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1.
Heliyon ; 10(16): e36207, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39253121

RESUMO

The turnover rate of melanogenesis in retinal pigment epithelium (RPE) and its molecular signaling remain unclear. This study aimed to investigate the role of cholinergic signaling in the process of melanogenesis of cultured RPE cells. Here, a human retinal pigment epithelia cell line, ARPE-19 cell, was used to study the process of melanogenesis. The mRNA and protein expressions of cholinergic molecules, e.g., acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and melanogenic molecules i.e., tyrosinase (TYR), microphthalmia-associated transcription factor (MITF), and melanin pigment were measured during melanogenesis of cultured ARPE-19 cells. Forskolin (a cAMP inducing agent), acetylcholine (ACh) and bethanechol (Bch; a muscarinic AChR agonist) were used to induce melanogenesis in the cultures. Muscarinic acetylcholine receptor (mAChR) antagonists were employed to identify the receptor subtype. During melanogenesis of ARPE-19 cells, the mRNA and protein expressions of cholinergic molecules, e.g., AChE and BChE, were increased along with melanogenic molecules, i.e., TYR, MITF and melanin pigment. Forskolin, ACh, and Bch induced an upregulation of melanogenesis in cultured ARPE-19 cultures: the induction was parallel to an increase of AChE expression. The Bch-induced enzymatic activities and mRNA levels of AChE and TYR were fully blocked by the treatments of gallamine (a M2 specific antagonist), tropicamide (a M4 specific antagonist) and atropine (non-specific antagonist for mAChRs). Cholinergic signaling via M2/M4 mAChRs regulates melanogenesis in cultured ARPE-19 cells through a cAMP-dependent pathway. This study provides insights into the regulation of RPE cell melanogenesis via a non-neuronal function of cholinergic system.

2.
Quant Imaging Med Surg ; 14(9): 6362-6373, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39281141

RESUMO

Background: In many clinical situations, it is critical to exclude or identify abnormally lymph nodes (LNs). The nature of superficial abnormally LNs is closely related to the stage, treatment, and prognosis of the disease. Ultrasound (US) is an important method for examining superficial LNs due to its cheap and safe characteristics. However, it is still difficult to determine the nature of some LNs with overlapping benign and malignant features in images. Contrast-enhanced ultrasound (CEUS) can be used to evaluate the microperfusion status of tissues in real time, and it can improve diagnostic accuracy to a certain extent. Therefore, in this study, we will analyze the correlation between CEUS quantitative parameters and benign and malignant superficial abnormally LNs, to evaluate the efficacy and value of CEUS in distinguishing benign and malignant superficial LNs. Methods: This study retrospectively analyzed 120 patients of abnormal LNs who underwent US and CEUS at the China-Japan Union Hospital of Jilin University from December 2020 to August 2023. All 120 cases of abnormal LNs underwent US-guided coarse needle biopsy, and accurate pathological results were obtained, along with complete US and CEUS images. According to the pathological results, LNs were divided into benign and malignant groups, and the qualitative and quantitative parameters of US and CEUS between the two groups were analyzed. The cutoff value is determined by the receiver operating characteristic (ROC) curve of the subjects, and sensitivity, specificity, and accuracy are applied to evaluate the ability of the cutoff value to distinguish between the two groups. Results: There were a total of 120 LNs, including 36 in the benign group and 84 in the malignant group. The results showed that malignant LNs were usually characterized by the disappearance of lymphatic hilum, round ness index (L/T) <2, irregular morphology, and the manifestation of uneven perfusion (P<0.05). The differences in the quantitative parameters peak enhancement (PE), rise time (RT), time to peak (TTP), wash-in rate (WIR), and wash-out rate (WOR) were statistically significant (P<0.05). The result showed that RT and TTP in the malignant LNs were higher than those in the benign LNs, while the PE, WIR, and WOR were lower. A comparison of the ∆ values showed that the differences in ∆PE, ∆WIR, and ∆fall time (FT) were statistically significant (P<0.05), Among them, the ∆PE and ∆WIR of malignant LNs were higher than those of benign LNs, while the ∆FT was lower than that of benign LNs. Conclusions: Quantitative analysis of CEUS features is valuable in the diagnosis of benign and malignant LNs, and US combined with CEUS helps to improve the accuracy of identifying the nature of LNs.

3.
Cell Biol Toxicol ; 40(1): 71, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39147926

RESUMO

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.


