Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
1.
Diabetes Metab Syndr Obes ; 14: 4469-4482, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795494

RESUMO

Purpose: To analyze the impact of hyperglycemia on the clinical outcome of COVID-19 in patients with newly diagnosed diabetes (NDD). Patients and Methods: We performed a retrospective study of 3114 cases of COVID-19 without pre-existing diabetes, 351 of which had NDD, in Hubei Province, China. The Cox regression model was used to calculate the risk of adverse clinical outcomes comparing the NDD vs non-NDD group before and after propensity score-matched (PSM) analysis. Patients with NDD were further divided into a sustained hyperglycemia group, a fluctuating group, and a remitted group based on their blood glucose levels during hospitalization as well as into hypoglycemic agent users and nonusers. Results: Compared to the non-NDD individuals, individuals with NDD had a significantly increased risk of all-cause mortality (adjusted HR after PSM, 2.65; 95% CI, 1.49-4.72; P = 0.001) and secondary outcomes involving organ damage during the 28-day follow-up period. Subgroup analyses indicated that among individuals with NDD, the individuals with remitted hyperglycemia had the lowest 28-day mortality, whereas those with sustained hyperglycemia had the highest (IRR 24.27; 95% CI, 3.21-183.36; P < 0.001). Moreover, individuals treated with hypoglycemic agents had significantly lower all-cause mortality than those not treated with hypoglycemic agents (IRR 0.08; 95% CI, 0.01-0.56; P < 0.001). Conclusion: Our study reinforces the clinical message that NDD is strongly associated with poor outcomes in COVID-19 patients. Furthermore, resolved hyperglycemia in the later phase of the disease and the use of hypoglycemic agents were associated with improved prognosis in patients with NDD.

2.
Oxid Med Cell Longev ; 2021: 1806344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804360

RESUMO

NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome-mediated pyroptosis is a crucial event in the preeclamptic pathogenesis, tightly linked with the uteroplacental TLR4/NF-κB signaling. Trophoblastic glycometabolism reprogramming has now been noticed in the preeclampsia pathogenesis, plausibly modulated by the TLR4/NF-κB signaling as well. Intriguingly, cellular pyroptosis and metabolic phenotypes may be inextricably linked and interacted. Metformin (MET), a widely accepted NF-κB signaling inhibitor, may have therapeutic potential in preeclampsia while the underlying mechanisms remain unclear. Herein, we investigated the role of MET on trophoblastic pyroptosis and its relevant metabolism reprogramming. The safety of pharmacologic MET concentration to trophoblasts was verified at first, which had no adverse effects on trophoblastic viability. Pharmacological MET concentration suppressed NLRP3 inflammasome-induced pyroptosis partly through inhibiting the TLR4/NF-κB signaling in preeclamptic trophoblast models induced via low-dose lipopolysaccharide. Besides, MET corrected the glycometabolic reprogramming and oxidative stress partly via suppressing the TLR4/NF-κB signaling and blocking transcription factor NF-κB1 binding on the promoter PFKFB3, a potent glycolytic accelerator. Furthermore, PFKFB3 can also enhance the NF-κB signaling, reduce NLRP3 ubiquitination, and aggravate pyroptosis. However, MET suppressed pyroptosis partly via inhibiting PFKFB3 as well. These results provided that the TLR4/NF-κB/PFKFB3 pathway may be a novel link between metabolism reprogramming and NLRP3 inflammasome-induced pyroptosis in trophoblasts. Further, MET alleviates the NLRP3 inflammasome-induced pyroptosis, which partly relies on the regulation of TLR4/NF-κB/PFKFB3-dependent glycometabolism reprogramming and redox disorders. Hence, our results provide novel insights into the pathogenesis of preeclampsia and propose MET as a potential therapy.

