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2.
Rev Sci Instrum ; 95(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38445995

RESUMO

Knowledge about nonequilibrium dynamics in spin systems is of great importance to both fundamental science and technological applications. Inelastic neutron scattering (INS) is an indispensable tool to study spin excitations in complex magnetic materials. However, conventional INS spectrometers currently only perform steady-state measurements and probe averaged properties over many collision events between spin excitations in thermodynamic equilibrium, while the exact picture of re-equilibration of these excitations remains unknown. In this paper, we report on the design and implementation of a time-resolved laser-neutron pump-probe capability at hybrid spectrometer (beamline 14-B) at the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory. This capability allows us to excite out-of-equilibrium magnons with a nanosecond pulsed laser source and probe the resulting dynamics using INS. Here, we discussed technical aspects to implement such a capability in a neutron beamline, including choices of suitable neutron instrumentation and material systems, laser excitation scheme, experimental configurations, and relevant firmware and software development to allow for time-synchronized pump-probe measurements. We demonstrated that the laser-induced nonequilibrium structure factor is able to be resolved by INS in a quantum magnet. The method developed in this work will provide SNS with advanced capabilities for performing out-of-equilibrium measurements, opening up an entirely new research direction to study out-of-equilibrium phenomena using neutrons.

4.
Zhonghua Er Ke Za Zhi ; 62(2): 153-158, 2024 Feb 02.
Artigo em Chinês | MEDLINE | ID: mdl-38264815

RESUMO

Objective: To investigate the DMD genetic variants of the Chinese population with Duchenne (DMD) and Becker muscular dystrophies (BMD). Methods: A cross-sectional study was conducted on 2 690 unrelated patients with DMD and BMD aged 0-18 who visited the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2005 to February 2022. The clinical data, such as gender, age, clinical manifestations, and address, were collected. Multiplex ligation-dependent probe amplification, next generation sequencing panel, Sanger sequencing, and PCR amplification were used to detect the variants of the DMD gene in the patients, whose clinical information and gene detection results were descriptively analyzed. Results: The 2 690 patients included 2 648 males and 42 females, with an age of 6.0 (4.0, 9.0) years. The serum creatine kinase increased in all patients. Pathogenic DMD gene variants were detected in the 2 618 patients, including 1 875 cases (71.6%) large deletions, 231 cases (8.8%) duplications, and 512 cases (19.6%) small variants. Among the deletion variants, the deletion of 3 exons was the most common, accounting for 15.4% (288/1 875); and hotspot deletion involved exons 45 to 50, accounting for 6.3% (119/1 875). Exon 2 was the most common type duplication region, accounting for 13.0% (30/231). Small variants were distributed in all 79 exons of the DMD gene, with no hotspots. In addition, the 46 small variants were previously unreported. Conclusion: Exon deletion is the most common type of DMD gene variant, followed by small variants and exon duplication.


Assuntos
Distrofina , Distrofia Muscular de Duchenne , Feminino , Humanos , Masculino , Gravidez , Estudos Transversais , Distrofina/genética , Éxons , Deleção de Genes , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Diagnóstico Pré-Natal/métodos
6.
Zhonghua Er Ke Za Zhi ; 61(11): 1024-1030, 2023 Nov 02.
Artigo em Chinês | MEDLINE | ID: mdl-37899342

RESUMO

Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ2 test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced ß-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Feminino , Adolescente , Criança , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Vancomicina/uso terapêutico , Clindamicina/uso terapêutico , Ceftriaxona/uso terapêutico , Tigeciclina/uso terapêutico , Linezolida/uso terapêutico , Levofloxacino/uso terapêutico , Estudos Retrospectivos , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Infecções Estafilocócicas/tratamento farmacológico , Eritromicina/uso terapêutico , Meticilina , Penicilina G/uso terapêutico , Escherichia coli , Farmacorresistência Bacteriana
7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 51(6): 642-647, 2023 Jun 24.
Artigo em Chinês | MEDLINE | ID: mdl-37312483

RESUMO

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.


