Effectiveness of kumquat decoction for the improvement of cough caused by SARS-CoV-2 Omicron variants, a multicentre, prospective observational study.

BACKGROUND: Kumquat decoction is a traditional Chinese medicine formula and has been widely used to alleviate the coronavirus disease 2019 (COVID-19)-related cough in China. However, the effectiveness and safety of kumquat decoction remain unclear. PURPOSE: To assess the effectiveness and safety of kumquat decoction for COVID-19-related cough. STUDY DESIGN: A multicentre, prospective observational study. METHODS: We enrolled consecutive patients with mild-to-moderate COVID-19 from December 31, 2022, to January 3, 2023, during the Omicron phase in Yangshuo County, China. The primary outcome was the time from study baseline to sustained cough resolution by the last follow-up day on January 31, 2023. The effectiveness was evaluated by Cox proportional hazards models based on propensity score analyses. The secondary outcomes were the resolution of cough and other COVID-19-related symptoms by Days 3, 5, and 7. RESULTS: Of 1434 patients, 671 patients were excluded from the analysis of cough resolution. Among the remaining 763 patients, 481 (63.04%) received kumquat decoction, and 282 (36.96%) received usual care. The median age was 38.0 (interquartile range [IQR] 29.0, 50.0) years, and 55.7% were women. During a median follow-up of 7.000 days, 68.2% of patients in the kumquat group achieved sustained cough resolution (93.77 per 1000 person-days) compared to 39.7% in the usual care group (72.94 per 1000 person-days). The differences in restricted mean survival time (RMST) (kumquat decoction minus usual care group) for cough resolution were -0.742 days (95% CI, -1.235 to -0.250, P = 0.003) on Day 7. In the main analysis using propensity-score matching, the adjusted hazard ratio (HR) for cough resolution (kumquat decoction vs. usual care group) was 1.94 (95% CI, 1.48 to 2.53, P < 0.001). Similar findings were found in multiple sensitivity analyses. In addition, the use of kumquat decoction was associated with the resolution of cough, and a stuffy nose on Days 5 and 7, as well as the resolution of sore throat on Day 7 following medication. CONCLUSION: In this study among patients with COVID-19-related cough, receiving kumquat decoction was associated with an earlier resolution of cough symptoms.

Acupuncture for post-stroke depression: a systematic review and network meta-analysis.

BACKGROUND: Patients with post-stroke depression (PSD) usually experience anxiety, hopelessness, and insomnia, which have a negative impact on their daily activities and post-stroke rehabilitation. Acupuncture (AC), as a minimally invasive technique, has become a popular choice for improving depression symptoms. However, it is still unclear which therapy is associated with the best outcomes for PSD. In this review, we aimed to explore the impact of AC in alleviating symptoms of PSD and to evaluate the difference in effectiveness between AC combined with pharmacotherapies and various non-pharmacotherapies. METHODS: Six databases and three clinical trials registration platforms were searched from inception to March 2023. Randomized clinical trial comparing needle-based AC with pharmacotherapy, and other non-pharmacotherapy or invalid group were included. Two independent reviewers identified eligible studies, and collected data using a pre-made form. A Bayesian network meta-analysis was conducted to assess and compare different techniques using RStudio 3.6.0 with the package 'GEMTC' V.0.8.1. The primary outcome was the efficacy for PSD assessed by scales measuring depressive symptoms. The secondary outcomes were effectiveness for neurological function and the quality of life. The ranking probabilities for all treatment interventions was performed using the Surface Under the Cumulative Ranking curve (SUCRA). The risk of bias was assessed by using the Revised Cochrane Risk of Bias tool 2. RESULTS: Sixty-two studies, involving 5308 participants published from 2003 to 2022, were included. The results showed that compared with western medicine (WM) (defined as pharmacotherapy for PSD), AC alone or with repetitive transcranial magnetic stimulation (RTMS), Traditional Chinese medicine (TCM) alone or with WM, were superior for alleviating depression symptoms. Compared to Usual Care, AC alone or plus other therapies could significantly decrease scores on the Hamilton Depression Rating scale. According to result of SUCRA, AC plus RTMS had the highest probability of improving depressive symptoms with a probability of 49.43%. CONCLUSIONS: The results of this study indicate that AC alone or combined with other therapies appears to be effective in improving depression symptoms of stroke survivors. Moreover, in comparison to WM, AC alone or plus RTMS, TCM, TCM with WM, or WM, were more effective in improving depression symptoms of PSD. Also, AC with RTMS seems to be the most effective with the highest probability. REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database in November 2020 and updated in July 2021. The registration number is CRD42020218752.

A framework on developing integrative medicine clinical practice guideline for stroke management and rehabilitation in Hong Kong.

