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1.
PLoS Biol ; 20(8): e3001741, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35972936

RESUMEN

Mitochondrial DNA (mtDNA) mutations are often associated with incurable diseases and lead to detectable pathogenic variants in 1 out of 200 babies. Uncoupling of the inheritance of mtDNA and the nuclear genome by spindle transfer (ST) can potentially prevent the transmission of mtDNA mutations from mother to offspring. However, no well-established studies have critically assessed the safety of this technique. Here, using single-cell triple omics sequencing method, we systematically analyzed the genome (copy number variation), DNA methylome, and transcriptome of ST and control blastocysts. The results showed that, compared to that in control embryos, the percentage of aneuploid cells in ST embryos did not significantly change. The epiblast, primitive endoderm, and trophectoderm (TE) of ST blastocysts presented RNA expression profiles that were comparable to those of control blastocysts. However, the DNA demethylation process in TE cells of ST blastocysts was slightly slower than that in the control blastocysts. Collectively, our results suggest that ST seems generally safe for embryonic development, with a relatively minor delay in the DNA demethylation process at the blastocyst stage.


Asunto(s)
Blastocisto , Variaciones en el Número de Copia de ADN , Aneuploidia , Blastocisto/metabolismo , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Desarrollo Embrionario/genética , Femenino , Humanos , Embarazo
2.
Chemistry ; : e202402124, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937823

RESUMEN

Decarboxylative cross-coupling reactions are powerful tools for carbon-heteroatom bonds formation, but typically require pre-activated carboxylic acids as substrates or heteroelectrophiles as functional groups. Herein, we present an electrochemical decarboxylative cross-coupling of carboxylic acids with structurally diverse fluorine, alcohol, H2O, acid, and amine as nucleophiles. This strategy takes advantage of the ready availability of these building blocks from commercial libraries, as well as the mild and oxidant-free conditions provided by electrochemical system. This reaction demonstrates good functional-group tolerance and its utility in late-stage functionalization.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39002105

RESUMEN

OBJECTIVE: Development of a nomogram model for predicting the magnitude of risk of transferring hospitalized children with influenza to the ICU. METHODS: In a single-center retrospective study, 318 children with influenza who were hospitalized in our hospital from January 2018 to August 2023 were collected as study subjects. Children with influenza were randomly assigned to the training set and validation set in a ratio of 4:1. In the training set, risk factors were identified using univariate and multivariate logistic regression analyses, and a nomogram model was created on this basis. The validation set was used to evaluate the predictive power of the model. RESULTS: Multifactorial logistic regression analysis revealed six independent risk factors for transfer to the ICU in hospitalized children with influenza, including elevated peripheral white blood cell counts, elevated large platelet ratios, reduced mean platelet width, reduced complement C3, elevated serum globulin levels, and reduced total immunoglobulin M levels. Using these six metrics as predictors to construct a nomogram graphical model, the C-index was 0.970 (95% Cl: 0.953-0.988). The areas under the curve for the training and validation sets were 0.966 (95%Cl 0.947-0.985) and 0.919 (95%Cl 0.851-0.986), respectively. CONCLUSION: A nomogram for predicting the risk of transferring to the ICU for children with influenza was developed and validated, which demonstrates good calibration and clinical benefits.

