Optimized strategy to improve the outcomes of acute type A aortic dissection with malperfusion syndrome.

BACKGROUND: The mortality of acute type A aortic dissection (ATAAD) with malperfusion syndrome (MPS) is high. However, the management strategy remains controversial. We aimed to evaluate the strategy for MPS at our institution. METHODS: Among 724 patients with ATAAD, 167 patients with MPS were treated with immediate central repair (first stage) or an optimized strategy (second stage). In the second stage, the optimized strategy used was based on 6-hour threshold from symptom onset. For MPS with symptom onset within 6 hours, immediate central repair was performed, followed by endovascular reperfusion if malperfusion persisted. With symptom onset beyond 6 hours, individualized delayed central repair was performed. We compared outcomes between the first and second stages. RESULTS: The in-hospital mortality of ATAAD was significantly decreased when the optimized strategy was used (4.3% in the second stage vs 12.5% in the first stage; P < .01). In the second stage, the in-hospital mortality for MPS was decreased (10.2% vs 33.9%; P < .01). Moreover, the in-hospital mortality for MPS with symptom onset within 6 hours and beyond 6 hours decreased from 24% to 7.5% and from 41.2% to 11.8%, respectively. The operative mortality of MPS in the second stage was comparable to that in patients without MPS (4.0% vs 2.4%; P > .05). CONCLUSIONS: The optimized strategy significantly improved the outcomes of MPS. The 6-hour threshold from symptom onset could be very useful in determining the timing of central repair. For patients with MPS symptom onset within 6 hours, immediate central repair is reasonable; for those with symptom onset beyond 6 hours, individualized delayed central repair should be considered.

NCDN is a Potential Biomarker and Therapeutic Target for Glioblastoma.

Background: Glioblastoma (GBM) is a type of central nervous system malignancy. In our study, we determined the effect of NCDN in GBM patients through The Cancer Genome Atlas (TCGA) data analysis, and studied the effects of NCDN on GBM cell function to estimate its potential as a therapeutic target. Methods: Gene expression profiles of glioblastoma cohort were acquired from TCGA database and analyzed to look for central genes that may serve as GBM therapeutic targets. Then the cell function of NCDN in glioblastoma cell was explored through in vitro cell experiments. Results: Through gene ontology (GO) analysis, weighted gene co-expression network analysis (WGCNA), and survival analysis, we identified three key genes (NCDN, PAK1 and SPRYD3) associated with poor prognosis in glioblastoma. In vitro experiments showed impaired cell migration, apoptosis, and cell cycle arrest in NCDN knockdown cells. Conclusion: NCDN affects the progress and prognosis of glioblastoma by promoting cell migration and inhibiting apoptosis.

LRRC1 knockdown downregulates MACF1 to inhibit the malignant progression of acute myeloid leukemia by inactivating ß-catenin/c-Myc signaling.

Acute myeloid leukemia (AML) is a hematologic disease associated with genetic abnormalities. This study aimed to explore the role of leucine-rich repeat-containing protein 1 (LRRC1) in the malignant activities of AML and to reveal the molecular mechanism related to microtubule actin cross-linking factor 1 (MACF1). GEPIA database was used to analyze the expression of LRRC1 in bone marrow tissues of AML patients and the correlation between LRRC1 expression and survival analysis. LRRC1 was knocked down to assess the change of AML cell proliferation, cell cycle and apoptosis using CCK-8 assay and flow cytometry. Besides, the contents of extracellular acidification and oxygen consumption rates were measured to evaluate the glycolysis. Additionally, the interaction between LRRC1 and MACF1 predicted by MEM database and was verified by co-immunoprecipitation (Co-IP) assay. Then, MACF1 was overexpressed to conduct the rescue experiments. Expression of proteins in ß-catenin/c-Myc signaling was detected by western blot. Finally, AML xenograft mouse model was established to observe the impacts of LRRC1 silencing on the tumor development. Notably upregulated LRRC1 expression was observed in bone marrow tissues of AML patients and AML cells, and patients with the higher LRRC1 expression displayed the lower overall survival. LRRC1 depletion promoted cell cycle arrest and apoptosis and inhibited the glycolysis. Co-IP confirmed the interaction between LRRC1 and MACF1. MACF1 upregulation relieved the impacts of LRRC1 knockdown on the malignant activities of AML cells. Moreover, LRRC1 silencing inhibited the development of xenograft tumor growth of HL-60 cells in nude mice, suppressed MACF1 expression and inactivated the ß-catenin/c-Myc signaling. Collectively, LRRC1 knockdown suppressed proliferation, glycolysis and promoted apoptosis in AML cells by downregulating MACF1 expression to inactivate ß-catenin/c-Myc signaling.

