Effectiveness and safety of Shexiang Baoxin Pill (MUSKARDIA) in patients with stable coronary artery disease and concomitant diabetes mellitus: a subgroup analysis of a randomized clinical trial / 中华医学杂志(英文版)

BACKGROUND@#Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM).@*METHODS@#This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty.@*RESULTS@#MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95).@*CONCLUSION@#As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM.@*TRIAL REGISTRATION@#ChiCTR.org.cn, ChiCTR-TRC-12003513.

Feasibility of deep learning for renal artery detection in laparoscopic video / 中华泌尿外科杂志

Objective:To explore the feasibility of deep learning technology for renal artery recognition in retroperitoneal laparoscopic renal surgery videos.Methods:From January 2020 to July 2021, the video data of 87 cases of laparoscopic retroperitoneal nephrectomy, including radical nephrectomy, partial nephrectomy, and hemiurorectomy, were retrospectively analyzed. Two urological surgeons screened video clips containing renal arteries. After frame extraction, annotation, review, and proofreading, the labeled targets were divided into training set and test set by the random number table in a ratio of 4∶1. The training set was used to train the neural network model. The test set was used to test the ability of the neural network to identify the renal artery in scenes with different difficulties, which was uniformly transmitted to the YOLOv3 convolutional neural network model for training. According to the opinion of two senior doctors, the test set was divided into high, medium, and low discrimination of renal artery and surrounding tissue. High identification means a clean renal artery and a large exposed area. For middle recognition degree, the renal artery had a certain degree of blood immersion, and the exposed area was medium. Low identification means that the exposed area of the renal artery was small, often located at the edge of the lens, and the blood immersion was severe, which may lead to lens blurring. In the surgical video, the annotator annotated the renal artery truth box frame by frame. After normalization and preprocessing, all images were input into the neural network model for training. The neural network output the renal artery prediction box, and if the overlap ratio (IOU) with the true value box was higher than the set threshold, it was judged that the prediction was correct. The neural network test results of the test set were recorded, and the sensitivity and accuracy were calculated according to IOU.Results:In the training set, 1 149 targets of 13 videos had high recognition degree, 1 891 targets of 17 videos had medium recognition degree, and 349 targets of 18 videos had low recognition degree. In the test set, 267 targets in 9 videos had high recognition degree, 519 targets in 11 videos had medium recognition degree, and 349 targets in 18 videos had low recognition degree. When the IOU threshold was 0.1, the sensitivity and accuracy were 52.78% and 82.50%, respectively. When the IOU threshold was 0.5, the sensitivity and accuracy were 37.80% and 59.10%, respectively. When the IOU threshold was 0.1, the sensitivity and accuracy of high, medium and low recognition groups were 89.14% and 87.82%, 45.86% and 78.03%, 32.95%, and 76.67%, respectively. The frame rate of the YOLOv3 algorithm in real-time surgery video was ≥15 frames/second. The false detection rate and missed detection rate of neural network for renal artery identification in laparoscopic renal surgery video were 47.22% and 17.49%, respectively (IOU=0.1). The leading causes of false detection were similar tissue and reflective light. The main reasons for missed detection were image blurring, blood dipping, dark light, fascia interference, or instrument occlusion, etc.Conclusions:Deep learning-based renal artery recognition technology is feasible. It may assist the surgeon in quickly identifying and protecting the renal artery during the operation and improving the safety of surgery.

Prognostic value of N-terminal B-type natriuretic peptide on all-cause mortality in heart failure patients with preserved ejection fraction / 中华心血管病杂志

