Publications by authors named "Wen-Hui Wu"

75 Publications

Reproductive and hormonal factors and risk of incident rosacea among US White women.

J Am Acad Dermatol 2021 Jul 15. Epub 2021 Jul 15.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China; Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, Rhode Island; Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.06.865DOI Listing
July 2021

Potential for inhibition of checkpoint kinases 1/2 in pulmonary fibrosis and secondary pulmonary hypertension.

Thorax 2021 Jul 5. Epub 2021 Jul 5.

Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre (IUCPQ), Quebec, Quebec, Canada

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterised by exuberant tissue remodelling and associated with high unmet medical needs. Outcomes are even worse when IPF results in secondary pulmonary hypertension (PH). Importantly, exaggerated resistance to cell death, excessive proliferation and enhanced synthetic capacity are key endophenotypes of both fibroblasts and pulmonary artery smooth muscle cells, suggesting shared molecular pathways. Under persistent injury, sustained activation of the DNA damage response (DDR) is integral to the preservation of cells survival and their capacity to proliferate. Checkpoint kinases 1 and 2 (CHK1/2) are key components of the DDR. The objective of this study was to assess the role of CHK1/2 in the development and progression of IPF and IPF+PH.

Methods And Results: Increased expression of DNA damage markers and CHK1/2 were observed in lungs, remodelled pulmonary arteries and isolated fibroblasts from IPF patients and animal models. Blockade of CHK1/2 expression or activity-induced DNA damage overload and reverted the apoptosis-resistant and fibroproliferative phenotype of disease cells. Moreover, inhibition of CHK1/2 was sufficient to interfere with transforming growth factor beta 1-mediated fibroblast activation. Importantly, pharmacological inhibition of CHK1/2 using LY2606368 attenuated fibrosis and pulmonary vascular remodelling leading to improvement in respiratory mechanics and haemodynamic parameters in two animal models mimicking IPF and IPF+PH.

Conclusion: This study identifies CHK1/2 as key regulators of lung fibrosis and provides a proof of principle for CHK1/2 inhibition as a potential novel therapeutic option for IPF and IPF+PH.
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http://dx.doi.org/10.1136/thoraxjnl-2021-217377DOI Listing
July 2021

Adult-onset hypoxaemia, diffuse lung lesions, and pulmonary hypertension in cobalamin C defect: a case report.

Eur Heart J Case Rep 2021 Jun 30;5(6):ytab251. Epub 2021 Jun 30.

Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507, Zhengmin Road, Shanghai 200433, China.

Background: Cobalamin C (cbl-C) defect is an inherited autosomal recessive disorder that commonly affects the central nervous system of infants. Severe pulmonary hypertension (PH) and diffuse lung lesions are unusual clinical manifestations, especially among adults.

Case Summary: A 25-year-old man with hypoxaemia, diffuse lung lesions, and PH, suddenly developed nausea, vomiting, headache, and worsening of dyspnoea. Metabolic screening showed elevated serum levels of methylmalonic acid and homocysteine, and genetic testing revealed gene mutations. He was eventually diagnosed with severe PH secondary to cbl-C defect and was successfully managed with vitamin B12, betaine, L-carnitine, folate, as well as ambrisentan and sildenafil.

Discussion: cbl-C is a rare cause of PH and can present with severe PH and diffuse lung lesions in adults. Given that the condition is treatable, a careful metabolic screening should be considered when a diagnosis of PH is made.
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http://dx.doi.org/10.1093/ehjcr/ytab251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243222PMC
June 2021

Fetal Gene Reactivation in Pulmonary Arterial Hypertension: GOOD, BAD, or BOTH?

Cells 2021 Jun 11;10(6). Epub 2021 Jun 11.

Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, Canada.

Pulmonary arterial hypertension is a debilitating chronic disorder marked by the progressive obliteration of the pre-capillary arterioles. This imposes a pressure overload on the right ventricle (RV) pushing the latter to undergo structural and mechanical adaptations that inexorably culminate in RV failure and death. Thanks to the advances in molecular biology, it has been proposed that some aspects of the RV and pulmonary vascular remodeling processes are orchestrated by a subversion of developmental regulatory mechanisms with an upregulation of a suite of genes responsible for the embryo's early growth and normally repressed in adults. In this review, we present relevant background regarding the close relationship between overactivation of fetal genes and cardiopulmonary remodeling, exploring whether the reawakening of developmental factors plays a causative role or constitutes a protective mechanism in the setting of PAH.
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http://dx.doi.org/10.3390/cells10061473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231250PMC
June 2021

Plasma exosomal miR-596: a novel biomarker predicts survival in patients with idiopathic pulmonary artery hypertension.

J Int Med Res 2021 Mar;49(3):3000605211002379

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.

