LncRNA MIAT stimulates oxidative stress in the hypoxic pulmonary hypertension model by sponging miR-29a-5p and inhibiting Nrf2 pathway.

OBJECTIVE: To elucidate the potential biological functions of long non-coding RNA (lncRNA) MIAT in the development of hypoxic pulmonary hypertension (HPH) and the underlying mechanism. MATERIALS AND METHODS: Twenty Sprague Dawley (SD) rats were randomly assigned into normoxia group (n=10) and hypoxia group (n=10), respectively. In vivo HPH model in rats was established by hypoxic induction. Expression levels of MIAT and miR-29a-5p in rats were detected. Meanwhile, hemodynamic indicators in rats were examined. In vitro HPH model was conducted in hypoxia-induced HPAECs. The interaction between MIAT and miR-29a-5p was assessed by Dual-Luciferase reporter assay. Moreover, their regulatory effects on viability, migratory ability, oxidative stress, and the Nrf2 pathway in hypoxia-induced HPAECs were examined. RESULTS: MIAT was upregulated in both in vivo and in vitro HPH models, while miR-29a-5p was downregulated. Knockdown of MIAT suppressed viability, migratory ability, and oxidative stress in hypoxia-induced HPAECs. MiR-29a-5p was the target gene binding MIAT, and silence of miR-29a-5p partially relieved the inhibitory effects of MIAT on the above regulations in HPAECs. CONCLUSIONS: MIAT promotes proliferative and migratory abilities, as well as oxidative stress in hypoxia-induced HPAECs by targeting miR-29a-5p, thus aggravating the development of HPH.

[Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China].

Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus (2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces (autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months-17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted >3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 10%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate (19%, 4/21), procalcitonin (4%,1/28), liver enzyme (22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions: In this case series, 2019-nCoV infection in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis of 2019-nCoV infection. After general treatment, the short-term prognosis is good.

[Value of low-dose multi-slice spiral CT chest scan in diagnosis of coal workers' pneumoconiosis].

Objective: To investigate the value of low-dose multi-slice CT (MSCT) chest scan in the diagnosis of coal workers' pneumoconiosis. Methods: A total of 90 patients with a confirmed diagnosis of coal workers' pneumoconiosis were enrolled, and under the conditions of fixed tube voltage, pitch, and slice thickness, they underwent CT scan with a normal dose (150 mA) and a low dose (30-50 mA). The quality of images obtained from two scans was compared, and the imaging findings, opacity profusion, stage, and radiation doses were also compared. Results: Compared with the normal-dose scan, low-dose scan increased the image noise, and the images obtained from scans with doses of 30, 40, and 50 mA did not show significant reductions in signal-to-noise ratio or contrast-to-noise ratio (P>0.05). There was no significant difference in the percentage of image quality between low-dose and normal-dose scans (P>0.05). There were no significant differences in the percentage of various imaging findings, opacity profusion, or percentage of different stages between low-dose (30, 40, and 50 mA) and normal-dose (150 mA) scans (P>0.05). Conclusion: There are no significant differences between low-dose MSCT chest scan and normal-dose CT in image quality, imaging findings of coal workers' pneumoconiosis, opacity profusion, and stage. Meanwhile, low-dose MSCT chest scan greatly reduces the radiation dose and can be used to assist the diagnosis and follow-up reexamination of coal workers' pneumoconiosis and cover the shortage of high-kilovoltage chest X-ray.

Characterization of the expression of macrophage inflammatory protein-1α (MIP-1α) and C-C chemokine receptor 5 (CCR5) after kainic acid-induced status epilepticus (SE) in juvenile rats.

