Objective To predict the mechanism of herbal couple Curcumae Rhizoma-Sparganii Rhizoma(CR-SR)in modulation of angiogenesis against lung cancer based on network pharmacology and molecular docking technology,and validate by zebrafish model.Methods The active ingredients and potential targets for anti-lung cancer and antiangiogenesis of CR and SR were screened by network pharmacology.The targets were intersected with those screened from the OMIM database and GeneCards database for lung cancer and antiangiogenesis.Herbal couple-lung cancer and herbal couple-antiangiogenesis of protein-protein interaction(PPI)network was constructed by taking intersecting targets to screen the common and core targets of the herbal couple in lung cancer and anti-angiogenesis.Herbal couple-lung cancer and herbal couple-antiangiogenesis of Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses were performed by Metascape database.The binding ability and the amino acid residues involved of core targets to major components were evaluated by molecular docking technique.In vitro,CCK-8 method was applied to investigate the effects of herbal couple and single drugs on the cell viability of human umbilical vein endothelial cells(HUVECs).Zebrafish embryos were randomly divided into blank control group,different concentration of drug pairs and single drug group,and positive drug control group,and the number of intersegmental vessels of zebrafish in each group was counted after 72 hour.The mRNA expression levels of angiogenesis-related genes,VEGFA,VEGFR2,VEGFR3,EGFR,etc.,were detected by qRT-PCR.Results 106 herbal couple-lung cancer common targets and 130 herbal couple-antiangiogenesis common targets were screened by network pharmacology.Meanwhile,85 of targets were identical.GO function enrichment analyses of herbal couple-lung cancer resulted in 1648 GO analysis entries,KEGG pathway enrichment analyses resulted in 186 signaling pathways.GO function enrichment analyses herbal couple-antiangiogenesis resulted in 1844 GO analysis entries,KEGG pathway enrichment analyses resulted in 188 signaling pathways.The molecular docking results showed a better affinity between the target and the components,and the forces between them mainly included hydrogen bonding and hydrophobic interactions.In vitro cellular experiments demonstrated that the two drugs were used as a drug pair to enhance the inhibitory effect on the cell viability of HUVECs.The zebrafish experiments indicated that the toxicity order of herbal couple and single drugs was CR>CR-SR>SR.The results of transgenic zebrafish vascular fluorescence model confirmed that CR-SR and single drugs had anti-angiogenic activity,with the anti-angiogenic activity order of herbal couple and single drugs was CR-SR>SR>CR.The results of qRT-PCR showed that CR-SR drug pairs and single drugs significantly reduced the expression levels of angiogenesis-related genes VEGFA,VEGFR2,EGFR,MMP9,etc.,and had anti-angiogenic effects.Conclusion CR-SR and single drugs had anti-lung cancer effects on multiple identical targets and regulated multiple identical signaling pathways,and their combination had a synergistic effect.The treatment of lung cancer may be through the regulation of angiogenesis-related target VEGFA,VEGFR2,EGFR,etc.,in order to play an anti-angiogenic effect.

Objective:To investigate the relationship between the early pregnancy triglyceride-glucose (TyG) index and gestational diabetes mellitus (GDM) in twin pregnancies.Methods:This retrospective study involved twin-pregnant women who visited Beijing Obstetrics and Gynecology Hospital, Capital Medical University from October 2015 to February 2021. Based on the results of the 75 g oral glucose tolerance test (OGTT) performed at 24-28 weeks of gestation, the women were divided into the GDM and the control groups. The groups were further stratified based on maternal age (<35 years or ≥35 years), pre-pregnancy body mass index (BMI) (<24.0 or ≥24.0 kg/m2), and conception method [assisted reproductive technology (ART) or natural conception]. The correlation between