Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 119
Filtrar
2.
Front Mol Biosci ; 8: 697273, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790697

RESUMO

It has been recognized that rebalancing the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) helps relieve vascular injury. Presently, we aim to investigate whether long non-coding RNA (lncRNA) maternally expressed 8 (MEG8) plays a role in affecting the excessive proliferation and migration of VSMCs following hypoxia stimulation. A percutaneous transluminal angioplasty balloon dilatation catheter was adopted to establish vascular intimal injury, the levels of MEG8 and miR-195-5p in the carotid artery were tested by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Hypoxia was used to stimulate VSMCs, then the cell counting kit-8 (CCK-8) assay, Transnwell assay, and wound healing assay were conducted to evaluate the proliferation, and migration of VSMCs. The protein levels of RECK (reversion inducing cysteine rich protein with kazal motifs), MMP (matrix metalloproteinase) 3/9/13, COX2 (cytochrome c oxidase subunit II), macrophage inflammatory protein (MIP)-1beta, VCAM-1 (vascular cell adhesion molecule 1), ICAM-1 (intercellular adhesion molecule 1), and HIF-1α (hypoxia inducible factor 1 subunit alpha) were determined by western blot or cellular immunofluorescence. As the data showed, MEG8 was down-regulated in the carotid artery after balloon injury in rats and hypoxia-treated VSMCs, and miR-195-5p was overexpressed. Forced MEG8 overexpression or inhibiting miR-195-5p attenuated hypoxia-promoted cell proliferation and migration of VSMCs. In addition, miR-195-5p up-regulation reversed MEG8-mediated effects. Hypoxia hindered the RECK expression while boosted MMP3/9/13 levels, and the effect was markedly reversed with MEG8 up-regulation or miR-195-5p down-regulation. Mechanistically, MEG8 functioned as a competitive endogenous (ceRNA) by sponging miR-195-5p which targeted RECK. Moreover, the HIF-1α inhibitor PX478 prevented hypoxia-induced proliferation, and migration of VSMCs, upregulated MEG8, and restrained miR-195-5p expression. Overall, lncRNA MEG8 participated in hypoxia-induced excessive proliferation, inflammation and migration of VSMCs through the miR-195-5p/RECK axis.

3.
Aging (Albany NY) ; 13(undefined)2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34788230

RESUMO

AIM: To explore the immunoregulatory effects of circ_CELF1 in non-small cell lung cancer (NSCLC). METHODS: The mRNA level of circ_CELF1 in primary tissue samples was analyzed by qRT-PCR. The assays of CCK-8, colony formation, wound healing as well as Transwell were employed for measurement of cancer cell malignant transformation. The murine subcutaneous tumor model was used to assess the tumorigenesis of NSCLC in vivo. The assays of circRNA precipitation, RNA immunoprecipitation, and luciferase reporter were performed to study the relationship between circ_CELF1, miR-491-5p, and EGFR. RESULTS: circ_CELF1 is upregulated in primary cancer tissues from patients with NSCLC, and a high level of circ_CELF1, is associated with malignant characteristics and poor outcomes of patients with NSCLC. Enforced expression of circ_CELF1 exacerbated the malignant transformation of NSCLC cells. Mechanistically, through directly interacting with miR-491-5p, circ_CELF1 acted as a miRNA sponge that increased the expression of the miR-491-5p target gene EGFR, eventually promoting the progression of NSCLC and increasing cancer resistance to immunotherapy. CONCLUSION: Our data demonstrate that upregulation of circ_CELF1 elicits both oncogenic and immunoregulatory effects on the development of NSCLC. We believe that circ_CELF1 can act as a potential therapeutic target for the treatment of NSCLC.

4.
Sheng Li Xue Bao ; 73(5): 707-722, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34708228

RESUMO

Glucose and lipid metabolism is the most fundamental metabolic activity of higher organisms. This process is affected by both genetic polymorphisms and environmental factors. Excessive uptake and accumulation of lipids lead to obesity and disorder of glucose metabolic homeostasis characterized by insulin resistance and hyperglycemia, suggesting that the cross-regulation between lipid and glucose metabolism happens precisely at organ, cellular and molecular levels by known mechanisms. Adenine nucleotides and their metabolites have emerged as mediators in the mutual regulation of glucose and lipid metabolism. This review summarizes the roles of purinergic signaling induced by fatty acids in glucose metabolism and the development of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Nucleotídeos de Adenina , Glucose , Homeostase , Humanos , Metabolismo dos Lipídeos
5.
J Otolaryngol Head Neck Surg ; 50(1): 51, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384505

