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1.
Comput Biol Med ; 169: 107952, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38194779

RESUMO

Diabetes, a common chronic disease worldwide, can induce vascular complications, such as coronary heart disease (CHD), which is also one of the main causes of human death. It is of great significance to study the factors of diabetic patients complicated with CHD for understanding the occurrence of diabetes/CHD comorbidity. In this study, by analyzing the risk of CHD in more than 300,000 diabetes patients in southwest China, an artificial intelligence (AI) model was proposed to predict the risk of diabetes/CHD comorbidity. Firstly, we statistically analyzed the distribution of four types of features (basic demographic information, laboratory indicators, medical examination, and questionnaire) in comorbidities, and evaluated the predictive performance of three traditional machine learning methods (eXtreme Gradient Boosting, Random Forest, and Logistic regression). In addition, we have identified nine important features, including age, WHtR, BMI, stroke, smoking, chronic lung disease, drinking and MSP. Finally, the model produced an area under the receiver operating characteristic curve (AUC) of 0.701 on the test samples. These findings can provide personalized guidance for early CHD warning for diabetic populations.


Assuntos
Doença das Coronárias , Diabetes Mellitus , Humanos , Inteligência Artificial , Diabetes Mellitus/diagnóstico , Doença das Coronárias/epidemiologia , Doença das Coronárias/etiologia , China/epidemiologia , Aprendizado de Máquina
2.
Adv Sci (Weinh) ; 11(9): e2306923, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38088530

RESUMO

Transition metal-catalyzed direct decarboxylative transformations of aromatic carboxylic acids usually require high temperatures, which limit the substrate's scope, especially for late-stage applications. The development of the selective decarbonylative of carboxylic acid derivatives, especially the most fundamental aroyl chlorides, with stable and cheap electrophiles under mild conditions is highly desirable and meaningful, but remains challenging. Herein, a strategy of nickel-catalyzed decarbonylative alkylation of aroyl chlorides via phosphine/nitrogen ligand relay is reported. The simple phosphine ligand is found essential for the decarbonylation step, while the nitrogen ligand promotes the cross-electrophile coupling. Such a ligand relay system can effectively and orderly carry out the catalytic process at room temperature, utilizing easily available aroyl chlorides as an aryl electrophile for reductive alkylation. This discovery provides a new strategy for direct decarbonylative coupling, features operationally simple, mild conditions, and excellent functional group tolerance. The mild approach is applied to the late-stage methylation of various pharmaceuticals. Extensive experiments are carried out to provide insights into the reaction pathway and support the ligand relay process.

3.
Org Lett ; 25(23): 4329-4334, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37262417

RESUMO

An inexpensive iron-catalyzed alkoxyl radical-induced C-C bond cleavage/gem-difluoroalkylation cascade is presented. Regulated by the structure of alkoxyl radical precursors, fluorinated distal diketones were synthesized through a ring-opening strategy and difluoroalkylated medium-sized lactones and macrolactones were constructed via a ring-expansion strategy. Both protocols proceeded under mild and redox neutral conditions with a broad substrate scope and good functional group compatibility.


Assuntos
Ferro , Cetonas , Lactonas , Catálise
4.
Dalton Trans ; 52(15): 4737-4751, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-36942929

