Humans ; Amyotrophic Lateral Sclerosis/drug therapy* ; Benzofurans/therapeutic use* ; Double-Blind Method ; Treatment Outcome

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.

The 30th International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease was held in Perth, Australia from December 4 to 6, 2019. This article mainly introduces the clinical research of this meeting, including epidemiology, non-motor symptoms, auxiliary examinations and biomarkers, etc., while the basic research includes genomics and genetics, protein metabolism abnormalities, neuroimmunity and inflammation, synapse pathology and preclinical treatment strategies,

Objective:To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods:From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ 2 test, and χ 2 test was used for association analysis. Results:For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group ( P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups ( P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion:It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

Objective:To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods:From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ 2 test, and χ 2 test was used for association analysis. Results:For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group ( P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups ( P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion:It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

The 29th International Symposium on Amyotrophic Lateral Sclerosis (ALS)?Motor Neuron Disease was held in Glasgow from December 7 to 9, 2018. The symposium was divided into 23 topics, with 109 special reports and paper′s exchange and 515 posters exchange. This article briefly introduces some topics of the symposium, involving basic researches, clinical researches and clinical trials. Among these, basic researches include genetics and genomics, axonal degeneration, disease models, and preclinical therapeutic strategies; Clinical researches include epidemiology, clinical progression, cognitive and psychological change, neuropathology, neurophysiology, neuroimaging and biomarkers.

The 29th International Symposium on Amyotrophic Lateral Sclerosis (ALS)-Motor Neuron Disease was held in Glasgow from December 7 to 9, 2018. The symposium was divided into 23 topics, with 109 special reports and paper′s exchange and 515 posters exchange. This article briefly introduces some topics of the symposium, involving basic researches, clinical researches and clinical trials. Among these, basic researches include genetics and genomics, axonal degeneration, disease models, and preclinical therapeutic strategies; Clinical researches include epidemiology, clinical progression, cognitive and psychological change, neuropathology, neurophysiology, neuroimaging and biomarkers.

Objective: This study aimed to explore whether high pressure would increase expression of TNF-a and IL-1β. Methods: BV2 microglia cells were treated with a self-made device. BV2 microglia cells were randomly divided into five groups according to different pressures: control group, 20 mmHg group, 25 mmHg group, 30 mmHg group, and 35 mmHg group. BV2 microglia cells were randomly divided into five groups according to different intervention time: control group, 6 h group, 12 h group, 24 h group. TNF-α and IL-1β expression were assessed by Western Blotting or double immunofluorescence. Results: The 30 mmHg group had the highest expression levels of TNF-α and IL-1β as compared with control group (both P<0.01), 6 h group (both P<0.01)、12 h group (TNF-α: P<0.05; IL-1β: P< 0.01).30 mmHg group had the highest expression levels of TNF-α and IL-1β as compared with control group (bothP<0.01), 20 mmHg group (both P<0.01), and 25 mmHg group (TNF-α: P<0.05; IL-1β: P<0.01). The expression levels of TNF-α and L-1β were not different between 30 mmHg group and 35 mmHg group (both P>0.05). Conclusions High pressure may increase the expression levels of TNF-α and IL-1β of microglia.

Objective? To observe the effects of continuous quality improvement on the incidence rate of ventilator-associated pneumonia (VAP) in intensive care unit (ICU). Methods? Totally 158 patients using ventilators in ICU of Hangzhou Red Cross Hospital between January and June 2016 were selected as the control group using convenient sampling, and another 165 patients using ventilators between January and June 2017 were selected as the observation group. Patients in the control group received conventional nursing care, while patients in the observation group received Plan-Do-Check-Act (PDCA) Cycle Management with the quality of standardized nursing process, standardized upper respiratory tract management and hand hygiene continuously improved. Incidence rate of ventilator-associated pneumonia(VAP), rate of pass in oral nursing care and hand hygiene compliance in medical and nursing workers were compared between the two groups before and after improvement. SPSS 17.0 was used for statistical analysis. Results? The incidence rate of VAP during the first half of 2017 totaled 5.07‰, a decrease of 6.42‰ compared with the first half of 2016. There was statistically significant difference in the incidence rate of VAP between the two groups (P＜0.01); the rate of pass in oral nursing care after improvement (93.17%) was statistically higher than that before improvement (57.31%) (P＜ 0.01); and the hand hygiene compliance after improvement (93.67%) was statistically higher than that before improvement (67.33%) (P＜ 0.01). Conclusions? Continuous quality improvement can reduce the incidence rate of VAP in ICU, which is operable and worth promoting in clinical practice.

Objective To investigate the risk of hemorrhagic transformation and the curative effect in patients with atrial fibrillation(AF)treated by intravenous thrombolysis with alteplase after acute cerebral infarct. Methods The clinical data of 246 patients with acute cerebral infarct treated with intravenous alteplase within 4.5 h from the onset were analyzed.According to the presence or absence of AF, the patients were divided into AF group (74 cases) and non AF group (172 cases). The outcomes were the incidence of hemorrhagic transformation within 36 h and the curative effect after 2 weeks. Results The incidence of hemorrhagic transformation in AF group was 31.1%(23/74), in non AF group was 7.6%(13/172),and there was significant difference(χ2=22.917,P=0.000).The effective rate in AF group was 54.1%(40/74), in non AF group was 76.7%(132/172), and there was significant difference (χ2=12.665,P=0.000).Conclusions Patients with acute cerebral infarction combined with AF have a high risk of hemorrhagic transformation and poor prognosis after intravenous thrombolysis.