Novo Modelo Incremental para Predição de Mortalidade na Hipertensão Pulmonar Pré-Capilar / New Incremental Model for Predicting Mortality in Pre-Capillary Pulmonary Hypertension

Resumo Fundamento: Na hipertensão pulmonar (HP), é necessária a identificação de marcadores prognósticos de fácil obtenção associados com disfunção do ventrículo direito (VD) e sobrevida. Objetivo: Avaliar a associação do índice de anisocitose eritrocitária (RDW, do inglês red cell distribution width) com parâmetros ecocardiográficos e sobrevida em pacientes com HP pré-capilar, com o desenvolvimento de um modelo de predição de mortalidade. Métodos: Estudo observacional, longitudinal, prospectivo, conduzido entre maio de 2019 e dezembro de 2022. Trinta e quatro pacientes com HP pré-capilar submeteram-se à realização de ecocardiograma bidimensional e hemograma. Um ponto de corte de 14,5% foi adotado para definir o RDW como alterado (≥14,5%) ou normal (<14,5%). Valores de p<0,05 foram considerados significativos. Resultados: O RDW médio foi 14,4%. Houve uma diferença significativa na saturação periférica de oxigênio (SpO2) (p=0,028), strain do VD (p=0,047) e derrame pericárdico (p=0,002) entre os grupos com RDW normal e elevado. Durante um período mediano de 15 meses, 20,6% dos pacientes foram a óbito. Os pacientes com RDW aumentado tiveram uma sobrevida global mais curta (44,7%, log-rank p=0,019), sendo um preditor de mortalidade na regressão univariada de Cox. A adição do strain do VD < 16% e da SpO2 ≤93% ao modelo incluindo somente RDW mostrou valor incremental na predição de mortalidade (χ2=8,2, p=0,049; χ2=12,4, p=0,041), com área sob a curva ROC (do inglês, Receiver Operating Characteristic) aumentada (0,729 vs. 0,837 vs. 0,909) e probabilidade de sobrevida diminuída (44.7% vs. 35.6% vs. 25%, log-rank p=0,019). Conclusões: O RDW fornece informações sobre a gravidade da HP pré-capilar pela sua correlação com parâmetros ecocardiográficos de disfunção do VD e mortalidade, a qual é melhor predita por um modelo incluindo RDW, strain do VD e SpO2.

Abstract Background: In pulmonary hypertension (PH), the identification of easily obtainable prognostic markers associated with right ventricular (RV) dysfunction and survival is needed. Objective: To evaluate the association of red cell distribution width (RDW) with clinical, echocardiographic parameters and survival in patients with pre-capillary PH, with the development of a mortality prediction model. Methods: Observational, longitudinal, and prospective study conducted from May 2019 to December 2022. Thirty-four patients with pre-capillary PH underwent two-dimensional echocardiography and complete blood count. A cutoff point of 14.5% was considered to define RDW as altered (≥14.5%) or normal (<14.5%). P values <0.05 were considered significant. Results: The median RDW was 14.4%. There was a significant difference in peripheral arterial oxygen saturation (SpO2) (p=0.028), RV strain (p=0.047), and pericardial effusion (p=0.002) between the normal and elevated RDW groups. During a median follow-up of 15 months, 20.6% died. Patients with increased RDW had a shorter overall survival (44.7%, log-rank p=0.019), which was a predictor of mortality in univariate Cox regression (HR 8.55, p=0.048). The addition of RV strain <16% and SpO2 ≤93% to the model including RDW alone showed incremental value in predicting mortality (χ2=8.2, p=0.049; χ2=12.4, p=0.041), with increased area under the receiver operating characteristic curve (0.729 vs. 0.837 vs. 0.909) and decreased probability of survival (44.7% vs. 35.6% vs. 25%, log-rank p=0.019). Conclusions: RDW provides information on the severity of pre-capillary PH by correlating with echocardiographic parameters of RV dysfunction and mortality, which is best predicted by a model including RDW, RV strain and SpO2.

