High-quality chromosome-level genome assembly and multi-omics analysis of rosemary (Salvia rosmarinus) reveals new insights into the environmental and genome adaptation.

High-quality genome of rosemary (Salvia rosmarinus) represents a valuable resource and tool for understanding genome evolution and environmental adaptation as well as its genetic improvement. However, the existing rosemary genome did not provide insights into the relationship between antioxidant components and environmental adaptability. In this study, by employing Nanopore sequencing and Hi-C technologies, a total of 1.17 Gb (97.96%) genome sequences were mapped to 12 chromosomes with 46 121 protein-coding genes and 1265 non-coding RNA genes. Comparative genome analysis reveals that rosemary had a closely genetic relationship with Salvia splendens and Salvia miltiorrhiza, and it diverged from them approximately 33.7 million years ago (MYA), and one whole-genome duplication occurred around 28.3 MYA in rosemary genome. Among all identified rosemary genes, 1918 gene families were expanded, 35 of which are involved in the biosynthesis of antioxidant components. These expanded gene families enhance the ability of rosemary adaptation to adverse environments. Multi-omics (integrated transcriptome and metabolome) analysis showed the tissue-specific distribution of antioxidant components related to environmental adaptation. During the drought, heat and salt stress treatments, 36 genes in the biosynthesis pathways of carnosic acid, rosmarinic acid and flavonoids were up-regulated, illustrating the important role of these antioxidant components in responding to abiotic stresses by adjusting ROS homeostasis. Moreover, cooperating with the photosynthesis, substance and energy metabolism, protein and ion balance, the collaborative system maintained cell stability and improved the ability of rosemary against harsh environment. This study provides a genomic data platform for gene discovery and precision breeding in rosemary. Our results also provide new insights into the adaptive evolution of rosemary and the contribution of antioxidant components in resistance to harsh environments.

Association between the triglyceride-glucose index and 1-year major adverse cardiovascular events in patients with coronary heart disease and hypertension.

BACKGROUND: The triglyceride-glucose (TyG) index has been proposed as a potential predictor of adverse prognosis of coronary heart disease (CHD). However, its prognostic value in patients with CHD and hypertension remains unclear. This study aimed to evaluate the association between the TyG index and the 1-year risk of major adverse cardiovascular events (MACEs) in patients with CHD and hypertension. METHODS: The data for the study were taken from the Hospital Information System database in China-Japan Friendship Hospital which contained over 10,000 cardiovascular admissions from 2019 to 2022. The Boruta algorithm was performed for feature selection. The study used univariable analysis, multivariable logistic regression analysis, and restricted cubic spline (RCS) regression to evaluate the association between the TyG index and the 1-year risk of MACEs in patients with CHD and hypertension. RESULTS: After applying inclusion and exclusion criteria, a total of 810 patients with CHD and hypertension were included in the study with a median TyG index of 8.85 (8.48, 9.18). Using the lowest TyG index quartile as the reference, the fully adjusted ORs (95% CIs) for 1-year MACEs for TyG index Q2, Q3, and Q4 were 1.001 (0.986 ~ 1.016), 1.047 (1.032 ~ 1.062), and 1.760 (1.268 ~ 2.444), respectively. After adjusting for all confounders, we found that those with the highest TyG index had a 47.0% increased risk of MACEs over the 1-year follow-up (OR 1.470, 95% CI 1.071 ~ 2.018). The results in the subgroup analysis were similar to the main analyses. RCS model suggested that the TyG index was nonlinearly associated with the 1-year risk of MACEs (P for nonlinear < 0.001). CONCLUSION: This study shows that the elevated TyG index is a potential marker of adverse prognosis among patients with CHD and hypertension and informs the development of clinical decisions to improve outcomes.

