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1.
Hum Mol Genet ; 32(3): 462-472, 2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36001342

RESUMO

YWHAZ encodes an adapter protein 14-3-3ζ, which is involved in many signaling pathways that control cellular proliferation, migration and differentiation. It has not been definitely correlated to any phenotype in OMIM. To investigate the role of YWHAZ gene in intellectual disability and global developmental delay, we conducted whole-exon sequencing in all of the available members from a large three-generation family and we discovered that a novel variant of the YWHAZ gene was associated with intellectual disability and global developmental delay. This variant is a missense mutation of YWHAZ, p.Lys49Asn/c.147A > T, which was found in all affected members but not found in other unaffected members. We also conducted computational modeling and knockdown/knockin with Drosophila to confirm the role of the YWHAZ variant in intellectual disability. Computational modeling showed that the binding energy was increased in the mutated protein combining with the ligand indicating that the c147A > T variation was a loss-of-function variant. Cognitive defects and mushroom body morphological abnormalities were observed in YWHAZ c.147A > T knockin flies. The YWHAZ knockdown flies also manifested serious cognitive defects with hyperactivity behaviors, which is consistent with the clinical features. Our clinical and experimental results consistently suggested that YWHAZ was a novel intellectual disability pathogenic gene.


Assuntos
Deficiência Intelectual , Malformações do Sistema Nervoso , Criança , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/complicações , Proteínas 14-3-3/genética , Mutação de Sentido Incorreto , Encéfalo , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/complicações
2.
J Biol Chem ; 299(6): 104657, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37001814

RESUMO

The mechanisms underlying atherosclerosis (AS) that seriously affect human health, such as those involved in endothelial cell injury and monocyte/macrophage aggregation and infiltration, have not been fully elucidated. To investigate these processes, we established human umbilical vein endothelial cells (HUVECs) injured by oxidized low-density lipoprotein (ox-LDL) to mimic AS in vitro. Apolipoprotein E knockout (ApoE-/-) C57BL/6 mice were fed with a high-cholesterol diet to establish an AS model in vivo. We detected HUVEC apoptosis, and apoptosis-related proteins by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide and lactate dehydrogenase, flow cytometry, and Western blot assays, respectively, and we observed monocytes (THP-1 cells) adhering to HUVECs. Furthermore, miR-147a and its downstream target gene ZEB2 (zinc finger E-box binding homeobox 2) were predicted by bioinformatics analysis to be involved in AS, and their correlation was confirmed by several experiments. We determined the localization of miR-147a and ZEB2 within macrophages of AS mice by in situ hybridization and immunofluorescence. Atherosclerotic plaques in whole aortas were detected by histology observation. miR-147a attenuated adherence of monocytes to HUVECs and the upregulation of mononuclear chemotactic adhesion receptors in THP-1 cells induced by ox-LDL-injured HUVEC supernatants through directly downregulating ZEB2 levels. Moreover, miR-147a influenced M1/M2 macrophage polarization from THP-1 cells and the roles of their supernatants (THP-1 cells) in HUVEC apoptosis. miR-147a targeted ZEB2 to impact lipid accumulation and atherosclerotic plaque formation through regulating M1/M2 polarization and macrophage adhesion in AS mice. In summary, miR-147a attenuates ox-LDL-induced adherence of monocytes to HUVECs and modulates atherosclerotic plaque formation and stability through targeting ZEB2 during AS.


Assuntos
Aterosclerose , MicroRNAs , Placa Aterosclerótica , Humanos , Camundongos , Animais , Placa Aterosclerótica/genética , Monócitos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos Endogâmicos C57BL , Aterosclerose/metabolismo , Lipoproteínas LDL/farmacologia , Lipoproteínas LDL/metabolismo , Apoptose , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo
3.
Plant J ; 115(2): 494-509, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37035898

