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1.
EClinicalMedicine ; 69: 102466, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361995

RESUMO

Background: Voiding cystourethrography (VCUG) is the gold standard for the diagnosis and grading of vesicoureteral reflux (VUR). However, VUR grading from voiding cystourethrograms is highly subjective with low reliability. This study aimed to develop a deep learning model to improve reliability for VUR grading on VCUG and compare its performance to that of clinicians. Methods: In this retrospective study in China, VCUG images were collected between January 2019 and September 2022 from our institution as an internal dataset for training and 4 external data sets as external testing set for validation. Samples were divided into training (N = 1000) and validation sets (N = 500), internal testing set (N = 168), and external testing set (N = 280). An ensemble learning-based model, Deep-VCUG, using Res-Net 101 and the voting methods was developed to predict VUR grade. The grading performance was assessed using heatmaps, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, and F1 score in the internal and external testing set. The performances of four clinicians (2 pediatric urologists and 2 radiologists) with and without the Deep-VCUG assisted to predict VUR grade were explored in external testing sets. Findings: A total of 1948 VCUG images were collected (Internal dataset = 1668; multi-center external dataset = 280). For assessing unilateral VUR grading, the Deep-VCUG achieved AUCs of 0.962 (95% confidence interval [CI]: 0.943-0.978) and 0.944 (95% [CI]: 0.921-0.964) in the internal and external testing sets, respectively, for bilateral VUR grading, the Deep-VCUG also achieved high AUCs of 0.960 (95% [CI]: 0.922-0.983) and 0.924 (95% [CI]: 0.887-0.957). The Deep-VCUG model using voting method outperformed single model and clinician in terms of classification based on VCUG image. Moreover, Under the Dee-VCUG assisted, the classification ability of junior and senior clinicians was significantly improved. Interpretation: The Deep-VCUG model is a generalizable, objective, and accurate tool for vesicoureteral reflux grading based on VCUG imaging and had good assistance with clinicians to VUR grading applicability. Funding: This study was supported by Natural Science Foundation of China, "Fuqing Scholar" Student Scientific Research Program of Shanghai Medical College, Fudan University, and the Program of Greater Bay Area Institute of Precision Medicine (Guangzhou).

2.
J Am Chem Soc ; 146(7): 4363-4368, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38329963

RESUMO

The total syntheses of penicibilaenes A and B are described. The key step is the tBuOK/DMSO-mediated tandem 5-exo-dig Conia-ene type reaction and 6-exo-dig Conia-ene type reaction to install the tricyclic [6.3.1.01,5] dodecane core of penicibilaenes from dibutynyl cyclohexanone in a single step, together with a sequence of copper-mediated conjugate addition and Crabtree's hydrogenation to forge the stereogenic centers at C5 and C2, respectively.

3.
Nat Med ; 30(2): 584-594, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38177850

RESUMO

Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754-0.846 and integrated Brier scores of 0.153-0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1-5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.


Assuntos
Aprendizado Profundo , Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Cegueira
4.
Cell Rep Med ; 4(10): 101213, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37788667

RESUMO

The increasing prevalence of diabetes, high avoidable morbidity and mortality due to diabetes and diabetic complications, and related substantial economic burden make diabetes a significant health challenge worldwide. A shortage of diabetes specialists, uneven distribution of medical resources, low adherence to medications, and improper self-management contribute to poor glycemic control in patients with diabetes. Recent advancements in digital health technologies, especially artificial intelligence (AI), provide a significant opportunity to achieve better efficiency in diabetes care, which may diminish the increase in diabetes-related health-care expenditures. Here, we review the recent progress in the application of AI in the management of diabetes and then discuss the opportunities and challenges of AI application in clinical practice. Furthermore, we explore the possibility of combining and expanding upon existing digital health technologies to develop an AI-assisted digital health-care ecosystem that includes the prevention and management of diabetes.


