Diagnostic efficacy of contrast-enhanced gastric ultrasonography in staging gastric cancer: a meta-analysis.

BACKGROUND: As comprehensive surgical management for gastric cancer becomes increasingly specialized and standardized, the precise differentiation between ≤T1 and ≥T2 gastric cancer before endoscopic intervention holds paramount clinical significance. OBJECTIVE: To evaluate the diagnostic efficacy of contrast-enhanced gastric ultrasonography in differentiating ≤T1 and ≥T2 gastric cancer. METHODS: PubMed, Web of Science, and Medline were searched to collect studies published from January 1, 2000 to March 16, 2023 on the efficacy of either double contrast-enhanced gastric ultrasonography (D-CEGUS) or oral contrast-enhanced gastric ultrasonography (O-CEGUS) in determining T-stage in gastric cancer. The articles were selected according to specified inclusion and exclusion criteria, and the quality of the included literature was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale. Meta-analysis was performed using Stata 12 software with data from the 2 × 2 crosslinked tables in the included literature. RESULTS: In total, 11 papers with 1124 patients were included in the O-CEGUS analysis, which revealed a combined sensitivity of 0.822 (95% confidence interval [CI] = 0.753-0.875), combined specificity of 0.964 (95% CI = 0.925-0.983), and area under the summary receiver operating characteristic (sROC) curve (AUC) of 0.92 (95% CI = 0.89-0.94). In addition, five studies involving 536 patients were included in the D-CEGUS analysis, which gave a combined sensitivity of 0.733 (95% CI = 0.550-0.860), combined specificity of 0.982 (95% CI = 0.936-0.995), and AUC of 0.93 (95% CI = 0.91-0.95). According to the I2 and P values ​​of the forest plot, there was obvious heterogeneity in the combined specificities of the included papers. Therefore, the two studies with the lowest specificities were excluded from the O-CEGUS and D-CEGUS analyses, which eliminated the heterogeneity among the remaining literature. Consequently, the combined sensitivity and specificity of the remaining studies were 0.794 (95% CI = 0.710-0.859) and 0.976 (95% CI = 0.962-0.985), respectively, for the O-CEDUS studies and 0.765 (95% CI = 0.543-0.899) and 0.986 (95% CI = 0.967-0.994), respectively, for the D-CEGUS studies. The AUCs were 0.98 and 0.99 for O-CEGUS and D-CEGUS studies, respectively. CONCLUSION: Both O-CEGUS and D-CEGUS can differentiate ≤T1 gastric cancer from ≥T2 gastric cancer, thus assisting the formulation of clinical treatment strategies for patients with very early gastric cancer. Given its simplicity and cost-effectiveness, O-CEGUS is often favored as a staging method for gastric cancer prior to endoscopic intervention.

miR-324-3p Suppresses Hepatic Stellate Cell Activation and Hepatic Fibrosis Via Regulating SMAD4 Signaling Pathway.

In hepatic fibrosis (HF), hepatic stellate cells (HSCs) form the extracellular matrix (ECM), and the pathological accumulation of ECM in the liver leads to inflammation. Our previous research found that miR-324-3p was down-regulated in culture-activated human HSCs. However, the precise effect of miR-324-3p on HF has not been elucidated. In this study, the HF mouse models were induced through directly injecting carbon tetrachloride (CCl4) into mice; the HF cell models were constructed using TGF-ß1-treated LX-2 cells. Next, real-time-quantitative polymerase chain reaction (RT-qPCR), western blot (WB) and immunohistochemistry (IHC) were applied to assess the expression levels of miR-324-3p, α-smooth muscle actin (α-SMA), Vimentin or SMAD4; hematoxylin and eosin (H&E), Masson' s trichrome and Sirius red staining to evaluate the liver injury; luciferase reporter assay to verify the targeting relationship between miR-324-3p and SMAD4; enzyme-linked immunosorbent assay (ELISA) to determine the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and cell counting kit-8 (CCK-8) and flow cytometry to evaluate the effects of miR-324-3p on cell proliferation and cycle/apoptosis, respectively. The experimental results showed a reduction in miR-324-3p level in CCl4-induced HF mice as well as transforming growth factor (TGF)-ß1-activated HSCs. Interestingly, the miR-324-3p level was rescued following the HF recovery process. In HF mice induced by CCl4, miR-324-3p overexpression inhibited liver tissue damage, decreased serum ALT and AST levels, and inhibited fibrosis-related biomarkers (α-SMA, Vimentin) expression, thereby inhibiting HF. Similarly, miR-324-3p overexpression up-regulated α-SMA and Vimentin levels in HF cells, while knockdown of miR-324-3p had the opposite effect. Besides, miR-324-3p played an antifibrotic role through inhibiting the proliferation of hepatocytes. Further experiments confirmed that miR-324-3p targeted and down-regulated SMAD4 expression. SMAD4 was highly expressed in HF cells, and silencing SMAD4 significantly decreased the α-SMA and Vimentin levels in HF cells. Collectively, the miR-324-3p may suppress the activation of HSCs and HF by targeting SMAD4. Therefore, miR-324-3p is identified as a potential and novel therapeutic target for HF.

