[Clinical and genetic characteristics of four children with Kabuki syndrome due to de novo variants of KMT2D gene].

OBJECTIVE: To explore the clinical and genetic characteristics of four children with Kabuki syndrome (KS) due to variants of KMT2D gene. METHODS: Four children with KS diagnosed at the Children's Hospital of Shanxi Province between January 2020 and December 2022 were selected as the study subjects. Whole exome sequencing was carried out for the children and their family members. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. RESULTS: The KS phenotype scores for the four children were 7, 8, 6, and 6, respectively. Child 2 also presented with a rare solitary kidney malformation. Genetic testing revealed that all children had harbored novel de novo variants of the KMT2D gene, including c.16472_16473del, c.858dup, c.11899C>T, and c.12844C>T, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were classified as pathogenic. CONCLUSION: For children showing phenotypes such as distinctive facial features, intellectual disability, developmental delay, cardiac abnormalities, and urinary system anomalies, KS should be considered. Early diagnosis and intervention can be achieved through genetic testing, especially in the presence of KMT2D gene mutations.

Regulatory Mechanism of MicroRNA-30b on Neonatal Hypoxic-Ischemic Encephalopathy (HIE).

OBJECTIVE: This study is to investigate the role of microRNA (miR)-30b in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonates. METHODS: Totally 26 cases of neonatal HIE were included in this study. The protein expression levels of CD26P and PAI-1 were detected with ELISA. Serum levels of miR-30b and PAI-1 mRNA was measured by quantitative real-time PCR. Human brain microvascular endothelial cells (HBMECs) were cultured under hypoxic condition, and the intracellular expression levels of miR-30b and PAI-1 were evaluated. Dual-luciferase reporter assay was performed to confirm the interaction between miR-30b and PAI-1. RESULTS: Compared with the control group, both the mRNA and protein expression levels of PAI-1 in the serum were up-regulated in the neonates with HIE, together with up-regulated serum CD26P levels. However, the serum expression level of miR-30b was down-regulated in neonatal HIE. In hypoxia-induced HBMECs, the mRNA and protein expression levels of PAI-1 were significantly up-regulated, while the miR-30b expression level was significantly down-regulated. Dual-luciferase reporter assay showed that PAI-1 was the direct target of miR-30b. CONCLUSION: Neonatal HIE is accompanied with abnormal platelet activation, significantly up-regulated serum PAI-1 expression levels, and down-regulated miR-30b expression. MiR-30b might regulate the disease pathogenesis and immune responses via modulating PAI-1.

[The in vivo thrombosis evaluation for the biodegradable polymer stent].

New biodegradable intravascular stent can reduce risk of foreign bodies retained, thus, it is widely concerned and some of the products have been introduced into the clinic. However, the characteristic of biodegradable may lead to more safety concerns associated with thrombosis. To ensure the safety, the thrombus formation experiment in vivo needs to be carefully designed and evaluated based on GB/T 16886.4 standard, but current standard do not provide explicit testing and evaluating methods. Establishing animal model with experimental pigs, the study compares biodegradable coronary stents and metal stents by simulating clinical implantation in vivo on the thrombus formation in the implanting process, and after the short-term and long-term implantation. The evaluation methods include gross observation, digital subtraction angiography intraoperative analysis, optical coherence tomography analysis, scanning electron microscopy and so on. The results show that combining these methods could comprehensively evaluate the whole process of the thrombus formation from the beginning of implantation to the end of preclinical animal experiments, so that, it may better predict the clinical thrombosis risk, and the selection of the control was very important. The study tries to use the comparison examples of thrombosis on the new medical instrument to provide the clue for thrombosis evaluation in vivo on similar instruments and show the methodology on the preclinical evaluation.

Extraction Optimization and Antioxidant Activities of Ethanol Extract of the Brown Roll-Rim Mushroom Paxillus involutus (Agaricomycetes).

Box Behnken design (BBD) was used to optimize the extraction of Paxillus involutus (EPI) in ethanol. The optimum extraction conditions were as follows: temperature 45°C; solid:liquid ratio 1:35; time 5 h. Under these conditions, the yield of EPI was 13.57%. The antioxidant activity of EPI was evaluated in vitro, and DPPH free radical scavenging, ABTS free radical scavenging, and hydroxyl free radical scavenging effects were found to be equal to or close to that of the positive control vitamin C (VC). The antioxidant activity of EPI was next evaluated in vivo using aging mice; it was found to have appreciable effect on scavenging malonic dialdehyde (MDA) and could increase the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and total superoxide dismutase (T-SOD) in mice. Overall, EPI showed antioxidant effects in aging mice, thereby delaying aging, and has potential for application as a natural antioxidant and in medical applications.