early pregnancy TyG index and GDM, as well as the predictive value of the early pregnancy TyG index for the risk of GDM in twin pregnancies, were analyzed. The TyG index in early pregnancy was then divided into tertiles, and the risks of GDM in low, medium, and high TyG index groups were analyzed. Statistical analyses were performed using independent sample t-test, non-parametric test, Chi-square test, and binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the early pregnancy TyG index for GDM in twin pregnancies. Results:(1) A total of 1 684 twin-pregnant women were included, with an average age of 32.3 years (29.8-34.9 years) and a pre-pregnancy BMI of 22.0 kg/m2 (20.0-24.3 kg/m2). Among them, 319 (18.9%) were multiparas, 982 (58.3%) conceived through ART, and 357 (21.2%) were monochorionic twins. Of the 1 684 women, 367 (21.8%) were diagnosed with GDM (GDM group), whereas the remaining 1 317 were classified as the control group. (2) Compared to the control group, the GDM group had older maternal age [(32.2±3.7) years vs. (33.3±3.8) years, t=－4.92], higher pre-pregnancy weight, and BMI [57.5 kg (52.0-65.0 kg) vs. 60.0 kg (55.0-67.3 kg), U=279 901.50; 21.8 kg/m2 (19.8-24.0 kg/m2) vs. 22.9 kg/m2 (20.9-25.5 kg/m2), U=288 435.00]. The proportions of a family history of diabetes, history of GDM and polycystic ovary syndrome (PCOS) were all higher in the GDM group compared to the control group [9.6% (127/1 317) vs. 19.1% (70/367), χ 2=24.71; 0.8% (2/1 317) vs. 10.8% (8/367), χ 2=20.00; 9.1% (120/1 317) vs. 15.3% (56/367), χ 2=11.59] (all P<0.001). The GDM group had higher early pregnancy fasting blood glucose, triglyceride, and TyG indices compared to the control group [4.51 mmol/L (4.28-4.75 mmol/L) vs. 4.68 mmol/L (4.42-4.97 mmol/L), U=7.14; 1.23 mmol/L (0.93-1.57 mmol/L) vs. 1.43 mmol/L (1.09-1.89 mmol/L), U=4.81; 8.39±0.41 vs. 8.59±0.43, t=6.46]. The incidence of gestational anemia and weight gain were lower in the GDM group compared to the control group [39.2% (516/1 317) vs. 33.0% (121/367), χ 2=4.71; 17.0 kg (13.7-20.5 kg) vs. 15.0 kg (12.0-18.3 kg), U=187 966.00] (all P<0.05). The proportion of male newborns in the GDM group was higher than in the control group [52.5% (1 384/2 634) vs. 46.7% (343/734), χ 2=7.77, P=0.005]. (3) Early pregnancy TyG index was associated with GDM in twin pregnancies ( OR=3.164, 95% CI: 2.371-4.220, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, history of macrosomia, and family history of diabetes, the early pregnancy TyG index remained associated with GDM ( OR=2.560, 95% CI: 1.884-3.478, P<0.001). Analysis of the early pregnancy TyG index divided into tertiles (corresponding TyG indices of 8.25 and 8.59) revealed that, compared to those with a low TyG index, those with a mid TyG index had a 0.555-fold increased risk of GDM ( OR=1.555, 95% CI: 1.119-2.159, P=0.008), and those with a high TyG index had a 1.564-fold increased risk of GDM ( OR=2.564, 95% CI: 1.836-3.530, P<0.001). Stratified analysis by age, BMI, and mode of conception showed that the early pregnancy TyG index was associated with GDM in twin pregnancies (all P<0.001). (4) The threshold value for the early pregnancy TyG index to predict GDM in twin pregnancies was 8.33, with an area under the curve (AUC) of 0.632, 95% CI: 0.600-0.665, sensitivity of 0.744, and specificity of 0.436. The AUC in twin pregnancies for those who conceived via ART was 0.635 (95% CI: 0.593-0.676, P<0.001), slightly higher than in those who conceived naturally (AUC=0.628, 95% CI: 0.576-0.681, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, and family history of diabetes, the AUC for the early pregnancy TyG index to predict GDM in twin pregnancies was 0.675 (95% CI: 0.644-0.707). For those who conceived via ART, the AUC (95% CI) was 0.675 (0.634-0.717), slightly lower than for those who conceived naturally [0.682 (0.632-0.733)] (all P<0.001). Conclusion:A high TyG index in the first trimester is a risk factor for GDM in twin pregnancies, but its predictive value for GDM in twin pregnancies needs further research to be confirmed.

