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2.
Toxicol Sci ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439560

RESUMO

Prednisone, a widely used glucocorticoid drug in human and veterinary medicine, has been reported to cause developmental toxicity. However, systematic studies about the effect of prednisone on fetal liver development are still unclear. We investigated the potential effects of maternal exposure to clinically equivalent doses of prednisone during different gestational stages on cell proliferation and apoptosis, cell differentiation, glucose and lipid metabolism, and hematopoiesis in the liver of fetal mice, and explored the potential mechanisms. Results showed that prenatal prednisone exposure (PPE) could suppress the cell proliferation, inhibit hepatocyte differentiation and promote cholangiocyte differentiation in fetal liver. Meanwhile, PPE could result in the enhancement of glyconeogenesis and bile acid synthesis and the inhibition of fatty acid ß-oxidation and hematopoiesis in fetal liver. Further analysis found that PPE-induced alterations in liver development had obvious stage- and sex-differences. Overall, the alteration in fetal liver development and function induced by PPE was most pronounced during the whole pregnancy (GD0-10), and the males were relatively more affected than the females. Additionally, fetal hepatic insulin-like growth factor 1 (IGF1) signaling pathway was inhibited by PPE. In conclusion, PPE could impact fetal liver development and multiple functions, and these alterations might be partially related to the inhibition of IGF1 signaling pathway.

3.
J Cardiothorac Surg ; 19(1): 107, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409055

RESUMO

BACKGROUND: Broncho-esophageal fistula (BEF) secondary to esophageal diverticulum is a rare clinical condition, which is often misdiagnosed for a long time. The aim of our study is to summarize and clarify the advantages of MSCT in diagnosing BEF secondary to esophageal diverticulum. METHODS: We retrospectively analyzed patients clinically diagnosed with BEF from January 2005 to January 2022 at Jilin University First Hospital. Only those patients with BEF secondary to esophageal diverticulum and complete clinical data met our enrolled standard. All patients' clinicopathologic characteristics and MSCT features were systemically evaluated. RESULTS: 17 patients were eligible for our cohort study, including male 10 and female 7. The patient's mean age was 42.3 ± 12.5. The chronic cough occurred in all seventeen patients and bucking following oral fluid intake was documented in nine patients. MSCT distinctly suggested the fistulous tract between the bronchi and the esophagus in all patients. The mean diameter of the orifices in the wall of the esophagus was 4.40 ± 1.81 mm. The orifice in the midthoracic esophagus side was 15 cases and 2 cases at the lower thoracic esophagus. The involved bronchus included 13 cases at the right lower lobe bronchus, 1 at the right middle lobe bronchus and 3 at the left lower lobe bronchus. The contrast agent was observed in the pulmonary parenchyma in 10 of 13 patients who underwent esophagogram. No definite fistula was observed in 3 of 11 who underwent gastroscopy, while the intra-operative findings supported the existence of fistula. CONCLUSIONS: BEF secondary to esophageal diverticulum tends to occur between the midthoracic esophagus and the right lower lobe bronchus. Compared with esophagography and gastroscopy, MSCT shows more comprehensive information about the fistulous shape, size, course and lung involvement, which are helpful for establishing diagnosis and guiding subsequent treatment.


Assuntos
Fístula Brônquica , Divertículo Esofágico , Fístula Esofágica , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos de Coortes , Divertículo Esofágico/diagnóstico , Divertículo Esofágico/diagnóstico por imagem , Fístula Esofágica/diagnóstico por imagem , Fístula Esofágica/etiologia , Fístula Brônquica/diagnóstico por imagem , Fístula Brônquica/etiologia , Fístula Brônquica/cirurgia
4.
Cell Rep Med ; 5(2): 101398, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38301654

RESUMO

Prenatal dexamethasone exposure (PDE) can lead to increased susceptibility to various diseases in adult offspring, but its effect on gut microbiota composition and the relationship with disease susceptibility remains unclear. In this study, we find sex-differential changes in the gut microbiota of 6-month-old infants with prenatal dexamethasone therapy (PDT) that persisted in female infants up to 2.5 years of age with altered bile acid metabolism. PDE female offspring rats show abnormal colonization and composition of gut microbiota and increased susceptibility to cholestatic liver injury. The aberrant gut microbiota colonization in the PDE offspring can be attributed to the inhibited Muc2 expression caused by decreased CDX2 expression before and after birth. Integrating animal and cell experiments, we further confirm that dexamethasone could inhibit Muc2 expression by activating GR/HDAC11 signaling and regulating CDX2 epigenetic modification. This study interprets abnormal gut microbiota and disease susceptibility in PDT offspring from intrauterine intestinal dysplasia.