Prognostic value of triglyceride-glucose index in patients with chronic coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The triglyceride-glucose (TyG) index has been proposed as a reliable surrogate marker of insulin resistance and an independent predictor of major adverse cardiovascular events (MACEs). Several recent studies have shown the relationship between the TyG index and cardiovascular outcomes; however, the role of the TyG index in chronic coronary syndrome (CCS) progression has not been extensively assessed especially in population after revascularization. This study aimed to investigate the prognostic value of the TyG index in predicting MACEs in CCS patients undergoing percutaneous coronary intervention (PCI). METHODS: The data for the study were taken from the Hospital Information System database in China-Japan Friendship Hospital over the period 2019-2021. Eligible participants were divided into groups according to the TyG index tertiles. The Boruta algorithm was performed for feature selection. Multivariate Cox proportional hazards models and restricted cubic spline (RCS) analysis were applied to examine the dose-response relationship between the TyG index and endpoint, and the results were expressed with hazard ratio (HR) and 95% confidence interval (CI) values. The area under the receiver operating characteristic (ROC) curve (AUC), decision curve analysis (DCA), and clinical impact curve (CIC) were plotted to comprehensively evaluate the predictive accuracy and clinical value of the model. The goodness-of-fit of models was evaluated using the calibration curve and χ2 likelihood ratio test. RESULTS: After applying inclusion and exclusion criteria, 1353 patients with CCS undergoing PCI were enrolled in the study. After adjusting for all confounders, we found that those with the highest TyG index had a 59.5% increased risk of MACEs over the 1-year follow-up (HR 1.595, 95% CI 1.370 ~ 1.855). Using the lowest TyG index tertile as the reference (T1), the fully adjusted HRs (95% CIs) for endpoints was 1.343 (1.054 ~ 1.711) in the middle (T2) and 2.297 (1.842 ~ 2.864) in highest tertile (T3) (P for trend < 0.001). The TyG index had an excellent predictive performance according to the results of AUC 0.810 (0.786, 0.834) and χ2 likelihood ratio test (χ2 = 7.474, P = 0.486). DCA and CIC analysis also suggested a good overall net benefit and clinical impact of the multivariate model. The results in the subgroup analysis were consistent with the main analyses. RCS model demonstrated that the TyG index was nonlinearly associated with the risk of MACEs within one year (P for nonlinear < 0.001). CONCLUSION: The elevated TyG index is associated with an increased risk of cardiovascular events and predicts future MACEs in patients with CCS undergoing PCI independently of known cardiovascular risk factors, indicating that the TyG index may be a potential marker for risk stratification and prognosis in CCS patients undergoing PCI.

Development and validation of a clinical prediction model for detecting coronary heart disease in middle-aged and elderly people: a diagnostic study.

OBJECTIVE: To develop and validate a multivariate prediction model to estimate the risk of coronary heart disease (CHD) in middle-aged and elderly people and to provide a feasible method for early screening and diagnosis in middle-aged and elderly CHD patients. METHODS: This study was a single-center, retrospective, case-control study. Admission data of 932 consecutive patients with suspected CHD were retrospectively assessed from September 1, 2020 to December 31, 2021 in the Department of Integrative Cardiology at China-Japan Friendship Hospital. A total of 839 eligible patients were included in this study, and 588 patients were assigned to the derivation set and 251 as the validation set at a 7:3 ratio. Clinical characteristics of included patients were compared between derivation set and validation set by univariate analysis. The least absolute shrinkage and selection operator (Lasso) regression analysis method was performed to avoid collinearity and identify key potential predictors. Multivariate logistic regression analysis was used to construct a clinical prediction model with identified predictors for clinical practice. Bootstrap validation was used to test performance and eventually we obtained the actual model. And the Hosmer-Lemeshow test was carried out to evaluate the goodness-fit of the constructed model. The area under curve (AUC) of receiver operating characteristic (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were plotted and utilized with validation set to comprehensively evaluate the predictive accuracy and clinical value of the model. RESULTS: A total of eight indicators were identified as risk factors for the development of CHD in middle-aged and elderly people by univariate analysis. Of these candidate predictors, four key parameters were defined to be significantly related to CHD by Lasso regression analysis, including age (OR 1.034, 95% CI 1.002 ~ 1.067, P = 0.040), hemoglobin A1c (OR 1.380, 95% CI 1.078 ~ 1.768, P = 0.011), ankle-brachial index (OR 0.078, 95% CI 0.012 ~ 0.522, P = 0.009), and brachial artery flow-mediated vasodilatation (OR 0.848, 95% CI 0.726 ~ 0.990, P = 0.037). The Hosmer-Lemeshow test showed a good calibration performance of the clinical prediction model (derivation set, χ2 = 7.865, P = 0.447; validation set, χ2 = 11.132, P = 0.194). The ROCs of the nomogram in the derivation set and validation set were 0.722 and 0.783, respectively, suggesting excellent predictive power and suitable performance. The clinical prediction model presented a greater net benefit and clinical impact based on DCA and CIC analysis. CONCLUSION: Overall, the development and validation of the multivariate model combined the laboratory and clinical parameters of patients with CHD, which could be beneficial to the individualized prediction of middle-aged and elderly people, and helped to facilitate clinical assessments and decisions during treatment and management of CHD.