BACKGROUND: Stroke is the second leading cause of death worldwide. In Hong Kong, the proportion of deaths caused by cerebrovascular disease accounted for approximately 6.8% of total deaths. Although integrative medicine approaches are widely adapted by patients, there is a lack of guideline to support the corresponding clinical practice for stroke management and rehabilitation. Therefore, we design this framework for the development of an integrative medicine clinical practice guideline (CPG) for stroke. METHODS: The framework follows the instructions of World Health Organization (WHO) handbook for guideline development, Guideline International Network (GIN), Appraisal of Guidelines for Research and Evaluation Instrument (AGREE II), and Reporting Items for Practice Guidelines in Healthcare (RIGHT). Three stages with ten steps are conducted. CONCLUSION: Clinical practice guidelines are essential to provide optimal recommendations for patients' prognosis. With proper methodology, this framework will facilitate the formation of clinical practice guideline for stroke through synthesizing evidences in the scope of integrative medicine.

Would integrated Western and traditional Chinese medicine have more benefits for stroke rehabilitation? A systematic review and meta-analysis.

BACKGROUND: Stroke is a major cause of death or long-term disability worldwide. Many patients with stroke receive integrative therapy consisting of Western medicine (WM) and routine rehabilitation in conjunction with Chinese medicine (CM), such as acupuncture and Chinese herbal medicine. However, there is no available evidence on the effectiveness of the combined use of WM and CM interventions in stroke rehabilitation. AIMS: The purpose of this meta-analysis is to evaluate the results of all individual studies to assess the combined use of CM and WM in stroke rehabilitation compared with WM only. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. MEDLINE, EMBASE, Cochrane and China National Knowledge Infrastructure (CNKI) were searched. The included outcomes were dependency, motor function, depression and swallowing function. Subgroup analysis was performed, and publication bias was assessed using funnel plots. SUMMARY OF REVIEW: 58 studies and 6339 patients were included in the meta-analysis. Subgroup analysis revealed that combined therapy comprising both acupuncture and WM had a superior effect on improving dependency and swallowing function compared with standard WM therapy alone. Potential superiority of combined therapy comprising CM and WM in improving depression compared with standard WM therapy was also found. CONCLUSIONS: Our results indicate that the combined use of CM and WM could be more efficacious in stroke rehabilitation compared with the use of WM therapy alone. However, most studies were short in duration (2 to 4 weeks) and prone to different types of biases, which prevents making any conclusion regarding the long-term effects and raises concerns regarding true efficacy in context of high likelihood of Hawthorn bias. So, more randomised controlled trials with more rigorous design and longer duration of treatment and follow-up need to be conducted to compare WM alone versus WM and CM combined. PROSPERO REGISTRATION NUMBER: CRD42020152050.

Effect and safety of Chinese herbal medicine granules in patients with severe coronavirus disease 2019 in Wuhan, China: a retrospective, single-center study with propensity score matching.

BACKGROUND: Chinese herbal medicine (CHM) has been used for severe illness caused by coronavirus disease 2019 (COVID-19), but its treatment effects and safety are unclear. PURPOSE: This study reviews the effect and safety of CHM granules in the treatment of patients with severe COVID-19. METHODS: We conducteda single-center, retrospective study on patients with severe COVID-19 in a designated hospital in Wuhan from January 15, 2020 to March 30, 2020. The propensity score matching (PSM) was used to assess the effect and safety of the treatment using CHM granules. The ratio of patients who received treatment with CHM granules combined with usual care and those who received usual care alone was 1:1. The primary outcome was the time to clinical improvement within 28 days, defined as the time taken for the patients' health to show improvement by decline of two categories (from the baseline) on a modified six-category ordinal scale, or to be dischargedfrom the hospital before Day 28. RESULTS: Using PSM, 43 patients (45% male) aged 65.6 (57-70) yearsfrom each group were exactly matched. No significant difference was observed in clinical improvement of patients treated with CHM granules compared with those who received usual (p = 0.851). However, the use of CHM granules reduced the 28-day mortality (p = 0.049) and shortened the duration of fever (4 days vs. 7 days, p = 0.002). The differences in the duration of cough and dyspnea and the difference in lung lesion ratio on computerized tomography scans were not significant.Commonly,patients in the CHM group had an increased D-dimer level (p = 0.036). CONCLUSION: Forpatients with severe COVID-19, CHM granules, combined with usual care, showed no improvement beyond usual care alone. However, the use of CHM granules reduced the 28-day mortality rate and the time to fever alleviation. Nevertheless, CHM granules may be associated with high risk of fibrinolysis.

The add-on effect of Chinese herbal medicine on COVID-19: A systematic review and meta-analysis.

