Tetramethylpyrazine-loaded electroconductive hydrogels promote tissue repair after spinal cord injury by protecting the blood-spinal cord barrier and neurons.

Spinal cord injury (SCI) usually induces profound microvascular dysfunction. It disrupts the integrity of the blood-spinal cord barrier (BSCB), which could trigger a cascade of secondary pathological events that manifest as neuronal apoptosis and axonal demyelination. These events can further lead to irreversible neurological impairments. Thus, reducing the permeability of the BSCB and maintaining its substructural integrity are essential to promote neuronal survival following SCI. Tetramethylpyrazine (TMP) has emerged as a potential protective agent for treating the BSCB after SCI. However, its therapeutic potential is hindered by challenges in the administration route and suboptimal bioavailability, leading to attenuated clinical outcomes. To address this challenge, traditional Chinese medicine, TMP, was used in this study to construct a drug-loaded electroconductive hydrogel for synergistic treatment of SCI. A conductive hydrogel combined with TMP demonstrates good electrical and mechanical properties as well as superior biocompatibility. Furthermore, it also facilitates sustained local release of TMP at the implantation site. Furthermore, the TMP-loaded electroconductive hydrogel could suppress oxidative stress responses, thereby diminishing endothelial cell apoptosis and the breakdown of tight junction proteins. This concerted action repairs BSCB integrity. Concurrently, myelin-associated axons and neurons are protected against death, which meaningfully restore neurological functions post spinal cord injury. Hence, these findings indicate that combining the electroconductive hydrogel with TMP presents a promising avenue for potentiating drug efficacy and synergistic repair following SCI.

Tetramethylpyrazine inhibits the inflammatory response by downregulating the TNFR1/IκB-α/NF-κB p65 pathway after spinal cord injury.

Previous studies have demonstrated that tetramethylpyrazine (TMP) can enhance the recovery of motor function in spinal cord injury (SCI) rats. However, the underlying mechanism involved in this therapeutic effect remains to be elucidated. We conducted RNA sequencing with a network pharmacology strategy to predict the targets and mechanism of TMP for SCI. The modified Allen's weight-drop method was used to construct an SCI rat model. The results indicated that the nuclear transfer factor-κB (NF-κB) pathway was identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and an inflammatory response was identified through the Gene Ontology (GO) enrichment analysis. Tumor necrosis factor (TNF) was identified as a crucial target. Western blotting revealed that TMP decreased the protein expression of TNF superfamily receptor 1 (TNFR1), inhibitor κB-α (IκB-α), and NF-κB p65 in spinal cord tissues. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) demonstrated that TMP inhibited TNF-α, interleukin-1ß (IL-1ß), reactive oxygen species (ROS), and malondialdehyde (MDA) expression and enhanced superoxide dismutase (SOD) expression. Histopathological observation and behavior assessments showed that TMP improved morphology and motor function. In conclusion, TMP inhibits inflammatory response and oxidative stress, thereby exerting a neuroprotective effect that may be related to the regulation of the TNFR1/IκB-α/NF-κB p65 signaling pathway.

[Experimental study of tetramethylpyrazine-loaded electroconductive hydrogel on angiogenesis and neuroprotection after spinal cord injury].

