Effect of cytochrome P450 2C19 (CYP2C19) gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI.

Objective: To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with long-term clinical outcome in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). Methods: In total, 675 patients were enrolled. Based on the platelet inhibition rate, patients were categorized into two groups: clopidogrel low responsiveness (CLR) and normal clopidogrel responsiveness (NCR). The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment. Patients were classified into three groups (normal metabolizer, intermediate metabolizer, and poor metabolizer) based on the CYP2C19 genotype. We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity. The cumulative rates of 12-month all-cause deaths, major adverse cardiovascular events (MACCEs), and bleeding events were calculated. Results: CLR was observed in 44.4% of the overall population. Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes (P < 0.05). At the 12-month follow-up, 13 patients (1.9%) died and 96 patients (14.2%) experienced MACCEs. Patients with CLR (9.6% vs. 11.7% vs. 22.1%, P < 0.05) or poor metabolizer (10.7% vs. 16.4% vs. 22.6%, P = 0.026) experienced a higher rate of MACCEs. A MACCEs risk score between zero and two was calculated. The highest incidence of MACCEs significantly increased with the 2-positive results, and the area under the curve (AUC) was 0.712 (95% CI: 0.650-0.774, P < 0.05). There was no significant difference between the group with a score of one and the occurrence of MACCEs (P > 0.05). Conclusions: Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism. CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI, which is better than either test alone.

Bckdk-Mediated Branch Chain Amino Acid Metabolism Reprogramming Contributes to Muscle Atrophy during Cancer Cachexia.

SCOPE: Branched chain amino acids (BCAAs) are essential amino acids and important nutrient signals for energy and protein supplementation. The study uses muscle-specific branched-chain α-keto acid dehydrogenase kinase (Bckdk) conditional knockout (cKO) mice to reveal the contribution of BCAA metabolic dysfunction to muscle wasting. METHOD AND RESULTS: Muscle-specific Bckdk-cKO mice are generated through crossbreeding of Bckdkf/f mice with Myf5Cre mice. Lewis lung cancer (LLC) tumor transplantation is used to establish the cancer cachexia model. The occurrence of cancer cachexia is accelerated in the muscle-specific Bckdk-cKO mice after bearing LLC tumor. Wasting skeletal muscle is characterized by increased protein ubiquitination degradation and impaired protein synthesis. The wasting muscle gastrocnemius is mechanized as a distinct BCAA metabolic dysfunction. Based on the atrophy phenotype resulting from BCAA metabolism dysfunction, the optimized BCAA supplementation improves the survival of cancer cachexia in muscle-specific Bckdk-cKO mice bearing LLC tumors, and improves the occurrence of cancer cachexia. The mechanism of BCAA supplementation on muscle mass preservation is based on the promotion of protein synthesis and the inhibition of protein ubiquitination degradation. CONCLUSIONS: Dysfunctional BCAA metabolism contributes to the inhibition of protein synthesis and increases protein degradation in the cancer cachexia model of muscle-specific Bckdk-cKO mice bearing LLC tumors. The reprogramming of BCAA catabolism exerts therapeutic effects by stimulating protein synthesis and inhibiting protein degradation in skeletal muscle.

Effects of warming and drought on growth and development of soybean in Hailun region.

As a result of global warming, drought, flooding, change in the rainfall pattern, etc. occur frequently. All these natural disasters could cause serious damage to the food security. Soybean is one of the most important oil crops in China. In recent years, the changing climate has brought many uncertain risks to the growth and production of soybean. In this study, based on the local meteorological, soil, and soybean growth-related experimental data, the effects of high temperature and drought stress on soybean were tested. The test parameters were leaf area index (LAI) and dry matter weight, while the analytical tool used was World Food Studies Model crop model. The research was carried out in Hailun City, Heilongjiang Province, China. The results showed that warming stress shortened the growth period of soybean and reduced the LAI and dry matter accumulation. On the other hand, drought stress also showed a significant impact on the growth period as well as reduced LAI and dry matter accumulation. Comparing the whole growth as well as the flowering-stage to seed-filling-stage treatments of soybean, the results were found very similar. It indicated that the soybean growth from flowering to seed-filling stage was strongly affected by the external environmental factors. The high temperature and drought disasters in the fruiting stages would have a greater impact on the growth and production of soybean crop.

Oncometabolite D-2-hydroxyglutarate-dependent metabolic reprogramming induces skeletal muscle atrophy during cancer cachexia.

