Tracking moisture contents in the pollution layer on a composite insulator surface using hyperspectral imaging technology.

Electrical insulators used in transmission lines and outdoor substations are exposed to severe environmental pollution, which significantly increases the risk of power system failure, especially when the pollution layer is highly humid due to adverse weather conditions. The focus of this paper is to establish an effective method for assessing the moisture content (MC) in pollution layers as it serves as a crucial indicator for evaluating the risk of failure in insulators. Hyperspectral imaging (HSI) technology with a spectral range of 371.08-1037.89 nm was applied to determine significant changes in reflectance spectral characteristics in insulators during dynamic wetting and drying periods. Partial least squares regression (PLSR) models were utilized to evaluate the data presentation enhancement abilities of spectral transformation models and the data dimensionality reduction abilities of characteristic band selection methods. Furthermore, PLSR models were developed to calculate the MC along the pixel dimension to visually retrieve the dynamic wetting and drying processes of the pollution layer. The R-squared and root-mean-square error (RMSE) results in the cross-verification set and prediction set of the RE-RF(70%)-PLSR model with two characteristic bands with a wavelength of 543.28 nm and 848.01 nm were as follows: RCV2 = 0.9824, RMSECV = 0.0367, RP2 = 0.9818, RMSEP = 0.0369, respectively. This research contributes towards the visualization retrieval of the MC and offers an important technique for analyzing flashover evolution, optimizing insulator design, and preparing coating materials for insulators.

Investigation of amino acid profile alterations in maternal serum for early diagnosis of anembryonic pregnancy with high performance liquid chromatography-mass spectrometry.

BACKGROUND: Anembryonic pregnancy affects 12-15 % of clinically recognized pregnancies and a previous anembryonic pregnancy is an independent risk factor for future anembryonic pregnancy. This study aimed to investigate alternations in maternal amino acid profiles and analyze the diagnostic accuracy of amino acid biomarkers for anembryonic pregnancy in the early stage. METHODS: Fasting serum from anembryonic pregnancy patients (n = 103) and healthy pregnancies (n = 97) was collected, and amino acid concentrations were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of each of the amino acid biomarkers and the amino acid profile index for anembryonic pregnancy screening. RESULTS: The concentrations of 15 amino acids were significantly different between anembryonic pregnancy patients and healthy controls, and most of them were significantly higher at 7 weeks' gestational age in anembryonic pregnancy subjects. The area under the curve (AUC) based on an amino acid profile index combined with alanine, citrulline, aspartic acid, threonine, serine and isoleucine was 0.90 (sensitivity 82.76 %, specificity 83.64 %) for distinguishing early anembryonic pregnancy from healthy controls. CONCLUSION: Maternal serum amino acid concentrations were significantly elevated in anembryonic pregnancy patients. The diagnostic potential of amino aicds for anembryonic pregnancy was verified, and the diagnostic efficiency was improved in the use of the amino acid profile index. The amino acid profile is expected to be applied for the risk screening of early-stage of anembryonic pregnancy in the future.

Advances in device-based treatment of heart failure with preserved ejection fraction: evidence from clinical trials.

Heart failure with preserved ejection fraction (HFpEF) is a group of clinical syndromes that exhibit a remarkably heterogeneous phenotype, characterized by symptoms and signs of heart failure, left ventricular diastolic dysfunction, elevated levels of natriuretic peptides, and an ejection fraction greater than or equal to 50%. With the aging of the population and the escalating prevalence of hypertension, obesity, and diabetes, the incidence of HFpEF is progressively rising. Drug therapy options for HFpEF are currently limited, and the associated high risk of cardiovascular mortality and heart failure rehospitalization significantly impact patients' quality of life and longevity while imposing a substantial economic burden on society. Recent research indicates that certain device-based therapies may serve as valuable adjuncts to drug therapy in patients with specific phenotypes of HFpEF, effectively improving symptoms and quality of life while reducing the risk of readmission for heart failure. These include inter-atrial shunt and greater splanchnic nerve ablation to reduce left ventricular filling pressure, implantable heart failure monitor to guide diuresis, left atrial pacing to correct interatrial dyssynchrony, cardiac contractility modulation to enhance cardiac calcium handling, as well as renal denervation, baroreflex activation therapy, and vagus nerve stimulation to restore the autonomic imbalance. In this review, we provide a comprehensive overview of the mechanisms and clinical evidence pertaining to these devices, with the aim of enhancing therapeutic strategies for HFpEF.

