Mechanical Thrombectomy for Acute Ischemic Stroke in Patients With Cardiac Myxoma: A Case Series and Pooled Analysis.

Background and Purpose: Acute ischemic stroke (AIS) is a common and life-threatening complication of patients with cardiac myxoma (CM). The role of the mechanical thrombectomy (MT) technique in CM-AIS patients remains unclear, and no guidelines exist for this population. Therefore, we conducted a case series study of MT in CM-AIS patients to investigate its safety and efficacy via a pooled analysis of published literature. Methods: Eleven CM-AIS patients who underwent MT between 2016 and 2021 were screened from multicenter stroke databases. Clinical, procedural, and outcome data were obtained from medical records. A systematic review was conducted to identify additional cases from published studies by searching PubMed and China National Knowledge Infrastructure databases. We then performed a pooled analysis of the published cases. Results: In the case series study, most patients were male (81.8%), with a median age of 51 years. All patients had CM located in the left atrium. The rate of successful reperfusion using the first-line thrombectomy technique was 100% with stent retriever (SR) and 66.7% with direct aspiration (DA), which resulted in overall successful reperfusion in 94.1% of all occlusions. The retrieved emboli of the five patients who underwent histopathology examination were identified as myxoma components. Hemorrhagic transformation was observed in five (45.5%) patients, of whom one was symptomatic (9.1%). Three-month favorable functional outcomes were achieved in five (45.5%) patients with a 3-month mortality rate of 18.2%. For the literature review, 35 cases with 51 target vessel occlusions were identified and included in the pooled analysis. The rate of successful reperfusion following first-line thrombectomy did not differ between SR (30 patients, 90.9%) and DA (10 patients, 83.3%). The overall successful reperfusion rate was 91.8% of all occlusions. Three-month favorable functional outcomes were achieved in 21 (60.0%) patients, and the mortality rate was 8.6%. Conclusions: Our findings suggest that MT is not only an effective technique but also a safe option for CM-AIS patients with large vessel occlusion. MT has several advantages for this population, which include a high recanalization rate, low bleeding risk, and the ability to evaluate the source of emboli and the etiology of stroke.

Efficacy and Safety of Chinese Herbal Medicine for Primary Intracerebral Hemorrhage: A Systematic Review of Randomized Controlled Trials.

Background: Primary intracerebral hemorrhage (ICH) is the most harmful subtype of stroke, but there have yet been no specific proven therapies. Chinese herbal medicine (CHM) has been used for ICH for more than a thousand years; however, currently it is still lacking of available evidence. The objective of this study is to assess the current available evidence of CHM for acute ICH according to randomized controlled trials. Methods: Eight databases were searched from the year of their respective inception to November 2017. Only the studies that assessed at least four domains with "yes" according to the Cochrane risk of bias tool were selected for analysis. All the data were analyzed by using Review Manager 5.3 software. P < 0.05 was considered to be statistically significant. Results: Forty-five studies with 4,517 individuals were identified. CHM paratherapy can improve dependency, neurological function deficit, volume of hematoma, clinical effective rate, and volume of perihematomal edema compared with CHM alone or placebo (all P < 0.05). By contrast, it was not significant for improving the mortality rate of ICH patients (P > 0.05). In addition, adverse events were reported in 16 studies, whereas 29 studies did not mention it. The frequency of adverse events was 70/972 in the trial group and 48/944 in the control group. Conclusion: The present study provided supportive evidence of CHM for improving dependency of ICH and showed generally safety; however, there is still lack of evidence for improving mortality rate, and it opens for further study.

Preclinical Evidence and Possible Mechanisms of Extracts or Compounds from Cistanches for Alzheimer's Disease.

Currently, disease-modified strategies to prevent, halt or reverse the progress of Alzheimer's disease (AD) are still lacking. Previous studies indicated extracts or compounds from Cistanches (ECC) exert a potential neuroprotective effect against AD. Thus, we conducted a preclinical systematic review to assess preclinical evidence and possible mechanisms of ECC in experimental AD. A systematical searching strategy was carried out across seven databases from their inceptions to July 2018. Twenty studies with 1696 rats or mice were involved. Neurobehavioral function indices as primary outcome measures were established by the Morris water maze test (n = 11), step-down test (n = 10), electrical Y-maze test (n = 4), step-through test (n = 3), open field test (n = 2) and passage water maze test (n = 1). Compared with controls, the results of the meta-analysis showed ECC exerted a significant effect in decreasing the escape latency, error times and wrong reaction latency in both the training test and the retention test, and in increasing the exact time and the percentage of time in the platform-quadrant and the number of platform crossings (all P<0.01). In conclusion, ECC exert potential neuroprotective effects in experimental AD, mainly through mechanisms involving antioxidant stress and antiapoptosic effects, inhibiting Aß deposition and tau protein hyperphosphorylation and promoting synapse protection. Thus, ECC could be a candidate for AD treatment and further clinical trials.

