The quality of reporting of randomized controlled trials of HuatuoZaizao pill for stroke.

Background: HuatuoZaizao pill (HZP), a Chinese patent medicine, is often used in the treatment of stroke. However, there is still a lack of enough evidence to recommend the routine use of HZP for stroke. This study is aimed at evaluating the quality of reporting of randomized controlled trials (RCTs) on HZP for stroke. Methods: RCTs on HuatuoZaizao pill for stroke were evaluated by using Consolidated Standards of Reporting Trials (CONSORT) guidelines and CONSORT extension criteria on reporting herbal interventions (CONSORT-CHM) guidelines. Microsoft Excel 2007 and SPSS20.0 was used for statistics analyses. Results: Seventeen studies involving 1801 stroke patients were identified. CONSORT-CHM has expanded 24.3% (9/37) items in CONSORT and added a small item. The average scores of CONSORT evaluation is 14.6, while the average scores of the CONSORT-CHM evaluation is 11.6. The central items in CONSORT as eligibility criterion, sample size calculation, primary outcome, method of randomization sequence generation, allocation concealment, implementation of randomization, description of blinding, and detailed statistical methods were reported in 77%, 6%, 100%, 47%, 6%, 6%, 6%, and 94% of trials, respectively. In terms of the CONSORT-CHM, none of the articles reported in detail the dosage form, origin, formula basis and so on of HZP, and only half of studies reported the outcome indicators related to Traditional Chinese Medicine syndromes. Conclusion: The overall report quality of RCT related to HZP is low. HZP still needs to report higher quality RCTs to prove its effectiveness and safety.

Buyang Huanwu Decoction Enhances Revascularization via Akt/GSK3ß/NRF2 Pathway in Diabetic Hindlimb Ischemia.

BACKGROUND: Peripheral arterial disease (PAD) is a typical disease of atherosclerosis, most commonly influencing the lower extremities. In patients with PAD, revascularization remains a preferred treatment strategy. Buyang Huanwu decoction (BHD) is a popular Chinese herbal prescription which has showed effects of cardiovascular protection through conducting antioxidant, antiapoptotic, and anti-inflammatory effects. Here, we intend to study the effect of BHD on promoting revascularization via the Akt/GSK3ß/NRF2 pathway in diabetic hindlimb ischemia (HLI) model of mice. MATERIALS AND METHODS: All db/db mice (n = 60) were randomly divided into 6 groups by table of random number. (1) Sham group (N = 10): 7-0 suture thread passed through the underneath of the femoral artery and vein without occlusion. The remaining 5 groups were treated differently on the basis of the HLI (the femoral artery and vein from the inguinal ligament to the knee joint were transected and the vascular stump was ligated with 7-0 silk sutures) model: (2) HLI+NS group (N = 15): 0.2 ml NS was gavaged daily for 3 days before modeling and 14 days after occlusion; (3) HLI+BHD group (N = 15): 0.2 ml BHD (20 g/kg/day) was gavaged daily for 3 days before modeling and 14 days after occlusion; (4) HLI+BHD+sh-NC group (N = 8): local injection of adenovirus vector carrying the nonsense shRNA (Ad-GFP) in the hindlimbs of mice before treatment; (5) HLI+BHD+sh-NRF2 group (N = 8): knockdown of NRF2 in the hindlimbs of mice by local intramuscular injection of adenovirus vector carrying NRF2 shRNA (Ad-NRF2-shRNA) before treatment; and (6) HLI+BHD+LY294002 group (N = 4): intravenous injection of LY294002 (1.5 mg/kg) once a day for 14 days on the basis of the HLI+BHD group. Laser Doppler examination, vascular cast, and immunofluorescence staining were applied to detect the revascularization of lower limbs in mice. Western blot analysis was used to detect the expression of vascular endothelial growth factor (VEGF), interleukin-1beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor- (TNF-) α, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase quinone-1 (NQO-1), catalase (CAT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphorylated protein kinase B (p-AKT), and phosphorylated glycogen synthase kinase-3 beta (p-GSK3ß). HE staining was used to assess the level of muscle tissue damage and inflammation in the lower extremities. Local multipoint injection of Ad-NRF2-shRNA was used to knock down NRF2, and qPCR was applied to detect the mRNA level of NRF2. The blood glucose, triglyceride, cholesterol, MDA, and SOD levels of mice were tested using corresponding kits. The SPSS 20.0 software and GraphPad Prism 6.05 were used to do all statistics. Values of P < 0.05 were considered as statistically significant. Results and Conclusions. BHD could enhance the revascularization of lower limbs in HLI mice, while BHD has no effect on blood glucose and lipid level in db/db mice (P > 0.05). BHD could elevate the protein expression of VEGF, HO-1, NQO-1, and CAT (P < 0.05) and decrease the expression of IL-1ß, IL-6, and TNF-α (P < 0.05) in HLI mice. Meanwhile, BHD could activate NRF2 and promote the phosphorylation of AKT/GSK3ß during revascularization (P < 0.05). In contrast, knockdown of NRF2 impaired the protective effects of BHD on HLI (P < 0.05). LY294002 inhibited the upregulation of NRF2 activated by BHD through inhibiting the phosphorylation of the AKT/GSK3ß pathway (P < 0.05). The present study demonstrated that BHD could promote revascularization on db/db mice with HLI through targeting antioxidation, anti-inflammation, and angiogenesis via the AKT/GSK3ß/NRF2 pathway.

