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We retrospectively evaluated the echocardiographic data of ambrisentan-treated patients with pulmonary arterial hypertension (PAH) (NCT01808313).Change from baseline in right ventricle (RV) systolic function, right heart structure, and pulmonary artery systolic pressure (PASP) prognosis to Weeks 12 and 24 was evaluated by echocardiography.In the overall population, the mean tissue Doppler-derived tricuspid lateral annular systolic velocity (S') increased by 0.6 cm/s at both Weeks 12 (p 0.001) and 24 (p = 0.004) and tricuspid annular plane systolic excursion increased by 0.13 cm at Week 12 and 0.15 cm at Week 24 (both p 0.001). A marked decrease in transverse and longitudinal RV and RA diameter at Weeks 12 and 24 was observed. A significant decrease in diastolic eccentricity index at both Weeks 12 (-0.1; p = 0.02) and 24 (-0.1; p = 0.001). The decrease in PASP from baseline was significant at both Weeks 12 (-9.5 mmHg; p0.001) and 24 (-7.6 mmHg; p0.001), while a decrease in the estimated right atrium pressure was found to be significant at Week 24 (-0.8mmHg; p = 0.01).Significant improvements in a number of RV echocardiographic parameters were observed at Weeks 12 and 24 after ambrisentan treatment in patients with PAH.

BACKGROUND Acute vasoreactivity testing (AVT) which reflects the compliance of the pulmonary vascular bed has been proven to be of prognostic value. The purpose of the present study is to explore the sex differences of hemodynamics during the AVT and their impact on event-free survival in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS Eighty-six patients underwent a right heart catheterization and AVT at Shanghai Pulmonary Hospital from February 2009 to February 2018. Univariate and multiple stepwise regression analysis were performed to determine the predictors of independent event-free survival, and receiver operating characteristic curve was plotted to determine the cut-off value of independent parameters in CTEPH. RESULTS There were no significant differences in both demographics and hemodynamics between male and female patients with CTEPH. Except ΔPVR/PVR showed a significantly higher difference in female than male patients (P = 0.034). Male patients had higher mRAP of pre- and post-AVT than female patients in the event-free subgroup, while, female patients showed higher PVR of pre-AVT than male patients in the event subgroup (P

please go to the Account Update page (http://mts.hindawi.com/update/) in our Manuscript Tracking System and after you have logged in click on the ORCID link at the top of the page. This link will take you to the ORCID website where you will be able to create an account for yourself. Once you have done so, your new ORCID will be saved in our Manuscript Tracking System automatically."?>Differences between early-onset and late-onset asthma in elderly subjects have not been comprehensively described in China. We conducted a cross-sectional study to determine the phenotypic differences between early-onset asthma (EOA) and late-onset asthma (LOA) in elderly patients. We collected clinical and physiological data from 176 elderly patients with asthma. Participants were divided into two groups: EOA group and LOA group. Demographics, comorbidities, inflammatory parameters, lung function, severity, asthma control, and medication use among EOA and LOA elderly patients were compared. Elderly subjects with EOA had more atopic disease, a stronger positive family history of asthma, higher IgE, and exhaled nitric oxide levels as compared to those with LOA. In contrast, elderly subjects with LOA had lower lung function and more marked fixed airflow obstruction (FAO). Elderly subjects with LOA had a higher incidence of chronic obstructive pulmonary disease (COPD). No differences were observed in age, gender, BMI, history of smoking, severity, and asthma control between the two groups. Both similarities and differences exist between elderly subjects with EOA and those with LOA in China. Further work is required to determine the pathophysiological, clinical, and therapeutic implications for different asthma phenotypes in elderly subjects.

BACKGROUND Although there exists potential risk of bleeding, extended 'lifelong' conventional-intensity [international normalized ratio (INR): 2.0-3.0] warfarin anticoagulation is recommended for unprovoked venous thromboembolism (VTE) patients because of risk of recurrent VTE. Whether long-term low-intensity (INR: 1.5-2.0) warfarin therapy reduced the risk of major bleeding without substantially lowered antithrombotic efficacy is not well understood. The aim of this study was to perform a systematic review and meta-analysis to evaluate the risk-benefits of low-intensity warfarin therapy. METHODS We conducted a comprehensive search of electronic databases and included randomized control trials (RCTs) that reported efficacy (recurrent VTE) and safety (bleeding episodes) of low-intensity warfarin therapy compared with conventional-intensity warfarin or placebo from inception through Jun 2016. RESULTS Four RCTs reporting high GRADE quality evidence were included. Although the relative risk of recurrent VTE with low-intensity therapy was significantly increased [2.96 (95% CI: 1.40 to 6.24), P

Aims Nerve growth factor (NGF) has been reported to prevent neuronal damage and contributes to the functional recovery in animal brain injury models and human ischemic disease as well. We aimed to investigate a potential therapeutic effect of NGF gene treatment in ischemic stroke and to estimate the functional recovery both at the cellular and cognitive levels in an ischemia rat model. Methods After microinjection of pseudolentivirus-delivered β-NGF into an established ischemic stroke model in rats (tMCAO), we estimated neuronal cell apoptosis with TUNEL labeling and neurogenesis by cell proliferation marker Ki67 staining in both ischemic core and penumbra of striatum. Furthermore, we used behavioral functional tests, Morris water maze performance, to evaluate cognitive functional recovery in vivo and propose a potential underlying mechanism. Results We found that pseudolentivirus-mediated delivery of β-NGF gene into the brain induced high expression in striatum of the infarct core area after ischemia in rats. The β-NGF overexpression in the striatal infarction core after ischemia not only improved neuronal survival by reducing cell apoptosis and increasing cell proliferation, but also rescued cognitive functional impairment through upregulation of GAP-43 protein expression in tMCAO rat model of ischemia. Conclusion This study demonstrates a potential β-NGF gene therapy by utilization of pseudolentivirus in ischemia and indicates future applications of NGF gene treatment in ischemic patients.

Tian-Xiang Chen,1 Bigyan Pudasaini,1 Jian Guo,2 Su-Gang Gong,1 Rong Jiang,1 Lan Wang,1 Qin-Hua Zhao,1 Wen-Hui Wu,1 Ping Yuan,1 Jin-Ming Liu1 1Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China; 2Department of Pulmonary Function Test, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China Background: Sex differences in chronic thromboembolic pulmonary hypertension (CTEPH) have been revealed in few studies. Although right heart catheterization (RHC) is the gold standard for clinical diagnosis and assessment of prognosis in pulmonary hypertension (PH), cardiopulmonary exercise testing (CPET) has been a more widely used assessment of functional capacity, disease severity, prognosis, and treatment response in PH. We hypothesized that the “sex-specific” CPET indices could estimate the severity of inoperable CTEPH.Methods: Data were retrieved for 33 male (age, mean ± standard deviation [SD] =62.5±13.4 years) and 40 female (age, mean ± SD =56.3±11.8 years) patients with stable CTEPH who underwent both RHC and CPET at Shanghai Pulmonary Hospital from February 2010 to February 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the predictive value of CPET indices to hemodynamic parameters. Event-free survival was estimated using the Kaplan–Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the independent event-free survival predictors.Results: Numerous CPET parameters were different between male and female patients with CTEPH and the control group. There were no significant differences in both clinical variables and RHC parameters between male and female patients with CTEPH. O2 pulse, workload, minute ventilation (VE), and end-tidal partial pressure of O2 (PETO2) at anaerobic threshold, as well as peak O2 pulse, workload, VE, and nadir VE/CO2 were significantly higher in male patients than in female patients (P

Lan Wang,1,* Yuan-Zhe Jin,2,* Qin-Hua Zhao,1 Rong Jiang,1 Wen-hui Wu,1 Su-Gang Gong,1 Jing He,1 Jin-Ming Liu,1 Zhi-Cheng Jing1,3 1Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; 2Department of Cardiology, The Fourth Affiliated Hospital of China Medical University, Liaoning, China; 3Thrombosis and Vascular Medicine Center, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China *These authors contributed equally to this work Abstract: Studies have shown that vasodilators such as iloprost can be useful for treating pulmonary hypertension (PH). However, in patients with COPD, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange. The efficacy and safety of iloprost inhalation was assessed in 67 patients with PH associated with COPD (COPD-PH), diagnosed by right heart catheterization. Of these, 37 patients had severe PH (mean pulmonary arterial pressure [mPAP] >35 mmHg or mPAP 25–35 mmHg with low cardiac index [