Cardiometabolic index: A new predictor for metabolic associated fatty liver disease in Chinese adults.

Objective: Cardiometabolic index (CMI) is a well promising indicator for predicting obesity-related diseases, but its predictive value for metabolic associated fatty liver disease (MAFLD) is unclear. This study aimed to investigate the relationship between CMI and MAFLD and to evaluate the predictive value of CMI for MAFLD. Methods: A total of 943 subjects were enrolled in this cross-sectional study. CMI was calculated by multiplying the ratio of triglycerides and high-density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Multivariate logistic regression analysis was used to systematically evaluate the relationship between CMI and MAFLD. Receiver operating characteristic (ROC) curves were used to assess the predictive power of CMI for MAFLD and to determine the optimal cutoff value. The diagnostic performance of high CMI for MAFLD was validated in 131 subjects with magnetic resonance imaging diagnosis. Results: Subjects with higher CMI exhibited a significantly increased risk of MAFLD. The odds ratio for a 1-standard-deviation increase in CMI was 3.180 (2.102-4.809) after adjusting for various confounding factors. Further subgroup analysis showed that there were significant additive interactions between CMI and MAFLD risk in gender, age, and BMI (P for interaction < 0.05), and the area under the ROC curve(AUC) of CMI for predicting MAFLD were significantly higher in female, young, and nonobese subgroups than that in male, middle-aged and elderly, and obese subgroups (all P < 0.05). Moreover, among nonobese subjects, the AUC of CMI was significantly higher than that of waist circumference, BMI, TG/HDL-C, and TG (all P < 0.05). The best cutoff values of CMI to diagnose MAFLD in males and females were 0.6085 and 0.4319, respectively, and the accuracy, sensitivity, and specificity of high CMI for diagnosing MAFLD in the validation set were 85.5%, 87.5%, and 80%, respectively. Conclusions: CMI was strongly and positively associated with the risk of MAFLD and can be a reference predictor for MAFLD. High CMI had excellent diagnostic performance for MALFD, which can enable important clinical value for early identification and screening of MAFLD.

Knowledge domain and emerging trends in diabetic cardiomyopathy: A scientometric review based on CiteSpace analysis.