Assuntos
Microbioma Gastrointestinal , Efeitos Tardios da Exposição Pré-Natal , Humanos , Gravidez , Ratos , Animais , Feminino , Lactente , Dexametasona/efeitos adversos , Ratos Wistar , Suscetibilidade a Doenças , Epigênese Genética
5.
Microbiome ; 11(1): 245, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37932832

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) has been associated with intrauterine growth restriction (IUGR), but the underlying mechanisms are unclear. RESULTS: We found that the IUGR rat model induced by prenatal caffeine exposure (PCE) showed ASD-like symptoms, accompanied by altered gut microbiota and reduced production of indole 3-propionic acid (IPA), a microbiota-specific metabolite and a ligand of aryl hydrocarbon receptor (AHR). IUGR children also had a reduced serum IPA level consistent with the animal model. We demonstrated that the dysregulated IPA/AHR/NF-κB signaling caused by disturbed gut microbiota mediated the hippocampal microglia hyperactivation and neuronal synapse over-pruning in the PCE-induced IUGR rats. Moreover, postnatal IPA supplementation restored the ASD-like symptoms and the underlying hippocampal lesions in the IUGR rats. CONCLUSIONS: This study suggests that the microbiota-IPA-brain axis regulates ASD susceptibility in PCE-induced IUGR offspring, and supplementation of microbiota-derived IPA might be a promising interventional strategy for ASD with a fetal origin. Video Abstract.


Assuntos
Transtorno do Espectro Autista , Microbioma Gastrointestinal , Animais , Feminino , Gravidez , Ratos , Encéfalo , Cafeína/toxicidade , Retardo do Crescimento Fetal/induzido quimicamente , Microbioma Gastrointestinal/fisiologia , Hipocampo , Microglia , Plasticidade Neuronal
6.
Free Radic Biol Med ; 208: 684-699, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37743032

RESUMO

Epidemiological evidence has revealed that non-alcoholic fatty liver disease (NAFLD) harbors an intrauterine origin. Autophagy is known to be involved in the protective mechanism in the development of adult NAFLD, but whether it engages in the occurrence of fetal-originated NAFLD remains unclear. In this study, a rat model of fetal-originated NAFLD was established by giving a high-fat diet or chronic stress after birth on prenatal caffeine exposure (PCE) male offspring. The alterations of liver morphologic analysis, lipid metabolism, and autophagy before and after birth were determined to confirm autophagy mechanism, NAFLD susceptibility, and intrauterine origin in PCE male adult offspring. Our results revealed that PCE-induced intrauterine high concentration of corticosterone exposure blocked autophagic flux by inhibiting cathepsin D expression in hepatocytes, leading to ß-oxidation inhibition and lipid accumulation in the liver. Moreover, high concentration of corticosterone upregulated miR-665 by activating the glucocorticoid receptor to suppress cathepsin D, thus causing lysosomal degradation dysfunction and autophagy flux blockade. Notably, hepatic overexpression of cathepsin D could reverse PCE-induced postnatal NAFLD susceptibility in male rat offspring. This study elucidates the epigenetic programming mechanism of intrauterine autophagy-related fetal-originated NAFLD susceptibility, and identifies cathepsin D as its early intervention target, providing an experimental basis for exploring early prevention and treatment strategies for fetal-originated NAFLD.


Assuntos
MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Humanos , Ratos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/genética , Cafeína/efeitos adversos , Corticosterona , Catepsina D/genética , Ratos Wistar , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Autofagia
7.
Ann Hematol ; 102(12): 3431-3444, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37550503

RESUMO

To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).


