Effects of sacral nerve electrical stimulation on 5­HT and 5­HT3AR/5­HT4R levels in the colon and sacral cord of acute spinal cord injury rat models.

Spinal cord injury (SCI) often leads to defecation dysfunction. Sacral nerve electrical stimulation (SNS) therapy could improve defecation function. The present study aimed to assess SNS therapy, with regard to the levels of serotonin (5­HT) and its receptors (5­HT3AR and 5­HT4R) in the colon and sacral cord, a rat model of acute severe SCI was used. This rat model was made using the New York University Impactor device. Model rats were randomized to the SCI and SNS (electrical stimulation on the S3 nerve) groups. After 14 days of treatment, enteric transmission function was assessed. 5­HT and 5­HT3AR/5­HT4R were measured by ELISA, quantitative PCR, immunohistochemistry and western blotting. In SCI rats, SNS significantly increased the quantity of feces, shortened the time to the first fecal passage, and improved fecal texture and colon histology. SNS elevated 5­HT contents in the colon and spinal cord, and enhanced 5­HT3AR/5­HT4R protein expression and distribution in the colonic myenteric plexus and mucosa, sacral intermediolateral nucleus and dorsal horn. SNS upregulated the relative expression levels of 5­HT3AR/5­HT4R mRNA and protein in the colon and spinal cord. SNS can improve defecation and accelerate the recovery of colonic transmission functions in rat models of acute SCI. These effects involved upregulation of the 5­HT/5­HT3AR/5­HT4R axes.

Effect of Zuogui pill and Yougui pill on osteoporosis: a randomized controlled trial.

OBJECTIVE: To evaluate the effect and safety of Zuogui pill and Yougui pill, classic Yin and Yang tonic formula (CYYTF), in the treatment of osteoporosis and the underlying mechanism. METHODS: Participants aged 55 to 75 with osteoporosis and Kidney deficiency in Traditional Chinese Medicine (TCM) will be included and randomly allocated into two groups: treatment group and control group. Participants in the treatment group were treated with Zuogui pill or Yougui pill TCM formula granule, while the control group received placebo. Primary outcomes are the lumbar spine on bone mineral density (BMD) (L1-4) and femoral BMD. Secondary outcomes include pain intensity, health-related quality of life (HRQoL), bone turnover markers and safety. RESULTS: Totally 200 patients were enrolled from December 2014 to April 2016 from four hospitals. There were no statistically significant differences between the two groups at baseline (P > 0.05) and it was good to comparability. Statistically significant differences between the two groups were observed for the lumbar BMD (L1-4), pain VAS scores and HRQoL at six months and twelve months and femoral BMD at twelve months (P < 0.05), but no significant differences for femoral BMD and bone turnover markers at six months (P > 0.05). Moreover, significant difference was observed at different time before and after treatment in terms of lumbar spine (L1-4) BMD, femoral BMD, pain VAS scores and health-related quality of life, and there was an crossover effect between the time and groups before and after treatment. In additional, in the treatment group, 8 patients lost to follow-up and 3 patients had adverse events (AEs) and in the control group, 10 patients lost to follow-up and 2 patients had AEs. No remarkable differences were observed between the two groups with regard to AEs, lost rate and safety (P > 0.05). CONCLUSION: Zuogui pill or Yougui pill could improve BMD, ease pain, relieve Kidney deficiency syndrome, improve the quality of life osteoporosis patients, inhibit bone conversion and regulate the coupling balance of bone formation and bone resorption, but long-term efficacy should be confirmed by a longer term follow-up and larger of samples clinical randomized controlled trials.