Identification and bioinformatics analysis of lncRNAs in serum of patients with ankylosing spondylitis.

OBJECTIVES: The aim of this study was to explore the long non-coding RNA (lncRNA) expression profiles in serum of patients with ankylosing spondylitis (AS). The role of these lncRNAs in this complex autoimmune situation needs to be evaluated. METHODS: We used high-throughput whole-transcriptome sequencing to generate sequencing data from three patients with AS and three normal controls (NC). Then, we performed bioinformatics analyses to identify the functional and biological processes associated with differentially expressed lncRNAs (DElncRNAs). We confirmed the validity of our RNA-seq data by assessing the expression of eight lncRNAs via quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 20 AS and 20 NC samples. We measured the correlation between the expression levels of lncRNAs and patient clinical index values using the Spearman correlation test. RESULTS: We identified 72 significantly upregulated and 73 significantly downregulated lncRNAs in AS patients compared to NC. qRT-PCR was performed to validate the expression of selected DElncRNAs; the results demonstrated that the expression levels of MALAT1:24, NBR2:9, lnc-DLK1-35:13, lnc-LARP1-1:1, lnc-AIPL1-1:7, and lnc-SLC12A7-1:16 were consistent with the sequencing analysis results. Enrichment analysis showed that DElncRNAs mainly participated in the immune and inflammatory responses pathways, such as regulation of protein ubiquitination, major histocompatibility complex class I-mediated antigen processing and presentation, MAPkinase activation, and interleukin-17 signaling pathways. In addition, a competing endogenous RNA network was constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs (MALAT1:24 and NBR2:9). We further found the expression of MALAT1:24 and NBR2:9 to be positively correlated with disease severity. CONCLUSION: Taken together, our study presents a comprehensive overview of lncRNAs in the serum of AS patients, thereby contributing novel perspectives on the underlying pathogenic mechanisms of this condition. In addition, our study predicted MALAT1 has the potential to be deeply involved in the pathogenesis of AS.

Chondroitin Polymerizing Factor (CHPF) promotes cell proliferation and tumor growth in human osteosarcoma by inhibiting SKP2's ubiquitination while activating the AKT pathway.

Osteosarcoma is a common malignant tumor occurring in children and young adults. Chondroitin sulfate (CS) participates in cell adhesion, cell division, and the formation of neural networks in the body, the biosynthesis of which requires the participation of glycosyltransferases. CHPF, a glycosyltransferase, plays a role in the extension of CS. Recently, CHPF's biological roles and functional importance in human diseases including malignant tumors have been widely discussed. However, whether CHPF is involved in osteosarcoma development and growth has not been revealed. The present work aimed to investigate the expression levels, functional significance and molecular mechanism of CHPF in osteosarcoma progression. Our results revealed that CHPF is strongly expressed in osteosarcoma tissues and cells. Furthermore, CHPF serves as a tumor promoter in the development and progression of osteosarcoma through enhancing cell proliferation and migration while suppressing apoptosis. Exploration of the mechanism by which CHPF promotes osteosarcoma indicated that CHPF promotes osteosarcoma through counteracting SKP2's ubiquitination and activating the Akt signaling pathway. For the first time, we clarified the roles of CHPF in osteosarcoma, and our results suggested that CHPF might be a novel therapeutic target in the treatment strategies for osteosarcoma.

