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BACKGROUND: Empty sella is an anatomical and radiological finding of the herniation of the subarachnoid space into the pituitary fossa leading to a flattened pituitary gland. Patients with empty sella may present with various symptoms, including headache due to intracranial hypertension and endocrine symptoms related to the specific pituitary hormones affected. Here, we report a female patient who developed persistent postoperative hypotension caused by subclinical empty sella syndrome after a simple surgery. CASE SUMMARY: A 47-year-old woman underwent vocal cord polypectomy under general anesthesia with endotracheal intubation. She denied any medical history, and her vital signs were normal before the surgery. Anesthesia and surgery were uneventful. However, she developed dizziness, headache and persistent hypotension in the ward. Thus, intravenous dopamine was started to maintain normal blood pressure, which improved her symptoms. However, she remained dependent on dopamine for over 24 h without any obvious anesthesia- and surgery-related complications. An endocrine etiology was then suspected, and further examination showed a high prolactin level, a low normal adrenocorticotropic hormone level and a low cortisol level. Magnetic resonance imaging of the brain revealed an empty sella. Therefore, she was diagnosed with empty sella syndrome and secondary adrenal insufficiency. Her symptoms disappeared one week later after daily glucocorticoid supplement. CONCLUSION: Endocrine etiologies such as pituitary and adrenal-related dysfunction should be considered in patients showing persistent postoperative hypotension when anesthesia- and surgery-related factors are excluded.
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The mammalian target of rapamycin (mTOR) signaling pathway is a powerful regulator of cell proliferation, growth, synapse maintenance and cell fate. While intensely studied for its role in cancer, the role of mTOR signaling is just beginning to be uncovered in specific cell types that are implicated in neurodevelopmental disorders. Previously, loss of the Tsc1 gene, which results in hyperactive mTOR, was shown to affect the function and molecular properties of GABAergic cortical interneurons (CINs) derived from the medial ganglionic eminence. To assess if other important classes of CINs could be impacted by mTOR dysfunction, we deleted Tsc1 in a caudal ganglionic eminence-derived interneuron group, the vasoactive intestinal peptide (VIP)+ subtype, whose activity disinhibits local circuits. Tsc1 mutant VIP+ CINs reduced their pattern of apoptosis from postnatal days 15-20, resulting in increased VIP+ CINs. The mutant CINs exhibited synaptic and electrophysiological properties that could contribute to the high rate of seizure activity in humans that harbor Tsc1 mutations.
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Transtornos do Neurodesenvolvimento , Peptídeo Intestinal Vasoativo , Humanos , Apoptose , Interneurônios , Serina-Treonina Quinases TORRESUMO
OBJECTIVE: This study aimed to investigate the role of computed tomography angiography (CTA) and three-dimensional (3D) reconstruction of renal arteries in the evaluation of bleeding after mini- percutaneous nephrolithotomy (PCNL). METHODS: Thirty-one consecutive patients with continuous renal hemorrhage after mini-PCNL were enrolled from January 2015 to January 2022. Demographic and clinical data were retrospectively recorded and analyzed. All patients had received CTA evaluation and subsequently digital subtraction angiography (DSA) embolization to manage renal bleeding. CTA and 3D reconstruction of renal arteries were performed using the 320 multi-detector computed tomography technique and the images were evaluated by experienced radiologists. DSA embolization were performed by an interventional radiologist with more than 10 years of experiences. RESULTS: CTA and 3D construction of renal arteries showed 28 cases of vascular lesions (28/31, 90.3%), including 15 cases of pseudoaneurysm (15/28, 53.6%), 9 cases of arteriovenous fistula (9/28, 32.1%), and 4 cases of suspicious bleeding spot (4/28, 14.3%). While DSA revealed 31 cases of vascular lesions (100%), including 15 cases of pseudoaneurysm (15/31, 48.4%), 10 cases of arteriovenous fistula (10/31, 32.3%), 6 cases of bleeding spot and (6/31, 19.4%). The serum creatinine level was elevated slightly before mini-PCNL and after DSA embolization (73.1±18.1 vs 92.1±33.6, P <.01). 15 patients (15/31, 48.4%) required blood transfusion, with mean blood transfusion volume of 700 ml ±660 ml (range, 400 ml-1800 ml). The bleeding was controlled without any further severe complications. CONCLUSION: CTA and 3D reconstruction of renal arteries were safe and effective in diagnosing renal arterial bleedings after mini-PCNL, with a sensitivity of 90.3% and a specificity of 100%.