RESUMO

Twenty new zinc(II) complexes with 8-hydroxyquinoline (H-Q1-H-Q6) in the presence of 1,10-phenanthroline derivatives (D1-D10) were synthesized and formulated as [Zn(Q1)2(D1)] (DQ1), [Zn(Q2)2(D2)]·CH3OH (DQ2), [Zn(Q1)2(D3)] (DQ3), [Zn(Q1)2(D4)] (DQ4), [Zn(Q3)2(D5)] (DQ5), [Zn(Q3)2(D4)] (DQ6), [Zn(Q4)2(D5)]·CH3OH (DQ7), [Zn(Q4)2(D6)] (DQ8), [Zn(Q4)2(D3)]·CH3OH (DQ9), [Zn(Q4)2(D1)]·H2O (DQ10), [Zn(Q5)2(D4)] (DQ11), [Zn(Q6)2(D6)]·CH3OH (DQ12), [Zn(Q5)2(D2)]·5CH3OH·H2O (DQ13), [Zn(Q5)2(D7)]·CH3OH (DQ14), [Zn(Q5)2(D8)]·CH2Cl2 (DQ15), [Zn(Q5)2(D9)] (DQ16), [Zn(Q5)2(D1)] (DQ17), [Zn(Q5)2(D5)] (DQ18), [Zn(Q5)2(D10)]·CH2Cl2 (DQ19) and [Zn(Q5)2(D3)] (DQ20). They were characterized using multiple techniques. The cytotoxicity of DQ1-DQ20 was screened using human cisplatin-resistant SK-OV-3/DDP ovarian cancer (SK-OV-3CR) cells and normal hepatocyte (HL-7702) cells. Complex DQ6 showed low IC50 values (2.25 ± 0.13 µM) on SK-OV-3CR cells, more than 3.0-8.0 times more cytotoxic than DQ1-DQ5 and DQ7-DQ20 (≥6.78 µM), and even 22.2 times more cytotoxic than the standard cisplatin, the corresponding free H-Q1-H-Q6 and D1-D10 alone (>50 µM). As a comparison, DQ1-DQ20 displayed nontoxic rates against healthy HL-7702 cells. Furthermore, DQ6 and DQ11 induced significant apoptosis via mitophagy pathways. DQ6 also significantly inhibited tumor growth in an in vivo SK-OV-3-xenograft model (ca. 49.7%). Thus, DQ6 may serve as a lead complex for the discovery of new antitumor agents.


Assuntos
Antineoplásicos , Cisplatino , Humanos , Zinco/farmacologia , Oxiquinolina/farmacologia , Antineoplásicos/farmacologia
5.
Biomech Model Mechanobiol ; 22(2): 467-478, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36513945

RESUMO

Studying the insertion process of cochlear implant (CI) electrode array (EA) is important to ensure successful, sufficient, and safe implantation. A three-dimensional finite element (FE) model was developed to simulate the insertion process. The cochlear structures were reconstructed from an average statistical shape model (SSM) of human cochlea. The electrode is simplified as a long and tapered beam of homogeneous elastic materials, contacting and interacting with the stiff cochlear structures. A quasi-static insertion simulation was conducted, the insertion force and the contact pressure between the electrode and the cochlear wall, were calculated to evaluate the smoothness of insertion and the risk of potential cochlear trauma. Based on this model, different EA designs were analyzed, including the Young's modulus, the straight or bended shape, the normal or a more tapped section size. The influence of the insertion angle was also discussed. Our simulations indicate that reducing the EA Young's modulus, tapering and pre-bending are effective ways to ensure safe and successful EA implantation. This model is beneficial for optimizing EA designs and is potentially useful for designing patient-specific CI surgery.


Assuntos
Implante Coclear , Implantes Cocleares , Humanos , Implante Coclear/métodos , Análise de Elementos Finitos , Cóclea , Eletrodos Implantados
6.
Plant Cell Environ ; 46(2): 567-591, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36358019

RESUMO

Wheat plants are ubiquitously simultaneously exposed to salinity and limited iron availability caused by soil saline-alkalisation. Through this study, we found that both low Fe and NaCl severely inhibited the growth of seminal roots in wheat seedlings; however, sufficient Fe caused greater growth cessation of seminal roots than low Fe under salt stress. Low Fe improved the root meristematic division activity, not altering the mature cell sizes compared with sufficient Fe under salt stress. Foliar Fe spray and split-root experiments showed that low Fe-alleviating the salinity-induced growth cessation of seminal roots was dependent on local low Fe signals in the roots. Ionomics combined with TEM/X-ray few differences in the root Na+ uptake and vacuolar Na+ sequestration between two Fe levels under salt stress. Phytohormone profiling and metabolomics revealed salinity-induced overaccumulation of ACC/ethylene and tryptophan/auxin in the roots under sufficient Fe than under low Fe. Differential gene expression, pharmacological inhibitor addition and the root growth performance of transgenic wheat plants revealed that the rootward auxin efflux and was responsible for the low Fe-mediated amelioration of the salinity-induced growth cessation of seminal roots. Our findings will provide novel insights into the modulation of crop root growth under salt stress.


