Protective effect and mechanism of acellular nerve allografts combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury / 解剖学报

Objective To investigate the protective effect and mechanism of acellular nerve allografts(ANA)combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury(SNI).Methods Totally 50 male adult SD rats were randomly selected for this experiment.Ten rats were prepared for the ANA.Forty male SD rats were randomly divided into normal group,model group,ANA group and combinational group,with 10 rats in each group.The SNI model was established by cutting off the nerves 10 mm at the 5 mm on the inferior border of piriformis after separating the right sciatic nerves.The rats in the ANA group were bridged with ANA to the two broken ends of injured nerves.The rats in the combinational group were treated with electroacupuncture 2 days after ANA bridging,Huantiao(GB30)and Yanglingquan(GB34)were performed as the acupuncture points,each electroacupuncture lasted 15 minutes and 7 days as a course of treatment,4 courses in all.Sciatic nerve conduction velocity was measured by electrophysiology to evaluate the regeneration of damaged axons.Morphology of spinal ganglia was observed by Nissl staining.The expression of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected by Western blotting and immunofluorescent staining.Results Compared with the normal group,the sciatic nerve conduction velocity in model group decreased significantly(P<0.01),Nissl bodies in neurons of spinal ganglia were swollen and dissolved,with incomplete structure and the number decreased dramatically(P<0.01),while the level of NGF and BDNF also decreased significantly(P<0.01).Compared with the model group,the sciatic nerve conduction velocity in ANA and combinational groups strongly increased(P<0.01),the damage of Nissl bodies in neurons of spinal ganglia reduced and the number obviously increased(P<0.01),the level of NGF and BDNF increased considerably(P<0.01).Compared with the ANA group,the sciatic nerve conduction velocity in combinational group increased significantly(P<0.01),the morphology of Nissl bodies in neurons of spinal ganglia were more regular and the number increased(P<0.01),moreover,the level of NGF also increased significantly(P<0.01).Conclusion ANA combined with electroacupuncture can enhance the sciatic nerve conduction velocity,improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of NGF and BDNF proteins,especially the expression of NGF protein.

The role of neurotrophic factors in the effects of transcranial direct current stimulation among ischemic stroke survivors / 中华物理医学与康复杂志

Objective:To explore the impact of transcranial direct current stimulation (tDCS) on ischemic stroke survivors in terms of its association with neurotrophic factors in a person′s peripheral blood.Methods:Forty ischemic stroke survivors were randomly allocated into a control group and a treatment group, each of 20. Both groups were given routine medication and rehabilitation, while the treatment group was additionally provided with 20 minutes of tDCS daily at an intensity of 2.0mA. There were 14 sessions over two weeks. The control group received sham stimulation. Before and after the experiment, both groups were assessed using the Modified Barthel Index (MBI), the Mini-mental State Examination (MMSE), the Hamilton Depression Scale (HAMD), and the Self-rated Depression Scale (SDS). The concentrations of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the subjects′ peripheral blood were quantified using enzyme-linked immunosorbent assays (ELISAs).Results:Baseline comparisons revealed no significant disparities between the two groups in their average MBI, MMSE, HAMD, or SDS results, nor in their average BDNF or NGF levels. Post-treatment assessments indicated significant enhancements across these metrics within both groups. Notably, the treatment group then exhibited average MBI and MMSE scores superior to those of the control group, alongside a lower average HAMD score. Furthermore, elevated levels of BDNF [(108.20±36.96)pg/ml] and NGF [(2.90±1.03)pg/ml] were observed in the treatment group.Conclusion:tDCS appears to significantly enhance cognition, minimize symptoms of depression, and augment self-care ability after an ischemic stroke. These benefits are possibly mediated through the increase of neurotrophic factor levels.

Research Progress on NGF and TrkA Receptors in Pediatric Overactive Bladder / 中山大学学报(医学科学版)

Nerve growth factor （NGF） has been widely studied because it plays an important role in the survival， growth and differentiation of nerve cells. It is distributed throughout the body and plays different pathophysiological roles according to the combined receptors. TrkA is its high affinity receptor， and many studies have shown that NGF plays different roles according to its downstream signal transduction pathways after combining with it. After combining with NGF， it also has a cross-effect on other signal transduction pathways that occur in the body. This paper reviews the signal transduction pathways combined with NGF and TrkA from different disease symptoms， so as to explore the role of NGF/TrkA signal pathways in children with overactive bladder.

Evaluation of the efficacy of cenegermin in the treatment of neurotrophic keratitis / 中华实验眼科杂志

