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1.
Int J Clin Oncol ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731352

RESUMO

AIM: Currently, the optimal treatment strategy for locally advanced esophageal cancer (LAEC) remains controversial. We perform the present study to compare the outcomes of LAEC treated with neoadjuvant chemotherapy (neo-CT) or chemoradiotherapy (neo-CRT). MATERIALS AND METHODS: A population cohort with histologically diagnosed of esophageal cancer was identified from SEER database between 2004 and 2015. The Kaplan-Meier method and Cox-regression proportional hazards model were used to assess the impact of neoadjuvant treatment regimens on the cause-specific survival (CSS) and overall survival (OS) of LAEC. A propensity score model was utilized to balance baseline covariates. RESULTS: After propensity score matching, a total of 1986 LAEC patients were included for analysis, 1,655 patients treated with neo-CRT and 331 with neo-CT, respectively. The survival outcomes of LAEC treated with neo-CRT were comparable to those treated with neo-CT in terms of 5-year OS (39% vs. 36%, p = 0.63) and CSS (51% vs. 51%, p = 0.77). In the multivariate Cox analyses, sex, histological grade, ypT stage, ypN( +), and number of LN examined were independent factors for predicting OS and CSS among LAEC treated with neoadjuvant treatment. CONCLUSION: The present study based on large cohort demonstrated that no significant survival difference was observed between LAEC patients treated with neo-CRT versus neo-CT. However, the results needed to be confirmed in well-designed prospective trials.

4.
Materials (Basel) ; 14(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34772059

RESUMO

Powder metallurgy (PM) is a versatile process to manufacture nearly net-shaped metallic materials in industry. In this study, the PM process was used to fabricate two Fe-based laminated metal composites (LMCs), Fe-4Ni-3Cr-0.5Mo-0.5C/Fe and 410/304L. The results showed that after sintering, the LMCs were free of interfacial cracks and distortion, indicating that the PM process is a feasible means for producing these LMCs. In the Fe-4Ni-3Cr-0.5Mo-0.5C/Fe LMC, the diffusion of C resulted in the generation of a continuous pearlite layer between the Fe-4Ni-3Cr-0.5Mo-0.5C and Fe layers and a ferrite/pearlite mixture in the Fe layer. In the 410/304L LMC, the difference in the chemical potentials of C between the 304L and 410 layers led to the uphill diffusion of C from the 410 layer to the 304L layer. A continuous ferrite layer was thus formed near the interface of the 410 layer. Furthermore, a martensite layer of about 50 µm thickness was generated at the interface due to the high Cr and Ni content.

5.
Antimicrob Agents Chemother ; : AAC0129521, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34662187

RESUMO

The emergence of daptomycin-resistant (DAP-R) Staphylococcus aureus strains has become a global problem. Point mutations in mprF are the main cause of daptomycin (DAP) treatment failure. However, the impact of these specific point-mutations in methicillin-resistant S. aureus (MRSA) strains associated with DAP resistance and the "see-saw effect" of distinct beta-lactams remains unclear. In this study, we used three series of clinical MRSA strains with three distinct mutated mprF alleles from clone complexes (CC) 5 and 59 to explore the "see-saw effect" and the combination effect of DAP plus beta-lactams. Through construction of mprF deletion and complementation strains of SA268, we determined that mprF-S295A, mprF-S337L and one novel mutation of mprF-I348del within the bifunctional domain lead to DAP resistance. Compared with wild-type mprF cloned from a DAP-susceptible (DAP-S) strain, these three mprF mutations conferred the "see-saw effect" to distinct beta-lactams in the SA268ΔmprF strains and mutated-mprF (I348del and S337L) did not alter the cell surface positive charge (P > 0.05). The susceptibility to beta-lactams increased significantly in DAP-R CC59 strains and the "see-saw effect" was found to be associated with distinct mutated mprF alleles and the category of beta-lactams. The synergistic activity of DAP plus oxacillin was detected in all DAP-R MRSA strains. Continued progress in understanding the mechanism of restoring susceptibility to beta-lactam antibiotics mediated by the mprF mutation and its impact on beta-lactam combination therapy will provide fundamental insights into treatment of MRSA infections.