Objective:To investigate the characteristics of weight gain in the mid and late pregnancy of women with early pregnancy weight loss, and the relationship between weight gain and weight gain rate before the diagnosis of gestational diabetes mellitus (GDM) and GDM.Methods:A retrospective study was conducted on 2 614 singleton pregnant women who underwent prenatal care and delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from January 2014 to December 2021, and whose weight decreased compared to pre-pregnancy weight by 16 weeks of gestation. The rate of weight gain in mid and late pregnancy, also weight gain and weight gain rate at each stage were analyzed. Multivariate logistic regression was used to analyze the impact of total weight gain and weight gain rate at each stage before the diagnosis of GDM on the risk of GDM.Results:The rates of weight gain in mid and late pregnancy for women with early pregnancy weight loss who were underweight, normal weight, overweight, and obese before pregnancy were (0.60±0.15), (0.59±0.18), (0.53±0.20), and (0.42±0.20) kg/week, respectively, all higher than the "Chinese Recommended Standards for Weight Gain During Pregnancy" [which are (0.37-0.56), (0.26-0.48), (0.22-0.37), and (0.15-0.30) kg/week, respectively]. The weight gain rates at each stage of mid and late pregnancy in women with early pregnancy weight loss showed a "bimodal" trend, with the first peak in weight gain rate occurring at 16-20 or 20-24 weeks of gestation [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.75 kg/week (0.44-1.00 kg/week), 0.74 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.39-0.86 kg/week), and 0.50 kg/week (0.25-0.74 kg/week), respectively] and the second peak occurring at 28-32 weeks [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.63 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.38- 0.88 kg/week), 0.60 kg/week (0.25-0.88 kg/week), and 0.50 kg/week (0.22-0.75 kg/week). As of 28 weeks and 36 weeks of gestation, 53.7% (1 404/2 614) and 77.4% (1 946/2 512) of pregnant women, respectively, reached the lower limit of the recommended weight gain for the corresponding gestational weeks. No association was found between insufficient weight gain ( aOR=0.828, 95% CI: 0.639-1.071, P=0.151) or excessive weight gain ( aOR=0.936, 95% CI: 0.598-1.465, P=0.773) before the diagnosis of GDM and the risk of GDM. However, obese women with a weight loss greater than 5% of their pre-pregnancy weight in early pregnancy and a rapid weight gain rate (> P 75) between 16-20 weeks of gestation had an increased risk of developing GDM ( aOR=32.870, 95% CI: 1.625-664.775, P=0.023). Conclusions:In clinical practice, dynamic monitoring of weight changes at various stages of pregnancy in women who lose weight in early pregnancy is recommended. Targeted weight management during mid-pregnancy for women who are obese before pregnancy and experience significant weight loss in early pregnancy may help prevent excessive gestational weight gain and decrease the risk of GDM.

Objective:To investigate the relationship between the early pregnancy triglyceride-glucose (TyG) index and gestational diabetes mellitus (GDM) in twin pregnancies.Methods:This retrospective study involved twin-pregnant women who visited Beijing Obstetrics and Gynecology Hospital, Capital Medical University from October 2015 to February 2021. Based on the results of the 75 g oral glucose tolerance test (OGTT) performed at 24-28 weeks of gestation, the women were divided into the GDM and the control groups. The groups were further stratified based on maternal age (<35 years or ≥35 years), pre-pregnancy body mass index (BMI) (<24.0 or ≥24.0 kg/m2), and conception method [assisted reproductive technology (ART) or natural conception]. The correlation between early pregnancy TyG index and GDM, as well as the predictive value of the early pregnancy TyG index for the risk of GDM in twin pregnancies, were