An effective pre-treatment method for eliminating interference by serum albumin for analysis of anti-rHSA antibodies.

Analysis of anti-drug antibodies (ADAs) is important for risk assessment in clinical trials. ADA detection can be very difficult in the presence of high circulating levels of drugs or target proteins. We present an effective pretreatment method for eliminating interference by endogenous albumin for analyses of recombinant human serum albumin (rHSA) ADAs. Polyethylene glycol (PEG) precipitation was used to extract albumin-ADA immune complexes from serum samples. Following acid dissociation, albumin-reactive antibodies could be detected through an electrochemiluminescence (ECL) method. Normal human serum was used to establish detectable cut points. Goat anti-human albumin was used as the positive control to evaluate the assay performance. With regard to detection of anti-HSA antibodies, pretreatment with PEG could reduce the interference from albumin in serum. We discovered that the optimized PEG precipitation and acid dissociation (PandA) method had good performance in terms of sensitivity, drug tolerance, and selectivity.

Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of Gerilimzumab (GB224), a recombinant humanized interleukin-6 monoclonal antibody, in healthy Chinese adults: A randomized controlled dose-escalation study.

OBJECTIVES: This study aimed to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of Gerilimzumab (GB224), a recombinant humanized IgG1λ monoclonal antibody against interleukin-6, in healthy Chinese adults. METHODS: Fifty-eight subjects were randomly assigned to receive a single subcutaneous dose of 2, 5, 10, 15, 20, 30 mg GB224 or placebo. Safety assessments were performed, and blood samples were collected for PK, PD, and immunogenicity analyses during a follow-up of 112 days. RESULTS: The most frequent adverse event was decreased fibrinogen (43.1%). GB224 was absorbed relatively fast with a median Tmax of 48 h (24-168 h) but eliminated slowly with a long mean half-life (839.38-981.63 h). Dose proportionality was shown to be in the dose range of 10-30 mg. A dose-dependent increase in serum interleukin-6 concentration from baseline was observed in the subjects receiving GB224. Only two subjects tested positive for antidrug antibodies after administration of GB224. CONCLUSION: GB224 had a well-tolerated safety profile, desirable PK, and a low immunogenicity following a single-dose subcutaneous administration in healthy Chinese subjects. These findings warrant further investigation.

Clinical features of ST-segment elevation myocardial infarction in young Chinese patients.

BACKGROUND: To investigate the clinical characteristics, angiographic findings and clinical outcomes (in-hospital) of young adults with acute myocardium infarction in a Chinese population. METHODS: This was an observational study. Five hundred and forty-nine patients who suffered with ST-segment elevation myocardial infarction (STEMI) firstly between January 2013 and December 2015 were enrolled consecutively. All patients were divided into two groups: "young group" patients were ≤ 50 years old; and "non-young group" patients were > 50 years old. Clinical features were compared, angiographic findings and clinical outcomes were observed between the two groups. RESULTS: There were 131 and 418 patients included in the young group and the non-young group, respectively. Twenty-eight patients suffered deaths during the hospital stay and only one death occurred in the young group. Compared with non-young group, the young group was associated with male, smoke, fewer chronic diseases, Killip class I on admission, lower level of N-terminal pro B-type natriuretic peptide (NT-proBNP), higher level of triglyceride and lower level of high-density lipoprotein cholesterol (HDL-C), single-vessel lesion and intracoronary thrombus (p < 0.005). The average length of hospital stay of non-young group was 1.5 days longer than the young group. Compared with the non-young group, the young group inclined not to use or use only one stent (p = 0.026). Multivariable logistic regression analysis showed that older age, shorter hospital stay, advanced Killip class III/IV, increased white blood cell and NT-proBNP were independent risk factors for survival in acute STEMI patients during hospitalization (p < 0.005). CONCLUSIONS: Compared with non-young group, the young group was associated with male, smoke, higher level of triglyceride and lower level of HDL-C. The condition of patients in young group were relatively mild and the risk of death during hospitalization was lower than the other group.

Study on the Effect of Torrefaction on Pyrolysis Kinetics and Thermal Behavior of Cornstalk Based On a Combined Approach of Chemical and Structural Analyses.

