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BACKGROUND: Influenza-Associated Encephalopathy/Encephalitis (IAE) is characterized by high incidence and poor prognosis. The aim of this study is to describe the clinical features and outcomes of IAE in pediatric patients. METHODS: We performed a retrospective review of hospitalized cases of laboratory-confirmed influenza infection between January 2018 and December 2021. Demographic, clinical, imaging, treatment and outcome data were collected. Statistical analysis was performed using SPSS software. RESULTS: Of 446 children hospitalized with influenza, 71 cases were identified with a diagnosis of IAE. The median age was 3 years and 46 (64.8 %) were younger than 5 years. Only one patient was vaccinated for seasonal influenza. 46 (64.8 %) patients had abnormal electroencephalogram examination and 47 (66.2 %) had abnormal brain MRI or CT findings. 68 (95.8 %) patients were treated with oseltamivir/peramivir. 12 (16.9 %) patients suffered mortality. Non-survivors were more likely to have lower Glasgow coma score (median 7), longer duration of fever (median 3 days), with underlying medical conditions (P = 0.006), and complications including sepsis (P = 0.003), shock (P < 0.001), respiratory failure (P = 0.006), acute renal failure (P = 0.001), myocardial damage (P < 0.001), coagulation disorders (P = 0.03), electrolyte disturbance (P = 0.001) and hyperlactacidemia (P = 0.003). Non-survivors had higher percentages of corticosteroids (P = 0.003) and immunoglobulin (P = 0.003) treatments compared to survivors. CONCLUSIONS: Children with IAE have a high mortality rate. Lower Glasgow coma score, longer duration of fever, with underlying medical conditions and complications pose a great risk to poor prognosis. Influenza vaccination is recommended to all eligible children.
Subject(s)
Influenza, Human , Humans , Female , Retrospective Studies , Male , Influenza, Human/complications , Child, Preschool , China/epidemiology , Child , Infant , Antiviral Agents/therapeutic use , Encephalitis, Viral , Oseltamivir/therapeutic use , Prognosis , Adolescent , Electroencephalography , Treatment Outcome , Magnetic Resonance ImagingABSTRACT
Background: After quarantine-related measures were completely lifted in China, the respiratory infection rate of children caused by Mycoplasma pneumoniae (MP) increased significantly, and MP infection may lead to rare severe intra- and extrapulmonary manifestation. Hemophagocytic lymphohistiocytosis (HLH) and diffuse alveolar hemorrhage (DAH) are life-threatening clinical syndromes. Timely recognition may contribute to timely treatment and an improved prognosis. Currently there are no reports of children with DAH secondary to MP infection complicated with HLH. Case presentation: We successfully treated a previously healthy school-aged child who was admitted to the pediatric intensive care unit with fever, cough, drowsiness, and progressive dyspnea. HLH was confirmed by clinical and testing criteria, DAH was indicated by computed tomography scan of the chest, and Mycoplasma antibody detection and endotracheal aspirates pathogen metagenomic next-generation sequencing (mNGS) confirmed MP infection. After invasive mechanical ventilation, antibiotics, and glucocorticoid treatment, the patient recovered well and was discharged. At follow-up, she did not experience any more initial symptoms. For the fourth consecutive month, all indexes remained normal. Conclusion: mNGS can be considered for identifying the causative agent of infection in patients with DAH and/or HLH. The clinical manifestations of DAH in children may only present as acute hypoxic respiratory failure, significantly decreased hemoglobin without bleeding elsewhere, and chest imaging findings may assist in the diagnosis of DAH. When MP infection is associated with hemocytopenia, HLH should be considered.
