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OBJECTIVE@#To explore the clinical characteristics and genetic etiology for a child with atypical Hemolytic uremic syndrome (aHUS) in conjunct with nephrotic level proteinuria.@*METHODS@#A child patient who had visited the Affiliated Hospital of Qingdao University on June 25, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing of the child and his parents.@*RESULTS@#The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. Genetic testing revealed that he has harbored compound heterozygous variants of the DGKE gene, namely c.12_18dupGAGGCGG (p.P7fs*37) and c.1042G>T (p.D348Y), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as likely pathogenic and variant of uncertain significance, respectively. By combining his clinical manifestations and results of genetic testing, the child was diagnosed with aHUS with nephrotic level proteinuria.@*CONCLUSION@#For infants and young children with aHUS in conjunct with nephrotic level proteinuria, variants of the DGKE gene should be screened. Above finding has expanded the mutational spectrum of the DGKE gene.
Subject(s)
Infant , Female , Humans , Child , Male , Child, Preschool , Atypical Hemolytic Uremic Syndrome/diagnosis , Mutation , Genetic Testing , Thrombocytopenia/genetics , Proteinuria/geneticsABSTRACT
Objective:To investigate the value of preoperative enhanced CT combined with serum cytokeratin fragment 19 (CYFER21-1) and neuron-specific enolase (NSE) in the diagnosis of lymph node metastasis in patients with non-small cell lung cancer (NSCLC).Methods:160 patients with NSCLC admitted to Linyi Cancer Hospital from October 2018 to October 2021 were retrospectively selected. All patients received surgical treatment in our hospital, and 84 patients with lymph node metastasis (metastatic group) and 76 patients without lymph node metastasis (non-metastatic group) were confirmed after surgery. The features of enhanced CT images and serum CYFER21-1 and NSE levels were compared between the two groups before operation, and the value of each index in the diagnosis of lymph node metastasis in patients with NSCLC alone and in combination was analyzed by receiver operating characteristic (ROC) curve.Results:The proportions of patients with lesion diameter ≥3.0 cm, pleural depression, lymph node enlargement shown by CT, lymph node short diameter ≥10 mm, lymph node boundary ambiguity and lymph node enhancement in metastatic group were significantly higher than those in non-metastatic group, with statistical significance (all P<0.05). Serum CYFER21-1 and NSE levels in metastatic group were significantly higher than those in non-metastatic group, with statistical significance (all P<0.05). The area under curve (AUC) of CYFER21-1 and NSE levels in the diagnosis of lymph node metastasis in NSCLC patients were 0.652 and 0.845, respectively, and the diagnostic cut-off values were 4.81 ng/ml and 24.14 ng/ml, respectively. The sensitivity and specificity of CYFER21-1+ NSE+ enhanced CT in the diagnosis of lymph node metastasis in NSCLC patients were 91.67% and 94.74%. Conclusions:Preoperative enhanced CT is of certain clinical value in the diagnosis of lymph node metastasis in NSCLC patients. Combined with serum CYFER21-1 and NSE levels, enhanced CT can further improve the sensitivity and specificity of diagnosis.
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Objective:To investigate the correlation between time within the glucose target range(TIR) and hyperuricemia(HUA) in patients with type 2 diabetes mellitus(T2DM).Methods:A total of 215 patients with T2DM in the First Affiliated Hospital of Bengbu Medical College from June 2021 to May 2022 were selected and divided into HUA group and non-HUA group according to serum uric acid level. The clinical characteristics and biochemical indicators of the patients were collected. The association of 72 h glucose monitoring system(FGMS) related indicators TIR, mean blood glucose fluctuation range(MAGE), blood glucose variability(CV), blood glucose standard deviation(SDBG), and mean blood glucose(MBG) with serum uric acid level was analyzed. The influencing factors of T2DM combined with HUA were analyzed with binary logistic regression, and receiver operating characteristic(ROC) curve was drawn to evaluate their predictive values.Results:TIR of HUA group was significantly decreased compared with non-HUA group, while HbA 1C, MAGE, CV, SDBG, and MBG were increased( P<0.001). Spearman correlation analysis showed that serum uric acid levels were negatively correlated with TIR, but positively correlated with MAGE, CV, SDBG, and MBG( P<0.001). After dichotomous logistic regression analysis, TIR was found to be an independent protective factor for T2DM with HUA. The ROC curve results showed that the area under the curve(AUC) of TIR for predicting HUA in T2DM was 0.856(95% CI 0.803-0.909, P<0.001), with the best cut-off value being 64.5%, the sensitivity being 76.8%, and the specificity being 90.3%. Conclusion:TIR in patients with T2DM combined with HUA was significantly decreased. TIR is an independent protective factor for T2DM combined with HUA, and TIR shows a certain predictive value for T2DM combined with HUA.
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Objective:To investigate the clinical characteristics, diagnosis and treatment methods of children with gene mutation-negative essential thrombocytosis (ET).Methods:The clinical data of a child with gene mutation-negative ET in the Blood Diseases Hospital of Chinese Academy of Medical Sciences were collected, and the related literature was reviewed.Results:The epistaxis was the main clinical symptom of this child. He was diagnosed as ET (gene mutation-negative) by bone marrow aspiration and gene detection. After hydroxyurea treatment, the platelet count increased and the clinical symptoms were improved.Conclusions:The incidence rate of ET in children is low, and the frequency of gene mutation-negative ET in children reported in the literature is different. The large number of samples and long-term follow-up studies are needed.