Assuntos
Plântula , Triticum , Plântula/metabolismo , Triticum/genética , Salinidade , Plantas Geneticamente Modificadas , Ferro/metabolismo , Ácidos Indolacéticos/metabolismo , Raízes de Plantas/metabolismo
7.
J Exp Bot ; 73(22): 7516-7537, 2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-36063365

RESUMO

Cadmium (Cd) is a highly toxic heavy metal that readily enters cereals, such as wheat, via the roots and is translocated to the shoots and grains, thereby posing high risks to human health. However, the vast and complex genome of allohexaploid wheat makes it challenging to understand Cd resistance and accumulation. In this study, a Cd-resistant cultivar of wheat, 'ZM1860', and a Cd-sensitive cultivar, 'ZM32', selected from a panel of 442 accessions, exhibited significantly different plant resistance and grain accumulation. We performed an integrated comparative analysis of the morpho-physiological traits, ionomic and phytohormone profiles, genomic variations, transcriptomic landscapes, and gene functionality in order to identify the mechanisms underlying these differences. Under Cd toxicity, 'ZM1860' outperformed 'ZM32', which showed more severe leaf chlorosis, poorer root architecture, higher accumulation of reactive oxygen species, and disordered phytohormone homeostasis. Ionomics showed that 'ZM32' had a higher root-to-shoot translocation coefficient of Cd and accumulated more Cd in the grains than 'ZM1860'. Whole-genome re-sequencing (WGS) and transcriptome sequencing identified numerous DNA variants and differentially expressed genes involved in abiotic stress responses and ion transport between the two genotypes. Combined ionomics, transcriptomics, and functional gene analysis identified the plasma membrane-localized heavy metal ATPase TaHMA2b-7A as a crucial Cd exporter regulating long-distance Cd translocation in wheat. WGS- and PCR-based analysis of sequence polymorphisms revealed a 25-bp InDel site in the promoter region of TaHMA2b-7A, and this was probably responsible for the differential expression. Our multiomics approach thus enabled the identification of a core transporter involved in long-distance Cd translocation in wheat, and it may provide an elite genetic resource for improving plant Cd resistance and reducing grain Cd accumulation in wheat and other cereal crops.


Assuntos
Cádmio , Triticum , Multiômica , Triticum/genética
8.
Aesthetic Plast Surg ; 46(4): 1706-1712, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35386006

RESUMO

OBJECTIVE: Temporoparietal fascia is important for auricular reconstruction or repair after auricular reconstruction. Thus, the course of the superficial temporal artery (STA) is of vital importance to prevent destruction of the artery. The purpose of this study was to evaluate the course of the superficial temporal artery in patients with congenital microtia and its relationship with remnants. METHODS: This was a prospective study. Patients with microtia who underwent auricular reconstruction in our hospital from January 2021 to July 2021 underwent ultrasound examination of the STA. Under the guidance of ultrasound, the superficial temporal artery and its branches were located and marked on the body surface before the operation, ranging from the zygomatic arch plane to the temporal parietal artery. In addition, the hemodynamics of the STAs were recorded. RESULTS: A total of 108 patients with microtia were collected, including 106 patients with unilateral microtia and 2 patients with bilateral microtia. There were 82 cases of lobule type, 21 cases of small concha type, and 7 cases of large concha type. The superficial temporal artery in 103 ears was divided into two branches: the parietal branch and the frontal branch, but there was only one branch in 7 ears. The parietal branch was absent in 5 cases, and the frontal branch was absent in 2 cases. In most of the ears, the bifurcation was located above the zygomatic arch plane. Only in 2 ears was the bifurcation located below the zygomatic arch, and the most common bifurcation position was the eyebrow arch level (43.7%). Regarding the shortest distances between the STA and the remnant, they were less than 0.5 cm in 47 ears, more than 1 cm in 30 ears, and 0.5 cm to 1 cm in 33 ears. CONCLUSION: The course of STA varied greatly and there were occasional single branches. The distances between the STA and remnant were often near 0.5 cm by ultrasonography. Therefore, when removing the remnant and separating the pocket, care should be taken to avoid arterial injury. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Microtia Congênita , Pavilhão Auricular , Procedimentos de Cirurgia Plástica , Microtia Congênita/diagnóstico , Microtia Congênita/cirurgia , Pavilhão Auricular/diagnóstico por imagem , Pavilhão Auricular/cirurgia , Humanos , Estudos Prospectivos , Artérias Temporais , Zigoma/cirurgia
9.
Sci Rep ; 12(1): 5712, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35383254

