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1.
Int J Chron Obstruct Pulmon Dis ; 19: 2073-2095, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39346628

RESUMO

Purpose: To employ bioinformatics and machine learning to predict the characteristics of immune cells and genes associated with the inflammatory response and ferroptosis in chronic obstructive pulmonary disease (COPD) patients and to aid in the development of targeted traditional Chinese medicine (TCM). Mendelian randomization analysis elucidates the causal relationships among immune cells, genes, and COPD, offering novel insights for the early diagnosis, prevention, and treatment of COPD. This approach also provides a fresh perspective on the use of traditional Chinese medicine for treating COPD. Methods: R software was used to extract COPD-related data from the Gene Expression Omnibus (GEO) database, differentially expressed genes were identified for enrichment analysis, and WGCNA was used to pinpoint genes within relevant modules associated with COPD. This analysis included determining genes linked to the inflammatory response in COPD patients and analyzing their correlation with ferroptosis. Further steps involved filtering core genes, constructing TF-miRNA‒mRNA network diagrams, and employing three types of machine learning to predict the core miRNAs, key immune cells, and characteristic genes of COPD patients. This process also delves into their correlations, single-gene GSEA, and diagnostic model predictions. Reverse inference complemented by molecular docking was used to predict compounds and traditional Chinese medicines for treating COPD; Mendelian randomization was applied to explore the causal relationships among immune cells, genes, and COPD. Results: We identified 2443 differential genes associated with COPD through the GEO database, along with 8435 genes relevant to WGCNA and 1226 inflammation-related genes. A total of 141 genes related to the inflammatory response in COPD patients were identified, and 37 core genes related to ferroptosis were selected for further enrichment analysis and analysis. The core miRNAs predicted for COPD include hsa-miR-543, hsa-miR-181c, and hsa-miR-200a, among others. The key immune cells identified were plasma cells, activated memory CD4 T cells, gamma delta T cells, activated NK cells, M2 macrophages, and eosinophils. Characteristic genes included EGF, PLG, PTPN22, and NR4A1. A total of 78 compounds and 437 traditional Chinese medicines were predicted. Mendelian randomization analysis revealed a causal relationship between 36 types of immune cells and COPD, whereas no causal relationship was found between the core genes and COPD. Conclusion: A definitive causal relationship exists between immune cells and COPD, while the prediction of core miRNAs, key immune cells, characteristic genes, and targeted traditional Chinese medicines offers novel insights for the early diagnosis, prevention, and treatment of COPD.


Assuntos
Biologia Computacional , Aprendizado de Máquina , Medicina Tradicional Chinesa , Análise da Randomização Mendeliana , MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Medicina Tradicional Chinesa/métodos , MicroRNAs/genética , MicroRNAs/metabolismo , Bases de Dados Genéticas , Ferroptose/genética , Ferroptose/efeitos dos fármacos , Simulação de Acoplamento Molecular , Valor Preditivo dos Testes , Redes Reguladoras de Genes , Perfilação da Expressão Gênica/métodos , Biomarcadores/sangue , Medicamentos de Ervas Chinesas/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pulmão/imunologia , Fenótipo , Marcadores Genéticos , Predisposição Genética para Doença , Transcriptoma
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(9): 841-844, 2024 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-39266483

RESUMO

Primary ciliary dyskinesia (PCD) is a heterogeneous genetic disorder associated with abnormalities in ciliary structure and function. Here, we report A 22-year-old non-smoking Chinese man with recurrent episodes of respiratory tract infections and sinusitis since high school period. The diagnosis is more complicated by the atypical symptoms and the late age of onset. We summarized the clinical characteristics of this case and literature review. This report aimed to improve the clinical understanding of primary ciliary dyskinesia.


