[How do we respond to the newly-revised haemodynamic definitions of pulmonary hypertension].

In August 2022, the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) jointly issued the 2022 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension, which updated the hemodynamic diagnostic criteria for pulmonary hypertension, causing widespread debate among experts. How should we respond to the updated diagnostic criteria for pulmonary hypertension? This paper analyzes the origin of the diagnostic criteria for pulmonary hypertension, how to understand the newly revised diagnostic criteria for hemodynamics, the definition of the new criteria for exercise pulmonary hypertension, and the important impact of the new diagnostic criteria on clinical practice, and puts forward countermeasures.

[Evaluation effect of COMPERA 2.0 risk assessment model on prognosis of Chinese patients with pulmonary arterial hypertension].

Objectives: To clarify the evaluation effect of COMPERA 2.0 risk assessment model on prognosis of pulmonary arterial hypertension (PAH) in China. Methods: Patients with newly diagnosed PAH admitted in Fuwai hospital between April 2019 and March 2022 were enrolled retrospectively and divided in low, intermediate-low, intermediate-high and high strata by scores of COMPERA 2.0 risk assessment model. All the patients were followed up by clinic or telephone. The primary endpoint was defined as a composite of all-cause mortality, exacerbated heart failure and aggravated symptoms. Kaplan-Meier analysis and log-rank trend test were used to determine the risk of endpoints among the 4 groups. Multivariate Cox proportional hazards regression were used to analyze the association between COMPERA 2.0 scores and prognosis in patients with PAH. Results: A total of 951 patients with PAH were enrolled in this study. The age [M (Q1, Q3)] of the patients was 35 (28, 47) years, of which 706 cases (74.2%) were females. A total of 328 cases (34.5%) were assigned in low strata, 264 cases (27.8%) in intermediate-low strata, 193 cases (20.3%) in intermediate-high strata, and 166 cases (17.5%) in high strata. During the duration [M (Q1, Q3)] of follow-up after discharge of 1.8 (1.0, 2.8) years, the primary endpoint was occurred in 12.8% (42/328), 21.2% (56/264), 28.5% (55/193) and 42.8% (71/166) of low, intermediate-low, intermediate-high and high strata, respectively. The rates of primary endpoint were significantly increased with strata rising (P<0.001). Multivariate Cox proportional hazards regression showed that COMPERA 2.0 risk scores were associated with the primary endpoints in PAH patients (HR=1.801, 95%CI: 1.254-2.588, P=0.001) after adjusting confounders. Conclusion: COMPERA 2.0 risk assessment model is a simple and effective tool for evaluating the prognosis of newly diagnosed PAH patients in China.

[Improve the understanding of hepatic disease related pulmonary vascular disease].

Hepatic disease-related pulmonary vascular disease refers to the changes in the structure or function of pulmonary circulation caused by liver parenchymal or hepatic vascular diseases, mainly including hepatopulmonary syndrome characterized by hypoxemia, portopulmonary hypertension characterized by pulmonary hypertension, and hepatic vascular shunt characterized by increased cardiac output and pulmonary hypertension. Early diagnosis and treatment of liver disease and early evaluation of liver transplantation may significantly improve the prognosis for patients with hepatic disease-related pulmonary vascular disease. Moreover, it is necessary to improve clinicians' understanding of this disease and strengthen multidisciplinary cooperation, improve the level of diagnosis and treatment.

[Differential diagnosis between pulmonary artery sarcoma and central chronic pulmonary thromboembolism:a preliminary study on CT signs].