Abdominal Ultrasonography After Transrectal Filling With Contrast Agents in Colorectal Cancer With Severely Stenotic Lesions.

OBJECTIVE: Abdominal ultrasonography after transrectal filling with contrast agent (AU-TFCA) was retrospectively evaluated with respect to determination of T stage and lesion length in patients with colorectal cancer (CRC) who had previously failed colonoscopy because of severe intestinal stenosis. METHODS: The population comprised 83 patients with CRC with intestinal stenosis and previously failed colonoscopy who underwent AU-TFCA, and in addition contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI), 2 wk before surgery. The diagnostic performance of AU-TFCA and CECT/MRI was evaluated relative to the post-operative pathological results (PPRs) by paired sample t-test, receiver operator characteristic (ROC) curve, Pearson's χ2-test and κ and intraclass correlation coefficients. RESULTS: The T staging identified via AU-TFCA, but not CECT/MRI, was relatively consistent with that of the PPRs (linearly weighted κ coefficient: 0.558, p < 0.001, and linearly weighted κ coefficient: 0.237, p < 0.001, respectively). The overall diagnostic accuracy of T staging based on AU-TFCA (83.1%) was significantly higher than that based on CECT/MRI (50.6%). Regarding lesion length, the results of AU-TFCA and PPRs were comparable (t = 1.852, p = 0.068), but those of CECT/MRI and PPRs were significantly different (t = 8.450, p < 0.001). CONCLUSION: AU-TFCA is effective in evaluation of lesion length and T stage in patients with severely stenotic CRC lesions who previously failed colonoscopy. The diagnostic accuracy of AU-TFCA is significantly better compared with that of CECT/MRI.

Proprotein convertase subtilisin/kexin type 9 inhibitor non responses in an adult with a history of coronary revascularization: A case report.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder that is characterized by severely increased low-density lipoprotein (LDL) cholesterol levels. At the same time, elevated LDL levels accelerated the development of coronary heart disease. Several classes of drugs are currently in use to treat FH. Proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is novel one of these. CASE SUMMARY: This manuscript reports a case of FH that responded modestly after treatment with PCSK9i and statin drugs. Of even more concern is that the patient frequently admitted to the hospital during a 12-year follow-up period. Subsequently, we identified a heterozygous mutation, 1448G>A (W483X) of the LDL receptor (LDLR) in this patient. The serum levels of PCSK9 (proprotein convertase subtilisin/kexin type 9) in the patient was 71.30 ± 26.66 ng/mL, which is close the average level reported in the literature. This LDLR mutation affects LDLR metabolism or structure, which may make it unsuitable for use of PCSK9i. CONCLUSION: Our outcome demonstrates that LDLR-W483X represents a partial loss-of-function LDLR and may contribute to PCSK9i ineffective. In the meanwhile, additional measures are therefore required (particularly with gene sequencing or change the treatment plan) must be initiated as early as possible. Genetic testing for clinically challenging cases who do not respond to PCSK9i therapy is very helpful.

Role of Whole-exome Sequencing in Phenotype Classification and Clinical Treatment of Pediatric Restrictive Cardiomyopathy.

