High-precision nonisothermal transient wellbore drift flow model suitable for the full flow pattern domain and full dip range

A reliable multiphase flow simulator is an important tool to improve wellbore integrity and production decision-making.To develop a multiphase flow model with high adaptability and high accuracy,we first build a multiphase flow database with 3561 groups of data and developed a drift closure relationship with stable continuity and high adaptability.Second,a high-order numerical scheme with strong fault capture ability is constructed by effectively combining MUSCL technology,van Albada slope limiter and AUSMV numerical scheme.Finally,the energy equation is coupled into the AUSMV numerical scheme of the drift flow model in the form of finite difference.A transient non-isothermal wellbore multiphase flow model with wide applicability is formed by integrating the three technologies,and the effects of various factors on the calculation accuracy are studied.The accuracy of the simulator is verified by comparing the measurement results with the blowout experiment of a full-scale experimental well.

中国高血压患者外周动脉疾病患病率的Meta分析

目的系统评价我国高血压患者外周动脉疾病的患病率。方法基于Web of Science、Pubmed、Embase、The Cochrane Library、万方、维普、中国知网、中国生物医学文献数据库,检索从建库至2023年4月18日相关的横断面研究,使用Stata 15.0软件分析患病率。结果共纳入13篇文献,包含32190名高血压患者。我国高血压患者的外周动脉疾病总患病率为21.00%[95%CI(18.00%,24.00%),P<0.001]。亚组分析结果显示,男性、西北地区、糖尿病、冠心病和中风的高血压患者,外周动脉疾病的患病率更高。结论我国高血压患者外周动脉疾病的患病率较高,对于我国高血压患者来说,外周动脉疾病仍需更多的关注。

Clinical characteristics and management of coexistent cardiomyopathy in patients with bicuspid aortic valve

BACKGROUND Bicuspid aortic valve(BAV)is the most common congenital heart disease.However,the prevalence,clinical characteristics,and current management of BAV associated with inherited cardiomyopathy,including hypertrophic cardiomy-opathy(HCM),dilated cardiomyopathy(DCM),and left ventricular noncompaction(LVNC)have not been well described.METHODS Consecutive patients diagnosed with BAV at a large tertiary cardiovascular referral center between 2009 and 2018 were retrospectively assessed for HCM,DCM,and LVNC based on clinical and echocardiographic criteria.Patients with coexist-ent conditions were investigated further.RESULTS Of 3533 patients with BAV screened,57(1.6%)had concomitant cardiomyopathy.BAV was combined with HCM in 30 of these patients,with DCM in 19,and with LVNC in eight.Forty-six patients(80.7%)were male,and the mean age at first dia-gnosis was 47 years for BAV with HCM,49 years for BAV with DCM,and 35 years for BAV with LVNC.Heart failure and aortic valve dysfunction were common in these patients,and the prevalence of coexisting aortopathy was 43.3%,26.3%and 25.0%,re-spectively,for BAV with HCM,DCM and LVNC.During the index hospitalization,24 of the 57 patients(42.1%)underwent sur-gery,16(28%)underwent aortic valve and/or aortic surgery,and 16 of the 30 patients with HCM had a Morrow procedure.There were no deaths or other major adverse cardiovascular events.CONCLUSIONS The prevalence of inherited cardiomyopathy was higher in our patients with BAV than in the general popula-tion.Aortopathy and heart failure were common,with almost half of patients requiring surgery at diagnosis.

Anemia in patients with Takayasu arteritis: prevalence, clinical features, and treatment

Background Anemia is a common comorbidity of patients with Takayasu arteritis(TA). This study evaluated the prevalence, clinical characteristics, and treatment in Chinese TA patients with anemia. Methods This retrospective study included 533 consecutive patients hospitalized for TA from January 2009 to April 2018. Anemia was diagnosed on the basis of hemoglobin level, according to World Health Organization criteria. Results A total of 194 patients(36.4%) were diagnosed with anemia. Most had mild anemia(177, 91.2%). Female patients were predominant(92.8% of anemic patients). Normocytic anemia(62.9%) was the most common pattern. Anemic patients were more likely than non-anemic patients to have dizziness(29.4% vs. 21.2%), low body mass index(22.0 ± 3.6 vs. 22.9 ± 3.4 kg/m2), and active disease stage(64.9% vs. 50.1%);pulmonary involvement(12.4% vs. 26.8%), pulmonary hypertension(12.9% vs. 20.1%) and pulmonary hypertensive-target drugs(2.8% vs. 11.6%) were less common among anemic than non-anemic patients(all P < 0.05). Larger left ventricular end-diastolic diameter and lower left ventricular ejection fraction were observed in anemic patients. Over a median follow-up of four months, the increase of hemoglobin in anemic patients was associated with the use of iron supplementation. Conclusions Anemia is a very common concurrent condition in TA, especially in young, female patients. Patients with anemia are more likely to be in the active disease stage. Iron supplementation helps increase hemoglobin.

