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1.
World J Gastroenterol ; 27(35): 5946-5957, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34629811

RESUMO

BACKGROUND: Crohn's disease (CD) is an incurable intestinal disorder with unclear etiology and pathogenesis. Currently, there is a lack of specific biomarkers and drug targets for CD in clinical practice. It is essential to identify the precise pathophysiological mechanism of CD and investigate new therapeutic targets. AIM: To explore a new biomarker and therapeutic target for CD and verify its role in the CD pathological mechanism. METHODS: Proteomics was performed to quantify the protein profile in the plasma of 20 CD patients and 20 matched healthy controls. Hub genes among the selected differentially expressed proteins (DEPs) were detected via the MCODE plugin in Cytoscape software. The expression level of one hub gene with an immunoregulatory role that interested us was verified in the inflamed intestinal tissues of 20 CD patients by immunohistochemical analysis. After that, the effects of the selected hub gene on the intestinal inflammation of CD were identified in a CD cell model by examining the levels of proinflammatory cytokines by enzyme-linked immunosorbent assays and the expression of the NF-κB signalling pathway by quantitative real-time PCR analysis and Western blot assays. RESULTS: Thirty-five DEPs were selected from 393 credible proteins identified by proteomic analysis. Among the DEPs, fibrinogen-like protein 1 (FGL1), which attracted our attention due to its function in the regulation of the immune response, had 1.722-fold higher expression in the plasma of CD patients and was identified as a hub gene by MCODE. Furthermore, the expression of FGL1 in the intestinal mucosal and epithelial tissues of CD patients was also upregulated (P < 0.05). In vitro, the mRNA levels of FGL1 and NF-κB; the protein expression levels of FGL1, IKKα, IKKß, p-IKKα/ß, p-IκBα, and p-p65; and the concentrations of the proinflammatory cytokines IL-1ß, IL-6, IL-17, and TNF-α were increased (P < 0.05) after stimulation with lipopolysaccharide, which were reversed by knockdown of FGL1 with siRNA transfection (P < 0.05). Conversely, FGL1 overexpression enhanced the abovementioned results (P < 0.05). CONCLUSION: FGL1 can induce intestinal inflammation by activating the canonical NF-κB signalling pathway, and it may be considered a potential biomarker and therapeutic target for CD.


Assuntos
Doença de Crohn , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Fibrinogênio , Humanos , NF-kappa B , Proteômica , Fator de Necrose Tumoral alfa
2.
Nucleic Acids Res ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551433

RESUMO

Enhancer RNAs (eRNAs) are a class of non-coding RNAs transcribed from enhancers. As the markers of active enhancers, eRNAs play important roles in gene regulation and are associated with various complex traits and characteristics. With increasing attention to eRNAs, numerous eRNAs have been identified in different human tissues. However, the expression landscape, regulatory network and potential functions of eRNAs in animals have not been fully elucidated. Here, we systematically characterized 185 177 eRNAs from 5085 samples across 10 species by mapping the RNA sequencing data to the regions of known enhancers. To explore their potential functions based on evolutionary conservation, we investigated the sequence similarity of eRNAs among multiple species. In addition, we identified the possible associations between eRNAs and transcription factors (TFs) or nearby genes to decipher their possible regulators and target genes, as well as characterized trait-related eRNAs to explore their potential functions in biological processes. Based on these findings, we further developed Animal-eRNAdb (http://gong_lab.hzau.edu.cn/Animal-eRNAdb/), a user-friendly database for data searching, browsing and downloading. With the comprehensive characterization of eRNAs in various tissues of different species, Animal-eRNAdb may greatly facilitate the exploration of functions and mechanisms of eRNAs.