Assuntos
Cocaína , DNA Mitocondrial , Hipuratos , Hepatopatias Alcoólicas , Proteínas de Membrana , Transdução de Sinais , Animais , Cocaína/farmacologia , Cocaína/toxicidade , Transdução de Sinais/efeitos dos fármacos , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , DNA Mitocondrial/metabolismo , DNA Mitocondrial/efeitos dos fármacos , Camundongos , Hipuratos/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Etanol/toxicidade , Camundongos Endogâmicos C57BL , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo
4.
Eur Radiol ; 34(1): 715-723, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37581653

RESUMO

OBJECTIVES: Microwave ablation (MWA) has achieved excellent long-term efficacy in treating unifocal papillary thyroid microcarcinoma (UPTMC). The therapeutic effect of this treatment on multifocal papillary thyroid microcarcinoma (MPTMC) is unknown. Therefore, we evaluated the long-term efficacy of MWA for low-risk MPTMC and to provide evidence-based medicine for the revision of clinical guidelines. METHODS: This study included 66 MPTMC patients with a total of 158 lesions, all of whom received MWA. We collected and retrospectively analyzed the patients' follow-up data before MWA, at 1, 3, 6, and 12 months posttreatment and every 6 months thereafter until 5 years posttreatment. We evaluated the MWA complication rate, technical success rate (TSR), lesion volume reduction rate (VRR), and complete disappearance rate (CDR) during follow-up and in those patients with tumor progression and delayed surgery. RESULTS: After 60 months of follow-up, all 158 lesions disappeared in 66 patients, and the volume was reduced from 43.82 mm3 to 0.00 mm3. The TSR and VRR were both 100%. The CDRs at 1 year, 2 years, and 3 years were 57.59%, 93.67%, and 100%, respectively. The complication rate was 3.03% (2/66), and the incidence of tumor progression was 3.03% (2/66), including one new intrathyroidal lesion and one cervical lymph node metastasis (LNM). These lesions were retreated with MWA, and the lesions disappeared during the follow-up period. CONCLUSIONS: Ultrasound-guided MWA for low-risk MPTMC is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance (AS). CLINICAL RELEVANCE STATEMENT: This study concludes that ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance. KEY POINTS: • Ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective. • During 5 years of follow-up, multifocal papillary thyroid microcarcinoma patients treated with microwave ablation had a favorable prognosis. • To provide evidence-based medicine for the revision of clinical guidelines.


Assuntos
Carcinoma Papilar , Micro-Ondas , Neoplasias da Glândula Tireoide , Humanos , Seguimentos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento , Ultrassonografia de Intervenção
5.
Endocrine ; 83(3): 691-699, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37889469

RESUMO

PURPOSE: To investigate the diagnostic value of contrast-enhanced ultrasound (CEUS) quantitative analysis parameters combined with shear wave elastography (SWE) quantitative parameters in the differentiation of benign and malignant ACR TI-RADS category 4 thyroid nodules and to provide a more effective reference for clinical work. METHODS: We analyzed 187 category 4 nodules, including 132 nodules in the development cohort and 55 nodules in the validation cohort, divided the development cohort into benign and malignant groups, and analyzed the differences in all CEUS and SWE quantitative parameters between the two groups. We selected the highest AUC of the two parameters, performed binary logistic regression analysis with the ACR TI-RADS score and constructed a diagnostic model. ROC curves were applied to evaluate their diagnostic efficacy. RESULTS: 1) The diagnostic model had an AUC of 0.926, sensitivity of 87.5%, specificity of 86.8%, diagnostic threshold of 3, accuracy of 87.12%, positive predictive value of 86.15%, and negative predictive value of 88.06%. 2) The diagnostic model had an AUC of 0.890 in the validation cohort, sensitivity of 81.5%, specificity of 79.6%, and accuracy of 80.00%. CONCLUSION: The combined multiparameter construction of the nodule diagnostic model can effectively improve the diagnostic efficacy of 4 types of thyroid nodules and provide a new reference index for clinical diagnostic work.