4.
Eur J Clin Microbiol Infect Dis ; 43(6): 1231-1239, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38656425

RESUMEN

INTRODUCTION: The occurrence of pulmonary consolidation in children with Mycoplasma pneumoniae pneumonia (MPP) can lead to exacerbation of the disease. Therefore, early identification of children with MPP in combination with pulmonary consolidation is critical. The purpose of this study was to develop a straightforward, easy-to-use online dynamic nomogram for the identification of children with MPP who are at high risk of developing pulmonary consolidation. METHODS: 491 MPP patients were chosen and divided randomly into a training cohort and an internal validation cohort at a 4:1 ratio. Multi-factor logistic regression was used to identify the risk variables for mixed pulmonary consolidation in children with Mycoplasma pneumoniae (MP). The selected variables were utilized to build the nomograms and validated using the C-index, decision curve analysis, calibration curves, and receiver operating characteristic (ROC) curves. RESULTS: Seven variables were included in the Nomogram model: age, fever duration, lymphocyte count, C-reactive protein (CRP), ferritin, T8 lymphocyte percentage, and T4 lymphocyte percentage. We created a dynamic nomogram that is accessible online ( https://ertong.shinyapps.io/DynNomapp/ ). The C-index was 0.90. The nomogram calibration curves in the training and validation cohorts were highly comparable to the standard curves. The area under the curve (AUC) of the prediction model was, respectively, 0.902 and 0.883 in the training cohort and validation cohort. The decision curve analysis (DCA) curve shows that the model has a significant clinical benefit. CONCLUSIONS: We developed a dynamic online nomogram for predicting combined pulmonary consolidation in children with MP based on 7 variables for the first time. The predictive value and clinical benefit of the nomogram model were acceptable.


Asunto(s)
Mycoplasma pneumoniae , Nomogramas , Neumonía por Mycoplasma , Humanos , Neumonía por Mycoplasma/diagnóstico , Neumonía por Mycoplasma/microbiología , Masculino , Femenino , Niño , Preescolar , Curva ROC , Lactante , Factores de Riesgo , Adolescente , Proteína C-Reactiva/análisis
5.
Eur J Clin Microbiol Infect Dis ; 43(7): 1437-1444, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38789887

RESUMEN

OBJECTIVE: To investigate the clinical characteristics and risk factors for pneumonia in children co-infected with influenza A virus (IAV) and Mycoplasma pneumoniae (MP). METHODS: Children who were diagnosed with IAV and MP infection between January and December, 2023 were enrolled and divided into a non-pneumonia group and a pneumonia group. Univariate analysis and logistic regression analysis were used to evaluate each index, and the risk factors for pneumonia caused by coinfection in the two groups were explored. RESULTS: A total of 209 patients were enrolled, of which 107 and 102 patients were in the pneumonia and non-pneumonia groups, respectively. The patients in the pneumonia group were older and had a longer duration of fever (P < 0.05). Univariate analysis revealed that the median age, duration of fever, and CD3+, CD4+, CD8+ and IL-10 levels were significantly correlated with pneumonia (P < 0.05). Multivariate logistic regression analysis revealed that the median age, duration of fever, and CD4+, CD8+ and IL-10 levels were independent risk factors for pneumonia. Area under the curve of the five combined indicators in the ROC (receiver operator characteristic) analysis was 0.883, was higher than single factor. CONCLUSION: Children with IAV and MP infection whose age older than 6.08 years, had a fever longer than 4 days, had a CD4+ count < 22.12%, had a CD8+ count < 35.21%, had an IL-10 concentration > 22.08 ng/ml were more likely to develop pneumonia.


Asunto(s)
Coinfección , Virus de la Influenza A , Gripe Humana , Mycoplasma pneumoniae , Neumonía por Mycoplasma , Humanos , Coinfección/epidemiología , Coinfección/microbiología , Coinfección/virología , Masculino , Factores de Riesgo , Neumonía por Mycoplasma/complicaciones , Neumonía por Mycoplasma/epidemiología , Femenino , Preescolar , Gripe Humana/complicaciones , Niño , Lactante
6.
Eur J Clin Microbiol Infect Dis ; 43(3): 567-575, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38240989