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Objective:To investigate the clinical features and prognosis of children with positive flow cytometry of cerebrospinal fluid(CNSI + )in maintained acute lymphoblastic leukemia(ALL). Methods:Clinical data including clinical characteristics, diagnosis, treatment and prognosis of 12 patients with ALL CNSI diagnosis in maintenance period were analyzed to explore the prognostic factors.Results:The 12 children with CNSI + in maintenance were mainly male, and all of them were B-ALL.High leukemia cell count at first diagnosis( χ2=6.374, P=0.012), insensitivity to glucocorticoid pretherapy( χ2=5.048, P=0.025), increased rate of abnormal CSF cells(≥60%, χ2=7.024, P=0.008), course of CNSI + ≤14 months( χ2=4.873, P=0.027)and complex karyotype( χ2=9.356, P=0.002)are the adverse prognostic factors.Karyotype is an independent factor( P=0.017). Conclusion:The prognosis of children with CNSI + is unfavourable.Intrathecal injection and chemotherapy are the important treatment for children with CNSI + in maintenance period.Hematopoietic stem cell transplantation is an important choice for children with relapse.
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Epilepsy is one of the most common diseases of the central nervous system, affecting tens of millions of people around the world. Most of clinically used antiepileptic drugs are based on ion mechanism to antagonize epileptic seizures, targeted to various ion channels or ion channel receptors. However, with the in-depth research on the pathogenesis of epilepsy, the non-ionic antiepileptic mechanism has increasingly become the key to the control of various intractable epilepsy, and the relevant drugs have gradually achieved clinical transformation. In this paper, non-ionic antiepileptic mechanisms are classified to clinical and preclinical types according to whether clinical transformation has been achieved. The application of non-ionic antiepileptic drugs in refractory epilepsy was mainly introduced, including everolimus, cannabidiol, fenfluramine, padsevonil, medium chain triglyceride modified ketogenic diet, and anakinra. Additionally, some preclinical non-ionic antiepileptic mechanisms such as prostaglandin, adenosine, metabolic glutamate receptor and mitochondrial mechanism are briefly introduced. The authors believe that the current stage of ionic antiepileptic drugs research has reached the bottleneck of transformation and it is difficult to achieve a major breakthrough in the mechanism, but there are broader research prospects in non-ionic antiepileptic mechanisms because a large number of them have not yet been clinically transformed. From a deeper perspective, some non-ionic antiepileptic mechanisms may have been involved in the fundamental mechanism of epileptogenesis, and they may be the prospect for the future treatment of refractory epilepsy.
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Objective To study the effect of macrophage migration inhibitory factor(MIF) antibody on the rat colonic aberrant crypt foci(ACF) induced by 1,2-dimethylhydrazine(DMH),carcinoma number and expression of MIF in rat colonic carcinogenesis.Methods Rat colonic carcinogenesis model was induced by DMH.In this model,the inhibitory effect of MIF antibody on the number of ACF and carcinoma was observed.ELISA and immunohistochemical staining were adopted to investigate the effect of MIF antibody in early cancerative intestinal mucosa and MIF expression after cancer formation.Results The number of ACF and carcinoma was significantly inhibited by MIF antibody intervention(P< 0.01).The expression of MIF in the colonic carcinoma model was significantly higher than that in the pre-carcinoma ACF model(P<0.01).Applying MIF antibody could significantly inhibit the expression of MIF in both rat colonic ACF and colonic carcinoma model.Conclusion MIF antibody can significantly inhibit the rat colonic mucosal carcinogenesis,which may be related with inhibiting number of ACF and expression of MIF.MIF antibody may be expected to become a new target spot of precaution and treatment of colonic carcinoma.
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Background and purpose:This study was to investigate the effect of miRNA-486 on the growth of human colorectal cancer cell line SW620 xenograft in nude mice and to explore the possible mechanism of action. Methods:Eighteen mice were randomly divided into three groups, including the experimental group, the negative control group and the blank control group. Each group contained 6 mice. The SW620 cell line was inoculated subcutaneously into nude mice to establish the model of human colorectal cancer xenografts. Peritumoral injection of miRNA-486 overexpres-sion plasmid, or blank vector and PBS were performed every 3 days. The volumes of subcutaneous tumors in each group of inoculated mice were compared. Then mice were sacrificed 3 weeks after infection. Immunohistochemistry and Western blot were used to measure the expression of neuropilin-2 (NRP2).Results:The growth rate of tumors in the experimental group was significantly lower than that in the negative control group and the blank control group. After 21 days, the size of transplanted tumors in the experimental group nude mice was (0.32±0.12) cm3, that in the negative control group was (0.77±0.31) cm3, and that in blank control group was (0.82±0.18) cm3. Tumor mass in the experimental group was sig-nificantly smaller than that in the other two groups (P=0.006<0.05). Tumor mass in the experimental group was (0.40±0.08) g, significantly smaller than that in the negative control group (0.75±0.18) g and in the blank control group (0.79±0.18) g (P=0.008<0.05). Compared with the expression of NRP2 in other groups, the growth of tumor in the experimental group de-clined (P=0.000<0.05).Conclusion:Colorectal cancer cell line SW620 xenografted tumor in nude mice can be suppressed after injection of miR-486, which may decrease the expression of NRP2.
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Angiogenesis plays an important role in tumor growth and metastasis,anti-angiogenic therapy is becoming the center point in tumor therapy,endostatin is a recently discovered endogenous inhibitor of angiogenesis.Endostatin can specifically target endothelial cells,inhibiting proliferation and migration and inducting apoptosis.This review describes the mechanism of endostatin in inhibiting angiogenesis,induction of apoptosis in tumor cells and clinical trials.