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Objective: To explore the correlation between blastomere count variations "skip value" which extracted from by time-lapse technology (TLT) combined with artificial intelligence (AI) and morphological features of in vitro fertilization (IVF) embryo, and to test its feasibility in clinical applications. Methods: This study was a diagnostic experiment (AI reassessment of embryo transferred patients), a total of 6 545 embryos from 1 226 patients who underwent IVF at the Women and Children's Hospital of Chongqing Medical University from December 2020 to December 2021 were retrospectively analyzed, of which 2 869 embryos were attempted to cultured to blastocyst stage by TLT. The embryo dynamic map (EDM) was drawn by Embryo Viewer, a TLT recording software, based on embryo developmental kinetics. The self-developed AI embryo evaluation software identified and recorded the number of cleavages in real time during embryonic development, and compared with the EDM, the correlation between the skip value formed by the change of cleavage sphere counts and the outcomes of the embryos was analyzed. The correlation among skip value, morphological score of embryo, implantation rate and live birth rate were performed by Spearman and step-up logistic regression. The receiver operating characteristic (ROC) curve was selected for reporting there relationship of skip value and morphology. Finally, predicting power of skip value for implantation and live birth rate were performed by ROC analysis. Results: The total skip values extracted from the blastomere count of embryos (72 hours post-fertilization) were negatively correlated with abnormal cleavage, blastocyst formation rate, day 3 (D3)-cell score, uneven size and fragmentation (the ß values were -0.268, -0.116, -0.213, -0.159 and -0.222, respectively; all P<0.001); positively correlated with D3-cell number (ß=0.034; P<0.001); negatively correlated with blastocyst formation rate and implantation rate (OR=0.97, 95%CI: 0.93-0.99, P=0.034; OR=0.96, 95%CI: 0.93-0.98, P=0.044). The power of predicting implantation were similar between the order selection of skip values and traditional morphology criteria [area under curve (AUC): 0.679 vs 0.620]. Live birth rate were negatively correlated with female age (OR=0.91, 95%CI: 0.88-0.93; P<0.001), D3 general score (OR=0.77, 95%CI: 0.59-0.99; P=0.045) and order selection of skip values (OR=0.98, 95%CI: 0.96-0.99; P=0.038), while positively correlated with retrieved oocyte number and endometrial thickness in embryo transferred (OR=1.08, 95%CI:1.05-1.11, P<0.001; OR=1.09, 95%CI:1.06-0.12, P<0.001, respectively) from multivariate regression analysis, and the power of predicting live birth was 0.666 for AUC. Conclusions: The skip value and its order form is a systematic quantification of embryo development, correlated with embryo developmental quality and clinical outcome. It could be an addition parameter for embryo culture and selection.
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Inteligencia Artificial , Blastocisto , Blastómeros , Técnicas de Cultivo de Embriones , Desarrollo Embrionario , Fertilización In Vitro , Humanos , Fertilización In Vitro/métodos , Estudios Retrospectivos , Femenino , Blastómeros/citología , Embarazo , Técnicas de Cultivo de Embriones/métodos , Blastocisto/citología , Transferencia de Embrión/métodos , Índice de Embarazo , Implantación del Embrión , Adulto , Programas Informáticos , Embrión de Mamíferos/citologíaRESUMEN
Objective: To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE). Methods: Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children's Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children's characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed. Results: Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.
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Electroencefalografía , Genotipo , Mutación , Fenotipo , Oxidorreductasa que Contiene Dominios WW , Humanos , Oxidorreductasa que Contiene Dominios WW/genética , Masculino , Femenino , Lactante , Espasmos Infantiles/genética , Epilepsia/genética , Epilepsia/diagnóstico , Recién Nacido , Imagen por Resonancia Magnética , Convulsiones/genética , Microcefalia/genética , Discapacidades del Desarrollo/genética , Preescolar , Proteínas Supresoras de Tumor/genéticaRESUMEN
Objective: To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin â ¡ (Ang â ¡)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis. Methods: C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×106 mmol/L Ang â ¡, which was the Ang â ¡ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang â ¡+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang â ¡+sh-NC group). The impact of Ang â ¡ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang â ¡-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang â ¡+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang â ¡ group (infused with Ang â ¡ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang â ¡+sh-Mettl3 group (infused with Ang â ¡ solution and injected with Mettl3 shRNA lentivirus solution), and Ang â ¡+sh-Mettl3+SC79 group (administered Ang â ¡ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson's trichrome to assess the extent of renal fibrosis. Results: Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×106 mmol/L Ang â ¡ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang â ¡ group compared to the control group (P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang â ¡ group compared to the control group (both P<0.05). In the Ang â ¡+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang â ¡ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type â collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang â ¡ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang â ¡+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang â ¡+sh-Mettl3 group than that in the Ang â ¡+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang â ¡-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang â ¡ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang â ¡+sh-Mettl3 group than that in the Ang â ¡ group (P<0.05), but increased again upon addition of SC79. Conclusion: Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang â ¡-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.