RESUMEN

OBJECTIVE: The study analyzed the clinical features of children who had severe influenza and discussed on the risk factors associated with death in this population. METHODS: A total of 167 children with severe influenza admitted to the intensive care unit of our hospital from January 2018 to August 2023 were selected and divided into the death group (27 cases) and the survival group (140 cases). Demographic characteristics and clinical data were collected and compared between the two groups. Logistic regression analysis was used to explore the risk factors for death in children with severe influenza. RESULTS: The male-to-female ratio of the 167 children with severe influenza was 2.21:1, the median age was 3 years, and influenza A accounted for 70.66%. The CD4+ T cells percentage and CD4/CD8 were lower in the death group; the percentage of comorbid underlying diseases, mechanical ventilation, other systemic involvement, comorbid associated encephalopathy or encephalitis, and red blood cell distribution width (RDW), lactate dehydrogenase, activated partial thromboplastin time (APTT), and interleukin 6 were higher in the death group. The mechanical ventilation, associated encephalopathy or encephalitis, RDW, APTT, and CD4/CD8 were the independent risk factors for death. CONCLUSION: Mechanical ventilation, comorbid encephalopathy or encephalitis, increased RDW, prolonged APTT, and decreased CD4/CD8 are independent risk factors for death in children with severe influenza.


Asunto(s)
Encefalopatías , Encefalitis , Gripe Humana , Niño , Humanos , Masculino , Femenino , Preescolar , Gripe Humana/complicaciones , Gripe Humana/epidemiología , Linfocitos T , Encefalopatías/complicaciones , Factores de Riesgo , Estudios Retrospectivos
7.
BMC Infect Dis ; 24(1): 386, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594638

RESUMEN

BACKGROUND: Since December 2019, COVID-19 has spread rapidly around the world, and studies have shown that measures to prevent COVID-19 can largely reduce the spread of other infectious diseases. This study explored the impact of the COVID-19 outbreak and interventions on the incidence of HFMD. METHODS: We gathered data on the prevalence of HFMD from the Children's Hospital Affiliated to Zhengzhou University. An autoregressive integrated moving average model was constructed using HFMD incidence data from 2014 to 2019, the number of cases predicted from 2020 to 2022 was predicted, and the predicted values were compared with the actual measurements. RESULTS: From January 2014 to October 2022, the Children's Hospital of Zhengzhou University admitted 103,995 children with HFMD. The average number of cases of HFMD from 2020 to 2022 was 4,946, a significant decrease from 14,859 cases from 2014 to 2019. We confirmed the best ARIMA (2,0,0) (1,1,0)12 model. From 2020 to 2022, the yearly number of cases decreased by 46.58%, 75.54%, and 66.16%, respectively, compared with the forecasted incidence. Trends in incidence across sexes and ages displayed patterns similar to those overall. CONCLUSIONS: The COVID-19 outbreak and interventions reduced the incidence of HFMD compared to that before the outbreak. Strengthening public health interventions remains a priority in the prevention of HFMD.


Asunto(s)
COVID-19 , Enfermedad de Boca, Mano y Pie , Niño , Humanos , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/prevención & control , Estudios Retrospectivos , COVID-19/epidemiología , COVID-19/prevención & control , Brotes de Enfermedades/prevención & control , Incidencia , China/epidemiología
8.
BMC Public Health ; 24(1): 1938, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030529

RESUMEN

BACKGROUND: Influenza is a contagious respiratory disease posing a huge burden of disease for children around the world. The purpose of this study was to investigate the epidemiologic changes in childhood influenza in Zhengzhou, China, before, during, and after the COVID-19 outbreak. The aim of this study was to determine the impact of the COVID-19 outbreak and related prevention and control policies on the children's influenza epidemiological trend. METHODS: All influenza report card data from the Children's Hospital Affiliated with Zhengzhou University's Disease Surveillance Reporting Management System were collected and analyzed monthly from January 2018 to December 2023. The period of the study was divided into three phases for comparison: the pre-pandemic period, the pandemic period, and the post-pandemic period. RESULTS: Between January 2018 and December 2023, a total of 82,030 children with influenza were diagnosed at our hospital, including 46,453 males and 35,577 females. A total of 11,833 of them had to be hospitalized for influenza, and 321 of them were brought to the ICU. Influenza showed low-level epidemiologic status during the COVID-19 pandemic, and there was a substantial rise in influenza and a surge in the number of cases after the COVID-19 pandemic period. The year 2023 will had the most influenza cases (40,785). The peak incidence of influenza changes in 2022, from July to October, and in 2023, from February to April and from October to December. During the post-pandemic period, the proportion of new-borns and young children among influenza patients decreased, while the proportion of school-age children increased significantly, and the proportion of influenza patients hospitalized and the proportion of ICU admissions decreased. CONCLUSION: Influenza showed low-level epidemiologic status during the COVID-19 pandemic. In the post-pandemic period, there is a large increase in influenza incidence, with a double peak in influenza incidence. The proportion of school-age children with influenza has also increased. As a result, we recommend that influenza vaccination for key populations, particularly school-age children, be completed by October of each year in Henan Province, and that the government and schools increase education about nonpharmacological influenza prevention approaches.


