Clinical characteristics of concurrent primary aldosteronism and renal artery stenosis: A retrospective case-control study.

Background: Rare cases of concurrent primary aldosteronism (PA) and renal artery stenosis (RAS) have been reported. Methods: In this retrospective case-control study, we selected a cohort of 10 PA with RAS patients and a control group of 20 PA without RAS patients from January 1, 2006, to January 1, 2016.  Results: All patients presented with refractory hypertension, and a nonstatistically significant trend toward lower mean serum potassium was seen in the PA with RAS group (p =.07). PA with RAS patients had lower mean orthostatic aldosterone-to-renin ratios (38.4 ± 41.4 ng dL-1/ng mL-1 h-1 vs. 87.4.4 ± 38.4 ng dL-1/ng mL-1 h-1, respectively; p < .01) and a higher false-negative rate (50% vs. 15%, respectively; p < .05) compared with controls. All misdiagnosed patients had the diagnosis of PA confirmed when we revaluated the repeated screening and confirmative tests because of residual hypertension or hypokalemia after successful revascularization of renal artery stenosis.  Conclusions: PA is easily missed in patients with RAS because of the high false-negative rate for screening tests. RAS patients with residual hypertension after successful renal angioplasty should be monitored for coexisting PA. Reevaluation of screening and confirmatory tests is helpful in establishing the correct diagnoses.

Transcatheter closure or surgical repair of right pulmonary artery-left atrial fistula.

Right pulmonary artery-left atrial fistula is a rare congenitalcardiac anomaly, and only a few articles published so far have reported the diagnosis and treatment of right pulmonary artery-left atrial fistula. In this study, we report three cases of successful transcatheter closure or surgical repair of right pulmonary artery-left atrial fistula.

Lack of association between polymorphisms in interleukin (IL)-12, IL-12R, IL-23, IL-23R genes and Takayasu arteritis in a Chinese population.

OBJECTIVE: The goal of this study was to investigate the relationship between polymorphisms in interleukin (IL)-12, IL-12R, IL-23, and IL-23R genes and Takayasu arteritis (TA) in a Chinese population. METHODS: A case-control study was performed to investigate the associations of 19 single nucleotide polymorphisms (SNPs) mapping to IL12A, IL12B, IL12RB1, IL12RB2 and IL23R with susceptibility to TA in 145 Chinese TA patients and 300 healthy controls. Genotype identification was performed with the MassARRAY system from Sequenom. The statistical analysis was conducted by Chi square test and unconditional logistic regression with plink. RESULTS: No significant differences were found for the distribution of allele and genotype frequencies of these SNPs between TA patients and healthy controls. However, a trend for IL12A rs582054 and IL23R rs1004819 in association with the TA phenotype was detected. TA patients carrying the rs582054/rs568408 haplotype (P' = 0.019) appeared less likely to progress to a more severe form of disease. And the C allele (P' = 0.082) of IL23R rs1004819 appeared to be a protective factor to refractory disease. CONCLUSIONS: These findings suggest that the polymorphisms of IL12A, IL12B, IL12RB1, IL12RB2 and IL23R might make no contribution to the susceptibility of TA in the Chinese population.

Percutaneous Transluminal Renal Angioplasty for Fibromuscular Dysplasia and Prognostic Risk Factors: A Retrospective Chinese Cohort Study.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory vascular disease involving small-to-medium-sized arteries. The characteristics of Chinese patients with FMD remain unclear. We retrospectively analyzed the data of patients with renal FMD who underwent percutaneous transluminal renal angioplasty (PTRA) for the first time at Fuwai Hospital between 2010 and 2021. The variables were selected through least absolute shrinkage and selection operator regression (LASSO), and logistic regression models were constructed to identify independent risk factors. A total of 116 patients (52 males, median age at diagnosis, 25.0 years) were enrolled. Elevated blood pressure was the leading complaint. After a median follow-up period of 18.0 months (interquartile range: 6.0-48.0 months), hypertension recurred in 34 patients and restenosis in nine patients, among whom four patients underwent secondary intervention and one patient underwent surgical revascularization. Bilateral renal artery involvement (odds ratio [OR]: 2.61, 95% confidence interval [CI]: 1.11-6.15; p = 0.028) and age at hypertension onset (OR: 0.93, 95% CI: 0.88-0.99; p = 0.018) were independent prognostic factors for adverse outcomes. The results indicate that patients with bilateral renal artery involvement and younger age at hypertension onset are more likely to have poorer clinical outcomes after PTRA, and should be more closely monitored.

