RESUMO
Heparin-induced thrombocytopenia (HIT) is a serious adverse drug reaction characterized by antibodies that recognize platelet factor 4/heparin complexes (PF4/H) and activate platelets to create a prothrombotic state. Although a high percentage of heparin-treated patients produce antibodies to PF4/H, only a subset also makes antibodies that are platelet activating (PA). A close correlation between PA antibodies and the likelihood of experiencing HIT has been demonstrated in clinical studies, but how PA (presumptively pathogenic) and nonactivating (NA) (presumptively benign) antibodies differ from each other at the molecular level is unknown. To address this issue, we cloned 7 PA and 47 NA PF4/H-binding antibodies from 6 patients with HIT and characterized their structural and functional properties. Findings showed that PA clones differed significantly from NA clones in possessing 1 of 2 heavy chain complementarity-determining region 3 (HCDR3) motifs, RX1-2R/KX1-2R/H (RKH) and YYYYY (Y5), in an unusually long complementarity-determining region 3 (≥20 residues). Mutagenic studies showed that modification of either motif in PA clones reduced or abolished their PA activity and that appropriate amino acid substitutions in HCDR3 of NA clones can cause them to become PA. Repertoire sequencing showed that the frequency of peripheral blood IgG+ B cells possessing RKH or Y5 was significantly higher in patients with HIT than in patients without HIT given heparin, indicating expansion of B cells possessing RKH or Y5 in HIT. These findings imply that antibodies possessing RKH or Y5 are relevant to HIT pathogenesis and suggest new approaches to diagnosis and treatment of this condition.
Assuntos
Regiões Determinantes de Complementaridade , Trombocitopenia , Humanos , Regiões Determinantes de Complementaridade/genética , Trombocitopenia/induzido quimicamente , Trombocitopenia/genética , Heparina , Anticorpos/efeitos adversos , Plaquetas/metabolismo , Fator Plaquetário 4RESUMO
CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily and expressed in both normal and malignant lymphoid cells. However, the role of CD30 in lymphopoiesis is not known. In this study, we showed CD30 was expressed both in T and B cells, but its deficiency in mice had no effect on T- and B-cell development. In fact, CD30 deficiency attenuated B-cell response to T-cell-dependent antigens. The impaired B cell response in CD30-deficient mice is caused by the reduction of activation-induced cytidine deaminase (AID) expression. Moreover, CD30-deficient mice exhibited decreased TCR-mediated T cell proliferation and slightly impaired TCR signaling. High-throughput RNA sequencing analysis revealed that CD30 deficiency led to a decrease of FOXO-autophagy axis in T cells upon TCR stimulation. Thus, CD30 positively regulates T-cell-dependent immune response and T cell proliferation.
Assuntos
Antígeno Ki-1 , Ativação Linfocitária , Linfócitos T , Animais , Camundongos , Proliferação de Células , Antígeno Ki-1/genética , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologiaRESUMO
AIM: To estimate the causal associations of type 2 diabetes and glycaemic traits with cognitive function, and to determine the potential mediating role of various brain imaging-derived phenotypes (IDPs) using Mendelian randomization (MR) analysis. METHODS: Using publicly available summary data, we performed a series of univariable and multivariable MR analysis to infer causality. Two-step MR analysis was then conducted in turn to evaluate the potential mediating role of each brain IDP. RESULTS: There was no evidence of causal associations between type 2 diabetes and cognitive function outcomes. Each 1-SD unit higher genetically predicted fasting proinsulin was associated with worse cognitive performance, as evidenced by both univariable (beta: -0.022; 95% confidence interval [CI] -0.038, -0.007) and multivariable MR analysis (beta: -0.027; 95% CI -0.048, -0.005). In addition, the univariable MR analysis identified several causal associations between fasting proinsulin and brain IDPs, and between brain IDPs and cognitive performance. The inverse association of genetically predicted fasting proinsulin with cognitive performance did not attenuate after adjusting for each of the brain IDPs in multivariable MR analysis. CONCLUSIONS: The present MR study provided credible evidence for the causal association between genetically predicted fasting proinsulin and cognitive function, informing a potential diagnosis and intervention target for patients with cognitive impairment. No significant brain IDP included in this study was identified as lying on the causal pathway from fasting proinsulin to cognitive performance. Future research involving more specific and granular brain IDP or other brain process is warranted to explore the potential biological mechanism underlying the association.