analyzed. The TyG index in early pregnancy was then divided into tertiles, and the risks of GDM in low, medium, and high TyG index groups were analyzed. Statistical analyses were performed using independent sample t-test, non-parametric test, Chi-square test, and binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the early pregnancy TyG index for GDM in twin pregnancies. Results:(1) A total of 1 684 twin-pregnant women were included, with an average age of 32.3 years (29.8-34.9 years) and a pre-pregnancy BMI of 22.0 kg/m2 (20.0-24.3 kg/m2). Among them, 319 (18.9%) were multiparas, 982 (58.3%) conceived through ART, and 357 (21.2%) were monochorionic twins. Of the 1 684 women, 367 (21.8%) were diagnosed with GDM (GDM group), whereas the remaining 1 317 were classified as the control group. (2) Compared to the control group, the GDM group had older maternal age [(32.2±3.7) years vs. (33.3±3.8) years, t=－4.92], higher pre-pregnancy weight, and BMI [57.5 kg (52.0-65.0 kg) vs. 60.0 kg (55.0-67.3 kg), U=279 901.50; 21.8 kg/m2 (19.8-24.0 kg/m2) vs. 22.9 kg/m2 (20.9-25.5 kg/m2), U=288 435.00]. The proportions of a family history of diabetes, history of GDM and polycystic ovary syndrome (PCOS) were all higher in the GDM group compared to the control group [9.6% (127/1 317) vs. 19.1% (70/367), χ 2=24.71; 0.8% (2/1 317) vs. 10.8% (8/367), χ 2=20.00; 9.1% (120/1 317) vs. 15.3% (56/367), χ 2=11.59] (all P<0.001). The GDM group had higher early pregnancy fasting blood glucose, triglyceride, and TyG indices compared to the control group [4.51 mmol/L (4.28-4.75 mmol/L) vs. 4.68 mmol/L (4.42-4.97 mmol/L), U=7.14; 1.23 mmol/L (0.93-1.57 mmol/L) vs. 1.43 mmol/L (1.09-1.89 mmol/L), U=4.81; 8.39±0.41 vs. 8.59±0.43, t=6.46]. The incidence of gestational anemia and weight gain were lower in the GDM group compared to the control group [39.2% (516/1 317) vs. 33.0% (121/367), χ 2=4.71; 17.0 kg (13.7-20.5 kg) vs. 15.0 kg (12.0-18.3 kg), U=187 966.00] (all P<0.05). The proportion of male newborns in the GDM group was higher than in the control group [52.5% (1 384/2 634) vs. 46.7% (343/734), χ 2=7.77, P=0.005]. (3) Early pregnancy TyG index was associated with GDM in twin pregnancies ( OR=3.164, 95% CI: 2.371-4.220, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, history of macrosomia, and family history of diabetes, the early pregnancy TyG index remained associated with GDM ( OR=2.560, 95% CI: 1.884-3.478, P<0.001). Analysis of the early pregnancy TyG index divided into tertiles (corresponding TyG indices of 8.25 and 8.59) revealed that, compared to those with a low TyG index, those with a mid TyG index had a 0.555-fold increased risk of GDM ( OR=1.555, 95% CI: 1.119-2.159, P=0.008), and those with a high TyG index had a 1.564-fold increased risk of GDM ( OR=2.564, 95% CI: 1.836-3.530, P<0.001). Stratified analysis by age, BMI, and mode of conception showed that the early pregnancy TyG index was associated with GDM in twin pregnancies (all P<0.001). (4) The threshold value for the early pregnancy TyG index to predict GDM in twin pregnancies was 8.33, with an area under the curve (AUC) of 0.632, 95% CI: 0.600-0.665, sensitivity of 0.744, and specificity of 0.436. The AUC in twin pregnancies for those who conceived via ART was 0.635 (95% CI: 0.593-0.676, P<0.001), slightly higher than in those who conceived naturally (AUC=0.628, 95% CI: 0.576-0.681, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, and family history of diabetes, the AUC for the early pregnancy TyG index to predict GDM in twin pregnancies was 0.675 (95% CI: 0.644-0.707). For those who conceived via ART, the AUC (95% CI) was 0.675 (0.634-0.717), slightly lower than for those who conceived naturally [0.682 (0.632-0.733)] (all P<0.001). Conclusion:A high TyG index in the first trimester is a risk factor for GDM in twin pregnancies, but its predictive value for GDM in twin pregnancies needs further research to be confirmed.