6.
Cardiovasc Res ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648001

RESUMO

AIMS: Abnormal intracellular calcium handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signaling pathway contributes to atrial remodeling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models. METHODS AND RESULTS: Expression levels of NFATc1-c4 isoforms were assessed by quantitative reverse transcription-polymerase chain reaction in right atrial appendages from patients with chronic AF. NFATc1 and NFATc2 mRNA levels were elevated in chronic AF (cAF) patients compared with those in sinus rhythm (SR). Western blotting revealed increased cytosolic and nuclear levels of NFATc2 in AF patients. Similar findings were obtained in CREM-IbΔC-X transgenic (CREM) mice, a model of progressive AF. Telemetry ECG recordings revealed age-dependent spontaneous AF in CREM mice, which was prevented by NFATc2 knockout in CREM: NFATc2-/- mice. Programmed electrical stimulation revealed that CREM: NFATc2-/- mice lacked an AF substrate. Morphometric analysis and histology revealed increased atrial weight and atrial fibrosis in CREM mice compared with WT controls, which was reversed in CREM: NFATc2-/- mice. Confocal microscopy showed an increased Ca2+ spark frequency despite a reduced sarcoplasmic reticulum (SR) Ca2+ load in CREM mice compared with controls, whereas these abnormalities were normalized in CREM: NFATc2-/- mice. Western blotting revealed that genetic inhibition of Ca2+/calmodulin-dependent protein kinase II-mediated phosphorylation of S2814 on RyR2 in CREM: RyR2-S2814A mice suppressed NFATc2 activation observed in CREM mice, suggesting that NFATc2 is activated by excessive SR Ca2+ leak via RyR2. Finally, chromatin immunoprecipitation sequencing from AF patients identified Ras And EF-Hand Domain-Containing Protein (RASEF) as a direct target of NFATc2 mediated transcription. CONCLUSION: Our findings reveal activation of the NFAT signaling pathway in patients of Chinese and European descent. NFATc2 knockout prevents the progression of AF in the CREM mouse model. TRANSLATIONAL PERSPECTIVE: Atrial fibrillation (AF) is a progressive disease characterized by electrical and structural remodeling which promotes atrial arrhythmias. This study provides evidence for increased 'nuclear factor of activated T-cell' (NFAT) signaling in patients with chronic AF. Studies in the CREM transgenic model of progressive AF revealed that the NFATc2 isoform mediates atrial remodeling associated with AF substrate development. Chromatin immunoprecipitation sequencing of atrial biopsies from AF patients identified 'Ras And EF-Hand Domain-Containing Protein' (RASEF) as a downstream target of NFATc2-mediated transcription, suggesting that targeting these factors might be beneficial for curtailing AF progression.

7.
Int J Gen Med ; 14: 6563-6571, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675623

RESUMO

Objective: To evaluate the feasibility, clinical efficacy and imaging results of preoperative traction (PT) followed by percutaneous kyphoplasty (PKP) combined with percutaneous cement discoplasty (PCD) for treating severe thoracolumbar osteoporotic vertebral compression fractures (OVCFs). Methods: A total of 13 patients with severe thoracolumbar OVCFs treated by PT followed by PKP combined with PCD were enrolled. General information, PT time, operation time, postoperative hospital stay, perioperative complications, visual analog scale (VAS) score, Oswestry disability index (ODI) score, local kyphosis angle, intervertebral angle (IVA), anterior vertebral height (AVH) and posterior vertebral height (PVH) were recorded. Results: The average VAS score at admission was 7.4±3.5, decreased to 4.3±1.7 after PT and 2.3±0.7 three days after operation, and 1.5±0.9 at last follow-up. The average ODI score was 73.7±21.4 before operation, decreased to 26.6±9.3 three days after operation and 13.7±7.1 at last follow-up. Compared to VAS and ODI scores at admission, these at the third day after operation and last follow-up were significantly different. At admission, the IVA was 3.4°±6.8°, the disc height was 5.7±1.2mm, the AVH was 10.7±3.2mm, and the PVH was 25.7±4.2 mm, which, after PT, changed to 8.1°±7.3°, 8.6±2.6mm, 18.5±2.8mm, and 26.2±7.1mm, respectively, and the differences were significant. The average kyphotic angle was 43.4°±17.8° at admission, and decreased to 26.3°±6.7° after PT, 17.5°±8.4° three days after operation and 19.1°±10.3° at last follow-up, and the differences were significant. Conclusion: PT followed by PKP combined with PCD for the treatment of severe thoracolumbar OVCFs was an effective and simple procedure with satisfactory short-term clinical outcomes by relieving pain and improving kyphosis.

