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1.
Horm Metab Res ; 54(2): 94-103, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35130570

RESUMO

Glycated hemoglobin (HbA1c) variability is emerging as an indicator of long-term glycemic control, which may play a significant role during vascular complications. We conducted a systematic review and meta-analysis to assess the association between the scope of HbA1c variability and vascular complications in patients with type 2 diabetes mellitus. PubMed and Embase were searched for studies that evaluated the association of HbA1c variability with vascular complications in patients with type 2 diabetes. Two reviewers independently completed data extraction. Random-effects meta-analysis was conducted with stratification according to the type of vascular complications. Nine studies were eligible for inclusion in our systematic review and meta-analysis. Six studies evaluated the impact of the standard deviation of HbA1c (HbA1c-SD) on cardiovascular events and showed an association of HbA1c-SD with cardiovascular events (HR: 1.25, 95% CI 1.18-1.32, 5 studies). Six studies evaluated renal disease associated with HbA1c-SD and showed that HbA1c-SD was correlated with an increased risk of renal disease (HR: 1.19, 95% CI 1.13-1.24). Two studies evaluated HbA1c-SD and the risk of retinopathy and showed that no significant association was found between retinopathy and HbA1c-SD (HR 1.08, 95% CI 0.92-125). For HbA1c-SD ranging from 0.6 to 0.8%, HbA1c-SD was associated with an increased risk of cardiovascular events (HR: 1.25, 95% CI 1.15-1.35) and renal disease (HR: 1.16, 95% CI 1.11-1.22). For individuals with index HbA1c variability greater than or equal to 0.6%, HbA1c variability was significantly associated with vascular complications in patients with type 2 diabetes mellitus.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Glicemia/análise , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Hemoglobina A Glicada/análise , Humanos , Estudos Prospectivos
3.
Polymers (Basel) ; 14(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36235968

RESUMO

Shape-morphing hydrogels have drawn great attention due to their wide applications as soft actuators, while asymmetric responsive shape-morphing behavior upon encountering external stimuli is fundamental for the development of hydrogel actuators. Therefore, in this work, bilayer hydrogels were prepared and the shrinkage ratios (LA/LN) of the AAm/AAc layer to the NIPAM layer immersed in different metal ion solutions, leading to bending in different directions, were investigated. The difference in the shrinkage ratio was attributed to the synergistic effect of the osmolarity difference between the inside and outside of the hydrogels and the interaction difference between the ion and hydrogel polymer chains. Additionally, under thermal stimuli, the hydrogel actuator would bend toward the NIPAM layer due to the shrinkage of the hydrogel networks caused by the hydrophilic-hydrophobic phase transition of NIPAM blocks above the LCST. This indicates that metal ion and thermal-responsive shape-morphing hydrogel actuators with good mechanical properties could be used as metal ion or temperature-controllable switches or other smart devices.

4.
Carbohydr Polym ; 297: 120048, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36184184

RESUMO

This study aimed to develop chitosan/bacterial cellulose-based films loaded with tea polyphenol-loaded chitosan coated nanoliposomes (CS-TP-lip) as an active agent for food preservation. The effects of the CS-TP-lip on the physicochemical properties of composite films were systematically evaluated. The CS-TP-lip exhibited spherical shapes with an average particle size of about 300 nm. Scanning electron microscopy and Fourier transform infrared spectroscopy analyses suggested high compatibility between the CS-TP-lip and film matrix through intermolecular interactions. Furthermore, due to the CS-TP-lip's presence, the elongation at break and thermal stability of the films could be enhanced to reach 75.14 ± 1.2 % and 395.33 °C, respectively, and the stability of tea polyphenol could be increased to prolong its functioning time. The films were successfully used as packaging materials for fish fillet preservation. Therefore, the developed nanocomposite films exhibit great promise as a new generation of biodegradable, sustainable, and bioactive film for food preservation.