Cancer cachexia is characterized by weight loss and skeletal muscle wasting. Based on the up-regulation of catabolism and down-regulation of anabolism, here we showed genetic mutation-mediated metabolic reprogramming in the progression of cancer cachexia by screening for metabolites and investigating their direct effect on muscle atrophy. Treatment with 93 µM D-2-hydroxyglutarate (D2HG) resulted in reduced myotube width and increased expression of E3 ubiquitin ligases. Isocitrate Dehydrogenase 1 (IDH1) mutant patients had higher D2HG than non-mutant patients. In the in vivo murine cancer cachexia model, mutant IDH1 in CT26 cancer cells accelerated cachexia progression and worsened overall survival. Transcriptomics and metabolomics revealed a distinct D2HG-induced metabolic imbalance. Treatment with the IDH1 inhibitor ivosidenib delayed the progression of cancer cachexia in murine GL261 glioma model and CT26 colorectal carcinoma models. These data demonstrate the contribution of IDH1 mutation mediated D2HG accumulation to the progression of cancer cachexia and highlight the individualized treatment of IDH1 mutation associated cancer cachexia.

The incidence of subclinical atherosclerosis in subjects with low and moderate cardiovascular risk.

BACKGROUND: The cardiovascular risk models and subclinical atherosclerotic indicators are both recommended for cardiovascular risk stratification. The accordance between the incidence of subclinical atherosclerosis and subjects with low and moderate cardiovascular risk is unclear. HYPOTHESIS: Subjects with low and moderate cardiovascular risk have a lower incidence of subclinical atherosclerosis compared with subjects with high risk. METHODS: Brachial-ankle pulse wave velocity (BaPWV) and brachial flow-mediated dilation (BFMD) were measured in 421 subjects without a history of atherosclerotic cardiovascular disease (ASCVD) from October 2016 to January 2020. All subjects were classified into low, moderate, and high risk based on Framingham and China-par risk models respectively. RESULTS: Mean age was 57.05 ± 9.35 years and 248 (58.9%) were male. In subjects with low, moderate, and high risk assessed by Framingham and China-par risk models, the percentage of abnormal BaPWV ( > 1400 cm/s) was 42.9%, 70.1%, 85.7%, and 40.4%, 71.4%, 89.7%, respectively. Meanwhile, the percentage of abnormal BFMD ( ≤ 7%) was 43.8%, 68.5%, 77.3%, and 44.9%,72.1%, and 76.6%. According to Framingham-based high-risk categories, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for BaPWV abnormality were 85.7%, 39.4%, 36.1%, and 87.5%, respectively. For BFMD abnormality, the values were 77.3%, 40.1%, 34.1%, and 81.8%, respectively. According to China-par high-risk categories, the values for BaPWV abnormality were 89.7%, 43.8%, 45.6%, and 89.0%, respectively. For BFMD abnormality, the values were 76.6%, 41.3%, 40.7%, and 77%, respectively. In multivariate analysis, age and blood pressure were the independent predictors for subclinical atherosclerosis in subjects with low-moderate risk. CONCLUSIONS: More than one-half of subjects with low and moderate risk already have detectable subclinical atherosclerosis, indicating higher cardiovascular risk beyond the traditional stratification.

Cucurbitacin IIb attenuates cancer cachexia induced skeletal muscle atrophy by regulating the IL-6/STAT3/FoxO signaling pathway.

The main features of cancer cachexia include skeletal muscle atrophy, which can significantly reduce the quality of life of patients. Clinical treatment of cancer cachexia is mainly based on nutritional therapy and physical exercise; medication only improves appetite but does not reverse the symptoms of skeletal muscle wasting. In this work, we systematically studied the underlying molecular mechanisms by which cucurbitacin IIb (CuIIb) ameliorates muscle wasting in cancer cachexia both in vitro and in vivo. CuIIb significantly ameliorated the chief features of cancer cachexia in vivo, alleviating weight loss, food intake, muscle wasting, adipose tissue depletion, and organ weight reductions. In vitro, CuIIb (10 and 20 µM) dose-dependently attenuated conditioned medium (CM)-induced C2C12 myotube atrophy. Collectively, our findings demonstrated that CuIIb prevented the upregulation of the E3 ubiquitin ligase muscle atrophy Fbox protein (MAFbx), myosin heavy chain (MyHC), and myogenin (MyoG) and impacted protein synthesis and degradation. In addition, CuIIb decreased the phosphorylation of Tyr705 in STAT3 by regulating the IL-6/STAT3/FoxO pathway to reduce skeletal muscle atrophy in cancer cachexia.

