RESUMO
OBJECTIVE: To compare the effect of low and standard pneumoperitoneal pressure (PP) on the occurrence of gas embolism during laparoscopic liver resection (LLR). BACKGROUND: LLR has an increased risk of gas embolism. Although animal studies have shown that low PP reduces the occurrence of gas embolism, clinical evidence is lacking. METHODS: This parallel, dual-arm, double-blind, randomized controlled trial included 141 patients undergoing elective LLR. Patients were randomized into standard ("S," 15 mm Hg; n = 70) or low ("L," 10 mm Hg; n = 71) PP groups. Severe gas embolism (≥ grade 3, based on the Schmandra microbubble method) was detected using transesophageal echocardiography and recorded as the primary outcome. Intraoperative vital signs and postoperative recovery profiles were also evaluated. RESULTS: Fewer severe gas embolism cases (n = 29, 40.8% vs n = 47, 67.1%, P = 0.003), fewer abrupt decreases in end-tidal carbon dioxide partial pressure, shorter severe gas embolism duration, less peripheral oxygen saturation reduction, and fewer increases in heart rate and lactate during gas embolization episodes was found in group L than in group S. Moreover, a higher arterial partial pressure of oxygen and peripheral oxygen saturation were observed, and fewer fluids and vasoactive drugs were administered in group L than in group S. In both groups, the distensibility index of the inferior vena cava negatively correlated with central venous pressure throughout LLR, and a comparable quality of recovery was observed. CONCLUSIONS: Low PP reduced the incidence and duration of severe gas embolism and achieved steadier hemodynamics and vital signs during LLR. Therefore, a low PP strategy can be considered a valuable choice for the future LLR.
Assuntos
Embolia Aérea , Laparoscopia , Animais , Humanos , Dióxido de Carbono/efeitos adversos , Embolia Aérea/etiologia , Embolia Aérea/prevenção & controle , Embolia Aérea/diagnóstico , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Fígado/cirurgia , Pneumoperitônio Artificial/efeitos adversosRESUMO
OBJECTIVES: Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). This study assessed potential risk factors for VWE in MMD. METHODS: We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE and non-VWE groups based on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors was compared using Kaplan-Meier survival and Cox regression. RESULTS: We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (p = 0.014) and a higher incidence of ischaemia and haemorrhage (p = 0.002) than did the non-VWE group. Risk factors for VWE included the ring finger protein 213 (RNF213) p.R4810K variant (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.08-3.76, p = 0.028), hyperhomocysteinaemia (HHcy) (OR 5.08, 95% CI 2.34-11.05, p < 0.001), and smoking history (OR 3.49, 95% CI 1.08-11.31, p = 0.037). During the follow-up of 63.9 ± 13.2 months (median 65 months), 18 recurrent stroke events occurred. Cox regression showed that VWE and the RNF213 p.R4810K variant were risk factors for stroke. CONCLUSION: The RNF213 p.R4810K variant is strongly associated with VWE and poor prognosis in MMD. HHcy and smoking are independent risk factors for VWE. CLINICAL RELEVANCE STATEMENT: Vessel wall enhancement in moyamoya disease is closely associated with poor prognosis, especially related to the ring finger protein 213 p.R4810K variant, hyperhomocysteinaemia, and smoking, providing crucial risk assessment information for the clinic. KEY POINTS: ⢠The baseline presence of vessel wall enhancement is significantly associated with poor prognosis in moyamoya disease. ⢠The ring finger protein 213 p.R4810K variant is strongly associated with vessel wall enhancement and poor prognosis in moyamoya disease. ⢠Hyperhomocysteinaemia and smoking are independent risk factors for vessel wall enhancement in moyamoya disease.