In this study, the effects of torrefaction pretreatment on physicochemical characteristics and pyrolysis behavior of cornstalk were investigated based on the changes in its chemical and structural characteristics. The results indicated that torrefaction treatment improved the fuel properties with elevated torrefaction temperature, including the lower volatile content, higher carbon content, and higher heating value. In addition, serious torrefaction promoted complete degradation of hemicellulose, while the lignin was increased obviously. The crystallinity degree of cornstalk increased first and then reduced with the torrefaction temperature. Slight torrefaction enhanced the devolatilization and thermochemical reactivity of cornstalk, but serious torrefaction discouraged the volatile release. Kinetic parameter analysis indicated that the Ozawa-Flynn-Wall model was more accurate in calculating the activation energy, and the average activation energy gradually increased from 196.06 to 199.21, 203.17, and 217.58 kJ/mol. Furthermore, the thermodynamic parameters also showed an increasing trend with elevated torrefaction temperature. These results provide important basic data support for the thermochemical conversion of cornstalk to energy and chemicals.

Exploring the Communal Pathogenesis, Ferroptosis Mechanism, and Potential Therapeutic Targets of Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy via a Microarray Data Analysis.

Background: Cardiomyopathies are a heterogeneous group of heart diseases that can gradually cause severe heart failure. In particular, dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are the two main types of cardiomyopathies, yet the independent and communal biological mechanisms of both remain far from elucidated. Meanwhile, ferroptosis is a non-apoptotic form of cell death that has been proven to be associated with cardiomyopathies, but the concrete nature of the interaction remains unclear. Hence, this study explored the pathogenesis and ferroptosis mechanism of HCM and DCM via a bioinformatics analysis. Methods: Six datasets were downloaded from the Gene Expression Omnibus (GEO) database based on the study inclusion/exclusion criteria. After screening the differentially expressed genes (DEGs) and hub genes of HCM and DCM, subsequent analyses, including functional annotation, co-expression, validation, and transcription factors (TF)-mRNA-microRNA (miRNA) regulatory network construction, were performed. In addition, ferroptosis-related DEGs were also identified and verified in HCM and DCM. Results: We found 171 independent DEGs of HCM mainly enriched in the regulation of ERK1 and ERK2 cascade, while 171 independent DEGs of DCM were significantly involved in cell adhesion. Meanwhile, 32 communal DEGs (26 upregulated genes and 6 downregulated genes) and 3 hub genes [periostin (POSTN), insulin-like growth factor-binding protein-5 (IGFBP5), and fibromodulin (FMOD)] were determined to be shared between HCM and DCM and the functional annotation of these genes highlighted the important position of growth hormone in HCM and DCM. Moreover, we identified activating transcription factor 3 (ATF3), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and solute carrier family 1 member 5 (SLC1A5) as ferroptosis-related genes in HCM and STAT3 as a ferroptosis-related gene in DCM. Conclusion: The identified independent and communal DEGs contribute to uncover a potentially distinct and common mechanism of HCM and DCM and ferroptosis-related genes could provide us with a novel direction for exploration. In addition, 3 hub genes could be potential biomarkers or therapeutic targets in patients with cardiomyopathy.

Breeding of a thermostable xylanase-producing strain of Myceliophthora thermophila by atmospheric room temperature plasma (ARTP) mutagenesis.

Introduction: Hemicellulose is an important component in lignocellulose materials, which is second only to cellulose, accounting for 15%-35% of the dry weight of plants. In the current situation of energy shortage, making full use of lignocellulose materials to produce fuel ethanol has become an important way to solve the energy problem. Xylanase plays a crucial role in the utilization of hemicellulose. It is a necessary means to reduce the cost of hemicellulose utilization by improving the activity of xylanase. Moreover, most naturally xylanases are mesophilic enzymes, which limits their industrial application. Methods:In this study, Myceliophthora thermophila was used to produce xylanases and a thermostable mutant M 2103 was obtained by atmospheric room temperature plasma (ARTP) mutagenesis. The research work started with exploring the effects of ARTP mutagenesis on the antioxidase system [superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), polyphenol oxidase (PPO), and antioxidant capacity (AOC)] of M. thermophile, and found that superoxide dismutase activity increased by 221.13%, and polyphenol oxidase activity increased by 486.04% as compared with the original strain when the implantation time was 300 s. So as to determine the conditions for subsequent mutagenesis. Results and Discussion:For the mutant M 2103, the reaction temperature for xylanase production remained stable in the range of 70°C-85°C. Its optimum temperature was 75°C, which was 15°C higher than that of the original strain. And its xylanase activity increased by 21.71% as compared with the original strain. M 2103 displayed a significantly higher relative xylanase activity than the original strain in the acidic (pH 4.0-7.0) range, and the xylanase activity was relatively stable in the pH range of 6.0-8.5. These results provide an alternative biocatalyst for the production of xylooligosaccharide, and a potential usage of ARTP in the mutagenesis of thermostable mutant.