Assuntos
Glicemia , Encéfalo , Cognição , Diabetes Mellitus Tipo 2 , Análise da Randomização Mendeliana , Proinsulina , Humanos , Diabetes Mellitus Tipo 2/genética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/metabolismo , Cognição/fisiologia , Glicemia/metabolismo , Glicemia/análise , Proinsulina/sangue , Proinsulina/metabolismo , Fenótipo , Jejum/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/epidemiologia , Polimorfismo de Nucleotídeo Único , MasculinoRESUMO
BACKGROUND: Macrophages play an important role in maintaining the chronic inflammatory of atherosclerosis (AS) and are hallmark of atherosclerotic plaques. They differentiate into different subpopulations under the influence of oxidized lipids and cytokines and play different roles in the formation and development of plaque. To explore the differences in the amount and distribution of different macrophage subpopulations around different carotid plaque pathological features in human AS, and based on these results, to explore the correlation between some macrophage subpopulations and AS pathological features. METHODS: First, we analyzed the single cells RNA-sequence data from the Gene Expression Omnibus DataSets (GSE159677). Second, we investigated the distribution difference of macrophage subpopulations in 61 surgically resected AS plaques by markers staining include CD68, inducible nitric oxide synthase, Arg-1, CD163 and HO-1. RESULTS: The result of single cells RNA-Sequence analysis showed that there were a large number of macrophages infiltrated in AS and they can be categorized into different subpopulations with different transcriptional features and functions; moreover in different part of AS (calcified AS core versus proximal adjacent), the total number and subpopulation ratios were all different. The result of staining analysis showed that macrophages mainly distributed in some pathological lesions such as necrosis, fibrous tissue degeneration, cholesterol crystallization etc., and different subpopulations were distributed differently in these lesions. CONCLUSIONS: This study confirmed that macrophages were heavily infiltrated in atherosclerotic plaques, and there existed subtype variability in different pathological lesions; meanwhile, these results suggested that different macrophage subpopulations may contribute differently in different pathological lesions.
Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Resultado do Tratamento , Artérias Carótidas/patologia , Macrófagos/metabolismo , Aterosclerose/patologia , RNA/metabolismoRESUMO
BACKGROUND: Although current treatments are effective in dealing with congenital heart disease (CHD), non-cardiac comorbidities such as attention-deficit hyperactivity disorder (ADHD) have received widespread attention. The purpose of this systematic review and meta-analysis is to assess the risk of ADHD associated with CHD. METHODS: The literature search was carried out systematically through eight different databases by the end of September 2022. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. The heterogeneity of the studies was assessed by the Cochran Q test and the I2 statistic. Subgroup and sensitivity analyses were used to explore the potential sources of heterogeneity. RESULTS: Eleven studies were included in this study, which involved a total of 296 741 participants. Our study showed that the children with CHD were at a significantly increased risk of ADHD compared with the reference group (OR = 2.98, 95% CI: 2.18-4.08). The results were moderately heterogeneous. These factors including study design, geographic region and study quality were identified as the first three of the most relevant heterogeneity moderators by subgroup analyses. Sensitivity analysis yielded consistent results. There was no evidence of publication bias. CONCLUSIONS: The present study suggests that CHD children have a significantly higher risk of ADHD when compared with those without CHD. Early identification and intervention of ADHD is important to reduce its symptoms and adverse effects; therefore, clinicians should increase screening for ADHD in children with CHD and intervene promptly to reduce its effects whenever possible.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Cardiopatias Congênitas , Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Projetos de Pesquisa , Comorbidade , Medição de RiscoRESUMO