A scale-down model of 4000-L cell culture process for inactivated foot-and-mouth disease vaccine production.

The anticipated increasing demand for inactivated foot-and-mouth (FMD) disease vaccine calls for its larger production capacity, while development of a large-scale process typically requires high running cost and has very limited experimental throughput at manufacturing scale. Thus, an economic scale-down model of representing a large-scale process becomes necessary and essential. In this study, we used a systematic approach to establish a scale-down model representing a 4000-L culture process for FMD vaccine production by suspension BHK-21 cells. In detail, we firstly compared hydrodynamic properties of three bioreactors (14-L, 800-L and 4000-L) under three different conditions (equivalent mixing time, equivalent shear stress and equivalent volumetric power). We figured out equivalent volumetric power (P/V) potentially as an appropriate scale-down strategy, since it resulted in comparable calculated hydrodynamic parameters among three bioreactors. Next, we used computational fluid dynamics (CFD) simulation to provide more details about hydrodynamic environments inside the bioreactors, which supports the reliability of this scale-down strategy. Finally, we compared cell growth, metabolites, vaccine productivity and product quality attributes during FMD vaccine production by BHK-21 cells and observed very close performances among three bioreactors, which once again demonstrates the robustness of this scale-down model. This scale-down strategy can be applied to study variations and critical quality attributes (CQAs) in the resultant production process based on quality by design (QbD) principles, aiming at further more efficient optimization of vaccine production.

[The synergism between Mtx1 from Bacillus sphaericus and Cyt1 Aa from Bacillus thuringiensis to Culex quinquefasciatus].

Mosquitocidal toxin 1 (Mtx1) was synthesized during vegetative phase of Bacillus sphaericus and it had been proved to have higher activity to Aedes spp. larvae and Binary toxin (Bin) resistance Culex larvae. The truncated 97 kDa Mtx1 with a deletion of the signal peptide and the Cyt1 Aa crystal protein, a 27.3 kDa delta-endotoxin from Bacillus thuringiensis subsp. israelensis (Bti), were purified from Escherichia coli and B. thuringiensis recombinant strains respectively. Both purified toxins had high toxicity against Culex quinquefasciatus larvae. Bioassay result revealed the purified Mtx1 toxin had high toxicity against the target mosquito larvae, with LCso of 45.2 ng/mL. However, the mixture of Mtx1 and Cytl Aa exhibited higher toxicity against the mosquito larvae, with a lowest LC50 value of 20.19 ng/mL at the ratio of 1:3. (Mtx1:Cyt1 Aa). The calculated synergistic factor of different mixtures suggested a strong synergistic effect between Cyt1 Aa toxin and Mtx1. Furthermore, the presence of Cyt1Aa in the mixture could induce early larval mortality, enhancing the activity of Mtx1 to the target mosquito larvae. The synergistic effect of Cyt1 Aa on mortality of Mtx1 to mosquito larvae might be caused by the damage of the larval midgut-hemocoel barrier induced by the activated CytlAa toxin, which enhanced the specific pathogenesis of Mtx1 on mosquito larvae. It is suggested that the co-application of Mtx1 and Cyt1 Aa in future will be integrated for mosquito management.

Left Ventricular Noncompaction in Older Patients.

