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1.
Front Oncol ; 12: 754967, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847870

RESUMO

Malignant myoepithelioma of the head and neck (HNMM) is a rare malignancy, and its characteristics and survival rates have not been well-defined. This study aimed to define the epidemiology of HNMM and identify the prognostic factors associated with the disease. Data on all patients diagnosed with HNMM between 1991 and 2016 were gathered from the Surveillance Epidemiology and End Results (SEER) database. The demographics, clinicopathological characteristics, treatment, and prognoses of the patients were described. Cox regression analysis was used to identify the prognostic factors, and the prognostic nomograms for overall survival (OS) and disease-specific survival (DSS) were constructed. A total of 333 cases of HNMM were identified. The average age at diagnosis was 60.6 years, and 50.1% of the patients were men. After diagnosis, 46.2% of patients underwent surgery alone, 43.5% of patients underwent surgery and radiotherapy, and 3.6% of patients received only radiotherapy. Survival analysis showed that the 5-year OS and DSS for all HNMM patients were 69.7 and 82.1%, respectively. In the multivariate analysis model, the undifferentiated pathological grade (P <0.05) and M1 in the M category (P <0.01) were independent prognostic factors for poor OS and DSS, whereas the use of surgical resection was an independent favorable prognostic factor for both OS and DSS (P <0.05). The prognostic nomograms for OS and DSS prediction were constructed; the C-index values for OS and DSS prediction were 0.78 (95% CI 0.70-0.86) and 0.79 (95% CI 0.67-0.90), respectively. In conclusion, this SEER data-based study demonstrated that HNMM patients often had a favorable prognosis, and distant metastasis, pathological grade, and the use of surgery contributed to their survival. Furthermore, we developed a prognostic nomogram to predict OS and DSS for HNMM patients to aid physicians in the clinical management of this rare disease.

2.
Angew Chem Int Ed Engl ; : e202207579, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35833470

RESUMO

The separation of C2 H2 /CO2 is not only industrially important for acetylene purification but also great scientific challenge due to their very similar molecular size and physical properties. To address this difficulty, herein, we present an ultramicroporous hydrogen-bonded organic framework (HOF-FJU-1) from tetracyano bicarbazole to separate C2 H2 from CO2 by taking advantage of differences in their electrostatic potential distribution. This material possesses a suitable pore environment and electrostatic potential distribution fitting well to C2 H2 , thus showing extra strong affinity to C2 H2 (46.73 kJ mol-1 ) and the highest IAST selectivity of 6675 for C2 H2 /CO2 separation among the adsorbents reported. The single crystal X-ray diffraction reveals that the suitable pore environment in HOF-FJU-1 provides multiple C-H⋅⋅⋅π and hydrogen-bonded interactions N⋅⋅⋅H-C with C2 H2 molecules. Dynamic breakthrough experiments demonstrate its outstanding separation performance to C2 H2 /CO2 mixtures.

3.
Materials (Basel) ; 15(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35683088

RESUMO

Using high-strength steel (yield strength fy ≥ 460 MPa) in concrete-filled steel tubes is expected to provide a superior bearing capacity by achieving light weight and efficient construction, but the existing design limitation on diameter-to-thickness (D/t) ratios for concrete-filled high-strength steel tubular (CFHST) members inevitably obstructs its wide application. In this study, aiming at the application of circular CFHST members using Q690 steel (fy ≥ 690 MPa), a total of 15 CFHST beams were examined using a three-point loading test to investigate the failure mode, bearing capacity and plasticity evolution. Subsequently, finite element models (FEMs) were established to analyze the full-range curves, composite effect, failure mechanism and influences of key parameters including material strengths, D/t ratios, and shear-span ratios. A simplified calculation method for bearing capacity was finally proposed and verified. The results indicate that the full-range performance of tested CFHST members with out-of-code D/t ratios have ductile behavior, though they fail through the mode of steel fracture and concrete cracks in the tension zone as well as through local buckling in the compression zone; out-of-code CFHST members (e.g., D/t = 120) can perform reasonable composite behavior because of contact pressure larger than 2.5 MPa, where a thin-walled steel tube experiences an arch failure mechanism similar to core concrete at a trussed angle of 45°; the simplified bearing capacity model achieves a mean value of 0.97, and can be accepted as a primary tool to perform structural design and performance evaluation.