Assuntos
População do Leste Asiático , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Causas de Morte , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
8.
J Phys Chem Lett ; 14(31): 6998-7006, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37523256

RESUMO

Due to the chaotic structure of amorphous materials, it is challenging to identify defects in metallic glasses. Here we tackle this problem from a thermodynamic point of view using atomic vibrational entropy, which represents the inhomogeneity of atomic contributions to vibrational modes. We find that the atomic vibrational entropy is correlated to the vibrational mean-square displacement and polyhedral volume of atoms, revealing the critical role of vibrational entropy in bridging dynamics, thermodynamics, and structure. On this method, the local vibrational entropy obtained by coarse-graining the atomic vibrational entropy in space can distinguish more effectively between liquid-like and solid-like atoms in metallic glasses and establish the correlation between the local vibrational entropy and the structure of metallic glasses, offering a route to predict the plastic events from local vibrational entropy. The local vibration entropy is a good indicator of thermally activated and stress-driven plastic events, and its predictive ability is better than that of the structural indicators.

9.
Life Sci ; 329: 121985, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37516432

RESUMO

AIMS: Azithromycin is widely used in clinical practice for treating maternal infections during pregnancy. Meanwhile, azithromycin, as an "emerging pollutant", is increasingly polluting the environment due to the rapidly increasing usage (especially after the COVID-19). Previous studies have suggested a possible teratogenic risk of prenatal azithromycin exposure (PAzE), but its effects on fetal multi-organ development are still unclear. This study aimed to explore the potential impacts of PAzE. MATERIALS AND METHODS: We focused on pregnancy outcomes, maternal/fetal serum phenotypes, and fetal multiple organ development in mice at different doses (50/200 mg/kg·d) during late pregnancy or at 200 mg/kg·d during different stages (mid-/late-pregnancy) and courses (single-/multi-course). KEY FINDINGS: The results showed PAzE increased the rate of the absorbed fetus during mid-pregnancy and increased the intrauterine growth retardation rate (IUGR) during late pregnancy. PAzE caused multiple blood phenotypic changes in maternal and fetal mice, among which the number and degree of changes in fetal blood indicators were more significant. Moreover, PAzE inhibited long bone/cartilage development and adrenal steroid synthesis, promoting hepatic lipid production and ovarian steroid synthesis in varying degrees. The order of severity might be bone/cartilage > liver > gonads > other organs. PAzE-induced multi-organ alterations differed in stages, courses doses and fetal sex. The most apparent changes might be in high-dose, mid-pregnancy, multi-course, and female, while there was no typical rule for a dose-response relationship. SIGNIFICANCE: This study confirmed PAzE could cause fetal developmental abnormalities and multi-organ functional alterations, which deepens the comprehensive understanding of azithromycin's fetal developmental toxicity.


Assuntos
Azitromicina , COVID-19 , Gravidez , Camundongos , Feminino , Animais , Humanos , Azitromicina/toxicidade , Tratamento Farmacológico da COVID-19 , Desenvolvimento Fetal , Retardo do Crescimento Fetal , Esteroides/farmacologia
10.
J Chem Phys ; 158(13): 134511, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37031140

RESUMO

The origin of ß-relaxation in metallic glasses is still not fully understood, and the guidance of slow atoms for caged dynamics and ß-relaxation is rarely mentioned. Using molecular dynamics simulations, we reveal the bridging role of slow atoms on unusual caged dynamics and ß-relaxation. In the stage of unusual caged dynamics, slow atoms are bounded by neighboring atoms. It is difficult for the slow atoms to break the cage, producing more high-frequency vibration, which causes more atoms to jump out of the cage randomly in the next stage. Precisely, the movement of the slow atoms changes from individual atoms vibrating inside the cage and gradually breaking out of the cage into a string-like pattern. The string-like collective atomic jumps cause decay of the cages, inducing ß-relaxation. This situation generally exists in binary systems with the large atomic mass difference. This work offers valuable insights for understanding the role of slow atoms in unusual caged dynamics and ß-relaxation, complementing studies on the origin of ß-relaxation in metallic glasses and their glass-forming liquids.