Assuntos
Inteligência Artificial , Diabetes Mellitus , Humanos , Diabetes Mellitus/terapia
5.
Front Immunol ; 14: 1136343, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275867

RESUMO

Objective: Whether fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS) is effective in improving outcomes remains controversial. We assessed the safety and efficacy of FMT for patients with IBS. Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, the Cochrane Library, the clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP) up to February 25, 2022, updated to March 28, 2023. Randomized controlled trials (RCTs) compared the stool and capsule FMT with placebo in patients with IBS were included. Two authors independently assessed study eligibility, extracted the data, and assessed risk of bias. We did meta-analysis with RevMan, and the Stata software was used for sensitivity analysis and meta-regression. The GRADE system was used to assess the quality of evidences. Mean difference (MD) or standardized Mean difference (SMD) with 95% CI for continuous data, and risk ratios (RR) with 95% CI for dichotomous data were used with random-effects models. The primary outcomes included the clinical response rate and IBS-SSS score. This study is registered with PROSPERO: CRD42022328377. Results: Nineteen reports from nine RCTs were included finally. Compared with the placebo, a single stool FMT could significantly decrease the IBS-SSS score at 1 month (MD=-65.75, 95%CI [-129.37, -2.13]), 3 months (MD=-102.11, 95% CI [-141.98, -62.24]), 6 months (MD=-84.38, 95%CI [-158.79, -9.97]), 24 months (MD=-110.41, 95%CI [-145.37, -75.46]), and 36 months (MD=-104.71, 95%CI [-137.78, -71.64]). It also could improve the clinical response rate at 3 months (RR=1.91, 95% [1.12, 3.25]), 24 months (RR=2.97, 95% [1.94, 4.54]), and 36 months (RR=2.48, 95% [1.65, 3.72]), and increase the IBS-QoL score at 3 months, 24 months, and 36 months. FMT did not increase the serious adverse event. The risk of bias was low, and the quality of evidence based on GRADE system was moderate in the stool FMT group. However, we did not find positive effect of capsule FMT on patients with IBS based on the current available data. Conclusion: A single stool FMT is effective and safe for patients with IBS. However, some factors may affect the effectiveness of FMT, and the relationship between the gut microbiome and the effect of FMT for IBS is still unclear. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022328377.


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/terapia , Transplante de Microbiota Fecal/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fezes , Microbioma Gastrointestinal/fisiologia
6.
Theor Appl Genet ; 136(1): 16, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36662257

RESUMO

KEY MESSAGE: Long intergenic non-coding RNA (lincRNA), cis-acting expression quantitative trait locus (cis-eQTL), maize, regulatory evolution. The law of genetic variation during domestication explains the evolutionary mechanism and provides a theoretical basis for improving existing varieties of maize. Previous studies focused on exploiting regulatory variations controlling the expression of protein-coding genes rather than of non-protein-coding genes. Here, we examined the genetic and evolutionary features of long non-coding RNAs from intergenic regions (long intergenic non-coding RNAs, lincRNAs) using population-scale transcriptome data and identified 1168 lincRNAs with cis-acting expression quantitative trait loci (cis-eQTLs). We found that lincRNAs are more likely to be regulated by cis-eQTLs, which exert stronger effects than the protein-coding genes. During maize domestication and improvement, upregulated alleles of lincRNAs, which originated from both standing variation and new mutation, accumulate more frequently and show larger effect sizes than the coding genes. A stronger signature of genetic differentiation was observed in their regulatory regions compared to those of randomly sampled lincRNAs. In addition, we found that cis-regulatory differentiation of lincRNAs is related to the sequence conservation of lincRNA transcripts. Non-conserved lincRNAs more tend to gain upregulated alleles and show a stronger relationship with selected traits than conserved lincRNAs between maize and its wild relatives. Our findings in maize improve the understanding of cis-regulatory variation in lincRNA genes during domestication and improvement and provide an effective approach for prioritizing candidates for further investigation.