4.
Toxins (Basel) ; 14(6)2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35737029

RESUMO

Aflatoxin B1 (AFB1) is a common crop contaminant, while aflatoxin M1 (AFM1) is implicated in milk safety. Humans are likely to be simultaneously exposed to AFB1 and AFM1; however, studies on the combined interactive effects of AFB1 and AFM1 are lacking. To fill this knowledge gap, transcriptomic, proteomic, and microRNA (miRNA)-sequencing approaches were used to investigate the toxic mechanisms underpinning combined AFB1 and AFM1 actions in vitro. Exposure to AFB1 (1.25-20 µM) and AFM1 (5-20 µM) for 48 h significantly decreased cell viability in the intestinal cell line, NCM460. Multi-omics analyses demonstrated that additive toxic effects were induced by combined AFB1 (2.5 µM) and AFM1 (2.5 µM) in NCM460 cells and were associated with p53 signaling pathway, a common pathway enriched by differentially expressed mRNAs/proteins/miRNAs. Specifically, based on p53 signaling, cross-omics showed that AFB1 and AFM1 reduced NCM460 cell viability via the hsa-miR-628-3p- and hsa-miR-217-5p-mediated regulation of cell surface death receptor (FAS), and also the hsa-miR-11-y-mediated regulation of cyclin dependent kinase 2 (CDK2). We provide new insights on biomarkers which reflect the cytotoxic effects of combined AFB1 and AFM1 toxicity.


Assuntos
Aflatoxina M1 , MicroRNAs , Aflatoxina B1/análise , Aflatoxina B1/toxicidade , Aflatoxina M1/análise , Animais , Humanos , MicroRNAs/genética , Leite/química , Proteômica , Proteína Supressora de Tumor p53
5.
Biochem Biophys Res Commun ; 613: 34-40, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35526486

RESUMO

Anacardic acid (AA) is a phenolic acid extract found in a number of plants, crops, and fruits. It exhibits a wide range of biological activities. This study displayed that AA effectively alleviated EAE, a classical mouse model of multiple sclerosis. AA administered to the EAE greatly decreased inflammatory cell infiltration to the CNS and protected the myelin integrity in the white matter of the spinal cord. AA could block lipopolysaccharide-induced DC activation. inhibited the polarization of 2D2 mice-derived T cells by inhibiting the DCs activity. Immunoblot results indicated that the phosphorylation of NF-κB is significantly suppressed in AA-treated DCs. This work displayed that AA possessed a potential anti-inflammatory therapeutic effect for the treatment of autoimmune disease.


Assuntos
Encefalomielite Autoimune Experimental , Ácidos Anacárdicos , Animais , Células Dendríticas , Encefalomielite Autoimune Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias , Medula Espinal
6.
J Pharm Biomed Anal ; 217: 114833, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35594777

RESUMO

Zeng-Sheng-Ping (ZSP) tablets, made from six Chinese herbs, are widely used in the chemoprevention and treatment of precancerous lesions in patients with gastrointestinal cancer. However, sporadic cases of liver injury have occurred. Herein, the serum metabolites in hamsters with ZSP-induced liver damage were analyzed by NMR-based metabolomics. Twelve metabolites associated with ZSP-induced hepatoxicity were identified. Amino acid metabolism and the urea cycle were significantly altered, and three associated amino acid metabolic enzymes (PAH, GS, and GLS) were further validated by ELISA. Therefore, 12 metabolites and 3 amino acid metabolic enzymes were proposed as potential biomarkers in ZSP-induced liver injury. The chemical constituents of ZSP tablets were profiled using liquid chromatography-mass spectrometry. The furanoids in two herbs, Dioscorea bulbifera L. and Dictamnus dasycarpus Turcz., were proposed to be the major hepatotoxic constituents in ZSP, leading to an improved preparation method with low hepatotoxicity for ZSP.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Espectrometria de Massas em Tandem , Aminoácidos/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Cromatografia Líquida , Humanos , Fígado/metabolismo , Metabolômica/métodos
7.
J Am Heart Assoc ; 11(11): e025853, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35621204