11.
Reprod Toxicol ; 118: 108366, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36958465

RESUMO

Corn oil, sodium carboxymethyl cellulose (CMC-Na), and dimethyl sulfoxide (DMSO) are widely used as solvents or suspensions in animal experiments, but the effects of prenatal exposure to them on fetal development have not been reported. In this study, Kunming mice were given a conventional dose of corn oil (9.2 g/kg·d), CMC-Na (0.05 g/kg·d) or DMSO (0.088 g/kg·d) during gestation days 10-18, and the pregnancy outcome, fetal physical development, serum phenotype, and multi-organ function changes were observed. The results showed that corn oil decreased serum triglyceride level in males but increased their serum testosterone and CORT levels, and affected female placenta and female/male multi-organ functions (mainly bone, liver, kidney). CMC-Na increased female/male body lengths and tail lengths, decreased serum glucose and total cholesterol levels in males as well as increased their serum LDL-C/HDL-C ratio and testosterone level, decreased female serum bile acid level, and affected male/female placenta and multi-organ functions (mainly bone, liver, hippocampus). DMSO decreased male body weight and serum glucose level, decreased male/female serum bile acid levels, and affected male/female placenta and multi-organs functions (mainly bone, hippocampus, adrenal gland). In conclusion, prenatal exposure to a conventional dose of corn oil, CMC-Na or DMSO could affect fetal physical development and multi-organ functions, and has the characteristics of "multi-pathway, multi-organ and multi-target". This study provides the experimental basis for the rational selection of solvents or suspensions in pharmacology and toxicology studies.


Assuntos
Dimetil Sulfóxido , Efeitos Tardios da Exposição Pré-Natal , Camundongos , Ratos , Humanos , Feminino , Masculino , Gravidez , Animais , Dimetil Sulfóxido/toxicidade , Camundongos Endogâmicos , Óleo de Milho/toxicidade , Ratos Endogâmicos F344 , Testes de Carcinogenicidade , Solventes , Testosterona , Ácidos e Sais Biliares , Glucose
12.
J Cardiothorac Surg ; 18(1): 11, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611192

RESUMO

BACKGROUND: Behcet's disease is a form of systematic vasculitis that affects vessels of various sizes anywhere in the body. Aortic pseudoaneurysm is the most hazardous lesion in Behcet's disease and is associated with high mortality rate once rupture. CASE PRESENTATION: In this report, we presented a patient with a known history of Behcet's disease, whose recurrent aortic-arch pseudoaneurysm eroding into the left main bronchus was identified after a 4-year duration of thoracic endovascular aortic repair for thoracic descending aortic pseudoaneurysm ruptured into the left lung. Repeated thoracic endovascular aortic repair combined with the chimney stent effectively controlled massive hemoptysis under the life-threatening circumstance, and the patient was in good condition at the 7-year follow-up. CONCLUSIONS: Thoracic endovascular aortic repair can be used as an effective and problem-solving treatment approach for thoracic aortic aneurysms eroded into the lung, even recurrent pseudoaneurysm after thoracic endovascular aortic repair in BD patients. Among the imaging methods assessing the technical success, outcome and complications, computed tomography angiography offers a fast, accessible and sensitive imaging modality.


Assuntos
Falso Aneurisma , Aneurisma da Aorta Torácica , Síndrome de Behçet , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Falso Aneurisma/cirurgia , Falso Aneurisma/complicações , Síndrome de Behçet/complicações , Implante de Prótese Vascular/métodos , Aneurisma da Aorta Torácica/complicações , Aorta Torácica/cirurgia , Stents/efeitos adversos , Brônquios , Procedimentos Endovasculares/métodos , Resultado do Tratamento , Prótese Vascular/efeitos adversos
13.
J Cardiothorac Surg ; 17(1): 230, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068632