RESUMO

Pulmonary cryptococcosis (PC) is a common fungal infectious disease, and infection can occur in patients with any immune function. To better understand PC, we compared the CT findings and histopathological results in immunocompetent and immunocompromised patients. The clinical data of 68 patients with PC were collected retrospectively and divided into the immunocompetent group and immunocompromised group. The clinical characteristics, CT manifestations and histopathological characteristics of the two groups of patients were compared. Forty-two patients (61.8%) were immunocompetent, and 26 patients (38.2%) were immunocompromised. Compared with immunocompromised patients, 57.14% (24/42) of immunocompetent patients were asymptomatic (p = 0.002). Compared with immunocompetent patients, cough (14/26, 53.9%) and fever (13/26, 50.0%) were the main symptoms in immunocompromised patients (p = 0.044, p = 0.007). Nodular lesions (97.6%, 41/42) were the most common CT type in immunocompetent patients, and the CT characteristic was a single lesion (25/42, 59.5%); the main histopathological type was nodular fibrogranuloma (30/42, 71.4%), and the main histopathological characteristic was inflammatory granuloma (31/42, 73.81%) formed by macrophage phagocytosis of Cryptococcus. Consolidation (15/26, 57.7%) was more common in the CT type of immunocompromised patients. Multiple lesions (24/26, 92.31%), air bronchial signs (19/26, 73.081%) and cavities (9/26, 34.62%) were the main CT characteristics. The mucinous colloid type (19/26, 73.1%) was its main histopathological type, which was mainly characterized by a small amount of surrounding inflammatory cell infiltration (17/26, 65.4%). There were significant differences in the classification and characteristics of CT and pathology between the two groups (p < 0.05). Through the CT manifestations and histopathological characteristics of PC under different immune function states, it was found that immune function has a significant impact on the CT manifestations and histopathological characteristics of patients with PC.


Assuntos
Criptococose , Pneumopatias Fúngicas , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
10.
Acta Pharmacol Sin ; 43(10): 2666-2677, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35228654

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high vascularity and frequent metastasis. Tumor-associated abnormal vasculature was reported to accelerate TNBC metastasis. Scutellarin (SC) is a natural flavonoid with a cardiovascular protective function. In this study, SC reduced TNBC metastasis and alleviated tumor-associated vascular endothelial barrier injury in vivo. SC rescued the tumor necrosis factor-α (TNFα)-induced diminishment of endothelial junctional proteins and dysfunction of the endothelial barrier in vitro. SC reduced the increased transendothelial migration of TNBC cells through a monolayer composed of TNFα-stimulated human mammary microvascular endothelial cells (HMMECs) or human umbilical vein endothelial cells (HUVECs). TNFα induced the nuclear translocation of enhancer of zeste homolog-2 (EZH2), and its chemical inhibitor GSK126 blocked TNFα-induced endothelial barrier disruption and subsequent TNBC transendothelial migration. TNF receptor 2 (TNFR2) is the main receptor by which TNFα regulates endothelial barrier breakdown. Extracellular signal-regulated protein kinase (ERK)1/2 was found to be downstream of TNFα/TNFR2 and upstream of EZH2. Additionally, SC abrogated the TNFR2-ERK1/2-EZH2 signaling axis both in vivo and in vitro. Our results suggest that SC reduced TNBC metastasis by suppressing TNFα-initiated vascular endothelial barrier breakdown through rescuing the reduced expression of junctional proteins by regulating the TNFR2-ERK1/2-EZH2 signaling pathway.