RESUMO

Background Despite successful recanalization, up to half of patients with acute ischemic stroke caused by large-vessel occlusion treated with endovascular treatment (EVT) do not recover to functional independence. We aim to evaluate the role of cerebral circulation time (CCT) as outcome predictor after EVT. Methods and Results We retrospectively enrolled consecutive patients with acute ischemic stroke-large-vessel occlusion undergoing EVT. Three categories of CCT based on digital subtraction angiography were studied: CCT of the stroke side, CCT of the healthy side), and change of CCT of the stroke side versus CCT of the healthy side. Dramatic clinical recovery was defined as a 24-hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. A modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. Logistic regression analysis was performed to evaluate the prediction of CCT on prognosis. One hundred patients were enrolled, of which 38 (38.0%) experienced a dramatic clinical recovery and 43 (43.0%) achieved a favorable outcome. Logistic regression analysis found that shorter change of CCT of the stroke side versus CCT of the healthy side and CCT of the stroke side were independent positive prognostic factors for dramatic clinical recovery (odds ratio [OR], 0.189; P=0.033; OR, 0.581; P=0.035) and favorable outcomes (OR, 0.142; P=0.020; OR, 0.581; P=0.046) after adjustment for potential confounders. A model including the change of CCT of the stroke side versus CCT of the healthy side also had significantly higher area under the curve values compared with the baseline model in patients with dramatic clinical recovery (0.780 versus 0.742) or favorable outcome (0.759 versus 0.713). Conclusions To our knowledge, this is the first report that CCT based on digital subtraction angiography data exhibits an independent predictive performance for clinical outcome in patients with acute ischemic stroke-large-vessel occlusion after EVT. Given that this readily available CCT can provide alternative perfusion information during EVT, a prospective, multicenter trial is warranted.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Circulação Cerebrovascular , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/terapia , Estudos Prospectivos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Trombectomia/métodos , Resultado do Tratamento
8.
Nano Lett ; 22(10): 3983-3992, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35548949

RESUMO

Lysosome-targeting self-assembling prodrugs had emerged as an attractive approach to overcome the acquisition of resistance to chemotherapeutics by inhibiting lysosomal sequestration. Taking advantage of lysosomal acidification induced intracellular hydrolytic condensation, we developed a lysosomal-targeting self-condensation prodrug-nanoplatform (LTSPN) system for overcoming lysosome-mediated drug resistance. Briefly, the designed hydroxycamptothecine (HCPT)-silane conjugates self-assembled into silane-based nanoparticles, which were taken up into lysosomes by tumor cells. Subsequently, the integrity of the lysosomal membrane was destructed because of the acid-triggered release of alcohol, wherein the nanoparticles self-condensed into silicon particles outside the lysosome through intracellular hydrolytic condensation. Significantly, the LTSPN system reduced the half-maximal inhibitory concentration (IC50) of HCPT by approximately 4 times. Furthermore, the LTSPN system realized improved control of large established tumors and reduced regrowth of residual tumors in several drug-resistant tumor models. Our findings suggested that target destructing the integrity of the lysosomal membrane may improve the therapeutic effects of chemotherapeutics, providing a potent treatment strategy for malignancies.


Assuntos
Nanopartículas , Neoplasias , Pró-Fármacos , Linhagem Celular Tumoral , Resistência a Medicamentos , Humanos , Lisossomos/patologia , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Silanos/farmacologia , Silanos/uso terapêutico
9.
Biomaterials ; 284: 121523, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35462306