3.
HGG Adv ; 2(3)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34485947

RESUMO

Chromatin spatial organization (interactome) plays a critical role in genome function. Deep understanding of chromatin interactome can shed insights into transcriptional regulation mechanisms and human disease pathology. One essential task in the analysis of chromatin interactomic data is to identify long-range chromatin interactions. Existing approaches, such as HiCCUPS, FitHiC/FitHiC2, and FastHiC, are all designed for analyzing individual cell types or samples. None of them accounts for unbalanced sequencing depths and heterogeneity among multiple cell types or samples in a unified statistical framework. To fill in the gap, we have developed a novel statistical framework MUNIn (multiple-sample unifying long-range chromatin-interaction detector) for identifying long-range chromatin interactions from multiple samples. MUNIn adopts a hierarchical hidden Markov random field (H-HMRF) model, in which the status (peak or background) of each interacting chromatin loci pair depends not only on the status of loci pairs in its neighborhood region but also on the status of the same loci pair in other samples. To benchmark the performance of MUNIn, we performed comprehensive simulation studies and real data analysis and showed that MUNIn can achieve much lower false-positive rates for detecting sample-specific interactions (33.1%-36.2%), and much enhanced statistical power for detecting shared peaks (up to 74.3%), compared to uni-sample analysis. Our data demonstrated that MUNIn is a useful tool for the integrative analysis of interactomic data from multiple samples.

4.
Cell Metab ; 33(10): 1943-1956.e2, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478633

RESUMO

Metabolic dysfunction is becoming a predominant risk for the development of many comorbidities. Ischemic heart disease (IHD) still imposes the highest disease burden among all cardiovascular diseases worldwide. However, the contributions of metabolic risk factors to IHD over time have not been fully characterized. Here, we analyzed the global disease burden of IHD and 15 associated general risk factors from 1990 to 2019 by applying the methodology framework of the Global Burden of Disease Study. We found that the global death cases due to IHD increased steadily during that time frame, while the mortality rate gradually declined. Notably, metabolic risk factors have become the leading driver of IHD, which also largely contributed to the majority of IHD-related deaths shifting from developed countries to developing countries. These findings suggest an urgent need to implement effective measures to control metabolic risk factors to prevent further increases in IHD-related deaths.

5.
Placenta ; 106: 67-78, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33684599

RESUMO

INTRODUCTION: Preeclampsia is characterized by overactive inflammation at the uteroplacental interface, leading to trophoblasts dysfunction. 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) is a crucial glycolytic regulator which has recently been found to participate in the pathological inflammatory states. This study aimed to investigate the role of PFKFB3 in the inflammation-induced damage in trophoblasts, and elucidate the underlying mechanisms. METHODS: Immunohistochemistry, qRT-PCR, and Western blot analysis (WB) were used to detect the expression of PFKFB3 in preeclamptic and normal placentas. Lipopolysaccharide (LPS)-induced HTR8/SVneo cells were established as the in vitro model to simulate the overactive inflammation at the uteroplacental interface of PE, which were subsequently transfected with PFKFB3 siRNA. The expression of PFKFB3, NF-κB-p-p65, phosphorylation states of NF-κB-p65, ICAM-1, Bcl-2, BAX, and MMP2 were detected by WB. qRT-PCR was used to detect the expression of TNF-α and IL-1ß. The ICAM-1 expression was also reflected by monocyte adhesion assay. Reactive Oxygen Species (ROS) levels were detected by DCFH-DA (2,7-Dichlorodi-hydrofluorescein diacetate). Apoptosis was detected using Annexin V-FITC staining. Migration and invasion were measured by wound-healing and transwell assays. RESULTS: PFKFB3 was up-regulated in the preeclamptic placenta. In LPS-treated HTR-8/Svneo cells, the inhibition of PFKFB3 blocked the NF-κB signal pathway, thereby downregulating the expression of proinflammatory cytokines and adhesion molecules, meanwhile, PFKFB3 knockdown significantly alleviated monocyte adhesion, oxidative stress, apoptosis, and reinstated migration and invasive capacity. DISCUSSION: PFKFB3 controls the LPS-induced inflammation via the NF-κB pathway and impacts trophoblasts function such as adhesion, oxidative stress, apoptosis, migration, and invasion, thereby potentially participating in the preeclamptic etiopathogenesis.

