, growth and nonfusion of the spine, and fixation. RESULTS: One swine (control group) was excluded from the analysis because of a deep wound infection at 1 week after the initial operation. No complications were observed in the remaining 11 swine. In the experimental group, the average lengthening operation lasted 12.1 +/- 3.1 minutes, and average incision length was 1.1 +/- 0.2 cm; both values were significantly less compared with the control group (P < 0.001). No significant between-group differences in mean trunk length, body mass, or thickness of cephalad-instrumented or caudad-instrumented vertebrae and intervertebral disks were present before the initial operation or at the final assessment (12 weeks after operation; P > 0.05). Spinal growth and motion of instrumented spinal segments were conserved. CONCLUSIONS: The novel growing rod system is safe and effective in immature swine, preserving spine growth potential and involving less surgical trauma.

Scoliosis, a complex three-dimensional deformity of the spine with the Cobb angle (a measure of the spinal lateral curvature) >10 degree, encompasses a spectrum of pathologies, including congenital, idiopathic, syndromic and neuromuscular aetiologies. The pathogenesis is multifactorial involving both environmental and genetic factors but the exact cellular and molecular mechanisms of disease development remain largely unknown. Emerging evidence showed that non-coding RNAs (ncRNAs), namely microRNAs, long ncRNAs and circular RNAs, are deregulated in many orthopaedic diseases, including scoliosis. Importantly, these deregulated ncRNAs functionally participate in the initiation and progression of scoliosis. Here, we review recent progress in ncRNA research on scoliosis.

Congenital spinal deformities are a result of defective somitogenesis and are associated with vitamin A deficiency (VAD). However, the molecular mechanisms of VAD-associated congenital spinal deformities remain largely unknown. Increasing number of studies suggested that microRNAs and melatonin played important roles in the development of congenital spinal deformities. In this study, we showed that the whole-embryo expression of miR-363 was upregulated in VAD rats. Furthermore, we demonstrated that miR-363 inhibited the proliferation and neuronal differentiation of primary cultured NSCs, accompanied by downregulation of Notch1. To this end, melatonin suppressed miR-363 expression and rescued the effects of miR-363 on NSC proliferation and neuronal differentiation together with restoration of Notch signaling. The present study provided new insights into the mechanism of VAD-associated spinal deformities and the therapeutic effect of melatonin that may lead to novel understanding of the molecular mechanisms of congenital spinal deformities.

Spinal cord injury (SCI) may lead to persistent locomotor dysfunction and somatosensory disorders, which adversely affect the quality of life of patients and cause a significant economic burden to the society. The efficacies of current therapeutic interventions are still far from satisfaction as the secondary damages resulting from the complex and progressive molecular alterations after SCI are not properly addressed. Recent studies revealed that long non-coding RNAs (lncRNAs) are abundant in the brain and might play critical roles in several nervous system disorders. At the cellular level, lncRNAs have been shown to regulate the expression of protein-coding RNAs and hence participate in neuronal death, demyelination and glia activation. Notably, SCI is characterized by these biological processes, suggesting that lncRNAs could be novel modulators in the pathogenesis of SCI. This review describes recent progresses in the lncRNA transcriptome analyses and their molecular functions in regulating SCI progression.

Background/Aims: Congenital scoliosis (CS) is a result of anomalous development of vertebrae and is frequently associated with somitogenesis malformation. Although noncoding RNAs (ncRNAs) have been recently determined to be involved in the pathogenesis of CS, the competing endogenous RNA (ceRNA) regulatory networks in CS remain largely unknown. Methods: Sequencing was conducted to explore the ncRNA expression profiles in rat embryos (gestation day 9) following vitamin A deficiency (VAD) (n = 9 for the vitamin A deficiency-induced congenital scoliosis (VAD-CS) group and n = 4 for the control group). Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was conducted to verify the expression levels of selected mRNAs, long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). Bioinformatics analysis was used to discover the possible relationships and functions of the ceRNAs. Results: A total of 749 mRNAs, 56 miRNAs, 685 lncRNAs, and 70 circRNAs were identified to have significantly different expression levels in the two groups. Wnt, PI3K-ATK, FoxO, EGFR, and mTOR were found to be the most significant pathways involved in VAD-CS pathogenesis. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of CS were built, and the gene expression mechanisms regulated by ncRNAs were unveiled via the ceRNA regulatory networks. Conclusion: We comprehensively identified ceRNA regulatory networks of embryonic somite development in VAD-CS as well as revealed the contribution of different ncRNA expression profiles. Our data demonstrate the association between mRNAs and ncRNAs in the pathogenic mechanism of CS.