3.
ISA Trans ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34493382

RESUMO

This paper proposes a digital twin solution for unsteady flow state estimation in a pumping station. Digital twin is expected to accurately estimate the real-time hydraulic parameters of blind spots of the pumping station system even under some adverse conditions including the interference of observation noise and model parameters drift. To solve these challenges, a digital twin framework integrating the model-driven method, control theory and data-driven method is presented. In this framework, an unsteady flow state estimation method combining frequency domain analysis and generalized predictive control theory is developed for the first time, which is superior to traditional time-domain numerical discrete methods in terms of computational efficiency and anti-noise interference. In the model parameter calibration process, the novelty concerns modeling of the optimization problem considering the dynamic operation control of the station and unsteady flow of pipelines. And this process is accomplished through the comprehensive application of the model-free adaptive control algorithm, the transient flow model and the particle swarm optimization algorithm. This work is applied to a pumping station in a product pipeline to verify its effectiveness in estimating the transient flow state of data blind spots and map the dynamic operation behavior under the interference of colored noise and parameter drift.

4.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34544865

RESUMO

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.


Assuntos
Aminoidrolases/genética , COVID-19/genética , Formiato-Tetra-Hidrofolato Ligase/genética , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Complexos Multienzimáticos/genética , Pandemias , Aminoidrolases/antagonistas & inibidores , Animais , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/virologia , Linhagem Celular , Quirópteros/genética , Quirópteros/virologia , Formiato-Tetra-Hidrofolato Ligase/antagonistas & inibidores , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/antagonistas & inibidores , Antígenos de Histocompatibilidade Menor , Complexos Multienzimáticos/antagonistas & inibidores , Vírus de RNA/genética , SARS-CoV-2/patogenicidade , Replicação Viral/genética
6.
Invest New Drugs ; 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34562230

RESUMO

BACKGROUND: Carboplatin and paclitaxel (CT) is one of the standard chemotherapy regimens used in various tumor types. Preclinical models have suggested that selinexor, a first-in-class oral potent selective inhibitor of nuclear export Exportin-1, and CT exerts antitumor activity in multiple malignancies. METHODS: This was a single-center, multi-arm phase Ib study utilizing a "basket type" expansion. CT and selinexor was employed as one of the 13 parallel arms. Advanced relapsed/refractory solid tumors following standard therapy or where the addition of selinexor to standard regimens deemed appropriate, were eligible. RESULTS: Of 13 patients treated, 12 patients were evaluable for response. The most common cancers were breast (n = 4), esophageal (n = 2), ovarian (n = 2) and non-small cell lung cancers (n = 2). All 13 patients had at least one treatment-related adverse events (TRAEs) and the most common were neutropenia (85%), leukopenia (85%), thrombocytopenia (85%), anemia (69%), nausea (54%), vomiting (46%), and fatigue (46%). One patient at 60 mg QW experienced DLT with grade 3 nausea and vomiting lasting 3 days. Unconfirmed partial response (uPR) was observed in 3 patients; one patient each with esophageal, breast, and ovarian cancer. One patient with esophageal adenocarcinoma had confirmed PR, however, was discontinued from the study due to clinical progression. Five patients achieved stable disease (SD). Disease control rate was 8%. Majority of patients (77%), including two patients who had uPR, had prior exposure to carboplatin and/or paclitaxel. Time-to-treatment failure (TTF) ranged from 1 to 153 weeks. CONCLUSION: The RP2D of selinexor was 60 mg QW in combination with CT. The combination conferred viable clinical activity with durable objective responses which should further be explored in tumor types for which CT is used as standard of care. Trial information. ClinicalTrials.gov Identifier: NCT02419495. Sponsor(s): Karyopharm Therapeutics. (Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495 ).