Objective: To improve the diagnostic accuracy of pulmonary artery sarcoma, and to distinguish it from central chronic pulmonary thromboembolism using CT scans. Methods: In this retrospective study, two groups of pulmonary artery sarcoma (PAS group) and central chronic pulmonary thromboembolism (central CPTE group) confirmed by pathology at our hospital between August 2009 and July 2019 were enrolled, clinical features and pre-operative CT pulmonary artery manifestation were collected, and the key points of differential diagnosis were summarized. Results: The study was composed of 13 cases in the PAS group including 10 males (76.9%), with an average age of (45.4±15.5) years. There were 19 patients in the central CPTE group including 14 males (73.7%), with an average age of (38.6±14.1) years. There were no significant differences in gender and age between the two groups. Deep venous thrombosis in the lower extremities was significantly higher in the central CPTE group than in the PAS group (7/19 vs. 0/13, P=0.025), and the N-terminal pro-brain natriuretic peptide value was higher in the central CPTE group than in the PAS group [674.50(261.70-1 977.70) vs. 66.00(28.10-505.50),P=0.001]. In CT pulmonary angiography, the involvement of the main pulmonary artery, and the proximal lesion showing an acute angle to the pulmonary artery wall were more common in the PAS group [11(84.6%) vs. 5(26.3%), P=0.003; 11(84.6%) vs. 2(10.5%), P<0.001, respectively]. The swelling index of the main pulmonary and the left/right main pulmonary arteries in the PAS group were significantly higher, as well as the dilatation in the lobar and segmental pulmonary arteries [1.19±0.17 vs. 0.99±0.19,P=0.006, 10(76.9%) vs. 2(10.5%), P<0.001, respectively]. The right ventricular transverse diameter/left ventricular transverse diameter (RVd/LVd) and pulmonary artery diameter/ascending aortic diameter ratio (Pad/Aod) were significantly lower in PAS group than those in the central CPTE group (0.97±0.19 vs. 1.23±0.35,P=0.020; 0.98±0.25 vs. 1.15±0.20,P=0.039). Conclusions: In CT pulmonary angiography, filling defects involving the main pulmonary artery and showing expansive growth were highly suggestive of pulmonary artery sarcoma. The history of deep venous thrombosis of the lower extremities was helpful for the diagnosis of chronic pulmonary embolism.

[Strengthening multidisciplinary collaboration and promoting the construction of standardized system for pulmonary hypertension in China].

In recent years, pulmonary hypertension (PH) has attracted increasing attention from scholars worldwide, which involves diverse etiology and complicated pathogenesis. Due to changes in the structure and function of pulmonary vasculatures, it can lead to an increase in pulmonary vascular resistance and pulmonary artery pressure, and then progress to right ventricular heart failure or even death. The diagnosis of PH involves multiple disciplines, which could easily give rise to missed diagnosis and misdiagnosis and non-standardized treatment. Recently, we have made great progress in the field of clinical diagnosis, treatment and research of PH. However, many issues remain to be solved. Accordingly, this article aims to call for further strengthening of multidisciplinary collaboration in PH field and promote the construction of a standardized system for PH in China.

[Clinical features of post-splenectomy pulmonary hypertension and effects of its target therapy].

Objective: To analyze the clinical features of post-splenectomy pulmonary hypertension and effects of its target therapy, and improve the diagnosis and treatment of the disease. Methods: Clinical data of 18 patients with post-splenectomy pulmonary hypertension admitted to Fuwai Hospital from October 2006 to March 2017 were systematically reviewed and analyzed. Results: Among the 18 patients with a mean age of (41±11) years old, 11 were women and 7 were men. The interval between splenectomy and the diagnosis of pulmonary hypertension was (11±6) years. Shortness of breath (14/18) and chest distress (12/18) were the most common clinical manifestations. Nine patients were in World Health Organization functional class (WHO-FC) Ⅲ-Ⅳ, and two patients were combined with pulmonary embolism. According to the cause of splenectomy, the pulmonary hypertension patients were divided into hepatocirrhosis portal hypertension group (10/18) and non-hepatocirrhosis portal hypertension group (8/18). In hepatocirrhosis portal hypertension group, patients were combined with chronic liver abnormalities presentation, and no pulmonary embolism was found in these patients. Cardiac output and cardiac index were significantly higher (P=0.007 and 0.011, respectively) and pulmonary vascular resistance was significantly lower (P=0.013) in hepatocirrhosis portal hypertension group as compared with non-hepatocirrhosis portal hypertension group. There was no difference in WHO-FC and mean pulmonary arterial pressure between two groups (P=0.448 and 0.379, respectively). After 3 months of target treatment in 8 patients, WHO-FC of 3 patients improved, systolic pulmonary artery measured by ultrasonic cardiogram was significantly decreased[(84±10) vs (71±12) mmHg(1 mmHg=0.133 kPa), P=0.005]and right ventricular end diastolic diameter/left ventricular end diastolic diameter was significantly reduced[(0.78±0.17) vs (0.62±0.16), P=0.010]compared to the baseline. The level of NT-proBNP also tended to be decreased, although not to a significant extent. Conclusions: Post splenectomy pulmonary hypertension has various clinical features. Post splenectomy pulmonary hypertension resulted from hepatocirrhosis portal hypertension has better hemodynamics. Target treatment is effective for the patients with post splenectomy pulmonary hypertension.

