Inhibitory Effect of PPARδ Agonist GW501516 on Proliferation of Hypoxia-induced Pulmonary Arterial Smooth Muscle Cells by Regulating the mTOR Pathway.

OBJECTIVE: This study aimed to investigate the effects of the peroxisome proliferator-activated receptor δ (PPARδ) agonist GW501516 on the proliferation of pulmonary artery smooth muscle cells (PASMCs) induced by hypoxia, in order to search for new drugs for the treatment and prevention of pulmonary vascular remodeling. METHODS: PASMCs were incubated with different concentrations of GW501516 (10, 30, 100 nmol/L) under the hypoxic condition. The proliferation was determined by a CCK-8 assay. The cell cycle progression was analyzed by flow cytometry. The expression of PPARδ, S phase kinase-associated protein 2 (Skp2), and cell cycle-dependent kinase inhibitor p27 was detected by Western blotting. Then PASMCs were treated with 100 nmol/ L GW501516, 100 nmol/L mammalian target of rapamycin (mTOR) inhibitor rapamycin and/or 2 µmol/L mTOR activator MHY1485 to explore the molecular mechanisms by which GW501516 reduces the proliferation of PASMCs. RESULTS: The presented data demonstrated that hypoxia reduced the expression of PPARδ in an oxygen concentration- and time-dependent manner, and GW501516 decreased the proliferation of PASMCs induced by hypoxia by blocking the progression through the G0/G1 to S phase of the cell cycle. In accordance with these findings, GW501516 downregulated Skp2 and upregulated p27 in hypoxia-exposed PASMCs. Further experiments showed that rapamycin had similar effects as GW501516 in inhibiting cell proliferation, arresting the cell cycle, regulating the expression of Skp2 and p27, and inactivating mTOR in hypoxia-exposed PASMCs. Moreover, MHY1485 reversed all the beneficial effects of GW501516 on hypoxia-stimulated PASMCs. CONCLUSION: GW501516 inhibited the proliferation of PASMCs induced by hypoxia through blocking the mTOR/Skp2/p27 signaling pathway.

Prognostic factors of hyperbaric oxygen therapy for patients with delayed encephalopathy after acute carbon monoxide poisoning.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a disease with an incomplete pathological mechanism, long treatment time, and uncertain factors affecting the therapeutic effect. This study explored prognostic factors for DEACMP patients treated with hyperbaric oxygen therapy (HBOT) in 15 hospitals in China. The findings might provide a theoretical basis for further improving the prognosis of DEACMP patients. In this study, data from 330 patients with DEACMP who were admitted to HBOT centers of 15 hospitals in Hunan Province (China) from June 2015 to June 2020 were retrospectively analyzed, and their medical records related to disease prognosis were collected and followed up by telephone. Univariate and multivariate analyses were used to identify independent risk factors for the prognosis of DEACMP patients after HBOT. Univariate analysis revealed 11 possible prognostic factors. Consistent with univariate analysis, multivariate analysis found that underlying diseases (Odds radio(OR) = 2.886, P = 0.048), hypermyotonia (OR = 5.2558, P = 0.008), and HBOT pressure no less Than 2.3 atm absolute (ATA) ((OR = 7.812, P = 0.004) were identified as independent prognostic factors among 20 variables for poor prognosis of DEACMP patients treated with HBOT in the study. This multicenter retrospective analysis revealed that the adverse prognostic markers for DEACMP patients treated with HBOT might be underlying diseases, hypermyotonia, and an HBOT pressure of 2.3 ATA or higher.

CT Imaging Features and Clinical Characteristics of 2019 Novel Coronavirus Pneumonia (COVID-19) During Rehabilitation.

This study aims to explore the clinical characteristics of the patients with novel coronavirus pneumonia (COVID-19) during rehabilitation. One hundred and twelve confirmed patients were enrolled, while 72 were females (64.3%) and 40 were males (35.7%). The age of the patients was 51.63 ± 4.07 years old. Those patients were divided into mild group, moderate group and severe group based on lesion volume and proportion of total lesion on CT images. The age, gender, past medical history, finger pulse oxygen (SPO2), heart rate (HR) and body temperature and other clinical characteristics of patients were collected. Lesion volume was measured by CT. Compared with mild group, age, lesion volume and total lesion proportion in moderate group were significantly higher. Age, lesion volume and total lesion proportion in severe group were also higher than those in moderate group. Age and past medical history were the risk factors for the lesion volume of COVID-19. Older the patient has larger CT lesion range (R = 0.232, P = 0.045). Without past medical history or combination of post-medical history, the COVID-19 patients had smaller CT lesion ranges, and the history of previous cardiovascular disease and pulmonary disease was important risk factors for the larger CT lesion ranges. The patients who were older or combined with chronic diseases, especially cardiovascular diseases, respiratory disease and diabetes, tended to have the larger lesions. Age and past medical history of patients with COVID-19 period are significantly related to the lesion volume and total lesion proportion on CT images.

Clinical study of pulmonary CT lesions and associated bronchiectasis in 115 convalescent patients with novel coronavirus pneumonia (COVID-19) in China.

A total of 115 convalescent inpatients with COVID-19 were enrolled. According to the results of scans of lung lesions via computed tomography (CT), the patients were divided into mild, moderate, and severe groups. The clinical data of the patients were collected, including age, gender, finger pulse oxygen pressure, ventricular rate, body temperature, etc. The correlation between the clinical indicators and the lesions of high-resolution CT (HRCT) and bronchiectasis was analyzed. Among the 115 patients, 82 had no bronchiectasis and 33 had bronchiectasis. The bronchodilation-prone layers mainly included the left and right lower lobe of the lung. The probability of branching in the inflamed area was greater than that in the noninflamed area in patients with COVID-19. There were significant differences in gender, CT lesion range, and number of incidents of bronchiectasis between noninflamed and inflamed areas (P < 0.05). Moreover, there were significant differences in age, total proportion of CT lesions, volume of CT lesions, and total number of patients with bronchiectasis among the three groups (P < 0.05). CT lesion range was positively correlated with the total number of patients with bronchiectasis and patient age (respectively, r = 0.186, P < 0.05; r = 0.029, P < 0.05). The lesion range in HRCT images of lungs in patients with COVID-19 is correlated with bronchodilation. The larger the lesion, the higher the probability of bronchiectasis and the more incidents of bronchiectasis.