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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(12): 1541-1545, 2023 Dec 10.
Artigo em Zh | MEDLINE | ID: mdl-37994139

RESUMO

OBJECTIVE: To explore the genetic basis for a child with multiple malformations. METHODS: A child who had presented at Shanxi Provincial Children's Hospital in February 2021 was selected as the study subject. Clinical data of the patient was collected, and whole exome sequencing (WES) was carried out to screen pathogenic variants associated with the phenotype. Candidate variant was validated by Sanger sequencing of her family members. RESULTS: The child had normal skin, but right ear defect, hemivertebral deformity, ventricular septal defect, arterial duct and patent foramen ovale, and separation of collecting system of the left kidney. Cranial MRI showed irregular enlargement of bilateral ventricles and widening of the distance between the cerebral cortex and temporal meninges. Genetic testing revealed that she has harbored a heterozygous variant of NM_178014.4: c.217A>G (p.Met73Val) in the TUBB gene, which was unreported previously and predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The child was diagnosed with Complex cortical dysplasia with other brain malformations 6 (CDCBM6). CONCLUSION: CDCBM is a rare and serious disease with great genetic heterogeneity, and CDCBM6 caused by mutations of the TUBB gene is even rarer. Above finding has enriched the variant and phenotypic spectrum of the TUBB gene, and provided important reference for summarizing the genotype-phenotype correlation of the CDCBM6.


Assuntos
Anormalidades Múltiplas , Antígenos de Grupos Sanguíneos , Malformações do Desenvolvimento Cortical , Humanos , Criança , Feminino , Família , Malformações do Desenvolvimento Cortical/genética , Encéfalo , Mutação
2.
Breast Cancer Res Treat ; 196(1): 45-56, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36056297

RESUMO

INTRODUCTION: Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). MATERIALS AND METHODS: We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. RESULTS: We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. CONCLUSION: Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Inibidores de Checkpoint Imunológico , Ligantes , Linfócitos do Interstício Tumoral , Mutação , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/terapia , Tirosina/metabolismo
3.
J Musculoskelet Neuronal Interact ; 22(2): 261-268, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35642705

RESUMO

OBJECTIVES: MicroRNAs (miRNAs) have been considered as a new class of novel diagnostic and predictive biomarker in many diseases. However, there are few studies on miRNA in osteosarcoma (OS). This study aimed to investigate the roles of miR-30 on OS occurrence and development. METHODS: PCR was used to detect mRNA levels of miR-30 and MTA1 in cancer tissues, adjacent non-cancerous tissues from OS patients. Western blot was used to detect MTA1 protein expression in all tissues and cell lines (hFOb1.19,Saos-2, MG63, and U2OS). The correlation between miR-30 and MTA1 was predicted through bioinformatics software, and identified by a luciferase reporting experiment. In vitro, functional test detected the specific effects of miR-30 and MTA1 on the development of OS. RESULTS: miR-30 expression was significantly reduced, while the expression of MTA1 was increased in OS tissues and cells. Luciferase reporting experiment showed that miR-30 sponged MTA1 which was negatively correlated with miR-30 expression. Furthermore, rescue tests revealed that MTA1 restrained the functions of miR-30 on cell proliferation and migration of OS. CONCLUSION: Our finding showed that miR-30 modulated the proliferation and migration by targeting MTA1 in OS.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Proteínas Repressoras , Transativadores , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transativadores/genética , Transativadores/metabolismo
4.
J Clin Lab Anal ; 35(1): e23567, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32909271

