Registration of intervention trials of Traditional Chinese Medicine for four neurological diseases on Chinese Clinical Trial Registry and ClinicalTrials.gov: a narrative review.

OBJECTIVE: To analyze the current status of clinical trial registration of Traditional Chinese Medicine (TCM) for the treatment of neurological diseases. METHODS: Interventional clinical trials of TCM treatment for ischemic stroke, hemorrhagic stroke, vascular cognitive impairment, tension-type headache before September 22, 2020 on the platform of Chinese Clinical Trial Registry (ChiCTR), and ClinicalTrials.gov were searched. Two researchers independently selected the literature and extracted data. RESULTS: A total of 180 interventional clinical trials were included for analysis. Out of 180 trials, 127 were from ChiCTR and 53 from ClinicalTrials.gov. The countries primary sponsoring the included trials were China (176, 97.8%), and the common categories of primary sponsors were hospital (131, 72.8%). Among the study design, the largest proportion of allocation was randomized (172, 95.6%), interventional model assignment was parallel (163, 90.6%), masking was double blind 49 (27.2%), and the sample size was ≤ 400 (144, 80.0%). The trials were most carried out at a single center (102, 56.7%). Among the included studies, 112 (62.2%) registered on ChiCTR attached the ethical approval documents. In terms of trial stages, 50 (27.7%) studies were in phase IV. The mostly used intervention was Chinese herbal medicines (99, 55%), acupuncture (68, 37.8%) was the second. By searching the registration number on China National Knowledge Infrastructure Database and PubMed, 38 (21.1%) registered trials were published, including 25 protocol studies and 14 research results with one (NCT02275949) published both the protocol and the results. CONCLUSIONS: Irregular and inadequate reporting, untimely update and publication, insufficient information on traditional medicine unique characteristics, and lack of international collaborations are the problems existing in the interventional clinical registration trials of traditional medicine treatment on neurological diseases. More efforts need to be made from the above aspects to standardize and improve the registration of traditional medicine trials.

[Systematic review and Meta-analysis on efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage].

To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],P<0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],P<0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],P<0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.

[Situation analysis of outcome indicators of randomized controlled trials of traditional Chinese medicine in treatment of hypertensive intracerebral hemorrhage in recent three years].

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.

[Overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treatment of intracerebral hemorrhage].

To overview of systematic reviews/Meta-analysis of Xingnaojing Injection(XNJ) in the treatment of intracerebral hemorrhage(ICH). The systematic reviews concerning XNJ in the treatment of ICH were retrieved from four Chinese databases, four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, with the retrieval time set from their inception to September 2020. Following the independent screening and data extraction by two researchers, a measurement tool to assess systematic evaluation 2(AMSTAR 2) and grades of recommendation, assessment, development and evaluation(GRADE) system were used to evaluate the metho-dological, reporting and evidence qualities of the 10 included systematic reviews. The results showed that XNJ was superior to the wes-tern medicine or conventional treatment in improving the effective rate and National Institutes of Health stroke scale(NIHSS) score, Barthel index(BI), and Glasgow coma scale(GCS) score and Chinese stroke scale(CSS) score, and reducing the mortality and cerebral hematoma volume, without inducing obvious adverse reactions. In general, the methodological, reporting and evidence qualities of the 10 included systematic reviews were poor. The AMSTAR 2 scores showed that key items No. 2 and No. 16 failed to meet the stan-dard, resulting in poor methodological quality. There was only one outcome indicator graded by GRADE as intermediate quality, 43% indicators as low quality, 42% indicators as extremely low quality, and none as high quality. These available evidences have suggested that the methodological, reporting and evidence qualities of the systematic evaluation concerning XNJ for the treatment of ICH need to be improved. Most evidences support that XNJ was better than the western medicine or conventional treatment in the treatment of ICH, but the methodological quality and the reliability of outcome indicators in relevant systematic review were low. More high-quality studies are still required for further verification.

[Systematic review and Meta-analysis of efficacy and safety of acupuncture therapy on hypertensive intracerebral hemorrhage].