GaN surface acoustic wave filter with low insertion loss.

Surface acoustic wave (SAW) filter with a low insertion loss (IL) of 4.415 dB has been demonstrated on Carbon-doped semi-insulating c-plane bulk GaN without external lumped element matching. The center frequency, 3 dB bandwidth, out-of-band attenuation, return loss of the filter are 477.05 MHz, 0.308 MHz, 32.5 dB, and -9.72 dB, respectively. The electromechanical coupling coefficient (Kt2), and temperature coefficient of frequency (TCF) of the filter are 0.21 % and -26.0 ppm/°C, respectively. The impact of the number of interdigital transducers (NIDT) and acoustic propagation direction on filter performance has been studied. The IL of filters reduces from 16.07 dB to 4.415 dB with the increase of NIDT from 50 to 150 due to the enhanced acoustic superposition. The numerical distribution of elastic stiffness ([cij]), and piezoelectric constants ([eik]) of GaN has been calculated in Euler angle space, indicating that they are isotropic on c-plane. The small performance difference of filters along the m- and a-direction on c-plane bulk GaN can be attributed to the small offset angle of 0.5° of the bulk GaN wafer or IDT quality variation.

[Biocompatibility analysis of hyaluronic acid sodium gels for medical application].

Hyaluronan acid sodium gels are used in ophthalmic surgery, orthopedic treatment and cosmetic surgery. In 2009,there were 12 domestic manufacturers in China producing 33 kinds of products. 23 kinds of imported products were allowed by SFDA to sale in the meantime. Since manufacturers use different production processes, product performances are quite different. According to the GB/T 16886. 1-2001, we designed a pilot program to evaluate the sodium hyaluronate gel products comprehensively in this paper. The results showed that, except chromosome aberration test of gel A and subchronic systemic toxicity of gel C appeared positive, the remaining samples of the test results were negative. This article provides a reference to write standard of cross-linked hyaluronic sodium gel and the revision of standard YY0308-2004.

[The comparing study between subchronic toxicity and local implantation response of sodium hyaluronan gels for different application].

According to the requirements of ISO10993-11.2006 and ISO10993-6:r2007 standards, we used SD rats for evaluating the subchronic systemic toxicity and local implantation response of two kinds of sodium hyaluronan gels with different application. The results of 90d subchronic toxicity study by intraperitoneal route showed that the animals of the tested group and control group grew normally. There were no differences in the increases of the body weight, haematological index and clinical biochemistry indexes. The examination of gross pathology and histopathology revealed no abnormal changes caused by the test substance during the process. But there was different degree test article residual in the body of the animals at the end of the experiment. It was observed in the local subcutaneous implantation that at the early stage, gel A had mild inflammatory response, cysts were seen clearly, and new blood capillaries were visible at local area. Later, the wall got thinner and dense with little tissue reaction. Gel B also had mild inflammatory response earlier, but it totally disappeared after 14 days of implantation. It can be concluded that the gel products with different characteristics decided its degradation and metabolic process in the body of the test animals and therefore the areas of application of the products clinically. Meanwhile, we compared the evaluation method of subchronic systemic toxicity and local implantation response in risk assessment, providing reference for the choice of biological safe testing.

Intradialytic BP variability is associated with cardiovascular mortality and hospitalization in HD patients.