BACKGROUND: To research the effect of China's many-child policy on the number of births and the prevalence of serious teratogenic and disabling defects (STDDs) in Hunan province. METHODS: We performed an observational study based on the Birth Defect (BD) Surveillance System of Hunan Province and chose STDD case cards. From 2012-2022, we defined the following 4 periods: the one-child policy (OCP) (2012.01-2013.12), partial two-child policy (PTCP) (2014.1-2015.12), universal two-child policy (UTCP) (2016.1-2020.12), and the early stage of the three-child policy (ETCP) (2021.1-2022.12). Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine the association of policy changes with STDDs. Crame'r's V was calculated to estimate the effect sizes. Joinpoint regression analysis and annual percent change (APC) were used for each segment of the trend. RESULTS: A total of 1,652,079 births were included in this analysis. Joinpoint regression analysis showed that the number of perinatal births increased from 2012 to 2017, with APC = 9.52 (95% CI: 7.2 to 11.8), and decreased from 2017 to 2022, with an APC = -10.04 (95% CI: -11.9 to -8.1). The number of mothers over 30 years old gradually increased, from 25.54% during the OCP period to 54.05% during the ETCP period (Ptrend < 0.001). With policy changes, the total prevalence of STDDs increased from 28.10 per 10,000 births during the period of OCP into 46.77 per 10,000 births during the ETCP period by 66.44%. The live birth prevalence of STDDs increased only during the ETCP period (PTCP: OR = 1.27, 95% CI: 0.99-1.24, p = 0.057, UTCP: OR = 1.22, 95% CI: 0.99-1.52, p = 0.067, ETCP: OR = 1.75, 95% CI: 1.37-2.24, p < 0.001). Over the past ten years, there was a decrease in the gestational age at diagnosis (*F = 772.520, p < 0.001), from 24.49 ± 5.65 weeks in 2012 to 20.77 ± 5.17 weeks in 2022. From 2012 to 2022, the percentage of deaths within 7 days decreased with APC = -18.85 (95% CI: -26.4- -10.5, P > 0.05). CONCLUSION: Many-child policies were associated with a moderate increase in fertility especially for women in urban areas and older women. However, they have lost the ability to control birth since 2017. The total prevalence of STDDs increased over the entire period, but the live birth prevalence increased only during the ETCP period. The gestational age at diagnosis decreased and the percentage of deaths within 7 days decreased.
Assuntos
Política de Planejamento Familiar , Teratogênicos , Gravidez , Humanos , Feminino , Idoso , Adulto , Prevalência , Fertilidade , China/epidemiologiaRESUMO
African swine fever (ASF) leads to high mortality in domestic pigs and wild boar, and it is caused by the African swine fever virus (ASFV). Currently, no commercially available vaccine exists for its prevention in China. In this study, we engineered a pseudorabies recombinant virus (PRV) expressing ASFV CD2v and p54 proteins (PRV-∆TK-(CD2v)-∆gE-(p54)) using CRISPR/Cas9 and homologous recombination technology. PRV-∆TK-(CD2v)-∆gE-(p54) effectively delivers CD2v and p54, and it exhibits reduced virulence. Immunization with PRV-∆TK-(CD2v)-∆gE-(p54) neither induces pruritus nor causes systemic infection and inflammation. Furthermore, a double knockout of the TK and gE genes eliminates the depletion of T, B, and monocytes/macrophages in the blood caused by wild-type viral infection, decreases the proliferation of granulocytes to eliminate T-cell immunosuppression from granulocytes, and enhances the ability of the immune system against PRV infection. An overexpression of CD2v and p54 proteins does not alter the characteristics of PRV-∆TK/∆gE. Moreover, PRV-∆TK-(CD2v)-∆gE-(p54) successfully induces antibody production via intramuscular (IM) vaccination and confers effective protection for vaccinated mice upon challenge. Thus, PRV-∆TK-(CD2v)-∆gE-(p54) demonstrates good immunogenicity and safety, providing highly effective protection against PRV and ASFV. It potentially represents a suitable candidate for the development of a bivalent vaccine against both PRV and ASFV infections.
Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Herpesvirus Suídeo 1 , Pseudorraiva , Suínos , Animais , Camundongos , Herpesvirus Suídeo 1/genética , Vírus da Febre Suína Africana/genética , Febre Suína Africana/prevenção & controle , Granulócitos , Sus scrofaRESUMO
MicroRNAs are known to regulate cell proliferation, differentiation, and apoptosis. However, the immunological mechanism and role of microRNA9-3 (miR9-3) are unknown. This study used CRISPR/cas9 technology to knock out miR9-3 to modulate its expression level. FACS results showed that the absolute number of total B cells declined in miR9-3-deficiency in the spleen (Sp), bone marrow (BM), and lymph node (LN) to different levels compared to the wild-type. Also, the absolute numbers of Fo, T1, and T2 cells decreased both in Sp and LN. The absolute numbers of total T cells in Sp and LN declined sharply; CD4+ and CD8+ T cells showed a dramatic decrease in Sp, LN, and Th (thymus) of the miR9-3- group. In BM, the cells number of immature B cells, pro-pre-B cells, pro-B cells, and pre-B cells reduced to different levels, while mature B cells were comparable to wild-type. These data illustrated that miR9-3-deficiency impaired the development of B cells in BM. Also, the development of T cells was severely impaired. In Th, the numbers of DN and DP cells were remarkably reduced in the miR9-3 mutant mice. Also, the numbers of DN-1, DN-3, and DN-4 cells decreased. The absolute number of cells in the hematopoietic stem cell (HSC) system such as LT-HSC (long-term HSC), ST-HSC (short-term HSC), MPP (multipotent progenitor), GMP (granulocyte-macrophage progenitor), CMP (common myeloid progenitors), MEP (megakaryocyte-erythroid progenitor), and CLP (common lymphoid progenitor) all were decreased in miR9-3 deficient mice. These results showed that miR9-3 deficiency initiated the damage to the entire hematopoietic system. Moreover, the absolute number of myeloid cells in both Sp and BM decreased in mutant mice. The cells number of NK cells showed a sharp reduction in Sp whereas the change was not significant in BM. The above results suggest that miR9-3 participates in the immune regulation of B cells, T cells, and the HSC system, highlighting its regulatory roles.
Assuntos
Linfócitos B , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Células-Tronco Hematopoéticas , MicroRNAs , Animais , Medula Óssea/patologia , Células da Medula Óssea , Diferenciação Celular , Células-Tronco Hematopoéticas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/imunologiaRESUMO
OBJECTIVE: To evaluate the global prevalence of malnutrition in children with congenital heart disease (CHD). STUDY DESIGN: A systematic review and meta-analysis were performed. Web of Science, PubMed, Embase, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine disc databases were searched for studies published through April 2021. Random-effect model meta-analyses were performed to derive the pooled the prevalence of preoperative underweight, stunting, and wasting in children with CHD. Time-trend analyses of postoperative malnutrition prevalence were undertaken. Subgroup and sensitivity analyses were conducted to explore sources of heterogeneity. Egger test and funnel plots were used to explore public bias. RESULTS: A total of 39 studies were included in this meta-analysis. The pooled estimates of preoperative malnutrition in children with CHD were 27.4% (95% CI, 21.7-34.0) for underweight, 24.4% (95% CI, 19.5-30.0) for stunting, and 24.8% (95% CI, 19.3-31.3) for wasting. Catch-up growth was found in the postoperative period among some children. Different continents were identified as heterogeneity moderators by subgroup analyses. CONCLUSIONS: Children with CHD have a high prevalence of preoperative malnutrition and some show catch-up growth postoperatively. These data can be used as benchmarks in efforts to improve the nutritional status of children with CHD.
Assuntos
Transtornos da Nutrição Infantil , Cardiopatias Congênitas , Desnutrição , Criança , Transtornos da Nutrição Infantil/epidemiologia , Transtornos do Crescimento/epidemiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/cirurgia , Humanos , Desnutrição/epidemiologia , Prevalência , Magreza/epidemiologiaRESUMO
BACKGROUND: MTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations. METHODS: A case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association. RESULTS: Mothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13-2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57-3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01-2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38-4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01-2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02-2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure. CONCLUSIONS: Maternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings. TRIAL REGISTRATION: Registration number: ChiCTR1800016635 .
