Charlson Comorbidity Index is correlated with all-cause readmission within six months in patients with heart failure: a retrospective cohort study in China.

BACKGROUND: Charlson Comorbidity Index (CCI) is positively associated with all-cause readmission in patients with heart failure (HF) in western countries. However, there is a scarcity of strong scientific evidence supporting the correlation in China. This study aimed at testing this hypothesis in Chinese.   METHODS: We conducted a secondary analysis of 1,946 patients with HF in Zigong Fourth People's Hospital in China between December 2016 to June 2019. Logistic regression models were used to study the hypotheses, with adjustments for the four regression models. We also explore the linear trend and possible nonlinear relationship between CCI and readmission within six months. We further conducted subgroup analysis and tests for interaction to examine the possible interaction between CCI and the endpoint. Additionally, CCI alone and several combinations of variables based on CCI were used to predict the endpoint. Under the curve (AUC), sensitivity and specificity were reported to evaluate the performance of the predicted model. RESULTS: In the adjusted II model, CCI was an independent prognostic factor for readmission within six months in patients with HF (OR = 1.14, 95% CI: 1.03-1.26, P = 0.011). Trend tests revealed that there was a significant linear trend for the association. A nonlinear association was identified between them and the inflection point of CCI was 1. Subgroup analyses and tests for interaction indicated that cystatin played an interactive role in the association. ROC analysis indicated neither CCI alone nor combinations of variables based on CCI were adequate for prediction. CONCLUSION: CCI was independently positively correlated with readmission within six months in patients with HF in Chinese population. However, CCI has limited value on predicting readmission within six months in patients with HF.

The efficacy of Yiqi Huoxue method in treating coronary artery disease after percutaneous coronary intervention: A meta-analysis in accordance with PRISMA guideline.

BACKGROUND: Percutaneous coronary intervention (PCI), the most common method in treating coronary artery disease (CAD), has a variety of side effects. Yiqi Huoxue therapy (YQHX) can effectively alleviate the symptoms of patients and reduce the side effects. However, a reliable and systematic assessment of the methodologies is not available. METHODS: Seven electronic databases were searched to identify randomized controlled trials of YQHX method for CAD after PCI. The quality assessment of the trials included was performed by employing the Cochrane Risk of Bias tool. RESULTS: One thousand eight hundred sixty-eight patients from 23 randomized controlled trials were included in this review. The aggregated results showed that the experimental group got better effect in increasing ORR, TCMSRR, ECG, HDL-C, and in lowering the level of CRP, TC, and MACE in comparison with the control group. CONCLUSION: YQHX method is a valid complementary and alternative therapy in the management of CAD after PCI, and is an effective and safe therapy for CAD.

The efficacy of Yiqi Huoxue therapy for chronic heart failure: A meta-analysis in accordance with PRISMA guideline.