Cierre de conducto arterioso persistente con dispositivo OcclutechTM, experiencia en un país andino / Closure of patent ductus arteriosus with OcclutechTM device, experience in an andean country

Resumen Objetivo: Presentar la experiencia en un país andino con el dispositivo OcclutechTM Duct Occluder para el cierre del conducto arterioso persistente. Método: Estudio observacional, retrospectivo, de corte transversal con análisis estadístico básico. Periodo: diciembre/2014 a diciembre/2022. Datos: historia clínica, informes de laboratorio de cateterismo. Resultados: Cuarenta y seis pacientes; de sexo femenino 71.3%, de sexo masculino 28.7%; edad: 0.6-38 años (mediana [Me]: 5.2); peso: 6.3-60 kg (Me: 16.5). Procedencia: andina 91.3%, costa 8.7%. Tipos de conducto arterioso persistente: E 54.4%, A 32.6%, D 13%. Diámetro ductal mínimo: 1.8-11.8 mm (Me: 3.5). Presión media de la arteria pulmonar previo a la oclusión: 14-67 mmHg (Me: 27). Índice de resistencias vasculares pulmonares previo a la oclusión: 0.28-4.9 UW/m2 (Me: 1.3). Fueron catalogados como conductos arteriosos persistentes hipertensivos seis de ellos. Tasa de oclusión: inmediata el 47.8%, a las 24 horas el 81%, a los seis meses el 100%. Tiempo de fluoroscopia: 2-13.8 minutos (Me: 4). Complicaciones: un dispositivo migrado. Seguimiento: 1-6.5 años. Conclusiones: El dispositivo OcclutechTM Duct Occluder fue efectivo y seguro para el cierre de conducto arterioso persistente tipo E, A y D en habitantes de baja y alta altitud, ya sea que estos hubieran sido niños o adultos, incluso cuando estos conductos arteriosos fueron hipertensivos.

Abstract Objective: To communicate the experience in an Andean country with the OcclutechTM Duct Occluder device for the closure of patent ductus arteriosus. Method: Observational, retrospective, cross-sectional study with basic statistical analysis. Period: December/2014 to December/2022. Data: medical chart, reports of catheterization. Results: Forty-six patients, female 71.3%, male 28.7%; age: 0.6-38 years-old (median [Me]: 5.2); weight: 6.3-60 kg (Me: 16.5). Origin: andean 91.3%, coast 8.7%. Types of patent ductus arteriosus: E 54.4%, A 32.6%, D 13%. Minimum ductal diameter: 1.8-11.8 mm (Me: 3.5). Mean pulmonary artery pressure prior to occlusion: 14-67 mmHg (Me: 27). Pulmonary vascular resistance index prior to occlusion: 0.28-4.9 WU/m2 (Me: 1.3). Six of them were classified as hypertensive patent ductus arteriosus. Occlusion rate: 47.8% immediate, 81% at 24 hours, 100% after six months. Fluoroscopy time: 2-13.8 minutes (Me: 4). Complications: a migrated device. Follow-up: 1-6.5 years. Conclusions: OcclutechTM Duct Occluder device was effective and safe for the closure of patent ductus arteriosus type E, A and D in low-altitude and high-altitude dwellers, whether they were children or adults, even when these ductus arteriosus were hypertensive.

Fisiopatología de la hernia diafragmática congénita en el recién nacido / Pathophysiology of congenital diaphramatic hernia in the newborn

La hernia diafragmática congénita es una discontinuidad del diafragma con herniación de los órganos abdominales a la cavidad torácica, actualmente se postula una hipótesis dual para su origen. Su fisiopatología está determinada por la hipoplasia pulmonar, la hipertensión pulmonar y la disfunción ventricular, entender estos elementos es necesario para un adecuado manejo y la mejoría del pronóstico.

Congenital diaphragmatic hernia is a discontinuity of the diaphragm with herniation of the abdominal organs into the thoracic cavity, currently a dual hypothesis for its origin is postulated. Its pathophysiology is determined by pulmonary hypoplasia, pulmonary hypertension and ventricular dysfunction, understanding these elements is necessary for adequate management and improve prognosis.