8.
J Cardiothorac Surg ; 16(1): 287, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627311

RESUMO

OBJECTIVE: Postoperative pulmonary complications (PPCs) are common incidents associated with an increased hospital stay, readmissions into the intensive care unit (ICU), increased costs, and mortality after cardiac surgery. Our study aims to analyze whether minimally invasive valve surgery (MIVS) can reduce the incidence of postoperative pulmonary complications compared to the full median sternotomy (FS) approach. METHODS: We reviewed the records of 1076 patients who underwent isolated mitral or aortic valve surgery (80 MIVS and 996 FS) in our institution between January 2015 and December 2019. Propensity score-matching analysis was used to compare outcomes between the groups and to reduce selection bias. RESULTS: Propensity score matching revealed no significant difference in hospital mortality between the groups. The incidence of PPCs was significantly less in the MIVS group than in the FS group (19% vs. 69%, respectively; P < 0.0001). The most common PPCs were atelectasis (P = 0.034), pleural effusions (P = 0.042), and pulmonary infection (P = 0.001). Prolonged mechanical ventilation time (> 24 h) (P = 0.016), blood transfusion amount (P = 0.006), length of hospital stay (P < 0.0001), and ICU stay (P < 0.0001) were significantly less in the MIVS group. Cardiopulmonary bypass (CBP), aortic cross-clamping, and operative time intervals were significantly longer in the MIVS group than in the matched FS group (P < 0.001). A multivariable analysis revealed a decreased risk of PPCs in patients undergoing MIVS (odds ratio, 0.25; 95% confidence interval, 0.006-0.180; P < 0.0001). CONCLUSION: MIVS for isolated valve surgery reduces the risk of PPCs compared with the FS approach.


Assuntos
Implante de Prótese de Valva Cardíaca , Esternotomia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Incidência , Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos , Valva Mitral/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Esternotomia/efeitos adversos , Resultado do Tratamento
9.
BMC Pediatr ; 21(1): 429, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592941

RESUMO

BACKGROUND: Z score utility is emphasized in classifying coronary artery lesions in Kawasaki disease patients. The present study is the largest such multicenter Chinese pediatric study about coronary artery diameter reference values and Z score regression equation to date. It is useful in Chinese pediatric echocardiography. METHODS: A multicenter cohort was assembled, which consisted of 852 healthy children between 1 month and 17 years of age, ten children were excluded because their ultrasound images were not clear, or lost in following up. Diameters of the right coronary artery, left coronary artery, and left anterior descending coronary artery were assessed using echocardiography. Data were body surface area (BSA)-corrected using BSA calculated via either the Stevenson BSA formula or the Haycock BSA formula. Coronary artery diameter reference values and Z score regression equations were established for use in the Chinese pediatric population. RESULTS: No difference was observed between coronary artery diameter data corrected using BSAste or BSAhay. Of the five assessed regression models, the exponential model exhibited the best fit and was therefore selected as the basis for derivation of the SZ method. When comparing Z scores, those produced by the SZ method conformed to the standard normal distribution, while those produced by the D method did not. In addition, there was a statistically significant difference between Z scores produced by the SZ and D methods (P < 0.05). CONCLUSIONS: Coronary artery diameter reference values for echocardiography were successfully established for use in the Chinese pediatric population, and a Z score regression equation more suitable for clinical use in this population was successfully developed.