Assuntos
Carpas , Quitosana , Animais , Celulose , Quitosana/química , Embalagem de Alimentos/métodos , Polifenóis , Chá
5.
J Clin Med ; 11(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36294374

RESUMO

Accumulated hard tissue debris (AHTD) is an inevitable by-product during endodontic treatment and is difficult to remove completely using traditional syringe and needle irrigation (SNI). Adjunctive irrigation is proposed to assist the clean-up of AHTD. This systematic review and meta-analysis aimed to evaluate the AHTD removal efficacy of different root canal irrigation devices using micro-computed tomography (Micro-CT). A literature search was carried out within the main scientific databases until 20 June 2022. All results were screened with detailed eligibility criteria. Eleven studies were included for analysis. SNI, passive ultrasonic irrigation (PUI), negative pressure systems, sonically activated irrigation (SAI), mechanical-activated system and laser-activated irrigation (LAI) were assessed. PUI is superior to SNI for debris removal and LAI has better AHTD removal performance than PUI. The negative pressure system and mechanical-activated system were proved to be less effective. Registration: PROSPERO (CRD42021273892).

6.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 51(3): 306-313, 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-36207832

RESUMO

OBJECTIVE: To investigate molecular and clinical characteristics of children with permanent congenital hypothyroidism (CH) in Yunnan, China. METHODS: The clinical data of 40 children with CH diagnosed and treated in the First People's Hospital of Yunnan Province during January 2016 and January 2019 were retrospectively analyzed. All children were followed up to 3 years old, and Gesell intelligent score was evaluated at age of 1, 2 and 3 years, respectively. Developmental status and prognosis were evaluated. Next-generation sequencing (NGS) was used to screen all exons and exon-intron boundary sequences of the 27 known CH associated genes, and the relationship between genotypes and clinical phenotypes was analyzed. RESULTS: Among the 40 children, the thyroid related pathogenic gene mutations were detected in 23 cases with a rate of 57.5%, and a total of 32 mutations of 8 genes were detected. Mutations in DUOX2, TPO and TSHR genes were the most common ones with mutation frequencies of 65.9%(29/44), 11.4%(5/44) and 9.1%(4/44), respectively. DUOX2 gene mutations were detected in 17 children with CH, and a total of 17 mutation types were detected. p.K530* was the most common mutation in DUOX2 gene, accounting for 20.7%(6/29). There was no significant difference in physical development and intelligence assessment between children with DUOX2 heterozygous mutation and compound heterozygous mutations. None of patients could terminate medication at 3 years of the follow-up and all of them were provisionally assessed as permanent CH. The physical and mental development assessment of children with other gene mutations were also in the normal range. CONCLUSION: The detection rate of DUOX2, TPO and TSHR pathogenic mutations are high among children with permanent CH in Yunnan area, and no correlation is observed between gene mutation types and prognosis in children with CH.


Assuntos
Hipotireoidismo Congênito , China , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , Oxidases Duais/genética , Humanos , Mutação , Estudos Retrospectivos
7.
Artigo em Inglês | MEDLINE | ID: mdl-36226442

RESUMO

To examine the association between human leukocyte antigen (HLA) and nevirapine (NVP)- and efavirenz (EFV)-induced cutaneous adverse reactions in human immunodeficiency virus (HIV) patients, we conducted a case-control study at our center consisting of 96 patients. Patients were further assigned based on the occurrence of cutaneous adverse events and the drugs involved. All patients were subjected to next generation sequencing (NGS)-based screening with focus on HLA phenotype, including the presence of HLA-B, HLA-C, and HLA-DRB1. Our data indicated that the HLA-C*01:02:01 allele presence was observed in 47.4% (18/38) of patients in the EFV-hypersensitivity group compared with 18.9% (7/30) in the control group [odds ratio (OR) = 5.837; 95% confidence interval (CI) = 1.727-19.722, p = .005]. In contrast, the occurrence of HLA-DRB1*08:03 was found to be significantly lower in the EFV-hypersensitivity group (4/38, 10.5%) compared with the corresponding control group (12/37, 32.4%) (OR = 0.148; 95% CI = 0.035-0.625, p = .009). In addition, the HLA-DRB1*04:05:01 antigen was expressed more frequently in the NVP-hypersensitivity group (23.8%, 5/21) compared with the control group (10.8%, 4/37) (OR = 7; 95% CI = 1.265-38.793, p = .026). Our data not only revealed a significant association between HLA-C*01:02:01 and EFV-induced cutaneous adverse reactions but may also shed light on defining the treatment for Chinese HIV patients.

8.
ACS Sens ; 7(11): 3461-3469, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36273329

RESUMO

Most label-free techniques rely on measuring refractive index or mass change on the sensor surface. Thus, it is challenging for them to measure small molecules or enzymatic processes that only induce a minor mass change on the analyte molecules. Here, we have developed a technique by combining Surface Plasmon Resonance sensing with an Oscillating Biomolecule Layer approach (SPR-OBL) to enhance the sensitivity of traditional SPR. In addition to the inherent mass sensitivity, SPR-OBL is also sensitive to the charge and conformational change of the analyte; hence it overcomes the mass limit and is able to detect small molecules. We show that the multimetric SPR-OBL measurement allows for sensing any changes regarding mass, charge, and conformation, which expands the detection capability of SPR.