[Clinical features of Takayasu arteritis patients with pulmonary hypertension due to pulmonary artery involvement].

OBJECTIVE: To summarize the clinical features of Takayasu arteritis (TA) patients with pulmonary hypertension due to pulmonary artery involvement. METHODS: Ninety-four TA patients with pulmonary artery involvement treated in Fuwai Hospital from Jun 1988 to Jun 2014 were retrospectively summarized. Patients were divided into two groups according to whether aorta and its main branches affected (APTA, n=48) or not (PTA, n=46). Clinical features and angiographic data were further analyzed. RESULTS: Of all the patients, male to female rate was 1∶3.3, age ranged from 8 to 60 years with median age of 33.5 years when symptom onset. Main symptoms included dyspnea on exertion. Heart murmur and mid-systolic murmur in pulmonic area were commonly found by physical examination. All patients had pulmonary hypertension by echocardiographic examination. Angiographic data showed that multi-lobular and multi-segmental pulmonary branches were predominantly affected, followed by sub-segmental and peripheral branches. Both sides of pulmonary artery involvement were more common than one side involvement, while the right pulmonary arteries were more often affected than the left. Most of the clinical symptoms and signs between APTA group and PTA group were comparable. However, erythrocyte sedimentation rate and N-terminal pro-natriuretic peptide were significant higher in APTA group than that in PTA group when admission [14.0(5.0, 28.0) vs 8.5(3.0, 19.3) mm/1 h and (1 936±1 769) vs (1 627±1 153) ng/L, both P<0.05]. CONCLUSIONS: Dyspnea on exertion may be the main manifestation of TA with pulmonary artery involvement. All patients present with pulmonary hypertension and moderate to severe heart failure when symptom onset.

VIP gene variants related to idiopathic pulmonary arterial hypertension in Chinese population.

A variety of studies has linked vasoactive intestinal peptide (VIP) to idiopathic pulmonary arterial hypertension (IPAH). In this study, we investigated the correlation between VIP gene variants and IPAH in Chinese population. A total of 81 consecutive unrelated patients diagnosed as IPAH from 2006 to 2008 and 250 controls were included in the study. VIP gene variants were screened by direct sequencing, and VIP serum level was determined by enzyme-linked immunosorbent assay. Clinical and hemodynamic data of all patients were also obtained. The variant g.8129T-->C in exon 7 was found to be the only variant in the coding region of VIP gene with a significantly higher frequency in patients (40.7%) than in control samples (15.2%). Moreover, there was marked difference in VIP serum level and hemodynamic data between IPAH patients with and without the variant. The variant g.8129T-->C in exon 7 of VIP gene was correlated with the clinical phenotype of lower VIP serum level, higher mean pulmonary artery pressure and pulmonary vascular resistance in patients with IPAH comparing to those in patients without this variant. The VIP gene variant g.8129T-->C may be one of the risk factors in the pathogenesis of IPAH.

Gate dependence of upper critical field in superconducting (110) LaAlO3/SrTiO3 interface.