BACKGROUND: Restrictive cardiomyopathy (RCM) is the least common cardiomyopathy in which the walls are rigid and the heart is restricted from stretching and filling properly. Cardiac troponin I (cTnI) mutation-caused myofibril Ca2+ hypersensitivity has been shown to be associated with impaired diastolic function. This study aimed to investigate the linkage between the genotype and clinical therapy of RCM. METHODS: Five sporadic pediatric RCM patients confirmed by echocardiography were enrolled in this study. Whole-exome sequencing (WES) was performed for the cohort to find out candidate causative gene variants. Sanger sequencing confirmed the WES-identified variants. RESULTS: TNNI3 variants were found in all of the five patients. R192H mutation was shared in four patients while R204H mutation was found only in one patient. Structure investigation showed that the C terminus of TNNI3 was flexible and mutation on the C terminus was possible to cause the RCM. Catechins were prescribed for the five patients once genotype was confirmed. Ventricular diastolic function was improved in three patients during the follow-up. CONCLUSIONS: Our data demonstrated that TNNI3 mutation-induced RCM1 is the most common type of pediatric RCM in this study. In addition, WES is a reliable approach to identify likely pathogenic genes of RCM and might be useful for the guidance of clinical treatment scheme.

Value of the Ratio of Occluder Versus Atrial Septal Length for Predicting Arrhythmia Occurrence after Transcatheter Closure in Children with Ostium Secundum Atrial Septal Defect.

BACKGROUND: Transcatheter occlusion has been applied to treat ostium secundum atrial septal defect (OS ASD) since 1997. During the clinical practice, several postoperative complications including arrhythmia have been reported. This study aimed to evaluate the value of the ratio of atrial septal occluder (ASO) versus atrial septal length (ASL) for predicting arrhythmia occurrence after transcatheter closure in children with OS ASD. METHODS: Six hundred and fifty-one children diagnosed with OS ASD underwent occlusion procedures after completing routine examinations. The onsets and types of arrhythmia both during and after the occlusion procedures were monitored. Treatments were given based on the individual types of arrhythmia. The binary logistic regression analysis and receiver-operating characteristic (ROC) curve were used in the analysis of value of the ratio of ASO/ASL for predicting postoperative arrhythmia occurrence. RESULTS: Transcather occlusions were conducted in 651 children, among whom 7 children had different types and degrees of arrhythmia, with an incidence of 1.1%. The types of arrhythmia included sinus bradycardia, atrial premature beats, bundle branch block, and different degrees of atrioventricular block. Normal electrocardiograph findings were resumed in these 7 patients following active therapies such as corticoids, nutrition, and surgeries. The binary logistic regression and ROC analysis suggested that the ratio of ASO/ASL exhibited an intermediate predictive value for predicting arrhythmia occurrence after occlusion procedures. A cut-off value of 0.576 in the ratio provided a sensitivity of 87.5% and a specificity of 76.2% with an area under the ROC curve of 0.791 (95% confidence intervals, 0.655-0.926; P < 0.05) in predicting arrhythmia occurrence after the closure procedures. CONCLUSIONS: The ratio of ASO/ASL might be a useful index for predicting arrhythmia occurrence after closure procedures in children with OS ASD.

Is serum cystatin C an early predictor for acute kidney injury following cardiopulmonary bypass surgery in infants and young children?

Acute kidney injury (AKI) is a potential complication following cardiopulmonary bypass (CPB) surgery in infants and young children with congenital heart disease (CHD). The current pilot study evaluates the predictive value of serum cystatin C (CysC) for AKI after pediatric CPB surgery. We prospectively enrolled 43 children with CHD (30 males and 13 females) who underwent CPB surgery. They were aged 3 years or younger. Serum CysC was measured at baseline and at 6 hours, 12 hours, 24 hours, and 48 hours after initiating CBP. Twenty-one (48.8%) patients developed AKI after cardiac surgery. Children who developed AKI had more complex cardiac surgical procedures (based on the Risk Adjustment for Congenital Heart Surgery 1 [RACHS-1] category), a longer CPB duration, and a longer aortic clamping time (ACT). Serum concentrations of CysC postoperatively demonstrated an initial decline at 6 hours, a subsequent increase at 12 hours, and stabilized at 24-48 hours. The best predictive performance was achieved 6 hours after CPB with an area under receiver operating characteristic curve (AUC) value of 0.69. The optimal cut-off value was 0.47 mg/L (sensitivity, 85.7%; specificity, 50%). By contrast, the RACHS-1 category, CPB duration, and ACT had higher AUC values at 0.735, 0.791, and 0.731, respectively. In conclusion, serum CysC had limited predictive capacity and was not superior to clinical risk factors for the early detection of AKI after CPB surgery in this pilot study, which focused on infants and young children.