Objective:To explore the clinical efficacy of cenegermin in the treatment of neurotrophic keratitis (NK).Methods:An observational case series study was adopted.Twenty-two patients (26 eyes) with moderate and severe NK diagnosed in Xi'an No.1 Hospital from June to November 2021 were collected and locally treated with cenegermin eye drop.After the corneal epithelium of the affected eye healed, the treatment ended.Relevant index data of patients before and after treatment were obtained through eye examination.The main indicators were the fiber length of corneal sensation measured by Cochet-Bonnet aesthesiometer, the morphological and quantitative indexes of corneal nerves by in vivo confocal microscopy, including the density of corneal nerve fibers and the number of nerve bifurcation points, and tear meniscus height measured by Keratograph Ocular Surface Analyzer.The secondary indicators were best corrected visual acuity (BCVA) and adverse reactions.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xi'an No.1 Hospital (No.2021-11). Written informed consent was obtained from each subject. Results:The average treatment duration of patients receiving cenegermin was (4.42±1.86) weeks.After treatment, the corneal epithelial defect of moderate and severe patients healed completely.After treatment, the fiber length of sensation of corneal epithelial defect area and superior defect area were improved, the differences were statistically significant ( Z=-2.45, -3.22; both at P<0.05). There was no significant difference in corneal sensation in inferior, nasal and temporal of corneal epithelial defect area between before and after treatment ( Z=-1.89, -0.31, -1.86; all at P>0.05). After treatment, the average corneal nerve fiber density and the number of corneal nerve fiber bifurcation points in the affected eyes were significantly increased ( Z=-3.95, -3.48; both at P<0.01). There was no significant difference in the tear meniscus height between before and after treatment ( Z=-1.58, P=0.11). After treatment, the BCVA (LogMAR) of patients was 0.22(0.10, 0.40), which was higher than 0.52(0.30, 0.70) at baseline, and the difference was statistically significant ( Z=-3.63, P<0.01). During the treatment of cenegermin eye drops, transient pain occurred in 3 eyes, and intraocular pressure increased in 1 eye, which all returned to normal after symptomatic treatment. Conclusions:Topical application of cenegermin can repair corneal nerve morphology and function in patients with NK.

Correlation analysis of miR-4500,NGF expressions with preoperative magnetic resonance signs in breast cancer / 局解手术学杂志

Objective To analyze the correlations of the expressions of miR-4500 and nerve growth factor(NGF)in breast cancer patients with preoperative magnetic resonance(MR)signs.Methods A total of 105 patients with breast cancer admitted to our hospital were selected,the mRNA expression levels of miR-4500 and NGF in breast cancer tissues and adjacent tissues of patients were detected by qRT-PCR,and the positive expression rates of NGF in breast cancer tissues and adjacent tissues were determined by immunohistochemistry method.The correlations of the expressions of miR-4500 and NGF in breast cancer tissues with clinicopathological features and MR signs of patients were analyzed.The targeting relationship between miR-4500 and NGF was predicted by the bioinformatics website,and the correla-tion between the expressions of the two was analyzed.Results Compared with the adjacent tissues,the expression level of miR-4500 in breast cancer tissue decreased(P<0.05),while the level of NGF mRNA and the positive expression rate of NGF increased(P<0.05).There was no significant difference in age,pathological type,tumor classification,parenchymal background,apparent diffusion coefficient or enhancement curve among different expressions of miR-4500 and NGF(P>0.05).The histological grade,lymph node metastasis,tumor diameter,tumor morphology,ring-like enhancement,and peritu-moral brain edema were related to the expressions of miR-4500 and NGF(P<0.05).The bioinformatics website prediction showed that miR-4500 and NGF had binding sites,and the expressions of miR-4500 and NGF mRNA in breast cancer tissues were negatively correlated(r=-0.576,P<0.05).Conclusion The expression of miR-4500 in breast cancer tissue is low,and the expression of NGF is high,which are correlated with the preoperative MR signs in patients,providing a molecu-lar basis for MR signs.

Effect of nerve growth factor on elderly degenerative knee osteoarthritis pain / 中国骨伤

OBJECTIVE@#To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model.@*METHODS@#Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA, and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling, and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment, 1 and 2 weeks after treatment. Three weeks after treatment, right dorsal root ganglia (DRG) were excised on L4-L6 level, immunostained for calcitonin gene-related peptide (CGRP), and the number of DRGS was counted.@*RESULTS@#In terms of gait analysis using cat track system, duty cycle, swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group, duty cycle and swing speed of treatment group were significantly improved (P<0.05), and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated, and differences were statistically significant compared with treatment group (P<0.05).@*CONCLUSION@#Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.

Rita Levi-Montalcini: the neurologist who challenged fascism / Rita Levi-Montalcini: a neurologista que desafiou o fascismo

Abstract Rita Levi-Montalcini was a researcher in the field of neuroscience, Italian and Jewish in origin, who discovered the nerve growth factor and rightfully earned the 1986 Nobel Prize in Physiology or Medicine, alongside her collaborator Stanley Cohen. She was persecuted by the fascist dictatorship of Benito Mussolini and experienced gender and religious discrimination throughout her entire life. Despite these obstacles, she carried out her activities with diligence and grace, becoming a role model in the field. This paper reviews the life and career of Rita Levi-Montalcini.

Resumo Rita Levi-Montalcini foi uma pesquisadora no campo das neurociências, de origem Italiana e Judia, que descobriu o fator de crescimento neural e merecidamente recebeu o Prêmio Nobel de Fisiologia ou Medicina de 1986, em conjunto ao seu colaborador Stanley Cohen. Ela foi perseguida pela ditadura fascista de Benito Mussolini, e sofreu discriminação de gênero e religião durante sua vida inteira. A despeito desses obstáculos, sempre exerceu suas atividades com diligência e graça, tornando-se um exemplo nesse campo de estudo. O presente artigo faz uma revisão sobre a vida e carreira de Rita Levi-Montalcini.