Assuntos
Doença de Moyamoya , Humanos , Doença de Moyamoya/diagnóstico por imagem , Masculino , Feminino , Fatores de Risco , Adulto , Pessoa de Meia-Idade , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Adenosina Trifosfatases/genética , Prognóstico , Estudos Retrospectivos , Hiper-Homocisteinemia/complicações , Ubiquitina-Proteína LigasesRESUMO
OBJECTIVE: To evaluate the benefits of combining omalizumab with specific immunotherapy (SCIT) in the treatment of children with bronchial asthma. METHODS: In this study, 83 children with asthma were treated at the Allergy Department of Qingdao University from January 2019 to February 2020. Participants were divided into three groups: SCIT, combination (omalizumab + SCIT), and control (standard asthma medications). We assessed Asthma Control Questionnaire (ACQ) scores, Visual Analogue Scale (VAS) scores, and lung function at baseline, 24 wk, and 48 wk. Additionally, asthma medication scores were compared at 24 and 48 wk. Adverse reactions were monitored in both the SCIT and combination groups. RESULTS: The combination group demonstrated lower ACQ scores at both 24 and 48 wk, and improved VAS scores at 48 wk compared to the other groups. Additionally, lung function parameters (FEV1 and FEF50) showed significant improvement in the combination group. Reduced asthma medication scores were noted in the combination group at 24 and 48 wk. Local adverse reactions were fewer in the combination group, and no systemic adverse reactions were reported. CONCLUSION: Combining omalizumab with SCIT provides quicker asthma control, lowers medication requirements, and enhances lung function with fewer adverse effects, making it a safe and effective treatment for children with bronchial asthma.
RESUMO
BACKGROUND: HSK3486 (ciprofol), a new candidate drug similar to propofol, exerts sedative and hypnotic effects through gamma-aminobutyric acid type A receptors; however, its potential role in colorectal cancer is currently unknown. AIMS: This study aimed to evaluate the effects of HSK3486 on colorectal cancer cell proliferation. METHODS: Imaging was performed to detect reactive oxygen species and mitochondrial membrane potential. Western blotting was used to determine the expression of target signals. The HSK3486 molecular mechanism was investigated through ATPase inhibitory factor 1 knockdown and xenograft model experiments to assess mitochondrial function in colorectal cancer cells. RESULTS: Cell Counting Kit-8 and Annexin V/propidium iodide double staining assays showed that HSK3486 inhibited colorectal cancer cell proliferation in a concentration-dependent manner. In addition, HSK3486 treatment increased the expression of B-cell lymphoma-2-associated X, cleaved caspase 3, and cleaved poly (ADP-ribose) polymerase, whereas myeloid cell leukemia-1 and B-cell lymphoma 2 expression decreased. HSK3486 promoted mitochondrial dysfunction by inducing ATPase inhibitor factor 1 expression. Furthermore, HSK3486 promoted oxidative stress, as shown by the increase in reactive oxygen species and lactate dehydrogenase levels, along with a decrease in mitochondrial membrane potential and ATP levels. ATPase inhibitor factor 1 small interfering RNA pretreatment dramatically increased the mitochondrial membrane potential and tumor size in a xenograft model following exposure to HSK3486. CONCLUSION: Collectively, our findings revealed that HSK3486 induces oxidative stress, resulting in colorectal cancer cell apoptosis, making it a potential candidate therapeutic strategy for colorectal cancer.
Assuntos
Apoptose , Neoplasias Colorretais , Humanos , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/farmacologia , Adenosina Trifosfatases/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Potencial da Membrana Mitocondrial , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteína Inibidora de ATPase/efeitos dos fármacosRESUMO
Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and the etiology is unknown. Metabolic dysfunction is present in patients with ASD. In the current study, untargeted metabolomics was employed to screen the differential metabolites in the liver of BTBR mouse model of autism, and MetaboAnalyst 4.0 was used for metabolic pathway analysis. Mice were killed, and liver samples were collected for untargeted metabolomics analysis and examination of histopathology. Finally, 12 differential metabolites were identified. The intensities of phenylethylamine, 4-Guanidinobutanoic acid, leukotrieneD4, and SM(d18:1/24:1(15Z)) were significantly upregulated (p < .01), and the intensities of estradiol, CMP-N-glycoloylneuraminate, retinoyl ß-glucuronide,4-phosphopantothenoylcysteine, aldophosphamide, taurochenodesoxycholic acid, taurocholic acid, and dephospho-CoA were significantly downregulated (p < .01) in the BTBR group compared with C57 control group, indicating that differences between BTBR and C57 groups were observed in metabolic patterns. Disturbed pathways of the BTBR mice involved lipid metabolism, retinol metabolism, and amino acid and energy metabolism, revealing that bile acid-mediated activation of LXRα might contribute to metabolic dysfunction of lipid and leukotriene D4 produced by the activation of 5-LOX led to hepatic inflammation. Pathological changes in the liver tissue, such as hepatocyte vacuolization, and small amounts of inflammatory and cell necrosis, further supported metabolomic results. Moreover, Spearman's rank correlation revealed that there is a strong relationship between metabolites across liver and cortex, suggesting liver may exert action by connecting peripheral and neural systems. These findings were likely to be of pathological importance or a cause/consequence of autism, and may provide insight into key metabolic dysfunction to target potential therapeutic strategies relating to ASD.