Neuroprotective Effect of Astragaloside IV on Cerebral Ischemia/Reperfusion Injury Rats Through Sirt1/Mapt Pathway.

Background: Ischemic stroke is a common disease with poor prognosis, which has become one of the leading causes of morbidity and mortality worldwide. Astragaloside IV (AS-IV) is the main bioactive ingredient of Astragali Radix (which has been used for ischemic stroke for thousands of years) and has been found to have multiple bioactivities in the nervous system. In the present study, we aimed to explore the neuroprotective effects of AS-IV in rats with cerebral ischemia/reperfusion (CIR) injury targeting the Sirt1/Mapt pathway. Methods: Sprague-Dawley rats (male, 250-280 g) were randomly divided into the Sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, AS-IV group, MCAO/R + EX527 (SIRT1-specific inhibitor) group, and AS-IV + EX527 group. Each group was further assigned into several subgroups according to ischemic time (6 h, 1 d, 3 d, and 7 days). The CIR injury was induced in MCAO/R group, AS-IV group, MCAO/R + EX527 group, and AS-IV + EX527 group by MCAO surgery in accordance with the modified Zea Longa criteria. Modified Neurological Severity Scores (mNSS) were used to evaluate the neurological deficits; TTC (2,3,5-triphenyltetrazolium chloride) staining was used to detect cerebral infarction area; Western Blot was used to assess the protein levels of SIRT1, acetylated MAPT (ac-MAPT), phosphorylated MAPT (p-MAPT), and total MAPT (t-MAPT); Real-time Quantitative Polymerase Chain Reaction (qRT-PCR) was used in the detection of Sirt1 and Mapt transcriptions. Results: Compared with the MCAO/R group, AS-IV can significantly improve the neurological dysfunction (p < 0.05), reduce the infarction area (p < 0.05), raise the expression of SIRT1 (p < 0.05), and alleviate the abnormal hyperacetylation and hyperphosphorylation of MAPT (p < 0.05). While compared with the AS-IV group, AS-IV + EX527 group showed higher mNSS scores (p < 0.05), more severe cerebral infarction (p < 0.05), lower SIRT1 expression (p < 0.01), and higher ac-MAPT and p-MAPT levels (p < 0.05). Conclusion: AS-IV can improve the neurological deficit after CIR injury in rats and reduce the cerebral infarction area, which exerts neuroprotective effects probably through the Sirt1/Mapt pathway.

Preclinical systematic review of ginsenoside Rg1 for cognitive impairment in Alzheimer's disease.