Assuntos
RNA Longo não Codificante , Transcriptoma , RNA Longo não Codificante/genética , Zea mays/genética , Zea mays/metabolismo , Genômica , Locos de Características Quantitativas
7.
Cancers (Basel) ; 15(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36672374

RESUMO

Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Understanding the factors influencing the therapeutic effects in gastric cancer patients and the molecular mechanism behind gastric cancer is still facing challenges. In addition to genetic alterations and environmental factors, it has been demonstrated that epigenetic mechanisms can also induce the occurrence and progression of gastric cancer. Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressor complex 2 (PRC2), which trimethylates histone 3 at Lys-27 and regulates the expression of downstream target genes through epigenetic mechanisms. It has been found that EZH2 is overexpressed in the stomach, which promotes the progression of gastric cancer through multiple pathways. In addition, targeted inhibition of EZH2 expression can effectively delay the progression of gastric cancer and improve its resistance to chemotherapeutic agents. Given the many effects of EZH2 in gastric cancer, there are no studies to comprehensively describe this mechanism. Therefore, in this review, we first introduce EZH2 and clarify the mechanisms of abnormal expression of EZH2 in cancer. Secondly, we summarize the role of EZH2 in gastric cancer, which includes the association of the EZH2 gene with genetic susceptibility to GC, the correlation of the EZH2 gene with gastric carcinogenesis and invasive metastasis, the resistance to chemotherapeutic drugs of gastric cancer mediated by EZH2 and the high expression of EZH2 leading to poor prognosis of gastric cancer patients. Finally, we also clarify some of the current statuses of drug development regarding targeted inhibition of EZH2/PRC2 activity.

8.
Cancers (Basel) ; 14(23)2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36497204

RESUMO

The accumulation of oxidative DNA base damage can severely disrupt the integrity of the genome and is strongly associated with the development of cancer. DNA glycosylase is the critical enzyme that initiates the base excision repair (BER) pathway, recognizing and excising damaged bases. The Nei endonuclease VIII-like 3 (NEIL3) is an emerging DNA glycosylase essential in maintaining genome stability. With an in-depth study of the structure and function of NEIL3, we found that it has properties related to the process of base damage repair. For example, it not only prefers the base damage of single-stranded DNA (ssDNA), G-quadruplex and DNA interstrand crosslinks (ICLs), but also participates in the maintenance of replication fork stability and telomere integrity. In addition, NEIL3 is strongly associated with the progression of cancers and cardiovascular and neurological diseases, is incredibly significantly overexpressed in cancers, and may become an independent prognostic marker for cancer patients. Interestingly, circNEIL3, a circular RNA of exon-encoded origin by NEIL3, also promotes the development of multiple cancers. In this review, we have summarized the structure and the characteristics of NEIL3 to repair base damage. We have focused on NEIL3 and circNEIL3 in cancer development, progression and prognosis.

9.
Clin Transl Oncol ; 24(9): 1673-1681, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35416599

RESUMO

Colorectal cancer (CRC) is one of the most common cancers in the world. The incidence rate of cancer is high. The overall response to traditional treatment methods such as surgery, radiotherapy, and chemotherapy is not very satisfactory. Therefore, finding new therapeutic targets is very important for improving CRC treatment. In recent reports, the role of circRNAs in regulating colorectal angiogenesis has been gradually revealed. CircRNAs can indirectly act on angiogenesis pathways and regulate the expression of growth factors such as vascular endothelial growth factor (VEGF). CircRNAs are endogenous noncoding RNAs formed by pre-mRNAs through exon circular splicing. The covalent closed-loop structure makes these RNAs highly conserved and stable. CircRNAs have been found in human plasma, serum, urine, and other body fluids. Their highly conserved characteristics play important roles in many biological activities. CircRNAs can participate in the progression of many diseases by sponging miRNAs, interacting with proteins, and regulating transcription. Angiogenesis can provide nutrients and oxygen for tumour proliferation and metastasis. Angiogenesis is an important sign of the formation of the tumour microenvironment. Here, we will summarize the role of the latest circRNAs in the mechanism of angiogenesis in CRC and provide potential therapeutic targets for clinical treatment.