RESUMO

BACKGROUND: Multiple surgical approaches have been proposed to repair the congenital choanal atresia. However, there remains no general consensus about the optimal surgical technique. This study aimed to describe and evaluate outcomes of the endoscopic septonasal flap technique combined with bioabsorbable steroid-eluting stents for repair of congenital choanal atresia in neonates and infants. METHODS: Clinical data of 37 neonates and infants with congenital choanal atresia who received nasal endoscopic surgery with the flap technique between January 2018 and July 2020 were analyzed retrospectively. All patients underwent the ultra­low­dose paranasal sinus computed tomography imaging preoperatively to confirm diagnosis and plan the surgery. In these patients, the mirrored L-shaped flap technique was performed for bilateral atresia and the cross-over L-shaped flap technique was performed for unilateral atresia. A total of 22 patients had silicone stents postoperatively and 15 patients had bioabsorbable steroid-eluting stents postoperatively. Silicone stents were removed at one month postoperatively under secondary general anesthesia, while no anesthesia was needed to remove the bioabsorbable steroid-eluting stents. Postoperative follow-up ranged from 10 months to 3 years. RESULTS: The septonasal flap technique was performed in all patients. Compared with the silicone stents group, the average operative duration and the hospital length of stay in the bioabsorbable steroid-eluting stents group were decreased [(97.46 ± 15.37) min vs (83.49 ± 19.16) min t = 13.733, P < 0.001] [(12.8 ± 3.22) d vs (7.67 ± 3.91) d t = 15.082, P < 0.001], the average number of procedures was reduced [(2.04 ± 0.64) vs (1.00 ± 0.001), t = 82.689, P < 0.001], the differences were statistically significant. There were no reports of postoperative restenosis and complications in the bioabsorbable steroid-eluting stents group, and follow-up endoscopic examinations showed patency and stable nasal passages in all cases. CONCLUSIONS: The endoscopic septonasal flap technique can effectively expose and expand the choanal bony structure for repair of congenital choanal atresia in neonates and infants. The combined use of this technique along with bioabsorbable steroid-eluting stents can help prevent the need for revision procedures and also against stent-related injuries.

6.
Pest Manag Sci ; 77(11): 4971-4979, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34223694

RESUMO

BACKGROUND: The striped rice stem borer, Chilo suppressalis (Lepidoptera: Pyraidae), is one of the most serious rice pests in China. Chlorantraniliprole was used extensively for C. suppressalis control over the past ten years, and some field populations have developed high resistance. In this study, we report the chlorantraniliprole resistance status of C. suppressalis in China and the resistance mechanism. RESULTS: Significant geographical variations of chlorantraniliprole susceptibility were observed among 28 C. suppressalis field populations in 2019-2020. The LC50 values varied from 2907.874 mg L-1 (XS19) to 1.524 mg L-1 (QW19). Most tested field populations collected from Zhejiang, Jiangxi, Hunan and Anhui provinces in 2020 showed a high level of resistance to chlorantraniliprole (RR = 311.9-2060.1), whereas Jiangsu and Sichuan province populations remained susceptible. Analysis of RyR mutations showed that mutations of I4758M, Y4667D, Y4667C and Y4891F were present in resistant populations of C. suppressalis with different levels of chlorantraniliprole resistance. The frequency of the Y4667C mutation was correlated with chlorantraniliprole resistance in YY19 (RR = 702.6) and YY20 (RR = 1426.8) populations, with the homozygous mutation frequencies of 15.6% and 29.4%, respectively. High contributions of the I4758M and Y4667C double mutation to diamide resistance was demonstrated with CRISPR/Cas9-modified D. melanogaster. Flies bearing the Y4667C mutation (I4758M and Y4667C double mutation in C. suppressalis) exhibited high resistance to chlorantraniliprole (RR = 172.1), and moderate resistance to cyantraniliprole (RR = 79.2) and tetra chlorantraniliprole (RR = 43.6), which were higher than that of single mutations. CONCLUSIONS: Chlorantraniliprole resistance in C. suppressalis is intensifying in China. RyR double mutations (i.e. I4758M and Y4667C) confer higher diamide resistance than single mutations.


