Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Role of brown adipose tissue in phlegm-dampness metabolic syndrome based on infrared thermal imaging / 中国中药杂志

This study aimed to explore the infrared manifestation and role of brown adipose tissue(BAT) in phlegm-dampness me-tabolic syndrome(MS), and to provide objective basis for clinical diagnosis and treatment of phlegm-dampness MS. Subjects were selected from the department of endocrinology and ward in the South District of Guang'anmen Hospital, China Academy of Chinese Medical Sciences from August 2021 to April 2022, including 20 in healthy control group, 40 in non phlegm-dampness MS group and 40 in phlegm-dampness MS group. General information, height and weight of the subjects were collected and body mass index(BMI) was calculated. Waist circumference(WC), systolic blood pressure(SBP) and diastolic blood pressure(DBP) was measured. Triglyceride(TG), high density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), leptin(LP), adiponectin(ADP) and fibroblast growth factor-21(FGF-21) were detected. The infrared thermal image of the supraclavicular region(SCR) of the subjects before and after cold stimulation test was collected by infrared thermal imager and the changes of infrared thermal image in the three groups were observed. In addition, the differences in the average body surface temperature of SCR among the three groups were compared, and the changes of BAT in SCR were analyzed. The results showed compared with the conditions in healthy control group, the levels of WC, SBP, DBP, TG and FPG in MS groups were increased(P<0.01), and the HDL-C level was decreased(P<0.01). Compared with non phlegm-dampness MS group, phlegm-dampness MS group had higher conversion score of phlegm dampness physique(P<0.01). According to the infrared heat map, there was no difference in the average body surface temperature of SCR among the three groups before cold stimulation. while after cold stimulation, the average body surface temperature of SCR in MS groups was lower than that in healthy control group(P<0.05). After cold stimulation, the maximum temperature of SCR and its arrival time in the three groups were as follows: healthy control group(3 min)>non phlegm-dampness MS group(4 min)>phlegm-dampness MS group(5 min). The thermal deviation of SCR was increased and the average body surface temperature of left and right sides were higher(P<0.01) in healthy control group and non phlegm-dampness MS group, while the thermal deviation of SCR did not change significantly in the phlegm-dampness MS group. Compared with that in healthy control group, the elevated temperature between left and right sides was lower(P<0.01, P<0.05), and compared with that in non phlegm-dampness MS group, the elevated temperature of left side was lower(P<0.05). The changes of the average body surface temperature of SCR in the three groups were in the order of healthy control group>non phlegm-dampness MS group>phlegm-dampness MS group. Compared with the conditions in healthy control group and non phlegm-dampness MS group, FINS, BMI and FGF-21 levels were increased(P<0.01,P<0.05), while ADP level was decreased(P<0.01, P<0.05) in phlegm-dampness MS group. Moreover, the LP level in phlegm-dampness MS group was higher than that in non phlegm-dampness MS group(P<0.01). It was observed in clinical trials that after cold stimulation, the average body surface temperature of SCR in MS patients was lower than that of the healthy people; the thermal deviation of SCR did not change significantly in the phlegm-dampness MS patients, and the difference in their elevated temperature was lower than that in the other two groups. These characteristics provided objective basis for clinical diagnosis and treatment of phlegm-dampness MS. With abnormal BAT related indicators, it was inferred that the content or activity of BAT in SCR of phlegm-dampness MS patients were reduced. There was a high correlation between BAT and phlegm-dampness MS, and thus BAT might become an important potential target for the intervention in phlegm-dampness MS.

Early risk factors for death in neonates with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide / 中国当代儿科杂志

OBJECTIVES@#To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO).@*METHODS@#A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk.@*RESULTS@#A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO2/FiO2 within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO2/FiO2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2.@*CONCLUSIONS@#Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO2/FiO2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.

Analysis of potential factors contributing to refusal of invasive strategy after ST-segment elevation myocardial infarction in China / 中华医学杂志(英文版)

BACKGROUND@#Reduced application of percutaneous coronary intervention (PCI) is associated with higher mortality rates after ST-segment elevation myocardial infarction (STEMI). We aimed to evaluate potential factors contributing to the refusal of PCI in STEMI patients in China.@*METHODS@#We studied 957 patients diagnosed with STEMI in the emergency departments (EDs) of six public hospitals in China. The differences in baseline characteristics and 30-day outcome were investigated between patients who refused PCI and those who underwent PCI. Multivariable logistic regression was used to evaluate the potential factors associated with refusing PCI.@*RESULTS@#The potential factors contributing to refusing PCI were older than 65 years (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.56-4.52, P 12 h) (OR 3.31, 95% CI 1.83-6.02, P < 0.001) and not being hospitalized in a tertiary hospital (OR 0.45, 95% CI 0.27-0.75, P = 0.002). Compared to men, women were older, were less often married, had a lower BMI and were less often hospitalized in tertiary hospitals.@*CONCLUSIONS@#Patients who were older, had lower economic or social status, and had poorer health status were more likely to refuse PCI after STEMI. There was a sex difference in the potential predictors of refusing PCI. Targeted efforts should be made to improve the acceptance of PCI among patients with STEMI in China.

