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BACKGROUND: Dent disease is an X-linked form of progressive renal disease. This rare disorder was characterized by hypercalciuria, low molecular weight (LMW) proteinuria and proximal tubular dysfunction, caused by pathogenic variants in CLCN5 (Dent disease 1) or OCRL (Dent disease 2) genes. Fanconi syndrome is a consequence of decreased water and solute resorption in the proximal tubule of the kidney. Fanconi syndrome caused by proximal tubular dysfunction such as Dent disease might occur in early stage of the disease. CASE PRESENTATION: Three cases reported in this study were 3-, 10- and 14-year-old boys, and proteinuria was the first impression in all the cases. All the boys presented with LMW proteinuria and elevated urine albumin-to-creatinine ratio (ACR). Case 1 revealed a pathogenic variant in exon 11 of CLCN5 gene [NM_001127899; c.1444delG] and a nonsense mutation at nucleotide 1509 [p.L503*], and he was diagnosed as Dent disease 1. Case 2 carried a deletion of exon 3 and 4 of OCRL1 gene [NM_000276.4; c.120-238delG A] and a nonsense mutation at nucleotide 171 in exon 5 [p.E57*], and this boy was diagnosed as Dent disease 2. Genetic analysis of Case 3 showed a missense mutation located in exon 2 of HNF4A gene [EF591040.1; c.253C > T; p.R85W] which is responsible for Fanconi syndrome. All of three pathogenic variants were not registered in GenBank. CONCLUSIONS: Urine protein electrophoresis should be performed for patients with proteinuria. When patients have LMW proteinuria and/or hypercalciuria, definite diagnosis and identification of Dent disease and Fanconi syndrome requires further genetic analyses.
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Doença de Dent/diagnóstico , Síndrome de Fanconi/diagnóstico , Adolescente , Criança , Pré-Escolar , Doença de Dent/complicações , Doença de Dent/genética , Síndrome de Fanconi/complicações , Síndrome de Fanconi/genética , Humanos , Masculino , Peso Molecular , Proteinúria/etiologiaRESUMO
Background and objectives: The intercornual distance in the sacral hiatus has yet to be studied precisely in children. This age-stratified, observational study aimed to clarify the changes in sacral hiatus dimensions and to quantify the correlations between the intercornual distance of the sacral hiatus and age, height, weight, and head circumference by using real-time ultrasonography. Methods: The patients were stratified into three groups: neonates and infants, toddlers, and schoolchildren. In the operating room, the ultrasonic probe was placed at the sacral cornua to obtain a transverse view of the sacral hiatus, and the intercornual distance was measured three times in millimetres. Results: The study included a total of 156 patients. The mean ± SD (95%CI) of intercornual distance in neonates and infants (<12 months) was 11.58 ± 1.79 (11.11-12.04) mm, 13.29 ± 1.97 (12.71-13.86) mm in toddlers (13-36 months), and 13.36 ± 2.49 (12.64-14.08) mm in schoolchildren (>36 months).The mean values of neonates and infants were different from those of toddlers and schoolchildren (p < 0.001), but it was similar between toddlers and schoolchildren (p > 0.05, 95 % CI mean difference -1.10 to 0.95).Intercornual distance was correlated with age, height, weight, and head circumference before one year of age (Spearman's R values > 0.7), but there was no correlation thereafter (Spearman's p value > 0.05). Conclusion: In the first year after birth, the intercornual distance increases rapidly with body growth; after one year of age, the sacral hiatus dimension changes significantly. Ultrasound is superior for assessing the gradually ossified cartilage components in older children.