Assuntos
Aterosclerose , Fibrilação Atrial , Doenças Cardiovasculares , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Dislipidemias/tratamento farmacológico
8.
J Am Soc Nephrol ; 34(9): 1547-1559, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37261792

RESUMO

SIGNIFICANCE STATEMENT: Rapid progression of CKD is associated with poor clinical outcomes. Most previous studies looking for genetic factors associated with low eGFR have used cross-sectional data. The authors conducted a meta-analysis of genome-wide association studies of eGFR decline among 116,870 participants with CKD, focusing on longitudinal data. They identified three loci (two of them novel) associated with longitudinal eGFR decline. In addition to the known UMOD/PDILT locus, variants within BICC1 were associated with significant differences in longitudinal eGFR slope. Variants within HEATR4 also were associated with differences in eGFR decline, but only among Black/African American individuals without diabetes. These findings help characterize molecular mechanisms of eGFR decline in CKD and may inform new therapeutic approaches for progressive kidney disease. BACKGROUND: Rapid progression of CKD is associated with poor clinical outcomes. Despite extensive study of the genetics of cross-sectional eGFR, only a few loci associated with eGFR decline over time have been identified. METHODS: We performed a meta-analysis of genome-wide association studies of eGFR decline among 116,870 participants with CKD-defined by two outpatient eGFR measurements of <60 ml/min per 1.73 m 2 , obtained 90-365 days apart-from the Million Veteran Program and Vanderbilt University Medical Center's DNA biobank. The primary outcome was the annualized relative slope in outpatient eGFR. Analyses were stratified by ethnicity and diabetes status and meta-analyzed thereafter. RESULTS: In cross-ancestry meta-analysis, the strongest association was rs77924615, near UMOD / PDILT ; each copy of the G allele was associated with a 0.30%/yr faster eGFR decline ( P = 4.9×10 -27 ). We also observed an association within BICC1 (rs11592748), where every additional minor allele was associated with a 0.13%/yr slower eGFR decline ( P = 5.6×10 -9 ). Among participants without diabetes, the strongest association was the UMOD/PDILT variant rs36060036, associated with a 0.27%/yr faster eGFR decline per copy of the C allele ( P = 1.9×10 -17 ). Among Black participants, a significantly faster eGFR decline was associated with variant rs16996674 near APOL1 (R 2 =0.29 with the G1 high-risk genotype); among Black participants with diabetes, lead variant rs11624911 near HEATR4 also was associated with a significantly faster eGFR decline. We also nominally replicated loci with known associations with eGFR decline, near PRKAG2, FGF5, and C15ORF54. CONCLUSIONS: Three loci were significantly associated with longitudinal eGFR change at genome-wide significance. These findings help characterize molecular mechanisms of eGFR decline and may contribute to the development of new therapeutic approaches for progressive CKD.


Assuntos
Estudo de Associação Genômica Ampla , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/terapia , Estudos Transversais , Rim , Genótipo , Taxa de Filtração Glomerular/genética , Progressão da Doença , Apolipoproteína L1/genética , Isomerases de Dissulfetos de Proteínas/genética
9.
Artigo em Chinês | MEDLINE | ID: mdl-36992642

RESUMO

Objective: To analyze the difference of application methods and effects of local flap in small and medium-sized defects of different aesthetic subunits of nose, in order to provide reference for clinical work. Methods: A retrospective analysis was made on 59 patients with external nasal masses and scars who underwent surgical treatment in the Department of Aesthetic Plastic Surgery of the Affiliated Hospital of Qingdao University from July 1, 2021 to January 30, 2022, including 27 females and 32 males, aged 15 to 69 years. Using Likert scale, the repair methods and effects of local flap for nasal soft tissue defects were evaluated and summarized from three aspects of texture, flatness and scar concealment. GraphPad Prism 5.0 software was used for data statistics and analysis. Results: The use of skin flaps to repair small and medium-sized areas of the nose could achieve satisfactory results. For patients with different subunits, in terms of skin flatness and scar concealment degree in the operation area, patients' satisfaction with the dorsal and lateral nasal areas was higher than that of the alar and tip areas, respectively (F=6.40, P=0.001; F=10.57, P<0.001). For patients with different skin flap repair methods, the satisfaction of patients with Z-plasty and Dufourmentel skin flap was higher than that of other skin flap repair methods (F=4.38, P=0.002), and the satisfaction of patients with Dufourmentel skin flap was the highest in the degree of scar concealment (F=2.57, P=0.038). Conclusions: In the small and medium-sized defects of the nose, the use of multiple local flaps can achieve good cosmetic effects and functional recovery. The operator should select the appropriate flap repair method according to the characteristics of different aesthetic subunits of the nose.