RNA sequencing and bioinformatics analysis of differentially expressed genes in the peripheral serum of ankylosing spondylitis patients.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive autoimmune disease characterized by spinal and sacroiliac arthritis, but its pathogenesis and genetic basis are largely unclear. METHODS: We randomly selected three serum samples each from an AS and a normal control (NC) group for high-throughput sequencing followed by using edgeR to find differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes, Reactome pathway analyses, and Gene Set Enrichment Analysis were used to comprehensively analyze the possible functions and pathways involved with these DEGs. Protein-protein interaction (PPI) networks were constructed using the STRING database and Cytoscape. The modules and hub genes of these DEGs were identified using MCODE and CytoHubba plugins. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the expression levels of candidate genes in serum samples from AS patients and healthy controls. RESULTS: We successfully identified 100 significant DEGs in serum. When we compared them with the NC group, 49 of these genes were upregulated in AS patients and 51 were downregulated. GO function and pathway enrichment analysis indicated that these DEGs were mainly enriched in several signaling pathways associated with endoplasmic reticulum stress, including protein processing in the endoplasmic reticulum, unfolded protein response, and ubiquitin-mediated proteolysis. We also constructed a PPI network and identified the highly connected top 10 hub genes. The expression levels of the candidate hub genes PPARG, MDM2, DNA2, STUB1, UBTF, and SLC25A37 were then validated by RT-qPCR analysis. Finally, receiver operating characteristic curve analysis suggested that PPARG and MDM2 may be the potential biomarkers of AS. CONCLUSIONS: These findings may help to further elucidate the pathogenesis of AS and provide valuable potential gene biomarkers or targets for the diagnosis and treatment of AS.

Three-dimension chitosan hydrogel loading melanin composite nanoparticles for wound healing by anti-bacteria, immune activation and macrophage autophagy promotion.

Application of Combined photodynamic therapy (PDT) and photothermal therapy (PTT) has become one of the most promising strategy to replace antibiotics and avoid the epidemic of drug-resistant strains during wound healing. However, high amount of reactive oxygen species (ROS) and high temperature cause severe stress response to normal tissues, leading to potential risks of wound healing. Herein, a three-dimension chitosan hydrogel melanin-glycine-C60 nanoparticles (MGC NPs) were prepared to realized effective anti-bacterial activity, immune activation and macrophage autophagy promotion in three-dimensional wound space without triggering stress response. MGC NP is a composite polymer material composed of natural melanin polymer, oligopeptide and carbon-based material, which showed excellent biological safety. By regulating the peptide length between melanin and C60 and nanoparticle content, a high ROS/heat environment at the upper wound site and a low ROS/heat environment at the lower region adjacent to the wound tissue were established to obtain a three-dimension hydrogel with precise PDT and PTT efficiency in different regions. Highly effective PDT/PTT was used to kill microorganisms in upper region, thus providing a barrier to reduce microbial infection. Mild PDT/PTT in lower region promoted the polarization of M1 macrophage to M2 macrophage and activated autophagy of M2 macrophages, regulating the immune microenvironment and promoting wound repair. In conclusion, the novel three-dimensional PDT/PTT therapy based on natural macromolecules proposed in this study accelerates wound healing through dual pathways on the premise of avoiding wound stress response, which is of great significance for the development of clinical strategies for phototherapy.

Transdural circumferential decompression for thoracic spinal stenosis caused by beak-type ossification of the posterior longitudinal ligament: a technical note.

PURPOSE: Thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine is usually progressive and responds poorly to conservative therapy, making surgery the only effective treatment option. A variety of surgical procedures have been developed to treat thoracic OPLL. However, the optimal surgical approach for removal of thoracic OPLL remains unclear. In the present study, we described a newly modified posterior approach for the removal of OPLL: circular decompression via dural approach, and complete removal of OPLL can be achieved under direct vision and without neurological deficit. MATERIALS AND METHODS: Three patients with beak-type thoracic OPLL presented with progressive thoracic myelopathy and leg weakness. Magnetic resonance imaging showed the spinal cord severely compressed. The surgical management of the three patients involved the 'cave-in' circular decompression and transdural resection of OPLL. RESULTS: Transdural circumferential decompression was successfully performed in all three patients. Clinical outcome measures, including pre- and postoperative radiographic parameters, were assessed. All of the patients were followed up for an average of 12 months (ranging from 10 to 15 months), and no surgery-related complications occurred. Weakness relief and neural function recovery were satisfactorily achieved in all patients by the final follow-up. CONCLUSIONS: Transdural circumferential decompression was an effective method for thoracic spinal stenosis caused by concurrent beak-type OPLL, by which OPLL could be safely removed. It is especially useful when there is a severe adhesion between the dura OPLL.

Rare EGFR E709-T710delinsX: Molecular characteristics and superior response to afatinib treatment in NSCLC patients.