7.
Huan Jing Ke Xue ; 42(10): 4916-4924, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581135

RESUMO

The accumulation of some harmful elements in plants from intensive production systems pose a serious threat to human health. In this study, seven heavy metals(Cu, Pb, Zn, Cr, Cd, As, and Hg) and their distribution characteristics in the crops, vegetables, and fruits were analyzed alongside single factor evaluation and Nemero index analysis. Combined with dietary recommended consumption data from the Chinese Nutrition Society, the dietary exposure of heavy metals were further analyzed, and a consequent safety risk assessment was conducted. A total of 673 crop, vegetable, and fruit samples were collected from typical intensive production systems in Hainan Province. The results showed that the content of Cu, As, and Hg in the 673 plant samples was below the value of the national food standard. The exceed rates of Pb, Zn, Cr, and Cd were 2.67%, 3.71%, 2.53%, and 3.71%, respectively. The heavy metal comprehensive pollution degree of six species of plants showed the trend of leafy vegetables > tuber crops > non-leafy vegetables > legume crops > fruits > cereals. In particular, Cr in leafy vegetables showed significantly higher hazard quotients(HQ) than that in other types, and exceeded 1, suggesting a high potential health risk via the ingestion of heavy metals through leafy vegetables. The relatively lower hazard index(HI) values of tuber crops, non-leafy vegetables, legume crops, fruits, and cereals suggest that these types of plants are more suitable for intensive production systems.


Assuntos
Metais Pesados , Poluentes do Solo , China , Grão Comestível/química , Monitoramento Ambiental , Frutas/química , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise , Verduras
8.
J Mol Diagn ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34543749

RESUMO

Progressive familial intrahepatic cholestasis type 1 (PFIC1) results from biallelic pathogenic variants in ATP8B1. This study sought second pathogenic variants in ATP8B1 by whole-genome sequencing (WGS) in four unrelated low γ-glutamyl transpeptidase cholestasis patients in whom clinical suspicion of PFIC1 was high and gene-panel or Sanger sequencing had identified only one pathogenic variant in ATP8B1. Sanger sequencing confirmed WGS findings and determined the origin of each variant. Novel nonrecurrent structural variants in three patients (patient 1 to patient 3) were identified in trans: g.55396652_55403080del (6427-bp deletion), g.55335906_55346620dup (10,715-bp duplication), and g.55362063_55364293dup (2231-bp duplication). One synonymous variant in patient 4 was recognized in trans (c.1029G>A, p. Thr343Thr) and demonstrated as deleterious. In conclusion, WGS improves genetic diagnostic yield in PFIC1. These findings expand the gene-variant spectrum associated with FIC1 disease and for the first time report tandem duplication in ATP8B1 associated with cholestasis.

9.
J Chem Neuroanat ; 118: 102032, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34562585

RESUMO

OBJECTIVE: To investigate the effects of DUSP1 on the hippocampal injury of young rats with epilepsy (EP) through mediating ERK1/2 signaling pathway. METHODS: Young SD rats were selected and divided into Control, EP, EP + LV-GFP, EP + LV-DUSP1, EP + LV-siDUSP1, and EP + LV-siDUSP1 + U0126 groups. Morris Water Maze Test was used to detect the spatial learning and memory. Nissl staining and TUNEL staining were conducted and the inflammatory factors and oxidative stress-related indicators were also measured. Western blotting was utilized to detect the expression of DUSP1 and ERK1/2 pathway. EP cell model was constructed in vitro to verify the in vivo results. RESULTS: Compared with Control group, young rats in EP group had decreased spatial learning and memory abilities and increased apoptotic rate and decreased number of Nissl positive cells. Besides, the up-regulated levels in inflammatory factors (IL-1ß, IL-6), MDA content, and p-ERK1/2/ERK1/2 protein expression, as well as the down-regulated levels in DUSP1 protein expression and SOD content were also observed in EP rats. The EP rats treated with LV-DUSP1 showed obvious improvements regarding the above indicators, while those treated with LV-siDUSP1 had aggravated injury. But the effect of LV-siDUSP1 can be reversed by the treatment with ERK1/2 pathway inhibitor U0126. Further in vitro investigation verified the in vivo results. CONCLUSION: DUSP1 may ameliorate the oxidative stress and inflammatory injury, as well as improve spatial learning and memory abilities via inhibiting ERK1/2 pathway, eventually playing protective roles in hippocampal injury of young rats with EP.