Effects of Blood Hemoadsorption Therapy with HA-380 in Total Arch Replacement for Acute Type A Aortic Dissection: A Retrospective Observational Study.

INTRODUCTION: This study aimed to evaluate whether the addition of a hemoadsorption (HA) cartridge, HA-380, in the cardiopulmonary bypass (CPB) circuit in acute type A aortic dissection (ATAAD) surgery reduced inflammatory cytokine levels and decreased postoperative complications. METHODS: A retrospective observational cohort study was conducted between March 1, 2021, and February 28, 2022. Patients with ATAAD undergoing emergent total arch replacement surgery were divided into the control (CON) and HA groups on the basis of the addition of the HA-380 cartridge in the CPB circuit. RESULTS: Overall, 121 patients met the eligibility criteria; 2 patients in each group who died within the first postoperative week were excluded. Further, 57 and 60 patients in the CON and HA groups, respectively, were included in the pooled analysis. The major perioperative data, baseline values of interleukin-6 (IL-6) and C-reactive protein, and therapeutic interventions were similar in the two groups (all, p > 0.05). The serum IL-6 levels increased more rapidly in the CON group than those in the HA group postoperatively (205.73 ± 174.72 vs. 146.13 ± 64.15 pg/mL, p = 0.020). The HA group had a lower incidence of postoperative acute kidney injury (AKI) and severe acute respiratory distress syndrome than the CON group (25.4 vs. 44.6%, p = 0.032 and 18.3 vs. 35.1%, p = 0.040, respectively). Logistic regression analyses showed that HA may be a protective factor against postoperative AKI. The incidence of bleeding, delirium, and stroke as well as the lengths of intensive care unit and hospital stay in both groups were similar (all, p > 0.05). CONCLUSIONS: The use of HA-380 in the CPB circuit may attenuate inflammatory response and reduce major complications following ATAAD surgery. HA may be associated with lower rate of postoperative AKI.

Management Strategies for Acute Type A Aortic Dissection Complicated By Limb Malperfusion.

BACKGROUND: Acute type A aortic dissection complicated by limb malperfusion presents a risk of mortality to the patients. Debates exist regarding management, whether focused on reperfusion first or immediate repair. Here, we aimed to describe our experience with the management of acute type A aortic dissection (ATAAD) complicated by limb malperfusion. METHODS: From January 1, 2020 to December 31, 2021, 22 consecutive patients were admitted to Xiamen Cardiovascular Hospital, due to acute type A aortic dissection complicated by limb malperfusion. All perioperative variables were recorded and analyzed. Limb malperfusion was diagnosed, according to the clinical symptoms, computed tomography angiography, and laboratory test. We adopted the clinical categories of acute limb ischemia to stratify severity of limb ischemia. Surgery strategies are as follows: Reperfusion first followed by central repair, immediate central repair, and immediate central repair followed by stenting. RESULTS: There were 21 males and one female with an average of 53.3±11.7 years. Management strategies were as follows: immediate central repair using total arch replacement with frozen elephant trunk in 15 patients, endovascular stenting followed by central repair in four patients, and endovascular stenting after central repair in two patients. The average extracorporeal circulation time was 258.8 ± 70.5 min; the average aortic cross-clamp time was 177.9 ± 54.2 min; and the average circulatory arrest time was 45.5 ± 13.1 min. The early mortality rate was 13.6% (3/22). Two patients left the hospital voluntarily, due to cerebral infarction and bleeding. One patient underwent fasciotomy for osteofascial compartment syndrome and uneventfully was discharged. Six patients underwent continuous renal replacement therapy and hemoperfusion. CONCLUSION: Central repair is safe and feasible for ATAAD complicated with limb malperfusion. For serious limb malperfusion, endovascular stenting followed by central repair is a good choice with continuous renal replacement therapy (CRRT) and hemoperfusion. Hospital mortality rate is high in cases with multiple organ malperfusion.

