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.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Light is the main source for plants to obtain energy.Asarum forbesii is a typical shade medicinal plant, which generally grows in the shady and wet place under the bushes or beside the ditches.It can grow and develop without too much light intensity.This experiment explores the effects of shading on the growth, physiological characteristics and energy metabolism of A.forbesii, which can provide reference and guidance for its artificial planting.In this experiment, A.forbesii was planted under 80%, 60%, 40%, 20% and no shade.During the vigorous growth period, the photosynthetic physiological characteristics such as fluorescence parameters, photosynthetic parameters, photosynthetic pigment content and ultrastructure, as well as the content of mitochondrial electron transport chain(ETC) synthase and nutrients were measured.The results showed that the photosynthetic pigment content, chlorophyll fluorescence parameters and net photosynthesis rate(P_n) decreased with the decrease of shading.Under 20%-40% shading treatment, the plants had damaged ultrastructure, expanded and disintegrated chloroplast, disordered stroma lamella and grana lamella, and increased osmiophi-lic granules and starch granules.The activities of nicotinamide adenine dinucleotide dehydrogenase(NADH), succinate dehydrogenase(SDH), cytochrome C oxidoreductase(CCO) and adenosine triphosphate(ATP) synthasewere positively related to light intensity.With the reduction of shading, the content of total sugar and protein in nutrients increased first and then decreased, and the content was the highest under 60% shade.In conclusion, under 60%-80% shading treatment, the chloroplast and mitochondria had more complete structure, faster energy metabolism, higher light energy-conversion efficiency, better absorption and utilization of light energy and more nutrient synthesis, which was more suitable for the growth and development of A.forbesii.
Asarum ; Chlorophyll/metabolism* ; Chloroplasts ; Energy Metabolism ; Photosynthesis/physiology* ; Plant Leaves/metabolism*

ObjectiveThis study aims to explore the potential molecular mechanism of Gegen Qinliantang （GQL） in the intervention of atherosclerosis （AS） based on network pharmacology and molecular docking. MethodThe active components and targets of each medicinal in GQL were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and AS-related genes from 7 databases. Thereby， the anti-AS targets of GQL were screened out. Cytoscape 3.8.0 was employed to construct the "component-target" network， and STRING the protein-protein interaction （PPI） network. Core targets were screened out with CytoNCA. R clusterProfiler was used for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of target genes， which were then visualized. Finally， molecular docking of the top ten active components with the core targets of AS was performed and the binding affinity was compared with that between atorvastatin and the core targets. ResultIn the end， 150 active components of GQL， 20 289 AS targets， and 213 common targets were retrieved， and 48 core common targets were screened out. They were mainly involved in the GO terms of nuclear receptor activity， ligand activation， and transcription factor activity and the pathways of fluid shear force and AS， advanced glycation end products-receptor for advanced glycation end products （AGE/RAGE）， interleukin-17 （IL-17）， tumor necrosis factor （TNF）， Toll-like receptor pathways and other signaling pathways closely related to AS. The molecular docking results showed that the effective components of GQL had high binding affinity to core targets of AS， and the binding affinity was even higher than that between the atorvastatin and core targets. The five groups with high binding affinity were puerarin-TNF， baicalein-inducible nitric oxide synthase 2 （NOS2）， puerarin-NOS2， and formononetin-NOS2， wogonin-NOS2. ConclusionThe above result provides new ideas for further exploration of this classical decoction.

Aim To research the effect of PDG on bone metabolism in young rats. Methods The experimental rats were randomly divided into contro group, PDG-25 group and PDG-50 group. PDG-25 group and PDG-50 group were given PDG at the dose of 25 mg·kg