RESUMO

Seed dormancy is an important adaptive trait to prevent germination occurring at an inappropriate time. The mechanisms governing seed dormancy and germination are complex. Here, we report that FACTOR INTERACTING WITH POLY(A) POLYMERASE 1 (FIP1), a component of the pre-mRNA 3' end processing machinery, is involved in seed dormancy and germination processes in Arabidopsis thaliana. FIP1 is mainly expressed in seeds and the knockout of FIP1 causes reduced seed dormancy, indicating that FIP1 positively influences seed dormancy. Meanwhile, fip1 mutants are insensitive to exogenous ABA during seed germination and early seedling establishment. The terms 'seed maturation' and 'response to ABA stimulus' are significantly enriched in a gene ontology analysis based on genes differentially expressed between fip1-1 and the wild type. Several of these genes, including ABI5, DOG1 and PYL12, show significantly decreased transcript levels in fip1. Genetic analysis showed that either cyp707a2 or dog1-5 partially, but in combination completely, represses the reduced seed dormancy of fip1, indicating that the double mutant cyp707a2 dog1-5 is epistatic to fip1. Moreover, FIP1 is required for CFIM59, another component of pre-mRNA 3' end processing machinery, to govern seed dormancy and germination. Overall, we identified FIP1 as a regulator of seed dormancy and germination that plays a crucial role in governing these processes through the DOG1 and ABA pathways.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Germinação/genética , Mutação , Dormência de Plantas/genética , Precursores de RNA/genética , Precursores de RNA/metabolismo , Sementes/metabolismo
4.
Physiol Genomics ; 55(1): 27-40, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36440907

RESUMO

Pectic polysaccharides (PPs) could exert functions on ulcerative colitis (UC), which is classified as a nonspecific inflammatory disorder. This study investigated the molecular mechanism of PPs derived from Rauwolfia in UC. First, the dextran sodium sulfate (DSS)-induced mouse colitis models and lipopolysaccharide (LPS)-treated colonic epithelial cell (YAMC) models were established and treated with PP. Subsequently, the effects of PPs on mucosal damages in DSS mice were detected, and the levels of inflammatory cytokines, pyroptosis-related factors, oxidative stress-related markers, and the tight junction-related proteins in the tissues or cells were examined, and the results suggested that PPs ameliorated colonic mucosal damages and cell pyroptosis in DSS mice, and limited colonic epithelial cell pyroptosis in in vitro UC models. Subsequently, the binding relations of retinol-binding protein 4 (RBP4) to miR-124-3p and NLR pyrin domain-containing 3 (NLRP3) were analyzed. miR-124-3p targeted RBP4 and reduced the binding of RBP4 to NLRP3, thus inhibiting NLRP3-mediated pyroptosis. Finally, functional rescue experiments revealed that miR-124-3p suppression or RBP4 overexpression promoted colonic epithelial cell pyroptosis. Collectively, Rauwolfia-derived PPs limited miR-124-3p and targeted RBP4 and reduced the binding potency of RBP4 to NLRP3 to inhibit NLRP3-mediated pyroptosis, resulting in the alleviation of colonic epithelial cell pyroptosis and mucosal damages in UC.


Assuntos
Colite Ulcerativa , Colite , MicroRNAs , Rauwolfia , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Rauwolfia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pectinas/efeitos adversos , Piroptose , Domínio Pirina , Colite/induzido quimicamente , Células Epiteliais/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
5.
Am J Pathol ; 192(1): 104-111, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34756873

RESUMO

The proinflammatory cytokine tumor necrosis factor-α (TNF-α) augments intracellular Ca2+ signaling and contractile responses of airway smooth muscles, leading to airway hyperresponsiveness. However, the underlying mechanism has not been fully elucidated. This study aimed to investigate the cellular mechanism of the potentiated contraction of mouse tracheal smooth muscle induced by TNF-α. The results showed that TNF-α triggered facilitation of mouse tracheal smooth muscle contraction in an epithelium-independent manner. The TNF-α-induced hypercontractility could be suppressed by the protein kinase C inhibitor GF109203X, the tyrosine kinase inhibitor genistein, the Src inhibitor PP2, or the L-type voltage-dependent Ca2+ channel blocker nifedipine. Following TNF-α incubation, the α1C L-type Ca2+ channel (CaV1.2) was up-regulated in cultured primary mouse tracheal smooth muscle cells. Pronounced phosphotyrosine levels were observed in mouse tracheas. In conclusion, this study shows that TNF-α enhanced airway smooth muscle contraction via protein kinase C-Src-CaV1.2 pathways, which provides novel insights into the pathologic role of proinflammatory cytokines in mediating airway hyperresponsiveness.