11.
Clin Oncol (R Coll Radiol) ; 35(4): 245-254, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36764878

RESUMO

PURPOSE: To characterize on-treatment changes in GTV morphology in children with parameningeal rhabdomyosarcoma receiving upfront proton therapy with concurrent chemotherapy and thereby provide guidance on the timing of on-treatment imaging and adaptive replanning. METHODS AND MATERIALS: GTV was delineated on 86 simulation and weekly MR images of 15 prospectively enrolled patients (aged 1-21 years). Temporal changes from baseline in volume and surface (95% Hausdorff distance) were analyzed in relation to the need for plan verification and the resultant doses with hypothetical no treatment adaptation. RESULTS: The median time was 6 days from the initiation of chemotherapy to CT+MR simulation and 15 days from the simulation to the start of radiotherapy. All but 1 patient showed a continuous decrease in GTV (0.16-1.52%/day) after simulation. At 3 weeks from simulation, 10 of 15 patients exhibited a significant reduction in volume (median, 20%; range, 6-29%). Without replanning, these changes could lead to a reduction in CTV V95 by 7-14% (n = 2) and/or an increase in D0.01 cc/Dmean of adjacent organs at risk by 6-21% of the prescribed target dose (n = 7). Significant dosimetric consequences occurred in cases with (1) a considerable weight gain, (2) shrinkage of the skin surface, or (3) tumor regression in the oral or nasal cavity and sinus that altered air-tissue components in the beam path. The subsequent GTV and dosimetry after 3 weeks from simulation (4 weeks from chemotherapy initiation) demonstrated a relatively stable trend. CONCLUSIONS: On-treatment imaging at 3 weeks after simulation is recommended, if the simulation is performed at 1 week after the initiation of chemotherapy, to detect significant anatomic changes that could result in >5% deviation from planned target coverage and/or organ doses in pediatric patients with parameningeal rhabdomyosarcoma receiving early proton therapy.


Assuntos
Terapia com Prótons , Radioterapia de Intensidade Modulada , Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Humanos , Criança , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/radioterapia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos
13.
Zhonghua Yi Xue Za Zhi ; 102(2): 130-135, 2022 Jan 11.
Artigo em Chinês | MEDLINE | ID: mdl-35012302

RESUMO

Objective: To investigate the characteristics and effect factors of collateral blood supply of patients with early trimester cesarean scar pregnancy(CSP). Methods: This study was a multicenter case-control study, with 219 inpatients with CSP in First People's Hospital of Zhengzhou, Zhengzhou Central Hospital, Third People's Hospital of Zhengzhou and Henan No3 Provincial People's Hospital from January 1, 2017 to June 30, 2020 who were selected to obtain their clinical data. Double-blind method was performed in digital subtraction angiography imaging analysis. The patients were divided into collateral blood supply group and non-collateral blood supply group, and the incidence of collateral blood supply of patients with early trimester CSP was calculated. Multivariate binary logistic regression analysis was performed to find the independent risk factors of collateral blood supply of patients with early trimester CSP. As well, clinical outcomes after uterine artery embolization (UAE) were compared between the two groups. Results: A total of 219 patients with early trimester CSP have average age of (32.4±5.0) years old and average pregnancy of (51.0±10.6) days. The incidence of collateral blood supply was 12.3% (27 cases), of which16 cases were on the left, 6 on the right and 5 in both sides. A total of 43 collateral vessels were found, with 1.59 vessels per patient on average. Bladder artery was the most common source of collateral blood supply, accounting for 74.4% (32/43), followed by internal pudendal artery for 18.6% (8/43). Multivariate binary logistic regression analysis showed that gestational weeks ≥8 weeks, maximum diameter of gestational sac ≥50 mm and rich blood supply of gestational sac are independent risk factors for collateral blood supply of patients with early trimester CSP, with OR (95%CI) 3.68 (1.06-12.76), 7.00 (1.52-32.19)、9.96 (3.59-27.58), respectively, all P<0.05. The success rates of UAE were 100% in both groups. The reduction in serum ß-Human chorionic gonadotropin (ß-HCG) level at 24 hours after UAE, vaginal bleeding during uterine curettage, hysterectomy and menstrual recovery time were not found to have significant difference between groups (all P>0.05). Conclusions: Early trimester CSP leads to a certain occurrence of collateral blood supply, which may have adverse impact on the efficacy of UAE and patient safety. Gestational weeks, the maximum diameter of gestational sac and the degree of vascularization of gestation sac have certain value in suggesting the collateral blood supply of patients with early trimester CSP, which is helpful for the complete embolization of gestational sac in the process of UAE.