Nomgram model for individual prediction of coronary heart disease with pulmonary hypertension / 公共卫生与预防医学

Objective To establish an individual Nomgram model for predicting the risk of coronary heart disease complicated with pulmonary hypertension. Methods From January 2017 to December 2021 , 352 patients with coronary heart disease (CHD) complicated with pulmonary hypertension in our hospital were selected, and 352 patients with coronary heart disease but without pulmonary hypertension were selected as the control group. The clinical baseline data of the two groups were analyzed first, and then logistics multivariate analysis was performed. To explore the risk factors of coronary heart disease complicated with pulmonary hypertension, the Nomgram model was established to predict the risk, and the predictive value of the model was tested by receiver characteristic curve (ROC). Results Logistics multivariate analysis showed that alcoholism, smoking, stroke history, hypertension course, CHD course, PASP, HCT, PaCO2, D-dimer, NIHSS score and low PaO2 were all independent risk factors for CHD complicated with pulmonary hypertension. Nomgram model prediction results for patients with coronary heart disease showed that Alcohol abuse, smoking, stroke history, duration of hypertension (5.66 years), duration of coronary heart disease (2.12 years), NIHSS (12.33 points), PASP (75.22mmHg), HCT (33.22%), PaCO2 (56.11mmHg), D-dimer (255.12μg/L), PaO2 (56.22mmHg) is a risk factor for coronary heart disease complicated with pulmonary hypertension. ROC curve showed that the area under the prediction curve of Nomgram model for coronary heart disease complicated with pulmonary hypertension was 0.675. Conclusion Nomgram model can predict pulmonary hypertension in patients with coronary heart disease to a certain extent.

Effects of Polydatin on Proliferation and Apoptosis of Pulmonary Artery Smooth Muscle Cells in Neonatal Rats with Hypoxic Pulmonary Hypertension by Regulating YAP1/TAZ Signaling Pathway / 华中科技大学学报(医学版)

Objective To investigate the effects of polydatin(PD)on the proliferation and apoptosis of pulmonary artery smooth muscle cells(PASMCs)in hypoxic pulmonary hypertension(HPH)neonatal rats,and its mechanism of action.Methods Neonatal rats were randomly separated into six groups:control group,model group,low dose PD group,medium dose PD group,high dose PD group,and high dose PD+Hippo pathway inhibitor(high dose PD+XMU-MP-1)group,with 10 rats in each group.After 2 weeks of hypoxia treatment,the right ventricular systolic blood pressure(RVSP)and right ventricular hypertro-phy index(RVHI)of rats in each group were measured.Hematoxylin-eosin(HE)staining was applied to observe pathological changes in lung tissue,and the percentage of pulmonary artery wall thickness to total thickness(WT)and the percentage of wall area to total area(WA)were calculated.Neonatal rat PASMCs were separated from each group,which were divided into NC group,hypoxia group,low dose PD group,medium dose PD group,high dose PD group,and high dose PD+XMU-MP-1 group.Cell counting kit 8(CCK-8)and 5-ethynyl-2'-deoxyuridine(EdU)were applied to detect cell proliferation.Flow cytometry was applied to detect cell apoptosis.Western blot was applied to detect the expression of Yes-associated protein 1(YAP1),tran-scriptional coactivator with PDZ-binding motif(TAZ),mammalian sterile 20-like kinase 1(MST1),B-cell lymphoma 2(Bcl-2),and Bcl-2 associated protein(Bax)in lung tissue and PASMCs.Results Compared with the control group,the pulmonary artery wall in the model group was significantly thickened,lumen was narrowed,and protein expressions of RVSP,RVHI,WT％,WA％,YAP1,MST1 and TAZ were significantly increased(all P＜0.05).Compared with the model group,pulmonary artery thickening and lumen enlargement were observed in the low,medium and high dose PD groups,and the protein expressions of RVSP,RVHI,WT％,WA％,YAP1,MST1 and TAZ were significantly decreased,which showed a dose-dependent relationship(all P＜0.05).The effect could be reversed by XMU-MP-1.Compared with the NC group,the cell A450nm value,EdU positive rate,the protein expression of YAP1,MST1,TAZ and Bcl-2 in the hydropoxia group were significantly increased.The apoptosis rate and the expression of Bax protein were obviously reduced(all P＜0.05).Compared with the hypoxia group,the cell A450nm value,EdU positive rate,the protein expression of YAP1,MST1,TAZ and Bcl-2 in the low,medium and high dose PD groups were obviously reduced.The apoptosis rate and the expression of Bax were significantly increased,which showed a dose-depend-ent relationship(all P＜0.05).The effect could be reversed by XMU-MP-1.Conclusion PD may inhibit the proliferation of PASMCs in HPH neonatal rats and promote apoptosis by inhibiting YAP1/TAZ signaling pathway.

