Effect of Huatan Tongluo Prescription on Vulnerability of Carotid Atherosclerotic Plaque in Hypertension / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Huatan Tongluo prescription on the vulnerability of atherosclerotic plaques in the carotid arteries of patients with hypertension of phlegm-stasis combination syndrome. MethodA total of 132 eligible patients were randomly divided into an observation group （66 cases） and a control group （66 cases）. The control group received oral atorvastatin calcium tablets and enteric-coated aspirin tablets， while the observation group received Huatan Tongluo prescription in addition to the treatment received by the control group. The treatment duration was 6 months. A carotid artery ultrasound examination was performed to record the number of plaques， the maximum plaque area， the maximum plaque cross-sectional thickness， and the intima-media thickness （IMT） of the carotid artery. Crouse score， plaque vulnerability score， and phlegm-stasis combination syndrome score were assessed. Blood lipid levels ［total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）］， inflammatory markers ［neutrophil-to-lymphocyte ratio （NLR）， monocyte-to-lymphocyte ratio （MLR）， interleukin-6 （IL-6）， and high-sensitivity C-reactive protein （hs-CRP）］， vascular endothelial function ［endothelin-1 （ET-1）， von Willebrand factor （vWF）， and nitric oxide （NO）］， and relevant proteins ［pentraxin 3 （PTX3） and galectin-3 （Gal-3）］ levels were measured. Safety evaluation was conducted， and comparisons were made in terms of carotid artery stenosis rate， plaque regression efficacy， and traditional Chinese medicine （TCM） syndrome efficacy. ResultCompared with the results before treatment， both groups showed significant reductions in IMT， plaque number， maximum plaque area， and maximum plaque cross-sectional thickness （P<0.05）. After treatment， the observation group exhibited more significant reductions in the above indicators compared with the control group （P<0.05）. After treatment， Crouse scores， plaque vulnerability scores， and phlegm-stasis combination syndrome scores in both groups were lower than those before treatment （P<0.05）. After treatment， the observation group had lower scores in these indicators than the control group （P<0.05）. In terms of blood lipid levels， both groups showed decreases in TC， TG， and LDL-C levels， and an increase in HDL-C levels after treatment compared to those before treatment （P<0.05）. The observation group exhibited greater improvements in these lipid parameters than the control group （P<0.05）. Inflammatory markers NLR， MLR， IL-6， and hs-CRP significantly decreased in both groups after treatment compared with those before treatment （P<0.05）. The observation group showed more significant reductions in these markers than the control group after treatment （P<0.05）. After treatment， both groups demonstrated decreases in levels of ET-1， vWF， PTX3， and Gal-3， along with an increase in NO levels compared with those before treatment （P<0.05）. The observation group showed more significant improvements in these markers than the control group after treatment （P<0.05）. After treatment， the observation group had a lower carotid artery stenosis rate than the control group （P<0.05）. The plaque regression efficacy rate was 51.72% （30/58） in the observation group， and the total effective rate of TCM syndrome was 84.48% （49/58）， both of which were higher than 18.64% （11/59） and 52.54% （31/59） in the control group （χ²=10.061， 13.799， P<0.05）. No adverse reactions related to the Huatan Tongluo prescription were observed during the treatment period. ConclusionIn addition to statin therapy， Huatan Tongluo prescription can effectively reverse carotid artery atherosclerotic plaques in patients with hypertension and carotid artery stenosis， reduce plaque vulnerability， exhibit lipid-lowering and anti-inflammatory effects， and improve vascular endothelial function. The treatment demonstrates favorable clinical efficacy and safety. Therefore， it is very worthy of clinical promotion and application.

Effect of febuxostat on vascular endothelial function and elasticity in patients with asymptomatic hyperuricemia / 中华内分泌代谢杂志