INTRODUCTION: Studies showed that pre-dialysis BP variability (BPV) was an independent risk factor of cardiovascular disease (CVD) among HD patients, but which is limited on how intradialytic BPV affects prognosis. METHODS: In this study, we designed a retrospective cohort study to examine the association between intradialytic BPV and CVD outcomes in HD patients. A total of 202 patients who underwent HD in our center were included, and all intradialytic BP measurements of November 2017 were obtained from the database. Patients were divided into four groups according to variability independent of the mean (VIM) interquartile. RESULTS: The mean age was 62.1 ± 14.3 years, 60.9% were male, and median VIM was 14.75 (12.60-18.59). Multiple-regression analyses showed patients age, dialysis vintage, serum albumin, and the percentage of intradialytic weight gain as significant predictors of VIM (all p values were <0.05). Kaplan-Meier survival curves showed that CVD mortality was greater in patients with higher VIM (p = 0.05), whereas all-cause mortality had no significant difference between the four groups overall (p = 0.149). Furthermore, multivariate regression analyses demonstrated that VIM (HR = 1.091, p < 0.004) and age (HR = 1.059, p = 0.003) were significant independent predictors for CVD death. Logistic-regression models revealed that higher VIM groups were more likely to have CVD-related hospitalization (OR = 1.085, p = 0.030), whereas the association between VIM and all-cause hospitalization was not statistically significant (OR = 1.015, p = 0.669). CONCLUSIONS: This retrospective study suggested that higher intradialytic BPV was associated with increasing age, longer dialysis vintage, lower albumin, and greater ultrafiltration; intradialytic BPV could be an effective predictor for CVD mortality and hospitalization in the HD population.

A review on the GaN-on-Si power electronic devices.

The past decades have witnessed a tremendous development of GaN-based power electronic devices grown on Si substrate. This article provides a concise introduction, review, and outlook of the research developments of GaN-on-Si power device technology. The comprehensive review has discussed the crucial issues in the state-of-the-art device technology based on both GaN materials epitaxy including stress control and point defects study, and device fabrication including normally off solutions like Cascode, trench MIS-gate, and p-GaN gate. Device reliability and other common fabrication issues in GaN high electron mobility transistors (HEMTs) are also discussed. Lastly, we give an outlook on the GaN-on-Si power devices from two aspects, namely high frequency, and high power GaN ICs, and GaN vertical power devices.

E/D-Mode GaN Inverter on a 150-mm Si Wafer Based on p-GaN Gate E-Mode HEMT Technology.

AlGaN/GaN E/D-mode GaN inverters are successfully fabricated on a 150-mm Si wafer. P-GaN gate technology is applied to be compatible with the commercial E-mode GaN power device technology platform and a systematic study of E/D-mode GaN inverters has been conducted with detail. The key electrical characters have been analyzed from room temperature (RT) to 200 °C. Small variations of the inverters are observed at different temperatures. The logic swing voltage of 2.91 V and 2.89 V are observed at RT and 200 °C at a supply voltage of 3 V. Correspondingly, low/high input noise margins of 0.78 V/1.67 V and 0.68 V/1.72 V are observed at RT and 200 °C. The inverters also demonstrate small rising edge time of the output signal. The results show great potential for GaN smart power integrated circuit (IC) application.

An Experimental and Theoretical Study of Impact of Device Parameters on Performance of AlN/Sapphire-Based SAW Temperature Sensors.

The impact of device parameters, including AlN film thickness (hAlN), number of interdigital transducers (NIDT), and acoustic propagation direction, on the performance of c-plane AlN/sapphire-based SAW temperature sensors with an acoustic wavelength (λ) of 8 µm, was investigated. The results showed that resonant frequency (fr) decreased linearly, the quality factor (Q) decreased and the electromechanical coupling coefficient (Kt2) increased for all the sensors with temperature increasing from -50 to 250 °C. The temperature coefficients of frequency (TCFs) of sensors on AlN films with thicknesses of 0.8 and 1.2 µm were -65.57 and -62.49 ppm/°C, respectively, indicating that a reduction in hAlN/λ favored the improvement of TCF. The acoustic propagation direction and NIDT did not obviously impact the TCF of sensors, but they significantly influenced the Q and Kt2 of the sensors. At all temperatures measured, sensors along the a-direction exhibited higher fr, Q and Kt2 than those along the m-direction, and sensors with NIDT of 300 showed higher Q and Kt2 values than those with NIDT of 100 and 180. Moreover, the elastic stiffness of AlN was extracted by fitting coupling of modes (COM) model simulation to the experimental results of sensors along different directions considering Euler transformation of material parameter-tensors. The higher fr of the sensor along the a-direction than that along the m-direction can be attributed to its larger elastic stiffness c11, c22, c44, and c55 values.

[Analysis of the parental origin of MECP2 mutations in patients with Rett syndrome].