Ginseng has been used for the treatment of aging and memory impairment for thousands of years. Several studies have found that ginsenoside Rg1, as one of the main active components of ginseng, could potentially improve cognitive function in several different animal models. A preclinical systematic review to evaluate the efficacy and mechanisms of ginsenoside Rg1 for ameliorating cognitive impairments in Alzheimer's disease is reported here. We searched six databases from their inceptions to January 2019. Thirty-two studies were selected, which included a total of 1,643 animals. According to various cognitive behavioral tests, the results of the meta-analyses showed that ginsenoside Rg1 significantly improved cognitive behavioral impairments in most Alzheimer's disease models (P < 0.05), but there were no significant effects in animals with neuronal degeneration induced by chronic stress or in SAMP8 transgenic mice. The potential mechanisms included antioxidant and anti-inflammatory effects, amelioration of Alzheimer's disease-related pathology, synapse protection, and up-regulation of nerve cells via multiple signaling pathways.

History and Development of TCM Case Report in a Real-World Setting.

OBJECTIVE: The medical record of Chinese medicine is a miniature of the theoretical system of traditional Chinese medicine (TCM), with a time-honored history in a real-world setting and a firm place in medicine. In modern times, people have emphasized the value and standardization of TCM cases. The aim of this study was to explore the historical origins and developments of TCM case records. METHODS: A chronological narrative style was used to divide the development history of TCM case records into early (1600 BC-220 AD), middle (220-1911 AD), and modern periods (1912-till now). The historical context of the origin and development of TCM case records was analyzed through the evolution of the format and content of the case recording files with the specific documents and distinctive cases. RESULTS: From the early to middle period, the development of TCM case record had experienced four periods: the budding, blossoming, maturity, and heyday. In modern times, they presented the following characteristics: A, the establishment and development of the discipline of TCM medical records; B, the standardization of the writing format of TCM medical records; C, a large number of books concentrating on recording and studying TCM medical records, especially those of prestigious veteran TCM doctors; D, the proliferation of TCM case reports published in journals; E, the establishment of TCM medical records databases and application platforms integrating computer programs and artificial intelligence; F, many reporting guidelines have been developed in order to improve the reporting quality of case report in TCM. CONCLUSIONS: The study analyzed and illustrated the characteristics of TCM case records of different dynasties in terms of writing content and format. TCM case record is a relatively young discipline in spite of its ancient origins. TCM case records still have far-reaching significance for the inheritance and development of TCM theory and clinical experience. From the wisdom of history, its positive impact has just been revalued to be validated and it will continue to develop.

Clinical and Preclinical Systematic Review of Astragalus Membranaceus for Viral Myocarditis.

Astragalus membranaceus (AM) is a traditional Chinese medicine, which possesses a variety of biological activities in the cardiovascular systems. We conducted a clinical and preclinical systematic review of 28 randomized clinical control studies with 2522 participants and 16 animal studies with 634 animals to evaluate the efficacy, safety, and possible mechanisms of AM for viral myocarditis (VM). The search strategies were performed in 7 databases from inception to January 2020. Application of the Cochrane Collaboration's tool 7-item checklist, SYRCLE's tool 10-item checklist, and Rev-Man 5.3 software to analyze the risk of bias of studies and data. The results show the score of clinical study quality ranged from 3 to 7 points with an average of 3.32, and the score of animal study quality ranged from 2 to 5 points with an average of 3. In clinical study, AM significantly reduced serum myocardial enzymes and cardiac troponin I levels and improved the clinical treatment efficiency in VM patients compared with the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions (P > 0.05). Significant increase of the survival rate and decrease of the cardiac cardiology score, cardiac enzymes, and cardiac troponin I were compared with the placebo group in animal studies (P < 0.05). The possible mechanisms of AM are largely through antivirus and antivirus receptors, anti-inflammatory, antioxidation, antiapoptotic, antifibrosis, and reducing cardiac calcium load. In conclusion, the findings suggested that AM is a cardioprotection candidate drug for VM.

Extracts or Active Components from Acorus gramineus Aiton for Cognitive Function Impairment: Preclinical Evidence and Possible Mechanisms.