Objective:To evaluate the effect of febutostat on vascular endothelial function, intima-media thickness(C-IMT) and elasticity of the carotid artery in patients with asymptomatic hyperuricemia.Methods:This study was a randomized controlled clinical trial that enrolled asymptomatic hyperuricemia patients from the outpatient and inpatient departments of Huai′an First People′s Hospital from October 2018 to October 2020. The participants were randomly divided into two groups: the Febuxostat group and the control group. Serum triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), nitric oxide(NO), endothelin-1(ET-1), malondialdehyde(MDA), and superoxide dismutase(SOD) were measured at baseline and 1, 3, and 6 months after treatment, and brachial artery flow-mediated dilation(FMD) was quantified by color Doppler ultrasound. The following parameters of the common carotid artery were detected at baseline and 12 months after treatment: C-IMT, arterial compliance(AC), one-point pulse wave velocity(PWV), stiffness index(β), and pressure-strain elasticity modulus(Ep). The differences before and after treatment and between the two groups were compared. Pearson correlation was used to analyze the correlation between ΔUA and ΔNO, ΔET-1, ΔC-IMT, ΔAC, Δβ, ΔEp, and ΔPWVβ after treatment with febuxostat. Results:Compared with baseline, TG, HOMA-IR, ET-1 and MDA were significantly lower, while FMD, NO and SOD were significantly higher after 3-months treatment with febuxostat. After 12-months treatment, there was no significant difference in C-IMT or Ep, but there was an increase in AC and a decrease in PWVβ or β compared with baseline. There was a negative correlation between ΔFMD and ΔUA( r=-0.403, P=0.004), but there were no correlations between ΔNO and ΔUA( r=-0.187, P=0.194), ΔET-1 and ΔUA( r=0.038, P=0.791) after 6-months treatment. And ΔUA was an independent factor for ΔFMD( F=2.94, P=0.003, adjusted R2=0.139). After 12-months treatment, there was a negative correlation between ΔAC and ΔUA, and a positive correlation between ΔPWVβ and ΔUA, but there were no correlations between the following indicators: ΔC-IMT and ΔUA( r=0.169, P=0.240), Δβ and ΔUA( r=-0.214, P=0.136), ΔEp and ΔUA( r=-0.077, P=0.597). In the control group, there were no differences among the above indicators between each follow-up time and baseline. Conclusion:Febuxostat improves vascular endothelial function and elasticity in patients with asymptomatic hyperuricemia, which may be related to the decreased oxidative stress response.

Effect of Guizhi Gegentang on Hemodynamics and Vascular Endothelial Function in Cervical Vertigo / 中国实验方剂学杂志

ObjectiveTo evaluate the therapeutic effect of Guizhi Gegentang on cervical vertigo and its impact on hemodynamics and vascular endothelial function. MethodA total of 144 patients with cervical vertigo treated from April 2019 to June 2022 were included in the study and randomly divided into a control group and an observation group， with 72 patients in each group. During the study， three patients dropped out from the observation group and two patients from the control group. The control group received conventional treatment （oral betahistine mesylate tablets）， while the observation group received conventional treatment combined with Guizhi Gegentang. The clinical efficacy， changes in the frequency and duration of dizziness attacks per month before and after treatment， changes in symptoms and functional evaluation scores of cervical vertigo assessed by the European Scale for Cervical Vertigo （ESCV）， changes in the average blood flow velocity of the left vertebral artery， right vertebral artery， and basilar artery， changes in indicators such as endothelin-1 （ET-1）， neuropeptide Y （NPY）， calcitonin gene-related peptide （CGRP）， changes in the Neck Disability Index （NDI） score， changes in the Functional Assessment of Cancer Therapy-General （FACT-G） score， and adverse reactions were observed and compared between the two groups. ResultThe total effective rate in the observation group was 95.65% （66/69）， significantly higher than 84.29% （59/70） in the control group （χ2=4.957， P<0.05）. Before treatment， there were no significant differences in the frequency and duration of dizziness attacks per month， ESCV scores， average blood flow velocity of the left vertebral artery， right vertebral artery， and basilar artery， levels of ET-1， NPY， CGRP， NDI score， and FACT-G score between the two groups. After treatment， compared with the baseline within each group， there were improvements in the frequency and duration of dizziness attacks per month， ESCV scores， average blood flow velocity of the left vertebral artery， right vertebral artery， and basilar artery， levels of ET-1， NPY， CGRP， NDI score， and FACT-G score in both groups （P<0.05， P<0.01）. Compared with the control group， the observation group showed better improvements in the frequency and duration of dizziness attacks per month， ESCV score， average blood flow velocity of the left vertebral artery， right vertebral artery， and basilar artery， levels of ET-1， NPY， CGRP， NDI score， and FACT-G score （P<0.05， P<0.01）. During the study period， one case of nausea occurred in the control group， and one case of dizziness occurred in the observation group. There was no statistically significant difference in the incidence of adverse reactions between the two groups. ConclusionGuizhi Gegentang can improve the therapeutic effect of cervical vertigo， effectively improve patients' hemodynamics and vascular endothelial function， and enhance their quality of life with few adverse reactions. It is worth applying in clinical practice.

Effect of Jiawei Shenqi Yixin Prescription on Cardiovascular Risk Factors in Patients with Heart Failure with Preserved Ejection Fraction and Insulin Resistance / 中国实验方剂学杂志