Amplification of an Electrochemiluminescence-Emissive Aptamer into DNA Nanotags for Sensitive Fecal Calprotectin Determination.

The precision additive manufacturing and tessellated multitasking out of the structural DNA nanotechnology enable a configurable expression of densified electrochemiluminescent (ECL) complexes, which would streamline the bioconjugation while multiplying signals. Herein, a completely DNA-scaffold ECL "polyploid" was replicated out via the living course of rolling circle amplification. The amplicon carried the aptameric sequences of ZnPPIX/TSPP porphyrin as photoreactive centers that rallied at periodical intervals of the persistent extension into a close-packed nanoflower, ZnPDFI/II. Both microscopies and electrophoresis proved the robust nesting of guests at their deployed gene loci, while multispectral comparisons among cofactor substituents pinpointed the pivotal roles of singlet seclusion and Zn2+-chelation for the sake of intensive ECL irradiation. The adversity-resilient hydrogel texture made lipoidal filmogens as porphyrinic ECL prerequisites to be of no need at all, thus not only simplifying assay flows but also inspiring an in situ labeling plan. Upon bioprocessing optimization, an enriched probe ZnPDFIII was further derived that interpolated the binding motif related to calprotectin as validated by molecular docking and affinity titration. With it being a strongly indicative marker of inflammatory bowel disease (IBD), a competitive ECL aptasensing strategy was contrived, managing a signal-on and sensitive detection in mild conditions with a subnanogram-per-milliliter limit of detection by 2 orders of magnitude lower than the standard method as well as a comparable accuracy in clinical stool sample testing. Distinct from those conventional chemophysical rebuilding routes, this de novo biosynthetic fusion demonstrated a promising alternative toward ECL-source bioengineering, which may intrigue vibrant explorations of other ECL-shedding fabrics and, accordingly, a new bioanalytic mode downstream.

Luteolin inhibits angiogenesis and enhances radiotherapy sensitivity of laryngeal cancer via downregulating Integrin ß1.

AIM: To demonstrate the role and mechanism of luteolin in radio-sensitization and angiogenesis of laryngeal cancer. METHODS: Firstly, we analyzed the cytotoxicity of Luteolin and radiation sensitive cytotoxicity through CCK8, and selected subsequent radiation doses and Luteolin concentrations. Next, we further analyzed the effects of Luteolin on radiation sensitivity and neovascularization of laryngeal cancer, and conducted CCK8, plate cloning, and angiogenesis experiments, respectively. At the same time, the effects of individual treatment and combination treatment on the expression of Integrin ß1 and VEGFA were analyzed through immunofluorescence analysis. We also analyzed the regulation of Integrin ß1 protein expression by Luteolin through Western blot. To investigate the mechanism of Integrin ß1, we transfected overexpressed and silenced Integrin ß1 vectors and analyzed the role of Integrin ß1 in Luteolin enhancing radiation sensitivity of laryngeal cancer by repeating the above experiments. We have also constructed an in vivo subcutaneous tumor transplantation model to further validate the cell experimental results. The expression of Integrin, KI67, VEGFA, and CD31 was analyzed through Western blot and immunohistochemistry experiments. RESULTS: Radiation inhibited cell proliferation and decreased Integrin ß1 expression, and increased the radiosensitivity through inhibiting cell proliferation, and inhibit angiogenesis during radiation. Overexpression of Integrin ß1 weakened radiotherapy sensitivity on the basis of cells treated with combined administration. Integrin ß1 is considered as the downstream molecule of luteolin, participating in radiosensitivity of luteolin to FaDu cells. Animal experiments also demonstrated that luteolin strengthened tumor suppression and anti-angiogenesis during radiation via Integrin ß1. CONCLUSION: In summary, our results manifested that radio-sensitivity effect of luteolin depended on downregulating Integrin ß1 in laryngocarcinoma.

Point-of-Care Diagnosis on Selenium Nutrition Based on Time-Resolved Fluorometric Glycoaffinity Chromatography.