Objective: To explore the mechanisms for repairing spinal cord injury (SCI) with tetramethylpyrazine-loaded electroconductive hydrogel (hereinafter referred to as "TGTP"). Mehtods: A total of 72 female Sprague-Dawley rats were randomly divided into 4 groups: sham operation group (group A), SCI group (group B), SCI+electroconductive hydrogel group (group C), and SCI+TGTP group (group D). Only the vertebral plate was removed in group A, while the remaining groups were subjected to a whole transection model of spinal cord with a 2 mm gap in the lesions. The recovery of hindlimb motor function was evaluated by Basso, Beattie, Bresnahan (BBB) score and modified Rivlin-Tator inclined plate test before operation and at 1, 3, 7, 14, and 28 days after operation, respectively. Animals were sacrificed at 7 days and 28 days after modeling. Neovascularisation was observed by immunofluorescence staining of CD31 and the expression levels of angiopoietin 1 (Ang-1) and Tie-2 were assessed by Western blot assay. At 28 days postoperatively, the expression levels of pro-angiogenic related proteins, including platelet-derived growth factor B (PDGF-B), PDGF receptor ß (PDGFR-ß), vascular endothelial growth factor A (VEGF-A), and VEGF receptor 2 (VEGFR-2), were also assessed by Western blot. The fibrous scar in the injured area was assessed using Masson staining, while neuronal survival was observed through Nissl staining. Furthermore, LFB staining was utilized to detect myelin distribution and regeneration. Immunofluorescence and Western blot assay were employed to evaluate the expression of neurofilament 200 (NF200). Results: The hindlimb motor function of rats in each group gradually recovered from the 3rd day after operation. The BBB score and climbing angle in group D were significantly higher than those in group B from 3 to 28 days after operation, and significantly higher than those in group C at 14 days and 28 days after operation ( P<0.05). Masson staining showed that the collagen volume fraction in groups B-D were significantly higher than that in group A, and that in group D was significantly lower than that in groups B and C ( P<0.05); a small amount of black conductive particles were scattered at the broken end in group D, and the surrounding collagen fibers were less than those in group C. Nissl and LFB staining showed that the structure of neurons and myelin sheath in the injured area of spinal cord in group D was relatively complete and continuous, and the number of Nissl bodies and the positive area of myelin sheath in group D were significantly better than those in groups B and C ( P<0.05). NF200 immunofluorescence staining and Western blot assay results showed that the relative expression of NF200 protein in group D was significantly higher than that in groups B and C ( P<0.05). CD31 immunofluorescence staining showed that the fluorescence intensity of group D was better than that of groups B and C at 28 days after operation, and tubular or linear neovascularization could be seen. The relative expressions of Ang-1 and Tie-2 proteins in group D were significantly higher than those in groups B and C at 7 and 28 days after operation ( P<0.05). The relative expressions of PDGF-B and PDGFR-ß proteins in group D were significantly higher than those in groups B and C, and group B was significantly higher than group C at 28 days after operation ( P<0.05). The relative expressions of VEGF-A and VEGFR2 proteins in group D were higher than those in groups B and C, showing significant difference when compared with group B ( P<0.05), but only the expression of VEGF-A protein was significantly higher than that in group C ( P<0.05). There was significant difference only in VEGFR-2 protein between groups B and C ( P<0.05). Conclusion: TGTP may enhance the revascularization of the injured area and protect the neurons, thus alleviating the injury of spinal cord tissue structure and promoting the recovery of neurological function after SCI in rats.

Neuroprotective effects of tetramethylpyrazine on spinal cord injury-Related neuroinflammation mediated by P2X7R/NLRP3 interaction.

OBJECTIVE: The inflammatory response is acknowledged as a crucial pathological aspect of spinal cord injury (SCI). Tetramethylpyrazine (TMP) has been demonstrated to possess neuroprotective properties within the central nervous system via its anti-inflammatory mechanisms. This study aims to investigate the molecular mechanism by which TMP alleviates SCI from an anti-inflammatory standpoint. METHODS: The SCI model was established using the MASCIS impactor device. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was utilised to assess rat locomotion. Nissl and Golgi staining were used to observe neuron and dendritic spine morphology, respectively. A transmission electron microscope was used to observe the microcosmic morphology of the axon. ELISA kits were used to measure the concentrations of IL-1ß and IL-18 in the spinal cord. Immunofluorescence staining was used to detect P2X7R+/IBA-1+ cells, and Western blot and RT-qPCR were used to analyze the protein and mRNA expression of P2X7R in the spinal cord. Additionally, Western blot was used to detect NLRP3 and Cleaved-Caspase-1 (p20), the critical proteins in the NLRP3 inflammasome pathway. RESULTS: TMP ameliorated the microcosmic morphology of the axon and had an inhibitory effect on the concentrations of IL-1ß and IL-18 after SCI. Furthermore, TMP inhibited the expression of both P2X7R and critical proteins of the NLRP3 inflammasome pathway on microglia after SCI. The aforementioned effects of TMP exhibit similarities to those of BBG (P2X7R antagonist); however, they can be effectively reversed by BzATP (P2X7R activator). CONCLUSION: TMP alleviated SCI via reducing tissue damage, neuroinflammation, and the expression of P2X7R, NLRP3, IL-1ß, and IL-18.