Assuntos
Neoplasias Colorretais , RNA Circular , Neoplasias Colorretais/patologia , Humanos , MicroRNAs/genética , Splicing de RNA , RNA Circular/genética , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Int J Mol Sci ; 23(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35269656

RESUMO

In flowering plants, RNA editing is a post-transcriptional process that selectively deaminates cytidines (C) to uridines (U) in organellar transcripts. Pentatricopeptide repeat (PPR) proteins have been identified as site-specific recognition factors for RNA editing. Here, we report the map-based cloning and molecular characterization of the defective kernel mutant dek504 in maize. Loss of Dek504 function leads to delayed embryogenesis and endosperm development, which produce small and collapsed kernels. Dek504 encodes an E+-type PPR protein targeted to the mitochondria, which is required for RNA editing of mitochondrial NADH dehydrogenase 3 at the nad3-317 and nad3-44 sites. Biochemical analysis of mitochondrial protein complexes revealed a significant reduction in the mitochondrial NADH dehydrogenase complex I activity, indicating that the alteration of the amino acid sequence at nad3-44 and nad3-317 through RNA editing is essential for NAD3 function. Moreover, the amino acids are highly conserved in monocots and eudicots, whereas the events of C-to-U editing are not conserved in flowering plants. Thus, our results indicate that Dek504 is essential for RNA editing of nad3, which is critical for NAD3 function, mitochondrial complex I stability, and seed development in maize.


Assuntos
Edição de RNA , Zea mays , Complexo I de Transporte de Elétrons/metabolismo , Regulação da Expressão Gênica de Plantas , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes/metabolismo , Zea mays/metabolismo
11.
Org Lett ; 23(11): 4088-4093, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33988367

RESUMO

The structurally intriguing tetracyclic core of complex harziane diterpenoid was constructed in 14 steps from commercially available 3-ethoxycyclohex-2-en-1-one. The key steps were a Mn/Cu-mediated oxidative 1,3-dicarbonyl radical cascade cyclization reaction, which diastereoselectively formed the core of dimethylbicyclo[3.2.1]octane structure, and a Au-catalyzed diastereoselective formal [2 + 2] cycloaddition for construction of the harziane diterpenoid tetracyclic framework. The developed method paves the way for achieving total synthesis of this type of complex natural product.

12.
Plant Cell Physiol ; 62(2): 293-305, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33377894

RESUMO

Splicing of plant organellar group II introns from precursor-RNA transcripts requires the assistance of nuclear-encoded splicing factors. Maturase (nMAT) is one such factor, as its three homologs (nMAT1, 2 and 4) have been identified as being required for the splicing of various mitochondrial introns in Arabidopsis. However, the function of nMAT in maize (Zea mays L.) is unknown. In this study, we identified a seed development mutant, empty pericarp 2441 (emp2441) from maize, which showed severely arrested embryogenesis and endosperm development. Positional cloning and transgenic complementation assays revealed that Emp2441 encodes a maturase-related protein, ZmnMAT3. ZmnMAT3 is highly expressed during seed development and its protein locates to the mitochondria. The loss of function of ZmnMAT3 resulted in the reduced splicing efficiency of various mitochondrial group II introns, particularly of the trans-splicing of nad1 introns 1, 3 and 4, which consequently abolished the transcript of nad1 and severely impaired the assembly and activity of mitochondrial complex I. Moreover, the Zmnmat3 mutant showed defective mitochondrial structure and exhibited expression and activity of alternative oxidases. These results indicate that ZmnMAT3 is essential for mitochondrial complex I assembly during kernel development in maize.