OBJECTIVES: Currently, whether patients with rare epidermal growth factor receptor (EGFR) mutations could benefit from EGFR tyrosine kinase inhibitors (TKIs) demands further studies. Limited clinical data are available regarding the molecular characteristics and clinical response in non-small-cell lung cancer (NSCLC) patients harboring EGFR E709-T710delinsX mutations, a rare mutation type in exon 18 of EGFR. In this study, we aimed to explore the molecular distribution and clinical outcome of EGFR E709-T710delinsX mutated Chinese patients. METHODS: Next-generation sequencing (NGS) tests were performed in 15,078 NSCLC patients. A multicenter retrospective cohort involving 17 advanced lung cancer patients with EGFR E709-T710delinsX was collected to evaluate clinical responses to diverse therapies. In silico protein structure modeling was conducted to predict drug response. RESULTS: 5905 EGFR mutant patients (39.2%, 5905/15078) were identified, with 26 cases (0.44%, 26/5905) harbored EGFR E709-T710delinsD. Afatinib showed a better overall objective response rate (ORR) compared with the first-generation (1G) EGFR TKIs and chemotherapy with significant difference. Superior progression free survival (PFS) was also observed in patients treated with afatinib (afatinib 10.85 m vs 1G EGFR TKIs 4.0 m vs chemotherapy 2.8 m, p = 0.0007). In silico protein structure modeling predicts better binding of afatinib with EGFR E709-T710delinsD compared with other EGFR TKIs. CONCLUSIONS: This is the largest studies for EGFR E709-T710delinsX, with 26 cases with EGFR E709-T710delinsX being identified (0.44% in EGFR mutant NSCLC, 0.17% in NSCLC patients). This study also firstly revealed that afatinib might exert superior antitumor activity to the 1G EGFR TKIs and chemotherapy in EGFR E709-T710delinsX mutant patients.

Application of open-door laminoplasty with ARCH plate fixation in cervical intraspinal tumors.

BACKGROUND: The open-door laminoplasty is an effective procedure for the treatment of cervical spondylotic myelopathy. However, little information is available about the surgical results of open-door laminoplasty in the treatment of intraspinal tumors. In the present study, we aimed to investigate the clinical effect of open-door laminoplasty with ARCH plate fixation in the treatment of cervical intraspinal tumors. METHODS: This was a retrospective study. From January 2013 to May 2018, 38 patients (13 males and 25 females, the average age of 44 ± 17 years) with cervical intraspinal tumors underwent open-door laminoplasty with ARCH plate fixation in our hospital. The operation time, blood loss, pre- and postoperative visual analog scale (VAS), and Japanese Orthopedic Association (JOA) scores were determined. To determine the radiographic outcomes, cervical X-ray film and magnetic resonance imaging (MRI) were performed before and after the operation, and cervical X-ray sagittal film was used to measure Cobb angle. The clinical data before and after the operation were compared by t-test. RESULTS: A total of 38 patients underwent a successful operation and demonstrated primary healing. The average operation time was 113 ± 12 min. The average blood loss was 120 ± 19 mL. All patients were followed up for 26.1 ± 2.8 months, and the final follow-up time was more than 24 months. VAS scores were much better at 24 months after operation compared with those before the operation, which were decreased from 6.1 ± 1.1 to 1.4 ± 0.7 (t = 32.63, P < 0.01). The JOA score was improved from 9.9 ± 1.5 to 15.5 ± 0.6 (t = - 18.36, P < 0.01), and the mean JOA recovery rate was 79% ± 11% at 24 months after the operation. There was no significant difference in Cobb angle between pre-operation and 24 months after the operation, which was 9.8 ± 2.6 and 10.3 ± 3.1 respectively (t = - 0.61, P > 0.05). Neither spinal malalignment on the coronal plane nor displacement of the laminoplasty flap was observed on postoperative cervical X-ray and MRI examinations at the final follow-up. CONCLUSIONS: Open-door laminoplasty with ARCH plate fixation was a safe and effective surgical approach for the treatment of cervical intraspinal tumors.

Culture-negative versus culture-positive in pyogenic spondylitis and analysis of risk factors for relapse.