Effect of use of NSAIDs or steroids during the acute phase of pain on the incidence of chronic pain: a systematic review and meta-analysis of randomised trials.

BACKGROUND: This study is the first to summarize the evidence on how the use of anti-inflammatory drugs during acute pain has an impact on the development of chronic pain. METHODS: Randomized controlled trials retrieved from nine databases included anti-inflammatory drugs (NSAIDs or steroids) versus non-anti-inflammatory drugs in patients with acute pain and reported the incidence of chronic pain. No specified date, age, sex, or language restrictions. Subgroup analyses were performed according to pain classification, follow-up time, and medication. The GRADE method was used to evaluate quality of evidence. RESULTS: A total of 29 trials (5220 patients) were included. Steroids or NSAIDs did not reduce the incidence of chronic nociceptive pain. Steroid use in acute phase significantly reduced the incidence of chronic neuropathic pain. In subgroup analysis, benefits were observed for methylprednisolone and dexamethasone, with some adverse effects. Steroids or NSAIDs were statistically significant in reducing pain intensity over 1 year, but the effect size was too small, and whether the long-term effect is clinically relevant needs to be further studied. CONCLUSION: Quality of the evidence was low to moderate. No drug can be recommended to prevent chronic nociceptive pain. Injections of steroids (methylprednisolone or dexamethasone) during the acute phase reduce the incidence of chronic neuropathic pain, but most included studies also used local anesthetics. The results are indirect and need to be interpreted with caution. The pooled data effect sizes for pain intensity were small, so the clinical relevance was unclear. Study registration PROSPERO (CRD42022367030).

Temporal profiling and validation of oxidative stress-related genes in spinal cord injury.

Oxidative stress (OS) plays a pivotal role in the pathogenesis of spinal cord injury (SCI), yet its underlying mechanisms remain elusive. In this study, we explored the OS phenotype in a rat model of SCI. Subsequently, comprehensive bioinformatic analyses were conducted on microarray data pertaining to SCI (GSE45006). Notably, KEGG enrichment analysis revealed a pronounced enrichment of pivotal pathways, namely MAPK, FoxO, Apoptosis, NF-κB, TNF, HIF-1, and Chemokine across distinct phases of SCI. Furthermore, GO enrichment analysis highlighted the significance of biological processes including response to hypoxia, response to decrease oxygen levels, response to reactive oxygen species, cellular response to oxidative stress, reactive oxygen species metabolic process, and regulation of neuron death in the context of OS following SCI. Notably, our study underscores the prominence of nine genes, namely Itgb1, Itgam, Fn1, Icam1, Cd44, Cxcr4, Ptprc, Tlr4, and Tlr2 as OS key genes in SCI, consistently expressed in both the acute phase (1, 3, 7 days) and sub-acute phase (14 days). Subsequently, the relative mRNA expression of these key genes in different time points (1, 3, 7, 14 days) post-SCI. Finally, leveraging the DsigDB database, we predicted ten potential compounds potentially targeting OS and facilitating the repair of SCI, thus providing novel insights into the mechanisms underlying OS and identifying potential therapeutic targets for SCI.

Coagulation parameters correlate to venous thromboembolism occurrence during the perioperative period in patients with spinal fractures.