RESUMO

BACKGROUND: Treacher Collins syndrome (TCS) is a rare autosomal dominant or recessive disorder, that involves unique bilateral craniofacial malformations. The phenotypes of TCS are extremely diverse. Interventional surgery can improve hearing loss and facial deformity in TCS patients. METHOD: We recruited seven TCS families. Variant screening in probands was performed by targeted next-generation sequencing (NGS). The variants identified were confirmed by Sanger sequencing. The pathogenicity of all the mutations was evaluated using the guidelines of the American College of Medical Genetics and Genomics (ACMG) and InterVar software. RESULTS: Three frameshift variants, two nonsense variants, one missense variant, and one splicing variant of TCOF1 were identified in the seven TCS probands. Five variants including c.1393C > T, c.4111 + 5G>C, c.1142delC, c.2285_2286delCT, and c.1719delG had not been previously reported. Furthermore, we report the c.149A > G variant for the first time in a Chinese TCS patient. We provided prenatal diagnosis for family 4. Proband 7 chose interventional surgery. CONCLUSION: We identified five novel variants in TCOF1 in Chinese patients with TCS, which expands the mutation spectrum of TCOF1 in TCS. Bone conduction hearing rehabilitation can improve hearing for TCS patients and prenatal diagnosis can provide fertility guidance for TCS families.


Assuntos
Disostose Mandibulofacial/genética , Mutação/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , China , Análise Mutacional de DNA , Orelha/patologia , Face/patologia , Feminino , Perda Auditiva Condutiva/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Masculino
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(2): 138-140, 2021 Feb 10.
Artigo em Zh | MEDLINE | ID: mdl-33565066

RESUMO

OBJECTIVE: To explore the genetic basis for a child with unexplained global developmental delay (GDD), seizure, and facial deformity. METHODS: Whole exome sequencing (WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of the patient and his parents. RESULTS: WES revealed that the patient has carried a previously unreported de novo heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene, Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.4906C>T variant of KMT2A gene was predicted to be pathogenic (PVS1+ PS2+ PM2+PP3). CONCLUSION: The heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene probably underlay the disease in the child. Above finding has enriched the spectrum of pathogenic variants of the KMT2A gene.


Assuntos
Anormalidades Múltiplas/genética , Histona-Lisina N-Metiltransferase/genética , Deficiência Intelectual/genética , Proteína de Leucina Linfoide-Mieloide/genética , Criança , Humanos , Masculino , Síndrome
6.
Molecules ; 24(17)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438521

RESUMO

Many studies have shown that Orthosiphon stamineus extract (OE) has antioxidant activity, and we previously reported that OE protects the intestine against injury from a high-fat diet. However, the molecular mechanism underlying this protective effect of OE was unclear. Here, OE was separated according to polarity and molecular weight, and the antioxidant activity of each component was compared. The components with the highest antioxidant activity were analyzed by HPLC, which confirmed that rosmarinic acid (RA) was the main effective constituent in OE. OE and RA were then tested in a mouse high-fat diet-induced intestinal injury model. The antioxidant indices and morphological characteristics of the mouse jejunum were measured, and activation of the nuclear factor E2-related factor 2 (Nrf2) pathway and apoptosis of jejunal epithelial cells were analyzed. Of all the constituents in OE, RA contributed the most. Both RA and OE activated the Nrf2 pathway and increased downstream antioxidant enzyme activity. RA and OE protected the mouse intestine against high-fat diet-induced oxidative stress by preventing intestinal epithelial cell apoptosis via both extracellular and intracellular pathways. Thus, RA, the main effective constituent in OE, inhibits intestinal epithelial apoptosis by regulating the Nrf2 pathway in mice.


Assuntos
Cinamatos/farmacologia , Depsídeos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Orthosiphon/química , Animais , Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Intestinos/citologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ácido Rosmarínico
7.
J Reprod Med ; 62(5-6): 305-10, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30027725