Assuntos
Contração Muscular , Músculo Liso/fisiologia , Traqueia/fisiologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Canais de Cálcio Tipo L/metabolismo , Carbacol/farmacologia , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Fosfotirosina/metabolismo , Proteína Quinase C/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/fisiologia , Transdução de Sinais/efeitos dos fármacos , Traqueia/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Quinases da Família src/metabolismo
6.
Int J Mol Sci ; 24(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36982543

RESUMO

Through the salification reaction of carboxylation, successful attachment of the long-chain alkanoic acid to the two ends of 1,3-propanediamine was realized, which enabled the doubling of the long-chain alkanoic acid carbon chain. Hydrous 1,3-propanediamine dihexadecanoate (abbreviated as 3C16) and 1,3-propanediamine diheptadecanoate (abbreviated as 3C17) were synthesized afterward, and their crystal structures were characterized by the X-ray single crystal diffraction technique. By analyzing their molecular and crystal structure, their composition, spatial structure, and coordination mode were determined. Two water molecules played important roles in stabilizing the framework of both compounds. Hirshfeld surface analysis revealed the intermolecular interactions between the two molecules. The 3D energy framework map presented the intermolecular interactions more intuitively and digitally, in which dispersion energy plays a dominant role. DFT calculations were performed to analyze the frontier molecular orbitals (HOMO-LUMO). The energy difference between the HOMO-LUMO is 0.2858 eV and 0.2855 eV for 3C16 and 3C17, respectively. DOS diagrams further confirmed the distribution of the frontier molecular orbitals of 3C16 and 3C17. The charge distributions in the compounds were visualized using a molecular electrostatic potential (ESP) surface. ESP maps indicated that the electrophilic sites are localized around the oxygen atom. The crystallographic data and parameters of quantum chemical calculation in this paper will provide data and theoretical support for the development and application of such materials.


Assuntos
Compostos de Amônio , Sais , Modelos Moleculares , Cristalografia por Raios X
7.
Compr Rev Food Sci Food Saf ; 22(3): 1763-1793, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36871162

RESUMO

Citrus is an important source of flavonoids in our daily diet. Citrus flavonoids have antioxidant, anticancer, anti-inflammatory, and cardiovascular disease prevention functions. Studies have shown that some pharmaceutical values of flavonoids may be related to their binding to bitter taste receptors, thus activating downstream signal transduction pathways; however, the underlying mechanism has not been systematically elucidated. In this paper, the biosynthesis pathway and the absorption and metabolism of citrus flavonoids were briefly reviewed, and the relationship between flavonoid structure and bitter taste intensity was investigated. In addition, the pharmacological effects of bitter flavonoids and the activation of bitter taste receptors in combating various diseases were discussed. This review provides an important basis for the targeted design of citrus flavonoid structures to make them more biologically active and more attractive as powerful drugs for the effective treatment of chronic diseases such as obesity, asthma, and neurological diseases.


Assuntos
Citrus , Flavonoides , Flavonoides/farmacologia , Flavonoides/metabolismo , Paladar , Citrus/química , Transdução de Sinais
8.
Chin J Traumatol ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38129241

RESUMO

PURPOSE: To explore the effect of green channel for stroke patients on the treatment of severe aneurysmal subarachnoid hemorrhage. METHODS: This is a retrospective case-control study. The clinical data of patients with severe aneurysmal subarachnoid hemorrhage admitted to the emergency department of our hospital from January 2015 to June 2022 were retrospectively analyzed. Patients diagnosed with subarachnoid hemorrhage, confirmed intracranial aneurysm by preoperative CT angiography or digital subtraction, graded Hunt-Hess grade III, IV, and V, < 72 h from the onset to the time of consultation received surgical treatment in our hospital were included in this study. Patients with serious underlying diseases, such as heart, liver, kidney diseases, or malignant tumors, traumatic subarachnoid hemorrhage, previous history of cerebral hemorrhage, and incomplete data were excluded. The control group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2015 to December 2018 before the establishment of the green channel for stroke patients, and the observation group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2019 to June 2022 after the establishment of the green channel. The control group received routine treatment in the emergency department; the observation group received improved treatment of green channel for stroke patients. Gender, age, Hunt-Hess grade on admission, modified Rankin scale (mRS) on admission, aneurysm location, aneurysm size and whether accompanied by intracerebral hemorrhage, the time from onset to emergency department, the time from emergency department to vascular diagnostic examination, the time from onset to surgery, the time from emergency department to surgery, the time from hospital admission to surgery, length of hospital stay, complications, treatment effect were analyzed and compared between the 2 groups. SPSS 23.0 software was utilized to conduct comparisons between the 2 groups. The t-test, Chi-square test, or Mann-Whitney U test was chosen based on the data type. Statistical significance was established when p < 0.05. RESULTS: A total of 71 patients were included in this study, of whom 37 were in the control group and 34 were in the observation group. There were no statistical differences in age, gender, Hunt-Hess grade, mRS scores, aneurysm location, aneurysm size, intracerebral hemorrhage, the time from onset to emergency department, length of hospital stay, complications between the observation group and the control group (all p > 0.05). The time (min) from visit to vascular diagnostic test (60.50 vs. 120.00, p = 0.027), the time (min) from onset to surgery (1792.00 vs. 2868.00, p = 0.023), the time (min) from emergency department to surgery (1568.50 vs. 2778.00, p = 0.016), the time (min) from hospital admission to surgery (1188.50 vs. 2708.00, p = 0.043), all of them were shorter in the observation group than those in the control group. The relative values of admission and 7-day postoperative mRS scores and the relative values of admission and discharge mRS scores ≥ 2 were used as the criteria for determining better efficacy, and the treatment effect was better than that in the control group, and the differences were statistically significant (admission to 7 days postoperative mRS score ≥ 2, 17 (50.0 %) vs. 8 (21.6 %), p = 0.012; admission to discharge mRS score ≥ 2, 19 (55.9 %) vs. 11 (29.7 %), p = 0.026). CONCLUSION: The green channel for stroke patients with severe aneurysmal subarachnoid hemorrhage can effectively shorten the time from arrival at the emergency department to vascular diagnostic examination and the time from the emergency department to surgery, and achieve a better therapeutic effect, which is worth popularizing and applying.