6.
Curr Med Res Opin ; 37(6): 917-927, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33729889

RESUMO

BACKGROUND: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources. METHODS: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses. RESULTS: Eight factors, namely, Oxygen saturation, blood Urea nitrogen, Respiratory rate, admission before the date the national Maximum number of daily new cases was reached, Age, Procalcitonin, C-reactive protein (CRP), and absolute Neutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71; p < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts. CONCLUSIONS: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.


Assuntos
COVID-19 , Medição de Risco/métodos , COVID-19/epidemiologia , COVID-19/mortalidade , China , Hospitalização/estatística & dados numéricos , Humanos , Itália , Fatores de Risco
7.
Med (N Y) ; 2(4): 435-447.e4, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33521746

RESUMO

Background: To develop a sensitive risk score predicting the risk of mortality in patients with coronavirus disease 2019 (COVID-19) using complete blood count (CBC). Methods: We performed a retrospective cohort study from a total of 13,138 inpatients with COVID-19 in Hubei, China, and Milan, Italy. Among them, 9,810 patients with ≥2 CBC records from Hubei were assigned to the training cohort. CBC parameters were analyzed as potential predictors for all-cause mortality and were selected by the generalized linear mixed model (GLMM). Findings: Five risk factors were derived to construct a composite score (PAWNN score) using the Cox regression model, including platelet counts, age, white blood cell counts, neutrophil counts, and neutrophil:lymphocyte ratio. The PAWNN score showed good accuracy for predicting mortality in 10-fold cross-validation (AUROCs 0.92-0.93) and subsets with different quartile intervals of follow-up and preexisting diseases. The performance of the score was further validated in 2,949 patients with only 1 CBC record from the Hubei cohort (AUROC 0.97) and 227 patients from the Italian cohort (AUROC 0.80). The latent Markov model (LMM) demonstrated that the PAWNN score has good prediction power for transition probabilities between different latent conditions. Conclusions: The PAWNN score is a simple and accurate risk assessment tool that can predict the mortality for COVID-19 patients during their entire hospitalization. This tool can assist clinicians in prioritizing medical treatment of COVID-19 patients. Funding: This work was supported by National Key R&D Program of China (2016YFF0101504, 2016YFF0101505, 2020YFC2004702, 2020YFC0845500), the Key R&D Program of Guangdong Province (2020B1111330003), and the medical flight plan of Wuhan University (TFJH2018006).

8.
Mol Ther Nucleic Acids ; 23: 897-907, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33614238

RESUMO

6-phosphofructo-2-kinase (PFKFB3) is a crucial regulator of glycolysis that has been implicated in angiogenesis and the development of diverse diseases. However, the functional role and regulatory mechanism of PFKFB3 in early-onset preeclampsia (EOPE) remain to be elucidated. According to previous studies, noncoding RNAs play crucial roles in EOPE pathogenesis. The goal of this study was to investigate the functional roles and co-regulatory mechanisms of the metastasis-associated lung adenocarcinoma transcript-1 (MALAT1)/microRNA (miR)-26/PFKFB3 axis in EOPE. In our study, decreased MALAT1 and PFKFB3 expression in EOPE tissues correlates with endothelial cell (EC) dysfunction. The results of in vitro assays revealed that PFKFB3 regulates the proliferation, migration, and tube formation of ECs by modulating glycolysis. Furthermore, MALAT1 regulates PFKFB3 expression by sponging miR-26a/26b. Finally, MALAT1 knockout reduces EC angiogenesis by inhibiting PFKFB3-mediated glycolysis flux, which is ameliorated by PFKFB3 overexpression. In conclusion, decreased MALAT1 expression in EOPE tissues reduces the glycolysis of ECs in a PFKFB3-dependent manner by sponging miR-26a/26b and inhibits EC proliferation, migration, and tube formation, which may contribute to abnormal angiogenesis in EOPE. Thus, strategies targeting PFKFB3-driven glycolysis may be a promising approach for the treatment of EOPE.

