Secondary damage is a critical determinant of the functional outcome in patients with spinal cord injury (SCI), and involves multiple mechanisms of which the most important is the loss of nerve cells mediated by multiple factors. Autophagy can result in cell death, and plays a key role in the development of SCI. It has been recognized that valproic acid (VPA) is neuroprotective in certain experimental animal models, however, the levels of autophagic changes in the process of neuroprotection by VPA treatment following SCI are still unknown. In the present study, we determined the extent of autophagy after VPA treatment in a rat model of SCI. We found that both the mRNA and protein levels of Beclin-1 and LC3 were significantly increased at 1, 2, and 6 h after SCI and peaked at 2 h; however, Western blot showed that autophagy was markedly decreased by VPA treatment at 2 h post-injury. Besides, post-SCI treatment with VPA improved the Basso-Beattie-Bresnahan scale, increased the number of ventral horn motoneurons, and reduced myelin sheath damage compared with vehicle-treated animals at 42 days after SCI. Together, our results demonstrated the characteristics of autophagy expression following SCI, and found that VPA reduced autophagy and enhanced motor function.

BackgroundNeurogenic detrusor overactivity (NDO) affects the quality of life (QoL) of millions of individuals worldwide. The purpose of this study was to assess the efficacy and safety of onabotulinumtoxinA in patients with NDO using a network meta-analytic approach, which can also quantify and compare the efficacy of onabotulinumtoxinA across different dosages.MethodsPubMed, EMBASE, and the Controlled Trials Register were searched to identify randomized controlled trials comparing onabotulinumtoxinA to a control for NDO in adult patients. The primary outcome was the mean number of urinary incontinence (UI) episodes per week. Urodynamic parameters included the maximum cystometric capacity (MCC) and the maximum detrusor pressure (MDP). The safety of onabotulinumtoxinA was determined by the incidence of various frequent adverse events (AEs). Two authors extracted data independently, and the statistical analyses were performed using RevMan 5.1.0 software.ResultsA total of 1,915 patients from six randomized controlled trials were included in this meta-analysis. The onabotulinumtoxinA-treated groups had a significantly decreased mean number of urinary incontinence episodes per week (at week 6) (onabotulinumtoxinA200U: MD: -10.72, 95% CI: -13.4 to -8.04, P<0.00001; 300 U: MD: -11.42, 95% CI: -13.91 to -8.93, P<0.00001), MDP (200 U: MD: -33.46, 95% CI: -39.74 to -27.18, P<0.00001; 300 U: MD: -31.72, 95% CI: -37.69 to -25.75, P<0.00001), and greater increased MCC (200 U: MD: 141.30, 95% CI: 121.28 to 161.32, P<0.00001; 300 U: MD: 151.39, 95% CI: 130.43 to 172.34, P<0.00001) compared to the placebo-treated groups. However, there were no significant differences between the onabotulinumtoxinA-treated groups for the number of weekly UI episodes at 6 weeks (MD: 0.08, 95% CI: -2.57 to 2.73, P = 0.95). Similarly, we also observed that there were no significant differences in MCC (MD: -9.97, 95% CI: -33.15 to 13.20, P = 0.40) and MDP (MD: -1.86, 95% CI: -8.09 to 4.37, P = 0.56). Considering the AEs, the onabotulinumtoxinA-treated groups were often associated with more complications, including urinary tract infections (UTIs) (RR: 1.47, 95% CI: 1.29 to 1.67, P<0.00001), urinary retention (RR: 5.58, 95% CI: 3.53 to 8.83, P<0.00001), hematuria (RR: 1.70, 95% CI: 1.01 to 2.85, P = 0.05), and muscle weakness (RR: 2.59, 95% CI: 1.36 to 4.91, P = 0.004).ConclusionsOnabotulinumtoxinA can significantly reduce the frequency of urge urinary incontinence and improve urodynamic parameters (MCC and MDP) in patients with NDO at 6 weeks after treatment. This meta-analysis indicates that onabotulinumtoxinA is effective and safe for treating patients with NDO compared to placebo. Additionally, we did not observe any statistical or clinical differences in efficacy between 300 and 200 U dosages.

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Aims/Introduction: To systematically review the risk factors for new-onset diabetes mellitus after kidney transplantation, and to provide a theoretical basis for the prevention and management of new-onset diabetes mellitus after kidney transplantation. Materials and Methods: We searched PubMed, Web of Science, Embase, the Cochrane Library databases and other databases for case-control studies related to risk factors for newonset diabetes mellitus after kidney transplantation published between January 2005 and July 2019. A meta-analysis of data on risk factors for new-onset diabetes mellitus after kidney transplantation from the included studies was carried out. A narrative review of risk factors for new-onset diabetes mellitus after kidney transplantation was also carried out. Results: A total of 24 case-control studies were included in the meta-analysis, with a total of 7,140 patients. There were 1,598 patients with new-onset diabetes mellitus after kidney transplantation, and 5,542 patients without new-onset diabetes mellitus after kidney transplantation. The meta-analysis results showed that age, polycystic kidney disease, family history of diabetes, body mass index, acute rejection, tacrolimus use, hepatitis B virus infection, hepatitis C virus infection and hypertension were associated with new-onset diabetes mellitus after kidney transplantation, whereas sex, sirolimus use, cyclosporin A use, steroid use and cytomegalovirus infection were not associated with new-onset diabetes mellitus after kidney transplantation. Conclusions: Older age, body mass index, family history of diabetes, tacrolimus use, history of hypertension, polycystic kidney disease, acute rejection, hepatitis B virus infection and hepatitis C virus infection are risk factors for new-onset diabetes mellitus after kidney transplantation. Therefore, the clinical implications of these factors warrant attention.

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