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.

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.

[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.

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.

High failure rate after Beta-tricalcium phosphate grafting for the treatment of femoral head osteonecrosis: a retrospective analysis.

BACKGROUND: Non-vascularized bone grafting is a promising head-preserving technique for younger patients diagnosed as non-traumatic osteonecrosis of the femoral head (NONFH). Among the various types of bone grafting techniques, "light-bulb" procedure grafting with synthetic bone substitute is an attractive option. We aimed to assess the effectiveness of using beta-tricalcium phosphate (ß-TCP) for the treatment of pre-collapse and early post-collapse lesions NONFH. METHODS: From April 2010 to June 2014, 33 patients (47 hips) with NONFH were treated using the afore-mentioned technique. The clinical and radiological outcomes were recorded and compared statistically between pre- and post-operation. Harris hip score (HHS) was used to evaluate the clinical results, and Association Research Circulation Osseous (ARCO) stage was applied to assess the radiological outcomes. RESULTS: The 5-years survival rate of using ß-TCP grafting was accounting for 25.5%. HHS was decreased from 78.47 to 52.87 points, and a very significant worsening of radiological results were revealed (P <  0.05). Two hips collapsed more than 2 mm were awaiting for THA, and 33 of the 47 hips had converted to THAs in an average time to failure of 24.24 months postoperatively. Meanwhile, only 4 hips survived without collapse, and 8 hips collapsed less than 2 mm. After surgery, the time onset of head collapse was 3.65 months on average, and the first conversion to THA was performed at 5 months postoperative. CONCLUSIONS: Our results suggest that "light-bulb" procedure grafting with ß-TCP sticks presented with a high failure rate in the early postoperative period. It is not proposed for the treatment of pre-collapse and early post-collapse lesions NONFH.

[Role of JAK2/STAT3 signaling pathway in microglia activation after hypoxic-ischemic brain damage].

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal death and neurodevelopmental disorders in infants. Part of patients have different degrees of neurological sequelae, such as cerebral palsy, cognitive and motor function development disorders. Hypoxia-ischemia may activate JAK2/STAT3 signaling pathway, which leads to the microglia activation and neuroinflammation. Down-Regulating JAK2/STAT3 signaling pathway can inhibit microglia activation and regulate the inflammatory injury of nervous system. At present, the treatment of hypoxic ischemic encephalopathy is limited, so the study of regulatory mechanism about microglia activation has important value for the treatment of hypoxic-ischemic encephalopathy. This paper summarizes the role of JAK2/STAT3 signaling pathway in microglia activation and analyzes the relationship between them, in order to provide new ideas and strategies for treatment on hypoxic-ischemic encephalopathy.

[Clinical observation of selective posterior rhizotomy for improving spasticity and gross movement in patients with cerebral palsy].

OBJECTIVE: To explore the effect of selective lumbosacral posterior rhizotomy(SPR) on lower limb spasticity and gross motor function in patients with cerebral palsy. METHODS: From January 2018 to October 2018, 47 patients with cerebral palsy were treated with rehabilitation alone and SPR combined with rehabilitation. According to whether SPR was performed, the patients were divided into group A and group B. Group A was treated with rehabilitation combined with SPR at lumbosacral level, and group B was treated with rehabilitation alone. There were 23 cases in group A, including 15 males and 8 females, with an average age of (7.30±3.25) years old; 24 cases in group B, 13 males and 11 females, with an average age of (7.00±3.09) years old. Forty-seven patients were assessed with modified Ashworth(MAS) and Gross Motor Function Scale(GMFM-88 items) before and after treatment. The changes of MAS and GMFM-88 scores before and after treatment were compared to evaluate the degree of spasm and the improvement of gross motor function in the two groups. RESULTS: All 47 patients were followed up. At 6 months after treatment, the MAS classification of the two groups was significantly improved(P<0.05), and the improvement of group A was more obvious than that of group B(P<0.05). Six months after treatment, the D, E and total scores of GMFM-88 between two groups were significantly improved compared with those before operation(P<0.05). The improvement of D and total scores in group A was more obvious than that in group B. There was no significant difference in the improvement of area E between two groups. CONCLUSIONS: Selective posterior rhizotomy combined with rehabilitation can significantly improve the spastic state and gross motor function of lower limbs in children with cerebral palsy, and can effectively promote the reconstruction and recovery of motor function of lower limbs in children with cerebral palsy.

Tanshinone IIA improves functional recovery in spinal cord injury-induced lower urinary tract dysfunction.

Tanshinone IIA, extracted from Salvia miltiorrhiza Bunge, exerts neuroprotective effects through its anti-inflammatory, anti-oxidative and anti-apoptotic properties. This study intravenously injected tanshinone IIA 20 mg/kg into rat models of spinal cord injury for 7 consecutive days. Results showed that tanshinone IIA could reduce the inflammation, edema as well as compensatory thickening of the bladder tissue, improve urodynamic parameters, attenuate secondary injury, and promote spinal cord regeneration. The number of hypertrophic and apoptotic dorsal root ganglion (L6-S1) cells was less after treatment with tanshinone IIA. The effects of tanshinone IIA were similar to intravenous injection of 30 mg/kg methylprednisolone. These findings suggested that tanshinone IIA improved functional recovery after spinal cord injury-induced lower urinary tract dysfunction by remodeling the spinal pathway involved in lower urinary tract control.