Objective@#To investigate the prognostic value of N-terminal B-type natriuretic peptide (NT-proBNP) on all-cause mortality in heart failure patients with preserved ejection fraction (HFpEF) at real world scenarios.@*Methods@#Patients who met the diagnostic criteria of HFpEF in the China National Heart Failure Registration Study (CN-HF) were divided into death and survival groups. The demographic data, physical examination, results of the first echocardiography, laboratory results at admission, complications, drug use and clinical outcomes were obtained from CN-HF. The univariate Cox proportional hazard model was used to screen the variates that might predict prognosis, and then the covariates with statistical significance were included in the multivariate Cox regression model to analyze the predictive value of baseline NT-proBNP on all-cause death. Spearman correlation analysis was used to evaluate the relationship between NT-proBNP and estimated glomerular filtration rate (eGFR), so as to further explore the predictive value of the interaction between renal dysfunction and NT-proBNP on death. Since NT-proBNP did not obey the binary normal distribution, it was expressed by the natural logarithm of NT-proBNP (LnNT-proBNP).@*Results@#A total of 1 846 HFpEF patients were enrolled in this study, with an average age of 71.5 years, 1 017 males(55.1%), median NT-proBNP 860 ng/L, and median eGFR 73.9 ml·min-1·1.73m-2. After a median follow-up of 34 months, 213 (11.5%) patients died. Patients in the death group were older, with higher NYHA classification Ⅲ-Ⅳ ratio, longer hospital stay, higher serum potassium and NT-proBNP level, prevalence of complications of diabetes mellitus, arrhythmia and atrial fibrillation, use of angiotensin receptor antagonist(ARB), mineralocorticoid receptor antagonists (MRA), diuretic and digoxin was significantly higher in death group than in survival group. Body mass index (BMI), diastolic blood pressure, left ventricular ejection fraction (LVEF), hemoglobin, serum cholesterol(TC), serum triglycerides (TG) and eGFR, and use of angiotensin converting enzyme inhibitors (ACEI), statins and aspirin were lower in death group than in survival group. Univariate Cox regression analysis showed that NT-proBNP was a predictor of all-cause death in HFpEF patients (HR=2.522, 95%CI 2.040-3.119, P<0.001). Multivariate Cox regression analysis showed that the elevated NT-proBNP remains as the independent predictor of all-cause death in patients with HFpEF (HR=1.230, 95%CI 1.049-1.442, P=0.011) after adjusting for age, BMI, diastolic blood pressure, LVEF, hemoglobin, serum potassium, serum sodium, TC, serum high-density lipoprotein cholesterol (HDL-C), TG, eGFR, atrial fibrillation, as well as the treatment of ACEI/ARB, MRA, diuretics and digoxin. Spearman correlation analysis showed that LnNT-proBNP was negatively correlated with eGFR (r=-0.361, P<0.001), but there was no interaction between NT-proBNP and renal dysfunction in predicting death in HFpEF patients (P>0.05).@*Conclusion@#The elevated level of NT-proBNP at admission is an independent predictor of all-cause mortality in HFpEF patients.

Contemporary epidemiology and treatment of hospitalized heart failure patients in real clinical practice in China / 中华心血管病杂志