Analysis of Communal Molecular Mechanism and Potential Therapeutic Targets in Heart Failure and Type 2 Diabetes Mellitus.

BACKGROUND: Although increasing evidence has suggested an interaction between heart failure (HF) and Type 2 diabetes mellitus (T2DM), the common mechanisms of the two diseases remain unclear. Therefore, this study aimed to obtain the differentially expressed genes (DEGs) and potential biomarkers or therapeutic targets in HF and T2DM. METHODS: The communal DEGs of HF and T2DM were identified by analyzing the two microarray datasets (GSE84796 and GSE95849), and functional annotation was performed for the communal DEGs to uncover the potential molecular mechanisms of HF and T2DM. Subsequently, STRING database and Cytoscape software were used to construct the protein-protein interaction (PPI) network and screen the hub genes. Finally, co-expression and drug-gene interaction prediction analysis and mRNA-miRNA regulatory network analysis were performed for hub genes. RESULTS: A total of 233 up-regulated genes and 3 down-regulated genes were found between HF and T2DM. The functional enrichment of DEGs and genes in each four modules were mainly involved in immunity. In addition, five hub genes were identified from PPI network, including SYK, SELL, RAC2, TLR8 and ITGAX. CONCLUSION: The communal DEGs and hub genes identified in this research contribute to discover the underlying biological mechanisms and presents potential biomarkers or therapeutic targets in HF and T2DM.

Heterogeneous Diels-Alder tandem catalysis for converting cellulose and polyethylene into BTX.

Producing biomass-derived aromatic hydrocarbons via controllable Diels-Alder reactions is a promising approach to recover energy and chemicals from waste streams. A tandem Diels-Alder catalysis consisting of SAPO-34 and Fe/HZSM-5 (stacked catalysis or mixed catalysis) was evaluated for thermochemical conversion of cellulose and polyethylene blends into benzene, toluene, and xylenes (BTX). Aromatization catalyst type significantly affected the activity of tandem catalysis, and the BTX obtained from the HZSM-5 stacked catalysis was ~2.3 times higher than that of the USY stacked one. An introduction of Fe active promoters into HZSM-5 increased the Lewis to Brønsted acid sites molar ratio (L/B) from 0.4 to 4.1. The comparison between Fe/HZSM-5 stacked catalysis and parent HZSM-5 single catalysis indicated that the former was more effective for BTX production, obtaining a nearly two-fold increase in yield with a high selectivity of 82.8%. A close proximity between Fe/HZSM-5 and SAPO-34 in the mixed catalysis increased the BTX enhancement to 1.8. A synergistic effect was provided by the coordination of Lewis and Brønsted acid sites in the Fe/HZSM-5 mixed catalysts for facilitating BTX generation, achieving a maximum of 25.9% at a Fe/HZSM-5 to SAPO-34 mass ratio of 1:1 with a theoretical L/B of 7.2. This work provides a sustainable strategy to produce biomass-derived aromatic hydrocarbons.

Promoting Aromatic Hydrocarbon Formation via Catalytic Pyrolysis of Polycarbonate Wastes over Fe- and Ce-Loaded Aluminum Oxide Catalysts.

Converting polycarbonate (PC) plastic waste into value-added chemicals and/or fuel additives by catalytic pyrolysis is a promising approach to dispose of solid wastes. In this study, a series of Fe-Ce@Al2O3 metal oxides were prepared by coprecipitation, impregnation, and a direct mixing method. The synthesized catalysts were then employed to investigate the catalytic conversion of PC wastes to produce aromatic hydrocarbons. Experimental results indicated that Fe-Ce@Al2O3 prepared by coprecipitation possessed superior catalytic activity because of its high content of weak acid sites, large pore volume, high surface area, and well dispersion of Fe and Ce active species, leading to an ∼3-fold increase in targeted monocyclic aromatic hydrocarbons compared to that achieved noncatalytically. Moreover, an increase in the catalyst to feedstock (C/F) mass ratio was beneficial to the production of aromatic hydrocarbons at the expense of phenolic products, and elevating the C/F ratio from 1:1 to 3:1 considerably increased the benzene formation as the enhancement factor was increased from 2.3 to 8.8.