Mitochondrial dysfunction causes renal tubular epithelial cell injury and promotes cell apoptosis and renal tubulointerstitial fibrosis (TIF) progression. TNF receptor-associated protein 1 (TRAP1) is a molecular chaperone protein that is localized in mitochondria. It plays an important role in cell apoptosis; however, its functional mechanism in TIF remains unclear. In this study, we observed the effects of TRAP1 in renal tubular epithelial cell mitochondria in mice with unilateral ureteral obstruction and its function in cell apoptosis and TIF. Results show that TRAP1 could protect the mitochondrial structure in renal tubular epithelial cells; maintain the levels of mitochondrial membrane potential, ATP, and mitochondrial DNA copy number; inhibit reactive oxygen species production; stabilize the expression of the mitochondrial inner membrane protein mitofilin; reduce renal tubular epithelial cell apoptosis; and inhibit TIF. These results provide new theoretical foundations for additional understanding of the antifibrotic mechanism of TRAP1 in the kidney.-Chen, J.-F., Wu, Q.-S., Xie, Y.-X., Si, B.-L., Yang, P.-P., Wang, W.-Y., Hua, Q., He, Q. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria.

Rong Jiang,1 Cheng Wu,2 Bigyan Pudasaini,1 Lan Wang,1 Qin-Hua Zhao,1 Rui Zhang,1 Wen-Hui Wu,1 Ping Yuan,1 Zhi-Cheng Jing,1 Jin-Ming Liu1 1Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 2Department of Health Statistics, Second Military Medical University, Shanghai, People’s Republic of China Background: Severe pulmonary hypertension (PH) resulting from a chronic lung disease (CLD) (severe CLD-PH) requires more aggressive treatment due to its increased mortality compared with mild PH. Therefore, we developed a Doppler echocardiography scoring index (ESI) to predict severe CLD-PH.Methods: A derivation cohort of 107 patients with CLD who underwent echocardiography was classified into two groups, the normal/mild PH group and the severe PH group, based on the right heart catheterization. Meanwhile, we designed the ESI by multivariate logistic regression to validate the predicted outcomes. The ESI was calculated using the following formula: ESI=ESIRVEDTD + ESIPASP + ESIPAd - ESITAPSE. Additionally, the ESI was weighted by +2points for right ventricular end-diastolic transverse dimension ≥3.8 cm or pulmonary artery diameter≥2.7 cm, +3 points for systolic pulmonary artery pressure (PASP) ≥61 mmHg, and-3points for tricuspid annular plane systolic excursion ≥1.65 cm.Results: In the derivation cohort, PASP ≥61 mmHg estimated by echocardiography exhibited 80.4% sensitivity and 84.3% specificity with area under receiver-operating characteristic curve of 0.823 (95% CI: 0.797–0.942, P

Cardiopulmonary exercise testing (CPET) has been used for prognosis in idiopathic pulmonary arterial hypertension (IPAH). We explored whether sex differences had an impact on prognostic assessments of CPET in IPAH. Data were retrieved from 21 male and 36 female incident IPAH patients who underwent both right heart catheterization and CPET from 2010 to 2016 at Shanghai Pulmonary Hospital. Cox proportional hazards analysis was used to assess the prognostic value of CPET. The mean duration of follow-up was 22±15 months. Nine men and 15 women had an event. The differences in clinical parameters in the whole population were not the same as the inter-subgroup differences. Event-free women had significantly higher cardiac output, lower pulmonary vascular resistance and percentage of predicted FVC compared with event men (all P

Background: Pulmonary hypertension (PH) is an important complication of interstitial lung disease (ILD). The aim of the present study was to investigate characteristics and prognosis of ILD associated PH in a predominantly Chinese patient cohort. Methods: Consecutive patients with ILD associated PH, confirmed by right heart catheterization at shanghai pulmonary hospital were included in the study. Characteristics at baseline and during follow-up, as well as survival, were analyzed. Results: This observational study was conducted in 26 patients with a mean age of 60.0 ± 12.2 years old. The six-minutes walking distance was 335.0 ± 190.9 meters. Mean pulmonary arterial pressure (PAP) was 42.9 ± 10.9 mm Hg, cardiac output was 4.4 ± 1.0 L/min, and pulmonary vascular resistance (PVR) was 8.6 ± 4.1 Wood Units. Mean PAP was ≥35 mmHg in 69.2% of cases. There were no difference in lung function parameters between ILD with PH and ILD without PH. The overall survival rate was 92% at 1 year, 82% at 3 years, and 62% at 5 years. PVR was the only variable significantly associated with death. Conclusions: Severe hemodynamic impairment along with PH can occur in patients with ILD. These patients have more severely impaired exercise capacity and cardiac function than ILD patients without PH. PVR was the only prognostic factor identified in this group of patients. This article is protected by copyright. All rights reserved.

Background Pulmonary hypertension patients with mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg had impaired cardiopulmonary exercise testing (CPET). Borderline mean pulmonary pressures (boPAP; 21-24 mm Hg) represent early pulmonary vasculopathy. The CPET characteristics of boPAP are a matter of discussion. We aimed to determine the CPET profile of such borderline hemodynamics. Methods A matched case-control study was conducted on consecutive boPAP patients at the Shanghai Pulmonary Hospital between Jan 2012 and Jan 2017. Hemodynamics, echocardiography, the pulmonary function test (PFT) and CPET parameters were compared between boPAP patients and normal mPAP patients which were matched 1:1 by sex and age. Conditional logistic regression analysis was performed to determine the efficacy of CPET in detecting boPAP. Results A total of 48 patients underwent RHC and CPET (24 Normal, 24 boPAP). There were no differences in the demographics, echocardiography and PFT. BoPAP patients had significantly decreased VO2 at the anaerobic threshold and peak VO2 /kg (858.4 ± 246.5 mL/min vs 727.9 ± 228.0 mL/min, P = 0.037; 21.1 ± 6.4 mL/min/kg vs. 15.5 ± 5.6 mL/min/kg, P = 0.001, respectively). Significant differences were not observed in ventilation efficiency. A trend of impaired oxygen pulse and submaximal exercise tolerance were observed in boPAP patients. Conditional logistical regression analysis revealed the risk of boPAP increased by 2.493 (95% confident interval: 1.388 to 4.476, P = 0.002) with every 5 mL/min/kg decrease in peak VO2 /kg. Conclusions Patients with boPAP have a greater prevalence of exercise intolerance, a trend of impaired oxygen pulse and submaximal exercise tolerance.

Pulmonary hypertension (PH), as a complication of bronchiectasis, is associated with increased mortality. However, hemodynamic characteristics and the efficacy of pulmonary arterial hypertension (PAH) therapies in patients with bronchiectasis and PH remain unknown. Patients with bilateral bronchiectasis and concurrent PH were included in the study. Patient characteristics at baseline and during follow-up, as well as survival, were analyzed. This observational study was conducted in 36 patients with a mean age of 51.5 years (range, 17‒74 years). The 6 min walking distance was 300.8 ± 3.3 m. The mean pulmonary arterial pressure (PAP) was 41.5 ± 1.7 mmHg, cardiac output was 5.2 ± 1.4 L/min, and pulmonary vascular resistance was 561.5 ± 281.5 dyn∙s∙cm(-5). The mean PAP was > 35 mmHg in 75% of the cases. Mean PAP was inversely correlated with arterial oxygen saturation values (r =-0.45, P = 0.02). In 24 patients who received oral PAH therapy, systolic PAP was reduced from 82.4 ± 27.0 mmHg to 65.5 ± 20.9 mmHg (P = 0.025) on echocardiography after a median of 6 months of follow-up. The overall probability of survival was 97.1% at 1 year, 83.4% at 3 years, and 64.5% at 5 years. Given the results, we conclude that PH with severe hemodynamic impairment can occur in patients with bilateral bronchiectasis, and PAH therapy might improve hemodynamics in such patients. Prospective clinical trials focusing on this patient population are warranted.