BACKGROUND: Venous thromboembolism (VTE) is one of the leading causes of mortality in hospitalized patients. However, whether the coagulation-related parameters of the hospitalized patients could be used to predict the occurrence of VTE in patients with spinal injury surgery remained unclear. METHOD: The patients with spinal fractures who met the inclusion and exclusion criteria were enrolled to be analyzed using a retrospective analysis approach. The association of risk factors of enrolled patients and operations to VTE occurrence were analyzed. The activated partial thromboplastin time, prothrombin time, thrombin time, D-dimer (D-D), fibrinogen (FIB) and fibrinogen degradation products (FDP) were detected. ROC and HR analysis were applied to evaluate the correlation of coagulation-related parameters and other parameters to VTE occurrence. RESULT: The indicators of D-D, FIB and FDP were significantly elevated in VTE patients compared to non-VTE patients. The multivariate analysis of OR showed that six risk factors, including age ≥ 60, spinal cord injury, postoperative bedtime over 5 days, plasma D-dimer ≥ 0.54 mg/L, plasma fibrinogen ≥ 3.75 g/L and plasma FDP ≥ 5.19 mg/L, were positively correlated to VTE. CONCLUSION: The six risk factors, including D-D, FIB, FDP, age ≥ 60, spinal cord injury, and postoperative bedtime over 5 days, could be used to predict the occurrence of VTE.

Early-stage effect of HIBD on neuro-motor function and organic composition of neurovascular units in neonatal rats.

Objective: This study aimed to investigate the effects of neonatal hypoxic-ischemic brain damage (HIBD) on early-stage neuro-motor function, cerebral blood flow, and the neurovascular unit. Methods: Twenty-four Sprague-Dawley newborn rats aged 7 days were obtained and randomly assigned to either the sham or the model group using a random number table. The HIBD model was established using the Rice-Vannucci method. After the induction of HIBD, the body weight of the rats was measured and their neuro-motor function was assessed. Further, cerebral blood flow perfusion was evaluated using laser speckle flow imaging, and immunofluorescent staining techniques were employed for examining the activation of specific markers and their morphological changes in different cell populations, which included vascular endothelial cells, neurons, astrocytes, and microglia within the motor cortex. Results: After HIBD, the model group exhibited impaired neuro-motor function and growth. Cerebral blood flow perfusion decreased in both the hemispheres on day 1 and in the ipsilateral brain on day 4. However, no significant difference was observed between the two groups on day 7. Moreover, the CD31 and NeuN showed a sharp decline on day 1, which was followed by a gradual increase in the expression levels. The activated microglia and astrocytes formed clusters in the injured cortex. Notably, the regions with positive staining for Arg-1, Iba-1, CD68, and GFAP consistently displayed higher values in the model group as compared to that in the sham group. The total number of branch endpoints and microglia branches was higher in the model group than in the sham group. Immunofluorescent co-localization analysis revealed no co-staining between Iba-1 and Arg-1; however, the Pearson's R-value for the co-localization of Iba-1 and CD68 was higher in the model group, which indicated an increasing trend of co-staining in the model group. Conclusion: Early-stage neuro-motor function, cerebral blood flow, microvasculature, and neurons in neonatal rats exhibited a trend of gradual recovery over time. The activation and upregulation of neuroglial cells continued persistently after HIBD. Furthermore, the impact of HIBD on early-stage neuro-motor function in newborn rats did not synchronize with the activation of neuroglial cells. The recovery of neuro-motor function, microvasculature, and neurons occurred earlier than that of neuroglial cells.

Granulocyte colony-stimulating factor effects on neurological and motor function in animals with spinal cord injury: a systematic review and meta-analysis.