RESUMO

BACKGROUND: Osteochondromas, also known as exostoses, are the most common benign tumors of bone and can be classified into isolated and multiple osteochondromas. A great majority of osteochondromas is asymptomatic, painless, slow-growing mass, and incidentally found. However, osteochondromas occurring in adolescence or in adult patients can grow in size and become symptomatic as a result of mechanical irritation of the surrounding soft tissues or peripheral nerves, spinal cord compression, or vascular injury. CASE PRESENTATION: We present a case of a 13-year-old girl with spontaneous hemothorax, the cause of which was identified by limited thoracotomy with the aid of video-assisted thoracic surgery to be bleeding from a diaphragmatic laceration incurred by a costal exostosis on the left sixth rib. Preoperative chest computed tomography (CT) depicted a bony projection arising from the rib and bloody effusion in the intrathoracic cavity, but was unable to discern the bleeding cause from the lung or the diaphragm. This case will highlight our awareness that costal exostosis possibly results in bloody pleural effusion. Meanwhile, English literatures about solitary costal exostosis associated with hemothorax were searched in PubMed and nineteen case reports were obtained. Combined our present case with available literature, a comprehensive understanding of this rare disease entity will further be strengthened. CONCLUSIONS: Injury to the diaphragm is the primary cause of hemothorax caused by costal osteochondroma, including the present case. Thoracic CT scan can help establish a diagnosis of preoperative diagnosis of costal osteochondroma. Surgical intervention should be considered for those patients with symptomatic osteochondroma of the rib. Combined with our case and literature, prophylactic surgical removal of intrathoracic exostosis should be advocated even in asymptomatic patients with the presentation of an inward bony spiculation.


Assuntos
Neoplasias Ósseas , Exostose , Osteocondroma , Adolescente , Adulto , Neoplasias Ósseas/cirurgia , Diafragma/patologia , Diafragma/cirurgia , Exostose/complicações , Exostose/patologia , Feminino , Hemotórax/diagnóstico , Hemotórax/etiologia , Hemotórax/cirurgia , Humanos , Osteocondroma/complicações , Osteocondroma/diagnóstico , Osteocondroma/cirurgia , Costelas/cirurgia
14.
Front Public Health ; 10: 885067, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35570947

RESUMO

The negative impact of COVID-19 pandemic has seen SME's struggling around the world. With many quickly adopting digital technologies, such as AI, in their manufacturing or services operations to achieve sustainable development. This study aims to develop a framework that informs AI-enabled sustainable development for SMEs by integrating the relevant research in the field. In this framework, we identify the opportunities that the deployment of AI technology can do to alleviate the plights of SMEs in the post-pandemic era, including the impacts on work, organizations, and performance. We further explore the challenges that SMEs face in AI transformation and recommend strategies to take on those challenges. Finally we propose an agenda for future research based on technological challenges and environmental threats.


Assuntos
COVID-19 , Pandemias , Inteligência Artificial , COVID-19/epidemiologia , Humanos , SARS-CoV-2 , Tecnologia
15.
Front Psychol ; 12: 759974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899503

RESUMO

The COVID-19 pandemic has caused serious economic and social consequences. Recent research shows that the pandemic has not only caused a physical health crisis but also caused many psychological and mental crises. Based on the contemporary cognitive-behavioral models, this article offers a conceptual analysis of how the pandemic affects individual mental health and coping behaviors from the perspective of individual economic status, individual context, and social context. The analysis shows that (1) the pandemic has led to increased economic uncertainty, increased unemployment and underemployment pressure, increased income uncertainty, and different degrees of employment pressure and economic difficulties; (2) these difficulties have stimulated different levels of mental health problems, ranging from perceived insecurity (environmental, food safety, etc.), worry, fear, to stress, anxiety, depression, etc., and the mental health deterioration varies across different groups, with the symptoms of psychological distress are more obvious among disadvantageous groups; and (3) mental health problems have caused behavior changes, and various stress behaviors such as protective behaviors and resistive behaviors. Future research directions are suggested.