Association of vascular endothelial function and quality of life in patients with ischemia and non-obstructive coronary artery disease.

Improvements are required in the quality of life (QoL) of patients with ischemia and non-obstructive coronary artery disease (INOCA). Several patients with INOCA experience vascular endothelial dysfunction. However, the relationship between endothelial function and QoL remains unelucidated. This study aimed to initially investigate the relationship between endothelial function and QoL in patients with INOCA. This prospective observational study included 121 patients with INOCA (aged 31-85 years). Vascular endothelial function was assessed by flow-mediated dilatation (FMD) of the peripheral brachial artery. QoL was evaluated using the 36-Item Short-Form Health Survey (SF-36). Patients with INOCA were divided into two groups according to the median FMD change during the 1-year follow-up (group A, ≥ median FMD change cut-off; group B, < median FMD change cut-off). The median change in FMD was 0.92%. The mean baseline SF-36 scores were comparable between the two groups (53.95 ± 6.46 vs. 53.92 ± 4.29, p = 0.98). The QoL at follow-up was better in group A than in group B (56.61 ± 5.50 vs. 53.32 ± 5.58, p = 0.002). The change in FMD (r = 0.34, p < 0.01), rather than FMD at baseline (r = - 0.01, p = 0.89) or follow-up (r = 0.13, p = 0.15), was related to the follow-up SF-36 scores. FMD improvement was an independent predictor of increased QoL (odds ratio, 3.90; 95% confidence interval: 1.59-9.53, p = 0.003). Endothelial function change is associated with QoL, and patients with improved endothelial function have a better QoL than those without.

Scutellarin Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Myocardial Fibrosis, Apoptosis and Autophagy in Rats.

The anthracycline antibiotic doxorubicin (DOX) is an effective anticancer agent, but its clinical use is limited by dose-dependent cardiotoxicity. Scutellarin (SCU), a natural polyphenolic flavonoid, is used as a cardioprotective agent for infarction and ischemia-reperfusion injury. This study investigated the beneficial effect of SCU on DOX-induced chronic cardiotoxicity. Rats were injected intraperitoneally (i. p.) with DOX (2.5 mg/kg) twice a week for four weeks and then allowed to rest for two weeks to establish the chronic cardiotoxicity animal model. A dose of 10 mg/kg/day SCU was injected i. p. daily for six weeks to attenuate cardiotoxicity. SCU attenuated DOX-induced elevated oxidative stress levels and cardiac troponin T (cTnT), decreased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), elevated isovolumic relaxation time (IVRT), electrophysiology and histopathological alterations. In addition, SCU significantly attenuated DOX-induced cardiac fibrosis and reduced extracellular matrix (ECM) accumulation by inhibiting the TGF-ß1/Smad2 signaling pathway. Furthermore, SCU also prevented against DOX-induced apoptosis and autophagy as evidenced by upregulation of Bcl-2, downregulation of Bax and cleaved caspase-3, inhibited the AMPK/mTOR pathway. These results revealed that the cardioprotective effect of SCU on DOX-induced chronic cardiotoxicity may be attributed to reducing oxidative stress, myocardial fibrosis, apoptosis and autophagy.

Predictive value of hemoglobin-to-red blood cell distribution width ratio for contrast-induced nephropathy after emergency percutaneous coronary intervention.

BACKGROUND: Although the relationship of either hemoglobin or red blood cell distribution width (RDW) with contrast-induced nephropathy (CIN) has been reported individually. To date, no studies have evaluated the predictive value of hemoglobin-to-red blood cell distribution width ratio (HRR) for CIN. METHODS: A total of 1658 elderly patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI) were retrospectively screened. Preoperative complete blood count was collected and the HRR was calculated as the ratio of hemoglobin to RDW. CIN was defined as an absolute ≥0.5 mg/dL (44.2 µmol/L) or a relative ≥25% increase in creatinine level at 72 h after contrast administration. Univariate and multivariate regression analysis were conducted to determine the effective predictors for CIN. The ROC curve analysis was plotted to determine the optimal cutoff value for HRR in predicting CIN. RESULTS: The overall incidence of CIN was 8.38%. The HRR was significantly lower in the CIN group compared with the non-CIN group (0.87 ± 0.15 vs 1.24 ± 0.23, p < 0.001). After multivariate regression analysis was performed, HRR was noted to be an effective predictor for the development of CIN (OR 1.617, 95% CI 1.439-2.706, p = 0.014), along with age, creatinine, eGFR, hs-CRP and contrast volume. An optimal cutoff value of 0.94 or lower for HRR was identified with 82.4% sensitivity and 63.5% specificity to predict CIN. CONCLUSION: Lower HRR on admission was an effective predictor for CIN in elderly patients with STEMI undergoing emergency PCI. HRR may be a convenient, economical and reliable biomarker for risk stratification.