Assuntos
Técnicas de Imagem por Elasticidade , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Diagnóstico Diferencial , Modelos Logísticos , Ultrassonografia , Estudos Retrospectivos
6.
Int J Nanomedicine ; 18: 6667-6687, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026520

RESUMO

Purpose: Sonodynamic therapy (SDT), with its high tissue penetration and noninvasive advantages, represents an emerging approach to eradicating solid tumors. However, the outcomes of SDT are typically hampered by the low oxygen content and immunosuppression in the tumor microenvironment (TME). Accordingly, we constructed a cascade nanoplatform to regulate the TME and improve the anti-tumor efficiency of SDT. Methods: In this study, we rationally design cascade nanoplatform by incorporating immunostimulant hyaluronic acid (HA) and sonosensitizer chlorin e6 (Ce6) on the polydopamine nanocarrier that is pre-doped with platinum nanozymes (designated Ce6/Pt@PDA-HA, PPCH). Results: The cascade reactions of PPCH are evidenced by the results that HA exhibits reversing immunosuppressive that converts M2 macrophages into M1 macrophages in situ, while producing H2O2, and then platinum nanozymes further catalyze the H2O2 to produce O2, and O2 produces abundant singlet oxygen (1O2) under the action of Ce6 and low-intensity focused ultrasound (LIFU), resulting in a domino effect and further amplifying the efficacy of SDT. Due to its pH responsiveness and mitochondrial targeting, PPCH effectively accumulates in tumor cells. Under LIFU irradiation, PPCH effectively reverses immunosuppression, alleviates hypoxia in the TME, enhances reactive oxygen species (ROS) generation, and enhances SDT efficacy for eliminating tumor cells in vivo and in vitro. Meanwhile, an in vivo dual-modal imaging including fluorescence and photoacoustic imaging achieves precise tumor diagnosis. Conclusion: This cascade nanoplatform will provide a promising strategy for enhancing SDT eradication against tumors by modulating immunosuppression and relieving hypoxia.


Assuntos
Nanopartículas , Porfirinas , Terapia por Ultrassom , Humanos , Terapia por Ultrassom/métodos , Peróxido de Hidrogênio , Platina , Linhagem Celular Tumoral , Porfirinas/farmacologia , Porfirinas/química , Espécies Reativas de Oxigênio , Hipóxia , Nanopartículas/química , Microambiente Tumoral
7.
Front Endocrinol (Lausanne) ; 14: 1140360, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37305060

RESUMO

Aim: Accurate preoperative prediction of cervical lymph node metastasis (LNM) in patients with mPTMC provides a basis for surgical decision making and the extent of tumor resection. This study aimed to develop and validate an ultrasound radiomics nomogram for the preoperative assessment of LN status. Methods: A total of 450 patients pathologically diagnosed with mPTMC were enrolled, including 348 patients in the modeling group and 102 patients in the validation group. Univariate and multivariate logistic regression analyses were performed on the basic information, ultrasound characteristics, and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) scores of the patients in the modeling group to identify independent risk factors for LNM in mPTMC and to construct a logistic regression equation and nomogram to predict the risk of LNM. The validation group data were used to evaluate the predictive performance of the nomogram. Results: Male sex, age <40 years, a single lesion with a maximum diameter >0.5 cm, capsular invasion, a maximum ACR score >9 points, and a total ACR score >19 points were independent risk factors for the development of cervical LNM in mPTMC. Both the area under the curve (AUC) and concordance index (C-index) of the prediction model constructed from the above six factors were 0.838. The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, decision curve analysis (DCA) demonstrated a significantly greater net benefit of the model. The external validation demonstrated the reliability of the prediction nomogram. Conclusions: The presented radiomics nomogram, which is based on ACR TI-RADS scores, shows favorable predictive value for the preoperative assessment of LNs in patients with mPTMC. These findings may provide a basis for surgical decision making and the extent of tumor resection.


Assuntos
Nomogramas , Nódulo da Glândula Tireoide , Humanos , Masculino , Adulto , Metástase Linfática , Reprodutibilidade dos Testes
8.
J Cancer Res Clin Oncol ; 149(4): 1645-1656, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35831762

RESUMO

Tumor immunotherapy has become an important means of tumor therapy by enhancing the immune response and triggering the activation of immune cells. However, currently, only a small number of patients respond to immunotherapy alone, and patients may experience immune-related adverse events (irAEs) during the course of treatment. Sonodynamic therapy (SDT) can produce cytotoxic substances to tumor tissue, induce apoptosis and enhance immunity. SDT combined with immunotherapy is considered a promising strategy for cancer treatment. In this mini review, we summarize the role of SDT in immunotherapy in recent years, including the application of SDT-triggered immunotherapy and the combination of SDT and immunotherapy.