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Falso Aneurisma , Fístula Arteriovenosa , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Humanos , Nefrolitotomia Percutânea/efeitos adversos , Artéria Renal/diagnóstico por imagem , Imageamento Tridimensional , Nefrostomia Percutânea/efeitos adversos , Falso Aneurisma/complicações , Angiografia por Tomografia Computadorizada/efeitos adversos , Estudos Retrospectivos , Hemorragia/diagnóstico , Hemorragia/etiologia , Hemorragia/terapia , Fístula Arteriovenosa/complicações , Angiografia Digital/efeitos adversos , Tomografia Computadorizada MultidetectoresRESUMO
BACKGROUND: The incidence of aberrant catheterization into a ureter is extremely low, and there is a 20% chance that the balloon cannot be deflated. Regrettably, the mechanism underlying this complication remains unknown. There has been no reported case of a Foley catheter successfully removed from the ureter via percutaneous puncture. CASE PRESENTATION: A 86-year-old man complained of increasing abdominal pain after an 18F Foley catheter was inserted into his urethra. His attending physician attempted but failed to deflate the balloon. A bedside ultrasound and CT scan revealed that the catheter tip was in the right lower ureter. Several measures, including cutting the catheter and inserting a rigid guidewire, were then attempted but failed to deflate the balloon. Finally, the inflated balloon was punctured with a PTC needle under ultrasound-guidance, and the misplaced Foley catheter was removed. Two days after the pelvic drainage tube was removed, the patient was discharged. CONCLUSION: This is the first reported case of a Foley catheter being removed from the ureter via percutaneous puncture. The mechanism by which the balloon is unable to deflate may be related to the passive twist of the catheter. In such a case, an overall assessment of the patient's condition should be performed, and non-invasive to invasive interventions should be phased in.
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Ureter , Idoso de 80 Anos ou mais , Catéteres , Humanos , Masculino , Punções , Uretra , Cateterismo Urinário/efeitos adversosRESUMO
Background: Acute necrotizing encephalopathy of childhood (ANE) is a rare but rapidly progressing encephalopathy. Importantly, the exact pathogenesis and evidence-based treatment is scarce. Thus, we aimed to identify the clinical, imaging, and therapeutic characteristics that associated with prognosis of pediatric ANE patients. Methods: A retrospective study was conducted on pediatric patients with ANE who were admitted to Wuhan Children's Hospital between January 2014 and September 2019. All cases met the diagnostic criteria for ANE proposed by Mizuguchi in 1997. The clinical information and follow-up data were collected. The prognostic factors were analyzed by trend chi-square test and Goodman-Kruskal gamma test. Results: A total of 41 ANE patients ranging in age from 8.9 to 142 months were included in this study. Seven cases (17%) died, and the other 34 survivors had different degrees of neurological sequelae. Factors tested to be significantly correlated with the severity of neurological sequelae were the intervals from prodromal infection to acute encephalopathy (G = -0.553), conscious disturbance (r = 0.58), endotracheal intubation (r = 0.423), elevation of alanine aminotransferase (r = 0.345), aspartate aminotransferase (r = 0.393), and cerebrospinal fluid protein (r = 0.490). In addition, dynamic magnetic resonance imaging (MRI) evaluation on follow-up revealed that the total numbers of brain lesion location (χ2 = 6.29, P < 0.05), hemorrhage (r = 0.580), cavitation (r = 0.410), and atrophy (r = 0.602) status were significantly correlated with the severity of neurological sequelae, while early steroid therapy (r = -0.127 and 0.212, respectively) and intravenous immunoglobulin (IVIG) (r = 0.111 and -0.023, respectively) within 24 h or within 72 h after onset showed no association. Conclusions: Intervals from prodromal infection to acute encephalopathy (≤1 day), total numbers of brain lesion location (≥3), the recovery duration of hemorrhage and atrophy (>3 months), and the presence of cavitation predict severe neurological sequelae in pediatric patients with ANE. Early treatments, including steroid therapy and IVIG, had no correlation with better outcomes. Further studies are needed to establish a consensus guideline for the management of ANE.