Assuntos
Refratometria , Ressonância de Plasmônio de Superfície , Ressonância de Plasmônio de Superfície/métodos , Cinética
9.
Cell Death Dis ; 13(9): 763, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057625

RESUMO

Genetic abnormalities in histone methyltransferases (HMTs) frequently occur in diffuse large B-cell lymphoma (DLBCL) and are related to its progression. SET and MYND domain containing 3 (SMYD3) is an HMT that is upregulated in various tumors and promotes their malignancy. However, to the best of our knowledge, the function of SMYD3 in DLBCL has not been investigated thus far. In the present study, 22 HMT genes related to cancer development were first selected according to current literature, and it was found that high SMYD3 expression was significantly associated with poor progression-free survival in patients with DLBCL. SMYD3 protein levels were upregulated and positively associated with poor prognosis and poor responsiveness to chemotherapy in patients with DLBCL. Functional examinations demonstrated that SMYD3 increased cell proliferation and the flux of aerobic glycolysis in DLBCL cells in vitro and in vivo and decreased cell sensitivity to doxorubicin in vitro. Moreover, SMYD3 could directly bind to specific sequences of Pyruvate Kinase M2 (PKM2) and promote DLBCL cell proliferation and aerobic glycolysis via H3K4me3-mediated PKM2 transcription. Clinically, SMYD3 expression positively correlated with that of PKM2, and high SMYD3 was significantly associated with high maximum standardized uptake value (SUVmax) detected by [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (PET/CT) in DLBCL samples. Concomitant expression of SMYD3 and PKM2 positively correlated with poor progression-free and overall survival in patients with DLBCL and may serve as novel biomarkers in DLBCL.


Assuntos
Proteínas de Transporte/genética , Linfoma Difuso de Grandes Células B , Proteínas de Membrana/genética , Hormônios Tireóideos/genética , Fluordesoxiglucose F18 , Glicólise , Histona-Lisina N-Metiltransferase/metabolismo , Histonas , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Piruvato Quinase
10.
BMC Oral Health ; 22(1): 424, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138429

RESUMO

BACKGROUND: The COVID-19 pandemic challenged all healthcare providers including dental practitioners. This cross-sectional study aimed to investigate the dental practitioners' perceptions and attitudes towards the impacts of COVID-19 on their professional practice, career decision and patient care. METHODS: Data was collected from dental practitioners registered in New South Wales (NSW), Australia using an online survey. RESULTS AND CONCLUSION: Responses received from 206 dental practitioners revealed their perceptions and attitudes towards COVID-19 infection risk, clinical guidelines, and measures adopted to deliver patient care. Majority of participants perceived the risk of infection in dentistry was higher compared with other health professionals. Most dental practices have followed guidelines received from professional associations and adopted multiple measures such as providing hand sanitizer, social distancing, and risk screen, to ensure safe delivery of oral health care. Over 80% of dental practitioners raised concerns on patients' accessibility to dental care during the pandemic. Despite tele-dentistry was introduced, almost half of the participants did not recognize tele-dentistry as an effective alternative. Moreover, negative impacts of COVID-19 pandemic on dental practitioner's professional career have been reported, including lower practice safety, reduction in working hours and income. Noteworthy, one quarter of participants even considered changing their practice environment, moving sectors or even leaving their career in dentistry. However, majority of the dental practitioners are willing to stay in their current practice environment and continue their career in dentistry. Our observations demonstrate the systematic disruption to dental practice faced in Australia due to the COVID-19 pandemic. Providing dental practitioners with timely educational training and support is important to minimise negative impacts of the challenges and to optimise dental care.