9.
World J Clin Cases ; 9(4): 919-926, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33585640

RESUMO

BACKGROUND: Occult breast cancer (OBC) is a special type of breast cancer presenting as axillary lymph node metastasis with undetectable primary lesions in the breast. Due to its low incidence and unique clinical manifestations, there is a lack of consensus on the diagnosis and treatment of OBC. We report a case of OBC treated with neoadjuvant chemotherapy combined with anlotinib. The treatment was well tolerated, and the patient achieved a pathologic complete response. CASE SUMMARY: A 53-year-old woman presented with a lump in her right axillary area with no primary lesions in the breast. Pathological biopsy confirmed right axillary metastatic carcinoma. Immunohistochemical staining results were positive for progesterone receptor, cytokeratin 7, specific breast markers GATA3 and gross cystic disease fluid protein-15. Tumor cells were negative for estrogen receptor, human epidermal growth factor receptor-2, cytokeratin 5/6, cytokeratin 20, and villin. The patient was diagnosed with OBC, and she underwent neoadjuvant chemotherapy combined with anlotinib. Mastectomy plus axillary lymph node dissection was performed. The patient achieved pathologic complete response with no residual invasive tumor cells in the breast or axillary lymph nodes. Postoperatively, she received adjuvant radiotherapy and endocrine therapy. CONCLUSION: Neoadjuvant chemotherapy and anlotinib had good efficacy and safety in the treatment of OBC and may be a new therapeutic option.

10.
Sci Rep ; 11(1): 199, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420241

RESUMO

The present study aimed to investigate the efficacy and toxicity of pegylated liposomal doxorubicin (PLD) in preoperative neoadjuvant chemotherapy for patients with breast cancer by comparing with conventional anthracycline. This study is a non-randomized controlled trial. Prospective analysis was conducted after matching as required. A total of 146 patients with confirmed diagnosis of breast cancer by histopathological examinations were enrolled into the observation group and control group in 1:1 ratio. Each of the cases in the observation group was required to correspond to another in the control group according to the requirements including age, molecular subtype, axillary node status, and regimen of the preoperative neoadjuvant chemotherapy. The chemotherapy was based on regimens consisting of anthracyclines, paclitaxel or docetaxel, and/or platinum. PLD was used at least twice in the observation group, with traditional anthracycline as a contrast in the control group. Clinical responses as well as cardiac side effects and other adverse reactions were evaluated by clinical and imaging examinations such as electrocardiogram (ECG) and color Doppler ultrasound during the chemotherapy. Pathologic examinations were performed following the surgeries after preoperative neoadjuvant chemotherapy. All the patients in both groups completed the preoperative neoadjuvant chemotherapy according to their original regimens. The postoperative pathological evaluation revealed a higher pathologic complete response (PCR) rate and significantly more patients of grade V of the Miller-Payne grading system in the observation group as compared to the control group (p = 0.047). In addition, the observation group recorded an evidently lower occurrence of the adverse cardiac events (p = 0.014), ECG changes (p = 0.048), and the relatively severe adverse reactions such as myelosuppression. Compared with conventional anthracycline drugs, PLD has a better pathologic response and safety performance, as well as a similar clinical effectiveness in preoperative neoadjuvant chemotherapy for breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/efeitos adversos , Doxorrubicina/análogos & derivados , Doxorrubicina/efeitos adversos , Lipossomos/química , Terapia Neoadjuvante/efeitos adversos , Polietilenoglicóis/química , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/patologia , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias
11.
Nature ; 587(7835): 644-649, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33057195

RESUMO

Lineage-specific epigenomic changes during human corticogenesis have been difficult to study owing to challenges with sample availability and tissue heterogeneity. For example, previous studies using single-cell RNA sequencing identified at least 9 major cell types and up to 26 distinct subtypes in the dorsal cortex alone1,2. Here we characterize cell-type-specific cis-regulatory chromatin interactions, open chromatin peaks, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational samples of the human cortex. We show that chromatin interactions underlie several aspects of gene regulation, with transposable elements and disease-associated variants enriched at distal interacting regions in a cell-type-specific manner. In addition, promoters with increased levels of chromatin interactivity-termed super-interactive promoters-are enriched for lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of transcription. Finally, we develop CRISPRview, a technique that integrates immunostaining, CRISPR interference, RNAscope, and image analysis to validate cell-type-specific cis-regulatory elements in heterogeneous populations of primary cells. Our findings provide insights into cell-type-specific gene expression patterns in the developing human cortex and advance our understanding of gene regulation and lineage specification during this crucial developmental window.