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Fusobacterium necrophorum (F. necrophorum) infection is rare in pediatrics. In addition, the detection time of F. necrophorum by blood culture is long, and the positive rate is low. Infection with F. necrophorum bacilli usually follows rapid disease progression, resulting in high mortality. In previous reports of F. necrophorum-related cases, the most dangerous moment of the disease occurred after the appearance of Lemierre's syndrome. We report an atypical case of a 6-year-old female patient who developed septic shock within 24 h of admission due to F. necrophorum infection in the absence of Lemierre's syndrome. F. necrophorum was identified in a blood sample by metagenomics next-generation sequencing (mNGS) but not by standard blood culture. The patient was finally cured and discharged after receiving timely and effective targeted anti-infection treatment. In the present case study, it was observed that the heightened virulence and invasiveness of F. necrophorum contribute significantly to its role as a primary pathogen in pediatric septic shock. This can precipitate hemodynamic instability and multiple organ failure, even in the absence of Lemierre's syndrome. The use of mNGS can deeply and rapidly identify infectious pathogens, guide the use of targeted antibiotics, and greatly improve the survival rate of patients.
Subject(s)
Lemierre Syndrome , Shock, Septic , Female , Humans , Child , Shock, Septic/diagnosis , Fusobacterium necrophorum/genetics , High-Throughput Nucleotide Sequencing , Anti-Bacterial Agents/therapeutic useABSTRACT
Objective: To evaluate the effect of scalp nerve block (SNB) on postoperative analgesia and stress response in patients undergoing craniotomy by meta-analysis. Methods: PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials involving SNB for elective craniotomy under general anesthesia from inception to August 1, 2022. Meta-analysis was performed using RevMan 5.4 and Stata MP17.0. Based on scalp block operation time (preoperative block, postoperative block), different control groups (no block, normal saline), local anesthetic types (bupivacaine, levobupivacaine, ropivacaine), the postoperative pain score at different time points was analyzed by subgroup analysis. Results: 23 studies involving 1515 patients were included. The combined results showed that SNB could significantly reduce the pain scores at all time points compared with the control group (P < .05). Subgroup analysis showed that the analgesic effect of preoperative scalp nerve block was better than that of postoperative block, and the effect of ropivacaine and levobupivacaine was better than bupivacaine. SNB could reduce morphine consumption within 48 hours after surgery (SMD = -1.51, 95% CI -2.80 -0.21, P = .02, I2 = 89%). The first rescue analgesia time was significantly longer in the SNB group than the control group (SMD = 0.57, 95% CI 0.16-0.99, P = .01, I2 = 68.76%). Compared with the control group, the levels of postoperative angiotensin, intraoperative blood glucose, and both intraoperative and postoperative cortisol levels were significantly decreased (P < .05). SNB can inhibit hemodynamic changes caused by surgical stimulation and effectively reduce the incidence of postoperative nausea and vomiting (RR = 0.71, 95% CI 0.51~0.97, P = .03). Conclusion: Scalp nerve block is an effective analgesic that reduces pain within 48 hours after craniotomy. It effectively inhibit the stress response caused by surgical stimulation, stabilize hemodynamics, and reduce the incidence of postoperative nausea and vomiting.
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Succinimide intermediates play the crucial role in the nucleation process for protein amyloid fibril formation, as they can usually induce a non-native conformation in a fraction of soluble proteins to render amyloidogenicity and neurotoxicity. Thus, in situ detection of succinimide intermediates during amyloid fibrillation kinetics is of considerable importance, albeit challenging, because these succinimides are generally unstable in physiological conditions. Here, we found an in situ Raman spectral fingerprint to trace the succinimide intermediates in amyloid fibril formation, wherein the carbonyl symmetric stretching of cyclic imide in the succinimide derivative is located at ca. 1790 cm-1. Using its intensity as an indicator of succinimide intermediates, we have in situ detected and unravelled the role of succinimide intermediates during the oligomer formation from the Bz-Asp-Gly-NH2 dipeptide or the amyloid fibrillation kinetics of lysozyme with thermal/acid treatment.