Assuntos
Mitocôndrias/metabolismo , Proteínas de Plantas/fisiologia , Sementes/crescimento & desenvolvimento , Zea mays/crescimento & desenvolvimento , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Íntrons , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Fatores de Processamento de RNA/fisiologia , Sementes/metabolismo , Zea mays/genética , Zea mays/metabolismo
13.
Can J Gastroenterol Hepatol ; 2020: 8839098, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33354559

RESUMO

Aim: Portal hypertension is a series of syndrome commonly seen with advanced cirrhosis, which seriously affects patient's quality of life and survival. This study was designed to access the efficacy and safety of selective esophagogastric devascularization in the modified Sugiura procedure for patients with cirrhotic hemorrhagic portal hypertension. Methods: Sixty patients with hepatitis B cirrhotic hemorrhagic portal hypertension and meeting the inclusion criteria were selected and randomly divided by using computer into the selective modified Sugiura group (sMSP group, n = 30) and the modified Sugiura group (MSP group, n = 30). The primary endpoint measurement is the postoperative rebleeding rate. Secondary endpoint measurements included free portal venous pressure, liver Child-Pugh score, liver volume, portal vein width and blood flow velocity, survival rate, quality of life, and dysphagia as well as other complications one year postoperatively. This trial is registered with ChiCTR, number ChiCTR2000033468. Results: There was no statistically significant difference in rebleeding rates within one year after surgery between patients in the sMSP and MSP groups (χ = 0.11, p=0.73). In comparison with the MSP group, the Child-Pugh score of liver function in the sMSP group significantly increased (χ = 6.4, p=0.04) and the incidence of dysphagia was significantly reduced (χ = 6.23, p=0.01) one year after surgery. There was a statistically significant difference in the quality of life between the two groups. However, there were no statistically significant differences in free portal venous pressure (MD = -3.44, 95% CI: -7.87 to 0.98, p=0.12), postoperative liver volume (3 months: MD = -258.81, 95% CI: -723.21 to 205.57, p=0.24; 1 year: MD = -320.12, 95% CI: -438.43 to 102.78, p=0.16), postoperative portal vein width (3 months: MD = -0.06, p=0.50; 1 year: MD = 0.17, p=0.21), portal vein flow velocity (3 months: MD = 1.64, p=0.21; 1 year: MD = -1.19, p=0.57), 1-year survival rate (χ = 1.01, p=0.31), and other complications between the two groups. Conclusions: Selective esophagogastric devascularization in the modified Sugiura procedure may not lower the incidence of rebleeding in the short term based on our findings. However, it may significantly improve quality of life of patients with cirrhotic hemorrhagic portal hypertension, improve liver function, and reduce postoperative dysphagia.


Assuntos
Varizes Esofágicas e Gástricas , Hipertensão Portal , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Hemorragia , Humanos , Hipertensão Portal/cirurgia , Cirrose Hepática/complicações , Veia Porta/cirurgia , Qualidade de Vida
14.
Medicine (Baltimore) ; 99(41): e22699, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031342

RESUMO

BACKGROUND: Pressure ulcer (PU) is defined as a lesion or trauma to the skin and underlying tissue resulting from unrelieved pressure, shear, friction, moisture, or a combination of all these, usually appearing over a bony prominence. We aim to evaluate the credibility of systematic reviews and meta-analyses that assess the effectiveness, safety, and economy of the dressing treatments for PU through an overview. METHODS: We searched the following electronic bibliographic databases: PubMed, Embase, Cochrane Library, CINAHL Complete, PsycARTICLES, PsycINFO, DynaMed Plus, as well as the Chinese databases without any language restriction. We will include meta-analyses that dressings treatments in the management of PUs. For each meta-analysis, we will estimate the effect size of a treatment through the random-effect model and the fixed-effect model, and we will evaluate between-study heterogeneity (Cochrane's Q and I statistics) and small-study effect (Egger's test); we will also estimate the evidence of excess significance bias. Methodological quality of each meta-analysis will be evaluated by using Assessment of Multiple Systematic Reviews 2. RESULTS: This study is ongoing and the results will be submitted to a peer-reviewed journal for publication. ETHICS AND DISSEMINATION: Ethical approval is not applicable, since this is an overview based on published articles. PROTOCOL REGISTRATION NUMBER: The protocol has been registered on PROSPERO under the number CRD42020161232.