Objective: To review the literature related to diabetic cardiomyopathy (DCM), and investigate research hotspots and development trends of this field in the relevant studies based on CiteSpace software of text mining and visualization in scientific literature. Methods: The relevant literature from the last 20 years was retrieved from the Web of Science (WoS) Core Collection database. After manual selection, each document record includes title, authors, year, organization, abstract, keywords, citation, descriptors, and identifiers. We imported the downloaded data into CiteSpace V (version 5.8.R2) to draw the knowledge map and conduct cooperative network analysis, cluster analysis, burst keyword analysis, and co-citation analysis. Results: After manual screening, there were 3,547 relevant pieces of literature published in the last 18 years (from 2004 to 2021), including 2,935 articles and reviews, which contained 15,533 references, and the number was increasing year by year. The publications of DCM were dedicated by 778 authors of 512 institutions in 116 countries. The People's Republic of China dominated this field (1,117), followed by the USA (768) and Canada (176). In general, most articles were published with a focus on "oxidative stress," "heart failure," "diabetic cardiomyopathy," "dysfunction," "cardiomyopathy," "expression," "heart," "mechanism," and "insulin resistance." Then, 10 main clusters were generated with a modularity Q of 0.6442 and a weighted mean silhouette of 0.8325 by the log-likelihood ratio (LLR) algorithm, including #0 heart failure, #1 perfused heart, #2 metabolic disease, #3 protective effect, #4 diabetic patient, #5 cardiac fibrosis, #6 vascular complication, #7 mitochondrial dynamics, #8 sarcoplasmic reticulum, and #9 zinc supplementation. The top five references with the strongest citation bursts include "Boudina and Abel", "Jia et al.", "Fang et al.", "Poornima et al.", and "Aneja et al.". Conclusion: The global field of DCM has expanded in the last 20 years. The People's Republic of China contributes the most. However, there is little cooperation among authors and institutions. Overall, this bibliometric study identified the hotspots in DCM research, including "stress state," "energy metabolism," "autophagy," "apoptosis," "inflammation," "fibrosis," "PPAR," etc. Thus, further research focuses on these topics that may be more helpful to identify, prevent DCM and improve prophylaxis strategies to bring benefit to patients in the near future.

[Evaluation of diagnostic efficacy of artery elasticity and endothelial function indexes for coronary heart disease with blood stasis syndrome in postmenopausal women by Logistic regression combined with ROC curve model].

The present study explored the correlation of coronary heart disease(CHD) with blood stasis syndrome in postmenopausal women with artery elasticity and endothelial function indexes and evaluated the diagnostic efficacy of the prediction model via logistic regression and receiver operating characteristic(ROC) curve model. A retrospective comparison was made between 366 postmenopausal CHD patients from August 1, 2020, to September 30, 2021, in the Department of Cardiology of Integrated Traditional Chinese and Western Medicine of China-Japan Friendship Hospital, who were divided into the blood stasis syndrome group(n=196) and the non-blood stasis syndrome group(n=170). General clinical characteristics of the two groups were compared. Multivariate logistic regression analysis was used to probe the correlation of CHD with blood stasis syndrome in postmenopausal women with brachial-ankle pulse wave velocity(baPWV), ankle-brachial index(ABI), and flow-mediated dilatation(FMD), and the ROC curve was drawn to evaluate the diagnostic efficiency of the prediction model. Multivariate logistic regression analysis showed that the correlation coefficients of CHD with blood stasis syndrome in postmenopausal women with baPWV, ABI, and FMD were 1.123, 0.109, and 0.719, respectively(P=0.004, P=0.005, P<0.001),and the regression equation for predicting probability P was P=1/[1+e~(-(3.131+0.116×baPWV-2.217×ABI-0.330×FMD))]. ROC curve analysis suggested that in the context of baPWV≥19.19 m·s~(-1) or ABI≤1.22 or FMD≤9.7%, it was of great significance to predict the diagnosis of CHD with blood stasis syndrome in postmenopausal women. The AUC of baPWV, ABI, FMD, and prediction probability P was 0.763, 0.607, 0.705, and 0.836, respectively. The AUC of prediction probability P was higher than that of each index alone(P<0.001), and the sensitivity and specificity were 0.888 and 0.647, respectively. The results demonstrate that baPWV, ABI, and FMD are independently correlated with CHD with blood stasis syndrome in postmenopausal women, and show certain independent predictive abilities(P<0.05). The combined evaluation of the three possesses the best diagnostic efficiency.

Mechanism of SQQX Decoction's Protective Effect on SHR: A Serum Metabolomics-Based Analysis.

