Background
Sacral nerve stimulation (SNS) has revolutionized the management of certain intractable cases of fecal and urinary incontinence; however, the management of functional anorectal pain (FAP) has been addressed in only a few studies.
Objective
The aim of this study was to evaluate the treatment effect of SNS in improving FAP symptoms.
Methods
A total of 120 patients with FAP who had undergone temporary SNS probe placement were investigated at Qianfoshan Hospital between January 2014 and December 2016. Pre‐ and post‐SNS treatment outcomes were assessed using the VAS, anorectal manometry, and the 36‐item short‐form health survey (SF‐36) medical outcomes study instrument.
Results
A total of 120 patients proceeded to insertion of an SNS probe at the S3 nerve root (2 Hz, 1.50 mA, 0.10 milliseconds). Of these, 75 patients were cured, 41 improved, and 4 had an ineffective outcome. The total effectiveness rate was 96.7% 1 year after treatment. There was a significant reduction in the median VAS score pre‐SNS and post‐SNS, from 8 to 3, respectively. Patients post‐SNS had lower anal maximum contraction pressure and anal rest pressure than did patients pre‐SNS. Compared with the pretreatment group, there were no substantial differences between anal longest contraction time and rectal rest pressure. In addition to general health, there was a substantial improvement in the remaining dimension scores of the SF‐36.
Conclusion
The effect of SNS in treating FAP was positive, and the improvement of symptoms was substantial and worthy of clinical promotion.
Objectives
In this study, we administered immunity‐and‐matrix regulatory cells (IMRCs) via tail vein (IV) and intracerebroventricular (ICV) injection to 3‐month‐old 5×FAD transgenic mice to assess the effects of IMRC transplantation on the behaviour and pathology of early‐stage Alzheimer's disease (AD).
Materials and methods
Clinical‐grade human embryonic stem cell (hESC)‐derived IMRCs were produced under good manufacturing practice (GMP) conditions. Three‐month‐old 5×FAD mice were administered IMRCs via IV and ICV injection. After 3 months, the mice were subjected to behavioural tests and electrophysiological analysis to evaluate their cognitive function, memory ability and synaptic plasticity. The effect of IMRCs on amyloid‐beta (Aβ)‐related pathology was detected by thioflavin‐S staining and Western blot. Quantitative real‐time PCR, ELISA and immunostaining were used to confirm that IMRCs inhibit neuroinflammation. RNA‐seq analysis was performed to measure changes in gene expression and perform a pathway analysis in response to IMRC treatment.
Results
IMRC administration via tail vein injection significantly ameliorated cognitive deficits in early‐stage AD (5×FAD) mice. However, no significant change was observed in the characteristic pathology of AD in the ICV group. Plaque analysis revealed that IMRCs did not influence either plaque deposition or BACE1 expression. In addition, IMRCs inhibited inflammatory responses and reduced microglial activation in vivo.
Conclusions
We have shown that peripheral administration of IMRCs can ameliorate AD pathology and associated cognitive deficits.
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