Assuntos
Cesárea , Cicatriz , Adulto , Estudos de Casos e Controles , Método Duplo-Cego , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Resultado do Tratamento
16.
J Synchrotron Radiat ; 28(Pt 3): 977-986, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33950006

RESUMO

We report on the development of a high-resolution and highly efficient beamline for soft X-ray resonant inelastic X-ray scattering (RIXS) located at the Taiwan Photon Source. This beamline adopts an optical design that uses an active grating monochromator (AGM) and an active grating spectrometer (AGS) to implement the energy compensation principle of grating dispersion. Active gratings are utilized to diminish defocus, coma and higher-order aberrations, as well as to decrease the slope errors caused by thermal deformation and optical polishing. The AGS is mounted on a rotatable granite platform to enable momentum-resolved RIXS measurements with scattering angles over a wide range. Several high-precision instruments developed in-house for this beamline are described briefly. The best energy resolution obtained from this AGM-AGS beamline was 12.4 meV at 530 eV, achieving a resolving power of 4.2 × 104, while the bandwidth of the incident soft X-rays was kept at 0.5 eV. To demonstrate the scientific impact of high-resolution RIXS, we present an example of momentum-resolved RIXS measurements on a high-temperature superconducting cuprate, i.e. La2-xSrxCuO4. The measurements reveal the A1g buckling phonons in superconducting cuprates, opening a new opportunity to investigate the coupling between these phonons and charge-density waves.

17.
Ann Dermatol Venereol ; 148(3): 168-171, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33858692

RESUMO

BACKGROUND: There is no consensus on the treatment of drug reaction with eosinophilia and systemic symptoms (DRESS). At our center, systemic steroids (SS) are used for severe cases while topical steroids (TS) are used for mild and moderate forms. OBJECTIVES: To investigate the short-term outcome for patients with DRESS receiving SS as first-line therapy before being transferred to our department and then switched to TS after admission. METHODS: A retrospective monocenter study in DRESS patients (RegiSCAR score≥4) transferred to our dermatology department from a different setting between 07/2012 and 06/2018 and who had received SS before being transferred. Epidemiological, clinical and laboratory data were collected, as well as details of treatment modalities and outcome. RESULTS: Twenty patients were included. On admission to our department, 4 were assessed as having severe DRESS and continued on SS, while 16 were assessed as mild/moderate DRESS and were switched to TS. Among these 16 patients, the outcome on TS was favorable for 12 and quickly unfavorable for 4, who had to be switched back to SS. Retrospective analysis of the initial data (before transfer) showed that these 4 patients had previously had a greater number of severity criteria than the other 12. CONCLUSION: Caution is needed not only when deciding to initiate SS in DRESS but also on withdrawal of these drugs. Our series suggests that when SS are used as first-line therapy in DRESS patients with initial severity criteria, they should not be withdrawn quickly for a switch to TS, even where progression appears favorable, due to the risk of relapse.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Eosinofilia , Esteroides/administração & dosagem , Administração Tópica , Adulto , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/epidemiologia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Eosinofilia/induzido quimicamente , Eosinofilia/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(4): 353-359, 2021 Apr 24.
Artigo em Chinês | MEDLINE | ID: mdl-33874685