Background: Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury. Objective: To investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI. Methods: We searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria. Results: Results revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35 days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92-2.87, p < 0.00001, I2 = 69%]; inclined plane test score; electrophysiologic exam; quantitative analysis of TUNEL-positive cell numbers; quantitative analysis of GFAP immunostaining images in animal models of SCI. Subgroup analysis revealed that treatment with normal saline, phosphate-buffered saline, and no treatment resulted in significantly different neurological function effectiveness compared to the G-CSF therapy. SD rats and Wistar rats with SCI resulted in significant neurological function effectiveness. C57BL/6 mice showed no difference in the final effect. The T9-T10 or T10 segment injury model and the T8-T9 or T9 segment injury model resulted in significant neurological function effectiveness. The BBB score data showed no clear funnel plot asymmetry. We found no bias in the analysis result (Egger's test, p = 0.42). In our network meta-analysis, the SUCRA ranking showed that 15 mg/kg-20 mg/kg was an optimal dose for long-term efficacy. Conclusion: Our meta-analysis suggests that G-CSF therapy may enhance the recovery of motor activity and have a specific neuroprotective effect in SCI animal models.Systematic review registration: PROSPERO, identifier: CRD42023388315.

3D Printing Model of a Patient's Specific Lumbar Vertebra.

Selective dorsal rhizotomy (SDR) is a difficult, risky, and sophisticated operation, in which a laminectomy should not only expose an adequate surgical field of view but also protect the patient's spinal nerves from injury. Digital models play an important role in the pre-and intra-operation of SDR, because they can not only make doctors more familiar with the anatomical structure of the surgical site, but also provide precise surgical navigation coordinates for the manipulator. This study aims to create a 3D digital model of a patient-specific lumbar vertebra that can be used for planning, surgical navigation, and training of the SDR operation. The 3D printing model is also manufactured for more effective work during these processes. Traditional orthopedic digital models rely almost entirely on computed tomography (CT) data, which is less sensitive to soft tissues. Fusion of the bone structure from CT and the neural structure from magnetic resonance imaging (MRI) is the key element for the model reconstruction in this study. The patient's specific 3D digital model is reconstructed for the real appearance of the surgical area and shows the accurate measurement of inter-structural distances and regional segmentation, which can effectively help in the preoperative planning and training of SDR. The transparent bone structure material of the 3D-printed model allows surgeons to clearly distinguish the relative relationship between the spinal nerve and the vertebral plate of the operated segment, enhancing their anatomical understanding and spatial sense of the structure. The advantages of the individualized 3D digital model and its accurate relationship between spinal nerve and bone structures make this method a good choice for preoperative planning of SDR surgery.

Effects of microcurrent therapy in promoting function and pain management of knee osteoarthritis: a systematic review and meta-analysis protocol.

INTRODUCTION: Microcurrent therapy (MCT) is a rising conservative treatment for patients with knee osteoarthritis (OA). Considering its potential benefits and convenience, MCT's application in those individuals with knee OA is capacious. However, no plausible clinical evidence has proved its unequivocal advantages in treating knee OA conservatively. The purpose of this study is to determine whether MCT is helpful in pain management and promoting function of knee OA and is safe in the treatment of knee OA in adult patients. METHODS AND ANALYSIS: We will search through MEDLINE, Embase, Cochrane Library, Web of Science and Google Scholar from inception to 15 March 2023. Original studies will include randomised controlled trials of patients treated with MCT. Two authors will independently screen, select studies, extract data and perform risk of bias assessment. Data consistently reported across studies will be pooled using random-effects meta-analysis. Heterogeneity will be evaluated using Cochrane's Q statistic and quantified using I2 statistics. Graphical and formal statistical tests will be used to assess for publication bias. ETHICS AND DISSEMINATION: Ethical approval will not be needed for this study as the data will be extracted from already published studies. The results of this review will be published in a peer-reviewed journal and presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42022319828.

[Relationship between the gross motor function classification system and hip and lumbar spine development in children with spastic cerebral palsy].