Extracts or active components from Acorus gramineus Aiton (EAAGA) have been clinically used for cognition impairment more than hundreds of years and are still used in modern times in China and elsewhere worldwide. Previous studies reported that EAAGA improves cognition impairment in animal models. Here, we conducted a preclinical systematic review to assess the current evidence of EAAGA for cognition impairment. We searched 7 databases up until June 2019. Methodological quality for each included studies was accessed according to the CAMARADES 10-item checklist. The primary outcome measures were neurobehavioral function scores evaluated by the Morris water maze test, electrical Y-maze test, step-down test, radial eight-arm maze test, and step-through test. The secondary outcome measures were mechanisms of EAAGA for cognition function. Finally, 34 studies involving 1431 animals were identified. The quality score of studies range from 1 to 6, and the median was 3.32. Compared with controls, the results of the meta-analysis indicated EAAGA exerted a significant effect in decreasing the escape latency and error times and in increasing the length of time spent in the platform quadrant and the number of platform crossings representing learning ability and memory function (all P < 0.01). The possible mechanisms of EAAGA are largely through anti-inflammatory, antioxidant, antiapoptosis activities, inhibition of neurotoxicity, regulating synaptic plasticity, protecting cerebrovascular, stimulating cholinergic system, and suppressing astrocyte activation. In conclusion, EAAGA exert potential neuroprotective effects in experimental cognition impairment, and EAAGA could be a candidate for cognition impairment treatment and further clinical trials.

Sanhua Decoction, a Classic Herbal Prescription, Exerts Neuroprotection Through Regulating Phosphorylated Tau Level and Promoting Adult Endogenous Neurogenesis After Cerebral Ischemia/Reperfusion Injury.

Background: Ischemia stroke is the leading cause of death and long-term disability. Sanhua Decoction (SHD), a classic Chinese herbal prescription, has been used for ischemic stroke for about thousands of years. Here, we aim to investigate the neuroprotective effects of SHD on cerebral ischemia/reperfusion (CIR) injury rat models. Methods: The male Sprague-Dawley rats (body weight, 250-280 g; age, 7-8 weeks) were randomly divided into sham group, CIR group, and SHD group and were further divided into subgroups according to different time points at 6 h, 1, 3, 7, 14, 21, and 28 d, respectively. The SHD group received intragastric administration of SHD at 10 g kg-1 d-1. The focal CIR models were induced by middle cerebral artery occlusion according to Longa's method, while sham group had the same operation without suture insertion. Neurological deficit score (NDS) was evaluated using the Longa's scale. BrdU, doublecortin (DCX), and glial fibrillary acidic protein (GFAP) were used to label proliferation, migration, and differentiation of nerve cells before being observed by immunofluorescence. The expression of reelin, total tau (t-tau), and phosphorylated tau (p-tau) were evaluated by western blot and RT-qPCR. Results: SHD can significantly improve NDS at 1, 3, 7, and 14 d (p < 0.05), increase the number of BrdU positive and BrdU/DCX positive cells in subventricular zone at 3, 7, and 14 d (p < 0.05), upregulate BrdU/GFAP positive cells in the ischemic penumbra at 28 d after CIR (p < 0.05), and reduce p-tau level at 1, 3, 7, and 14 d (p < 0.05). There was no significant difference on reelin and t-tau level between three groups at each time points after CIR. Conclusions: SHD exerts neuroprotection probably by regulating p-tau level and promoting the proliferation, migration, and differentiation of endogenous neural stem cells, accompanying with neurobehavioral recovery.

A Survey of Application of Complementary and Alternative Medicine in Chinese Patients with Parkinson's Disease: A Pilot Study.

OBJECTIVE: To investigate the prevalence and spectrum of complementary and alternative medicine (CAM) application and its related-factors in Parkinson's disease (PD) patients in China. METHODS: A structured questionnaire regarding the use of CAMs was administered to PD patients by face-to-face interview. Demographic and social variables, clinical characteristics and treatments, and the related factors of PD were also surveyed. RESULTS: Ninety out of 113 patients (79.6%) reported that they had received CAMs treatment, of which 48.6% (55/113) patients had received CAMs treatment for PD. The top 3 kinds of CAMs for PD were Chinese materia medica, rehabilitation exercise, and acupuncture ordinally. The source of information regarding CAMs treatment mainly came from relatives and friends (51.8%, 73 cases), followed by physicians (31.9%, 45 cases), and medias such as television, newspapers or the internet (16.3%, 28 cases). Fifty percent of CAM users reported a good therapeutic efficacy, whereas 39% patients reported that they felt neither better nor worse after the treatment, while 11% patients claimed worsening of symptoms. Multiple correspondence analyses survey found the main factors affecting the selectivity of CAMs ranked in the following order: income, education, occupation, habitation, age at onset, Hoehn and Yahr staging, PD duration, and gender. CONCLUSION: CAMs, especially Chinese materia medica, rehabilitation exercise, and acupuncture, are widely used for PD patients in China.