Effects of early and late aerobic exercise on right heart failure induced by monocrotaline in rats with pulmonary hypertension / 中国组织工程研究

BACKGROUND:Clinical studies have shown that aerobic exercise is an important supplement to the clinical treatment of patients with pulmonary hypertension,which can alleviate the disease condition,increase exercise tolerance and improve the quality of life.However,it is not clear whether patients at different stages of pulmonary hypertension can benefit equally from exercise training. OBJECTIVE:To compare the intervention effects of early or late aerobic training on right heart failure in rats with pulmonary hypertension and explore its possible mechanism. METHODS:Sixty male Wistar rats were randomly divided into control group,model sedentary group,model early exercise group and model late exercise group,with 15 rats in each group.The model of pulmonary hypertension was established by intraperitoneal injection of monocrotaline(60 mg/kg)in the latter three groups.The model early exercise group was given 8 weeks of treadmill aerobic exercise(60%maximum running speed,60 minutes per day,5 days a week)after modeling,while the model late exercise group was trained for 6 weeks after 2 weeks of modeling.The control and model sedentary groups were fed quietly in the rat cage for 8 weeks.After training,the exercise performance,right ventricular hemodynamics,cardiopulmonary function,cardiopulmonary histopathology,reactive oxygen species level in mitochondria,activity of mitochondrial respiratory chain complex and expressions of myocardial tissue proteins were detected. RESULTS AND CONCLUSION:Compared with the model sedentary group,exercise performance and right ventricular function improved(P<0.05),myocardial collagen content,endothelin-1,tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio decreased(P<0.05),vascular endothelial growth factor and sarcoplasmic reticulum calcium-adenosine triphosphate enzyme expression increased(P<0.05),immunofluorescence intensity of mitochondrial reactive oxygen species and the protein expression of 3-nitrotyrosine decreased(P<0.05),the activities of complex I,II,IV and V increased in the model early exercise and model late exercise groups(P<0.05),but there were no significant changes in right ventricular maximum pressure,pulmonary acceleration time and pulmonary artery wall area/total vascular area ratio(P>0.05).Compared with the model late exercise group,the model early exercise group further improved exercise performance and right ventricular function,and downregulated collagen content,brain natriuretic peptide protein expression,tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio(P<0.05).To conclude,although pulmonary vascular remodeling and right ventricular overload persist in rats with pulmonary hypertension,exercise training at different stages of the disease has a cardioprotective effect.The mechanism is related to the improvement of cardiac remodeling,neurohormone system imbalance,inflammatory response and mitochondrial oxidative stress.Greater benefit is gained from initiating exercise in the early stage of the disease.

Progress of N-terminal pro-brain natriuretic peptide in early diagnosis of bronchopulmonary dysplasia and pulmonary hypertension in premature infants / 中国小儿急救医学

Bronchopulmonary dysplasia（BPD）is a significant complication that greatly impacts the prognosis of preterm infants.The incidence of pulmonary hypertension（PH）in preterms with moderate to severe BPD is relatively high，which further increases the mortality among infants with BPD.Diagnosis of BPD could be made until 36 weeks corrected gestational age，and the clinical manifestations of BPD-PH are also not specific enough for accurate identification.Cardiac catheterization is considered the gold standard for diagnosis，which is an invasive procedure，while echocardiography heavily relies on the experience of operator，limiting early detection of both BPD and BPD-PH.N-terminal pro-brain natriuretic peptide（NT-proBNP），secreted by ventricular myocytes in response to volume or pressure overload，has been widely utilized in assessing cardiac load in cases of congenital heart disease.Recent studies have shown that the blood NT-proBNP levels significantly elevate in infants with BPD within one week after birth and during the development stage of BPD.Additionally，there is a substantial increase in NT-proBNP levels from 28 to 36 weeks corrected gestational age，which has both high sensitivity and high specificity in predicting the occurrence of BPD-PH.Therefore，NT-proBNP is expected to serve as a biomarker for the early prediction of BPD and BPD-PH.This review summarized the biological function，metabolic characteristics，and current research advancements regarding NT-proBNP in BPD and BPD-PH.The aim is to utilize NT-proBNP as an early predictor for BPD and BPD-PH，enabling timely identification of premature infants with high risk factors of these diseases，and facilitating prompt intervention to ultimately enhance prognosis.