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Background and Purpose: To assess the safety and effectiveness of oral methylprednisolone (oMP) in comparison with intramuscular adrenocorticotropic hormone (imACTH) and oral prednisolone (oP) therapies in children with infantile spasms (IS). Methods: In this prospective, open-label, non-blinded, uncontrolled observational study, children (aged 2-24 months) with newly diagnosed IS presenting with hypsarrhythmia or its variants on electroencephalogram (EEG) were included. It was followed by imACTH, oP, or oMP (32-48 mg/day for 2 weeks followed by tapering) treatments. Electroclinical remission/spasm control, relapse, and adverse effects were evaluated in the short-term (days 14 and 42) and intermediary-term (3, 6, and 12 months) intervals. Results: A total of 320 pediatric patients were enrolled: 108, 107, and 105 in the imACTH, oMP, and oP groups, respectively. The proportion of children achieving electroclinical remission on days 14 and 42 was similar among the three groups (day 14: 53.70 vs. 60.75 vs. 51.43%, p = 0.362; day 42: 57.55 vs. 63.46 vs. 55.34%, p = 0.470). The time to response was significantly faster in the oMP group (6.5 [3.00, 10.00] days vs. 8.00 [5.00, 11.00] days for imACTH and 8.00 [5.00, 13.00] days for oP, p = 0.025). Spasm control at 3, 6, and 12 months was also similar in the three groups (P = 0.775, 0.667, and 0.779). The relapse rate in the imACTH group (24.10%) was lower than oMP (30.77%) and oP groups (33.33%), and the time taken for relapse in the imACTH group (79.00 [56.50, 152.00] days) was longer than oMP (62.50 [38.00, 121.75] days) and oP groups (71.50 [40.00, 99.75] days), but the differences were not statistically significant (p = 0.539 and 0.530, respectively). The occurrence of adverse effects was similar among the three groups. Conclusions: The short and intermediary-term efficacy and recurrence rates of oMP are not inferior to those of imACTH and oP for the treatment of IS. Significantly, the time to achieve electroclinical remission with oMP was quicker than that with imACTH and oP. Considering its convenience, affordability, and the absence of irreversible side effects, oMP can serve as a form of first-line treatment for newly diagnosed IS.
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The present study investigated the use of retrograde flexible ureteroscopy (RFU) in the discrimination of the etiology of hematuria that originates from the upper urinary tract (UUT). The present study collected retrospective data for patients who presented with hematuria and cystoscopy-detected bleeding from the UUT between June 2006 and August 2018 in Ningbo First Hospital. All patients accepted RFU to determine the etiology of hematuria. Data regarding imaging examinations, surgery, pathology and complications were also collected and analyzed. In total, 65 patients (males, 38; females, 27) with a mean age of 63 years underwent RFU to determine the etiology of hematuria originating from the UUT. Using RFU, UUT tumors were found in 29 cases. Stones, polyps and atypical hyperplasia were found in two cases, and a definite diagnosis was not found in three cases. There were 17 cases without obvious abnormalities and nine cases were unable to undergo RFU due to ureteral stenosis. In patients who could not be diagnosed by imaging examination, 34.4% (11/32) were diagnosed with urothelial carcinoma by RFU, and these results were also confirmed by postoperative pathology. In the present study, no patient had severe complications after RFU. The present results suggested RFU may be used as a sensitive method to diagnose UUT tumors (78.4%; 29/37) and has strong specificity. RFU could be performed as a routine examination for patients with hematuria from the UUT.