Factor de crecimiento nervioso en neuropatía óptica traumática

La neuropatía óptica traumática (TON) es una entidad asociada al trauma facial y craneal, y constituye una causa importante para el desarrollo de la ceguera; es una complicación grave del trauma craneofacial que daña directa (dTON) o indirectamente (iTON) el nervio óptico (ON), cuya incidencia global de TON es de 0,7 a 2,5 %. El objetivo del presente estudio es presentar el caso de un paciente que padecía de TON y a la vez de una afección bilateral asimétrica, y que fue tratado con el factor de crecimiento nervioso mNGF. Este medicamento fue el primero que se descubrió y demostró eficacia en mantener la supervivencia de las neuronas centrales y periféricas y facilitar su crecimiento, diferenciación y regeneración. Se trata de un paciente de 13 años, sexo masculino, quien acude a la emergencia del Instituto Nacional de Ciencias Neurológicas y, posteriormente, su seguimiento clínico es por consultorio de Neuroftalmología, con un cuadro de amaurosis traumática, producto de un traumatismo encéfalo craneano con hematoma epidural, que recibió dos ciclos de tratamiento con factor de crecimiento nervioso. Luego del primer ciclo de tratamiento, se evidenció hiporreactividad de ambos ojos; al finalizar el segundo ciclo de tratamiento, se observó un aumento considerable de la agudeza visual. El mNGF está aprobado y comercializado en China desde el año 2015 y es un producto que ha demostrado su eficacia y seguridad en varios ensayos clínicos. Por ello, el presente estudio pretende convertir al factor de crecimiento nervioso como el tratamiento prometedor de iTON; en ese sentido, se necesita de amplias investigaciones clínicas en este caso en particular.

Traumatic optic neuropathy (TON) is an entity associated with facial and cranial trauma, and a leading cause of blindness. It is a severe complication of craniofacial trauma that directly (DTON) or indirectly (ITON) damages the optic nerve (ON) and whose global incidence is 0.7 to 2.5 %. The objective of this study is to present the case of a patient who suffered from TON and, at the same time, an asymmetrical bilateral condition, and was treated with nerve growth factor (NGF). This drug was the first to be discovered and demonstrate efficacy in maintaining the survival of central and peripheral neurons and facilitating their growth, differentiation and regeneration. A 13-year-old male patient attended the emergency room of Instituto Nacional de Ciencias Neurológicas and was later followed up at the Neuro-Ophthalmology Service. He was diagnosed with post-traumatic amaurosis caused by traumatic brain injury and epidural hematoma, and received two treatment cycles of NGF. After the first treatment cycle, hyporeactivity of both eyes occurred. And, at the end of the second treatment cycle, visual acuity improved significantly. NGF has been approved and marketed in China since 2015 and is a product that has demonstrated its efficacy and safety in several clinical trials. Therefore, this study aims to make NGF a promising ITON treatment; in that sense, further clinical research is needed in this particular case.

Efficacy and mechanism of scalp acupuncture for spastic cerebral palsy / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of scalp acupuncture for spastic cerebral palsy (CP), and to explore its possible mechanism based on brain white matter fiber bundles, nerve growth related proteins and inflammatory cytokines.@*METHODS@#A total of 90 children with spastic CP were randomly divided into a scalp acupuncture group and a sham scalp acupuncture group, 45 cases in each group. The children in the two groups were treated with conventional comprehensive rehabilitation treatment. The children in the scalp acupuncture group were treated with scalp acupuncture at the parietal temporal anterior oblique line, parietal temporal posterior oblique line on the affected side, and parietal midline. The children in the sham scalp acupuncture group were treated with scalp acupuncture at 1 cun next to the above point lines. The needles were kept for 30 min, once a day, 5 days a week, for 12 weeks. Before and after treatment, the diffusion tensor imaging (DTI) indexes of magnetic resonance (FA values of corticospinal tract [CST], anterior limb of internal capsule [ICAL], posterior limb of internal capsule [ICPL], genu of internal capsule [ICGL], genu of corpus callosum [GCC], body of corpus callosum [BCC] and splenium of corpus callosum [SCC]), serum levels of nerve growth related proteins (neuron-specific enolase [NSE], glial fibrillary acidic protein [GFAP], myelin basic protein [MBP], ubiquitin carboxy terminal hydrolase-L1 [UCH-L1]) and inflammatory cytokines (interleukin 33 [IL-33], tumor necrosis factor α [TNF-α]), cerebral hemodynamic indexes (mean blood flow velocity [Vm], systolic peak flow velocity [Vs] and resistance index [RI], pulsatility index [PI] of cerebral artery), surface electromyography (SEMG) signal indexes (root mean square [RMS] values of rectus femoris, hamstring muscles, gastrocnemius muscles, tibialis anterior muscles), gross motor function measure-88 (GMFM-88) score, modified Ashworth scale (MAS) score, ability of daily living (ADL) score were observed in the two groups. The clinical effect of the two groups was compared.@*RESULTS@#After treatment, the FA value of each fiber bundle, Vm, Vs, GMFM-88 scores and ADL scores in the two groups were higher than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were higher than those in the sham scalp acupuncture group (P<0.05). After treatment, the serum levels of NSE, GFAP, MBP, UCH-L1, IL-33, TNF-α as well as RI, PI, MAS scores and RMS values of each muscle were lower than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were lower than those in the sham scalp acupuncture group (P<0.05). The total effective rate was 95.6% (43/45) in the scalp acupuncture group, which was higher than 82.2% (37/45) in the sham scalp acupuncture group (P<0.05).@*CONCLUSION@#Scalp acupuncture could effectively treat spastic CP, improve the cerebral hemodynamics and gross motor function, reduce muscle tension and spasticity, and improve the ability of daily life. The mechanism may be related to repairing the white matter fiber bundles and regulating the levels of nerve growth related proteins and inflammatory cytokines.