Assuntos
COVID-19 , Higienizadores de Mão , Estudos Transversais , Odontologia , Odontólogos , Humanos , Pandemias , Papel Profissional , Inquéritos e Questionários
11.
Brain Res Bull ; 190: 84-96, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36174874

RESUMO

Patients with diabetes mellitus (DM) have an increased risk of diabetic encephalopathy symptoms such as depressive-like behaviour and cognitive impairment. Exercise is an effective strategy for preventing and treating DM and diabetic complications. The aim of this study is to investigate the effects and potential mechanisms of treadmill exercise training on diabetes-induced depressive-like behavior and cognitive impairment in db/db mice. In this study, the mice were divided into three groups (n = 10 per group) as follows: healthy-sedentary (db/m), diabetes-sedentary (db/db), and diabetes-treadmill exercise training (db/db-TET). The db/db-TET mice were performed five days per week at a speed of 8 m/min for 60 min/day for 8 weeks, following which body weight, fasting blood glucose, insulin resistance, behavioral, synaptic ultrastructure, oxidative stress, apoptotic signaling, and inflammatory responses were evaluated. As a result, treadmill exercise training significantly decreased body weight and fasting blood glucose levels, increased insulin sensitivity, protected synaptic ultrastructure, reduced depression-like behavior, and improved learning and memory deficits in db/db mice. In addition, treadmill exercise training significantly suppressed NOX2-mediated oxidative stress, resulting in a decrease in NOX2-dependent ROS generation in the db/db mouse hippocampus CA1 region. Reduced ROS generation prevented the apoptotic signaling pathway and NLRP3 inflammasome activation, thereby ameliorating hippocampus neuronal damage. In summary, the results indicated that treadmill exercise training significantly ameliorates hippocampus injury by suppressing oxidative stress-induced apoptosis and NLRP3 inflammasome activation, consequently ameliorating diabetes-induced depressive-like behavior and cognitive impairment in db/db mice.


Assuntos
Disfunção Cognitiva , Complicações do Diabetes , Diabetes Mellitus , Resistência à Insulina , Condicionamento Físico Animal , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Glicemia , Espécies Reativas de Oxigênio/metabolismo , Hipocampo/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Disfunção Cognitiva/metabolismo , Neurônios/metabolismo , Camundongos Endogâmicos , Complicações do Diabetes/metabolismo , Peso Corporal , Diabetes Mellitus/metabolismo
12.
Front Oncol ; 12: 912882, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059706

RESUMO

Background: Early diagnosis of colorectal cancer could significantly improve the prognosis and reduce mortality. However, indeterminate diagnosis is often met in pathology diagnosis in biopsy samples. Abnormal expression of long non-coding RNA (lncRNA) is associated with the initiation and progression of colorectal cancer. It is of great value and clinical significance to explore lncRNAs as candidate diagnostic biomarkers in colorectal cancer. Methods: Based on the within-sample relative expression levels of lncRNA pairs, we identified a group of candidate diagnostic biomarkers for colorectal cancer. In addition, we validated it in independent datasets produced by different laboratories and different platforms. We also tested it in colorectal cancer tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). Results: A biomarker consisting of six lncRNA pairs including nine lncRNAs was identified for the diagnosis of colorectal cancer. For a total of 950 cancer samples and 247 non-cancer samples, both of the sensitivity and specificity could achieve approximately 90%. For adenoma samples, the accuracy could achieve 73%. For normal tissues from inflammatory bowel disease patients, 93% (14/15) were correctly classified as non-cancer. Furthermore, the lncRNA pair biomarker showed excellent performance in all clinical stages; even in the early stage, the accuracy could achieve 87% and 82% in stage I and II. Meanwhile, the biomarker was also robust to the microsatellite instability status. More importantly, we measured the biomarker in 35 colorectal cancer and 30 cancer-adjacent tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). The accuracy could achieve 93.3% (70/75). Specially, even in early-stage tumors (I and II), the accuracy could also achieve 90.9% (30/33). The enrichment analysis revealed that these lncRNAs were involved in highly associated cancer pathways and immune-related pathways. Immune analysis showed that these marker lncRNAs were associated with multiple immune cells, implying that they might be involved in the regulation of immune cell functions in colorectal cancer. Most of the biomarker lncRNAs were also differentially expressed between the mutant group and wild-type group of colorectal cancer driver genes. Conclusion: We identified and validated six lncRNA pairs including nine lncRNAs as a biomarker for assisting in the diagnosis of colorectal cancer.