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Mafb and c-Maf transcription factor (TF) expression is enriched in medial ganglionic eminence (MGE) lineages, beginning in late-secondary progenitors and continuing into mature parvalbumin (PV+) and somatostatin (SST+) interneurons. However, the functions of Maf TFs in MGE development remain to be elucidated. Herein, Mafb and c-Maf were conditionally deleted, alone and together, in the MGE and its lineages. Analyses of Maf mutant mice revealed redundant functions of Mafb and c-Maf in secondary MGE progenitors, where they repress the generation of SST+ cortical and hippocampal interneurons. By contrast, Mafb and c-Maf have distinct roles in postnatal cortical interneuron (CIN) morphological maturation, synaptogenesis, and cortical circuit integration. Thus, Mafb and c-Maf have redundant and opposing functions at different steps in CIN development.
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Linhagem da Célula , Córtex Cerebral/metabolismo , Interneurônios/metabolismo , Fator de Transcrição MafB/metabolismo , Proteínas Proto-Oncogênicas c-maf/metabolismo , Potenciais de Ação , Animais , Animais Recém-Nascidos , Apoptose , Membrana Celular/metabolismo , Movimento Celular , Proliferação de Células , Hipocampo/metabolismo , Eminência Mediana/metabolismo , Camundongos Knockout , Neuritos/metabolismo , Neurogênese , Parvalbuminas/metabolismo , Somatostatina/metabolismo , Sinapses/metabolismoRESUMO
The present study assessed the clinical efficacy of guide sheath-assisted ureteroscope lithotripsy in the treatment of upper ureteral calculi. A total of 81 patients with upper ureteral calculi underwent ureteroscope lithotripsy assisted by a guide sheath between January 2012 and June 2014; of these, 63 patients were successfully treated with simple rigid ureteroscope lithotripsy assisted by a ureteral access sheath, and 18 patients were successfully treated with rigid and flexible ureteroscope lithotripsy assisted by a guide sheath. At 1 day after the surgery, ultrasound examination of kidneys, ureters and bladder, and urinary system computed tomography were used to re-check for residual stones, and 69 patients had stones with a diameter of <2 mm in the renal pelvis, while 12 had stones of 2-4 mm in diameter. The operation time was 30-115 min (average, 56.0±4.8 min); all patients underwent a successful surgical procedure. A total of 7 patients had an elevated temperature 37.4-39.1°C (mean temperature, 37.7±0.3°C) after the surgery, but no other major complications were noted. After 1 month, the residual stones were completely discharged, so that the stone clearance rate was 100%. All patients were followed up for 3-12 months and no associated complications occurred. Overall, ureteroscope lithotripsy assisted by a guide sheath for the treatment of upper ureteral calculi had the benefit of water injection and reflux functions, as well as enhanced vision, reduced pressure within the renal pelvis, good discharge of stones as well as an improved efficiency and success rate compared with simple ureteroscopic lithotripsy.
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Cortical interneurons are a diverse group of neurons that project locally and are crucial for regulating information processing and flow throughout the cortex. Recent studies in mice have advanced our understanding of how these neurons are specified, migrate and mature. Here, we evaluate new findings that provide insights into the development of cortical interneurons and that shed light on when their fate is determined, on the influence that regional domains have on their development, and on the role that key transcription factors and other crucial regulatory genes play in these events. We focus on cortical interneurons that are derived from the medial ganglionic eminence, as most studies have examined this interneuron population. We also assess how these data inform our understanding of neuropsychiatric disease and discuss the potential role of cortical interneurons in cell-based therapies.