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Camundongos , Animais , Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Transtorno do Espectro Autista/metabolismo , Camundongos Endogâmicos , Fígado/metabolismo , Metabolômica , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Familial exudative vitreoretinopathy (FEVR) is a genetic eye disorder that leads to abnormal development of retinal blood vessels, resulting in vision impairment. This study aims to identify pathogenic variants by targeted exome sequencing in 9 independent pedigrees with FEVR and characterize the novel pathogenic variants by molecular dynamics simulation. METHODS: Clinical data were collected from 9 families with FEVR. The causative genes were screened by targeted next-generation sequencing (TGS) and verified by Sanger sequencing. In silico analyses (SIFT, Polyphen2, Revel, MutationTaster, and GERP + +) were carried out to evaluate the pathogenicity of the variants. Molecular dynamics was simulated to predict protein conformation and flexibility transformation alterations on pathogenesis. Furthermore, molecular docking techniques were employed to explore the interactions and binding properties between LRP5 and DKK1 proteins relevant to the disease. RESULTS: A 44% overall detection rate was achieved with four variants including c.4289delC: p.Pro1431Argfs*8, c.2073G > T: p.Trp691Cys, c.1801G > A: p.Gly601Arg in LRP5 and c.633 T > A: p.Tyr211* in TSPAN12 in 4 unrelated probands. Based on in silico analysis and ACMG standard, two of them, c.4289delC: p.Pro1431Argfs*8 and c.2073G > T: p.Trp691Cys of LRP5 were identified as novel pathogenic variants. Based on computational predictions using molecular dynamics simulations and molecular docking, there are indications that these two variants might lead to alterations in the secondary structure and spatial conformation of the protein, potentially impacting its rigidity and flexibility. Furthermore, these pathogenic variants are speculated to potentially influence hydrogen bonding interactions and could result in an increased binding affinity with the DKK1 protein. CONCLUSIONS: Two novel genetic variants of the LRP5 gene were identified, expanding the range of mutations associated with FEVR. Through molecular dynamics simulations and molecular docking, the potential impact of these variants on protein structure and their interactions with the DKK1 protein has been explored. These findings provide further support for the involvement of these variants in the pathogenesis of the disease.
Assuntos
Oftalmopatias Hereditárias , Doenças Retinianas , Humanos , Vitreorretinopatias Exsudativas Familiares , Doenças Retinianas/genética , Doenças Retinianas/metabolismo , Simulação de Acoplamento Molecular , Oftalmopatias Hereditárias/genética , Tetraspaninas/genética , Análise Mutacional de DNA , Mutação , Linhagem , Fenótipo , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismoRESUMO
PURPOSE: To compare the multimodal techniques (including neuronavigation, intraoperative MRI [iMRI], and neuromonitoring [IONM]) and conventional approach (only guided by neuronavigation) in removing glioblastoma (GBM) with corpus callosum (CC) involvement (ccGBM), their effectiveness and safety were analyzed and compared. METHODS: Electronic medical records were retrospectively reviewed for ccGBM cases treated in our hospital between January 2016 and July 2020. Patient demographics, tumor characteristics, clinical outcomes, extent of resection (EOR), progression-free survival (PFS), and overall survival (OS) were obtained and compared between the multimodal group (used multimodal techniques) and the conventional group (only used neuronavigation). Both groups only included patients that had maximal safe resection (not biopsy). Postoperative radiochemotherapy was also performed or not. Univariate and multivariate analyses were performed to identify significant prognostic factors and optimal EOR threshold. RESULTS: Finally 56 cases of the multimodal group and 21 cases of the conventional group were included. The multimodal group achieved a higher median EOR (100% versus 96.1%, P = 0.036) and gross total resection rate (60.7% versus 33.3%, P = 0.032) and a lower rate of permanent motor deficits (5.4% versus 23.8%, P = 0.052) than the conventional approach. The multimodal group had the longer median PFS (10.9 versus 7.0 months, P = 0.023) and OS (16.1 versus 11.6 months, P = 0.044) than the conventional group. Postoperative language and cognitive function were similar between the two groups. In multivariate analysis, a higher EOR, radiotherapy, and longer cycles of temozolomide chemotherapy were positive prognostic factors for survival of ccGBM. An optimal EOR threshold of 92% was found to significantly benefit the PFS (HR = 0.51, P = 0.036) and OS (HR = 0.49, P = 0.025) of ccGBM. CONCLUSION: Combined use of multimodal techniques can optimize the safe removal of ccGBM. Aggressive resection of EOR > 92% using multimodal techniques combined with postoperative radiochemotherapy should be suggested for ccGBM.