9.
Plant J ; 107(3): 909-924, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34037275

RESUMO

Ectopic expression of specific genes in seeds could be a tool for molecular design of crops to alter seed dormancy and germination, thereby improving production. Here, a seed-specific vector, 12S-pLEELA, was applied to study the roles of genes in Arabidopsis seeds. Transgenic lines containing FLOWERING LOCUS T (FT) driven by the 12S promoter exhibited significantly increased seed dormancy and earlier flowering. Mutated FT(Y85H) and TERMINAL FLOWER1 (TFL1) transgenic lines also showed increased seed dormancy but without altered flowering time. FT(Y85H) and TFL1 caused weaker seed dormancy enhancement compared to FT. The FT and TFL1 transgenic lines showed hypersensitivity to paclobutrazol, but not to abscisic acid in seed germination. The levels of bioactive gibberellin 3 (GA3 ) and GA4 were significantly reduced, consistent with decreased expression of COPALYL DIPHOSPHATE SYNTHASE (CPS), KAURENE OXIDASE (KO), GIBBERELLIN 3-OXIDASE2 (GA3ox2), and GA20ox1 in p12S::FT lines. Exogenous GA4+7 could recover the germination ability of FT transgenic lines. These results revealed that FT regulates GA biosynthesis. A genetic analysis indicated that the GA signaling regulator SPINDLY (SPY) is epistatic to FT in GA-mediated seed germination. Furthermore, DELAY OF GERMINATION1 (DOG1) showed significantly higher transcript levels in p12S::FT lines. Seed dormancy analysis of dog1-2 spy-3 p12S::FT-2 indicated that the combination of SPY and DOG1 is epistatic to FT in the regulation of dormancy. Overall, we showed that ectopic expression of FT and TFL1 in seeds enhances dormancy through affecting GA and DOG1 pathways.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Oxigenases de Função Mista/metabolismo , Dormência de Plantas/fisiologia , Sementes/fisiologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Oxigenases de Função Mista/genética , Mutagênese Sítio-Dirigida , Dormência de Plantas/genética , Plantas Geneticamente Modificadas
10.
Planta ; 255(2): 34, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35006338

RESUMO

MAIN CONCLUSION: The SNF5-type protein BUSHY plays a role in the regulation of seed germination via the gibberellin pathway dependent on HUB1 in Arabidopsis thaliana. SWITCH/SUCROSE NONFERMENTING (SWI/SNF) complexes play diverse roles in plant development. Some components have roles in embryo development and seed maturation, however, whether the SNF5-type protein BUSHY (BSH), one of the components, plays a role in Arabidopsis seed related traits is presently unclear. In our study, we show that a loss-of-function mutation in BSH causes increased seed germination in Arabidopsis. BSH transcription was induced by the gibberellin (GA) inhibitor paclobutrazol (PAC) in the seed, and BSH regulates the expression of GA pathway genes, such as Gibberellin 3-Oxidase 1 (GA3OX1), Gibberellic Acid-Stimulated Arabidopsis 4 (GASA4), and GASA6 during seed germination. A genetic analysis showed that seed germination was distinctly improved in the bshga3ox1ga3ox2 triple mutant, indicating that BSH acts partially downstream of GA3OX1 and GA3OX2. Moreover, the regulation of seed germination by BSH in response to PAC is dependent on HUB1. These results provide new insights and clues to understand the mechanisms of phytohormones in the regulation of seed germination.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Germinação , Giberelinas , Sementes/metabolismo
11.
Plant Cell ; 31(4): 832-847, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30837295