RESUMO

OBJECTIVE: To investigate the function and underlying mechanism of transforming growth factor­beta (TGF-ß)/bone morphogenetic protein (BMP) signaling pathway in early unexplained miscarriage. STUDY DESIGN: Expression profiles of genes involved in TGF-ß/BMP signaling pathway were compared between placental villous tissue samples from 2 women with missed abortion and those from 2 women with induced abortion by microarray assay. The protein expression level of the most downregulated gene­LEFTY1­was further measured using western blotting in another 8 women with missed abortion and 7 women with induced abortion. RESULTS: A total of 24 genes showed differential expression level between the 2 groups. Their functions were further investigated, of which 6 of 13 upregulated genes were TGF-ß responsive genes. The most reduced gene is LEFTY1, an antagonist of TGF-ß ligand. The protein expression level of LEFTY1 was confirmed to show the same trend as microarray using western blotting. CONCLUSION: A reduced expression of LEFTY1 in women with missed abortion was identified as com-pared with women with induced abortion, which may result in a dysregulation of TGF-ß signaling and may be the underlying mechanism of missed abortion.


Assuntos
Aborto Retido/metabolismo , Vilosidades Coriônicas , Fatores de Determinação Direita-Esquerda , Adulto , Vilosidades Coriônicas/química , Vilosidades Coriônicas/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Fatores de Determinação Direita-Esquerda/análise , Fatores de Determinação Direita-Esquerda/genética , Fatores de Determinação Direita-Esquerda/metabolismo , Gravidez
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 31(1): 56-9, 2014 Feb.
Artigo em Zh | MEDLINE | ID: mdl-24510564

RESUMO

OBJECTIVE: To determine the origin of chromosomal aberration for a child featuring multiple malformation, and to correlate the genotype with phenotype. METHODS: Routine G-banding was performed to analyze the karyotype of the patient and her parents, and array comparative genomic hybridization (array CGH) was used for fine mapping of the aberrant region. RESULTS: The karyotype of the child was ascertained as 46,XY. Array CGH has mapped a 14.21 Mb deletion to 5p15.2p15.33, and a very small 3.67 Mb duplication to 5q35.3. The patient has presented features such as mental retardation, heart defect, low-set ears, hypertelorism and down-slanting palpebral fissures. CONCLUSION: Chromosome 5 copy number variation can cause multiple malformation. In contrast to routine karyotype analysis, array CGH can map aberrant region with much higher resolution and accuracy.


Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 5 , Variações do Número de Cópias de DNA , Anormalidades Múltiplas/diagnóstico , Genótipo , Humanos , Lactente , Masculino , Fenótipo
9.
Mol Genet Genomic Med ; 12(1): e2326, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38014478

RESUMO

BACKGROUND: Isoleucinyl-tRNA synthetase (IARS) is encoded by the IARS1 gene and catalyzes the binding of isoleucine to specific tRNA. OBJECTIVE: This study aims to investigate the pathogenicity of novel IARS1 variants and the genotype-phenotype association, in order to expand the spectrum of pathogenic variants and phenotypes of IARS1-related disease and provide new evidence for the phenotypic spectrum of IARS1 variants. METHODS: Clinical data of the proband were collected, and trio whole-exome sequencing (WES) was performed on the proband and the parents. Candidate variants were validated using Sanger sequencing. Bioinformatics software was utilized to analyze the functional consequences of identified variants and predict their potential deleteriousness. RESULTS: A 17-month-old female patient presented with microcephaly, left external ear malformation, decreased muscle strength and tone in all limbs, epileptic seizures, global developmental delay, and developmental regression. Trio WES identified compound heterozygous variants in the IARS1 gene, c.120-1G>A and c.2164C>A, which were novel pathogenic and likely pathogenic variants, respectively. The phenotype of developmental regression has not been reported before. Only one patient with IARS1 compound heterozygous variants has been reported in the world to have an epileptic phenotype, and this is the second patient with an epileptic phenotype. Bioinformatics analysis revealed that the splicing variant disrupted the canonical splice donor site, while the missense variant altered the local electrostatics of the IARS1 protein surface, potentially leading to functional abnormalities. CONCLUSION: This study identified novel IARS1 variants and the phenotype of developmental regression, expanding the spectrum of pathogenic variants and phenotypes of IARS1-related diseases and providing new evidence for the rare phenotype of epileptic seizures caused by IARS1 variants.