Subject(s)
Amyloid , Succinimides , Amyloid/chemistry , Succinimides/chemistry , KineticsABSTRACT
Background: Clinically, Carbapenem-resistant Pseudomonas aeruginosa (CRPA) meningitis is extremely difficult to cure and has a high mortality rate. Intrathecal injection of polymyxins B is suggested to be an effective anti-infective means to treat intracranial infection with CRPA. However, due to the potential drug toxicity of polymyxin B in children, this regimen has rarely been reported in pediatrics. Case Description: A 5-year-old male patient diagnosed with Epstein-Barr virus-induced hemophagocytic syndrome (HPS) exhibited persistent fever for over a month despite antibacterial and chemotherapy regimens. During hospitalization, the patient presented with unconsciousness, nystagmus, and myasthenia. Cerebrospinal fluid (CSF) analysis indicated elevated leukocyte counts and protein levels. Sputum and blood cultures, as well as metagenomic next-generation sequencing (mNGS) of CSF, identified CRPA. Intravenous and intrathecal polymyxin B administration resulted in temperature normalization and amelioration of consciousness disturbances and nystagmus. Subsequent CSF analysis yielded normal results, while polymyxin B treatment exhibited no nephrotoxicity or neurotoxicity. Conclusion: Intrathecal injection of polymyxin B in children with meningitis caused by CRPA is an effective treatment without remarkable adverse events.
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Heritable thoracic aortic aneurysms are complex conditions characterised by the dilation or rupture of the thoracic aorta, often occurring as an autosomal-dominant disorder associated with life-threatening complications. In this case report, we present a de novo variant, MFAP5 c.236_237insA (p.N79Kfs9), which is implicated in the development of inherited thoracic aortic aneurysm. The proband, a 15-year-old male, presented with recurrent cough, dull chest pain, chest distress, vomiting, and reduced activity tolerance, leading to the diagnosis of heritable thoracic aortic aneurysms. Whole-exome sequencing identified a novel heterozygous variant in MFAP5 (NM_003480, c.236_237insA, and p.N79Kfs9). MutationTester and PolyPhen-s predicted this variant to be damaging and disease-causing (probability = 1), while the SFIT score indicated protein damage (0.001). Structural analysis using the AlphaFold Protein structure database revealed that this mutation disrupted the N-linked glycosylation site, resulting in a frameshift, amino acid sequence alteration, and truncation of an essential protein site. To our knowledge, this is the first case report describing a young patient with heritable thoracic aortic aneurysm carrying the novel MFAP5 c.236_237insA (p.N79Kfs*9) variant. This variant represents the third identified mutation site associated with heritable thoracic aortic aneurysm. Given the high mortality and morbidity rates associated with thoracic aortic aneurysms, the prevention of severe and fatal complications is crucial in the clinical management of this condition. Our case highlights the importance of whole-exome sequencing and genetic screening in identifying potential pathogenic or likely pathogenic variants, particularly in early-onset patients with aortic dilation, to inform appropriate management strategies.
Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Male , Humans , Adolescent , Pedigree , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/genetics , Genetic Testing , MutationABSTRACT
In clinical trials, the responses of patients usually depend on the assigned treatment as well as some important covariates, which may cause heteroscedasticity in treatment responses. As clinical trials are generally designed to demonstrate efficacy for the overall population, they are usually not adequately powered for detecting interactions. To improve the power of interaction tests, this article develops two model-based adaptive randomization procedures for heteroscedasticity of treatment responses, and derives their limiting allocation proportions, which are generalizations of the Neyman allocation. Issues of hypothesis testing and sample size estimation are also addressed. Simulation studies show that compared with complete randomization, the two model-based randomization procedures have greater power to detect differences in systematic effects, main treatment effects and treatment-covariate interactions. In addition, the validity of limiting allocation proportion is also verified through simulations.