BACKGROUND: Chinese herbal medicine (CHM) is thought to be a potential intervention in the treatment of coronavirus disease (COVID-19). PURPOSE: This study aimed to investigate the efficacy and safety of CHM or CHM combination therapy for COVID-19. STUDY DESIGN: Systematic review and meta-analysis METHODS: We searched for relevant studies in the CNKI, CBM, Wanfang Data, PubMed, Cochrane Library, Embase, and other resources from their inception to April 15, 2020. Randomized controlled trials, cohort studies, and case-control studies on CHM or CHM combination therapy for COVID-19 were included. Meta-analysis was performed according to the Cochrane Handbook. RESULTS: Overall, 19 studies with 1474 patients were included. Meta-analysis showed that the overall clinical effectiveness (OR = 2.67, 95% CI 1.83-3.89, I2 = 0%), improvement in the CT scan (OR = 2.43, 95% CI 1.80-3.29, I2 = 0%), percentage of cases turning to severe/critical (OR = 0.40, 95% CI 0.24-0.67, I2 = 17.1%), reverse transcription-polymerase chain reaction (RT-PCR) negativity rate (OR = 2.55, 95% CI 1.06-6.17, I2 = 56.4%) and disappearance rate of symptoms (fever, cough, and fatigue) were superior by combined CHM treatment of COVID-19. However, there was no statistical difference between the two groups in terms of length of hospital stay (WMD = -0.46, 95% CI -3.87 - 2.95, I2 = 99.5%), and rate of adverse effects (OR = 1.21, 95% CI 0.48-3.07, I2 = 43.5%). The quality of evidence was very low to low. CONCLUSION: The combined treatment of COVID-19 with Chinese and Western medicine may be effective in controlling symptoms and reducing the rate of disease progression due to low quality evidence.

The add-on effect of dengzhan shengmai capsules on secondary prevention of ischemic stroke: A multicentre, randomised, placebo-controlled clinical trial.

OBJECTIVE: The Dengzhan Shengmai (DZSM) capsule is a commercially available type of Chinese herbal medicine frequently administered to improve neurological impairment after stroke. Its ability to prevent recurrent stroke, however, has not been determined. This study therefore evaluated the ability of DZSM as an add-on to conventional secondary preventive agents to prevent recurrent ischemic stroke. METHODS: In this randomised, double-blind, placebo-controlled trial, conducted at 83 hospitals in Mainland China, 3143 patients in 14-180 days after the initial onset of ischemic stroke, were randomly allocated to the DZSM (0.36 g, twice daily for 12 months) or the placebo group. All patients in both groups received standard secondary preventive medications. The primary outcome was the 1-year incidence of stroke. Between group differences were assessed using the Cox proportional hazards model. RESULTS: Intent-to-treat analysis showed that 58 (3.8%) participants in the DZSM group and 82 (5.4%) in the placebo group experienced new stroke events (hazard ratio = 0.70, 95% confidence interval = 0.50-0.98, P = 0.036). The type and incidence of adverse events were similar in the DZSM and placebo groups. CONCLUSIONS: The addition of DZSM capsules to standard secondary preventive agents provides additional benefits after the initial onset of ischemic stroke, reducing recurrent stroke without increasing severe adverse events. However, further study is needed to elucidate the role of DZSM on the updated practice of conventional secondary prevention for ischemic stroke.

Safety and Efficacy of the C-117 Formula for Vulnerable Carotid Artery Plaques (Spchim): A Randomized Double-Blind Controlled Pilot Study.

OBJECTIVE: To investigate the safety and efficacy of the Herbal Medicine C-117 (C-117) formula in the treatment of carotid atherosclerotic vulnerable plaques. METHODS: This was a prospective, single-centre, randomized, double-blind study. A total of 120 eligible patients were randomly divided into two groups to receive the C-117 formula or placebo. As the basic treatment, both groups were treated according to the Guidelines for Secondary Prevention of Ischemic Stroke/Transient Ischemic Stroke in China using statins to regulate blood lipids, blood pressure lowering drugs, drugs for controlling blood sugar, and antiplatelet drugs according to the indications. The primary outcomes were the change in stability, the mean change of the plaque Crouse score, and the area and number of bilateral carotid artery plaques before and after 6 months of treatment. The secondary outcomes were the total number of cardiocerebrovascular events during the treatment and follow-up and the mean changes of lipid levels. RESULT: After 180 days of treatment, the plaque Crouse score(95% CI, 0.39 (0.01-0.77), P=0.046) and plaque area (95% CI, 2.14 (-10.10-14.39), P=0.727) were lower in the C-117 formula group than that before treatment. The plaque Crouse score of the control group (95% CI, 0.17 (-0.24-0.57), P=0.417) was lower than that before treatment, while the plaque area (95% CI, -0.35 (-9.35-8.65), P=0.938) increased, but without statistical significance. There was no significant difference in the reduction of the intima-media thickness (IMT), plaque Crouse score, or plaque area between the two groups after treatment (P>0.05). Subgroup analysis of patients whose Lipitor medication time ≥ 20% of the 6-month treatment showed that the levels of total cholesterol, triglycerides, and low-density lipoprotein were lower in the two groups after treatment than before, and the low-density lipoprotein levels in the C-117 formula group significantly decreased (95% CI, 2.99 (-0.08-0.39), P=0.005), but there was no statistical difference between the two groups after treatment (P>0.05). No serious adverse events occurred in the two groups after 180 days of treatment. CONCLUSION: The C-117 formula may be antiatherosclerotic by strengthening statins to reduce the low-density lipoprotein levels and reducing the carotid plaque Crouse scores. Clinical trials with large sample sizes, long-term interventions, and follow-up are needed to investigate the efficacy of the C-117 formula. CLINICAL TRIALS REGISTRATION: This trial is registered with clinicaltrials.gov identifier: NCT03072225 (registered retrospectively on 1st March 2017).