10.
AJR Am J Roentgenol ; 217(3): 664-675, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34259544

RESUMO

OBJECTIVE. The purpose of our study was to develop a radiomics model based on preoperative MRI and clinical information for predicting recurrence-free survival (RFS) in patients with advanced high-grade serous ovarian carcinoma (HGSOC). MATERIALS AND METHODS. This retrospective study enrolled 117 patients with HGSOC, including 90 patients with recurrence and 27 without recurrence; 1046 radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images using a manual segmentation method. L1 regularization-based least absolute shrinkage and selection operator (LASSO) regression was performed to select features, and the synthetic minority oversampling technique (SMOTE) was used to balance our dataset. A support vector machine (SVM) classifier was used to build the classification model. To validate the performance of the proposed models, we applied a leave-one-out cross-validation method to train and test the classifier. Cox proportional hazards regression, Harrell concordance index (C-index), and Kaplan-Meier plots analysis were used to evaluate the associations between radiomics signatures and RFS. RESULTS. The fusion radiomics-based model yielded a significantly higher AUC value of 0.85 in evaluating RFS than the model using contrast-enhanced T1-weighted imaging features alone or T2-weighted imaging features alone (AUC = 0.79 and 0.74 and p = .02 and .01, respectively). Kaplan-Meier survival curves showed significant differences between high and low recurrence risk in patients with HGSOC by different models. The fusion model combining radiomics features and clinical information showed higher performance than the clinical model (C-index = 0.62 and 0.60, respectively). CONCLUSION. The proposed MRI-based radiomics signatures may provide a potential way to develop a prediction model and can help identify patients with advanced HGSOC who have a high risk of recurrence.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Máquina de Vetores de Suporte , Feminino , Humanos , Pessoa de Meia-Idade , Ovário/diagnóstico por imagem , Ovário/patologia , Estudos Retrospectivos , Análise de Sobrevida
11.
Cancers (Basel) ; 13(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209366

RESUMO

This study aims to develop a deep neural network (DNN)-based two-stage risk stratification model for early lung adenocarcinomas in CT images, and investigate the performance compared with practicing radiologists. A total of 2393 GGNs were retrospectively collected from 2105 patients in four centers. All the pathologic results of GGNs were obtained from surgically resected specimens. A two-stage deep neural network was developed based on the 3D residual network and atrous convolution module to diagnose benign and malignant GGNs (Task1) and classify between invasive adenocarcinoma (IA) and non-IA for these malignant GGNs (Task2). A multi-reader multi-case observer study with six board-certified radiologists' (average experience 11 years, range 2-28 years) participation was conducted to evaluate the model capability. DNN yielded area under the receiver operating characteristic curve (AUC) values of 0.76 ± 0.03 (95% confidence interval (CI): (0.69, 0.82)) and 0.96 ± 0.02 (95% CI: (0.92, 0.98)) for Task1 and Task2, which were equivalent to or higher than radiologists in the senior group with average AUC values of 0.76 and 0.95, respectively (p > 0.05). With the CT image slice thickness increasing from 1.15 mm ± 0.36 to 1.73 mm ± 0.64, DNN performance decreased 0.08 and 0.22 for the two tasks. The results demonstrated (1) a positive trend between the diagnostic performance and radiologist's experience, (2) the DNN yielded equivalent or even higher performance in comparison with senior radiologists, and (3) low image resolution decreased model performance in predicting the risks of GGNs. Once tested prospectively in clinical practice, the DNN could have the potential to assist doctors in precision diagnosis and treatment of early lung adenocarcinoma.

