CDK5R1 promotes Schwann cell proliferation, migration, and production of neurotrophic factors via CDK5/BDNF/TrkB after sciatic nerve injury.

Cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) is necessary for central nervous system development and neuronal migration. At present, there are few reports about the role of CDK5R1 in peripheral nerve injury, and these need to be further explored. The CCK-8 and EdU assay was performed to examine cell proliferation. The migration ability of Schwann cells was tested by the cell scratch test. The apoptosis of Schwann cells was detected by flow cytometry. Sciatic nerve injury model in rats was established by crush injury. The sciatic function index (SFI) and the paw withdrawal mechanical threshold (PWMT) were measured at different time points. The results revealed that overexpression of CDK5R1 promoted the proliferation and migration of Schwann cells, and inhibited the apoptosis. Further studies found that pcDNA3.1-CDK5R1 significantly upregulated the expression of CDK5, BDNF and TrkB. More importantly, CDK5R1 promoted the recovery of nerve injury in rats. In addition, the CDK5 mediated BDNF/TrkB pathway was involved in the molecular mechanism of CDK5R1 on Schwann cells. It is suggested that the mechanism by which CDK5R1 promotes functional recovery after sciatic nerve injury is by CDK5 mediated activation of BDNF/TrkB signaling pathways.

Relapse of Graves' disease in Chinese children: a retrospective cohort study.

Background: Graves' disease (GD) among children has attracted wide attention. However, data on long-term follow-up are scarce, especially in China. This study aimed to investigate the prognosis after regular treatments of GD and to identify possible influencing factors. Methods: A total of 204 newly diagnosed GD children in the Children's Hospital of Nanjing Medical University between 2013 and 2019 were included in this study. The cases involved were divided into remission group, relapse group, and continuing treatment group according to therapy outcomes. Relationships between prognosis and possible influencing factors in remission and relapse groups were analyzed. Results: All 204 cases were treated with methimazole at presentation with GD. Due to severe complications, 4 (2.0%) cases changed medication to propylthiouracil. Of all the GD children included, 79 (38.7%) had remission, and 40 (50.6%) relapsed after remission. For each additional month before free thyroxine fell into the reference range with treatment, the risk of relapse increased 1.510 times (adjusted odds ratio (OR)=2.510, 95%CI: 1.561-4.034) compared to those in the remission group. On the contrary, the risk of relapse was reduced by 0.548 times for each additional hour of sleep duration per day (adjusted OR=0.452, 95%CI: 0.232-0.879). Conclusion: GD children have a high relapse rate after remission, and most of them occur within 1 year. Thyroid function should be reexamined regularly after drug withdrawal. The response to medication and lifestyle of GD children may affect the prognosis.

LncRNA HAGLR promotes the proliferation, migration, and neurotrophic factor production of Schwann cells via miR-204/CDK5R1 after sciatic nerve injury.

Peripheral nerve injury induces motor and sensory defects and has serious impacts on patients' quality of life. Schwann cells (SCs) are the major glial cells in the peripheral nervous system and play important roles in the repair and regeneration of peripheral nerves. Long noncoding RNA HAGLR has been reported to be highly expressed in neurons and to promote neuronal differentiation but its expression decreases after nerve injury, suggesting that HAGLR may be involved in the process of nerve injury repair. This study aimed to investigate the role and mechanism of HAGLR in neural repair functions of SCs. We found that HAGLR promoted SC proliferation and migration and facilitated the secretion of neurotrophic factors. Furthermore, HAGLR functions as a competing endogenous RNA to regulate CDK5R1 expression via sponging miR-204. Overexpression of miR-204 or silencing of CDK5R1 partially abolished the promoting effect of HAGLR on SCs. Moreover, overexpression of HAGLR promoted the functional recovery of sciatic nerve crush (SNC) model rats. In summary, HAGLR promoted SC proliferation, migration, neurotrophic factor production, and facilitated functional recovery of SNC rats via miR-204/CDK5R1. Therefore, it may provide a potential therapeutic target for peripheral nerve repair and regeneration.

Characteristics of Graves' disease in children and adolescents in Nanjing: A retrospective investigation study.

Objective: This cross-sectional study analyzed the clinical characteristics of newly diagnosed Graves' disease (GD) in children and adolescents to provide clinical evidence for the early diagnosis of GD. Method: From 2013 to 2019, information on children and adolescents with newly diagnosed GD admitted to the Department of Endocrinology, Children's Hospital of Nanjing Medical University, was collected, including clinical features and laboratory tests. The data were summarized and statistically analyzed. Result: This study included 204 cases of newly diagnosed GD, with 158 females and 46 males. The average age at initial diagnosis was 8.9 ± 2.9 years. A total of 132 cases (64.7%) had symptoms before puberty, and 72 cases (35.3%) had symptoms during puberty. Goiter was detected in 193 cases (94.6%). There were 140 cases (68.6%) of exophthalmos, and 21.4% (30/140) were infiltrative. At initial diagnosis, 10 cases (4.9%) reported leukopenia, 18 cases (8.8%) reported neutropenia, and 15 cases (7.4%) reported mild anemia. There was 1 (0.5%) case of thrombocytopenia and 1 (0.5%) case of agranulocytosis. Fifty-four cases (26.5%) had impaired liver function. Conclusion: GD is more common in female children and adolescents. Parents may ignore their children's hypermetabolic symptoms in the early stages of GD. Routine blood and liver function tests are recommended at initial diagnosis to exclude abnormal hemogram and liver function.

Global and subtype-specific modulation of cortical inhibitory neurons regulated by acetylcholine during motor learning.