Assuntos
Bandagens , Úlcera por Pressão/terapia , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
15.
Org Lett ; 22(11): 4440-4443, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32380832

RESUMO

An efficiently stereoselective [4 + 2] cycloaddition of 3-alkylenyloxindoles and α-diazoketones through sequential visible-light photoactivation and N-heterocyclic carbene catalysis was achieved. A series of tetrahydropyrano[2,3-b]indoles with an all-carbon quaternary stereocenter were obtained in good yields with excellent diastereo- and enantioselectivities.

16.
J Am Chem Soc ; 142(14): 6511-6515, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32203659

RESUMO

The asymmetric total synthesis of (+)-waihoensene, which has a cis-fused [6,5,5,5] tetracyclic core bearing an angular triquinane, a cis-fused six-membered ring, and four contiguous quaternary carbon atoms, was achieved through a sequence of chemical reactions in a stereochemically well-defined manner. The total synthesis features the following: (1) Cu-catalyzed asymmetric conjugated 1,4-addition; (2) diastereoselective Conia-ene type reaction; (3) diastereoselective intramolecular Pauson-Khand reaction; (4) Ni-catalyzed diastereoselective conjugated 1,4-addition; and (5) radical-initiated intramolecular hydrogen atom transfer (HAT). Control experiments and density functional theory calculations support the proposed HAT process.

17.
Pathol Res Pract ; 215(3): 499-505, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30638858

RESUMO

Profilin 1 (PFN1) is a critical actin-regulatory protein; however, its functional role in hepatocellular carcinoma (HCC) progression remains to be further elucidated. In the present study, we observed that the expression levels of PFN1 were significantly decreased in HCC tissues and cell lines. Low PFN1 expression was significantly correlated with aggressive clinicopathological characteristics and poor prognosis of HCC patients. Further in vitro experiments demonstrated that overexpression of PFN1 remarkably inhibited the proliferation, migration, invasion and EMT of HCC cells. Moreover, we also found that PFN1 was a direct target gene of miR-19a-3p, and in HCC tissues, and there was a significantly inverse correlation between PFN1 mRNA and miR-19a-3p expression. Collectively, our results showed that PFN1 functions as a tumor suppressor in HCC, and might serve as a diagnostic and therapeutic target for HCC patients.


Assuntos
Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Profilinas/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Movimento Celular/genética , Proliferação de Células/genética , Intervalo Livre de Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Profilinas/genética , Prognóstico , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
18.
Medicine (Baltimore) ; 97(51): e13710, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572502

RESUMO

OBJECTIVE: We aimed to systematically evaluate the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus. METHODS: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, Google, Web of Science and the Chinese Science Citation Database were searched up to March 2018. Randomized controlled trials determining the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus were eligible for inclusion. Two authors independently extracted the data in a prespecified Microsoft Excel spreadsheet. A meta-analysis was performed using Review Manager 5.3 software. Weighted mean difference (WMD) and relative risk (RR) together with their corresponding 95% confidence intervals (CIs) were estimated, and only the random effects model was used in order to achieve a more conservative estimate of the efficacy and safety. RESULTS: Fourteen multicenter randomized controlled trials involving 11,947 patients were eligible for inclusion. Compared to placebo, lixisenatide could more significantly reduce the level of HbA1c (WMD=-0.44; 95% confidence interval [CI] [-0.55,-0.33]), and a higher proportion of lixisenatide-treated patients achieved the HbA1c level of < 7.0% (RR = 1.89, 95% CI [1.75-2.03]) and < 6.5% (RR = 3.03, 95% CI [2.54-3.63]) than the placebo-treated patients. Lixisenatide was also associated with a significant reduction in fasting plasma glucose and 2-hour postprandial plasma glucose levels. The risks for any adverse events, gastrointestinal adverse events, and symptomatic hypoglycemia significantly increased in the lixisenatide-treatedment group compared to those in the placebo group. However, lixisenatideit did not increase the risks of serious adverse events, death, or severe hypoglycemia. CONCLUSIONS: Lixisenatide was more effective than placebo in patients with type 2 diabetes mellitus, and the mild-to-moderate adverse events were found to be tolerated during the follow-up.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Peptídeos/efeitos adversos , Peptídeos/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Med Biol Eng Comput ; 56(10): 1807-1821, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29560548