Assuntos
Cardiopatias Congênitas/genética , Doenças do Recém-Nascido/genética , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Antígenos de Histocompatibilidade Menor/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático , Estudos de Casos e Controles , China/epidemiologia , Feminino , Cardiopatias Congênitas/induzido quimicamente , Humanos , Recém-Nascido , Doenças do Recém-Nascido/induzido quimicamente , Modelos Logísticos , Exposição Materna/efeitos adversos , Gravidez , Poluição por Fumaça de Tabaco/efeitos adversos , Fumar Tabaco/efeitos adversosRESUMO
BACKGROUND: Although many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring. METHODS: A case-control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed. RESULTS: Our study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95-19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77-9.71]). And six haplotypes of G-C (involving rs4846048 and rs2274976), A-C (involving rs1801133 and rs4846052), G-T (involving rs1801133 and rs4846052), G-T-G (involving rs2066470, rs3737964 and rs535107), A-C-G (involving rs2066470, rs3737964 and rs535107) and G-C-G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene-gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed. CONCLUSIONS: Our study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.
Assuntos
Cardiopatias Congênitas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Cardiopatias Congênitas/diagnóstico , Heterozigoto , Homozigoto , Humanos , Desequilíbrio de Ligação , Fenótipo , Gravidez , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVES: To investigate the epidemic situation of hand-foot-mouth disease (HFMD) in Hunan Province, China, from 2008 to 2019, as well as its spatial autocorrelation characteristics and spatial-temporal clustering, and to provide a reference for the prevention and control of HFMD in Hunan Province. METHODS: Spatial autocorrelation and spatial-temporal clustering analyses were used to analyze the monitoring data of HFMD in Hunan Province from 2008 to 2019. RESULTS: The epidemic situation of HFMD in Hunan Province from 2008 to 2019 showed obvious seasonal distribution, with a low incidence rate in January to March and a high incidence rate in April to July. As for population distribution, children aged 0-5 years had the highest number of HFMD cases and accounted for 95.89% (1 460 391/1 522 910) of all cases, with a mean annual incidence rate of 2 197.784/100 000, and scattered children had the highest number of cases and accounted for 82.59% (1 257 739/1 522 910) of all cases. The global spatial autocorrelation analysis showed that the onset of HFMD in Hunan Province showed a significant clustering distribution, and the local spatial autocorrelation analysis showed that the high clustering areas of HFMD were mainly the districts and counties of Changsha, Zhuzhou, and Yueyang cities. Time-space scanning showed that clustering time was mainly April to July; the cases were clustered in the northeast of Hunan Province from 2008 to 2010 and in the central part of Hunan Province from 2011 to 2019. CONCLUSIONS: The high incidence rate of HFMD is observed in April to July in Hunan Province. Children under 5 years of age are at a high risk of this disease. Spatial-temporal clustering is observed for the epidemic of HFMD, mainly clustered in the northeastern and central areas of Hunan Province. It is suggested that the results may be used as guidance to determine the key areas for HFMD prevention and control in Hunan Province and optimize the allocation of health resources.
Assuntos
Doença de Mão, Pé e Boca , Criança , Pré-Escolar , China/epidemiologia , Análise por Conglomerados , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Incidência , Lactente , Análise Espaço-TemporalRESUMO
The purpose of this study was to investigate the role of Poly (C)-binding protein 2 (PCBP2) and the related signaling pathway in glioma progression. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were performed to measure PCBP2 messenger RNA and protein expression in glioma tissues or cells. Cell transfection was completed using Lipofectamine 2000. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Transwell assay and flow cytometry assay were used to explore the effects of PCBP2 expression on biological behaviors of glioma cells. Western blot assay was used for the detection of pathway related proteins. Expression of PCBP2 in glioma tissues and cells were higher than that in paracancerous tissues and normal cells (both p < .01). Moreover, the elevated expression of PCBP2 was significantly correlated with tumor size (p = .001) and WHO stage (p = .010). Knockdown of PCBP2 could suppress proliferation, migration and invasion of glioma cells and promote apoptosis. Besides, the expression of transforming growth factor-ß (TGF-ß) pathway related proteins TGF-ß1, p-Smad2 and p-Smad7 were decreased following the downregulation of PCBP2. PCBP2 also inhibited FHL3 expression by binding to FHL3-3'UTR. The inhibition of FHL3 could reverse the antitumor action caused by PCBP2 silencing. In vivo assay, PCBP2 was also found to inhibit the tumor growth of glioma. PCBP2 activates TGF-ß/Smad signaling pathway by inhibiting FHL3 expression, thus promoting the development and progression of glioma.