Assuntos
Deficiências do Desenvolvimento , Epilepsia , Criança , Humanos , Feminino , Lactente , Deficiências do Desenvolvimento/genética , Fenótipo , Epilepsia/genética , Convulsões , China
10.
Antioxidants (Basel) ; 13(4)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38671889

RESUMO

Cordycepin is considered a major bioactive component in Cordyceps militaris extract. This study was performed to evaluate the ameliorative effect of Cordyceps militaris extract (CME) and cordycepin (CPN) supplementation on intestinal damage in LPS-challenged piglets. The results showed that CPN or CME supplementation significantly increased the villus height (p < 0.01) and villus height/crypt depth ratio (p < 0.05) in the jejunum and ileum of piglets with LPS-induced intestinal inflammation. Meanwhile, CPN or CME supplementation alleviated oxidative stress and inflammatory responses by reducing the levels of MDA (p < 0.05) and pro-inflammatory cytokines in the serum. Additionally, supplementation with CPN or CME modulated the structure of the intestinal microbiota by enriching short-chain fatty acid-producing bacteria, and increased the level of butyrate (p < 0.05). The RNA-seq results demonstrated that CME or CPN altered the complement and coagulation-cascade-related genes (p < 0.05), including upregulating gene KLKB1 while downregulating the genes CFD, F2RL2, CFB, C4BPA, F7, C4BPB, CFH, C3 and PROS1, which regulate the complement activation involved in inflammatory and immune responses. Correlation analysis further demonstrated the potential relation between the gut microbiota and intestinal inflammation, oxidative stress, and butyrate in piglets. In conclusion, CPN or CME supplementation might inhibit LPS-induced inflammation and oxidative stress by modulating the intestinal microbiota and its metabolite butyrate in piglets.

11.
Mol Genet Genomic Med ; 12(3): e2409, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38511267

RESUMO

BACKGROUND: Congenital myasthenic syndrome is a heterogeneous group of inherited neuromuscular transmission disorders. Variants in RAPSN are a common cause of CMS, accounting for approximately 14%-27% of all CMS cases. Whether preimplantation genetic testing for monogenic disease (PGT-M) could be used to prevent the potential birth of CMS-affected children is unclear. METHODS: Application of WES (whole-exome sequencing) for carrier testing and guidance for the PGT-M in the absence of a genetically characterized index patient as well as assisted reproductive technology were employed to prevent the occurrence of birth defects in subsequent pregnancy. The clinical phenotypes of stillborn fetuses were also assessed. RESULTS: The family carried two likely pathogenic variants in RAPSN(NM_005055.5): c.133G>A (p.V45M) and c.280G>A (p.E94K). And the potential birth of CMS-affected child was successfully prevented, allowing the family to have offspring devoid of disease-associated variants and exhibiting a normal phenotype. CONCLUSION: This report constitutes the first documented case of achieving a CMS-free offspring through PGT-M in a CMS-affected family. By broadening the known variant spectrum of RAPSN in the Chinese population, our findings underscore the feasibility and effectiveness of PGT-M for preventing CMS, offering valuable insights for similarly affected families.


Assuntos
Síndromes Miastênicas Congênitas , Criança , Feminino , Gravidez , Humanos , Síndromes Miastênicas Congênitas/diagnóstico , Síndromes Miastênicas Congênitas/genética , Testes Genéticos , Fenótipo
12.
Cancer Lett ; 586: 216642, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38278470

