Efficacy of growth factor gene-modified stem cells for motor function after spinal cord injury in rodents: a systematic review and meta­analysis.

The efficacy of growth factor gene-modified stem cells in treating spinal cord injury (SCI) remains unclear. This study aims to evaluate the effectiveness of growth factor gene-modified stem cells in restoring motor function after SCI. Two reviewers searched four databases, including PubMed, Embase, Web of Science, and Scopus, to identify relevant records. Studies on rodents assessing the efficacy of transplanting growth factor gene-modified stem cells in restoring motor function after SCI were included. The results were reported using the standardized mean difference (SMD) with a 95% confidence interval (95% CI). Analyses showed that growth factor gene-modified stem cell transplantation improved motor function recovery in rodents with SCI compared to the untreated (SMD = 3.98, 95% CI 3.26-4.70, I2 = 86.8%, P < 0.0001) and stem cell (SMD = 2.53, 95% CI 1.93-3.13, I2 = 86.9%, P < 0.0001) groups. Using growth factor gene-modified neural stem/histone cells enhanced treatment efficacy. In addition, the effectiveness increased when viral vectors were employed for gene modification and high transplantation doses were administered during the subacute phase. Stem cells derived from the human umbilical cord exhibited an advantage in motor function recovery. However, the transplantation of growth factor gene-modified stem cells did not significantly improve motor function in male rodents (P = 0.136). Transplantation of growth factor gene-modified stem cells improved motor function in rodents after SCI, but claims of enhanced efficacy should be approached with caution. The safety of gene modification remains a significant concern, requiring additional efforts to enhance its clinical translatability.

Effect of Yiyuan moxibustion on urodynamics and TRPV4/ATP/P2X5 signal pathway of bladder tissue in rats with neurogenic bladder after sacral cord injury. / ç›Šå ƒç¸å¯¹éª¶é«“æŸä¼¤åŽç¥žç»æºæ€§è†€èƒ±å¤§é¼ å°¿æµåŠ¨åŠ›å­¦åŠè†€èƒ±ç»„ç»‡TRPV4/ATP/P2X5信号通路的影响.

OBJECTIVES: To observe the effect of Yiyuan moxibustion on urodynamics and the expressions of transient receptor potential vanilloid 4 (TRPV4), adenosine triphosphate (ATP), tyrosine protein kinase KIT (C-Kit) and adenosine triphosphate receptor P2X5 in bladder tissue of rats with detrusor reflex-free neurogenic bladder (NB) after sacral cord injury (SCI), so as to explore its mechanism in promoting the recovery of urination function of NB rats. METHODS: Female SD rats were randomly divided into sham operation, model, Yiyuan moxibustion, Yiyuan moxibustion+inhibitor (combination) and inhibitor groups, with 12 rats in each group. The model of detruser reflex-free NB after sacral SCI was established by modified Hassan Shaker spinal cord transection method. The behavioral score of Basso Beasttie Bresnahan (BBB) and urodynamic indexes were used to evaluate the model of rats after operation. Fifteen days after modeling, Yiyuan moxibustion was applied to "Shenque" (CV8) and "Guanyuan" (CV4) for 20 min, once daily for 14 days. Rats of the inhibitor and combination groups were given intravesical instillation of HC067047 (1 mL, 1 µmol/L, 30 min). After the interventions, urodynamics was used to evaluate the bladder function of rats. HE staining was used to observe the morphology of bladder tissue. ATP content in bladder tissue was detected by colorimetric method. The positive expression rates of C-Kit and their receptor P2X5 in bladder tissue were observed by immunofluorescence double labeling method, and TRPV4, C-Kit, and P2X5 protein expression levels in bladder tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the maximum bladder capacity and bladder compliance of rats in the model group were increased (P<0.01), the leak point pressure, ATP content, the possitive expression rates of C-Kit and P2X5, and the protein expression levels of TRPV4, C-Kit, P2X5 in bladder tissue were decreased (P<0.01). In comparison with the model and combination groups, the Yiyuan moxibustion group showed a decrease in maximum bladder capacity and bladder compliance (P<0.01), an increase in leakage point pressure, ATP content, the possitive expression rates of C-Kit and P2X5, and TRPV4, C-Kit, and P2X5 protein expression levels (P<0.01, P<0.05)；However, these indicators showed opposite trends in the inhibitor group (P<0.01, P<0.05). CONCLUSIONS: Yiyuan moxibustion can improve the urodynamics and bladder function in rats with bladder detrusor nonreflective after SCI, which may be related to its effect in activating the TRPV4 channel in bladder tissue, promoting the release of ATP from bladder epithelium, thus increasing the expression of bladder Cajal interstitial cells and their purinergic P2X5 receptors.