Scr eening of key genes and pathways of brain aging and prediction of potential effective Chinese medicinals: based on bioinformatics / 中国中药杂志

Microarray data of hippocampal tissue(HC) of the cognitively intact elderly(60-99 years old) were compared with those of the middle-aged and the young(20-59 years old) by bioinformatics techniques to initially screen out differentially expressed genes(DEGs) and then predict potential effective Chinese medicinals for the treatment of brain aging. The gene expression profile(accession: GSE11882) was downloaded from the Gene Expression Omnibus(GEO) and DEGs were screened based on R package. The key DEGs were identified by STRING, Cytoscape and the plug-in, followed by Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Then the key genes and the medical ontology information retrieval platform(Coremine Medical) were mapped against each other to single out the Chinese medicinals for the treatment of brain aging and construct the " Chinese medicinal-active constituent-target" network. Among the resultant 268 DEGs(246 down-regulated and 22 up-regulated), the 15 key genes were mainly involved in biological processes such as leukocyte migration, neutrophil activation, cell chemotaxis, microglia activation and response to external stimulus, and pathways such as inflammatory process, immune response, cytokine-cytokine receptor interaction, PI3 K-Akt signaling pathway, Rap1 signaling pathway, chemokine signaling pathway and Toll-like receptor signaling pathway. The potential effective Chinese medicinals were Notoginseng Radix et Rhizoma, Ginseng Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma and Astragali Radix. The analysis of DEGs and key genes enhances the understanding of the mechanisms of brain aging. This study provides potential gene targets and ideas for the development of Chinese medicine for brain aging.

Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts on intestinal flora of vascular aging mice induced by high glucose and high lipid / 中国中药杂志

The aim of this paper was to observe the changes of intestinal flora in vascular aging mice, in order to explore the relationship between vascular aging and intestinal flora and the effects of extracts of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma on intestinal flora of vascular aging mice. A model of vascular aging in mice was induced through intrape-ritoneal injection with streptozotocin(STZ) combined with high-fat diet. Biochemical detection was performed on serum cholesterol(CHO), triglyceride(TG), high-density liptein cholesterol(HDL-C), low-density liptein cholesterol(LDL-C) and blood glucose(GLU). HE staining was used to detect mice thoracic aorta morphology, and the expressions of cyclin-dependent kinase inhibitor 2 A(p16) and cyclin-dependent kinase inhibitor 1 A(p21) protein in mice thoracic aorta were detected by Western blot. The 16 S rDNA gene of mice intestinal flora was detected by Illumina MiSeq high-throughput sequencing technology to explore the changes of intestinal flora in each group. The results demonstrated that the GLU level in low-dose and high-dose TCM groups decreased, but with unobvious changes in blood lipid indexes. Metformin could significantly decrease the levels of GLU(P<0.01), CHO and LDL-C in mice(P<0.05). Intravascular injury was not obvious in each drug group, and the expressions of p16 and p21 protein were significantly decreased(P<0.05). The intestinal flora of each group was mainly composed of Firmicutes(F) and Bacteroidetes(B) at the level of the phylum, but the B/F ratio was different from that of the youth group and the blank control group. The B/F ratio of the model group was significantly lower(P<0.01), and compared with the model group, the B/F ratio of the high-dose group and the metformin group was signi-ficantly higher(P<0.05). There were dominant and differential floras in the intestine of each group of mice. The results showed that extracts of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma could improve the intestinal flora structure and create a good intestinal environment by increasing the B/F ratio, which provides a new possible pathway for lowering blood glucose and blood lipids and delaying vascular aging.

Explore Protective Mechanism of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extract on Cardiac Aging in Diabetic Mice Through AMPK/mTOR Pathway / 中国实验方剂学杂志