Red blood cell distribution width-to-albumin ratio: a new inflammatory biomarker to predict contrast-induced nephropathy after emergency percutaneous coronary intervention.

PURPOSE: Contrast-induced nephropathy (CIN) remains a dreaded complication in the cardiac diagnostic and interventional area. We investigated the relationship between red blood cell distribution width-to-albumin ratio (RAR) and CIN in elderly patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI). METHODS: A total of 1532 elderly patients were enrolled and divided into the CIN group and the non-CIN group. The risk factors of CIN were evaluated by univariate and multivariate regression analysis. Receiver-operating characteristic (ROC) curve analysis was used to identify the best predictive value. RESULTS: CIN occurred in 129 (8.42%) patients. Patients in the CIN group had significantly higher RAR than those in the non-CIN group (4.69 ± 0.73 vs. 3.18 ± 0.64, P < 0.001). In multivariate regression analysis, RAR was an independent risk factor for the development of CIN (OR: 1.506, 95% CI: 1.227-2.083, P = 0.025), along with age, creatinine, eGFR, hs-CRP and contrast agent dose. The AUC of RAR was 0.755 (95% CI 0.703-0.807), and an optimal cutoff value of 3.64 or higher predicted CIN with a sensitivity of 76.2% and specificity of 65.7%. CONCLUSION: As a combined inflammatory-related index, RAR was an independent risk factor for the development of CIN in elderly patients with STEMI undergoing emergency PCI. The RAR could be a simple but relatively reliable parameter for identifying high-risk patients.

Tongmai Yangxin Pill combined with metoprolol or metoprolol alone for the treatment of symptomatic premature ventricular complex: a multicenter, randomized, parallel-controlled clinical study.

OBJECTIVE: To investigate the effects of Tongmai Yangxin Pill (TMYXP) combined with metoprolol tartrate or metoprolol alone for the treatment of premature ventricular complex (PVC) in patients with symptomatic frequent PVC. METHODS: A total of 584 patients with symptomatic frequent PVC were randomly assigned (in a 1:1 ratio) into two groups: study group [n = 292, TMYXP (40 pills twice/day, orally) combined with metoprolol tartrate (25 mg twice/day, orally)] and control group [n = 292, metoprolol tartrate (25 mg twice/day, orally) plus placebo pill (40 pills twice/day, orally)]. The total treatment period was eight weeks. RESULTS: After eight weeks of treatment, the total effective rate of reduction of PVC in the study group and the control group were 76.4% and 51.4%, respectively (P < 0.001). TMYXP combined with metoprolol tartrate demonstrated a significantly greater reduction of the frequency of PVCs compared with the metoprolol tartrate alone (-4537 times/24 h vs. -3013 times/24 h, P < 0.001). The study group also showed a better result compared with the control group with respect to PVC related symptoms. In terms of New York Heart Association classification improvement, the total effective rates were 21.9% in the study group and 12.4% in the control group ( P < 0.05). Both the study group and the control group exhibited improvements in echocardiographic indexes. Left ventricular ejection fraction was significantly improved in the study group compared with the control group ( P < 0.05). There was no significant difference in the incidence of adverse events between the two groups. CONCLUSIONS: Compared with metoprolol tartrate alone, TMYXP combined with metoprolol tartrate could more effectively reduce the frequency of PVC and alleviated PVC related symptoms, and improve cardiac function in patients with symptomatic PVC.

Scutellarin attenuates doxorubicin-induced oxidative stress, DNA damage, mitochondrial dysfunction, apoptosis and autophagy in H9c2 cells, cardiac fibroblasts and HUVECs.