[Efficacy differences between electroacupuncture and moxibustion for neurogenic bladder after spinal cord injury: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between electroacupuncture(EA) and moxibustion for neurogenic bladder (NB) after spinal cord injury (SCI). METHODS: One hundred and twenty patients with NB after SCI were randomly divided into an EA group, a moxibustion group, and an intermittent catheterization group, with 40 patients in each group. The patients in the intermittent catheterization group were treated with routine treatment and intermittent catheterization, while the patients in the EA group and the moxibustion group were treated with additional treatments of EA (discontinuous wave, with a frequency of 1.3-1.6 Hz, and intensity based on patient tolerance) and moxibustion, respectively. The acupoints used in both groups were Zhongji (CV 3) and Guanyuan (CV 4), bilateral Zusanli (ST 36), Yinlingquan (SP 9), and Baliao points. Each session lasted for 30 min, once daily, six times a week, for a total of six weeks.The maximum bladder capacity (MBC), residual urine vdume (RUV), detrusor pressure (Pdet) during the filling phase, bladder compliance (BC), maximum renal pelvis separation width of both kidneys, urine white blood cell count, TCM syndrome score, and World Health Organization quality of life assessment-BREF (WHOQOL-BREF) score were compared before and after treatment in the 3 groups. The number of patients in each group who achieved bladder functional balance was recorded, and the clinical efficacy was assessed after treatment. RESULTS: After treatment, the MBC, Pdet, BC, and WHOQOL-BREF scores in the EA group and the moxibustion group were increased (P<0.05), while the RUV, maximum renal pelvis separation width of both kidneys, urine white blood cell count, and TCM syndrome scores were decreased (P<0.05, P<0.01). In the intermittent catheterization group, MBC, RUV, maximum renal pelvis separation width of both kidneys, and urine white blood cell count were decreased (P<0.05), while BC and WHOQOL-BREF score were increased (P<0.05) after treatment. After treatment, the MBC, Pdet, BC, and WHOQOL-BREF scores in the EA group and the moxibustion group were higher than those in the intermittent catheterization group (P<0.05), while the RUV and TCM syndrome scores were lower than those in the intermittent catheterization group (P<0.05). Moreover, after treatment, the MBC and Pdet in the moxibustion group were higher than those in the EA group (P<0.05), while the RUV, maximum renal pelvis separation width of both kidneys, and TCM syndrome score in the EA group were lower than those in the moxibustion group (P<0.05). The number of patients who achieved bladder functional balance after treatment in the EA group and the moxibustion group was higher than that in the intermittent catheterization group (P<0.05). The cured and effective rate was 85.0% (34/40) in the EA group and 82.5% (33/40) in the moxibustion group, which were both higher than 65.0% (26/40) in the intermittent catheterization group (P<0.05), there was no significant difference between the EA group and the moxibustion group (P>0.05). CONCLUSION: EA and moxibustion could effectively improve the functional state of bladder in patients with NB after SCI. EA is more effective in reducing residual urine volume and excessive activity of the urethral sphincter, and relieving TCM syndromes, while moxibustion is more effective in increasing the pressure of the detrusor during the filling period and establishing the detrusor reflex.

[Effects of eye acupuncture on motor evoked potential and somatosensory evoked potential in patients with incomplete spinal cord injury based on neuroelectrophysiological technology].