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Angiotensina II , Transdiferenciación Celular , Metiltransferasas , Ratones Endogámicos C57BL , Miofibroblastos , Pericitos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Pericitos/metabolismo , Metiltransferasas/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Angiotensina II/farmacología , Miofibroblastos/metabolismo , Riñón , Células CultivadasRESUMEN
OBJECTIVE: The aim of our study was to analyze the factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease (CKD). PATIENTS AND METHODS: One hundred and sixteen patients with CKD admitted to our hospital from January 2022 to September 2022 were picked as the subjects. Fasting venous blood of these subjects was collected to value the serum uric acid (SUA) levels on an automatic biochemical analyzer. Patients were then grouped as the CKD-only group (n=80) and hyperuricemia group (n=36), according to the SUA results, or the good prognosis group (n=88) and poor prognosis group (n=28), according to the presence of cardiovascular diseases. The changes in laboratory indexes and clinical data were analyzed and compared. Multivariate logistic regression analysis was used to analyze the risk factors for combined hyperuricemia and the risk factors for poor cardiac and renal outcomes in patients with CKD. The correlation between SUA level and cardiac and renal indexes was analyzed by Pearson analysis. RESULTS: Patients in the CKD hyperuricemia group had markedly higher content of systolic blood pressure (SBP), diastolic blood pressure (DBP), B-type natriuretic peptide (BNP), urinary retinol-binding protein (RBP), urinary N-acetyl-ß-D glucosidase (NAG), much higher proportion of heart failure episodes history, and much lower content of total cholesterol (TC), albumin (Alb), hemoglobin (Hb), urinary α1-microglobulin (α1-MG), and glomerular filtration rate (eGFR) than the CKD-only group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for combined hyperuricemia in CKD patients (p < 0.05). Besides, eGFR, albumin, and hemoglobin were independent protective factors for combined hyperuricemia in CKD patients (p < 0.05). Compared with the good prognosis group, the content of BNP, SBP, DBP, urinary RBP, urinary NAG, and SUA was much higher, the proportion of heart failure episodes history was obviously higher, and the levels of Alb, Hb, TC, eGFR, and urinary α1-MG were sharply lower in the poor prognosis group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for poor cardiac and renal outcomes (p < 0.05), and eGFR was an independent protective factor for poor cardiac and renal outcomes in patients with CKD (p < 0.05). The SUA level in CKD patients was positively correlated with BNP and SBP (r=0.463, 0.215, p < 0.05), but negatively correlated with eGFR (r=0.463, 0.215, p < 0.05). CONCLUSIONS: The serum SUA level was elevated with the aggravation of the CKD stage. High serum SUA level is a risk factor for the development of hyperuricemia and poor cardio-renal outcomes in CKD patients, suggesting that early monitoring of changes in SUA levels may help assess the risk of cardio-renal outcomes in CKD patients.
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Insuficiencia Cardíaca , Hiperuricemia , Insuficiencia Renal Crónica , Humanos , Hiperuricemia/complicaciones , Ácido Úrico , Insuficiencia Renal Crónica/complicaciones , Factores de Riesgo , Insuficiencia Cardíaca/complicaciones , Tasa de Filtración Glomerular , Albúminas , HemoglobinasRESUMEN
Inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting the gastrointestinal tract, with a global incidence increasing year by year, and the incidence of IBD in developing countries has been increasing since the end of the last century. The pathogenesis of IBD remains unclear, which is the combined result of genetic, immune, diet, environmental and other factors. There is no gold standard for the diagnosis of IBD. Colonoscopy and mucosal biopsy are the preferred clinical tests, but these invasive and time-consuming methods are not conducive to early screening and frequent monitoring. Therefore, convenient, fast, non-invasive and reliable methods are urgently needed to assist the clinical diagnosis and evaluation of IBD. This paper aims to elaborate the laboratory diagnosis and monitoring methods of IBD based on fecal and blood indicators, which can provide ideas for the prevention, screening, diagnosis and monitoring of IBD, and help reduce its burden on people's living standards, public health and society.
