Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Epidemiology and Clinical Characteristics of Pediatric Sepsis in PICUs in Southwest China: A Prospective Multicenter Study.

OBJECTIVES: To describe the epidemiological characteristics of pediatric sepsis in Southwest China PICUs. DESIGN: A prospective, multicenter, and observational study. SETTING: Twelve PICUs in Southwest China. PATIENTS: The patients admitted to the PICU from April 1, 2022, to March 31, 2023. The age ranged from 28 days to 18 years. All patients met the criteria of severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 31 PICUs invited to participate, 12 PICUs (capacity of 292 beds) enrolled patients in the study. During the study period, 11,238 children were admitted to the participating PICUs, 367 (3.3%) of whom met the diagnosis of severe sepsis or septic shock. The most prevalent sites of infection were the respiratory system (55%) and the digestive system (15%). The primary treatments administered to these patients included antibiotics (100%), albumin (61.3%), invasive mechanical ventilation (58.7%), glucocorticoids (55.6%), blood products (51%), gammaglobulin (51%), and vasoactive medications (46.6%). Sepsis-related mortality in the PICU was 11.2% (41/367). Nearly half of the sepsis deaths occurred within the first 3 days of PICU admission (22/41, 53.7%). The mortality rate of septic shock (32/167, 19.2%) was significantly higher than that of severe sepsis (9/200, 4.5%; p < 0.001). The outcomes of a multivariate logistic regression analysis suggested that a higher pediatric Sequential Organ Failure Assessment score, and the use of invasive mechanical ventilation and vasoactive medications were independently associated with PICU mortality in children with sepsis. CONCLUSIONS: This report updates the epidemiological data of pediatric sepsis in PICUs in Southwest China. Sepsis is still a life-threatening disease in children.

Highly expressed miR-144-3p promotes the proliferation, migration and invasion of colon carcinoma cells by activating the Wnt/ß-catenin signaling pathway through targeting SFRP1.

Background: To investigate the influence of miR-144-3p on the proliferation, migration and invasion of colon carcinoma by targeting secreted frizzled-related protein 1 (SFRP1) as well as of the Wnt/ß-catenin signaling pathway. Methods: Based on the TCGA database, the association between the expression of miR-144-3p and the clinical information and prognosis of patients with colon carcinoma was examined, and SFRP1 was selected as the target gene for further studies based on bioinformatics prediction tools. CCK8 assay, wound healing assay and transwell invasion assay were employed to examine the impact of miR-144-3p on colon carcinoma cells. The regulation of SFRP1 by miR-144-3p was investigated using a dual-luciferase reporter system, and a rescue experiment was conducted to further elucidate whether miR-144-3p promotes the migration of colon carcinoma cells through targeting SFRP1 or not. The Wnt/ß-catenin signaling pathway-mediated effect of miR-144-3p in colon carcinoma was finally validated through the targeting of SFRP1. Results: The bioinformatics analysis showed that the miR-144 expression levels were substantially greater in colon carcinoma tissue than in para-carcinoma tissue and were closely with clinical stage and prognosis. The findings obtained from the trial indicated that miR-144-3p substantially expressed in colon carcinoma tissue sample and the colon carcinoma cells, and the overexpressed miR-144-3p boosted the colon carcinoma cells' proliferation, migration and invasion. The results of dual-luciferase reporter gene assay revealed that miR-144-3p targeted SFRP1, and rescue experiment was carried out and its results indicated that miR-144-3p increased colon carcinoma cells' migration through targeting SFRP1. In addition, the molecular axis of miR-144-3p/SFRP1 may over-activate the Wnt/ß-catenin signaling pathway. Conclusions: The present study has identified a novel malignant biological behavior, namely the ability of miR-144-3p to enhance the proliferation, migration and invasion of colon carcinoma cells by targeting SFRP1 and activating the Wnt/ß-catenin signaling pathway. Consequently, miR-144-3p emerges as a promising diagnostic and therapeutic target for colon carcinoma.

Finite Element Analysis of Flexural Behavior of Shape Memory Alloy Hybrid Composites Laminates.