Given the lack of timely evaluation of the well-received selenium fortification, a neat lateral-flow chromatographic solution was constructed here by using the recently identified urinary selenosugar (Sel) as a strongly indicative marker. As there are no ready-made receptors for this synthetic standard, phenylboronic acid (PBA) esterification and Dolichos biflorus agglutinin (DBA) affinity joined up to pinch and pin down the analyte into a sandwich-type glycol complex. Pilot lectin screening on homemade glycan microarrays verified such a new pairing between dual recognizers as PBA-Sel-DBA with a firm monosaccharide-binding constant. To quell the sample autofluorescence, europium nanoparticles with efficient long-life afterglow were employed as conjugating probes under 1 µs excitation. After systematic process optimizations, the prepared Sel-dipstick achieved swift and sensitive fluorometry over the physiological level of the target from 0.1 to 10 µM with a detection limit down to 0.06 µM. Further efforts were made to eliminate matrix effects from both temperature and pH via an approximate formula. Upon completion, the test strips managed to quantify the presence of Sel in not just imitated but real human urine, with comparable results to those in the references. As far as we know, this would be the first in-house prototype for user-friendly and facile diagnosis of Se nutrition with fair accuracy as well as selectivity. Future endeavors will be invested to model a more traceable Se-supplementary plan based on the rhythmic feedback of Sel excretion.

Dried blood spot reference intervals for 18 amino acids in a 1 to 6 years old pediatric cohort.

OBJECTIVES: Reference intervals are indispensable for the accurate clinical interpretation of clinical laboratory tests. The reference intervals of amino acids in dried blood spots (DBS) from nonnewborn children are limited. In this study, we aim to establish the pediatric reference intervals for amino acids in DBS from healthy Chinese children aged from 1 to 6 years and to investigate the effect of sex and age. DESIGN AND METHODS: In 301 healthy subjects aged from 1 to 6 years old, eighteen DBS amino acids were determined using ultra-performance chromatography-tandem mass spectrometry method. Amino acid concentrations were examined in relation to sex and age. Reference intervals were established according to the CLSI C28-A3 guidelines. RESULTS: Reference intervals of 18 amino acids bounded by the 2.5 and 97.5 percentiles were calculated in DBS specimen. No significant influence of age was observed for all the target amino acid concentrations in 1- to 6-year-olds. Sex differences were found in leucine and aspartic acid. CONCLUSIONS: The RIs established in the present study added value for diagnosing and managing the amino acid-related diseases in the pediatric population.

Effects of Vitamin D Supplementation on Children with Autism Spectrum Disorder: A Systematic Review and Meta-analysis.

The effect of vitamin D supplementation on individuals with autism spectrum disorder (ASD) is inconclusive. We aimed to conduct a meta-analysis of the available randomized controlled trials (RCTs) to explore whether vitamin D supplementation can improve core symptoms and coexisting conditions in children with ASD. Data were obtained by searching the PubMed, Embase, Web of Science, CINAHL and Cochrane Library databases up to February 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a random-effects model, mean differences with 95% confidence intervals (CIs) were calculated through a meta-analysis. There were eight RCTs with 266 children with ASD in the present review, among which six RCTs were included in the meta-analysis. Children who received vitamin D supplementation showed a significant improvement in stereotypical behavior scores (pooled mean difference (MD): -1.39; 95% CI: -2.7, -0.07; P = 0.04) with low heterogeneity (I2 = 34%), and there was a trend toward decreased total scores on the Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS, P = 0.05); however, there were no other significant differences in the core symptoms of ASD and coexisting conditions between groups as measured by the Aberrant Behavior Checklist (ABC). Vitamin D supplementation appears to improve stereotypical behaviors but does not improve other core symptoms and coexisting conditions. Further randomized controlled trials with large sample sizes and individualized doses are needed.

Effect of divalent cations on electrochemiluminescence of metal-organic frameworks in bioassay.

