The arousal effect of An-Gong-Niu-Huang-Wan on alcoholic-induced coma rats: A research based on EEG.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication is one of the leading causes of coma. A well-regarded Chinese herbal formula, known as An-Gong-Niu-Huang-Wan (AGNHW), has garnered recognition for its efficacy in treating various brain disorders associated with impaired consciousness, including acute alcohol-induced coma. Despite its clinical effectiveness, the scientific community lacks comprehensive research on the mechanistic aspects of AGNHW's impact on the electroencephalogram (EEG) patterns observed during alcohol-induced coma. Gaining a deeper understanding of AGNHW's mechanism of action in relation to EEG characteristics would hold immense importance, serving as a solid foundation for further advancing its clinical therapeutic application. AIM OF THE STUDY: The study sought to investigate the impact of AGNHW on EEG activity and sleep EEG patterns in rats with alcoholic-induced coma. MATERIALS AND METHODS: A rat model of alcohol-induced coma was used to examine the effects of AGNHW on EEG patterns. Male Sprague-Dawley rats were intraperitoneally injected with 32% ethanol to induce a coma, followed by treatment with AGNHW. Wireless electrodes were implanted in the cortex of the rats to obtain EEG signals. Our analysis focused on evaluating alterations in the Rat Coma Scale (RCS), as well as assessing changes in the frequency and distribution of EEG patterns, sleep rhythms, and body temperature subsequent to AGNHW treatment. RESULTS: The study found a significant increase in the δ-band power ratio, as well as a decrease in RCS scores and ß-band power ratio after modeling. AGNHW treatment significantly reduced the δ-band power ratio and increased the ß-band power ratio compared to naloxone, suggesting its superior arousal effects. The results also revealed a decrease in the time proportion of WAKE and REM EEG patterns after modeling, accompanied by a significant increase in the time proportion of NREM EEG patterns. Both naloxone and AGNHW effectively counteracted the disordered sleep EEG patterns. Additionally, AGNHW was more effective than naloxone in improving hypothermia caused by acute alcohol poisoning in rats. CONCLUSION: Our study provides evidence for the arousal effects of AGNHW in alcohol-induced coma rats. It also suggests a potential role for AGNHW in regulating post-comatose sleep rhythm disorders.

Efficacy and safety of Dengyinnaotong Capsule in patients with Cognitive impairment caused by cerebral Small Vessel Disease: study protocol of a multicenter, randomized, open-label, controlled trial (De-CSVD trial).

BACKGROUND: Cerebral small vessel disease (CSVD) is a common syndrome in the older population, with a prevalence ranging from 5% in subjects aged 50 years to almost 100% in those aged 90 years and older. It is regarded to be a major cause of vascular cognitive impairment. Existing prevention and treatment approaches have not yet shown ideal clinical outcomes. Dengyinnaotong Capsule has shown great potential for improving cognitive function. This trial (De-CSVD trial) is designed to investigate the efficacy and safety of Dengyinnaotong Capsule on cognitive function in patients with CSVD . METHODS: This multicenter, randomized, open-label, controlled trial is planned to recruit at least 270 patients with mild cognitive impairment related to CSVD in 25 centers in China. Recruitment started on 10 May 2021 and is foreseen to end on 31 December 2022. The final follow-up of participants will be completed by the end of March 2023. Participants will be randomized in a ratio of 1:1 to the experimental group (routine basic treatment plus Dengyinnaotong Capsule) or the control group (routine basic treatment). The primary outcome is the change in the Montreal Cognitive Assessment score from baseline to week 12. Secondary outcomes are changes in Shape Trail Test, Activities of Daily Living, Geriatric Depression Scale, and Dizziness Handicap Inventory score from baseline to week 12, new vascular events, and the changes in serum level of homocysteine, high-sensitivity C-reactive protein, and D-dimer from baseline to week 4 and 12, respectively. The exploratory outcome is the changes in the Tinetti performance-oriented mobility assessment score from baseline to week 12. Safety assessment is performed by monitoring vital signs, general biochemical examinations, 12-lead electrocardiogram examinations, and incidence of cardiovascular and cerebrovascular ischemia or bleeding events. Visits will be performed at week 0 (baseline, pre-randomization), week 4, and week 12 in the treatment period (post-randomization). DISCUSSION: This trial is the first to investigate the efficacy and safety of Dengyinnaotong Capsule on cognitive impairment in patients with CSVD. The findings of this study might provide convincing evidence regarding the efficacy of Dengyinnaotong Capsule in patients with mild cognitive impairment related to CSVD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045831. Registered on 25 April 2021.

Crocin inhibits proliferation and induces apoptosis through suppressing MYCN expression in retinoblastoma.