Chinese Herbal Medicine for Wilson's Disease: A Systematic Review and Meta-Analysis.

Wilson's disease (WD) is a rare autosomal recessive inherited disorder of chronic copper toxicosis. Currently, Chinese herbal medicines (CHM) is widely used for WD. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for WD and its possible mechanisms. Randomized-controlled clinical trials (RCTs), which compared CHM with Western conventional medicine or placebo for WD, were searched in six databases from inception to July 2017. The methodological quality was assessed using 7-item criteria from the Cochrane's collaboration tool. All the data were analyzed using Rev-Man 5.3 software. Eighteen studies involving 1,220 patients were identified for the final analyses. A score of study quality ranged from 2/7 to 4/7 points. Meta-analyses showed that CHM could significantly increase 24-h urinary copper excretion and improve liver function and the total clinical efficacy rate for WD compared with control (p < 0.05). Additionally, CHM was well tolerated in patients with WD. The underlying mechanisms of CHM for WD are associated with reversing the ATP7B mutants, exerting anti-oxidation, anti-inflammation, and anti-hepatic fibrosis effects. In conclusion, despite the apparent positive results, the present evidence supports, to a limited extent because of the methodological flaws and CHM heterogeneity, that CHM paratherapy can be used for patients with WD but could not be recommended as monotherapy in WD. Further rigorous RCTs focusing on individual CHM formula for WD are warranted.

The reporting quality of acupuncture for neurogenesis in experimental ischemic stroke study.

BACKGROUND: There is increasing evidence demonstrating the highly inadequate reporting of preclinical research in multiple scientific publications. The purpose of this study is to systematically investigate the reporting quality of acupuncture for neurogenesis in animal models of acute ischemic stroke. METHODS: We searched eight databases, including PubMed, EMBASE, CINAHL, AMED, Chinese National Knowledge Infrastructure, VIP information database, Wanfang data Information Site, and Chinese Biomedical Literature Database. The methodological quality of included studies was assessed by using the CAMARADES 10-item checklist. The STRICTA statement was modified to gear to animal acupuncture research. The reporting quality was assessed according to the ARRIVE guidelines and the modified STRICTA statement. Data were analyzed with descriptive statistics. RESULTS: Ultimately, 44 studies containing 2,411 subjects were identified. The overall compliance with the CAMARADES 10-item checklist has a mean of 4.3. The reporting quality indicated that the overall compliance with ARRIVE guidelines has a mean of 59.9% and with the modified STRICTA statement a mean of 71.8%. The findings suggest that the reporting quality of acupuncture for preclinical stroke was generally poor. CONCLUSIONS: Full compliance with ARRIVE guidelines and/or modified STRICTA statement in designing, conducting and reporting preclinical acupuncture research is urgently needed in the future.

Rhodiola rosea L. Improves Learning and Memory Function: Preclinical Evidence and Possible Mechanisms.

Rhodiola rosea L. (R. rosea L.) is widely used to stimulate the nervous system, extenuate anxiety, enhance work performance, relieve fatigue, and prevent high altitude sickness. Previous studies reported that R. rosea L. improves learning and memory function in animal models. Here, we conducted a systematic review and meta-analysis for preclinical studies to assess the current evidence for R. rosea L. effect on learning and memory function. Ultimately, 36 studies involving 836 animals were identified by searching 6 databases from inception to May 2018. The primary outcome measures included the escape latency in Morris water maze (MWM) test on behalf of learning ability, the frequency and the length of time spent on the target quadrant in MWM test representing memory function, and the number of errors in step down test, dark avoidance test and Y maze test on behalf of memory function. The secondary outcome measures were mechanisms of R. rosea L. for learning and/or memory function. Compared with control, the pooled results of 28 studies showed significant effects of R. rosea L. for reducing the escape latency (P < 0.05); 23 studies for increasing the frequency and the length of time spent on the target quadrant (P < 0.05); and 6 studies for decreasing the number of errors (P < 0.01). The possible mechanisms of R. rosea L. are largely through antioxidant, cholinergic regulation, anti-apoptosis activities, anti-inflammatory, improving coronary blood flow, and cerebral metabolism. In conclusion, the findings suggested that R. rosea L. can improve learning and memory function.

