Anticoagulation status and adherence in patients with atrial fibrillation hospitalized for ACS and the impact on 1-year prognosis: a multicenter cohort study / 中华心血管病杂志

Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.

Impact of empagliflozin on peak oxygen uptake in HFmrEF patients: a randomized controlled trial / 中华心血管病杂志

Objective: To evaluate the impact of empagliflozin on peak oxygen uptake (VO2peak) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods: In this randomized controlled trial, consecutive HFmrEF patients admitted to the Department of Cardiology of China-Japan Friendship Hospital from September 2019 to October 2020 were screened, and randomly assigned to empagliflozin group (EG) or conventional group (CG) using a random number table. The enrolled patients were treated according to the guidelines, and patients in the empagliflozin group received additional empagliflozin (10 mg, once a day, orally) on top of the conventional treatment. The primary end points were VO2peak at 6 months after treatment, and the secondary end points included other parameters of cardiopulmonary exercise test (CPET), 6-minute walking distance, N-terminal B-type pro-natriuretic peptide (NT-proBNP) level, and Kansas City Cardiomyopathy Questionnaire (KCCQ) score. Results: A total of 112 patients were included (mean age 69 (57, 78) years, 84 male (75.0%)). There were 55 cases in CG group and 57 cases in EG group. There were no significant differences in baseline data including age, sex, body mass index, left ventricular ejection fraction, systolic blood pressure, heart rate, estimated glomerular filtration rate, glycosylated hemoglobin, hemoglobin, NT-proBNP, daily dose of tolasemi, combined medication, CPET parameters, the proportion of New York Heart Association heart function Ⅲ/Ⅳ, history of coronary heart disease, history of hypertension, history of diabetes (all P>0.05). At 6 months after treatment, VO2peak was significantly higher in EG group than in CG group(P=0.023). VE/VCO2 slope was significantly lower in EG group than in CG group(P=0.034). Oxygen uptake efficiency slope was significantly higher in EG group than in CG group(P=0.038). The level of NT-proBNP was significantly lower in EG group than in CG group(P=0.020). Six-minute walking distance was significantly higher in EG group than in CG group(P=0.037). KCCQ score was significantly higher in EG group than in CG group(P=0.048). Exercise oscillatory ventilation decreased in both groups (1 case in each group, P>0.05). Conclusion: Empagliflozin can significantly improve VO2peak in patients with HFmrEF.

Network Meta-analysis of Efficacy of Five Classical Prescriptions for Acute Attack of Asthma in Children / 中国实验方剂学杂志

ObjectiveTo compare and evaluate the clinical efficacy of five classical prescriptions for acute attack of bronchial asthma （BA） and cough variant asthma （CVA） in children， and to further compare and assess the effect of them on cold-induced asthma or heat-induced asthma. MethodRandomized controlled trials （RCT） on the treatment of acute attack of asthma with five classical prescriptions （Sanzi Yangqintang， Maxing Shigantang， Shegan Mahuangtang， Xiao Qinglongtang， and Dingchuantang） were retrieved from China Science and Technology Journal Database （VIP）， China National Knowledge Infrastructure （CNKI）， and Wanfang Data （from establishment to August 15， 2021）. The eligible RCT were evaluated and the data were extracted for network Meta-analysis by Stata 16.0. ResultA total of eligible 47 RCT were screened out， involving 5 114 children with acute attack of asthma and 10 intervention measures. Among them， 16 RCT （1 912 children， 6 intervention measures） were about the cold-induced asthma and 10 RCT （1 054 cases， 4 intervention measures） focused on the heat-induced asthma. According to the Meta-analysis， among the 10 interventions， Maxing Shigantang + routine treatment of western medicine demonstrated the most significant effect， and the effect of the interventions was in the following order： Maxing Shigantang + routine treatment of western medicine > routine treatment of western medicine， Shegan Mahuangtang + routine treatment of western medicine> Xiao Qinglongtang + routine treatment of western medicine > Shegan Mahuangtang > Dingchuantang + routine treatment of western medicine. For the cold-induced asthma， the effect of Shegan Mahuangtang + routine treatment of western medicine was remarkable， and for the heat-induced asthma， the corresponding intervention was Dingchuantang + routine treatment of western medicine. Shegan Mahuangtang was outstanding in improving the percentage of forced expiratory volume in the first second in predicted value （FEV1%）. ConclusionThe combination of western medicine with the five prescriptions was more effective than the western medicine alone， particularly the combination with Maxing Shigantang. The combination of Shegan Mahuangtang and western medicine was outstanding in the treatment of cold-induced asthma， while the corresponding intervention for heat-induced asthma was the combination of Dingchuantang and western medicine. However， a large number of RCT with scientific design and higher quality are still needed to verify the conclusion.