Assuntos
Células/classificação , Células/metabolismo , Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Epigenoma , Epigenômica , Organogênese/genética , Sistemas CRISPR-Cas , Linhagem da Célula/genética , Células Cultivadas , Cromatina/genética , Cromatina/metabolismo , Elementos de DNA Transponíveis , Histonas/química , Histonas/metabolismo , Humanos , Imageamento Tridimensional , Metilação , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Elementos Reguladores de Transcrição , Reprodutibilidade dos Testes , Transcrição Genética
12.
Placenta ; 99: 70-77, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32758718

RESUMO

INTRODUCTION: Abnormal placental vascular development is a possible cause of preeclampsia. Mesenchymal stem cell (MSC)-based therapy is a promising approach for tissue repair and angiogenesis. Further, heme oxygenase-1 (HO-1) has beneficial effects on the angiogenic balance during pregnancy. We explored the effects of HO-1 overexpression on placental vascularization using human placenta-derived MSCs (hPMSCs). METHODS: hPMSCs were isolated from term placenta, and the HO-1 gene was transfected with a lentivirus. Proliferation, migration, and apoptosis of hPMSCs and HO-hPMSCs were examined using CCK8 assay, trans-well assay, and flow cytometry, respectively. Paracrine secretion of the angiogenesis factors VEGF and PlGF, as well as the anti-angiogenesis factors sFlt-1 and sEng, from hPMSC/HO-hPMSCs was measured by qRT-PCR and ELISA. Human umbilical cord endothelial cells and a villus-decidua co-culture were treated with conditioned media to study the effect of HO-1-hPMSCs on tube formation and villus vascular remodeling. RESULTS: HO-1 significantly improved the proliferation and migration of hPMSCs. Additionally, HO-1 reduced hPMSCs apoptosis. The levels of VEGF were increased in HO-1-hPMSCs, whereas those of sFlt-1 decreased. Tube formation assays showed that the conditioned media from HO-1-hPMSCs resulted in more branching points than those from the controls. The villus-decidua co-culture system confirmed that HO-1-hPMSCs are conducive to angiogenesis and vascular remodeling. DISCUSSION: HO-1-modified hPMSCs improve placental vascularization by promoting a balance of pro- and anti- angiogenesis factors, which is worthy of further study as an alternative treatment for preeclampsia.


Assuntos
Indutores da Angiogênese/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica/fisiologia , Placenta/metabolismo , Remodelação Vascular/fisiologia , Apoptose/fisiologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Endoteliais/metabolismo , Feminino , Humanos , Placenta/irrigação sanguínea , Fator de Crescimento Placentário/metabolismo , Gravidez , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Cell Metab ; 32(4): 537-547.e3, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32861268

RESUMO

The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.


Assuntos
Acidose/induzido quimicamente , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Metformina/efeitos adversos , Pneumonia Viral/complicações , Acidose Láctica/induzido quimicamente , Idoso , COVID-19 , China/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hospitalização , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Estudos Retrospectivos
14.
Hepatology ; 72(2): 389-398, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32359177

RESUMO

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID-19 pneumonia in Hubei Province. APPROACH AND RESULTS: We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non-severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. CONCLUSION: The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID-19-associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.


Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Fígado/fisiopatologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores , COVID-19 , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2
15.
Orthop J Sports Med ; 8(4): 2325967120914273, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32426403

RESUMO

Background: The evaluation of glenoid bone defects in the preoperative stage for patients with anterior shoulder instability is critical for surgical decision making. A novel method that predicts the intact glenoid width based purely on the measurement of the glenoid height has been advocated. Despite the convenience, all studies to date have focused on the Western population, and there is no similar research based on an East Asian population. Purpose: To determine the relationship between glenoid height and width in an East Asian population. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Spiral computed tomography (CT) scans of both sides of the shoulder joints were obtained from 205 patients of Han nationality (China) who had no history of shoulder trauma or pain. The maximal height and width of each glenoid were measured on the en face view by 2 radiologists who were blinded to each other's results. Pearson correlation coefficients and multivariable linear regression were calculated from all data measured to evaluate the relationship between maximal glenoid height and width between the sexes. Results: A total of 205 patients (410 shoulder CT scans) were analyzed. The mean glenoid height was 34.45 ± 2.82 mm, and the mean glenoid width was 23.35 ± 2.40 mm. There was a statistical difference between male and female patients with regard to glenoid height (36.61 vs 32.39 mm, respectively; t = 9.76; P < .001) and width (25.26 vs 21.54 mm, respectively; t = 20.73; P < .001). Analysis of the measured glenoid height and width demonstrated a strong linear correlation of 0.82 (R 2 = 0.68; P < .001) for the entire cohort and similarly strong linear correlations when each sex was analyzed separately. For male patients, the glenoid width was measured as: glenoid height × 0.50 + 7 mm (R 2 = 0.36; P < .001); for female patients, the glenoid width was measured as: glenoid height × 0.45 + 7 mm (R 2 = 0.31; P < .001). Conclusion: In an East Asian population, the mean glenoid height and width were 34.45 and 23.35 mm, respectively. The formulas that represent the relationship between glenoid width and height for male and female patients are the following: glenoid width = glenoid height × 0.50 + 7 mm and glenoid width = glenoid height × 0.45 + 7 mm, respectively.

16.
Inorg Chem ; 59(7): 4349-4356, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32208647

RESUMO

Low-dimensional lead-free organic-inorganic hybrid perovskites have gained increasing attention as having low toxicity, ease of processing, and good optoelectronic properties. Seeking for lead-free and narrow band gap organic-inorganic hybrid perovskites are of great importance for the development and application of photoelectric materials. Here, we reported a Sb-based organic-inorganic hybrid perovskite (MV)[SbI3Cl2], which has one-dimensional inorganic frameworks of the I-sharing double octahedra. (MV)[SbI3Cl2] shows a narrow direct band gap of 1.5 eV, and displays obvious photoresponse for the 532 nm light with rapid response speed of trise = 0.69 s, tdecay = 0.28 s. With an illumination power of 5 mW and a 50 V bias, the responsivities (R) and external quantum efficiency (EQE) for (MV)[SbI3Cl2] photodetector under 532 nm laser are 29.75 mA/W and 6.69% respectively. This Sb-based halide double perovskite material will provide an alternative material for photodetector devices.

17.
Eur Radiol ; 30(6): 3567-3575, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32064559

RESUMO

OBJECTIVES: To take advantage of the deep learning algorithms to detect and calculate clot burden of acute pulmonary embolism (APE) on computed tomographic pulmonary angiography (CTPA). MATERIALS AND METHODS: The training set in this retrospective study consisted of 590 patients (460 with APE and 130 without APE) who underwent CTPA. A fully deep learning convolutional neural network (DL-CNN), called U-Net, was trained for the segmentation of clot. Additionally, an in-house validation set consisted of 288 patients (186 with APE and 102 without APE). In this study, we set different probability thresholds to test the performance of U-Net for the clot detection and selected sensitivity, specificity, and area under the curve (AUC) as the metrics of performance evaluation. Furthermore, we investigated the relationship between the clot burden assessed by the Qanadli score, Mastora score, and other imaging parameters on CTPA and the clot burden calculated by the DL-CNN model. RESULTS: There was no statistically significant difference in AUCs with the different probability thresholds. When the probability threshold for segmentation was 0.1, the sensitivity and specificity of U-Net in detecting clot respectively were 94.6% and 76.5% while the AUC was 0.926 (95% CI 0.884-0.968). Moreover, this study displayed that the clot burden measured with U-Net was significantly correlated with the Qanadli score (r = 0.819, p < 0.001), Mastora score (r = 0.874, p < 0.001), and right ventricular functional parameters on CTPA. CONCLUSIONS: DL-CNN achieved a high AUC for the detection of pulmonary emboli and can be applied to quantitatively calculate the clot burden of APE patients, which may contribute to reducing the workloads of clinicians. KEY POINTS: • Deep learning can detect APE with a good performance and efficiently calculate the clot burden to reduce the physicians' workload. • Clot burden measured with deep learning highly correlates with Qanadli and Mastora scores of CTPA. • Clot burden measured with deep learning correlates with parameters of right ventricular function on CTPA.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Aprendizado Profundo , Ventrículos do Coração/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Função Ventricular Direita , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/fisiopatologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
Rheumatology (Oxford) ; 59(10): 2829-2837, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32065646