Assuntos
Neoplasias de Mama Triplo Negativas , Apigenina/farmacologia , Linhagem Celular Tumoral , Glucuronatos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Proteínas Quinases , Receptores Tipo II do Fator de Necrose Tumoral , Neoplasias de Mama Triplo Negativas/patologia , Fator de Necrose Tumoral alfa/metabolismo
12.
Stem Cell Rev Rep ; 18(2): 660-671, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34787794

RESUMO

BACKGROUND: Tissue ischemia usually leads to necrosis and is a threatening condition associated with reconstructive surgery. Promoting the survival of ischemic tissue is critical for improving clinical outcomes. Although various solutions based on stem cells have been reported, there are still limitations to clinical translation. The aim of this study was to develop an effective method to promote the survival of ischemic tissue. METHODS: Adipose-derived CD34 + and CD34- cells were obtained by magnetic bead sorting from the stromal vascular faction (SVF). Adipose-derived stem cells (ADSCs) were collected by subculture. The angiogenic capacities of CD34 + cells, CD34- cells and ADSCs were evaluated in vitro by comparing mRNA and protein expression. Random axial flaps in nude mice were used to evaluate the efficacy of these cells in protecting tissue from necrosis. The effect of these cells in preventing inflammation was also evaluated. RESULTS: Our data suggest that CD34 + cells expressed higher levels of angiogenetic factors and lower levels of inflammatory factors than the other cell types. More vessel branches were formed when human umbilical vein endothelial cells (HUVECs) were treated with conditioned medium from CD34 + cells than conditioned medium from the other cell types. Compared to ADSCs, CD34 + cells showed significantly higher efficacy in promoting tissue survival. More CD31 + cells and higher levels of angiogenic factors were observed in tissues from the CD34 + group than in those from the other groups. Lower levels of the proinflammatory factors TNF-α and IL-1b and higher levels of anti-inflammatory factors were found in the CD34 + group than in the other groups. CONCLUSION: Adipose-derived CD34 + cells showed better efficacy in improving ischemic tissue survival than ADSCs by reducing tissue inflammation and promoting angiogenesis. CD34 + cells can be obtained easily and may be suitable for clinical applications.


Assuntos
Neovascularização Fisiológica , Células-Tronco , Animais , Antígenos CD34/metabolismo , Células Cultivadas , Meios de Cultivo Condicionados/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/metabolismo , Isquemia/metabolismo , Isquemia/terapia , Camundongos , Camundongos Nus , Necrose/metabolismo , Sobrevivência de Tecidos
13.
BMC Plant Biol ; 21(1): 372, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388971

RESUMO

BACKGROUND: Oilseed rape (B. napus L.) has great potential for phytoremediation of cadmium (Cd)-polluted soils due to its large plant biomass production and strong metal accumulation. Soil properties and the presence of other soluble compounds or ions, cause a heterogeneous distribution of Cd. RESULTS: The aim of our study was to reveal the differential responses of B. napus to different Cd abundances. Herein, we found that high Cd (50 µM) severely inhibited the growth of B. napus, which was not repressed by low Cd (0.50 µM) under hydroponic culture system. ICP-MS assays showed that the Cd2+ concentrations in both shoots and roots under 50 µM Cd were over 10 times higher than those under 0.50 µM Cd. Under low Cd, the concentrations of only shoot Ca2+/Mn2+ and root Mn2+ were obviously changed (both reduced); under high Cd, the concentrations of most cations assayed were significantly altered in both shoots and roots except root Ca2+ and Mg2+. High-throughput transcriptomic profiling revealed a total of 18,021 and 1408 differentially expressed genes under high Cd and low Cd conditions, respectively. The biological categories related to the biosynthesis of plant cell wall components and response to external stimulus were over-accumulated under low Cd, whereas the terms involving photosynthesis, nitrogen transport and response, and cellular metal ion homeostasis were highly enriched under high Cd. Differential expression of the transporters responsible for Cd uptake (NRAMPs), transport (IRTs and ZIPs), sequestration (HMAs, ABCs, and CAXs), and detoxification (MTPs, PCR, MTs, and PCSs), and some other essential nutrient transporters were investigated, and gene co-expression network analysis revealed the core members of these Cd transporters. Some Cd transporter genes, especially NRAMPs and IRTs, showed opposite responsive patterns between high Cd and low Cd conditions. CONCLUSIONS: Our findings would enrich our understanding of the interaction between essential nutrients and Cd, and might also provide suitable gene resources and important implications for the genetic improvement of plant Cd accumulation and resistance through molecular engineering of these core genes under varying Cd abundances in soils.