ADSC-Exosomes Alleviate MTX-induced Rat Neuronal Damage by Activating Nrf2-ARE Pathway.

The aim of this study was to analyze the efficacy and underlying mechanism of adipose-derived mesenchymal stem cell exosome (ADSC-exosomes)-mediated protection on methotrexate (MTX)-induced neuronal damage. We established a H2O2-induced oxidative stress model in vitro, as well as an MTX-induced neuronal damage rat model in vivo. We analyzed the effects of ADSC-exosomes on neuronal damage and Nrf2-ARE signaling pathway in rats and related mechanisms. The morphological and functional recovery of rat hippocampal neurons by ADSC-exosomes was examined by Nissl staining and modified neurological severity score (mNSS) score. The activation of Nrf2-ARE pathway effectively inhibited H2O2-induced oxidative stress. ADSC-exosomes treatment restored the activity of hippocampal neuronal cells, reduced ROS production, and inhibited hippocampal neuronal cells apoptosis. In in vivo experiments, ADSC-exosomes ameliorates MTX-induced hippocampal neuron damage by triggering Nrf2-ARE pathway, decreasing IL-6, IFN-, and TNF-a levels and TUNEL positive cells in hippocampus, and repairing hippocampal neuronal cell damage. ADSC-exosomes ameliorated MTX-induced neuronal damage and suppressed oxidative stress induced by neuronal damage through the activation of Nrf2-ARE signaling pathway.

Decitabine combined with minimally myelosuppressive therapy for induction of remission in pediatric high-risk acute myeloid leukemia with chromosome 5q deletion: a report of three cases.

Cases of pediatric acute myeloid leukemia (AML) with complex karyotypes including chromosome 5 abnormalities are rare and have a very poor prognosis. Management of AML with monosomy 5/del(5q) has been inconsistent. We treated three adolescents with this AML subtype using combined low-dose cytarabine and mitoxantrone, concurrently with decitabine and G-CSF, for remission induction. Decitabine was also included in the conditioning regimen before hematopoietic cell transplantation (HCT). All three patients achieved complete remission after treatment with this combination therapy. The treatment was well tolerated, and the patients are alive and free of disease at 3.6, 3.2, and 3.0 years after HCT, respectively.

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Investigation of the Relationship between CMYC Gene Polymorphisms and Glioma Susceptibility in Chinese Children.

Glioma is a common central nervous system tumors in children. CMYC has a range of functions that are disrupted in various tumor cells, and may contribute to the occurrence and development of glioma. Two CMYC single nucleotide polymorphisms (rs4645943C>T and rs2070583 A>G) were genotyped in 190 cases and 248 controls from Wenzhou and Guangzhou hospitals. After adjusting for age and sex, odds ratio and 95% confidence interval values were calculated by logistic regression to evaluate the correlation between CMYC gene polymorphisms and glioma risk; no significant associations were detected. These results require future validation in a larger sample cohort.

Isochromosome 11q is Associated with Unique Characteristics and Poor Prognosis in Patients with Acute Myeloid Leukemia.