BACKGROUND: Information on left ventricular noncompaction (LVNC) in older people is sparse. This study aimed to investigate the clinical profile of LVNC in an older cohort. MATERIALS AND METHODS: Between August 2007 and September 2015, older patients (age ≥ 60 years) who were diagnosed with LVNC using cardiovascular magnetic resonance were prospectively enrolled at our hospital. RESULTS: A total of 35 patients (male, 80%; mean age, 65 ± 5 years) were prospectively included in this study. LVNC was not detected in 18 patients (51%) at the initial echocardiographic evaluation. Of the 21 patients who received coronary imaging, 8 patients (38%) had coronary artery disease. Left ventricular (LV) dysfunction and dilation were detected in 31 patients (89%) and 30 patients (86%), respectively. Nine patients (26%) died during a follow-up period of 2.9 ± 2.3 years. Cox analysis showed that patients with syncope (hazard ratio [HR] = 20.51; 95% CI: 1.70-246.60; P = 0.02), increased LV end-diastolic diameter (HR = 1.12; 95% CI: 1.01-1.24; P = 0.03), decreased LV ejection fraction (HR = 0.87; 95% CI: 0.77-0.98; P = 0.02) and the presence of late gadolinium enhancement on cardiovascular magnetic resonance (HR = 8.9; 95% CI: 1.07-74.08; P = 0.04) had a higher risk for death. CONCLUSIONS: The diagnosis of LVNC is easily missed at echocardiographic assessment in older patients. Coronary artery disease is a common concomitant disorder in these patients. Older patients with LVNC have a high risk for mortality. Syncope, LV dilation, systolic dysfunction and late gadolinium enhancement are related to adverse outcomes in older patients.

Clinical characteristics and outcomes of left ventricular pseudoaneurysm: A retrospective study in a single-center of China.

Left ventricular (LV) pseudoaneurysm is a fatal and rare condition with a high risk of rupture. The symptoms are nonspecific and diagnosis is often delayed. The purpose of this study is to analysis a series of cases in our institution.Between March 2009 and April 2016, 10 patients (5 males and 5 females) with LV pseudoaneurysm were retrospectively enrolled. Clinical information, diagnostic imaging modalities, treatment, and outcomes were evaluated.The mean age was 58.2 ±â€Š11.0 years (28-71 years). The common symptoms were chest pain (3 cases), dyspnea (3 cases), and syncope (2 cases). All patients had nonspecific abnormalities on the electrocardiogram, and 7 patients had chest X-ray abnormalities. Three etiologies including myocardial infarction (6 cases), mitral valve replacement (3 cases), and suspected endocarditis (1 case) were identified. LV pseudoanerysm was diagnosed in 8 patients by transthoracic echocardiography, and the other 2 patients were diagnosed by computed tomography angiogram. Posterior (4 cases) and lateral (4 cases) of the left ventricle were the most common positions of the rupture orifice. Eight patients accepted surgery repair and 2 patients were treated conservatively. In 2 patients, residual apical aneurysm was found, 1 patient was detected with a residual LV pseudoaneurysm, and 1 patient had myocardial infarction at 61 months' follow-up.Myocardial infarction was the most common etiology of patients with LV pseudoaneurysm. The most frequently ruptured orifices were lateral and posterior walls of the left ventricle. Surgery is recommended as the first option, and conservative therapy can be considered for appropriate patients.

A novel PRKAG2 mutation in a Chinese family with cardiac hypertrophy and ventricular pre-excitation.

PRKAG2 syndrome is a rare autosomal dominant inherited disorder that is characterized by cardiac hypertrophy, ventricular pre-excitation and conduction system abnormalities. There is little knowledge in cardiovascular magnetic resonance (CMR) characteristics of PRKAG2 cardiomyopathy. This study investigated the genetic defect in a three-generation Chinese family with cardiac hypertrophy and ventricular pre-excitation using whole-exome sequencing. A novel missense mutation, c.1006 G > T (p.V336L), was identified in PRKAG2. This mutation had not been identified in the ExAC database, and the prediction result of MutationTaster indicated a deleterious effect. Furthermore, it cosegregated with the disease in the present family and was absent in unrelated 300 healthy controls. cDNA analysis did not detect any splicing defects, although the variant occurred in the first base of exon 9. CMR evaluation in five affected members showed diffuse hypertrophy in a concentric pattern, with markedly increased left ventricular mass above age and gender limits (median 151.3 g/m2, range 108.4-233.4 g/m2). Two patients in progressive stage and one patient with sudden cardiac death exhibited extensive subendocardial late gadolinium enhancement. In conclusion, molecular screening for PRKAG2 mutations should be considered in patients who exhibit cardiac hypertrophy coexisting with ventricular pre-excitation. CMR offers promising advantages for evaluation of PRKAG2 cardiomyopathy.