Assuntos
Brassica napus/genética , Brassica napus/metabolismo , Cádmio/metabolismo , Transporte Biológico , Brassica napus/crescimento & desenvolvimento , Quelantes/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Íons/metabolismo , Solo/química , Tetraploidia , Transcriptoma
14.
Eur J Pharmacol ; 906: 174205, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34048740

RESUMO

The K+-Cl- co-transporter 2 (KCC2) is a neuron-specific Cl- extruder in the dorsal horn of spinal cord. The low intracellular Cl- concentration established by KCC2 is critical for GABAergic and glycinergic systems to generate synaptic inhibition. Peripheral nerve lesions have been shown to cause KCC2 dysfunction in adult spinal cord through brain-derived neurotrophic factor (BDNF) signaling, which switches the hyperpolarizing inhibitory transmission to be depolarizing and excitatory. However, the mechanisms by which BDNF impairs KCC2 function remain to be elucidated. Here we found that BDNF treatment enhanced KCC2 ubiquitination in the dorsal horn of adult mice, a post-translational modification that leads to KCC2 degradation. Our data showed that spinal BDNF application promoted KCC2 interaction with Casitas B-lineage lymphoma b (Cbl-b), one of the E3 ubiquitin ligases that are involved in the spinal processing of nociceptive information. Knockdown of Cbl-b expression decreased KCC2 ubiquitination level and attenuated the pain hypersensitivity induced by BDNF. Spared nerve injury significantly increased KCC2 ubiquitination, which could be reversed by inhibition of TrkB receptor. Our data implicated that KCC2 was one of the important pain-related substrates of Cbl-b and that ubiquitin modification contributed to BDNF-induced KCC2 hypofunction in the spinal cord.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hiperalgesia/patologia , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Corno Dorsal da Medula Espinal/patologia , Simportadores/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Hiperalgesia/etiologia , Masculino , Camundongos , Células do Corno Posterior/metabolismo , Proteólise , Proteínas Proto-Oncogênicas c-cbl/genética , Transdução de Sinais , Corno Dorsal da Medula Espinal/citologia , Ubiquitinação , Cotransportadores de K e Cl-
16.
Orthop Surg ; 13(1): 202-206, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33438343

RESUMO

OBJECTIVE: Lumbar spondylolisthesis (LS) is a common lumbar disease, and the prevalence of LS in different countries or regions was not consistent in the past. This study intends to make statistics on the prevalence of lumbar spondylolisthesis in middle-aged people in Beijing community. METHODS: This is an epidemiological study. 4548 people in Beijing community aged 50 to 64 years were recruited from the local communities by advertisements placed in housing estates and community centres for people to take part in a prospective cohort study from August from September 2013 to March 2014. There is no intervention on the subjects. RadiAnt DICOM Viewer is adopted to read the lateral CT positioning images of all the studied objects, adjust the image as bone window, observe and evaluate the slide of L1 to L5 vertebra in the lateral CT positioning image. RESULTS: Among the 4,548 subjects included in the study, 2,490 (54.75%) were male and 2,058 (45.25%) were female. A total of 785 subjects had lumbar spondylolisthesis, with a total incidence of 17.26%. There was no significant difference between prevalence of males and females in the subgroup 50-54 years old (13.55% males / 12.53% females) and 55-59 years old (14.77% males / 14.93% females). But the prevalence of LS in 60-64 years old females (28.57%) increased significantly, compared with 55-59 years old females (14.93%) and 60-64 years old males (18.76%). There were 847 levels that had slipped, L5S1 > L4/5 > L3/4 > L2/3 > L1/2. The retrolisthesis was the most, accounting for 61.51% (521/847), and the anterolisthesis was 38.49% (326/847), including anterolisthesis gradeI for 95.71% (312/326), anterolisthesis gradeII for 4.29% (14/326). Neither of anterolisthesis and retrolisthesis presented more than grade III. Among all the subjects, 318 had anterolisthesis, with a total incidence of 6.99%, and 467 subjects only had retrolisthesis. CONCLUSION: The total prevalence of LS in the middle-aged people in Beijing community was 17.26%, 15.98% in males and 18.80% in females, and women are more likely to suffer from LS after 60 years old.