Synergy of Hydrothermal and Organic Acid Washing Treatments in Chinese Fir Wood Vinegar Preparation.

Pretreatment is an effective method to change the pyrolysis behavior and improve the product properties of biomass. In this study, the effects of hydrothermal treatment (HTT) and hydrothermal treatment combined with organic acid washing (HTT-A) on Chinese fir waste (CF) pyrolysis and preparation of wood vinegar (WV) were investigated. The results indicated that HTT promoted the decomposition of hemicellulose and disrupted the chemical structure, while HTT-A partly removed the lignin as well as hemicellulose. HTT-A showed a more effective removal efficiency of alkali/alkaline earth metals (AAEMs) than HTT. Both HTT and HTT-A delayed the initial decomposition temperature but promoted the pyrolysis process. The yields of WVs increased after HTT and HTT-A, while the moisture contents reduced, obviously. HTT increased the relative contents of phenols from 47.04 to 59.85% but reduced the relative contents of acids from 24.31 to 18.38%, whereas HHT-A reduced the relative contents of phenols but increased those of aldehydes. In addition, HTT and HTT-A showed the different effects on chemical compositions of WVs, especially for phenolic and acid compounds. This study indicated that HTT and HTT-A were the efficient methods to produce WVs with target chemical components, which would be conducive to the efficient application of WVs.

Converting polycarbonate and polystyrene plastic wastes intoaromatic hydrocarbons via catalytic fast co-pyrolysis.

Thermochemical conversion of plastic wastes is a promising approach to produce alternative energy-based fuels. Herein, we conducted catalytic fast co-pyrolysis of polycarbonate (PC) and polystyrene (PS) to generate aromatic hydrocarbons using HZSM-5 (Zeolite Socony Mobil-5, hydrogen, Aluminosilicate) as a catalyst. The results indicated that employing HZSM-5 in the catalytic conversion of PC facilitated the synthesis of aromatic hydrocarbons in comparison to the non-catalytic run. A competitive reaction between aromatic hydrocarbons and aromatic oxygenates was observed within the studied temperature region, and catalytic degradation temperature of 700 °C maximized the competing reaction towards the formation of targeted aromatic hydrocarbons at the expense of phenolic products. Catalyst type also played a vital role in the catalytic decomposition of PC wastes, and HZSM-5 with different Si/Al molar ratios produced more aromatic hydrocarbons than HY (Zeolite Y, hydrogen, Faujasite). Regarding the effect of Si/Al molar ration in HZSM-5 on the distribution of monocyclic aromatic hydrocarbons (MAHs), a Si/Al molar ratio of 38 maximized benzene formation with an advanced factor of 5.1. Catalytic fast co-pyrolysis of PC with hydrogen-rich plastic wastes including polypropylene (PP), polyethylene (PE), and polystyrene (PS) favored the production of MAHs, and PS was the most effective hydrogen donor with a ∼2.5-fold increase. The additive effect of MAHs increased at first and then decreased when the PC percentage was elevated from 30 % to 90 %, achieving the maximum value of 32.4 % at 70 % PC.

Magnetic bio-activated carbon production from lignin via a streamlined process and its use in phosphate removal from aqueous solutions.

Lignin and ferrous salt were mechanically mixed, melted, carbonized and steam activated to produce magnetic bio-activated carbons (MBACs). Phosphate adsorption capacity measurement was conducted on representative MBAC, which has a high surface iron oxide proportion and mesoporous volume. The results indicate that iron species are embedded into the carbon matrix by lignin melting. Steam is not only an activation agent for pore generation and widening but is also effective for the oxidization of Hagg iron carbide produced via ferrous salt decomposition and subsequent reduction during the carbonization process to form magnetite. The porous and magnetic properties and surface iron oxide content of the produced MBACs can be modified by controlling the steam/magnetic biochar (MBC) ratio. The MBAC production process is streamlined and novel, compared with conventional coprecipitation or impregnation methods. The maximum phosphate adsorption onto the representative MBAC product using the best fitting model, i.e., the Langmuir-Freundlich model, is estimated to be 21.18 mg/g, suggesting that the representative MBAC product has a comparable phosphate adsorption capacity to most of the reported MBCs and MBACs.