Mouse nerve growth factor combined with rehabilitation in the treatment of global developmental delay: a prospective multicenter clinical randomized controlled trial / 中华实用儿科临床杂志

Objective:To observe the clinical efficacy of mouse nerve growth factor (mNGF) combined with rehabilitation on children with global developmental delay(GDD).Methods:It was a prospective multicenter clinical randomized controlled trial (RCT) involving 120 children with GDD admitted to 5 hospitals in China from May 2020 to January 2022.They were randomly divided into mNGF group and conventional rehabilitation group using block randomization method.All children were managed by standardized rehabilitation after recruitment, and those in the mNGF group were additionally given mNGF injections.All subjects were surveyed using the Gesell Development Diagnosis Schedules(GDDS) at baseline, 90 days and 120 days after treatment, and their developmental quotient (DQ) was recorded.Clinical efficacy was analyzed by the paired t-test, rank sum test and Chi- squared test. Results:After 90 days of treatment and the continuous follow-up to 120 days, the increases in the DQ of gross motor (7.520±13.900 vs.0.450±11.459), fine motor (7.800±15.346 vs.1.250±11.581), adaptive behavior (7.730±13.428 vs.2.100±12.022) and personal-social behavior (6.780±11.651 vs.1.780±10.120) than baseline were significantly higher in mNGF group than those of conventional rehabilitation group (all P<0.05). Serious adverse events and important drug-related medical events were not reported. Conclusions:mNGF combined with rehabilitation effectively enhances the development levels of gross motor, fine motor, adaptive behavior and personal-social behavior, and continuously improves the condition of GDD in children with a high safety.

Expression and Clinical Significance of NGF and Syncytin - 1 in Pregnant Women with Severe Preeclampsia / 医学研究杂志

Objective To study the expression levels and clinical significance of nerve growth factor(NGF)and Syncytin-1 in ser-um and placental tissues of pregnant women with severe preeclampsia(SPE).Methods A total of 90 pregnant women who underwent ce-sarean delivery in the Department of Obstetrics,the Affiliated Hospital of Xuzhou Medical University in December 2021 to June 2022 were selected,and they were divided into 30 cases of early-onset SPE(early-onset group),30 cases of late-onset SPE(late-onset group),and 30 cases of normal women in the same period(control group).The maternal blood and placental tissues of the three groups were collected,and the expression levels of NGF and Syncytin-1 in each group were detected by enzyme-linked immunosorbent assay(ELISA)and immunohistochemical(IHC)staining,and their clinical significance was analyzed.Results The results of the ELISA showed that compared with healthy pregnant women in the third trimester,the expression of NGF and Syncytin-1 in the serum of pregnant women with SPE was reduced,and the early-onset group was lower than those in the late-onset group(P<0.05).The results of IHC staining showed that compared with healthy pregnant women in the third trimester,the expression levels of NGF and Syncytin-1 in pla-cental tissues were reduced in pregnant women with SPE,early-onset group was lower than those in the late-onset group(P<0.05).Conclusion The expression of NGF and Syncytin-1 in serum and placental tissues of the three groups of pregnant women was succes-sively reduced,and the expression was successively reduced in normal pregnant women,late-onset SPE and early-onset SPE,which may be involved in the occurrence and development of SPE by affecting the normal development of the placenta.

Effects of Cistanches Herba polysaccharides on rats with constipation-predominant irritable bowel syndrome / 中国药房

OBJECTIVE To investigate the effects of Cistanches Herba polysaccharides （abbreviated as CDPS） on rats with constipation-predominant irritable bowel syndrome （IBS-C）. METHODS SD rats were divided into control group （20 rats） and modeling group. The modeling group was given 2 mL of normal saline at 0-4 ℃ intragastrically （once a day， for 14 consecutive days） to induce IBS-C model. After modeling， model rats were grouped into model group， positive control group （mosapride citrate， 1.35 mg/kg）， CDPS low-dose group （50 mg/kg） and CDPS high-dose group （100 mg/kg）， with 20 rats in each group. Administration groups were given corresponding drug solution intragastrically， and control group and model group were given a constant volume of water intragastrically， once a day， for 28 consecutive days. The fecal water content， serum content of 5-hydroxytryptamine （5-HT）， and charcoal powder propulsion rate of rats were determined in each group；the pathological morphology of colon tissue was observed， and mRNA and protein expressions of nerve growth factor （NGF） and tropomyosin receptor kinase A （TrkA） in colon tissue were detected. RESULTS Compared with control group， the fecal water content and carbon powder propulsion rate in the model group were decreased significantly （P＜0.05）； the rupture of mucosal muscle layer in colon tissue， significant infiltration of inflammatory cells and cellular edema were observed； the content of 5-HT in serum， and relative mRNA and protein expressions of NGF and TrkA were increased significantly （P＜0.05）. Compared with model group， the fecal water content and carbon powder propulsion rate of rats were increased significantly in administration groups （P＜0.05）， and pathological changes of colon tissue were relieved significantly， while the content of 5-HT in serum， the mRNA and protein expressions of NGF and TrkA in colon tissue were decreased significantly （P＜0.05）； among them， the above indicators inthe positive control group and CDPS high-dose group were generally close to those in the control group （P＞0.05）. CONCLUSIONS CDPS can alleviate the symptoms of IBS-C rats， which may be related to the inhibition of NGF/TrkA signaling pathway.