ObjectiveTo observe the effect of Jiawei Shenqi Yixin prescription on cardiovascular risk factors in the patients with heart failure with preserved ejection fraction and insulin resistance. MethodFrom January 2021 to January 2022， a total of 82 patients with heart failure with preserved ejection fraction were enrolled in the ward of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine. The patients were randomly assigned into two groups （ 41 cases） and received the same basic treatment. The observation group was additionally treated with Jiawei Shenqi Yixin prescription for 8 weeks. The clinical efficacy， traditional Chinese medicine （TCM） efficacy， cardiac function indexes ［NT-probrain natriuretic peptide （NT-proBNP） and 6-min walking test （6MWT）］， echocardiographic parameters ［left atrial volume index （LAVI）， left ventricular mass index （LVMI）， peak early diastolic to peak late diastolic mitral flow velocity （E/A） ratio］， insulin resistance-related indexes ［fasting insulin （FINS）， fasting plasma glucose （FPG）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， homeostatic model assessment of insulin resistance （HOMA-IR）， triglyceride-glucose index （TYG）， and triglyceride to high-density lipoprotein cholesterol （TG/HDL-C） ratio］， inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， adiponectin （ADP）， and C-reactive protein （CRP）］， vascular endothelial function indicators ［nitric oxide （NO）， endothelial nitric oxide synthase （eNOS）， inducible nitric oxide synthase （iNOS）， and endothelin-1 （ET-1）］， and the safety of treatment were determined. In addition， Pearson correlation analysis was performed to analyze the correlations of insulin resistance， inflammatory cytokines， and vascular endothelial factors with the mitigation of heart failure. ResultIn terms of clinical efficacy， the therapy of the observation group was significantly effective in 26 patients， effective in 12 patients， ineffective in 3 patients， with the total effective rate of 92.68%， the therapy of the control group was significantly effective in 14 patients， effective in 12 patients， and ineffective in 15 patients， with the total effective rate of 63.41%. The clinical total effective rate of the observation group was higher than that of the control group （χ2=11.6， P<0.05）. In terms of TCM efficacy， the therapy of the observation group was significantly effective in 26 patients， effective in 11 patients， and ineffective in 4 patients， with the total effective rate of 90.24%； the therapy of the control group was significantly effective in 9 patients， effective in 13 patients， and ineffective in 19 patients， with the total effective rate of 53.66%. The TCM total effective rate of the observation group was higher than that of the control group （χ2=8.19， P<0.05）. Compared with those before treatment， the levels of NT-proBNP， LAVI， LVMI， FPG， FINS， HOMA-IR， TYG， TG/HDL-C， TNF-α， IL-6， CRP， ET-1， and iNOS in two groups declined after treatment （P<0.05）， while the levels of 6MWT， E/A， ADP， NO， and eNOS elevated （P<0.05）. After treatment， the observation group had lower levels of NT-proBNP， LAVI， LVMI， FPG， FINS， HOMA-IR， TYG， TG/HDL-C， TNF-α， CRP， and ET-1 （P<0.05） and higher levels of 6MWT， E/A， ADP， and NO than the control group （P<0.05）. In addition， the increase in 6MWT after treatment was positively correlated with the increase in NO and the decrease in ET-1. The decrease in LVMI after treatment was positively correlated with the increase in NO and the decrease in FINS. The increase in left ventricular ejection fraction after treatment was positively correlated with the decreases in TNF-α and TYG （P<0.05）. Adverse reactions were observed in neither group. ConclusionJiawei Shenqi Yixin prescription can significantly mitigate the symptoms， reduce inflammation， and improve vascular endothelial function in the patients with heart failure with preserved ejection fraction and insulin resistance， being safe without causing adverse reactions.

Endothelial METRNL determines circulating METRNL level and maintains endothelial function against atherosclerosis

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.

Mental stress induces endothelial dysfunction by AT1R-mediated redox imbalance in overweight/obese men

The main goal of this study was to determine whether oxidative imbalance mediated by AT1 receptor (AT1R) is responsible for deleterious endothelial responses to mental stress (MS) in overweight/obese class I men. Fifteen overweight/obese men (27±7 years old; 29.8±2.6 kg/m2) participated in three randomized experimental sessions with oral administration of the AT1R blocker olmesartan (40 mg; AT1R blockade) or ascorbic acid (AA; 3g) infusion or placebo [both intravenously (0.9% NaCl) and orally]. After two hours, endothelial function was determined by flow-mediated dilation (FMD) before (baseline), 30 min (30MS), and 60 min (60MS) after a five-minute acute MS session (Stroop Color Word Test). Blood was collected before (baseline), during MS, and 60 min after MS for redox homeostasis profiling: lipid peroxidation (TBARS; thiobarbituric acid reactive species), protein carbonylation, and catalase activity by colorimetry and superoxide dismutase (SOD) activity by an ELISA kit. At the placebo session, FMD significantly decreased 30MS (P=0.05). When compared to baseline, TBARS (P<0.02), protein carbonylation (P<0.01), catalase (P<0.01), and SOD (P<0.01) increased during the placebo session. During AT1R blockade, FMD increased 30 min after MS (P=0.01 vs baseline; P<0.01 vs placebo), while AA infusion increased FMD only 60 min after MS. No differences were observed during MS with the AT1R blockade and AA regarding TBARS, protein carbonylation, catalase, and SOD. AT1R-mediated redox imbalances played an important role in endothelial dysfunction to mental stress.