Objective::To explore the protective mechanism of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma (GNC) extracts on cardiac aging in diabetic mice by observing the activation of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, changes of cardiac pathomorphological and related senescent proteins. Method::C57BL/6 male mice, SPF level, were randomly divided into normal control group and high-glucose group. The mice in high-glucose group were intraperitoneally injected with streptozotocin (STZ) and fed with high-fat diet. After successful modeling, they were randomly divided into model group, low-dose GNC group (0.819 g·kg-1), high-dose GNC group (1.638 g·kg-1) and metformin group (150 mg·kg-1). The drug was administered by gavage once a day for a continuous period of 9 weeks. 4-week-old male C57BL/6 mice were normally fed for 1 week as a youth group. General conditions of mice were observed. Hematoxylin-eosin (HE) staining combined with transmission electron microscope (TEM) was used to observe the cardiac pathomorphology in mice. Von Kossa staining was used to determine the degree of calcium salt deposition in cardiac micro vessels. Western blot was used to detect the activation of signaling pathways in myocardial tissue of mice, as well as the expression levels of matrix metalloproteinases-2 (MMP-2), tumor suppressor p53 (p53), and phospho-tumor suppressor p53 (p-p53). Result::As compared with the normal group, the blood glucose in the model group increased (P<0.01), as compared with the model group, the blood glucose in each administration group decreased significantly (P<0.05, P<0.01). The results of three pathological morphology experiments (HE, TEM, and Von Kossa) showed that as compared with the normal control group, the mice in model group showed cardiomyocytes hypertrophy, disordered arrangement of myocardial fibers, focal dissolving and necrosis, mitochondria swelling, degeneration, crest fracture, vacuolar alteration, disordered microvascular structure of the heart, uneven staining, and a large amount of calcium deposition in tunica media and intima. As compared with the model group, the pathomorphological changes of mice in each administration group were improved in varying degrees. Compared with the normal group, the expression levels of MMP-2, p53 and p-p53 protein in the model group were significantly increased (P<0.05, P<0.01), the protein ratios of p-liver kinase B2(LKB1)/LKB1, p-AMPK/AMPK were significantly decreased (P<0.05, P<0.01), and the average gray level of p-mTOR/mTOR and p-p70S6 kinase(p70S6k)/p70S6k protein was significantly increased (P<0.05, P<0.01), while the protein ratios of p-mTOR/mTOR, p-p70S6k/p70S6k were increased (P<0.01). As compared with the model group, the expression levels of MMP-2, p53 and p-p53 protein in each administration group were significantly decreased (P<0.05, P<0.01), the protein ratios of p-LKB1/ LKB1, p-AMPK/AMPK were significantly increased (P<0.05, P<0.01), while the protein ratios of p-mTOR/mTOR and p-p70S6k/p70S6k were decreased (P<0.05, P<0.01). Conclusion::STZ combined with high-fat diet can induce cardiac aging in mice, and GNC can improve cardiac aging in diabetic mice, which may be related to the inhibition of AMPK/mTOR pathway related protein expression.

Protective Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extracts on Myocardial Fibrosis in Diabetic Mice / 中国实验方剂学杂志

Objective::To investigate the protective effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma (GNC) extracts on myocardial fibrosis in diabetic mice by observing the degree of myocardial fibrosis and collagen types I (Collagen Ⅰ), collagen types Ⅲ (Collagen Ⅲ) and transforming growth factor-β1 (TGF-β1) protein expression in myocardial tissues. Method::A diabetic mice model was induced by streptozotocin (STZ) and high-fat diet. A normal control group was established. According to random number table method, diabetic mice were divided into model group, GNC low-dose and high-dose groups (0.819, 1.638 g·kg-1), and metformin group (150 mg·kg-1). Intragastrical administration was given in all groups, and the mice in normal control group received an equal dose of deionized water once a day for 9 weeks. The myocardial interstitial fibrosis in mice was observed by Masson trichromatic staining. Image-pro plus 6.0 analysis software was used to calculate the ratio of collagen area to total area. Immunohistochemistry was used to detect Collagen I, Collagen Ⅲ and TGF-β1 protein expression in myocardial tissues. The protein expression electrophoresis and gray value levels of Collagen I, Collagen Ⅲ and TGF-β1 in the myocardial tissues were detected by Western blot. Result::The results of Masson staining showed that as compared with the normal control group, the myocardial cells of diabetic mice were hypertrophic and disordered, and the myocardial stroma, especially the blue-stained collagenous fibers around the blood vessels, were heavily deposited and connected to each other in a network (P<0.01). As compared with the model group, the arrangement of myocardial cells was significantly improved in GNC low-dose and high-dose groups and metformin group, and the collagenous fibers in the myocardial stroma were significantly decreased (P<0.05). Immunohistochemistry and Western blot results showed positive expression of Collagen Ⅰ, Collagen Ⅲ and TGF-β1 in myocardial tissues, with significantly increased content of protein expression in diabetic mice (P<0.05, P<0.01). As compared with the model group, the positive protein expression decreased and the protein content tended to be normal in each administration group (P<0.05, P<0.01). Conclusion::High-fat diet combined with STZ can induce myocardial fibrosis in diabetic mice, and increase Collagen I, Collagen Ⅲ and TGF-β1 protein expression. Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts can improve myocardial fibrosis in diabetic mice by regulating the expression of Collagen I, Collagen Ⅲ and TGF-β1 protein.

Effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extracts on Expression of α-SMA and Runx2 Protein After High Glucose-induced Vascular aging in Mice / 中国实验方剂学杂志