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Corpo Caloso/cirurgia , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Monitorização Intraoperatória/métodos , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Recent studies have shown that the prognosis of low-grade glioma (LGG) patients is closely correlated with the immune infiltration and the expression of long-stranded non-coding RNAs (lncRNAs). It's meaningful to find the immune-related lncRNAs (irlncRNAs). METHODS: The Cancer Genome Atlas (TCGA) data was employed in the study to identify irlncRNAs and Cox regression model was applied to construct the risk proportional model based on irlncRNAs. RESULTS: In the study, we retrieved transcriptomic data of LGG from TCGA and identified 10 lncRNA signatures consisting of irlncRNAs by co-expression analysis. Then we plotted 1-year receiver operating characteristic (ROC) curves and calculated the area under the curve (AUC). LGG patients were divided into high-risk and low-risk groups according to the risk model. We found there were differences in survival prognosis, clinical characteristics, degree of immune cell infiltration, expression of immune gene checkpoint genes, and sensitivity to the commonly used chemotherapeutic agents of high-risk and low-risk groups. CONCLUSIONS: IrlncRNA-based risk assessment model can be used as a prognostic tool to predict the survival outcome and clinical characteristics of LGG and to guide treatment options.
Assuntos
Glioma , RNA Longo não Codificante , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/terapia , Humanos , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
OBJECTIVES: The psychological distress caused by COVID-19 may be pronounced among the parents of children with autism spectrum disorder (ASD). This study aimed to investigate psychological distress among parents of children with ASD during the COVID-19 pandemic. METHODS: A total of 1764 parents of children with ASD and 4962 parents of typically developing (TD) children were recruited. The participants completed an online survey which contained demographic information, the impact due to COVID-19 crisis, resilience, coping styles, anxiety and depression. Hierarchical linear regression was used to assess the contributions of these variables to anxiety and depression. RESULTS: After adjusting for demographic variables, the following factors were associated with parents' anxiety and depression symptoms: (i) Whether or not the participants had a child with ASD; (ii) resilience; (iii) coping strategies, and; (iv) the impact due to COVID-19. Among these, the psychological stress caused by COVID-19 played the most important role in parental anxiety (ß = 0.353) and depression (ß = 0.242) symptoms. Parents of children with ASD had lower levels of resilience and positive coping, and used more negative coping strategies than parents of TD children. Among all participants, 8.0 and 24.2% of parents had symptoms of anxiety and depression, respectively. Compared to parents of TD children, more parents of children with ASD exhibited symptoms of anxiety and depression (12.2% vs. 6.6%; 31.0% vs. 21.7%, respectively). CONCLUSIONS: During the COVID-19 pandemic, parents experienced varying levels of anxiety and depression, particularly, parents of children with ASD. More specific attention should be paid to parental mental health and long-term effective intervention programs, that are targeted towards parents of children with ASD, and such programs should be promoted around China in the wake of the COVID-19 crisis.
Assuntos
Transtorno do Espectro Autista , COVID-19/psicologia , Pais/psicologia , Angústia Psicológica , Adolescente , Adulto , Ansiedade/epidemiologia , COVID-19/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Depressão/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia Mieloide Aguda , Proteínas de Fusão Oncogênica , Proteína FUS de Ligação a RNA , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Adulto , Proteínas de Fusão Oncogênica/genética , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Proteína FUS de Ligação a RNA/genética , Idoso , Proteínas RepressorasRESUMO
This study was performed to investigate the prognostic significance of a cumulative score based on the preoperative plasma fibrinogen and serum albumin (FA score) in operable esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative fibrinogen, and albumin concentrations were retrospectively reviewed in patients who underwent transthoracic esophagectomy. The optimal cutoff value was defined as 4.0 g/L for fibrinogen according to previous studies and as 41.0 g/L for albumin for the lower quartile. Subjects with elevated fibrinogen and decreased albumin levels were allocated a score of 2, those with only one of these two abnormalities were assigned a score of 1, and those with neither of the abnormalities were allocated a score of 0. The preoperative FA score was significantly associated with tumor length, depth of invasion, lymph node involvement, tumor-node-metastasis (TNM) stage, and the modified Glasgow Prognostic Score (mGPS). No significant differences in age, gender, tumor location, degree of differentiation, smoking or alcohol consumption were found between groups. Univariate survival analysis revealed that high preoperative FA score (1/2) was significantly associated with unfavorable disease-free survival (DFS) [hazard ratio (HR), 1.675; 95% confidence interval (CI), 1.278-2.195; P < 0.001] and overall survival (OS) (HR, 1.685; 95% CI, 1.268-2.239; P < 0.001). Furthermore, it remained an independent prognostic indicator for both DFS (HR, 1.394; 95% CI, 1.035-1.879; P = 0.029) and OS (HR, 1.369; 95% CI, 1.010-1.878; P = 0.048) in multivariable Cox regression analysis. A high preoperative FA score could significantly predict impaired long-term survival for ESCC patients who underwent transthoracic esophagectomy.