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Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/patología , Colonoscopía , Dieta , HecesRESUMEN
Liquid-liquid phase separation of proteins occur in a number of biological processes, such as regulation of transcription, processing, and RNA maturation. Sm-like protein 4 (LSM4) is involved in multiple processes, including pre-mRNA splicing and P-bodies assembly. Before investigating the involvement of LSM4 in the separation of the two liquid phases during RNA processing or maturation, the separation of the liquid phases in an in vitro preparation of LSM4 protein should be first be detected. The mCherry-LSM4 plasmid was derived from pET30a and used to isolate mCherry-LSM4 protein from prokaryotic cells (Escherichia coli strain BL21). The mCherry LSM4 protein was purified using Ni-NTA resin. The protein was further purified by fast protein liquid chromatography. Delta-Vision wide-field fluorescence microscopy was used to observe the dynamic liquid-liquid phase separation of the LSM4 protein in vitro. Analysis of the LSM4 protein structure using the Predictor of Natural Disordered Regions database revealed that its C-terminus contains a low complexity domain. A purified preparation of full-length human LSM4 protein was obtained from E. coli. Human LSM4 was shown to provide concentration-dependent separation of liquid-liquid phases in vitro in buffer with crowding reagents. Salts in high concentration and 1,6-hexanediol block the LSM4-induced separation of the two liquid phases. In addition, in vitro fusion of LSM4 protein droplets is observed. The results suggest that full-length human LSM4 protein can undergo liquid-liquid phase separation in vitro.
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Escherichia coli , ARN , Humanos , Escherichia coli/genética , Proteínas , Empalme del ARNRESUMEN
OBJECTIVE: To evaluate the relationship between 24 h urinary ion content and kidney stones, and to explore the diagnostic values of kidney stone in primary gout patients. METHODS: Patients diagnosed with primary gout had ultrasound scanning of both feet and kidneys in Peking University First Hospital from Jan. 2020 to May 2021. Their clinical characteristics were compared between the positive and negative kidney stone groups, and the relationship between kidney stone and urinary ion composition were analyzed. Risk factors of kidney stone were analyzed. The explored diagnostic values were evaluated for urinary oxalate and citrate according with uric acid kidney stones by dual-energy computed tomography (DECT). RESULTS: Among the 100 gouty patients, 80 patients had uric acid crystal deposition in lower joints of extremity by ultrasonography, 61 patients had kidney stone, and 34 had kidney uric acid stones by DECT. All the multiple kidney stones were proved as uric acid kidney stones by DECT. Compared with patients without kidney stone group proved by ultrasonography, patients with kidney stone had longer gouty duration [(48.7±26.6) months vs. (84.0±30.6) months, P=0.01], higher 24 h urinary oxalate [(20.1±9.6) mg vs. (28.6±20.7) mg, P=0.001] and lower 24 h urinary citrate [(506.3±315.4) mg vs. (355.7±219.6) mg, P=0.001]. Compared with the patients without kidney stone by DECT, the patients with uric acid kidney stone also had longer disease duration [(49.1±28.4) months vs. (108.3±72.2) months, P=0.001], higher 24 h urinary oxalate [(23.6±16.9) mg vs. (28.5±18.8) mg, P < 0.05], lower 24 h urinary citrate [(556.0±316.3) mg vs. (391.7±261.2) mg, P < 0.05], higher serum uric acid [(466.2±134.5) µmol/L vs. (517.2±18.1) µmol/L, P < 0.05] and higher 24 h urinary uric acid [(1 518.1±893.4) mg vs. (1 684.2±812.1) mg, P < 0.05]. Logistic regression analysis showed long gout disease duration (OR=1.229, 95%CI: 1.062-1.522, P < 0.05), high serum uric acid level (OR=1.137, 95%CI: 1.001-1.213, P=0.01), low 24 h urinary citrate (OR=0.821, 95%CI: 0.659-0.952, P=0.01) were all risk factors of kidney stones by ultrasonography. Also, long gout disease duration (OR=1.201, 95%CI: 1.101-1.437, P=0.005), high serum creatine uric level (OR=1.145, 95%CI: 1.001-1.182, P=0.04), low 24 h urinary citrate (OR=0.837, 95%CI: 0.739-0.931, P=0.02) were all risk factors of kidney uric acid stones by DECT. CONCLUSION: Long disease duration and low 24 h urinary citrate were risk factors for kidney stones.