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.

Herbal Compatibility of Ginseng and Rhubarb Exerts Synergistic Neuroprotection in Cerebral Ischemia/Reperfusion Injury of Rats.

OBJECTIVE: Ischemic stroke is a complex multifactorial disease caused by interactions among polygenetic, environmental, and lifestyle factors with limited effective treatments. Multi-herbal formulae have long been used for stroke through herbal compatibility in traditional Chinese medicine (TCM); however, there is still a lack of evidence due to their unimaginable complexity. Herbal pairs represent the simplest and basic features of multi-herbal formulae, which are of great significance in clarifying herbal compatibility. Here, we aim to investigate the neuroprotective effects of the herbal compatibility of Ginseng and Rhubarb on a cerebral ischemia/reperfusion (I/R) injury model of rats. METHODS: Male adult SD rats were randomly divided into a sham group, a normal saline (NS) group, a Ginseng group, a Rhubarb group, and a Ginseng + Rhubarb (GR) group, a Carbenoxolone [CBX, gap junction (GJ) specific inhibitor] group, and a GR + CBX group. Each group was further assigned into four subgroups according to ischemic time (6 h, 1 day, 3 days, and 7 days). The cerebral I/R injury model was established according to the modified Zea Longa method. The Neurological Deficiency Score (NDS) was assessed by the Zea-Longa scale; the cerebral infarction area was detected by TTC (2,3,5-triphenyltetrazolium chloride) staining; and the expression of connexin-43 (Cx43) and aquaporin-4 (AQP4) were detected based on an immunofluorescence technique and quantitative real-time-PCR. RESULTS: Compared to the I/R group, both the independent and combined use of Ginseng and Rhubarb can significantly improve NDS (P < 0.05), decrease the percentage of the cerebral infarction area around the infarction penumbra (P < 0.05) and down-regulate the expression of Cx43 and AQP4 after I/R injury (P < 0.05). The GR had more significant effects than that of Ginseng and Rhubarb (P < 0.05). Compared with the GR group, the GR + CBX group significantly improved in NDS (P < 0.05), and decreased the percentage of the cerebral infarction area (P < 0.05) and expression of Cx43 and AQP4 protein (P < 0.05). CONCLUSION: The herbal compatibility of Ginseng and Rhubarb synergistically exerts neuroprotective function during acute cerebral I/R injury, mainly through reducing the expression of Cx43 and AQP4.

Traditional Chinese Medicine for Coronary Heart Disease: Clinical Evidence and Possible Mechanisms.

Coronary heart disease (CHD) remains a major cause of mortality with a huge economic burden on healthcare worldwide. Here, we conducted a systematic review to investigate the efficacy and safety of Chinese herbal medicine (CHM) for CHD based on high-quality randomized controlled trials (RCTs) and summarized its possible mechanisms according to animal-based researches. 27 eligible studies were identified in eight database searches from inception to June 2018. The methodological quality was assessed using seven-item checklist recommended by Cochrane Collaboration. All the data were analyzed using Rev-Man 5.3 software. As a result, the score of study quality ranged from 4 to 7 points. Meta-analyses showed CHM can significantly reduce the incidence of myocardial infarction and percutaneous coronary intervention, and cardiovascular mortality (P < 0.05), and increase systolic function of heart, the ST-segment depression, and clinical efficacy (P < 0.05). Adverse events were reported in 11 studies, and CHMs were well tolerated in patients with CHD. In addition, CHM exerted cardioprotection for CHD, possibly altering multiple signal pathways through anti-inflammatory, anti-oxidation, anti-apoptosis, improving the circulation, and regulating energy metabolism. In conclusion, the evidence available from present study revealed that CHMs are beneficial for CHD and are generally safe.