13.
Front Pharmacol ; 13: 964829, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120358

RESUMO

Liver fibrosis is a pathological process which can progress to hepatocirrhosis, even hepatocellular carcinoma. Phosphatidylethanolamine-binding protein 4 (PEBP4) is a secreted protein involved in regulating many molecular pathways, whereas its roles in diseases including hepatic fibrosis remain undefined. The nuclear factor-κappa B (NF-κB) signaling pathway has been found to be involved in the development of liver fibrosis. In this study, we generated a hepatocyte-conditional knockout (CKO) mouse model of PEBP4, and explored the potential functions of PEBP4 on liver fibrosis and the NF-κB signaling pathway in a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis. We demonstrated that PEBP4 CKO aggravated CCl4-triggered liver fibrosis, as evidenced by altered histopathology, an increase in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hydroxyproline (HYP) levels, and more collagen deposition, as well as by enhanced expression of fibrotic markers including α-smooth muscle actin (α-SMA), collagen I and collagen III. Mechanistically, PEBP4 deficiency activated the NF-κB signaling pathway, as indicated by increased phosphorylation of NF-κB p65 and inhibitor protein κB inhibitor-α (IκB-α), and nuclear NF-κB p65 expression in the fibrotic liver. Notably, the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) partially blocked the activation of the NF-κB pathway, and reversed the pro-fibrotic effect of PEBP4 deletion in CCl4-treated mice. Together, these results suggest that PEBP4 deficiency results in aggravation of liver fibrosis and activation of the NF-κB signaling pathway, supporting a novel concept that PEBP4 is a crucial player in hepatic fibrosis, but also might be a negative regulator of the NF-κB signaling in liver fibrosis.

16.
Eur J Pharmacol ; 931: 175229, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36002039

RESUMO

Tumour-associated macrophages (TAMs) have been found to be of great importance in tumorigenesis and in promoting malignant progression, including tumour angiogenesis and metastasis. Moreover, the TAM phenotype is more likely to be an M2 type. Transforming TAMs by M2-polarization into the tumour-suppressive M1-phenotype is an important approach for tumour therapy. In this review, we analysed the effects of the tumour microenvironment on macrophage phenotype-switching, including hypoxia and cytokines, and the mechanisms of drugs targeting TAMs. Furthermore, we analysed the effects of exosomes on macrophage polarization, phenotype switching of macrophages, and the mechanisms of lipid mediators targeting TAMs.


Assuntos
Macrófagos , Neoplasias , Humanos , Ativação de Macrófagos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fenótipo , Microambiente Tumoral
17.
Front Comput Neurosci ; 16: 942979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034935

RESUMO

Objectve: Emotional brain-computer interface can recognize or regulate human emotions for workload detection and auxiliary diagnosis of mental illness. However, the existing EEG emotion recognition is carried out step by step in feature engineering and classification, resulting in high engineering complexity and limiting practical applications in traditional EEG emotion recognition tasks. We propose an end-to-end neural network, i.e., E2ENNet. Methods: Baseline removal and sliding window slice used for preprocessing of the raw EEG signal, convolution blocks extracted features, LSTM network obtained the correlations of features, and the softmax function classified emotions. Results: Extensive experiments in subject-dependent experimental protocol are conducted to evaluate the performance of the proposed E2ENNet, achieves state-of-the-art accuracy on three public datasets, i.e., 96.28% of 2-category experiment on DEAP dataset, 98.1% of 2-category experiment on DREAMER dataset, and 41.73% of 7-category experiment on MPED dataset. Conclusion: Experimental results show that E2ENNet can directly extract more discriminative features from raw EEG signals. Significance: This study provides a methodology for implementing a plug-and-play emotional brain-computer interface system.

18.
ACS Appl Mater Interfaces ; 14(35): 40460-40468, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36006960

RESUMO

Cross-section wood (CW) is generally used as a host for free-standing electrodes, as the abundant opened pores can provide large space for loading guest materials with high electrical conductivity and electrochemical activity. However, there is still a challenge for CW to be used in flexible supercapacitors (SCs) because of its low mechanical strength. Herein, as an alternative to CW, vertical-section wood (VW) with excellent mechanical strength and good flexibility is developed and used as a free-standing and flexible electrode by using Ti3C2Tx (MXene) with ultrahigh conductivity and good electrochemical activity as a guest material. In particular, the highly accessible bonding interface for Ti3C2Tx is first built by delignification on VW to generate abundant pores for continuously absorbing Ti3C2Tx and to expose cellulose with abundant oxygen-containing groups for stable combination with Ti3C2Tx. Then, cyclic pressing is used to form negative pressure to pump the Ti3C2Tx suspension into VW, combining with a preheating process to trigger layer-by-layer self-assembly of Ti3C2Tx nanosheets onto a wood cell wall by evaporating water in the suspension. As a result, the free-standing electrode has a large Ti3C2Tx loading mass proportion of 33 wt %, a high conductivity of 3.14 S cm-1, and good flexibility with much higher mechanical strength of 15.1 MPa than 0.4 MPa of CW. The symmetric SC delivers a good specific capacitance of 805 mF cm-2 at 0.5 mA cm-2, a remarkably high rate capability of 84% to 10 mA cm-2, and an energy density of 13.85 µW h cm-2 at 87.5 µW cm-2. Additionally, this SC shows a long lifespan of 90.5% after 10,000th charge and discharge cycles even at a constant bending angle of 90°, suggesting promising potential in flexible devices.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35939113