The fundamental parameters of the superconducting state such as coherence length and pairing strength are essential for understanding the nature of superconductivity. These parameters can be estimated by measuring critical parameters such as upper critical field, Hc2. In this work, Hc2 of a superconducting (110) LaAlO3/SrTiO3 interface is determined through magnetoresistive measurements as a function of the gate voltage, VG. When VG increases, the critical temperature has a dome-like shape, while Hc2 monotonically decreases. This relationship of independence between the variation of Tc and of Hc2 suggests that the Cooper pairing potential is stronger in the underdoped region and the coherence length increases with the increase of VG. The result is as for high temperature superconducting cuprates and it is different than for conventional low temperature superconductors.

Ent-16ß,17-dihydroxy-kauran-19-oic acid, a kaurane diterpene acid from Siegesbeckia pubescens, presents antiplatelet and antithrombotic effects in rats.

The antiplatelet and antithrombotic effects of ent-16ß,17-dihydroxy-kauran-19-oic acid (DDKA) isolated from Siegesbeckia pubescens were investigated with different methods both in vitro and in vivo. We tested the antithrombotic activity of DDKA in arterio-venous shunt model. The effects of DDKA on adenosine diphosphate (ADP)-, Thrombin-, Arachidonic acid-induced rat platelets aggregation were tested in vitro. We also assessed its bleeding side effect by measuring coagulation parameters after intravenous administration for 5 days and investigated the potential mechanisms underlying such activities. In vivo, DDKA significantly reduced thrombus weight in the model of arterio-venous shunt. Meanwhile, DDKA increased plasma cAMP level determined by radioimmunoassay in the same model. Notably, DDKA prolonged PT and APTT in rats after intravenous administration DDKA for successive 5 days. In vitro, pretreatment with DDKA on washed rat platelets significantly inhibited various agonists stimulated platelet aggregation and caused an increase in cAMP level in platelets activated by ADP. These findings support our hypothesis that DDKA possesses antiplatelet and antithrombotic activities. The mechanisms underlying such activities may involve the anticoagulatory effect and cAMP induction.

In vitro and in vivo antitumor activity of Macrothelypteris torresiana and its acute/subacute oral toxicity.

The aim of this study was to evaluate the antitumor potential of Macrothelypteris torresiana by studying in vitro antitumor activity of the protoapigenone, as well as in vivo antitumor activity and acute/subacute oral toxicity of the total flavonoid fraction from the roots of M. torresiana. Considering that the protoapigenone is a main constituent of the total flavonoid fraction and it might play a key role in the antitumor activity of M. torresiana, the MTT assay was used to investigate the in vitro antitumor activity of the protoapigenone. Our study revealed that the protoapigenone of M. torresiana showed significant antitumor activity towards Hep G2, Tca-8113, MCF-7, M5 and K562 with IC(50) values of 2.3, 0.6, 0.8, 0.3 and 0.9 µg/ml, respectively. The antitumor potential of the total flavonoid fraction was evaluated using preparations 1, 2 and 3, which were prepared by total flavonoid fraction directly diluted with sterile saline, dissolved using sodium carboxymethyl cellulose (CMC-Na) and included by hydroxypropyl-ß-cyclodextrin, respectively. These were investigated in vivo using mouse sarcoma S-180 in BALB/c mice after completing tumor inoculation for 24h. Pronounced antitumor activity was observed in the treated groups for preparations 2 and 3, and the high and medium doses in particular showed very high inhibition ratio of tumor growth (>50%). No significant difference was observed when compared to the positive control group (5-fluorouracil). The acute/subacute oral toxicity test was performed, and the results of acute oral toxicity showed that the LD(50) values of preparations 2 and 3 were 2.76 and 0.87 g/kg body wt., respectively. According to the results of the subacute oral toxicity study, the total flavonoid fraction had low toxicity. The overall results of this study suggest that the total flavonoid fraction from the roots of M. torresiana shows significant antitumor activity and represents a potential source of medicine for the treatment of cancer.