Effects of therapeutic ultrasound on the endothelial function of patients with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction that causes micro- and macrovascular complications. Low intensity therapeutic ultrasound (LITUS) may improve endothelial function, but its effects have not been investigated in these patients. The aim of our study was to compare the effects of pulsed (PUT) and continuous (CUT) waveforms of LITUS on the endothelium-dependent vasodilation of T2DM patients. The present randomized crossover trial had a sample of twenty-three patients (7 men) diagnosed with T2DM, 55.6 (±9.1) years old, with a body mass index of 28.6 (±3.3) kg/m2. All patients were randomized and submitted to different waveforms (Placebo, CUT, and PUT) of LITUS and the arterial endothelial function was evaluated. The LITUS of 1 MHz was applied in pulsed (PUT: 20% duty cycle, 0.08 W/cm2 SATA), continuous (CUT: 0.4 W/cm2 SPTA), and Placebo (equipment off) types of waves during 5 min on the brachial artery. Endothelial function was evaluated using the flow-mediated dilation (FMD) technique. PUT (mean difference 2.08%, 95% confidence interval 0.65 to 3.51) and CUT (mean difference 2.32%, 95% confidence interval 0.89 to 3.74) increased the %FMD compared to Placebo. In the effect size analysis, PUT (d=0.65) and CUT (d=0.65) waveforms presented moderate effects in the %FMD compared to Placebo. The vasodilator effect was similar in the different types of waves. Pulsed and continuous waveforms of LITUS of 1 MHz improved the arterial endothelial function in T2DM patients.

Ácidos grasos omega-3 y función endotelial en pacientes con síndrome coronario agudo / Omega-3 fatty acids and endothelial function in patients with acute coronary syndrome

Las enfermedades cardiovasculares son la principal causa de muerte a nivel mundial, manifestándose principalmente como enfermedad isquémica coronaria. El pronóstico y desenlace del Síndrome Coronario Agudo (SCA) depende en gran proporción de la disfunción endotelial asociado a este cuadro. Objetivo:Evaluar el efecto de los ácidos grasos omega­3, sobre la función endotelial en el Síndrome Coronario Agudo (SCA). Métodos: Se realizó estudio con 16 pacientes con síndrome coronario agudo (SCA) tratados con Omega-3 a dosis de 3 gramos/día+Terapia Convencional (O3+Tc) durante 30 días. Se les realizó a las 12 horas del ingreso y los a 30 días, perfil lipídico, proteína C reactiva ultrasensible (PCRus), Endotelina 1 (ET-1), y Péptido Natriurético cerebral (NTproBNP). Resultados: Durante 4 semanas de seguimiento, el uso de 3 gramos/día de ácidos grasos omega-3, añadido a la terapia convencional en el Síndrome Coronario Agudo, mostró una reducción significativa de la concentración plasmática de NTproBNP (p = 0,000), PCRus (p =0,000) y triglicéridos (p = 0,004). Conclusión: Tres gramos al día de ácidos grasos omega-3 contribuye a la reducción de la concentración plasmática de Triglicéridos y NTproBNP en pacientes con síndrome coronario agudo(AU)

Mainly as coronary ischemic disease. the prognosis and outcome of Acute Coronary Syndrome (ACS) depend largely on the endothelial dysfunction associated with this condition. Objective: To evaluate the effect of omega-3 fatty acids on endothelial function in Acute Coronary Syndrome (ACS). Method: A study was conducted with 16 patients with acute coronary syndrome (ACS) treated with Omega-3 at a dose of 3 grams/day+Conventional erapy (O3+Tc) for 30 days. Lipid profile, ultrasensitive C-reactive protein (usCRP), Endothelin 1 (ET-1), and Brain Natriuretic Peptide (NTproBNP) were performed 12 hours aer admission and 30 days later. Results: During 4 weeks of follow-up, the use of 3 grams/day of omega-3 fatty acids, added to conventional therapy in Acute Coronary Syndrome, showed a significant reduction in the plasma concentration of NTproBNP (p = 0.000), hsCRP (p =0.000) and Triglycerides (p = 0.004). Conclusion: three grams a day of omega-3 fatty acids contributes to the reduction of the plasmatic concentration of Triglycerides and NTproBNP in patients with acute coronary syndrome(AU)

Dietary n-3 polyunsaturated fatty acids improve endothelial markers in metabolic syndrome: A systematic review

ABSTRACT Metabolic syndrome (MS) is a global health problem. Dietary factors, especially fatty acids, may affect MS pathology. However, the associations between omega-3 polyunsaturated fatty acids (n-3 PUFAs) and MS risk demonstrate inconsistent results. To clarify the relationship between dietary n-3 PUFA and endothelial function on MS, we carried out a systematic review. An electronic literature search based on controlled clinical trials (CCTs) between 2004 and 2020 was conducted. A total of 28 articles were included in the systematic review. Studies were analyzed according intervention type: dietary interventions (12 CCTs), dietary supplementation interventions (9 CCTs) and mixed interventions (7 CCTs). Studies with dietary interventions characterized by n-3 PUFAs increased by food source, such as Mediterranean and Nordic-style diets, reported significant reduction in systolic and diastolic blood pressure, and also in inflammatory endothelial biomarkers. The same effect was also observed in mixed interventions and in CCTs with n-3 PUFAs supplementation. Dietary interventions with n-3 PUFAs contributes to improved endothelial and cardiovascular health in SM and associated risk factors.