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Córtex Cerebral/citologia , Interneurônios/citologia , Animais , Linhagem da Célula , Modelos Biológicos , Fatores de Tempo , Transcrição GênicaRESUMO
Distinct cortical interneuron (CIN) subtypes have unique circuit functions; dysfunction in specific subtypes is implicated in neuropsychiatric disorders. Somatostatin- and parvalbumin-expressing (SST+ and PV+) interneurons are the two major subtypes generated by medial ganglionic eminence (MGE) progenitors. Spatial and temporal mechanisms governing their cell-fate specification and differential integration into cortical layers are largely unknown. We provide evidence that Coup-TF1 and Coup-TF2 (Nr2f1 and Nr2f2) transcription factor expression in an arc-shaped progenitor domain within the MGE promotes time-dependent survival of this neuroepithelium and the time-dependent specification of layer V SST+ CINs. Coup-TF1 and Coup-TF2 autonomously repress PV+ fate in MGE progenitors, in part through directly driving Sox6 expression. These results have identified, in mouse, a transcriptional pathway that controls SST-PV fate.
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Fator II de Transcrição COUP/metabolismo , Fator I de Transcrição COUP/metabolismo , Interneurônios/metabolismo , Neocórtex/citologia , Animais , Fator I de Transcrição COUP/genética , Fator II de Transcrição COUP/genética , Células Cultivadas , Imunoprecipitação da Cromatina , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Imuno-Histoquímica , Hibridização In Situ , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Parvalbuminas/genética , Parvalbuminas/metabolismo , Fatores de Transcrição SOXD/genética , Fatores de Transcrição SOXD/metabolismo , Somatostatina/genética , Somatostatina/metabolismoRESUMO
OBJECTIVE: To study the correlation between the excessive activation of Hedgehog signal and the drug resistance of multiple myeloma. METHODS: The resistant cell line RPMI 8226/R of multiple myeloma was established by an ascending concentration gradient method. The experiment consisted of 4 groups: RPMI8226/R, RPMI8226/S, GANT61+RPMI8226/R and GANT61+RPMI8226/S. The CCK-8 (cell counting kit-8) assay was used to detect the cell proliferation inhibition rate in 4 groups; the RT-PCR was used to detect the expression of Gli1, Gli2, Shh, Ihh, Smo and Sufu in the RPMI8226/S and RPMI8226/R cells. The Western blot was used to detect the expression of the resistant protein Cyclin D1, P21 and BCL-2 and MDR-related signaling pathways protein p-Akt, p-MAPK and STAT3 in the RPMI8226/S and RPMI8226/R cells. After adding different concentration of GANT61, the Western blot was used to detect the expression of Gli2 in RPMI8226/R and RPMI8226/S cells. RESULTS: The expression of Shh, Ihh, Smo Gli2 was enhanced significantly in the RPMI8226/R cells, but the expression of Sufu inhibitor was reduced, the expression level of related protein in Hedgehog signaling pathway was significanly higher in RPMI8226/R than that in RPMI8226/S. After theatment of GANT61 in vitro, the expression level of Gli2 in multiple myelom cells obviously decreased, the decreasing effect of GANT61 on Gli2 expression in RPMI8226/R cells was more significant than that in RPMI8226/S cells. The sensitivity of RPMI8226/R cells to DOX after treatment with GANT61 (IC50) was risen from 7.11±0.061 µmol/L to 0.99±0.053 µmol/L, the corresponding cell resistance index decreased from 5.51 to 1.69. CONCLUSION: the activation of Hedgehog signaling pathway is closely related with the resistance of multiple myeloma cells, and GANT61 can block the Hedgehog signaling pathway, thus Hedgehog signaling may be used as a new target for multiple myeloma treatment.
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Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Hedgehog/metabolismo , Mieloma Múltiplo/genética , Transdução de Sinais , Linhagem Celular Tumoral , Humanos , Mieloma Múltiplo/tratamento farmacológico , Fatores de Transcrição , Proteína GLI1 em Dedos de ZincoRESUMO
The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors and chromatin are thought to regulate gene expression. In the medial ganglionic eminence, the NKX2-1 transcription factor controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. Here, we dissected the molecular functions of NKX2-1 by defining its chromosomal binding, regulation of gene expression, and epigenetic state. NKX2-1 binding at distal regulatory elements led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, NKX2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub-ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach provides a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.