Assuntos
Inseticidas , Mariposas , Animais , Diamida , Drosophila melanogaster , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mariposas/genética , Mutação , Canal de Liberação de Cálcio do Receptor de Rianodina/genética
7.
Artigo em Inglês | MEDLINE | ID: mdl-34206752

RESUMO

To accurately assess the potential ecological risk posed by heavy metals in lime concretion black soil and quantify the risk contributions from different sources, an investigation of 217 surface soil samples and 56 subsoil samples was performed in the southern part of Suzhou City. Geochemical baseline values of soil heavy metals (Cr, Zn, Pb, Ni, Hg, Cu, Cd, As, Mn and Co) in the study area were calculated as 53.6, 61.5, 19.8, 27.6, 0.08, 18.4, 0.13, 12.9, 416.1 and 11.0 mg/kg, respectively, by using reference metal normalization and cumulative frequency curve methods. Subsequently, four potential sources of soil heavy metals were identified by the positive matrix factorization. Finally, the potential ecological risks arising from the identified sources were determined by the integrated model of positive matrix factorization and Hakanson potential ecological risk index. Results showed that the ecological risk posed by soil heavy metals in the study area ranged from low to moderate level. Hg and Cd were the two largest risk contributors, supplying 36.0% and 30.3% of total risk value. The origin of heavy metals in the soils is mostly related to four sources including agricultural activities, natural dispersion, coal consumption and traffic pollution. Source apportionment of the potential ecological risks revealed that the dominant risk source in the study area was natural dispersion (42.0%), followed by coal related industries (26.5%), agricultural activities (20.4%) and traffic pollution (11.1%). This work gives a clear baseline information of the heavy metal accumulations in lime concretion black soil and provides a successful case study for the source-oriented ecological risk assessment.


Assuntos
Metais Pesados , Poluentes do Solo , Compostos de Cálcio , China , Cidades , Monitoramento Ambiental , Metais Pesados/análise , Metais Pesados/toxicidade , Óxidos , Medição de Risco , Solo , Poluentes do Solo/análise
8.
J Inflamm Res ; 14: 2301-2315, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34103963

RESUMO

Objective: Perioperative neurocognitive disorders (PND) are a common complication in the elderly. Histone deacetylases (HDACs) are a class of enzymes that control the acetylation status of intracellular proteins. Thus, we explored whether HDACs trigger the release of high mobility group box 1 (HMGB1) through altering the acetylation status in the hippocampi of aged mice. Materials and Methods: The effect of the Class IIa HDAC in PND was explored using an in vivo form of splenectomy. Sixteen-month-old healthy male C57BL/6J mice were randomly divided into five groups: control, anesthesia plus sham surgery, anesthesia plus splenectomy, LMK235 treatment, and PBS treatment. The hippocampi were harvested on either first, third, or seventh postoperative day. Cognitive function was assessed via a Morris water maze (MWM) test. Quantitative RT-PCR, Western blots and ELISAs were carried out to assess the targeted gene expression at transcriptional and translational levels. Results: Splenectomy led to a significant deficiency in spatial memory acquisition, marked decreases in mRNA and protein levels of HDAC4 and HDAC5 in the hippocampus, and increases in the levels of total HMGB1 and acetylated HMGB1. In a similar fashion to splenectomy, treatment with the HDAC4/5 inhibitor LMK235 produced impaired spatial memory and an increase in the expression of HMGB1 and its acetylated counterpart in the hippocampus. Conclusion: These results suggest that surgery leads to PND through class IIa HDAC downregulation-triggered HMGB1 release in hippocampus of aged mice. HDACs may be a potential therapeutic target for postoperative cognitive dysfunction.

9.
Mol Divers ; 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34105049

RESUMO

Traditional Chinese medicine (TCM) has exerted positive effects in controlling the COVID-19 pandemic. HuaShi XuanFei Formula (HSXFF) was developed to treat patients with mild and general COVID-19 in Zhejiang Province, China. The present study seeks to explore its potentially active compounds and pharmacological mechanisms against COVID-19 based on network pharmacology, molecular docking, and molecular dynamics (MD) simulation. All components of HSXFF were harvested from the pharmacology database of the TCMSP system. COVID-19-related targets were retrieved from using OMIM and GeneCards databases. The herb-compound-targets network was constructed by Cytoscape. The target protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to discover the potential key target genes and mechanism. The main active compounds of HSXFF were docked with 3C-like (3CL) protease hydrolase and angiotensin-converting enzyme 2 (ACE2). The MD simulation confirmed the binding stability of docking results. The herbs-targets network mainly contained 52 compounds and 70 corresponding targets, including key targets such as RELA, TNF, TP53, IL6, MAPK1, CXCL8, IL-1ß, and MAPK14. The GO and KEGG indicated that HSXFF may be mainly acting on the IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway, etc. The molecular docking results indicated that isovitexin and procyanidin B1 showed the highest affinity with 3CL and ACE2, respectively, which were confirmed by MD simulation. These findings suggested HSXFF exerted therapeutic effects involving "multi-compounds and multi-targets." It might be working through directly inhibiting the virus, improving immune function, and reducing the inflammatory in response to anti-COVID-19. In summary, the present study would provide a valuable direction for further research of HSXFF.