Borneol, a messenger agent, improves central nervous system drug delivery through enhancing blood-brain barrier permeability: a preclinical systematic review and meta-analysis.

To achieve sufficient blood-brain barrier (BBB), penetration is one of the biggest challenges in the development of diagnostic and therapeutic for central nervous system (CNS) disorders. Here, we conducted a systematic review and meta-analysis to assess the preclinical evidence and possible mechanisms of borneol for improving co-administration of CNS drug delivery in animal models. The electronic literature search was conducted in six databases. Fifty-eight studies with 63 comparisons involved 1137 animals were included. Among 47 studies reporting the assessments of CNS drug concentration, 45 studies showed the significant effects of borneol for improving CNS drug delivery (p<.05), whereas 2 studies showed no difference (p>.05). Nineteen comparisons showed borneol up-regulated BBB permeability (p<.05) using brain EB content (n = 8), Rh 123 content (n = 4), brain imaging agent content (n = 2), brain water content (n = 1) and observing ultrastructure of BBB (n = 4), whereas three studies showed no difference or unclear results. Seven studies reported the safety, in which one study showed borneol was reversible changes in the BBB penetration; six studies showed borneol did not increase co-administration of blood drugs concentration of peripheral tissues (p > .05). Effects of borneol are closely associated with inhibition of efflux protein function, releasement of tight junction protein, increasement of vasodilatory neurotransmitters, and inhibition of active transport by ion channels. In conclusion, borneol is a promising candidate for CNS drug delivery, mainly through mediating a multi-targeted BBB permeability.

Chinese Herbal Medicine for Myasthenia Gravis: A Systematic Review and Meta-Analysis.

Myasthenia gravis (MG) is an acquired autoimmune disease with the disorder of the neuromuscular junction transmission caused by autoantibodies. Currently, various Chinese herbal medicines (CHMs) are widely used for MG. This meta-analysis was conducted to assess the effectiveness and safety of CHMs for MG and its possible mechanisms. Fourteen studies with 1039 individuals were identified by searching seven databases from inception to March 2017. The methodological quality was assessed by using 7-item criteria from the Cochrane's Collaboration tool, and which assessed ≥4 "yes" in the domains were selected for detailed assessment and meta-analysis. All the data were analyzed using Rev-Man 5.3 software. Meta-analysis showed a significant effect of CHM as adjuvant therapy for improving the effectiveness compared with WCM alone or placebo in treating MG (p < 0.01). Moreover, there were fewer adverse effects and relapse rate in total when compared with the control group. The possible mechanisms of CHM for MG are associated with immunoregulation by reconstituting the functional ability of Tregs. In conclusion, despite the apparent positive results, the present evidence supports, to an extent, that CHM can be used for MG patients because of the methodological flaws and CHM heterogeneity. Further rigorous RCT for MG is needed.

Suanzaoren Formulae for Insomnia: Updated Clinical Evidence and Possible Mechanisms.

Insomnia disorder is a widespread and refractory disease. Semen Ziziphi Spinosae, Suanzaoren, a well-known Chinese herbal medicine, has been used for treating insomnia for thousands of years. Here, we aimed to assess the available evidence of Chinese herbal formulae that contains Suanzaoren (FSZR) for insomnia according to high-quality randomized controlled trials (RCTs) and reviewed their possible mechanisms based on animal-based studies. Electronic searches were performed in eight databases from inception to November 2016. The primary outcome measures were polysomnography index and Pittsburgh sleep quality index. The secondary outcome measures were clinical effective rate and adverse events. The methodological quality of RCTs was assessed by Cochrane's collaboration tool, and only RCTs with positive for 4 out of 7 for the Cochrane risk of bias domains were included in analyses. Thirteen eligible studies with 1,454 patients were identified. Meta-analysis of high-quality RCTs showed that FSZR monotherapy was superior to placebo (P < 0.01); FSZR plus Diazepam was superior to Diazepam alone (P < 0.05); there were mixed results comparing FSZR with Diazepam (P > 0.05 or P < 0.05). Furthermore, FSZR caused fewer side effects than that of Diazepam. Suanzaoren contains complex mixtures of phytochemicals including sanjoinine A, Jujuboside A, spinosin and other flavonoids, which has sedative and hypnotic functions primarily mediated by the GABAergic and serotonergic system. In conclusion, the findings of present study supported that FSZR could be an alternative treatment for insomnia in clinic. FSZR exerted sedative and hypnotic actions mainly through the GABAergic and serotonergic system.