OBJECTIVES: This study aims to compare and analyze the clinical features, diagnosis, treatment and prognosis of culture-negative and culture-positive primary pyogenic spondylitis. METHODS: In a retrospective analysis, 202 cases of adult primary pyogenic spondylitis with complete clinical data in our hospital from January 2013 to January 2020 were divided into two groups according to bacterial culture results: culture negative (n = 126) and culture positive (n = 76). We compare the clinical characteristics, diagnosis, treatment and prognosis of patients with different culture results. RESULTS: The culture positive rate was 37.62% (76/202). There were no significant differences in age, gender, affected segment, spinal abscess, diabetes mellitus, course of disease, surgery, recurrence, and follow-up time between the two groups (p>.05). There were statistically significant differences in hospital admission erythrocyte sedimentation rate (ESR), admission C-reactive protein (CRP), admission white blood cell (WBC) count, discharge ESR, discharge CRP, ESR decline rate, CRP (p<.05). There were statistically significant differences in the rate of decline, hospitalization days, and body temperature ≥38 °C (p<.05). Higher CRP levels on admission, antibiotic treatment time <6 weeks, and body temperature ≥ 38 °C are independent risk factors for infection recurrence. CONCLUSIONS: The culture-negative group's admission WBC, admission ESR, admission CRP, discharge ESR, discharge CRP, ESR decline rate, CRP decline rate, and hospital stay were lower than the culture positive group, the difference was statistically significant (p<.05). The independent risk factors for infection recurrence are higher CRP levels in hospital admission, antibiotic treatment time <6 weeks, and body temperature ≥ 38 °C.

Studies on 11 Cases of Spinal Epidural Abscess and Literature Review.

OBJECTIVE: In the present study, we aimed to describe the clinical features, diagnosis, treatment, and prognosis of spinal epidural abscess (SEA). METHODS: The complete clinical data of 11 SEA patients who were treated in our hospital system from January 2015 to June 2018 were retrospectively analyzed. Moreover, the clinical features, diagnosis, treatment, and prognosis of 642 SEA cases collected from the foreign literature from 2010 to 2019 were also investigated. RESULTS: Among our 11 SEA patients, nine cases had purulent inflammation, two cases had tuberculosis, two cases had infection caused by Staphylococcus aureus, one case had infection caused by Streptococcus constellatus, one case had infection caused by Klebsiella pneumoniae, five cases showed negative bacterial culture, and two cases had Mycobacterium tuberculosis. All 11 cases showed focal spinal pain, eight cases exhibited neurological deficits, and six cases experienced fever. Nine of the 11 cases involved the lumbosacral spine, one case involved the thoracic spine, and one case involved the cervical spine. Eight patients had a longer course of disease (>2 weeks), all 11 patients had vertebral osteomyelitis, and nine patients had intervertebral discitis. One patient had motor dysfunction of arms and legs, one patient had lower limb motor dysfunction, one patient had limb numbness, one patient experienced relapse after the conservative treatment, and one patient experienced relapse after the surgical treatment. The follow-up time was 15-24 months. CONCLUSION: The classic diagnosis of triads (focal spine pain, neurological deficit, and fever) was less specific for SEA. MRI examination, blood culture, tissue culture, and biopsy could be used for the diagnosis for SEA. Suppuritis was a common cause of SEA. Early detection, early diagnosis and early treatment, as well as the selection of the most suitable treatment regimen based on comprehensive evaluation, played crucial roles in a better prognosis of SEA. There was no statistically significant difference in terms of the general condition, diagnosis, treatment and prognosis between the patients with negative and positive culture results (P>0.05). For SEA patient with negative culture, antibiotic treatment should be used empirically.

Application of Laminoplasty Combined with ARCH Plate in the Treatment of Lumbar Intraspinal Tumors.