Assuntos
Dineínas do Axonema , Transtornos da Motilidade Ciliar , Humanos , Masculino , Adulto Jovem , Dineínas do Axonema/genética , Mutação , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/genética , Sinusite/diagnóstico , Sinusite/tratamento farmacológico , Sinusite/genética , Transtornos da Motilidade Ciliar/complicações , Transtornos da Motilidade Ciliar/diagnóstico , Transtornos da Motilidade Ciliar/tratamento farmacológico , Transtornos da Motilidade Ciliar/genética
3.
Animal ; 18(9): 101284, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39226781

RESUMO

Analysis of correlation between the early testable phenotypes of piglets and the final performance of pigs can serve the early selection for breeding. The objectives of this study were to estimate the genetic parameters for birth weight (BtW), age (AGE) and backfat thickness (BF) up to 115 kg BW and to analyse the relationships among these three traits, and to estimate the accuracy of using BtW to predict estimated breeding values (EBVs) of AGE and BF in Landrace and Duroc pigs. Data on 26 614 Landrace and 19 984 Duroc pigs, born between 2001 and 2018, were collected from the core breeding group of a farm. All pigs were recorded for phenotypes including BtW, AGE and BF. The factors affecting these three traits were analysed using R v4.2.0 Software. The population genetic parameters and breeding values of three traits were estimated by using a multitrait animal model based on AI plate of DMU software. Heritabilities for BtW, AGE and BF were moderate to high for Landrace (0.437, 0.282and 0.137, respectively) and Duroc breeds (0.369, 0.279 and 0.148). BtW was genetically correlated with AGE and BF in Landrace (-0.213, 0.037) and Duroc (-0.214, 0.025). AGE was negatively genetically correlated with BF in both Landrace (-0.036) and Duroc (-0.057) pigs. The heritability of BtW, AGE and BF of Landrace pigs and Duroc pigs were 0.148, 0.182 and 0.075 and 0.168, 0.159 and 0.120, respectively, by taking into account of the litter effect. BtW was genetically correlated with AGE and BF in Landrace (-0.094, 0.002) and Duroc (-0.199, -0.052). AGE was negatively genetically correlated with BF in both Landrace (-0.034) and Duroc (-0.153) pigs. The variances between total individual BtW and AGE and BF were then used to predict the EBV of AGE and BF for individuals with AGE or BF phenotypes missing under 10-fold cross-validation. Prediction accuracy was calculated as the Kendall tau-b correlation coefficient between EBVs and EBVs via 10-fold cross-validation. Prediction accuracy for AGE and BF was 0.655 and 0.611 in Landrace, 0.665 and 0.617 in Duroc. After incorporation of the litter effect, the prediction accuracy for AGE and BF increased to 0.690 and 0.665 in Landrace and to 0.705 and 0.649 in Duroc. So, the EBV of AGE and BF phenotypes missing individuals could be predicted by using the available phenotypic data and the easily measured BtW, and litter effect could boost the accuracy of prediction.


Assuntos
Peso ao Nascer , Cruzamento , Fenótipo , Animais , Peso ao Nascer/genética , Feminino , Masculino , Sus scrofa/genética , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/fisiologia , Suínos/genética , Suínos/crescimento & desenvolvimento , Característica Quantitativa Herdável
4.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 59(9): 971-976, 2024 Sep 09.
Artigo em Chinês | MEDLINE | ID: mdl-39289988

RESUMO

In salivary gland disease, accessory parotid gland (APG) lesions are relatively low, and tumor is the most common manifestation. Currently, surgery is the primary treatment method for APG tumors. Although numerous surgical procedures are available, there is no standard protocol. Due to the location of the APG in the midcheek area, the complications and aesthetic concerns connected with conventional surgery for treating APG tumors sometimes cause significant distress to patients. With the progress of medical technology as well as improving patients' aesthetic and functional requirements, surgical excision methods and incision design are constantly improving. More beautiful and minimally invasive treatments, such as concealed transoral approach and endoscopically aided extracapsular dissection of APG, have been gradually developed. This review focuses on surgical techniques, benefits, and drawbacks of APG tumor surgery that have been carried out and provides an outlook based on the preliminary application of endoscopically assisted accessory parotid tumor resection.


Assuntos
Glândula Parótida , Neoplasias Parotídeas , Humanos , Endoscopia/efeitos adversos , Endoscopia/métodos , Glândula Parótida/anormalidades , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia
5.
J Phys Condens Matter ; 37(1)2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39321833

RESUMO

We report the structure and properties of a new Ce-based compound Ce3TiAs5synthesized under high-pressure and high-temperature conditions. It crystallizes in a hexagonal Hf5Sn3Cu-anti type structure with zig-zag like Ce chains along thecaxis. This compound is metallic and undergoes a magnetic phase transition atTN= 13 K. A metamagnetic transition occurs at ∼0.7 T. The Sommerfeld coefficient for the compound is determined to be about 215 mJ/(Ce-mol*K2), demonstrating a heavy Fermion behavior. The resistivity is featured with two humps, which arises from the synergistic effect of crystal electric field and magnetic scattering. The magnetic ordering temperatureTNgradually increases in the sequence of Ce3TiPn5with Pn = Bi, Sb, and As, which implies that the Ruderman-Kittel-Kasuya-Yosida interaction should be still predominant in Ce3TiAs5.