Etiology spectrum and clinical characteristics of renal artery stenosis in a Chinese cohort

OBJECTIVE To analyze the causes of renal artery stenosis(RAS)and compare the clinical characteristics in accordance with the primary disease among patients aged from 30 to 50.METHODS Patients were grouped by etiologies of RAS.Groups were retrospectively examined and compared regarding demographic data,clinical manifestations,laboratory findings,and imaging findings.RESULTS A total of 152 patients(74 females,78 males;mean age:40.70±6.01 years)were enrolled,including 84 patients(55.3%)with atherosclerosis(AS),46 patients(30.3%)with Takayasu arteritis(TA),18 patients(11.8%)with fibromuscular dysplasia(FMD),and four patients(2.6%)with other etiologies.Patients in AS group had greater body mass index,higher prevalence of comorbidities and higher rate of smoking and drinking history.TA patients showed more constitutional symptoms and vascular findings,and higher erythrocyte sedimentation rate.RAS in both AS group and TA group mainly located on ostia and proximal segments,but RAS in FMD group mainly involved middle to distal segment of renal artery.The AS group had significantly lesser stenosis than the other groups.Although renal function evaluated by the estimated glomerular filtration rate did not significantly differ among the groups,the incidence of kidney shrinkage was significantly higher in the TA and FMD groups(39.1%and 50%,respectively)than in the AS group(8.3%).The FMD group had milder cardiac damage than other groups.CONCLUSIONS AS was the most common cause of RAS in patients aged from 30 to 50,followed by TA and FMD.The etiology of RAS should be carefully distinguished based on clinical manifestations,laboratory findings,and imaging to ensure that proper treatment is provided.

Implication of a novel truncating mutation in titin as a cause of autosomal dominant left ventricular noncompaction

BACKGROUND Mutation in the titin gene(TTN)in left ventricular noncompaction(LVNC)has been reported with a highly heterogeneous prevalence,and the molecular mechanisms underlying the pathogenesis of TTN gene mutation are uncharacteri-zed.In the present study,we identified a novel TTN mutation in a pedigree with LVNC and investigated the potential pathogenic mechanism by functional studies.METHODS The whole-genome sequencing with linkage analysis was performed in a 3-generation family affected by autoso-mal dominant LVNC cardiomyopathy.The clustered regularly interspaced short palindromic repeats associated protein 9(CRISPR/Cas9)technology was used to establish novel truncating mutation in TTN in a rat cardiomyoblast H9C2 cell line in vitro,in which functional studies were carried out and characterized in comparison to its wild-type counterpart.RESULTS A novel truncating mutation TTN p.R2021X was identified as the only plausible disease-causing variant that segreg-ated with disease among the five surviving affected individuals,with an interrogation of the entire genome excluding other po-tential causes.Quantitative reverse transcription-polymerase chain reaction and cellular immunofluorescence supported a haplo-insufficient disease mechanism in titin truncation mutation cardiomyocytes.Further functional studies suggested mitochondrial abnormities in the presence of mutation,including decreased oxygen consumption rate,reduced adenosine triphosphate produc-tion,impaired activity of electron translation chain,and abnormal mitochondrial structure on electron microscopy.Impaired aut-ophagy under electron microscopy accompanied with activation of the Akt-mTORC1 signaling pathway was observed in TTN p.R2021X truncation mutation cardiomyocytes.CONCLUSIONS The TTN p.R2021X mutation has a function in the cause of a highly penetrant familial LVNC.These findings expand the spectrum of titin’s roles in cardiomyopathies and provide novel insight into the molecular basis of titin-truncating variants-associated LVNC.

A novel missense mutation in obscurin gene in a Chinese consanguineous family with left ventricular noncompaction

BACKGROUND Left ventricular noncompaction(LVNC) is an increasingly recognised cardiomyopathy of which a significant percentage are genetic in origin. The purpose of the present study was to identify potential pathogenic mutation leading to disease in a Chinese LVNC family.METHODS A 3-generation family affected by LVNC was recruited. Clinical assessments were performed on available family members, with clinical examination, ECG, echocardiography and cardiac MRI. The proband(Ⅰ-2), the proband’s daughter(Ⅱ-1, affected) and mother(Ⅲ-1, unaffected) were selected for WGS. Sanger sequencing were performed in all of the 4 surviving family members.RESULTS Combined whole genome sequencing with linkage analysis identified a novel missense mutation in the giant protein obscurin(OBSCN NM_001098623, c.C19063T), as the only plausible disease-causing variant that segregates with disease among the four surviving individuals, with interrogation of the entire genome excluding other potential causes. This c.C19063T missense mutation resulted in p.R6355W in the encoded OBSCN protein. It affected a highly conserved residue in the C terminus of the obscurin-B-like isoform between the PH and STKc domains, which was predicted to affect the function of the protein by different bioinformatics tools.CONCLUSIONS Here we present clinical and genetic evidence implicating the novel R6355W missense mutation in obscurin as the cause of familial LVNC. This expands the spectrum of obscurin’s roles in cardiomyopathies. It furthermore highlights that rare obscurin missense variants, currently often ignored or left uninterpreted, should be considered to be relevant for cardiomyopathies and can be identified by the approach presented here. This study also provided new insights into the molecular basis of OBSCN mutation positive LVNC.

A novel phenotype with splicing mutation identified in a Chinese family with desminopathy

Background:Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations.Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia.Combined with genotype, it helps us precisely diagnose and treat for desminopathy.Methods:Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing.Phenotypes were analyzed based on clinical characteristics associated with desminopathy.Results:A splicing mutation (c.735+1G>T) in DES was detected in the proband.A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons.Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium.There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified.Conclusions:We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy.Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.