10.
FASEB J ; 35(7): e21751, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34156114

RESUMO

Rat Thy-1 nephritis (Thy-1N) is an animal model of human mesangioproliferative glomerulonephritis (MsPGN), accompanied by glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) deposition. Although sublytic C5b-9 formed on GMC membrane could induce cell proliferation, the mechanism is still unclear. In this study, we first demonstrated that the level of SRY related HMG-BOX gene 9 (SOX9), general control nonderepressible 5 (GCN5), fibroblast growth factor 1 (FGF1) and platelet-derived growth factor α (PDGFα) was all elevated both in the renal tissues of Thy-1N rats (in vivo) and in the GMCs (in vitro) with sublytic C5b-9 stimulation. Then, we not only discovered that sublytic C5b-9 caused GMC proliferation through increasing SOX9, GCN5, FGF1 and PDGFα expression, but also proved that SOX9 and GCN5 formed a complex and combined with FGF1 and PDGFα promoters, leading to FGF1 and PDGFα gene transcription. More importantly, GCN5 could mediate SOX9 acetylation at lysine 62 (K62) to enhance SOX9 binding to FGF1 or PDGFα promoter and promote FGF1 or PDGFα synthesis and GMC proliferation. Besides, the experiments in vivo also showed that FGF1 and PDGFα expression, GMC proliferation and urinary protein secretion in Thy-1N rats were greatly reduced by silencing renal SOX9, GCN5, FGF1 or PDGFα gene. Furthermore, the renal tissues of MsPGN patients also exhibited positive expression of these genes mentioned above. Collectively, our findings indicate that GCN5, SOX9 and FGF1/PDGFα can form an axis and play an essential role in sublytic C5b-9-triggered GMC proliferation, which might provide a novel insight into the pathogenesis of Thy-1N and MsPGN.


Assuntos
Proliferação de Células/genética , Proliferação de Células/fisiologia , Complexo de Ataque à Membrana do Sistema Complemento/genética , Rim/fisiologia , Células Mesangiais/fisiologia , Nefrite/genética , Transcrição Genética/genética , Acetilação , Animais , Linhagem Celular , Matriz Extracelular/genética , Fator 1 de Crescimento de Fibroblastos/genética , Humanos , Masculino , Fator de Crescimento Derivado de Plaquetas/genética , Regiões Promotoras Genéticas/genética , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição SOX9/genética , Antígenos Thy-1/genética , Fatores de Transcrição de p300-CBP/genética
11.
Xenobiotica ; 51(7): 818-830, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33952086

RESUMO

Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.


Assuntos
Diabetes Mellitus Experimental , Metformina , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Alcaloides Indólicos , Fígado , Metformina/farmacologia , Quinazolinas , Ratos , Regulação para Cima
12.
Nat Prod Res ; : 1-7, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33960222

RESUMO

Two new chemical constituents, japopenoid D (1), and japopenoid E (2), were isolated and identified from the flower buds of Lonicera japonica Thunb. The structures of these compounds were elucidated based on spectroscopic analysis (HR-ESI-MS, NMR), and the absolute configurations of 1 and 2 were determined by comparison of their electronic circular dichroism (ECD) spectra with literature and theoretical calculation. The anti-inflammatory activities of the isolates were evaluated by measuring their inhibitory effects on PGE2 and IL-6 production in LPS stimulated RAW 264.7 macrophages. As a result, compound 1 could reduce PGE2 and IL-6 levels in LPS-activated RAW 264.7 macrophages with IC50 values of 6.78 and 42.07 µM, respectively.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34007294