Efficacy of mouse nerve growth factor combined with edaravone in the treatment of carbon monoxide poisoning and its influence on oxygen free radical-related indicators / 中国医师进修杂志

Objective:To investigate the therapeutic effect of the combination of mouse nerve growth factor and edaravone in the treatment of carbon monoxide poisoning and its effect on patients′ cognitive function, lactic acid clearance rate, and related indicators of oxygen free radicals.Methods:A selection of 158 patients with carbon monoxide poisoning in the Huxi Hospital Affilliated Jining Medical College from May 2017 to June 2020 were divided into study group (80 cases) and control group (78 cases) according to the treatment plan. Both groups were given conventional treatment. On this basis, the control group was given edaravone, and the study group was given mouse nerve growth factor combined with edaravone, both of which were treated for 2 weeks. The clinical efficacy of the two groups was compared with those before treatment and 1 week and 2 weeks after treatment. Neurological impairment score (NIHSS), disease severity score (APACHE Ⅱ), cognitive function score (MMSE), serum inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP)], oxygen free radical related indicators [lipid peroxide (LPO), superoxide dismutase (SOD), gluten Glutathione peroxidase (GSH-PX), malondialdehyde (MDA)] levels, blood lactic acid levels before treatment and lactic acid clearance rates after 12 h, 24 h, 72 h treatment, and statistics of adverse reactions and 30-day mortality.Results:The total effective rate of the study group was higher than that of the control group after 2 weeks of treatment [95.00% (76/80) vs. 78.21% (61/78)] ( P<0.05); NIHSS and APACHEⅡ scores of the study group after 1 week and 2 weeks of treatment Lower than the control group: (6.08 ± 1.15) points vs. (8.94 ± 1.71) points, (4.58 ± 0.74) points vs. (6.32 ± 0.93) points and (6.79 ± 1.03) points vs. (8.02 ± 1.47) points, (5.94 ± 1.47) points vs. (7.25 ± 0.94) points, the MMSE score was higher than that of the control group: (22.09 ± 4.35) points vs. (19.34 ± 5.32) points, (26.05 ± 2.37) points vs. (22.47 ± 4.64) points ( P<0.05) After 1 and 2 weeks of treatment, the serum TNF-α, IL-6, CRP, LPO and MDA levels in the study group were lower than those in the control group: (22.62 ± 4.12) ng/L vs. (29.43 ± 4.68) ng/L and (18.21 ± 2.09) ng/L vs. (24.37 ± 3.16) ng/L, (39.67 ± 4.35) ng/L vs. (52.14 ± 5.48) ng/L and (34.83 ± 3.75) ng/L vs. (41.07 ± 4.09) ng/L, (12.63 ± 1.85) mg/L vs. (17.02 ± 2.47) mg/L and (8.27 ± 1.16) mg/L vs. (11.05 ± 1.62) mg/L, (11.06 ± 1.28) μmol/L vs. (15.97 ± 1.85) μmol/L and (8.24 ± 1.12) μmol/L vs. (12.97 ± 1.40) μmol/L, (7.15 ± 1.16) μmol/L vs. (9.02 ± 1.47) μmol/L and (6.12 ± 0.96) μmol/L vs. (7.84 ± 1.25) μmol/L, the levels of SOD and GSH-PX were higher than those in the control group ( P<0.05); the lactate clearance rate in the study group was higher than that in the control group after 12, 24 and 72 h of treatment: (18.49 ± 3.63)% vs. (14.62 ± 2.95)%, (23.19 ± 4.20)% vs. (17.42 ± 3.57)%, (29.86 ± 6.37)% vs. (25.38 ± 5.21)% ( P<0.05); the incidence of adverse reactions in the study group during treatment Compared with the control group, there was no significant difference ( P>0.05); there was no significant difference in the 30-day mortality between the study group and the control group ( P>0.05). Conclusions:The combination of mouse nerve growth factor and edaravone in the treatment of carbon monoxide poisoning can reduce the severity of disease and neurological deficits, improve cognitive function and lactate clearance rate, reduce inflammation and oxidative stress, improve efficacy, and have good safety.

Evaluation of alprostadil combined with different doses of mouse nerve growth factor in diabetic peripheral neuropathy / 中国医师进修杂志