6.
Animal ; 18(9): 101258, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39126800

RESUMO

The uncertainty resulting from missing genotypes in low-coverage whole-genome sequencing (LCWGS) data complicates genotype imputation. The aim of this study is to find out an optimal strategy for accurately imputing LCWGS data and assess its effectiveness for genomic prediction (GP) and genome-wide association study (GWAS) on economically important traits of Large White pigs. The LCWGS data of 1 423 Large White pigs were imputed using three different strategies: (1) using the high-coverage whole-genome sequencing (HCWGS) of 30 key progenitors as the reference panel (Ref_LG); (2) mixing HCWGS of key progenitors with LCWGS (Mix_HLG) and (3) self-imputation in LCWGS (Within_LG). Additionally, to compare the imputation effects of LCWGS, we also imputed SNP chip data of 1 423 Large White pigs to the whole-genome sequencing level using the reference panel consisting of key progenitors (Ref_SNP). To evaluate effects of the imputed sequencing data, we compared the accuracies of GP and statistical power of GWAS for four reproductive traits based on the chip data, sequencing data imputed from chip data and LCWGS data using an optimal strategy. The average imputation accuracies of the Within_LG, Ref_LG and Mix_HLG were 0.9893, 0.9899 and 0.9875, respectively, which were higher than that of the Ref_SNP (0.8522). Using the imputed sequencing data from LCWGS with the Ref_LG imputation strategy, the accuracies of GP for four traits improved by approximately 0.31-1.04% compared to the chip data, and by 0.7-1.05% compared to the imputed sequencing data from chip data. Furthermore, by using the sequence data imputed from LCWGS with the Ref_LG, 18 candidate genes were identified to be associated with the four reproductive traits of interest in Large White pigs: total number of piglets born - EPC2, MBD5, ORC4 and ACVR2A; number of piglets born healthy - IKBKE; total litter weight of piglets born alive - HSPA13 and CPA1; gestation length - GTF2H5, ITGAV, NFE2L2, CALCRL, ITGA4, STAT1, HOXD10, MSTN, COL5A2 and STAT4. With the exception of EPC2, ORC4, ACVR2A and MSTN, others represent novel candidates. Our findings can provide a reference for the application of LCWGS data in livestock and poultry.


Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Sus scrofa , Sequenciamento Completo do Genoma , Animais , Estudo de Associação Genômica Ampla/veterinária , Sequenciamento Completo do Genoma/veterinária , Sus scrofa/genética , Genótipo , Genômica/métodos , Cruzamento , Masculino , Suínos/genética , Feminino
7.
Trop Biomed ; 41(2): 134-141, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-39154264

RESUMO

Malaria is an insect-borne disease transmitted by Anopheles mosquitoes or the importation of Plasmodium-infected blood, posing a serious threat to human health and life safety. This study aims to analyze the incidence of malaria in Qingdao at various stages from 1949 to 2021, to collate the control measures taken at different epidemic stages to assess the effectiveness of malaria control, and to identify a set of malaria control strategies suitable for Qingdao, while providing Chinese experience for other countries or cities in their malaria elimination efforts. A retrospective survey was used to collect information on malaria cases, control measures and prevention and control effects in Qingdao from 1949 to 2021, and to evaluate malaria control strategies and measures in Qingdao. 704 155 cases have been reported from 1949 to 2021, with three epidemic peaks: the incidence rate was 1715.9/100 000 in 1961, 1409.7/100 000 in 1965, and the most severe case occurred in 1972, with an incidence rate of 1635.6/100 000 and a case count exceeding 90 000. Throughout the various stages of malaria epidemics, Qingdao has effectively eliminated indigenous malaria by implementing diverse preventive and control measures. Since the last indigenous case of Plasmodium vivax was reported in 2002, all locally reported cases have been imported, mainly by returning migrant workers from Africa. This study examines a range of malaria prevention and control strategies and interventions that are appropriate for Qingdao. These measures have enabled Qingdao to successfully eliminate malaria and maintain malaria-free status for more than 20 years. These measures can also serve as a reference for similarly situated cities in Africa and Southeast Asia.