The structural characteristics of electrochemiluminescent (ECL) microreticula enabled flexible designs for probing specific molecules. However, bioanalysts paid little attention to the impact of concomitant electrolytic carriers on ECL responsiveness of these grids. Our previous finding confirmed the collisional quenching of ECL radiative secondary building units from polarized Br- and I-. To further address this concern, herein typical cationic commonplaces including Na+, K+, Ca2+, … in buffer plus regular transition metals - their influences upon the ECL performance of a well-defined zinc porphyrin-organic framework (ZnPOF) were inspected in a one-by-one manner. Except for Na+/K+, a dozen of divalent metal chlorides exerted an adverse effect in the form of Stern-Volmer quenching on the ECL brightness, which was illuminated to be cation channeling in open voids of ZnPOFs and bonding with O2-reactive sites as exemplified by the model Ca2+ via systematic compositional investigation. Following this principle, a simplistic Ca2+-sensitive sensor was developed for quantitative evaluation of health-care calcium supplements with high precision. Above all, this work highlighted the non-negligible interference from those Mn + requisites to the susceptible MOF-based ECL, which should be paid extra attention in bioassays and mechanistic analyses.

A novel LC-MS/MS method for the simultaneous analysis of selected fat-soluble vitamins in serum obtained from pediatric patients with pneumonia.

Several observational studies have reported associations between low levels of fat-soluble vitamins (A, D and E) and the incidence of pneumonia. Whether infection affects or negatively regulates serum vitamin levels remains controversial. Our aims were to develop and validate a simple-pretreatment and fast method to determine the serum levels of selected fat-soluble vitamins, namely vitamin A (retinol), vitamin D (25-OH-D3, 25-OH-D2, and 3-epi-25-OH-D3), and vitamin E (α-tocopherol), in children suffering from pneumonia during the acute phase and after inflammatory marker recovery. The sample preparation procedure involving protein precipitation and filtration was finished in one step, and separation took 8 min per sample. The calibrations were linear, with R2 > 0.99. Both the intra-run (n = 6) and inter-run (n = 3) precision (relative standard deviation, RSD%) values were below 14.61%. The spiked recoveries at 3 concentrations ranged from 80.97 to 111.91%. Accuracies were calibrated using both National Institute of Standards and Technology serum (NIST 968f) and external quality assurance (EQA) samples offered by the National Center of Clinical Laboratories of China, and the relative error (RE%) values ranged from -13.17% to 12.53%. Clinical sample analysis revealed that infection did alter the serum retinol concentration and it did not alter the 25-OH-D and α-tocopherol levels in young children with pneumonia.

Silencing PLOD2 attenuates cancer stem cell-like characteristics and cisplatin-resistant through Integrin ß1 in laryngeal cancer.

Laryngeal cancer (LC) is an aggressive malignancy resistant to drug treatments. It has been postulated that cancer stem cells (CSCs) persist in a unique population of cancer cells involved in tumor progression and drug-resistance. In the present study, the effects of PLOD2 expression on ordinary and Cisplatin (DDP)-resistance (R) cells were investigated in TU686 and TU138 cells and Xenograft model. Cell viability, invasion and cell apoptosis, CD44 and CD133 expressions, MRP1 and P-gp expressions were measured by CCK-8 assay, Transwell, flow cytometry, immunofluorescence and Western blotting respectively. The results of our study demonstrated that suppressing the expression of PLOD2 could meditate LC stem cell-like features by decrease cell viability and invasion, increase apoptotic rate, decrease CD44 and CD133 expressions via Integrin ß1. Meanwhile, the inhibition of PLOD2 expression could decrease P-gp and MRP1expression thus markedly regulate DDP-R LC cells stemness and drug-resistance via Integrin ß1. Our findings provided a new rationale for subsequent academic and clinical research on LC drug-resistance.

Influencing Factors of International Students' Anxiety Under Online Learning During the COVID-19 Pandemic: A Cross-Sectional Study of 1,090 Chinese International Students.