Objective:To investigate the application of alprostadil combined with different doses of mouse nerve growth factor in diabetic peripheral neuropathy (DPN) and its effect on motor and sensory nerve conduction and inflammatory factors.Methods:One hundred and fiftypatients with DPN treated in Beihai People′s Hospital from June 2018 to March 2020 were randomly divided into low-dose group and high-dose group, with 75 cases in each group. On the basis of routine treatment, the low-dose group was given alprostadil + mouse nerve growth factor 18 μg/time, once a day. The high-dose group was given alprostadil+mouse nerve growth factor 30 μg/time, once a day, both two groups were treated for 3 weeks. The curative effect, motor and sensory nerve conduction velocity and inflammatory index tumor necrosis factor-α(TNF-α)interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC) and cost-effectiveness analysis, adverse reactions between the two groups were compared.Results:There was no significant difference in the total effective rate between the low dose group and the high dose group ( P>0.05). After 1 and 3 weeks of treatment, the levels ofmotor and sensory nerve conduction velocity and TNF-α, IL-6, hs-CRP and WBC in the two groups has no significant differences ( P>0.05). The cost of each unit effect in the low-dose group was 43.11 Yuan, and the cost of each unit effect in the high-dose group was 57.58 Yuan. The high-dose group was higher than that in the low-dose group, and the high-dose group paid 572.56 Yuan more than the low-dose group for each additional unit effect. There was no significant difference in the total incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Alprostadil combined with 18 μg mouse nerve growth factor in the treatment of DPN has a similar improvement effect on clinical symptoms, motor and sensory nerve conduction and inflammatory factors, and has advantages in cost-effectiveness.

Effects of tandospirone combined with venlafaxine on neurotransmitters and related factors in patients with comorbid anxiety and depression / 中国基层医药

Objective:To investigate the efficacy of tandospirone combined with venlafaxine in the treatment of comorbid anxiety and depression and its effects on neurotransmitters and related factors.Methods:A total of 92 patients with comorbid anxiety and depression who received treatment in the Second People's Hospital of Lishui between June 2019 and June 2020 were included in this study. They were randomly divided into an observation group and a control group ( n = 46/group). The control group was treated with venlafaxine, while the observation group was treated with tandospirone and venlafaxine. Before and after treatment, the scores of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), the levels of 5-hydroxytryptamine, brain-derived neurotrophic factor, nerve growth factor, and adverse drug reactions were compared between the two groups. Results:At 4 and 8 weeks after treatment, HAMA scores in the observation group were (11.39 ± 3.11) points and (8.26 ± 2.18) points, respectively, which were significantly lower than (14.72 ± 3.57) points and (10.46 ± 2.37) points in the control group ( t = 4.77, 4.63, both P < 0.05). At 4 and 8 weeks after treatment, HAMD scores in the observation group were (15.95 ± 2.90) points and (9.33 ± 1.54) points, respectively, which were significantly lower than (17.43 ± 2.87) points and (13.28 ± 2.65) points in the control group ( t = 2.46, 8.74, both P < 0.05). After treatment, 5-hydroxytryptamine, nerve growth factor, and brain-derived neurotrophic factor levels in the observation group were (154.59 ± 45.26) μg/L, (13.62 ± 1.16) ng/L, (28.54 ± 2.33) ng/L, respectively, which were significantly higher than (129.99 ± 48.31) μg/L, (11.98 ± 1.04) ng/L, and (25.69 ± 2.51) ng/L in the control group ( t = 2.52, 7.14, 5.64, all P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( χ2 = 0.81, P = 0.369). Conclusion:The adjuvant treatment with tandospirone can markedly improve anxiety and depression and protect neurological function of patients with comorbid anxiety and depression, and is highly safe.

Mechanism of anterior cingulate cortex in modulating pain and anxiety-like behavior in chronic non-specific low back pain model rats / 中华行为医学与脑科学杂志

Objective:To explore the potential mechanisms of anterior cingulate cortex (ACC) in modulating pain behavior and anxiety-like behavior of rats with chronic non-specific low back pain induced by nerve growth factor (NGF).Methods:Ninety-six male SPF grade SD rats aged 8 weeks were randomly divided into four groups according the random number table method: control group, model group, control+ D-2-amino-5-phosphonopentanoate (D-AP5) group (control+ D-AP5 group) and model+ D-AP5 group, with 24 rats in each group.Low back pain model of rat was established by injection of NGF into multifidus muscle (left side) of the low backs of rats(two times with a five-day interval). Five days after modeling, rats in model+ D-AP5 group and control+ D-AP5 group were injected with the N-methyl-D-aspartate (NMDA) receptor antagonist D-AP5(2 μg, 0.3 μL) at the right side of the ACC once a day for consecutive 3 days, and rats in control group and model group were injected with the same amount of 0.9% sodium chloride solution. Seven days after modeling, the pain threshold of rats was evaluated by mechanical stimulation test and hot and cold plate test.The anxiety-like behavior was tested by open field test.The density of glial fibrillary acidic protein (GFAP) positive cells and c-Fos(a kind of immediate early gene) positive cells of the spinal cord were observed by immunofluorescence. The expression of GFAP, c-Fos, phosphorylated-c-Jun N-terminal kinases (p-JNK), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-X-C motif) ligand 1 (CXCL-1) proteins in the L2 segment of the spinal cord were detected by Western blot. SPSS 23.0 software was used for statistical analysis. One-way ANOVA was used to analyze normal distribution measurement data for comparison among multiple groups, and Tukey test was used for further pairwise comparisons. The Kruakal-Wallis H test was used for non-normal distribution measurement data, and Mann-Whitney U test was used for further pairwise comparisons with Bonferroni-corrected P-values. Results:In the experiments measuring pressure pain threshold (PPT) and paw withdrawal threshold (PWT), there were statistically significant differences in the PPT and PWT of rats among the four groups ( F=53.498, 41.939, both P<0.001). Seven days after modeling, PPT ((418.5±46.9) g) and PWT ( (55.6±7.1) g) in the ipsilateral side of the rats in model+ D-AP5 group were higher than those in model group ((290.0±32.0) g, (30.5±7.5) g) (both P<0.001). In the open field test, there were statistically significant differences in percentage of the inner zone distance ( H=11.922, P<0.01) and the percentage of inner zone time ( H=21.614, P<0.001) of rats among the four groups. The percentage of inner zone time in model+ D-AP5 group was higher than that in model group (5.6(4.3, 7.9) %, 3.1(2.1, 3.8) %) ( P<0.01). The results of immunofluorescence showed that there were statistically significant differences in the density of GFAP positive cells and c-Fos positive cells at the ipsilateral side of the superficial laminae of rats among the four groups ( H=49.085, F=18.120, both P<0.001). The density of GFAP positive cells (34.3(21.1, 47.5) cells/mm 2) and c-Fos positive cells ((52.7±39.4) cells/mm 2) at the ipsilateral side of the superficial laminae in model+ D-AP5 group were less than those in model group (76.5(68.6, 94.9) cells/mm 2, (112.4±63.7) cells/mm 2) (both P<0.001). The Western blot results showed that there were statistically significant differences in the protein expression of GFAP, c-Fos, p-JNK, MCP-1 and CXCL-1 in the L2 segment of rats among the four groups ( F=49.413, 38.437, 41.867, 36.735, 130.951, all P<0.001). The protein expression of GFAP (1.7±0.5), c-Fos (1.1±0.1), p-JNK (1.7±0.3), MCP-1 (1.0±0.4) and CXCL-1 (0.8±0.1) in the L2 segment in model+ D-AP5 group were lower than those in model group ((4.3±0.7), (2.6±0.5), (2.8±0.4), (2.9±0.4), (3.5±0.4)) (all P<0.01). Conclusion:ACC modulates mechanical hyperalgesia and anxiety-like behavior in chronic non-specific low back pain rats, which might be associated with the involvement of spinal astrocytes, p-JNK signal pathway and chemokines such as MCP-1 and CXCL-1.

