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BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.
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Pruebas Genéticas , Atrofia Muscular Espinal , Tamizaje Neonatal , Humanos , Recién Nacido , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Proyectos Piloto , Pruebas Genéticas/normas , Pruebas Genéticas/métodos , Tamizaje Neonatal/normas , Tamizaje Neonatal/métodos , China , Pruebas con Sangre Seca/normas , Pruebas con Sangre Seca/métodos , Garantía de la Calidad de Atención de Salud , Laboratorios Clínicos/normas , Proteína 1 para la Supervivencia de la Neurona Motora/genéticaRESUMEN
BACKGROUND: Down syndrome (DS) is the most common human chromosomal abnormality. About 1200 laboratories carry out antenatal screening for DS in second trimester pregnancies in China. Their prenatal assessment of DS pregnancy risk is based on biometric calculations conducted on maternal serum biochemical markers and ultrasonic markers of fetal growth. However, the performance of this triple test for DS in second trimester pregnancies has a false positive rate of 5%, and a detection rate of about 60%â¼65%. METHOD: A total of 58,972 pregnant women, including 49 DS cases, who had undergone DS screening in the second trimester were retrospectively included and a machine learning (ML) model based on random forest was built to predict DS. In addition, the model was applied to another hospital data set of 27,170 pregnant women, including 27 DS cases, to verify the predictive efficiency of the model. RESULTS: The ML model gave a DS detection rate of 66.7%, with a 5% false positive rate in the model data set. In the external verification data set, the ML model achieved a DS detection rate of 85.2%, with a 5% false positive rate . In comparison with the current laboratory risk model, the ML model improves the DS detection rate with the same false positive rate, while the difference has no significance. CONCLUSIONS: The ML model for DS detection described here has a comparable detection rate with the same false positive rate as the DS risk screening software currently used in China. Our ML model exhibited robust performance and good extrapolation, and could function as an alternative tool for DS risk assessment in second trimester maternal serum.
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Síndrome de Down , Biomarcadores , Síndrome de Down/diagnóstico , Femenino , Humanos , Aprendizaje Automático , Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Diagnóstico Prenatal , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the correlation of serum vitamin A and vitamin E levels with the occurrence and severity of preeclampsia. METHODS: The clinical data of 5,000 pregnant women in our hospital were retrospectively studied. Five hundred and sixty-five pregnant women with preeclampsia were divided into a mild group (259 cases) and a severe group (306 cases). The rest 4435 healthy pregnant women were classified as the healthy group. The concentrations of serum vitamin A and vitamin E in each group were compared to analyze the risk factors for preeclampsia. RESULTS: The levels of vitamin A and vitamin E were negatively correlated with the severity of preeclampsia (P<0.001). The logistic regression analysis showed that older age (OR=1.674), vitamin A deficiency (OR=2.463) and vitamin E deficiency (OR=2.206) were independent risk factors for preeclampsia (all P<0.05). CONCLUSION: Older age, vitamin A deficiency and vitamin E deficiency are the risk factors for preeclampsia. The concentrations of vitamin A and vitamin E are negatively correlated with the severity of preeclampsia. Vitamin A and vitamin E deficiencies in preeclampsia can increase the risk of adverse pregnancy outcomes, which needs timely intervention.
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OBJECTIVE: To explore the value of a novel prenatal diagnosis model using combined chromosomal karyotyping and BACs-on-BeadsTM(BoBs), a newly-developed technique. METHODS: 1048 single pregnancy pregnant women with various diagnostic indications were performed amniocentesis for prenatal diagnosis with karyotyping and BoBs simultaneously. RESULTS: Among 1047 successfully cultured specimens, 50 chromosomal abnormalities were identified with BoBs, including 43 common chromosomal trisomies, 3 chimeric chromosomes and 4 structural abnormalities, of which 3 microdeletions/microduplications were not detected with karyotyping. Except for extra yield of 1 Robertsonian translocation, the other numerical chromosomal abnormalities were detected with both karyotyping and BoBs. Ten fetal chromosome abnormalities were confirmed with karyotyping, including 8 structural abnormalities and 2 chimeric chromosomes. CONCLUSION: Combination of karyotyping and BoBs turned out to be a rapid, complementary and effective diagnostic model for fetal chromosomal abnormalities and microdeletion syndromes, which could yield a higher detection rate of fetal chromosomal abnormalities and chromosomal microdeletions/microduplications.