OBJECTIVE: To investigate the bone fusion and clinical effect of laminoplasty combined with ARCH plate fixation in the treatment of lumbar intraspinal tumors. METHODS: This was a clinical study. From June 2017 to January 2019, 24 patients (seven males and 17 females, average age 40 ± 16 years) with lumbar intraspinal tumors underwent laminoplasty combined with ARCH plate fixation in our hospital. The bone fusion was evaluated by X-ray and computed tomography (CT) scans that were taken 15.2 ± 2.17 months postoperatively. Each segment showed a bone bridge on one side, which was classified as "segmental partial fusion." Each segment showed bilateral bone bridges, which were classified as "segmental complete fusion". When all segments of the patient showed bilateral bone bridging so that the replanted lamina and the host lamina became a unit on the CT scan, it was defined as "complete fusion". In addition, the operation time and blood loss were recorded. Fisher's exact test was used to analyze the potential influencing factors of bone healing, including age (≤40 years vs >40 years), gender, number of operated levels (single vs two). Paired t-test was used to analyze pre- and postoperative Oswestry Disability Index (ODI) scale and low back and leg pain visual analog scale (VAS). RESULTS: A total of 33 segments of laminoplasty were successfully performed in 24 patients. The average operation time was 128 ± 18 minutes. The average blood loss was 110 ± 19 mL. All patients were followed up at least 12 months after operation (average, 15.2 ± 2.17 months). At the final follow-up, according to the definition of this study, the proportion of "segmental partial fusion" and "segmental complete fusion" were 30.3% (10/33) and 69.7% (23/33), respectively. And the proportion of patients with "complete fusion" was 70.8% (17/24). Age, gender, and number of operated levels were not associated with the fusion (P = 1.0, 0.37, and 0.06, respectively). ODI and VAS were much better at 1 month after operation and the final follow-up than those before the operation (P < 0.01). At 6 months after operation, the results of magnetic resonance imaging (MRI) showed that the supraspinous ligament was repaired, and there were no complications, such as spinal epidural scar recompression. CONCLUSIONS: Laminoplasty combined with ARCH plate was a better surgical method, and 70.8% of the patients showed complete bone fusion and there was no case of bilateral nonunion.

Aspergillus spondylitis: case series and literature review.

BACKGROUND: Spinal fungal infections, especially spinal Aspergillus infections, are rare in the clinic. Here, we introduce the clinical features, diagnosis, treatment, and prognoses of 6 cases of Aspergillus spondylitis. METHODS: We retrospectively analysed the complete clinical data of patients with Aspergillus spondylitis treated in our hospital from January 2013 to January 2020. RESULTS: Aspergillus fumigatus was isolated in 4 cases, and Aspergillus spp. and Aspergillus niger were isolated in 1 case each. All six patients reported varying degrees of focal spinal pain; one patient reported radiating pain, one patient experienced bowel dysfunction and numbness in both lower limbs, and three patients had fever symptoms. One case involved the thoracic spine, one case involved the thoracolumbar junction, and 4 cases involved the lumbar spine. Three patients were already in an immunosuppressed state, and three patients entered an immunosuppressed state after spinal surgery. All six patients were successfully cured, and five required surgery. Of the 5 patients who underwent surgical treatment, 2 had spinal cord compression symptoms, and 3 had spinal instability. At the end of follow-up, 1 patient reported left back pain and 1 patient reported left limb numbness. CONCLUSION: The clinical manifestations of Aspergillus spondylitis are non-specific, and the diagnosis depends on typical imaging findings and microbiological and histopathological examination results. When there is no spinal instability, spinal nerve compression symptoms, or progressive deterioration, antifungal therapy alone may be considered. If spinal instability, spinal nerve compression, or epidural abscess formation is present, surgery combined with antifungal therapy is recommended.

Profiling and Bioinformatics Analysis of Differentially Expressed circRNAs in Spinal Ligament Tissues of Patients with Ankylosing Spondylitis.