Assuntos
Vasos Coronários , Ecocardiografia , Criança , China , Estudos de Coortes , Vasos Coronários/diagnóstico por imagem , Humanos , Lactente , Estudos Prospectivos , Valores de Referência
10.
Chaos ; 31(10): 103124, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34717320

RESUMO

This study investigates the synchronizability of a typical type of two-layer correlation networks formed by two regular networks interconnected with two interlayer linking patterns, namely, positive correlation (PC) and negative correlation (NC). To analyze the network's stability, we consider the analytical expressions of the smallest non-zero and largest eigenvalues of the (weighted) Laplacian matrix as well as the linking strength and the network size for two linking patterns. According to the master stability function, the linking patterns, the linking strength, and the network size associated with two typical synchronized regions exhibit a profound influence on the synchronizability of the two-layer networks. The NC linking pattern displays better synchronizability than the PC linking pattern with the same set of parameters. Furthermore, for the two classical synchronized regions, the networks have optimal intralayer and interlayer linking strengths that maximize the synchronizability while minimizing the required cost. Finally, numerical results verify the validity of the theoretical analyses. The findings based on the representative two-layer correlation networks provide the basis for maximizing the synchronizability of general multiplex correlation networks.

11.
Magn Reson Imaging ; 84: 115-123, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34619291

RESUMO

OBJECTIVES: Liver vessel density can be evaluated by DDVD (diffusion derived vessel density): DDVD(b0b1) = Sb0/ROIarea0 - Sb1/ROIarea1, where Sb0 and Sb1 refer to the liver signal when b is 0 or 1 s/mm2. Sb1 and ROIarea1 may be replaced by other b-values. With a rat biliary duct ligation (BDL) model, this study assesses the usefulness of liver DDVD computed from a simplified IVIM imaging protocol using b = 25 and b = 50 to replace b = 1 s/mm2, alone and in combination with other IVIM parameters. METHODS: Male Sprague-Dawley rats were used. The rat number was 5, 5, 5, and 3 respectively, for the timepoints of 7, 14, 21, 28 days post-BDL surgery. 12 rats had partial biliary duct recanalization performed after the rats had BDL for 7 days and then again followed-up for a mean of 14 days. Liver diffusion MRIs were acquired at 3.0 T with a b-value distribution of 0, 25, 50, 75, 100, 150, 300, 700, 1000 s/mm2. DDVDmean (control rats n = 6) was the mean of DDVD(b0b25) and DDVD(b0b50). IVIM fitting started from b = 0 s/mm2 with segmented fitting and a threshold b of 50 s/mm2 (n = 5 for control rats). Three 3-D spaces were constructed using a combination of the four diffusion parameters. RESULTS: The control rats and BDL rats (n = 18) had a liver DDVDmean of 84.0 ± 26.2 and 44.7 ± 14.4 au/pixel (p < 0.001). All 3-D spaces totally separated healthy livers and all fibrotic livers (n = 30, BDL rats and recanalization rats). The mean relative distance between healthy liver cluster and fibrotic liver cluster was 0.331 for PF, Dslow, and Dfast; 0.381 for PF, Dfast, and DDVDmean; and 0.384 for PF, Dslow, and DDVDmean. CONCLUSION: A combination of PF, Dslow, and Dfast allows total separation of healthy livers and fibrotic livers and the integration of DDVD improved the separation.

12.
Biomed Opt Express ; 12(8): 4889-4900, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34513231

RESUMO

The segmentation of en face retinal capillary angiograms from volumetric optical coherence tomographic angiography (OCTA) usually relies on retinal layer segmentation, which is time-consuming and error-prone. In this study, we developed a deep-learning-based method to segment vessels in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) directly from volumetric OCTA data. The method contains a three-dimensional convolutional neural network (CNN) for extracting distinct retinal layers, a custom projection module to generate three vascular plexuses from OCTA data, and three parallel CNNs to segment vasculature. Experimental results on OCTA data from rat eyes demonstrated the feasibility of the proposed method. This end-to-end network has the potential to simplify OCTA data processing on retinal vasculature segmentation. The main contribution of this study is that we propose a custom projection module to connect retinal layer segmentation and vasculature segmentation modules and automatically convert data from three to two dimensions, thus establishing an end-to-end method to segment three retinal capillary plexuses from volumetric OCTA without any human intervention.