RESUMO

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer. Anti-PD-1/PD-L1 treatment for advanced TNBC is still limited to PD-L1-positive patients. Ataxia telangiectasia mutated (ATM) is a switch molecule for homologous recombination and repair. In this study, we found a significant negative correlation between ATM and PD-L1 in 4 TNBC clinical specimens by single-cell RNA sequencing (scRNA-seq), which was confirmed by immunochemical staining in 86 TNBC specimens. We then established ATM knockdown TNBC stable cell lines to perform in vitro studies and animal experiments, proving the negative regulation of PD-L1 by ATM via suppression of tumor necrosis factor-alpha (TNF-α), which was confirmed by cytokine array analysis of TNBC cell line and analysis of clinical specimens. We further found that ATM inhibits TNF-α via inactivating JNK/c-Jun by scRNA-seq, Western blot and luciferase reporter assays. Finally, we identified a negative correlation between changes in phospho-ATMS1981 and PD-L1 levels in TNBC post- and pre-neoadjuvant therapy. This study reveals a novel mechanism by which ATM negatively regulates PD-L1 by downregulating JNK/c-Jun/TNF-α in TNBC, shedding light on the wide application of immune checkpoint blockade therapy for treating multi-line-resistant TNBC.


Assuntos
Ataxia Telangiectasia , Neoplasias de Mama Triplo Negativas , Animais , Humanos , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Antígeno B7-H1/metabolismo , Citocinas/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Fator de Necrose Tumoral alfa/metabolismo
13.
Soc Psychol Educ ; : 1-15, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37362053

RESUMO

The changes that COVID-19 pandemic has brought upon the world are unprecedented. Its impact on students' learning is equally profound, making it critical to heed students' academic achievement effects that may derive from these alterations. Therefore, the present study explored an integrative model of mental health, self-regulated learning and academic achievement among adolescents during the pandemic. Participants were 1001 senior high school students (Mage = 17.00, SDage = 0.78, 48.7% female) from China. Results showed that the degree to which students were mentally healthy was not significantly related to academic achievement, whereas academic achievement and mental health were positively associated with self-regulated learning. Following structural equation modelling analysis, the effect of mental health on academic achievement was fully mediated by self-regulated learning. Taken together, the findings emphasised the necessity of developing self-regulated learning strategies during public health emergencies and have clinical and educational implications for planning psychological interventions in order to improve mental health and academic performance as well.

14.
Front Psychiatry ; 14: 1086282, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37032943

RESUMO

Introduction: Reduced fixation to the eye area is the main characteristic of social deficits associated with Autism Spectrum Disorder; a similar pattern may exist in individuals with high autistic traits. However, their scanning patterns to the eye area of emotional faces are still unclear on the time scale. Methods: In the present study, we recruited 46 participants and divided them into the high autistic traits (HAT) group (23 participants) and the low autistic traits (LAT) group (20 participants) based on their Autism Spectrum Quotient (AQ) scores. Moreover, we captured their eye movement patterns when observing different angular emotional faces. We extracted the proportional fixation time to the eye area under different time windows. Results: The results showed that the fixation time of the HAT group was always significantly smaller than that of the LAT group (p < 0.05), and the difference between the two groups increased in the middle and late stages of face presentation. The results of the linear regression analysis showed that the proportional fixation time was negatively correlated with AQ scores (p < 0.05), indicating that the proportional fixation time to the eye area could be a potential indicator to measure the level of autistic traits. We then calculated the latency to orient the eye area and the latency to disengage the eye area to explore the priority of observation of the eyes. The results showed that compared with the LAT group, the HAT group has a longer latency to orient the eye area (p < 0.05) and has longer latency to disengage the eye area (p < 0.05), illustrating that the HAT group saw the eyes more slowly and left them faster.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38083266