OBJECTIVE: To identify the parental origin of methyl-CpG-binding protein 2 (MECP2) gene mutations in Chinese patients with Rett syndrome. METHODS: Single nucleotide polymorphisms (SNPs) in intron 3 of the MECP2 gene were analyzed by PCR and sequencing in 115 patients with Rett syndrome. Then sequencing of the SNP region was performed for the fathers of the patients who had at least one SNP, to determine which allele was from the father. Then allele-specific PCR was performed and the products were sequenced to see whether the allele from father or mother harbored the mutation. RESULTS: Seventy-six of the 115 patients had at least one SNP. Three hot SNPs were found in these patients. They were: IVS3+22C >G, IVS3+266C >T and IVS3+683C>T. Among the 76 cases, 73 had a paternal origin of MECP2 mutations, and the other 3 had a maternal origin. There were multiple types of MECP2 mutation of the paternal origin, including 4 frame shift, 2 deletion and 67 point (56C >T, 6C >G, 2A >G, 2G >T and 1A >T) mutations. The mutation types of the 3 patients with maternal origin included 2 frame shift and 1 point (C >T) mutation. CONCLUSION: In Chinese RTT patients, the MECP2 mutations are mostly of paternal origin.

Method of the out-of-band rejection improvement of the AlN based surface acoustic wave filters.

AlN based surface acoustic wave (SAW) filters with an acoustic wavelength (λ) of 8 µm have been fabricated based on sputtered AlN films on sapphire. The acoustic velocity of 1-µm-AlN/Sapphire bilayer structure is 5536 m/s, 60% higher than that of LiNbO3. The central frequency, insertion loss, out-of-band rejection, and bandwidth of fabricated AlN based two-port type SAW filters with a delay gap of λ are 692 MHz, 25.58 dB, 35.40 dB, and 2.7 MHz, respectively. The impact of delay gap on the performance of AlN based filters have been studied experimentally. By the analysis of frequency response of SAW filters with delay gaps of λ, 15λ, and 30λ with and without time gating technique, we find that increase the delay gap of AlN based SAW resonators can improve the out-of-band rejection effectively because of the reduction of electromagnetic coupling, with a cost of a little degradation of insertion loss due to the small propagation loss of AlN/Sapphire bilayer. When the delay gap is increased from λ to 15λ, out-of-band rejection of AlN based filters is increased by 4.75 dB, while the insertion loss is only increased by 0.81 dB. When the delay gap is further increased from 15λ to 30λ, the suppression of out-of-band rejection is not obvious.

[Cloning, expression and bioinformatics analysis of cathepsin B of Echinococcus granulosus].

OBJECTIVE: To clone and express cathepsin B gene of Echinococcus granulosus (EgCatB) and analyze EgCatB protein by using bioinformatics tools and online databases. METHODS: The total RNA of E. granulosus was extracted and reversely transcribed into cDNA as the template sequence for PCR. The EgCatB gene was cloned by using the In-Fusion PCR cloning method and expressed by a wheat germ cell-free system, and then the recombinant protein was identified by Western blotting. The signal peptide, transmembrane helices and subcellular location of the EgCatB sequence were predicted by the online software SignalP 4.1, TMHMM sever v. 2.0 and TargetP 1.1 respectively. Subsequently, the homologue sequence and conserved sites were aligned by using BLASTP and GeneDoc software. Finally, the structures and the glycosylation modification site of the EgCatB encoding protein were analyzed and predicted in turn by ProtParam, SMART, Predictprotein, Swiss-model, NetOGlyc 4.0 and NetNGlyc 1.0 approaches. RESULTS: The EgCatB gene was successfully amplified from cDNA of E. granulosus and expressed in the soluble fractions. The molecular weight of the expressed protein was estimated 35 kDa. The bioinformatics analysis revealed that EgCatB was a classical secreted protein containing a Pept_C1 domain. The homology analysis indicated that the amino acid sequence of EgCatB was highly conserved in the active enzyme sites. The protein structure prediction showed a catalytic active center was formed through Gln106, Cys112, His282 and Asn302. It was found that there were nine O-glycosylation sites in the EgCatB sequence, but no N-glycosylation sites. CONCLUSIONS: The EgCatB gene is cloned and expressed successfully, and the recombinant protein is analyzed by bioinformatics approaches and structure predication. The study provides useful information for further functional study of the EgCatB protein.