Assuntos
Neoplasias Esofágicas/sangue , Carcinoma de Células Escamosas do Esôfago/sangue , Esofagectomia/mortalidade , Fibrinogênio/análise , Albumina Sérica/análise , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos , Adulto JovemRESUMO
Triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer in which the cell surface lacks usual targets for drug to exhibit its effects. Epirubicin (Epi) is widely used for TNBC, but a substantial number of patients develop Epi resistance that is usually associated with poor prognosis. Transforming growth factor (TGF-ß) is a multifunctional cytokine. In recent study, it appears that TGF-ß influences the cancer stem cell population, thus, the drug resistance of cancer may also be affected. We used epirubicin to treat MDA-MB-231 (MB-231) cells and found that TGF-ß and breast cancer stem cell markers CD44+CD24- were increased and were dose-dependent of epirubicin. We established drug-resistant cell line from parental MB-231â¯cells by chronic treatment with low-concentration epirubicin. The MB-231/Epi cell line showed relatively slow growth rate with varied morphology. Transwell assay and drug sensitivity assay revealed that the malignant cell behaviors in terms of migration, invasion and epirubicin-resistant properties were markedly increased in the MB-231/Epi cells. Western blot, immunofluorescence assay, and flow cytometry were used to analyze the expression levels of the breast cancer stem cell markers, CD44 and CD24. Mammospheres assay showed that the stemness of MB-231/Epi was increased compared to their parental cells. Interestingly, MB-231/Epi cells showed different expression levels of apoptosis-related markers: Bcl2, Bax; EMT-related markers E-cadherin, N-cadherin and cell cycle-related marker cyclinD1. These genes have all been shown to be regulated by the TGF-ß pathway. Taken together, our findings suggest that TGF-ß plays a vital role in TNBC epirubicin-resistance through regulating stemness, EMT and apoptosis.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Epirubicina/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUD: Autism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders with a genetic basis. The role of long-chain polyunsaturated fatty acids (LC-PUFAs) and the occurrence of autism has been the focus of many recent studies. The present study investigates whether genetic variants of the fatty acid desaturase (FADS) 1/2 and elongation of very long-chain fatty acids protein (ELOVL) 2 genes, which are involved in LC-PUFA metabolism, are associated with ASD risk. METHODS: A cohort of 243 ASD patients and 243 unrelated healthy controls were enrolled in this case control study. Sixteen tag single nucleotide polymorphisms from the FADS1-2 and ELOVL2 genes were genotyped using the Sequenom Mass Array. RESULTS: There were significant differences in allelic distribution of FADS2 rs526126 (OR = 0.55, 95% CI = 0.42-0.72, pFDR < 0.05) between autistic children and controls. FADS2 rs526126 and ELOVL2 rs10498676 were associated with decreased ASD risk in recessive model (OR = 0.07, 95% CI = 0.02-0.22, pFDR < 0.01; OR = 0.56, 95% CI = 0.35-0.89, pFDR = 0.042), while ELOVL2 rs17606561, rs3756963, and rs9468304 were associated with increased ASD risk in overdominant model (OR = 1.63, 95% CI = 1.12-2.36, pFDR = 0.036; OR = 1.64, 95% CI = 1.14-2.37, pFDR = 0.039; OR = 1.75, 95% CI = 1.22-2.50, pFDR = 0.017). The A/A genotype of rs10498676 was correlated with a decline in the Autism Diagnostic Interview-Revised communication (verbal and nonverbal) domain. CONCLUSIONS: These findings provide evidence of an association between FADS2 and ELOVL2 polymorphisms and ASD susceptibility in Chinese children.