Mechanisms of platelet-derived growth factor-BB regulation of hypoxia-inducible factor-1α expression in pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension / 中国新生儿科杂志

Methods:A total of 160 Wistar neonatal rats were assigned into normoxia group, HPH group, normoxia+PDGF-BB group, HPH+PDGF-BB group and HPH+PDGF-BB inhibitor (STI571) group using random number table method (32 rats in each group), each group was further assigned into 4 subgroups on d3, d7, d14 and d21 (8 rats in each subgroup). HPH model was established using nitrogen-oxygen mixture with an oxygen concentration of 10%±0.5%. PDGF-BB groups were injected with adenovirus encoding PDGF-BB in the tail vein. HPH+STI571 group was given STI571 intragastrically. On d3, d7, d14 and d21 after modeling, mean right ventricular systolic pressure (RVSP) was examined. Morphological changes of small pulmonary arteries were observed using HE staining and indicators of pulmonary vascular remodeling calculated. Immunohistochemistry was used to determine the protein levels of PDGF-BB, HIF-1α and proliferation-associated protein nuclear protein Ki67 in the pulmonary vasculature of each group. RT-qPCR was used to determine the mRNA levels of PDGF-BB, HIF-1α and Ki67 in lung tissue.Results:At all time points, RVSP was higher in the HPH group than the normoxia group ( P<0.05), higher in the HPH+PDGF-BB group than the HPH group ( P<0.05), and lower in the HPH+STI571 group than both the HPH+PDGF-BB group and the HPH group ( P<0.05). On d3 after modeling, pulmonary vascular remodeling occurred in the HPH+PDGF-BB group; on d7, pulmonary vascular remodeling occurred in the PDGF-BB group and the HPH group. Pulmonary vascular remodeling appeared later and to a lesser extent in the HPH+STI571 group than the other hypoxic groups. On d3, d7 and d21 after modeling, protein and mRNA levels of PDGF-BB, HIF-1α and Ki67 in the HPH+PDGF-BB group were higher than the other groups ( P<0.05). The protein and mRNA expression levels of PDGF-BB, HIF-1α and Ki67 in the HPH+STI571 group were lower than the HPH+PDGF-BB group and the HPH group at all timepoints ( P<0.05). Conclusions:PDGF-BB up-regulates HIF-1α expression, participates in PASMC proliferation, exacerbates pulmonary vascular remodeling and increases pulmonary artery pressure in neonatal rats with HPH.Obiective:To study the roles of platelet-derived growth factor-BB (PDGF-BB) in hypoxic pulmonary hypertension (HPH) and the mechanisms of regulating hypoxia-inducible factor-1α (HIF-1α) expression, promoting the proliferation of pulmonary arterial smooth muscle cells (PASMC) and participating in the remodeling of pulmonary vessels.

Correlation between right atrial function parameters and prognosis in patients with chronic obstructive pulmonary disease complicated with pulmonary hypertension / 中国医师进修杂志