Objective This study aims to investigate the predictive factors for the spontaneous recanalization of occluded arteries in patients with acute ischemic stroke. Methods A total of 139 patients with consecutive acute ischemic stroke were enrolled from June 2010 to June 2013. The clinical and biochemical parameters were measured in each participant. Occlusion and recanalization of the carotid artery, the middle cerebral artery, and the vertebral and basilar arteries were identified by using computed tomographic angiography or digital subtraction angiography. Results Among the 139 patients, 23 showed spontaneous recanalization, whereas 116 did not. In the patients with spontaneous recanalization, the proportion of atrial fibrillation was significantly lower (0% versus 29.31%, P = .01), whereas the proportion of stage 3 hypertension was significantly higher (60.87% versus 32.76%, P = .01) than that of those without recanalization. Logistic regression analysis showed that the proportion of atrial fibrillation was negatively (odds ratio [OR]: .117, 95% confidence interval [CI]: .015-.918, P = .04) associated with spontaneous recanalization, whereas the proportion of stage 3 hypertension was positively (OR: 4.316, 95% CI: 1.533-12.154, P = .01) associated with it. Conclusions Atrial fibrillation is associated with reduced spontaneous recanalization of the large and middle cerebral arteries in patients after acute ischemic stroke-induced occlusion, whereas stage 3 hypertension may contribute to the promotion of the recanalization.

Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease with high heritability; however, the bone morphogenetic protein receptor 2 (BMPR2) gene only accounts for 17% of IPAH. The genetic basis of IPAH needs further investigation.To identify novel IPAH susceptibility genes other than BMPR2.This 2-stage, case-control genetic association study enrolled 230 patients with IPAH from 2 referral pulmonary hypertension centers in China. Eligible patients had no BMPR2 variants and were compared with 968 healthy control participants. Data were collected from January 1, 2000, to July 31, 2015, and analyzed from August 1, 2015, to May 30, 2018.PTGIS rare variants.Whole-genome sequencing was performed to identify putative IPAH genes in a discovery cohort, with validation in an independent referral cohort. Correlation of genotype and hemodynamic characteristics was then evaluated at baseline and after pulmonary vasodilator testing. Functional assessments were conducted to analyze the effects of identified genetic variants on transcript splicing, enzymatic activity, and endothelial cell phenotypes.Among 230 patients with IPAH (164 female [71.3%]; mean [SD] age, 34 [18] years), an enrichment of rare variants in a gene encoding prostacyclin synthase (PTGIS) was identified in the discovery cohort. The association of PTGIS rare variants with IPAH was confirmed in the replication cohort. In the combined data set, PTGIS rare variants were found in 14 of 230 cases (6.1%) and 8 of 968 controls (0.8%) (odds ratio, 7.8; 95% CI, 3.2-18.8; P = 5 × 10-6, logistic regression). Compared with patients without PTGIS variants, inhaled iloprost induced a more significant decrease of pulmonary vascular resistance (difference in the least square mean, -21.7%; 95% CI, -31.4% to -12.0%; P .001, linear regression model) and an increase of cardiac index (difference in the least square mean, 18.3%; 95% CI, 8.8%-27.8%; P .001, linear regression model) in patients with PTGIS variants. The minigene assay indicated that the c.521 + 1GA variant resulted in aberrant messenger RNA transcripts. The functional studies showed that the 2 missense rare variants (R252Q and A447T) resulted in a decrease in prostacyclin production and increased cell death of pulmonary microvascular endothelial cells.This study identified 3 rare loss-of-function variants in the PTGIS gene from 2 independent cohorts with IPAH. The genetic variants of PTGIS predispose pulmonary vascular responses to the iloprost stimulation. These findings suggest that PTGIS variants may be involved in the pathogenesis of IPAH.

Background Earlier vascular healing after drug-eluting stent (DES) implantation may reduce the incidence of late stent thrombosis and provide theoretical evidence to shorten dual antiplatelet therapy duration in patients with high bleeding risks. The BuMA supreme stent is a newly developed DES-coated with the sirolimus by using the international patent electronic grafted eG™ technology. Previous randomized trials showed that BuMA stents had better stent-strut coverage at 3-month follow-ups, which were evaluated by optical coherence tomography (OCT). However, there have been a limited number of studies that are directly evaluating the extent of neointima formation at the first and second months after stent implantation in high-bleeding-risk patients with coronary artery disease. This clinical trial is designed to demonstrate the non-inferiority of the BuMA supreme stent compared to the XIENCE stent in early neointimal formation. Methods/design This is a prospective, multicenter, randomized trial. Forty patients will be assigned into the first-month OCT group, and another 40 patients into the second-month OCT group. The patients in each cohort will be randomized again into two groups in a 1:1 ratio, either being implanted with the BuMA Supreme stent or the Xience V/Prime/Xpedition stent. The primary endpoint is stent-strut neointimal coverage rate (%) at the first and second months, respectively. Secondary endpoints include neointimal hyperplasia area/volume, neointimal hyperplasia thickness, stent-strut malapposition rate, late lumen loss (LLL), restenosis rate, device/lesion/clinical success rate, device-oriented composite endpoints at the first and second months, stent thrombosis and other serious adverse events and bleeding events at follow-up. Discussion The results will provide the first accurate imaging evidence on neointimal formation of the BuMA Supreme stent and the Xience stent at 1–2 months post PCI. The result should inspire further exploration and adjustment of DAPT treatments. Trial registration ClinicalTrials.gov, ID: NCT02747329. Registered on 21 April 2016. Last updated 17 May 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3361-0) contains supplementary material, which is available to authorized users.

Background and objective: Two endothelin receptor antagonists (ETRAs), bosentan and ambrisentan, are approved for patients with pulmonary arterial hypertension (PAH). However, there is little information about the transition strategy between these two ETRAs. We aimed to evaluate the safety and efficacy from ambrisentan to bosentan. Methods: Twenty PAH patients were enrolled into the single-center, open-labelled prospective study. Echocardiogram, WHO functional class (WHO-FC), 6-minute walking distance (6MWD), right heart catheterization, and hemotology were collected. After receiving oral 5 mg ambrisentan daily initially for one year, the patients were divided into two arms: eight patients switched to bosentan, while the remaining 12 patients continued ambrisentan. Characteristics at baseline, 1-and 2-year follow-up points were compared. Results: There were no significant differences in echocardiogram, WHO-FC, hemodynamics, demographics and liver function at baseline, 1-and 2-year points in both arms. 6MWD in bosentan group was significantly shorter at baseline. But there were no significant differences of 6MWD at 1- and 2-year points. Conclusions: It is safe for stable PAH patients to transition from ambrisentan to bosentan without hemodynamic or hematologic deterioration.

Distinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence.A prospective single-center study investigated 174 patients undergoing liver transplantation due to acute decompensation of hepatitis B virus (HBV)-associated liver cirrhosis. Two groups were distinguished by the presence or absence of submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant). Core clinical features of ACLF were compared between these groups. Disease severity scoring systems were applied to describe liver function and organ failure. Serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes were used to study systemic and local inflammatory responses.SMHN was identified in 69 of 174 patients proven to have cirrhosis by histological means. Characteristic features of SMHN were extensive necrosis along terminal hepatic veins and spanning multiple adjacent cirrhotic nodules accompanied by various degrees of liver progenitor cell-derived regeneration, cholestasis, and ductular bilirubinostasis. Patients with SMHN presented with more severely impaired hepatic function, a higher prevalence of multiple organ failure (as indicated by higher CLIF-SOFA and SOFA scores) and a shorter interval between acute decompensation and liver transplantation than those without SMHN (p0.01 for all parameters). Further analyzes based on serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes revealed higher levels of anti-inflammatory cytokines in patients with SMHN.SMHN is a critical histological feature of HBV-associated ACLF. Identification of a characteristic pathological feature strongly supports that ACLF is a separate entity in end-stage liver disease.