RESUMO

Huo-Xue-Qu-Yu formula (HXQYF) is a prescription consisting of Ginkgo biloba leaf and Paeonia lactiflora Pall. for treating hyperlipidemia and NAFLD in China. Here, we investigated the hepatic and renal function, oxidative stress and lipid metabolism, and potential mechanisms of HXQYF on nonalcoholic fatty liver disease (NAFLD) rat models. NAFLD rat models were induced with high-fat diet (HFD) and 10% fructose water for 18 weeks and orally administered with or without HXQYF simultaneously. The results showed that HXQYF (22.5, 45, 90 mg/kg) significantly improved blood lipid levels via reducing serum TC, TG, LDL-C, and APOB values and elevating HDL-C and APOA1 levels in NAFLD rats. The higher levels of ALT, AST, CR, and BUN in serum induced by HFD were reduced by HXQYF. HE staining showed that HXQYF (90 mg/kg) reduced the accumulation of fat droplets and alleviated inflammatory response in liver cells. Three doses of HXQYF exhibited notable antioxidant effects by elevating SOD, GSH, and CAT activities and decreasing MDA and OH-1 levels in the liver. Furthermore, abnormal lipid metabolism caused by HFD was alleviated by HXQYF, which was associated with the upregulation of PPAR-α, AdipoR2, and CPT1 mRNAs as well as the downregulation of CYP2E1 and SREBP-1c mRNAs in liver tissue. In conclusion, our work verified that HXQYF could reduce the degree of hepatic steatosis, suppress oxidative stress, and attenuate lipid metabolism, thus preventing NAFLD.

14.
Sensors (Basel) ; 21(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33802190

RESUMO

In laser systems, beam pointing usually drifts as a consequence of various disturbances, e.g., inherent drift, airflow, transmission medium variation, mechanical vibration, and elastic deformation. In this paper, we develop a laser beam pointing control system with Fast Steering Mirrors (FSMs) and Position Sensitive Devices (PSDs), which is capable of stabilizing both the position and angle of a laser beam. Specifically, using the ABCD matrix, we analyze the kinematic model governing the relationship between the rotation angles of two FSMs and the four degree-of-freedom (DOF) beam vector. Then, we design a Jacobian matrix feedback controller, which can be conveniently calibrated. Since disturbances vary significantly in terms of inconsistent physical characteristics and temporal patterns, great challenges are imposed to control strategies. In order to improve beam pointing control performance under a variety of disturbances, we propose a data-driven disturbance classification method by using a Recurrent Neural Network (RNN). The trained RNN model can classify the disturbance type in real time, and the corresponding type can be subsequently used to select suitable control parameters. This approach can realize the universality of the beam stabilization pointing system under various disturbances. Experiments on beam pointing control under several typical external disturbances are carried out to verify the effectiveness of the proposed control system.

15.
World J Clin Cases ; 9(11): 2688-2695, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33889637

RESUMO

BACKGROUND: Abnormalities in the melanocortin receptor 4 (MC4R) gene often lead to obesity, but are rarely associated with other conditions such as epilepsy and sleep disorder. CASE SUMMARY: Here, we present a case of a male obese child with a heterozygous variant in MC4R (c.494G>A, p.Arg165Gln) inherited from his father, who presented with disordered sleep and abnormal facial movements. Examination through melatonin rhythm testing and electroencephalography led to a diagnosis of sleep disorder and epilepsy, as his melatonin rhythm was markedly distorted and the electroencephalography revealed epileptic discharges. He received treatment with an antiepileptic drug; however, the therapy was ineffective and the sleep disorder appeared to be deteriorating. Subsequently, we initiated adjuvant treatment with melatonin. Upon re-examination, his body mass index had decreased, the sleep disturbance had resolved, and his seizures were well controlled. Electro-encephalography review was normal, and a typical melatonin rhythm was restored. CONCLUSION: We concluded that, in addition to causing obesity, abnormalities in the MC4R gene may contribute to the development of sleep disorders and epilepsy, and that melatonin can be used as an adjuvant therapy to alleviate these symptoms.

16.
J Natl Cancer Inst ; 113(4): 471-480, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33094348

RESUMO

BACKGROUND: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC. METHODS: We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided. RESULTS: We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed. CONCLUSIONS: The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.