RESUMEN El síndrome metabólico (SM) es un problema sanitario global. Los factores dietéticos, especialmente los ácidos grasos, pueden afectar la patología del SM. Sin embargo, las asociaciones entre los ácidos grasos poliinsaturados omega-3 (AGPI n-3) y el riesgo de SM pueden ser inconsistentes. Para aclarar esta relación entre AGPI n-3 dietarios y la función endotelial en el SM, realizamos una revisión sistemática. Se realizó una búsqueda bibliográfica en fuentes electrónicas de ensayos clínicos controlados (ECC) entre 2004 y 2020. Se incluyeron un total de 28 artículos en la revisión. Los estudios fueron analizados según intervención realizada: intervención dietaria (12 ECC), intervención con suplementación dietética (9 ECC) e intervenciones mixtas (7 ECC). Los estudios que utilizaron intervenciones dietéticas con aumento de AGPI n-3 a través de alimentos, como las dietas mediterráneas y nórdicas, reportaron una reducción significativa de la presión arterial sistólica (PAS), diastólica (PAD) y de biomarcadores endoteliales inflamatorios. El mismo efecto se observó en intervenciones mixtas y ECC con suplementación de AGPI n-3. Las intervenciones dietéticas con AGPI n-3 contribuyen a mejorar la salud endotelial y cardiovascular y sus factores de riesgo asociados.

Protective effects and mechanism of icariin against vascular function in diabetic mice / 中国药科大学学报

@#To explore the effects and molecular mechanism of icariin on the vascular function of mice with type 1 diabetes induced by alloxan, type 1 diabetic mice model was established by intraperitoneal injection with 200 mg/kg alloxan.After oral administration with icariin (60, 120 mg/kg) daily for 2 weeks, blood glucose, body weight, food intake and water intake were detected.To evaluate the impact of icariin on the function of isolated vascular ring contraction and relaxation, thoracic aortas of mice were removed and the Ach-induced vascular ring relaxation, Phe-induced vascular ring contraction, SNP-induced vascular ring relaxation and KCl-induced vascular ring contraction response were detected.To further confirm the mechanism of icariin to improve vascular function, human umbilical vein endothelial cells (HUVECs) were induced by high glucose (HG) in vitro.Western blot was used to detect the effect of icariin on eNOS, p-eNOS, p38 MAPK and p-p38 MAPK expressions in HG-induced human umbilical vein endothelial cells (HUVECs).The results indicated that icariin significantly ameliorated the weight loss and dampened the increase in water intake of the diabetic mice.Meanwhile, icariin had a certain ameliorative effect on blood glucose and food intake without significant difference.The results of isolated thoracic aortas vascular rings contraction and vasodilation function indicated that icariin significantly improved Phe-induced vascular contraction and Ach‐induced vascular relaxation.Meanwhile, icariin had a certain ameliorative effect on KCl-induced vascular contraction response without significant difference.However, no significant change was observed on endothelium‐independent vascular rings relaxation response induced by SNP after treatment with icariin.Results of Western blot showed that icariin inhibited the expression of p-p38 MAPK and induced expression of p-eNOS in the high glucose-induced HUVECs cell model.Therefore, icariin may attenuate alloxan-induced type 1 diabetic mice vascular diastolic function by inhibiting expression of p-p38 MAPK and inducing expression of p-eNOS.

Association of asymmetric dimethylarginine with the pathological process of persistent pulmonary hypertension of the newborn / 中国当代儿科杂志

OBJECTIVES@#To study the change in asymmetric dimethylarginine (ADMA) in the circulation system of full-term infants with persistent pulmonary hypertension of the newborn (PPHN) and its association with treatment response, as well as the possibility of ADMA as a therapeutic target and a marker for treatment response.@*METHODS@#A prospective study was performed. A total of 30 full-term neonates who were diagnosed with PPHN within 3 days after birth were enrolled as the PPHN group, and the neonates without PPHN, matched for gestational age and age, who were treated or observed in the department of neonatology were enrolled as the control group. Serum samples were collected on days 1, 7, and 14 of treatment. The high-performance liquid chromatography-tandem mass spectrometry was used to measure the serum concentrations of L-arginine, ADMA, and its isomer symmetric dimethylarginine (SDMA).@*RESULTS@#For the neonates in the control group, the serum concentrations of ADMA and L-arginine continuously increased and the serum concentration of SDMA continuously decreased within the first 14 days of treatment. On days 1 and 14, there was no significant difference in the serum concentration of ADMA between the control and PPHN groups (P>0.05). On day 7, the PPHN group had a significantly higher serum concentration of ADMA than the control group (P<0.05), while there were no significant differences in serum concentrations of SDMA or L-arginine (P>0.05). Moreover, after 7 days of treatment, the PPHN neonates with a systolic pulmonary arterial pressure (sPAP) of >35 mmHg had a significantly higher serum concentration of ADMA than those with an sPAP of ≤35 mm Hg.@*CONCLUSIONS@#There are continuous increases in the ADMA concentration and the ADMA/SDMA ratio in the circulation system of full-term infants within the first 2 weeks after birth, and this process is accelerated by the pathological process of PPHN, suggesting that ADMA may be involved in the pathologic process of PPHN. A high level of ADMA is associated with the resistance to PPHN treatment, suggesting that inhibition of ADMA might be a potential target of drug intervention to improve the treatment response of PPHN.