OBJECTIVE: To investigate the relationship among the gross motor function classification system (GMFCS)and the development of hip joint and lumbar spine in children with spastic cerebral palsy. METHODS: The clinical data of 125 children with spastic cerebral palsy admitted from January 2018 to July 2021 were retrospectively analyzed. There were 85 males and 40 females, aged from 4 to 12 years old with an average of (8.4±2.9) years. According to GMFCS, the patients were divided into gradeⅠ, Ⅱ, Ⅲ and Ⅳ groups. There were 27 cases in gradeⅠgroup, 40 cases in gradeⅡgroup, 35 cases in grade Ⅲ group and 23 cases in grade Ⅳ group. The migration percentage(MP), central edge angle(CE), neck-shaft angle(NSA), acetabular index(AI) were measured by the radiograph of pelvis, abnormal parameters were selected to evaluate the relationship between different GMFCS grades and hip joint development. Lumbar sagittal Cobb angle, lumbar sacral angle, lumbar lordosis index and apical distance were measured by lateral lumbar radiographs to evaluate the relationship between different GMFCS grades and lumbar spine development. RESULTS: ①Among the 125 spastic cerebral palsy children, there were 119 cases of pelvic radiographs that met the measurement standards. In the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, MP was (22.72±3.88), (26.53±4.36), (33.84±4.99), and (49.54±7.87)%, CE was(30.10±6.99) °, ( 22.92±4.19) °, ( 17.91±5.50) °, and (-0.70±17.33)°, AI was (16.41±2.77) °, (20.46±4.63) °, (23.76±5.10) °, and ( 29.15±7.35)°, respectively, there were significant differences between the two comparisons (P<0.05). And the higher GMFCS grade, the greater MP and AI, and the smaller CE.The NSA was(142.74±10.03) °, (148.66±9.09) °, (151.66±10.52) °, and (153.70±8.05)° in four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, respectively. The differences between the two comparisons of the GMFCS gradeⅠgroup and the other three groups were statistically significant (P<0.05). NSA of GMFCSⅠgroup was significantly lower than that of the others, there was no significant difference among other groups(P>0.05). ② Among the 125 spastic cerebral palsy children, there were 88 cases of lumbar spine radiographs that met the measurement standards. ③The lumbar sagittal Cobb angle was(32.62±11.10) °, (29.86±9.90) °, (31.70±11.84) °, and (39.69±6.80)° in the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, respectively;GMFSS of grade Ⅳ group was significantly higher than that of other three groups, there was significant difference between the two comparisons (P<0.05);there were no significant differences between other groups (P>0.05). In the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, the lumbosacral angle was (31.02±9.91) °, ( 26.57±9.41) °, (28.08±8.56) °, and ( 27.31±11.50)°, the lumbar lordosis index was (4.14±12.89), (8.83±13.53), (13.00±11.78), and (10.76±9.97) mm, the arch apex distance was (9.50±6.80), (6.68±3.20), (7.16±4.94), and (6.62±4.13) mm, respectively, there were no significant differences between the two comparisons(P>0.05). CONCLUSION: ①In children with GMFCS gradeⅠ-Ⅳ, the higher the GMFCS grade, the worse the hip develops. ② Children with GMFCS grade Ⅲ-Ⅳ may be at greater risk for lumbar kyphosis.

[Experimental study on the repair of spinal cord injury by conducting hydrogel loaded with tetramethylpyrazine sustained-release microparticles].