BACKGROUND: Chronic heart failure (CHF) is the final destination of most cardiovascular diseases and the most important cause of death. The main clinical manifestations were pulmonary congestion and decreased cardiac output. The purpose of this systematic review is to evaluate the effectiveness of Yiqi Huoxue therapy on CHF. METHODS: Seven electronic databases were searched to identify randomized controlled trials of Yiqi Huoxue (YQHX) method for CHF until April 30, 2020. The quality assessment of the included trials was performed by employing the Cochrane Risk of Bias tool and Jadad scale. RESULTS: Nineteen randomized controlled trials were included in our review. Most of the included trials were considered as low quality. The aggregated results suggested that experimental group with YQHX therapy got better effect in increasing overall response rate (risk ratio, RR = 1.21, 95% confidence interval, CI 1.15-1.27), traditional Chinese medicine (TCM) syndrome response rate (RR = 1.26, 95% CI 1.17-1.36), 6-minute walk test (RR = 2.14, 95% CI 1.05-3.22), left ventricular ejection fraction (RR = 0.97, 95% CI 0.60-1.34), and stroke volume (standardized mean difference, SMD = 0.94, 95% CI 0.23-1.56), and in lowering down the TCM syndrome scores (SMD = -0.78, 95% CI -0.91 to -0.64), Minnesota Living with Heart Failure questionnaire (SMD = -1.01, 95% CI -1.56 to -0.45), 6-month readmission rate (RR = 0.50, 95% CI 0.28-0.89), B-type natriuretic peptide (SMD = -0.89, 95% CI -1.52 to -0.25), NT-proBNP (SMD = -2.07, 95% CI -3.34 to -0.08), and C-reactive protein (SMD = -2.04, 95% CI -4.12 to -0.67) as compared to using conventional Western medicine alone. There were no significant differences found in left ventricular end diastolic diameter and E/E' between experimental groups and control groups. Moreover, the included sample capacity is small and the trails are all in Chinese. Quality of the evidence for outcomes were "low" and "very low" according to the GRADE assessment. CONCLUSION: YQHX is a valid complementary and alternative therapy in the management of CHF, especially in improving overall response rate, TCM syndrome response rate, 6-minute walk test, left ventricular ejection fraction, and stroke volume and in decreasing TCM syndrome scores, Minnesota Living with Heart Failure questionnaire, 6-month readmission rate, B-type natriuretic peptide, NT-proBNP, and C-reactive protein levels. Hence, YQHX is a relatively effective and safe therapy for CHF patients, which can be popularized and applied in the clinic. More long-term follow-up studies are still needed to substantiate and confirm the current findings.

Hypermethylation Effects of Yiqihuoxue Decoction in Diabetic Atherosclerosis Using Genome-Wide DNA Methylation Analyses.

PURPOSE: To investigate if a traditional Chinese medicine formulation, called "Yiqihuoxue" (YQHX), could improve diabetic atherosclerosis (DA) and explore potential mechanisms based on DNA methylation. METHODS: Apolipoprotein E-knockout mice were administered streptozotocin (50 mg/d, i.p.) for 5 days and fed a high-fat diet for 16 weeks. Mice were divided randomly into DA model, rosiglitazone, as well as low-, medium-, and high-dose YQHX groups. Ten healthy C57BL/6J mice were the control group. Serum levels of fasting insulin, blood glucose, homeostasis model-insulin resistance index (HOMA-IR), serum lipids, and inflammatory factors were analyzed after the final treatment. Aorta tissues were collected for staining (hematoxylin and eosin, and Oil red O). Genomic DNA was extracted for methyl-capture sequencing (MC-seq). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases were used to analyze differentially methylated genes. Pyrosequencing was used to verify MC-seq data. RESULTS: Low-dose and high-dose YQHX could reduce the HOMA-IR (P < 0.05). Low-dose YQHX reduced expression of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), TNF-α, andI L-6 in serum compared with that in the model group (P < 0.05). Medium-dose YQHX decoction inhibited the expression level of TNF-α (P < 0.05). High-dose YQHX decreased the expression level of IL-6 (P < 0.05). Staining also showed the anti-atherosclerosis effects of YQHX (P < 0.05). MC-seq revealed many abnormally hypermethylated and hypomethylated genes in DA mice compared with those in the control group. KEGG database analysis showed that the hypermethylated genes induced by YQHX treatment were related to pathways in cancer, Hippo signaling, and mitogen activated protein kinase. The network analysis suggested that the hypermethylated genes epidermal growth factor receptor(Egfr) and phosphoinositide-3-kinase regulatory subunit 1(Pik3r1) induced by YQHX treatment had important roles in DA. Pyrosequencing revealed that YQHX treatment increased methylation of AKT1, Nr1h3 and Fabp4 significantly (P < 0.05). CONCLUSION: YQHX decoction had positive treatment effects against DA, because it could regulate aberrant hypomethylation of DNA.

Network Pharmacology-Based Exploration of Synergistic Mechanism of Guanxin II Formula (II) for Coronary Heart Disease.