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 / 中国中药杂志

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.

Effects of morning blood pressure on vascular endothelial function and chronic inflammatory response in the elderly / 中国医师杂志

Objectives:To investigate the effects of morning blood pressure on vascular endothelial function and chronic inflammatory response in the elderly.Methods:349 elderly people aged ≥60 who underwent 24-hour ambulatory blood pressure monitoring in Gaomi Municipal Hospital from April 2018 to October 2019 were selected to detect brachial artery flow mediated vasodilation (FMD) and chronic inflammatory factors [high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α) and interleukin (IL)-17] levels. According to the results of 24-hour ambulatory blood pressure monitoring, the subjects were divided into normal blood pressure group ( n=108), simple morning hypertension group ( n=114) and hypertension group ( n=127). The clinical data, 24-hour ambulatory blood pressure parameters, vascular endothelial function and inflammatory factors of the three groups were compared. The correlation between 24-hour ambulatory blood pressure parameters and FMD and inflammatory factors was analyzed by partial correlation. Results:Compared with the normal blood pressure group, the simple morning hypertension group and the hypertension group had lower FMD (all P<0.05), higher serum hsCRP and TNF-α , IL-17 levels (all P<0.05). Compared with the simple morning hypertension group, the hypertension group had lower FMD ( P<0.05), higher serum hsCRP, TNF-α and IL-17 levels (all P<0.05). After controlling for age, sex, smoking history, drinking history, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood glucose and 24 h average blood pressure, the morning systolic blood pressure was negatively correlated with FMD ( P<0.05), and positively correlated with serum hsCRP and TNF-α and IL-17 levels (all P<0.05); the morning diastolic blood pressure was negatively correlated with FMD ( P<0.05) and positively correlated with serum hsCRP and TNF-α levels (all P<0.05). Conclusions:Morning blood pressure level is closely related to vascular endothelial function and chronic inflammation level, and is independent of 24-hour average blood pressure. The increase of morning blood pressure may be an important risk factor for endothelial dysfunction and chronic inflammation in the elderly.

Effectiveness of early intervention with levothyroxine sodium in pregnancy complicated with hypothyroidism / 中华内分泌外科杂志

Objective:To investigate the effectiveness of early levothyroxine intervention in pregnancy complicated with hypothyroidism.Methods:A retrospective analysis was performed on 132 pregnant patients with hypothyroidism admitted to the Department of Endocrinology, Anyang People’s Hospital from Nov. 2018 to Sep. 2021. Among them, 68 cases with levothyroxine sodium early intervention were included in the intervention group, and 64 cases without intervention were included in the non-intervention group. The differences in vascular endothelial function indexes, thyroid function indexes, and blood lipid indexes before and after treatment in the intervention group were compared with those in the non-intervention group. The incidence of obstetric complications such as preeclampsia, fetal growth restriction, and adverse pregnancy outcomes of abortion and neonatal asphyxia were compared between the two groups. SPSS 21.0 software was used to process data, measurement data were subjected to t test, and enumeration data were subjected to χ 2 test. Results:After treatment, the endothelium-dependent brachial artery blood flow-mediated vasodilation index (FMD) index, nitric oxide (NO) , and endothelin-1 (ET-1) levels in the intervention group were significantly better than those in the non-intervention group [ (10.37%) ±1.54%) vs (7.25% ± 1.09%) , (60.85 ± 7.03) umol/L vs (39.11 ± 4.31) umol/L, (112.96 ± 13.58) umol/L vs (238.85 ± 26.05) umol/L]. After treatment, the serum thyroid stimulating hormone (TSH) in the intervention group was significantly lower than that in the non-intervention group [ (2.25±0.26) mU/L vs (8.79±1.60) mU/L] ( P<0.001) . After treatment, the levels of total cholesterol (TC) , triacylglycerol (TG) and low-density lipoprotein cholesterol (LDL-C) in the intervention group were significantly lower than those in the non-intervention group [ (3.52±0.91) mmol/L vs (6.51±1.31) mmol/L L, (1.30±0.31) mmol/L vs (1.44±0.36) mmol/L, (2.29±0.31) mmol/L vs (3.32±0.44) mmol/L] ( P<0.001, P=0.036, P<0.001) . The incidence of obstetric complications such as preeclampsia, fetal growth restriction, premature rupture of membranes, and abnormal amniotic fluid volume in the intervention group were significantly lower than those in the non-intervention group (5.88% vs 17.19%, 1.47% vs 9.38%, 10.29% vs. 23.44%, 2.94% vs 12.50%) ( P=0.041, 0.043, 0.043, 0.038) ; the incidence of miscarriage, premature birth, neonatal asphyxia, cesarean section and other adverse pregnancy outcomes in the intervention group were significantly lower than those in the non-intervention group (1.47% vs 9.38%, 4.69% vs 15.36%, 2.94% vs 10.94%, 57.35% vs 75.00%) ( P=0.043, 0.031, 0.038, 0.033) . Conclusion:Early intervention with levothyroxine in pregnancy complicated with hypothyroidism is beneficial to improve thyroid function, reduce blood lipid level, protect vascular endothelial function, reduce related obstetric complications, and reduce the incidence of adverse pregnancy outcomes for mothers and infants.