The in-hospital mortality of severe pulmonary hypertension (PH) with right heart failure (RHF) is high despite the use of vasoactive and PH-specific therapies. We conducted a prospective analysis evaluating the safety and outcomes of fasudil hydrochloride (Chuan Wei) therapy in acute RHF. PH patients hospitalized between April 2009 and November 2010 were treated with 30 mg of i.v. fasudil three times daily over 30 min, until they experienced relief of RHF symptoms. Adverse and serious adverse events were recorded. Odds ratios (ORs) and 95% confidence intervals were calculated for both in-hospital mortality and re-hospitalization. Multivariate adjustments were made for age, gender and World Health Organization functional class. There were no significant differences between the fasudil group and the control group in demographics, hemodynamics, and PH-specific and vasoactive therapies. Of the 209 study patients, 3 of the 74 patients (4.1%) in the fasudil arm died, and 19 of the 135 patients (14.1%) in the control arm died (P=0.005). Fasudil decreased both in-hospital mortality (OR=0.258 (0.074-0.903); P=0.034) and 30-day re-hospitalization (OR=0.200 (0.059-0.681); P=0.010). Fasudil was well tolerated; one patient discontinued treatment. Intravenous fasudil may be given safely in patients with PH and acute RHF, and may reduce the rates of both in-hospital mortality and 30-day re-hospitalization.

Exacerbation and relapse of inflammatory bowel disease (IBD) is associated with reduced antibacterial immunity and increased immune regulatory activity, but the source of increased immune regulation during episodes of disease activity is unclear. Myeloid-derived suppressor cells (MDSCs) are a cell type with a well-recognized role in limiting immune reactions. MDSC function in IBD and its relation to disease activity, however, remains unexplored. Here we show that patients with either ulcerative colitis (UC) or Crohn's disease (CD) have high peripheral blood levels of mononuclear MDSCs. Especially exacerbation of disease is associated with higher levels of mononuclear MDSC counts compared with those in remission of disease. Interestingly, chronic experimental colitis in mice coincides with increased MDCS mobilization. Thus, our results suggest that mononuclear MDCS are endogenous antagonists of immune system functionality in mucosal inflammation and the depression of antibacterial immunity associated with exacerbation of disease might involve increased activity of the MDSC compartment.

Background: The footprint of most prostheses is designed according to Caucasian data. Total disc replacement (TDR) has been performed widely for cervical degenerative diseases in China. It is essential to analyze the match sizes of prostheses footprints and Chinese cervical anatomic dimensions in our study. Methods: The anatomic dimensions of the C4-C7 segments of 138 patients (age range 16-77 years) in a Chinese population were measured by computed tomography scans. We compared the footprints of the most commonly used cervical disc prostheses (Bryan: Medtronic, Minneapolis, MN, USA; Prestige LP: Medtronic, Fridley, Minnesota, USA; Discover: DePuy, Raynham, MA, USA; Prodisc-C: Synthes, West Chester, PA, USA) in China with Chinese cervical anatomic dimensions and assessed the match of their size. Results: The mismatch of available dimensions of prostheses and anatomic data of cervical endplates ranged from 17.03% (C4/C5, Prestige LP, Prodisc-C) to 57.61% (C6/C7, Discover) in the anterior-posterior (AP) diameter, and 35.51% (C4/C5, Prodisc-C, Prestige LP) to 94.93% (C6/C7, Bryan) in the center mediolateral (CML) diameter. About 21.01% of endplates were larger than the largest prostheses in the AP diameter and 57.25% in the CML diameter. All available footprints of prostheses expect the Bryan with an unfixed height, can accommodate the disc height (DH), however, 36.23% of the middle DH was less than the smallest height of the prostheses. The average disc sagittal angles (DSAs) of C4-C7 junctions were 5.04°, 5.15°, and 4.13° respectively. Only the Discover brand had a built-in 7° lordotic angle, roughly matching with the DSA. Conclusions: There is a large discrepancy between footprints of prostheses and Chinese cervical anatomic data. In recent years, possible complications of TDR related with mismatch sizes are increasing, such as subsidence, displacement, and heterotopic ossification. Manufacturers of prostheses should introduce or produce additional footprints of prostheses for Chinese TDR.

Cardiac c-kit+ cells isolated from cardiac explant-derived cells modestly improve cardiac functions after myocardial infarction; however, their full potential has not yet been realized. The present study was undertaken to determine the isolation and culture of c-kit+ cardiac stem cells (CSCs), and the roles of myocardial injection of CSCs on the survival of rat cardiac allograft. Recipient Sprague-Dawley rats were transplanted with hearts from Wistar rats. In the in vitro experiment, c-kit+ cells were isolated from mouse heart fragment culture by magnetic cell sorting. CSCs expressed of cardiomyocyte specific protein cardiac troponin I, α smooth muscle actin and von Willebrand factor in conditioned culture. CSC injection increased graft survival of cardiac allograft rats. The effects of CSCs on increase in graft survival of cardiac allograft rats were blocked by stromal-derived factor-1 (SDF-1) knockdown. The expression of SDF-1 was increased after CSC injection into the cardiac of cardiac allograft rats. These results indicate that CSC injection into the cardiac prolongs graft survival of cardiac allograft rats. SDF-1 plays an important role in the effects of CSCs on the graft survival of cardiac allograft rats.

Background The Rho-kinase pathway has been shown to be involved in the pathogenesis of PAH. As yet, however, the acute effects of the Rho-kinase inhibitor fasudil have not been compared with established pulmonary selective vasodilators in patients with PAH. We compared the acute effects of intravenous fasudil with inhaled iloprost in patients with pulmonary arterial hypertension (PAH). Methods Using a crossover design, 50 patients with PAH (idiopathic PAH, PAH associated with repaired left-to-right cardiac shunts, or connective tissue disease) were randomized to iloprost inhalation (5μg) and intravenous fasudil (30mg over 30min). Hemodynamic data were collected at baseline and during acute drug exposure. Results Comparable decreases were observed in mean pulmonary artery pressure (−4.6±4.3mmHg vs. −4.8±4.2mmHg) and pulmonary vascular resistance (−3.0±3.0 Wood U vs. −2.2±2.7 Wood U) with fasudil infusion and iloprost inhalation, respectively, during acute challenge. However, fasudil infusion resulted in a more pronounced increase in mean cardiac output and mixed venous oxygen saturation compared with iloprost inhalation (13.7±17.1% vs. 6.9±15.0%; p =0.044 and 4.5±5.3% vs. 2.7±8.2%; p =0.044, respectively). Whereas inhaled iloprost resulted in a non-significant increase in mean systemic arterial oxygen saturation (0.8±3.6%), infused fasudil resulted in a non-significant reduction (−0.6±1.1%). Conclusion Infused fasudil improved pulmonary hemodynamics in patients with PAH without significant toxicity.

Background: Many studies have highlighted sex preponderance in idiopathic pulmonary arterial hypertension (IPAH). It is well established that there are differences in exercise capacities in the two sexes but how much of that difference reflects on disease severity or correlates to markers of severity in the two sexes is still not clear. Right heart catheterization (RHC) and cardiopulmonary exercise testing (CPET) have been widely used for assessing functional capacity, prognosis and treatment response in IPAH. We aimed to investigate the ‘sex-specific’ CPET parameters in relation to hemodynamics in IPAH. Methods: Data were retrieved from 30 males and 53 females [mean ± standard deviation (SD) age: 39.6 ± 17.2 and 37.5 ± 12.0] stable IPAH patients who underwent both RHC and CPET at Shanghai Pulmonary Hospital from 2010 to 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the prognostic value of CPET and hemodynamic parameters. Results: There were no significant differences in clinical variables between men and women. Peak workload, peak oxygen uptake, anaerobic threshold (AT), peak minute ventilation, carbon dioxide output, O2 pulse and oxygen uptake efficiency slope were significantly higher in men compared with women ( p < 0.05). Several CPET indexes correlated with hemodynamics. Pulmonary vascular resistance (PVR) and cardiac output (CO) were distinctly different between the sexes. Peak end-tidal partial pressure of CO2 (PETCO2) was an independent predictor of PVR elevation in all patients and in men. Peak maximum oxygen consumption (VO2) was independently predictive of CO decline in all patients and in men. Only peak O2 pulse was an independent predictor of increased PVR and decreased CO in women. Conclusions: Even after adjusting for age, body mass index and World Health Organization functional class, different CPET parameters correlated with PVR elevation and CO decline in men and women differently, which could potentially better predict severity in men and women with IPAH.