Objective::To investigate the effects of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts (GNC) on the protein expression of α-smooth muscle actin (α-SMA) and runt-related transcription factor2(Runx2) after high glucose-induced vascular aging in mice, and elucidate the protective mechanism of GNC in delaying vascular aging. Method::Totally 130 male C57BL/6 mice were randomly divided into normal control group and high glucose group. The mice in high glucose group were intraperitoneally injected with streptozotocin (STZ). After successful modeling, the mice received high-fat diet for 7 months, and then they were randomly divided into model group, GNC low-dose and high-dose groups (0.819, 1.638 g·kg-1), and metformin group (150 mg·kg-1). The drug was given by intragastric administration once a day for 9 weeks. Seven days before tissues collection, a new batch of 4-week-old male C57BL/6 mice were purchased and fed normally for 1 week as a youth group. The general condition of the mice was observed. Morphological changes of the common carotid artery in mice were determined by hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Masson trichromatic staining was used to observe the fibrosis of common carotid artery in mice. The expression levels of matrix metalloproteinases-2 (MMP-2), cyclin-dependent kinase inhibitor 2A (p16), cyclic-dependent kinase inhibitor 1A (p21), α-SMA and Runx2 in the common carotid arteries of mice were detected by immunohistochemistry. Result::The results of HE, TEM and Masson showed that there was almost no change in the inimal and adventitial thickness, ultrastructure and relative contents of collagen and elastic fibers in the common carotid arteries of mice between the youth group and normal control group. As compared with the normal control group, the intima of the common carotid artery in the model group was not smooth, the endothelial cells were almost completely detached, the cytoplasm was lysed, the inner elastic membrane became thinner, fractured, or even detached, and the proliferating collagen fibers sneaked into the tunica media. The hyperplasia of tunica media and tunica adventitia was obvious and disordered (P<0.01). The vascular smooth muscle cells showed deformations, protuberances, bifurcations, and even fragmentation, and focal necrosis was observed. There were significantly more vacuoles, lysosomes, and obvious autophagy vesicles. The relative content of collagen and elastic fibers in vascular walls increased significantly (P<0.01). Compared with the model group, the above situation was relieved in each administration group (P<0.01). The results of immunohistochemistry showed that high glucose induced high expression of MMP-2, p16, p21 and Runx2 in the common carotid arteries(P<0.01), low expression of α-SMA(P<0.01), and the protein expression tended to be normal after drug intervention(P<0.05, P<0.01). Conclusion::High glucose can induce the aging of common carotid artery in mice and change the expression of α-SMA and Runx2 proteins. The Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts can delay vascular aging by regulating the protein expression of α-SMA and Runx2.

Mechanism of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma Extracts in Delaying High Glucose-induced Vascular Calcification in Mice / 中国实验方剂学杂志

Objective::To investigate the protective effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts on vascular calcification induced by high glucose in mice by observing the expression of osteopontin (OPN) and smooth muscle 22α (SM22α) as well as vascular calcium deposition in the common carotid artery and thoracic aorta of mice. Method::Totally 130 male C57BL/6 mice were randomly divided into normal control group and high glucose group. The mice in high glucose group were intraperitoneally injected with streptozotocin(STZ), and fed on a high-fat diet for 7 months. Then, the mice were randomly divided into model group, low-dose and high-dose Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts groups (0.819, 1.638 g·kg-1), and metformin group (150 mg·kg-1). Each group was intragastrically administered once a day for 9 weeks. The changes in blood glucose were measured. Seven days before the end of the administration, a group of 4-week old male C57BL/6 mice were purchased and fed normally for one week as a youth group. At the end of the administration, the common carotid artery and thoracic aorta tissues of the mice were collected. Von Kossa staining was used to determine the degree of calcium deposition in the common carotid artery and thoracic aorta. The expression levels of OPN and SM22α protein in the common carotid artery and thoracic aorta were detected by immunohistochemistry. The expression of OPN and SM22α protein in the common carotid artery of mice was determined by Western blot. Result::As compared with the young group, the blood glucose of the normal control group was slightly increased without statistical difference, the common carotid artery and thoracic aorta were uniformly stained, and no black granular precipitate was observed. As compared with the normal control group, the blood glucose of the model group was increased (P<0.01), with a large amount of brown-black particles deposited in the intimal elastic fibers, showing obvious calcium salt deposition. As compared with the model group, blood glucose was significantly decreased in each administration group (P<0.05, P<0.01), and the degree of vascular calcium salt deposition was significantly reduced. There were no significant changes in expression levels of OPN protein and SM22α protein in the common carotid artery and thoracic aorta between the youth group and normal control group. As compared with the normal control group, the expression of intimal OPN protein in the common carotid artery and thoracic aorta of the model group was positive, SM22α protein expression was weakly positive, and the gray value of OPN protein expression in the common carotid artery was significantly increased (P<0.01), while the gray value of SM22α protein was decreased significantly (P<0.01). As compared with the model group, the expression levels of intimal OPN protein and SM22α protein in the common carotid artery and thoracic aorta of each administration group were significantly improved, and the gray value of OPN protein expression in the common carotid artery was reduced (P<0.05, P<0.01), while SM22α protein expression was significantly increased (P<0.01). Conclusion::High glucose can induce calcification of common carotid artery and thoracic aorta in mice and accelerate vascular aging. This formation process may be related to the expression of OPN and SM22α. Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts can reduce vascular calcification and delay vascular aging by regulating the expression of OPN and SM22α.

