Ji-huang Li

Diabetes and Risk of Parkinson's Disease: An Updated Meta-Analysis of Case-Control Studies

Background Whether diabetes increases the risk of Parkinsons disease (PD) is still inconclusive. The objective of this updated meta-analysis is to synthesize evidence from case-control studies that evaluated the association between diabetes and the risk of PD. Methods Seven databases were searched to identify case-control studies that evaluated the association between diabetes and PD. The methodological quality of included studies was assessed using Newcastle-Ottawa scale. All data were analyzed using Review Manager 5.1 software. Subgroup analyses were also adopted, according to stratification on gender, geographic location, source of the control group, smoking, anti-diabetes drug prescription and duration of DM. Results Fourteen studies fulfilled inclusion criteria for meta-analysis, yielding a total of 21395 PD patients and 84579 control subjects. Individuals with diabetes were found to have a negative association with future PD (OR 0.75; 95% CI 0.58–0.98) in spite of significant heterogeneity. In subgroup analyses, the negative correlation was still found in studies from North America, non-PD control groups from general population, never smoking individuals, and DM ascertainment based on questionnaire or self-report. Stratification of gender and DM duration showed no significant association. No association was also found in European and Asian individuals, hospital-based controls, ever smoking subjects, DM assessment by medical record or physician diagnosis, and insulin prescription for DM. Conclusion Evidence from case-control studies suggested that diabetic individuals may have a decreased incidence of PD despite significant heterogeneity. More researches are warranted to clarify an understanding of the association between diabetes and risk of PD.

Ginsenoside Rg1 provides neuroprotection against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion through downregulation of aquaporin 4 expression

Ginsenoside Rg1 is regarded as one of main bioactive compounds responsible for pharmaceutical actions of ginseng with little toxicity and has been shown to have possibly neuroprotective effects. However, the mechanism of its neuroprotection for acute ischemic stroke is still elusive. The purpose of present study is thus to assess the neuroprotective effects of the ginsenoside Rg1 against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion, and then to explore the mechanisms for these neuroprotective effects by targeting aquaporin 4. Focal cerebral ischemia was induced by middle cerebral artery occlusion. Neurological examinations were performed by using Longas 5-point scale. Evans blue dye was used to investigate the effects of ginsenoside Rg1 on blood brain barrier permeability. Immunohistochemical analysis and real-time fluorescence quantitative polymerase chain reaction were used to assess aquaporin 4 expression. As a result, general linear model with repeated measures analysis of variance for neurological scores at 5 repeated measures showed that ginsenoside Rg1-treated group could significantly reduce the changing trend of neurological deficit scores when compared with the middle cerebral artery occlusion model group (p<0.05). Compared with the middle cerebral artery occlusion model group, ginsenoside Rg1 group has significantly decreased Evans blue content and reduced aquaporin 4 expression at each time point (p<0.05). In conclusion, ginsenoside Rg1 as a ginsenoside neuroprotective agent could improve neurological injury, attenuate blood brain barrier disruption and downregulate aquaporin 4 expression induced by cerebral ischemia/reperfusion insults in rats.

Neuroprotective effect of ginsenoside-Rg1 on cerebral ischemia/reperfusion injury in rats by downregulating protease-activated receptor-1 expression

AIMS Ginsenoside-Rg1 (G-Rg1), a saponin that is a primary component of ginseng, is very useful and important in traditional Chinese medicine for stroke. The objective of this study was to explore the mechanisms underlying the neuroprotective effect of G-Rg1 on focal cerebral ischemia/reperfusion. MAIN METHODS Focal cerebral ischemia was induced by middle cerebral artery occlusion. Neurological examinations were performed by using Longas 5-point scale. The brain infarct volume was determined by the 2,3,5-triphenyltetrazolium chloride staining. The permeability of the blood-brain barrier (BBB) was evaluated by Evans blue dye. Western blot and quantitative RT-PCR were used to assess protease-activated receptor-1 (PAR-1) expression. KEY FINDINGS After G-Rg1 treatment, there was a significant decrease in the neurobehavioral function score compared with normal saline (NS) treatment after ischemia/reperfusion (P<0.05). G-Rg1 significantly reduced the infarct volume compared with NS treatment after ischemia/reperfusion (P<0.001). The permeability of the BBB was significantly decreased in the G-Rg1 group compared with the NS group (P<0.05 or P<0.01). Western blot and quantitative real time RT-PCR indicated that G-Rg1 administration down-regulated the expression of PAR-1 in the ischemic hemisphere compared with NS administration (P<0.01 and P<0.05, respectively). The level of PAR-1 expression strongly correlated with BBB permeability in both the G-Rg1- and NS-treated rats (r=0.856 and r=0.908, respectively, P<0.01). SIGNIFICANCE G-Rg1 may ameliorate the neurological injury, the brain infarct volume and the BBB permeability induced by focal cerebral ischemia in rats and its neuroprotective mechanism is related to the down-regulation of PAR-1 expression.

Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials

BackgroundInsomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia.MethodsA systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions.ResultsTwelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information.ConclusionsDespite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed.

Xiaoxuming decoction for acute ischemic stroke: A systematic review and meta-analysis

ETHNOPHARMACOLOGICAL RELEVANCE Xiaoxuming decoction (XXMD) is a well-known traditional Chinese herbal prescription in treatment of patients with stroke. The objective of this study is to assess the efficacy and safety of XXMD for acute ischemic stroke. MATERIALS AND METHODS A systematic literature search was conducted in 6 databases until June 2012 to identify randomized controlled trials (RCTs) of XXMD for acute ischemic stroke compared with western conventional medicine (WCM). The primary outcome measures were National Institutes of Health Stroke Scale (NIHSS) scores and modified Rankin Scale (mRS) scores. The secondary outcome measures were the clinical effective rate and adverse events at the end of treatment course. The methodological quality of RCTs was assessed independently using 12-item criteria according to the Cochrane Back Review Group. All data were analyzed using Review Manager 5.0 software. RESULTS Eight RCTs with 601 individuals published from 1992 to 2012 were identified. The studies were deemed to have a high risk of bias. Compared with WCM, 1 RCT showed significant effects of XXMD for improving mRS after stroke (p<0.05); 3 RCTs for improving NIHSS scores [n=186, weighted mean difference (WMD): -1.86, 95% CI: -3.25 to -0.48, z=2.63, p<0.01]; 7 RCTs for improving the clinical effective rate [n=531, risk ratio (RR)=1.17, 95% CI, 1.09 to 1.26, z=4.38, p<0.01]. Five trials contained safety assessments and stated that no adverse event was found, whereas the other 3 trials did not provide the information about adverse events. CONCLUSIONS This systematic review showed positive but weak evidence of XXMD for acute ischemic stroke because of the poor methodological quality and the small quantity of the included trials. The difficulties of fitting Chinese herbal medicine (CHM) into the double blinded RCTs have raised as follows: (A) traditional Chinese medicine (TCM) as whole systems of healthcare offers unique methodological and theoretical challenges for RCTs; (B) suspicions against the placebo and unwillingness to stop taking other CHMs make recruitment more difficulty, time-consumption, and cost; (C) the shortcomings of the TCM diagnostic process includes the lack of standardization in terminology, disagreement of pattern differentiation (Bianzheng), and neglect of formula corresponding to syndrome (TCM Zheng); (D) It is difficult to design credible herbal placebos with similar appearance, smells and tastes to the experimental CHM and at the same time is absent of any pharmacological activity; (E) the achieving efficacy of CHM complex interventions is often nonspecific and the outcome measures is subjective using Chinese quantitative instrument.

A Randomized Controlled Pilot Study of the Triple Stimulation Technique in the Assessment of Electroacupuncture for Motor Function Recovery in Patients with Acute Ischemic Stroke

The objective of this pilot study was to objectively assess electroacupuncture for motor function recovery in patients with acute ischemic stroke using the triple-stimulation technique (TST). The patients received either electroacupuncture plus western conventional medication (WCM) (n = 32) or single WCM (n = 31) for 14 days. The total clinical effective rate was statistically significantly superior in electroacupuncture group to that in WCM group (P < 0.01). Fugl-Meyer Assessment Scale (FMA) score, National Institutes of Health Stroke Scale (NIHSS) score, and TSTratio were statistically more significant in electroacupuncture group than those in WCM group (P < 0.01). There was positive correlation between TSTratio and NIHS score both before and after treatment (P < 0.01) and negative correlation between TSTratio and FAM score both before treatment and after treatment (P < 0.01). Comparing between the two groups or between pretreatment and posttreatment, adverse events, electrocardiogram, liver function, and kidney function showed no statistically significant difference (P > 0.05). In conclusion, electroacupuncture was beneficial for the motor function recovery of patients with acute ischemic stroke and was generally safe. TST can be used for quantitative evaluation of electroacupuncture for motor function recovery in patients with acute ischemic stroke because it can objectively analyze the injury and recovery of corticospinal tract impairments.

Buyang huanwu decoction for healthcare: evidence-based theoretical interpretations of treating different diseases with the same method and target of vascularity.

Buyang Huanwu Decoction (BHD) is a famous herbal prescription that has been used to treat stroke for centuries. Recent studies reported that the use of BHD had been extended to treat various kinds of disorders according to the TCM syndrome theory of Treating Different Diseases with the Same Method (TDDSM). Here, an overview of systematic reviews (SRs) of BHD for healthcare was conducted to interpret the TCM theory of TDDSM and its target of vascularity in an evidence-based manner. Literature searches were carried out in 5 databases to search SRs of BHD for any indication up to August 2013. Thirteen eligible SRs were identified which reported a wide range of vascular conditions. Based on the Overview Quality Assessment Questionnaire scores, the quality of included SRs was varied, with an average score of 4 points. We found that there is premature evidence for the use of BHD for healthcare, whereas BHD was well tolerable in all patients. BHD can be used to treat many disorders with the same therapeutic principle of invigorating Qi to activate blood circulation, which is essentially a manifestation of the TDDSM and is likely to account for targeting the specific pathogenesis of vascular diseases.