We show by this study that a decrease in HRR1 in IPAH patients is associated with severe limitation of exercise capacity. HRR1 < 16 beats and CI just after completion of a CPET could be an indicator of poor prognosis.

Background In our previous study, we had shown that high diastolic blood pressure (DBP) was positively related to well-developed coronary collateral circulation (CCC). This study sought to find out the more precise relationship between DBP and CCC. Methods and results To investigate this, we conducted a study of 671 patients with single chronic total occlusion of coronary artery. The DBP of the patients was divided into six groups: ≤65 mmHg, >65–≤75 mmHg, >75–≤85 mmHg, >85–≤95 mmHg, >95–≤105 mmHg, >105 mmHg). The extent of CCC was graded as poorly-developed or well-developed collaterals according to Rentrop classification. There was a J-curve relationship between the level of DBP and the incidence of poorly-developed collaterals. Conclusion The relationship between DBP and CCC is similar to the J-curve relationship between DBP and cardiovascular risk. The influence of DBP on the development of CCC may be one of the pathophysiologic mechanisms of the J-curve phenomenon relating DBP to cardiovascular risk.

This study aimed to investigate the genetic background of mitochondrial genes in young patients with Coronary heart disease (CHD) to provide a foundation for the early prevention of young patients with CHD.115 cases of young (⋜ 45 years) CHD Chinese Han patients (case group), 100 cases of older (45 years) Chinese Han CHD patients (experimental group) hospitalized and 100 cases of healthy people through physical examination (control group) at the General Hospital of PLA between January 2014 and December 2015 were selected. General information, clinical assessment, pedigree analysis, and mitochondrial full sequence scanning were performed. The pedigrees of one patient harbouring the C5263T mutation were recruited. Mitochondrial functional analysis including cellular reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were performed on pedigrees with the C5263T mutation (mutation group) and without the mutation (non-mutation group).The differences in biochemical tests (P0.05) between the case group and experimental group were not significant. The C5263T single-nucleotide mutation of the mitochondrial ND2 gene was observed in 2 young CHD patients in the case group. The premature CHD of these 2 patients followed a pattern of maternal inheritance. The mutation group (I1, II2) had higher ROS levels (4750.82 ± 1045.55 vs. 3888.58 ± 487.60, P = 0.022) and lower MMP levels (P = 0.045) than the non-mutation group (II1, III1, III2).We speculated that the mitochondrial C5263T mutation might be associated with the occurrence CHD in Chinese Han young people.

The precision of the measurement of the angulation of coronary stents or lesions using coronary angiography (CA) and computed tomographic angiography (CTA) has not been established, and obtaining a rotating artery tree to measure angulation based on CTA is time-consuming. The aim of this study was to evaluate the utility of a new three-dimensional centerline method that we have developed for the measurement of coronary stent angulation based on CTA and to compare it with other conventional methods. We used the centerline method compacted by means of our new software, the conventional artery rotation method based on CTA and the simple CA method to measure the angulations of phantoms in vitro and stents implanted in patients. The precision and repetition of this new method was compared with those of the other two methods. The angulation values obtained from both the centerline and artery rotation methods based on CTA had high correlation and agreement with the true angulation values measured using a phantom; the 95 % confidence intervals (CIs) for the differences were −0.67° to 0.91° and −0.59° to 2.93°, respectively, while the difference between the value determined using the CA method and the true angulation of the phantoms ranged from 3° to 21.8° (median 8.1°). In clinical coronary stent measurement, the difference between artery rotation and centerline measurement was small (95 % CI −9.0° to 7.6°), and both methods had good repeatability. The time required to complete the measurement was considerably shorter (p

This study was performed to evaluate effects of Armillariella tabescens (A. tabescens) on the growth performance and intestinal immune response and microflora in early-weaned pigs when used as feed additive. A. tabescens mycelia were added to basal diets at concentrations of 0%, 0.1%, 0.3% or 0.9% (w/w). A total of 144 commercial cross-bred piglets were randomly allocated to one of these four diets and fed for 30 days. The growth performance of early-weaned piglets displayed improvement with diets containing 0.1% and 0.3% dried mycelia powder from A. tabescens. Supplementing with 0.1% or 0.3% A. tabescens mycelia induced a 2.6- and three-fold increase in secretory immunoglobulin A (sIgA) content in the jejunal mucosa, respectively, but had only a marginal effect on sIgA in the ileal mucosa. Expression of interleukin-2, interferon-γ, and tumor necrosis factor-α in the jejunal mucosa were elevated with A. tabescens mycelia administration. Increased amounts of Lactobacillus spp. and Bifidobacterium spp. in the jejunum, and decreased amounts of Escherichia coli in the jejunum and ileum were observed with the administration of A. tabescens-containing diets. This study demonstrated that A. tabescens had beneficial effects on the growth performance and intestinal microflora of early-weaned pigs.

Background To study the relationship between chronotropic incompetence (CI) and disease severity and to assess the effect of CI on exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods Arterial blood gas analysis, pulmonary function test and cardiopulmonary exercise testing were conducted in 60 patients with stable COPD and 45 healthy volunteers. CI was defined using the chronotropic response index (CRI = (peak heart rate-resting heart rate) / (220-age-resting heart rate). Based on CRI, patients with COPD were divided into the normal chronotropic group ( n = 23) and CI group ( n = 37). Results CI was present in 61.7% of the patients with COPD. Exercise capacity (peak oxygen uptake as percentage of predicted value, peak VO 2 %pred), peak heart rate and CRI were significantly lower in patients with COPD than in controls. However, resting heart rate was significantly higher than in controls. FEV 1 %pred and exercise capacity were significantly decreased in the CI group when compared with those in the normotropic group. There was significant association between CRI with FEV 1 %pred and peak VO 2 %pred. Multivariate regression analysis showed that CRI and FEV 1 %pred were independent predictors of exercise capacity in patients with COPD. A cutoff of 0.74 for the CRI showed a specificity of 94.1% in predicting patients with a peak VO 2 %pred Conclusions CRI was associated with disease severity in patients with COPD. CI may be an important parameter to reflect exercise capacity in patients with COPD.

BACKGROUND: Doppler echocardiography is usually the first diagnostic investigation for patients suspected with pulmonary hypertension (PH), but it is often inaccurate when used alone, especially in mild PH. HYPOTHESIS: Cardiopulmonary exercise testing (CPET) may serve as a complementary tool to improve diagnostic accuracy in echocardiography‐suspected “PH possible” patients. METHODS: Eighty‐eight consecutive patients with suspected PH (referred to as “PH possible” hereafter) based on echocardiography were included in the study. CPET was assessed subsequently and PH was confirmed by right‐heart catheterization in all subjects. We analyzed CPET data from patients and derived a CPET prediction rule to hemodynamically differentiate PH. RESULTS: Eighty‐eight patients (27 patients with confirmed PH, and PH ruled out in 61 patients) were included in the study. Compared with non‐PH patients, the PH subjects had lower peak oxygen uptake (VO(2)), aerobic capacity (AT), peak partial pressure of end‐tidal CO(2) (P(ET)CO(2)), oxygen uptake efficiency plateau (OUEP), and oxygen uptake efficiency slope (OUES), along with higher minute ventilation (VE)/carbon dioxide output (VCO(2)) slope and lowest VE/VCO(2) (P < 0.001). VE/VCO(2) slope and AT were independent predictors of PH derived from multivariate logistic regression adjusted for age and body mass index. A score combining VE/VCO(2) slope and AT reached a high area under the curve value of 0.98. A score ≥0.5 had 95% specificity and 92.6% sensitivity for diagnosis of PH. CONCLUSIONS: A score combining VE/VCO(2) slope and AT provides high specificity in screening out PH from a pool of echocardiography‐suspected PH patients.

Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing in situ images of tissues at near histologic resolution. In this study we examine the utility of OCT in identifying vascular changes related to pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).OCT of four different distal pulmonary arteries was performed during right heart catheterization in 87 patients, 64 patients with PAH and 23 patients with CTEPH. The mean luminal diameter measured by OCT for all patients was 2.26mm. Intimal thickening was significantly increased in all PAH patients (0.26±0.05mm in idiopathic PAH, 0.24±0.03mm in connective tissue disease related PAH, 0.26±0.06mm in congenital heart disease related PAH and 0.22±0.04mm in CTEPH, respectively) compared with controls (0.13±0.03mm) (all p0.05). An intimal thickness of ≥0.176mm had a 91% positive predictive value for pulmonary hypertension. The anatomic abnormalities revealed by OCT tended to be severe in the idiopathic PAH group and mild in the CTEPH group. Signs of intravascular webs were found in 60.9% of CTEPH patients, but no other patients. Intimal thickness was moderately correlated with pulmonary arterial pressure and pulmonary vascular resistance (r=0.423 and 0.439, respectively, p0.001).OCT provides important information for assessment of pulmonary arterial remodeling in patients with PAH and improves diagnostic capability of angiographically undetected distal-thrombotic lesions in patients with CTEPH.

Objective The objective of this article was to study the oxygen uptake efficiency, an index of cardiopulmonary functional reserve that can be based upon a submaximal exercise effort, in pulmonary thromboembolism (PE) by performing the cardiopulmonary exercise test. Materials and Methods The cardiopulmonary exercise test with simultaneous respiratory gas measurement was performed in 50 patients with PE and in 50 healthy individuals. All subjects also underwent the pulmonary function test. Peak oxygen uptake (peak VO 2 ), anaerobic threshold (AT), oxygen uptake efficiency slope (OUES), oxygen uptake efficiency plateau (OUEP) and oxygen uptake efficiency at anaerobic threshold (OUE@AT), were determined. Results (1) Compared with the controls, the patients with PE had lower peak VO 2 , AT, OUES, OUEP and OUE@AT ( P 2 /VE) at warming up, AT and peak exercise but not rest, were indicated statistically lower than the controls. The OUE in normal subjects increased as unloaded exercise began, and then increased further to OUEP just before the AT. Thereafter, the OUE decreased gradually until peak exercise. In contrast, the rate of changes of the OUE in patients with PE was relatively mild during exercise. (3) Of all the submaximal parameters, OUES correlated best with peak VO 2 ( r = 0.712, P Conclusions The oxygen uptake efficiency of patients with PE was lower than the controls during exercise. The OUE is an objective measure of cardiopulmonary reserve that does not require a maximal exercise effort. Therefore, OUES could be helpful to assess exercise performance in patients with PE who are unable to perform a maximal exercise test in early recovery stage.

Pulmonary arteriovenous fistulas (PAVFs) are rare. Diffuse type PAVFs with pulmonary arterial hypertension (PAH) are even rarer and can elude anatomy imaging like a plain chest film or a computed tomography. The rapid blood flow that ensues due to lack of a capillary bed leads to various degrees of ischemia depending on the number and size of the PAVF. This is a case report of diffuse PAVF in a patient with PAH. This case report describes a patient with recurrent hemoptysis and chest pain. Systemic examination was unremarkable except for P2 attenuation on auscultation. Echocardiograghy showed confirmed pulmonary hypertension with mild dilation of right atrium and ventricle and a tricuspid regurgitation pressure gradient of 40 mm Hg and ruled out congenital heart diseases. Right heart catheterization revealed precapillary PAH with mean pulmonary arterial pressure of 88 mm Hg. Pulmonary angiography showed enlarged pulmonary arterial trunk and diffuse spiral tortuous pulmonary arterial branches indicting diffuse PAVFs. The patient was diagnosed as PAH and began treatment of 25 mg tid of sildenafil. The case highlights a rare and unique presentation of PAH.

Intact nitric oxide (NO) signalling is critical to maintaining appropriate pulmonary vascular tone. NO bioavailability is reduced in patients with pulmonary arterial hypertension. This study aimed to examine the impact of NO plasma metabolites (NOx) relative to haemodynamic dysfunction and mortality in patients with idiopathic pulmonary arterial hypertension (IPAH).A total of 104 consecutive adult IPAH patients who had undergone genetic counselling when first diagnosed were enrolled in this prospective study.The median concentration of NOx (μmol·L−1) was significantly lower in IPAH patients compared with healthy subjects, and was decreased further in 19 carriers of the bone morphogenetic protein-receptor type-2 (BMPR2) mutation compared to non-carriers. Reduced concentrations of NOx were correlated with mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and cardiac output. Compared with higher baseline NOx concentrations, patients with a NOx concentration of ≤10 μmol·L−1 had a markedly worse survival. After adjustment for clinical features, a BMPR2 mutation and haemodynamics, a lower NOx level remained an increased risk of mortality.Patients with IPAH had lower levels of plasma NOx, which correlated inversely with mPAP, PVR and survival. Plasma NOx may be an important biomarker and prognostic indicator, suggesting that reduced NO synthesis contributes to the pathogenesis of IPAH.

High-density lipoprotein (HDL) cholesterol levels are a strong, independent inverse predictor of cardiovascular disease. The present study aimed to determine whether serum HDL cholesterol levels correlated with disease severity and clinical outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH). The serum HDL cholesterol levels were measured in 76 Chinese patients with IPAH and 45 healthy controls, together with other clinical variables. Univariate and multivariate Cox proportional hazards analysis was performed to assess the prognostic value of HDL cholesterol and event-free survival. Event-free survival was estimated using the Kaplan-Meier method. Serum HDL cholesterol levels were significantly decreased in patients with IPAH compared with controls (1.0 ± 0.3 vs 1.5 ± 0.3 mmol/L; p0.001). The serum HDL cholesterol levels decreased in proportion to the severity of World Health Organization functional class. Compared to the high HDL cholesterol group, the low HDL cholesterol group demonstrated a significantly lower 6-minute walking distance, cardiac index, mixed venous saturation, and arterial carbon dioxide pressure but significantly greater pulmonary vascular resistance and serum uric acid levels. The serum HDL cholesterol levels correlated positively with the cardiac index (r = 0.42; p = 0.002) and negatively with the pulmonary vascular resistance (r = -0.25; p = 0.04). Serum HDL cholesterol was independently related to event-free survival on multivariate Cox proportional hazards analysis. Kaplan-Meier survival curves according to the median HDL cholesterol value showed that lower HDL cholesterol levels were associated with lower event-free survival. In conclusion, serum HDL cholesterol levels might serve as an indicator of disease severity and prognosis in patients with IPAH.

Although sildenafil has been shown to be safe and effective in idiopathic pulmonary arterial hypertension (PAH) and PAH related to connective tissue disease, its effects in Eisenmenger syndrome are less clear.To investigate whether long-term treatment (12 months) with the phosphodiesterase type 5 inhibitor sildenafil improves clinical and haemodynamic parameters in patients with Eisenmenger syndrome.Prospective, open-label, multicentre study.Four pulmonary hypertension centres in China.84 Eisenmenger syndrome functional class II-IV patients.Oral sildenafil 20 mg orally three times a day.6-min walk distance (6MWD) test, resting systemic arterial blood oxygen saturation (SaO(2)) in room air, haemodynamic parameters assessed by right heart catheterisation, safety and tolerability.The overall treatment effects at 12 months versus baseline (mean changes with 95% CIs) were 56 m increase (42 to 69, p0.0001) in 6MWD, and 2.4% increase (1.8% to 2.9%, p0.0001) in resting room air SaO(2). Improvements were also seen in mean pulmonary arterial pressure and pulmonary vascular resistance index (-4.7 mm Hg (-7.5 to -1.9), p=0.001; and -474 dyn×s×cm(-5)×m(2) (-634 to -314), p0.0001, respectively). Sildenafil was well tolerated. Most adverse events were mild and transient, and occurred in the first 2 weeks of treatment.Twelve months of oral sildenafil treatment was well tolerated and appeared to improve exercise capacity, systemic arterial oxygen saturation and haemodynamic parameters in patients with Eisenmenger syndrome.