BACKGROUND: Isochromosome 11q in patients with acute myeloid leukemia is rarely reported, and little is known about its main features. METHODS: The presence of isochromosome 11q was identified in four patients (three adults and one child) from screening 441 patients with an acute myeloid leukemia diagnosis between 2009 and 2018 by using R-banding and fluorescence in situ hybridization. RESULTS: The child, patient 1 with unreported isochromosome (partial 11q isochromosome), accompanied with t(1;11) translocation, initially achieved remission after receiving chemotherapy. However, 4 months later this patient experienced a relapse. While multiple treatments were tried, it had no effect and the patient survived for 16 months. The remaining patients with isochromosome 11q exhibited numerical/structural chromosomal abnormal-ities involving myelodysplastic syndrome-related chromosomes 5, 7, 8, and 20. In patients 2 and 3, we found a derivative chromosome 21. Patient 3 was newly diagnosed with acute myeloid leukemia and was treated with many chemotherapy protocols, unfortunately with no effect. The patient then received traditional Chinese medicine and survived for 10 months, although she still has not achieved complete remission. Patients 2 and 4 received chemotherapy but experienced rapid disease progression and died within 2 months. CONCLUSIONS: In summary, patients with isochromosome 11q/partial 11q isochromosome have a poorer prognosis, especially for isochromosome 11q. Furthermore, these chromosome aberrations may be risk factors for the presence of isochromosome 11q or myelodysplastic syndrome-related genes, both of them may be associated with a failure to respond to treatment and poor outcomes. Hence, these discoveries may lay a foundation to study mechanisms and explore treatments.

Pharmacokinetics and Bioequivalence of Rasagiline Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions: An Open, Randomized, Single-Dose, Double-Cycle, Two-Sequence, Crossover Trial.

Objective: This study evaluated the pharmacokinetics, safety, and bioequivalence (BE) of two formulations of rasagiline tablets in healthy Chinese subjects under fasting and fed conditions. Methods: An open, randomized, single-dose, double-cycle, two-sequence, self-crossover pharmacokinetic study in healthy Chinese subjects under fasting and high-fat postprandial conditions was performed. A total of 108 healthy subjects (36 in the fasting group and 72 in the postprandial group) were recruited. In each cycle of the study under both conditions, subjects received a single oral dose of 1 mg of a test or reference preparation of rasagiline tablets (1 mg each). A washout period of 3 days was observed. Blood samples were obtained up to 10 h post-intake. Primary endpoints were the BE of major pharmacokinetic parameters (AUC0-t and AUC0-∞) and the maximum observed serum concentration (Cmax). Secondary endpoints were safety parameters. Results: The 90% confidence interval (CI) of the geometric mean ratio (GMR) of the test drug vs. the reference drug for rasagiline was 94.16-105.35% for the AUC0-t under fasting conditions and 99.88-107.07% under postprandial conditions. The 90% CIs for the AUC0-∞ were 93.55-105.01% and 99.59-107.05% under fasting and postprandial conditions, respectively. The 90% CIs for the Cmax were 88.26-108.46% and 89.54-118.23% under fasting and postprandial conditions, respectively. The 90% CIs for the test/reference AUC ratio and Cmax ratio were within the acceptable range (0.80-1.25) for BE. In this BE study, there were no serious adverse events (AEs). Conclusion: BE between the test and the reference products was established in both fasting and postprandial conditions. The two formulations of rasagiline showed good tolerability and a similar safety profile. Clinical Trial Registration: chinaDrugtrials.org.cn, identifier CTR20181466.

Multiple cross displacement amplification-a more applicable technique in detecting Pseudomonas aeruginosa of ventilator-associated pneumonia (VAP).

