Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats.

This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 inflammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery. Moreover, C-fiber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroinflammation and synaptic plasticity in spinal dorsal horn of each group were examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were significantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral analgesic mechanisms of perineural injection of BoNT/A might be related to the protective effect on myelin sheath by inhibiting NLRP3 inflammasome and promoting autophagy flow, while the central analgesic mechanisms might be associated with inhibition of neuroinflammation and synaptic plasticity in spinal dorsal horn due to inhibiting SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central analgesic mechanisms.

Effects of variations in meteorological factors on daily hospital visits for asthma: A time-series study.

Few studies have explored the relationships between meteorological factors and asthma. This study explored the associations between daily variations in meteorological factors and hospital visits for asthma among different ages, genders, and asthma subtypes in Shenyang, China. A distributed lag non-linear model with Poisson regression was used; confounding factors included day of the week, holidays, and seasonal patterns, and long-term trends and air pollutants were adjusted using natural cubic splines. The meteorological factor with the largest cumulative effect was barometric pressure, which increased the risk of hospital visits for adult asthma (relative risk [RR] = 2.414), followed by maximum wind speed, which increased hospital visits for asthma for children aged 0-5 years old (RR = 1.47), and pressure, which increased hospital visits for bronchial asthma (RR = 1.298). Meteorological factors showed stronger associations with asthma than air pollutants. Further research should focus more on the effects of meteorological factors on asthma.

Long-term treatment of blepharospasm with botulinum toxin A: a service-based study over a 16-year follow-up in southern China.

OBJECTIVE: To elucidate the effect of long-term treatment with botulinum toxin A (BTX-A) for blepharospasm. Prevalence data and clinical features in southern China and influencing factors for selecting BTX-A treatment were explored. METHODS: We collected data retrospectively from 338 consecutive patients diagnosed with blepharospasm over 16 years to assess prevalence data and clinical features. Thereafter, all patients were classified into BTX-A (n = 135) or non-BTX-A (n = 203) treatment groups according to the patients' requests in order to explore the factors influencing whether BTX-A treatment was chosen. Furthermore, dynamic follow-up data were analyzed to evaluate the long-term efficacy in the BTX-A group. RESULTS: The prevalence was 23.3 per million, with an onset age of 50.3 ± 12.3 years and a female:male ratio of 2.4:1; the most common symptom was excessive blinking (91.2%). The symptom severity and psychological assessment scores were significantly decreased by treatment with BTX-A (p < 0.01), and there was no significant difference in response duration with the prolongation of BTX-A injections. Adverse events occurred 52 times (5.0%) among 1038 injections. The symptom severity and psychological assessment scores and the occurrence of eye-opening difficulty were higher, and medical expenses and the symptom tolerability rate were lower in the BTX-A group than in the non-BTX-A group (p < 0.05). CONCLUSION: The onset age was earlier than that in Western countries. However, starting BTX-A treatment early is justified, even though a higher dosage was needed to maintain reliable long-term efficacy. Additionally, symptom severity and medical expenses are the primary factors affecting whether patients select BTX-A treatment.

Association between air pollutants and outpatient and emergency hospital visits for childhood asthma in Shenyang city of China.

Effects of air pollution on asthma vary in different study areas, and long-term time series research on the effects of air pollution on asthma outpatients and emergency hospital visits has not been conducted in Northeast China. We assessed the impact of air pollutants on the risk of asthma outpatients and emergency hospital visits in Shenyang, China. A distributed lag non-linear model with a Poisson regression was used to assess the short-term effects of air pollutants on asthma outpatient and emergency hospital visits between January 1, 2013 and December 31, 2017. Confounding factors were adjusted using natural cubic splines. Ozone (O3), carbon monoxide (CO), and suspended particulates < 10 µm in aerodynamic diameter (PM10) were positively associated with the number of asthma hospital visits. The largest cumulative effects of O3, CO, and PM10 on hospital visits were on lag day 2 (RR = 1.163, 95% CI 1.051-1.287) for 0-5-year-old childhood asthma, on lag day 3 (RR = 1.386, 95% CI 1.136-1.69) for asthma in winter, and on lag day 10 (RR = 1.148, 95% CI 0.942-1.399) for female asthma, respectively. The cumulative effect of air pollution represented by the air quality index (AQI) was largest on lag day 10 for 0-5-year-old childhood asthma with an increase of 28.6% (95% CI 6.5-55.4) hospital visits every IQR increment of the AQI. CO, O3, and PM10 were the main air pollutants in Shenyang city. Children with bronchitis asthma were more vulnerable to air pollution during the cold season.

Synergistic effect of glucocorticoids and IGF-1 on myogenic differentiation through the Akt/GSK-3ß pathway in C2C12 myoblasts.

Purpose: Glucocorticoids are the only therapeutics that can delay the progression of Duchenne musculardystrophy (DMD), the most prevalent type of inherited neuromuscular disorder in males. However, beyond theiranti-inflammatory effects, glucocorticoids have other underlying mechanisms that remain unclear. Moreover, muscleand circulating levels of insulin growth factor-1 (IGF-1) often decrease in response to glucocorticoids. Therefore, wehypothesized that glucocorticoids, either alone or in combination with IGF-1, can improve myogenic differentiation.Materials and methods: Established C2C12 myoblasts were employed as an in vitro model of myogenic differentiation,and myogenic differentiation markers, as assessed by Western blot (myogenin, MyoD, and MyHC protein expression),cellular morphology analysis (fusion index) and RT-PCR (MCK mRNA expression), were measured.Results: Myogenic differentiation markers were increased by glucocorticoid treatment. Furthermore, this effect was furtherenhanced by IGF-1, and these results suggest that glucocorticoids, either alone or together with IGF-1, can promotemyogenic differentiation. Akt and GSK-3ß play important roles in myogenic differentiation. Interestingly, the levels ofboth phosphorylated Ser473-Akt and phosphorylated Ser9-GSK-3ß were increased by glucocorticoid and IGF-1 cotreatment.Pharmacological manipulation with LY294002 and LiCl was employed to inhibit Akt and GSK-3ß, respectively.We found that cellular differentiability was inhibited by LY294002 and enhanced by LiCl, indicating that theAkt/GSK-3ß signaling pathway is activated by glucocorticoid and IGF-1 treatment to promote myogenic differentiation.Conclusions: Glucocorticoids together with IGF-1 promote myogenic differentiation through the Akt/GSK-3ßpathway. Thus, these results further our knowledge of myogenic differentiation and may offer a potential alternativestrategy for DMD treatment based on glucocorticoid and IGF-1.