SangQiQingXuan (SQQX) decoction is a pharmaceutical preparation exerting good therapeutic efficacy on high blood pressure (BP) and has widely been accepted in primarily hypertensive patients as a herbal formula prescribed by Professor Li Huang from China-Japan Friendship Hospital according to her 30-year clinical experience. A previous study showed that SQQX could reduce BP by decreasing levels of many inflammatory factors such as transforming growth factor beta (TGFß) and elevating peroxisome proliferator activated receptor (PPAR) expression. However, a research focusing on SQQX's protection against HTN from a metabolomic perspective has never been done before. This study aimed to figure out the metabolic profiling variations due to oral administration of SQQX in spontaneous hypertensive rat (SHR) models and to find out the optimal dosage of SQQX. SHR in the intervention group orally received SQQX extract of three doses, namely, the low- (5.25 g/kg/d), middle- (10.5 g/kg/d), and high-dosage groups (21 g/kg/d) for 90 days. Rats were sacrificed at the end of the experiment, and their serum was collected for further examination. Serum metabolic profiling variations were analyzed using ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC/MS). Results showed that dealing with SQQX remarkably decreased systolic blood pressure (SBP) of SHRs and the high-dosage group was with the best therapeutic effect where a total of 11 metabolites were markedly changed in contrast to the model group. Orthogonal partial least square discriminant analysis (OPLS-DA) score plot showed that the 5 groups of serum samples were divided into 5 categories, and the metabolic trajectory of the high-dosage SQQX group was inclined to move to the control group. Glycochenodeoxycholic acid, nicotinamide-N-oxide, and tryptophan betaine might be biomarkers that specifically marked the protective effects of SQQX against high BP mainly involving in cholesterol metabolism, primary bile acid biosynthesis, bile secretion, and nicotinate and nicotinamide metabolism. To conclude, SQQX has a protective effect on SHR, which may be partially correlated to restoration of perturbed metabolism in serum.

The Effect of Chinese Herbal Medicine Combined With Western Medicine on Vascular Endothelial Function in Patients With Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Vascular endothelium plays a fundamental role in regulating endothelial dysfunction, resulting in structural changes that may lead to adverse outcomes of hypertension. The aim of this study was to systematically evaluate the effect of a combination of Chinese herbal medicine (CHM) and Western medicine on vascular endothelial function in patients with hypertension. METHODS: We systematically searched the literature for studies published in Chinese and English in PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China Knowledge Resource Integrated Database, Wanfang Data, and China Science and Technology Journal Database. Databases were searched using terms concerning or describing CHM, hypertension, vascular endothelium, and randomized controlled trials. RevMan 5.3.0 was used for data analysis. If the included studies were sufficiently homogeneous, quantitative synthesis was performed; if studies with different sample sizes and blind methods were used, subgroup analyses were performed. GRADEpro was selected to grade the current evidence to reduce bias in our findings. RESULTS: In this review, 30 studies with 3,235 patients were enrolled. A relatively high selection and a performance bias were noted by risk of bias assessments. Meta-analysis showed that the combination of CHM and conventional Western medicine was more efficient than conventional Western medicine alone in lowering blood pressure (risk ratio, 1.21; 95% CI, 1.16 to 1.26) and increasing nitric oxide (95% CI, 1.24 to 2.08; P < 0.00001), endothelin-1 (95% CI, -1.71 to -1.14; P < 0.00001), and flow-mediated dilation (95% CI, 0.98 to 1.31; P <0.00001). No significant difference was observed between the combination of CHM and conventional Western medicine and conventional Western medicine alone for major cardiovascular and cerebrovascular events. CHM qualified for the treatment of hypertension. The GRADEpro presented with low quality of evidence for the available data. CONCLUSION: CHM combined with conventional Western medicine may be effective in lowering blood pressure and improving vascular endothelial function in patients with hypertension. To further confirm this, more well-designed studies with large sample sizes, strict randomization, and clear descriptions about detection and reporting processes are warranted.

Effects of sang-qi granules on blood pressure and endothelial dysfunction in stage I or II hypertension: study protocol for a randomized double-blind double-simulation controlled trial.