Objective: To determine if plasma exosomal microRNAs (miRNAs) can predict survival in patients with idiopathic pulmonary arterial hypertension (IPAH).

Methods: The study enrolled patients with IPAH that underwent right heart catheterization. Plasma was collected and exosomal miRNAs were extracted. Exosomes were evaluated using transmission electron microscopy, Western blot analysis and particle size distribution analysis. MiRNAs were evaluated using a miRNA microarray and validated using real-time polymerase chain reaction.

Results: This study included 12 patients with IPAH in the study group and 48 patients with IPAH in the validation group. The mean ± SD follow-up duration was 60.3 ± 35.4 months in the overall cohort. The levels of miR-596 were higher in the nonsurvivors compared with the survivors. The levels of miR-596 significantly correlated with survival time, mean right atrial pressure, pulmonary vascular resistance (PVR) and cardiac index. High levels of miR-596 and PVR were significantly associated with poor overall survival. Multivariate analysis demonstrated that exosomal miR-596 (hazard ratio [HR] = 2.119; 95% confidence interval [CI] 1.402, 3.203) and PVR (HR = 1.146; 95% CI 1.010, 1.300) were independent predictors of survival.

Conclusions: High levels of plasma exosomal miR-596 were significantly associated with disease severity and poor prognosis of patients with IPAH.
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http://dx.doi.org/10.1177/03000605211002379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020249PMC
March 2021

Body composition and risk of gastric cancer: A population-based prospective cohort study.

Cancer Med 2021 03 23;10(6):2164-2174. Epub 2021 Feb 23.

Department of Clinical Nutrition, The Seventh Affiliated Hospital, Sun Yat-sen University, Guangdong Province, China.

The recognition of adiposity as a risk factor for gastric cancer is mainly based on traditional anthropometric indices, such as body mass index, which are unable to discriminate between lean and fat mass. We undertook this study to examine body composition and subsequent risk of gastric cancer. This is a prospective analysis of participants free of cancer from the UK Biobank. We measured baseline body composition with electrical bioimpedance analysis and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders. We documented 326 cases of cancer from 474,929 participants over a median follow-up of 6.6 years. Both male (HR 1.70, 95% CI 1.01 to 2.89) and female participants (HR 2.47, 95% CI 1.15 to 5.32) in the highest quartile of whole body fat-free mass were associated with increased risk of gastric cancer as compared with those in the lowest quartile.Whole body fat mass was associated with a decreased risk of gastric cancer (HR per 5-unit increase 0.86, 95% CI 0.74 to 0.99) in females, but not in males. We concluded that fat-free mass and fat mass may have different effects on gastric cancer risk. This study provided evidence for individualized weight management for the prevention of gastric cancer.
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http://dx.doi.org/10.1002/cam4.3808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957174PMC
March 2021

Impact of circGSAP in Peripheral Blood Mononuclear Cells on Idiopathic Pulmonary Arterial Hypertension.

Am J Respir Crit Care Med 2021 06;203(12):1579-1583

Shanghai Pulmonary Hospital Affiliated to Tongji University Shanghai, China.

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http://dx.doi.org/10.1164/rccm.202005-2052LEDOI Listing
June 2021

R-Crizotinib predisposes to and exacerbates pulmonary arterial hypertension in animal models.

Eur Respir J 2021 05 13;57(5). Epub 2021 May 13.

Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, QC, Canada

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http://dx.doi.org/10.1183/13993003.03271-2020DOI Listing
May 2021

[Expression of Costimulatory Molecule Tim3 on NK Cells and Its Subsets in Patients with Acute Myeloid Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Dec;28(6):1899-1903

Department of Laboratory Medicine, The Second People's Hospital of Yixing City, Wuxi 214200, Jiangsu Province, China.

Objective: To investigate the expression of costimulatory molecule Tim3 and its subsets on NK cells in patients with acute myeloid leukemia.

Methods: 30 patients with acute myeloid leukemia treated in our hospital from August 2016 to August 2018 were randomly selected as the AML group, and 30 healthy persons in our hospital during the same period were randomly selected as the control group. The expression levels of CD56 NK cells/CD3CD56NK cells and Tim3 on CD56NK cells in peripheral blood, CD56 NK cells/CD3CD56NK cells and Tim3 on CD56NK cells in peripheral blood of the two groups were estimated. The expression of CD3CD56NK cells/lymphocytes and their Tim3, CD56NK cells/CD3CD56NK cells and their Tim3 expression, Tim3NK, Tim3NK IFN-gamma secretion levels before and after chemotherapy in the AML group were analyzed.