Recent studies have reported that circular RNAs (circRNAs) play a crucial regulatory role in a variety of human diseases. However, the roles of circRNAs in ankylosing spondylitis (AS) remain unclear. In this study, we conducted circRNA expression profiling of the spinal ligament tissues of patients with AS by RNA sequencing (RNA-seq) and analyzed the potential functions of differentially expressed circRNA by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to investigate the potential mechanisms associated with AS. The results showed that a total of 1,172 circRNAs were detected in the spinal ligament tissue samples, of which 123 circRNAs were significantly differentially expressed by a fold change ≥ 1.5 and p value < 0.05. Among these, 57 circRNAs were upregulated, and 66 were downregulated. GO and KEGG analyses demonstrated that the differentially expressed circRNAs were mainly involved in the regulation of biological processes of peptidyl-serine phosphorylation and human immune system that may be related to AS. In addition, the circRNA/miRNA interaction networks were established to predict the potential roles of differentially expressed circRNAs by bioinformatics analysis. Taken together, these results revealed the expression profiles of circRNAs and the potential functions of the differentially expressed circRNAs in the spinal ligament tissue of patients with AS, which may provide new clues for understanding the mechanisms associated with AS, and proceed to identify novel potential molecular targets for the diagnoses and treatment of AS.

A posterior-only approach for ankylosing spondylitis (AS) with thoracolumbar pseudoarthrosis: a clinical retrospective study.

BACKGROUND: Surgical treatment has been recommended by most surgeons to treat pseudarthrosis in ankylosing spondylitis (AS). However, there is still some debate on the necessity of anterior fusion. There is very limited literature on the treatment and surgical outcomes of thoracolumbar pseudarthrosis in AS patients treated through a posterior-only approach. METHODS: From January 1, 2012 to December 31, 2017, a total of 42 cases diagnosed with thoracolumbar pseudarthrosis in AS patients with moderate kyphosis were included in this study. All of the patients received posterior-only kyphosis correction, internal fixation and fusion without anterior fusion, and underwent at least 2 years of follow-up. Clinical and radiographic results and complications were assessed. RESULTS: All of the patients were followed up for an average of 35.3 months (range, 24-48 months), and they achieved successful bone graft fusion at the pseudarthrosis sites. Satisfactory radiographic changes were achieved in these patients. The Cobb angles of global kyphosis (GK) were corrected from 53.2 ± 5.4 degrees preoperatively to 33.2 ± 4.3 degrees postoperatively, and to 36.1 ± 5.3 degrees at the latest follow-up. The Cobb angles of local kyphosis (LK) were corrected from 43.3 ± 4.6 degrees preoperatively to 26.8 ± 3.3 degrees postoperatively, and to 28.2 ± 3.6 degrees at the latest follow-up. The mean sagittal vertical axis (SVA) were corrected from 7.6 ± 4.2 cm preoperatively to 4.3 ± 2.1 cm postoperatively, and to 4.8 ± 2.3 cm at the latest follow-up. No serious neurological complication or deep wound infection was found in these 42 patients. CONCLUSION: Posterior-only kyphosis correction and fixation without anterior fusion can achieve excellent bone fusion and satisfactory improvement in AS patients with thoracolumbar pseudarthrosis. This method may be a good choice for treating thoracolumbar pseudarthrosis in AS patients with moderate kyphosis.

Repair mechanism of astrocytes and non-astrocytes in spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a destructive disease that incurs huge personal and social costs, and there is no effective treatment. Although the pathogenesis and treatment mechanism of SCI has always been a strong scientific focus, the pathogenesis of SCI is still under investigation. AIM: To determine the key genes based on the modularization of in-depth analysis, in order to identify the repair mechanism of astrocytes and non-astrocytes in SCI. METHODS: Firstly, the differences between injured and non-injured spinal cord of astrocyte (HA), injured and non-injured spinal cord of non-astrocyte (FLOW), injured spinal cord of non-injured astrocyte (HA) and non-injured spinal cord of non-astrocyte (FLOW), and non-injured spinal cord of astrocyte (HA) and non-astrocyte (FLOW) were analyzed. The total number of differentially expressed genes was obtained by merging the four groups of differential results. Secondly, the genes were co-expressed and clustered. Then, the enrichment of GO function and KEGG pathway of module genes was analyzed. Finally, non-coding RNA, transcription factors and drugs that regulate module genes were predicted using hypergeometric tests. RESULTS: In summary, we obtained 19 expression modules involving 5216 differentially expressed genes. Among them, miR-494, XIST and other genes were differentially expressed in SCI patients, and played an active regulatory role in dysfunction module, and these genes were recognized as the driving genes of SCI. Enrichment results showed that module genes were significantly involved in the biological processes of inflammation, oxidation and apoptosis. Signal pathways such as NF-kappa B/A20, AMPK and MAPK were significantly regulated. In addition, non-coding RNA pivot (including miR-136-5p and let-7d-5p, etc.) and transcription factor pivot (including NFKB1, MYC, etc.) were identified as significant regulatory dysfunction modules. CONCLUSION: Overall, this study uncovered a co-expression network of key genes involved in astrocyte and non-astrocyte regulation in SCI. These findings helped to reveal the core dysfunction modules, potential regulatory factors and driving genes of the disease, and to improve our understanding of its pathogenesis.