Comparative strategies for stem cell biodistribution in a preclinical study.

Stem cell therapy represents the potential alternative effective strategy for some diseases that lack effective treatment currently. Correspondingly, it is crucial to establish high-sensitive and reliable quantification assay for tracing exogenous cell migration. In the present study, we first used both bioluminescence imaging (BLI) indirect labeling (human norepinephrine transporter-luciferase reporter system) and 89zirconium (89Zr)-hNSCs direct labeling combined with positron emission tomography/computer tomography (PET/CT) system for tracking human neural stem cells (hNSCs) migration into the brain via nasal administration in preclinical study. But the above two methods failed to give the biodistribution profile due to their low sensitivity. Considering its superior sensitivity and absolute quantitation capability, we developed and validated the droplet digital PCR (ddPCR) targeting species-specific gene in frozen and paraffin sections, slices, and whole blood with the sensitivity of 100-200 hNSCs. Accurate and high throughput quantification could be performed using ddPCR with the coefficient of variation (CVs) of lower quality control (LQC) below 30%. In combination with immunohistochemistry and ddPCR, we confirmed the migration of hNSCs into the brain via nasal administration, which supported the efficacy of hNSCs in MPTP-treated mice, an animal model of Parkinson's disease. In conclusion, the present study is the first to report the application of ddPCR in the pharmacokinetics profile description of tracking of hNSCs in preclinical studies.

Effect of Pyrolysis Temperature on the Characteristics of Wood Vinegar Derived from Chinese Fir Waste: A Comprehensive Study on Its Growth Regulation Performance and Mechanism.

As a high value-added product from biomass pyrolysis, wood vinegar (WV) has been used as a growth regulator for many plant species in agriculture based on the diverse active chemical compounds present. To reveal the relationship between chemical constituents and regulation performance, four kinds of WVs were prepared by slow pyrolysis from Chinese fir waste at different temperature ranges. The chemical constituents of WVs were analyzed by gas chromatography-mass spectrometry, and the regulation performance of WVs was investigated from the aspects of seed germination and root growth of wheat. The results indicated that the chemical constituents of WVs were affected obviously by pyrolysis temperature and the major components were acids and phenols. All types of WVs showed regulation performance but with different effects and levels. The WV collected from 20 to 150 °C exhibited a promoting effect and other three WVs exhibited inhibiting effects. It was considered that the regulation performance of WV was relevant to acids and phenols through a synergy mechanism. Acids caused intercellular acidification and increased root activity, which promoted the seed germination and root growth, while phenols increased the content of malonaldehyde, indicating that phenols caused the oxidative stress to damage cell structure and inhibit growth. All these results could be a reference for further utilization of WVs as a sustainable alternative to chemicals for plant growth regulation in agriculture.

The association between self-perceptions of aging and antihypertensive medication adherence in older Chinese adults.

BACKGROUND: Approximately one billion adults worldwide are hypertensive and most aged 60 or above. Poor adherence with medication treatment is still one of the main causes of failure in achieving blood pressure control. Compared to younger individuals, aging perception may be the main factor influencing elders receiving preventive care. Some studies have investigated the impact of self-perceptions of aging on some preventive health behaviors including "followed the directions for taking prescription medications" in developed countries in the West. However, there is a scarcity of studies evaluating the self-perceptions of aging and its association with antihypertensive adherence among Chinese older adults. AIM: This study aimed to identify the association between aging perceptions and antihypertensive drug adherence among Chinese older adults. METHODS: A cross-sectional investigation was conducted in wards and outpatient clinic of a University Hospital and communities in Suzhou, China. Older adults who were taking at least one antihypertensive drug currently were invited to complete a self-administered questionnaire, including basic socio-demographic and clinical information, self-reported medication adherence and self-perceptions of aging. RESULTS: From 585 old patients, 34.2 % was determined to have good medication adherence. Logistic regression analysis demonstrated that good adherence to antihypertensive agents was more common among those with lower scores on "timeline cyclical" (p = 0.004) and "identity" (p < 0.001) dimensions, and higher scores on "control positive" (p = 0.004) dimension of aging perceptions. CONCLUSION: Self-perceptions of aging, being significantly associated with medication adherence, are an important starting point when conducting intervention programmes for elder patients.