Assuntos
Expressão Gênica , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Adulto , Idoso , Área Sob a Curva , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Sensibilidade e Especificidade , Resultado do Tratamento
17.
Heart Lung Circ ; 30(2): 288-295, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32690359

RESUMO

BACKGROUND: Renal dysfunction is independently associated with increased early and late mortality after coronary artery bypass graft (CABG) surgery. Off-pump CABG (OPCABG) avoids postoperative complications from the cardiopulmonary bypass, but it is unclear how it is impacted by occult renal dysfunction (ORD). This study aimed to investigate the effects of ORD on early and late outcomes after OPCABG. METHODS: This retrospective and observational cohort study reviewed data on 1,188 patients who underwent first isolated OPCABG with normal serum creatinine (SCr) levels. According to preoperative estimated creatinine clearance (eCrCl) by the Cockcroft-Gault formula, the patients were divided into an ORD group (n=260, eCrCl <60 mL/min/1.73 m2) and a control group (n=928, eCrCl ≥60 mL/min/1.73 m2). RESULTS: The ORD patients presented with older age, higher incidence of small body surface area, hypertension, low preoperative eCrCl, cerebrovascular accident, peripheral vascular disease, New York Heart Association (NYHA) Ⅲ, and high risk score. The prevalence of hospital mortality, postoperative acute kidney injury (AKI), peak postoperative SCr, and prolonged hospital stay were greater in the ORD patients than the control patients. Multivariable logistic regression analysis showed that the ORD patients were at significantly higher risk of postoperative AKI (OR, 2.702; 95% CI, 1.994-3.662) and in-hospital mortality (OR, 2.884; 95% CI, 1.293-6.432). Multivariate Cox proportional hazard models confirmed that ORD was significantly associated with high later mortality (HR, 2.847; 95% CI, 1.262-6.425). CONCLUSIONS: Occult renal dysfunction is an independent risk factor for postoperative AKI in-hospital and later mortality in patients undergoing OPCABG with normal SCr levels.


Assuntos
Injúria Renal Aguda/etiologia , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Taxa de Filtração Glomerular/fisiologia , Complicações Pós-Operatórias , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório
18.
Clin Imaging ; 72: 91-96, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33217676

RESUMO

OBJECTIVE: Congenital mesoblastic nephroma (CMN) is a rare renal tumor mainly observed in infants and young children. This study aims to analyze the imaging manifestations of CMN to improve the understanding of the disease. METHODS: The imaging manifestations and clinical records of all pediatric patients with CMN admitted to our hospital over the last 7 years were retrospectively analyzed. The diagnosis of CMN was confirmed by postoperative pathology. All patients underwent computed tomography (CT) scans; 2 patients additionally underwent magnetic resonance imaging (MRI) scans (including one prenatal MRI scan). RESULTS: We evaluated 10 pediatric patients (6 males and 4 females) aged 7 days to 12 months (median age: 4 months) with CMN located on the left kidney in six cases and the right kidney in four cases. The CT imaging manifested as solid lesions (5 cases), solid-cystic lesions with solid predominance (4 cases), or solid-multicystic lesions with cystic predominance (1 case). Enhanced CT showed moderately and heterogeneously enhanced solid component and intracystic septations at the corticomedullary phase that were further enhanced at the nephrographic phase, although their CT values were still lower than those of the renal parenchyma. The "double-layer sign" were seen in 4 cases of classic type of CMN, and the "intratumor pelvis sign" were seen in 9 cases that include 5 classic, 3 cellular and 1 mixed type of CMN. In the 2 patients who underwent MRI, the scans showed solitary masses. The lesions had hypointense signals on the T1WI sequence and isointensity or slightly lower-intensity signals than the surrounding renal parenchyma on the fluid-sensitive sequences, whereas the lesions showed hyperintense signals on the diffusion-weighted imaging (DWI) sequence. CONCLUSIONS: The imaging manifestations of CMN are closely correlated with the pathological subtype and have certain characteristics. The "double-layer sign" was seen with most classic type CMN, and "intratumor pelvis sign" was seen in 90% cases.