AIMS: To identify the potential role of macrophage inflammatory protein-1α (MIP-1α) with its C-C chemokine receptor 5 (CCR5) in epileptogenic brain injury, we examined their expression in juvenile rat hippocampus and explored the potential link between MIP-1α, CCR5 and neuropathological alterations after status epilepticus (SE) induced by intracerebroventricular (i.c.v.) kainic acid (KA) injection. METHODS: Based on the determination of the development of spontaneous seizures initiated by SE in developing rat brain, we firstly examined hippocampal neurone damage through Nissl and Fluoro-Jade B staining, and evaluated microglial reaction during the early phase following KA-induced SE in 21-day-old rats. MIP-1α and CCR5 protein were quantified by ELISA and Western blot respectively following mRNA by real-time PCR. We also mapped MIP-1α and CCR5 expression in the hippocampus by immunohistochemistry and identified their cellular sources using double-labelling immunofluorescence. RESULTS: In juvenile rats, KA caused characteristic neurone damage in the hippocampal subfields, with accompanying microglial accumulation. In parallel with mRNA expression, MIP-1α protein in hippocampus was transiently increased after KA treatment, and peaked from 16 to 72 h. Double-labelling immunofluorescence revealed that MIP-1α was localized to microglia. Up-regulated CCR5 remained prominent at 24 and 72 h and was mainly localized to activated microglia. Further immunohistochemistry revealed that MIP-1α and CCR5 expression were closely consistent with microglial accumulation in corresponding hippocampal subfields undergoing degenerative changes. CONCLUSIONS: Our data indicated that MIP-1α as a regulator, linking with the CCR5 receptor, may be involved within the early stages of the epileptogenic process following SE by i.c.v. KA injection.

The antioxidant tempol inhibits cardiac hypertrophy in the insulin-resistant GLUT4-deficient mouse in vivo.

Reactive oxygen species such as superoxide are implicated in cardiac hypertrophy, but their contribution to the cardiac complications of insulin resistance is unresolved. We tested the hypothesis that the antioxidant tempol attenuates cardiac hypertrophy in insulin-resistant mice. Mice with cardiac GLUT4 deletion (GLUT4-knockout), superimposed on global GLUT4 suppression (GLUT4-knockdown) were administered tempol for 4 weeks. Age-matched GLUT4-knockdown littermates were used as controls (14 mice/group). GLUT4-knockout mice exhibited marked cardiac hypertrophy: heart to body weight ratio was increased 61+/-7% and expression of the hypertrophic genes beta-myosin heavy chain and B-type natriuretic peptide (BNP) were elevated 5.5+/-0.7- and 6.2+/-1.5-fold relative to control, respectively. Pro-fibrotic pro-collagen III expression was also higher (3.8+/-0.7-fold) in the GLUT4-knockout myocardium (all p<0.001). Both gp91(phox) and Nox1 subunits of NADPH oxidase were also upregulated, 4.9+/-1.2- and 9.3+/-2.8-fold (both p<0.01). Tempol treatment significantly attenuated all of these abnormalities in GLUT4-knockout mice. Heart to body weight ratio was decreased, as was fold expression of beta-myosin heavy chain (to 3.8+/-0.8), BNP (to 2.5+/-0.5), pro-collagen III (to 1.9+/-0.4), gp91(phox) (to 0.9+/-0.3) and Nox1 (to 2.3+/-0.1, all p<0.05 versus untreated GLUT4-knockout mice). In addition, tempol upregulated ventricular expression of both thioredoxin-2 (confirming an antioxidant action) and glycogen synthase kinase-3beta (GSK-3beta). Tempol did not elicit any other significant changes in control mice. Cardiac superoxide generation, however, was not altered by GLUT4-knockout or tempol. In conclusion, tempol treatment reduced morphological and molecular evidence of cardiac hypertrophy in the GLUT4-knockout insulin-resistant mouse in vivo, even at doses insufficient to lower cardiac superoxide. Parallel reductions in pro-collagen III and NADPH oxidase have important implications for our understanding of the molecular basis of cardiac hypertrophy in the setting of insulin resistance. Antioxidants may offer new alternatives in this disorder.