RESUMO

Tumor cells intensively engage in metabolic reprogramming for enhancing the availability of glycolytic metabolites and support cell proliferation. As the most important rate-limiting enzyme in aerobic glycolysis, activating the pyruvate kinase muscle isoform 2 (PKM2) from dimers to tetramers has become a key tumor chemotherapy method to control glucose metabolism. Herein, we developed a glycopeptide-based PKM2 nano-activator, which could induce the tetramerization of PKM2 based on serine bonding to Domain C of PKM2. The bound and trapped PKM2 tetramers significantly hindered glycolytic intermediates, prevented the nucleus translocation of dimeric PKM2, and ultimately inhibited the proliferation, chemoresistance and metastasis of tumor. The glycopeptide assembled into nanoparticles under aqueous conditions and in the circulation, which in situ transformed into PKM2 nano-activator with nanofibrillar structure after specifically activated by O-GlcNAcase recognition upregulated in a wide range of human tumors. Moreover, the glycopeptide-based PKM2 nano-activator successfully accumulated at the tumor sites and boosted the chemo-drug sensitivity against prostate and breast cancers. Attributed to these intriguing results, the newly developed glycopeptide-based PKM2 nano-activator can be envisioned a promising candidate for the treatment of tumors by switching catabolic pathways.


Assuntos
Neoplasias da Mama , Piruvato Quinase , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Glicólise , Glicopeptídeos/metabolismo , Humanos , Masculino , Músculos/metabolismo , Isoformas de Proteínas/metabolismo , Piruvato Quinase/metabolismo
10.
Adv Mater ; 34(24): e2109432, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35426184

RESUMO

Targeted immunomodulation through biomolecule-based nanostructures, especially to dendritic cells (DCs), holds great promise for effective cancer therapy. However, construction of high-performance agonist by mimicking natural ligand to activate immune cell signaling is a great challenge so far. Here, a peptide-based nanoagonist toward CD40 (PVA-CD40) with preorganized interfacial topological structure that activates lymph node DCs efficiently and persistently, achieving amplified immune therapeutic efficacy is described. The on-site fabrication of PVA-CD40 is realized through the click conjugation of two functional peptides including the "CD40 anchoring arm" and the "assembly-driving motor." The resultant polyvalent interface rapidly triggers the receptor oligomerization and downstream signaling. Strikingly, one shot administration of PVA-CD40 elicits maturation period of DCs up to 2.3-fold comparing to that of CD40 antibody. Finally, combining the PVA-CD40 with anti-PD-1 antibody results in subsequent inhibition of tumor growth in both B16F10 and 4T1 mice tumor models with survival rate up to 37%, while none of the mice survives in the clinically relevant CD40 mAb and anti-PD-1 combination-treated group. It is envisioned that the fabrication of antibody-like superstructures in vivo provides an efficient platform for modulating the duration of immune response to achieve optimal therapeutic efficacy.


Assuntos
Células Dendríticas , Neoplasias , Animais , Antígenos CD40 , Imunoterapia/métodos , Camundongos , Neoplasias/tratamento farmacológico , Peptídeos/farmacologia
11.
J Mater Chem B ; 10(19): 3624-3636, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35420616

RESUMO

Burn injuries without the normal skin barrier usually cause skin wound infections, and wound dressings are necessary. Although various dressings with antibacterial ability have already been developed, the biosafety and administration mode are still bottleneck problems for further application. Herein, we designed skin-like wound dressings based on silk fibroin (SF), which are modified with the gelatinase-cleavable self-assembled/antibacterial peptide (GPLK) and epidermal growth factor (EGF). When a skin wound is infected, the gelatinase over-secreted by bacteria can cut the GPLK peptides, leading to the in situ self-assembly of peptides and the resultant high-efficiency sterilization. Compared with the commercial antibacterial dressing, the SF-GPLK displayed a faster wound healing rate. When a skin wound is not infected, the GPLK peptides remain in the SF, realizing good biosafety. Generally, the EGF can be released to promote wound healing and skin regeneration in both cases. Therefore, skin-like SF-GPLK wound dressings with on-demand release of antibacterial peptides provide a smart administration mode for clinical wound management and skin regeneration.