Assuntos
Glioma/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas com Domínio LIM/genética , Proteínas de Ligação a RNA/genética , Fator de Crescimento Transformador beta1/genética , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Glioma/patologia , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Transdução de Sinais , Proteína Smad7/genéticaRESUMO
OBJECTIVE: The objective of this study was to investigate the relationship between lipoprotein (a) (Lp(a)), triglyceride/high-density lipoprotein cholesterol (TG/HDL-C), and the stability of carotid atherosclerotic plaque in patients with acute ischemic stroke. METHODS: A total of 142 patients with acute ischemic stroke were selected and divided into group A (59 cases of stable plaque formation) and group B (83 cases of unstable plaque formation) according to the characteristics of carotid artery plaque formation detected by carotid color Doppler ultrasound. The serum Lp(a), lipid metabolism indexes, peripheral blood routine indexes, and related serum inflammatory factors indexes were compared between the two groups. Receiver operating characteristic curve and multivariate logistic regression model were used to analyze the relationship between each index and the formation of carotid unstable plaque. RESULTS: There were no significant differences in serum total cholesterol (TC), HDL-C, and low-density lipoprotein cholesterol (LDL-C) between groups A and B (p > .05). The values of Lp(a), TG, and TG/HDL-C in group B were higher than those in group A, and the differences were statistically significant (p < .05). There were no significant differences in serum TC, HDL-C, and LDL-C between groups A and B (p > .05). The values of Lp(a), TG, and TG/HDL-C in group B were higher than those in group A, and the differences were statistically significant (p < .05). The values of HBA1C, Lp-PLA2, CRP, CysC, Hcy, TNF-α, neutrophils, and NLR in group B were higher than those in group A, and the differences were statistically significant (p < .05). There was no significant difference in FPG, systolic blood pressure, diastolic blood pressure, Hb, white blood cells, platelets, and lymphocytes between groups A and B (p > .05). The results of logistic regression model showed that the increase of Lp(a), TG/HDL-C, HBA1C, Lp-PLA2, CRP, CysC, Hcy, and NLR could increase the risk of carotid artery unstable plaque in patients with ischemic stroke (p < .05). CONCLUSION: Lp(a) and TG/HDL-C have certain value in evaluating the stability of carotid atherosclerotic plaque in patients with acute ischemic stroke, and the increased levels of LP (a) and TG/HDL-C will significantly increase the risk of carotid unstable plaque in patients.
Assuntos
Estenose das Carótidas , AVC Isquêmico , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/diagnóstico por imagem , AVC Isquêmico/diagnóstico por imagem , 1-Alquil-2-acetilglicerofosfocolina Esterase , LDL-Colesterol , Hemoglobinas Glicadas , Artérias Carótidas , Triglicerídeos , Estenose das Carótidas/diagnóstico por imagem , Lipoproteína(a) , Fatores de RiscoRESUMO
BACKGROUND: Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension, and surgery is currently the main treatment for hypertensive cerebral hemorrhage, but the bleeding caused by surgery will cause damage to the patient's nerve cells, resulting in cognitive and motor dysfunction, resulting in a decline in the patient's quality of life. AIM: To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage. METHODS: Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group, while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group. The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test (WCST) and cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA). The Hamilton Depression Rating Scale (HAMD-24) was used to evaluate the severity of depression of involved patients. Cerebral arterial blood flow was measured in both groups. RESULTS: The MoCA score, net scores I, II, III, IV, and the total net score of the scratch test in the observation group were significantly lower than those in the control group (P < 0.05). Concurrently, the total number of responses, number of incorrect responses, number of persistent errors, and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group (P < 0.05). Blood flow in the basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery was significantly lower in the observation group than in the control group (P < 0.05). The basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score (P < 0.05), and negatively correlated with each part of the WCST test (P < 0.05). In the observation group, the post-treatment improvement was more prominent in the Paddle Pin test, WCST test, HAMD-24 score, and MoCA score compared with those in the pre-treatment period (P < 0.05). Blood flow in the basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery significantly improved in the observation group after treatment (P < 0.05). CONCLUSION: Impaired attention, and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.