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BACKGROUND: A total upper eyelid defect is a rare problem that may result from tumor excision, trauma, or burns. Reconstruction of a total upper eyelid defect involves the reconstruction of 2 fundamental elements: anterior and posterior lamellae. Because an expander capsule looks like the palpebral conjunctiva with a moist, smooth, white glistening appearance, its use was investigated in the repair of total upper eyelid defects in rabbits. METHODS: Sixty-six tissue expanders with the autogeneic conchal chondro-grafts were implanted into the foreheads of 66 rabbits. After 6 to 8 weeks, the sandwich-prefabricated advancement flaps were designed to reconstruct rectangular excisions of the upper eyelid. The cartilage was preliminarily inserted in a flap, formed by tissue expansion, and then transferred to an upper eyelid defect in the rabbit. Histopathology was evaluated at 3 days, 1 week, 2 weeks, 1 month, 2 months, and 4 months after reconstruction. The upper palpebral length was measured after 4 months of reconstruction as a 1-dimension reference point of flap contracture. RESULTS: No edema, congestion, infection, corneal damage, or necrosis were observed during the reconstructions. Histopathologic studies revealed that the long-term capsule had a normal conjunctiva-like appearance with a stratified columnar epithelium. The average shortening, measured as the length between inner to outer canthal folds, was inconspicuous. CONCLUSIONS: The expander capsule has the potential to act as an effective posterior lamellar substitute of eyelid in a rabbit model. Further studies should be undertaken to see if this represents a good model for a potential human clinical application.
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Blefaroplastia/métodos , Pálpebras/cirurgia , Retalhos Cirúrgicos/cirurgia , Dispositivos para Expansão de Tecidos/classificação , Animais , Autoenxertos/transplante , Túnica Conjuntiva/patologia , Túnica Conjuntiva/cirurgia , Contratura/patologia , Córnea/patologia , Cartilagem da Orelha/transplante , Doenças Palpebrais/cirurgia , Pálpebras/patologia , Estudos de Viabilidade , Testa/cirurgia , Modelos Animais , Complicações Pós-Operatórias , Coelhos , Transplante de Pele/métodos , Fatores de Tempo , Expansão de Tecido/métodos , Cicatrização/fisiologiaRESUMO
Background: There is currently no effective treatment for cognitive impairment associated with schizophrenia (CIAS). Recent studies have shown that increased histamine levels in the brain may help to improve CIAS symptoms. Betahistine is an H1-receptor agonist and H3-receptor antagonist. This study evaluated the effect of high-dose betahistine on cognitive function as well as its safety in Chinese Han patients with schizophrenia. Methods: This randomized double-blind, placebo-controlled trial enrolled 89 patients with schizophrenia who were randomly administered betahistine (72 mg/d) or placebo for 12 weeks. At baseline and at 4, 8, and 12 weeks after commencing the intervention, we measured changes in cognitive function and clinical symptoms using the MATRICS Consensus Cognitive Battery (MCCB) and Positive and Negative Syndrome Scale (PANSS), respectively. Furthermore, we used the Treatment Emergent Symptom Scale (TESS) to assess the adverse effects of the patients' medications. Results: Compared to the placebo group, the betahistine group showed significant improvements in the MCCB composite score after 12 weeks of treatment (p = 0.003) as well as improvements in MCCB verbal learning (p = 0.02) and visual learning (p = 0.001) domain scores. However, there were no significant improvements in the PANSS total scores or subscores (p > 0.05). Generally, high-dose betahistine treatment was considered safe in patients with schizophrenia. Conclusions: Additional use of high-dose betahistine can effectively improve cognitive function but not psychiatric symptoms in patients with schizophrenia. Betahistine (72 mg/d) is well tolerated by Chinese Han patients with schizophrenia. Trial Registration: chictr.org.cn, identifier: ChiCTR1900021078. http://www.chictr.org.cn/edit.aspx?pid=35484&htm=4.