In this paper, experiments and finite element analysis methods were adopted to study the flexural performance of shape memory alloy hybrid composites (SMAHC). The effect of embedding content and position of shape memory alloy (SMA) wire on the flexural properties of composite laminates was analyzed, and the optimal content and position of SMA wire were obtained. The optimal number of SMA wires for SMAHC laminates (B-2) is four. Compared with GFRP laminates, the flexural modulus of B-2-4 laminates increases by 5.19%, while the strength decreases by 5.76% on average. The finite element model of the SMAHC laminate was established by using ABAQUS finite element analysis software, and the validity of the model was verified by the comparison between the simulation results and the experimental results. The microscopic morphology results show that the weak interface between the matrix and SMA has a certain influence on the flexural performance of SMAHC specimens.

Case Report: A Novel Mutation Identified in CHST14 Gene in a Fetus With Structural Abnormalities.

Background: Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a rare heritable connective tissue disease with various symptoms. The diagnosis of mcEDS is difficult because of the large overlap of clinical symptoms between different EDS subtypes. Methods: We performed karyotype analysis, gene copy number variation detection, whole-exome sequencing, and Sanger sequencing to reveal the underlying genetic etiology of a fetus with structural abnormalities in feet and kidneys. Results: A likely pathogenic mutation [NM_130468.3 c.958C>T (p.Arg320*)] and an uncertain significance mutation [NM_130468.3 c.896A>G (p.Tyr299Cys)] were identified in the carbohydrate sulfotransferase 14 (CHST14) gene by whole-exome sequencing and validated by Sanger sequencing. Conclusion: The two identified mutations appear highly likely to be the genetic causes of the fetal structural abnormalities.

Clinical effect of alfacalcidol in children with Henoch-Schönlein purpura: a prospective randomized controlled trial. / é˜¿æ³•éª¨åŒ–é†‡æ²»ç–—å„¿ç«¥è¿‡æ•æ€§ç´«ç™œçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the effects of alfacalcidol on serum 25-(OH)D3 level, cellular immune function, and inflammatory factors in children with Henoch-Schönlein purpura (HSP). METHODS: A total of 200 children with HSP were prospectively enrolled from June 2018 to June 2020. According to the random number table method, they were divided into an observation group and a control group (n=100 each). The control group was treated with vitamin C, rutin tablets, dipyridamole, cimetidine, calcium supplements, and glucocorticoids. In addition to the treatment for the control group, the observation group received alfacalcidol capsules (0.25 µg/d) orally before bed for 4 weeks. The two groups were compared in terms of the level of 25-(OH)D3, the percentages of T lymphocyte subsets (CD3+, CD4+, and CD8+) and NK cells, and the levels of inflammatory factors, interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-21 (IL-21), and tumor necrosis factor-α (TNF-α), before treatment and after 4 weeks of treatment. The children were followed up for 6 months to determine the recurrence rate and the incidence of renal damage. RESULTS: After treatment, the observation group showed a significantly higher serum 25-(OH)D3 level, significantly higher percentages of CD3+T cells, CD4+T cells, and NK cells, and significantly lower levels of IL-6, IL-17, IL-21, and TNF-α compared with the control group (P<0.05). After 6 months of follow-up, the recurrence rate and the incidence of renal damage in the observation group were significantly lower than those in the control group (P<0.05). CONCLUSIONS: Alfacalcidol can increase the serum 25-(OH)D3 level, improve cellular immune function, decrease inflammatory factor levels, and reduce recurrence and renal damage in children with HSP.

Preparation and luminescence properties of Tb3+ -doped garnet Y2 Mg2 Al2 Si2 O12 luminescent materials.

We prepared Y2 Mg2 Al2 Si2 O12 :xTb3+ (x = 0.02, 0.04, 0.06, 0.08, 0.10, 0.12, 0.14 and 0.16) luminescent materials using a nodulizing procedure. The phase and luminescence properties of these materials were investigated. X-ray diffraction results demonstrated that Tb3+ ions doped into Y2 Mg2 Al2 Si2 O12 hosts successfully and the Y2 Mg2 Al2 Si2 O12 :xTb3+ materials showed a pure cubic phase. Y2 Mg2 Al2 Si2 O12 :xTb3+ materials had the characteristic Tb3+ emission bands derived from 5 D4 →7 F6 , 7 F5 , 7 F4 , and 7 F3 transitions when excited at 365 nm. The green emission band that derived from the 5 D4 →7 F5 transition was highest due to the high possibility of both electric-dipole and magnetic-dipole transitions. Emission spectra indicated that the critical concentration of Tb3+ in the Y2 Mg2 Al2 Si2 O12 host was 0.14. The concentration quenching of Y2 Mg2 Al2 Si2 O12 :Tb3+ was derived from a dipole-dipole interaction.