Research Progress of Yiqi Huoxue Prescription in Treatment of Diabetic Angiopathy / 中国实验方剂学杂志

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia. Its main complications of diabetes, such as diabetic angiopathy, have seriously affected the quality of life for patients, and have become an important cause of death and disability. The underlying pathological changes include macrovascular lesions and microvascular lesions. Diabetic macrovascular lesions mainly involve thoracic aorta, coronary artery, carotid artery, cerebral artery and peripheral blood vessels, etc., and the common clinical diseases include coronary heart disease, stroke, peripheral neuropathy, lower extremity arteriosclerosis, etc. Diabetic microvascular lesions mainly involve the heart, brain, kidney and other microvessels. Nowadays, various new oral hypoglycemic agents and insulin have emerged in the society and are widely used in clinical practice. However, traditional Chinese medicines(TCMs) have stable curative effect, less side effect, and can improve glucose metabolism, lipid metabolism, insulin resistance, oxidative stress, expression of inflammatory cytokines, vascular endothelial injury, microcirculation disorders, balance of fibrinolysis system and blood coagulation system, and improve the syndromes of TCMs, etc. They have been widely recognized and applied in the prevention and treatment of diabetic angiopathy. A profound understanding on the etiology, pathogenesis and treatment of diabetic angiopathy has been formed in Chinese medicine. Therefore, in this paper, we would summarizes the understanding on Chinese medicine for diabetic angiopathy and the mechanism of Yiqi Huoxue prescription in the treatment of diabetic angiopathy in the past three years.

Exploration of Combinational Quality Control Method of Carbonized Ginger Based on HPLC Fingerprint and QAMS / 中国实验方剂学杂志

Objective::To establish the HPLC fingerprint of carbonized ginger and to determine the contents of zingerone, 6-gingerol, 6-shogaol, 10-gingerol, 8-shogaol and 10-shogaol with quantitative analysis of multi-components by single marker (QAMS). Method::The fingerprint of carbonized ginger was established by HPLC. All samples were analyzed by Waters SymmetryShield™ RP18 column (4.6 mm×250 mm, 5 μm) with gradient elution by acetonitrile(A)-water(B) (0-30 min, 25%-70%A; 30-50 min, 70%-90%A; 50-60 min, 90%A), the flow rate was 1.0 mL·min-1, the detection wavelength was set at 240 nm and the column temperature was 30 ℃. Zingerone, 6-gingerol, 8-gingerol, 6-shogaol, 10-gingerol, 8-shogaol and 10-shogaol was chosen as marker ingredients to establish HPLC fingerprint of carbonized ginger decoction pieces. Taking 6-gingerol as internal reference standard, the contents of zingerone, 6-shogaol, 10-gingerol, 8-shogaol and 10-shogaol were determined at the detection wavelength of 220 nm and 280 nm according to the relative correction factor. Result::The HPLC fingerprint of carbonized ginger was obtained and 10 common peaks were designated, and 7 of them were identified as zingerone, 6-gingerol, 8-gingerol, 6-shogaol, 10-gingerol, 8-shogaol and 10-shogaol, respectively. And there were no significant differences between the quantitative results of external standard method and QAMS. It is suggested that the content limits of carbonized ginger should be not less than 0.020%of zingerone (C11H14O3), 0.050%of 6-gingerol (C17H26O4), 0.120%of 6-shogaol (C17H24O3), 0.080%of 10-gingerol (C21H34O4), 0.030%of 8-shogaol (C19H28O3) and 0.050%of 10-shogaol (C21H32O3) calculated with reference to the dried products, respectively. Conclusion::The developed method is accurate and feasible, which can provide a simple and effective method for the quality control of carbonized ginger.

Research Progress of Traditional Chinese Medicine for Yiqi Huoxue Huatan in Treatment of Atherosclerosis / 中国实验方剂学杂志

The application of clinical medication and basic research progress of traditional Chinese medicine （TCM） for Yiqi Huoxue Huatan in the treatment of atherosclerosis （AS） were summarized. According to the different pathogenic sites of AS， the clinical research progress of TCM for Yiqi Huoxue Huatan in the treatment of AS and the commonly used TCM for the treatment of AS were summarized. Astragali Radix， Salviae Miltiorrhizae Radix， Quinquefolium Panax， Cocos Wolf Poria， Atractylodis Rhizoma， Rosea Rhodiola， which were Yiqi herbs， were mostly used for the treatment of AS. Wallichii Ligusticum， Salviae Miltiorrhizae Radix， Notoginseng Radix， Paeoniae Rubra Radix， Paeoniae Alba Radix， Angelicae Sinensis Radix， Semen Persicae， Tinctorius Carthamus， Achyranthis Bidentatae Radix， tea root， which were Huoxue herbs， were mostly used for the treatment of AS. Huatan herbs， including Kirilowii Maxim Trichosanthes， Pinelliae Rhizama， Acorus Tatarinowii Schott， Citri Reticulatae Pericarpium， Cum Bile Arisaema， Silicea Bambusae Concretio， Aurantii Immaturus Fructus， Bamboo Juice， were commonly used for the treatment of AS. According to the findings， TCM for Yiqi Huoxue was mostly combined with insect medicine and rattan medicine for the treatment of carotid atherosclerosis， combined with TCM for promoting Qi， relieving pain， dissipating blood stasis and reducing phlegm for the treatment of coronary heart disease， and combined with TCM for relaxing tendons and activating collaterals， resolving phlegm to benefit orifices， and invigorating spleen to remove dampness combined for the treatment of lower extremity sclerosis. In addition， the medication time， drug combination and improvement indexes were summarized. In basic studies， the experimental progress of this kind of medicine for the treatment of AS were summed up in the aspect of reducing inflammatory reaction， improving the abnormal lipid metabolism and improving the damage of inner membrane. At present， it was found that tanshinone， total saponins of stem and leaf of Panax Quinquefolium， extract of Trichosanthis Pericarpium. Qishen Yiqi dropping pill， Huxinkang tablet， Danlou tablet， Buyang Huanwutang combined with Gualou Xiebaitang， Huazhuo Tongmai powder were the main drugs for basic research， and the animal model， model characteristics and the mechanism of action were summarized. In order to provide a reference for the rational application of TCM for Yiqi Huoxue Huatan in the treatment of AS， the application law， the mechanism and characteristics of action and the future research directions of TCM for Yiqi Huoxue Huatan were summarized and reviewed.