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Gota , Cálculos Renales , Cálculos Urinarios , Humanos , Ácido Úrico/análisis , Ácido Cítrico , Cálculos Renales/diagnóstico por imagen , Gota/complicaciones , Gota/diagnóstico por imagen , Citratos , OxalatosRESUMEN
Objective: To establish a scoring scale for trial of labor after cesarean section (TOLAC), to explore the evaluation ability of this scoring scale for vaginal delivery after cesarean section (VBAC), and to improve the success rate of TOLAC. Methods: The delivery information of 661 TOLAC pregnant women admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from 2014 to 2017 was retrospectively analyzed, and the TOLAC scoring scale was established by referring to relevant literatures. A prospective cohort study of pregnant women with TOLAC from January 2018 to December 2019 in Zhengzhou Central Hospital was conducted, including 440 pregnant women who were excluded from contraindications in trial labor. According to TOLAC scoring scale, pregnant women were divided into 3 groups, 0-6 group (94 cases), 7-9 group (234 cases) and 10-15 group (112 cases). The success rate of trial labor, failure reasons and incidence of maternal and neonatal complications were compared among the three groups. Results: (1) The overall success rate of TOLAC in 440 pregnant women was 75.0% (330/440). The success rates of 0-6, 7-9 and 10-15 groups were 53.2% (50/94), 76.9% (180/234) and 89.3% (100/112), respectively. The success rate of 10-15 group were significantly higher than those of 0-6 and 7-9 groups (all P<0.05). (2) Among the causes of trial labor failure, there were statistically significant differences between the three groups in terms of threatened uterine rupture and maternal abandonment (all P<0.05). Pairings showed that the incidences of threatened uterine rupture and maternal abandonment in 0-6 group was lower than those in 7-9 and 10-15 groups, and the differences were statistically significant (all P<0.05). (3) Maternal and neonatal complications mainly included postpartum hemorrhage and neonatal asphyxia, but there were no significant difference in the incidence of TOLAC success or failure among the three groups (all P>0.05). There was no uterine rupture in all groups. (4) The main factors affecting TOLAC score of pregnant women in the three groups included natural labor, estimated weight of the fetus at this time, Bishop score of the cervix at admission and gestational age, and the scores of the above indexes in 10-15 group were significantly higher than those in 0-6 group and 7-9 group (all P<0.05). Conclusions: TOLAC scoring scale has more accurate evaluation ability for VBAC, which could improve the success rate of TOLAC and maternal and child safety. The score of 0-6 is not recommended for vaginal trial labor, the score of 7-9 is recommended for vaginal trial labor, and the score of 10-15 is strongly recommended for vaginal trial labor.
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Esfuerzo de Parto , Rotura Uterina , Parto Vaginal Después de Cesárea , Cesárea/efectos adversos , Femenino , Humanos , Recién Nacido , Embarazo , Estudios Prospectivos , Estudios Retrospectivos , Rotura Uterina/diagnóstico , Rotura Uterina/epidemiología , Rotura Uterina/etiología , Parto Vaginal Después de Cesárea/efectos adversosRESUMEN
Objective: To differentiate hyperintense hepatocellular carcinoma (HCC) with focal nodular hyperplasia (FNH) in the hepatobiliary phase by MRI multimodal parameters. Methods: A retrospective cross-sectional study method was adopted. Clinical data on 15 cases with hyperintense HCC and 15 cases with FNH in the hepatobiliary phase admitted to the First Affiliated Hospital of the Army Medical University from January 2012 to December 2019 were collected. All patients with solitary lesions who underwent Gd-EOB-DTPA-enhanced MRI examinations were included. Surgically resected specimens were verified by pathological and immunohistochemical examination. HCC and FNH imaging features were analyzed by two radiologists. Results: (1) HCC and FNH apparent diffusion coefficient (ADC) values were 1 205.07±239.65×10-3 mm2/s and 1 434.73±217.6×10-3 mm2/s, respectively, and the SIADC difference was statistically significant (P<0.05) between the two groups. (2) In the dynamic contrast-enhanced MRI sequence, 15 cases of HCC were significantly enhanced in the arterial phase, of which 13 cases were characterized by continuous enhancement, and 2 cases were characterized by wash-in and wash-out enhancement. There was no statistically significant difference (P>0.05) between the two groups. SIenhancement rate between HCC and FNH (1.39±0.60 vs. 1.33±0.50, P>0.05) had no significant difference. (3) HCC and FNH morphological features in the hepatobiliary phase included: annular hypointensity: HCC (8 cases) vs. FNH (0 cases); contrast filling defects: HCC (8 cases) vs. FNH (0 cases); linear hyposignal separation: HCC (10 cases) vs. FNH (0 cases); and stellate scars: HCC (0) vs. FNH (5 cases), and there were statistically significant differences (P<0.05) between the two groups . Conclusion: Multimodal MRI have significant value for differentiating hyperintense HCC and FNH in the hepatobiliary phase.