Assuntos
Neoplasias , Terapia por Ultrassom , Humanos , Terapia Combinada , Apoptose , Imunoterapia/efeitos adversos , Neoplasias/terapia , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio
9.
Int J Mol Sci ; 23(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36499214

RESUMO

Mitochondria play a central role in the pathophysiology of inflammatory bowel disease (IBD) and colorectal cancer (CRC). The maintenance of mitochondrial function is necessary for a stable immune system. Mitochondrial dysfunction in the gastrointestinal system leads to the excessive activation of multiple inflammatory signaling pathways, leading to IBD and increased severity of CRC. In this review, we focus on the mitochondria and inflammatory signaling pathways and its related gastrointestinal diseases.


Assuntos
Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Humanos , Mitocôndrias/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Transdução de Sinais , Neoplasias Colorretais/metabolismo
10.
Cancer Manag Res ; 14: 2861-2868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36171864

RESUMO

Background: In recent years, papillary thyroid microcarcinoma (PTMC) has been a main cause of the high incidence of thyroid carcinoma. No existing study has reported whether microwave ablation (MWA) affects patients' immunity. Therefore, this study explored the effects of MWA treatment on the immune functions of patients with PTMC. Methods: This study included 50 patients diagnosed with PTMC who received MWA treatment under ultrasound guidance at the ultrasound department of our hospital from January 2019 to October 2020. Changes in immune function after MWA treatment in PTMC patients were detected by T lymphocyte subsets and cytokines secreted by T helper cells. Results: At 1 day and 2 weeks after MWA treatment, the proportions of CD3+, CD4+ and CD4+/CD8+ T lymphocyte subsets and the levels of the cytokines interleukin (IL)-2 and interferon (IFN)-γ in the peripheral blood of the patients were significantly higher than those before MWA treatment (P<0.05). The levels of CD8+ T lymphocytes, tumour necrosis factor (TNF)-α, IL-4, IL-6, IL-10 and IL-17A were not significantly different from those before MWA treatment (P>0.05). One month after MWA treatment, the proportions of CD3+, CD4+, CD8+ and CD4+/CD8+ T lymphocytes and the levels of the cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α and IL-17A were not significantly different from those before MWA treatment (P>0.05). Conclusion: The immune functions of patients with PTMC are temporarily enhanced after MWA treatment, which has important clinical significance for patients' anti-PTMC ability.

12.
Endocrine ; 71(1): 113-121, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32419083

RESUMO

PURPOSE: To evaluate the safety and effectiveness of microwave ablation (MWA) versus lobectomy for the treatment of benign thyroid nodules > 4 cm. METHODS: We retrospectively analyzed the data of 48 patients who underwent MWA and 53 patients who underwent lobectomy to treat benign thyroid nodules > 4 cm. The patients were followed up for 12 months. The volume reduction ratio (VRR) was calculated. The operation time, incision length, hospitalization time, complications, thyroid function, symptoms, and cosmetic improvement were analyzed and compared between the two groups. RESULTS: During the 12-month follow-up, the mean nodule volume in the MWA group was reduced from 36.1 ± 23.1 to 4.0 ± 4.1 ml, and the mean VRR of the nodules was 90 ± 5% in the MWA group, which was comparable with that in the surgery group. No significant postoperative change in thyroid function was observed in the MWA group. Compared with the surgery group, the incidence of complications and postoperative pain in the MWA group were lower, the operation time, incision length, and hospitalization time in the MWA group were shorter, and satisfaction with the esthetic results in the MWA group was greater. CONCLUSION: MWA is safe and effective for the treatment of benign thyroid nodules > 4 cm. Moreover, MWA is associated with a faster recovery, fewer complications, better protection of thyroid function, and superior esthetic results relative to thyroid lobectomy.