OBJECTIVE: To study the pharmacological mechanism of Guanxin II formula (II) for treatment of coronary heart disease (CHD). METHODS: A network pharmacology-based method was utilized. First candidate compounds, targets of GX II were collected using PharmMapper, BATMAN-TCM, DrugBank and SwissTargetPrediction, and targets on CHD were mined from GeneCards, DisGenet, DrugBank and GEO. Afterwards, the big hub compounds and targets were chosen in the candidate compounds-direct therapeutic targets on the CHD (C-T) network and the direct therapeutic targets on the CHD (T-D) network. Furthermore, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were performed to identify the enriched terms. Finally, a molecular docking simulation strategy was adopted to verify the binding capacity between the big hub compounds and big hub targets on CHD. RESULTS: First, 114 candidate compounds were selected with the following criteria: OB⩾30%, DL⩾0.18, and HL ⩾4 h. Then, 1,035 targets of GX II were gathered, while 928 targets on CHD were collected. Afterwards, 196 common targets of compound targets and therapeutic targets on CHD were defined as direct therapeutic targets acting on CHD. In addition, the contribution index (CI) in the C-T network was calculated, and 4 centrality properties, including degree, betweenness, closeness and coreness, in the T-D network, 4 big hub compounds, and 6 big hub targets were eventually chosen. Furthermore, the GO and KEGG analysis indicated that GX II acted on CHD by regulating the reactive oxygen species metabolism, steroid metabolism, lipid metabolism, inflammatory response, proliferation, differentiation and apoptosis. The docking results manifested excellent binding capacity between the 4 big hub compounds and 6 big hub targets on CHD. CONCLUSION: This network pharmacology-based exploration revealed that GX II might prevent and inhibit the primary pathological processes of CHD.

Exploratory study on the safety and effectiveness of Yizhi Qingxin Decoction (capsules) in the treatment of hypertension in the elderly with mild cognitive impairment (deficiency of kidney essence syndrome).

BACKGROUND: Hypertension in the elderly with cognitive impairment has been one of the global health issues. Mild cognitive impairment (MCI) is the state of transition between the normal aging process and cognitive changes of unformed dementia. Diagnosis and treatment of MCI are the keys to prevent dementia, and hypertension is one of the important influencing factors of MCI. Our preclinical experiment found that Yizhi Qingxin Decoction (YQD) could effectively reduce the blood pressure of spontaneously hypertensive rats (SHR), improve their spatial learning and memory abilities in Morris water maze, and play a neuroprotective role. The objective is to estimate the safety and efficacy of YQD (capsules) in the treatment of hypertension in the elderly with MCI (deficiency of kidney essence syndrome) through this study. METHODS: According to the random number generated by the block random method, 100 participants will be randomly and equally divided into the treatment group (YQD) or the control group (Ginkgo biloba extract tablets). The conversion rate of dementia will be used as the main evaluating indicator by the CDR scale. The MoCA scale, MMSE scale, ADCS-MCI-ADL-24 scale, CGIC-KDS scale, and 24-h ambulatory blood pressure will be used as the secondary evaluating indicator. Safety will be evaluated based on specific manifestations of adverse reactions and the incidence of adverse events. OBJECTIVE: The objective is to estimate the curative effect of YQD (capsules) on hypertension in the elderly with MCI (deficiency of kidney essence syndrome), and to evaluate the safety of its clinical application. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ICTRP member): ChiCTR2000030292.

Traditional Chinese Medicine Containing Arsenic Treated MDS Patients Effectively through Regulating Aberrant Hypomethylation.

Aberrant hypermethylation and hypomethylation both play important roles in myelodysplastic syndrome (MDS). Hypomethylating agents targeting hypermethylation have been employed for the MDS treatment, but the treatment effect is limited. Novel drugs for DNA hypomethylation-targeted therapy may be needed to improve clinic efficacy for the treatment of MDS. Chinese medicine (CM) herbs have been used to treat MDS for many years in our hospital. However, the long-term treatment effect and mechanism remain unclear. In this study, all 135 patients received CM treatment for at least 36 months. The response rates for CM treatment were 81.53% (106/130) for hematological improvement in 130 MDS-RCMD patients and 80% (4/5) for bone marrow CR in 5 MDS-RAEB patients, respectively. The Human Methylation 850K BeadChip showed that 115 genes (50.88%) were aberrantly hypomethylated in 5 MDS patients compared with 3 healthy individuals. GO-analysis showed that these hypomethylated genes participated in many cancer-related biological functions and pathways. Furthermore, 60 genes were hypermethylated and the protein expression level of DNMT1 was significantly increased in the 5 MDS patients after 6 months of CM treatment. Our study suggests that CM can improve aberrant hypomethylation by increasing DNMT1 expression in MDS. The data support the clinical application of CM herbs containing arsenic as an innovative hypermethylation-inducing regimen for the treatment of MDS.