Results: The expression levels of CD56 NK cells/CD3CD56NK cells and their Tim3 in peripheral blood of the AML group were significantly lower than those of the control group (P<0.05). The expression levels of CD56 NK cells/CD3CD56NK cells and their Tim3 in peripheral blood of the AML group were significantly higher than those of the control group (P<0.05). CD3CD56NK cells/lymphocytes and Tim3/CD3CD56NK cells in complete remission patients were significantly higher than at initial diagnosis (P<0.05). CD3CD56NK cells/lymphocytes and Tim3/CD3CD56NK cells in patients with course of treatment ≥2 times and remission patients time more than 3 months were significantly higher than those in patients with chemotherapy course 1 time and remission time≤3 months (P<0.05). The expression levels of CD56 NK cells/CD3CD56NK cells and their Tim3 in peripheral blood of patients at complete remission were significantly higher than at initial diagnosis (P<0.05). The expression levels of CD56 NK cells/CD3CD56NK cells and Tim3 in peripheral blood of patients at complete remission were significantly lower than of the patients at initial diagnosis (P<0.05), and the IFN-gamma secretion level of Tim3 NK cells was significantly lower than that of Tim3NK cells in these patients (P<0.05).

Conclusion: The expression of costimulatory molecule Tim3 in NK cells and its subsets of patients with acute myeloid leukemia is down-regulated.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2020.06.018DOI Listing
December 2020

Identification of Long Noncoding RNA H19 as a New Biomarker and Therapeutic Target in Right Ventricular Failure in Pulmonary Arterial Hypertension.

Circulation 2020 10 23;142(15):1464-1484. Epub 2020 Jul 23.

Pulmonary Hypertension Research Group, Center de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, QC, Canada (J.O., K.H., T.S., W-H.W., S.B-B., E.T., S.M., V.N., K.G., F.M., J.P., R.P., S.P., O.B., S.B.).

Background: Right ventricular (RV) function is the major determinant for both functional capacity and survival in patients with pulmonary arterial hypertension (PAH). Despite the recognized clinical importance of preserving RV function, the subcellular mechanisms that govern the transition from a compensated to a decompensated state remain poorly understood and as a consequence there are no clinically established treatments for RV failure and a paucity of clinically useful biomarkers. Accumulating evidence indicates that long noncoding RNAs are powerful regulators of cardiac development and disease. Nonetheless, their implication in adverse RV remodeling in PAH is unknown.

Methods: Expression of the long noncoding RNA H19 was assessed by quantitative PCR in plasma and RV from patients categorized as control RV, compensated RV or decompensated RV based on clinical history and cardiac index. The impact of H19 suppression using GapmeR was explored in 2 rat models mimicking RV failure, namely the monocrotaline and pulmonary artery banding. Echocardiographic, hemodynamic, histological, and biochemical analyses were conducted. In vitro gain- and loss-of-function experiments were performed in rat cardiomyocytes.

Results: We demonstrated that H19 is upregulated in decompensated RV from PAH patients and correlates with RV hypertrophy and fibrosis. Similar findings were observed in monocrotaline and pulmonary artery banding rats. We found that silencing H19 limits pathological RV hypertrophy, fibrosis and capillary rarefaction, thus preserving RV function in monocrotaline and pulmonary artery banding rats without affecting pulmonary vascular remodeling. This cardioprotective effect was accompanied by E2F transcription factor 1-mediated upregulation of enhancer of zeste homolog 2. In vitro, knockdown of H19 suppressed cardiomyocyte hypertrophy induced by phenylephrine, while its overexpression has the opposite effect. Finally, we demonstrated that circulating H19 levels in plasma discriminate PAH patients from controls, correlate with RV function and predict long-term survival in 2 independent idiopathic PAH cohorts. Moreover, H19 levels delineate subgroups of patients with differentiated prognosis when combined with the NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels or the risk score proposed by both REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) and the 2015 European Pulmonary Hypertension Guidelines.

Conclusions: Our findings identify H19 as a new therapeutic target to impede the development of maladaptive RV remodeling and a promising biomarker of PAH severity and prognosis.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047626DOI Listing
October 2020

Variable predictors of acute pulmonary embolism recurrence with duration of follow-up.

J Thorac Dis 2020 Mar;12(3):403-413

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China.

Background: Acute pulmonary embolism (PE) is a critical disease and often leads to a high mortality and morbidity. Several studies have identified predictors of PE recurrence, but whether these predictors have prognostic value and how they vary during varied follow-up periods remain unclear.

Methods: We retrospectively assessed the occurrence of recurrent PE and the survival time of patients with a diagnosis of acute PE at Shanghai Pulmonary Hospital from May 2007 to May 2018. Potential predictors of recurrent PE were evaluated at different points (1, 3, 6, 12, 24, 60 and 120-month) during a long-term follow-up for each patient. Patients were stratified into two groups by gender to analyze the impact of sex in period-guided prognostic prediction. Receiver operating characteristic curve analysis, survival analysis and multivariate Cox proportional hazards analysis were implemented as statistical analysis methods.