Objective: To investigate the neuroprotective effect of conducting hydrogel loaded with tetramethylpyrazine sustained-release microparticles (hereinafter referred to as "TGTP hydrogel") on spinal cord injury rats. Methods: Forty-eight adult female Sprague Dawley rats were randomly divided into 4 groups: sham operation group (group A), model group (group B), conductive hydrogel group (group C), and TGTP hydrogel group (group D), with 12 rats in each group. Only laminectomy was performed in group A, and complete spinal cord transection was performed in groups B, C, and D. Basso-Bettie-Bresnahan (BBB) score was used to evaluate the recovery of hind limb motor function of each group before modeling and at 1, 3, 7, 14, and 28 days after modeling, respectively. At 28 days after modeling, the rats were sacrificed for luxol fast blue (LFB) staining to detect myelin regeneration. Nissl staining was used to detect the survival of neurons. Immunohistochemical staining was used to evaluate the expression of inflammation-related factors [nuclear factor кB (NF-кB), tumor necrosis factor α (TNF-α), and interleukin 10 (IL-10)]. Immunofluorescence staining and Western blot were used to evaluate the expression of neurofilament 200 (NF200). Rseults: BBB scores of group A were significantly better than those of the other three groups at all time points after modeling (P<0.05); at 14 and 28 days after modeling, there was no significant difference in BBB scores between groups C and D (P>0.05), but the BBB score of group D was significantly better than that of group B (P<0.05). LFB staining and Nissl staining showed that the structure of neurons and myelin in group A was intact, and the myelin integrity and survival number of neurons in group D were significantly better than those in groups B and C. Immunohistochemical staining showed that the absorbency (A) value of NF-кB and TNF-α in group A were significantly lower than those in groups B and C (P<0.05), the A value of IL-10 was significantly higher than that in the other three groups (P<0.05); the A value of NF-κB in group D was significantly lower than that in groups B and C, the A value of TNF-α in group D was significantly lower than that in group B, while the A value of IL-10 in group D was significantly higher than that in group B (P<0.05). Immunofluorescence staining showed that the structure of neurons and nerve fibers in group A was clear and the fluorescence intensity was high. The fluorescence intensity of NF200 in group D was higher than that in groups B and C, and some nerve fibers could be seen. Western blot analysis showed that the relative expression of NF200 in group A was the highest, and the relative expression of NF200 in group D was significantly higher than that in groups B and C (P<0.05). Conclusion: The TGTP hydrogel can effectively promote the recovery of motor function in rats with spinal cord injury, and its mechanism may be related to the regulation of inflammatory response.

Development of software enabling Chinese medicine-based precision treatment for osteoporosis at the gene and pathway levels.

BACKGROUND: Precision medicine aims to address the demand for precise therapy at the gene and pathway levels. We aimed to design software to allow precise treatment of osteoporosis (OP) with Chinese medicines (CMs) at the gene and pathway levels. METHODS: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP database), and the Wanfang database were searched to identify studies treating osteoporosis with CMs. The TCMSP was used to identify bioactive ingredients and related genes for each CM. Gene expression omnibus (GEO) database and the limma package were used to identify differentially expressed genes in osteoporosis. Perl software was used to identify the shared genes between the bioactive components in CM and osteoporosis. R packages and bioconductor packages were used to define the target relationship between shared genes and their related pathways. Third-party Python libraries were used to write program codes. Pyinstaller library was used to create an executable program file. RESULTS: Data mining: a total of 164 CMs were included, but Drynariae Rhizoma (gusuibu) was used to present this process. We obtained 44 precise relationships among the bioactive ingredients of Drynariae Rhizoma, shared genes, and pathways. Python programming: we developed the software to show the precise relationship among bioactive ingredients, shared genes, and pathways for each CM, including Drynariae Rhizoma. CONCLUSIONS: This study could increase the precision of CM, and could provide a valuable and convenient software for searching precise relationships among bioactive ingredients, shared genes, and pathways.