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OBJECTIVE: To establish the suitable review criteria for ADVIA 120/2120 and those for different series of hematology analyzers. METHODS: A total of 2400 samples, including 6 blood neoplasms, were detected with ADVIA 120/2120 hematology analyzer, in which 1200 samples were detected by Sysmex XE-2100 and Beckman-Coulter LH750 hematology analyzers. In the meantime, blood smears were reviewed, and the results were analyzed statistically. The new review criteria were established by consulting and modifying the one as recommended by an international consensus group. Finally 300 samples were selected to validate the new review criteria. RESULTS: The results of 2400 samples detected by ADVIA 120/2120 hematology analyzer were analyzed statistically according to the international consensus review rules and blood smear positive criteria formulated by Chinese experts. The true positive rate was 22.1% (n = 530), false positive rate 28.1% (n = 675), true negative rate 44.3% (n = 1063), false negative rate 5.5% (n = 132), and the smear review rate 50.2% (n = 1205). The false negative rate was over the acceptable limit of 5%. The new review criteria were established by amending the blood smear positive criteria, i. e. increasing the percentage of band neutrophils, eosinophils, basophils and monocytes and adjusting the international consensus review rules. Then the results were re-analyzed. The true positive rate, false positive rate, true negative rate and false negative rate were 15.5% (n = 371), 18.7% (n = 449), 61.6% (n = 1479) and 4.2% (n = 101) respectively. The smear review rate was 34.2% (n = 821) and no specimen of blood neoplasms was missed. On that basis, the current review criteria for ADVIA 120/2120, XE-2100 and LH750 hematology analyzer were proposed by adding some specific parameters. The results of 1200 samples with three instruments were analyzed according to the current criteria. And the false negative rates were 4.3%, 4.6% and 4.6%, and false positive rate 14.7%, 17.5% and 12.7% respectively. And no specimen of blood neoplasm was missed. The false negative rates of three instruments were 3.8%, 4.3% and 4.0% in validation teses. CONCLUSION: The review criteria for three different series of hematology analyzers have been formulated for large general hospitals.
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Automação Laboratorial/instrumentação , Contagem de Células Sanguíneas/instrumentação , Hematologia/instrumentação , Automação Laboratorial/métodos , Contagem de Células Sanguíneas/métodos , Estudos de Avaliação como Assunto , Reações Falso-Negativas , Reações Falso-Positivas , Hematologia/métodos , HumanosRESUMO
Purpose: To evaluate the effects of a single oral dose of pyridoxine on lysine metabolites including α-aminoadipic semialdehyde (a-AASA), piperideine-6-carboxylate (P6C), the sum of AASA and P6C (AASA-P6C), pipecolic acid (PA), and α-aminoadipic acid (α-AAA) in PDE patients. Methods: The lysine metabolites of 15 patients with molecularly confirmed PDE were detected before and 4 h after taking a single oral dose of pyridoxine, respectively, using liquid chromatography-mass spectrometry (LC-MS/MS) method. Five types of samples were freshly prepared, including plasma, serum, dried blood spots (DBS), urine, and dried urine spots (DUS). Results: All the patients had been treated with long-term oral pyridoxine for several months to years, with doses of 30-360 mg/d. The concentrations of a-AASA, P6C, AASA-P6C, PA, and a-AAA before and after taking a single oral dose of pyridoxine for the same analyte detected in the same type of sample varied among patients. The mean concentrations increased in almost all the metabolites after taking an oral dose of pyridoxine, with or without statistical significance. Whereas, the metabolites concentrations might increase or decrease among different patients, or in different samples of the same patient, without a regular tendency. There was no statistical correlation between the concentrations before and after taking pyridoxine in the same type of sample for most metabolites. Conclusions: No obvious relationship between the metabolite levels or concentration differences and the age, pyridoxine dose (a single oral dose and long-term maintenance dose), duration of treatment, or neurodevelopmental phenotype was found at present study. The large individual differences among patients, probably affected by various genotypes, leading to quite different effects of pyridoxine on the change degree of metabolites concentrations. Our study suggested that long-term pyridoxine treatment could control seizures rather than getting toxic lysine metabolites such as a-AASA and P6C back to normal. In the future, more therapies should be focused to alleviate the metabolites accumulation and further improve the prognosis of PDE.