RESUMO

The control of seed dormancy by ethylene has been well studied, but the underlying molecular mechanisms are not fully understood. Here, we report the characterization of the Arabidopsis (Arabidopsis thaliana) mutant reduced dormancy 3 (rdo3) and the cloning of the underlying gene. We demonstrate that rdo3 is a loss-of-function mutant of the ethylene receptor ETHYLENE RESPONSE1 (ETR1). ETR1 controls seed dormancy partially through the DELAY OF GERMINATION1 (DOG1) pathway. Molecular and genetic analyses demonstrated that ETHYLENE RESPONSE FACTOR12 (ERF12) is involved in the regulation of seed dormancy downstream of ETR1. ERF12 interacts with TOPLESS (TPL) and genetically requires TPL to function. ERF12 and TPL repress the expression of DOG1 by occupying its promoter. Thus, we identified the dormancy pathway ETR1-ERF12-TPL-DOG1 and provide mechanistic insights into the regulation of seed dormancy by linking the ethylene and DOG1 pathways.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Dormência de Plantas/fisiologia , Receptores de Superfície Celular/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Dormência de Plantas/genética , Receptores de Superfície Celular/genética , Sementes/genética , Sementes/metabolismo , Sementes/fisiologia
12.
Nanotechnology ; 34(4)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36265415

RESUMO

Triethylamine (TEA) exists widely in production and life and is extremely volatile, which seriously endangers human health. It is required to develop high-performance TEA sensors to protect human health. We fabricated Pt-Co3O4/WO3based on our previous work, and the performance was tested against volatile organic compounds. Compared with the previous work, its operating temperature was greatly reduced from 240 °C to 180 °C. The response value of Pt-Co3O4/WO3was increased from 1101 to 1532 for 10 ppm TEA with good selectivity. These results show a significant step toward practical use of the Pt-Co3O4/WO3sensor.

13.
BMC Emerg Med ; 22(1): 33, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35227198

RESUMO

BACKGROUND: To investigate current knowledge, attitudes, and practices for CPR quality control among emergency physicians in Chinese tertiary hospitals. METHODS: Anonymous questionnaires were distributed to physicians in 75 tertiary hospitals in China between January and July 2018. RESULTS: A total of 1405 respondents answered the survey without obvious logical errors. Only 54.4% respondents knew all criteria of high-quality CPR. A total of 91.0% of respondents considered CPR quality monitoring should be used, 72.4% knew the objective method for monitoring, and 63.2% always/often monitored CPR quality during actual resuscitation. The main problems during CPR were related to chest compression: low quality due to fatigue (67.3%), inappropriate depth (57.3%) and rate (54.1%). The use of recommended monitoring methods was reported as follows, ETCO2 was 42.7%, audio-visual feedback devices was 10.1%, coronary perfusion pressure was 17.9%, and invasive arterial pressure was 31.1%. A total of 96.3% of respondents considered it necessary to participate in regular CPR retraining, but 21.4% did not receive any retraining. The ideal retraining interval was considered to be 3 to 6 months, but the actual interval was 6 to 12 months. Only 49.7% of respondents reported that feedback devices were always/often used in CPR training. CONCLUSION: Chinese emergency physicians were very concerned about CPR quality, but they did not fully understand the high-quality criteria and their impact on prognosis. CPR quality monitoring was not a routine procedure during actual resuscitation. The methods recommended in guidelines were rarely used in practice. Many physicians had not received retraining or received retraining at long intervals. Feedback devices were not commonly used in CPR training.