Asunto(s)
COVID-19 , Gripe Humana , Humanos , China/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Masculino , Niño , Femenino , Preescolar , Lactante , Adolescente , Hospitalización/estadística & datos numéricos , Pandemias , SARS-CoV-2 , Recién Nacido , Incidencia
9.
BMC Pediatr ; 24(1): 156, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443804

RESUMEN

This paper reports a case of influenza complicated with influenza associated encephalopathy complicated with acute pancreatitis. This kind of disease is relatively rare, we hope to draw people's attention to it in order to improve early detection and prognosis.


Asunto(s)
Encefalopatías , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Pancreatitis , Humanos , Pancreatitis/complicaciones , Enfermedad Aguda , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Encefalopatías/complicaciones
10.
Hum Reprod ; 38(11): 2137-2153, 2023 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-37766497

RESUMEN

STUDY QUESTION: Is the chromosome copy number of the trophectoderm (TE) of a human reconstituted embryos after spindle transfer (ST) representative of the inner cell mass (ICM)? SUMMARY ANSWER: Single-cell multi-omics sequencing revealed that ST blastocysts have a higher proportion of cell lineages exhibiting intermediate mosaicism than conventional ICSI blastocysts, and that the TE of ST blastocysts does not represent the chromosome copy number of ICM. WHAT IS KNOWN ALREADY: Preimplantation genetic testing for aneuploidy (PGT-A) assumes that TE biopsies are representative of the ICM, but the TE and ICM originate from different cell lineages, and concordance between TE and ICM is not well-studied, especially in ST embryos. STUDY DESIGN, SIZE, DURATION: We recruited 30 infertile women who received treatment at our clinic and obtained 45 usable blastocysts (22 from conventional ICSI and 23 reconstituted embryos after ST). We performed single-cell multi-omics sequencing on all blastocysts to predict and verify copy number variations (CNVs) in each cell. We determined the chromosome copy number of each embryo by analysing the proportion of abnormal cells in each blastocyst. We used the Bland-Altman concordance and the Kappa test to evaluate the concordance between TE and ICM in the both groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a public tertiary hospital in China, where all the embryo operations, including oocytes retrieval, ST, and ICSI, were performed in the embryo laboratory. We utilized single-cell multi-omics sequencing technology at the Biomedical Pioneering Innovation Center, School of Life Sciences, Peking University, to analyse the blastocysts. Transcriptome sequencing was used to predict the CNV of each cell through bioinformatics analysis, and the results were validated using the DNA methylation library of each cell to confirm chromosomal normalcy. We conducted statistical analysis and graphical plotting using R 4.2.1, SPSS 27, and GraphPad Prism 9.3. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age of the volunteers, the blastocyst morphology, and the developmental ratewere similar in ST and ICSI groups. The blastocysts in the ST group had some additional chromosomal types that were prone to variations beyond those enriched in the blastocysts of the ICSI group. Finally, both Bland-Altman concordance test and kappa concordancetest showed good chromosomal concordance between TE and ICM in the ICSI blastocysts (kappa = 0.659, P < 0.05), but not in ST blastocysts (P = 1.000), suggesting that the TE in reconstituted embryos is not representative of ICM. Gene functional annotation (GO and KEGG analyses) suggests that there may be new or additional pathways for CNV generation in ST embryos compared to ICSI embryos. LIMITATIONS, REASONS FOR CAUTION: This study was mainly limited by the small sample size and the limitations of single-cell multi-omics sequencing technology. To select eligible single cells, some cells of the embryos were eliminated or not labelled, resulting in a loss of information about them. The findings of this study are innovative and exploratory. A larger sample size of human embryos (especially ST embryos) and more accurate molecular genetics techniques for detecting CNV in single cells are needed to validate our results. WIDER IMPLICATIONS OF THE FINDINGS: Our study justifies the routine clinical use of PGT-A in ICSI blastocysts, as we found that the TE is a good substitute for ICM in predicting chromosomal abnormalities. While PGT-A is not entirely accurate, our data demonstrate good clinical feasibility. This trial was able to provide correct genetic counselling to patients regarding the reliability of PGT-A. Regarding ST blastocysts, the increased mosaicism rate and the inability of the TE to represent the chromosomal copy number of the ICM are both biological characteristics that differentiate them from ICSI blastocysts. Currently, ST is not used clinically on a large scale to produce blastocysts. However, if ST becomes more widely used in the future, our study will be the first to demonstrate that the use of PGT-A in ST blastocysts may not be as accurate as PGT-A for ICSI blastocysts. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key R&D Program of China (2018YFA0107601) and the National Key R&D Program of China (2018YFC1003003). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Infertilidad Femenina , Diagnóstico Preimplantación , Embarazo , Femenino , Humanos , Variaciones en el Número de Copia de ADN , Diagnóstico Preimplantación/métodos , Reproducibilidad de los Resultados , Infertilidad Femenina/metabolismo , Multiómica , Blastocisto/metabolismo , Pruebas Genéticas/métodos , Cromosomas , Aneuploidia , Mosaicismo
11.
Brain Behav Immun ; 111: 76-89, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37011865

