Efficacy and safety evaluation of Ginkgo biloba dropping pill (GBDP) on stable angina pectoris complicated with depression: A placebo-controlled, randomized, double-blind, multicenter study.

BACKGROUND: Stable angina pectoris (SAP) is a clinical condition characterized by reversible and temporary myocardial ischemia and hypoxia. A majority of SAP patients also experience depressive disorders, which adversely affect their disease prognosis and overall quality of life. However, the clinical utility of existing antidepressants is constrained by their side effects. Ginkgo biloba dropping pill (GBDP), a Chinese patented medication, has demonstrated efficacy in the treatment of both coronary heart disease and mental disorders. This prospective, randomized, double-blind, multicenter clinical trial aimed to assess the effectiveness and safety of GBDP as an adjuvant therapy for SAP complicated by depression. METHODS: Participants were randomly assigned in a 1:1 ratio to receive either GBDP or a placebo (5 pills, three times a day) in addition to standard therapy for a duration of 12 weeks. The Seattle Angina Questionnaire (SAQ) was administered every 4 weeks during the treatment, and angina event frequency was assessed weekly. The 36-item Short-Form (SF-36) and Hamilton Depression Scale (HAMD) scores were measured both before and after the treatment. RESULTS: Out of the 72 patients, 68 (n = 34 per group) completed the entire study. At the first visit (4 weeks ± 3 days), the SAQ-Angina Stability score in the GBDP group was significantly higher than that in the placebo group (p < 0.05). While the average weekly frequency of angina episodes in the placebo group notably increased after 12 weeks of treatment (p < 0.05), it displayed an improving trend in the GBDP group (p > 0.05). By the endpoint, each subcategory score of SF-36 in the GBDP group exhibited significant improvement compared to baseline (p < 0.05). The comparison of score improvement between the two groups revealed that the SF-PCS score of the GBDP group was higher than that of the placebo group (p < 0.05). HAMD scores in both groups significantly increased after treatment (p < 0.05). No discernible difference in the incidence of adverse reactions was observed between the two groups (p > 0.05). CONCLUSION: In patients with SAP complicated by depression, GBDP, when combined with standard treatment, rapidly and safely alleviates angina pectoris symptoms. It demonstrates therapeutic potential in enhancing the quality of life and alleviating depressive symptoms.

Efficacy and safety of Ginkgo biloba dropping pills in the treatment of coronary heart disease with stable angina pectoris and depression: study protocol for a randomised, placebo-controlled, parallel-group, double-blind and multicentre clinical trial.

BACKGROUND: Coronary heart disease(CHD) with stable angina pectoris is a common cardiovascular disease. It has been reported that 10%-81.4% of these patients suffer from psychological conditions,such as depression, which has been associated with more frequent angina, lower treatment satisfaction and lower perceived quality of life. Ginkgo biloba extract (GBE), the raw material of Ginkgo biloba dropping pills (GBDPs), is widely used to treat various conditions, including cardiovascular disease, ischaemic cerebrovascular disease, and depression. This clinical trial aimed to examine the efficacy and safety of GBDPs in improving the frequency of angina pectoris and the life quality of patients with stable angina pectoris and depression symptoms. METHODS: This randomised, double-blind, placebo-controlled, parallel-group and multicentre clinical trial will be conducted in four medical centres in China. We aim to recruit approximately 72 participants aged 18-75 years with depression and coronary heart disease with stable angina pectoris. Based on conventional drug treatment, participants will be randomly assignedto the treatment group (GBDPs group; n=36) or the control group (placebo group; n=36) at a 1:1 allocation ratio. After randomisation,follow-up will be done at 4 weeks, 8 weeks and 12 weeks (±3 days). Additionally, 30 healthy individuals will be enrolled to investigate the underlying pharmacological mechanisms of the effects of GBE. The primary outcomes will be the Seattle Angina Questionnaire score and the frequency of angina pectoris-related symptoms each week. The secondary outcomes will include the 36-item Short Form Health Survey quality-of-life scale, Hamilton Depression Scale and composite endpoint incidence of major adverse cardiovascular events. ETHICS AND DISSEMINATION: This trial has been approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYECK [2020]030). Written informed consent will be obtained from all participants. The results of this trial will be publicly shared through academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04529148 and ChiCTR2200066908.