Safety and efficacy of herbal medicine for acute intracerebral hemorrhage (CRRICH): a multicentre randomised controlled trial.

OBJECTIVE: To evaluate the safety and efficacy of removing blood stasis (RBS) herbal medicine for the treatment of acute intracerebral haemorrhage (AICH) within a 6-hour time window. STUDY DESIGN: A randomised, multicentre, double-blind, placebo-controlled study performed in 14 hospitals in China. PARTICIPANTS AND INTERVENTIONS: Patients with AICH were randomly assigned to receive a placebo, the ICH-1 (Intracerebral Haemorrhage) formula (eight herbs, including the RBS herbs hirudo and tabanus) or the ICH-2 formula (six herbs without the RBS herbs hirudo and tabanus) within 6 hours of ICH onset. OUTCOMES: The primary safety outcome was the incidence of haematoma enlargement at 24 hours and at 10 days after treatment. The secondary outcome was the incidence of poor prognosis (mortality or modified Rankin Scale score ≥5) assessed at 90 days after symptom onset. RESULTS: A total of 324 subjects were randomised between October 2013 and May 2016: 105 patients received placebo; 108 patients received the ICH-1 formula; and 111 patients received the ICH-2 formula. The incidence of haematoma enlargement at 24 hours was 7.8% in the placebo group, 12.3% in the ICH-1 group and 7.5% in the ICH-2 group; the incidence of haematoma enlargement on day 10 was 1.1% in the placebo group, 1.1% in the ICH-1 group, and 3.1% in the ICH-2 group, with no significant differences among the groups (P>0.05). The mortality rates were 3.8% in the placebo group, 2.8% in the ICH-1 group, and 0.9% in the ICH-2 group; the incidences of poor prognosis were 7.1% in the placebo group, 6.0% in the ICH-1 group and 4.8% in the ICH-2 group at 3 months, with no significant differences among the groups (p>0.05). However, the overall frequency of treatment-emergent adverse events in the ICH-1 group (12.1%) was higher among the three groups (5.8% and 2.8%, respectively, p<0.05). All three cases of serious adverse events were in the ICH-1 group. CONCLUSIONS: Ultra-early administration of ICH-1 formula for AICH patients did not exert significant beneficial effects on clinical outcomes but increased the risk of bleeding, which probably resulted from the inclusion of RBS herbal medicines in ICH-1. TRIALREGISTRATION NUMBER: NCT01918722.

Clinical Evaluation of Herbal Medicine (ICH-012) in Treating Acute Cerebral Haemorrhage: Safety and Efficacy from 6- to 72-Hour Time Window (CRRICHTrial-II).

BACKGROUND: Hypertensive intracerebral haemorrhage (HICH), which is characterized by rapid change, high morbidity, and mortality, is extremely dangerous. Both medical and surgical treatments lack definitive evidence and remain controversial. A prospective RCT that we have conducted has shown that the usage of the herbal medicine ICH-012 within 6 h of the event may increase the risk of haematoma enlargement and gastrointestinal bleeding. However, the volume of haematoma remains stable after 6 h. Thus, we will increase the time window to the period from 6 to 72 h after onset to evaluate the safety and efficacy of ICH-012 treating ICH (ClinicalTrial.gov ID: NCT03354026). METHODS/DESIGN: The CRRICHTrial-II study, a prospective, double-blinded, controlled, multicentre RCT, includes three groups: A, B, and C. Group A patients were treated with 8 herbal medicines (with 2 herbal medicines of Hirudo and Tabanus as well as 6 other combined herbal medicines of Group B) and Group C were placebo. Patients should meet all the inclusion criteria: age between 18 and 80 and diagnosis of HICH by brain CT scan between 6 and 72 h from the onset. The CT scan will be taken at four critical time points: baseline, between 6 and 72h, 24h after onset, and between 10 and 14 days after onset. The drug intervention lasts 10 days, and there is a follow-up visit taken after 90 days. The haematoma enlargement after 24 h onset as demonstrated by CT is the primary outcome. DISCUSSION: A large amount of data from high-quality RCTs is needed for the extensive clinical application of herbal medicine. The CRRICHTrial-II will evaluate the safety and effectiveness of ICH-012 in a safer time window between 6 and 72 h and investigate the possible mechanisms of action and direction of herbal medicine in the haematoma growth after HICH. Trial registration at ClinicalTrial.gov, ID: NCT03354026, is registered on 23rd Nov. 2017.