Aortic Dissection in Takayasu Arteritis.

BACKGROUND: Aortic dissection (AD) is a rare complication of Takayasu arteritis (TA). The clinical presentation and long-term management outcomes of AD in patients with TA have not been well described. MATERIALS AND METHODS: We conducted a retrospective study of patients with TA along with AD admitted to Fuwai Hospital between January 1985 and March 2016. Clinical data and follow-up data were collected and analyzed. RESULTS: Of the 1,154 patients with TA, we identified 10 patients (0.87%) with AD, which was likely to be associated with vasculitis. All patients were females with a median age at TA onset of 26.5 years (range: 18.3-33.3 years), had type III TA and had a history of hypertension, which was much more common than that in previously reported cases. Stanford type B or DeBakey category III was the dominant anatomic classification of AD. Four patients developed AD after the diagnosis of TA, and 6 developed AD near the time of TA diagnosis. Nine patients underwent conservative treatment, whereas 1 patient underwent endovascular repair due to extensive dissection. At a median 70.5-month follow-up (range: 31.5-138.5), we found that 7 patients had no AD progression, 1 patient had progressed without symptoms, 1 patient was lost and 1 patient died. CONCLUSIONS: Patients with TA along with long-standing and poorly controlled hypertension are liable to develop AD. Those with extensive AD in TA should be carefully treated and intensively followed up.

Potential Harmful Effects of PM2.5 on Occurrence and Progression of Acute Coronary Syndrome: Epidemiology, Mechanisms, and Prevention Measures.

The harmful effects of particulate matter with an aerodynamic diameter of <2.5 µm (PM2.5) and its association with acute coronary syndrome (ACS) has gained increased attention in recent years. Significant associations between PM2.5 and ACS have been found in most studies, although sometimes only observed in specific subgroups. PM2.5-induced detrimental effects and ACS arise through multiple mechanisms, including endothelial injury, an enhanced inflammatory response, oxidative stress, autonomic dysfunction, and mitochondria damage as well as genotoxic effects. These effects can lead to a series of physiopathological changes including coronary artery atherosclerosis, hypertension, an imbalance between energy supply and demand to heart tissue, and a systemic hypercoagulable state. Effective strategies to prevent the harmful effects of PM2.5 include reducing pollution sources of PM2.5 and population exposure to PM2.5, and governments and organizations publicizing the harmful effects of PM2.5 and establishing air quality standards for PM2.5. PM2.5 exposure is a significant risk factor for ACS, and effective strategies with which to prevent both susceptible and healthy populations from an increased risk for ACS have important clinical significance in the prevention and treatment of ACS.