16.
Reprod Toxicol ; 104: 68-75, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242779

RESUMO

In quantitative real-time PCR (qRT-PCR) detection, the stability of reference genes varies with different organs, tissue locations, sex and developmental stages. This study aimed to screen out and determine the optimal panel of reference genes of the intestine in pre- and post-natal rats of different sex. We used qRT-PCR to detect the mRNA expression of six commonly used reference genes (ACTB, GAPDH, HPRT1, B2M, RPLPO and SDHA) in rat intestines at gestational day 21 (GD21) and postnatal week 12 (PW12). Using GeNorm, BestKeeper and NormFinder software comprehensively analyzed the stability of candidate reference genes and screened out stable reference genes. Further, we used the pathological model of prenatal dexamethasone exposure (PDE) to verify the stability of the selected panel of reference genes. Based on the results of the software analysis, the optimal panel of reference genes in the fetal rat intestine was SDHA + ACTB, and the adult rat small intestine and colon were ACTB + HPRT1 and RPLP0 + GAPDH, respectively. There was no significant sex difference in the above results. Besides, in the PDE model, the results were consistent with those under physiological conditions. Therefore, the stability of intestinal reference genes in fetal rats and adult rats was different, and the intestinal reference genes of adult rats were intestinal segments-specific. The selected panel of reference genes was still stable under pathological conditions. This study determined the optimal panel of reference genes of pre- and post-natal rat intestines and provided reliable reference genes for the qRT-PCR analysis of rat intestines.


Assuntos
Intestinos , Reação em Cadeia da Polimerase em Tempo Real , Animais , Feminino , Feto , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Gravidez , Cuidado Pré-Natal , Ratos , Padrões de Referência , Proteínas Ribossômicas , Caracteres Sexuais , Software
17.
Toxicology ; 449: 152664, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33359579

RESUMO

As a synthetic glucocorticoid, dexamethasone has been widely used in the clinical treatment of premature birth and related pregnant diseases, but its clinical use is still controversial due to developmental toxicity. This study aimed to confirm the proliferation inhibitory effect of pregnant dexamethasone exposure (PDE) on fetal liver development and elucidate its molecular mechanism. In vitro studies, we found that dexamethasone inhibited hepatocyte proliferation through autophagy activated by glucocorticoid receptor (GR)-forkhead protein O1 (FOXO1) pathway. Subsequently, in vivo, we confirmed in a PDE rat model that male fetal liver proliferation was inhibited, and the expression of the GR-FOXO1 pathway and autophagy were increased. Taken together, PDE induces autophagy by activating the GR-FOXO1 pathway, which leads to fetal liver proliferation inhibition and dysplasia in offspring rats. This study confirmed that dexamethasone activates cell autophagy in utero through the GR-FOXO1 pathway, thereby inhibiting hepatocyte proliferation and liver development, which provides theoretical basis for understanding the developmental toxicity of dexamethasone and guiding the rational clinical use.


Assuntos
Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dexametasona/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Autofagia/fisiologia , Proliferação de Células/fisiologia , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Desenvolvimento Fetal/fisiologia , Glucocorticoides/toxicidade , Fígado/embriologia , Fígado/patologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos , Ratos Wistar
18.
Transl Oncol ; 14(1): 100936, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33221688

RESUMO

In this study, we aimed to establish a radiomics nomogram that noninvasively evaluates the invasiveness of pulmonary adenocarcinomas manifesting as ground-glass nodules (GGNs). Computed tomography (CT) images of 509 patients manifesting as GGNs were collected: 70% of cases were included in the training cohort and 30% in the validation cohort. The Max-Relevance and Min-Redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to select the radiomics features and construct a radiomics signature. Univariate and multivariate logistic regression were used to select the invasiveness-related clinical and CT morphological predictors. Age, smoking history, long diameter, and average CT value were retained as independent predictors of GGN invasiveness. A radiomics nomogram was established by integrating clinical and CT morphological features with the radiomics signature. The radiomics nomogram showed good predictive ability in the training set (area under the curve [AUC], 0.940; 95% confidence interval [CI], 0.916-0.964) and validation set (AUC, 0.946; 95% CI, 0.907-0.986). This radiomics nomogram may serve as a noninvasive and accurate predictive tool to determine the invasiveness of GGNs prior to surgery and assist clinicians in creating personalized treatment strategies.