Results: In total, 597 acute PE patients were included, of whom 62 reported a PE recurrence. Male patients tend to have a lower risk of PE recurrence than female patients during 3- to 60-month follow-up period but have a higher risk of PE recurrence than female patients during 120-month follow-up period. The independent predictors of recurrence-free survival varied among different follow-up periods: In all patients, diabetes was an independent predictor only within 30 days follow-up period and female was considered as an independent predictor during 3- to 120-month follow-up period. Among male patients, hyperlipidemia and Log D-dimer (cut-off value =3.436) was observed as a predictor of recurrent PE within 6-month and over 12-month follow-up respectively. However, there is no unified independent prognostic indicator for female patients identified.

Conclusions: In the early stage of follow-up, male PE patients have better prognosis, but with the extension of follow-up, female PE patients have better prognosis. The independent predictors of recurrence-free survival vary in different follow-up periods in PE patients when stratified based on gender and associated medical conditions.
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http://dx.doi.org/10.21037/jtd.2020.01.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139025PMC
March 2020

Changed hemodynamics in acute vasoreactivity testing: prognostic predictors in chronic thromboembolic pulmonary hypertension.

Am J Transl Res 2020 15;12(3):959-973. Epub 2020 Mar 15.

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine Shanghai, China.

Chronic thromboembolic pulmonary hypertension (CTEPH) is similar to pulmonary arterial hypertension (PAH) in its pathogenesis. Changed hemodynamic parameters in acute vasoreactivity testing (AVT) have proved to be prognostic predictors of PAH. We wanted to determine whether these changed indices also impacted the prognosis of CTEPH. Data was retrieved for 86 CTEPH patients who underwent right heart catheterization (RHC) with AVT at Shanghai Pulmonary Hospital from 2009 to 2018 and following up for 20 ± 15 months for event. Cox proportional hazards models were performed to determine the predictors of independent event-free survival. Receiver operating characteristic curve was plotted to determine the cut-off value of independent parameters in CTEPH. Kaplan-Meier method and log-rank test were used to perform the Survival analyses. Forty seven patients had an event. Many hemodynamic indices improved after AVT. The event-free group had better mean right atrial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance (PVR) and oxygen saturation of mixed venous blood (SvO2) both at baseline and after AVT. The event-free group also showed higher cardiac output (CO) and cardiac index (CI) after AVT. Among the changed hemodynamic parameters during the AVT, ΔCO, ΔCO/baseline CO, ΔCI, ΔCI/baseline CI and ΔPVR/baseline PVR were significantly higher in the event-free group. Foremost, ΔPVR/baseline PVR, PVR after AVT and baseline SvO2 were independent predictors for event-free survival. Patients with SvO2 ≥ 61.65% at baseline or PVR < 8.09 WU after AVT or ΔPVR/baseline PVR ≥ 0.054 had significantly better survival. Hemodynamic indices both at baseline and after AVT as well as the changes in these indices reflected the severity of CTEPH. Baseline SvO2, PVR after AVT, and ΔPVR/baseline PVR could be used as independent predictors to estimate the outcomes of CTEPH patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137036PMC
March 2020

Sex differences of hemodynamics during acute vasoreactivity testing to predict the outcomes of chronic thromboembolic pulmonary hypertension.

Clin Respir J 2020 Jul 12;14(7):611-621. Epub 2020 Mar 12.

Department of Cardio-Pulmonary Circulation, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.

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 < 0.05). The mRAP and SvO were independent predictors of event-free survival in female patients both before and after the AVT, whereas ΔSvO was an independent predictor of event-free survival in male patients.

Conclusion: Hemodynamics during the AVT varied between male and female patients with CTEPH. Both sexes displayed unique hemodynamic responses that were independently able to predict event-free survival. Therefore, better estimates of prognosis in CTEPH can be made when sex differences are also taken into consideration.
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http://dx.doi.org/10.1111/crj.13173DOI Listing
July 2020

Natural Occurrence, Bioactivity and Biosynthesis of Elaiophylin Analogues.

Molecules 2019 Oct 25;24(21). Epub 2019 Oct 25.

School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.