Global endothelial function assessment using pulse wave analysis in hypercholesterolemia

To compare global endothelial function assessed by pulse wave analysis (PWA) using the ratio of endothelium dependent vasodilatation (EDV) to endothelium independent vasodilatation (EIV) in patients with hypercholesterolemia and controls. 92 subjects [46 hypercholesterolemics, 46 controls] were studied at standardized conditions. Baseline augmentation index (AIx) was assessed followed by the administration of 0.5 mg sublingual nitroglycerine, an endothelium independent vasodilator. AIx was assessed and the maximum change in AIx after nitroglycerine was recorded as EIV. After a washout period of 30 minutes, 400 µg of inhaled salbutamol, an endothelium dependent vasodilator was administered. AIx was assessed again and the maximum change in AIx after salbutamol was recorded as EDV. Global endothelial function was calculated as EDV:EIV ratio. EDV and EIV in patients with hypercholesterolemia compared to controls were 2.97 ± 3.95 and 6.65 ± 3.80 (p<0.001); and 13.41 ± 4.57 and 15.88 ± 4.78 (p=0.01) respectively. EDV:EIV ratio was significantly reduced in patients with hypercholesterolemia compared to controls; 0.21 ± 0.38 and 0.44 ± 0.24 (p<0.001) respectively. EDV:EIV ratio was significantly reduced in patients with hypercholesterolemia compared to controls. PWA is a potential clinical tool to assess global endothelial function in patients with hypercholesterole

Dietary supplementation with whey protein improves systemic microvascular function in heart failure patients: a pilot study

Endothelial dysfunction is a well-known component of the pathophysiology of heart failure (HF), with proven prognostic value. Dietary supplementation with whey protein (WP) has been widely used to increase skeletal muscle mass, but it also has vascular effects, which are less understood. This study aimed to evaluate the effects of WP supplementation on the systemic microvascular function of HF patients. This was a blinded, randomized, placebo-controlled clinical trial that evaluated the effects of 12-week WP dietary supplementation on systemic microvascular function, in patients with HF New York Heart Association (NYHA) classes I/II. Cutaneous microvascular flow and reactivity were assessed using laser speckle contrast imaging, coupled with pharmacological local vasodilator stimuli. Fifteen patients (aged 64.5±6.2 years, 11 males) received WP supplementation and ten patients (aged 68.2±8.8 years, 8 males) received placebo (maltodextrin). The increase in endothelial-dependent microvascular vasodilation, induced by skin iontophoresis of acetylcholine, was improved after WP (P=0.03) but not placebo (P=0.37) supplementation. Moreover, endothelial-independent microvascular vasodilation induced by skin iontophoresis of sodium nitroprusside, was also enhanced after WP (P=0.04) but not placebo (P=0.42) supplementation. The results suggested that dietary supplementation with WP improved systemic microvascular function in patients with HF.