Effects of granulocyte macrophage colony-stimulating factor, nerve growth factor and interleukin-17 on autoimmune prostatitis / 现代泌尿外科杂志

【Objective】 To investigate the significance of granulocyte macrophage colony-stimulating factor (GM-CSF), nerve growth factor (NGF) and interleukin-17 (IL-17) in the prostate tissue of rats with experimental autoimmune prostatitis(EAP). 【Methods】 EAP rat models were established and divided into control group, EAP group, anti-GM-CSF group (blocking control group) and anti-GM-CSFEAP group (blocking EAP group). Pain behaviors were tested. The pathological changes were observed with HE staining. The mRNA and protein expressions of GM-CSF, NGF and IL-17 were detected with RT-PCR and Western blot. 【Results】 Pain test showed the anti-GM-CSF group had less chronic pelvic pain than the EAP group. HE staining showed the anti-GM-CSF group had less tissue inflammatory response. The EAP inflammation score was higher in the control group than in the anti-GM-CSF group. Immunohistochemistry showed GM-CSF was positive in the EAP group (mainly in the nucleus). RT-PCR and Western blot results showed the mRNA and protein expressions of IL-17 and NGF significantly decreased 50 days after EAP in the anti-GM-CSF group. 【Conclusion】 Increased expressions of GM-CSF, NGF and IL-17 in prostate tissue of EAP rats may be important inflammatory mediators of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS);decreased expressions of NGF and IL-17 after resistance against GM-CSF indicate that GM-CSF may be a potential therapeutic target for CP/CPPS.

MASH1 induces neuron transdifferentiation of adrenal medulla chromaffin cells / 中南大学学报(医学版)

OBJECTIVES@#Nerve growth factor (NGF) induces neuron transdifferentiation of adrenal medulla chromaffin cells (AMCCs) and consequently downregulates the secretion of epinephrine (EPI), which may be involved in the pathogenesis of bronchial asthma. Mammalian achaete scute-homologous 1 (MASH1), a key regulator of neurogenesis in the nervous system, has been proved to be elevated in AMCCs with neuron transdifferentiation in vivo. This study aims to explore the role of MASH1 in the process of neuron transdifferentiation of AMCCs and the mechanisms.@*METHODS@#Rat AMCCs were isolated and cultured. AMCCs were transfected with siMASH1 or MASH1 overexpression plasmid, then were stimulated with NGF and/or dexamethasone, PD98059 (a MAPK kinase-1 inhibitor) for 48 hours. Morphological changes were observed using light and electron microscope. Phenylethanolamine-N-methyltransferase (PNMT, the key enzyme for epinephrine synthesis) and tyrosine hydroxylase were detected by immunofluorescence. Western blotting was used to test the protein levels of PNMT, MASH1, peripherin (neuronal markers), extracellular regulated protein kinases (ERK), phosphorylated extracellular regulated protein kinases (pERK), and JMJD3. Real-time RT-PCR was applied to analyze the mRNA levels of MASH1 and JMJD3. EPI levels in the cellular supernatant were measured using ELISA.@*RESULTS@#Cells with both tyrosine hydroxylase and PNMT positive by immunofluorescence were proved to be AMCCs. Exposure to NGF, AMCCs exhibited neurite-like processes concomitant with increases in pERK/ERK, peripherin, and MASH1 levels (all P<0.05). Additionally, impairment of endocrine phenotype was proved by a signifcant decrease in the PNMT level and the secretion of EPI from AMCCs (all P<0.01). MASH1 interference reversed the effect of NGF, causing increases in the levels of PNMT and EPI, conversely reduced the peripherin level and cell processes (all P<0.01). MASH1 overexpression significantly increased the number of cell processes and peripherin level, while decreased the levels of PNMT and EPI (all P<0.01). Compared with the NGF group, the levels of MASH1, JMJD3 protein and mRNA in AMCCs in the NGF+PD98059 group were decreased (all P<0.05). After treatment with PD98059 and dexamethasone, the effect of NGF on promoting the transdifferentiation of AMCCs was inhibited, and the number of cell processes and EPI levels were decreased (both P<0.05). In addition, the activity of the pERK/MASH1 pathway activated by NGF was also inhibited.@*CONCLUSIONS@#MASH1 is the key factor in neuron transdifferentiation of AMCCs. NGF-induced neuron transdifferentiation is probably mediated via pERK/MASH1 signaling.