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BACKGROUND: The purpose of this study was to explore the association between anaemia during early pregnancy and the risk of neonatal outcomes. METHODS: We collected clinical data from pregnant women (≥18 years) who received their first antenatal care between 8 and 14 weeks of gestation in Hunan Provincial Maternal and Child Health Care Hospital. Multiple logistic regression models and restricted cubic spline regression models were used to analyse the association between anaemia during early pregnancy and the risk of neonatal outcomes. In addition, sensitivity analysis was further performed to assess the robustness of the results. RESULTS: The prospective cohort study ultimately included 34 087 singleton pregnancies. In this study, the rate of anaemia during early pregnancy was 16.3%. Our data showed that there was a positive relationship between the rate of preterm birth, low birth weight as well as small for gestational age (SGA) and the severity of maternal anaemia (Ptrend<0.05). After adjustment, the association of early pregnancy anaemia and haemoglobin (Hb) levels with the risk of preterm birth (mild anaemia adjusted OR (aOR) 1.37 (95% CI 1.25 to 1.52), moderate anaemia aOR 1.54 (95% CI 1.35 to 1.76) and severe anaemia aOR 4.03 (95% CI 2.67 to 6.08), respectively), low birth weight (mild anaemia aOR 1.61 (95% CI 1.44 to 1.79), moderate anaemia aOR 2.01 (95% CI 1.75 to 2.30) and severe anaemia aOR 6.11 (95% CI 3.99 to 9.36), respectively) and SGA (mild anaemia aOR 1.37 (95% CI 1.25 to 1.52), moderate anaemia aOR 1.54 (95% CI 1.35 to 1.76) and severe anaemia aOR 2.61 (95% CI 1.74 to 4.50), respectively; Pnon-linear<0.05) was observed. However, no association was found between early pregnancy anaemia or Hb levels and the risk of congenital malformations. Sensitivity analysis verified the stability of the results. CONCLUSIONS: Maternal anaemia during early pregnancy was associated with an increased risk of preterm birth, low birth weight and SGA and their rates may increase with the severity of maternal anaemia. TRIAL REGISTRATION NUMBER: ChiCTR1800016635.
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Anemia , Nascimento Prematuro , Criança , Gravidez , Recém-Nascido , Feminino , Humanos , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Recém-Nascido de Baixo Peso , Anemia/epidemiologia , Retardo do Crescimento FetalRESUMO
Objective: To evaluate the prevalence and associated factors of undernutrition among children with congenital heart disease (CHD) who have not undergone surgeries in China. Methods: This cross-sectional study included 734 CHD children along with their parents. The outcome of interest was undernutrition, including underweight, wasting, and stunting, defined as Z-scores (i.e., weight-for-age, weight-for-height, and height-for-age) ≤-2, according to the World Health Organization (WHO) growth standard. Exposures of interest, containing demographics, obstetric factors, maternal dietary factors, parents' life behaviors and habits, birth-related factors, cardiac-related factors, and preoperative factors, were analyzed using a multivariate logistic regression model to test their associations with undernutrition in CHD children. Results: Overall, 36.1%, 29.7%, and 21.3% of cases were underweight, wasted, and stunted, respectively. Multivariate logistic regression indicated that underweight was associated with demographic factors (including parents' occupational status, family income, and maternal body mass index pre-pregnancy), low birth weight (OR = 4.60, 2.76-7.70), pulmonary hypertension (OR = 4.46, 3.09-6.43), and pneumonia (OR = 1.88, 1.28-2.76). Artificially-fed children were 2.34 (1.36-4.01) times more likely to be underweight. Occupied mothers (OR = 0.62, 0.44-0.88) and fathers (OR = 0.49, 0.26-0.92) served as protective factors, while mothers having gestational complications (OR = 1.56, 1.11-2.18) and exposed to noisy environment (OR = 1.64, 1.11-2.42) during this pregnancy, and pulmonary hypertension (OR = 3.21, 2.30-4.49) increased the chance of wasting in offspring. The odds of being stunted were greater in families with >2 children (OR = 1.88, 1.13-3.14), placental abruption during this pregnancy (OR = 25.15, 2.55-247.89), preterm births (OR = 1.84, 1.02-3.31), low birth weight (OR = 3.78, 2.16-6.62), pulmonary hypertension (OR = 2.35, 1.56-3.53) and pneumonia (OR = 1.93, 1.28-2.90). In subgroup analyses, the associations differed between patients with different feeding patterns (breastfeeding vs. non-breastfeeding), CHD classifications (cyanotic vs. acyanotic), and prematurity (preterm vs. non-preterm). Conclusion: Undernutrition is common in preoperative CHD children. Familial demographics, maternal factors (including having gestational complications and exposure to noisy environment during pregnancy), and patient-related factors (encompassing preterm births, low birth weight, pulmonary hypertension, pneumonia, and feeding pattern) were found to contribute to undernutrition in CHD cases. However, associated factors among the three subgroups of distinct feeding patterns, CHD categorization, and prematurity exhibited varied outcomes, suggesting the necessity for targeted interventions.