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Gânglios da Base/citologia , Gânglios da Base/metabolismo , Neurônios GABAérgicos/citologia , Neurônios GABAérgicos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Animais , Cromatina/metabolismo , Elementos E-Box/genética , Repressão Epigenética/genética , Proteínas de Homeodomínio/metabolismo , Interneurônios/metabolismo , Proteínas com Homeodomínio LIM/metabolismo , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Fator Nuclear 1 de TireoideRESUMO
BACKGROUND: Na + /Ca 2+ exchanger (NCX) plays a crucial role in pentylenetetrazol-induced convulsion. However, it is unclear whether NCX is critically involved in hyperthermia-induced convulsion. In this study, we examined the potential changes in NCX3 in the hippocampus and cerebrocortex of rats with hyperthermia-induced convulsion. METHODS: Twenty-one Sprague Dawley rats were randomly assigned to control group, convulsion-prone group and convulsion-resistant group (n = 7 in each group). Whole-cell patch-clamp method was used to record NCX currents. Both the Western blotting analysis and immunofluorescence labeling techniques were used to examine the expression of NCX3. RESULTS: NCX currents were decreased in rats after febrile convulsion. Compared to the control group, NCX3 expression was decreased by about 40% and 50% in the hippocampus and cerebrocortex of convulsion-prone rats, respectively. Furthermore, the extent of reduction in NCX3 expression seemed to correlate with the number of seizures. CONCLUSIONS: There is a significant reduction in NCX3 expression in rats with febrile convulsions. Our findings also indicate a potential link between NCX3 expression, febrile convulsion in early childhood, and adult onset of epilepsy.
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Córtex Cerebral/metabolismo , Febre/complicações , Hipocampo/metabolismo , Convulsões/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Animais , Regulação para Baixo , Feminino , Gravidez , Ratos , Ratos Sprague-Dawley , Convulsões/etiologiaRESUMO
The range-extended electric vehicle is proposed to improve the range anxiety drivers have of electric vehicles. Conventionally, a gasoline/diesel generator increases the range of an electric vehicle. Due to the zero-CO2 emission stipulations, utilizing fuel cells as generators raises concerns in society. This paper presents a novel charging strategy for fuel cell/battery electric vehicles. In comparison to the conventional switch control, a fuzzy control approach is employed to enhance the battery's state of charge (SOC). This approach improves the quick loss problem of the system's SOC and thus can achieve an extended driving range. Smooth steering experience and range extension are the main indexes for development of fuzzy rules, which are mainly based on the energy management in the urban driving model. Evaluation of the entire control system is performed by simulation, which demonstrates its effectiveness and feasibility.
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OBJECTIVE: To study the association between two single nucleotide polymorphisms (SNP), rs2295080 and rs2536, in mammalian target of rapamycin (mTOR) gene and the susceptibility to pediatric epilepsy. METHODS: A case- control study was performed on 480 children with epilepsy (116 cases of refractory epilepsy) and 503 healthy children. SNP rs2295080 and rs2536 in the mTOR gene were detected by polymerase chain reaction restriction and fragment length polymorphisms (PCR-RFLP). Genotype and allele frequencies of SNP rs2295080 and rs2536 were compared between the children with epilepsy and healthy controls. RESULTS: There were no significant differences in the genotype and allele frequencies of SNP rs2295080 between the children with epilepsy and healthy controls. There were no significant differences in the genotype frequencies of SNP rs2536 between the two groups either, but the frequency of G allele of SNP rs2536 was higher in children with epilepsy than that in healthy controls (P=0.042, OR=1.344, 95%CI: 1.010-1.789). CONCLUSIONS: SNP rs2536 of mTOR gene may be associated with the risk of pediatric epilepsy.