Efficacy and safety of Xinnaoning capsule in treating chronic stable angina (qi stagnation and blood stasis syndrome): Study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Chronic stable angina (CSA) is a cardiovascular disease with high prevalence. At present, drug treatment is still the main measure of stable angina pectoris. Traditional Chinese medicine has a long history in the treatment of CSA. Qi stagnation and Blood stasis syndrome is a common syndrome of CSA. Xinnaoning (XNN) capsule is considered as an effective adjuvant treatment for CSA with the efficacy of promoting qi and blood circulation but lack of high-quality clinical evidence. The purpose of this study is to evaluate the efficacy and safety of XNN capsule compared with placebo by clinical trial. METHODS: This multicenter, randomized, double-blind, placebo-controlled trial will be conducted with a total of 240 participants diagnosed with chronic stable angina (qi stagnation and blood stasis syndrome). The participants will be randomized (1:1) into groups receiving either XNN or placebo for 12 weeks. After a 2-week run-in period, they will receive either XNN or placebo (3 pills, 3 times daily) for 12 weeks on the basis of conventional therapy. The primary outcomes include changes in the integral scores of angina symptoms. The secondary outcome measures include changes in the total score of traditional Chinese medicine syndrome, severity grading of angina pectoris, the number of angina pectoris per week, nitroglycerin dosage, score of seattle angina scale, serum homocysteine, incidence of cardiovascular events. Safety outcomes will also be assessed. Adverse events will be monitored throughout the trial. RESULTS: This study will investigate whether XNN capsule can alleviate clinical symptoms, and improve quality of life of patients with chronic stable angina (qi stagnation and blood stasis syndrome). The results of this study will provide clinical evidence for the application of XNN capsule in the treatment of chronic stable angina. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03914131.

In the human sperm nucleus, nucleosomes form spatially restricted domains consistent with programmed nucleosome positioning.

In human sperm, a fraction of its chromatin retains nucleosomes that are positioned on specific sequences containing genes and regulatory units essential for embryonic development. This nucleosome positioning (NP) feature provides an inherited epigenetic mark for sperm. However, it is not known whether there is a structural constraint for these nucleosomes and, if so, how they are localized in a three-dimensional (3D) context of the sperm nucleus. In this study, we examine the 3D organization of sperm chromatin and specifically determine its 3D localization of nucleosomes using structured illumination microscopy. A fraction of the sperm chromatin form nucleosome domains (NDs), visible as microscopic puncta ranging from 40 µm to 700 µm in diameter, and these NDs are precisely localized in the post acrosome region (PAR), outside the sperm's core chromatin. Further, NDs exist mainly in sperm from fertile men in a pilot survey with a small sample size. Together, this study uncovers a new spatially-restricted sub-nuclear structure containing NDs that are consistent with NPs of the sperm, which might represent a novel mark for healthy sperm in human.