RESUMEN

BACKGROUND: Autism spectrum disorder (ASD) includes a range of multifactorial neurodevelopmental disabilities characterized by a variable set of neuropsychiatric symptoms. Immunological abnormalities have been considered to play important roles in the pathogenesis of ASD, but it is still unknown which abnormalities are more prominent. METHODS: A total of 105 children with ASD and 105 age and gender-matched typically developing (TD) children were recruited. An eating and mealtime behavior questionnaire, dietary habits, and the Bristol Stool Scale were investigated. The immune cell profiles in peripheral blood were analyzed by flow cytometry, and cytokines (IFN-γ, IL-8, IL-10, IL-17A, and TNF-α) in plasma were examined by Luminex assay. The obtained results were further validated using an external validation cohort including 82 children with ASD and 51 TD children. RESULTS: Compared to TD children, children with ASD had significant eating and mealtime behavioral changes and gastrointestinal symptoms characterized by increased food fussiness and emotional eating, decreased fruit and vegetable consumption, and increased stool astriction. The proportion of γδT cells was significantly higher in children with ASD than TD children (ß: 0.156; 95% CI: 0.888 âˆ¼ 2.135, p < 0.001) even after adjusting for gender, eating and mealtime behaviors, and dietary habits. In addition, the increased γδT cells were evident in all age groups (age < 48 months: ß: 0.288; 95% CI: 0.420 âˆ¼ 4.899, p = 0.020; age ≥ 48 months: ß: 0.458; 95% CI: 0.694 âˆ¼ 9.352, p = 0.024), as well as in boys (ß: 0.174; 95% CI: 0.834 âˆ¼ 2.625, p < 0.001) but not in girls. These findings were also confirmed by an external validation cohort. Furthermore, IL-17, but not IFN-γ, secretion by the circulating γδT cells was increased in ASD children. Machine learning revealed that the area under the curve in nomogram plots for increased γδT cells combined with eating behavior/dietary factors was 0.905, which held true in both boys and girls and in all the age groups of ASD children. The decision curves showed that children can receive significantly higher diagnostic benefit within the threshold probability range from 0 to 1.0 in the nomogram model. CONCLUSIONS: Children with ASD present with divergent eating and mealtime behaviors and dietary habits as well as gastrointestinal symptoms. In peripheral blood, γδT cells but not αßT cells are associated with ASD. The increased γδT cells combined with eating and mealtime behavior/dietary factors have a high value for assisting in the diagnosis of ASD.