Notoginsenoside R1 alleviates lipopolysaccharide-triggered PC-12 inflammatory damage via elevating microRNA-132.

BACKGROUND: Delayed inflammatory response is closely associated with the severity of Spinal cord injury (SCI). Herein, the function and molecular mechanism of notoginsenoside R1 (NGR1) in the in vitro model of SCI inflammation injury were explored. METHODS: PC-12 neuronal cells were subjected with LPS to construct a cell-based model of SCI inflammatory injury. NGR1 was applied in this cell model. miR-132 was silenced by transfection with miR-132 inhibitor. Cell viability and apoptosis were assessed, respectively. Then, the expression changes of pro-inflammatory cytokines and JNK pathway were examined. RESULTS: In this model, LPS was neurotoxic, with inhibiting PC-12 cell viability, inducing apoptosis, and enhancing concentrations of IL-6, IL-8 and TNF-α. However, NGR1 weakened the influence of LPS on PC-12 cells via elevating cell viability, decreasing apoptosis, decreasing pro-inflammatory cytokines expression, and suppressing activation of JNK signalling pathway. miR-132 was up-regulated by NGR1 treatment. Silence of miR-132 eliminated the influence of NGR1 on LPS-stimulated PC-12 cells. CONCLUSION: NGR1 relieved PC-12 cells from LPS-triggered inflammatory damage via elevating miR-132 and hereafter suppressing JNK pathway.

Upregulated miR-154 promotes ECM degradation in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD), a common global health issue, is a major cause for low back pain (LBP). Given the complex etiology of IDD, micro RNA (miRNA) recently has been demonstrated to play essential roles in the progression of IDD. Therefore, this study aims to investigate functions of the miR-154, which is well-documented in a series of cell activities, IDD, and other relevant mechanisms. Lumbar nucleus pulposus (NP) samples were collected from patients with IDD and the control group. After solexa sequencing and bioinformatical analysis, the results showed that miR-154 was increased in NP cells of patients with IDD. Inhibition of miR-154 increased type II collagen and aggrecan and decreased mRNA expressions of collagenase-3 (MMP13) and aggrecanase-1 (ADAMTS4), whereas overexpression of miR-154 reversed such effects in NP cells. In addition, the luciferase reporter assay revealed that fibroblast growth factor 14 (FGF14) is a direct target of miR-154 and that the overexpression of FGF14 leads to similar effects as inhibition of miR-154 did. In conclusion, the results suggested that miR-154 participates in the development of IDD and its effects are mediated via targeting FGF14. Thus, miR-154 may be thought as a potential etiological factor for IDD and may provide insights into a therapeutic target to treat IDD.

Surgical strategies for thoracic myelopathy due to ossification of ligamentum flavum: A technical note based on radiological type.

