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Pulmonary hypertension is a chronic vascular disease characterized by pulmonary vasoconstriction and pulmonary arterial remodeling. Pulmonary arterial remodeling is mainly due to small pulmonary arterial wall thickening and lumen occlusion. Previous studies have described intravascular changes in lung sections using histopathology, but few were able to obtain a fine detailed image of the pulmonary vascular system. In this study, we used Microfil compounds to cast the pulmonary arteries in a rat model of monocrotaline-induced pulmonary hypertension. High-quality images that enabled quantification of distal pulmonary arterial branching based on the number of vessel bifurcations/junctions were demonstrated in this model. The branch and junction counts of distal pulmonary arteries significantly decreased in the monocrotaline group compared to the control group, and this effect was inversely proportional to the mean pulmonary artery pressure observed in each group. The patterns of pulmonary vasculature and the methods for pulmonary vessel casting are presented to provide a basis for future studies of pulmonary arterial remodeling due to pulmonary hypertension and other lung diseases that involve the remodeling of vasculature.

Background: Renal and liver dysfunctions are risk factors for mortality in patients with severe aortic stenosis (AS). Transcatheter aortic valve implantation (TAVI) has the potential to break the vicious cycle between AS and hepatorenal dysfunction by relieving aortic valve obstruction. Hypothesis: A part of patients can derive hepatorenal function improvement from TAVI, and this noncardiac benefit improves the intermediate‐term outcomes. Methods: We developed this retrospective cohort study in 439 consecutive patients undergoing TAVI and described the dynamic hepatorenal function assessed by model for end‐stage liver disease model for end‐stage liver disease (MELD)‐XI score in subgroups. The endpoint was 2‐year all‐cause mortality. Results: Receiver‐operating characteristic analysis showed that the baseline MELD‐XI score of 10.71 was the cutoff point. A high MELD‐XI score (>10.71) at baseline was an independent predictor of the 2‐year mortality hazard ratio (HR: 2.65 [1.29–5.47], p =.008). After TAVI, patients with irreversible high MELD‐XI scores had a higher risk of 2‐year mortality than patients who improved from high to low MELD‐XI scores (HR: 2.50 [1.06–5.91], p =.03). Factors associated with reversible MELD‐XI scores improvement were low baseline MELD‐XI scores (≤12.00, odds ratio [OR]: 2.02 [1.04–3.94], p =.04), high aortic valve peak velocity (≥5 m/s, OR: 2.17 [1.11–4.24], p =.02), and low body mass index (≤25 kg/m2, OR: 2.73 [1.25–5.98], p =.01). Conclusion: High MELD‐XI score at baseline is an independent predictor for 2‐year mortality. Patients with hepatorenal function improvement after TAVI have better outcomes. For patients with irreversible hepatorenal dysfunction after TAVI, further optimization of the subsequent treatment after TAVI is needed to improve the outcomes. [ABSTRACT FROM AUTHOR]

Specific tumor-responsive capabilities and efficient synergistic therapeutic performance are the keys to effective tumor treatment. Herein, AuNRs@SiO2–RB@MnO2 was developed as a new type of tumor-responsive nanotheranostic for multimodal imaging and synergistic chemodynamic/photothermal therapy. In AuNRs@SiO2–RB@MnO2, the SiO2 layer wraps the AuNRs, providing light absorption in the second near-infrared (NIR-II) region. The SiO2 layer also adsorbs the MnO2 nanosheets, which have Fenton-like activity, resulting in a fluorescent sensing platform based on the fluorescence quenching properties of MnO2 for rhodamine B dye. The fluorescence can be recovered by the consumption of MnO2 by glutathione, which simultaneously produces Mn2+ in the tumor region. The recovery of fluorescence reflects the consumption of glutathione and the increase in Mn2+, which produces hydroxyl radicals via Fenton-like reaction in the tumor microenvironment to realize chemodynamic therapy. Meanwhile, the AuNRs are a good photothermal reagent that can effectively absorb NIR-II light and convert it into heat energy to kill tumor cells via photothermal therapy. The NIR-II absorption performance of the AuNRs provides good photoacoustic imaging and deep photothermal performance, which is favorable for efficient NIR-II photoacoustic imaging-guided photothermal therapy. As a result, the AuNRs@SiO2–RB@MnO2 nanotheranostic exhibits outstanding imaging and synergistic chemodynamic/photothermal therapeutic performance for tumor imaging and treatment. [ABSTRACT FROM AUTHOR]