[The research progress of Aurora-B kinase and its inhibitors].

Aurora-B as an important kinase to adjust the cell normal mitosis is a potent target for cancer treatment. Aurora-B is overexpressed in a broad range of tumor and tumor cells are more sensitive while Aurora-B is inhibited. Due to the key role of the Aurora-B in cell mitosis, the development of its inhibitors is becoming more and more important. Several small molecules inhibit with a similar efficacy both Aurora-A and Aurora-B, however, in most cases the effects resemble Aurora-B disruption by genetic methods, indicating that Aurora-B represents an effective therapeutic target. There were several Aurora-B kinase inhibitors which had entered the clinics and displayed good antitumor activity. In this review, we will outline the functions of Aurora kinase B in normal cell division and in malignancy. We will focus on recent preclinical and clinical studies that have explored the mechanism of action and clinical effect of Aurora-B inhibitors in cancer treatment.

Dyssynchronous ventricular contraction in Wolff-Parkinson-White syndrome: a risk factor for the development of dilated cardiomyopathy.

UNLABELLED: Emerging evidence suggests that significant left ventricular dysfunction may arise in right-sided septal or paraseptal accessory pathways (APs) with Wolff-Parkinson-White syndrome, even in the absence of recurrent or incessant tachycardia. During 1 year and 9 months, we identified four consecutive female children with median age of 8 years diagnosed as having dilated cardiomyopathy (DCM) combined with overt right-sided APs several years ago. Incessant or recurrent tachycardia as the cause of DCM could be excluded. Anti-heart failure chemotherapy did not produce satisfactory effects. The patients underwent radiofrequency ablations (RFCAs). This report describes the clinical and echocardiographic characteristics of the cases before and after the ablation. Dyssynchronous ventricular contraction was observed in all patients. The locations of the APs were the right-sided anteroseptum and the free wall (n = 2 each). All patients received successful RFCAs. Their physical activities and growth improved greatly, and the echocardiographic data demonstrated that their left ventricular (LV) contraction recovered to synchrony shortly after the ablation and that their LV function recovered to normal gradually during the follow-up. CONCLUSIONS: A causal relationship between overt ventricular preexcitation and the development of DCM is supported by the complete recovery of LV function and reversed LV remodeling after the loss of ventricular preexcitation. Preexcitation-related dyssynchrony was probably the crucial mechanism. Not only right-sided septal or paraseptal but also free wall overt APs may induce LV dysfunction and even DCM. AP-induced DCM is an indication for ablation with a good prognosis.

[Early prediction of acute kidney injury in infants and young children after cardiopulmonary bypass surgery].

OBJECTIVE: To understand the incidence of acute kidney injury (AKI) in infants and toddlers and evaluate the possibility of predicting AKI with urine neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-beta-D-glucosaminidase (NAG), microalbumin (MA) and α1-microglobulin (α1-MG) after surgeries for congenital heart diseases with cardiopulmonary bypass (CPB). METHOD: Fifty-eight children (ages ≤ 3 years) who had undergone surgery for congenital heart diseases with CPB were enrolled. Urinary samples were collected before and 4 h, 6 h, 12 h, 24 h post CPB to detect the concentration of NGAL, IL-18, NAG, MA and α1-MG. RESULT: The AKI group had 29 cases, none AKI group also had 29 cases. Urinary concentration of NGAL 4, 6, and 12 h post CPB were significantly higher in AKI group (2820 µg/g, 905.7 µg/g, 76.1 µg/g separately) than in none AKI group (27.6 µg/g, 19.5 µg/g, 16.0 µg/g separately, P < 0.01). Urinary concentration of IL-18 4, 6, 12 and 24 h post CPB were significantly higher in AKI group than in none AKI group (P < 0.05). Urinary concentration of NAG 4 h and 6 h post CPB were significantly higher in AKI group than in none AKI group (P < 0.01). Urinary concentration of MA/UCr post CPB 4 h, 6 h and 12 h were significantly higher in AKI group than in none AKI group (P < 0.05). Urinary concentration of α1-MG/UCr post CPB 4 h, 6 h and 12 h were significantly higher in AKI group than in none AKI group (P < 0.01). All the five biomarkers had predictive abilities at 4-hour after surgery. CONCLUSION: Urine biomarkers NGAL, IL-18, NAG, MA and α1-MG were valuable early predictors of AKI after CPB surgery.