13.
Neurochem Res ; 46(12): 3356-3364, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34524595

RESUMO

Sevoflurane is a widely used volatile anesthetic, that can cause long-term neurotoxicity and learning and memory impairment. Long non-coding RNAs (lncRNAs) have been demonstrated to function as key mediators in neurotoxicity. This study aimed to investigate the effects of lncRNA Neat1 on sevoflurane-induced neurotoxicity. The expression of Neat1, miR-298-5p, and Srpk1 was measured by RT-qPCR. Cell viability, cell apoptosis, inflammation markers, and reactive oxygen species (ROS) generation were examined by CCK-8, TUNEL, ELISA, and the ROS kit. The interaction between miR-298-5p and Neat1 or Srpk1 was confirmed by luciferase reporter assay. In our study, it was found that sevoflurane aggravated neurotoxicity through inhibiting cell viability and enhancing cell apoptosis, neuroinflammation, and ROS generation. Neat1 was up-regulated in sevoflurane-treated HT22 cells, and Neat1 knockdown improved sevoflurane-mediated neurotoxicity. Through the exploration of the ceRNA mechanism, we found that Neat1 bound with miR-298-5p, and Srpk1 was a direct target gene of miR-298-5p. Finally, rescue assays proved that up-regulation of Srpk1 reversed the effects of Neat1 knockdown on neurotoxicity. In conclusion, our study revealed that lncRNA Neat1 facilitated sevoflurane-stimulated neurotoxicity by sponging miR-298-5p to up-regulate Srpk1. These findings might provide novel insights into the treatment of sevoflurane-induced neurotoxicity.

14.
Clin Infect Dis ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554228

RESUMO

We studied the performance of an algorithm combining multiplex-PCR with phenotypic detection of ESBLs and carbapenemases directly from positive blood culture bottles in patients with Gram-negative bacteremia and found good concordance with routine cultures. Such an algorithm may be a tool to improve time-to-optimal therapy in patients with Gram-negative bacteremia.

15.
Front Cardiovasc Med ; 8: 690846, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485398

RESUMO

Filamins (FLNs) are actin cross-linking proteins, and as scaffolding proteins, FLNs are closely associated with the stabilization of the cytoskeleton. Nevertheless, the biological importance of FLNs in aortic dissection (AD) has not been well-elucidated. In this study, we first reanalyzed datasets downloaded from the Gene Expression Omnibus (GEO) database, and we found that in addition to the extracellular matrix, the actin cytoskeleton is a key structure associated with AD. Given that FLNs are involved in remodeling the cytoskeleton to affect cellular functions, we measured their expression levels in the aortas of patients with Stanford type A AD (TAAD). Our results showed that the mRNA and protein levels of FLNA were consistently decreased in dissected aortas of both humans and mice, while the FLNB protein level was upregulated despite decreased FLNB mRNA levels, and comparable expression levels of FLNC were observed between groups. Furthermore, the immunohistochemistry results demonstrated that FLNA was highly expressed in smooth muscle cells (SMCs) of aorta in non-AD samples, and downregulated in the medial layer of the dissected aortas of humans and mice. Moreover, we revealed that FOS and JUN, forming a dimeric transcription factor called AP-1 (activating protein-1), were positively correlated with the expression of FLNA in aorta. Either overexpression of FOS or JUN alone, or overexpression of FOS and JUN together, facilitated the expression of FLNA in primary cultured human aortic SMCs. In the present study, we not only detected the expression pattern of FLNs in aortas of humans and mice with or without AD, but we also found that the expression of FLNA in the AD samples was significantly reduced and that AP-1 might regulate the expression of FLNA. Our findings will contribute to the elucidation of the pathological mechanisms of AD and provide potential therapeutic targets for AD.