Asunto(s)
Trastorno del Espectro Autista , Masculino , Femenino , Humanos , Niño , Preescolar , Encuestas y Cuestionarios , Citocinas
12.
J Org Chem ; 88(20): 14601-14609, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37788335

RESUMEN

Guanidine has been known as an important class of N-containing molecules with a wide range of applications. Described here is a selective and efficient electrochemical approach to the synthesis of guanidines from easily accessible thioureas and amines. The key to success for this reaction is the in situ generation of a hypervalent iodine reagent as a catalyst from iodoarene by anodic oxidation. This mild desulfurizative amination presents ample substrate scope and good functional group tolerance without the use of extra stoichiometric chemical oxidants. As only electrons serve as the oxidation reagents, this method offers a more straightforward and sustainable manner toward versatile guanidines, including late-stage functionalization of pharmaceutically relevant molecules.

13.
Gynecol Endocrinol ; 39(1): 2181639, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36822227

RESUMEN

INTRODUCTION: Embryo implantation provides an efficient way for patients with repeated implantation failure (RIF) to achieve pregnancy. The aim of this study is to compare the implantation outcomes of RIF patients in artificial cycle to those in natural cycle, both were treated with RNA sequencing endometrial receptivity test (rsERT) based personalized embryo implantation. METHODS: The endometrial receptivity (ER) analysis was performed using rsERT followed by personalized embryo transfer at optimal window of implantation (WOI). The implantation rate (IR), clinical pregnancy rate (CPR) and live birth rate (LBR) were calculated. The expression levels of biomarkers involved in pregnancy process in the patients detected as in receptivity status were also analyzed. RESULTS: The rsERT shown that 44.8% (natural cycle) and 47.8% (artificial cycle) patients were in non-receptive status, which indicated a WOI displacement. After personalized embryo transfer, the IR of patients in artificial cycle was higher than those in natural cycle (52.2% vs 27.6%). The expressions of FKBP52, MUC1 and LPAR3 were significantly lower in artificial cycle than in natural cycle. CONCLUSION: Using artificial cycle for personalized embryo transfer based on rsERT may yield better pregnancy outcomes for RIF patients. A gene expression analysis of FKBP52, MUC1 and LPAR3 provided a potential way to increase implantation outcomes for RIF patients.


Asunto(s)
Implantación del Embrión , ARN , Embarazo , Femenino , Humanos , ARN/metabolismo , Implantación del Embrión/genética , Transferencia de Embrión , Endometrio/metabolismo , Análisis de Secuencia de ARN
14.
Neoplasma ; 68(2): 382-390, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33118830