Subject(s)
Research Design , Humans , Random Allocation , Sample Size , Computer SimulationABSTRACT
RATIONALE: Pertussis is an acute respiratory infection that often occurs in the pediatric population, especially in infants under 3 months old. Bordetella pertussis is the causative agent of pertussis, which can lead to pneumonia, encephalopathy, and pulmonary hypertension, causing death in severe cases. Therefore, an accurate and comprehensive diagnosis of the pathogen is essential for effective treatment. PATIENT CONCERNS: We report a case of 2-month-old male infant admitted to the pediatric intensive care unit of West China Second University due to hoarse cough for 7 days, accompanied by a crowing-like echo, fever and listlessness, occasional nonprojectile vomiting with anorexia, shortness of breath, accelerated heart rate, cyanosis of the lips, and convulsions. B pertussis was identified by metagenomic next-generation sequencing in blood and cerebrospinal fluid and polymerase chain reaction assay using blood. DIAGNOSES: The infant was diagnosed with pertussis. INTERVENTIONS: Intravenous infusion of erythromycin (50 mg/kg/d) for anti-infection and dexamethasone for alleviating intracranial inflammatory reaction were given. OUTCOMES: The patient was eventually recovered and discharged. LESSONS: This case report emphasized the importance of metagenomic next-generation sequencing using cerebrospinal fluid and blood for early diagnosis of pertussis-associated encephalopathy.
Subject(s)
Brain Diseases , Respiratory Tract Infections , Whooping Cough , Infant , Humans , Child , Male , Whooping Cough/complications , Bordetella pertussis/genetics , Respiratory Tract Infections/complications , Brain Diseases/complications , High-Throughput Nucleotide SequencingABSTRACT
Variety testing is an indispensable and essential step in the process of creating new improved varieties from breeding to adoption. The performance of the varieties can be compared and evaluated based on multi-trait data from multi-location variety tests in multiple years. Although high-throughput phenotypic platforms have been used for observing some specific traits, manual phenotyping is still widely used. The efficient management of large amounts of data is still a significant problem for crop variety testing. This study reports a variety test platform (VTP) that was created to manage the whole workflow for the standardization and data quality improvement of crop variety testing. Through the VTP, the phenotype data of varieties can be integrated and reused based on standardized data elements and datasets. Moreover, the information support and automated functions for the whole testing workflow help users conduct tests efficiently through a series of functions such as test design, data acquisition and processing, and statistical analyses. The VTP has been applied to regional variety tests covering more than seven thousand locations across the whole country, and then a standardized and authoritative phenotypic database covering five crops has been generated. In addition, the VTP can be deployed on either privately or publicly available high-performance computing nodes so that test management and data analysis can be conveniently done using a web-based interface or mobile application. In this way, the system can provide variety test management services to more small and medium-sized breeding organizations, and ensures the mutual independence and security of test data. The application of VTP shows that the platform can make variety testing more efficient and can be used to generate a reliable database suitable for meta-analysis in multi-omics breeding and variety development projects.
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The purposes of this study are to extract the essence from the in-depth study of entrepreneurial spirit and the exploration of China's sports culture construction, find out the beneficial parts in line with China's sports culture construction, and put forward operational suggestions and countermeasures for dealing with the relationship between entrepreneurial spirit and sports culture to help China's sports culture construction move toward a new level. This exploration discusses the influence of entrepreneurial spirit on sports culture from the perspective of cognitive regulation, and explores the importance of entrepreneurial spirit from the aspects of social psychology, system, economy, and ethics. The structure of sports culture is analyzed, and the role of entrepreneurial spirit in promoting the construction of sports culture is expounded. Moreover, a questionnaire survey is conducted to investigate the impact of entrepreneurial spirit on the construction of sports culture from the cognitive regulation perspective. The results show that most people agree with the development of the entrepreneurial spirit and positively impact the promotion of entrepreneurial spirit. Most people are not satisfied with the attention and level of sports culture construction. In China's sports culture, the proportion of the entrepreneurial spirit is still tiny. Thereby, entrepreneurial spirit education must be vigorously promoted to enhance the integration of entrepreneurial spirit and sports culture. The entrepreneurial spirit needs to be introduced in the construction of sports culture. It is essential to do a good job in promoting entrepreneurial spirit, improving the supporting facilities related to sports culture and strengthening the correlation between sports culture and the entrepreneurial spirit. By discussing the influence of entrepreneurial spirit on sports culture, this exploration puts forward relevant opinions for developing sports culture. It is expected that they can have some reference values. This exploration provides new ideas for promoting the combination of sports culture construction and the dissemination of entrepreneurial spirit, which has crucial theoretical and practical significance.