Studies on doxorubicin (DOX)-induced cardiotoxicity have mainly focused on cardiomyocytes (CMs), but it is unclear whether there are differences in the toxicity degree of DOX to CMs, cardiac fibroblasts (CFs) and endothelial cells (ECs). We used H9c2 cells, rat primary isolated CFs and human umbilical vein endothelial cells (HUVECs) to systematically research the cytotoxicity of DOX. Scutellarin (SCU) is a natural polyphenolic flavonoid that exerts a cardioprotective effect. In the present study, we explored the protective effects of SCU on DOX-induced cytotoxicity in H9c2 cells, CFs and HUVECs. The results showed that DOX decreased cell viability and increased the apoptosis rate, whereas DOX had a greater killing effect on H9c2 cells compared to CFs and HUVECs. DOX significantly elevated oxidative stress, but the malondialdehyde (MDA) levels in H9c2 cells were higher after DOX treatment. In all three cell types, DOX induced DNA damage and mitochondrial dysfunction, it activated apoptosis by activation of Bax/ Bcl-2 and it induced autophagy by inhibiting the Akt/ mTOR pathway. Pretreatment with different concentrations of SCU reversed these phenomena in a dose-dependent manner. Collectively, these results revealed that there were slight differences in DOX-induced cytotoxicity among H9c2 cells, CFs and HUVECs. Furthermore, the cardioprotective effect of SCU may be attributed to attenuation of DOX-induced oxidative stress, DNA damage, mitochondrial dysfunction, apoptosis and autophagy.

Superior antitumor immunotherapy efficacy of kynureninase modified CAR-T cells through targeting kynurenine metabolism.

Accumulated oncometabolites in the tumor microenvironment (TME) suppresses the metabolism, expansion, and function of T cells. Immunosuppressive TME also impeded Chimeric Antigen Receptor (CAR)-T cells mediated cytotoxicity since CAR-T cells had to adapt the in vivo metabolic characteristics with high levels of oncometabolites. We screened oncometabolites for the inhibition of glucose uptake in CD8 + T cells and found Kynurenine (Kyn) showed the strongest inhibiting effect on glucose uptake. In vitro experiments showed that 120 µM Kyn treatment in CD8 + T cells resulted in inhibiting the expansion of CD8 + T cells, decreasing the production of granzyme B and interferon-γ. CAR-T cells mediated cytotoxicity was also impaired by the high Kyn treatment from killing assay. We then explored the anti-tumor effect of Kynureninase (KYNU) modified CAR-T cells through catabolism o oncometabolites Kyn. KYNU over-expression (OE) CAR-T cells showed a superior killing effect against cancer cells even in the immunosuppressive TME with high Kyn levels. In vivo experiments confirmed KYNU-OE CAR-T cells showed an excellent anti-tumor effect in a TME with high Kyn levels since it improved the survival of mice bearing NALM6 cancer cells and NALM6-IDO1 cancer cells. The KYNU-modified CAR-T cells displayed distinct phenotypes related to the expansion, function, and memory differentiation status of CAR-T cells. This study explores an immunotherapy strategy for patients with alterations in Kyn metabolism. KYNU-OE CAR-T cells take advantage of Kyn catabolism to improve anti-tumor activity in the metabolic immunosuppressive TME with high Kyn.

Ailanthone Inhibits Proliferation, Migration and Invasion of Osteosarcoma Cells by Downregulating the Serine Biosynthetic Pathway.

Osteosarcoma (OS) is the most common primary bone sarcoma, chemoresistance becomes an obstacle to its treatment. Metabolic reprogramming is a hallmark of malignancy, targeting the metabolic pathways might provide a reasonable therapeutic strategy for OS. Here we demonstrated that Ailanthone (AIL), a major component of the Chinese medicine Ailanthus altissima, significantly suppressed OS cell growth in vitro and in vivo. Furthermore, AIL dose-dependently inhibited cell migration and invasion, induced cell cycle arrest and apoptosis in OS cells. Combined transcriptomics, proteomics and metabolomics analyses revealed that AIL induced widespread changes in metabolic programs in OS cells, while the serine biosynthetic pathway (SSP) was the most significantly altered pathway. qRT-PCR and Western blot assay confirmed that the transcript and protein levels of the SSP genes (PHGDH, PSAT1 and PSPH) were downregulated dose-dependently by AIL. In addition, we found out that many downstream pathways of the SSP including the one-carbon pool by folate, purine metabolism, pyrimidine metabolism, DNA replication and sphingolipid metabolism were downregulated after AIL treatment. In the revere test, PHGDH overexpression but not exogenous serine supplementation clearly attenuated the effects of AIL on OS cells. Taken together, AIL exerts antitumor effects on OS through mediating metabolic reprogramming, at least in part, by suppressing the SSP. Our findings suggest that AIL could emerge as a potential therapeutic strategy in OS.