To determine if multi-detector CT (MDCT) characterization of plaque is correlated with the classification of acute coronary syndrome (ACS).Altogether 1900 patients were examined by MDCT from December 2007 to May 2009, of whom 95 patients fulfilled the criteria of ACS. Those patients were divided into the discrete plaque group ( n=61) and diffuse plaque group ( n=34) based on the findings in MDCT. The clinical diagnosis of ACS and CT results were analyzed, including segment stenosis score, segment involvement score, 3-vessel plaque score, left main score, calcification score, and remodeling index. The incidences of major adverse cardiac events in follow-up period were also recorded.The patients of the diffuse plaque group were older than those of the discrete plaque group ( Pü0.0001). The diffuse plaque group presented more cases of hypertension, peripheral artery disease, diabetes, and heart failure than discrete plaque group (all P0.05). All the 5 patients with ST-segment elevation myocardial infarction were found in discrete plaque group. The segment stenosis score of the discrete plaque group was lower than that of the diffuse plaque group(5.15±3.55 vs. 14.91±5.37, Pü0.001). The other four scores demonstrated significant inter-group difference as well (all P0.05). The remodeling index of thediscrete plaque group was higher (1.12±0.16 vs.0.97±0.20, Pü0.05). Follow-up data showed that major adverse cardiac events occurred more frequently in diffuse plaque group than in discrete group (29.41% vs. 11.48%, P=0.0288).Characteristics of discrete and diffuse plaques may be significantly different among different classes of ACS. The diffuse plaque may present higher risk, correlated to higher mortality. The diagnosis of discrete and diffuse plaques by MDCT would provide a new insight into the prognosis and treatment of ACS.

Objective: The aim of this study is to investigate if dual-source computed tomography (DSCT) could guide the percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). Methods: We enrolled patients who were confirmed to have at least one native coronary artery CTO by DSCT before they underwent selective PCI in the period from December 2007 to October 2008. A CTO was defined as an obstruction of a native coronary artery with no luminal continuity. The CT-guided PCI procedure involved placing CT and fluoroscopic images side-by-side on the screen. DSCT images were analyzed for location, segment, plaque characteristics, calcification, and proximal lumen diameter of the CTO before PCI. The guidewire was advanced and manipulated under CT guidance. The PCI was carried out and the results were compared. Results: Seventy-four CTOs were assessed. PCI was successful in 57 cases of CTOs (77.0%). According to the results, CTOs were divided into two groups: successful-PCI and failed-PCI. All coronary artery paths of CTOs were clearly recognized by DSCT. In the successful-PCI group, soft plaques were detected much more often than those in the failed-PCI group, but fibrous and calcified plaques were seen more often in the failed-PCI group. Calcification severity in CTO segments showed a significant difference between the groups (P=0.014). Calcified plaques were detected in 20 (35.1%) lesions in the successful-PCI group. More than 70% of the failures were calcified plaques, of which there were two arc-calcified and one circular-calcified lesions. Occlusions were longer in the failed-PCI group than those in the successful-PCI group [(38.8±25.0) vs. (18.0±15.3) mm, respectively, P

This study aimed to explore the association between the percentage of reticulated platelets (RP%) and infection, and analyze the value of combined measurement of RP% with other inflammatory indicators in diagnosing infection. A total of 190 patients with signs and symptoms suspicious of infection were included in the infection group, and 70 healthy subjects with comparable percentages of gender and age were included in the control group. Peripheral white blood cell (WBC) count, percentage of neutrophils (N%), platelet count, C-reactive protein (CRP), procalcitonin (PCT), RP%, and axillary temperature were recorded. Dynamic changes in RP% with infection were measured to analyze the association between RP% and infection. The receiver operating characteristic curve was used to evaluate the value of each inflammatory indicator in diagnosing infection and analyze the diagnostic value of the combined adoption of multiple inflammatory indicators. RP% was significantly higher in the infection group than in the noninfection and control groups. The sensitivity and specificity for diagnosing infection were, respectively, 91.78% and 93.18% when RP% and CRP were used in combination, 90.41% and 90.90% when RP% and PCT were used in combination, and 100% and 100% when RP%, CRP, and PCT were used in combination. RP% changed dynamically with the progression of infection and recovered to lower than 5.5% at 2 to 7 days before the body temperature recovered to a normal level. The diagnostic value of RP% was the highest. A combined use with CRP/PCT could improve the sensitivity and specificity in the early diagnosis of infectious diseases.

Lateral diffusion of glutamate receptors was proposed as a mechanism for regulating receptor numbers at synapses and affecting synaptic functions, especially the efficiency of synaptic transmission. However, a direct link between receptor lateral diffusion and change in synaptic function has not yet been established. In the present study, we demonstrated NMDA receptor (NMDAR) lateral diffusion in CA1 neurons in hippocampal slices by detecting considerable recovery of spontaneous or evoked EPSCs from the block of (+)-MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], an irreversible NMDAR open-channel blocker. We observed changes on both the number and the composition of synaptic NMDAR on recovery. More importantly, after the recovery, long-term potentiation (LTP)-producing protocol induced only LTD (long-term depression) instead of LTP. In contrast, a complete recovery from competitive NMDAR blockerd,l-AP-5 was observed without subsequent changes on synaptic plasticity. Our data suggest a revised model of NMDAR trafficking wherein extrasynaptic NMDARs, mostly NR1/NR2B receptors, move laterally into synaptic sites, resulting in altered rule of synaptic modification. Thus, CA1 synapses exhibit a novel form of metaplasticity in which the direction of synaptic modification can be reverted through subtype-specific lateral diffusion of NMDA receptors.

Background Adipose-derived stem cells (ADSCs) are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of ADSCs into myocardial scar may regenerate infracted myocardium and restore cardiac function. Methods ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscoves modified dulbeccos medium. Three weeks after ligation of left anterior descending coronary artery of rabbits, either a graft of untreated ADSCs (UASCs, n = 14), 5-azacytidine-pretreated ADSCs (AASCs, n = 13), or phosphate buffer saline (n = 13) were injected into the infarct region. Transmural scar size, cardiac function, and immunohistochemistry were performed 5 weeks after cell transplantation. Results ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29, CD44 and CD105. Five weeks after cell transplantation, transmural scar size in AASC-implanted hearts was smaller than that of the other hearts. Many ADSCs were differentiated into cardiomyocytes. The AASCs in the prescar appeared more myotube-like. AASCs in the middle of the scar and UASCs, in contrast, were poorly differentiated. Some ADSCs were differentiated into endothelial cells and participate in vessel-like structures formation. All the ADSC-implanted hearts had a greater capillary density in the infarct region than did the control hearts. Statistical analyses revealed significant improvement in left ventricular ejection fraction, myocardial performance index, end-diastolic pressure, and peak +dP/dt, in two groups of ADSC-implanted hearts relative to the control hearts. AASC-implanted hearts had higher peak -dP/dt values than did control, higher ejection fraction and peak +dP/dt values than did UASC-implanted hearts. Conclusions ADSCs transplanted into the myocardial scar tissue formed cardiac islands and vessel-like structures, induced angiogenesis and improved cardiac function. 5-Azacytidine pretreatment before implantation is desirable for augmenting myogenesis. Transplantation of 5-azacytidine-treated ADSCs into the myocardial scar was more efficient than that of untreated ADSCs in preservation of cardiac function.

BACKGROUND: Previous studies demonstrated a relationship between pulmonary hemodynamics and shape of pulmonary artery (PA) Doppler‐flow profiles in a mixed pulmonary hypertension (PH) cohort. HYPOTHESIS: Shape of PA Doppler‐flow profiles could illustrate the hemodynamic characteristics of pulmonary venous hypertension (PVH), especially identifying it with or without pulmonary vascular disease (PVD). METHODS: We retrospectively analyzed hemodynamic, echocardiographic, and clinical data from 47 patients referred for PH caused by left‐sided heart disease (PH‐LHD). All patients underwent right‐sided heart catheterization within 1 week of echocardiography. We concluded a simple echocardiographic prediction rule to give hemodynamic differentiation of PVH with PVD, defined as capillary wedge pressure >15 mm Hg and pulmonary vascular resistance (PVR) >3 Wood units (WU). The PA Doppler‐flow profiles were categorized into 2 groups, no notch (NN) and MSN/LSN. RESULTS: The PVR was higher in the MSN/LSN group at 4.04 WU (interquartile range, 3.1–5.3) vs the NN group at 1.91 WU (interquartile range, 1.8–3.0; P < 0.001). Pulmonary artery Doppler‐flow notching (MSN and LSN) was highly associated with PVR >3 WU, whereas the NN pattern predicted a PVR ≤3 WU (odds ratio: 19.8, 95% confidence interval: 4.3‐91.3) and normal transpulmonary pressure gradient ≤12 mm Hg (odds ratio: 4.7, 95% confidence interval: 1.3‐16.2). The NN pattern had 74% specificity and 88% sensitivity for PVR ≤3 WU. CONCLUSIONS: Absence of PA Doppler‐flow notching was highly associated with PVH, and a notching pattern indicated PVH with PVD in the PH‐LHD cohort.