Application value of NIPT for uncommon fetal chromosomal abnormalities.

OBJECTIVE: To investigate the clinical value of noninvasive prenatal testing (NIPT) for fetal chromosomal deletion, duplication, and sex chromosome abnormalities. METHODS: The study included 6239 pregnant women with singletons in the first and second trimester of pregnancy who received NIPT from December 2017 to June 2019. For pregnant women at high risk of deletion, duplication, and sex chromosome abnormalities indicated by NIPT, amniocentesis was recommended for karyotype analysis and chromosome copy number variation detection to verify the NIPT results and analyze chromosome abnormalities. Women at low risk and with no other abnormal results continued with their pregnancies. RESULTS: Among the 6239 pregnant women who received NIPT, there were 15 cases of chromosomal deletion (12 cases confirmed by amniocentesis), 16 cases of chromosomal duplication (9 cases confirmed by amniocentesis), and 17 cases of sex chromosome abnormalities (11 cases confirmed by amniocentesis). Of these cases, 32 were finally confirmed by amniotic fluid cell karyotype analysis. The coincidence rate was 66.7% (32/48). There were no abnormalities found for the remaining low risk pregnant women during follow-up. CONCLUSION: NIPT has good application value in predicting fetal chromosomal deletion, duplication, and sex chromosome abnormalities. It can improve the detection rate of fetal chromosomal abnormalities, but further prenatal diagnosis is needed.

Sodium butyrate protects against oxidative stress in human nucleus pulposus cells via elevating PPARγ-regulated Klotho expression.

We investigated the involvement of klotho in the inhibition of oxidative stress by sodium butyrate (NaB) in human nucleus pulposus cells (NPCs). NPCs were pretreated with different concentrations of NaB for 2 h before stimulation with tert-butyl hydroperoxide (TBHP). NaB alleviated TBHP-induced oxidative injury in the NPCs, as evident by the reduced accumulation of mitochondrial superoxide, intracellular reactive oxygen species, and malondialdehyde, and increased activities of superoxide dismutase and glutathione peroxidase. Flow cytometry and western blotting showed that TBHP-induced apoptosis of NPCs was inhibited by NaB. NaB also reduced the TBHP-induced release of proteases that degrade the extracellular matrix, including matrix metalloproteinases 3 and 13, and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs 4). Intriguingly, NaB significantly reversed TBHP-induced klotho suppression. However, the protective effects of NaB on NPCs were abolished by klotho-specific small interfering RNA (siRNA). TBHP stimulation had no obvious effects on total or nuclear expression of peroxisome proliferator-activated receptor γ (PPARγ), but significantly reduced PPARγ acetylation and transcriptional activity, which were restored by NaB. TBHP stimulation also promoted the nuclear translocation of histone deacetylase 3 (HDAC3) and enhanced the association between HDAC3 and PPARγ in the nucleus, but this interaction was substantially disrupted by NaB. siRNA-induced HDAC3 knockdown significantly increased PPARγ acetylation and transactivation, reversing the TBHP-induced suppression of klotho. Therefore, NaB alleviates TBHP-induced oxidative stress in human NPCs by elevating PPARγ-regulated klotho expression. HDAC3 may be a critical HDAC subtype that mediates the regulation of PPARγ activity by NaB under oxidative stress.

Correction: A multi-center randomized prospective study on the treatment of infant bronchiolitis with interferon α1b nebulization.

[This corrects the article DOI: 10.1371/journal.pone.0228391.].

A multi-center randomized prospective study on the treatment of infant bronchiolitis with interferon α1b nebulization.