RESUMO

PURPOSE: To better understand the clinicopathological characteristics and molecular alterations in different intratumoral components of colorectal cancer (CRC) with heterogeneity of mismatch repair (MMR) protein expression and microsatellite instability (MSI) status. METHODS: The histopathological features, MSI status, and other molecular alterations were analyzed in separately microdissected intratumoral regions and matched metastatic lymph nodes in four cases with intratumoral heterogenous MMR expression screened from 500 CRC patients, using PCR-based MSI testing, MLH1 promoter methylation, and targeted next-generation sequencing (NGS). RESULTS: High microsatellite instability (MSI-H) was identified in MLH1/PMS2-deficient regions in Cases 1 to 3 and in MSH2/MSH6-deficient regions in Case 4, while microsatellite stability (MSS) was detected in all the intratumoral regions and metastatic lymph nodes with proficient MMR expression (pMMR). Intratumoral heterogeneity of MLH1 promoter methylation and/or other common driving gene mutations of CRC, such as KRAS and PIK3CA mutations, was identified in all four CRCs. Further, three cases (75%) showed heterogeneous histomorphological features in intratumoral components and metastatic lymph nodes (Cases 1, 2, and 4), and the corresponding metastatic lymph nodes showed moderate differentiation with MSS/pMMR (Cases 2 and 3). CONCLUSIONS: Intratumoral heterogeneous MSI status is highly correlated with intratumoral histomorphological heterogeneity, which is also an important clue for the intratumoral heterogeneity of drive gene mutations in CRC. Thus, it is essential to detect MMR protein expression and other gene mutations in metastases before treatment, especially for CRCs with intratumoral heterogenous MMR protein expression or heterogenous histomorphological features.

20.
Behav Brain Res ; 435: 114058, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-35995263

RESUMO

BACKGROUND: The current diagnosis of major depressive disorder (MDD) is mainly based on the patient's self-report and clinical symptoms. Machine learning methods are used to identify MDD using resting-state functional magnetic resonance imaging (rs-fMRI) data. However, due to large site differences in multisite rs-fMRI data and the difficulty of sample collection, most of the current machine learning studies use small sample sizes of rs-fMRI datasets to detect the alterations of functional connectivity (FC) or network attribute (NA), which may affect the reliability of the experimental results. METHODS: Multisite rs-fMRI data were used to increase the size of the sample, and then we extracted the functional connectivity (FC) and network attribute (NA) features from 1611 rs-fMRI data (832 patients with MDD (MDDs) and 779 healthy controls (HCs)). ComBat algorithm was used to harmonize the data variances caused by the multisite effect, and multivariate linear regression was used to remove age and sex covariates. Two-sample t-test and wrapper-based feature selection methods (support vector machine recursive feature elimination with cross-validation (SVM-RFECV) and LightGBM's "feature_importances_" function) were used to select important features. The Shapley additive explanations (SHAP) method was used to assign the contribution of features to the best classification effect model. RESULTS: The best result was obtained from the LinearSVM model trained with the 136 important features selected by SVMRFE-CV. In the nested five-fold cross-validation (consisting of an outer and an inner loop of five-fold cross-validation) of 1611 data, the model achieved the accuracy, sensitivity, and specificity of 68.90 %, 71.75 %, and 65.84 %, respectively. The 136 important features were tested in a small dataset and obtained excellent classification results after balancing the ratio between patients with depression and HCs. CONCLUSIONS: The combined use of FC and NA features is effective for classifying MDDs and HCs. The important FC and NA features extracted from the large sample dataset have some generalization performance and may be used as a reference for the altered brain functional connectivity networks in MDD.


Assuntos
Transtorno Depressivo Maior , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Reprodutibilidade dos Testes
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