GV20-based acupuncture for animal models of acute intracerebral haemorrhage: a preclinical systematic review and meta-analysis

Background Spontaneous intracerebral haemorrhage (ICH) is the most devastating subtype of stroke, but there is currently no evidence-based treatment strategy. Acupuncture is a well-known traditional Chinese therapy for stroke-induced disability, and GV20 is the commonly used acupuncture point. Objective To evaluate the efficacy of GV20-based acupuncture in animal models of acute ICH. Methods Studies of GV20-based acupuncture in animal models of acute ICH were identified from six databases up to July 2013. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measures were neurological deficit scores and brain water content. All the data were analysed using RevMan V.5.1 software. Results Nineteen studies were identified describing procedures involving 1628 animals. The quality score of the studies ranged from 3 to 6, with a mean of 4.6. The global estimate of the effect of GV20-based acupuncture was 0.19 (95% CI 0.13 to 0.25, p<0.001) SDs improvement in outcome compared with controls. In subgroup analyses, size of effect was higher where the outcome was measured as the neurological deficit score than the brain water content or both (p<0.001). Conclusions These findings show the possible efficacy of GV20-based acupuncture in animal models of acute ICH, suggesting it as a candidate therapy for acute ICH.

Bioactive components of Chinese herbal medicine enhance endogenous neurogenesis in animal models of ischemic stroke: A systematic analysis

Background:Chinese herbal medicine (CHM) has been used to treat stroke for thousands of years. The objective of the study is to assess the current evidence for bioactive components of CHM as neurogenesis agent in animal models of ischemic stroke. Methods:We searched PubMed, China National Knowledge Infrastructure, WanFang Database, and VIP Database for Chinese Technical Periodicals published from the inception up to November 2015. The primary measured outcome was one of neurogenesis biomarker, including Bromodeoxyuridine (BrdU), Nestin, doublecortin (DCX), polysialylated form of the neural cell adhesion molecule (PSA-NCAM), neuronal nuclear antigen (NeuN), and glial fibrillary acidic protein (GFAP). Results:Thirty eligible studies were identified. The score of quality assessment ranged from 2 of 10 to 7 of 10. Compared with controls, 10 studies conducting neurobehavioral evaluation showed significant effects on bioactive components of CHM for improving neurological deficits score after ischemic insults (P < 0.01 or P < 0.05); 6 studies in Morris water-maze test showed bioactive components of CHM significantly decreased escape latency and increased residence time (P < 0.05); 5 studies demonstrated that bioactive components of CHM significantly reduced infarct volume after ischemic stroke (P < 0.05); 25 of 26 studies showed that bioactive components of CHM significantly increased the expression of BrdU and/or Nestin markers in rats/mice brain after ischemic injury (P < 0.05, or P < 0.01); 4 of 5 studies for promoting the expression of PSA-NCAM or DCX biomarker (P < 0.05); 5 studies for improving the expression of NeuN biomarker (P < 0.05); 6 of 7 studies for promoting the expression of GFAP biomarker in brain after ischemic stroke (P < 0.05). Conclusion:The findings suggest that bioactive components of CHM may improve neurological function, reduce infarct volume, and promote endogenous neurogenesis, including proliferation, migration, and differentiation of neural stem cells after ischemic stroke. However, evidences are supported but limited because only a few studies were available for each descriptive analysis. Further rigor study is still needed.

Neuroprotection of Sanhua Decoction against Focal Cerebral Ischemia/Reperfusion Injury in Rats through a Mechanism Targeting Aquaporin 4.

Sanhua decoction (SHD) is a famous classic Chinese herbal prescription for ischemic stroke, and aquaporin 4 (AQP4) is reported to play a key role in ischemic brain edema. This study aimed to investigate neuroprotection of SHD against focal cerebral ischemia/reperfusion (I/R) injury in rats and explore the hypothesis that AQP4 probably is the target of SHD neuroprotection against I/R rats. Lentiviral-mediated AQP4-siRNA was inducted into adult male Sprague-Dawley rats via intracerebroventricular injection. The focal cerebral ischemia/reperfusion model was established by occluding middle cerebral artery. Neurological examinations were performed according to Longa Scale. Brain water content, was determined by wet and dry weight measurement. Western blot was adopted to test the AQP4 expression in ipsilateral hippocampus. After the treatment, SHD alleviated neurological deficits, reduced brain water content and downregulated the expression of AQP4 at different time points following I/R injury. Furthermore, neurobehavioral function and brain edema after I/R were significantly attenuated via downregulation of AQP4 expression when combined with AQP4-siRNA technology. In conclusion, SHD exerted neuroprotection against focal cerebral I/R injury in rats mainly through a mechanism targeting AQP4.