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Background: Evidence-based clinical practice guidelines regarding high-flow nasal cannula (HFNC) use for respiratory support in critically ill children are lacking. Therefore, we aimed to determine the risk factors for early HFNC failure to reduce the failure rate and prevent adverse consequences of HFNC failure in children with acute respiratory dysfunction. Methods: Demographic and laboratory data were compared among patients, admitted to the pediatric intensive care unit between January 2017 and December 2018, who were included in a retrospective cohort study. Univariate and multivariate analyses were performed to determine risk factors for eventual entry into the predictive model for early HFNC failure and to perform an external validation study in a prospective observational cohort study from January to February 2019. Further, the association of clinical indices and trends pre- and post-treatment with HFNC treatment success or failure in these patients was dynamically observed. Results: In total, 348 pediatric patients were included, of these 282 (81.0%) were included in the retrospective cohort study; HFNC success was observed in 182 patients (64.5%), HFNC 0-24 h failure in 74 patients (26.2%), and HFNC 24-48 h failure in 26 patients (9.2%). HFNC 24 h failure was significantly associated with the pediatric risk of mortality (PRISM) III score [odds ratio, 1.391; 95% confidence interval (CI): 1.249-1.550], arterial partial pressure of carbon dioxide-to-arterial partial pressure of oxygen (PaCO2/PaO2) ratio (odds ratio, 38.397; 95% CI: 6.410-230.013), and respiratory rate-oxygenation (ROX) index (odds ratio, 0.751; 95% CI: 0.616-0.915). The discriminating cutoff point for the new scoring system based on the three risk factors for HFNC 24 h failure was ≥ 2.0 points, with an area under the receiver operating characteristic curve of 0.794 (95% CI, 0.729-0.859, P < 0.001), sensitivity of 68%, and specificity of 79%; similar values were noted on applying the model to the prospective observational cohort comprising 66 patients (AUC = 0.717, 95% CI, 0.675-0.758, sensitivity 83%, specificity 44%, P = 0.009). In this prospective cohort, 11 patients with HFNC failure had an upward trend in PaCO2/PaO2 ratio and downward trends in respiratory failure index (P/F ratio) and ROX index; however, opposite directions of change were observed in 55 patients with HFNC success. Furthermore, the fractional changes (FCs) in PaCO2/PaO2 ratio, P/F ratio, percutaneous oxygen saturation-to-fraction of inspired oxygen (S/F) ratio, and ROX index at 2 h post-HFNC therapy onset were statistically significant between the two groups (all, P < 0.05). Conclusion: In the pediatric patients with acute respiratory insufficiency, pre-treatment PRISM III score, PaCO2/PaO2 ratio, and ROX index were risk factors for HFNC 24 h failure, and the direction and magnitude of changes in the PaCO2/PaO2 ratio, P/F ratio, and ROX index before and 2 h after HFNC treatment were warning indicators for HFNC 24 h failure. Further close monitoring should be considered for patients with these conditions.
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Background: An anomalous aortic origin of a coronary artery (AAOCA) has been considered as a dominant cause of sudden cardiac death (SCD) among young age children. Therefore, it is critical to identify AAOCA timely to avoid lethal events. Recently, accumulating cases of right or left coronary arteries originating from inappropriate locations at the sinus of Valsalva have been identified. Here, we report a rare case of AAOCA with an intra-arterial wall course pretending normal migration on imaging screening in a patient who suffered from syncope. Case summary: A 7-year-old male without a previous history of cardiovascular and cerebrovascular diseases suddenly suffered from sharp chest pain and syncope after intensive exercise. The electrocardiogram showed that the ST segment of multiple leads was depressed by more than 0.05 mV, and biomarkers indicated severe myocardial injuries. The left ventricular ejection fraction (LVEF) decreased dramatically to 23%. Fulminant myocarditis and cardiomyopathy were therefore excluded. However, a relatively normal coronary artery origin, which arose from the left coronary sinus, presented on echocardiography and cardiac CT angiography (CTA). It is difficult to draw an association between severe clinical manifestations and slight malformations on echocardiography and CTA. Furthermore, selective coronary angiography revealed that an anomalous left coronary artery arose from the superior margin of the inappropriate sinus, developed an intramural wall course and finally exits the left sinus of Valsalva and migrated between the aorta and the pulmonary artery, which induced severe myocardial infarction during exercise. Then, the patient received surgical correction with a modified unroofing procedure. After 2 months of intensive treatment, the patient was discharged and remained asymptomatic through 18 months of follow-up. Conclusion: AAOCA, especially anomalous left coronary artery (ALCA), represents a major potential risk of SCD. We reported an atypical manifestation of ALCA arising from the inappropriate sinus of Valsalva and merging into the intra-arterial wall to develop a strange course and then sprout between the aorta and the pulmonary artery. The diversity of AAOCA might present as a relatively normal course under non-invasive radiological imaging scanning.