To systematically review the efficacy and safety of acupuncture combined with minimally invasive surgery or basic the-rapy in treating hypertensive intracerebral hemorrhage(HICH) patients compared with minimally invasive surgery or basic treatment. In this study, the four Chinese databases, the four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, all above were systematically and comprehensively retrieved from the time of database establishment to September 10, 2020. Rando-mized controlled trials(RCTs) were screened out according to inclusion criteria and exclusion criteria established in advanced. The methodological quality of included studies was evaluated by the tool named "Cochrane bias risk assessment 6.1". Meta-analysis of the included studies was performed using RevMan 5.4, and the quality of outcome indicators was evaluated by the GRADE system. Finally, 17 studies were included, involving 1 852 patients with HICH, and the overall quality of the included studies was not high. According to Meta-analysis,(1)CSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-3.50,95%CI[-4.39,-2.61],P<0.000 01);(2)NIHSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.78,95%CI[-5.55,-4.00],P<0.000 01);(3)the cerebral hematoma volume of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.44,95%CI[-5.83,-3.04],P<0.000 01);(4)ADL score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=20.81,95%CI[17.25,24.37],P<0.000 01);(5)the GCS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=2.41,95%CI[1.90,2.91],P<0.000 01). The GRADE system showed an extremely low level of evidence for the above outcome indicators. Adverse reactions were mentioned only in two literatures, with no adverse reactions reported. The available evidence showed that acupuncture combined with minimally invasive surgery or basic therapy had a certain efficacy in patients of HICH compared with minimally invasive surgery or basic therapy. However, due to the high risk of bias in the included studies, its true efficacy needs to be verified by more high-quality studies in the future.

Single-Session Video and Electromyography Feedback in Overhead Athletes With Scapular Dyskinesis and Impingement Syndrome.

CONTEXT: Subacromial impingement syndrome (SIS) is associated with scapular dyskinesis, or imbalanced scapular muscle activity. Evidence has shown that feedback can improve scapular control in patients with SIS. However, it is unknown whether real-time video feedback or electromyography (EMG) biofeedback is optimal for improving scapular kinematics and muscle activity during a functional task. OBJECTIVE: To compare the effects of video and EMG feedback sessions on absolute muscle activity (upper trapezius [UT], lower trapezius [LT], serratus anterior), muscle balance ratios (UT/LT, UT/serratus anterior), and scapular kinematics (anterior-posterior tilt, external-internal rotation, upward rotation) in SIS participants during arm elevation and lowering. DESIGN: Randomized controlled clinical trial. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Overhead athletes who were diagnosed with SIS and who also exhibited scapular dyskinesis (N = 41). MAIN OUTCOME MEASURE(S): Three-dimensional kinematics and EMG were recorded before and after feedback training. RESULTS: Lower trapezius muscle activity increased (4.2%-18%, P < .011) and UT/LT decreased (0.56-1.17, P < .013) in the EMG biofeedback training group as compared with those in the video feedback training group. Scapular upward rotation during arm elevation was higher in the video group than in the EMG group after feedback training (2.3°, P = .024). CONCLUSIONS: The EMG biofeedback improved muscle control and video feedback improved the correction of scapular upward rotation in patients with SIS. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT03252444.

Vasculoprotective Effects of Water Extracts of Black, Green and Dark Tea in Vitro.

To investigate the preventive effects of tea on hyperglycemia and vascular complications of diabetes, we report the extraction and composition as well as the vasculoprotective effects of black tea extract (BTE), green tea extract (GTE), and dark tea extract (DTE). High Performance Liquid Chromatography (HPLC) and colorimetric methods were conducted to analyze for tea catechins, caffeine, polyphenols, amino acids and polysaccharides of BTE, GTE and DTE. The inhibitory effects of α-glucosidase, aldose reductase (AR), advanced glycation end-products (AGEs) and glucose uptake promotion effect in BTE, GTE and DTE were explored in vitro. Contents of six major catechin forms and total catechin as well as polyphenols are higher in GTE and DTE than BTE. BTE, GTE, and DTE showed the inhibitory effects of a-glucosidase, AR, and AGEs, but only DTE exhibited the glucose uptake promotion effect in HepG2 cells. The results suggest that regular consumption of tea can help prevent the progression of hyperglycemia and the vascular complications of diabetes.

Nutrients Impact the Pathogenesis and Development of Colorectal Cancer.