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Trastornos de los Cromosomas/diagnóstico , Enfermedades Fetales/diagnóstico , Pruebas Genéticas/métodos , Cariotipificación/métodos , Diagnóstico Prenatal/métodos , Adulto , Aberraciones Cromosómicas , Trastornos de los Cromosomas/genética , Femenino , Enfermedades Fetales/genética , Humanos , Cariotipificación/instrumentación , Masculino , Embarazo , Diagnóstico Prenatal/instrumentación , Adulto JovenRESUMEN
Nitidine chloride (NC) exhibits anti-tumor properties in various types of tumor. However, to the best of our knowledge there is no previous evidence of NC involvement in the apoptosis or proliferation of ovarian cancer cells and the underlying molecular mechanisms. The present study aimed to investigate the influence of NC on the viability and apoptosis of ovarian cancer cells and the synergistic effect NC and doxorubicin (DOX) may have on ovarian cancer cells. The viability and proliferation of ovarian cancer cells were examined using a methyl thiazolyl tetrazolium assay and 3H-thymidine incorporation assay. The apoptotic rate of ovarian cancer cells was detected by flow cytometry. The expression of apoptosisassociated proteins and Akt serine/threonine kinase 1 (Akt) were determined by western blot analysis following NC treatment. The inhibitory effect of NC on the proliferation of ovarian cancer cells was demonstrated in a time and dosedependent manner. The pro-apoptotic effect of NC on ovarian cancer cells was also observed. It was determined that NC significantly downregulated the protein expression levels of Bcell CLL/lymphoma 2 (Bcl-2) and upregulated the expression of Bcl2associated X protein, p53, caspase3 and 9. NC suppressed Akt phosphorylation. Additionally, the present study demonstrated that the effect of NC on the proliferation and apoptosis of ovarian cancer cells was Aktdependent by using the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt signaling pathway inhibitor, LY294002. NC exhibited a synergistic inhibitory effect on the viability of ovarian cancer cells when combined with DOX. The current study demonstrated that NC inhibited the proliferation and induced the apoptosis of ovarian cancer cells via the Akt signaling pathway and highlighted its potential clinical application for the treatment of ovarian cancer.
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Antibióticos Antineoplásicos/farmacología , Benzofenantridinas/farmacología , Doxorrubicina/farmacología , Neoplasias Ováricas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Benzofenantridinas/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Ováricas/genética , FosforilaciónRESUMEN
Nitidine chloride (NC) has been demonstrated to exert anti-tumor effects on various types of tumor. However, no studies have investigated the antimetastatic effect of NC on ovarian cancer cells, and the underlying mechanisms have not yet been clearly established. The present study aimed to determine the effect of NC on the migration and invasion of ovarian cancer cells. Cell viability and proliferation of ovarian cancer cells were assessed by MTT assay. A scratch wound healing assay and Transwell assays were performed to detect migration and invasion of cells, respectively. The expression levels of matrix metalloproteinase (MMP)2 and 9 were detected at the mRNA and protein level following stimulation with NC. Subsequently, the expression of mitogenactivated protein kinases was detected by western blot analysis. Finally, an inhibitor of extracellular signalregulated kinase (ERK) was applied to investigate the effect of NC on the expression of MMP2/9 as well as the migration and invasion of cells. It was found that NC suppressed the proliferation, migration and invasion of A2780 ovarian cancer cells. NC downregulated MMP2 and MMP9 in a dose and timedependent manner. In addition, NC was also able to downregulate phosphorylation of ERK. Furthermore, by applying an ERK inhibitor, U0126, the effect of NC on the expression of MMP-2/9 and inhibition of cell migration and invasion was verified. Taken together, these results demonstrated that NC inhibited the migration and invasion of ovarian cancer cells via the ERK signaling pathway.