Assuntos
Acetiltransferases/genética , Povo Asiático/genética , Transtorno do Espectro Autista/genética , Ácidos Graxos Dessaturases/genética , Polimorfismo de Nucleotídeo Único/genética , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Dessaturase de Ácido Graxo Delta-5 , Elongases de Ácidos Graxos , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , MasculinoRESUMO
BACKGROUND: Early detection and diagnosis are very important for autism. Current diagnosis of autism relies mainly on some observational questionnaires and interview tools that may involve a great variability. We performed a metabolomics analysis of serum to identify potential biomarkers for the early diagnosis and clinical evaluation of autism. METHODS: We analyzed a discovery cohort of patients with autism and participants without autism in the Chinese Han population using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS/MS) to detect metabolic changes in serum associated with autism. The potential metabolite candidates for biomarkers were individually validated in an additional independent cohort of cases and controls. We built a multiple logistic regression model to evaluate the validated biomarkers. RESULTS: We included 73 patients and 63 controls in the discovery cohort and 100 cases and 100 controls in the validation cohort. Metabolomic analysis of serum in the discovery stage identified 17 metabolites, 11 of which were validated in an independent cohort. A multiple logistic regression model built on the 11 validated metabolites fit well in both cohorts. The model consistently showed that autism was associated with 2 particular metabolites: sphingosine 1-phosphate and docosahexaenoic acid. LIMITATIONS: While autism is diagnosed predominantly in boys, we were unable to perform the analysis by sex owing to difficulty recruiting enough female patients. Other limitations include the need to perform test-retest assessment within the same individual and the relatively small sample size. CONCLUSION: Two metabolites have potential as biomarkers for the clinical diagnosis and evaluation of autism.
Assuntos
Transtorno Autístico/sangue , Povo Asiático , Biomarcadores/sangue , Análise Química do Sangue , Criança , Pré-Escolar , China , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Ácidos Docosa-Hexaenoicos/sangue , Feminino , Humanos , Análise dos Mínimos Quadrados , Modelos Logísticos , Lisofosfolipídeos/sangue , Masculino , Metabolômica/métodos , Curva ROC , Esfingosina/análogos & derivados , Esfingosina/sangue , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: The present study aimed to (i) evaluate the reproducibility and validity of a designed FFQ, (ii) apply the FFQ for estimating the dietary intakes of four flavonols and two flavones in female adolescents and (iii) explain their major dietary sources. DESIGN: The reproducibility between the first and second FFQ administrations (1 year interval) was estimated using the intra-class correlation coefficient. The validity of the first FFQ relative to the average of four three-day 24 h dietary recalls (24-HR) from four seasons was assessed using the Spearman correlation coefficient. Using a flavonoid content database, the individual flavonol and flavone intakes were calculated and the major food sources were estimated. SETTING: Middle school in Suihua area of Heilongjiang Province, northern China. SUBJECTS: Female adolescents (n 887) aged 12-18 years. RESULTS: Better reproducibility and validity were obtained in the present study. The flavonol and flavone intakes were 16.29 and 4.31 mg/d, respectively. Quercetin and kaempferol were the major contributors (26.8 % and 23.7 %, respectively) to the total intake of flavonols and flavones. The main food sources of flavonols and flavones were apples (14.1 %), followed by potatoes (7.5 %), lettuce (7.3 %) and oranges (7.3 %). CONCLUSIONS: The dietary flavonol and flavone intakes among female adolescents in northern China were similar to those reported in several countries, but significant differences were observed in the food sources ascribed to the geographical location and dietary characteristics.