RESUMEN

Osteosarcoma (OS) is a common malignant bone tumor that occurs in adolescents or children under the age of 20, which is extremely difficult to cure and has a high recurrence rate. Recent studies showed that cell division cycle 20 (CDC20) overexpression is associated with poor prognosis in patients with osteosarcoma. However, the function of CDC20 in osteosarcoma has not been investigated clearly. In this study, we aim to explore the role of CDC20 in two independent human OS cell lines' biological phenotype and chemotherapy sensitivity. We applied multiple approaches to measure cell growth, cell cycle, and apoptosis with or without deregulation or overexpression of CDC20. We found that the downregulation of CDC20 by siRNA or apcin suppressed cell proliferation, induced apoptosis, and triggered cell cycle arrest. Consistently, overexpression of CDC20 in normal cells promoted cell growth, inhibited apoptosis. What's more, the additional treatment with siCDC20 or Apcin achieved better anticancer effects than that of cisplatin alone. Furthermore, Bim and p21 were upregulated in OS cells following Apcin treatment. Altogether, the results of the present study demonstrated that targeting CDC20 could be useful for the treatment of OS, and might be a promising solution for the treatment of the OS with cisplatin insensitivity.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Apoptosis , Neoplasias Óseas/tratamiento farmacológico , Proteínas Cdc20/genética , Proteínas Cdc20/metabolismo , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Cisplatino/farmacología , Regulación hacia Abajo , Humanos , Recurrencia Local de Neoplasia , Osteosarcoma/tratamiento farmacológico
15.
Adv Exp Med Biol ; 1300: 259-280, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33523438

RESUMEN

Spontaneous abortion has been a common obstetrical and gynecological disease, which occurs in 10-15% of all pregnancies. Recurrent miscarriage (RM) refers to the occurrence of three or more times abortions with the same partner. It is generally believed that environmental pollution associated with economic development may cause infertility and RM. When xenobiotics from the environment enter the body, they must be cleared from the body by various metabolic enzymes in the body. The absence or variation of these enzymes may be the genetic basis of RM caused by environmental pollution. The variation of metabolic detoxification enzyme can directly affect the removal of harmful substances from internal and external sources. Therefore, the determination of metabolic enzyme activity may become an important factor in the diagnosis of RM etiology and seeking methods to improve the detoxification ability has a great significance for the treatment of RM.


Asunto(s)
Aborto Habitual , Aborto Habitual/diagnóstico , Femenino , Humanos , Embarazo
16.
Angew Chem Int Ed Engl ; 59(18): 7193-7197, 2020 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-32073715

RESUMEN

Dearomative annulation of indoles has emerged as a powerful tool for the preparation of polycyclic indoline-based alkaloids. Compared with well-established methods towards five-membered-ring-fused indolines, the six-membered-ring-fused indolines are rarely accessed under thermal conditions. Herein, a dearomative [4+2] annulation between different indoles is developed through an electrochemical pathway. This transformation offers a remarkably regio- and stereoselective route to highly functionalized pyrimido[5,4-b]indoles under oxidant- and metal-free conditions. Notably, this electrochemical approach maintains excellent functional-group tolerance and can be extended as a modification tactic for pharmaceutical research. Preliminary mechanism studies indicate that the electrooxidation annulation proceeds through radical-radical cross-coupling between an indole radical cation and an N-centered radical generated in situ.


Asunto(s)
Alcaloides/síntesis química , Técnicas Electroquímicas , Indoles/química , Alcaloides/química , Radicales Libres/síntesis química , Radicales Libres/química , Hidrogenación , Estructura Molecular , Oxidación-Reducción
17.
Angew Chem Int Ed Engl ; 58(35): 12206-12210, 2019 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-31250953

RESUMEN

The [4+2] annulation represents an elegant and versatile synthetic protocol for the construction of benzene rings. Herein, a strategy for visible-light induced [4+2] annulation of thiophenes and alkynes, to afford benzene rings, is presented. Under simple and mild reaction conditions, the ready availability and structural diversity of thiophenes and alkynes permit the facile synthesis of several substituted aromatic rings. Valuable drugs and amino acids are also well tolerated. Moreover, DFT calculations explain the high regioselectivity of the reaction.

18.
Org Biomol Chem ; 16(14): 2375-2387, 2018 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-29546915

RESUMEN

Electrochemical oxidative cross-coupling with hydrogen evolution has become an environmentally friendly and efficient way to form new bonds. Direct electrosynthesis by anodic oxidation has been developed for the synthesis of complex molecules. However, in some cases, redox catalysts were needed to avoid over-oxidation and to achieve better reaction selectivity. Recently, the use of iodine as a mediator to achieve indirect electrochemical reactions has drawn increasing attention. This review article gives an overview of the recent development of iodine mediated electrochemical oxidative coupling reactions.