Assuntos
Fator de Crescimento Epidérmico , Fibroínas , Antibacterianos/farmacologia , Bandagens , Fator de Crescimento Epidérmico/farmacologia , Gelatinases , Peptídeos , Cicatrização
12.
J Comput Chem ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35420170

RESUMO

Actinoid tetroxide molecules AnO4 (An = Ac - Cm) are investigated with the ab initio density matrix renormalization group (DMRG) approach. Natural orbital shapes are used to read out the oxidation state (OS) of the f-elements, and the atomic orbital energies and radii are used to explain the trends. The highest OSs reveal a "volcano"-type variation: For An = Ac - Np, the OSs are equal to the number of available valence electrons, that is, AcIII , ThIV , PaV , UVI , and NpVII . Starting with plutonium as the turning point, the highest OSs in the most stable AnO4 isomers then decrease as PuV , AmV , and CmIII , indicating that the 5f-electrons are hard to be fully oxidized off from Pu onward. The variations are related to the actinoid contraction and to the 5f-covalency characteristics. Combined with previous work on OSs, we review their general trends throughout the periodic table, providing fundamental understanding of OS-relevant phenomena.

13.
Bioact Mater ; 14: 110-119, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35310363

RESUMO

Intraoperative fluorescence-based tumor imaging plays a crucial role in performing the oncological safe tumor resection with the advantage of differentiating tumor from normal tissues. However, the application of these fluorescence contrast agents in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) was dramatically hammered as a result of lacking active targeting and poor retention time in tumor, which limited the Signal to Noise Ratio (SNR) and narrowed the imaging window for complicated surgery. Herein, we reported an activated excretion-retarded tumor imaging (AERTI) strategy, which could be in situ activated with MMP-2 and self-assembled on the surface of tumor cells, thereby resulting in a promoted excretion-retarded effect with an extended tumor retention time and enhanced SNR. Briefly, the AERTI strategy could selectively recognize the Integrin αvß3. Afterwards, the AERTI strategy would be activated and in situ assembled into nanofibrillar structure after specifically cleaved by MMP-2 upregulated in a variety of human tumors. We demonstrated that the AERTI strategy was successfully accumulated at the tumor sites in the 786-O and HepG2 xenograft models. More importantly, the modified modular design strategy obviously enhanced the SNR of AERTI strategy in the imaging of orthotopic RCC and HCC. Taken together, the results presented here undoubtedly confirmed the design and advantage of this AERTI strategy for the imaging of tumors in metabolic organs.

15.
Toxins (Basel) ; 14(3)2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35324670

RESUMO

Aflatoxin M1 (AFM1) and ochratoxin A (OTA), which are occasionally detected in milk and commercial baby foods, could easily enter and reach the gastrointestinal tract, posing impairment to the first line of defense and causing dysfunction of the tissue. The objective of this study was to investigate the immunostimulatory roles of individual and combined AFM1 and OTA on the immature intestine. Thus, we used ELISA assays to evaluate the generation of cytokines from ex vivo CD-1 fetal mouse jejunum induced by AFM1 and OTA and explored the related regulatory pathways and pivot genes using RNA-seq analysis. It was found that OTA exhibited much stronger ability in stimulating pro-inflammatory cytokine IL-6 from jejunum tissues than AFM1 (OTA of 4 µM versus AFM1 of 50 µM), whereas the combination of the two toxins seemed to exert antagonistic actions. In addition, transcriptomics also showed that most gene members in the enriched pathway 'cytokine-cytokine receptor interaction' were more highly expressed in OTA than the AFM1 group. By means of PPI network analysis, NFKB1 and RelB were regarded as hub genes in response to OTA but not AFM1. In the human FHs 74 Int cell line, both AFM1 and OTA enhanced the content of reactive oxygen species, and the oxidative response was more apparent in OTA-treated cells in comparison with AFM1. Furthermore, OTA and AFM1 + OTA raised the protein abundance of p50/RelB, and triggered the translocation of the dimer from cytosol to nucleus. Therefore, the experimental data ex vivo and in vitro showed that OTA-induced inflammation was thought to be bound up with the up-regulation and translocation of NF-κB, though AFM1 seemed to have no obvious impact. Since it was the first attempt to uncover the appearances and inner mechanisms regarding inflammation provoked by AFM1 and OTA on immature intestinal models, further efforts are needed to understand the detailed metabolic steps of the toxin in cells and to clarify their causal relationship with the signals proposed from current research.