Efficacy and safety of Chinese herbal medicine for depression: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To conduct a systematic review to assess the current evidence available for the effectiveness and safety of Chinese herbal medicine (CHM) for depression. METHODS: An electronic search was conducted in eight databases from inception until April 2018. Randomized controlled trials with risk of bias (RoB) score ≥ 4 according to the Cochrane RoB tool were included for analyses. The primary outcome was the severity of depression. The secondary outcomes were total effective rate (TER) and adverse events. The minimally important difference (MID) of the severity of depression was a reduction in the Hamilton Rating Scale for Depression 17 items (HAMD-17) scores by 4. RevMan 5.3 Software was used for data analyses. GRADE system was used to assess the certainty of evidence. RESULTS: A total of 40 eligible studies with 3549 subjects were identified. Meta-analyses showed that CHM monotherapy had better clinically effects than placebo according to HAMD-17 score (Mean Difference (MD) = -4.53, 95% CI (-5.69, -3.37), P < 0.00001; Certainty of evidence: Moderate) and TER (Risk Ratio (RR) = 2.15, 95% CI (1.61, 2.88), P < 0.00001, Certainty of evidence: Low). Meta-analyses showed that CHM was as effective as western conventional medications (WCM) in TER (RR = 0.99, 95% CI (0.95, 1.02), P = 0.41, Certainty of evidence: High) and in reducing HAMD-17 score (MD = 0.44, 95% CI (-0.11, 0.99), P = 0.12, Certainty of evidence: Moderate). Meta-analyses showed that CHM in combination with WCM was better than WCM in TER (RR = 1.16, 95% CI (1.07, 1.27), P = 0.0004, Certainty of evidence: High), while had comparable clinically effects with WCM according to HAMD-17 score (MD = -2.51, 95% CI (-3.24, -1.77), P < 0.00001, Certainty of evidence: Moderate). In additional, CHM were associated with less adverse events than WCM, and adding CHM to WCM reduced adverse events. CONCLUSION: The findings of present systematic review, at least to a certain extent, provided supporting evidence for the routine use of CHM for depression.

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.

An Overview of Systematic Reviews of Chinese Herbal Medicine for Parkinson's Disease.

Parkinson's disease (PD) is a high prevalence neurodegenerative disorder without a disease-modifying therapy. Up to now, a number of systematic reviews have been conducted to evaluate efficacy and safety of Chinese herbal Medicine (CHM) for PD patients. Here, we aimed to assess the methodological quality and reporting quality of systematic reviews using an overview, and then synthesize and evaluate the available evidence level of CHM for PD. Six databases were searched from inception to September 2018. The literatures were selected and data were extracted according to prespecified criteria. A Measurement Tool to Assess Systematic Reviews (AMSTAR) was used to evaluate the quality of methodology, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to determine the evidence quality of the primary outcome measures. A total of 11 systematic reviews with 230 RCTs of CHM for PD were included. AMSTAR scores of the included reviews were range from 4 to 9. Compared with conventional western medicine (WCM), CHM paratherapy showed significant effect in improving UPDRS score, Webster scale score, PDQ-39, NMSQuest, CHM Syndrome Integral Scale, and PDSS. However, CHM monotherapy showed no difference relative to WCM according to various outcome measures. Adverse events were reported in 9 systematic reviews. The side effect in CHM paratherapy group was generally less than or lighter than that in WCM group. The quality of the evidence of primary outcomes was moderate (42%) to high (54%) according to the GRADE profiler. The present finding supported the use of CHM paratherapy for PD patients but we should treat the evidence cautiously because of the methodological flaws, whereas there is insufficient evidence of CHM monotherapy for PD.

Borneol for Regulating the Permeability of the Blood-Brain Barrier in Experimental Ischemic Stroke: Preclinical Evidence and Possible Mechanism.

