Nanog interact with CDK6 to regulates astrocyte cells proliferation following spinal cord injury.

Previous research had reported transcription factors Nanog expressed in pluripotent embryonic stem cells (ESCS) that played an important role in regulating the cell proliferation. Nanog levels are frequently elevated in ESCS, but the role in the spinal cord was not clear. To examine the biological relevance of Nanog, we studied its properties in spinal cord injury model. The expression of Nanog and PCNA was gradually increased and reached a peak at 3 day by western blot analysis. The expression of Nanog was further analyzed by immunohistochemistry. Double immunofluorescent staining uncovered that Nanog can co-labeled with PCNA and GFAP in the spinal cord tissue. In vitro, Nanog can promote the proliferation of astrocyte cell by Fluorescence Activating Cell Sorter (FACS) and CCK8. Meanwhile, the cell-cycle protein CDK6 could interact with Nanog in the spinal cord tissue. Taken together, these data suggested that both Nanog may play important roles in spinal cord pathophysiology via interact with CDK6.

Spatiotemporal Expression of EAPP Modulates Neuronal Apoptosis and Reactive Astrogliosis After Spinal Cord Injury.

E2F-associated phosphoprotein (EAPP) is a novel E2F binding protein that interacts with the activating members of the E2F transcription factors family and involved in various biological processes. However, the expression and function of EAPP in central nervous system (CNS) are still unknown. In this study, we performed an acute spinal cord injury (SCI) model in adult rats, we found that EAPP protein levels were significantly increased and reached a peak at day 3, and then gradually returned to normal level at day 14 after spinal cord injury and we observed that the expression of EAPP is enhanced in the gray and white matter. Spatially, increased levels of EAPP were striking in neurons and astrocytes. Moreover, colocalization of EAPP/active caspase-3 was detected in neurons, and colocalization of EAPP/proliferating cell nuclear antigen (PCNA) was detected in astrocytes after spinal cord injury. These results indicated that EAPP might play an important role in neuronal apoptosis and reactive astrogliosis. Furthermore in vitro, EAPP depletion by siRNA inhibited astrocyte proliferation, migration and CDK4/cyclinD1 expression. Meanwhile, EAPP knockdown also reduce neuronal apoptosis and cell cycle related proteins. Which indicated that EAPP might integrate cell cycle progression and play a crucial role in cell proliferation and apoptosis. Taken together, we speculated that EAPP was involved in biochemical and physiological responses after SCI.

Expression of SGTA correlates with neuronal apoptosis and reactive gliosis after spinal cord injury.

Small glutamine-rich tetratricopeptide repeat (TPR)-containing protein alpha (SGTA) is a novel TPR-containing protein involved in various biological processes. However, the expression and roles of SGTA in the central nervous system remain unknown. We have produced an acute spinal cord injury (SCI) model in adult rats and found that SGTA protein levels first significantly increase, reach a peak at day 3 and then gradually return to normal level at day 14 after SCI. These changes are striking in neurons, astrocytes and microglia. Additionally, colocalization of SGTA/active caspase-3 has been detected in neurons and colocalization of SGTA/proliferating cell nuclear antigen has been detected in astrocytes and microglial. In vitro, SGTA depletion by short interfering RNA inhibits astrocyte proliferation and decreases cyclinA and cyclinD1 protein levels. SGTA knockdown also reduces neuronal apoptosis. We speculate that SGTA is involved in biochemical and physiological responses after SCI.

Up-regulation of HDAC4 is associated with Schwann cell proliferation after sciatic nerve crush.

Histone deacetylase 4 (HDAC4), a member of the class IIa HDACs subfamily, has emerged as a critical regulator of cell growth, differentiation, and migration in various cell types. It was reported that HDAC4 stimulated colon cell proliferation via repression of p21. Also, HDAC4 contributes to platelet-derived growth factor-BB-induced proliferation and migration of vascular smooth muscle cells. Furthermore, HDAC4 may play an important role in the regulation of neuronal differentiation and survival. However, the role of HDAC4 in the process of peripheral nervous system regeneration after injury remains virtually unknown. Herein, we investigated the spatiotemporal expression of HDAC4 in a rat sciatic nerve crush model. We found that sciatic nerve crush induced up-regulated expression of HDAC4 in Schwann cells. Moreover, the expression of the proliferation marker Ki-67 exhibited a similar tendency with that of HDAC4. In cell cultures, we observed increased expression of HDAC4 during the process of TNF-α-induced Schwann cell proliferation, whereas the protein level of p21 was down-regulated. Interference of HDAC4 led to enhanced expression of p21 and impaired proliferation of Schwan cells. Taken together, our findings implicated that HDAC4 was up-regulated in the sciatic nerve after crush, which was associated with proliferation of Schwann cells.

Distribution and correlation of refractive parameters in children with different corneal curvatures in southeast China.