Assuntos
Ablação por Cateter , Ablação por Radiofrequência , Nódulo da Glândula Tireoide , Humanos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Nódulo da Glândula Tireoide/cirurgia , Resultado do Tratamento
13.
Brain Behav ; 11(5): e01492, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-31909567

RESUMO

OBJECTIVE: Neurologic deterioration (ND) and functional outcome after ischemic stroke (IS) are not accurately predicted by clinical pictures on admission. The aim of present study was to investigate the association of variants in P53 apoptotic pathway genes with ND and functional outcome after IS. METHODS: Genotypes of nine variants in apoptosis-relevant genes were measured in patients with acute IS. Gene-gene interactions were analyzed by generalized multifactor dimensionality reduction (GMDR). The primary outcome was ND. ND was diagnosed in patients who worsened ≥2 points (National Institutes of Health Stroke Scale [NIHSS] score) within the first 10 days of stroke onset. The secondary outcome was functional status at 90 days after IS as measured by modified Rankin Scale (mRS) score. RESULTS: A total of 705 enrolled patients, ND occurred in 174 (24.7%) patients, and 184 (26.1%) patients were poor functional outcome (mRS score > 2). Although the nine variants were not significantly associated with ND and functional outcome by univariate analysis, there was a gene-gene interaction among P53rs1042522, MDM-2rs2279744, and MMP-9 rs3918242 using GMDR analysis. The high-risk interaction among the three variants was independently associated with higher risk of ND (HR, 2.04, 95% CI: 1.22-5.64, p = .018) and poor functional outcome (OR, 2.68, 95% CI: 1.68-7.86, p = .004) after adjusting for the covariates. CONCLUSION: The interactions among P53 rs1042522, MDM-2 rs2279744, and MMP-9 rs3918242 may increase the risk of ND and poor functional outcome and may be considered as a genetic marker of predicting ND and poor functional outcome after stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/genética , Humanos , Metaloproteinase 9 da Matriz/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Fatores de Risco , Acidente Vascular Cerebral/genética , Proteína Supressora de Tumor p53/genética
14.
J Atheroscler Thromb ; 27(9): 978-994, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31956237

RESUMO

AIM: To examine the association between carotid plaque and variants in genes involved in inflammation and endothelial function. METHODS: This was a multicenter, cross-sectional survey in southwestern China. The residents aged ≥ 40 years volunteered to participate in the face-to-face survey in eight communities. A total of 2,377 subjects with high stroke risk were enrolled. Carotid plaque and plaque phenotype were assessed by carotid ultrasound. Genotypes of 19 variants in 10 genes related to inflammation and endothelial function were examined. Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction (GMDR). RESULTS: Carotid plaques were found in 852 (35.8%) subjects, and 454 (53.3%) had stable plaques, whereas 398 (46.7%) had vulnerable plaques. PPARA rs4253655, HABP2 rs7923349, and IL1A rs1609682 were associated with the presence of carotid plaque, and NOS2A rs2297518 and PPARA rs4253655 were associated with vulnerable plaque in univariate analysis. The GMDR analysis revealed that there was a significant gene-gene interaction among HABP2 rs7923349, ITGA2 rs1991013, IL1A rs1609682, and NOS2A rs8081248, and the high-risk interactive genotype among the four variants was independently associated with a higher risk of carotid vulnerable plaque after adjusting the covariates (OR, 2.86, 95% CI: 1.32-7.13, P=0.003). CONCLUSION: The prevalence of carotid plaque was very high in the high-risk stroke population in southwestern China. Variants in genes involved in the endothelial function and inflammation were associated with the carotid plaque. The high-risk interactive genotype among rs7923349, rs1991013, rs1609682, and rs8081248 was independently associated with a higher risk of vulnerable plaque.


Assuntos
Artérias Carótidas/patologia , Endotélio Vascular/patologia , Predisposição Genética para Doença , Inflamação/genética , Placa Aterosclerótica/patologia , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Artérias Carótidas/metabolismo , China/epidemiologia , Estudos Transversais , Endotélio Vascular/metabolismo , Feminino , Seguimentos , Humanos , Interleucina-1alfa/genética , Masculino , Pessoa de Meia-Idade , PPAR alfa/genética , Fenótipo , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/genética , Prognóstico , Fatores de Risco , Serina Endopeptidases/genética
15.
J Org Chem ; 84(17): 10805-10813, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31418570

RESUMO

In this work, selectivity-controllable base-promoted transition-metal-free borylation and dehalogenation of aryl halides are described. Under the conditions of borylation, the dehalogenation which emerges as a competitive side reaction has been well-controlled by carefully controlling the borylation conditions. On the other hand, the dehalogenation using benzaldehyde as a hydrogen source has also been accomplished. The applications of direct radical borylation and dehalogenation of aryl halides demonstrate their synthetic practicability in pharmaceutical-oriented organic synthesis. Based on the experimental evidences, the tBuOK/1,10-Phen-triggered radical nature of both competitive reactions has been revealed.