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The measurements of lysine metabolites provide valuable information for the rapid diagnosis of pyridoxine-dependent epilepsy (PDE). Here, we aimed to develop a sensitive method to simultaneously quantify multiple lysine metabolites in PDE, including α-aminoadipic semialdehyde (a-AASA), piperideine-6-carboxylate (P6C), pipecolic acid (PA) and α-aminoadipic acid (α-AAA) in plasma, serum, dried blood spots (DBS), urine and dried urine spots (DUS). Fifteen patients with molecularly confirmed PDE were detected using liquid chromatography-mass spectrometry (LC-MS/MS) method. Compared to the control groups, the concentrations of a-AASA, P6C and the sum of a-AASA and P6C (AASA-P6C) in all types of samples from PDE patients were markedly elevated. The PA and a-AAA concentrations ranges overlapped partially between PDE patients and control groups. The concentrations of all the analytes in plasma and serum, as well as in urine and DUS were highly correlated. Our study provided more options for the diverse sample collection in the biochemical tests according to practical requirements. With treatment modality of newly triple therapy investigated, biomarker study might play important role not only on diagnosis but also on treatment monitoring and fine tuning the diet. The persistently elevated analytes with good correlation between plasma and DBS, as well as urine and DUS made neonatal screening using DBS and DUS possible.
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Ácido 2-Aminoadípico/análogos & derivados , Ácido 2-Aminoadípico/sangue , Epilepsia/sangue , Ácidos Picolínicos/sangue , Ácidos Pipecólicos/sangue , Espectrometria de Massas em Tandem/métodos , Ácido 2-Aminoadípico/metabolismo , Ácido 2-Aminoadípico/urina , Biomarcadores/sangue , Biomarcadores/urina , Criança , Pré-Escolar , Cromatografia Líquida/métodos , Epilepsia/diagnóstico , Epilepsia/urina , Feminino , Humanos , Lactente , Lisina/metabolismo , Masculino , Programas de Rastreamento , Ácidos Picolínicos/metabolismo , Ácidos Picolínicos/urina , Ácidos Pipecólicos/metabolismo , Ácidos Pipecólicos/urinaRESUMO
OBJECTIVE: Fatty acid-binding protein 4 (FABP4) has been proposed to be a potential predictive factor of gestational hypertension or preeclampsia (GH/PE) because of its integrating metabolic and inflammatory responses. Women with gestational diabetes mellitus (GDM) are more likely to develop both GH/PE, than the normal population. The aim of our study was to examine the relationship between plasma FABP4 in the second trimester of pregnancy and the risk of GH/PE in women with GDM. METHODS: This was a nested case-control study conducted within a large on-going prospective cohort study conducted at Peking University First Hospital. A total of 1344 women, who were diagnosed with GDM, according to a 75 g oral glucose tolerance test, participated in the GDM One-Day Clinic at Peking University First Hospital from February 24, 2016 to February 9, 2017. Of the 748 GDM women who agreed to the blood sample collection, 637 were followed until their delivery. The cases included GDM patients who developed gestational hypertension or preeclampsia (GDM-GH/PE group, n = 41). Another 41 matched GDM women without major complications were selected as the control group (GDM group). RESULTS: The incidence of GH/PE was 6.44% and 3.30% for preeclampsia. The level of the second trimester plasma FABP4 in the GDM-GH/PE group was significantly higher than the GDM group (17.53±11.35 vs. 12.79±6.04 ng/ml, P = 0.020). The AUC ROC for the second trimester plasma FABP4 predicted GH/PE in the GDM patients alone was 0.647 (95%CI 0.529-0.766). Multivariate analysis showed that the elevated second trimester FABP4 level was independently associated with GH/PE in the GDM patients (OR 1.136 [95% CI 1.003-1.286], P = 0.045). CONCLUSIONS: Increased second trimester plasma FABP4 independently predicted GH/PE in GDM patients.