AIM: To analyze the distribution of refractive status in school-age children with different corneal curvatures (CC) and the correlation between CC and refractive status. METHODS: A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included. Uncorrected distance visual acuity (UCDVA), non-cycloplegic refraction, axial length (AL), horizontal and vertical corneal curvature (K1, K2) were measured and spherical equivalent (SE), corneal curvature radius (CCR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated. UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia. According to the different CCRs, the patients were divided into the lower corneal curvature (LCC) group (CCR≥7.92) and the higher corneal curvature (HCC) group (CCR<7.92). Each group was further divided into the normal AL subgroup and the long AL subgroup. The refractive parameters were compared to identify any differences between the two groups. RESULTS: Both SE and AL were greater in the LCC group (P=0.013, P<0.001). The prevalence of myopia was 38% in the LCC group and 44% in the HCC group (P<0.001). The proportion of children without screening myopia was higher in the LCC group (62%) than in the HCC group (56%). Among these children without screening myopia, the proportion of long AL in the LCC group (24%) was significantly higher than that in the HCC group (0.012%; P<0.001). The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group. CONCLUSION: School-aged children in the LCC group have a lower incidence of screening myopia and longer AL. Low CC can mask SE reduction and AL growth to some extent, and the change of AL growth change more in children with low CC than high CC. Before the onset of myopia, its growth rate is even faster than that after the onset of myopia.

RNA-Seq Reveals the mRNAs, miRNAs, and lncRNAs Expression Profile of Knee Joint Synovial Tissue in Osteoarthritis Patients.

Osteoarthritis (OA) is a chronic disease common in the elderly population and imposes significant health and economic burden. Total joint replacement is the only currently available treatment but does not prevent cartilage degeneration. The molecular mechanism of OA, especially the role of inflammation in disease progression, is incompletely understood. We collected knee joint synovial tissue samples of eight OA patients and two patients with popliteal cysts (controls), measured the expression levels of lncRNAs, miRNAs, and mRNAs in these tissues by RNA-seq, and identified differentially expressed genes (DEGs) and key pathways. In the OA group, 343 mRNAs, 270 lncRNAs, and 247 miRNAs were significantly upregulated, and 232 mRNAs, 109 lncRNAs, and 157 miRNAs were significantly downregulated. mRNAs potentially targeted by lncRNAs were predicted. Nineteen overlapped miRNAs were screened based on our sample data and GSE 143514 data. Pathway enrichment and functional annotation analyses showed that the inflammation-related transcripts CHST11, ALDH1A2, TREM1, IL-1ß, IL-8, CCL5, LIF, miR-146a-5p, miR-335-5p, lncRNA GAS5, LINC02288, and LOC101928134 were differentially expressed. In this study, inflammation-related DEGs and non-coding RNAs were identified in synovial samples, suggesting that competing endogenous RNAs have a role in OA. TREM1, LIF, miR146-5a, and GAS5 were identified to be OA-related genes and potential regulatory pathways. This research helps elucidate the pathogenesis of OA and identify novel therapeutic targets for this disorder.

Effect of postoperative urinary retention in older patients with hip fracture on self-efficacy, resilience, and quality of life.

BACKGROUND: Hip fracture (HF) is a major health problem for older patients. Postoperative urinary retention (POUR) is a common complication in HF patients. It extends the length of the hospital stay and affects the recovery of mobility. This study aims to explore the relationship between self-efficacy, resilience, and quality of life in older patients with HF after HF combined with POUR and to improve the rehabilitation plan for HF patients. METHODS: A retrospective case-control study was conducted to assess 221 older patients with HF who underwent surgery for the first time at the Department of Orthopedics, Xishan People's Hospital from June 2018 to June 2021. Of these, 111 patients were in the POUR group (Group A), and the remaining 110 patients were in the non-POUR group (Group B). Three months after the operation, a questionnaire was administered to assess the relationship between POUR and self-efficacy, resilience, and quality of life. RESULTS: Self-efficacy scores of Group A (23.52±3.18) were lower than those of Group B (27.23±2.40), and the difference was statistically significant (P<0.05). Except for self-improvement, subscores and total scores of all resilience measures in Group A were lower than those of Group B, and these differences were statistically significant (P<0.05). The scores of all quality of life measures of Group A were lower than those of Group B, and the differences were statistically significant except for role-emotional (RE) (P<0.05). The correlation analysis between self-efficacy and resilience in older patients with HF after the operation showed that self-efficacy was positively correlated with the total resilience score and the toughness optimism dimensions (P<0.01). Correlation analysis between self-efficacy and quality of life showed that self-efficacy was positively correlated with role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), and social functioning (SF) (P<0.01). Correlation analysis between resilience and quality of life showed that total resilience scores, toughness, and optimism were positively correlated with physical functioning (PF), RP, BP, GH, VT, and SF (P<0.05). CONCLUSIONS: The combination of POUR after HF significantly reduces self-efficacy, resilience, and quality of life in older adults.

MGMT-Mediated neuron Apoptosis in Injured Rat Spinal Cord.