16.
J Org Chem ; 84(12): 8267-8274, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31188594

RESUMO

A transition metal-free radical process for the selective α,ß-dehydrogenation of saturated amides under mild conditions is developed. Utilizing radical activation strategy, the challenging issue associated with the low α-acidity of amides is resolved. For the first time, α,ß-unsaturated Weinreb amides and acrylamides could be efficiently prepared directly from corresponding saturated amides. Mechanistic studies confirm the radical nature of this transformation. Two gram scale α,ß-dehydrogenation have also been performed to demonstrate the utility of this method.

17.
Brain Behav ; 9(6): e01294, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31074588

RESUMO

OBJECTIVE: The potential effect of matrix metalloproteinase-9 (MMP-9) variants and these variants interactions on hemorrhagic transformation (HT) risk after ischemic stroke (IS) remain unclear. The aims of present study were to investigate the associations of six variants in MMP-9 with HT, and these variants interactions whether related to increased HT risk. METHOD: A total of 705 patients with IS who were admitted to the participating hospitals within 48 hr of symptom onset were consecutively enrolled between March 2014 and December 2016. HT was confirmed by brain computed tomography (CT) scan during 14 days from stroke onset. Six variants of MMP-9 gene were measured by mass spectrometry. Interactions of gene variant-gene variant were assessed through generalized multifactor dimensionality reduction method (GMDR). RESULTS: HT occurred in 104 (14.8%) patients. There were no differences in genotypes for the six variants between patients with and without HT using univariate analysis (all p > 0.05). GMDR analysis revealed that there was a synergistic effect of gene variant-gene variant interactions between rs3918242 and rs3787268 in MMP-9 gene. Cox regression analysis showed that high-risk interactions of rs3918242 and rs3787268 were associated with increased risk of HT after adjusting for covariates (hazard ratio: 2.08; 95% confidence interval: 1.34-7.85; p = 0.016). CONCLUSION: Incidence of HT is common in acute IS in Chinese population. The mechanisms leading to HT are most likely multifactorial. Two-loci interactions of rs3918242 and rs3787268 in MMP-9 gene may confer a higher risk for HT.


Assuntos
Isquemia Encefálica/genética , Hemorragia Cerebral/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/genética , Idoso , Povo Asiático/genética , Aterosclerose/genética , Isquemia Encefálica/complicações , Angiografia Cerebral , Doenças Arteriais Cerebrais/genética , Artérias Cerebrais , Angiografia por Tomografia Computadorizada , Epistasia Genética/genética , Feminino , Genótipo , Heterozigoto , Humanos , Embolia Intracraniana/genética , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral/complicações , Trombose/genética
18.
Brain Behav ; 9(6): e01291, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31012282

RESUMO

OBJECTIVES: The mechanisms of ischemic stroke severity and early neurologic deterioration (END) are not fully understood. The aim of the present study was to investigate the association of six variants in MMP-9 gene with ischemic stroke severity and the risk for END in ischemic stroke (IS) patients with atrial fibrillation (AF). METHODS: This was a multi-center, prospective, observational study of 615 acute IS patients with AF admitted to six participating hospitals between June 2016 and October 2017. Ischemic stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score on admission. END was defined as an increase of four or more points in NIHSS within 10 days of admission. Six variants of MMP-9 gene were examined using mass spectrometry. RESULTS: Among the 615 enrolled patients, 112 (18.2%) patients presented with moderate or severe stroke (NIHSS score ≥16), and 108 (17.6%) patients suffered from END within 10 days of admission. Multiple logistic analysis showed that prestroke antiplatelet therapy, prestroke anticoagulant therapy, rs3918242 CT/TT, and rs3787268 AG/GG were independent predictors for stroke severity. Cox proportional hazard regression revealed that diabetes mellitus, prestroke antiplatelet therapy, prestroke anticoagulant therapy, rs1056628 AC/CC, and rs3918242 CT/TT were independently associated with the risk of END. CONCLUSIONS: The incidence of moderate or severe stroke and END was very common in acute IS patients with AF. MMP-9 polymorphisms were independently associated with severe stroke and higher risk of END, and prestroke antithrombotic treatment was associated with less severe stroke and lower risk of END in patients with AF.