Assuntos
Vértebras Lombares/fisiopatologia , Espondilolistese/epidemiologia , Pequim/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
17.
Cancer Immunol Immunother ; 70(2): 463-474, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32809049

RESUMO

Dendritic cell (DC) vaccine has been proved to be an effective way in cancer immunotherapy in both preclinical and clinical studies. However, limitations in DC isolation and culture have hampered its practice and promoted the development of other antigen-presenting cells (APCs) sources to fulfill that role. Our previous studies have shown that B cells loaded by tumor cell-derived autophagosomes, which we named as DRibbles (defective ribosomal products-containing blebs), could reactivate DC-induced effector T cell response. In this study, the roles of DRibble-loaded B cells in priming naïve CD8+ T cell responses and controlling tumors were investigated. We found that high-mobility group box 1 protein (HMGB1) on DRibbles was involved in DRibble-induced B cell activation, and the DRibble-triggered B cell phagocytosis via the caveolae-mediated endocytosis pathway. By using OT-I mouse-derived T cells, we demonstrated that DRibble-loaded B cells could activate specific naïve CD8+ T cells in vitro and ex vivo. In a tumor-bearing mouse model, DRibble-loaded B cells elicited systemic antitumor immunity and significantly suppressed the tumor growth. Moreover, the antitumor efficacy of DRibble-loaded B cells was enhanced when they were combined with CpG and anti-CD40 stimulation. These results suggest that DRibble-loaded B cells represent a viable and practical therapeutic vaccination strategy that might have important clinical implications for tumor immunotherapy.


Assuntos
Autofagossomos/imunologia , Linfócitos B/imunologia , Vacinas Anticâncer/uso terapêutico , Células Dendríticas/metabolismo , Imunoterapia/métodos , Neoplasias/genética , Animais , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Humanos , Camundongos
18.
BMC Musculoskelet Disord ; 21(1): 792, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256689

RESUMO

BACKGROUND: Vertebral augmentation is the first-line treatment for the osteoporosis vertebral compression fractures. Bone cement leakage is the most common complication of this surgery. This study aims to assess the risk factors for different types of cement leakage and provides a nomogram for predicting the cement intradiscal leakage. METHODS: We retrospectively reviewed 268 patients who underwent vertebral augmentation procedure between January 2015 and March 2019. The cement leakage risk factors were evaluated by univariate analysis. Different types of cement leakage risk factors were identified by the stepwise logistic analysis. We provided a nomogram for predicting the cement intradiscal leakage and used the concordance index to assess the prediction ability. RESULTS: A total of 295 levels of vertebrae were included, with a leakage rate of 32.5%. Univariate analysis showed delayed surgery and lower vertebral compression ratio were the independent risk factors of cement leakage. The stepwise logistic analysis revealed percutaneous vertebroplasty was a risk factor in vein cement leakage; delayed surgery, preoperative compression ratio, and upper endplate disruption were in intradiscal cement leakage; age, preoperative fracture severity, and intravertebral vacuum cleft were in perivertebral soft tissue cement leakage; no factor was in spinal canal cement leakage. The nomogram for intradiscal cement leakage had a precise prediction ability with an original concordance index of 0.75. CONCLUSIONS: Delayed surgery and more vertebral compression increase the risk of cement leakage. Different types of cement leakage have different risk factors. We provided a nomogram for precise predicting the intradiscal cement leakage.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Cimentos Ósseos/efeitos adversos , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Nomogramas , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Fatores de Risco , Coluna Vertebral , Vertebroplastia/efeitos adversos
19.
Int J Ophthalmol ; 13(10): 1538-1545, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33078102