Efficacy and Safety of QiShen YiQi Dripping Pills in the Treatment of Coronary Heart Disease Complicating Chronic Heart Failure (Syndrome of Qi Deficiency with Blood Stasis): Study Protocol for a Randomized, Placebo-Controlled, Double-Blind and Multi-Centre Phase II Clinical Trial.

Background: Heart failure (HF) is a serious and terminal stage of various cardiac diseases and the most common complication of coronary heart disease (CHD). Previous clinical studies have shown that Qishen Yiqi dropping pills (QSYQ) have the effect of treating chronic heart failure. This study aims to evaluate the clinical efficacy, safety and optimal effective dose of QSYQ in treating CHD complicating chronic HF with reduced ejection fraction (HFrEF). Methods: We will conduct a randomized, double-blind, placebo controlled, multicenter clinical trial. A total of 228 individuals from 16 hospitals in China will be randomly assigned to the low-dose, high-dose, and placebo groups in a ratio of 1:1:1. The trial consists of a screening period (standard medical treatment for at least 2 weeks) and a 12-week treatment period. After randomization, follow-up will be conducted at the 4th, 8th and 12th week. The primary outcomes will be the 6-Minute Walk Test (6MWT) at Week 12. Secondary outcomes will include 6MWT distance at Week 4 and 8, New York Heart Association (NYHA) functional classification, Traditional Chinese Medicine (TCM) Syndrome score, echocardiography indices, N-terminal pro-B-type natriuretic peptide (NT-proBNP), oxyhemoglobin saturation, Minnesota living with heart failure questionnaire (MLHFQ) score, grasp strength body mass index test and cardiovascular adverse events (AE). Ethics and Dissemination: This trial has been approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYEC [2021]005). Written informed consent will be obtained from all participants. The results of this trial will be publicly shared through academic conferences and peer-reviewed journals. Study Registration: Clinical Trials Registry (NCT04983043, Date: 07/08/2021, https://clinicaltrials.gov/ct2/show/NCT04983043).

A Simplified Herbal Formula Improves Cardiac Function and Reduces Inflammation in Mice Through the TLR-Mediated NF-κB Signaling Pathway.

Nuanxinkang tablet (NXK), a Chinese herbal formula, can improve heart function and quality of life in patients with chronic heart failure (CHF). However, the mechanisms of action of NXK are not fully understood. In this study, we investigated the effects of NXK on inflammation in the CHF mouse model. This model was established by transverse aortic constriction (TAC) and treated with NXK for 8 weeks. Then, the cardiac function and myocardial fibrosis were evaluated. The monocytes/macrophages were evaluated by immunofluorescence. The mRNA levels of IL-1ß, IL-6, TNF-α, ICAM-1, and VCAM-1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while TLR4, MyD88, NF-κB p65, P-IκBα, TLR2, TLR7 and TLR9 protein levels were evaluated by Western blot. The results showed that NXK improved the left ventricular ejection fraction (LVEF) and left ventricular end-systolic dimension, reversed myocardial fibrosis, and inhibited pro-inflammatory (CD11b + Ly6C+) monocytes/macrophages in the TAC mouse model. NXK also reduced the mRNA and protein levels of the above markers. Taken together, NXK improved heart function and reduced inflammation through the TLR-mediated NF-κB signaling pathway, suggesting that it might be used as an innovative treatment strategy for CHF.

Effectiveness and safety of Xinyin tablet in treatment of chronic heart failure: A protocol of systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Xinyin Tablet (XYT) has been widely used in the treatment of CHF, Which helping to improve the clinical symptoms, enhance exercise, and even may improve the long-term prognosis of patients. However, the exact effectiveness and safety of XYT for CHF has not be comprehensively researched, so we want to generalize the effectiveness and safety of XYT for CHF through the meta-analysis, which may benefit the design of future clinical trials and provide valuable references. METHODS: This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. From the inception until September 2020, a systematic and comprehensive electronic search about Relevant randomized controlled trials will be conducted in 4 English literature databases and 4 Chinese literature databases. The registration number: INPLASY2020100015. 2 investigators will be arranged to deal with the study selection and data extraction independently. The New York Heart Function Classification, traditional Chinese medicine (TCM) symptom scores, the scores of quality of life, 6-min walk distance (6MWD), etc. will be systematically measured as outcomes. At last, the data will be handled by Review Manager 5.3 and Stata 15.0. RESULTS AND CONCLUSION: This study is hoping to provide a high-level evidence to prove the therapeutic effect of XYT on CHF, which may enhance the application of Chinese medicine.