Spinal cord injury (SCI) induces a series of endogenous biochemical changes that lead to secondary degeneration, including apoptosis. The aim of this study was to investigate the potential effect and mechanism of action of MGMT in strengthing neuronal apoptosis following SCI. To determine MGMT-mediated apoptosis in spinal cord injury, we performed western blot and analyzed the expression change of MGMT with different timepoints. Western blot analysis showed the upregulation of MGMT has a peak at 21 days in injured spinal cord tissues. Expression and location was observed in the neurons after SCI. Upregulation of p53, Bax, cleaved caspase3 and cleaved caspase9 and downregulation of Bcl2 were detected after SCI. Co-localization of cleaved caspase3 with MGMT indicated MGMT involved in apoptosis taking place after SCI. In addition, we carried out H2O2 stimulation to further confirm MGMT played a role in neuron apoptosis process and activated p53 signaling pathway in vitro. Finally, based above data, we packaged lenti-associated virus inhibit MGMT expression and injected into rat spinal cords after SCI model was built. LV-MGMT not only reduces the neuron apoptosis, but also increases GAP43 expression and promotes hindlimbs locomotor function recovery. Taken together, the in vivo data and the in vitro observations prove MGMT-mediated apoptosis in the injured spinal cord.

[Research progress in treatment of femoral neck fracture in the elderly].

OBJECTIVE: To introduce the research progress of conservative treatment, internal fixation, hip arthroplasty, and multidisciplinary team (MDT) modes in the treatment of femoral neck fracture in the elderly. METHODS: By consulting domestic and foreign literature in recent years, the characteristics and application of various treatment methods and new treatment modes for femoral neck fracture in the elderly were summarized and analyzed. RESULTS: The elderly non-displaced femoral neck fracture should be treated surgically, and conservative treatment has a high risk of secondary displacement. The displaced fracture should be operated as soon as possible. There is no difference in long-term functional outcome between hemiarthroplasty and total hip arthroplasty. Hemiarthroplasty has less intraoperative blood loss, shorter operation time, and is suitable for the elderly patients with poor basic condition. Total hip arthroplasty is suitable for the elderly patients with better basic condition and higher demand of life quality. MDT can effectively reduce preoperative waiting time and length of stay, reduce the incidence of medical complications, improve the nutritional status of patients, and reduce the mortality of patients. CONCLUSION: Significant results have been achieved in the treatment of femoral neck fractures in the elderly by methods such as internal fixation, hip arthroplasty, and MDT.

Up-regulation of Dyrk1b promote astrocyte activation following lipopolysaccharide-induced neuroinflammation.

Astrocytes become activated in response to different stimulation. Dyrk1b is an arginine-directed serine/threonineprotein kinase that is expressed at elevated levels in many cancers but remains unknown in the pathologies of neuroinflammation. In this study, in vivo, we demonstrated that Dyrk1b expression was significantly increased and reached a peak at 12 h after LPS injection via Western blot. Double immunofluorescence staining showed that Dyrk1b co-located with GFAP and Ki67. In vitro, the expression of Dyrk1b, Ki67 and cyclinD1 was gradually increased and reached a peak at 12 h in a time-dependent manner after 1 µg/mL LPS stimulation. Knockdown of Dyrk1b significantly reduced the expression of Ki67 and cyclinD1. In addition, the data exhibited that silenced Dyrk1b decreased the expression of p-STAT3 in primary astrocyte cells, and Dyrk1b interacted with STAT3 in LPS-induced neuroinflammation. In conclusion, these results suggested that Dyrk1b is increased and may play a crucial role in regulating astrocyte cell activation via interact with STAT3 in LPS-induced neuroinflammation.

[Modified single-stage transpedicular decompression, debridement, and posterior instrumentation in treatment of thoracic tuberculosis].

OBJECTIVE: To investigate the effectiveness and feasibility of modified single-stage transpedicular decompression, debridement, and posterior instrumentation in treatment of thoracic tuberculosis. METHODS: Between January 2005 and December 2009, 22 cases of thoracic tuberculosis were treated with modified single-stage transpedicular decompression, debridement, and posterior instrumentation. There were 12 males and 10 females with an average age of 39.4 years (range, 22-52 years). The mean disease duration was 1.2 years (range, 3 months to 10 years). The involved vertebral bodies were T5-12, including 2 segments in 17 cases and 3 segments in 5 cases. The kyphosis Cobb angle was (31.2 +/- 14.5) degrees before operation. According to Frankel score system for neurological deficits, 2 cases were classified as grade A, 1 case as grade B, 8 cases as grade C, 5 cases as grade D, 1 case as grade E, and 5 cases had no neurological deficits before operation. RESULTS: All incisions healed by first intention. All patients were followed up 22.2 months on average (range, 12-65 months). Pain in low back was relieved in varying degrees 2 weeks after operation. Fusion was achieved in the bone implant area at 3 months after operation. According to Frankel score system, 1 case was rated as grade B, 2 cases as grade C, 4 cases as grade D, 7 cases as grade E, and 8 cases had no neurological deficits at last follow-up. The kyphosis Cobb angle was (16.2 +/- 3.6) degrees, showing significant difference when compared with the value before operation (t = 5.952, P = 0.001). No loosening, emersion, breakage of internal fixation or pneumothorax occurred 1 year after operation. CONCLUSION: Single-stage transpedicular decompression and posterior instrumentation is an effective and safe method in treatment of thoracic tuberculosis.