BACKGROUND: Worldwide, hypertension is an important public health challenge because of its high prevalence and the concomitant risks of cardiovascular disease. It induces half of the coronary heart disease and approximately two-thirds of the cerebrovascular disease burden. Vascular endothelial dysfunction has important roles in the pathophysiology of essential hypertension. Types I and II hypertension can be treated with sang-qi granules (SQG), a Chinese herbal formula. Several experimental studies on animals have shown that SQG can lower blood pressure and myocardial fibrosis by suppressing inflammatory responses. However, no standard clinical trial has confirmed this. Whether SQG can improve endothelial cell function is unknown. METHODS/DESIGN: In this randomized double-blind double-simulation controlled trial, 300 patients with stage I or II hypertension will be recruited and randomly allocated in a 1:1:1 ratio to group A (treatment with SQG and placebo instead of Losartan), group B (treatment with Losartan and placebo instead of SQG), and group C (treatment with SQG and Losartan). In this study, 10 g of SQG (or its placebo) will be administrated twice a day and 50 mg of Losartan (or its placebo) will be administrated once in the morning. The primary endpoint is the drug efficiency for each of the three groups. The secondary endpoints are the change in average systolic and diastolic blood pressure during the day and the night, the change in the rate at which blood pressure drops at night, assessment of target organ damage (heart rate variability, ankle-brachial pressure index, and pulse wave velocity), assessment of any improvement in symptoms (Hypertension Symptom Scale, syndrome integral scale in traditional Chinese medicine, Pittsburgh Sleep Quality Index Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the 36-Item Short Form Health Survey), blood lipids, serum indicators of vascular function (changes in serum levels of ET-1, TXA2, NO, and PGI2), and safety indicators. DISCUSSION: This study aims to provide clinical evidence on the efficacy and safety of SQG in the treatment of hypertension. Moreover, the possible mechanism by which SQG may lower blood pressure will be explored by observing the protective effect of SQG on vascular endothelial function, as well as its effect on related clinical symptoms, risk factors, and the target organs of hypertension. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR1800016427. Registered on 1 June 2018.

Velvet Antler Mobilizes Endothelial Progenitor Cells to Promote Angiogenesis and Repair Vascular Endothelial Injury in Rats Following Myocardial Infarction.

Objective: This investigation examined the effect of velvet antler (VA) on endothelial progenitor cells (EPCs) and the associated effects to promote angiogenesis and repair vascular endothelial injury in rats with myocardial infarction (MI). Methods: VA was analyzed by liquid chromatography-mass spectrometry. Male Sprague Dawley rats were randomly divided into four groups: sham, MI, VA, and VA + DAPT (gamma-secretase inhibitor IX, a specific blocker of the Notch signaling pathway) group. The rats underwent ligation of the left anterior descending coronary artery for the establishment of MI. Sham-operated rats were used as controls. Blood was taken from the orbital plexus on the first and third days after the operation, and all rats were euthanized on the 7th day after surgery. The blood samples were used to detect the contents of circulating endothelial progenitor cells (CEPCs) and vascular endothelial growth factor (VEGF). Echocardiography was used to test the cardiac function. Cardiac tissue was used for immunohistochemistry and electron microscope, and the marginal zone of the MI tissue was used for western blot and reverse transcription-quantitative polymerase chain reaction. Results: The number of basically qualitative metabolites is 445. Among them, there are 74 substances with relative content greater than 0.05%. VA increased the concentration of CEPCs and VEGF in serum, CD133 content and microvessel density (MVD), and protected the morphology of microvascular endothelial cells in the marginal area of MI at 7 days post-MI surgery. CEPCs and MVD in the VA +DAPT group were lower than those of VA group. VA increased the protein expressions of Jagged-1, Notch1, NICD and HES1, and the mRNA expressions of Hes1 and Hey2, while some of the effects could be suppressed by DAPT. Conclusion: These results suggest that VA promotes the mobilization of EPCs to promote angiogenesis and repair vascular endothelial cell damage in post-MI rats, and these effects may be due to activation of the Notch signal pathway.