Effects of Chinese herbal formula Erxian decoction for treating osteoporosis: a systematic review.

PURPOSE: The aim is to systematically assess the effectiveness and safety of Chinese herbal formula Erxian decoction (EXD) for treating osteoporosis. MATERIALS AND METHODS: Six databases were searched from inception through September 17, 2016, without language restriction. All randomized controlled trials of EXD for osteoporosis were included. One or more outcome measures including fracture, change in bone mineral density (BMD), pain symptom improvement, bone biochemical markers, quality of life, adverse event or adverse drug reaction were evaluated. Study selection, data extraction, quality assessment, and data analyses were conducted according to Cochrane standards. RESULTS: Eight trials including 644 patients investigated the effects of EXD in the treatment of osteoporosis. The methodological quality of the included trials was generally low. The meta-analysis from two trials showed favorable effects of EXD in improving BMD of lumbar spine (mean difference [MD]: 0.05 [0.03, 0.06]; I2=0%; P<0.00001) and BMD of femoral great trochanter (MD: 0.06 [0.02, 0.10]; I2=59%; P=0.005) compared with caltrate tablets. The other meta-analysis from two trials showed beneficial effects of EXD plus caltrate tablets and calcitriol in improving BMD of femoral neck (MD: 0.04 [0.00, 0.09]; I2=56%; P=0.04), the level of calcium (MD: 0.20 [0.15, 0.24]; I2=0%; P<0.00001), and phosphorus (MD: -0.28 [-0.39, -0.17]; I2=68%; P<0.00001) compared with caltrate tablets and calcitriol alone. The adverse drug reactions of EXD were mainly slight gastrointestinal symptoms. CONCLUSION: The study provides suggestive evidence of the superiority of EXD monotherapy or combination therapy over basic supplements for treating osteoporosis. However, the evidence remains weak. More rigorously designed and measured, randomized double-blind, placebo-controlled trials with larger sample size are needed to verify the current conclusions.

[Application of exercise therapy on rehabilitation after selective posterior rhizotomy (SPR) in children with cerebral palsy].

OBJECTIVE: To observe the clinical effect of exercise therapy on rehabilitation after selective posterior rhizotomy (SPR) in children with cerebral palsy, so as to provide reliable rehabilitation method for children with cerebral palsy. METHODS: Two hundred and twenty-six children with cerebral palsy were treated in the study during September 2003 to April 2007. All the patients were randomly divided into the training and control groups. There were 113 patients in the treatment group, including 66 males and 47 females, ranging in age from 3 to 8 years, with an average of (6.5 +/- 1.2) years, and the patients were treated with SPR as well as exercise therapy. Among 113 patients in the control group, 59 patients were male and 54 patients were female, ranging in age from 3 to 10 years, with an average of (6.9 +/- 1.5) years, and the patients were treated with SPR simply. Gross Motor Function Measure (GMFM), passive range of motion and muscle tension were used to evaluate therapeutic effects before and after treatment for both groups. RESULTS: All the patients were followed up for 6 to 18 months (averaged 8 months). There were significant improvements in training group compared with the control group on GMFM (134.29 +/- 46.43, P < 0.05), passive range of motion (dorsiflexion of the ankle 14.2 +/- 3.1 degree, P < 0.05) and muscle tension (1.27 +/- 0.42, P < 0.05). CONCLUSION: Physical therapy has more effective on rehabilitation after SPR for children with cerebral palsy, which can decrease spasticity and muscle tension and improve motor function.

[Treatment of equinovarus caused by cerebral palsy with neurotomy of muscular branch of tibial nerve].

OBJECTIVE: To evaluate clinical effect of neurotomy of muscular branch of tibial nerve for the treatment of equinovarus caused by cerebral palsy. METHODS: Fifty-two cases of equinovarus caused by cerebral palsy were treated with neurotomy of muscular branch of tibial nerve. The male was 33 (38 feet) and the female 19 (26 feet) with the average age of 7.8 years old (from 6 to 10). The muscular tension according to Ashworsh grade, 34 cases were grade III and 18 cases were grade IV. The ankle clonus was positive in 42 cases. RESULTS: All cases were followed up for 1-3 years with the average of 2.6 years. The spastic gait of cases had obviously improved and abnormity had no recurred. According to corrective degree of abnormity and satisfactive condition of patients, evaluation of the effect were excellent in 32 cases, good in 14, poor in 6. CONCLUSION: Neurotomy of muscular branch of tibial nerve is the safe and effective method for the treatment of equinovarus caused by cerebral palsy.