Smoking is one of the most serious but preventable causes of cardiovascular disease (CVD). Key aspects of pathological process associated with smoking include endothelial dysfunction, a prothrombotic state, inflammation, altered lipid metabolism, and hypoxia. Multiple molecular events are involved in smokinginduced CVD. However, the dysregulations of reactive oxygen species (ROS) generation and metabolism mainly contribute to the development of diverse CVDs, and NADPH oxidase (NOX) has been established as a source of ROS responsible for the pathogenesis of CVD. NOX activation and resultant ROS production by cigarette smoke (CS) treatment have been widely observed in isolated blood vessels and cultured vascular cells, including endothelial and smooth muscle cells. NOX-mediated oxidative stress has also been demonstrated in animal studies. Of the various NOX isoforms, NOX2 has been reported to mediate ROS generation by CS, but other isoforms were not tested thoroughly. Of the many CS constituents, nicotine, methyl vinyl ketone, and α,β-unsaturated aldehydes, such as, acrolein and crotonaldehyde, appear to be primarily responsible for NOX-mediated cytotoxicity, but additional validation will be needed. Human epidemiological studies have reported relationships between polymorphisms in the CYBA gene encoding p22phox, a catalytic subunit of NOX and susceptibility to smoking-related CVDs. In particular, G allele carriers of A640G and -930(A/G) polymorphisms were found to be vulnerable to smoking-induced cardiovascular toxicity, but results for C242T studies are conflicting. On the whole, evidence implicates the etiological role of NOX in smoking-induced CVD, but the clinical relevance of NOX activation by smoking and its contribution to CVD require further validation in human studies. A detailed understanding of the role of NOX would be helpful to assess the risk of smoking to human health, to define high-risk subgroups, and to develop strategies to prevent or treat smoking-induced CVD.

Background and Purpose— Positive effects of moxibustion for stroke rehabilitation may be seen in real clinical practice. Currently, no systematic reviews are available. The aim of this systematic review was to analyze the trial data on the effectiveness of moxibustion for stroke rehabilitation. Methods— Fourteen databases were searched without language restriction. Randomized clinical trials were included if moxibustion was tested as the sole treatment or as an adjunct to other treatments for stroke rehabilitation. Results— Nine randomized clinical trials met our inclusion criteria. Three randomized clinical trials reported favorable effects of moxibustion plus standard care on motor function versus standard care alone (N=142; standardized mean difference=0.72; 95% confidence interval, 0.37 to 1.08; P <0.0001). Three randomized clinical trials compared the effects of moxibustion on activities of daily living alone but failed to show favorable effects of moxibustion. Conclusion— This systematic review found limited effectiveness of moxibustion as an adjunct to standard care in stroke rehabilitation.

Contralateral acupuncture (CAT) involves inserting needles in the meridian on the side opposite the disease location and is often used in post-stroke rehabilitation. The aim of this systematic review is to summarize and critically evaluate the evidence for and against the effectiveness of CAT for post-stroke rehabilitation as compared to ipsilateral acupuncture (IAT). Seventeen databases were searched from their inceptions through June 2010. Prospective clinical trials were included if CAT was tested as the sole treatment or as an adjunct to other treatments for post-stroke rehabilitation and compared to IAT. Eight randomized clinical trials (RCTs) met our inclusion criteria. Four of them reported favorable effects of CAT compared to IAT for at least one outcome. A meta-analysis showed superior effects of CAT compared to IAT on recovery rate (n = 361; risk ratio (RR), 1.12; 95% confidence intervals (CIs), 1.04 to 1.22, P = 0.005). Subgroup analysis also showed favorable effects of using CAT on patients with cerebral infarction (n = 261; RR, 1.15; 95% CIs, 1.04 to 1.27, P = 0.006). Further analysis including patients with cerebral infarction and intracranial hemorrhage, however, failed to show these advantages (n = 100; RR, 1.11; 95% CIs, 0.85 to 1.46, P = 0.43). The results of our systematic review and meta-analysis suggest that there is limited evidence for CAT being superior to IAT in the treatment of cerebral infarction. The total number of RCTs included in our analysis was low, however, and the RCTs included had a high risk of bias. Future RCTs appear to be warranted.

While the use of herbal and traditional medicine (H&TM) has been extensive worldwide, the current status of H&TM management in pharmacovigilance remains to be investigated. To date, there is little information regarding the use of the classification/coding system (CCS) to detect signals for certain drugs within databases built on the basis of the spontaneous reporting system (SRS). The purpose of this study is to investigate the status of the SRS and CCS for H&TM in the pharmacovigilance systems of various countries around the world. An e-mail survey was performed from late December 2018 to early January 2019 with 54 experts in pharmacovigilance. The results based on the information provided by the respondents were summarized. Fourteen experts from 13 countries responded to the survey. Eleven countries/regions were found to already include H&TM in their SRSs, managing only limited range of H&TM. Of the 9 countries/regions that provided the information on the status of CCS for H&TM in their domestic pharmacovigilance systems, only China had a separate CCS for H&TM. Revising the current pharmacovigilance systems to include or expand the range of H&TM, and developing an internationally harmonized system to classify and code H&TM suitable to the unique characteristics of H&TM are critical and overall beneficial.