Assuntos
Dieta/estatística & dados numéricos , Ingestão de Alimentos/etnologia , Flavonas/administração & dosagem , Flavonóis/administração & dosagem , Inquéritos Nutricionais/métodos , Adolescente , China , Citrus sinensis , Dieta/etnologia , Feminino , Humanos , Quempferóis/análise , Lactuca , Malus , Quercetina/análise , Reprodutibilidade dos Testes , Instituições Acadêmicas , Solanum tuberosum , Estatísticas não Paramétricas , Estudantes , Inquéritos e QuestionáriosRESUMO
GOALS: The aim of this study was to perform a meta-analysis to evaluate the prognostic and diagnostic significance of serum/plasma osteopontin (OPN) in hepatocellular carcinoma (HCC). BACKGROUND: The prognostic and diagnostic value of serum/plasma OPN) in HCC remain controversial. STUDY: Eligible studies were identified through a systematic literature search. A meta-analysis of 8 studies (4 for prognosis and 4 for diagnosis, 1399 patients) was performed to estimate the association between serum/plasma-based OPN elevation and overall survival (OS) and disease-free survival (DFS) in HCC patients, and to evaluate the accuracy of plasma OPN and α-fetoprotein (AFP) in the diagnosis of HCC. Subgroup analyses were also performed in the meta-analysis. RESULTS: We found that serum/plasma-based OPN elevation was significantly associated with poor OS (HR, 1.96; 95% CI, 1.47-2.61; P<0.00001) and DFS (HR, 1.80; 95% CI, 1.43-2.26; P<0.00001) in HCC. The summary estimates for plasma OPN and AFP in diagnosing HCC in the studies included were as follows: sensitivity, 88% (95% CI, 84%-91%) versus 68% (95% CI, 63%-73%); specificity, 87% (95% CI, 83%-90%) versus 97% (95% CI, 94%-99%); diagnostic odds ratio, 62.87 (95% CI, 10.90-362.60) versus 49.09 (95% CI, 11.36-212.10); and area under SROS, 0.91 (95% CI, 0.85-0.97) versus 0.68 (95% CI, 0.45-1.03). CONCLUSIONS: The current evidence indicates that serum/plasma-based OPN seems to have significant predictive ability for estimating survival in HCC, and plasma OPN has a comparable accuracy to AFP for the diagnosis of HCC, although the diagnostic value of plasma OPN for early or AFP-negative HCC remains to be assessed by further studies.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Osteopontina/sangue , Carcinoma Hepatocelular/sangue , Humanos , Neoplasias Hepáticas/sangue , Valor Preditivo dos TestesRESUMO
Water vapor from respiration can severely accelerate the charge dissipation of the face mask, reducing filtration efficiency. Moreover, the foul odor from prolonged mask wear tends to make people remove their masks, leading to the risk of infection. In this study, an electro-blown spinning electroactive nanofibrous membrane (Zn/CB@PAN) with antibacterial and deodorization properties was prepared by adding zinc (Zn) and carbon black (CB) nanoparticles to the polyacrylonitrile (PAN) nanofibers, respectively. The filtration efficiency of Zn/CB@PAN for PM0.3 was > 99% and could still maintain excellent durability within 4 h in a high-humidity environment (25 â and RH = 95%). Moreover, the bacterial interception rate of the Zn/CB@PAN could reach 99.99%, and it can kill intercepted bacteria. In addition, the deodorization rate of Zn/CB@PAN in the moist state for acetic acid was 93.75% and ammonia was 95.23%, respectively. The excellent filtering, antibacterial, and deodorizing performance of Zn/CB@PAN can be attributed to the synergistic effect of breath-induced Zn/CB galvanic couples' electroactivity, released metal ions, and generated reactive oxygen species. The developed Zn/CB@PAN could capture and kill airborne environmental pathogens under humid environments and deodorize odors from prolonged wear, holding promise for broad applications as personal protective masks.
Assuntos
Nanofibras , Humanos , Antibacterianos , Ácido Acético , Zinco , Amônia , FiltraçãoRESUMO
Background: Strengthening the construction of community resilience and reducing disaster impacts are on the agenda of the Chinese government. The COVID-19 pandemic could alter the existing community resilience. This study aims to explore the dynamic change trends of community resilience in China and analyze the primary influencing factors of community resilience in the context of COVID-19, as well as construct Community Resilience Governance System Framework in China. Methods: A community advancing resilience toolkit (CART) was used to conduct surveys in Guangdong, Sichuan, and Heilongjiang provinces in China in 2015 and 2022, with community resilience data and information on disaster risk awareness and disaster risk reduction behaviors of residents collected. The qualitative (in-depth interview) data from staffs of government agencies and communities (n = 15) were pooled to explore Community Resilience Governance System Framework in China. Descriptive statistics analysis and t-tests were used to investigate the dynamic development of community resilience in China. Hierarchical regression analysis was performed to explore the main influencing factors of residential community resilience with such socio-demographic characteristics as gender and age being controlled. Results: The results indicate that community resilience in China has improved significantly, presenting differences with statistical significance (p < 0.05). In 2015, connection and caring achieved the highest score, while disaster management achieved the highest score in 2022, with resources and transformative potential ranking the lowest in their scores in both years. Generally, residents presented a high awareness of disaster risks. However, only a small proportion of residents that were surveyed had participated in any "community-organized epidemic prevention and control voluntary services" (34.9%). Analysis shows that core influencing factors of community resilience include: High sensitivity towards major epidemic-related information, particular attention to various kinds of epidemic prevention and control warning messages, participation in epidemic prevention and control voluntary services, and formulation of epidemic response plans. In this study, we have constructed Community Resilience Governance System Framework in China, which included community resilience risk awareness, community resilience governance bodies, community resilience mechanisms and systems. Conclusion: During the pandemic, community resilience in China underwent significant changes. However, community capital was, is, and will be a weak link to community resilience. It is suggested that multi-stages assessments of dynamic change trends of community resilience should be further performed to analyze acting points and core influencing factors of community resilience establishment at different stages.