Clinical features and long-term prognosis of patients with anomalous origin of the left coronary artery from the pulmonary artery.

BACKGROUND: Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital heart anomaly. We aimed to illustrate the clinical features and long-term prognosis of patients with ALCAPA. METHODS: Twenty three patients (13 males and 10 females, ages ranging from 2.5 months to 65 years) identified as ALCAPA in Beijing Anzhen Hospital from April 1984 to June 2009 were divided into two groups, based on the age of onset: group 1 (≤ 12 months, n = 16) and group 2 (> 12 months, n = 7). RESULTS: Fifty six point three percent of patients in group 1 had been misdiagnosed as endocardial fibroelastosis (9/16), 18.8% as dilated cardiomyopathy (3/16) and 6.3% as myocardial infarction (1/16). Patients in group 2 were usually diagnosed as coronary heart disease, myocarditis, or patent ductus arteriosus. Electrocardiography in group 1 revealed abnormal Q waves with T wave inversion in leads I, avL, V(4)-V(6), especially in lead avL (deep and wide Q wave); but no specific manifestations in group 2. A higher percentage of patients in group 1 had cardiomegaly on chest radiograph (86.7% vs. 33.3%, P = 0.031), while pulmonary artery protrusion was more common in group 2 (26.7% vs. 83.3%, P = 0.046). Lower left ventricular ejection fraction (LVEF) was present in group 1 than in group 2 ((48.5 ± 11.5)% vs. (65.0 ± 6.1)%, P < 0.001). Apical ventricular aneurysm (62.5% vs. 0%, P = 0.007), enhanced echogenicity of papillary muscles (87.5% vs. 28.6%, P = 0.011) and endocardial thickening (93.8% vs. 14.3%, P < 0.001) were more frequent in group 1 than in group 2. The ratio of the proximal right coronary artery (RCA) diameter to the aortic root diameter exceeded 0.14 in all cases, more prominent in group 2 (0.26 ± 0.05 vs. 0.33 ± 0.03, P = 0.009). Increased coronary artery collaterals within the interventricular septum were detected in 18 patients (78.3%) by Doppler imaging. Twenty one patients underwent cardiac surgery, including left coronary artery (LCA) ligation (1/21), LCA ligation plus coronary artery bypass grafting (1/21), Takeuchi operation (7/21), and LCA reimplantation surgery (12/21). Four patients underwent concomitant mitral valve repair and one received mitral valve replacement. Aneurysm resection was performed in 3 cases. Six patients died in hospital after surgery, and the rest of the cohort had no overt symptoms during a follow-up period of 6 to 166 months. Their abnormal Q waves gradually regressed or disappeared, and the LVEF and left ventricle size returned to normal range with alleviation of mitral insufficiency. CONCLUSIONS: The accurate diagnosis of ALCAPA can be made with serial diagnostic methods. ALCAPA can be successfully treated with several types of cardiac surgery, and surgeries of establishing two-coronary-artery circulation are the preferred operations nowadays, with good long-term prognosis.

[A long-term follow-up study on the clinical treatment of 75 cases with primary endocardial fibroelastosis].