Effect of Baofeikang Granule on Pulmonary Fibrosis in Rats by Regulating Wnt/β-catenin Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the intervention effect of Baofeikang granule （BFK） on the rat model of pulmonary fibrosis through the Wnt/β-catenin signaling pathway. MethodAfter adaptive feeding for one week， 50 healthy rats were randomly divided into a blank group （n=8） and an experimental group （n=42）. After anesthesia， the rats in the experimental group were injected with bleomycin sulfate solution （5 mg·kg-1） into the trachea for the induction of the pulmonary fibrosis model. Those in the blank group were injected with the same amount of normal saline under the same manipulation. On the 7th day after modeling， one of the remaining 33 rats alive was randomly removed， and the other 32 model rats were assigned into a model group （n=8）， a prednisone acetate （1.17 mg·kg-1） group （n=8）， a low-dose BFK （13.59 g·kg-1） group （n=8）， and a high-dose BFK （27.18 g·kg-1） group （n=8）. The rats in the groups with drug intervention were treated correspondingly by gavage once per day for 21 days， and those in the blank group and the model group received the same amount of normal saline. The pulmonary compliance and ventilatory function， the scores of pathological changes and fibrosis， the levels of type Ⅰ collagen （Col Ⅰ） in lung tissues and hydroxyproline （HYP） in the serum， and the relative expression of Wnt3a and β-catenin protein in lung tissues were compared. ResultCompared with the blank group， the model group showed reduced pulmonary function indexes， such as forced vital capacity （FVC）， peak expiratory flow （PEF）， the resistance of lung （RL）， and dynamic compliance （Cdyn） （P<0.05， P<0.01）， severely damaged lung tissue morphology， massive formed continuous fibrous foci， increased fibrosis score （P<0.01）， elevated levels of Col Ⅰ in lung tissues and HYP in the serum （P<0.01）， and up-regulated expression of Wnt3a and β-catenin （P<0.01）. FVC， PEF， and Cdyn levels in the prednisone acetate group and the BFK groups were higher than those in the model group （P<0.05， P<0.01）. Pathological changes were improved in the groups with drug intervention， and fibrosis scores were decreased as compared with the model group （P<0.05， P<0.01）. The scores in the BFK groups were lower than that in the prednisone acetate group （P<0.01）. The levels of Col Ⅰ and HYP in the groups with drug intervention were lower than those in the model group （P<0.05， P<0.01）. The level of Col Ⅰ in the prednisone acetate group was higher than that in the high-dose BFK group （P<0.01）. The levels of serum HYP in the BFK groups was lower than that in the prednisone acetate group （P<0.01）. The protein expression of Wnt3a in lung tissues of the high-dose BFK group was lower than that of the model group （P<0.05）. The protein expression of β-catenin in the prednisone acetate group and the BFK groups was lower than that in the model group （P<0.05， P<0.01）， and the expression level in the high-dose BFK group was lower than that in the prednisone acetate group （P<0.01）. ConclusionBFK can relieve bleomycin sulfate-induced pulmonary fibrosis， reduce collagen deposition， improve pulmonary compliance， and enhance pulmonary ventilatory function in rats. One of its mechanisms is presumedly the inhibition of the Wnt/β-catenin signaling pathway.