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BACKGROUND: Intravenous immunoglobulin (IVIG) resistance and cardiovascular complications prediction are pivotal topic of interests in Kawasaki disease (KD). The prognostic nutritional index (PNI) has been proposed to be valuable in predicting the severity of inflammatory status and prognosis in clinical circumstances, with limited data in KD. Therefore, we prospectively investigated the role of sampling-time specific PNI cut-off values in predicting initial IVIG resistance as well as cardiovascular complications in patients with KD for the first time. METHODS: A total of 755 patients with KD were prospectively recruited between January 2015 and December 2019. Patients with KD were subgrouped based on the presence of IVIG resistance or cardiovascular complications. The clinical and laboratory parameters were compared. Multivariate logistic regression analysis was performed to identify the independent risk factors for IVIG resistance and cardiovascular complications. The receiver operating characteristic (ROC) curve was further applied to assess the predictive values of PNI in IVIG resistance and cardiovascular complications. RESULTS: The lower level of PNI was identified as independent risk factors for initial IVIG resistance and cardiovascular complications. The discriminating cut-off values of the PNI for IVIG resistance, all cardiovascular complications, CALs, KDSS and myocarditis were 47.8, 52.2, 38.6, 48.2 and 52.0, with the corresponding sensitivities of 0.573, 0.679, 0.174, 0.750, 0.851, and specificities of 0.753, 0.549, 0.957, 0.679 and 0.576, respectively. After sampling time stratification, the sensitivities and specificities of the PNI obtained at the sixth day from fever onset for prediction of both IVIG resistance (0.778, 0.787) and all cardiovascular complications (0.667, 0.753) remarkably improved. CONCLUSION: PNI may serve as a promising predictor for KDSS in patients with KD. PNI obtained at sixth day from fever onset possess good predictive power for both IVIG resistance and all cardiovascular complications in KD.
Subject(s)
Heart Diseases , Mucocutaneous Lymph Node Syndrome , Fever/drug therapy , Heart Diseases/drug therapy , Humans , Immunoglobulins, Intravenous/therapeutic use , Infant , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , Nutrition Assessment , Prognosis , Retrospective StudiesABSTRACT
In this paper, the predefined-time synchronization of competitive neural networks (CNNs) is researched based on two different predefined-time stability theorems. In view of the bilayer structure of CNNs, we design two bilayer predefined-time controllers. The first controller utilizes sign function, while the second controller utilizes exponential function and Lyapunov function. In these two controllers, the predefined time is set as a controller parameter, and it can be an arbitrary positive constant. Under these two controllers, the considered CNNs can achieve synchronization within the predefined time regardless of the initial values. A specific example is presented to validate the theoretical results.