Assuntos
Reanimação Cardiopulmonar , Conhecimentos, Atitudes e Prática em Saúde , Reanimação Cardiopulmonar/educação , China , Serviço Hospitalar de Emergência , Humanos , Inquéritos e Questionários
14.
BMC Cardiovasc Disord ; 21(1): 537, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772347

RESUMO

OBJECTIVES: To evaluate the 3-year clinical outcomes of a polymer-free sirolimus-eluting, Nano plus stent for the treatment of coronary artery disease in the NANO multicenter Registry. BACKGROUND: The long-term clinical data evaluating the safety and efficacy of the novel polymer-free sirolimus-eluting Nano plus stent (Lepu Medical, Beijing, China) is limited. METHODS: The NANO all-comers Registry trial was a prospective, multicenter clinical registry conducted in 26 centers in China between August 2016 and January 2017. A total of 2481 consecutive patients were exclusively treated with the Nano plus stent. The primary clinical endpoint, target lesion failure (TLF, defined as cardiac death, target vessel nonfatal myocardial infarction, and clinically driven target lesion revascularization [CD-TLR]), was analyzed at 3 years. RESULTS: At 3 years, 2295 patients (92.5%) were followed. The incidence of TLF was 6.8% (168/2481). The rate of cardiac death was 3.8% (94/2481), target vessel nonfatal myocardial infarction 0.7% (18/2481), and CD-TLR 2.9% (68/2481). The rate of definite/probable stent thrombosis was 0.5% (13/2481). The risk factors of diabetes mellitus, acute myocardial infarction, age, chronic renal failure, in-stent restenosis, chronic total occlusion, and left ventricular ejection fraction < 40% were the independent predictors of 3-year TLF. CONCLUSIONS: At three years, the rate of TLF was relatively low in patients treated with the polymer-free Nano plus stent. The polymer-free Nano plus stent showed a favorable safety and efficacy profile in real-world patients. Clinical trial registration URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02929030.


Assuntos
Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos , Intervenção Coronária Percutânea , Idoso , China , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Stents Farmacológicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Polímeros , Estudos Prospectivos , Falha de Prótese , Sistema de Registros , Falha de Tratamento
15.
BMC Pregnancy Childbirth ; 21(1): 441, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34167519

RESUMO

BACKGROUND: Placenta previa, a serious obstetric issue, should be managed by experienced teams. The safe and appropriate mode of delivery for placenta previa is by cesarean delivery. However, no studies were found comparing either maternal or neonatal outcomes for different skin incision in women with placenta previa. The aim of this study was to compare maternal and neonatal outcomes by skin incision types (transverse compared with vertical) in a large cohort of women with placenta previa who were undergoing cesarean delivery. METHODS: This was a retrospective cohort study carried out between January 2014 and June 2019. All pregnant women with placenta previa had confirmed by ultrasonologist before delivery and obstetrician at delivery. The primary outcome was the estimated blood loss during the surgery and within the first 24 hours postoperatively. Mean (standard deviation), median (interquartile range) or frequency (percentage) was reported to variables. Appropriate parametric and nonparametric tests were used to analyses. RESULTS: The study included 1098 complete records, 332 (30.24%) cases in the vertical skin incision group and 766 (69.76%) cases in the transverse skin incision group. Those with vertical incision showed a higher percentage of preterm delivery, anterior placenta, abnormally invasive placenta, and history of previous cesarean delivery, and a lower percentage of first pregnancy, in vitro fertilization, and emergency cesarean delivery. After controlling for confounding factors, higher incidence of post-partum hemorrhage (OR 5.47, 95% CI 3.84-7.79), maternal intensive care unit (OR 4.30, 95% CI 2.86-6.45), transfusion (OR 5.97, 95% CI 4.15-8.58), and 5-min APGAR< 7 (OR 9.03, 95% CI 1.83-44.49), a more estimated blood loss (ß 601.85, 95%CI 458.78-744.91), and a longer length of hospital stay after delivery (ß 0.54, 95%CI 0.23-0.86) were found in the vertical skin incision group. CONCLUSIONS: Our data demonstrated that transverse skin incision group showed the better perinatal outcomes in women with placenta previa. Future collaborative studies are needed to be done by centers for placenta previa to have a better understanding of the characteristics and the outcomes of the disease in the choosing skin incision.


Assuntos
Cesárea/métodos , Placenta Prévia/cirurgia , Ferida Cirúrgica/complicações , Adulto , Transfusão de Sangue/estatística & dados numéricos , Cesárea/efeitos adversos , Feminino , Humanos , Incidência , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/etiologia , Gravidez , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos
16.
Int J Clin Pract ; 75(4): e13759, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33098255