Assuntos
COVID-19 , Resiliência Psicológica , Humanos , China/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Masculino , Feminino , Inquéritos e Questionários , Adulto , Pessoa de Meia-Idade , SARS-CoV-2 , PandemiasRESUMO
OBJECTIVE: Elevated parenting stress has been observed among mothers of children with autism spectrum disorders (ASDs) in western countries, but little is known about mothers of Han Chinese children. The aim of the current study was to further the knowledge about stress experienced by Chinese mothers of children with ASD by examining maternal parenting stress in Heilongjiang province of China. METHODS: In this cross-sectional study, data about participants' demographic characteristics, parenting stress, anxiety, depression, child's behavioral problems, coping strategies, and social support were collected though a questionnaire survey. The participants included 150 families with ASD children, who were consecutively admitted to the clinics of the Children Development and Behavior Research Center in Harbin Medical University, Heilongjiang Disabled Persons Federation, and Mudanjiang Child Welfare Home. RESULTS: The participants reported elevated parenting stress. Mothers' parenting stress was associated with levels of depression and anxiety, and child's behavioral symptoms. Child's behavioral symptoms, maternal anxiety, maternal depressive symptoms, and lack of governmental financial support were associated with overall parenting stress. CONCLUSIONS: Government support may play an important role in reducing parenting stress in this population.
Assuntos
Transtornos Globais do Desenvolvimento Infantil/psicologia , Mães/psicologia , Poder Familiar/psicologia , Estresse Psicológico , Adulto , Ansiedade/epidemiologia , Criança , Pré-Escolar , China , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Renda , Masculino , Estado Civil , Comportamento Materno/psicologia , Relações Mãe-Filho , Fatores de Risco , Apoio Social , Fatores SocioeconômicosRESUMO
The etiology and pathology of autism spectrum disorders (ASDs) are still poorly understood, which largely limit the treatment and diagnosis of ASDs. Emerging evidence supports that abnormal metabolites in the cerebral cortex of a BTBR mouse model of autism are involved in the pathogenesis of autism. However, systematic study on global metabolites in the cerebral cortex of BTBR mice has not been conducted. The current study aims to characterize metabolic changes in the cerebral cortex of BTBR mice by using an untargeted metabolomic approach based on UPLC-Q-TOF/MS. C57BL/6 J mice were used as a control group. A total of 14 differential metabolites were identified. Compared with the control group, the intensities of PI(16:0/22:5(4Z,7Z,10Z,13Z,16Z)), PC(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/18:1(9Z)), PA(16:0/18:1(11Z)), 17-beta-estradiol-3-glucuronide, and N6,N6,N6-trimethyl-L-lysine decreased significantly (p < 0.01) and the intensities of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, LysoPC(20:4(5Z,8Z,11Z,14Z)/0:0), adenosine monophosphate, adenosine-5'-phosphosulfate, LacCer(d18:1/12:0),3-dehydro-L-gulonate, N-(1-deoxy-1-fructosyl)tryptophan, homovanillic acid, and LPA(0:0/18:1(9Z)) increased significantly (p < 0.01) in the BTBR group. These changes in metabolites were closely related to perturbations in lipid metabolism, energy metabolism, purine metabolism, sulfur metabolism, amino acid metabolism, and carnitine biosynthesis. Notably, exacerbation of the oxidative stress response caused by differential prooxidant metabolites led to alteration of antioxidative systems in the cerebral cortex and resulted in mitochondrial dysfunction, further leading to abnormal energy metabolism as an etiological mechanism of autism. A central role of abnormal metabolites in neurological functions associated with behavioral outcomes and disturbance of sulfur metabolism and carnitine biosynthesis were found in the cerebral cortex of BTBR mice, which helped increase our understanding for exploring the pathological mechanism of autism.