Assuntos
Neoplasias Renais , Nefroma Mesoblástico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Neoplasias Renais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Nefroma Mesoblástico/diagnóstico por imagem , Gravidez , Estudos Retrospectivos
19.
Front Neurol ; 11: 497225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192961

RESUMO

Background: Infantile spasm (IS) is one of the most common catastrophic epilepsy syndromes in infancy characterized by epileptic spasm. While adrenocorticotropic hormone (ACTH) is the first-line treatment for IS, it is evident that the seizures associated with IS exhibit a clear circadian rhythm; however, the precise mechanisms underlying such seizures remain unclear. Melatonin is an important amine hormone and is regulated by circadian rhythm. Circadian proteins, especially Aryl Hydrocarbon Receptor Nuclear Trasnslocator-like Protein (ARNTL or BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), and their target proteins Period Circadian Regulator 1 (PER1), Period Circadian Regulator 2 (PER2), Cryptochrome 1 (CRY1), and Cryptochrome 2 (CRY2), play key roles in circadian rhythm. This study explored the relationships between melatonin, genes associated with circadian rhythm, and epileptic spasm. Materials and Methods: Eighteen female rats were mated with nine male rats and 16 became pregnant. Twelve pregnant rats were subjected to prenatal stress by forced swimming in cold water from the day of conception. Rat pups produced by stressed mothers received an intraperitoneal injection of N-methyl-D-aspartate (NMDA) on the 13th day after birth and were divided into four groups: NMDA (15 mg/kg), NMDA+ACTH (20 IU/kg), NMDA+melatonin (55 mg/kg), and NMDA+ACTH+melatonin (n = 36/group). Offspring from four dams that were not subjected to prenatal stress were used as controls. We then recorded latency and the frequency of flexion seizures. All offspring were sacrificed on the 14th day after birth and CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 expression was analyzed by western blotting, immunohistochemistry, and immunofluorescence. Results: NMDA induced spasm-like symptoms in rats. ACTH and melatonin significantly increased seizure latency and significantly reduced the frequency of seizures (P < 0.05). CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 expression was significantly lower in the NMDA group than the controls (P < 0.05). ACTH significantly increased the expression of CLOCK, BAML1, PER1, and CRY1 (P < 0.05) and melatonin significantly increased the expression of CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 (P < 0.05) compared with those of the NMDA group. There were no significant differences in the expression of BMAL1, CRY2, PER1, and PER2 when compared between the NMDA+ACTH+melatonin and control groups (P > 0.05). Conclusion: ACTH and melatonin significantly increased the expression of circadian genes and improved NMDA-induced seizures. The anticonvulsant effects of ACTH and melatonin are likely to involve regulation of the expression of these genes.

20.
BMC Cardiovasc Disord ; 20(1): 463, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115418

RESUMO

BACKGROUND: Preoperative risk evaluation systems are significant and important to the allocation of medical resources and the communication between doctors and patients. The European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is widely used in clinical practice. Cardiac troponin T (cTnT) can specifically and accurately reflect myocardial injury. Whether EuroSCORE II can improve the predictive power after integrating with cTnT is still unclear. This study was a retrospective single center study designed to assess the predictive ability of EuroSCORE II integrated with cTnT for patients undergoing isolated off-pump coronary artery bypass grafting (OPCABG). METHODS: This retrospective and observational cohort study included 1887 patients who underwent first isolated OPCABG. cTnT was detected within 48 h before operation in each patient. According to myocardial injury, patients were divided by cTnT into 4 stages. A new risk evaluation system was created through logistic regression with EuroSCORE II and myocardial injury classification as covariates. Then the two risk evaluation systems were comparatively assessed by regression analysis, receiver operator characteristic curves, net reclassification index, Bland-Altman plots and decision curve analysis. RESULTS: There were 43 in-hospital deaths, with a mortality of 2.30% (43/1887). The logistic regression analysis showed that preoperative myocardial injury classification was a significant risk factor for in-hospital mortality in both total cohort (OR 1.491, 95%CI 1.049-2.119) and subsets (OR 1.761, 95%CI 1.102-2.814). The new risk evaluation system has higher calibration and discrimination power than EuroSCORE II, both for overall cohort and subsets. Especially, the new system has obvious advantages in discrimination power in the subset of acute myocardial infarction (AUC 0.813 vs. 0.772, 0.906 vs. 0.841, and 0.715 vs. 0.646, respectively). CONCLUSIONS: Both myocardial injury classification and EuroSCORE II are independent risk factors of in-hospital mortality in OPCABG patients. The new risk evaluation system has higher predictive ability than EuroSCORE II, especially in patients with a recent history of AMI.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Doença da Artéria Coronariana/cirurgia , Técnicas de Apoio para a Decisão , Infarto do Miocárdio/cirurgia , Troponina T/sangue , Idoso , Biomarcadores/sangue , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Ponte de Artéria Coronária sem Circulação Extracorpórea/mortalidade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...