OBJECTIVE: To summarize and analyze the effects of treatment and prognosis of infants with endocardial fibroelastosis (EFE) in different states of the illness undergone relevant therapies, and to understand the roles of different treatments for improving the prognosis of the disease. METHODS: Data of 75 cases with EFE admitted into Anzhen Hospital Affiliated to Capital Medical University from August 1984 to June 2006 were analyzed retrospectively. RESULTS: (1) Of the 75 cases with EFE (40 males and 35 females), with the onset age ranged from 20-days to two years and eight months, 69 cases were treated normally and followed up in the Outpatient Department of the Hospital after discharge, the follow-up rate was 92%, with the follow-up span from six months to 23 years (5.7 years in average). During the follow-up, six cases (8.7%) died. (2) The total curative rate of EFE patients was 46.4% (32/69), while the improvement rate was 40.6% (28/69), the total rate of the cure and improvement was 87%. (3) The average value of ejection fraction (EF) of left ventricle of all the patients returned to normal two years after treatment (EF value was 55.86 ± 2.85), the percentage of patients with normal left ventricle EF at 1 year, 3 years, 5 years and 10 years after treatment was 42.6% (26/61), 64.4% (29/45), 70.7% (29/41) and 84.6% (22/26), respectively. The average value of cardiothoracic (C/T) ratio became normal three years after treatment through X ray examination (0.50 ± 0.01), however the average value of the LVDD had not been returned to normal 3 years after treatment. At 1 year, 3 years, 5 years and 10 years after treatment, the proportion of patients with normal LVDD was 0% (0/61), 13.3% (6/45), 53.7% (22/41) and 84.6% (22/26), respectively. (4) The average value of EF became normal one year after treatment in the glucocorticoid group (EF value 58.44 ± 5.10) in 37 cases scored < 22 at the first visit, while the average value of C/T normalized two years after treatment (0.50 ± 0.00); The average value of EF became normal three years after treatment in the glucocorticoid plus cyclophosphamide group (EF 57.33 ± 3.43) in 29 cases scored < 22 at the first visit, however the average value of the C/T and the LVDD did not return to normal 3 years after treatment. (5) Use of IVIG reduced the percentage of patients who received cyclophos-phamide. (6) The recovery of intimal thickness was slow in EFE patients, the span was four years on the average (1 - 8 years), the percentage of patients whose endocardium became normal 1 year, 3 years, 5 years and 10 years after treatment was 9.85% (6/61), 22.2% (10/45), 51.2% (21/41), 100% (29/29). CONCLUSION: The long-term continuous normal treatment of patients with EFE showed good therapeutic effects. For severe and refractory cases, immunotherapy must be strengthened and maintained for longer time. For those who clinically recovered, the quantity of activity should be restricted after the treatment is discontinued, and the re-examination should be done timely for further management.

[The mRNA expression of alpha1-adrenergic receptor subtypes in the outer lung tissues of hypoxia pulmonary hypertension rats].

OBJECTIVE: During the development of hypoxic pulmonary hypertension, the quantity of the protein and mRNA of alpha1-adrenergic receptor (alpha1-adrenergic receptor,alpha1-AR) in the lung tissue increased, while no particular reports were found about the change of the alpha1-AR subtypes during that course. The study aimed to understand the quantity and location of alpha1-AR subtypes mRNA expression in control and hypoxia rats,and the effect of phentolamine in hypoxic pulmonary hypertension. METHODS: Fifty-five male Wistar rats were divided randomly into 5 groups: control group (n = 10), hypoxia 2 weeks (n = 13), hypoxia 4 weeks (n = 10), saline control group (n = 10) and hypoxia 4 weeks plus phentolamine group (n = 12). Semi-quantitative reverse transcription and polymerase chain reaction (RT-PCR) were used to examine the mRNA expression of alpha1-AR subtypes in each group. In situ hybridization was also used to detect the location of the alpha1-AR in lungs of normal rats. RESULTS: (1) The pulmonary artery pressure increased with the extension of hypoxia. (2) The results of RT-PCR showed that the mRNA expression of alpha1A-AR was the most,alpha1B-AR the second and alphaZD-AR was the least in all of the groups. (3) The expression of alpha1A-AR and alpha1B-AR mRNA increased with the extension of hypoxia, and the expressions among groups showed difference. (4) The expression of alpha1D-AR also increased with the extension of hypoxia but no difference was found among groups. (5) No difference was found in mRNA quantity of all three subtypes between phentolamine group and hypoxia saline group. (6) In situ hybridization showed that mRNA of the three alpha1-AR subtypes located mainly in the artery and venous smooth muscle cells and endothelial cells. CONCLUSIONS: This study suggested that alpha1-AR subtypes worked in the development of hypoxia pulmonary hypertension. More research on alpha1-AR subtypes may help the clinical treatment of pulmonary hypertension.