Effect of Qingfei Xiegantang on Chronic Inflammation and Endothelial Function with Metabolic Syndrome / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of Qingfei Xiegantang on chronic inflammation and endothelial function of people of Taiyin constitution with metabolic syndrome （MS）. Method:Patients （162 cases） were divided into control group （80 cases） and observation group （82 cases）. Both groups got lifestyle intervention and treatment with lipid regulation， blood pressure reduction and hypoglycemia according to MS. Patients in observation group got Qingfei Xiegantang， 1 dose/day. Patients in control group got placebo granules of Qingfei Xiegantang. The treatment lasted for 4 months. Before and after treatment， weight， height， waist （WC）， hip， body mass index （BMI） and waist hip ratio （WHR） were calculated. Levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （2 hPG）， glycosylated hemoglobin （HbA1c） and fasting insulin （FINS） were measured. Insulin resistance index （HOMA-IR）， insulin sensitivity index （ISI） and islet beta cell function index （HOMA-<italic>β</italic>）， systolic blood pressure （SBD）， diastolic blood pressure （DBP）， tumor necrosis factor-α （TNF-<italic>α</italic>）， interleukin-6 （IL-6）， leptin （LP）， adiponectin （ADP）， nitric oxide （NO）， endothelin-1 （ET-1）， endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were detected and recorded. Then the safety was evaluated. Result:Levels of body mass， BMI， WHR， TG， TC， LDL-C， FBG， 2 hPG， HbA1c， HOMA-IR， SBD， DBP， TNF-<italic>α</italic>， IL-6， LP， ET-1 and iNOS were all lower than those in control group. Levels of HDL-C， InISI， HOMA-<italic>β</italic>， ADP， NO and eNOS were higher than those in control group （<italic>P</italic><0.01）. And score of syndrome differentiation of Taiyin people was lower than that in control group （<italic>P</italic><0.01）. The compliance rate of BMI in observation group was 70.27% （52/74）， which was higher than 53.42% （39/73） in control group （<italic>χ</italic>²=4.421， <italic>P</italic><0.05）. The compliance rate of blood pressure was 95.95% （71/74）， was higher than 84.93% （62/73） in control group （<italic>χ</italic>²=5.171， <italic>P</italic><0.05）. The compliance rate of blood fat was 87.84% （65/74）， which was higher than 72.60% （53/73） （<italic>χ</italic>²=5.386， <italic>P</italic><0.05）. Conclusion:Qingfei Xiegantang can regulate the obesity， blood pressure， blood glucose and blood lipid components of MS， relieve clinical symptoms， improve IR， insulin sensitivity and islet <italic>β</italic> cell function， reduce inflammatory reaction， and increase vascular endothelial function of people of taiyin constitution with metabolic Syndrome.

Effect of Fluid Sheer Stress on Atherosclerosis and Progress of Research on Treatment of Sheer Stress Injury with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Cells in the arterial wall are constantly subjected to the shear stress generated by the blood flow. Shear stress plays a pivotal role in the formation of atherosclerosis. The endothelial cells located between the blood and the vessel wall have a unique response to the shear stress of the blood flow， which can convert mechanical stimulation into intracellular signals， thereby affecting the pathological process of atherosclerosis. Endothelial function is not only regulated by hormones， growth factors and other biochemical substances， but also affected by mechanical forces such as blood flow shear stress. Physiologically， shear stress can play an anti-atherosclerotic role in maintaining the homeostasis of endothelial cells. Pathological shear stress will lead to endothelial dysfunction and promote the progression of atherosclerosis. Under the mediation of different shear stress， the endothelial function can be regulated through epigenetic pathways or mechanically sensitive cation channels. Therefore， it is necessary to understand how various signal transduction pathways are affected by pathological shear stress， so as to cause endothelial dysfunction and atherosclerosis. Traditional Chinese medicine（TCM） has been increasingly recognized for its curative effect in treating atherosclerosis， with the advantages of few side effects， multiple targets and multiple mechanisms. In recent years， the understanding of the anti-atherosclerosis mechanism of TCM mediated by shear stress has gradually deepened. This review will take endothelial function as the breakthrough point， systematically sort out the influence of shear stress on the pathological process of atherosclerosis and the related molecular mechanisms. Meanwhile， it is the first time to summarize the latest research progress of Chinese medicine against shear stress damage by sorting out the existing literature. This article mainly clarify the relationship between shear stress， endothelial function， atherosclerosis and TCM， in order to provide a theoretical basis for the clinical treatment and pathological mechanism of atherosclerosis.

Study of endothelial function in pregnant women with gestational diabetes mellitus by flow mediated dilation of brachial artery

Background: The objective of the study was to assess vascular function in normal pregnant women and women with gestational diabetes and to study its temporal relationship with gestational age at 24-28-week POG and at 36-38-week POG and changes in FMD in postpartum period.Methods: Assessment of vascular function was done at 24-28-week POG, 36-38-week POG and at 6-12-week postpartum by flow mediated dilation of brachial artery in 37 healthy pregnant women and 37 pregnant women with GDM.Results: In GDM group mean FMD at 24-28 weeks of POG, at 36-38 weeks POG was lower as compared to the control group (11.225±6.20,8.464±6.09 versus 14.49±5.21, 10.898±4.12) although the difference in mean FMD in two groups was not statistically significant. It was found that the decrease in FMD at 36-38-week POG as compared to 24-28 weeks POG was statistically significant in both the groups (p<0.001).Conclusions: This study revealed that when endothelial function as assessed by FMD was compared at different period of gestation, the mean decrease in FMD at 36-38-week POG as compared to 24-28-week POG and 6-week post-partum was statistically significant in patients with GDM and as well as the control group, however this trend of change was same in both the groups and was not statistically significant when compared between the two group (GDM versus control). A negative correlation of FMD was found with BMI, and HBA1c, that was stronger in GDM group.