Assuntos
Malária , Humanos , China/epidemiologia , Incidência , Estudos Retrospectivos , Malária/prevenção & controle , Malária/epidemiologia , Erradicação de Doenças , Adolescente , Criança , Masculino , Adulto , Feminino , Adulto Jovem , Pré-Escolar , Pessoa de Meia-Idade , Lactente , Idoso
8.
Animal ; 18(6): 101147, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38843669

RESUMO

Understanding the genetic characteristics of indigenous goat breeds is crucial for their conservation and breeding efforts. Hainan black goats, as a native breed of south China's tropical island province of Hainan, possess distinctive traits such as black hair, a moderate growth rate, good meat quality, and small body size. However, they exhibit exceptional resilience to rough feeding conditions, possess high-quality meat, and show remarkable resistance to stress and heat. In this study, we resequenced the whole genome of Hainan black goats to study the economic traits and genetic basis of these goats, we leveraged whole-genome sequencing data from 33 Hainan black goats to analyze single nucleotide polymorphism (SNP) density, Runs of homozygosity (ROH), Integrated Haplotype Score (iHS), effective population size (Ne), Nucleotide diversity Analysis (Pi) and selection characteristics. Our findings revealed that Hainan black goats harbor a substantial degree of genetic variation, with a total of 23 608 983 SNPs identified. Analysis of ROHs identified 53 710 segments, predominantly composed of short fragments, with inbreeding events mainly occurring in ancient ancestors, the estimates of inbreeding based on ROH in Hainan black goats typically exhibit moderate values ranging from 0.107 to 0.186. This is primarily attributed to significant declines in the effective population size over recent generations. Moreover, we identified 921 candidate genes within the intersection candidate region of ROH and iHS. Several of these genes are associated with crucial traits such as immunity (PTPRC, HYAL1, HYAL2, HYAL3, CENPE and PKN1), heat tolerance (GNG2, MAPK8, CAPN2, SLC1A1 and LEPR), meat quality (ACOX1, SSTR1, CAMK2B, PPP2CA and PGM1), cashmere production (AKT4, CHRM2, OXTR, AKT3, HMCN1 and CDK19), and stress resistance (TLR2, IFI44, ENPP1, STK3 and NFATC1). The presence of these genes may be attributed to the genetic adaptation of Hainan black goats to local climate conditions. The insights gained from this study provide valuable references and a solid foundation for the preservation, breeding, and utilization of Hainan black goats and their valuable genetic resources.


Assuntos
Variação Genética , Cabras , Polimorfismo de Nucleotídeo Único , Seleção Genética , Sequenciamento Completo do Genoma , Animais , Cabras/genética , Sequenciamento Completo do Genoma/veterinária , China , Cruzamento , Haplótipos , Endogamia , Homozigoto , Genoma
9.
Zhonghua Nei Ke Za Zhi ; 63(6): 613-617, 2024 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-38825931

RESUMO

To investigate the prevalence and epidemiological characteristics of diabetic retinopathy (DR) in Yunnan Province, explore its risk factors, and provide a basis for the prevention and treatment of chronic complications of diabetes mellitus (DM). This is a large cross-sectional study, in all, 1 524 DM patients in 16 communities and villages of Yunnan Province who were registered in health service centers were included in this study from August to November 2019. All patients completed a uniform questionnaire, anthropometric measurements, biochemical measurements, and auxiliary examinations. Logistic regression analysis was used to screen the risk factors of DR. The prevalence rates of DR, mild non-proliferative DR (mild-NPDR), and referable DR (RDR) were 16.0% (244/1 524), 4.5% (69/1 524), and 11.5% (175/1 524), respectively. Glycated hemoglobin A1c (HbA1c)≥7.0% was the risk factor of mild-NPDR (OR=1.872, 95%CI 1.055-3.323) and RDR (OR=4.821, 95%CI 2.917-7.969). Blood pressure≥130/80 mmHg (1 mmHg=0.133 kPa) was the risk factor of mild-NPDR (OR=1.933, 95%CI 1.112-3.358) and RDR (OR=1.505, 95%CI 1.063-2.130). In Yunnan Province, 16.0% DM patients had accompanying DR, wherein about 71.7% of them required an ophthalmology referral, and the high incidence of RDR in DM patients was associated with poor control of blood glucose and blood pressure.