RESUMO

Objective: To investigate the causes of death and predictors in patients with nonvalvular atrial fibrillation (AF) undergoing anticoagulation therapy. Methods: Consecutive anticoagulated nonvalvular AF patients were recruited from the China Atrial Fibrillation Registry (China-AF) Study from August 2011 to December 2018. After exclusion of patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, or loss of follow-up within 1 year, 2 248 patients were included in this analysis. Enrolled patients were followed up were followed up for 3 and 6 months, and then every 6 months. The primary endpoint was death, including cardiovascular death, non-cardiovascular death and undetermined death. The patients were divided into survival group and death group according to the survival status after follow-up. Clinical information such as age and sex was collected. Cox proportional hazards regression was performed to identify associated risk factors for all-cause mortality, and Fine-Gray competing risk model was used to identify associated risk factors for cardiovascular mortality. Results: A total of 2 248 patients with atrial fibrillation receiving anticoagulant therapy died over a mean follow-up of (42±24) months, mean age was (67±10) years old and 41.1% (923/2 248) patients were female. The mortality rate was 2.8 deaths per 100 patient-years. The most common cause of death was cardiovascular deaths, accounted for 55.0% (120/218). Worsening heart failure was the most common cause of cardiovascular deaths (18.3% (40/218)), followed by bleeding events (12.9% (28/218)) and ischemic stroke (8.7% (19/218)). Multivariate Cox regression analysis showed that age (HR = 1.05, 95%CI 1.04-1.07, P<0.001), anemia (HR = 1.81, 95%CI 1.02-3.18, P = 0.041), heart failure (HR=2.40, 95%CI 1.75-3.30, P<0.001), ischemic stroke/transient ischemic attack (TIA)(HR = 1.59, 95%CI 1.21-2.13, P = 0.001) and myocardial infarction (HR = 2.93, 95%CI 1.79-4.81, P<0.001) were independently associated with all-cause death. Fine-Gray competing risk model showed that age (HR=1.05, 95%CI 1.02-1.08, P<0.001), heart failure (HR=2.81, 95%CI 1.79-4.39, P<0.001), ischemic stroke/TIA (HR=1.50, 95%CI 1.02-2.22, P=0.041) and myocardial infarction (HR=3.31, 95%CI 1.72-6.37, P<0.001) were independently associated with cardiovascular death. Conclusions: In anticoagulated nonvalvular AF patients, ischemic stroke represents only a small subset of deaths, whereas worsening heart failure is the most common cause of cardiovascular deaths. Heart failure, ischemic stroke/TIA, and myocardial infarction are associated with increased mortality.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Causas de Morte , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
Eur Rev Med Pharmacol Sci ; 25(2): 678-686, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577022

RESUMO

OBJECTIVE: The aim of this study was to explore the effect of long non-coding ribonucleic acid (lncRNA) FOXD2-adjacent opposite strand RNA 1 (FOXD2-AS1) on the sensitivity of osteosarcoma cells to cisplatin and its possible underlying mechanism. Our findings might help to provide a certain reference for clinically preventing the drug resistance of osteosarcoma cells. MATERIALS AND METHODS: Cisplatin with a certain concentration gradient was used to induce the stable acquired resistance of human osteosarcoma U2-OS cell line. Subsequently, the expression level of lncRNA FOXD2-AS1 was determined in osteosarcoma cells in non-resistance group (Control group) and Cisplatin-resistance group (Cisplatin-RES group), respectively. Next, the cell line with stable lncRNA FOXD2-AS1 knockdown was constructed in Cisplatin-RES group using small interfering RNA (siRNA). The effects of stable knockdown of lncRNA FOXD2-AS1 on the proliferation of human osteosarcoma cells and the half-maximal inhibitory concentration (IC50) of cisplatin were detected by Cell Counting Kit-8 (CCK-8) assay. 5-ethynyl-2'-deoxyuridine (EdU) staining was performed to measure deoxyribonucleic acid (DNA) replication level in each group of cells. The protein expression levels of apoptosis-associated genes B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) in each group of cells were measured via Western blotting. The migration and invasion abilities of cells in each group were determined using wound-healing assay and transwell assay. In addition, the expression of micro RNA (miR)-143 in each group of cells was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). RESULTS: Compared with Control group, the expression level of lncRNA FOXD2-AS1 rose significantly in cells in Cisplatin-RES group (p<0.05). Knockdown of FOXD2-AS1 evidently decreased the IC50 of cisplatin in human osteosarcoma cells (p<0.05). According to EdU staining results, the knockdown of FOXD2-AS1 distinctly inhibited the proliferation of osteosarcoma cells (p<0.05). Western blotting results demonstrated that the knockdown of FOXD2-AS1 remarkably upregulated the expression of pro-apoptotic protein Bax and repressed that of anti-apoptotic protein Bcl-2 in drug-resistant human osteosarcoma cells (p<0.05). Moreover, the knockdown of FOXD2-AS1 significantly weakened the migration and invasion abilities of drug-resistant human osteosarcoma cells (p<0.05). Finally, it was found that the expression level of miR-143 was distinctly elevated in drug-resistant human osteosarcoma cells after knockdown of FOXD2-AS1 (p<0.05). CONCLUSIONS: LncRNA FOXD2-AS1 knockdown inhibits the resistance of human osteosarcoma cells to cisplatin, promotes their apoptosis and weakens their invasion and migration abilities. The possible underlying mechanism may be related to the inhibition of miR-143 expression by lncRNA FOXD2-AS1 in drug-resistant cell lines.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , MicroRNAs/genética , Osteossarcoma/tratamento farmacológico , RNA Longo não Codificante/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , RNA Longo não Codificante/genética , Células Tumorais Cultivadas
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