Clinical re-evaluation of removing blood stasis therapy in treating acute intracerebral hemorrhage safety and efficacy: a protocol for a randomized, controlled, multicenter study (CRRICH Trial).

BACKGROUND: Hypertensive intracerebral hemorrhage (HICH) is one of the most devastating forms of stroke. Currently, no specific therapies for HICH except general medical care. However, in China, medicine of promoting blood circulation (PBC) and removing blood stasis (RBS) are widely and efficiently used to treat HICH and become a potentially effective treatment for the secondary effects of HICH to alleviate brain injury, accelerate neuronal recovery, and improve the prognosis. In order to evaluate the safety and effect of PBC and RBS herbal drugs, we design a prospective, randomized, open, double-blind controlled clinical trial on the hematoma enlargement in HICH patients treating with PBC and RBS herbal medicine within 6 h time window from the symptom onset. METHODS/DESIGN: A multicenter, three-group, prospective, randomized, double-blinded and placebo-controlled clinical trial. Patients aged 18 or older with HICH confirmed by CT scan within 6 h from the onset are included. 360 patients will be randomized to 3 groups (PBC & RBS & Placebo) within 6 h of ictus. Stratified block randomization is undertaken using a sequentially numbered and opaque envelope. All subjects must take medicine within 6 h of ictus and have another CT scan at about 24 h to confirm hematoma expansion. A postal questionnaire to the patients to evaluate their recorvery at 3 months. Primary outcome is the percent change in the volume of hematoma at 24 h. Secondary outcomes include: mortality, disability, serious adverse events, etc. CONCLUSIONS: The CRRICH Trial is expected to confirm the safety and effect of acute intracerebral hemorrhage treated within 6 h of ictus with "RBS" therapy and to determine whether the traditional therapy can cause hematoma growth after intracerebral hemorrhage. DISCUSSIONS: This is the first  prospective, multicenter, randomized, placebo-controlled clinical trial to investigate herbal medicine whether can induce the incidence of hematoma enlargement of AICH patient within the 6 h time window from onset. We need the data to keep the herbal clinical usage safety. Trial registration clinicaltrials.gov: NCT01918722.

[Effect of Chinese Drugs for Breaking Blood Expelling Stasis on Acute Cerebral Hemorrhage: a Prospective Randomized Double-blind Controlled Study].

OBJECTIVE: To study the safety of using Chinese drugs for breaking blood expelling stasis (CDBBES) in hypertension patients with intracerebral hemorrhage within 6 h, and to observe whether they would result in hematoma enlargement. METHODS: A prospective randomized double-blind controlled clinical study was employed. Totally 128 cerebral hemorrhage patients within 6 h were recruited from 8 research centers from October 2013 to March 2015, and finally 76 of them were included. These patients were assigned to 3 groups by simple random sampling, group A, B, and C. Patients in group A (26 cases) took whole CDBBES recipe (containing leeches and equivalent insects). Those in group B (25 cases) took CDBBES recipe (removing leech and gradfly). Those in group C (25 cases) took placebos. Medication lasted for 10 successive days. The hematoma enlargement rate within 24 h, the occurrence of adverse reactions and adverse events were observed. To guarantee the safety of this trial, an interim analysis of first level unblinding was used. RESULTS: The hematoma enlargement rate was 11. 5% (3/26) in group A, 16. 0% (4/25) in group B, and 20. 0% (5/25) in group C. There was no statistical difference in the hematoma enlargement rate among the 3 groups (X² =0. 823, P =0. 682). Adverse reactions and adverse events occurred in 7 cases, 1 patient with acute myocardial infarction, 1 with chest op- pression and palpitation, 2 with diarrhea in group A. No patient had adverse reaction or adverse event in group B. And diarrhea occurred in 3 patients of group C. CONCLUSION: The interim analysis of first level unblinding showed that hematoma enlargement within 6 h was not resulted from using CDBBES.

Can Herbal Medicine Cause Hematoma Enlargement of Hypertensive Intracerebral Hemorrhage within 24 hrs Time Window? A Retrospective Study of 256 Cases from a Single Center in China.