[A cross-sectional study of pulmonary arterial hypertension in congenital heart disease by right heart catheterization].

OBJECTIVE: To explore the prevalence of pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) and analyze its independent risk factors. METHODS: During May 2007 to December 2008, a total of 704 consecutive CHD patients initially admitted into Fuwai Hospital were recruited. Their baseline data were collected and right heart catheterization (RHC) was performed. Those with a mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg (1 mmHg = 0.133 kPa) during RHC were diagnosed as PAH. Multiple Logistic regression was performed to analyze the independent risk factors of PAH. RESULTS: There were 319 males and 385 females with a median age of 5 years. The causes included atrial septal defect (n = 185), ventricular septal defect (VSD, n = 452), patent ductus arteriosus (PDA, n = 48) and a combinations of the above lesions (n = 19). And 280 (39.8%) CHD patients had PAH. Logistic regression analysis revealed that age, systemic artery systolic blood pressure, VSD, PDA and combined lesions were independent risk factors of PAH in CHD (age: OR = 1.017, 95%CI: 1.001-1.033, P = 0.040; systemic artery systolic blood pressure: OR = 0.959, 95%CI: 0.944-0.975, P < 0.001; VSD: OR = 4.402, 95%CI: 2.615-7.411, P < 0.001; PDA: OR = 6.417, 95%CI: 3.079-13.373, P < 0.001; combined lesions: OR = 10.513, 95%CI: 3.641-30.355, P < 0.001). CONCLUSIONS: PAH is a common complication of CHD. Age, peripheral artery systolic blood pressure and type of lesion are independent risk factors of PAH in CHD.

Red blood cell distribution width predicts survival in patients with Eisenmenger syndrome.

BACKGROUND: Previous studies identified an independent relationship between red blood cell distribution width (RDW) and prognosis in patients with pulmonary hypertension of mixed etiologies and idiopathic pulmonary arterial hypertension. This study aimed to investigate the significance of RDW for predicting survival in patients with Eisenmenger syndrome (ES). METHODS: We retrospectively reviewed the clinical records and collected baseline data for patients newly diagnosed with ES in our hospital between January 2005 and October 2009. Follow-up data were collected periodically using a specifically designed network database until December 31, 2012. The end point was all-cause death. RESULTS: A total of 109 patients with ES were included in the study. Twenty-one patients (19.3%) died during a median follow-up period of 4.2 years (interquartile range 3.7-5.0 years). Baseline RDW was significantly correlated with mixed venous oxygen saturation (r=-0.286, p=0.003), arterial oxygen saturation (r=-0.423, p<0.001), mean pulmonary arterial pressure (r=0.271, p=0.004) and total pulmonary resistance (r=0.465, p<0.001). The 1-, 3- and 5-year survival rates for all 109 patients were 94%, 87% and 78%, respectively. Kaplan-Meier analysis showed that patients with RDW ≥13.9% had a lower survival rate than patients with RDW <13.9% (p=0.001). Multivariate Cox regression analysis showed that RDW was an independent prognostic marker in ES, with a hazard ratio of 1.162 (95% CI 1.036-1.302; p=0.010). CONCLUSIONS: Baseline RDW correlates with hemodynamics and is an independent prognostic marker in ES.

Impact of sildenafil on survival of patients with Eisenmenger syndrome.

The favorable effects of short-term use of sildenafil on patients with Eisenmenger syndrome have been reported. We further studied the impact of long-term use of sildenafil on survival of these patients. In this study, the baseline data of patients newly diagnosed as Eisenmenger syndrome in our hospital between January 2005 and December 2009 were retrospectively collected. Patients were followed-up either by telephone contacts or during visits in our out-patient clinic. A total of 121 patients (68 patients in conventional group and 53 patients in sildenafil group) were finally included and 29 patients were re-evaluated after sildenafil therapy for 3-4 months. Compared with the baseline, a 6-minute walk distance, functional classes, plasma hemoglobin level, and hemodynamics were significantly improved after sildenafil treatment. During a median follow-up period of 35.8 months, 15 patients died (11 patients in conventional group). The 1- and 3-year survival rates in sildenafil group were 97.0% and 95.2%, significantly higher than 90.6% and 82.9% in conventional group P = .025). Multivariate analysis showed that sildenafil therapy, functional class and mean pulmonary arterial pressure were independently associated with survival. Therefore, long-term sildenafil therapy improved survival in patients with Eisenmenger syndrome.