Inhibitory neurons (INs) consist of distinct subtypes with unique functions. Previous studies on INs mainly focused on single brain regions, and thus it remains unclear whether the modulation of IN subtypes occurs globally across multiple regions. Here, we monitored the activity of different cortical IN subtypes at both macroscale and microscale in mice learning a lever-press task. Learning evoked a global modulation of IN subtypes throughout the cortex. The initial learning phase involved strong activation of vasoactive intestinal peptide-expressing INs (VIP-INs) and weak activation of somatostatin-expressing INs (SOM-INs). Inactivating VIP-INs increased SOM-IN activity and impaired initial learning. Concurrently, cortical cholinergic inputs from the basal forebrain were initially more active but became less engaged over learning. Manipulation of the cholinergic system impaired motor learning and differentially altered activity of IN subtypes. These results reveal that motor learning involves a global and subtype-specific modulation on cortical INs regulated by the cholinergic system.

Yam-Containing Serum Promotes Proliferation and Chondrogenic Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells and Synthesis of Glycosaminoglycan.

The chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is affected by a variety of factors, including environmental, physical, and chemical factors and growth factors, and traditional Chinese medicine (TCM) preparations can further influence this process. In this study, the effects of different concentrations of Yam-containing serum of rabbits on BMSC proliferation and chondrogenic differentiation were investigated, as were the underlying molecular mechanisms. The growth and proliferation of BMSCs were significantly enhanced upon treatment with Yam-containing serum. Under both monolayer and micromass culture conditions, Yam-containing serum promoted the differentiation of BMSCs into chondrocytes. Toluidine blue staining results revealed that chondrocyte differentiation in the group treated by Yam-containing serum was significantly more pronounced than in the control group. Glycosaminoglycan levels, as measured by 1,2-dimethylmethylene blue (DMMB) detection, were significantly higher in cells of the Yam-containing group relative to the control group. This is the first study to our knowledge that demonstrates that Yam-containing serum can promote BMSC proliferation and chondrogenic differentiation. This study therefore lays an experimental groundwork for further application of TCM as a means of treating degenerative cartilage diseases and provides an experimental and theoretical basis for the combination of TCM and stem cells for the treatment of such diseases.

Different Effects of Intravenous, Topical, and Combined Application of Tranexamic Acid on Patients with Thoracolumbar Fracture.

OBJECTIVE: To observe the efficacy of intravenous, topical, and combined application of tranexamic acid (TXA) in patients with thoracolumbar fracture fixed with percutaneous pedicle screw, and to identify the optimal application method of TXA. METHODS: A total of 181 patients with thoracolumbar fracture treated with percutaneous pedicle screw fixation were enrolled in this randomized controlled trial and were randomly classified into 3 groups, including group A (intravenous group), group B (topical group), and group C (combined group). The total blood loss (TBL), hidden blood loss (HBL), intraoperative blood loss (IBL), preoperative D-dimer, postoperative D-dimer, incidence of deep vein thrombosis (DVT), and incidence of other complications were compared and analyzed among the 3 groups. RESULTS: TBL, HBL, and IBL in the topical group 24 hours after operation were higher (P < 0.05) than those in the intravenous group and combined group, whereas the difference between the intravenous group and combined group was not statistically significant. Meanwhile, there was no statistically significant difference in operation time, preoperative D-dimer, and postoperative D-dimer among the 3 groups (P > 0.05), but D-dimer in all groups at 72 hours after surgery was higher than that before surgery. No DVT or other complication was observed in the patients. CONCLUSIONS: Preoperative intravenous drip of TXA can remarkably reduce intraoperative HBL and IBL in patients with thoracolumbar fracture fixed with percutaneous pedicle screw. Nonetheless, intraoperative topical application of TXA before wound closure is not recommended.

Selection of surgical treatment approaches for cervicothoracic spinal tuberculosis: A 10-year case review.

BACKGROUND: Cervicothoracic spinal tuberculosis is a rare disease. Due to its difficult and challenging surgical exposure, its surgical treatment approach remains inconclusive. Long-term follow-up studies to address this puzzling issue are rarely seen in the literature. The purpose of this study was to explore the selection of surgical treatment approaches for cervicothoracic spinal tuberculosis through a 10-year case review. METHODS: From January 2003 to January 2013, 45 patients suffering from cervicothoracic spinal tuberculosis were treated surgically. According to the relation between the tuberculosis lesion segments and the suprasternal notch on sagittal MRI, 19 patients were treated with a single-stage anterior debridement, fusion and instrumentation approach, and the other 26 patients were treated with a single-stage anterior debridement and fusion, posterior fusion and instrumentation approach. The clinical efficacy was evaluated using statistical analysis based on the Cobb angle of kyphosis, the Neck Disability Index (NDI) and the Japanese Orthopedic Association (JOA) scoring system. The neurofunctional recovery was assessed by the American Spinal Injury Association (ASIA) system. RESULTS: All patients were followed up for 6.6 years on average (range 3-13 years). No instrumentation loosening, migration or breakage was observed during the follow-up. The kyphosis angle and NDI and JOA scores were significantly changed from preoperative values of 34.7±6.8°, 39.6±4.6 and 10.7±2.8 to postoperative values of 10.2±2.4°, 11.4±3.6 and 17.6±2.4, respectively (p<0.05). Aside from one recurrent patient, bone fusion was achieved in the other 44 patients within 6 to 9 months (mean 7.2 months). No severe postoperative complications occurred, and patients' neurologic function was improved in various degrees. CONCLUSIONS: In the surgical treatment of cervicothoracic spinal tuberculosis, single-stage cervical anterior approach with or without partial manubriotomy is capable of complete debridement for tuberculosis lesions. The manner of fixation should be selected based on the anatomical relation of the suprasternal notch and the diseased segments as revealed on sagittal MRI images.