BACKGROUND: Early and rapid identification of Pseudomonas aeruginosa (P. aeruginosa) in patients with suspected ventilator-associated pneumonia (VAP) provides theoretical clinical advantages in therapeutic optimization strategies. METHODS: The P. aeruginosa-multiple cross displacement amplification (PA-MCDA) assay was conducted at an isothermal temperature during the amplification stage, and products were visually detected by color changes. The entire process was completed within 1 h. A total of 77 strains, including P. aeruginosa species and various other species of non-P. aeruginosa, were used to evaluate PA-MCDA assays. Bronchoalveolar lavage fluid (BALF) of suspected VAP patients was examined by the MCDA assay. RESULTS: The MCDA assay exhibited a 100% analytical specificity in detecting PA from all 77 strains, and the limit of detection was as low as 100 fg DNA per reaction. A temperature of 65 °C was recommended as standard during the amplification stage. The agreement between PA-MCDA and bacteria culture was 91.18% (κ = 0.787; p = 0.000) in the identification of P. aeruginosa in BALF from suspected VAP. The PA-MCDA assay showed values of 92.31%, 90.78%, 77.41%, and 97.18% for sensitivity, specificity, positive predictive value, and negative predictive value, respectively. PA-MCDA had a higher detective rate of P. aeruginosa than bacteria culture in patients with antipseudomonal therapy. CONCLUSIONS: The instrument-free platform of the MCDA assay makes it a simple, rapid, and applicable procedure for "on-site" diagnosis and point-of-care testing for the presence of P. aeruginosa without the need for specific bacterial culture.

Association of asparaginase-associated pancreatitis and ULK2 gene polymorphism.

The purpose of the study was to analyze the clinical characteristics and the course of diagnosis and therapy of asparaginase-associated pancreatitis (AAP) in childhood, improve the ability of diagnosis and treatment, and evaluate ULK2 gene polymorphism as a predictive factor for AAP. Data of 12 patients with childhood AAP were reviewed. Sanger sequencing of ULK2 gene was performed in AAP group (n=12) and control group (n=146). The main symptoms of AAP were abdominal pain and vomiting. Generally, the levels of amylase and lipase in the serum peaked within 72 h. Abdominal ultrasonography was performed in 11 patients; seven patients exhibited findings of pancreatic enlargement. Computed tomography was performed in 9 patients. Five patients exhibited findings of pancreatic enlargement and peri-pancreatic exudation. All patients were managed by fasting at the early stage, and seven patients underwent placement of a nasojejunal tube to receive enteral nutrition. One patient underwent endoscopic retrograde cholangiopancreatography (revealing dilation of the pancreatic duct) and endoscopic retrograde pancreatic drainage. Another patient developed signs of shock and received continuous renal replacement. There were no deaths caused by AAP. Therefore, early identification of patients at risk of AAP is of great importance. In addition, repeated elevation in the levels of pancreatic enzymes is indicative of complications. Sanger sequencing analysis of ULK2 gene showed that there was a significant difference of EXON1: -493C>T and EXON1: -308C>G between the AAP group and control group (P<0.0001). Thus, ULK2 gene polymorphism may be associated with the development of AAP. However, more validation of this finding is needed.

The association of miR34b/c and TP53 gene polymorphisms with Wilms tumor risk in Chinese children.

Wilms tumor is the most common pediatric malignancy in the kidney. The miR34b/c is a downstream target gene of the transcription factor p53. The important role of TP53 mutations, the methylation of miR34b/c, and the interaction between these two molecules in tumorigenesis have been well documented. Due to the biological connection between p53 and miR34b/c, in the present study, we investigated the association between polymorphisms in these two molecules and Wilms tumor susceptibility through genotyping two important functional polymorphisms (miR34b/c rs4938723 T>C and TP53 rs1042522 C>G) in 183 cases and 603 controls. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from the logistic regression analysis were used to assess the correlation of miR34b/c rs4938723 and TP53 rs1042522 polymorphisms with Wilms tumor risk. Our results indicated that the association of miR34b/c rs4938723 and TP53 rs1042522 polymorphisms with Wilms tumor susceptibility was not statistically significant. Stratified analysis by age, gender, and clinical stage, as well as combined effect analysis were also performed, yet, no significant association was found. In conclusion, our study indicated a lack of association between the two selected polymorphisms and Wilms tumor susceptibility. Our findings need to be verified in studies with larger sample size in the future.

Sub-60 mV per decade switching in ion-gel-gated In-Sn-O transistors with a nano-thick charge trapping layer.