Oral Chinese Herbal Medicine for Heart Failure with Preserved Ejection Fraction: A Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness and safety of oral Chinese herbal medicine (OCHM) for heart failure with preserved ejection fraction (HFpEF). METHODS: PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Chinese Biological Medicine Database (CBM), Wanfang Database, Chongqing VIP Information (VIP) and China National Knowledge Infrastructure (CNKI) were searched for appropriate articles from respective inceptions until June 3, 2018. Randomized controlled trials (RCTs) investigating the effectiveness of OCHM for the patients with HFpEF were eligible. Quality assessment was performed by employing the Cochrane Risk of Bias assessment tool. Papers were independently reviewed by two reviewers and analyzed using Cochrane software Revman 5.3. Dichotomous data were analyzed by relative risk (RR) with a 95% confidence interval (CI), while continuous variables were analyzed by using mean difference (MD) with 95% CI for effect size. RESULTS: A total of 16 RCTs involving 1,320 participants were identified. Fourteen of the trials used conventional Western medicine (CWM) as the control, the control of 1 trial was no treatment, and another was placebo. Three of the trials served Chinese patent medicine (CPM) as interventions, and other OCHM were Chinese medicine decoctions (CMDs). Only limited evidence showed experimental group with OCHM may get better effect on brain natriuretic peptide (BNP: MD -37.29, 95% CI -53.08 to -21.50, P<0.00001) or N terminal pro B type natriuretic peptide (NT-proBNP: MD -236.04, 95% CI -356.83 to -115.25, P=0.0001), Minnesota Living with Heart Failure questionnaire (MLHFQ, MD -9.94, 95% CI -16.77 to -3.11, P=0.004), but the results had high heterogeneities. With concerns on 12 of 16 trials, the meta-analysis found that the adjuvant therapy of OCHM might be more effective in increasing overall response rate (RR 1.17, 95% CI 1.11 to 1.24, P<0.00001), when compared with CWM alone. Subgroup meta-analysis between CPMs and CMDs showed that the two CPMs may have more therapeutic effect on MLHFQ, but not on NT-proBNP, and CMD came to the opposite conclusion. No significant differences were found between experimental groups and control groups on 6-min walk test (6MWT). Adverse events, such as more defecation, weakness, cardiopalmus, edema, cough and hypotension, were mild in all groups and disappeared after the easement of pharmacological intervention. CONCLUSIONS: Due to the insufficient quality of trials that were analyzed, it is not appropriate to confirm or deny the potency of OCHMs in treating HFpEF at the present time. More rigorously designed RCTs focusing on primary endpoints with long-term follow-up are warranted to validate the effect of OCHMs for patients with HFpEF.

Effect of Qinghuang Powder () Combined with Bupi Yishen Decoction () in Treating Patients with Refractory Cytopenia with Multilineage Dysplasia through Regulating DNA Methylation.

OBJECTIVE: To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula. METHODS: All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation. Gene Ontology (GO) and Pathway analysis were applied to analyze the methylation data. RESULTS: The overall MDS response rate to QHP was 61.68% (190/360) including hematologic improvement-neutrophil (HI-N) or hematologic improvement-erythroid (HI-E) or hematologic improvement-platelet (HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia (55.88% vs 31.54% or 55.88% vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions. CONCLUSIONS: QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement (HI-N, HI-P or HI-E) and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.

Effect of tetramethylpyrazine and hyperlipidemia on hepcidin homeostasis in mice.

Iron homeostasis is strictly regulated in mammals, and disordered iron metabolism is recognized as a risk factor for various diseases, including cardiovascular disease. The hepcidin­ferroportin axis is the key signaling mechanism that controls systemic iron homeostasis. Increased serum hepcidin is associated with multiple types of cancer and atherosclerosis (AS), and therapeutics that decrease hepcidin levels have been proposed to treat these diseases. However, the effects of abnormal circulating hepcidin on hyperlipidemia remain unexploited. The natural compound tetramethylpyrazine (TMP) has been reported to have therapeutic effects on cardiovascular diseases, whereas the mechanisms involved remain incompletely understood. Thus, the effects of TMP on the expression of hepcidin in hyperlipidemic mice were investigated and the mechanisms involved were explored. Hyperlipidemia increased serum hepcidin, which was inhibited by TMP intervention. The results also indicated that TMP may decrease hepcidin expression via inhibition of Stat3 signaling. These findings suggest a promising rationale to prevent and hyperlidemia by targeting hepcidin or its upstream regulators, and highlight the potential application of natural compounds in treating hepcidin disorder­associated diseases.