Silibinin Alleviates Muscle Atrophy Caused by Oxidative Stress Induced by Cisplatin through ERK/FoxO and JNK/FoxO Pathways.

Cisplatin (DDP), a widely used chemotherapeutic drug in cancer treatment, causes oxidative stress, resulting in cancer cachexia and skeletal muscle atrophy. This study investigated the effects and activity of silibinin (SLI) in reducing DDP-induced oxidative stress and skeletal muscle atrophy in vivo and in vitro. SLI alleviated weight loss, food intake, muscle wasting, adipose tissue depletion, and organ weight reduction induced by DDP and improved the reduction of grip force caused by DDP. SLI can attenuated the increase in reactive oxygen species (ROS) levels, the decrease in Nrf2 expression, the decrease in the fiber cross-sectional area, and changes in fiber type induced by DDP. SLI regulated the ERK/FoxO and JNK/FoxO pathways by downregulating the abnormal increase in ROS and Nrf2 expression in DDP-treated skeletal muscle and C2C12 myotube cells. Further, SLI inhibited the upregulation of MAFbx and Mstn, the downregulation of MyHC and MyoG, the increase in protein degradation, and the decrease of protein synthesis. The protective effects of SLI were reversed by cotreatment with JNK agonists and ERK inhibitors. These results suggest that SLI can reduce DDP-induced skeletal muscle atrophy by reducing oxidative stress and regulating ERK/FoxO and JNK/FoxO pathways.

Air pollution and recurrence of cardiovascular events after ST-segment elevation myocardial infarction.

BACKGROUND AND AIMS: The effects of air pollution on discharged patients after ST-segment elevation myocardial infarction (STEMI) still remain uncertain. We examined the association between air pollutants and recurrent cardiovascular events in STEMI survivors. METHODS: A retrospective cohort of 1641 discharged patients after STEMI was established in 2013 and followed until the end of 2019. Concentrations of air pollutants including fine particles <2.5 µm aerodynamic diameter (PM2.5), inhalable particles <10 µm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and ozone (O3) measured by fixed ambient air monitoring stations were collected for exposure assessment. Multivariate-adjusted Cox proportional hazards models were used to estimate the increased risks of recurrent cardiovascular events. RESULTS: Compared with the first exposure quartile, for short-term exposure, hazard ratios (HRs) of recurrent cardiovascular events associated with the fourth exposure quartiles of PM2.5, PM10, NO2, SO2, CO, and O3 were 4.06 (95% CI: 2.62-6.30), 3.79 (95% CI: 2.57-5.58), 2.22 (95% CI: 1.67-2.94), 4.47 (95% CI: 3.08-6.48), 3.73 (95% CI: 2.54-5.48), and 5.35 (95% CI: 3.12-9.20), respectively. For long-term exposure, HRs associated with the fourth exposure quartiles of PM2.5, PM10, NO2, SO2, CO, and O3 were 6.43 (95% CI: 3.60-11.47), 4.77 (95% CI: 2.85-7.99), 3.22 (95% CI: 2.00-5.19), 3.20 (95% CI: 2.05-5.01), 4.44 (95% CI: 2.65-7.45), and 1.07 (95% CI: 0.80-1.42), respectively. The risks of recurrent cardiovascular events brought by air pollutants mostly increased nonlinearly. CONCLUSIONS: Short- and long-term exposure to air pollutants except ozone increases the risks of recurrent cardiovascular events in STEMI survivors. Better environmental policies and secondary prevention strategies should be developed to protect STEMI survivors as a susceptible population.

Effect of Songlingxuemaikang on mild essential hypertension in patients: a randomized parallel-controlled study.