【Objective】 To retrospectively analyze the differences of clinicopathological parameters and molecular biological characteristics between ultrasound false negative and true positive breast cancer cases and summarize the clinical characteristics of these cases. 【Methods】 A total of 414 invasive breast cancer cases in Guangdong Women and Children Hospital between January 1st, 2018 and December 31st, 2019 were enrolled in this study. According to the BI-RADS classification standard of ultrasound, they were divided into false negative group and true positive group. The differences of onset age, tumor size, tumor histological grade, lymph node metastasis, estrogen receptor(ER), progesterone receptor (PR), human epidermal growth factor receptor(HER2), Ki-67, fiber reaction, vascular hyperplasia, lymphocyte infiltration and necrosis between the two groups were compared and analyzed. The differences with statistical significance were analyzed by multivariate logistic regression analysis. 【Results】 These 414 invasive breast cancer cases were composed of 43 false negative cases and 371 true positive cases. There was no significant difference in histopathological type between the two groups(P = 0.250). In the false negative group, the rate of luminal A(32.6%) and basal-like(27.9%) cases was respectively higher than that of the true positive group(17.8%, 14.3%), whereas the rate of HER2 overexpression (6.9%) cases was lower than that of the true positive group(32.1%), with statistical significance(P < 0.05). The rate of luminal B cases in the false negative group(32.6%) was not significantly different from that in the true positive group (35.8%, χ² = 0.182, P = 0.669). Compared with the true positive group, there was no significant difference in tumor histological grade(χ² = 5.129, P = 0.077), ER expression(χ² = 1.666, P = 0.197), PR expression(χ² = 0.290, P = 0.590), HER2 expression(χ² = 3.378, P = 0.066), fiber reaction(χ² = 5.353, P = 0.069), lymphocyte infiltration(χ² = 2.023, P = 0.155) and necrosis(χ² = 0.468, P = 0.494), whereas the differences of the tumor size(P < 0.001), lymph node metastasis(χ² = 43.184, P < 0.001), Ki-67 expression(χ² = 9.293, P = 0.010), age(χ² = 10.334, P = 0.006) and vascular hyperplasia(χ² = 5.937, P = 0.015) were statistically significant. In the false negative group, the rate of tumor size ≤ 2 cm(81.4%, 35/43 vs. 33.7%, 125/371), no lymph node metastasis(97.7%, 42/43 vs. 44.7%, 166/371), Ki-67 expression > 70%(18.6%, 8/43 vs. 5.9%, 22/371), age ≤ 45 years(65.1%, 28/43 vs. 41.2%, 153/371) and vascular hyperplasia number ≤ 3(74.4%, 32/43 vs. 55.0%, 204/371) were higher than that in the true positive group, respectively. Multivariate logistic regression analysis showed that only tumor size ≤ 2 cm(OR = 6.791, P < 0.001) and no lymph node metastasis(OR = 43.333, P < 0.001) were independent risk factors for the false negative ultrasound results. 【Conclusions】 Luminal A and HER2 overexpression breast cancer cases are easier to be underestimated by ultrasound BI-RADS classification. Patients with tumor size ≤ 2 cm and no lymph node metastasis are prone to have false negative breast ultrasound results, which should be regarded with more care.

OBJECTIVE: To study the clinical effect and safety of clopidogrel combined with aspirin in antithrombotic therapy for children with Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA). METHODS: A total of 77 KD children who were diagnosed with multiple small/medium-sized CAAs by echocardiography between January 2013 and June 2018 were enrolled. They were randomly divided into observation group with 38 children (treated with clopidogrel and aspirin) and control group with 39 children (treated with low-molecular-weight heparin and aspirin). All children were followed up regularly, and the first 3 months of the course of the disease was the observation period. The children were observed in terms of the change of the coronary artery and the incidence of complications. RESULTS: At month 3 of follow-up, among the children in the observation group, 6 had normal coronary artery, 11 had coronary artery retraction, 19 had stable coronary artery, and 2 progressed to giant coronary aneurysm; among the children in the control group, 7 had normal coronary artery, 12 had coronary artery retraction, 19 had stable coronary artery, and 1 progressed to giant coronary aneurysm; there was no significant difference in the change of the coronary artery between the two groups (P>0.05). There were 2 cases of epistaxis and 6 cases of skin ecchymosis in the observation group, and 1 case of epistaxis and 7 cases of petechiae and ecchymosis at the injection site in the control group, and no other serious bleeding events were observed in either group. CONCLUSIONS Clopidogrel combined with low-dose aspirin is safe and effective in antithrombotic therapy for children with KD complicated by CAA.
Aspirin ; therapeutic use ; Child ; Clopidogrel ; Coronary Aneurysm ; drug therapy ; etiology ; Coronary Vessels ; Fibrinolytic Agents ; Humans ; Mucocutaneous Lymph Node Syndrome ; complications

Objective To observe the effect of Kidney-nourishing, Blood-activating, Phlegm-resolving and Resuscitation-inducing Decoction(KBPRD)on the expression of N-methyl-D-aspartate(NMDA)receptor subtype 1,2A,2B(NR1,NR2A,NR2B)in the cochlear spiral ganglion neurons(SGN)of tinnitus rats and to explore its mechanism, thus to provide experimental evidence for the treatment of tinnitus with KBPRD. Methods Sixty rats were randomly divided into normal group,model group,western medicine group,and low-,middle-,and high-dose Chinese medicine groups, 10 rats in each group. Rats were given intraperitoneal injection of sodium salicylate combined with water deprivation to induce tinnitus model. After successful establishment of the model, the rats in low-,middle-,and high-dose Chinese medicine groups were given gastric administration of KBPRD in the dosage of 5.5, 11, 22 g·kg-1·d-1 respectively, the rats in western medicine group were given gastric administration of 5 mg·kg-1·d-1 of carbamazepine,and rats in the model group and normal group were given gastric administration of 2 mL of normal saline,once every day,treatment time covering 8 weeks. The expression levels of NR1,NR2A,and NR2B in the cochlear SGN was detected by immunoblotting and real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR)after 8 weeks of treatment. Results Compared with the normal group,the expression levels of NR1, NR2A and NR2B in the model group were increased, the difference being significant (P < 0.05). Compared with the model group,the expression of NR1,NR2A and NR2B in low-,middle-,and high-dose Chinese medicine groups were significantly decreased(P<0.05).Conclusion KBPRD is effective on relieving tinnitus of rats, and its mechanism is correlated with lowering the increased expression of NR1,NR2A and NR2B in SGN of tinnitus rats.

