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Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.
RESUMO
OBJECTIVE： To evaluate immunomodulatory drugs （IMiDs） in the treatment of deep venous thrombosis （DVT） in patients with multiple myeloma （MM） systematically， and to provide reference for safe drug use in clinic. METHODS： Retrieved and collected randomized controlled trials （RCTs） about the risk of DVT in MM patients treated with IMiDs from PubMed， Web of Science， Cochrane library， CJFD， Wanfang database， VIP， www.ClinicalTrials.gov during database and Dec. 31， 2018. Meta-analysis was conducted for the incidence and relative risk of DVT （RR） by using Stata 12.0 statistical software. Evidence was evaluated and graded by using GRADE system. RESULTS： A total of 11 RCTs were included， involving 3 365 patients （including 3 drugs）. Results of Meta-analysis showed that the incidence of DVT was 7.3％ [95％CI （4.5％， 10.2％）] during IMiDs in the treatment of MM. Compared with conventional chemotherapy， IMiDs had a higher risk of DVT in MM patients [RR＝3.57，95％CI（2.42，5.27）， P＜0.01]. Subgroup analysis in different treatment stage showed that after IMiDs treatment for MM patients at induction stage， the risk of DVT increased by 386％ compared with conventional chemotherapy plan [RR＝4.86， 95％CI （2.85， 8.30）， P＜0.01]， which evidence was moderate. Compared with conventional chemotherapy plan， there was no significant difference in the risk of DVT among MM patients treated with IMiDs at maintenance stage [RR＝2.40， 95％CI （0.70， 8.27）， P＝0.16] and relapse stage [RR＝2.01， 95％CI （0.74， 5.46）， P＝0.17]. The incidence of severe DVT caused by thalidomide and lenalidomide were 11％ [95％CI （9％， 13％）] and 3％ [95％CI （2％， 4％）]. CONCLUSIONS： The current evidence suggests that patients with MM treated with IMiDs are at a high risk of serious DVT， and clinical medication should be cautious.
RESUMO
AIM:To study the parameters of supercritical CO_2 extraction of essential oil from valeriana efficinalis by orthogonal design. METHODS: Four factors,such as extraction pressure,extraction temperature,extraction time and separation temperature were chosen by the observation of orthogonal design,each factor was assigned to three levels.Bornyl acetate content was selected as a marker in a position to determine optimal extraction. RESULTS: Pressure and temperature were the main factors in effecting the extraction of bornyl acetate,extraction time was minor factor relatively. CONCLUSION: The optimal extraction is as follow,parameters were extraction pressure:12 MPa,extraction temperature:45 ℃,extraction time:1 hour,separation temperature:35 ℃,it gave the best recoveries of essential oils and bornylacetate.