Beneficial effects of nanosuspensions of honokiol in mice on high fat diet through suppression of hepatic gluconeogenesis / 药学学报

To investigate the potential hypoglycemic effect of nanosuspensions of honokiol and explore the underlying mechanisms, a high fat diet (HFD) was studied in C57BL/6J mice divided into five groups: normal diet (ND), HFD, HFD/honokiol-sodium carboxymethyl cellulose (CMC-Na) (Hono-CMC, 100 mg·kg-1), HFD/honokiol- Nano (Hono-Nano, 80 mg·kg-1), HFD/metformin (HFD/Met, 200 mg·kg-1). Fasting blood glucose (FBG) and body weights (BW) of mice were measured every seven days. After 30-day treatment, an oral glucose tolerance test (OGTT) was performed, and blood and tissue samples were collected for analysis. All animal experiments were approved by the Research Animal Care Committee of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. The data showed Hono-Nano and metformin reduced FBG, BW, and markedly improved OGTT of mice compared to HFD group (P<0.05). Hono-CMC produced nonsignificant impact on FBG, BW of mice, while OGTT of mice was improved by Hono-CMC (P<0.05). Meanwhile, none of these treated groups showed significant effects on regulating serum insulin levels, but all of them exhibited decreased serum glucagon levels notably compared to the HFD group (P<0.05). Western blot analysis revealed that honokiol up-regulated levels of p-AMPK and p-FOXO1 in liver tissue of HFD mice (P<0.05), which resulted in activation of AMPK and inhibition of FOXO1. Moreover, the expression of PEPCK (a key enzyme of gluconeogenesis) was decreased by honokiol (P<0.05). Taken together, our findings demonstrate that nanosuspension of honokiol is more effective than CMC-Na-suspension of honokiol on blood glucose controlling in HFD mice. The hypoglycemic effects of honokiol might rely on suppressing hepatic gluconeogenesis via activating AMPK and inhibiting FOXO1.

Clinical effect of exogenous pulmonary surfactant in the treatment of severe neonatal infectious pneumonia: a multicenter prospective clinical trial / 中国当代儿科杂志

OBJECTIVE@#To study the clinical effect of calsurf, a domestic exogenous pulmonary surfactant, in the treatment of severe neonatal infectious pneumonia.@*METHODS@#A total of 208 neonates with severe infectious pneumonia who hospitalized in 5 hospitals of China were enrolled. According to their parents' wishes on admission, these neonates were administered with conventional treatment (control group; n=81) and calsurf  treatment + conventional treatment (calsurf treatment group, n=127). The two groups were compared in terms of the degree of oxygen dependence on admission, blood gas parameters before and after treatment, lung ultrasound results, duration of mechanical ventilation, length of hospital stay, hospital costs, complications and prognosis.@*RESULTS@#Compared with the control group on admission, the calsurf treatment group had significantly higher inhaled oxygen concentration and partial pressure of carbon dioxide and significantly lower arterial partial pressure of oxygen and oxygenation index (P<0.01). After 1 hour of treatment, both groups had significant improvements in the above indices (P<0.05), and the improvements were more significant in the calsurf treatment group (P<0.05). After 4-6 hours of calsurf administration, there was a significant reduction in the degree of pulmonary consolidation. The calsurf treatment group had significantly shorter duration of mechanical ventilation and length of hospital stay than the control group, while there was no significant difference in the incidence rate of complications between the two groups. The neonates of both groups had a good prognosis.@*CONCLUSIONS@#In neonates with severe infectious pneumonia, calsurf treatment can significantly improve oxygenation, reduce the degree of pulmonary consolidation, and shorten the duration of mechanical ventilation and length of hospital stay. Therefore, it should be considered in neonates with severe infectious pneumonia.