Objective@#To observe the etiology, comorbidities, clinical features and treatment patterns of hospitalized patients with heart failure (HF) in China.@*Methods@#Data were collected prospectively on hospitalized patients with HF who were enrolled in China Heart Failure Center Registry Study from 169 participating hospitals from January 2017 to August 2018. In this cross-sectional study, patients were stratified by left ventricular ejection fraction (LVEF) category: heart failure with reduced ejection fraction (HFrEF, LVEF<40%); heart failure with mid-ranged ejection fraction (HFmrEF, 40%≤LVEF<50%) and heart failure with preserved ejection fraction (HFpEF, LVEF≥50%). The clinical data were collected, including demographic information, diagnosis, signs, electrocardiogram, echocardiography, laboratory tests, and treatment.@*Results@#A total of 31 356 hospitalized patients with HF were included, 19 072 (60.8%) were males and the average age was (67.9±13.6) years old. The common causes of HF were hypertension (57.2%), coronary heart disease (54.6%), dilated cardiomyopathy (14.7%), valvular heart disease (9.2%). The common complications were atrial fibrillation/atrial flutter (34.1%), diabetes (29.2%), and anemia (26.7%). 32.8% of patients had a history of hospitalization for HF within the previous 12 months. There were 11 034 (35.2%) patients with HFrEF, 6 825 (21.8%) patients with HFmrEF and 13 497 (43.0%) patients with HFpEF. Compared with patients with HFpEF, patients with HFrEF had a lower systolic blood pressure ((124.7±21.1)mmHg(1 mmHg=0.133 kPa) vs. (134.9±22.9)mmHg), faster heart rate ((85±19) beats/minutes vs. (81±19)beats/minutes), and higher percentage of New York Heart Association (NYHA) class Ⅳ, smoking, alcohol, left bundle branch block, and QRS time≥130 ms, and higher levels of blood uric acid, BNP, and NT-proBNP (all P<0.05). Compared with patients with HFmrEF and HFrEF, patients with HFpEF were older, more women, and higher comorbidity burden including hypertension, atrial fibrillation/atrial flutter, anemia and chronic obstructive pulmonary disease (all P<0.05). HFmrEF took a mid-position between HFrEF and HFpEF in age, gender, heart rate, systolic blood pressure, hypertension, atrial fibrillation/atrial flutter, anemia, and chronic obstructive pulmonary disease (all P<0.05). Patients with HFmrEF had the highest proportion of coronary heart disease, myocardial infarction and percutaneous coronary intervention (all P<0.05). During hospitalization, loop diuretics were used in 90.2% of patients, and intravenous inotropics were used in 20.4% of patients. The use of ACEI/ARB/ARNI, β blockers and aldosterone receptor antagonists at discharge were 71.8%, 79.1% and 83.6% in HFrEF and 69.9%, 75.5% and 72.4% in HFmrEF, respectively. The use of digoxin at discharge was 25.3% (HFrEF 36.7%, HFmrEF 23.1%, HFpEF 17.0%). The rates of cardiac resynchronization therapy and implantable cardioverter defibrillator in HFrEF were 2.7% and 2.1%.@*Conclusions@#Among the hospitalized patients with HF in China, coronary heart disease and hypertension are the mostly prevalent causes. HFpEF accounts for a large proportion of hospitalized patients with HF. HFrEF, HFmrEF and HFpEF have different etiology and clinical features. In real-world, there are still large gaps in the effective application of the guideline recommended therapies to HF patients, especially the non-pharmacological therapy option, which needs to be improved further in China.

Role of novel risk factors in predicting risk of ischemic cardiovascular diseases in middle aged men in twenty years in Shanghai / 中华流行病学杂志

Objective To examine the existing Framingham Risk Score (FRS) and Chinese Risk Score (CRS) in predicting the development of ischemic cardiovascular diseases (ICVD),and determine potential added value of novel risk factors.Methods The China Multi-Provincial Cohort Study (CMCS) was a population-based prospective cohort study in 11 provinces of China.An annual follow up was conducted in 840 men aged 35 to 64 years in Shanghai cohort,who were without coronary heart disease and stroke at baseline examination in 1992,to collect the incidence data of ICVD events (coronary death,myocardial infarction,and ischemic stroke).The detection of novel risk factors were conducted for the cohort in 2007.The basic Framingham and Chinese prediction scores power were assessed by using C-statistic of ICVD events associated with risk scores,then the novel risk factors were evaluated by adding them independently to the basic Chinese models.The area under the curve (AUC),net reclassification improvement (NRI),and integrated discrimination improvement (IDI) were calculated to determine if each of the novel risk factors improved risk prediction.Results By the end of December 2014,24 cases of coronary heart disease (myocardial infarction or/and coronary death),45 cases of ischemic stroke had occurred in 840 subjects in Shanghai cohort with a follow-up of 22.3 years averagely.Both the FRS and CRS had predicting power for ICVD,the AUCs were 0.657 6 (95％ CI:0.594 2-0.724 0) and 0.726 5 (95％ CI:0.664 3-0.788 7),respectively.The incremental AUC was 0.068 9 (95％ CI:0.019 6-0.117 1) (P=0.006).None of the novel risk factors significantly improved the AUC.High-sensitive-CRP (hs-CRP) was the only novel risk factor resulting in a significant increase of NRI.CRS in 2007 significantly improved the IDI,but net changes were small.Conclusions CRS had high power in the 20-year risk prediction for ICVD in middle-aged men in Shanghai.The inclusion of hs-CRP could make some improvement in risk prediction,but is unlikely to be meaningful when reclassification or new discrimination strategy are made which can change the clinical risk.