Elaiophylins belong to a special family of 16-membered macrodiolides with C-symmetry. They have exhibited remarkable biological activities, such as antimicrobial, anthelmintic, anticancer, immunosuppressive, anti-inflammatory, antiviral, and α-glucosidase inhibitory activities. A member of elaiophylins, efomycin M, is as a specific small molecule inhibitor of selectin in preclinical trial for the treatment of psoriasis, ischemia-reperfusion, and allergy. The biosynthetic investigation of elaiophylins has uncovered a unique thioesterase, which is responsible for the formation of C-symmetric diolide. We herein summarize the natural occurrence, bioactivity, and biosynthesis of elaiophylins covering the literatures from 1959 to 2019. Hopefully, this review will inspire further research interests of these compounds and encourage the discovery of new analogues by metabolic engineering or genome mining.
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http://dx.doi.org/10.3390/molecules24213840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864862PMC
October 2019

Association Between High FSH, Low Progesterone, and Idiopathic Pulmonary Arterial Hypertension in Women of Reproductive Age.

Am J Hypertens 2020 01;33(1):99-105

Key Laboratory of Pulmonary Vascular Medicine and FuWai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China.

Background: While sex differences characterize susceptibility and severity of idiopathic pulmonary arterial hypertension (IPAH), our understanding of the relationship between levels of gonadotropins and sex hormones in fertile women and the disease is limited. We aimed to investigate whether gonadotropin and sex hormone levels in women of reproductive age were associated with risk and mortality of IPAH.

Methods: We did a matched case-control study. Cases were reproductive female patients with idiopathic pulmonary arterial hypertension admitted in Shanghai Pulmonary Hospital (Tongji University School of Medicine, Shanghai, China) during 2008-2014. Healthy controls were matched on age and body mass index. We also did a prospective cohort study to assess the effects of hormone levels on mortality in IPAH fertile female patients.

Results: One hundred sixty-four cases and 133 controls were included. After adjustment for age and body mass index, the odds ratios of having IPAH for follicle-stimulating hormone, testosterone, and progesterone as expressed on natural log scale were 1.51 (95% confidence interval: 1.06, 2.16), 0.42 (0.31-0.57), and 0.52 (0.43-0.63), respectively. In the cohort study with a median follow-up of 77 months, the hazard ratios for dying after adjustment for baseline characteristics and treatments among IPAH patients were 2.01 (95% confidence interval: 1.22-3.30) and 0.78 (95% confidence interval: 0.62-0.98) for follicle-stimulating hormone and progesterone in natural log scale, respectively.

Conclusions: In reproductive women with IPAH, high follicle-stimulating hormone and low progesterone tended to be associated with high risk of IPAH and mortality among patients.
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http://dx.doi.org/10.1093/ajh/hpz143DOI Listing
January 2020

Characteristics of cardiopulmonary exercise testing of patients with borderline mean pulmonary artery pressure.

Clin Respir J 2019 Mar 17;13(3):148-158. Epub 2019 Feb 17.

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

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 VO at the anaerobic threshold and peak VO /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 VO /kg.

Conclusions: Patients with boPAP have a greater prevalence of exercise intolerance, a trend of impaired oxygen pulse and submaximal exercise tolerance.
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http://dx.doi.org/10.1111/crj.12996DOI Listing
March 2019

Germline mutation causes idiopathic pulmonary arterial hypertension.

Eur Respir J 2019 03 14;53(3). Epub 2019 Mar 14.

Key Laboratory of Pulmonary Vascular Medicine and FuWai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease with high heritability. Although several predisposing genes have been linked to IPAH, the genetic aetiology remains unknown for a large number of IPAH cases.

Methods: We conducted an exome-wide gene-based burden analysis on two independent case-control studies, including a total of 331 IPAH cases and 10 508 controls. Functional assessments were conducted to analyse the effects of genetic mutations on protein biosynthesis and function.

Results: The gene encoding human bone morphogenetic protein 9 () was identified as a novel genetic locus displaying exome-wide association with IPAH in the discovery cohort (OR 18.8; p=1.9×10). This association was authenticated in the independent replication cohort (p=1.0×10). Collectively, the rare coding mutations in occurred in 6.7% of cases, ranking this gene second to , comprising a combined significance of 2.7×10 (OR 21.2). Intriguingly, the patients with mutations had lower plasma levels of BMP9 than those without. Functional studies showed that the mutations led to reduced BMP9 secretion and impaired anti-apoptosis ability in pulmonary arterial endothelial cells.

Conclusion: We identify as an IPAH culprit gene.
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http://dx.doi.org/10.1183/13993003.01609-2018DOI Listing
March 2019

Novel metabolites from Trichoderma atroviride against human prostate cancer cells and their inhibitory effect on Helicobacter pylori and Shigella toxin producing Escherichia coli.

Microb Pathog 2019 Jan 10;126:19-26. Epub 2018 Oct 10.