Chinese Medicine for Alzheimer's Disease: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the effificacy of oral Chinese medicine (CM) in comparison with donepezil, a cholinesterase inhibitor (ChEI), for the treatment of Alzheimer's disease (AD). METHODS: Randomized controlled trials (RCTs) have been searched, and the effect of CM compared with donepezil in AD has been investigated. An electronic search of MEDLINE, Excerpta Medica Database (EMBASE), Cochrane Library, Chinese Biological Medicine Database (CBMdisc), and China National Knowledge Infrastructure (CNKI) to identify articles in English and Chinese from the inception of the database until October 18, 2015. A modifified Jadad score (7-points) to judge the methodological quality of studies, comprehensive meta-analysis was performed with Cochrane Collaboration Revman 5.3. Dichotomous data were analyzed by relative risk (RR) with a 95% confifidence interval (CI), while continuous variables were analyzed by using mean differences (MD) with 95% CI for effect size. RESULTS: Six studies involving 596 AD patients through Jadad assessment with low bias were included in the meta-analysis. No signifificant difference was observed in cognitive improvement and daily abilities of patients using the Mini Mental State Examination (MMSE) (MD: 0.69, 95% CI:-0.17 to 1.56) and Activities of Daily Living (ADL) scale (MD: 0.94, 95% CI:-1.54 to 3.43). There were no signifificant differences in status of illness or MD for mild-moderate AD patients at 24 weeks (MD: 0.62, 95% CI:-2.99 to 4.23) and 48 weeks (MD:-0.73, 95% CI:-5.02 to 3.56). Severe AD patients were also assessed at 24 weeks (MD: 3.13, 95% CI:-6.92 to 13.18) and 48 weeks (MD: 4.23, 95% CI:-6.38 to 14.84). Furthermore, compared with donepezil, Xin (Heart)-regulating CM and Shen (Kidney)-tonifying groups were observed (MD:-1.50, 95% CI:-3.08 to 0.08; MD:-1.92, 95% CI:-3.50 to-0.33; respectively). CM had fewer side effects in AD patients. CONCLUSION: Compared with donepezil, oral CM showed no signifificant difference in effectiveness in AD patients, and more evidence is needed to verify the fifindings.

Clinical applicability of monitoring pulmonary artery blood flow acceleration time variations in monitoring fetal pulmonary artery pressure.

BACKGROUND: In recent years, pulmonary artery blood flow acceleration time (AT) has been believed to be applicable in the examination of fetal lung development. OBJECTIVES: This study aims to evaluate the clinical significance of pulmonary artery blood flow AT as a parameter in monitoring of fetal pulmonary artery pressure. MATERIAL AND METHODS: A total of 31 fetuses in midor late-term pregnancy with tricuspid regurgitation were set as the study group (congenital heart disease with a tricuspid regurgitation pressure difference of more than 20 mm Hg was excluded). A total of 68 normal fetuses in midor late-term pregnancy were selected as the control group (strictly screened for tricuspid regurgitation, congenital heart disease and other congenital diseases before inclusion). The average ATs of both groups were calculated. Correlations of pulmonary artery systolic pressure (PASP) and AT, as well as the ratio of AT to right ventricular ejection time (ET) (AT/ET ratio) of both groups were investigated by 1-way analysis of variance (ANOVA). RESULTS: The average AT of the study group was significantly lower than that of the control group (p < 0.0001). In the study group, AT negatively correlated with PASP (r = -0.52; p < 0.01), AT/ET ratio negatively correlated with PASP (r = -0.52; p < 0.01) and both showed statistical significance. CONCLUSIONS: The results indicated that fetuses in the study group showed lower ATs and AT/ET ratios than the control group. Acceleration times and AT/ET ratios decreased as PASP increased. Thus, AT and AT/ET ratio can be used clinically as new parameters for the qualitative and - to some extent - quantitative evaluation of fetal pulmonary artery pressure.

Effects of Zhizi Chuanxiong Capsule () on the Abnormal Methylation in Rabbits with Atherosclerosis.