Assuntos
Aflatoxina M1 , Intestinos , Aflatoxina M1/análise , Animais , Citocinas/genética , Contaminação de Alimentos/análise , Inflamação/induzido quimicamente , Intestinos/química , Camundongos , Leite/química , Ocratoxinas
16.
Protoplasma ; 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35277781

RESUMO

Glutamic acid (Glu) is not only an important protein building block, but also a signaling molecule in plants. However, the Glu-boosted thermotolerance and its underlying mechanisms in plants still remain unclear. In this study, the maize seedlings were irrigated with Glu solution prior to exposure to heat stress (HS), the seedlings' thermotolerance as well as osmoregulation, glyoxalase, and non-glyoxalase systems were evaluated. The results manifested that the seedling survival and tissue vitality after HS were boosted by Glu, while membrane damage was reduced in comparison with the control seedlings without Glu treatment, indicating Glu boosted the thermotolerance of maize seedlings. Additionally, root-irrigation with Glu increased its endogenous level, reinforced osmoregulation system (i.e., an increase in the levels of proline, glycine betaine, trehalose, and total soluble sugar, as well as the activities of pyrroline-5-carboxylate synthase, betaine dehydrogenase, and trehalose-5-phosphate phosphatase) in maize seedlings under non-HS and HS conditions compared with the control. Also, Glu treatment heightened endogenous methylglyoxal level and the activities of glyoxalase system (glyoxalase I, glyoxalase II, and glyoxalase III) and non-glyoxalase system (methylglyoxal reductase, lactate dehydrogenase, aldo-ketoreductase, and alkenal/alkenone reductase) in maize seedlings under non-HS and HS conditions as compared to the control. These data hint that osmoregulation, glyoxalase, and non-glyoxalase systems are involved in signaling molecule Glu-boosted thermotolerance of maize seedlings.

17.
BMC Med Educ ; 22(1): 154, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35255878

RESUMO

BACKGROUND: Undergraduate medical (UM) students faced the difficulties inherent in medical careers due to the coronavirus (COVID-19) outbreak. Thus, imperative containment measures might affect UM students' career intentions. Information on the factors that may be associated with these students' career change intentions is limited. METHODS: We conducted a cross-sectional survey in August 2020 to investigate the impact of the COVID-19 pandemic on career intention and the associated factors in UM students. Univariate analyses and logistic regression analysis were performed to identify said factors. RESULTS: A total of 2040 medical students from the Hubei University of Medicine were surveyed. Univariate analyses showed that grade, attitude towards healthcare, and the degree of the COVID-19 pandemic's impact on the students' lives were associated with changes in career choice (P<0.05). Logistic regression analysis showed that Grade 2, Grade 5, attitude towards a medical career, and having relatives with a medical background were associated with changes in career choice. The degree of the COVID-19 pandemic's impact was a common and significant factor associated with career preference, career perspective, and ideal workplace. CONCLUSIONS: Changes in career intentions were particularly influenced by grade, attitude towards being a health worker, and the degree of COVID-19's impact on the participants' lives. Treating large-scale public health emergencies rationally, setting up correct views of occupation choice, and building reasonable career planning may reduce the loss of medical talent.


Assuntos
COVID-19 , Estudantes de Medicina , COVID-19/epidemiologia , Escolha da Profissão , Estudos Transversais , Humanos , Intenção , Ocupações , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
18.
Toxins (Basel) ; 14(2)2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35202168

RESUMO

Aflatoxin M1 (AFM1) is the only toxin with the maximum residue limit in milk, and ochratoxin A (OTA) represents a common toxin in cereals foods. It is common to find the co-occurrence of these two toxins in the environment. However, the interactive effect of these toxins on hepatoxicity and underlying mechanisms is still unclear. The liver and serum metabolomics in mice exposed to individual AFM1 at 3.5 mg/kg b.w., OTA at 3.5 mg/kg b.w., and their combination for 35 days were conducted based on the UPLC-MS method in the present study. Subsequent metabolome on human hepatocellular liver carcinoma (Hep G2) cells was conducted to narrow down the key metabolites. The phenotypic results on liver weight and serum indicators, such as total bilirubin and glutamyltransferase, showed that the combined toxins had more serious adverse effects than an individual one, indicating that the combined AFM1 and OTA displayed synergistic effects on liver damage. Through the metabolic analysis in liver and serum, we found that (i) a synergistic effect was exerted in the combined toxins, because the number of differentially expressed metabolites on combination treatment was higher than the individual toxins, (ii) OTA played a dominant role in the hepatoxicity induced by the combination of AFM1, and OTA and (iii) lysophosphatidylcholines (LysoPCs), more especially, LysoPC (16:1), were identified as the metabolites most affected by AFM1 and OTA. These findings provided a new insight for identifying the potential biomarkers for the hepatoxicity of AFM1 and OTA.