Department of Medical Biotechnology, College of Biomedical Sciences, Kangwon National University, Chuncheon 24341, South Korea. Electronic address:

The present study aimed to purify and identify the metabolites from T. atroviride using high-performance liquid chromatography (HPLC) and H and C nuclear magnetic resonance spectrometer (NMR) followed by analyzing their toxicological, antibacterial and anticancer properties. This work identified two metabolites - TM1 and TM2. TM1 was in two forms: (i) 1, 3-dione-5, 5-dimethylcyclohexane; and, (ii) 2-enone-3hydroxy -5,5-dimethylcylohex, while TM2 was 4H-1,3-dioxin-4-one-2,3,6-trimethyl. These metabolites did not exhibit any irritant or allergic reaction as revealed by HET- CAM test. TM2 significantly inhibited the growth of H. pylori and Shigella toxin producing Escherichia coli (STEC) as evident by in vitro and microscopic observations of bacterial cell death. TM2 also induced the cell death and cytotoxicity, as revealed by cell viability test and western blot analysis. According to microscopic, flow cytometer and western blot analysis, TM2 treated cells displayed higher ROS, cell death, and apoptosis-related protein expression than TM1 and control. This study concluded that TM2 derived from T. atroviride was a potential therapeutic agent for anti-prostate cancer and antibiotic agent against MDR- H. pylori and STEC and it is also recommended to carry out further in vivo animal model experiments with improved stability of the metabolites for future pharmaceutical trails.
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http://dx.doi.org/10.1016/j.micpath.2018.10.011DOI Listing
January 2019

Zinc-chitosan nanoparticles induced apoptosis in human acute T-lymphocyte leukemia through activation of tumor necrosis factor receptor CD95 and apoptosis-related genes.

Int J Biol Macromol 2018 Nov 6;119:1144-1153. Epub 2018 Aug 6.

Department of Medical Biotechnology, College of Biomedical Sciences, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. Electronic address:

Chitosan (CS), a novel biomaterial is widely used as a drug nano-carrier for cancer treatments. Towards this aim, anticancer and antibacterial activities of CS-nanoparticles-linked zinc (Zn-CSNPs) were evaluated. The particle size of CSNPs was lowered (113.09 nm) compared to Zn-CSNPs (160.7 nm). Both nanoparticles (CSNPs and Zn-CSNPs) were spherical in shape, polydispersive and homogenous. Fourier transforms infrared spectrophotometer (FTIR) and energy dispersive X-ray spectroscopy (EDX) analysis confirmed the different molecular arrangement of NPs and the presence of Zn in Zn-CSNPs and CS in both NPs, respectively. Zn-CSNPs had higher inhibitory activity against tested pathogens with a minimal inhibitory concentration (MIC) of 9.25-13.5 μg·mL and showed the complete inhibition of Staphylococcus aureus and Escherichia coli. Zn-CSNPs have triggered the apoptosis through activation of first apoptosis signal receptor/cluster of differentiation 95 (Fas/CD95), and apoptotic-regulatory genes and caused 65-70% of cellular damage in human acute T-lymphocyte leukemia (6T-CEM) cells. Overall, internalizing properties of Zn from CSNPs is a promising therapeutic approach to treat Zn-deficiency related diseases particularly human acute leukemia (HAL).
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http://dx.doi.org/10.1016/j.ijbiomac.2018.08.017DOI Listing
November 2018

Transition from Ambrisentan to Bosentan in Pulmonary Arterial Hypertension: A Single-Center Prospective Study.

Can Respir J 2018 11;2018:9836820. Epub 2018 Apr 11.

Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.

: 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. : 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.
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http://dx.doi.org/10.1155/2018/9836820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924990PMC
April 2019

Impact of Pituitary-Gonadal Axis Hormones on Pulmonary Arterial Hypertension in Men.

Hypertension 2018 07 30;72(1):151-158. Epub 2018 Apr 30.

State Key Laboratory of Cardiovascular Disease, FuWai Hospital, and Key Laboratory of Pulmonary Vascular Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (X.J., S.-F.L., Q.-Q.L., J.-H.L., Z.-C.J.)

The association of sex hormone (estradiol, testosterone, and progesterone) with cardiopulmonary disease has already attracted great attention, especially in pulmonary arterial hypertension (PAH). However, the impact of sex hormones and their pituitary stimulators (follicle-stimulating hormone and luteinizing hormone) on PAH in men remains unclear. We conducted a prospective cohort study recruiting 95 patients with idiopathic PAH from 2008 to 2014 and following up for a median of 65 months for death. Compared with control, abnormal plasma levels of sex hormones were more common in patients with PAH. Higher estradiol and estradiol/testosterone levels were associated with risk of PAH diagnosis (odds ratio per ln estradiol, 3.55; <0.001; odds ratio per ln estradiol/testosterone, 4.30; <0.001), whereas higher testosterone and progesterone were associated with a reduced risk (odds ratio per ln testosterone, 0.48; =0.003; odds ratio per ln progesterone, 0.09; <0.001). Fifty patients died during follow-up. Men with higher estradiol had increased mortality (hazard ratio per ln estradiol, 2.02; =0.007), even after adjustment for baseline characteristics and PAH treatment. According to receiver operating characteristic analysis, patients with PAH with higher estradiol level (≥145.55 pmol/L) had worse 5-year survival rate compared with those with lower estradiol (38.6% versus 68.2%; log-rank test =0.001). Therefore, our data show higher estradiol, estradiol/testosterone ratio, lower testosterone, and progesterone were associated with increased risk of PAH. Meanwhile, higher estradiol was independently associated with higher mortality in men with PAH. Further studies are needed to explain the origin of these hormonal derangements and their potential pathophysiological implications in PAH.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.10963DOI Listing
July 2018