19.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(10): 831-834, 2018 Oct.
Artículo en Zh | MEDLINE | ID: mdl-30369358

RESUMEN

OBJECTIVE: To study the expression and significance of endothelial microparticles (EMPs) in children with Henoch-Schönlein purpura (HSP). METHODS: A total of 100 previously untreated children with HSP were classified to Henoch-Schönlein purpura nephritis (HSPN) group (n=40) and non-nephritis group (n=60). Thirty healthy children who underwent physical examination were enrolled as control group. Serum levels of EMPs, T helper 17 cells (Th17), and interleukin-17 (IL-17) were compared between groups. RESULTS: The HSPN and non-nephritis groups had significantly higher levels of Th17 and IL-17 than the control group, and the HSPN group had the highest levels (P<0.05). The HSPN and non-nephritis groups had a significantly higher level of EMPs than the control group, and the HSPN group had the highest level (P<0.05). In the HSPN group, the levels of Th17 and IL-17 were positively correlated with the level of EMPs (r=0.830 and 0.644 respectively; P<0.05). CONCLUSIONS: EMPs play an important role in the pathogenesis of HSP. The increase in EMPs might be one of the reasons for renal involvement in children with HSP.


Asunto(s)
Vasculitis por IgA , Niño , Humanos , Riñón , Nefritis , Células Th17
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(8): 635-640, 2018 Aug.
Artículo en Zh | MEDLINE | ID: mdl-30111472

RESUMEN

OBJECTIVE: To observe the effects of L-carnitine treatment on serum levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) and cardiac function in children with heart dysfunction and severe hand-foot-mouth disease (HFMD). METHODS: A total of 120 children with severe HFMD were enrolled and randomly and equally divided into routine treatment group and L-carnitine treatment group. Thirty healthy children served as the control group. HFMD patients were given anti-fever and antiviral treatment as the basic treatment, while the patients in the L-carnitine treatment group were given L-carnitine as an adjuvant treatment to the basic treatment. Treatment outcomes were observed in the two groups. For all the subjects, serum levels of BNP and NT-proBNP and cardiac function parameters including left ventricular ejection fraction (LVEF), fractional shortening (FS), and cardiac index (CI) were measured at different time points before and after treatment. RESULTS: Before treatment, HFMD patients had significantly higher serum levels of BNP and NT-proBNP and heart rate but significantly lower LVEF, FS, and CI compared with the control group (P<0.05). After treatment, the L-carnitine treatment group had a significantly higher response rate than the routine treatment group (P<0.05). After 3 days of treatment, the serum levels of BNP and NT-proBNP, LVEF, FS, and CI were significantly reduced in the L-carnitine group (P<0.05); the L-carnitine group had significantly lower serum levels of BNP and NT-proBNP, LVEF, FS, and CI than the routine treatment group (P<0.05); there were no significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine treatment and control groups (P>0.05). After 5 days of treatment, there were no significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine treatment and routine treatment groups (P>0.05). Heart rate recovery was significantly slower in the routine treatment group than in the L-carnitine treatment group (P<0.05). CONCLUSIONS: As an adjuvant therapy for severe HFMD, L-carnitine treatment has satisfactory short-term efficacy in reducing the serum levels of BNP and NT-proBNP and improving cardiac function, thus improving clinical outcomes.


Asunto(s)
Carnitina/administración & dosificación , Enfermedad de Boca, Mano y Pie/tratamiento farmacológico , Enfermedad de Boca, Mano y Pie/fisiopatología , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Biomarcadores/sangre , Preescolar , Femenino , Enfermedad de Boca, Mano y Pie/sangre , Corazón/efectos de los fármacos , Corazón/fisiopatología , Pruebas de Función Cardíaca , Humanos , Lactante , Masculino , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacos
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