Perivascular Innervation in the Nasal Mucosa and Clinical Findings in Patients with Allergic Rhinitis and Idiopathic Rhinitis

Abstract Introduction The nonspecific hyperreactivity of rhinitis has been attributed to neurotrophins activating sensory nerves and inflammatory cells. The relationship between these markers and the intensity of the symptoms is not well established and few studies have evaluated individuals with idiopathic rhinitis. Objective The present study aims to evaluate whether perivascular innervation and nerve growth factor (NGF) are related to the intensity of the clinical conditions in allergic rhinitis (AR) and idiopathic rhinitis (IR). Methods A total of 15 patients with AR and 15 patients with IR with the indication for inferior turbinectomy (associated or not with septoplasty) were selected. The patients received a score according to their signs and symptoms. After the surgery, we quantified eosinophils, mast cells, NGF, and nerve fibers in the nasal turbinate. Results The score of the signs and symptoms was higher in the AR group. Nerve growth factor was found in the cytoplasm of inflammatory cells in the submucosa in greater quantity in the AR group. The nerve fibers were distributed throughout the tissue, mainly in the subepithelial, glandular, and vascular regions, and there was no difference between the groups. Greater perivascular innervation was associated with a higher signs and symptoms score. Conclusions We concluded that these findings suggest that the NGF produced by submucosal inflammatory cells stimulates increased perivascular innervation in rhinitis, thus directly reflecting in more intense clinical conditions, especially in AR.

Adipose-derived stem cell transplantation for the treatment of peripheral nerve injury induced by 1-bromopropane in rats / 中国职业医学

@#Abstract: Methods - （ ） To investigate the repairing effect of adipose derived stem cells ADSCs transplantation in - - Methods 1 bromopropane induced peripheral nerve injury in rats. A total of 45 specific pathogen free male SD rats were （ ） （ ） randomly assigned to the control group 15 rats and exposure group 30 rats . The rats in the exposure group were gavaged with - ， ， 1 bromopropane at a dose of 800 mg/kg body weight while the control group were given with equal volume of corn oil once a ， - day five days per week for eight weeks. The rat model of peripheral nerve injury induced by 1 bromopropane was established - ， - and was randomly assigned to the self recovery group and ADSCs group 12 rats in each group. ADSCs group and self recovery （ 6 ） ， group were injected with 0.5 mL contains 1×10 cells ADSCs or 0.5 mL phosphate buffer solution respectively by tail vein once a week for four weeks. The control group was not administered any treatment. The rats in each group were assessed using - - （ ） ， ， inclined plane test and Basso Beattie Bresnahan BBB score on the first day before treatment as well as 7 14 21 and 28 day ， after treatment. At the end of treatment the sciatic nerve was isolated for histopathological examination. The oxidative stress - indexes in the cerebral motor cortex were detected by colorimetric analysis. The levels of brain derived neurotrophic factor （ ） （ ） - Results BDNF and nerve growth factor NGF in the sciatic nerve were detected by enzyme linked immunosorbent assay. The - maximum tilt angle of the inclined plate and the BBB score were lower in self recovery group at the five time points of treatment （ P< ） all 0.05 compared with the control group. The maximum tilt angle of the inclined plate test was higher in ADSCs group at 21 （ P< ）， ， ， （ P< ）， and 28 days of treatment all 0.05 and the BBB score was higher at 7 14 21 and 28 days of treatment all 0.05 - （ ） when compared with the self recovery group. The level of malondialdehyde MDA in the cerebral motor cortex increased （P< ）， （ ） （ ） （ P< ）， 0.05 while the superoxide dismutase SOD activity and glutathione GSH level decreased all 0.05 and the levels （ P< ） - of BDNF and NGF in the sciatic nerve decreased all 0.05 in self recovery group compared with the control group. There was ， ， no significant difference in SOD activity and MDA GSH BDNF and NGF levels between ADSCs group and control group （ P> ） （P< ）， （ all 0.05 . The level of MDA in cerebral motor cortex decreased 0.05 the SOD activity and GSH level increased all P< ）， （P< ） - 0.05 and the level of BDNF in sciatic nerve increased 0.05 in ADSCs group compared with the self recovery group. Conclusion - - ADSCs transplantation can repair peripheral nerve injury induced by 1 bromopropane via anti oxidative stress and regulating the secretion of neurotrophic factors.