Sex-specific cardiopulmonary exercise testing indices to estimate the severity of inoperable chronic thromboembolic pulmonary hypertension.

Int J Chron Obstruct Pulmon Dis 2018 26;13:385-397. Epub 2018 Jan 26.

Department of Cardio-Pulmonary Circulation, 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. O pulse, workload, minute ventilation (VE), and end-tidal partial pressure of O (PO) at anaerobic threshold, as well as peak O pulse, workload, VE, and nadir VE/CO were significantly higher in male patients than in female patients (<0.05). Only oxygen uptake efficiency plateau (OUEP) showed a significantly higher difference in female than male patients (<0.05). In addition, several CPET indices correlated with hemodynamic parameters, especially pulmonary vascular resistance (PVR), which was distinctly different between the sexes. Nadir VE/CO was an independent predictor of PVR in male patients with CTEPH, whereas OUEP was an independent predictor of PVR in female patients with CTEPH.

Conclusion: Even after confounding for age and body mass index, different CPET measurements of gas exchange efficiency correlated with PVR differently between male and female patients. This potentially could be used to estimate the severity of CTEPH.
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http://dx.doi.org/10.2147/COPD.S152971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790096PMC
September 2018

Is ERAS effective and safe in laparoscopic gastrectomy for gastric carcinoma? A meta-analysis.

World J Surg Oncol 2018 Jan 26;16(1):17. Epub 2018 Jan 26.

Department of Gastrointestinal Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, No.628 Zhenyuan Road, Guangming new district, Shenzhen, 518017, China.

Background: It is still unclear whether enhanced recovery after surgery is effective and safe in laparoscopic gastrectomy for gastric carcinoma.

Methods: Cochrane library databases, Medline, Embase, and Pubmed were searched from January 1, 1986, to December 31, 2016. Randomized controlled trials (RCTs) comparing fast-track recovery with conventional recovery strategies in laparoscopic radical gastrectomy for gastric carcinoma were included. The main outcomes measured were postoperative hospital stay, time to first flatus, hospital charge, and overall complication rate.

Results: Six RCTs with 400 patients were included in this study. Fast-track surgery has shorter postoperative hospital stays (weighted mean difference (WMD) - 2.65; 95% CI, - 4.01 to - 1.29, z = 3.82, P < 0.01) and less hospitalization expenditure (WMD - 523.43; 95% CI, - 799.79 to - 247.06, z = 3.71, P < 0.01) than conventional recovery strategies. There was no significant difference with respect to duration to first flatus (WMD - 17.72; 95% CI, - 39.46-4.02, z = 1.60, P = 0.11) and complication rate (OR 1.57; 95% CI, 0.82-2.98, z = 1.37, P = 0.17).

Conclusions: Enhanced recovery after surgery is effective and safe and is thus recommended in laparoscopic radical gastrectomy for gastric carcinoma.
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http://dx.doi.org/10.1186/s12957-018-1309-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787292PMC
January 2018

Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension.

Int J Chron Obstruct Pulmon Dis 2017 22;12:3353-3360. Epub 2017 Nov 22.

Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

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 [<2.0 L⋅min⋅m]). All patients received a single 20 µg dose of iloprost via a nebulizer (4.4 µg delivered at the mouthpiece). No serious adverse events were reported. Hemodynamic and gas exchange parameters (arterial blood gas and shunt fraction [Qs/Qt]) were measured or calculated at baseline and 10 min after iloprost inhalation. mPAP decreased by 2.1 mmHg (95% CI, -3.3 to -1.0), pulmonary vascular resistance (PVR) decreased by 62.4 dyn⋅s⋅cm (95% CI, -92.9 to -31.8), and cardiac output increased by 0.4 L⋅min (95% CI, 0.2-0.5). There was a more significant decline in PVR in patients with severe COPD-PH than in those with nonsevere COPD-PH. Hypoxemia and intrapulmonary shunt were more extreme in patients with severe COPD-PH. However, there were no significant differences in arterial blood gas and Qs/Qt between patients with nonsevere and severe forms of COPD-PH. In conclusion, iloprost improved pulmonary hemodynamics without detrimental effects on arterial oxygenation in patients with COPD-PH, even in those with severe PH. These findings suggest that the short-term use of iloprost in patients with COPD-PH is effective and well tolerated.
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http://dx.doi.org/10.2147/COPD.S141798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702173PMC
July 2018

Efficacy and safety of a calcium sensitizer, levosimendan, in patients with right heart failure due to pulmonary hypertension.