Objective:To explore the correlation between right atrial function parameters and prognosis in patients with chronic obstructive pulmonary disease(COPD) complicated with pulmonary hypertension.Methods:Eighty-four patients with COPD combined with pulmonary arterial hypertension treated with bosentan combined with milrinone admitted to the First Affiliated Hospital of Xinjiang Medical University during the period of February 2020 to June 2022 were selected as the study subjects, and they were divided into the effective group (63 cases) and the ineffective group (21 cases) according to the treatment effect. Right cardiac function parameters were measured by Philips iE33 color ultrasonography before treatment and 72 h after treatment. Logistic regression was used to analyze the risk factors affecting the treatment outcome of patients, and receiver operating characteristics (ROC) curve was used to analyze the predictive value of right atrial function parameters in the poor prognosis of patients with COPD complicated with pulmonary hypertension.Results:The main pulmonary artery diameter (MPA), right ventricular base transverse diameter (RVd1), right ventricular middle transverse diameter (RVd2), right atrial diameter (RAd) and right ventricular free wall thickness (RVWT) in the effective group were lower than those in the ineffective group: (2.65 ± 0.23) cm vs. (2.90 ± 0.44) cm, (3.46 ± 0.43) cm vs. (3.76 ± 0.72) cm, (3.48 ± 0.42) cm vs. (3.88 ± 0.69) cm, (3.53 ± 0.81) cm vs. (4.03 ± 1.20) cm, (0.63 ± 0.12) cm vs. (0.72 ± 0.21) cm; end-diastolic to end-systolic tricuspid ring displacement (TAPSE) was higher than that in the ineffective group: (2.08 ± 0.32) cm vs. (1.82 ± 0.46) cm, there were statistical differences( P<0.05). Logistic regression analysis showed that RVd1 increased ( OR = 3.717, P<0.05), RVd2 increased ( OR = 2.162, P<0.05), RAd increased ( OR = 2.838, P<0.05) and TAPSE reduction ( OR = 1.704, P<0.05) were risk factors for treatment failure in patients. The results of ROC curve showed that the area under the curve of RVd1, RVd2, RAd, TAPSE in predicting the therapeutic effect of COPD patients with pulmonary hypertension were 0.820, 0.831, 0.872, 0.909, respectively. Conclusions:The independent influencing factors of ineffective patients with COPD combined with pulmonary arterial hypertension treated with bosentan combined with milrinone are the increase of structural parameters of the right heart and the decrease of systolic function parameters. The therapeutic effect of patients can be evaluated clinically according to the level of each parameter.

Basic Research Progress of Zang Medicine in Treatment of Hypoxic Pulmonary Hypertension / 医药导报

Hypoxic pulmonary hypertension(HPH)is a kind of chronic high-altitude sickness disease,which is also the initiation link of high-altitude sickness such as pneumocardial disease and high-altitude pulmonary edema.Its main features are persistent vasoconstriction and irreversible remodeling of blood vessels.HPH has greatly impacted the health of people in the plat-eau section.As a typical representative of ethnic medicine,Zang medicine embodies the wisdom of the Zang people in their long-term struggle against diseases.Adapting to local conditions for a long time,Zang medicine has unique advantages in the treatment of HPH.By reviewing the pathogenesis of HPH and the research of single Zang medicine and the complex prescription of Zang medicine in the treatment of HPH,this article aims to provide a theoretical basis for the physiological and pathological research of HPH and to provide a reference for the clinical application of Zang medicine.

Investigation of Efficacy and Mechanism of Zukamu Granules on Hypoxic Pulmonary Hypertension / 医药导报

Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

The Effect of Yiqi Huoxue Formula （益气活血方） in the Treatment of Chronic Pulmonary Heart Disease and Heart Failure with Qi Deficiency and Blood Stasis Pattern of 58 Cases： A Randomized Controlled Trial / 中医杂志

ObjectiveTo explore the effectiveness and safety of Yiqi Huoxue Formula （益气活血方， YHF） in the adjuvant treatment of chronic pulmonary heart disease （CPHD） and heart failure （HF）with qi deficiency and blood stasis pattern. MethodsOne hundred and twenty patients with CPHD and HF with qi deficiency and blood stasis pattern were allocated randomly into treatment group and control group， with 60 case in each group. The control group was given conventional basic western medicine， while the treatment group was given oral administration of YHF granules in addition， one dose per day. The treatment course for both groups was 8 weeks. The TCM symptom scores， Minnesota Life Quality Scale （MLHF-Q） scores， echocardiographic indicators including right ventricular end-diastolic diameter （RVEDD）， left ventricular end-diastolic diameter （LVEDD）， left atrial end-diastolic diameter （LAEDD） and pulmonary artery mean pressure （PAMP）， six-minute walking distance （6MWD）， and plasma N-terminal pro-B-type natriuretic peptide （NT-ProBNP） level were compared between the groups. The effectiveness regarding cardiac function and TCM syndromes were compared between the two groups after treatment， and the occurrence of adverse events was observed. ResultsWith two drop-outs both in the treatment group and control group， and 58 cases in each group were included in the outcome analysis. The total effective rate regarding cardiac function and TCM syndromes in the treatment group were 91.38% （53/58） and 96.55% （56/58）， respectively， significantly higher than the corresponding 70.69% （41/58） and 48.27% （28/58） in the control group （P＜0.05）. After treatment， the TCM symptom scores and RVEDD level were significantly reduced in the treatment group， and MLHF-Q score， plasma NT-ProBNP level and PAMP level decreased significantly， while 6MWD increased in both groups （P＜0.01）. Compared to those in the control group， the TCM symptom scores， MLHF-Q score， plasma NT-ProBNP level and PAMP level significantly decreased， while 6MWD increased in the treatment group （P＜0.01）. There were no obvious abnormalities in the blood， urine， stool routine and liver and kidney function indicators in both groups. One adverse reaction each occurred in both groups， and there was no statistically significant difference in the incidence rates（P＞0.05）. ConclusionYHF combined with conventional western medicine can significantly improve the clinical efficacy， improve the clinical symptoms and cardiac function， increase the quality of life and exercise tolerance， and is relatively safe.