A retrospective review was performed of consecutive patients presenting with HICH within 24 hours of ictus presenting between March 2008 and March 2013 who were diagnosed as having HICH by CT scan. Of the 256 patients who matched study inclusion standard, 43 patients hematoma was enlarged (16.8%). The number of the patients who did not take PBC or RBC herbal medicine, took the PBC herbal medicine, and took RBS herbal medicine was 19 (44.2%), 2 (4.7%), and 22 (51.2%) in hematoma enlargement group and 78 (36.6%), 26 (12.2%), and 109 (51.2%) in nonhematoma enlargement group, individually. There was no significant difference between two groups (P = 0.671). PBC and RBS herbal medicine did not increase the incidence of hematoma expansion of ICH within 24 hours after onset of symptom.

Combinatorial effects of naomai yihao capsules and vascular endothelial growth factor gene-transfected bone marrow mesenchymal stem cells on angiogenesis in cerebral ischemic tissues in rats.

OBJECTIVE: To investigate the combinatorial effects of Naomai Yihao (NMYH) Capsules and vascular endothelial growth factor (VEGF) gene-transfected bone marrow mesenchymal stem cells (BMSCs) on angiogenesis in cerebral ischemic tissues in rats and the mechanism. METHOD: BMSCs were isolated and cultured from bone marrow by an adherence method. Then, BMSCs were transfected with the eukaryotic expression plasmid pEGFP-VEGF165 by positive ionic liposome transfection. A rat model of middle cerebral artery occlusion (MCAO) was established. Rats were allocated to six groups: model, BMSC, VEGF gene-transfected BMSC transplantation (BMSC/VEGF), NMYH, combined NMYH and BMSC/VEGF (combined treatment group) and sham operation groups. The behavioral rating score (BRS) of rats and the expression of CD34 and VEGF in brain tissue were measured by immunohistochemistry on days 7, 14 and 21 after reperfusion. Angiogenesis was observed and evaluated with laser scanning confocal microscopy. RESULTS: The BRS of rats in NMYH, BMSC transplantation and combined treatment groups was significantly lower than that of the model group (P < 0.001), with no significant difference between NMYH and transplantation groups (P = 0.619). The expression of CD34 and VEGF in NMYH, transplantation and combined treatment groups increased (P < 0.001), with a significant difference between NMYH and transplantation groups (P < 0.001). The blood vessel area in NMYH, transplantation and combined treatment groups was significantly increased (P < 0.05), without a significant difference between NMYH and transplantation groups (P = 0.873). CONCLUSIONS: VEGF gene-transfected BMSCs improve angiogenesis in the cerebral ischemic area. NMYH Capsules promote angiogenesis in MCAO rats treated with BMSC transplantation, which show an improved BRS. The mechanism of angiogenesis may be related to up-regulation of VEGF expression.

[Effect of integrative medical therapy on the prognosis of patients suffering from yin syndrome type acute ischemic stroke].

OBJECTIVE: To observe the effect of integrative medical therapy on the prognosis of patients suffering from yin syndrome type acute ischemic stroke (YS-AIS). METHODS: A multi-center, prospective, random and parallel controlled clinical trial was carried on 606 patients of YS-AIS. Excepting the 15 patients being excluded and dropped out in the trial period, all patients were assigned to the treatment group (274 patients) treated with integrated medical protocol (i. e. Chinese medical therapy plus conventional Western medical treatment), and the control group (263 patients) treated with conventional Western medical treatment plus placebo. Patients' quality of life (QOL) and their disability level were assessed by scoring based on SS-QOL and modified Rankin scale (mRS) respectively at the terminal of the 21-day treatment (T1) and at the ends of 60-day (T2) and 90-day (T3) following-ups. RESULTS: Patients' disability level, showed by mRS scores, was not significantly different between the two groups at T1 and T2 (P > 0.05), but with significant difference at T3 (P < 0.05). The recovery in the treatment group were more significant. Although the SS-QOL scores showed no statistical significant difference between groups (P > 0.05), improvement of QOL could be seen in the treatment group and the difference between groups was more significant as the time went by. CONCLUSION: Integrative medical therapy could reduce the severe disability rate in patients after YS-AIS, and showed an improving trend on patients' QOL at T3.

Outcome and safety assessment of an herbal medicine treatment protocol for yin pattern of acute ischemic stroke.