The impact of pulmonary arterial hypertension-targeted therapy on survival in Chinese patients with idiopathic pulmonary arterial hypertension.

The survival rates of Chinese patients with idiopathic pulmonary arterial hypertension (IPAH) and familial pulmonary arterial hypertension (PAH) on conventional therapy at 1 and 3 years were 68.0% and 38.9%, respectively. Our aim was to update recent knowledge on the demographics, clinical course, hemodynamic features, disease management, and survival of adult patients with IPAH. This retrospective and observational study was conducted at the largest tertiary referral center in China. Ninety patients with IPAH who underwent initial evaluation at Fu Wai Hospital from January 2006 through November 2009 were retrospectively enrolled. The primary outcome was death. Statistical analyses used included independent sample t test, nonparametric test, Kaplan-Meier method, and Cox proportional hazards analysis. Of the 90 patients enrolled, the median age was 32 years with female predominance. The median interval from onset of symptoms to diagnosis was 14 months. Patients exhibited severe exercise limitation and hemodynamic abnormalities at diagnosis. Only 10.6% had a positive vasoreactivity test, while calcium channel blockers were given to 22.2% of patients. Fifty-nine patients (65.6%) received PAH-targeted therapies during follow-up. Our survival rates of 84.1%, 73.7%, and 70.6% at 1-, 2-, and 3-years compared favorably with predicted survival based on the National Institutes of Health equation which showed 1-, 2-, and 3-years survival rates of 67.7%, 55.9%, and 47%, respectively. For the patients receiving conventional therapy solely, the 1- and 3-years survival rates were 67.0% and 49.3%, respectively. Younger age, lower body mass index, presence of pericardial effusion, and absence of PAH-targeted therapy were independently associated with mortality. We concluded that patients with IPAH were still diagnosed too late, and while survival rates have improved in the modern treatment era, there is still room for improvement.

[Clinical analysis of 150 patients with idiopathic pulmonary arterial hypertension].

OBJECTIVE: To explore the demographic characteristics and clinical features of patients with idiopathic pulmonary arterial hypertension (IPAH) in China. METHODS: Between March 2007 and September 2010, IPAH diagnosis was confirmed by right heart catheterization in 150 adult patients from 31 clinical centers in China. Clinical and hemodynamic data were analyzed and patients were divided into WHO functional class I/II and WHO functional class III/IV group. RESULTS: The mean age of 150 patients were 36 ± 13 years with female patient/male patient ratio of 2:1, and mean BMI was (21.3 ± 3.5) kg/m(2). Fatigue (n = 123, 82.0%) and dyspnea (n = 112, 74.7%) are the most common symptoms. Accentuated pulmonic second sound (P(2)) was detected in 92.0% (n = 138) of patients during physical examination, which was also the most common sign. About 49.0% (n = 73) patients were WHO functional class I/II patients and 46.0% (n = 68) patients were WHO functional class III/IV patients. Six minutes walking distance (6MWD) and Borg dyspnea score was (337 ± 101) m and 2.0 (2.0, 4.0), respectively. Right ventricular hypertrophy was suggested by ECG in 93.1% (n = 140) patients. Right atrial pressure was (10 ± 6) mm Hg, mean pulmonary artery pressure was (61 ± 16) mm Hg, cardiac index was (2.3 ± 0.8) L×min(-1)×m(-2) and pulmonary vascular resistance (1484 ± 699) dyn×s(-1)×cm(-5) in this cohort. 6 MWD (305 m ± 89 m vs. 377 m ± 88 m) was significantly shorter while Borg dyspnea score [3.0 (3.0, 5.0) vs. 2.0 (2.0, 3.0)] was significantly higher in WHO functional class III/IV patients than in WHO functional class I/II patients. Similarly hemodynamic parameters were also worse in WHO functional class III/IV patients than in WHO functional class I/II patients (all P < 0.05). CONCLUSION: Idiopathic pulmonary arterial hypertension patients in this cohort affect mostly young adults, dominated by female gender and lower body mass index. Fatigue and dyspnea are the most common symptoms and accentuated pulmonic second sound (P(2)) is the most common sign. IPAH patients are often displaying severe functional and hemodynamic disturbance at first visit to hospitals. Dyspnea and hemodynamic impairment are related to 6MWD and WHO functional class.