RESUMO

AIMS: To investigate current awareness and practices of neurological prognostication in comatose cardiac arrest (CA) patients. METHODS: An anonymous questionnaire was distributed to 1600 emergency physicians in 75 hospitals which were selected randomly from China between January and July 2018. RESULTS: 92.1% respondents fulfilled the survey. The predictive value of brain stem reflex, motor response and myoclonus was confirmed by 63.5%, 44.6% and 31.7% respondents, respectively. Only 30.7% knew that GWR value < 1.1 indicated poor prognosis and only 8.1% know the most commonly used SSEP N20. Status epilepticus, burst suppression and suppression were considered to predict poor outcome by only 35.0%, 27.4% and 20.9% respondents, respectively. Only 46.7% knew NSE and only 24.7% knew S-100. Only a few respondents knew that neurological prognostication should be performed later than 72 hours from CA either in TTM or non-TTM patients. In practice, the most commonly used method was clinical examination (85.4%). Only 67.9% had used brain CT for prognosis and 18.4% for MRI. NSE (39.6%) was a little more widely used than S-100ß (18.0%). However, SSEP (4.4%) and EEG (11.4%) were occasionally performed. CONCLUSIONS: Neurological prognostication in CA survivors had not been well understood and performed by emergency physicians in China. They were more likely to use clinical examination rather than objective tools, especially SSEP and EEG, which also illustrated that multimodal approach was not well performed in practice.


Assuntos
Parada Cardíaca , China/epidemiologia , Coma , Parada Cardíaca/diagnóstico , Humanos , Prognóstico , Sobreviventes
17.
BMC Anesthesiol ; 21(1): 247, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666687

RESUMO

BACKGROUND: The incidence of placenta preiva is rising. Cesarean delivery is identified as the only safe and appropriate mode of delivery for pregnancies with placenta previa. Anesthesia is important during the cesarean delivery. The aim of this study is to assess maternal and neonatal outcomes of patients with placenta previa managed with neuraxial anesthesia as compared to those who underwent general anesthesia during cesarean delivery. METHODS: A retrospective cohort study was performed of all patients with placenta preiva at our large academic institution from January 1, 2014 to June 30, 2019. Patients were managed neuraxial anesthesia and general anesthesia during cesarean delivery. RESULTS: We identified 1234 patients with placenta previa who underwent cesarean delivery at our institution. Neuraxial anesthesia was performed in 737 (59.7%), and general anesthesia was completed in 497 (40.3%) patients. The mean estimated blood loss at neuraxial anesthesia of 558.96 ± 42.77 ml were significantly lower than the estimated blood loss at general anesthesia of 1952.51 ± 180 ml (p < 0.001). One hundred and forty-six of 737 (19.8%) patients required blood transfusion at neuraxial anesthesia, whereas 381 out of 497 (76.7%) patients required blood transfusion at general anesthesia. The rate neonatal asphyxia and admission to NICU at neuraxial anesthesia was significantly lower than general anesthesia (2.7% vs. 19.5 and 18.2% vs. 44.1%, respectively). After adjusting confounding factors, blood loss was less, Apgar score at 1- and 5-min were higher, and the rate of blood transfusion, neonatal asphyxia, and admission to NICU were lower in the neuraxial group. CONCLUSIONS: Our data demonstrated that neuraxial anesthesia is associated with better maternal and neonatal outcomes during cesarean delivery in women with placenta previa.


Assuntos
Anestesia Geral , Raquianestesia , Cesárea , Placenta Prévia/cirurgia , Anestesia Obstétrica , Índice de Apgar , Asfixia Neonatal/epidemiologia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Admissão do Paciente/estatística & dados numéricos , Gravidez , Estudos Retrospectivos
18.
J Exp Bot ; 71(3): 919-933, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31641755

RESUMO

The molecular mechanisms underlying seed dormancy and germination are not fully understood. Here, we show that Arabidopsis thaliana SEED DORMANCY 4-LIKE (AtSdr4L) is a novel specific regulator of dormancy and germination. AtSdr4L encodes a protein with an unknown biochemical function that is localized in the nucleus and is expressed specifically in seeds. Loss of function of AtSdr4L results in increased seed dormancy. The germination of freshly harvested seeds of the Atsdr4l mutant is insensitive to gibberellin (GA). After-ripened mutant seeds are hypersensitive to the GA biosynthesis-inhibitor paclobutrazol but show unaltered sensitivity to abscisic acid. Several GA biosynthesis genes and GA-regulated cell wall remodeling genes are down-regulated in the mutant in both dormant and after-ripened seeds. These results suggest that the Atsdr4l mutation causes both decreased GA biosynthesis and reduced responses. In addition, a genetic analysis indicated that AtSdr4L is epistatic to DELAY OF GERMINATION1 (DOG1) for dormancy and acts upstream of RGA-LIKE 2 (RGL2) in the GA pathway. We propose that AtSdr4L regulates seed dormancy and germination by mediating both the DOG1 and GA pathways.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Germinação , Giberelinas/metabolismo , Dormência de Plantas , Sementes/metabolismo , Fatores de Transcrição/metabolismo
19.
Planta ; 250(1): 187-198, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30972483