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Carcinoma Hepatocelular , Hiperplasia Nodular Focal , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Hiperplasia Nodular Focal/diagnóstico por imagen , Hiperplasia Nodular Focal/patología , Estudios Retrospectivos , Estudios Transversales , Medios de Contraste , Gadolinio DTPA , Imagen por Resonancia Magnética/métodos , Diagnóstico DiferencialRESUMEN
Objective: To summarize the clinical characteristics and the features of electroencephalograph (EEG) of children with DEPDC5 gene variants related epilepsy. Methods: The clinical data, gene variation, EEG and head magnetic resonance image (MRI) of 20 epileptic children with DEPDC5 gene variants admitted to Department of Pediatrics, Peking University First Hospital from May 2017 to November 2020 were retrospectively analyzed. Results: Twenty patients with heterozygous DEPDC5 gene variants were enrolled, 8 of 20 patients were nonsense variants, 6 were missense variants, 3 were frame-shift variants, 2 were splicing variants, and 1 was large fragment deletion. Sixteen cases had hereditary variation and 4 had de novo variation. Fifteen of variations were novel. Nine were male, while 11 were female. Their latest follow-up age ranged from 10 months to 13 years and one month.The epilepsy onset age ranged from 3 hours to 11 years and 3 months, the median age was 10.5 months. Twelve (60%) patients had developmental delay. Nineteen patients had focal seizures, 7 had epileptic spasms, 1 had multiple seizure types including tonic, atypical absence, dystonic and myoclonic seizures. Epileptic form discharges were observed in 18 patients during the interictal phase, and 11 were focal discharges, 7 were multifocal discharges. Ten (50%) patients had abnormal brain MRI, including focal cortical dysplasia in 5 patients, undefined malformation of cortical development in 4 patients, hemimegalencephaly in 1 patient. Four patients were diagnosed as West syndrome and one patient was diagnosed as Lennox-Gastaut syndrome. Fourteen (70%) patients were diagnosed as drug-resistant epilepsy. Four patients became seizure-free by treatment with anti-epileptic drugs. Three children were treated with surgery, and 2 of them became seizure-free, 1 had more than 75% reduction in seizures. Conclusions: DEPDC5 gene variant epilepsy is inherited with incomplete penetrance and focal seizure is the major seizure type. However, epileptic spasms, generalized seizures can also be observed. Half of the patients brain malformations. Most of the patients are drug-resistant epilepsy. Patients with clear epileptogenic zones can be treated with surgery. Treatment-resistant patients are more likely to be complicated with developmental delay.
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Epilepsia , Espasmos Infantiles , Niño , Electroencefalografía , Epilepsia/genética , Femenino , Proteínas Activadoras de GTPasa , Genotipo , Humanos , Lactante , Masculino , Fenotipo , Estudios RetrospectivosRESUMEN
Objective: To summarize the genotype and phenotype of epilepsy in patients with interferon regulatory factor 2 binding protein-like (IRF2BPL) gene variants. Methods: Data of 6 epilepsy patients with IRF2BPL gene variants seen from May 2017 to September 2020 in the Department of Pediatrics of Peking University First Hospital were retrospectively collected. The clinical characteristics and genetic test results were analyzed. Results: A total of 6 patients with IRF2BPL gene variants (1 boy and 5 girls) were identified. The age of seizure onset was from 3.5 to 7.0 months. Epileptic spasms were observed in 6 patients, tonic seizures and tonic-spasms were observed in 1 patient and focal seizure was observed in 1 patient. All 6 patients presented with developmental delay, 5 patients presented with hypotonia, and 2 patients presented with dysphagia. Microcephaly,nystagmus,chorea and athetosis were observed in 1 patient. The electroencephalography (EEG) showed slow background activity in 2 patients. Hypsarrhythmia was observed in all 6 patients. Focal epileptic discharges were observed in 2 patients. Epileptic spasms were monitored in all 6 patients. Focal seizure and tonic-spasm were monitored in 2 patients respectively. The brain magnetic resonance imaging (MRI) showed cerebral atrophy and dysplasia of the corpus callosum in 1 patient, delayed myelination in 2 patients and normal in 3 patients. Two patients had missense variants c.1280C>T/p.L474F and c.1420C>T/p.S427L, 3 patients had frameshift variants c.232delG/p.V78Sfs*73, c.244del/p.A82Pfs*70 and c.283-308del/p.Ala95Thrfs*29, 1 patient had non-frameshift deletion variant c.1453-c.1455delTTC/p.F485del, and all of the 6 cases had de novo variants. All patients were diagnosed with infantile spasms. The last follow-up age ranged from 1 year to 3.8 years. Four patients achieved seizure-free and 2 patients still had frequent seizures after the treatment with antiepileptic drugs (adrenocorticotropic hormone, topiramate, and vigabatrin). Conclusions: IRF2BPL gene variants are mainly de novo. The age of seizure onset is mainly in infancy, and epilepsy and developmental delay are the main clinical manifestations. Infantile spasm is the main phenotype, some patients have hypotonia and dysphagia. Cerebral atrophy can be observed in a few patients.