16.
Front Cardiovasc Med ; 8: 724178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497838

RESUMO

Background: Postoperative pulmonary complications remain a leading cause of increased morbidity, mortality, longer hospital stays, and increased costs after cardiac surgery; therefore, our study aims to analyze whether minimally invasive valve surgery (MIVS) for both aortic and mitral valves can improve pulmonary function and reduce the incidence of postoperative pulmonary complications when compared with the full median sternotomy (FS) approach. Methods: A comprehensive systematic literature research was performed for studies comparing MIVS and FS up to February 2021. Randomized controlled trials (RCTs) and propensity score-matching (PSM) studies comparing early respiratory function and pulmonary complications after MIVS and FS were extracted and analyzed. Secondary outcomes included intra- and postoperative outcomes. Results: A total of 10,194 patients from 30 studies (6 RCTs and 24 PSM studies) were analyzed. Early mortality differed significantly between the groups (MIVS 1.2 vs. FS 1.9%; p = 0.005). Compared with FS, MIVS significantly lowered the incidence of postoperative pulmonary complications (odds ratio 0.79, 95% confidence interval [0.67, 0.93]; p = 0.004) and improved early postoperative respiratory function status (mean difference -24.83 [-29.90, -19.76]; p < 0.00001). Blood transfusion amount was significantly lower after MIVS (p < 0.02), whereas cardiopulmonary bypass time and aortic cross-clamp time were significantly longer after MIVS (p < 0.00001). Conclusions: Our study showed that minimally invasive valve surgery decreases the incidence of postoperative pulmonary complications and improves postoperative respiratory function status.

17.
J Vasc Surg ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34481899

RESUMO

OBJECTIVE: The optimal treatment of intramural hematoma (IMH) involving the ascending aorta remains controversial. This study aimed to analyze the results of the management of patients with acute IMH involving the ascending aorta and extending into the descending thoracic aorta, to compare outcomes of descending thoracic endovascular aortic repair (TEVAR) with that of medical therapy (MT), and to assess the risk factors associated with adverse aortic events. METHODS: We retrospectively analyzed all patients diagnosed with acute IMH involving the ascending aorta and extending into the descending thoracic aorta from January 2012 to December 2019. The primary end points during follow-up were aortic disease-related death and adverse aorta-related events that required surgical or endovascular treatment, such as aortic rupture, the progression of aortic disease, or endoleak. RESULTS: We identified a total of 135 patients with acute IMH involving the ascending aorta and extending into the descending thoracic aorta, of whom 104 underwent descending TEVAR (group 1) and 31 were managed with MT (group 2). Freedom from adverse aorta-related events at 1, 3, and 5 years was significantly higher for patients who underwent descending TEVAR compared with those managed with MT (89.2%, 88.2%, and 84.0% vs 74.2%, 74.2%, and 74.2%, respectively; P = .026). The 1-, 3-, and 5-year survival rates for patients in the descending TEVAR group was 100%, 100%, and 100%, respectively, which was significantly higher than the survival of the MT group: 93.5%, 93.5%, and 81.9%, respectively (P = .002). On a univariate analysis among patients receiving MT, those who suffered adverse aorta-related events showed a higher prevalence of renal insufficiency (55.6% vs 9.1%; P = .003). In MT patients, multivariate analysis showed that renal insufficiency was the only independent risk factor associated with adverse aorta-related events (hazard ratio, 8.691; 95% confidence interval, 2.056-36.737; P = .003). CONCLUSIONS: Based on our study, compared with MT, descending TEVAR might be the more favorable treatment for patients with IMH involving the ascending aorta and extending into the descending thoracic aorta. Patients with renal insufficiency are more likely to experience adverse aorta-related events, which implies the need for subsequent intervention or an increased risk of mortality. The risk factor would be helpful for clinical decision-making.