BACKGROUND: The morbidity of stroke is high. Traditional Chinese medicine is commonly used for patients with ischemic stroke in China, but the efficacy need be further proved. OBJECTIVE: To assess the efficacy and safety of an herbal medicine treatment regimen integrating traditional Chinese medicine and Western medicine for ischemic stroke patients with yin pattern syndrome. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A multicenter, randomized and controlled clinical trial was adopted. A total of 537 patients with acute ischemic stroke were enrolled in 22 hospitals from July 2005 to October 2006, among whom 274 were assigned to group A (herbal group) and administered with Western medicine plus herbal medicine treatment, and the other 263 in group B (control group) with Western medicine plus placebo. The patients in two groups were all treated for 21 days. MAIN OUTCOME MEASURES: The primary endpoint of outcome measures was Barthel index. The secondary endpoints included National Institutes of Health Stroke Scale, the modified Rankin criteria, Stroke Specific Quality of Life, and Stroke Scale of Traditional Chinese Medicine. The adverse effects of the treatment were also observed. RESULTS: A total of 622 randomization numbers were applied by the centers and 16 numbers were lost for mishandling, so a total of 606 patients were included. Fifteen patients were excluded (5 in group A, and 10 in group B), and 54 (25 in group A, and 29 in group B) lost in follow-up. A total of 537 patients completed the trial and a per-protocol set analysis was conducted. There were no statistical differences in age, sex, pulse rate, heart rate, respiratory rate, blood pressure, medical history, neurological deficit scores, scores on Glasgow Coma Scale, and lesion size of intracerebral ischemia between the two groups at baseline (P>0.05). Twelve patients, including 5 in group A and 7 in group B, died during the 90 days of research period, and no significant difference was found between the two groups. Compared with Western medicine alone, herbal medicine treatment could improve the neurological deficit at day 21, activities of daily living at day 90 of follow-up, and the patient-reported outcome at days 21, 60, and 90 (P<0.05). Independent living ability of the patients was also improved (67.9% of group A vs 59.3% of group B, 0-1 at modified Rankin criteria). Moreover, the herbal medicine treatment showed a tendency in improving quality of life at a time-dependent manner. Adverse events, including gastrointestinal adverse events, skin symptoms, hemorrhagic tendency, and aminotransferase increase, happened in 76 cases from both groups, and no significant difference was found between the two groups. Correlation analysis showed that aminotransferase increase was not related to the herbal medicine treatment, but to the lipid-lowering drugs. CONCLUSION: The present research demonstrates that the herbal medicine treatment shows effects on neurological deficit and patient-reported outcome at day 21, activities of daily living and handicap at day 60, and handicap, activities of daily living and patient-reported outcome at 3-month follow-up. TRIAL REGISTRATION NUMBER: NCT000351806

[Effects of Chinese medicine for regulating "sea of blood in brain" combined with bone marrow stromal stem cell transplantation on angiogenesis in ischemic brain tissue of rats].

OBJECTIVE: To observe whether Naomai Yihao (NM) Capsule, a compound traditional Chinese herbal medicine for regulating the "sea of blood in brain", and bone marrow stromal stem cell (BMSC) transplantation could improve angiogenesis in focal cerebral ischemia in rats. METHODS: A rat model of middle cerebral artery occlusion (MCAO) was established. The rats were divided into untreated group, NM group, BMSC group and combination of NM and BMSC group (combined treatment group). Another 8 normal rats were selected as sham-operated group. After 3-, 7- and 14-day reperfusion, behavioral rating scale (BRS) of the rats and histopathology of the cerebral tissue were evaluated. Expression of CD31 in the brain tissue was also measured by immunohistochemical method. RESULTS: Compared with the untreated group, BRSs of the NM group, BMSC group and combined treatment group were decreased significantly (P=0.000), but there was no interacting effect between NM and BMSC transplantation. Compared with the untreated group, the numbers of CD31 positive cells in NM group, BMSC group and combined treatment group were increased significantly (P=0.000), and there were interacting effects among NM, BMSC transplantation, and the observation time (P<0.01). After 14-day reperfusion, combination of NM and BMSC transplantation could largely increase the number of CD31 positive cells. CONCLUSION: NM is able to promote the angiogenesis and neurological impairment improvement in focal cerebral ischemia of rats which are administered with BMSC transplantation, and the effect is reinforced with the extension of treatment time.

[Dynamic changes in traditional Chinese medicine syndromes in patients with ischemic stroke treated by acupuncture].