Clinical Profile and Prognosis of Left Ventricular Apical Aneurysm in Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy with left ventricular apical aneurysm is a unique entity with diverse manifestations and varied prognoses among races. This study evaluated the prevalence, clinical characteristics and outcomes of apical aneurysm in Chinese patients with hypertrophic cardiomyopathy. METHODS: Consecutive patients with apical aneurysm were recruited from 1,844 patients with HCM treated at our hospital from 2002-2013. Basic clinical data and follow-up data were collected and analyzed. RESULTS: Apical aneurysm was identified in 24 patients (1.3%) (mean age: 52 ± 14 years). We identified an hourglass-shaped (71%) or distally hypertrophic (29%) left ventricle and found mural thrombi and nonsustained and sustained ventricular tachycardia in 11 (46%), 4 (17%) and 9 (38%) patients, respectively. During follow-up (5.0 ± 3.4 years [range: 1-14 years]), following were the clinical adverse events experienced by 14 patients (58%) (annual rate: 11.7%): sudden cardiac death (n = 4), appropriate discharge of an implantable cardioverter-defibrillator (n = 4), progressive heart failure (n = 4) or heart failure-related death (n = 1) and stroke (n = 4). The 4 patients who underwent aneurysmectomy had no adverse events. Patients with SCD had a lower ejection fraction (P = 0.004) and a larger left ventricular end-diastolic diameter (P < 0.001) than nonoperated survivors. CONCLUSIONS: Apical aneurysm is not rare in patients with HCM and it confers an extremely poor prognosis. Early aggressive therapies should be considered for this entity and prophylactic aneurysmectomy may be an option.

Xinfuli improves cardiac function, histopathological changes and attenuate cardiomyocyte apoptosis in rats with doxorubicin-induced cardiotoxicity.

BACKGROUND: Xinfuli Granule (XG), a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with doxorubicin-induced cardiotoxicity. METHODS: Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin (DOX, 2.5 mg/kg per week) for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline (control group) or different dosage of XG (0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively) for six weeks. Transthoracic echocardiography was performed to evaluate the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining. RESULTS: Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax. CONCLUSIONS: Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.

Coenzyme Q10 treatment of cardiovascular disorders of ageing including heart failure, hypertension and endothelial dysfunction.

Advancing age is a major risk factor for the development of cardiovascular diseases. The aetiology of several cardiovascular disorders is thought to involve impaired mitochondrial function and oxidative stress. Coenzyme Q10 (CoQ10) acts as both an antioxidant and as an electron acceptor at the level of the mitochondria. Furthermore, in cardiac patients, plasma CoQ10 has been found to be an independent predictor of mortality. Based on the fundamental role of CoQ10 in mitochondrial bioenergetics and its well-acknowledged antioxidant properties, several clinical trials evaluating CoQ10 have been undertaken in cardiovascular disorders of ageing including chronic heart failure, hypertension, and endothelial dysfunction. CoQ10 as a therapy appears to be safe and well tolerated.

Clinical Characteristics and Prognosis of End-stage Hypertrophic Cardiomyopathy.

BACKGROUND: End-stage hypertrophic cardiomyopathy (HCM) is complicated by substantial adverse events. However, few studies have focused on electrocardiographic features and their prognostic values in HCM. This study aimed to evaluate the clinical manifestations and prognostic value of electrocardiography in patients with end-stage HCM. METHODS: End-stage HCM patients were enrolled from a total of 1844 consecutive HCM patients from April 2002 to November 2013 at Fuwai Hospital. Clinical data, including medical history, electrocardiography, and echocardiography, were analyzed. Cox hazards regression analysis was used to assess the risk factors for cardiovascular mortality. RESULTS: End-stage HCM was identified in 99 (5.4%) patients, averaged at 52 ± 16 years old at entry. Atrial fibrillation was observed in 53 patients and mural thrombus in 19 patients. During 3.9 ± 3.0 years of follow-up, embolic stroke, refractory heart failure, and death or transplantation were observed in 20, 39, and 51 patients, respectively. The incidence of annual mortality was 13.2%. Multivariate Cox hazards regression analysis identified New York Heart Association Class (NYHA) III/IV at entry (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.05-3.80; P = 0.036), left bundle branch block (LBBB) (HR: 2.80; 95% CI: 1.47-5.31; P = 0.002), and an abnormal Q wave (HR: 2.21; 95% CI: 1.16-4.23; P = 0.016) as independent predictors of cardiovascular death, in accordance with all-cause death and heart failure-related death. CONCLUSIONS: LBBB and an abnormal Q wave are risk factors of cardiovascular mortality in end-stage HCM and provide new evidence for early intervention. Susceptibility of end-stage HCM patients to mural thrombus and embolic events warrants further attention.