18.
Zool Res ; 42(5): 637-649, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34472225

RESUMO

The insect brain is the central part of the neurosecretory system, which controls morphology, physiology, and behavior during the insect's lifecycle. Lepidoptera are holometabolous insects, and their brains develop during the larval period and metamorphosis into the adult form. As the only fully domesticated insect, the Lepidoptera silkworm Bombyx mori experienced changes in larval brain morphology and certain behaviors during the domestication process. Hormonal regulation in insects is a key factor in multiple processes. However, how juvenile hormone (JH) signals regulate brain development in Lepidoptera species, especially in the larval stage, remains elusive. We recently identified the JH receptor Methoprene tolerant 1 ( Met1) as a putative domestication gene. How artificial selection on Met1 impacts brain and behavioral domestication is another important issue addressing Darwin's theory on domestication. Here, CRISPR/Cas9-mediated knockout of Bombyx Met1 caused developmental retardation in the brain, unlike precocious pupation of the cuticle. At the whole transcriptome level, the ecdysteroid (20-hydroxyecdysone, 20E) signaling and downstream pathways were overactivated in the mutant cuticle but not in the brain. Pathways related to cell proliferation and specialization processes, such as extracellular matrix (ECM)-receptor interaction and tyrosine metabolism pathways, were suppressed in the brain. Molecular evolutionary analysis and in vitro assay identified an amino acid replacement located in a novel motif under positive selection in B. mori, which decreased transcriptional binding activity. The B. mori MET1 protein showed a changed structure and dynamic features, as well as a weakened co-expression gene network, compared with B. mandarina. Based on comparative transcriptomic analyses, we proposed a pathway downstream of JH signaling (i.e., tyrosine metabolism pathway) that likely contributed to silkworm larval brain development and domestication and highlighted the importance of the biogenic amine system in larval evolution during silkworm domestication.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Bombyx/metabolismo , Proteínas de Insetos/metabolismo , Hormônios Juvenis/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Bombyx/crescimento & desenvolvimento , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Sistemas CRISPR-Cas , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Proteínas de Insetos/genética , Tegumento Comum/fisiologia , Larva/crescimento & desenvolvimento , Larva/metabolismo , Filogenia , Conformação Proteica
19.
CNS Neurosci Ther ; 27(11): 1327-1338, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34346561

RESUMO

AIMS: Secondary bleeding and further hematoma expansion (HE) aggravate brain injury after intracerebral hemorrhage (ICH). The majority of HE results from hypertensive ICH. Previous study reported higher iron content in the brains of hypertensive patients. Iron overload exacerbates the risk of hemorrhagic transformation in thromboembolic stroke mice. Whether iron overload during the process of hypertension participates in secondary bleeding of hypertensive ICH remains unclear. METHODS: Hypertension was induced by continuous infusion of angiotensin II (Ang II) with an osmotic pump into C57BL/6 mice. ICH was simulated by intrastriatal injection of the liquid polymer Onyx-18. Iron chelation and iron overload was achieved by deferoxamine mesylate or iron dextran injection. Secondary bleeding was quantified by measuring the hemoglobin content in the ipsilateral brain hemisphere. RESULTS: Ang II-induced hypertensive mice showed increased iron accumulation in the brain and expanded secondary hemorrhage after ICH modeling. Moreover, iron chelation suppressed while iron overload aggravated secondary bleeding. Mechanistically, iron exacerbated the loss of contractile cerebral vascular smooth muscle cells (VSMCs), aggravated blood-brain barrier (BBB) leakage in Ang II-induced hypertensive mice, and increased glial and MMP9 accumulation after ICH. CONCLUSION: Iron overload plays a key role in secondary bleeding after ICH in Ang II-induced hypertensive mice. Iron chelation during the process of Ang II-induced hypertension suppresses secondary bleeding after ICH.

20.
Clin Infect Dis ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34423834

RESUMO

BACKGROUND: he impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with those with wild-type strains from early 2020. METHODS: National surveillance data from 1-January-2021 to 22-May-2021 were obtained from the Ministry of Health, and outcomes in relation to VOC were explored. Detailed patient level data from all patients with VOC infection admitted to our center between 20-December-2020 and 12-May-2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January-April 2020. RESULTS: 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, ICU admission, or death (adjusted odds ratio (aOR) 4.90, [95% CI 1.43-30.78]). 157 of these patients were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, aOR for pneumonia with B.1.617.2 was 1.88 [95% CI 0.95-3.76]) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower PCR Ct values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). CONCLUSIONS: There was a signal toward increased severity associated with B.1.617.2. The association of B.1.617.2 with lower Ct value and longer viral shedding provides a potential mechanism for increased transmissibility. These findings provide an impetus for the rapid implementation of vaccination programs.

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