Objective:To investigate the characteristics of weight gain in the mid and late pregnancy of women with early pregnancy weight loss, and the relationship between weight gain and weight gain rate before the diagnosis of gestational diabetes mellitus (GDM) and GDM.Methods:A retrospective study was conducted on 2 614 singleton pregnant women who underwent prenatal care and delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from January 2014 to December 2021, and whose weight decreased compared to pre-pregnancy weight by 16 weeks of gestation. The rate of weight gain in mid and late pregnancy, also weight gain and weight gain rate at each stage were analyzed. Multivariate logistic regression was used to analyze the impact of total weight gain and weight gain rate at each stage before the diagnosis of GDM on the risk of GDM.Results:The rates of weight gain in mid and late pregnancy for women with early pregnancy weight loss who were underweight, normal weight, overweight, and obese before pregnancy were (0.60±0.15), (0.59±0.18), (0.53±0.20), and (0.42±0.20) kg/week, respectively, all higher than the "Chinese Recommended Standards for Weight Gain During Pregnancy" [which are (0.37-0.56), (0.26-0.48), (0.22-0.37), and (0.15-0.30) kg/week, respectively]. The weight gain rates at each stage of mid and late pregnancy in women with early pregnancy weight loss showed a "bimodal" trend, with the first peak in weight gain rate occurring at 16-20 or 20-24 weeks of gestation [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.75 kg/week (0.44-1.00 kg/week), 0.74 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.39-0.86 kg/week), and 0.50 kg/week (0.25-0.74 kg/week), respectively] and the second peak occurring at 28-32 weeks [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.63 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.38- 0.88 kg/week), 0.60 kg/week (0.25-0.88 kg/week), and 0.50 kg/week (0.22-0.75 kg/week). As of 28 weeks and 36 weeks of gestation, 53.7% (1 404/2 614) and 77.4% (1 946/2 512) of pregnant women, respectively, reached the lower limit of the recommended weight gain for the corresponding gestational weeks. No association was found between insufficient weight gain ( aOR=0.828, 95% CI: 0.639-1.071, P=0.151) or excessive weight gain ( aOR=0.936, 95% CI: 0.598-1.465, P=0.773) before the diagnosis of GDM and the risk of GDM. However, obese women with a weight loss greater than 5% of their pre-pregnancy weight in early pregnancy and a rapid weight gain rate (> P 75) between 16-20 weeks of gestation had an increased risk of developing GDM ( aOR=32.870, 95% CI: 1.625-664.775, P=0.023). Conclusions:In clinical practice, dynamic monitoring of weight changes at various stages of pregnancy in women who lose weight in early pregnancy is recommended. Targeted weight management during mid-pregnancy for women who are obese before pregnancy and experience significant weight loss in early pregnancy may help prevent excessive gestational weight gain and decrease the risk of GDM.

Objective To predict the mechanism of herbal couple Curcumae Rhizoma-Sparganii Rhizoma(CR-SR)in modulation of angiogenesis against lung cancer based on network pharmacology and molecular docking technology,and validate by zebrafish model.Methods The active ingredients and potential targets for anti-lung cancer and antiangiogenesis of CR and SR were screened by network pharmacology.The targets were intersected with those screened from the OMIM database and GeneCards database for lung cancer and antiangiogenesis.Herbal couple-lung cancer and herbal couple-antiangiogenesis of protein-protein interaction(PPI)network was constructed by taking intersecting targets to screen the common and core targets of the herbal couple in lung cancer and anti-angiogenesis.Herbal couple-lung cancer and herbal couple-antiangiogenesis of Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses were performed by Metascape database.The binding ability and the amino acid residues involved of core targets to major components were evaluated by molecular docking technique.In vitro,CCK-8 method was applied to investigate the effects of herbal couple and single drugs on the cell viability of human umbilical vein endothelial cells(HUVECs).Zebrafish embryos were randomly divided into blank control group,different concentration of drug pairs and single drug group,and positive drug control group,and the number of intersegmental vessels of zebrafish in each group was counted after 72 hour.The mRNA expression levels of angiogenesis-related genes,VEGFA,VEGFR2,VEGFR3,EGFR,etc.,were detected by qRT-PCR.Results 106 herbal couple-lung cancer common targets and 130 herbal couple-antiangiogenesis common targets were screened by network pharmacology.Meanwhile,85 of targets were identical.GO function enrichment analyses of herbal couple-lung cancer resulted in 1648 GO analysis entries,KEGG pathway enrichment analyses resulted in 186 signaling pathways.GO function enrichment analyses herbal couple-antiangiogenesis resulted in 1844 GO analysis entries,KEGG pathway enrichment analyses resulted in 188 signaling pathways.The molecular docking results showed a better affinity between the target and the components,and the forces between them mainly included hydrogen bonding and hydrophobic interactions.In vitro cellular experiments demonstrated that the two drugs were used as a drug pair to enhance the inhibitory effect on the cell viability of HUVECs.The zebrafish experiments indicated that the toxicity order of herbal couple and single drugs was CR>CR-SR>SR.The results of transgenic zebrafish vascular fluorescence model confirmed that CR-SR and single drugs had anti-angiogenic activity,with the anti-angiogenic activity order of herbal couple and single drugs was CR-SR>SR>CR.The results of qRT-PCR showed that CR-SR drug pairs and single drugs significantly reduced the expression levels of angiogenesis-related genes VEGFA,VEGFR2,EGFR,MMP9,etc.,and had anti-angiogenic effects.Conclusion CR-SR and single drugs had anti-lung cancer effects on multiple identical targets and regulated multiple identical signaling pathways,and their combination had a synergistic effect.The treatment of lung cancer may be through the regulation of angiogenesis-related target VEGFA,VEGFR2,EGFR,etc.,in order to play an anti-angiogenic effect.