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Epilepsia , Espasmos Infantiles , Proteínas Portadoras , Niño , Electroencefalografía , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Femenino , Humanos , Lactante , Masculino , Proteínas Nucleares , Estudios Retrospectivos , Convulsiones , Espasmos Infantiles/genéticaRESUMEN
Objective: To analyze the incidence characteristics of occupational chronic benzene poisoning under two diagnostic criteria. Methods: In March 2020, 126 patients who were divided into the old criteria group (74 cases) and the new criteria group (52 cases) were retrospectively analyzed. These patients were diagnosed with occupational chronic benzene poisoning, and were diagnosed in our hospital during the period of January 2009 to December 2019. The gender composition, age of onset, years of benzene exposure, industry distribution, work type, benzene concentration in working environment and diagnostic grade of the two groups of patients were analyzed and compared. The follow-up of 22 benzene poisoning observation subjects under the old criteria were retrospectively analyzed. Results: There were no statistically significant differences in gender composition, age of onset, years of benzene exposure, industry distribution and work type between the old criteria group and the new criteria group (P>0.05) . In the old criteria group and the new criteria group, 41.9% (31/74) and 17.3% (9/52) of the patients' workplace benzene concentration exceeded the maximum allowable concentration, respectively. The composition of different benzene concentration in the workplace between the two groups showed statistically significant (P<0.05) . In the old criteria group, the proportion of mild poisoning (79.7%, 59/74) was the majority, while in the new criteria group, the proportion of moderate and severe poisoning (51.9%, 27/52) were the majority, and there was statistically significance in the composition ratio of diagnostic grade between the two groups (P<0.05) . Under the old criteria, after folow-up of 22 cases of benzene poisoning observation subjects, we observed that 8 cases (36.4%) progressed to the level of chronic benzene poisoning. Conclusion: The revision of diagnostic criteria for benzene poisoning may affect the composition of diagnosis classification. Based on the rights and interests of workers, formulating more complete diagnostic criteria and system policies will be more conducive to the development of occupational benzene poisoning prevention and control.
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Enfermedades Profesionales , Exposición Profesional , Intoxicación , Benceno , Enfermedad Crónica , Humanos , Incidencia , Estudios RetrospectivosRESUMEN
Cloned animals are prone to abnormal phenotypes such as enlarged tongue, fetal oversize, and progeria. In the present study, whole-genome bisulfite sequencing and mRNA sequencing were performed on tongue and biceps femoris muscles of cloned piglets with and without macroglossia, in an attempt to elucidate the epigenetic causes of the macroglossia phenotype. We identified 14 958 and 18 752 differentially methylated regions in the tongue and biceps femoris muscles, respectively, of macroglossia piglets and these correspond to 4574 and 4772 differentially methylated genes compared with the control group (piglets without macroglossia). Larger methylation difference was found in tongue muscle than in biceps femoris muscle. In total, 114 genes in tongue and 72 genes in biceps femoris muscles were found to be differentially expressed between the two groups. Of these differentially expressed genes in tongue muscle, 31 were also differentially methylated genes, among which DIO3 and ZIC1 were imprinting or predicted imprinting genes. These two and another six overlapping genes (ALDH1A2, MKX, MAB21L2, CA3, RANBP3L, and MYL10) are crucial factors involved in embryonic development or tissue and organ development. GO enrichment analysis suggested possible alteration of these processes. Our study provides novel molecular insights into the formation of macroglossia in cloned pigs.