The pathogenetic mechanisms of retinoblastoma are still not yet fully elucidated, putting limits to efficacious treatment. Crocin is the main component of saffron, which exhibits significant antitumorigenic properties. The aim of this paper is to investigate the effect of crocin on retinoblastoma. The effects of crocin on the proliferation of human retinoblastoma cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell number assay, and colony formation assay. Cell apoptosis induced by crocin was measured by flow cytometry analysis. Cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 were tested by western blot analysis. The expression levels of MYCN were assessed by western blot and quantitative polymerase chain reaction and the stability of MYCN messenger RNA was determined by in vitro RNA degradation assays. We found that crocin significantly inhibited the cell proliferation and clonogenicity and induced cell apoptosis in Y79 and WERI-RB-1 cells. In addition, crocin treatment significantly reduced the expression and the stability of MYCN. Besides, overexpression of MYCN rescued the inhibitory effect of crocin in Y79 cells. Our findings suggest that crocin exhibits antitumorigenic effects in human retinoblastoma cell lines through a MYCN-dependent manner, which may provide guidance to logical therapeutic designs in prevention and treatment of retinoblastoma.

Shikonin-mediated up-regulation of miR-34a and miR-202 inhibits retinoblastoma proliferation.

Retinoblastoma (RB) is an ocular tumor that occurs mainly in children. The pathogenesis of RB is not well understood, and its treatment strategies are very limited. Shikonin is widely reported as an anti-tumor agent. However, its effect on RB is still unknown. MTT assay was performed to detect the proliferation ability of two RB cell lines, Y-79 and WERI-Rb-1, upon treatment with Shikonin. Colony formation assay was conducted to examine the clonogenic ability of Shikonin-treated cells. Real-time PCR and western blotting were performed for expression analysis of miRNAs and MYCN, respectively. Luciferase activity assay was conducted to test the inhibition mechanism of miR-34a and miR-202 on MYCN. Shikonin could effectively inhibit the proliferation of RB cells and upregulate the expressions of miR-34a and miR-202. MiR-34a and miR-202 could directly target the mRNA degradation of oncogene MYCN, and the inhibitory effect of Shikonin was largely weakened by restoring the MYCN protein expression. Shikonin-mediated up-regulation of miR-34a and miR-202 inhibits RB proliferation, partially mediated through MYCN.

Effects of intracerebral hemorrhage and subsequent minimally invasive hematoma aspiration on expression of apoptosisrelated genes in rats.

This study was to investigate the effects of intracerebral hemorrhage (ICH) and subsequent minimally invasive hematoma aspiration on the expression of apoptosis-related genes in rats. IV-collagenase was injected to the caudate nucleus of the rats to make ICH models. In the control group, 30 Sprague-Dawley (SD) rats were mock treated with saline instead of collagenase. Thirty SD rats with successful modeling were designated as the ICH group. Twenty-five SD rats with successful modeling and subsequent minimally invasive hematoma aspiration were designated as the therapy group. Expression of heat shock protein 70 (Hsp70), B-cell leukemia/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in the brain tissues was detected by immunohistochemical assays. The expression of Hsp70, Bcl-2 and Bax in the control group was very low, and significantly increased in the ICH group and the therapy group. At each indicated time point, Hsp70 expression in the therapy group was significantly lower than that of the ICH group, Bax expression in the therapy group was significantly lower than that of the ICH group and Bcl-2 expression in the therapy group was significantly higher than that of the ICH group. These results suggest that ICH led to increased expression of apoptosis-related genes in the brain tissues. Hematoma aspiration up-regulated ICH induced Bcl-2 expression while down-regulated ICH induced Hsp70 and Bax expression.

Aspirin plus clopidogrel as secondary prevention after stroke or transient ischemic attack: a systematic review and meta-analysis.