Periostin is an extracellular matrix protein involved in fibrosis. The present study investigated the importance of periostin in hypertension‑induced myocardial fibrosis. Rats were randomly divided into either the normal group (0.4% NaCl diet; n=8) or hypertension group (8% NaCl diet; n=8). For 36 weeks, the blood pressure and heart rate of the rats were monitored. At week 36, the hearts were extracted for further analysis. Masson's staining and western blotting were performed to determine the levels of periostin protein expression, oxidative stress and fibrosis. In addition, fibroblasts were isolated from adult rats and cultured in vitro, and following treatment with angiotensin II (Ang II) and N-acetyl-L-cysteine (NAC), western blotting, immunofluorescence and 2',7' dichlorodihydrofluorescin staining were performed to examine reactive oxygen species production, and periostin and α‑smooth muscle actin (α‑SMA) expression levels. The results demonstrated that periostin expression and oxidative stress were increased in hypertensive hearts compared with normal hearts. The in vitro experiments demonstrated that Ang II upregulated the expression levels of periostin and α‑SMA compared with the control, whereas, pretreatment with NAC inhibited oxidative stress, periostin and α‑SMA expression in fibroblasts. In conclusion, the results of the current study suggested that oxidative stress‑induced periostin is involved in myocardial fibrosis and hypertension. The present study demonstrated that periostin inhibition may be a promising approach for the inhibition of hypertension-induced cardiac remodeling.

Atrial fibrosis contributes to development and recurrence of atrial fibrillation (AF). TGF-β and periostin have been reported to be involved in fibrogenesis. Here we investigated the role of TGF-β and periostin in atrial fibrosis of AF and in the recurrence of AF after surgery ablation. Western blot, Masson staining, immunohistochemistry and colorimetry were performed to detect the degree of atrial fibrosis and the expression of TGF-β, periostin and collagens in 70 biopsies of right atrial appendage (RAA) obtained in this study. Then the patients who received surgical ablation were followed up for about one year. The results showed an increasing gradient of atrial expression of TGF-β, periostin and collagens paralleled by a higher level of atrial fibrosis in control, SR and AF groups. The expression of TGF-β and periostin was significantly correlated with fibrotic markers. In addition, LAD and the expression of TGF-β were larger or higher in recurrence group than that in nonrecurrence group after surgery ablation. The results suggest that upregulated expression of TGF-β and periostin in RAAs is correlated with the degree of atrial fibrosis in patients with AF.

Oxidative stress and inflammation play critical roles in the development and maintenance of atrial fibrillation (AF). In addition, syndecan-4 (Synd4) shedding induced by oxidative stress or inflammation plays a role in the migration of inflammatory cells. Therefore, we hypothesized that Synd4 shedding was also involved in the inflammatory response in atrial fibrillation patients with valvular heart disease. To confirm this suppose, left atrial appendages and clinical data were obtained from 65 patients with valvular disease undergoing valve surgery. Ten left atrial appendages obtained from healthy heart donors were used as controls. Analyses including histopathology, western blotting, and enzyme kinetics were performed to assess the oxidative injury, inflammation responses, and Synd4 shedding. The results showed that the inflammatory response and oxidative injury were increased significantly, whereas as levels of the Synd4 ectodomain was decreased significantly in AF patients. Furthermore, Synd4 ectodomain levels were correlated with atrial oxidative and inflammatory markers. The results showed that Synd4 shedding is a molecular pathological alteration in the development and maintenance of inflammation-associated AF.

This study studied the use of ERCP and nasobiliary tube in the diagnosis of fungal infection of biliary tract and the efficacy of combined use of local administration via nasobiliary tube and intravenous antifungal treatment for severe biliary tract fungal infection. 5 patients in our series, with age ranging from 47 to 68 y (mean 55.8), were diagnosed as having mixed bacterial and fungal infection of biliary tract as confirmed by smear or/and culture of bile obtained by ERCP and nasobiliary drainage. Besides routine anti-bacteria therapy, all patients received local application of fluconazole through nasobiliary tube and intravenous administration of fluconazole or itraconazole in terms of the results of in vitro sensitivity test. The mean duration of intravenous fluconazole or itraconazole was 30 days (24-40 days), and that of local application of fluconazole through nasobiliary drainage tube was 19 days (8-24 days). During a follow-up period of 3-42 months, all patient's fungal infection of biliary tract was cured. It is concluded that on the basis of typical clinical features of biliary tract infection, fungal detection of smear/culture of bile obtained by ERCP was the key for the diagnosis of fungal infection of biliary tract. Local application antifungal drug combined with intravenous anti-fungal drugs might be an effective and safe treatment for fungal infection of biliary tract.

Objectives To identify the pulmonary hypertension (PH) patients who develop an exercise induced venous-to-systemic shunt (EIS) by performing the cardiopulmonary exercise test (CPET), analyse the changes of CPET measurements during exercise and compare the exercise physiology and resting pulmonary hemodynamics between shunt-PH and no-shunt-PH patients. Methods Retrospectively, resting pulmonary function test (PFT), right heart catheterization (RHC), and CPET for clinical evaluation of 104 PH patients were studied. Results Considering all 104 PH patients by three investigators, 37 were early EIS+, 61 were EIS-, 3 were late EIS+, and 3 others were placed in the discordant group. PeakVO2, AT and OUES were all reduced in the shunt-PH patients compared with the no-shunt-PH subjects, whereas VE/VCO2 slope and the lowest VE/VCO2 increased. Besides, the changes and the response characteristics of the key CPET parameters at the beginning of exercise in the shunt group were notably different from those of the no shunt one. At cardiac catheterization, the shunt patients had significantly increased mean pulmonary artery pressure (mPAP), mean right atrial pressure (mRAP) and pulmonary vascular resistance (PVR), reduced cardiac output (CO) and cardiac index (CI) compared with the no shunt ones (P

Supraventricular arrhythmias (SVA) may be risk factors of prognosis in patients with pulmonary arterial hypertension. SVA are increasingly reported in patients with pulmonary hypertension, but little is known about their incidence and outcomes for patients with idiopathic pulmonary arterial hypertension (IPAH) in a large cohort. In this 6-year prospective multicenter study, 280 patients with IPAH were enrolled to investigate the incidence of SVA and assess risk factors, clinical manifestation, management, and impact on survival. The cumulative 6-year incidence of SVA was 15.8%. The most common types of SVA were atrial fibrillation (n = 16) and atrial flutter (n = 13), followed by atrial tachycardia (n = 11). Most episodes of SVA were associated with significant clinical deterioration and right-sided cardiac failure. Sinus rhythm was successfully restored in most patients, resulting in clinical recovery. Increased right ventricular diameter, left atrial area, and higher right atrial pressure and pulmonary vascular resistance were associated with increased risk for experiencing SVA. SVA predicted a greater risk for mortality in a stepwise forward Cox analysis (hazard ratio 4.757, 95% confidence interval 2.695 to 8.397, p 0.001). Kaplan-Meier survival curves showed that patients with SVA, mainly permanent SVA, had a lower survival rate than those who did not develop SVA (p = 0.008). In conclusion, SVA often lead to clinical deterioration and may be associated with an increased risk for death in a large cohort of patients with IPAH. Restoration and maintenance of sinus rhythm are important treatment goals in patients with IPAH.