RESUMO

AIM: To investigate the alleviation of scutellarein (SN) against inner blood-retinal-barrier (iBRB) dysfunction in microglia cells stimulated by hyperglycemia and to elucidate the engaged mechanism. METHODS: Microglia BV2 cells were stimulated by using 25 mmol/L D-glucose. The same concentration of mannitol (25 mmol/L) was applied as an isotonic contrast. Real-time PCR, Western-blot assay and immunofluorescence staining assay was performed. The dysfunction of iBRB in vitro was detected by using transendothelial electrical resistance (TEER) assay. Additionally, the leakage of fluorescein isothiocyanate (FITC)-conjugated dextran (70 kDa) was detected. RESULTS: SN abrogated microglia BV2 cells activation and reduced the phosphorylated activation of extracellular signal-regulated protein kinase (ERK)1/2. SN also decreased the transcriptional activation of nuclear factor κB (NFκB) and the elevated expression of tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1ß in BV2 cells treated with D-glucose (25 mmol/L). SN attenuated iBRB dysfunction in human retinal endothelial cells (HRECs) or choroid-retinal endothelial RF/6A cells when those cells were treated with TNFα, IL-1ß or IL-6, or co-cultured with microglia cells stimulated by D-glucose. Moreover, SN restored the decreased protein expression of tight junctions (TJs) in TNFα-treated HRECs and RF/6A cells. CONCLUSION: SN not only alleviate iBRB dysfunction via directly inhibiting retinal endothelial injury caused by TNFα, IL-1ß or IL-6, but also reduce the release of TNFα, IL-1ß and IL-6 from microglia cells by abrogating hyperglycemia-mediated the activation of microglia cells.

20.
Int J Pediatr Otorhinolaryngol ; 137: 110233, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32896348

RESUMO

OBJECTIVE: To describe a measurement method for external auditory canal (EAC), especially in congenital aural stenosis (CAS). METHODS: High-resolution CT (HRCT) datasets of CAS were imported into the MIMICS 15.0 software for image processing. We used two methods to evaluate the degree of CAS. One is sagittal reconstruction measurement method, the minor axis of the bony ear canal was measured in each layer using sagittal reconstruction. The other is Matlab procedure calculation, we calculated the midpoint axis values of the EAC in each Frankfurt plane. Finally, we compared the minimum value of each method, and verified the sagittal reconstruction measurement method retrospectively in the CAS cases without cholesteatoma who had undergone meatoplasty. RESULTS: Twenty CAS cases were selected using the sagittal reconstruction measurement method and Matlab procedure calculation to evaluate the degree of CAS. The mean age was 9.55 ± 2.85 years old (range: 6-15). The mean degree of CAS was 2.09 ± 0.50 mm by sagittal reconstruction measurement method and 2.03 ± 0.58 mm by Matlab procedure calculation. There were no significant differences in the two groups (t = -1.371, p = 0.186). A total of 94 HRCT datasets were imported into MIMICS for verification. The mean age was 11.66 ± 6.56 years old (range: 6-39). Mean stenosis of EAC at surgery was 2.88 ± 0.93 mm (range: 1-4) by using sagittal reconstruction measurement method. CONCLUSIONS: Matlab procedure calculation is precise but relatively complicated and is only for scientific research. The sagittal reconstruction measurement method to calculate the most stenotic part of the bony ear canal is relatively simple and accurate to evaluate the degree of CAS. In cases of CAS without cholesteatoma, the precise measurement was critical for the next consultation.


Assuntos
Meato Acústico Externo/anormalidades , Meato Acústico Externo/diagnóstico por imagem , Otopatias/congênito , Otopatias/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Criança , Constrição Patológica , Meato Acústico Externo/cirurgia , Feminino , Humanos , Masculino , Procedimentos de Cirurgia Plástica , Estudos Retrospectivos , Software , Adulto Jovem
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