BACKGROUND: Antiplatelet agents are the mainstay for secondary prevention of non-cardioembolic stroke. This systematic review examined the safety and efficacy of short-, middle-, and long-term aspirin in combination with clopidogrel as secondary prevention of stroke or transient ischemic attack (TIA) of presumed arterial origin. METHODS: PubMed, EmBase, and CENTRAL were searched up to May 2014. Randomized controlled trials (RCTs) that compared aspirin plus clopidogrel versus aspirin or clopidogrel as secondary prevention of stroke or TIA of arterial origin were included. The analyses were stratified into short-term (≤3 months), middle-term (>3 months and <1 year), and long-term (≥1 year). Outcomes were compared using risk ratio (RR) and 95% confidence interval (95% CI). RESULTS: Eight RCTs (20,728 patients) were included in the overall analysis. Compared with aspirin or clopidogrel alone, the complete analysis of all the data indicated that the combination therapy significantly reduced the risk of stroke recurrence (RR, 0.82; 95% CI 0.70-0.96, p = 0.01) and major vascular events (RR, 0.84; 95% CI 0.73-0.96, p < 0.01). But the risk of hemorrhagic stroke (RR, 1.59; 95% CI 1.08-2.33, p = 0.02) and major bleeding (RR, 1.83; 95% CI 1.37-2.45, p < 0.01) was increased. No RCT studied middle-term combination therapy. The analyses were therefore stratified into only two subgroups, short- and long-term treatment. Stratified analysis of short-term treatment showed that relative to monotherapy, the drug combination reduced the risk of stroke recurrence (RR, 0.69; 95% CI 0.59-0.81, p < 0.01) and did not increase the risk of hemorrhagic stroke (RR, 1.23; 95% CI 0.50-3.04, p = 0.65) and major bleeding events (RR, 2.17; 95% CI 0.18-25.71, p = 0.54). Short-term combination therapy was associated with a significantly lower risk of major vascular events (RR, 0.70; 95% CI 0.69 to 0.82, p < 0.01). Stratified analysis of long-term treatment revealed that the combination treatment did not decrease the risk of stroke recurrence (RR, 0.92; 95% CI 0.83-1.03, p = 0.15), but was associated with a significantly higher risk of hemorrhagic stroke (RR, 1.67; 95% CI 1.10-2.56, p = 0.02) and major bleeding events (RR, 1.90; 95% CI 1.46-2.48, p < 0.01). Long-term combination therapy failed to reduce the risk of major vascular events (RR, 0.92; 95% CI 0.84-1.03, p = 0.09). CONCLUSIONS: Compared with monotherapy, short-term aspirin in combination with clopidogrel is more effective as secondary prevention of stroke or TIA without increasing the risk of hemorrhagic stroke and major bleeding events. Long-term combination therapy does not reduce the risk of stroke recurrence, and is associated with increased major bleeding events. The clinical applicability of the findings of this systematic review, however, needs to be confirmed in future clinical trials.

[Controlled study on treatment of cervical spondylopathy of the nerve root type with acupuncture, moxibustion and massage as main].

OBJECTIVE: To probe into clinical value of comprehensive program of acupuncture, moxibustion and massage as main for treatment of cervical spondylopathy of the nerve root type. METHODS: Five centers, single blind, randomized controlled method were used, 660 cases were divided into a treatment group of 317 cases and a control group of 311 cases. They were treated respectively with comprehensive program of acupuncture, moxibustion and massage as main, and comprehensive program of physical therapy as main. Establish syndrome detection scale and multiply dimensional effect assessment indexes, and evaluate the therapeutic effects and safety. RESULTS: The cured rate, the cured-markedly effective rate were 42.9%, 64.4% in the treatment group, respectively, better than 16.7%, 36.3% in the control group (P<0.01); after treatment of 2 weeks, clinical symptoms improved in the both groups, but the treatment group was better than the control group in the improvement degrees of neck-shoulder-limb pain, neck rigidity, abnormality of cervical anteflexion, etc. (P<0.01 or P<0.05); the treatment group was shorter than the control group in the time of producing the effect and therapeutic course (P<0.01). CONCLUSION: Comprehensive program of acupuncture, moxibustion and massage as main is safe and effective for treatment of cervical spondylopathy, with a better therapeutic effect compared with the comprehensive program of physical therapy.

[Controlled observation on electroacupuncture combined with cake-separated moxibustion for treatment of tennis elbow].

OBJECTIVE: To explore an effective method for treatment of tennis elbow. METHODS: One hundred and twenty-eight cases were randomly divided into a treatment group and a control group, 64 cases in each group. The treatment group were treated by electroacupuncture at Hegu (LI 4) and Taichong (LR 3), combined with cake-seperated moxibustion at Ashi points and Shousanli (LI 10) in the affected elbow, and the control group by routine block treatment of 1 mL lidocane and 25 mg prednisone. RESULTS: The cured rate and the effective rate were 40.6% and 93.7% in the treatment group, and 25.0% and 78.1% in the control group, respectively, with a significant difference between the two groups (P < 0.05). CONCLUSION: Electroacupuncture combined with cake-separated moxibustion is an effective method for tennis elbow.

[Clinical observation on moving cupping therapy combined with moxibustion for treatment of senile habitual constipation].

OBJECTIVE: To explore an effective method for treatment of senile habitual constipation. METHODS: Sixty-four cases were randomly divided into a treatment group treated with moving cupping at Hechelu plus Shenque (CV 8) Bazhenxue moxibustion, and a control group with oral administration of Tab phenolphthaleinum, 32 cases in each group. Improvement of constipation in the patients were observed and compared. RESULTS: The short-term (14 days) clinical cured-markedly effective rate was 84.4% in the treatment group, which was significantly better than 59.4% of the control group (P < 0.05), and there was a significant difference between the two groups in the long-term (2 months) therapeutic effect (P < 0. 01). CONCLUSION: Moving cupping at the Hechelu combined with Shenque (CV 8) Bazhenxue moxibustion is an effective method for senile habitual constipation.