AIM: Ossification of the ligamentumflavum (OLF) is a primary cause of thoracic myelopathy. A relatively safe surgical technique based on radiological type is described for the OLF-induced thoracic myelopathy. MATERIAL AND METHODS: Forty patients with thoracic myelopathy caused by OLF were studied retrospectively. The OLF was divided into fused and non-fused types according to the CT and MRI findings. All patients underwent posterior decompression. For the fused type, open-door laminectomy and for the non-fused type, French-door laminectomy surgical techniques were adopted. Pre-operation, post-operative, and follow-up neurological status were evaluated using the modified Japanese Orthopaedic Association (mJOA) score. RESULTS: The mean duration of symptoms was 9.2±11.5 and 8.4±9.7months in the non-fused and fused groups, respectively. The apex of OLF at the most severely compressed level was located at 2.7±1.9mm above the disc level: 2.4±1.6 and 3.0±2.2mm in the non-fused and fused groups, respectively. The preoperative mJOA scores were 5.0±1.1 and 4.2±0.9 in the non-fused and fused groups, respectively. After the operation, the neurological deficits in all patients improved. With an average follow-up of 33.9 months, the mJOA score ultimately improved in both groups. CONCLUSION: In OLF-induced thoracic myelopathy, the en bloc elevation of the laminae with the OLF plaque is emphasized at the key site for surgical decompression. Based on the present classification of OLF, different surgical strategies should be adopted for a safe neurological decompression.

Angiopoietin-1 alleviates LPS-induced inflammatory injury by up-regulation of miR-126 in pancreas cell line HPDE6-C7.

BACKGROUND: Acute pancreatitis is an inflammatory disorder of the pancreas, leading to multiple organ dysfunction syndrome in severe cases. Angiopoietin-1 (Ang-1), a Tie-2 receptor agonist, and microRNA-126 (miR-126) have been reported to be involved in angiogenesis and anti-inflammatory functions. In the present study, we explored the effects of Ang-1 and miR-126 on lipopolysaccharide (LPS)-induced inflammatory injury in pancreatic cells, HPDE6-C7. METHODS: The immortalized human pancreatic duct epithelial cell line, HPDE6-C7, was treated with LPS (10 µg/mL) to induce cell injury. Ang-1 was used at 300 ng/mL concentration. Cell viability was measured using CCK-8 assay and apoptosis was assessed using flow cytometry. Quantitative real time polymerase chain reaction (RT-PCR) was used to measure the mRNA expressions of different proteins. Enzyme linked immunosorbent assay (ELISA) was used to measure the concentrations of the pro-inflammatory cytokines. Luciferase activity assay was done to identify the target of miR-126. Western blot was used to measure the expressions of different proteins. RESULTS: Ang-1 promoted LPS-suppressed cell viability and inhibited LPS-induced cell apoptosis, pro-inflammatory cytokine (TNF-α, IL-1ß, IL-6, and IL-8) production, and activation of NF-κB and JNK pathways in HPDE6-C7 cells. Furthermore, Ang-1 promoted the expression of miR-126, which in turn protected PDE6-C7 cells against LPS-induced injury. PDCD4 was identified as a direct target of miR-126 and was negatively regulated by miR-126. Mechanistic study revealed that overexpression of PDCD4 reversed miR-126-mediated inhibition of LPS-induced activation of NF-κB and JNK pathways. CONCLUSION: Ang-1 alleviates LPS-induced inflammatory injury by up-regulation of miR-126 and down-regulation of PDCD4 in pancreatic cell line HPDE6-C7.

[Anatomic study of paths for transiliac screws in Galveston fixation].

OBJECTIVE: To describe the satisfactory intra-iliac paths in Galveston fixation combined with adult human cadaver and radiology study. METHODS: Five adult cadavers with 10 hemisected pelvises were harvested. Parallelly to the Chiotic line, the bone every other 5 mm till the superior rim of the acetabulum (SRA) observing the morphologic characteristics of each cross-sections of the iliac columns was cut. Fifty consecutive and randomly selected patients were measured using three-dimensional computed tomographic reformations. Three paths' valid bony canal lengths (LVBC), contractions' inner widths and positions were evaluated. RESULTS: The Path A with the longest LVBC (137 +/- 8) mm in male, (130 +/- 11) mm in female was the most satisfactory intra-iliac path according to both adult cadaver and radiographic measurement Path A and B allowed placement of 100 mm and 8 mm implants in male, 80 mm and 6 to 7 mm implants in female patients. CONCLUSION: The Path A, passing from the Click point towards the bottom of the anterior inferior iliac spine provides a longer and potentially safer anchor site compared with the traditional path.