BACKGROUND: The respiratory syncytial virus (RSV) is the main cause of bronchiolitis in infants and interferon (IFN) α is a commercial antiviral drug. The nebulization of IFN α1b could be a viable treatment method. In this study, the therapeutic effects and safety of IFN α1b delivery via nebulization in infant bronchiolitis were investigated in this multi-center prospective study. METHODS AND FINDINGS: Bronchiolitis patients admitted to 22 hospitals who met the inclusion criteria were enrolled and randomly allocated to four groups: control, IFN Intramuscular Injection, IFN Nebulization 1 (1 µg/kg), and IFN Nebulization 2 (2 µg/kg) groups. All patients were observed for 7 days. The therapeutic effects and safety of different IFN delivery doses and delivery modes were evaluated. Coughing severity change, as scored by the researchers and parents, between days 1 and 3 was significantly different between the IFN Nebulization 2 and control groups. Lowell wheezing score change between days 3 and 5 was significantly different between IFN Nebulization 1 and control groups. There were no significant differences among the four groups regarding the number of consecutive days with fever, three-concave sign, fatigue and sleepiness, and loss of appetite. There were no cases of severe complications, no recurrence of fever, and no regression of mental status. CONCLUSIONS: IFN-α1b could more effectively alleviate coughing and wheezing in bronchiolitis. IFN-α1b nebulization had significant advantages in shortening the duration of wheezing and alleviating coughing.

Study on miRNAs in Pan-Cancer of the Digestive Tract Based on the Illumina HiSeq System Data Sequencing.

OBJECTIVE: miRNA has gained attention as a therapeutic target in various malignancies. The proposal of this study was to investigate the biological functions of key miRNAs and target genes in cancers of the digestive tract which include esophageal carcinoma (ESCA), gastric adenocarcinoma (GAC), colon adenocarcinoma (COAD), and rectal adenocarcinoma (READ). MATERIALS AND METHODS: After screening differentially expressed miRNAs (DEMIs) and differentially expressed mRNAs (DEMs) in four digestive cancers from The Cancer Genome Atlas (TCGA) database, the diagnostic value of above DEMIs was evaluated by receiver-operating characteristic (ROC) curve analysis. Then, corresponding DEMIs' target genes were predicted by miRWalk 2.0. Intersection of predicted target genes and DEMs was taken as the target genes of DEMIs, and miRNA-mRNA regulatory networks between DEMIs and target genes were constructed. Meanwhile, the univariate Cox risk regression model was used to screen miRNAs with distinct prognostic value, and Kaplan-Meier analysis was used to determine their significance of prognosis. Furthermore, we performed bioinformatics methods including protein-protein interaction (PPI) networks, gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene group RIDA analysis by Gene-Cloud of Biotechnology Information (GCBI) to explore the function and molecular mechanisms of DEMIs and predicted target genes in tumor development. RESULTS: Eventually, 3 DEMIs (miR-7-3, miR-328, and miR-323a) with significant prognostic value were obtained. In addition, 3 DEMIs (miR-490-3p, miR-133a-3p, and miR-552-3p) and 281 target genes were identified, and the 3 DEMIs showed high diagnostic value in READ and moderate diagnostic value in ESCA, GAC, and COAD. Also, the miRNA-mRNA regulatory network with 3 DEMIs and 281 overlapping genes was successfully established. Functional enrichment analysis showed that 281 overlapping genes were mainly related to regulation of cell proliferation, cell migration, and PI3K-Akt signaling pathway. CONCLUSION: The diagnostic value and prognostic value of significant DEMIs in cancers of the digestive tract were identified, which may provide a novel direction for treatment and prognosis improvement of cancers of the digestive tract.

Noninvasive prenatal testing detects microdeletion abnormalities of fetal chromosome 15.

OBJECTIVE: Noninvasive prenatal testing (NIPT) is widely used in clinical detection of fetal autosomal duplications or deletions. The aim of this study was to investigate the clinical application of NIPT for detection of chromosomal microdeletions. METHODS: Microdeletions of about 5 Mb in the long arm of chromosome 15 (q11.2-q12) were detected by NIPT and were confirmed by karyotype analysis and copy number variation (CNV) analysis based on high-throughput sequencing technology. RESULTS: The CNV results of prenatal diagnosis showed that there were approximately 4.96 Mb of microdeletions in 15q11.2-q13.1, which was consistent with the NIPT results. The karyotype analysis showed no abnormalities. CONCLUSION: In this study, the microdeletion fragment of fetal chromosome 15 was successfully detected and diagnosed using NIPT. This suggests that NIPT is an efficient method to gain genetic information about chromosomal abnormalities.