In this paper, we present a new method for reducing the subthreshold swing (SS) of ionic-modulated oxide field-effect transistors (FETs) below 60 mV per decade. The electrical performances of ion gel-gated In-Sn-O FETs with and without a nano-thick Al2O3 charge trapping layer are compared and studied. A significant SS reduction in the In-Sn-O FETs is observed when naturally oxidized Al2O3 and an ion gel are used as the gate stacking dielectric layer. The back sweep SS reaches as low as ∼27 mV per decade and extends over three orders of magnitude in drain current. A theoretical explanation for these results based on energy band diagrams is presented. The proposed devices described here have the potential to open up new avenues for further development of low power electronics, as well as for energy efficient memristive devices and synaptic electronics.

Ultrasonographic optic nerve sheath diameter correlation with ICP and accuracy as a tool for noninvasive surrogate ICP measurement in patients with decompressive craniotomy.

OBJECTIVE: Increased intracranial pressure (ICP) results in enlarged optic nerve sheath diameter (ONSD). In this study the authors aimed to assess the association of ONSD and ICP in severe traumatic brain injury (TBI) after decompressive craniotomy (DC). METHODS: ONSDs were measured by ocular ultrasonography in 40 healthy control adults. ICPs were monitored invasively with a microsensor at 6 hours and 24 hours after DC operation in 35 TBI patients. ONSDs were measured at the same time in these patients. Patients were assigned to 3 groups according to ICP levels, including normal (ICP ≤ 13 mm Hg), mildly elevated (ICP = 14-22 mm Hg), and severely elevated (ICP > 22 mm Hg) groups. ONSDs were compared between healthy control adults and TBI cases with DC. Then, the association of ONSD with ICP was analyzed using Pearson's correlation coefficient, linear regression analysis, and receiver operator characteristic curves. RESULTS: Seventy ICP measurements were obtained among 35 TBI patients after DC, including 25, 27, and 18 measurements in the normal, mildly elevated, and severely elevated ICP groups, respectively. Mean ONSDs were 4.09 ± 0.38 mm in the control group and 4.92 ± 0.37, 5.77 ± 0.41, and 6.52 ± 0.44 mm in the normal, mildly elevated, and severely elevated ICP groups, respectively (p < 0.001). A significant linear correlation was found between ONSD and ICP (r = 0.771, p < 0.0001). Enlarged ONSD was a robust predictor of elevated ICP. With an ONSD cutoff of 5.48 mm (ICP > 13 mm Hg), sensitivity and specificity were 91.1% and 88.0%, respectively; a cutoff of 5.83 mm (ICP > 22 mm Hg) yielded sensitivity and specificity of 94.4% and 81.0%, respectively. CONCLUSIONS: Ultrasonographic ONSD is strongly correlated with invasive ICP measurements and may serve as a sensitive and noninvasive method for detecting elevated ICP in TBI patients after DC.

High-performance solar-blind SnO2 nanowire photodetectors assembled using optical tweezers.

One-dimensional semiconducting SnO2 nanowires with wide bandgaps are promising candidates to build many important optoelectronic devices. Because building these devices involves the assembly of nanowires into complex structures, manipulation of the active materials needs to be done with high spatial precision. In this paper, an optical tweezer system, comprising a spatial light-modulator, a microscope, and optical elements, is used to individually trap, transfer, and assemble SnO2 nanowires into two-terminal photodetectors in a liquid environment. After the assembly using optical trapping, the two ends of the SnO2 nanowire photodetectors, which are connected with the electrodes, were further stabilized using a focused laser. During exposure to 275 nm deep-ultraviolet light, the as-assembled photodetectors show a high Iph/Idark ratio of 2.99 × 105, a large responsivity of 4.3 × 104 A W-1, an excellent external quantum efficiency of 1.94 × 105, and a high detectivity of 2.32 × 1013 Jones. The photoresponse-speed of the devices could be improved further using passivation with a polymer. The rise and decay times are about 60 ms and 100 ms, respectively. As a result of this study, we can confirm that non-contact optical trapping can enable the construction of nanowire architectures for optoelectronic, bioelectronic, and other devices.

Flexible Neuromorphic Architectures Based on Self-Supported Multiterminal Organic Transistors.