OBJECTIVE: To explore the dynamic state of traditional Chinese medicine (TCM) syndromes in acute ischemic stroke patients within 30 days of onset when treated with acupuncture, and to analyze the discrimination effects of the functions based on "decision trees" in identification of TCM syndromes of ischemic stroke. METHODS: A total of 264 cases with acute ischemic stroke regularly treated by acupuncture were included. Unified syndrome questionnaire was made by document retrieval and expert advice. The syndrome elements of the patients with acute ischemic stroke were surveyed on any day of three time periods (days 0-3, 4-10 and 11-30). The study was performed on multi time dynamic state results and correlated factors of basic TCM syndromes of the 264 patients. Bayes discriminant function of four syndromes of acute ischemic stroke on the basis of "decision trees" was used for computing the rate of miscarriage justice by original test and cross-validation, and the discrimination effects of "decision trees" were evaluated too. RESULTS: Wind, phlegm, fire-heat, qi deficiency, blood stasis, and hyperactivity of yang due to yin deficiency syndromes were found in the patients with acute ischemic stroke treated by acupuncture on the first 30 days of onset, and the incidence rates were 80.7%, 68.9%, 52.7%, 50.8%, 29.2% and 25.0% respectively. The mean scores and incidence rates of the six syndromes decreased gradually on three-time-point, especially of blood stasis syndrome. The main combined-syndromes were two-syndrome, three-syndrome and four-syndrome, and three-syndrome was the most frequently encountered type. Single syndrome was not found in the patients with acute ischemic stroke on the first three days of onset. Two-syndrome combination types were wind-phlegm, wind-heat, wind combined with qi deficiency or phlegm stagnation due to qi deficiency, phlegm-heat and blood stasis combined with hyperactivity of yang due to yin deficiency, and the incidence rates were 54.5%, 42.8%, 40.9%, 39.4%, 35.6% and 3.8% respectively. The mean scores of phlegm and qi deficiency in high-age patients were higher than those in low-age patients. The mean score and incidence rate of qi deficiency in female patients were higher than those in male patients. The mean score of phlegm in female patients was higher than that in male patients. To simplify the "decision trees" composed of 21 items, the group of Bayes discriminant function including eight most significant items out of the original 21 items was set up. The discrimination effect of the eight items including reddish face, constipation, yellow tongue fur, short breath, bright-white or gray complexion, tinnitus, feverish palms and soles and scanty tongue fur was similar to that of the 21 items, and there was no significant difference between the two functions. CONCLUSION: Wind syndrome and phlegm syndrome are the major single syndromes occurring in acute ischemic stroke patients within 30 days of onset, and three-syndrome combination is the most frequent multiple syndrome type. After acupuncture treatment, some syndrome elements including wind, phlegm, fire-heat, qi deficiency, blood stasis, and hyperactivity of yang due to yin deficiency are gradually reduced, and combined syndrome type is gradually become simple. Eight syndrome element items including reddish face, constipation, yellow tongue fur, short breath, bright-white or gray complexion, tinnitus, feverish palms and soles and scanty tongue fur have important means in discriminating yin syndrome from yang syndrome and sthenia syndrome from asthenia syndrome.

[Characteristics of traditional Chinese medicine syndromes in patients with acute ischemic stroke of yin or yang syndrome: a multicenter trial].

OBJECTIVE: To explore the composition characteristics of traditional Chinese medicine (TCM) syndromes in patients with acute ischemic stroke of yin or yang syndrome by investigating the characteristics of TCM syndromes at different periods after onset. METHODS: One thousand two hundred and forty-six patients with acute ischemic stroke were admitted in twenty hospitals. According to the "diagnostic criteria of syndrome differentiation of stroke", the characteristics of syndromes in the patients were investigated at the periods of 1-3 days, 4-10 days and 11-30 days after they had ischemic stroke. General distribution of six basic syndromes was compared between the patients with yin syndrome and the patients with yang syndrome at the three periods. The six basic syndromes were wind syndrome, pathogenic fire syndrome, phlegm syndrome, blood stasis syndrome, qi deficiency syndrome, and syndrome of yin deficiency and yang hyperactivity. RESULTS: The percentages of wind, pathogenic fire, and phlegm syndromes in the patients were decreased at the period of 11-30 days as compared with the period of 1-3 days (87.1% vs 79.3%, 52.1% vs 38.7% and 67.1% vs 57.4% respectively, P<0.01). However, the percentages of the syndromes of blood stasis, qi deficiency, and yin deficiency and yang hyperactivity were similar at the three periods (P>0.05). There were no differences in the distribution of yin and yang syndromes among the three periods (P>0.05). The percentages of syndromes of wind, pathogenic fire, phlegm, and yin deficiency and yang hyperactivity were higher (P<0.01), and the percentages of syndromes of blood stasis and qi deficiency were lower (P<0.05, P<0.01) in patients with yang syndrome than in patients with yin syndrome. The complex of three syndromes was the most frequent composition pattern in the patients at the three periods. The percentages of complex syndromes of four or five syndromes were higher, and the percentages of single-syndromes and complex syndromes of two syndromes were lower in patients with yang syndrome than in patients with yin syndrome (P<0.05, P<0.01). The most frequent complex syndromes in patients with yin syndrome were complex syndrome of wind, phlegm, blood stasis and qi deficiency, and complex syndrome of wind, phlegm and qi deficiency; while the most frequent complex syndromes in patients with yang syndrome were complex syndrome of wind, pathogenic fire, phlegm and qi deficiency, and complex syndrome of wind, pathogenic fire and phlegm. CONCLUSION: The main discrimination between the yin and yang syndromes is that the yang syndrome is characterized by pathogenic fire. The syndromes of phlegm, qi deficiency, and blood stasis are not associated with the diagnosis of yin or yang syndrome.