RESUMO

A rodent behavior analysis system is presented, capable of automated tracking, pose estimation, and recognition of nine behaviors in freely moving animals. The system tracks three key points on the rodent body (nose, center of body, and base of tail) to estimate its pose and head rotation angle in real time. A support vector machine (SVM)-based model, including label optimization steps, is trained to classify on a frame-by-frame basis: resting, walking, bending, grooming, sniffing, rearing supported, rearing unsupported, micro-movements, and "other" behaviors. Compared to conventional red-green-blue (RGB) camera-based methods, the proposed system operates on 3D depth images provided by the Kinect infrared (IR) camera, enabling stable performance regardless of lighting conditions and animal color contrast with the background. This is particularly beneficial for monitoring nocturnal animals' behavior. 3D features are designed to be extracted directly from the depth stream and combined with contour-based 2D features to further improve recognition accuracies. The system is validated on three freely behaving rats for 168 min in total. The behavior recognition model achieved a cross-validation accuracy of 86.8% on the rat used for training and accuracies of 82.1 and 83% on the other two "testing" rats. The automated head angle estimation aided by behavior recognition resulted in 0.76 correlation with human expert annotation. Graphical abstract Top view of a rat freely behaving in a standard homecage, captured by Kinect-v2 sensors. The depth image is used for constructing a 3D topography of the animal for pose estimation, behavior recognition, and head angle calculation. Results of the processed data are displayed on the user interface in various forms.


Assuntos
Comportamento Animal , Imageamento Tridimensional , Movimento , Algoritmos , Animais , Automação , Análise de Componente Principal , Ratos
20.
IEEE Trans Biomed Eng ; 64(10): 2439-2449, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28410095

RESUMO

We have developed a new headstage architecture as part of a smart experimental arena, known as the EnerCage-HC2 system, which automatically delivers stimulation and collects behavioral data over extended periods with minimal small animal subject handling or personnel intervention in a standard rodent homecage. Equipped with a four-coil inductive link, the EnerCage-HC2 system wirelessly powers the receiver (Rx) headstage, irrespective of the subject's location or head orientation, eliminating the need for tethering or carrying bulky batteries. On the transmitter (Tx) side, a driver coil, five high-quality (Q) factor segmented resonators at different heights and orientations, and a closed-loop Tx power controller create a homogeneous electromagnetic (EM) field within the homecage 3-D space, and compensate for drops in power transfer efficiency (PTE) due to Rx misalignments. The headstage is equipped with four small slanted resonators, each covering a range of head orientations with respect to the Tx resonators, which direct the EM field toward the load coil at the bottom of the headstage. Moreover, data links based on Wi-Fi, UART, and Bluetooth low energy are utilized to enables remote communication and control of the Rx. The PTE varies within 23.6%-33.3% and 6.7%-10.1% at headstage heights of 8 and 20 cm, respectively, while continuously delivering >40 mW to the Rx electronics even at 90° rotation. As a proof of EnerCage-HC2 functionality in vivo, a previously documented on-demand electrical stimulation of the globus pallidus, eliciting consistent head rotation, is demonstrated in three freely behaving rats.


Assuntos
Fontes de Energia Elétrica/veterinária , Abrigo para Animais , Monitorização Ambulatorial/instrumentação , Monitorização Ambulatorial/veterinária , Tecnologia sem Fio/instrumentação , Animais , Transferência de Energia , Desenho de Equipamento , Análise de Falha de Equipamento , Masculino , Miniaturização , Ratos , Ratos Sprague-Dawley
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