OBJECTIVE: To observe the effects of eye acupuncture on motor evoked potential (MEP) and somatosensory evoked potential (SEP) in the patients with incomplete spinal cord injury so as to evaluate its clinical efficacy. METHODS: According to the random number table, 90 patients were divided into exercise therapy group, eye acupuncture group and eye acupuncture combined exercise therapy group (combined treatment group), 30 cases in each. In the exercise therapy group, patients were treated with the routine exercise and occupational therapy. Patients of the eye acupuncture group were treated with eye acupuncture at upper jiao region, lower jiao region, liver region and kidney region bilaterally. Patients of the combined treatment group were given the routine exercise and occupational therapy combined with eye acupuncture. All the treatments were conducted once daily, 7 days as one treatment course for 4 treatment courses. Before treatment and 4 weeks after treatment, the motor function, light touch sensation and pinprick sensation, injury grade and clinical efficacy were assessed separately, using the criteria developed by the American Spinal Injury Association. The modified Barthel index(MBI) was adopted to evaluate the activities of daily livings. By monitoring SEP and MEP, the neurophysiological conditions were assessed for spinal cord injury. RESULTS: The total effective rate was 56.7% (17/30), 66.7% (20/30) and 90.0% (27/30) in the exercise therapy group, the eye acupuncture group and the combined treatment group, respectively. The total effective rate in the combined treatment group was higher than those in the other two groups (P<0.05). Compared with those before treatment, the scores of motor function, light tough sensation and pinprick sensation were all increased after treatment in three groups (P<0.05), MBI score was increased in both the exercise therapy group and the combined treatment group (P<0.05), and the latency of SEP (N11, N20, N23, P38) and the Cortical (hand region), Csp, Cortical (leg region) and Lsp of MEP were all shortened in the three groups separately (P<0.05). After treatment, compared with the exercise therapy group, the score of motor function was increased (P<0.05), MBI score decreased (P<0.05) and MEP latency shortened (P<0.05) in the eye acupuncture group. After treatment, compared with the exercise therapy group and the eye acupuncture group, the scores of motor function, light touch sensation and pinprick sensation, as well as MBI score were all increased (P<0.05), and the latency of SEP (N11,N20,N23,P38) and MEP shortened (P<0.05) in the combined treatment group. CONCLUSION: In treatment of incomplete spinal cord injury, eye acupuncture combined with exercise therapy can significantly increase the excitability of sensory and motor nerve conduction in the spinal cord and cerebral cortex of patients, effectively promote the recovery of patients' motor and sensory function and improve the activities of daily living.

[Effect of moxibustion on M2 and P2X3 receptors of bladder tissue in rats with neurogenic bladder of detrusor areflexia after lumbar-sacral spinal cord injury].

OBJECTIVE: To observe the effect of moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) on acetylcholine (Ach), adenosine triphosphate (ATP) and muscarinic-type choline receptor (M2) and purine receptor P2X3 in bladder tissue in the rats with neurogenic bladder (NB) of detrusor areflexia after lumbar-sacral spinal cord injury and explore the underlying mechanism of moxibustion for promoting detrusor contraction. METHODS: Sixty SD rats were randomly divided into a model preparation group (n=45) and a sham-operation group (n=15). In the model preparation group, the modified Hassan Shaker spinal cord transection method was used to prepare the model of NB. In the sham-operation group, the spinal cord transection was not exerted except laminectomy and spinal cord exposure. Among the rats with successfully modeled, 30 rats were selected and divided randomly into a model group and a moxibustion group, with 15 rats in each one. On the 15th day after the operation, moxibustion was applied at "Guanyuan" (CV 4) and "Shenque" (CV 8) in the moxibustion group, 10 min at each acupoint, once a day. The consecutive 7-day treatment was as one course and the intervention for 2 courses was required. Urodynamic test was adopted to evaluate bladder function in rats. Using HE staining, the morphological changes in bladder tissue were observed. The content of Ach and ATP in bladder tissue was measured with biochemical method, and the protein and mRNA expression levels of M2 and P2X3 receptors in bladder tissue were detected with Western blot and real-time fluorescence quantification PCR method. RESULTS: Compared with the sham-operation group, the maximum bladder capacity, leakage point pressure and bladder compliance were increased in the rats of the model group (P<0.05). Compared with the model group, the maximum bladder capacity, the leakage point pressure and bladder compliance were decreased in the rats of the moxibustion group (P<0.05). In the model group, the detrusor fibres were arranged irregularly, bladder epithelial tissues were not tightly connected and cell arrangement was disordered, combined with a large number of vacuolar cells. In the moxibustion group, compared with the model group, the detrusor fibres were arranged regularly, bladder epithelial cells were well distributed and vacuolar cells were reduced. Compared with the sham-operation group, the content of Ach and ATP in bladder tissue was decreased (P<0.05), the protein and mRNA expression levels of M2 and P2X3 receptors were reduced (P<0.05) in the model group. In the moxibustion group, the content of Ach and ATP in bladder tissue was increased (P<0.05) and the protein and mRNA expression levels of M2 and P2X3 receptors were increased (P<0.05) as compared with the model group. CONCLUSION: Moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) may effectively improve bladder function in the rats with NB of detrusor areflexia after lumbar-sacral spinal cord injury and its underlying mechanism is related to promoting the release of Ach and up-regulating the expression of M2 receptor, thereby enhancing the release of ATP and increasing the expression of P2X3 receptor. Eventually, detrusor contraction is improved.