12.
Sci Total Environ ; 795: 148713, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34247090

RESUMO

Airborne bacteria have an important role in atmospheric processes and human health. However, there is still little information on the transmission and distribution of bacteria via the airborne route. To characterize the impact of foggy, haze, haze-fog (HF) and dust days on the concentration and viability of bacteria in atmospheric aerosols, size-segregated bioaerosol samples were collected in the Qingdao coastal region from March 2018 to February 2019. The total airborne microbes and viable/non-viable bacteria in the bioaerosol samples were measured using an epifluorescence microscope after staining with DAPI (4', 6-diamidino-2-phenylindole) and a LIVE/DEAD® BacLight Bacterial Viability Kit. The average concentrations of total airborne microbes on haze and dust days were 6.75 × 105 and 1.03 × 106 cells/m3, respectively, which increased by a factor of 1.3 and 2.5 (on average), respectively, relative to those on sunny days. The concentrations of non-viable bacteria on haze and dust days increased by a factor of 1.2 and 3.6 (on average), respectively, relative to those on sunny days. In contrast, the concentrations of viable bacteria on foggy and HF days were 7.13 × 103 and 5.74 × 103 cells/m3, decreases of 38% and 50%, respectively, compared with those on sunny days. Foggy, haze, dust and HF days had a significant effect on the trend of the seasonal variation in the total airborne microbes and non-viable bacteria. Bacterial viability was 20.8% on sunny days and significantly higher than the 14.1% on foggy days, 11.2% on haze days, 8.6% during the HF phenomenon and 6.1% on dust days, indicating that special weather is harmful to some bacterial species. Correlation analysis showed that the factors that influenced the bacterial concentration and viability depended on different weather conditions. The main influential factors were temperature, NO2 and SO2 concentrations on haze days, and temperature, particulate matter (PM2.5) and NO2 concentrations on foggy days. The median size of particles containing viable bacteria was 1.94 µm on sunny days and decreased to 1.88 µm and 1.74 µm on foggy and haze days, respectively, but increased to 2.18 µm and 2.37 µm on dust and HF days, respectively.


Assuntos
Poluentes Atmosféricos , Aerossóis/análise , Microbiologia do Ar , Poluentes Atmosféricos/análise , Bactérias , China , Monitoramento Ambiental , Humanos , Tamanho da Partícula , Material Particulado/análise , Material Particulado/toxicidade , Estações do Ano , Tempo (Meteorologia)
13.
Cancer Res ; 81(15): 4054-4065, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34117030

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is almost universally lethal. A critical unmet need exists to explore essential susceptibilities in PDAC and to identify druggable targets to improve PDAC treatment. KRAS mutations dominate the genetic landscape of PDAC and lead to activation of multiple downstream pathways and cellular processes. Here, we investigated the requirement of these pathways for tumor maintenance using an inducible KrasG12D -driven PDAC mouse model (iKras model), identifying that RAF-MEK-MAPK signaling is the major effector for oncogenic KRAS-mediated tumor maintenance. However, consistent with previous studies, MEK inhibition had minimal therapeutic effect as a single agent for PDAC in vitro and in vivo. Although MEK inhibition partially downregulated transcription of glycolysis genes, it failed to suppress glycolytic flux in PDAC cells, which is a major metabolic effector of oncogenic KRAS. Accordingly, an in vivo genetic screen identified multiple glycolysis genes as potential targets that may sensitize tumor cells to MEK inhibition. Inhibition of glucose metabolism with low-dose 2-deoxyglucose in combination with a MEK inhibitor induced apoptosis in KrasG12D -driven PDAC cells in vitro. The combination also inhibited xenograft PDAC tumor growth and prolonged overall survival in a genetically engineered PDAC mouse model. Molecular and metabolic analyses indicated that co-targeting glycolysis and MAPK signaling results in apoptosis via induction of lethal endoplasmic reticulum stress. Together, our work suggests that combined inhibition of glycolysis and the MAPK pathway may serve as an effective approach to target KRAS-driven PDAC. SIGNIFICANCE: This study demonstrates the critical role of glucose metabolism in resistance to MAPK inhibition in KRAS-driven pancreatic cancer, uncovering a potential therapeutic approach for treating this aggressive disease.