A Preclinical Systematic Review of Ginsenoside-Rg1 in Experimental Parkinson's Disease.

To date, no drug has been proven to be neuroprotective or disease-modifying for Parkinson's disease (PD) in clinical trials. Here, we aimed to assess preclinical evidence of Ginsenosides-Rg1 (G-Rg1), a potential neuroprotectant, for experimental PD and its possible mechanisms. Eligible studies were identified by searching six electronic databases from their inception to August 2016. Twenty-five eligible studies involving 516 animals were identified. The quality score of these studies ranged from 3 to 7. Compared with the control group, two out of the 12 studies of MPTP-induced PD showed significant effects of G-Rg1 for improving the rotarod test (P < 0.01), two studies for improving the swim-score values (P < 0.01), six studies for improving the level of TH protein expression (P < 0.01), and two studies for increasing the expression of TH mRNA in the substantia nigra of mice (P < 0.01). The studies reported that G-Rg1 exerted potential neuroprotective effects on PD model through different mechanisms as antineuroinflammatory activities (n = 10), antioxidant stress (n = 3), and antiapoptosis (n = 11). In conclusion, G-Rg1 exerted potential neuroprotective functions against PD largely by antineuroinflammatory, antioxidative, and antiapoptotic effects. G-Rg1 as a promising neuroprotectant for PD needs further confirmation by clinical trials.

Efficacy and safety of suanzaoren decoction for chronic insomnia disorder in adults: study protocol for randomised, double-blind, double-dummy, placebo-controlled trial.

BACKGROUND: Insomnia disorder is defined as a combination of dissatisfaction with sleep quantity or quality and a significant negative impact on daytime functioning. Chronic insomnia disorder refers to clinical symptoms of persistent insomnia at least three nights a week for at least 3 months. Prevalence estimates of insomnia disorder range from 12% to 20% in the adult population, with approximately 50% having a chronic course. The potential side effects of hypnotic medications hinder their clinical application. Thus, traditional Chinese medicine is considered as an alternative option for treating insomnia. OBJECTIVE: To evaluate the efficacy and safety of suanzaoren decoction (SZRD), a classic Chinese herbal prescription, for adult chronic insomnia disorder. METHODS/ANALYSIS: This is a randomised, double-blind, double-dummy, placebo-controlled clinical trial. A total of 150 patients with chronic insomnia disorder are randomised, allocated in a ratio of 1:1:1 to three groups: intervention group, control group and placebo group. The intervention group receives SZRD granule plus zolpidem tartrate (ZT) placebo; the control group receives ZT tablet plus SZRD granule placebo; and the placebo group receives ZT placebo and SZRD granule placebo. The patients receive medicine or placebo for 5 weeks and are followed up at 20 weeks. The primary outcome measures are polysomnography and Pittsburgh Sleep Quality Index. Secondary outcome measures are the Insomnia Severity Index, sleep diary and safety assessment. Outcomes will be assessed at baseline and after treatment. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16009198. pre-results.

Astragaloside IV for Experimental Focal Cerebral Ischemia: Preclinical Evidence and Possible Mechanisms.

Astragaloside IV (AST-IV) is a principal component of Radix Astragali seu Hedysari (Huangqi) and exerts potential neuroprotection in experimental ischemic stroke. Here, we systematically assessed the effectiveness and possible mechanisms of AST-IV for experimental acute ischemic stroke. An electronic search in eight databases was conducted from inception to March 2016. The study quality score was evaluated using the CAMARADES. Rev Man 5.0 software was used for data analyses. Thirteen studies with 244 animals were identified. The study quality score of included studies ranged from 3/10 to 8/10. Eleven studies showed significant effects of AST-IV for ameliorating the neurological function score (P < 0.05); seven studies for reducing the infarct volume (P < 0.05); and three or two studies for reducing the brain water content and Evans blue leakage (P < 0.05), respectively, compared with the control. The mechanisms of AST-IV for ischemic stroke are multiple such as antioxidative/nitration stress reaction, anti-inflammatory, and antiapoptosis. In conclusion, the findings of present study indicated that AST-IV could improve neurological deficits and infarct volume and reduce the blood-brain barrier permeability in experimental cerebral ischemia despite some methodological flaws. Thus, AST-IV exerted a possible neuroprotective effect during the cerebral ischemia/reperfusion injury largely through its antioxidant, anti-inflammatory, and antiapoptosis properties.