Introduction: The patients with pulmonary arterial hypertension (PAH) are commonly diagnosed at late stage with right heart failure, results in poor prognosis. Invasive cardiopulmonary exercise test is utilized to diagnose pulmonary vascular dysfunction in early stage, according to increased mean pulmonary arterial pressure (mPAP), but the pathologic changes of pulmonary artery and the effects of early intervention are unknown. Methods: Male Sprague-Dawley rats were administrated with monocrotaline (MCT, 60mg/kg) or vehicle by intraperitoneal injection. MPAP was measured via right heart catheter at rest and exercise on a treadmill every other day after MCT injection. Rats were divided into exercise-induced PAH group (EiPAH, mPAP < 25 mmHg at rest and > 30 mmHg at peak exercise), rest PAH group (rPAH, mPAP >25 mmHg at rest), treated with Tadanafil 9mg/kg by gavage for 14 days when diagnosed by RHC, respectively.Lung tissue was stained with Hematoxylin-Eosin, medial wall index of pulmonary artery was analyzed by Image-Pro. Results: The elevated peak mPAP during exercise test was presented at the day 7 (38.5 ± 2.7 mmHg versus vehicle 27.24 ± 0.46 mmHg, P <0.0001, Figure 1.a), rPAH was determined at the day 21 after MCT injection (34.7 ± 1.2 mmHg). Decreased mPAP was observed in the EiPAH group compared with the rPAH group (26.67 ± 0.11 mmHg versus 35.23 ± 0.47 mmHg, P <0.0001, Figure 1.b) after 14 days treatment with Tadanafil. Medial wall index of small pulmonary artery was 44.4% in EiPAH group and 61.2% in rPAH group (P =0.0003, Figure 1.c, pathology image Figure 2. a,b,c,d). Survival rate did not differ (P =0.427, Figure 1.d). Conclusion: This present study validates an exercise-induced rat model of pulmonary hypertension, early diagnosis and intervention decreases the mPAP and relieves the pulmonary vascular remodeling, which may offer a new avenue for testing potential mechanisms and clearing an early diagnosis and intervention for pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Specific tumor-responsive capabilities and efficient synergistic therapeutic performance are the keys to effective tumor treatment. Herein, AuNRs@SiO 2 -RB@MnO 2 was developed as a new type of tumor-responsive nanotheranostic for multimodal imaging and synergistic chemodynamic/photothermal therapy. In AuNRs@SiO 2 -RB@MnO 2 , the SiO 2 layer wraps the AuNRs, providing light absorption in the second near-infrared (NIR-II) region. The SiO 2 layer also adsorbs the MnO 2 nanosheets, which have Fenton-like activity, resulting in a fluorescent sensing platform based on the fluorescence quenching properties of MnO 2 for rhodamine B dye. The fluorescence can be recovered by the consumption of MnO 2 by glutathione, which simultaneously produces Mn 2+ in the tumor region. The recovery of fluorescence reflects the consumption of glutathione and the increase in Mn 2+ , which produces hydroxyl radicals via Fenton-like reaction in the tumor microenvironment to realize chemodynamic therapy. Meanwhile, the AuNRs are a good photothermal reagent that can effectively absorb NIR-II light and convert it into heat energy to kill tumor cells via photothermal therapy. The NIR-II absorption performance of the AuNRs provides good photoacoustic imaging and deep photothermal performance, which is favorable for efficient NIR-II photoacoustic imaging-guided photothermal therapy. As a result, the AuNRs@SiO 2 -RB@MnO 2 nanotheranostic exhibits outstanding imaging and synergistic chemodynamic/photothermal therapeutic performance for tumor imaging and treatment.