Mechanism of Xiaochuanning Granules in Treatment of Bronchial Asthma via PI3K/Akt Signaling Pathway Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo explore the underlying molecular mechanism of Xiaochuanning granules in the treatment of bronchial asthma based on the network pharmacology and experimental verification through the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway on ovalbumin （OVA） sensitization-induced bronchial asthma model in rats. MethodThe main active ingredients and targets of Xiaochuanning Granules were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to bronchial asthma were obtained from five disease databases such as GeneCards and Online Mendelian Inheritance in Man （OMIM）. The common targets were screened out through the Venn diagram. STRING was used to construct the protein-protein interaction （PPI） network of "compound-disease"， and Cytoscape 3.8.0 was used to establish a network of key active ingredients of Xiaochuanning granules and core target genes （"ingredient-gene" network）. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed through DAVID. The bronchial asthma model was induced by OVA stimulation in rats. Bronchial and lung tissue inflammation was observed by hematoxylin-eosin （HE） staining， and the enrichment analysis results of the network pharmacology were verified by Western blot. ResultIn this experiment， 232 active ingredients and 4 687 related targets of Xiaochuanning granules were screened out， and 233 common targets of Xiaochuanning granules and bronchial asthma were collected， including eosinophil-derived neurotoxin 1 （EDN1）， cyclic AMP response element-binding protein 1 （CREB1）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， mitogen-activated protein kinase 14 （MAPK14）， and Akt1. KEGG pathway analysis revealed 186 related signaling pathways， indicating that the PI3K/Akt signaling pathway presumedly played a key role in the treatment of bronchial asthma by Xiaochuanning granules. The animal experiment showed that Xiaochuanning granules relieved the airway inflammation and smooth muscle hyperplasia in rats and down-regulated the gene expression of PI3K and Akt as compared with the conditions in the model group （P<0.05）. ConclusionXiaochuanning granules have the characteristics of multi-component， multi-target， and multi-pathway synergistic effect in the treatment of asthma. Xiaochuanning granules may exert anti-inflammatory effects by regulating the expression of genes related to the PI3K/Akt signaling pathway. The present study is expected to provide a theoretical basis for follow-up in-depth research on the complex mechanism of Xiaochuanning granules in the treatment of bronchial asthma.

Clinical evaluation of Compound Chamomile and Lidocaine Hydrochloride Gel for postoperative hypospadias in children / 中华男科学杂志

Objective@#To evaluate the clinical efficacy of Compound Chamomile and Lidocaine Hydrochloride Gel for postoperative hypospadias in children.@*METHODS@#From January to December 2020, we treated 116 children with distal hypospadias in the Department of Urology, Department of Pediatrics and the Seventh Medical Center of the PLA General Hospital, 58 by primary Snodgrass urethroplasty only (the control group) and the other 58 with Compound Chamomile and Lidocaine Hydrochloride Gel smeared on the penis postoperatively in addition (the trial group). We compared the operation time and postoperative pain score, edema regression and incidence of infection between the two groups, followed by statistical analysis using T test and Chi-square test.@*RESULTS@#All the operations were successfully completed by the same surgeon under general anesthesia. There were no statistically significant differences between the trial and control groups in age (［2.5 ± 0.8］ vs ［2.4 ± 0.6］ yr, P > 0.05) or operation time (［95.6 ± 14.5］ vs ［97.1 ± 15.2］ min, P > 0.05). No incision infection occurred in any of the cases. The pain scores at dressing removal were remarkably lower in the trial than in the control group at 2 hours (1.4 ± 1.0 vs 2.6 ± 1.3, P < 0.05), 24 hours (2.2 ± 1.3 vs 3.9 ± 1.6, P < 0.05), 48 hours (1.2 ± 0.7 vs 1.6 ± 0.9, P < 0.05) and 72 hours after surgery (2.5 ± 0.8 vs 3.7 ± 1.8, P < 0.05). Significantly more cases of edema regression were achieved in the trial than in the control group at 2 weeks postoperatively (35 vs 19, P < 0.05).@*CONCLUSIONS@#Compound Chamomile and Lidocaine Hydrochloride Gel can effectively relieve pain, reduce edema and accelerate edema regression after surgery in children with hypospadias, and therefore deserves wide clinical application.、.

Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Acute cellular rejection (ACR) remains a major concern after liver transplantation. Predicting and monitoring acute rejection by non-invasive methods are very important for guiding the use of immunosuppressive drugs. Many studies have shown that exosomes and their contents are potential biomarkers for various liver diseases. Here, we identify and validate the role of exosomes and galectin-9 in ACR after liver transplantation. Exosomes were isolated from three sets of paired patients, with and without ACR, and the proteins within the exosomes were isolated and identified. Candidate proteins were then validated using a tissue microarray containing resected liver samples from 73 ACR and 63 non-rejection patients. Finally, protein expression and clinical manifestations were included in Kaplan-Meier survival and Cox regression analyses. Circulating exosomes were isolated from ACR and non-rejection patients and characterized using transmission electron microscopy and western blotting for CD63/CD81. Western blotting experiments revealed higher levels of galectin-9 protein in circulating exosomes from ACR recipients. Immunohistochemical analysis of the tissue microarray showed that the expression of galectin-9 in resected liver was significantly higher in the ACR group than in the non-rejection group (P<0.05). Higher levels of galectin-9 expression in resected livers were associated with poorer prognosis (P<0.05). Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation.

Application of "three-step teaching model" for minimally invasive simulation training in urologic clinical teaching / 基础医学与临床

Objective To explore the effectiveness of applying minimally invasive simulation training in urologic clinical teaching .Methods Interns, training clinicians and junior doctors in our hospital, each group of six people, participating in the newthree-step teaching model of "theory learning +simulation training +clinical practice".The score before and after training on their theoretical knowledge , simulation training skills and clinical practice were assessed and the results were analyzed .Results The test scores of minimal invasive techniques theoretical knowl-edge and clinical practice assessment were significantly enhanced before training and after training ( P<0.05 ) .We have established a standardized minimally invasive simulation training in urologic clinical teaching .Conclusions Minimally invasive simulation training provides an effective and safe learning cultivation method for clinician and medical students , which could improve the clinical practice skills of young doctors in minimally invasive surgery as well as shorten the learning curve .

Diagnosis and treatment of micro-paragangliomas in urinary bladdler / 基础医学与临床

Objective To develope the diagnostic criteria and surgical methods to treat micro-paraganagliomas (<1 cm) of urinary bladder ( PUB) , we now report a case series study including 5 individual cases .Methods Clinical data of 5 patients with micro-PUBs who underwent surgical treatment were obtained and analyzed retrospectively . Two male patients and three female patients were included in our study with the mean age of 51 ( range from 41 to 65 years) .4 patients were reported as symptomatic due to hypercatecholaminemia , while the other was free of symptoms.24-hour urine catecholamine ( CA) examination was utilized to qualitatively diagnose PUB , positive in 75%patients.Ultrasonography(USG), CT, MRI, 111In-DTPA-Octreotide scintigraphy (OctreoScan) and 131 I-MIBG scintigraphy were used to locate the tumor , positive in 80%, 20%, 75%, 25%and 33%patients respectively .What's more, all 5 patients underwent transurethral resection of tumor .Overfilling of bladder and puncture following ultra-sonography guidance were performed to locate the tumors , when tumors were absent in surgical vision .Results All tumors were located and resected completely with no open conversions .It took 0.5 to 26 minutes to locate the tumor and another 3 to 10 minutes to resect the tumors .All lesions were diagnosed by histopathological confirma-tion, especially by immunohistochemical staining.Blood pressure return to normal level after the procedures.No local recurrence or distal metastasis were observed by performing 24-hour urine CA test , USG, cystoscopy and MRI within adequate follow-up.The mean follow-up duration was 38.6 months, ranging from 6 to 120 months.Conclu-sions USG and MRI examination were considered better in detecting micro PUB than CT-scan.Overfilling of blad-der and puncture following USG guidance may support more accurate tumor location intraoperatively if the tumors were not found in transurethral resection procedures .