Assuntos
Retinopatia Diabética , Humanos , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Fatores de Risco , Estudos Transversais , Prevalência , China/epidemiologia , Hemoglobinas Glicadas/análise , Inquéritos e Questionários , Pressão Sanguínea , Masculino , Feminino , Pessoa de Meia-Idade
10.
Zhonghua Yi Xue Za Zhi ; 104(23): 2160-2166, 2024 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-38871474

RESUMO

Objective: To investigate the clinical and genetic mutation characteristics of patients with primary hemophagocytic lymphohistiocytosis (HLH) and their impact on prognosis. Methods: Sixty-three primary HLH patients with complete medical records admitted and diagnosed at Beijing Friendship Hospital of Capital Medical University from January 2013 to December 2022 were selected. The patients' clinical and laboratory features, genetic and rapid immunological indicator characteristics, treatment outcomes and prognosis were retrospectively analyzed. Follow-up was up to June 30, 2023, with a median follow-up time [M (Q1, Q3)] of 47 (21, 76) months. Overall survival was analyzed using Kaplan-Meier survival curve, and prognostic factors were analyzed using Cox proportional hazards regression model. Results: Sixty-three primary HLH patients included 35 males and 28 females, with a median age [M (Q1, Q3)] of 17 (7, 27) years. Clinical manifestations at the initial diagnosis mainly included fever (93.7%, 59/63), splenomegaly (87.3%, 55/63), hemophagocytosis (65.1%, 41/63), hepatomegaly (52.4%, 33/63) and central nervous system (CNS) involvement (38.1%, 24/63). A total of 39 patients (61.9%) were diagnosed with EB virus (EBV) infection at initial diagnosis.PRF1 and UNC13D gene mutations were the most common mutations, and the highest frequency mutation site in the PRF1 gene was c.1349C>T, and that of UNC13D gene was c.2588G>A. A total of 76.2% (48/63) of patients had reduced activity of natural killer (NK) cells. Cytotoxic cell degranulation function was impaired or absent in 52.7% (29/55) of patients, of which 79.2% (19/24) of patients with primary HLH with defects in degranulation-related genes had impaired degranulation function. The 1-year and 3-year overall survival rates were 74.8% and 66.7%, respectively. Cox multivariate analysis suggested that peripheral blood EBV≥10 000 copies/ml (HR=3.523, 95%CI: 1.418-8.757, P=0.007) was the risk factor for prognosis. Conclusions: The main clinical manifestations of primary HLH patients at the initial diagnosis include fever, splenomegaly, hemophagocytosis, hepatomegaly, and CNS involvement. PRF1 and UNC13D are the most commonly mutated genes. High copy number EBV infection in peripheral blood is the risk factor for prognosis.


Assuntos
Linfo-Histiocitose Hemofagocítica , Mutação , Humanos , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/diagnóstico , Masculino , Prognóstico , Feminino , Estudos Retrospectivos , Adolescente , Criança , Adulto , Adulto Jovem , Perforina/genética
12.
J Hosp Infect ; 151: 148-160, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38795904

RESUMO

BACKGROUND: Research on the effectiveness of pharmacist-led antimicrobial stewardship programmes (ASPs) in the urology department is limited. AIM: To evaluate the impact of pharmacist-led multi-faceted ASPs on antibiotic use and clinical outcomes. METHODS: A prescription review of inpatients receiving one or more antibiotics in the urology department of a large teaching hospital in Guangzhou, China, was conducted from April 2019 to March 2023. The pharmacist-led multi-faceted ASP intervention included guideline development, training, medication consultation, review of medical orders, indicator monitoring, and consultation. The primary outcome was antibiotic consumption. The data were analysed using interrupted time-series (ITS) analysis. FINDINGS: Following the implementation of ASPs, an immediate decrease was observed in total antibiotic consumption, antibiotic use rate, second-generation cephalosporins, third-generation cephalosporins, fluoroquinolones, and WHO Watch category antibiotics. No differences were observed in mortality rate before and after the intervention, and no significant short- or long-term effects were found on length of hospital stay (LOS) using ITS. However, there was a significant short-term effect on average antibiotic cost. CONCLUSION: The implementation of pharmacist-led multi-faceted ASPs had positive impacts on reducing antimicrobial consumption without increasing LOS, antibiotic cost, or mortality rate.