RESUMO

OBJECTIVES: To evaluate the distribution of radiological characteristics stratified by different myositis-specific autoantibodies, identify prognostic value of high-resolution CT (HRCT) patterns in DM-associated interstitial lung disease (DM-ILD), and explore the possible mechanism associated with macrophage activation. METHODS: We enrolled 165 patients with PM/DM-ILD. The distribution of HRCT radiological types with different myositis-specific autoantibodies and the relationship between radiological features and ILD course and prognosis were analysed. Additionally, the potential role of macrophage activation in rapidly progressive ILD (RP-ILD) with DM was studied. RESULTS: The organizing pneumonia pattern was dominant in HRCT findings of patients with DM-ILD, especially those with anti-SAE (6/6, 100%) and anti-MDA5 (46/62, 74.2%) antibodies. The ratios of organizing pneumonia and nonspecific interstitial pneumonia patterns were almost equal in patients with aminoacyl tRNA synthetase antibodies, and nonspecific interstitial pneumonia pattern was associated with a mild clinical course. Lower lung zone consolidation in HRCT was related to RP-ILD in both anti-MDA5 and anti-aminoacyl tRNA synthetase antibody-positive groups. Ferritin levels of >1000 ng/ml (odds ratio (OR), 12.3; P=0.009), elevated carcinoembryonic antigen (OR, 5.8; P=0.046) and carbohydrate antigen 19-9 (OR, 7.8; P=0.018) were independent predictors of a lower lung zone consolidation pattern in anti-MDA5 antibody-positive DM. The infiltration of CD163-positive macrophages into alveolar spaces was significantly higher in the DM-RP-ILD group than in the chronic DM-ILD group. CONCLUSION: HRCT patterns are different among variable myositis-specific autoantibodies positive patients with ILD and lower zone consolidation in HRCT correlated with RP-ILD in DM. Activated macrophages may contribute to the pathogenesis of RP-ILD in DM.


Assuntos
Dermatomiosite/complicações , Dermatomiosite/imunologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/imunologia , Ativação de Macrófagos , Doença Aguda , Idade de Início , Especificidade de Anticorpos , Autoanticorpos/análise , Doença Crônica , Dermatomiosite/sangue , Progressão da Doença , Feminino , Ferritinas/sangue , Humanos , Helicase IFIH1 Induzida por Interferon/imunologia , Ligases/imunologia , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
19.
Clin Respir J ; 14(3): 277-284, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31814279

RESUMO

INTRODUCTION: Quantification of hemodynamics and right ventricular (RV) function is crucial for pulmonary hypertension (PH). Cardiovascular magnetic resonance-based heart deformation analysis (CMR-HDA) has been used to assess the ventricular strain. OBJECTIVE: This study was to determine the correlation of right ventricular longitudinal strain (RVLS) assessed with CMR-HDA with RV function as well as hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirty-six CTEPH patients were prospectively included in this research. Each patients underwent CMR and right heart catheterization (RHC). RVLS and RV ejection fraction (RVEF) was quantified from cine images acquired with a retrospectively gated turbo FLASH gradient-echo sequence. The late gadolinium enhancement (LGE) images were acquired using a 2D inversion recovery phase-sensitive fast gradient-echo sequence. Hemodynamics were determined with RHC. RESULTS: Right ventricular longitudinal strain measured with CMR-HDA was -13.99 ± 4.94%. Bland-Altman plots showed statistical agreement with RVLS with low intra- and interobserver variability. RVLS correlated with serum N-terminal-pro-B-type natriuretic peptide (r = 0.615, P < .001). RVLS inversely correlated with RVEF (r = -0.699, P < .001), and it was positively correlated with both RVESV (r = 0.664, P < .001) and myocardial the volume of LGE (r = 0.447, P = .008). Receiver-operating characteristic (ROC) indicated that RVLS values of >-14.20% could be used to predict RVEF <40% with a 100% sensitivity and a 96.7% specificity. Hemodynamically, RVLS was positively correlated with mean pulmonary artery pressure (r = 0.598, P < .001) and pulmonary vascular resistance (r = 0.685, P < .001). CONCLUSION: Right ventricular longitudinal strain assessed by CMR-HDA is a readily available and reproducible parameters of RV function. RVLS >-14.20% suggests the presence of RV dysfunction.