Assuntos
Aflatoxina M1/metabolismo , Aflatoxina M1/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Metabolômica , Ocratoxinas/metabolismo , Ocratoxinas/toxicidade , Animais , Modelos Animais de Doenças , Contaminação de Alimentos , Humanos , Masculino , Camundongos
19.
Angew Chem Int Ed Engl ; 61(18): e202116893, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35181975

RESUMO

Intravesical administration of first-line drugs has shown failure in the treatment of bladder cancer owing to the poor tumor retention time of chemotherapeutics. Herein, we report an intracellular hydrolytic condensation (IHC) system to construct long-term retentive nano-drug depots in situ, wherein sustained drug release results in highly efficient suppression of bladder cancer. Briefly, the designed doxorubicin (Dox)-silane conjugates self-assemble into silane-based prodrug nanoparticles, which condense into silicon particle-based nano-drug depots inside tumor cells. Significantly, we demonstrate that the IHC system possesses highly potent antitumor efficacy, which leads to the regression and eradication of large established tumors and simultaneously extends the overall survival of air pouch bladder cancer mice compared with that of mice treated with Dox. The concept of intracellular hydrolytic condensation can be extended via conjugating other chemotherapeutic drugs, which may facilitate rational design of novel nanomedicines for augmentation of chemotherapy.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias da Bexiga Urinária , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Masculino , Camundongos , Nanopartículas/uso terapêutico , Silanos , Neoplasias da Bexiga Urinária/tratamento farmacológico
20.
Neurol Sci ; 43(6): 3901-3910, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35137351

RESUMO

OBJECTIVE: To investigate the potential detection rate of anti-thyroid antibodies' (ATAbs) positivity, thyroid dysfunctions, and autoimmune thyroid diseases (AITDs) in autoimmune encephalitis (AE) and to analyze whether thyroid autoimmunity/dysfunction can affect the clinical course of AE. METHODS: Two hundred twenty-one AE patients and 229 age- and sex-matched controls were included in this study. We measured the levels of ATAbs (anti-thyroglobulin antibodies [TgAb], anti-thyroid peroxidase anti-bodies [TPOAb]) and thyroid hormones in all the individuals. In addition, the association of thyroid autoimmunity/dysfunctions with functional outcomes of AE was identified by using logistic regression and Kaplan-Meier analyses. RESULTS: The prevalence of TPOAb-positive and TgAb-positive was significantly higher in AE patients (16.3% and 16.7%, respectively) as compared with controls (9.6% and 7.4%, respectively; P = 0.034 and P = 0.002, respectively). In addition, the free triiodothyronine (fT3) level was significantly lower in AE patients as compared to the controls (P < 0.001). However, the frequency of AITDs (Hashimoto's thyroiditis and Graves' disease) did not significantly differ between AE patients and control subjects. Importantly, low fT3 was found to be associated with poor functional outcomes at the 3-month follow-up in AE. Adjustment of potential confounders did not change the association. However, the presence of ATAbs did not significantly alert the disease course of AE. CONCLUSIONS: ATAbs-positive and/or AITD patients with symptomatic encephalopathy should undergo proper surveillance for AE. Moreover, low fT3 could serve as a possible predictor of poor short-term outcome in AE, thereby suggesting that monitoring of thyroid function in AE may be necessary.


Assuntos
Encefalite , Doença de Hashimoto , Doenças da Glândula Tireoide , Autoanticorpos , Encefalite/diagnóstico , Doença de Hashimoto/diagnóstico , Humanos , Estudos Retrospectivos , Doenças da Glândula Tireoide/complicações
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