Assuntos
Antibacterianos , Gestão de Antimicrobianos , Análise de Séries Temporais Interrompida , Farmacêuticos , Centros de Atenção Terciária , Humanos , Gestão de Antimicrobianos/métodos , China , Antibacterianos/uso terapêutico , Masculino , Feminino , Uso de Medicamentos/normas , Uso de Medicamentos/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Unidade Hospitalar de Urologia/estatística & dados numéricos , Resultado do Tratamento , Hospitais de Ensino , Adulto , Tempo de Internação/estatística & dados numéricos , Idoso de 80 Anos ou mais
13.
Cancer Radiother ; 28(2): 208-217, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519291

RESUMO

In recent years, with the development of artificial intelligence, deep learning has been gradually applied to clinical treatment and research. It has also found its way into the applications in radiotherapy, a crucial method for cancer treatment. This study summarizes the commonly used and latest deep learning algorithms (including transformer, and diffusion models), introduces the workflow of different radiotherapy, and illustrates the application of different algorithms in different radiotherapy modules, as well as the defects and challenges of deep learning in the field of radiotherapy, so as to provide some help for the development of automatic radiotherapy for cancer.


Assuntos
Aprendizado Profundo , Neoplasias , Humanos , Inteligência Artificial , Neoplasias/radioterapia , Algoritmos , Planejamento da Radioterapia Assistida por Computador/métodos
16.
Eur Rev Med Pharmacol Sci ; 28(1): 199-213, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38235871

RESUMO

OBJECTIVE: Colorectal adenomas are an important precancerous lesion of colorectal adenoma with a high incidence. This study aims to explore new prognostic targets for colorectal adenomas through bioinformatics techniques. MATERIALS AND METHODS: In this study, data from 29 colonic adenomas and 38 normal colonic mucosa in GSE37364 were analyzed to screen for differentially expressed genes (DEGs). Then, batch survival analysis, construction of risk model, mutation analysis, Cox regression analysis and expression analysis were performed on DEGs to determine the hub genes of this study. Finally, immune correlation analysis and cell experiments were carried out on the hub gene to explore its potential mechanism. RESULTS: In our study, a total of 431 up-regulated and 809 down-regulated differentially expressed genes (DEGs) were identified. Among these, Unc-5 Netrin Receptor D (UNC5D) emerged as a pivotal gene associated with colorectal adenoma. Notably, UNC5D expression levels were found to be significantly higher in normal tissues compared to colorectal adenoma tissues. Furthermore, our analysis demonstrated that UNC5D showed promising diagnostic potential for patients with colon adenocarcinoma. In vitro experiments revealed that the overexpression of UNC5D had a profound impact on the behavior of colorectal tumor cells. Specifically, it led to a substantial reduction in the proliferation, motility, and invasion of these tumor cells. Additionally, UNC5D was shown to exert control over STAT1/STAT3 phosphorylation, which in turn regulated the expression of PD-L1 in response to interferon (IFN) stimulation. These findings highlight the significant role of UNC5D in modulating immune responses and the development of colorectal adenoma. UNC5D emerges as a potential diagnostic biomarker and an attractive immunotherapeutic target in the context of colorectal malignancies. These results call for further exploration of UNC5D-based strategies for the diagnosis and treatment of colorectal adenoma and adenocarcinoma. CONCLUSIONS: In addition to having the potential to be used as a diagnostic biomarker and an immunotherapeutic target in colorectal malignancies, UNC5D is necessary for the growth of colorectal adenomas. Additionally, UNC5D controlled STAT1/STAT3 phosphorylation to suppress the growth of colorectal cancers by regulating IFN-induced PD-L1 expression.


