Mid-term efficacy of sacral nerve stimulation for the treatment of chronic constipation / 中华胃肠外科杂志

Objective: To investigate the mid-term efficacy of sacral nerve stimulation (SNS) for chronic constipation. Methods: A descriptive case series study was conducted. Patients with chronic constipation were treated in Xijing Hospital of Digestive Disease from February 2013 to December 2018 were retrospectively enrolled. The types of constipation were confirmed based on colon slow transit test, anorectal manometry and defecography in Xi'an Mayinglong Coloproctological Hospital. This study has been registered in China clinical trial registry (Registration No.: ChiCTR-ROC-16008945). Case inclusion criteria: (1) constipation was diagnosed according to Rome III criteria; (2) traditional treatment, including education, diet adjustment, laxative, biofeedback treatment, failed for at least 1 year; (3) there were no constipation-related organic diseases. After excluding neurogenic diseases, including spinal cord injury and multiple sclerosis, 21 patients were included in this study. There were 10 males and 11 females, with an average age of 50.9 (14-76) years. After the relevant examination and evaluation of patients, they underwent percutaneous nerve evaluation (PNE). If patient experienced a good response to PNE after 2 or 3 weeks (≥50%), permanent SNS implantation was performed. The improvement of clinical symptoms and quality of life between the baseline, PNE, and latest follow-up time points were compared. Improvement of clinical symptoms, including autonomic stool frequency per week, autonomic stool days per week, defecation time, visual analogue scale (VAS, lower score indicates more serious symptoms) score and Cleveland clinic constipation score (CCCS, higher score indacates more serious symptoms) criteria. The change of quality of life was scored by SF-36 questionnaires (the higher score indicates better quality of life). Results: Of 21 patients, 18 (85.7%) experienced significant improvement in symptoms with PNE, and 2 patients discontinued treatment due to their dissatisfaction. Sixteen patients (76.2%) received permanent SNS implantation, two of whom underwent bilateral PNE implantation. These patients were followed-up for mean 56 (34-72) months. The treatment was continuously effective in 13 patients (61.9%), including 3 of ODS, 1 of STC and 9 of mixed constipation. Compared with baseline, the score of constipation patients receiving permanent SNS implantation at latest follow-up was shown. The median autonomic stool frequency per week increased from 1.0 (0-7) to 7.5 (0-10) (P<0.001), the median autonomic stool days per week increased from 1.0 (0-7) d to 4.5 (0-7) d (P<0.001), the median defecation time decreased from 19.0 (8-40) minutes to 4.0 (3-31) minutes (P<0.001), the median CCCS decreased from 20.0 (13-30) to 9.0 (6-30) (P<0.001), and the median VAS score increased from 9.0 (7-40) to 80.0 (15-90) (P<0.001). The values of the 8 parts of the SF-36 questionnaire increased (all P<0.05). Conclusion: SNS implantation is safe and has obvious effects on severe constipation with stable mid-term efficacy.

Treadmill exercise inhibits amyloid-ß generation in the hippocampus of APP/PS1 transgenic mice by reducing cholesterol-mediated lipid raft formation.

The deposition of amyloid-ß (Aß) is one of the major pathological hallmarks of Alzheimer's disease (AD), and a higher cholesterol level is involved in the deposition of Aß. Previous evidence suggested that exercise exerts neuroprotective effects in a variety of AD models. In the present study, we investigated the effects of a 12-week treadmill exercise program on Aß deposits in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and the potential underlying mechanism. After 12 weeks of exercise, Aß deposits were significantly decreased in the hippocampus. Meanwhile, the amyloidogenic pathway of APP metabolism was inhibited, which was associated with a decrease in BACE1 expression. The APP metabolism mediated by the nonamyloidogenic pathway, as indicated by the increase in ADAM10 levels. Coincidentally, exercise reduced the cholesterol level, as evidenced by a significant decrease in the total cholesterol level and the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, as well as a reduction in the number of lipid rafts, as evidenced by a significant decrease in the flotillin 1 level. These finding suggested that the 12-week treadmill exercise program reduced Aß deposition in the hippocampus of APP/PS1 mice, possibly by regulating ADAM10 and BACE1 levels and by decreasing cholesterol-mediated lipid raft formation, indicating that exercise represents a therapeutic intervention to treat AD.