OBJECTIVE: To investigate the effects of Zhizi Chuanxiong Capsule (ZCC, ) on abnormal DNA methylation in a rabbit model of atherosclerosis (AS). METHODS: After 1 week of adaptive feeding, 48 New Zealand white rabbits were randomly divided into 4 groups: a control group (n=12) fed with normal diet for 22 weeks; a model group (n=12) fed with high fat diet for 14 weeks followed by 8 weeks of normal diet feeding; a low-dose ZCC group (n=12) fed with high fat diet and low-dose ZCC for 14 weeks, followed by 8 weeks of normal diet and low-dose drug; a high-dose ZCC group (n=12) fed with high fat diet and high-dose drug for 14 weeks, followed by 8 weeks of normal diet and high-dose drug. After 22 weeks of feeding, blood samples were taken from the rabbit ear vein, and the genomic DNA was extracted for methylation immunoprecipitation sequencing (Medip-seq). The aorta tissues were collected for hematoxylin-eosin (HE) staining. RESULTS: Eight rabbits died during the feeding process. HE staining showed that the size of the lipid deposition on vessel wall and atherosclerotic plaque formation were reduced in both low- and high-dose group. The Medip-seq results showed that there were 146 abnormally methylated genes (including both hypermethylated gene and hypomethylated genes) in the model group, compared with the control group. Gene Ontology (GO) and Pathway analysis showed that these abnormally methylated genes were found to be involved in multiple AS-related functions and pathways, such as protein kinase C activity, cholesterol transport, mitogen-activated protein kinase (MAPK) signaling pathway, peroxisome proliferater-activated receptor signaling pathway, vascular smooth muscle contraction, inflammation and so on. The abnormal methylated genes in AS model group were altered in both low- and high-dose groups: low-dose ZCC could change 72 of the 146 abnormally methylated genes, high-dose ZCC could change 71. Through GO and Pathway analysis, these altered methylated genes were involved in protein kinase C activity, inflammatory pathway, MAPK signaling pathway, vascular endothelial growth factor signaling pathway, etc. CONCLUSION: ZCC could treat AS through regulating the abnormal hypermethylated and hypomethylated genes in AS rabbit model.

Protective effects of Xiongshao Capsule () on anti-inflammatory function of high-density lipoprotein in an atherosclerosis rabbit model.

OBJECTIVE: To observe the effects of Xiongshao Capsule (, XSC) on anti-inflflammatory properties of high-density lipoprotein (HDL), myeloperoxidase (MPO) and paraoxonase 1 (PON1) in serum of atherosclerosis (AS) rabbit model and explore the anti-inflflammatory protective effects of XSC on HDL. METHODS: Sixty rabbits were randomized into the control, the model, XSC low-, medium- and high-dose (Rhizoma Chuanxiong + Radix Paeoniae rubra: 0.6+0.3, 1.2+0.6, 2.4+1.2g·kg-1·day-1, respectively), and simvastatin (1g·kg-1·day-1) groups. The model rabbits were fed with high-fat diet and drugs for 15 weeks. The blood and thoracic aortas samples were collected at the end of 15 weeks. The levels of serum MPO and PON1 as well as total cholesterol (TC) and free cholesterol (FC) in aorta wall cells were tested by enzyme linked immunosorbent assay. RESULTS: TC and FC in the model group were significantly higher than those in the control group (P<0.01). Compared with the model group, TC and FC in the XSC groups were signifificantly lower (P<0.05 or P<0.01), so was simvastatin group (P<0.01). There was no signifificant difference in PON1 level between groups (P>0.05), even between model and control groups (P>0.05). The serum MPO level in the model group was signifificantly higher than that in the control group (P<0.05), which was signifificantly lower in XSC groups as well as simvastatin group (P<0.05 or P<0.01), and no difference was found between XSC groups and simvastatin group (P>0.05). CONCLUSIONS: XSC can reduce the serum MPO level in AS rabbits to protect the anti-inflammatory function of HDL, maintaining the normal lipid transport function. TC and FC levels in aorta cells decline, and this process initiated by XSC plays an anti-AS role.