Assuntos
Adenocarcinoma , Adenoma , Neoplasias Colorretais , Receptores de Superfície Celular , Humanos , Adenocarcinoma/genética , Adenoma/genética , Antígeno B7-H1/genética , Biomarcadores , Proliferação de Células , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Receptores de Superfície Celular/genética
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 43(10): 1761-1770, 2023 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-37933652

RESUMO

OBJECTIVE: To investigate the expression levels of LINC00342 in gastric cancer (GC) tissues and cells and the pathways mediating its effects on biological behaviors of GC cells. METHODS: Bioinformatic analysis was performed to identify the lncRNAs and their downstream miRNAs involved in regulation of biological behaviors of GC cells. qRT-PCR was used to analyze the differential expression of LINC00342 and miR-596 in GC cell lines, human gastric mucosal cells, and GC and adjacent tissues. In human GC MGC-803 and MGC-823 cells, the effects of LINC00342 overexpression, miR-596 overexpression, LINC00342 knockdown, or miR-596 knockdown on cell proliferation, migration, invasion and cell cycle changes were examined using Edu assay, CCK-8 assay, wound healing assay, Transwell assay, and flow cytometry. The regulatory interaction between LINC00342 and miR-596 was investigated using a dual-luciferase reporter assay. RESULTS: Informatic analysis identified LINC00342 as the candidate lncRNA regulating biological behaviors of GC cells, with miR-596 as its downstream miRNA. LINC00342 expression levels were significantly higher while miR-596 expression levels were lower in GC tissues and cell lines than in the paired adjacent tissues and human gastric mucosal cell lines (all P<0.05). In MGC-803 and MGC-823 cells, overexpression of LINC00342 significantly enhanced cell proliferation (P<0.05), migration (P<0.01), and invasion (P<0.001) and reduced the percentage of G0/G1 phase cells (P<0.01), while knocking down LINC00342 significantly suppressed cell proliferation (P<0.05), migration (P<0.01), and invasion (P<0.001) and increased G0/G1 phase cell percentage (P<0.01). Modulation of miR-596 expression levels produced the opposite effects. Dual-luciferase reporter assay confirmed the specific binding between LINC00342 and miR-596 (P=0.0067). CONCLUSION: In GC cells, LINC00342 regulates cell proliferation, migration, and invasion by targeting miR-596.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Invasividade Neoplásica/genética , MicroRNAs/genética , Proliferação de Células , Luciferases/genética , Movimento Celular , Regulação Neoplásica da Expressão Gênica
19.
Zhonghua Xin Xue Guan Bing Za Zhi ; 51(11): 1137-1144, 2023 Nov 24.
Artigo em Chinês | MEDLINE | ID: mdl-37963748

RESUMO

Objective: To investigate the relationship between obstructive sleep apnea (OSA), apnea hypopnea index (AHI) and vascular injury in hypertensive patients. Methods: This cross-sectional study enrolled patients admitted to the Hypertension Department of TEDA International Cardiovascular Hospital from April 2020 to April 2023, who finished portable sleep monitoring. Sleep monitoring indicators, flow-mediated vasodilation (FMD), carotid artery ultrasound, carotid intima-media thickness, cervical and femoral pulse wave conduction velocity (cfPWV), brachial and ankle pulse wave conduction velocity (baPWV) were analyzed. OSA was classified into mild (5 times/h≤AHI<15 times/h), moderate (15≤AHI<30 times/h), and severe (AHI≥30 times/h) based on AHI levels. FMD<6.0% was defined as vascular endothelial injury, and cfPWV>10 m/s and/or baPWV>18 m/s was defined as arterial stiffness. Multivariate logistic regression analysis was used to explore the correlation between AHI, OSA severity and vascular injury, and subgroup analysis was performed in young (age≤45 years) and middle-to-old patients (age>45 years). Sensitivity analysis was performed by excluding patients with diabetes, cerebrovascular disease and coronary heart disease. The correlation between AHI and vascular injury index was analyzed by restricted cubic spline. Results: A total of 555 adult hypertensive patients were included, the mean age was (39.7±9.2) years, 422 were males (76.0%), and the prevalence of OSA was 66.7% (370/555). Multivariate logistic regression analysis showed that moderate OSA (OR=2.83, P=0.019) and severe OSA (OR=3.40, P=0.016) were positively correlated with vascular endothelial injury after adjusting for age, sex, body mass index and mean arterial pressure. Subgroup analysis showed that log AHI (OR=1.99, P=0.035), moderate OSA (OR=4.83, P=0.010) and severe OSA (OR=4.64, P=0.015) were associated with vascular endothelial injury in young hypertensive patients. The results of sensitivity analysis were similar to the above results. The results of restricted cubic spline analysis showed that AHI was correlated with FMD (P=0.022), and the slope of the curve was the largest when AHI was between 0 and 10 times/h. There was no correlation between log AHI and OSA severity and carotid intima-media thickening and arterial stiffness (all P<0.05). Conclusions: OSA is associated with vascular endothelial injury in hypertensive patients, especially in young patients.