Effect of a Roughness Element on the Hypersonic Boundary Layer Receptivity Due to Different Types of Free-Stream Disturbance with a Single Frequency.

The hypersonic flow field around a blunt cone was simulated using a high-order finite difference method. Fast acoustic waves, slow acoustic waves, entropy waves, and vortical waves were introduced into the free-stream to determine the influence of a free-stream with disturbances on the hypersonic flow field and boundary layer. The effect of disturbance type on the evolution of perturbations in the hypersonic boundary layer was analyzed. Fast Fourier Transform was adopted to analyze the effect of the disturbance type on the evolution of different modes in the boundary layer. A roughness element was introduced into the flow field to reveal the impact of the roughness element on hypersonic boundary layer receptivity. The results showed that a free-stream with disturbances affected the hypersonic flow field and boundary layer; acoustic waves had the greatest influence. The impact of slow acoustic waves on the flow field was mainly concentrated in the region between the shock and the boundary layer, whereas the influence of fast acoustic waves was mainly concentrated in the boundary layer. Multi-mode perturbations formed in the boundary layer were caused by the free-stream with disturbances, wherein the fundamental mode was the dominant mode of the perturbations in the boundary layer caused by fast acoustic waves, entropy waves, and vortical waves. The dominant modes of the perturbations in the boundary layer caused by slow acoustic waves were both the fundamental mode and the second harmonic mode. The roughness element changed the propagation process of different modes of perturbations in the boundary layer. In the downstream region of the roughness element, perturbations in the boundary layer caused by the slow acoustic waves had the greatest influence. The second harmonic mode in the boundary layer was significantly suppressed, and the fundamental mode became the dominant mode. The effects of fast acoustic waves and entropy waves on the boundary layer receptivity were similar, except the amplitude of the perturbations in the boundary layer caused by the fast acoustic waves was larger.

Effect of a Roughness Element on the Receptivity of a Hypersonic Boundary Layer over a Blunt Cone Due to Pulse Entropy Disturbance with a Single Frequency.

A high-order finite difference method was used to simulate the hypersonic flow field over a blunt cone with different height roughness elements. The unsteady flow field induced by pulse disturbances was analyzed and compared with that under continuous disturbances. The temporal and spatial evolution characteristics of disturbances in the boundary layer were investigated and the propagation of different disturbance modes in the boundary layer was researched through the fast Fourier transform (FFT) method. The effect of the roughness element on the receptivity characteristic of the hypersonic boundary layer under pulse entropy disturbances was explored. The results showed that the different mode disturbances near roughness in the boundary layer were enlarged in the upstream half of the roughness element and suppressed in the downstream half. However, the effect of roughness weakened gradually as the disturbance frequency increased in the boundary layer. A phenomenon of mode competition in the downstream region of the roughness element exited. As the disturbances propagated downstream, the fundamental mode gradually became the dominant mode. A certain promotion effect on the mode competition was induced by the roughness element and the effect was enhanced with the increase in the roughness element height.

Low intensity-pulsed ultrasound induced apoptosis of human hepatocellular carcinoma cells in vitro.

The present study was conducted to determine whether low intensity-pulsed ultrasound (LIPUS) could induce apoptosis of human hepatocellular carcinoma cells, SMMC-7721, and to define the mechanism of ultrasound-induced apoptosis, in vitro. MTT assay was used to measure cell proliferation. Apoptosis was investigated by multiple methods such as flow cytometry, DNA fragmentation, Ca(2+) mobilizations, pro- and anti-apoptotic protein expression, and light as well as ultramicroscopic morphology. The results provide evidence that LIPUS induced a dose-dependent effect on cell viability and apoptosis of SMMC-7721 cells. Specifically, exposure of cells to >0.5 W/cm(2) intensity significantly increased cell apoptosis, caused shifts in cell cycle phase, and induced structural changes. Ultrasound significantly increased intracellular Ca(2+) concentrations and modulated expression of caspase-3, Bcl-2 and Bax. The findings suggest that this novel technology can be used to induce SMMC-7721 apoptosis via the Ca(2+)/mitochondrial pathway and could potentially be of clinical use for the treatment of hepatocellular carcinoma (SMMC-7721 cell line) and other cancers.