Subject(s)
Algorithms , Neural Networks, Computer , Time FactorsABSTRACT
Quantum entanglement and correlations in the spin-1 Heisenberg chain with single-ion anisotropy are investigated using the quantum renormalization group method. Negativity and quantum discord (QD) are calculated with various anisotropy parameters â³ and single-ion anisotropy parametersD. We focus on the relations between two abovementioned physical quantities and on transitions between the Néel, Haldane, and large-Dphases. It is found that both negativity and QD exhibit step-like patterns in different phases as the size of the system increases. Interestingly, the single-ion anisotropy parameterD, which can be modulated using nuclear electric resonance (2020Nature579205), plays an important role in tuning the quantum phase transition (QPT) of the system. Both the first partial derivative of the negativity and QD with respect toDor â³ exhibit nonanalytic behavior at the phase transition points, which corresponds directly to the divergence of the correlation length. The quantum correlation critical exponents derived from negativity and QD are equal, and are the reciprocal of the correlation length exponent at each critical point. This work extends the application of quantum entanglement and correlations as tools for depicting QPTs in spin-1 systems.
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Objective To observe the effects of DNA methyltransferase 3B (DNMT3B) on the expression of secreted frizzled-related protein 1 (SFRP1) and regulation of Wnt/ß-catenin signaling pathway in renal tubular epithelial cells (RTECs) of mice under high glucose conditions. Methods in vitro cultured mouse RTECs were divided into normal glucose (NG) group and high glucose (HG) group. After DNMT3B short-hairclip RNA (sh-DNMT3B) and DNMT3B over-expression (DNMT3B-OE) plasmids were transfected separately into RTECs, mRNA expression of DNMT3B, SFRP1, collagen IV (Col4) and fibronectin (FN) were detected by reverse-transcription PCR. Protein expression of DNMT3B, SFRP1, glycogen synthase kinase 3ß (GSK3ß), phosphorylated glycogen synthase kinase 3ß (p-GSK3ß), ß-catenin, Col4 and FN were detected by Western blotting. The localization of DNMT3B and SFRP1 in RTECs was observed by immunofluorescence cytochemistry combined with confocal microscopy. Results Compared with the NG group, the protein expression of DNMT3B, ß-catenin, p-GSK3ß, Col4 and FN increased in the HG group, while SFRP1 protein expression was reduced in the HG group. Compared with the sh-vector group, SFRP1 mRNA and protein expression increased in the sh-DNMT3B group, while the expression of ß-catenin, p-GSK3ß and Col4 proteins decreased. FN mRNA and protein expression dropped in the sh-DNMT3B group, however, the expression of ß-catenin mRNA did not change significantly. Visually, DNMT3B over-expression reversed the above changes. Both DNMT3B and SFRP1 were expressed in the nucleus and cytoplasm of RTECs, and DNMT3B was aggregated in the nuclei of the cells in the HG group and the co-localization between DNMT3B and SFRP1 was also promoted in the HG group. Conclusion The expression of DNMT3B increases and the expression of SFRP1 decreases when the mouse RTECs were stimulated by HG. This subsequently leads to the activation of the Wnt/ß-catenin signaling pathway and promotes the formation of extracellular matrix.
Subject(s)
DNA (Cytosine-5-)-Methyltransferases , Epithelial Cells , Wnt Signaling Pathway , Animals , DNA (Cytosine-5-)-Methyltransferases/metabolism , Epithelial Cells/metabolism , Fibrosis , Glucose , Glycogen Synthase Kinase 3 beta/genetics , Mice , beta Catenin/genetics , beta Catenin/metabolism , DNA Methyltransferase 3BABSTRACT
A well-known issue when testing for treatment-by-subgroup interaction is its low power, as clinical trials are generally powered for establishing efficacy claims for the overall population, and they are usually not adequately powered for detecting interaction (Alosh, Huque, & Koch [2015] Journal of Biopharmaceutical Statistics, 25, 1161-1178). Hence, it is necessary to develop an adaptive design to improve the efficiency of detecting heterogeneous treatment effects within subgroups. Considering Neyman allocation can maximize the power of usual Z-test (see p. 194 of the book edited by Rosenberger and Lachin), we propose a subgroup-adaptive randomization procedure aiming to achieve Neyman allocation in both predefined subgroups and overall study population in this paper. To verify whether the proposed randomization procedure works as intended, relevant theoretical results are derived and displayed . Numerical studies show that the proposed randomization procedure has obvious advantages in power of tests compared with complete randomization and Pocock and Simon's minimization method.