Construction and validation of risk prediction model for serious adverse events in adult patients with congenital heart disease complicated with pulmonary hypertension after cardiac catheterization / 中国胸心血管外科临床杂志

@#Objective To construct a risk prediction score model for serious adverse event (SAE) after cardiac catheterization in patients with adult congenital heart disease (ACHD) and pulmonary hypertension (PH) and verify its predictive effect. Methods The patients with PH who underwent cardiac catheterization in Wuhan Asian Heart Hospital Affiliated to Wuhan University of Science and Technology from January 2018 to January 2022 were retrospectively collected. The patients were randomly divided into a model group and a validation group according to the order of admission. The model group was divided into a SAE group and a non-SAE group according to whether SAE occurred after the catheterization. The data of the two groups were compared, and the risk prediction score model was established according to the results of multivariate logistic regression analysis. The discrimination and calibration of the model were evaluated using the area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test, respectively. Results A total of 758 patients were enrolled, including 240 (31.7%) males and 518 (68.3%) females, with a mean age of 43.1 (18.0-81.0) years. There were 530 patients in the model group (47 patients in the SAE group and 483 patients in the non-SAE group) and 228 patients in the validation group. Univariate analysis showed statistical differences in age, smoking history, valvular disease history, heart failure history, N-terminal pro-B-type natriuretic peptide, and other factors between the SAE and non-SAE groups (P<0.05). Multivariate analysis showed that age≥50 years, history of heart failure, moderate to severe congenital heart disease, moderate to severe PH, cardiac catheterization and treatment, surgical general anesthesia, and N-terminal pro-B-type natriuretic peptide≥126.65 pg/mL were risk factors for SAE after cardiac catheterization for ACHD-PH patients (P<0.05). The risk prediction score model had a total score of 0-139 points and patients who had a score>50 points were high-risk patients. Model validation results showed an area under the ROC curve of 0.937 (95%CI 0.897-0.976). Hosmer-Lemeshow goodness-of-fit test: χ2=3.847, P=0.797. Conclusion Age≥50 years, history of heart failure, moderate to severe congenital heart disease, moderate to severe PH, cardiac catheterization and treatment, general anesthesia for surgery, and N-terminal pro-B-type natriuretic peptide≥126.65 pg/mL were risk factors for SAE after cardiac catheterization for ACHD-PH patients. The risk prediction model based on these factors has a high predictive value and can be applied to the risk assessment of SAE after interventional therapy in ACHD-PH patients to help clinicians perform early intervention.

Research progress of targeted pulmonary vascular endothelial dysfunction in treatment of pulmonary hypertension / 中国药理学通报

Pulmonary hypertension (PH) is a progressive and fatal disease. The dysfunction of pulmonary artery endothelial cells (PAECs) is one of its important pathogenic factors. PAECs are monolayer flat epithelial cells, which play an important role in maintaining pulmonary vascular homeostasis. Studies have found that PAECs show damage and apoptosis at the early stage of PH development, while PAECs show anti-apoptotic characteristics at the late stage of PH development. The transition of PAECs into mesenchymal cells induced by hypoxic and inflammatory factors is also involved in the pathogenesis of PH. Carcinoid metabolism and mitochondrial dysfunction, bone mor- phogenic type 2 receptor mutation, epigenetic changes and inflammation of PAECs are the main pathogenesis of pulmonary vascular endothelial dysfunction in PH patients. New therapeutic measures targeting PAECs dysfunction are expected to play an important role in the treatment of PH in the future.

