Electroacupuncture ameliorates gastrointestinal dysfunction by modulating DMV cholinergic efferent signals to drive the vagus nerve in p-MCAO rats.

Background: The use of proton pump inhibitors in the acute phase of cerebral infarction may lead to adverse long-term outcomes, this study aims to explore the potential of electroacupuncture (EA) in replacing omeprazole in exerting post-stroke gastrointestinal protection. Methods: A permanent middle cerebral artery infarction model was established using the modified Longa thread occlusion technique. Gastrointestinal motility, gastrointestinal mucosal damage, cerebral infarct volume, and alterations in choline acetyltransferase (ChAT)-positive neurons within the dorsal motor nucleus of the vagus nerve (DMV) were assessed after 7 days of EA at Zusanli (ST36) or omeprazole intervention. To evaluate the role of the vagal nerve in mitigating post-stroke gastrointestinal dysfunction, we employed subdiaphragmatic vagotomy and the ChAT-specific inhibitor α-NETA. Additionally, we utilized methyllycaconitine (MLA), a selective inhibitor of the α7-type nicotinic acetylcholine receptor (α7nAChR), and PNU282987, an agonist, to identify the target of EA. Results: EA restored ChAT neurons lost in the DMV, activated the vagus nerve and conferred cerebroprotection while ameliorating gastrointestinal mucosal injury and gastrointestinal motility disorders. In addition, following the administration of the α7nAChR antagonist, the attenuation of gastric mucosal injury and inflammatory factors induced by EA was hindered, although gastrointestinal motility still exhibited improvement. Conclusion: EA at ST36 promotes the restoration of cholinergic signaling in the DMV of stroke-afflicted rats, and its excitation of the vagal nerve inhibits gastrointestinal inflammation after stroke via α7nAChR, while improvement in gastrointestinal motility could be mediated by other acetylcholine receptors.

Sex differences in immune-related adverse events with immune checkpoint inhibitors: data mining of the FDA adverse event reporting system.

Background Although immune-related adverse events (irAEs) have been reported in patients receiving immune checkpoint inhibitor (ICI) therapy, sex differences in irAEs are not known. Aim The present study described, evaluated and compared differences in irAEs between females and males treated with ICIs. Method irAE reports were obtained from the FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2020. Disproportionality analysis and Bayesian analysis were used to explore differences in irAEs between females and males. The onset time and fatality proportion of irAEs in different ICIs between females and males were further evaluated. Results A total of 30,342 irAE cases were obtained, including 11,097 female cases and 19,245 male cases. Consistent disproportionality signals were detected in females and males, including endocrine toxicity, hepatitis, lung toxicity, nervous system toxicity, and ocular toxicity. Renal toxicity was only detected in male patients receiving ICI therapy (PRR 2.37, 95% CI: 2.25-2.51; IC: 1.24, 95% CI: 1.05-1.43). Males had a longer onset time (females 35 days [IQR 14-87] vs. males 39 days [IQR 14-92], P = 0.041) and higher fatality proportion (females 20.5% vs. males 25.6%, P < 0.01). Conclusion This analysis revealed that males had a higher chance of exhibiting ICI-associated renal toxicity, longer median onset time and worse prognosis of irAEs than females. Greater attention to sex differences in ICI therapy is needed.

Electroacupuncture Activates Neuroplasticity in the Motor Cortex and Corticospinal Tract via the mTOR Pathway in a Rat P-MCAO Model.