RESUMO

Autism has become one of the primary diseases causing disability in children, and the incidence has risen rapidly in recent years. The preclinical study on individuals with high autistic traits is extremely important to reduce genetic risks of autism because high autistic traits is the susceptibility marker of autism. However, few studies explored the face scanning pattern of people with high autistic traits in typical developing populations. In this study, we designed a facial emotion recognition experiment including four emotions (happy, neutral, sad, angry) and three angles (0°, 45°, 90°) , and informed the participants to identify the facial emotion. Forty-two college students with typical development were recruited and divided into high autistic traits (HAT) group and low autistic traits (LAT) group by the Autism-Spectrum Quotient, and we collected the eye movement data using eye-tracking technology when they performed the task. The response time, recognition accuracy, AOI based proportional fixation time and pupil diameter were computed and analyzed for both groups. HATs showed significantly lower recognition accuracy and lower pupil diameter than LATs when recognizing negative emotions (P<0.05) , indicating HATs kept poor autonomic nervous arousal. What ' s more, the proportional fixation time of HATs were significantly more in mouth area but less in eye area than that of LAT group (P<0.05) , revealed HATs had an atypical emotional faces scanning strategies that paid less attention to eyes and more attention to mouth. Our research provides a feasible objective biomarker for screening high autistic traits population.


Assuntos
Transtorno Autístico , Criança , Humanos , Transtorno Autístico/diagnóstico , Expressão Facial , Emoções/fisiologia , Felicidade , Movimentos Oculares
16.
Medicine (Baltimore) ; 102(43): e35697, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37904417

RESUMO

BACKGROUND: The association of key genes in the transforming growth factor-ß (TGF-ß) signaling pathway and their gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) is unclear. OBJECTIVE: To investigate the association of gene polymorphisms related to the TGF-ß signaling pathway in URSA women. METHODS: The study population consisted of 80 women with URSA and 90 normal control women, of which 10 women with URSA and 10 normal control women underwent high-throughput sequencing to select loci, and the remaining 70 women with URSA and 80 normal control women underwent flight mass spectrometry experiments to verify gene loci polymorphism. A total of 7 polymorphic loci in interleukin-6 (IL-6), TGF-ß1, TNF-α, SMAD1, and TNFRSF4 genes were screened by high-throughput sequencing combined with a review of databases. An SNP flight mass spectrometer (Mass ARRAY detection system) was applied to detect the polymorphisms and their frequencies in 70 women with URSA and 80 normal control women at the 7 gene loci. RESULTS: Among the 7 loci of IL-6, TGF-ß1, TNF-α, SMAD1, and TNFRSF4 genes, 2 loci were found to have significantly different allele and genotype frequency distributions between the 70 URSA and 80 normal controls, one was the IL-6 gene -174G/C locus (rs1800795), the risk of disease was 2.636 and 3.231 times higher in individuals carrying the C allele and CC genotype than in those carrying the G allele and GG genotype, respectively; the other was the TGF-ß1 gene -509T/C locus (rs1800469), and the risk of disease was 1.959 and 3.609 times higher in individuals carrying the T allele and TT genotype than in those carrying the C allele and CC genotype, respectively. The remaining 5 genetic loci have no statistically significant. CONCLUSION: IL-6 gene -174G/C locus (rs1800795) genotype CC and allele C may be the causative factor of URSA, TGF-ß1 gene -509T/C locus (rs1800469) genotype TT and allele T may be the causative factor of URSA, and polymorphisms of the 2 loci may be associated with URSA.


Assuntos
Aborto Habitual , Fator de Crescimento Transformador beta1 , Feminino , Humanos , Gravidez , Aborto Habitual/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Interleucina-6/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genética , Fator de Crescimento Transformador beta1/genética , Fator de Necrose Tumoral alfa/genética
17.
Front Genet ; 14: 1037345, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37501721

RESUMO

A fetal clenched hand with overlapping fingers is more common in aneuploidy syndrome and was not well-documented in MED12 deficiency. This study reports the clinical and genetic findings of three affected siblings from a Chinese family. The chromosome karyotype analysis diagram shows that karyotypes of the three children were normal. Trio whole-exome sequencing and Sanger sequencing verification found that there was a MED12 R296Q variant in normal mothers and their two offspring. A pattern of clenched hand with overlapping fingers (clinodactyly) and clubfoot was found in all the three affected siblings by three-dimensional ultrasound. The discovery of this case shows that even if the chromosome karyotype is normal, comprehensive prenatal genetic diagnosis is required when the ultrasound results show a clenched hand with clinodactyly and clubfoot symptoms.

