Therapies of varicose veins: Protocol for the reporting and methodological quality of pairwise meta-analyses.

BACKGROUND: Many pairwise meta-analyses (MAs) related to therapies of varicose veins have been published, but their reporting and methodological quality remain unclear. The present study was designed to assess the overall quality of pairwise MAs related to therapies of varicose veins. METHODS: We will systematically search 4 electronic databases, including PubMed, EMBASE, Cochrane Library, Chinese Biomedical Database, to identify pairwise MAs related to therapies of varicose veins. The search time-span was set from inception to March 2019. The pairwise MAs related to therapies of varicose veins will be included in our overview. The reporting and methodological quality of included MAs will be assessed using preferred reporting items for systematic review and meta-analysis and a measurement tool to assess systematic reviews 2, respectively. Meanwhile, we will extract some general characteristics of included MAs, including first author; published year, journal, sample size, number of studies, number of randomized controlled trials and intervention details, and so on. All literatures screening, quality assessment, and data extraction will be independently completed by 2 of all reviewers, and any disagreement will be resolved by discussion. Besides, an increasingly popular method - evidence mapping, will be used to present the whole evidence landscape related to therapies of varicose veins. The assessment results will be presented as percentage and event/total. The Excel 2016 will be used to manage and analyze data. RESULTS: The results of the overview will be submitted to a peer-reviewed journal for publication. CONCLUSION: This overview will summarize the overall reporting and methodological quality related to therapies of varicose veins. PROSPERO REGISTRATION NUMBER: CRD42019126722.

Differential mechanisms underlying neuroprotection of hydrogen sulfide donors against oxidative stress.

This study investigated whether slow-releasing organic hydrogen sulfide donors act through the same mechanisms as those of inorganic donors to protect neurons from oxidative stress. By inducing oxidative stress in a neuronal cell line HT22 with glutamate, we investigated the protective mechanisms of the organic donors: ADT-OH [5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione], the most widely used moiety for synthesizing slow-releasing hydrogen sulfide donors, and ADT, a methyl derivative of ADT-OH. The organic donors were more potent than the inorganic donor sodium hydrogensulfide (NaHS) in protecting HT22 cells against glutamate toxicity. Consistent with previous publications, NaHS partially restored glutamate-depleted glutathione (GSH) levels, protected HT22 from direct free radical damage induced by hydrogen peroxide (H2O2), and NaHS protection was abolished by a KATP channel blocker glibenclamide. However, neither ADT nor ADT-OH enhanced glutamate-depleted GSH levels or protected HT22 from H2O2-induced oxidative stress. Glibenclamide, which abolished NaHS neuroprotection against oxidative stress, did not block ADT and ADT-OH neuroprotection against glutamate-induced oxidative stress. Unexpectedly, we found that glutamate induced AMPK activation and that compound C, a well-established AMPK inhibitor, remarkably protected HT22 from glutamate-induced oxidative stress, suggesting that AMPK activation contributed to oxidative glutamate toxicity. Interestingly, all hydrogen sulfide donors, including NaHS, remarkably attenuated glutamate-induced AMPK activation. However, under oxidative glutamate toxicity, compound C only increased the viability of HT22 cells treated with NaHS, but did not further increase ADT and ADT-OH neuroprotection. Thus, suppressing AMPK activation likely contributed to ADT and ADT-OH neuroprotection. In conclusion, hydrogen sulfide donors acted through differential mechanisms to confer neuroprotection against oxidative toxicity and suppressing AMPK activation was a possible mechanism underlying neuroprotection of organic hydrogen sulfide donors against oxidative toxicity.