Preliminary study on pathogenesis of bronchial asthma in children.

BACKGROUND: The etiology and pathogenesis of bronchial asthma remain unclear. This study is to investigate the risk factors related to bronchial asthma onset in children from genetics and immunology and preliminarily reveal the pathogenesis of bronchial asthma in children. METHODS: Real-time quantitative PCR was adopted to detect the expression level of TRPV1 gene and mRNA and enzyme-linked immunosorbent assay method to the total immunoglobulin E level and levels of IL-4, IL-5, and IFN-γ in serum in peripheral venous blood for children in two groups. Logistic regression analysis was applied to analyze the most essential factors inducing bronchial asthma in children. RESULTS: The mRNA level of TRPV1 in peripheral blood in the case group was higher than that in the control group (P < 0.01). The levels of IL-4, IL-5, and eosinophils in serum in the case group were markedly higher than those in the control group (P < 0.01), while IFN-γ level in the case group was lower than that in the control group (P < 0.01). The results of logistic regression analysis indicated that TRPV1 expression level, IL-4 level, and rs4790522 site mutation were the main risk factors inducing bronchial asthma in children. CONCLUSION: The levels of TRPV1 gene expression and Th1/Th2 cytokines have a close relationship with asthma onset in children, which provides theoretical evidences for molecular targeted treatment in children with bronchial asthma.

[Clinical observation on moxibustion combined with intermittent urethral catheterization for treatment of neurogenic vesical dysfunction].

OBJECTIVE: To observe the effect of moxibustion combined with intermittent urethral catheterization on vesical function in the patient of neurogenic vesical dysfunction. METHODS: Seventy-six cases were randomly divided into an observation group and a control group, 38 cases in each group. The control group was treated with routine intermittent urethral catheterization and the observation group with the intermittent urethral catheterization and moxibustion on Guanyuan (CV 4), Mingmen (GV 4), Zusanli (ST 36), etc. Changes of residual urine volume, white cell count and the balance state of the urinary bladder were selected as the indexes of therapeutic effect and the therapeutic effects were compared between the two groups. RESULTS: The total effective rate was 97.4% in the observation group and 79.0% in the control group with a significant difference between the two groups (P < 0.05); after treatment, there were significant differences between the two groups in the residual urine volume, the bladder volume and the case numbers reaching to the functional balance state of bladder (all P < 0.05), and there was no significant difference between the two groups in white cell count change (P > 0.05). CONCLUSION: Moxibustion combined with intermittent urethral catheterization can significantly improve vesical function in the patient of neurogenic vesical dysfunction, reducing residual urine volume, increasing volume of bladder, promoting the balance state of vesical function, but it is basically same as intermittent urethral catheterization in prevention of urinary infection and therapeutic effect.