14.
Sci Adv ; 7(21)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34138728

RESUMO

Leukemia stem cells (LSCs) sustain the disease and contribute to relapse in acute myeloid leukemia (AML). Therapies that ablate LSCs may increase the chance of eliminating this cancer in patients. To this end, we used a bioreducible lipidoid-encapsulated Cas9/single guide RNA (sgRNA) ribonucleoprotein [lipidoid nanoparticle (LNP)-Cas9 RNP] to target the critical gene interleukin-1 receptor accessory protein (IL1RAP) in human LSCs. To enhance LSC targeting, we loaded LNP-Cas9 RNP and the chemokine CXCL12α onto mesenchymal stem cell membrane-coated nanofibril (MSCM-NF) scaffolds mimicking the bone marrow microenvironment. In vitro, CXCL12α release induced migration of LSCs to the scaffolds, and LNP-Cas9 RNP induced efficient gene editing. IL1RAP knockout reduced LSC colony-forming capacity and leukemic burden. Scaffold-based delivery increased the retention time of LNP-Cas9 in the bone marrow cavity. Overall, sustained local delivery of Cas9/IL1RAP sgRNA via CXCL12α-loaded LNP/MSCM-NF scaffolds provides an effective strategy for attenuating LSC growth to improve AML therapy.

15.
Insect Biochem Mol Biol ; 137: 103610, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34182106

RESUMO

Cuticular proteins analogous to peritrophin 3 (CPAP3)-type cuticle proteins constitute a family of proteins with three chitin-binding domains (CBDs) that play an important role in cuticle formation by associating with chitin. In our previous study, we identified CPAP3-type cuticle proteins in the silkworm genome, of which we characterized CPAP3-A2 (BmCBP1), a protein highly expressed in the epidermis. In this study, to elucidate the digestion mechanism of CPAP3-type cuticle proteins, we incubated CPAP3-A2 with molting fluid in vitro and found that its hydrolysis, which was inhibited by serine and cysteine protease inhibitors, produced two major bands with a molecular weight of approximately 22 kD and 11 kD. A trypsin-type serine protease, p37k, was presumed to be responsible for hydrolyzing CPAP3-A2 based on liquid chromatography-tandem mass spectrometry analysis of naturally purified molting fluid. To verify this, p37k was subsequently expressed in Sf9 cells using the Bac-to-Bac baculovirus expression system. In its active form, the recombinant protease could successfully hydrolyze CPAP3-A2. Finally, we analyzed the CPAP3-A2 molting fluid digestion site. When arginine 169 of CPAP3-A2 was mutated to alanine, a weaker hydrolysis of mutant CPAP3-A2 was observed compared to that of normal CPAP3-A2. Collectively, we identified a trypsin-type serine protease that is involved in the degradation of CPAP3-type cuticle proteins, including CPAP3-A2, suggesting that this protease plays an important role during molting in Bombyx mori. These findings provide the basis for further elucidation of the mechanisms underlying insect molting and metamorphosis.

16.
J Int Med Res ; 49(6): 3000605211019190, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34162259

RESUMO

OBJECTIVE: To investigate the utility of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) for the preoperative diagnosis of cervical cancer. METHODS: We retrospectively analyzed 114 patients who were diagnosed with cervical cancer and underwent PET/MRI (n = 59) or PET/computed tomography (PET/CT) (n = 65) before surgery. The maximal standardized uptake value (SUVmax) and mean SUV (SUVmean) were determined for regions of interest in the resultant radiographic images. RESULTS: Relative to PET/CT, 18F-FDG PET/MRI exhibited higher specificity and sensitivity in defining the primary tumor bounds and higher sensitivity for detection of bladder involvement. The SUVmax and SUVmean of PET/MRI were remarkably higher than those of PET/CT as a means of detecting primary tumors, bladder involvement, and the lymph node status. However, no significant differences in these values were detected when comparing the two imaging approaches as a means of detecting vaginal involvement or para-aortic lymph node metastasis. CONCLUSIONS: These outcomes may demonstrate the capability of 18F-FDG PET/MRI to clarify preoperative cervical cancer diagnoses in the context of unclear PET/CT findings. However, studies directly comparing SUVs in different lesion types from patients who have undergone both PET/MRI and PET/CT scans are essential to validate and expand upon these findings.