Nrf2 participates in the anti-apoptotic role of zinc in Type 2 diabetic nephropathy through Wnt/ß-catenin signaling pathway.

Zinc (Zn), as an essential trace element, has been approved to serve many roles in diabetic studies. Also Zn deficiency will aggravate renal damage in diabetes through suppression of nuclear factor-erythroid 2-related factor 2 (Nrf2) expression and function. The purpose of this study was to illustrate the role of Zn in renal apoptosis in diabetes and whether Nrf2 participated in the process. Type 2 diabetes mice model was induced by a single dose of streptozotocin (STZ) injection after high-fat diet (HFD) feeding for 3 months, then the mice were given diets supplemented with different concentrations of Zn (control, 30 ppm; low-concentration, 0.85 ppm). After 12-week treatment, morphology and associated protein expressions were examined. The results showed that low Zn diet significantly aggravated the level of renal apoptosis during diabetes, performed as the upregulation of caspase-3 expression. In addition, either low Zn diet or diabetes or both dramatically decreased the expression of Nrf2 and P-AKT in kidney. Moreover, the expression of ß-catenin in kidney was increased markedly in diabetic groups. Mechanistic study applying human renal tubular epithelial cells (HK11) confirmed the role of Nrf2, as silencing Nrf2 expression abolished Zn supplementation protection against high sugar + high fat + low Zn-induced apoptosis and downregulation of ß-catenin expression. All these results suggest that Nrf2 plays a key role in Zn protection against Type 2 diabetes induced renal apoptosis, which might be through Wnt/ß-catenin signaling pathway.

[Ultrasound-guided suprascapular nerve block combined with acupuncture for the treatment of calcified tendinitis of rotator cuff].

OBJECTIVE: To explore the method and effect of ultrasound-guided suprascapular nerve block combined with acupuncture in the treatment of calcified tendinitis of rotator cuff. METHODS: From January 2015 to December 2017, total 30 patients with calcified tendinitis, including 23 cases of supraspinatus tendon, 5 cases of infraspinatus tendon and 2 cases of subscapular tendon, were treated with ultrasound-guided suprascapular nerve block combined with acupuncture. There were 7 males and 23 females, ranging in age from 36 to 71 years old, with an average of 51.6 years old. There were 17 cases on the right and 13 cases on the left. VAS pain score, Constant-murley score, UCLA score and X-ray examination were used to evaluate the clinical results before and after surgery. RESULTS: The mean follow-up was 14.3 months (6 to 30 months). The preoperative VAS score was 3.82±1.13, Constant-Murley score was 36.91±7.95 and UCLA score was 11.35±2.17. The final follow-up scores were 1.32±1.06, 90.61±2.89 and 33.22±1.51, respectively. The final follow-up scores were improved significantly(P<0.05). CONCLUSIONS: Conservative treatment of calcified rotator cuff tendinitis is ineffective. Suprascapular nerve block guided by ultrasound combined with acupuncture has a good therapeutic effect. It is a minimally invasive, economic, safe and effective method, which is worth promoting.

Nutritional Requirements for Mycelial Growth of Milk-White Toothed Mushroom, Irpex lacteus (Agaricomycetes), in Submerged Culture.