Relationship Between the Changes of Left Atrium, Pulmonary Vein Ostia and AF Recurrence After Radiofrequency Catheter Ablation by Enhanced Cardiac MRI Evaluation / 中国循环杂志

Objectives: To evaluate the changes of left atrial volume (LAV) and the maximum ostial cross-sectional area (CAS) of pulmonary vein (PV) in atrial fibrillation (AF) patients after circumferential pulmonary vein isolation radiofrequency catheter ablation (CPVA-RFCA) and to explore their relationship to AF recurrence by enhanced cardiac MRI evaluation. Methods: Our research included in 2 groups: Control group, n=20 healthy subjects and AF group, n=78 patients whom were classified into 2 subgroups as Paroxysmal AF subgroup, n=46 and Persistent AF subgroup, n=32; 66 patients received CPVA-RFCA and based on 6 months post-operative recurrence, they were divided into another set of 2 groups: AF recurrent subgroup, n=17 and Non-AF recurrent subgroup, n=49. Pre- and 6 months post-operative maximum ostial CSA of PV were measured by enhanced cardiac MRI, LAV were obtained by 3D reconstruction and the differences were compared between AF group and Control group, Paroxysmal AF subgroup and Persistent AF subgroup, AF recurrent subgroup and Non-AF recurrent subgroup; their relationships to AF recurrence were studied.Results: Compared with Control group, AF group had increased LAV and elevated ostial CSA of superior PV (SPV), both P<0.05. Compared with Paroxysmal AF subgroup, Persistent AF subgroup had increased LAV and elevated ostial CSA of SPV, both P<0.05. Compared with pre-operative condition, at 6 months after the operation, Non-AF recurrent subgroup showed reduced ostial CSAs in left SPV (LSPV), right SPV (RSPV), right inferior PV (RIPV) and decreased LAV, all P<0.05;while AF recurrent subgroup showed expanded RSPV and increased LAV,allP<0.05.Post-operative reductions of LAV and ostial CSA of SPV had close correlation; multivariate Logistic regression analysis indicated that LAV (HR=1.05, P<0.01)and ostial CSA of RSPV(HR=1.09,P=0.05)were related to AF recurrence after RFCA. Conclusions: CAPV-RFCA could reverse left atrial and PV remodeling in AF patients, LAV and ostial CSA of RSPV were related to post-operative AF recurrence.

Study on screening antitumor active fractions and chemical components in active fractions from root of Anaycclus pyrethrum / 中国中药杂志

Components that systematic separated from the root of Anaycclus pyrethrum were identified, in order to lay a foundation for future study of the root of A. pyrethrum. The CCK-8 assay showed that dichloromethane fraction exhibited the highest degree of cytotoxicity than others. Ten monomeric components were obtained from dichloromethane fraction and ethyl acetate fraction extracted from the root of A. pyrethrum, including 7 N-alkylamides, one coumarin and two flavonoid glycosides. They were identified as tetradeca-2E,4E,8E-trienoic acid 4-hydroxyphenylethylamide(1), deca-2E,4E-dienoicacid isobutylamide(2), undeca-2E,4E-diene-8,10-diynoic acid phenylethylamide(3), tetradeca-2E,4E-dienoic acid 4-hydroxyphenylethylamide(4), tetradeca-2E,4E-diene-8,10-diynoic acid isobutylamide(5), deca-2E,4E- dienoic acid 4-hydroxyphenylethylamide(6), dodeca-2E,4E-dienoic acid 4-hydroxy -phenyl-ethylamide(7), isoscopoletin(8), quercetin-7-O-β-D-glucopyranoside(9), isorhamnetin-7-O-β-D-glucopyranoside(10). Among them, compound 1 was identified as a new compound, Compounds 2-4, 8-10 were isolated from this herb for the first time.

Clinical value of multi-detector computed tomography source image on detecting extracoronary abnormalities / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess the clinical value of multi-detector computed tomography (MDCT) source image on detecting extracoronary abnormalities in a large cohort of patients with suspected coronary artery disease (CAD).</p><p><b>METHOD</b>MDCT source images from 3240 consecutive patients (mean 64.5 years) with suspected CAD were reviewed retrospectively by 2 readers.Extra-coronary findings were classified according to involved organ and level of clinical significance.Following organs were examined:lungs, upper abdomen, spine, chest wall, mediastinum and vascularatures. Clinical relevance of extracoronary findings was considered as either "significant" or "non-significant"."Significant" findings were subclassified as score 1:findings necessitating immediate therapeutic actions, or score 2:findings with uncertain clinical or prognostic relevance, requiring clinical awareness, follow-up or further investigations (non-urgent)."Non-significant" findings were assigned to score 3:findings without clinical implication. The irrelevant incidental findings (e.g. spinal degenerative changes, aortic calcification) were not analyzed.</p><p><b>RESULTS</b>Extracoronary findings was evidenced in 330 patients with 424 abnormalities, 20.3% (67/330) patients had multiple lesions, 16.5% lesions were located in the lungs, 13.2% lesions found in the upper abdomen, 56.8% (241/424) lesions evidenced in the mediastinum,0.9% (4/424) lesions seen in the spine and chest wall, 13.9% (53/424) lesions were related to other vascular disease. Pleural effusion accounts for 5.5% of the mediastinum lesions.Incidence of heart cavity enlargement, heart valve disease, pericardial effusion/calcification, atrial/ventricular perfusion defects, myocardial disease, congenital heart disease, ventricular aneurysm was 14.7% (56/380), 15.5% (59/380), 10.8% (41/380), 3.9% (15/380), 0.8% (3/380), 1.6% (6/380), and 1.8% (7/380) respectively. The clinical significance score 1-3 was 8.5% (36/424) , 81.1% (344/424) , and 10.4% (44/424) respectively.Incidence of detected extracoronary findings was the highest by bone window and the lowest by lung window.Incidence of extracoronary findings was not related to CAD (χ2 = 81.76, C = 0.155, P > 0.05).Inter-reader agreement on extracoronary findings was excellent (Kappa = 0.934, P > 0.05).</p><p><b>CONCLUSION</b>Our data show that it is of clinical value to observe and report extracoronary findings with source image of cardiac MDCT.</p>