Assuntos
Hipertensão Pulmonar/diagnóstico por imagem , Espectroscopia de Ressonância Magnética/métodos , Embolia Pulmonar/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico por imagem , Adulto , Cateterismo Cardíaco/métodos , Doença Crônica , Meios de Contraste , Ecocardiografia/métodos , Feminino , Gadolínio/administração & dosagem , Hemodinâmica/fisiologia , Humanos , Hipertensão Pulmonar/fisiopatologia , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Variações Dependentes do Observador , Fragmentos de Peptídeos/metabolismo , Embolia Pulmonar/complicações , Embolia Pulmonar/fisiopatologia , Pressão Propulsora Pulmonar/fisiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Volume Sistólico/fisiologia , Resistência Vascular , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular Direita/fisiologia
20.
Mol Reprod Dev ; 86(6): 686-695, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31066488

RESUMO

Extravillous trophoblasts (EVTs) migrate into uterine decidua and induce vascular smooth muscle cell (VSMC) loss through mechanisms thought to involve migration and apoptosis, achieving complete spiral artery remodeling. Long noncoding RNA maternally expressed gene 3 (MEG3) can regulate diverse cellular processes, such as proliferation and migration, and has been discovered highly expressed in human placenta tissues. However, little is known about the role of MEG3 in modulating EVT functions and EVT-induced VSMC loss. In this study, we first examined the location of MEG3 in human first-trimester placenta by in situ hybridization. Then, exogenous upregulation of MEG3 in HTR-8/SVneo cells was performed to investigate the effects of MEG3 on EVT motility and EVT capacity to displace VSMCs. Meanwhile, the molecules mediating EVT-induced VSMC loss, such as tumor necrosis factor-α (TNF-α), Fas ligand (FasL), and tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) were detected at transcriptional and translational levels. Finally, VSMCs were cocultured with MEG3-upregulated HTR-8/SVneo to explore the role of MEG3 on EVT-mediated VSMC migration and apoptosis. Results showed that MEG3 was expressed in trophoblasts in placental villi and decidua, and MEG3 enhancement inhibited HTR-8/SVneo migration and invasion. Meanwhile, the displacement of VSMCs by HTR-8/SVneo and the expression of TNF-α, FasL and TRAIL in HTR-8/SVneo were reduced following MEG3 overexpression in HTR-8/SVneo. Furthermore, HTR-8/SVneo with MEG3 upregulation impaired VSMC migration and apoptosis. The PI3K/Akt pathway, which is possibly downstream, was inactivated in MEG3-upregulated HTR-8/SVneo. These findings suggest that MEG3 might be a negative regulator of spiral artery remodeling via suppressing EVT invasion and EVT-mediated VSMC loss.


Assuntos
Movimento Celular , Decídua/metabolismo , Músculo Liso Vascular/metabolismo , RNA Longo não Codificante/metabolismo , Trofoblastos/metabolismo , Artéria Uterina/metabolismo , Remodelação Vascular , Linhagem Celular , Decídua/citologia , Feminino , Humanos , Músculo Liso Vascular/citologia , Gravidez , Primeiro Trimestre da Gravidez , Trofoblastos/citologia , Artéria Uterina/citologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...