Clin Respir J 2018 Apr 26;12(4):1518-1525. Epub 2017 Sep 26.

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.

Background: Despite using vasoactive and pulmonary hypertension (PH) specific therapies, the in-hospital mortality of severe PH with right heart failure (RHF) is high. We conducted a prospective analysis evaluating the efficacy and safety of levosimendan in PH patients with severe acute RHF.

Methods: Forty-five PH patients hospitalized between January 2016 and November 2016 were recruited into a single arm, prospective, open-label study. Levosimendan was administered at the rate of .05-0.1 μg/kg/min, up to a total dose of 12.5 mg. The primary endpoints were changes of World Health Organization Function Class (WHO-FC) and Borg dyspnoea scores. Secondary endpoints included changes in 6-min walk distance (6-MWD), biochemical markers and right heart structure and function together with adverse events on day 7 and incidence of major cardiovascular events (death or readmission due to RHF) on day 30.

Results: Forty-five PH patients were enrolled. On the 7th day after levosimendan infusion, seven out of 13 PH patients with WHO-FC IV improved by one class (P = .008). Borg dyspnoea scores, 6-MWD and NT-proBNP improved significantly (P < .001). Compared with baseline, the right atrial transverse dimension, end-systolic eccentricity index and tricuspid annular plane systolic excursion improved significantly (58.8 ± 13.1 mm vs 53.7 ± 12.4 mm; 1.50 ± 0.27 vs 1.38 ± 0.23; 15.0 (13.0, 16.0) mm vs 15.8 (14.0, 17.4) mm, P < .005, respectively). One patient occurred sudden death after discharge during follow-up.

Conclusions: Intravenous levosimendan can effectively improve severe RHF of PH patients in hospital and well tolerated.
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http://dx.doi.org/10.1111/crj.12699DOI Listing
April 2018

A novel scoring index by Doppler echocardiography for predicting severe pulmonary hypertension due to chronic lung diseases: a cross-sectional diagnostic accuracy study.

Int J Chron Obstruct Pulmon Dis 2017 14;12:1741-1751. Epub 2017 Jun 14.

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine.

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 = ESI + ESI + ESI - ESI. Additionally, the ESI was weighted by +2 points 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 -3 points 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, <0.0001). Compared with PASP, ESI ≥1.0 exhibited 91.1% sensitivity and 80.4% specificity, resulting in a net improvement in model performance with a change in the -statistic from 0.823 to 0.937 and an integrated discrimination improvement of 11.3% (95% CI: 4.5%-18.2%, =0.001). The ESI was applied to the validation cohort, resulting in 84.2% sensitivity and 81.3% specificity with 82.9% accuracy.

Conclusion: The ESI showed high capacity for predicting severe CLD-PH, further implying the value of noninvasive examinations in clinic.
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http://dx.doi.org/10.2147/COPD.S133854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476678PMC
April 2018

Sex-specific cardiopulmonary exercise testing indices related to hemodynamics in idiopathic pulmonary arterial hypertension.

Ther Adv Respir Dis 2017 03 2;11(3):135-145. Epub 2017 Jan 2.

Shanghai Pulmonary Hospital, Tongji University, School of Medicine, No. 507 Zhengmin Road, Shanghai 200433, China.

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, O 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 CO (PCO) was an independent predictor of PVR elevation in all patients and in men. Peak maximum oxygen consumption (VO) was independently predictive of CO decline in all patients and in men. Only peak O 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.
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http://dx.doi.org/10.1177/1753465816684424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933651PMC
March 2017

Shape of the Pulmonary Artery Doppler-Flow Profile Predicts the Hemodynamics of Pulmonary Hypertension Caused by Left-Sided Heart Disease.

Clin Cardiol 2016 Mar;39(3):150-6

Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.

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.
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http://dx.doi.org/10.1002/clc.22493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490949PMC
March 2016

One-stage Hybrid Procedure for Patients with Valvular Pulmonary Stenosis and Coronary Artery Disease.

Chin Med J (Engl) 2016 Mar;129(5):624-5

Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.

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http://dx.doi.org/10.4103/0366-6999.177005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804452PMC
March 2016
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