Objective:To observe any effects of repetitive high-frequency transcranial magnetic stimulation (rTMS) on the upper limb motor function of stroke survivors with right hemiplegia.Methods:Forty stroke survivors with right hemiplegia were divided at random into a high-frequency rTMS group and a sham stimulation group, each of 20. In addition to routine rehabilitation, the high-frequency rTMS group was given daily high-frequency rTMS 5d per week for 2 weeks, while the sham stimulation group was provided with sham rTMS. Before and after the treatment, both groups were evaluated using the Fugl-Meyer Upper Extremity motor function evaluation scale (FMA-UE), surface electromyography (sEMG), and electroencephalographic microstatus testing. Any adverse reactions in the course of the treatment were recorded.Results:After the treatment, the average FMA-UE scores of both groups had improved significantly, with the average of the high-frequency rTMS group significantly higher than the other group′s average. After the treatment the peak-to-peak sEMG value of the radial long extensor carpi radialis longus muscle in the high-frequency rTMS group was significantly higher than before the treatment and significantly higher than that of the other group. The temporal coverage of microstate B, the average duration and temporal coverage of microstate C, and the temporal coverage and frequency of occurrence of microstate D after treatment of both groups were also significantly improved. The mean duration of electroencephalographic (EEG) microstate A was negatively correlated with the FMA-UE scale scores ( r=-0.57) and its temporal coverage was positively correlated with the peak-to-peak sEMG value of the ulnar lateral wrist flexor. The mean duration of EEG microstate B was positively correlated with the peak-to-peak sEMG value of the triceps brachii and deltoid, and the mean duration of EEG microstate C was also positively correlated with the peak-to-peak sEMG value of the deltoid muscle. Conclusions:High-frequency rTMS can effectively improve the upper limb motor functioning of stroke survivors with right hemiparesis. After high-frequency rTMS, the functional network activity related to EEG microstate B increases significantly, while that related to microstates C and D decreases significantly.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.

Objective:To explore the effect of Bushen Huoxue Decoction on ventricular remodeling and myocardial nuclear factor-kappaB (NF-κB) protein in rats with chronic heart failure.Methods:60 male SD rats were randomly divided into sham operation group (15 rats) and experimental group (45 rats). The rats of the experimental group was established CHF model by ligating the left anterior descending coronary artery combined with exhaustive swimming and starvation. Rats with chronic heart failure were randomly divided into model group, Bushen Huoxue group and lisinopril group.The Bushen Huoxue group was perfused with 15.75 g/(kg·d) Bushen Huoxue Decoction, the lisinopril group was perfused with 1.8 mg/(kg·d) of lisinopril suspension, and the sham operation group and model group were perfused with equal volume of distilled water. After 4 weeks of administration, the general mental state of rats was observed. The left ventricular internal systolic diameter (LVIDs) and internal diastolic diameter (LVIDd) were measured by cardiac color Doppler ultrasound, and the left ventricular ejection fraction (LVEF) and short axis shortening fraction (LVFS) were calculated. The expression of NF-κB protein in rat myocardium was detected by Western blot, and the morphology of left ventricular myocytes was observed by hematoxylin eosin staining.Results:Compared with the model group, the myocardial fibers of rats in Bushen Huoxue group and lisinopril group were arranged orderly, with few pyknosis, a small amount of inflammatory cell infiltration. Compared with the model group, the levels of LVIDs [(6.00±0.58)mm vs. (6.99±0.90)mm] and LVIDd [(3.96±0.51)mm vs. (5.14±0.57)mm] significantly decreased, LVEF [(54.48±6.75)% vs. (30.28±4.85)%] and LVFS [(33.86±4.27)% vs. (26.10±4.96)%] significantly increased, as well as the expression of myocardial NF-κB (1.06±0.10 vs. 1.58±0.29) protein significantly decreased ( P<0.05). Conclusion:Bushen Huoxue Decoction can resist ventricular remodeling,improve cardiac function and treat heart failure of CHF rats and the possible mechanism might be it could down-regulate myocardial NF-κB expression.