19.
World J Surg Oncol ; 18(1): 32, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32028965

RESUMO

BACKGROUND: Unilateral absence of pulmonary artery (UAPA) is a rare congenital disease of pulmonary circulation, which is often accompanied by other cardiovascular anomalies. Infrequently, it may remain undiagnosed until adulthood. More rarely, it is to be found with lung cancer in the ipsilateral or contralateral lung simultaneously. CASE PRESENTATION: A 56-year-old man with complaints of intermittent left chest pain for 2 months was referred to our hospital. Chest computed tomography(CT) revealed a cavitary lesion measuring 5.5 cm × 5.7 cm in the superior segment of the left lower lobe. Absence of left pulmonary artery and right-sided aortic arch were found on chest computed tomography angiography (CTA). The tumor was successfully removed via left pneumonectomy, and postoperative histopathology showed that the tumor was a squamous cell carcinoma (T2bN1). At a postoperative 24-month follow-up, the patient was free of disease and no evidence of recurrence or metastasis. Based on literature review, this is the ninth case of lung cancer in UAPA patients. CONCLUSIONS: Lung cancer and UAPA occurred ipsilaterally in 66.7% of these cases (6/9), including the present case. For those patients who occurred contralaterally, surgical treatment may be more challenging. CT and CTA could provide an accurate diagnosis for this disease entity. Identification and recognition of this rare and special disease entity may facilitate timely diagnosis and appropriate treatment.


Assuntos
Anormalidades Múltiplas/patologia , Pneumopatias/congênito , Pneumopatias/patologia , Neoplasias Pulmonares/patologia , Pulmão/anormalidades , Artéria Pulmonar/patologia , Malformações Vasculares/patologia , Anormalidades Múltiplas/cirurgia , Humanos , Pulmão/patologia , Pulmão/cirurgia , Pneumopatias/complicações , Pneumopatias/cirurgia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Prognóstico , Artéria Pulmonar/cirurgia , Malformações Vasculares/complicações , Malformações Vasculares/cirurgia
20.
Phys Med Biol ; 65(5): 055012, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-31978901

RESUMO

To predict the epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma using quantitative radiomic biomarkers and semantic features. We analyzed the computed tomography (CT) images and medical record data of 104 patients with lung adenocarcinoma who underwent surgical excision and EGFR mutation detection from 2016 to 2018 at our center. CT radiomic and semantic features that reflect the tumors' heterogeneity and phenotype were extracted from preoperative non-enhanced CT scans. The least absolute shrinkage and selection operator method was applied to select the most distinguishable features. Three logistic regression models were built to predict the EGFR mutation status by combining the CT semantic with clinicopathological characteristics, using the radiomic features alone, and by combining the radiomic and clinicopathological features. Receiver operating characteristic (ROC) curve analysis was performed using five-fold cross-validation and the mean area under the curve (AUC) values were calculated and compared between the models to obtain the optimal model for predicting EGFR mutation. Furthermore, radiomic nomograms were constructed to demonstrate the performance of the model. In total, 1025 radiomic features were extracted and reduced to 13 features as the most important predictors to build the radiomic signature. The combined radiomic and clinicopathological features model was developed based on the radiomic signature, sex, smoking, vascular infiltration, and pathohistological type. The AUC was 0.90 ± 0.02 for the training, 0.88 ± 0.11 for the verification, and 0.894 for the test dataset. This model was superior to the other prediction models that used the combined CT semantic and clinicopathological features (AUC for the test dataset: 0.768) and radiomic features alone (AUC for the test dataset: 0.837). The prediction model built by radiomic biomarkers and clinicopathological features, including the radiomic signature, sex, smoking, vascular infiltration, and pathological type, outperformed the other two models and could effectively predict the EGFR mutation status in patients with peripheral lung adenocarcinoma. The radiomic nomogram of this model is expected to become an effective biomarker for patients with lung adenocarcinoma requiring adjuvant targeted treatment.


Assuntos
Adenocarcinoma de Pulmão/genética , Carcinoma Papilar/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Nomogramas , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Área Sob a Curva , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
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