Advances in relationship between pyroptosis and pulmonary arterial hypertension and therapeutic drugs / 中国药理学通报

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Effect Xuefu Zhuyu decoction on endothelial-to-mesenchymal transition of pulmonary artery endothelial cells and its mechanism / 中国药理学通报

Aim To investigate the effect of Xuefu Zhuyu decoction on transforming growth factor-β1(TGF-β1 ) -induced endothelial-to-mesenchymal transition (EndMT) of pulmonary microvascular endothelial cells ( PMVEC), and further analyze the mechanism related to the TGF-β1/Smad signaling pathway. Method To construct an EndMT cell model, PMVEC was treated with TGF-β1 (5 μg · L

Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology / 中国药理学通报

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Research progress in hypoxia-induced endothelial-to-mesenchymal transition induced pulmonary vascular remodeling and drug interventions / 中国药理学与毒理学杂志

Pulmonary hypertension(PH)is the pulmonary vascular remodeling caused by endothe-lial dysfunction and other factors,which leads to the increase of pulmonary artery pressure and finally right heart failure and patient death.Medications can significantly improve the symptoms of patients with pulmonary hypertension,but drugs can't cure vascular remodeling and right heart failure once for all,so it is urgent to find new treatments.Endothelial cells can obtain mesenchymal phenotypes after hypoxia stimulation,that is,endothelial-to-mesenchymal transition(EndMT).Increasing studies have shown that EndMT plays an important role in pulmonary vascular remodeling of PH.In this review,three signaling pathways related to induction of endothelial-to-mesenchymal transition under hypoxic conditions and research progress in related drugs are elaborated:① Transforming growth factor-β/bone morphogenetic protein(TGF-β/BMP)signaling pathway.The TGF-β/BMP pathway is mediated by Smad,and hypoxia regulates the expressions of EndMT-related genes by inhibiting or inducing the phosphorylation level of Smad in the downstream medium.② Notch signaling pathway.Hypoxia can enhance Jagged/Notch signaling pathway and promote the EndMT process.③Wnt/β-catenin signaling pathway.Hypoxia increases the expression of β-catenin,activates the Wnt signaling pathway,and regulates the expressions of EndMT regulatory genes.The significance of hypoxia-induced EndMT as an impor-tant pathogenic factor in PH is clarified in order to provide new ideas for the improvement of pulmonary vascular remodeling and recommend new effective strategies for the prevention and treatment of PH.

Characteristics and Diagnostic Value of Ventricular Blood Pool T2 Map in Chronic Thromboembolic Pulmonary Hypertension / 中国医学影像学杂志

Purpose To observe the right ventricle and left ventricle blood pool T2 map in chronic thromboembolic pulmonary hypertension(CTEPH)and healthy controls,and to analyze the value of T2 mapping technique in evaluating CTEPH.Materials and Methods A total of 42 patients with CTEPH and 42 healthy volunteers had been prospectively recruited from January 2020 to January 2022 in China-Japan Friendship Hospital.All CTEPH patients underwent cardiac magnetic resonance with T2 mapping and right heart catheterization.Cardiac magnetic resonance was performed on healthy controls.Diastolic T2 mapping was performed in cardiac magnetic resonance,and then the ratio of right ventricular to left ventricular T2 values(RVT2/LVT2)between the CTEPH group and the healthy group was calculated and compared.Meanwhile,the correlation between RVT2/LVT2 and hemodynamic parameters in the CTEPH group was analyzed.Results RVT2/LVT2 in the CTEPH group was significantly lower than that in the healthy group(0.74±0.16 vs.0.86±0.12;t=3.673,P<0.001).RVT2/LVT2 in CTEPH group was negatively correlated with pulmonary vascular resistance(r=-0.534,P<0.001);while it was positively correlated with cardiac index,right atrium oxygen saturation,right ventricle oxygen saturation and pulmonary arteries oxygen saturation(r=0.600,0.603,0.648,0.582,P<0.001).Conclusion RVT2/LVT2 in the CTEPH group is positively correlated with right cardiac oxygen saturation and negatively correlated with pulmonary vascular resistance.T2 mapping may be a noninvasive evaluation of hemodynamics in CTEPH.