Causes of insufficient anticoagulation in Chinese patients with non-valvlar atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the factors responsible for the insufficient application of oral anticoagulation (OAC) in Chinese patients with non-valvular atrial fibrillation.</p><p><b>METHODS</b>The research is a single center registration study in a tertiary referral hospital in Beijing. The general characteristics, history of atrial fibrillation, comorbidities and anticoagulation treatment were obtained from all patients.Factors affecting the oral Walfarin use were evaluated by univariable and multivariable regression analysis.</p><p><b>RESULTS</b>OAC therapy with Walfarin was applied on Only 214(39.4%) out of 576 consecutive patients with non-valvular atrial fibrillation. The OAC rate was 30.3% among non-ablation patients. Patients with persistent atrial fibrillation, diabetes, chronic heart failure, history of ischemic stroke/TIA and higher CHA2DS2-VASc score were more likely prescribed with Walfarin. Multivariable regression analysis showed that persistent fibrillation, history of chronic heart failure, ischemic stroke/TIA and non-coronary heart disease predicted the treatment with Walfarin.</p><p><b>CONCLUSIONS</b>OAC use is extremely low in Chinese patients with non-valvular atrial fibrillation. More efforts are warranted to improve OAC use in these patients.</p>

Transesophageal echocardiography guided cannulation for peripheral cardiopulmonary bypass during robotic cardiac surgery / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Minimally invasive cardiac surgery and closed chest cardiopulmonary bypass (CPB) techniques continue to evolve. Previous reports have demonstrated the benefits of fluoroscopy guided cannulation for endovascular CPB during port access cardiac surgery. However, few data are available on the role of transesophageal echocardiography (TEE) guided cannulation for peripheral CPB during robotic cardiac surgery. The purpose of this study was to evaluate TEE guided cannulation for peripheral CPB during robotic cardiac surgery.</p><p><b>METHODS</b>We performed a retrospective analysis of intraoperative data of 129 consecutive patients underwent robotic cardiac surgical procedures requiring peripheral CPB from September 2007 to August 2011, which was established using femoral arterial inflow and kinetic venous drainage by way of the femoral vein and right internal jugular vein and a transthoracic aortic cross clamp. TEE was used to guide cannulation of the inferior vena cava (IVC), superior vena cava (SVC), and ascending aorta (AAO). The success rate and the complication rate of TEE guided cannulation for peripheral CPB were evaluated and compared with the results of fluoroscopy guided cannulation in a historical control group.</p><p><b>RESULTS</b>One hundred and twenty-nine consecutive patients underwent robotic cardiac surgical procedures requiring peripheral CPB. There were 67 female (51.9%) and 62 male (48.1%) patients, ranging in age from 13 to 70 years (mean (43.94 ± 13.82) years) and body surface area 1.32 to 2.39 m(2) (mean (1.71 ± 0.20) m(2)). Some 61 (47.3%) patients underwent mitral valve repair, 27 (20.9%) mitral valve replacement, 27 (20.9%) left atrial myxoma removal, and 14 (10.9%) ventricular septal defect repair. Of the 129 patients, TEE guided cannulation of the IVC or SVC was successful in all patients (100%), and no puncture related complications occurred in all patients. Of the 129 patients, successful cannulation of the AAO was achieved in all patients (100%), and aortic perforation occurred in 1 patient (0.78%) under TEE guidance. Of the 42 patients in the historical control group, successful cannulation occurred in 39 patients (92.86%), and major complications occurred in 3 patients (7.14%) under fluoroscopy guidance. TEE guided cannulation of the AAO significantly improved success rate (100% vs. 92.86%, P = 0.014) and decreased complication rate (0.78% vs. 7.14%, P = 0.046).</p><p><b>CONCLUSION</b>TEE may be useful in guiding successful placement of the cannulae in the IVC, SVC, and AAO in the establishment of peripheral CPB during robotic cardiac surgery.</p>