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Investigating the influences of soil characteristic factors on dinoseb adsorption parameter with different statistical methods would be valuable to explicitly figure out the extent of these influences. The correlation coefficients and the direct, indirect effects of soil characteristic factors on dinoseb adsorption parameter were analyzed through bivariate correlation analysis, and path analysis. With stepwise regression analysis the factors which had little influence on the adsorption parameter were excluded. Results indicate that pH and CEC had moderate relationship and lower direct effect on dinoseb adsorption parameter due to the multicollinearity with other soil factors, and organic carbon and clay contents were found to be the most significant soil factors which affect the dinoseb adsorption process. A regression is thereby set up to explore the relationship between the dinoseb adsorption parameter and the two soil factors: the soil organic carbon and clay contents. A 92% of the variation of dinoseb sorption coefficient could be attributed to the variation of the soil organic carbon and clay contents.
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2,4-Dinitrofenol/análogos & derivados , Poluentes do Solo/análise , Poluentes do Solo/química , Solo/análise , Solo/química , 2,4-Dinitrofenol/análise , 2,4-Dinitrofenol/química , Interpretação Estatística de Dados , Praguicidas/análise , Praguicidas/químicaRESUMO
OBJECTIVE: To investigate the efficacy of neurointervention combined with intravenous thrombolysis in ischemic stroke patients and the risk factors affecting cognitive function recovery. METHODS: A total of 114 patients with acute ischemic stroke (AIS) treated in Baoji People's Hospital from January 2017 to December 2020 were retrospectively selected and divided into an observation group and a control group according to different treatment methods. The observation group was treated with neurointervention + intravenous thrombolysis (n = 64), and the control group underwent intravenous thrombolysis (n = 50). The efficacy, recanalization rate, incidence of adverse events, National Institutes of Health Stroke Scale (NIHSS) score, Mini-Mental State Examination (MMSE) score and modified Rankin Scale (mRS) score were evaluated and compared between the two groups. Patients were further divided into a cognitive dysfunction group and a non-disorder group according the MMSE score after treatment, and logistics regression was used to analyze the risk factors of cognitive dysfunction. RESULTS: The overall response rate and the total recanalization rate of the observation group were significantly higher than those of the control group (both P < 0.05). Compared with those before operation, the NIHSS score at 7 d after operation and the mRS score 3 months after operation decreased, while the MMSE score increased in both groups (P < 0.05). The postoperative NIHSS score and mRS score were lower and MMSE score was higher in the observation group than those in the control group (P < 0.05). No significant difference was identified in the incidence of adverse events between the two groups (P > 0.05). Logistics regression analysis revealed that age, diabetes mellitus, hyperlipidemia and lesions at critical sites were independent risk factors for cognitive impairment in patients with AIS. CONCLUSION: Interventional thrombectomy combined with intravenous thrombolysis is effective in the treatment of cerebral infarction. This regimen can reduce neurological deficits and improve the recanalization rate. In addition, age, diabetes, hyperlipidemia and lesions at critical sites are independent risk factors for the development of cognitive impairment in AIS patients.