Objective To explore the clinical value of indocyanine green (ICG) fluorescence navigation combined with carbon nanoparticles (CNP) in sentinel lymph node biopsy (SLNB) for patients with early breast cancer. Methods A total of 294 early breast cancer patients with axillary node negative in Department of Breast Surgery, Foshan Hospital Affiliated to Sun Yat-Sen University from June 2013 to April 2016 were retrospectively analyzed. Of the patients, 149 cases underwent SLNB with ICG combined with CNP (combination group), while 145 cases underwent SLNB with methylene blue alone (MB group). If the intraoperative pathology results of sentinel lymph nodes (SLNs) were negative, axillary lymph node dissection (ALND) was avoided. The SLNs detection rate, detection number, metastatic SLNs detection rate in SLNB were compared between two groups. The influence of age and body mass index (BMI) on SLNs detection rate was also analyzed. Results In the combination group, subcutaneous lymphatic channels were successfully visualized in 145 patients, and the detection rate was 97.3％(145/149). The fluorescence of SLNs was successfully detected in 143 patients, and the detection rate was 95.9％(143/149). The detection rate of SLNs was higher in the combination group than that of methylene dye alone group (97.9％vs. 91.0％,χ2=6.902,P<0.05). The average number of detected SLNs was higher in the combination group than that of methylene dye alone group (4.5±1.6 vs. 3.2±1.5,t=4.476,P<0.05). Fifty-eight metastatic SLNs were found in 715 SLNs in the combination group (8.1％), and 26 in 544 SLNs in MB group (4.7％). The detection rate was significantly higher in the combination group than that of methylene dye alone group (χ2=13.714,P<0.01). Age and BMI showed no influence on the detection rate and accuracy of SLNB in two groups (P>0.05). Conclusion The combined tracing of ICG fluorescence and carbon nanoparticles for SLNB has showed a better stability and operability in patients with early breast cancer, which is recommended to be a new SLNB method.

Objective To observe the effects of therapy of wound-pus promoting granulation tissue growth guided by drug-wound interaction theory on the related factors in granulation tissue during the healing of chronic skin ulcer in rats based on drug-wound interaction. Methods Twenty-four rats were randomly divided into normal group, model group, control group, and treatment group, 6 rats in each group. The rats in the normal group had no skin ulcer and was given normal feeding,and the rats with chronic skin ulcer in the other 3 groups were induced by compound factors-overlapped method of hormone intervention-skin defect-bacterial infection. After modeling,the model group was given external use of saline gauze dressing,the control group given external use of vaseline gauze dressing,and the treatment group given external use of Shengji Xiangpi Ointment,changing fresh dressing for wound daily,the treatment lasting for 14 days. Wound sample was taken from the left back of rats, and therapeutic effect was evaluated according to the changes in the wound surface of the rat right back. After intervention for 3,7,and 14 d,the secreta and granulation tissue in the wound surface of rats were observed, the expression levels of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase(iNOS), arginine-1 (Arg-1), and Notch1 in granulation tissue of rat ulcer wound were measured by enzyme-linked immunosorbent assay (ELISA). Results The wound in the treatment group has been healed after treatment for 14 days (P < 0.05 or P < 0.01 as compared with the diameter of the ulcer in the model group and the control group) . At the early stage of wound repairing (3 d),the expression levels of VEGF and Arg-1 in the treatment group were increased, and Notch1 expression level was decreased, the difference being statistically significant as compared with those of the model group and the control group (P < 0.05). At the late stage of wound repairing (14 d),the expression level of iNOS in the treatment group was increased,and the difference was statistically significant as compared with that of the model group(P < 0.05). Conclusion The therapy of wound-pus promoting granulation tissue growth guided by drug-wound interaction theory can promote the healing of chronic skin ulcerative wound in rats and improve the general condition of rats. The therapeutic mechanism may be associated with firstly inhibiting the expression of iNOS induced by M1 type macrophage at early stage and then promoting M2 type macrophage phenotype index Arg-1 expression,and regulating the expression of VEGF and Notch1 in the granulation tissue.

MicroRNAs (miRNAs) are a family of non-coding RNA that are able to adjust the expression of many proteins, including ATP-binding cassette transporter and organic cation transporter. We sought to evaluate the effect of miR-511 on the regulation of OATP1B1 expression by free fatty acids. When using free fatty acids to stimulate Chang liver cells, we found that the expression of miR-511 increased significantly while the expression of OATP1B1 decreased. We also proved that SLCO1B1 is the target gene of miR-511 with a bioinformatics analysis and using the dual luciferase reporter assay. Furthermore, the expressions of SLCO1B1 and OATP1B1 decreased if transfecting Chang liver cells with miR-511, but did not increase when transfecting the inhibitors of miR-511 into steatosis cells. Our study indicates that miR-511 may play an important role in the regulation of OATP1B1 expression by free fatty acids.
Computational Biology ; Fatty Acids, Nonesterified ; Humans ; Liver ; Luciferases ; MicroRNAs ; RNA, Untranslated