Borneol, a natural product in the Asteraceae family, is widely used as an upper ushering drug for various brain diseases in many Chinese herbal formulae. The blood-brain barrier (BBB) plays an essential role in maintaining a stable homeostatic environment, while BBB destruction and the increasing BBB permeability are common pathological processes in many serious central nervous system (CNS) diseases, which is especially an essential pathological basis of cerebral ischemic injury. Here, we aimed to conduct a systematic review to assess preclinical evidence of borneol for experimental ischemic stroke as well as investigate in the possible neuroprotective mechanisms, which mainly focused on regulating the permeability of BBB. Seven databases were searched from their inception to July 2018. The studies of borneol for ischemic stroke in animal models were included. RevMan 5.3 was applied for data analysis. Fifteen studies investigated the effects of borneol in experimental ischemic stroke involving 308 animals were ultimately identified. The present study showed that the administration of borneol exerted a significant decrease of BBB permeability during cerebral ischemic injury according to brain Evans blue content and brain water content compared with controls (P < 0.01). In addition, borneol could improve neurological function scores (NFS) and cerebral infarction area. Thus, borneol may be a promising neuroprotective agent for cerebral ischemic injury, largely through alleviating the BBB disruption, reducing oxidative reactions, inhibiting the occurrence of inflammation, inhibiting apoptosis, and improving the activity of lactate dehydrogenase (LDH) as well as P-glycoprotein (P-GP) and NO signaling pathway.

Chinese herbal medicine for headache: A systematic review and meta-analysis of high-quality randomized controlled trials.

BACKGROUND: Chinese herbal medicines (CHMs) are widely used to relieve headache in Asia. However, it is uncertain whether there is robust evidence on the effects of CHMs for headache. PURPOSE: To assess the effectiveness and safety of CHMs for headache using systematic review of high-quality randomized controlled trials (RCTs). METHODS: Electronic search was conducted on six databases from inception to January 2018. We included the RCTs that met the requirement of at least 4 out of the 7 domains according to the Cochrane risk of bias tool. RESULTS: Thirty RCTs with 3447 subjects were ultimately included for analysis and all trials were conducted in Asia. Meta-analysis showed that CHMs monotherapy were superior to placebo in reducing headache frequency [SMD -0.48 (95% CI -0.76, -0.20); p < 0.01], headache days [SMD -0.29 (95% CI -0.45, -0.13); p < 0.01], headache duration[SMD -0.58 (95% CI -0.81, -0.36); p < 0.01], headache intensity [SMD -0.42 (95% CI -0.62, -0.23); p < 0.01] and analgesic consumption [SMD -0.36 (95% CI -0.52, -0.21); p < 0.01] and improving clinical efficacy rate (p < 0.01). Similarly, CHMs monotherapy were superior to western conventional medicines (WCMs) in headache frequency [SMD -0.57 (95% CI -0.84, -0.29); p < 0.01], headache days (p < 0.01), analgesic consumption [SMD -1.63 (95% CI -1.98, -1.28); p < 0.01], headache intensity [SMD -0.81 (95% CI -1.06, -0.57); p < 0.01], and clinical efficacy rate [RR 1.24 (95% CI 1.18, 1.31); p < 0.01], except reducing headache duration (p > 0.05). CHMs adjunct therapy can improve clinical efficacy rate compared with WCMs alone [RR 1.15 (95% CI 1.09, 1.22); p < 0.01]. Meanwhile, CHMs had fewer adverse events than that of controls. CONCLUSION: The findings supported, at least to an extent, the use of CHM for headache patients; however, we should treat the results cautiously because the clinical heterogeneity.