A multicenter, randomized, double-blind clinical study on Wufuxinnaoqing Soft Capsule () in treatment of chronic stable angina patients with blood stasis syndrome.

OBJECTIVE: To confirm the efficacy and safety of Wufuxinnaoqing Soft Capsule (, WSC) in the treatment of chronic stable angina (blood stasis syndrome). METHODS: A multicenter, randomized, double-blind, placebo-controlled trial with superiority test was designed. A total of 240 patients with chronic stable angina (blood stasis syndrome) from multiple centers were randomly and equally assigned to the treatment group and the control group. Based on standard treatment of Western medicine, the treatment group was given WSC, while the control group was given WSC mimetic, both for 12 weeks. Observed indicators included the efficacy in angina, the efficacy in Chinese medicine syndrome, the withdrawal or reduce rate of nitroglycerin and routine safety indices. RESULTS: After 12-week treatment, the significant effective rate and total effective rate of the treatment group were significantly better than those of the control group (23.5% vs. 9.2%, 64.7% vs. 30.8%), respectively, with statistically significant difference (P<0.01). After 12-week treatment, the decreased points and the decreased rate of angina symptom score in the treatment group were better than in the control group (5.1±4.2 points vs. 2.8±3.5 points, 44.9%±37.2% vs. 25.4%±30.7%) respectively, with significant difference (P<0.01). After 12-week treatment, the significant effective rate and total effective rate of the treatment group were better than the control group (respectively, 30.3% vs. 15.0%, 67.2% vs. 45.0%,P<0.01). After 8- or 12-week treatment, the decreased points and the decreased rate of Chinese medicine syndrome score in the treatment group were better than the control group (P<0.05 orP<0.01). After 12-week treatment, nitroglycerin withdrawal rate and the withdrawal or reduce rate in treatment group were better than the control group (P<0.01). On safety evaluation, the incidence of adverse events (7.563% vs. 7.500%) and the incidence of cardiovascular events (0.840% vs. 0.000%) in the treatment group were similar with the control group, and the difference was not statistically significant (P>0.05). CONCLUSION: In treatment of chronic stable angina (blood stasis syndrome), WSC can reduce angina attacks and consumption of nitroglycerin, decrease angina severity degree, effectively relieve the blood stasis syndromes, such as chest pain, chest tightness, palpitations, dark purple tongue and other symptoms. Besides, adverse events and cardiovascular adverse events in the treatment group and the control group showed no difference. All shows that the drug is safe and effective. [This study was registered in Chinese Clinical Trial Registry (ChiCTR), with registration number: ChiCTR-TRC-14005158.].

Embryo selection strategy in sibling oocytes: a novel approach to measuring the likelihood of single­embryo transfer using a mouse embryo transfer model.

The present study investigated the effect of embryo transfer on post-implantation development using different fertilization approaches in sibling oocyte procedures. C57BL/6, DBA/2, C3H/HeJ and ICR mice were used at 8-10 weeks of age. Mature oocytes were collected, divided into two groups and fertilized using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Different numbers of the resulting blastocysts were then transferred into recipients and designated as either: The single embryo transfer (SET) I model (one transferred embryo), the SET II model (six transferred embryos) or the multiple embryo transfer (MET) model (24 transferred embryos). The development efficiency, cell number, number of apoptotic cells in blastocysts, pregnancy efficiency, delivery rate and cumulative pregnancy efficiency were analyzed. IVF-fertilized embryos exhibited higher blastocyst development competence and embryo quality compared with ICSI embryos. The pregnancy and delivery efficiency was not identified to be significantly different between the two SET models, but it was lower in these two models than in the MET model. The cumulative pregnancy efficiency in SET models, calculated using a mathematical equation, was not decreased. In conclusion, embryo quality was shown to be the primary factor in selecting embryos prior to embryo transfer using sibling oocytes. In addition, single blastocyst transfer can be performed in sibling oocytes without compromising cumulative pregnancy rates, independent of the fertilization approach.