Assuntos
Hipertensão , Apneia Obstrutiva do Sono , Rigidez Vascular , Lesões do Sistema Vascular , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Espessura Intima-Media Carotídea , Estudos Transversais , Hipertensão/complicações , Apneia Obstrutiva do Sono/complicações , Artérias Carótidas
20.
Zhonghua Er Ke Za Zhi ; 61(11): 1031-1037, 2023 Nov 02.
Artigo em Chinês | MEDLINE | ID: mdl-37899343

RESUMO

Objective: To assess the clinical features and relative factors of left ventricular hypertrophy (LVH) in children with primary hypertension. Methods: In this retrospective cohort study, 430 children diagnosed with primary hypertension in Children's Hospital, Capital Institute of Pediatrics from January 2019 to September 2022 were enrolled. Their clinical data was analyzed and LVH was assessed by echocardiography. According to left ventricular geometry, these children were assigned to the LVH group and normal geometry group. General conditions, laboratory indicators and ambulatory blood pressure parameters between two groups were compared by independent sample t-test or Mann-Whitney U test. Spearman correlation coefficient was used to analyze the correlation between LVH and clinical indicators including blood pressure, biochemical and metabolic indicators. The independent risk factors of LVH were analyzed by multivariable logistic regression. The receiver operating characteristic (ROC) curve was used to explore the value of risk factors in the diagnosis of LVH. Results: Among the 430 children with primary hypertension, 342 (79.5%) were males and 88 (20.5%) females. Their age was (12.6±2.3) years, and 123 children (28.6%) of them had LVH. Body mass index (BMI) ((30.0±5.2) vs. (26.2±4.3) kg/m2), ratio of stage 2 hypertension (75.6% (93/123) vs. 59.6% (183/307)), 24-hour systolic blood pressure (24 h SBP)((131±10) vs. (128±10) mmHg,1 mmHg=0.133 kPa), daytime systolic blood pressure (SBP) ((135±11) vs. (131±11) mmHg), nighttime SBP ((128±11) vs. (123±10) mmHg), cholesterol level ((4.0±0.7) vs. (3.9±0.7) mmol/L), serum uric acid level ((447±81) vs. (426±91) µmol/L) and incidence of hyperinsulinemia (69.9% (86/123) vs.59.0% (181/307)) were significantly elevated in the LVH group compared with those in the normal geometry group (all P<0.05). There were more patients with a disease course over 5 years in the LVH group than in the normal geometry group, with a statistically significant difference (χ2=8.90,P=0.031). Spearman correlation analysis showed that BMI, 24 h SBP, daytime SBP, nighttime SBP, triglyceride, uric acid, and serum sodium level were positively correlated with LVMI (r=0.43, 0.20, 0.18, 0.18, 0.18, 0.16, and 0.12, all P<0.05). BMI, hyperinsulinemia, and cholesterol level were positively correlated with relative wall thickness (RWT) (r=0.22, 0.12, and 0.16, all P<0.05). The multivariate logistic regression analysis showed that BMI (OR=1.17, 95%CI 1.10-1.25) and 24 h SBP (OR=1.04, 95%CI 1.01-1.08) were the independent risk factors for LVH (both P<0.05). The area under the receiver operator characteristic curve, combined with BMI and 24 h SBP, was 0.72 (95%CI 0.67-0.77, P<0.05), with a sensitivity and specificity of 71.5% and 64.8%, respectively. Conclusions: BMI and 24 h SBP are the independent risk factors for LVH in children with primary hypertension, and the combination of BMI and 24 h SBP has an acceptable diagnostic value for LVH. Early monitoring of these indexes is necessary to predict preclinical cardiac damage.


Assuntos
Hiperinsulinismo , Hipertensão , Masculino , Feminino , Humanos , Criança , Adolescente , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Ácido Úrico , Monitorização Ambulatorial da Pressão Arterial , Estudos Retrospectivos , Pressão Sanguínea/fisiologia , Fatores de Risco , Hipertensão Essencial , Colesterol
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