Erxian decoction, a Chinese herbal formula, for menopausal syndrome: An updated systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Erxian decoction (EXD), a famous Chinese herbal prescription, consists of Rhizoma Curculiginis, Herba Epimedii, Radix Morindae Officinalis, Radix Angelicae Sinensis, Cortex Phellodendri, Rhizoma Anemarrhenae, all of which are recorded in the Chinese Pharmacopoeia. OBJECTIVE: To conduct an updated systematic and meta-analysis investigating efficacy and safety of EXD for menopausal syndrome. METHODS: An electronic search was conducted in eight databases from inception until July 2018. Randomized controlled trials with risk-of-bias score ≥ 7 according to the Cochrane Back Review Group were included for analyses. All participants with a diagnosis of menopausal syndrome met the established criteria. The treatment group was EXD monotherapy or adjunct therapy. Comparators were placebo, hormone replace therapy, hormone plus nonhormonal agents, nonhormonal agents and no treatment. The primary outcome measurements were the Kupperman index, total hot flush scores, total menopause rating scale (MRS) scores and total menopause-specific quality of life (MENQOL) scores. The secondary outcomes were total clinical effective rate, traditional Chinese medicine (TCM) syndrome scores, Hamilton depression (HAMD) scale scores, self-rating depression scale (SDS) scores, self-Rating Anxiety Scale (SAS) scores, athens insomnia scale (AIS) scores, serological indicators, blood pressure, and adverse events. RevMan 5.3 Software was used for data analyses. GRADE system was used to assess the level of evidence. RESULTS: Sixteen eligible studies with 1594 subjects were identified. Five studies showed EXD was contradictory results according to Kupperman index of menopausal syndrome compared with hormone. One study showed EXD significantly improved total hot flush scores, total MRS scores and total MENQOL scores compared with placebo (P < 0.05). Meta-analysis of 10 EXD monotherapy or 2 paratherapy studies showed that both can significantly improve total effective rate compared with hormone (P < 0.05); 3 studies showed that EXD plus hormone significantly reduces the TCM syndrome scores, HAMD scale scores, SDS scores and SAS scores compared with hormone (P < 0.05). One study showed a significant effect of EXD for reducing AIS scores compared with hormone (P < 0.05); 7 studies showed contradictory effects for improving serological indicators compared with hormone. Two studies reported adverse effects, whereas the other studies did not mention. The quality of the evidence of primary outcomes was moderate to high according to the GRADE profiler. CONCLUSIONS: The present findings do not allow an assessment of the evidence because the low-quality studies included cannot be reproduced. However, we identified an area, which is worthy of further research. Rigorous RCTs are still needed in the future.

Kaixinsan, a Well-Known Chinese Herbal Prescription, for Alzheimer's Disease and Depression: A Preclinical Systematic Review.

Alzheimer's disease (AD), the most common cause of dementia, is highly prevalent worldwide with no modifying therapy. Behavioral and psychological symptoms of dementia (BPSD) occur in most patients with AD, and depression is one of the most common AD-related BPSD. Kaixinsan (KXS) is an ancient Chinese herbal prescription widely used to treat dementia and forgetfulness. In this systematic review, we conducted a meta-analysis to assess preclinical evidence for the effects of KXS on cognitive impairment and depression. Thirty-eight articles involving 1,050 animals were included after searching from six databases from the inception up to June 2019. The primary outcome measures were behavioral outcome. Indicators of cognitive function in AD included escape latency, time spent on the target quadrant, and the number of target platform crossings in the Morris water maze (MWM) test. Indicators of depression included number of rearing events and total distance in the open-field test, duration of immobility in the forced swim test, and sucrose consumption or sucrose preference index in the sucrose preference test. The secondary outcomes were mechanisms of KXS for treatment of AD and depression. The results showed that KXS significantly reduced escape latency (P < 0.01), increased time spent in the target quadrant (P < 0.01), and increased the number of target platform crossings (P < 0.01) in the MWM test in AD models compared with control. The possible mechanisms for KXS-mediated improvements in cognitive function were antioxidant activity, anti-inflammatory activity, antiapoptotic activity, neuroprotection, and synapse protection. In addition, the results demonstrated that KXS significantly increased the number of rearing instances (P < 0.01) in the open-field test, decreased the duration of immobility (P < 0.01) in forced swim test, and increased sucrose consumption or sucrose preference index (P < 0.01) in the sucrose preference test in depression models compared with control. The mechanisms of KXS-mediated anti-depressive effects were HPA axis regulation, antioxidant activity, anti-inflammatory activity, synapse protection, and neuroprotection. The results of this study suggested that KXS can be used to effectively treat AD and depression through multiple mechanisms, extrapolating the therapeutic potential of KXS for treating AD-related BPSD.