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Epilepsia/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Serina-Treonina Quinases TOR/genética , Epilepsia/etiologia , Frequência do Gene , Genótipo , Humanos , RiscoRESUMO
This study was aimed to investigate the molecular mechanism of doxorubicin resistance in multiple myeloma cell line and certify the effect of Notch signal over-expression on drug resistance of myeloma cells. The doxorubicin RPMI 8226 cell line (RPMI8226/DOX) was established by culturing 8226 cells with continuous low concentration and intermittent gradually-increasing-concentration of doxorubicin in vitro, the mRNA expression of Notch2,Jagged1, Jagged2, HES1 were measured by RT-PCR and the P-170 protein expression was detected by Western blot in RPMI 8226 cell line; the changes of IL-6 and VEGF were tested by ELISA. The results showed that the Notch mRNA expression (Notch2, Jagged1, Jagged2 increased gradually along with the increase of chemotherapeutic drug resistance, but the expression of HESI mRNA gradually decreased along with the increase of drug resistance. The expression level of P-170 protein was upregulated gradually along with the increase of drug resistance. The level of VEGF and IL-6 in culture supernatants of RPMI8226/DOX was higher than that in RPMI 8226. It is concluded that the establishment of RPMI 8226/DOX cell line is a useful model to analyze the mechanism of chemotherapeutic drug resistance in multiple myeloma, Notch activation is closely correlated with the drug resistance of multiple myeloma and Notch signaling may to be used as a new target for multiple myeloma treatment.
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Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo/patologia , Linhagem Celular Tumoral , Humanos , Interleucina-6 , Mieloma Múltiplo/metabolismo , Transdução de SinaisRESUMO
OBJECTIVE: To study the clinical features and mutations in methyl-CpG-binding protein 2 (MECP2) gene among children with classical Rett syndrome in China. METHODS: PCR and direct sequencing were employed to analyze the three exons of MECP2 gene in 9 children recently diagnosed with Rett syndrome and their parents. RESULTS: Heterozygous mutations were identified in 5 out of 9 patients, with a mutation rate of over 50%; there was one case of insert mutation (c.913insT) and 4 cases of missense mutation (exon 3: c.316C>T (R106W); exon 4: c.502C>T (R168X), c.808C>T (R270X), and c.1126C>T (P376S). A new mutation (c.913insT) was found. No mutations were detected in their parents. Two patients had MECP2 mutations in the transcriptional repression domain (TRD). They had almost lost language functions and were found to have significantly delayed development compared with other patients. CONCLUSIONS: Mutations in MECP2 gene were detected in 5 confirmed cases of Rett syndrome, and most of them were on exon 4. Mutations in the TRD of MECP2 protein may affect the language ability and development in children with Rett syndrome.
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Proteína 2 de Ligação a Metil-CpG/genética , Mutação , Síndrome de Rett/genética , Pré-Escolar , Feminino , Humanos , Lactente , Desenvolvimento da Linguagem , Síndrome de Rett/psicologiaRESUMO
Borders are important as they demarcate developing tissue into distinct functional units. A key challenge is the discovery of mechanisms that can convert morphogen gradients into tissue borders. While mechanisms that produce ultrasensitive cellular responses provide a solution, how extracellular morphogens drive such mechanisms remains poorly understood. Here, we show how Bone Morphogenetic Protein (BMP) and Fibroblast Growth Factor (FGF) pathways interact to generate ultrasensitivity and borders in the dorsal telencephalon. BMP and FGF signaling manipulations in explants produced border defects suggestive of cross inhibition within single cells, which was confirmed in dissociated cultures. Using mathematical modeling, we designed experiments that ruled out alternative cross inhibition mechanisms and identified a cross-inhibitory positive feedback (CIPF) mechanism, or "toggle switch", which acts upstream of transcriptional targets in dorsal telencephalic cells. CIPF explained several cellular phenomena important for border formation such as threshold tuning, ultrasensitivity, and hysteresis. CIPF explicitly links graded morphogen signaling in the telencephalon to switch-like cellular responses and has the ability to form multiple borders and scale pattern to size. These benefits may apply to other developmental systems.