Assuntos
Fibrilação Atrial/genética , Isquemia Encefálica/genética , Metaloproteinase 9 da Matriz/genética , Doenças do Sistema Nervoso/genética , Polimorfismo Genético/genética , Acidente Vascular Cerebral/genética , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico
19.
Endocrine ; 65(1): 121-131, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30830584

RESUMO

OBJECTIVES: (1) To compare the American College of Radiology (ACR) thyroid imaging reporting and data system (TIRADS) and American Thyroid Association (ATA) guidelines for thyroid nodules with regard to diagnostic performance and effectiveness at reducing the number of fine-needle aspiration (FNA) biopsies and to preliminarily discuss the reasons for the differences and (2) to compare the diagnostic performance of the two guidelines in the subgroup of nodules <1 cm in diameter. MATERIALS AND METHODS: In the present study, 1000 thyroid nodules in 894 consecutive patients with final diagnoses were included; these thyroid nodules were investigated via FNA biopsies in our hospital. The ultrasound (US) features of the thyroid nodules were reviewed and stratified according to the categories defined by the ACR TIRADS and ATA guidelines. RESULTS: Compared with the ACR TIRADS guidelines, the ATA guidelines had a higher sensitivity (93.4% (P < 0.001)) and a larger negative predictive value (NPV) (85.3% (P= 0.034)). Compared with the ATA guidelines, the ACR TIRADS guidelines had a higher specificity (66.0% (P < 0.001)), a greater PPV (73.6% (P= 0.001)), and greater accuracy (75.5% (P= 0.017)). Compared with the ATA guidelines, the ACR TIRADS guidelines resulted in significantly fewer unnecessary FNA biopsies (P= 0.007). CONCLUSIONS: This study suggests that both the ACR TIRADS and ATA guidelines have unique strengths with regard to their diagnostic performance. In terms of reducing the number of FNA biopsies, the ACR TIRADS guidelines were superior to the ATA guidelines.


Assuntos
Técnicas de Diagnóstico Endócrino/normas , Guias de Prática Clínica como Assunto , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina/normas , China/epidemiologia , Estudos de Coortes , Diagnóstico Diferencial , Humanos , Guias de Prática Clínica como Assunto/normas , Valor Preditivo dos Testes , Dados Preliminares , Estudos Retrospectivos , Sensibilidade e Especificidade , Sociedades Médicas/normas , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/epidemiologia , Carga Tumoral , Ultrassonografia/métodos , Estados Unidos
20.
Endocrine ; 64(1): 109-117, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30771153

RESUMO

PURPOSE: To assess the safety and efficacy of microwave ablation (MWA) for primary papillary thyroid microcarcinoma (PTMC) with a large sample of 185 patients. METHODS: A total of 185 patients underwent MWA for 206 primary PTMC nodules. They received ultrasound follow-up at 1, 3, 6, and 12 months after MWA and every 6 months thereafter. Nodule volumes were calculated at each follow-up and compared with those before MWA. Additionally, the volume reduction rate (VRR) of the nodules was calculated. Patients' thyroid functions were tested before and 1 month after MWA. RESULTS: The mean follow-up time of the 185 patients was 20.7 ± 8.8 months (range 12-36 months). During the follow-up period, the mean volume of the 206 nodules was 100.1 ± 92.9 mm3 (range 3.6-423.9) before MWA, which decreased to 2.2 ± 5.6 mm3 (range 0-20.3 mm3) after MWA (P = 0.000). The mean VRR of the nodules was 98.65 ± 3.60% after MWA (range 83.85-100%). One hundred and seventy four of 206 nodules (84.5%) were fully absorbed. Compared with the preoperative results, no significant variation in thyroid function was observed 1 month after MWA. Thirty-eight patients (20.5%) had different types of complications, ranging from minor to major. Five patients (2.7%) had hoarseness, 11 patients (5.9%) had bleeding, 21 patients (11.4%) had earache or toothache, and one patient had another lesion 1 month after MWA. CONCLUSIONS: This preliminary study suggests that MWA is safe and effective in the treatment of primary PTMC and offers a new alternative for clinical treatment.


Assuntos
Técnicas de Ablação/métodos , Carcinoma Papilar/terapia , Neoplasias da Glândula Tireoide/terapia , Adolescente , Adulto , Idoso , Carcinoma Papilar/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Humanos , Masculino , Micro-Ondas , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia , Adulto Jovem
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