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Clonación de Organismos , Metilación de ADN , Músculos Isquiosurales , Macroglosia/genética , Sus scrofa/genética , Lengua , Animales , Epigénesis Genética , Epigenoma , Fenotipo , PorcinosRESUMEN
Objective: To analyze the expression of CXC chemokine ligand 10 (CXCL10) in glioma and its clinical significance through bioinformatics. Methods: The expression level of CXCL10 in glioma, and its prognostic significance, gene ontology (GO) function annotation, Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment and the correlation of tumor cell purity were analyzed in TCGA, CGGA, MetaScape, TIMER databases. In addition, 34 clinical glioma tissues were collected for Western Blot and immunohistochemistry to further verify the correlation between CXCL10 and glioma. Results: CGGA and TCGA database analysis showed that with the increase of WHO grade, the expression of CXCL10 in gliomas increased (P<0.01). The overall survival rate of patients with high CXCL10 expression was significantly lower than that of patients with low expression (χ2 =148.1,P<0.05). Among patients with grade â £ glioblastoma who received radiotherapy or chemotherapy, the patients with low CXCL10 expression were associated with good survival (χ2 =6.714,P<0.05;χ2 =5.618,P<0.05). Moreover, GO and KEGG analysis showed that genes co-expressed with CXCL10 were mainly enriched in the biological processes such as cytokine-mediated signaling pathways, regulating adaptive immune responses and inflammatory responses. Furthermore, TIMER database analysis showed that CXCL10 was negatively correlated with the purity of glioma cells (LGG: r=-0.129;GBM: r=-0.165;P<0.05). Similarly, clinical sample analysis also showed that the expression level of CXCL10 increased in glioma, and it increased with the grade of glioma (all P<0.05). Conclusion: The expression of CXCL10 is up-regulated in glioma as well as it increased with the malignant degree of glioma. At the same time, the high expression of CXCL10 in glioma is closely related to the poor prognosis of patients.
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Neoplasias Encefálicas , Quimiocina CXCL10/genética , Glioblastoma , Glioma , Quimiocinas CXC , Humanos , LigandosRESUMEN
Objective: To analyze the relationship between migration time and the prevalence of myopia of children and adolescents aged between 6 and 18 years old in Shenzhen. Methods: From April to May 2019, 26 618 children and adolescents from 14 schools in six streets of Baoan District, including Fuyong, Shajing, Xin'an, Xixiang, Songgang and Shiyan, were included in the study by using random cluster sampling method. The demographic characteristics, migration status, self-reported myopia, screen time in the last seven days, outdoor activities in the last one month and other information were collected through the questionnaire. The differences of myopia among children and adolescents with different characteristics were compared by χ2 test, and the relationship between migration time and the prevalence of myopia was analyzed by multivariate unconditional logistic regression model. Results: The age of 26 618 study participants was (12.37±3.49) years old, and the overall prevalence of myopia was 49.4%. Multivariate logistic regression analysis showed that after controlling for relevant confounding factors, compared with migrant children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for more than 6 years had a higher risk of myopia [OR (95%CI): 1.48 (1.14-1.92)]. After being grouped by phase of school, in the lower grade group of primary school, the children and adolescents of migrant workers who had migrated for more than 6 years had a higher risk of myopia compared with those of migrant workers who migrated for 1-2 years [OR (95%CI): 1.96 (1.20-2.74)]. In the high school group, compared with the children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for 3-5 years and ≥6 years had a higher risk of myopia [OR (95%CI): 6.03 (1.29-28.15) and 6.52 (1.51-28.11), respectively]. Conclusion: The migration time is related to the prevalence of myopia of the children and adolescents of migrant workers.
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Miopía , Migrantes , Adolescente , Niño , China/epidemiología , Humanos , Miopía/epidemiología , Prevalencia , Factores de Riesgo , Instituciones Académicas , Encuestas y CuestionariosRESUMEN
To understand the prevalence and etiological characteristics of hand, foot and mouth disease(HFMD) in Yangzhou, so as to provide scientific basis for prevention and control of HFMD. HFMD cases from six sentinel hospitals in Yangzhou from January 2015 to December 2019 were taken as the subject of study. The epidemiological data of HFMD were analyzed by descriptive epidemiology method, the enterovirus were detected using RT-PCR method and the etiological characteristics were analyzed. The data were collected by Excel 2007 and statistically analyzed by SPSS22.0 software. A total of 1 151 positive cases were detected from all 2 129 HFMD clinical specimens collected in Yangzhou from 2015 to 2019, with a total positive rate of 54.06%, including 148 cases of EV71(6.95%), 382 cases of CA16(17.94%) and 621 cases of other enterovirus(29.17%). The difference of positive rate in different years(χ2=99.28, P<0.05), different months(χ2=92.09, P<0.05) and different districts(χ2=71.39, P<0.05)was statistically significant. Each subtype of enterovirus showed alternating prevalence in different years. The peak period of detection rate was from April to September (720 cases, 62.55%). The reported incidence for males was higher than females, with the male-female ratio of 1.58â¶1 and children under six (971 cases, 84.36%) as the major attacked population. There were obvious seasonal, regional and population characteristics of HFMD in Yangzhou City from 2015 to 2019. It reminds us that surveillance of HFMD should be continually implemented, more attention should be paid to the prevention and control of key population in high-risk seasons, and the booming HFMD cases caused by other enterovirus should be emphasized especially.