RESUMO

MAIN CONCLUSION: Totally, 23 and 26 loci for the first count germination ratio and the final germination ratio were detected by quantitative trait loci (QTL) mapping and association mapping, respectively, which could be used to facilitate wheat pre-harvest sprouting breeding. Weak dormancy can cause pre-harvest sprouting in seeds of common wheat which significantly reduces grain yield. In this study, both quantitative trait loci (QTL) mapping and genome-wide association study (GWAS) were used to identify loci controlling seed dormancy. The analyses were based on a recombinant inbred line population derived from Zhou 8425B/Chinese Spring cross and 166 common wheat accessions. Inclusive composite interval mapping detected 8 QTL, while 45 loci were identified in the 166 wheat accessions by GWAS. Among these, four loci (Qbifcgr.cas-3AS/Qfcgr.cas-3AS, Qbifcgr.cas-6AL.1/Qfcgr.cas-6AL.1, Qbifcgr.cas-7BL.2/Qfcgr.cas-7BL.2, and Qbigr.cas-3DL/Qgr.cas-3DL) were detected in both QTL mapping and GWAS. In addition, 41 loci co-located with QTL reported previously, whereas 8 loci (Qfcgr.cas-5AL, Qfcgr.cas-6DS, Qfcgr.cas-7AS, Qgr.cas-3DS.1, Qgr.cas-3DS.2, Qbigr.cas-3DL/Qgr.cas-3DL, Qgr.cas-4B, and Qgr.cas-5A) were likely to be new. Linear regression showed the first count germination ratio or the final germination ratio reduced while multiple favorable alleles increased. It is suggested that QTL pyramiding was effective to reduce pre-harvest sprouting risk. This study could enrich the research on pre-harvest sprouting and provide valuable information of marker exploration for wheat breeding programs.


Assuntos
Estudo de Associação Genômica Ampla , Dormência de Plantas/genética , Locos de Características Quantitativas/genética , Triticum/genética , Mapeamento Cromossômico , Germinação/genética , Melhoramento Vegetal , Sementes/genética , Sementes/fisiologia , Triticum/fisiologia
20.
BMC Pulm Med ; 17(1): 127, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28931394

RESUMO

BACKGROUND: Acute respiratory failure (ARF) is still one of the most severe complications in immunocompromised patients. Our previous systematic review showed noninvasive mechanical ventilation (NIV) reduced mortality, length of hospitalization and ICU stay in AIDS/hematological malignancy patients with relatively less severe ARF, compared to invasive mechanical ventilation (IMV). However, this systematic review was based on 13 observational studies and the quality of evidence was low to moderate. The efficacy of NIV in more severe ARF and in patients with other causes of immunodeficiency is still unclear. We aim to determine the efficacy of the initial ventilation strategy in managing ARF in immunocompromised patients stratified by different disease severity and causes of immunodeficiency, and explore predictors for failure of NIV. METHODS AND ANALYSIS: The VENIM is a multicentre randomized controlled trial (RCT) comparing the effects of NIV compared with IMV in adult immunocompromised patients with severe hypoxemic ARF. Patients who meet the indications for both forms of ventilatory support will be included. Primary outcome will be 30-day all-cause mortality. Secondary outcomes will include in-hospital mortality, length of stay in hospital, improvement of oxygenation, nosocomial infections, seven-day organ failure, adverse events of intervention, et al. Subgroups with different disease severity and causes of immunodeficiency will also be analyzed. DISCUSSION: VENIM is the first randomized controlled trial aiming at assessing the efficacy of initial ventilation strategy in treating moderate and severe acute respiratory failure in immunocompromised patients. The result of this RCT may help doctors with their ventilation decisions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02983851 . Registered 2 September 2016.


Assuntos
Hipóxia/complicações , Ventilação não Invasiva/efeitos adversos , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/terapia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Método Duplo-Cego , Feminino , Mortalidade Hospitalar , Humanos , Hospedeiro Imunocomprometido , Intubação Intratraqueal , Masculino , Pessoa de Meia-Idade , Ventilação não Invasiva/métodos , Escores de Disfunção Orgânica , Projetos de Pesquisa , Adulto Jovem
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