Neuropathic pain, a type of chronic and potentially disabling pain resulting from primary injury/dysfunction of the somatosensory nervous system and spinal cord injury, is one of the most intense types of chronic pain, which incurs a significant economic and public health burden. However, our understanding of its cellular and molecular pathogenesis is still far from complete. Long non-coding RNAs (lncRNAs) are important regulators of gene expression and have recently been characterized as key modulators of neuronal functions. Emerging evidence suggested that lncRNAs are deregulated and play pivotal roles in the development of neuropathic pain. This review summarizes the current knowledge about the roles of deregulated lncRNAs (eg, KCNA2-AS, uc.48+, NONRATT021972, MRAK009713, XIST, CCAT1) in the development of neuropathic pain. These studies suggested that specific regulation of lncRNAs or their downstream targets might provide novel therapeutic avenues for this refractory disease.

Intervertebral disc degeneration (IDD) is the major cause of low back pain which incurs a significant public-health and economic burden. The aetiology of IDD is complex, with developmental, genetic, biomechanical and biochemical factors contributing to the disease development. Deregulated phenotypes of nucleus pulposus cells, including aberrant differentiation, apoptosis, proliferation and extracellular matrix deposition, are involved in the initiation and progression of IDD. Non-coding RNAs, including long non-coding RNAs (lncRNAs), have recently been identified as important regulators of gene expression. Research into their roles in IDD has been very active over the past 5 years. Our review summarizes current research regarding the roles of deregulated lncRNAs (eg, RP11-296A18.3, TUG1, HCG18) in modulating nucleus pulposus cell functions in IDD. These exciting findings suggest that specific modulation of lncRNAs or their downstream signalling pathways might be an attractive approach for developing novel therapeutics for IDD.

OBJECTIVE: Scoliosis, especially thoracic curves, causes poor pulmonary function. As a result, scoliosis may impair sleep breathing. The literature regarding the relationship between scoliosis and sleep breathing is sparse. METHODS: Fifty-seven patients with adolescent idiopathic scoliosis or congenital scoliosis and 25 healthy control subjects were included. The wrist sleep monitors was used. Sleep breathing was evaluated with the following parameters: 1) Respiratory Disorders Index (pRDI), indicating mean respiratory events per hour of sleep including apnea, hypoxia, and respiratory effort-related arousal; 2) Apnea and Hypopnea Index (pAHI), expressing the number of apnea and hypopnea events per hour of sleep; and 3) mean and minimal oxygen saturation (SaO(2)) during sleep. RESULTS: No differences in age, sex distribution, and body mass index were found between the two groups. Patients with scoliosis had statistically significant higher pRDI (median, 10.10 vs. 8.65; P=0.039) and pAHI (median, 1.60 vs. 0.72; P=0.029) scores than the control group. The minimal SaO(2) value in patients with scoliosis was lower (median, 93% vs. 94%, respectively; P=0.005), whereas no difference was found in the mean SaO(2) value during sleep. In patients with scoliosis, pAHI scores were higher when lying on the convex side of the thoracic curve compared with the concave side (2.34 vs. 2.28, respectively; P = 0.044), whereas no such difference was observed in the control group. CONCLUSIONS: Patients with scoliosis have more respiratory events of apnea and hypopnea during sleep than the control group. The minimal SaO(2) value in patients with scoliosis is lower than the normal population. Sleeping on the convex side of the thoracic curve results in higher pAHI scores than on the concave side.