Comparative study of transurethral 1.9 pm thulium laser resection and standard transurethral electroresection for treating superficial bladder cancer / 国际外科学杂志

Objective To compare the efficacy and safety of 1.9 μm thulium laser with transurethral resection of bladder tumor(TURBT) for the treatment of superficial bladder cancer.Methods We reviewed 53 patients with superficial bladder cancer,who were divided into 1.9 μm laser (n =25) and TURBT groups (n =28) from January 2013 to December 2015.The operation time,blood loss volume in operation,catheter indwelling time,hospital stay time,and complications,cumulative recurrence rate were compared between the two groups.Results Compared to TURBT group,1.9 μm laser group showed significantly lower rate of blood loss volume in operation (21.6 ± 4.6) min,catheter indwelling time (22.4 ± 6.4) h,hospital stay time (2.2 ± 0.7) d,less complications (12％)and recurrence(16％) (P ＜ 0.05).Conclusions 1.9 μm thulium laser is safe and effective for the treatment of patients with superficial bladder cancer.The approach has less complications than TURBT.

Evaluation of the risk factors for hyperuricemia in patients younger than 45 with coronary artery disease / 中华风湿病学杂志

Objective To evaluate the risk of hyperuricemia in patients younger than 45 with coronary artery disease.Methods Six hundred and seventy-seven patients with coronary artery disease under 45 years old at disease onset were recruited retrospectively.The subjects were divided into hyperuricemia group (n=164) and normal uric acid group (n=513).Patients with coronary artery disease with hyperuricemia were analyzed for clinical characteristics.The risk of hyperuricemia was analyzed on the severity of coronary lesions.T-test,x2 test and Logistic regression analysis were used for statistical analysis.Results Comparing with patients with normal uric acid,patients in the hyperuricemia group were male predominant and more prevalent with hypertension [197(38.5％) and 93(56.7％) ; x2=16.85,P＜0.01],hypedipidemia [274(53.4％) and 130 (80.7％); x2=37.58,P＜0.01],and cardiac dysfunction [24 (4.7％) and 17 (10.4％); x2=7.18,P=0.01].Hyperuricemia increased the risk of coronary artery disease complicated with cardiac dysfunction [ORlcorrection=2.66,95％CI (1.28,5.53)],and it also increased the risk of coronary artery disease concurrent with cardiac arrhythmia [OR2correction=1.28,95％CI (1.00,1.65)] revealed by multivariate regression analysis.Conclusion In young patients under 45 years old with coronary artery disease,hyperuricemia is the independent risk factor for coronary artery disease complicated with cardiac dysfunction and arrhythmia.

Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients / 中国肺癌杂志

<p><b>BACKGROUND</b>Endostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.</p><p><b>METHODS</b>Four hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .</p><p><b>RESULTS</b>Of 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .</p><p><b>CONCLUSIONS</b>The addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .</p>

Neuregulin-1 therapy improved cardiac function and reduced ANPmRNA expression in post myocardial infarction rats with cardiac dysfunction / 老年心脏病学杂志（英文版）

To observe the influence of neuregulin-1 on the cardiac function of post-myocardial infarction rats. Methods Left ventricular MI was created in Sprague-Dawley rats by ligation of the left anterior descending coronary. Six months after the operation, rats were evaluated with echocardiology methods. 36 rats that had an infarct area and a EF around 60% were randomized into 3 groups: MI group(n=12) were injected a blank vehicle fluid intravenously for 5 days, after which they continued to be raised on standard food and water for 30 days. MI+NRG group(n=12), received NRG-110μg·kg-1 intravenously for 5 days, after which they continued to be raised on standard food and water for 30 days. MI+Capt group (n=12) received captopril orally (dissolved in their drinking water 2g/L) for 30days, after which tap water substituted the solution for 5 days. Final echocardiographic and hemodynamic measurements were made at the end of 1 month of therapy. Total RNA was extracted from frozen left ventricular tissues, and was reverse transcribed into firststrand PCR was performed with primers for BNP、 ANP. Results Rats treated with neuregulin had a smaller LVDs (P=0.014), a betterLVEF (P=0.004),and a tendency towards less lung perfusion than untreated rats. Neuregulin decreased the expression of ANP mRNA in the ventricle (P=0.025).Conclusion Neuregulin markedly improved the cardiac function of rats that survived myocardial infarction,and decreased the expression of ANP mRNA in the ventricle.