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Enterovirus Humano A , Infecciones por Enterovirus , Enterovirus , Enfermedad de Boca, Mano y Pie , Niño , China/epidemiología , Enterovirus/genética , Enterovirus Humano A/genética , Femenino , Enfermedad de Boca, Mano y Pie/epidemiología , Humanos , Incidencia , Lactante , MasculinoRESUMEN
OBJECTIVE: Coronavirus disease 2019 (COVID-19) is spreading worldwide. The onset of severe COVID-19 could lead to multiple organ damage and even death. It is worth paying attention to the warning index of the onset for severe COVID-19 so that patients can be identified and monitored carefully. PATIENTS AND METHODS: The report is a retrospective study that describes and analyzes the clinical features during the treatment of COVID-19. Four patients with COVID-19 were involved in this study, who were father-and-son pairs from two families. All patients were treated with the same combination of anti-microbial and anti-viral agents for 10-14 days, adjusting for the disease status. The primary outcome measure was SARS-CoV-2 detection using RT-qPCR with oropharyngeal swabs. Chest CT imaging served as a secondary outcome measure. RESULTS: One of the four patients progressed to severe disease, while the remaining patients recovered with the same treatment. A persistent decrease in the lymphocyte ratio and increase in the C-reactive protein (CRP) level were observed in the severe patient, along with other typical symptoms of COVID-19. CONCLUSIONS: The cases we described indicate that blood cell and CRP tests could be useful risk warnings of severe onset of COVID-19.
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Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , COVID-19/diagnóstico , SARS-CoV-2 , Adulto , Anciano , Antivirales/administración & dosificación , Proteína C-Reactiva/análisis , COVID-19/sangre , COVID-19/diagnóstico por imagen , Prueba de Ácido Nucleico para COVID-19 , Humanos , Pulmón/diagnóstico por imagen , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
This Retraction follows an Expression of Concern (https://www.europeanreview.org/article/22743) in Eur Rev Med Pharmacol Sci 2020; 24 (17): 8621-8621-DOI: 10.26355/eurrev_202009_22743-PMID: 32964943. The article "MiR-210 suppresses neuronal apoptosis in rats with cerebral infarction through regulating VEGF-notch signaling pathway, by Y.-L. Jiang, W.-W. Liu, Y. Wang, W.-Y. Yang, published in Eur Rev Med Pharmacol Sci 2020; 24 (9): 4971-4978-DOI: 10.26355/eurrev_202005_21188-PMID: 32432760" has been withdrawn from the authors due to some inaccuracies (Some data cannot be repeated by our further research). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21188.
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Arsenic trioxide poisoning can cause damage to the nervous system, heart, liver, kidney and other organs, with a lethal dose of 0.8-2.0 mg/kg. Acute poisoning is now rare. This article analyzes the clinical characteristics of 10 patients with acute poisoning caused by the absorption of arsenic trioxide through the respiratory tract, digestive tract, and skin, in order to improve clinicians' understanding of acute arsenic trioxide poisoning.
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Intoxicación por Arsénico , Arsenicales , Trióxido de Arsénico , Humanos , Hígado , ÓxidosRESUMEN
OBJECTIVE: To systematically evaluate the anesthetic effect and safety of sevoflurane combined with propofol in removing tracheal foreign bodies in children. MATERIALS AND METHODS: PubMed, EMbase, The Cochrane Library, China Biomedicine Database, China National Knowledge Internet, WanFang Data, and VIP databases were searched. Randomized controlled trials (RCTs) of sevoflurane combined with propofol for anesthesia during tracheal foreign body extraction in children were collected. The retrieval time was from the establishment of the database to April 10, 2019. RevMan 5.3 software was used for meta-analysis after two researchers independently screened the literature, extracted data, and evaluated the risk bias included in the study. RESULTS: Seven RCTs involving 473 patients were included. Meta-analysis showed that the time of loss of consciousness significantly reduced (MD=-38.27, 95% CI (-41.77, -34.77), p < 0.00001) and the recovery time significantly reduced (MD=-12.29, 95% CI (-2.77, -1.80), p < 0.00001) in the sevoflurane combined with propofol group compared with the control group. In terms of safety, the heart rate was slower [MD=-11.00, 95% CI (-21.64, -0.36), p=0.04 < 0.05] and the incidence of cough and breath holding was lower [MD=0.38, 95% CI (0.19, 0.78), p=0.008] in the sevoflurane combined with propofol group than in the control group. However, no significant difference in respiratory rate and SPO 2 < 90% was found between the two groups (p > 0.05). CONCLUSIONS: Sevoflurane combined with propofol is worth popularizing because of its high anesthetic effect and safety in the removal of tracheal foreign bodies in children. However, given the limited quantity and quality of the included studies, the above conclusions need to be verified by high-quality studies.