Irpex lacteus, a medicinal fungus, is used in traditional Chinese medicine to treat chronic glomerulonephritis. In this work, a strain of I. lacteus was isolated from the fruiting body of a wild specimen and identified by ITS-5.8S ribosomal DNA sequencing analysis. Then the nutritional requirements and culture conditions for mycelial growth of I. lacteus in semisynthetic liquid media were investigated using the one-factor-at-a-time and orthogonal matrix methods. Optimum growth occurred at 30°C and 35°C. I. lacteus mycelia grew well at pH values between 3 and 9, suggesting that this strain is not sensitive to pH. The nutritional components, including 9 carbohydrates, 9 nitrogen compounds, 11 vitamins, and 10 mineral elements, were studied for their effects on mycelial growth in submerged cultures of I. lacteus. Among these variables, soluble starch, peptone, yeast extract, and calcium chloride were identified as required for optimum mycelial growth. The concentrations of each component were optimized using an orthogonal design, and the effects of medium composition on mycelial growth were found in the order soluble starch > yeast extract > peptone > calcium chloride. The optimal concentrations of these components for mycelial growth were determined to be 60 g/L soluble starch, 35 g/L peptone, 15 g/L yeast extract, and 0.6 g/L calcium chloride. Under the optimum medium and culture conditions, the maximum biomass reached 13.73 g/L after 3 days in submerged culture, a value over twice that reached using the basal medium. These results provide a basis for further physiological study and industrial fermentation of I. lacteus.

The beneficial effects of zinc on diabetes-induced kidney damage in murine rodent model of type 1 diabetes mellitus.

Diabetes mellitus is a chronic multi-factorial metabolic disorder resulting from impaired glucose homeostasis. Zinc is a key co-factor for the correct functioning of anti-oxidant enzymes. Zinc deficiency therefore, impairs their synthesis, leading to increased oxidative stress within cells. Zinc deficiency occurs commonly in diabetic patients. The aim of this study is to investigate the effects of varying concentrations of zinc on diabetic nephropathy (DN) and the underlying mechanisms involved. FVB male mice aged 8 weeks were injected intraperitoneally with multiple low-dose streptozotocin at a concentration of 50mg/kg body weight daily for 5 days. Diabetic and age-matched control mice were treated with special diets supplemented with zinc at varying concentrations (0.85mg/kg, 30mg/kg, 150mg/kg) for 3 months. The mice were fed with zinc diets to mimic the process of oral administration of zinc in human. Zinc deficiency to some extent aggravated the damage of diabetic kidney. Feeding with normal (30mg/kg zinc/kg diet) and especially high (150mg/kg zinc/kg diet) concentration zinc could protect the kidney against diabetes-induced damage. The beneficial effects of zinc on DN are achieved most likely due to the upregulation of Nrf2 and its downstream factors NQO1, SOD1, SOD2. Zinc upregulated the expression of Akt phosphorylation and GSK-3ß phosphorylation, resulting in a reduction in Fyn nuclear translocation and export of Nrf2 to the cytosol. Thus, regular monitoring and maintaining of adequate levels of zinc are recommended in diabetic individuals in order to delay the development of DN.

Photoperiodic Responses and Characterization of the Cmvvd Gene Encoding a Blue Light Photoreceptor from the Medicinal Caterpillar Fungus Cordyceps militaris (Ascomycetes).

Light is a necessary environmental factor for production of conidia and pigment, formation of stroma, and development of Cordyceps militaris, a well-known edible and medicinal mushroom. In this study, an obvious rhythm loop was observed in certain strains of C. militaris under conditions of alternating 12-hour intervals of dark and light. A possibly related gene, Cmvvd, the homologue of the blue-light photoreceptor of Neurospora crassa, was cloned from the genome of C. militaris. The protein CmVVD is predicted to be 203 amino acids in length and is characterized by the presence of a light, oxygen, or voltage domain. Analysis of the CmVVD sensor domain (light, oxygen, or voltage) suggested that it is a blue-light receptor. Cysteine 108 is essential for the in vivo function of VIVID (VVD) in N. crassa photoadaptation. However, proline is in this position instead in all of the tested CmVVD proteins, suggesting that CmVVD may have a different function or may function in ways different from VVD in N. crassa. Genetic variation analysis of CmVVD in 6 representative strains indicated that 3 informative sites exist. Cmvvd messenger RNA was able to be induced by light, and the expression level increased over 10 times after irradiation and was maintained at high levels in the nascent fruiting body. The light-induced expression of Cmvvd was abolished in Cmwc-1 mutants, suggesting that the expression of Cmvvd is dependent on the photoreceptor CmWC-1 or on a functional CmWC-1/WC-2 complex. This article will help to open the still-unexplored field of circadian rhythms for this fungus.