OBJECTIVE: To evaluate the effect of songlingxuemaikang (SLXMK) on mild essential hypertension in patients in terms of endothelial function. METHODS: We enrolled 90 patients with mild essential hypertension in Xuanwu Hospital from January 2016 to December 2016. To evaluate the effects of SLXMK, the 90 patients were randomly assigned at a 2∶1 ratio into 2 groups: the SLXMK group (500 mg per capsule, 4500 mg/d, n = 60) and the losartan potassium group (50 mg per table, 50 mg/d, n = 30). The total study period was 12 weeks, and the changes of blood pressure, laboratory test and endothelium function were compared between two groups. RESULTS: After 12 weeks of treatment with SLXMK, blood pressure (BP) and plasma lipid levels significantly improved (P < 0.05). Meanwhile, the reactive hyperemia index (RHI) increased in the SLXMK group (P < 0.05). The results of multivariate logistic regression analyses examining the association of selected variables with showed that high level of oxidized low density lipoprotein (ox-LDL) was positively associated with endothelial dysfunction. CONCLUSION: SLXMK not only effectively decreased BP and plasma lipid levels, but also reduced ox-LDL and RHI in patients with mild essential hypertension. And SLXMK might improve endothelial function through decreasing the circulating ox-LDL.

Daidzein alleviates cisplatin-induced muscle atrophy by regulating Glut4/AMPK/FoxO pathway.

Cisplatin (DDP) is widely used in cancer treatment, but DDP can cause skeletal muscle atrophy and cachexia. This study explored the effect and mechanism of daidzein (DAI) in reducing DDP-induced skeletal muscle atrophy and cachexia in vivo and in vitro. DAI alleviated the weight, food intake, muscle, adipose tissue, kidney weight and forelimb grip of LLC tumour-bearing mice after DDP treatment, and did not affect the antitumour effect of DDP. DAI can reduce the decrease of the cross-sectional area of skeletal muscle fibre-induced by DDP and prevent the change of fibre type proportion. In skeletal muscle, it can inhibit Glut4/AMPK/FoxO pathway, down-regulate the expression of atrogin1 and MuRF1, and inhibit skeletal muscle protein degradation. In DDP treated C2C12 myotubes, DAI could inhibit Glut4/AMPK/FoxO pathway to reduce myotubes atrophy, while AMPK agonist MK-3903 could reverse the protective effect of DAI. These results suggest that DAI can alleviate DDP-induced skeletal muscle atrophy by downregulating the expression of Atrogin1 and MuRF1 through the regulation of Glut4/AMPK/FoxO pathway.

Association between serum uric acid level and endothelial dysfunction in elderly individuals with untreated mild hypertension.

BACKGROUND: Endothelial dysfunction is the initial stage in atherosclerotic formation and progression and is associated with high serum uric acid (SUA) level. We hypothesized that reactive hyperemia index (RHI), which reflects endothelial function, is associated with SUA levels in elderly individuals with untreated mild hypertension. METHODS: We recruited 123 patients ≥ 60 years with untreated mild hypertension. The association between SUA level and RHI was analyzed using univariate correlation analysis and multiple regression analysis. The receiver operating characteristic (ROC) curve was performed to validate the cutoff value of SUA that can be used to predict endothelial dysfunction. RESULTS: The serum uric acid level significantly increased in the RHI < 1.67 group, and this result was still observed in the subgroup of men. RHI was inversely associated with SUA level (P = 0.006) and the association was still observed after adjusting for factors, such as age, sex, smoking status, and creatinine level (P = 0.014). In the subgroup analysis, a positive association was observed only in men. In the ROC curve analysis, the optimal cutoff values of SUA for predicting endothelial dysfunction was 293.5 µmol/L in elderly mild hypertension patients and 287.0 µmol/L in men. CONCLUSION: A high SUA level was considered an independent predictor of endothelial dysfunction among elderly individuals, particularly men with untreated mild hypertension.

Matrine: A Promising Natural Product With Various Pharmacological Activities.

Matrine is an alkaloid isolated from the traditional Chinese medicine Sophora flavescens Aiton. At present, a large number of studies have proved that matrine has an anticancer effect can inhibit cancer cell proliferation, arrest cell cycle, induce apoptosis, and inhibit cancer cell metastasis. It also has the effect of reversing anticancer drug resistance and reducing the toxicity of anticancer drugs. In addition, studies have reported that matrine has a therapeutic effect on Alzheimer's syndrome, encephalomyelitis, asthma, myocardial ischemia, rheumatoid arthritis, osteoporosis, and the like, and its mechanism is mainly related to the inhibition of inflammatory response and apoptosis. Its treatable disease spectrum spans multiple systems such as the nervous system, circulatory system, and immune system. The antidisease effect and mechanism of matrine are diverse, so it has high research value. This review summarizes recent studies on the pharmacological mechanism of matrine, with a view to providing reference for subsequent research.