Extracellular vesicles-encapsulated microRNA-29b-3p from bone marrow-derived mesenchymal stem cells promotes fracture healing via modulation of the PTEN/PI3K/AKT axis.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are well-established as vital regulators of fracture healing, whereas angiogenesis is one of the critical processes during the course of bone healing. Accordingly, the current study sought to determine the functions of microRNA (miR)-29b-3p from BM-MSCs-derived extracellular vesicles (EVs) on the angiogenesis of fracture healing via the PTEN/PI3K/AKT axis. Firstly, BM-MSCs-EVs were extracted and identified. The lentiviral protocol was adopted to construct miR-29b-3pKD-BMSCs or miR-negative control-BMSCs, which were then co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro to determine the roles of EVs-encapsulated miR-29b-3p on the proliferation, migration, and angiogenesis of HUVECs in vitro with the help of a CCK-8 assay, scratch test, and tube formation assay. Subsequent database prediction, luciferase activity assay, RT-qPCR, and Western blot assay findings identified the downstream target gene of miR-29b-3p, PTEN, and a signaling pathway, PI3K/AKT. Furthermore, the application of si-PTEN attenuated the effects induced by miR-29b-3pKD-EVs. Finally, a mouse model of femoral fracture was established with a locally instilled injection of equal volumes of BM-MSCs-EVs and miR-29b-3pKD-BM-MSCs-EVs. Notably, the mice treated with BMSC-EVs presented with enhanced neovascularization at the fracture site, in addition to increased bone volume (BV), BV/tissue volume, and mean bone mineral density; whereas miR-29b-3pKD-BMSCs-EVs-treated mice exhibited decreased vessel density with poor fracture healing capacity. Collectively, our findings elicited that BM-MSCs-EVs carrying miR-29b-3p were endocytosed by HUVECs, which consequently suppressed the PTEN expression and activated the PI3K/AKT pathway, thereby promoting HUVEC proliferation, migration, and angiogenesis, and ultimately facilitating fracture healing.

Robotic-assisted unicompartmental knee arthroplasty: a review.

PURPOSE: Presented here is an up-to-date review concerning robotic-assisted unicompartmental knee arthroplasty (rUKA), including its rationale, operative system, pros and cons. METHODS: We did a systematic research in electronic databases, including PubMed, Cochrane Library, Web of Science, and Embase up to March 30, 2020 to retrieve literature pertaining to rUKA. The search strategies "(robotic* AND knee arthroplasty OR knee replacement)" and "(knee arthroplasty OR knee replacement NOT total)" were used. Studies describing rUKA and clinical trials, dry bone or cadaveric researches regarding technologies, positioning, alignment, function, or survivorship of implants were included in this review. All retrieved studies were first browsed for eligibility on the basis of title and abstract, and the selected studies were further evaluated by reading full text for final inclusion. RESULTS: Robotic-assisted technology has been found to increase the accuracy of bone preparation and implant placement, reduce technical variability and outliers, and enhance reproduction of limb alignment. Additionally, early clinical outcomes were excellent, but mid-term follow-up showed no superiority in component survivorship. The potential drawbacks of the robotic-assisted technology include relatively-low time- and cost-effectiveness, development of some rUKA-related complications, and lack of support by high-quality literature. CONCLUSION: This review shows that rUKA can decrease the number of outliers concerning the optimal implant positioning and limb alignment. However, due to absence of extensive studies on clinical outcomes and long-term results, it remains unclear whether the improved component positioning translates to better clinical outcomes or long-term survivorship of the implant. Nevertheless, since an accurate implant position is presumably beneficial, robotic-assisted technology is worth recommendation in UKA.

[Advances on selective posterior rhizotomy for lower limb function in patients with cerebral palsy].

Cerebral palsy is a common clinical syndrome of neurological disability in childhood, which seriously affects the quality of life of children and their families, and brings a heavy economic burden to the society. Domestic and foreign scholars had a long history of the application of selective posterior rhizotomy for the treatment of spastic cerebral palsy or mixed cerebral palsy with limb paralysis. It is effective in improving the lower extremity spasm of patients with cerebral palsy, and there are few cases with recurrences. After rehabilitation therapy, the muscle strength of patients with cerebral palsy was significantly improved compared with the previous one. The range of motion was significantly improved after operation, and there is no rebounded in aspect of joint activety in the long-term follow-up. The overall gait of the patient was significant improved. The author thought that selective posterior rhizotomy is effective in improving the motor function of lower limbs in patients with cerebral palsy, and it is worth being spread. However, it has to follow the principle of selecting appropriate cases before surgery, precise operation during operation, and timely and effective rehabilitation treatment after surgery, in order to achieve a better curative effect.