Electroacupuncture (EA) combines traditional Chinese medicine acupuncture theory with modern scientific technology. It is a promising therapy for the treatment of cerebrovascular diseases such as cerebral infarction. A large number of clinical studies have shown that EA promotes recovery of neurological function after cerebral infarction, however, the underlying mechanisms behind its effects remain unclear. We tested whether EA stimulation of the Zusanli (ST36) and Neiguan (PC6) acupoints activates neuroplasticity in rats with ischemic stroke and whether this involves the regulation of axonal regeneration through the mTOR pathway. 24 h after permanent middle cerebral artery occlusion (p-MCAO) in rats, EA treatment was started for 20 min, daily, for 14 days. We found that EA significantly reduced Modified Neurological Severity Scores (mNSS), cerebral infarct volume, and apoptosis of neuronal cells. EA also significantly increased the expression of the neuroplasticity-associated proteins GAP-43 and SYN and upregulated the phosphorylation levels of AKT, mTOR, S6, and PTEN to promote CST axon sprouting in the spinal cord at C1-C4 levels. The positive effects of EA were blocked by the administration of the mTOR inhibitor Rapamycin. In short, we found that EA of the Zusanli (ST36) and Neiguan (PC6) acupoints in p-MCAO rats induced neuroprotective and neuroplastic effects by regulating the mTOR signaling pathway. It promoted neuroplasticity activated by axon regeneration in the contralateral cortex and corticospinal tract. Activation of such endogenous remodeling is conducive to neurological recovery and may help explain the positive clinical effects seen in patients with infarcts.

Economic evaluations of clinical pharmacy services in China: a systematic review.

OBJECTIVE: This article reviewed research conducted on economic evaluations of clinical pharmacy services (CPS) in China. We aimed to identify the types of CPS and the possible economic effects of these services and to hopefully provide some suggestions for designing future economic evaluations of pharmacy interventions in the region. DESIGN: Systematic review. DATA SOURCES: Several English databases (PubMed, Embase, The Cochrane Library, National Health Service Economic Evaluation Database), Chinese databases (China National Knowledge Infrastructure, VIP, Chinese Biomedical Literature Database and WanFang Data) and search engines (Google Scholar and BaiDu Scholar) were searched through December 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies with an economic assessment of CPSs in China were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the studies, extracted the data, assessed the quality of the included studies and then qualitatively analysed the results. RESULTS: Forty articles were included in the final analysis. Most studies were performed in hospitals and the intervention populations mainly included adults. The types of pharmaceutical services included antimicrobial management, chronic disease state management and multidimensional clinical pharmaceutical services. A positive economic benefit associated with CPS was noted in 80% (n=32) of these articles, showing that CPS were associated with cost savings and improved patient outcomes. However, only three studies were full economic evaluations, using the method of cost-effectiveness analysis. CONCLUSION: CPS was associated with cost savings and generated positive economic value. With the expanding role of pharmacists in the healthcare sector, it is suggested that new pharmaceutical services be used in future studies and that high-quality full economic evaluations capturing both expenses and cost savings be conducted.

Enhanced BiFeO3/Bi2Fe4O9/H2O2 heterogeneous system for sulfamethoxazole decontamination: System optimization and degradation pathways.

Sulfonamides as the major antibiotic have become emerging contaminants worldwide in aquatic environments. Herein, a heterogeneous Fenton-like oxidation driven by a novel BF-PMCs bismuth ferrites reported firstly for efficient degradation of sulfamethoxazole (SMX) in which the possible degradation pathways are thoroughly analyzed through identifying some of key intermediates (i.e., C8H11N3O4S, C4H4NO2, etc.) using liquid chromatography-mass spectrum (LC-MS), monitoring organic acids (i.e., acetic acid, pyruvic acid) and inorganic anions (i.e., sulfate, nitrate) using ion chromatography (IC), and detecting radical species (i.e., HO) using both chemical quenchers and fluorescence technique, simultaneously. The optimal operations in BF-PMCs/H2O2 system for SMX degradation are recommended at the conditions of initial pH ~4.5, 1.5 mg L-1 [SMX], 70 mM [H2O2], and BF-PMCs loading of 0.2 g L-1. The degradation rates (kinetic value of kapp) for SMX, azoxystrobin, bisphenol A, and 2,4-dichlorophenol are 9.5 × 10-3, 13.6 × 10-3, 7.3 × 10-3, and 5.9 × 10-3 min-1, respectively. Meanwhile, the degradation rates in BF-PMCs/H2O2 system for SMX degradation are slightly slower in the presence of inorganic anions (e.g., Cl-, NO3-) and NOM (e.g., humic acid). Based on an overall consideration, the BF-PMCs/H2O2 system has great potential for degradation of emerging organic pollutants (EOPs) in natural water systems.