18.
Sci Rep ; 13(1): 9256, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37286786

RESUMO

High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2- and triple-negative breast cancer (TNBC). Among HR+HER2- breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2- or TNBC who may not benefit from NACT. HR+HER2- breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Linfócitos do Interstício Tumoral , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Terapia Neoadjuvante , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2
19.
Animals (Basel) ; 12(10)2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35625175

RESUMO

The health status of weaned pigs is crucial for their subsequent growth performance. Supplementation with fermented feedstuff is able to improve the feed intake and growth of weaned pigs; however, the exact mechanism behind this is not clear. Hence, in the present study a total of 320 Duroc × Landrace × Yorkshire weaned pigs were selected and allocated to the following two groups: unfermented diet group (UFD) and fermented diet group (FD). The experimental period lasted 21 days. At the end of the experiment, feces, blood, and gastrointestinal tissue samples (including the stomach, jejunum, and ileum) were collected and used for further analysis. The results of growth performance suggested that the FD group had significantly increased (p < 0.05) average daily feed intake (ADFI) and average daily gain (ADG) during the first week, during the last two weeks, and over the entire three-week period compared with the UFD group. The results of the apparent nutrient digestibility of pigs showed that, compared with the UFD group, the FD group showed increased phosphorus (p < 0.05) and CP (p < 0.1) digestibility. There were no significant differences in the serum biochemical parameters between the UFD and FD groups. Moreover, our results showed that the FD group showed significantly increased gene expression of SGLT1 and PepT1 in the jejunum (p < 0.05). Compared with the UFD group, the FD group showed an increased (p < 0.05) serum orexin level and prepro-orexin (PPOX) expression in the gastric fundus, jejunum, and ileum mucosa and increased IGF-1 and IGFR expression in the jejunum. Collectively, these results indicated that supplementation with fermented feedstuff in the diet effectively enhanced the feed intake and growth of weaned pigs and that this may have been caused by the increased orexin, IGF-1, and IGFR serum levels.

20.
J Knee Surg ; 34(9): 971-977, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31952093

RESUMO

The comparison of intrathecal ropivacaine with bupivacaine for knee arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the efficacy of intrathecal ropivacaine versus bupivacaine for knee arthroscopy. We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through August 2019 for randomized controlled trials (RCTs) assessing the effect of intrathecal ropivacaine versus bupivacaine for knee arthroscopy. This meta-analysis is performed using the random effects model. Five RCTs are included in the meta-analysis. Overall, compared with intrathecal bupivacaine for knee arthroscopy, intrathecal ropivacaine is associated with increased onset time of motor block (mean difference [MD] = 2.05, 95% CI: 1.43-2.67, p < 0.00001) and decreased duration of sensory block (MD = -26.82, 95% CI: -31.96 to -21.67, p < 0.00001) but shows no remarkable influence on onset time of sensory block (MD = -0.09; 95% CI: -1.89 to 1.70, p = 0.92), duration of motor block (MD = -59.76; 95% CI: -124.44 to 4.91, p = 0.07), time to maximum block (MD = 2.35; 95% CI: -0.16 to 4.86, p = 0.07), first urination time (MD = -26.42, 95% CI: -57.34 to 4.51, p = 0.09), or first ambulation time (MD = 3.63, 95% CI: -25.20 to 32.47, p = 0.80).Intrathecal ropivacaine can substantially increase onset time of motor block and decrease the duration of sensory block than intrathecal bupivacaine for knee arthroscopy.


Assuntos
Artroscopia , Amidas , Anestésicos Locais , Bupivacaína , Humanos , Articulação do Joelho/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ropivacaina
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