BACKGROUND: Colorectal cancer is a commonly diagnosed cancer and the cause of many cancer deaths worldwide. Nutrients might be crucial in the pathogenesis and development of colorectal cancer. Although a number of studies have demonstrated the potential effects of nutrients, many challenges still remain. SUMMARY: A tremendous amount of research has emerged concerning the roles of nutrients in colorectal cancer during the past decades. Here, we review the latest research progress on nutrients, including vitamins, folic acid, calcium, selenium and dietary fiber, involved in colorectal cancer prevention. KEY MESSAGE: Nutrients are commonly consumed in foods or dietary supplements. It is clear that nutrients could play an important role and influence colorectal cancer outcomes. The relationship between nutrients and colorectal risk is complex. Vitamins, folic acid, calcium, selenium and dietary fiber have been proposed as potential agents to prevent colorectal cancer. However, some studies found that these nutrients did not reduce the incidence of colorectal cancer. PRACTICAL IMPLICATIONS: The supplementary dose of nutrients, the length of time required to observe the effects and confounding factors during the study might influence the role of nutrients in the prevention of colorectal cancer. Therefore, more evidence from ongoing clinical trials with different population groups and longer follow-up periods is critical to determine the relationship between nutrients and colorectal cancer.

Hypoglycemic effect of the water extract of Pu-erh tea.

The water extraction and composition of pu-erh tea, as well as the hypoglycemic effect of the water extract of pu-erh tea (WEPT) in vivo and in vitro, are reported to investigate its hypoglycemic effect on diabetes. High-performance liquid chromatography and colorimetric methods are used to analyze the tea catechins, caffeine, polyphenols, amino acids, and polysaccharides of the WEPT. The effect of the WEPT on glucose uptake by cultured HepG2 cells and the inhibition effect of rat intestinal sucrase, maltase, and porcine pancreatic amylase are determined in vitro. Then, the blood glucose and insulin levels of intragastrically administered WEPT on fasting and oral glucose tolerance test (OGTT) using type 2 diabetic db/db (BKS.Cg-m +/+ Lepr(db)/J) mice are determined in vivo. The results showed that the WEPT dose-dependently and significantly increased glucose uptake by HepG2 cells and inhibited rat intestinal sucrase, maltase, and porcine pancreatic amylase activity. The WEPT intragastrically given for 4 weeks suppressed the increase in blood insulin and glucose levels of db/db mice fasted overnight. In OGTT, the WEPT improved impaired glucose tolerance and ameliorated retarded insulin response at 60 and 120 min in db/db mice. These results suggest that the WEPT has beneficial effects on glucose homeostasis in type 2 diabetes and in amendment of insulin resistance.

Age differences in clinical characteristics, health care, and outcomes after ischemic stroke in China.

BACKGROUND AND PURPOSE: Little information is available on the effects of age on health care and outcomes of ischemic stroke (IS) in China. Our aim was to evaluated risk factors, health care, and outcomes among age groups including ≤ 45, 46-65, 66-79, and ≥ 80 years and to find whether the outcome was affected by age and health care. METHODS: CNSR is a nationwide prospective registry for patients admitted with acute stroke and prospectively followed up 12-month outcomes. Demographics, socioeconomics, risk factors, health care, and outcomes were analyzed among age groups, and multivariate regression analysis was used to determine the association of outcome and age and health care. RESULTS: We identified 12,415 acute IS patients for analysis. Of 1179 (9.50%) were aged ≥ 80 years. In terms of risk factors, cardiac diseases were significantly more frequent in patients ≥ 80 years, behavioral risk factors were more common in younger patients, and hypertension, hyperlipidemia, and diabetes were more seen in 46-79 patients. The use of health care varied among groups and was significantly lower in ≥ 80 years especially in secondary prevention. The very old patients had the worst outcomes even after adjusting by prognostic factors; however, adjusting forward by health care, the extent of differences decreased. CONCLUSIONS: In CNSR, differences in stroke clinic characteristics and health care were observed among various age groups, and the old patients, receiving lower levels of stroke care, had the worst outcomes. Knowledge of the age differences in ischemic stroke may be helpful to appropriately allocate the limited health resources and to improve stroke outcomes.

Folate and fiber in the prevention of colorectal cancer: between shadows and the light.

Colorectal cancer (CRC) is one of the most common malignancies and causes of cancer deaths throughout the world. Endoscopy has its functional and financial limitations; therefore, chemoprevention might be crucial in reducing the incidence of CRC. Although a number of studies have demonstrated the potential chemopreventive effects of folate (or folic acid), many challenges still remain. The relationship between folate intake and CRC risk is a complex association that might depend on many factors including gender, age, alcohol consumption, and smoking, all of which interfere with folate metabolism. The supplementary dose of fiber, the length of time required to observe the effects, and confounding factors exposed during the trial might also influence these findings. Therefore, more evidence from clinical studies is needed regarding the mechanisms that underlie the actions of bioactive food components in minimizing the risk of CRC.