Assuntos
Fluordesoxiglucose F18 , Neoplasias do Colo do Útero , Feminino , Humanos , Linfonodos , Metástase Linfática , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/cirurgia
17.
Local Reg Anesth ; 14: 75-83, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935516

RESUMO

Background: The aim of this study is to evaluate the effect of ultrasound-guided bilateral cervical plexus block on general anesthesia, postoperative analgesia, and surgical outcomes in patients undergoing total parathyroidectomy with autotransplantation. Patients and Methods: Forty-eight ASA III-IV patients with hyperparathyroidism secondary to renal failure were included: 24 patients received ultrasound-guided bilateral superficial and deep cervical plexus block combined with general anesthesia (group A), and 24 patients received general anesthesia alone (group B). Postoperative patient-controlled intravenous analgesia was provided with sufentanil 2 µg/kg. The primary outcome is the postoperative pain scores. Secondary outcomes include intraoperative remifentanil dosage, changes in hemodynamics, extubation time, and sufentanil consumption. Surgical outcomes regarding calcium, phosphorus and parathormone values were also noted. Results: The patients in group A required less remifentanil than group B (2.56±0.92mg vs 3.38±0.84mg, P=0.002) and lower VAS scores at 1, 3, 10, 24, and 48h postoperatively (P < 0.001). While the systolic blood pressure in group A patients was significantly greater than that in group B at T3 (immediately after extubation, [138.33±11.36 vs 129.08±17.06 mmHg; P=0.032]), heart rates in group A were lower than in group B at 1 min before induction (T1 [89.46 ± 9.14 vs 96.71±14.19, P=0.042]) and 1 min after intubation (T2 [70.08 ± 5.35 vs 79.25 ± 11.81, P=0.002]). The extubation time in group A was shorter than that in group B (P < 0.001). There was no difference in calcium, phosphorus and parathormone values, nor in sufentanil consumption between the groups. Conclusion: Ultrasound-guided bilateral superficial and deep cervical plexus block combined with general anesthesia for TPTA is an effective strategy to improve anesthesia management and achieve better postoperative analgesia, and has no impact on surgical outcomes.

18.
BMC Endocr Disord ; 21(1): 111, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34044831

RESUMO

BACKGROUND: Low free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI. METHODS: Patients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality. RESULTS: One hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42-5.552, P = 0.003). CONCLUSIONS: Low FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.


Assuntos
COVID-19/epidemiologia , COVID-19/mortalidade , Síndromes do Eutireóideo Doente/epidemiologia , SARS-CoV-2 , Tireotropina/sangue , Tiroxina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , Estudos de Coortes , Comorbidade , Síndromes do Eutireóideo Doente/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Tireotropina/deficiência , Tiroxina/deficiência
19.
World J Clin Cases ; 9(15): 3607-3622, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34046460

RESUMO

BACKGROUND: Although several trials have shown that the addition of antifoaming agents to polyethylene glycol (PEG) can improve bowel preparation, whether PEG plus antifoaming agents have a beneficial role in the detection of benign tumors during colonoscopy has yet to be confirmed. Our aim was to clarify whether adding simethicone to PEG solution could improve the detection of benign colorectal tumors. AIM: To clarify whether adding simethicone to PEG solution could improve the detection of benign colorectal tumors. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched for articles published prior to September 2019. The outcomes included the detection rates of colorectal adenomas and polyps. RESULT: Twenty studies were eligible. Although there was no difference in the colorectal adenoma detection rate (ADR), a significant effect of simethicone for diminutive adenomas (< 10 mm) was revealed in the group taking simethicone. We also found that simethicone could significantly improve the ADR in the proximal colon but did not affect the colorectal polyp detection rate. Furthermore, the subgroup analyses revealed a beneficial effect of simethicone on the ADR among Asians (P = 0.005) and those with an ADR < 25% (P = 0.003). Moreover, it was a significant finding that the low dose simethicone was as effective as the high dose one with respect to the detection of benign colorectal tumors. CONCLUSION: In summary, the addition of simethicone to PEG might improve the detection of diminutive adenomas in the right colon by colonoscopy in Asia. Low-dose simethicone was recommended for the detection of benign colorectal tumors. However, large clinical trials are necessary to validate our results and determine the ideal dose of simethicone.

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