Because of the fast expansion of artificial intelligence, development and applications of neuromorphic systems attract extensive interest. In this paper, a highly interconnected neuromorphic architecture (HINA) based on flexible self-supported multiterminal organic transistors is proposed. Au electrodes, poly(3-hexylthiophene) active channels, and ion-conducting membranes were combined to fabricate organic neuromorphic devices. Especially, freestanding ion-conducting membranes were used as gate dielectrics as well as support substrates. Basic neuromorphic behavior and four forms of spike-timing-dependent plasticity were emulated. The fabricated neuromorphic device showed excellent electrical stability and mechanical flexibility after 1000 bends. Most importantly, the device structure is interconnected in a way similar to the neural architecture of the human brain and realizes not only the structure of the multigate but also characteristics of the global gate. Dynamic processes of memorizing and forgetting were incorporated into the global gate matrix simulation. Pavlov's learning rule was also simulated by taking advantage of the multigate array. Realization of HINAs would open a new path for flexible and sophisticated neural networks.

RAN/RANBP2 polymorphisms and neuroblastoma risk in Chinese children: a three-center case-control study.

The genetic etiology of sporadic neuroblastoma remains largely obscure. RAN and RANBP2 genes encode Ras-related nuclear protein and Ran-binding protein 2, respectively. These two proteins form Ran-RanBP2 complex that regulate various cellular activities including nuclear transport. Aberrant functions of the two proteins are implicated in carcinogenesis. Given the unknown role of RAN/RANBP2 single nucleotide polymorphisms (SNPs) in neuroblastoma risk, we performed a multi-center case-control study in Chinese children to assess the association of the RAN/RANBP2 SNPs with neuroblastoma risk. We analyzed three potentially functional SNPs in RAN gene (rs56109543 C>T, rs7132224 A>G, rs14035 C>T) and one in RANBP2 (rs2462788 C>T) in 429 cases and 884 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to access the association between these four polymorphisms and neuroblastoma risk. No single variant was found to statistically significantly associate with neuroblastoma risk. However, individuals with 3 protective genotypes were less likely to develop neuroblastoma, in comparison to non-carriers (adjusted OR=0.33; 95% CI=0.12-0.96; P=0.042), as well as those with 0-2 protective genotypes (adjusted OR=0.33; 95% CI=0.11-0.94; P=0.038). Stratified analysis revealed no significant association for any of the four polymorphisms. Further studies are warranted to validate the weak impact of RAN/RANBP2 SNPs on neuroblastoma risk.

Effects of cytochrome P450 family 3 subfamily A member 5 gene polymorphisms on daunorubicin metabolism and adverse reactions in patients with acute leukemia.

The present study aimed to investigate the association between the genetic polymorphism of cytochrome P450 family 3 subfamily A member 5 (CYP3A5) and the activity of CYP3A and plasma concentrations of daunorubicin (DNR) in patients with acute leukemia. A total of 36 children with newly diagnosed acute lymphoblastic leukemia were enrolled in the study. Polymerase chain reaction (PCR)­restriction fragment length polymorphism and PCR product sequencing were used to detect the genotype of CYP3A5*3. PCR was then used to express the mRNA expression of CYP3A5. A midazolam probe method was used to detect CYP3A enzyme activity, and DNR concentrations were measured using high performance liquid chromatography. Children with different genotypes had different mRNA expression levels of CYP3A5, and CYP3A enzyme activity in children with the CYP3A5*1 allele was higher, compared with that in children with the CYP3A5*3 allele. In addition, the area under the curve (AUC)0­24 h and AUC0­∞ of DNR were significantly different in children with different genotypes, however, no statistically significant differences were found in half­life or maximum concentration. The AUC of DNR was increased in children with acute lymphatic leukemia who suffered from cardiotoxicity, compared with those in the normal group. The CYP3A5*3 gene polymorphism was closely associated with the mRNA expression of CYP3A5, CYP3A enzyme activity and DNR plasma drug concentration, and exhibited different drug adverse reactions.