Objective: We conducted the following cross-sectional study to comprehensively assess the anxiety among Chinese international students who studied online during the COVID-19 pandemic and its influencing factors. Methods: Questionnaires were distributed through "Sojump," and a total of 1,090 valid questionnaires were collected. The questionnaire was divided into two parts: general situation and anxiety assessment of students. The former used a self-made questionnaire, and the international general GAD-7 scale was used to measure anxiety. Chi-square test was used to analyze the differences between groups, and logistic regression analysis was performed for the factors with differences. Results: Anxiety was found in 707 (64.9%) of 1,090 international students. Chi-square test and multivariate Logistic regression analysis showed that the incidence of anxiety was higher in the group under 22 years of age than in the group over 22 years of age (68% vs. 61%, p = 0.015; OR = 1.186, 95% CI 1.045-1.347, p = 0.008); International students living in big cities had a higher incidence of anxiety than those living in rural areas (67% vs. 60%, p = 0.022; OR = 1.419, 95%CI 1.038-1.859, p = 0.011); international students who socialized 3 times or less monthly had a higher incidence of anxiety than those who socialized more than 3 times per month (68% vs. 58%, p = 0.003; OR = 1.52, 95%CI 1.160-1.992, p = 0.002); international students who expected purely online teaching had a higher incidence of anxiety than those who expected purely offline teaching or dual-track teaching (72% vs. 64%, p = 0.037; OR = 1.525, 95%CI 1.069-2.177, p = 0.02); international students with a subjective score of online learning experience of 6 or less had a higher incidence of anxiety than those with subjective scores of more than 6 (70% vs. 60%, p = 0.001, OR = 1.25, 95%CI 1.099-1.422, p = 0.001). However, gender, emotional status, BMI, major of study, vaccination status, and degree type had no significant difference in the incidence of anxiety among international students who studied online during the COVID-19 pandemic. Conclusion: During COVID-19, international students who were younger, came from big cities, had low social frequency, expected purely online teaching, and had poor experience of online classes were risk factors for anxiety during online classes.

[A Method for Quantitative Determination of Amino Acids and Organic Acids in Trace Random Urine and Preliminary Application in Research on Vitamin B12 Nutritional Status and Related Metabolism].

Objective To develop a method for the quantification of amino acids and organic acids in trace urine by high performance liquid chromatography-tandem mass spectrometry.Methods Random urine samples(10 µl each)were precipitated by acetonitrile and underwent derivatization with 3 mol/L HCl in n-butanol.The analytes were separated by ACE Excel 2 AQ column(50×2.1 mm,2 µm).Electrospray ionization in positive ion mode was carried out and the analytes were detected in multiple reaction monitoring mode.According to existing guidelines,the method was systematically evaluated in terms of sensitivity,specificity,accuracy,precision,recovery,matrix effect,and stability.Then,the established method was employed to detect 19 target compounds in urine samples from 70 healthy children,27 children with suspected vitamin B12 deficiency,and 3 children with cblC type methylmalonic acidemia.Results The lower limit of quantification of the method for the 19 compounds ranged from 0.01 µmol/L to 1.00 µmol/L,and the calibration curves were linear,R2>0.990.The method showed good accuracy with relative error less than ±15% and the intra-day and intra-day precision less than 15%.The run time was 8 min.No obvious matrix effect was detected except for arginine,and the recovery ranged from 80.20% to 114.97%.The samples were stable after 8 h at room temperature and 3 freeze-thaw cycles.The measured values of the compounds in the urine of healthy children were within the children's reference intervals published by Labcorp.The levels of methylmalonic acid(P=0.030)and homocysteine(P<0.001)in the urine samples of children with suspected vitamin B12 deficiency were higher than those in healthy children.The levels of methylmalonic acid,methylcitric acid,and homocysteine in the urine samples of children with cblC type methylmalonic acidemia were 5.14-76.52 times higher than the median levels of healthy children. Conclusions The method established in this study has small sample demand and short run time,which can accurately quantify the levels of amino acids and metabolites in the urine of children.Moreover,it can provide data support for related studies about the metabolic characteristics of urine amino acids and their metabolites in children with vitamin B12 deficiency.

miR-222-3p is involved in neural tube closure by directly targeting Ddit4 in RA induced NTDs mouse model.

Previously our results showed miR-222-3p was significantly downregulated in retinoic acid-induced neural tube defect (NTD) mouse model through transcriptome. Down-regulation of miR-222-3p may be a causative biomarker in NTDs. In this study, RNA was extracted from mouse embryos at E8.5, E9.5 and E10.5, and the expression level of miR-222-3p was measured by quantitative real-time PCR analysis. The preliminary mechanism of miR-222-3p in NTDs involved in cell proliferation, apoptosis and migration was investigated in mouse HT-22 cell line. The expression of miR-222-3p was significantly decreased at E8.5, E9.5 and E10.5 developed in mouse embryos which were consistent with our transcriptome sequencing. Suppression of miR-222-3p in HT-22 cells resulted in the inhibition of cell proliferation and migration, cell cycle and apoptosis. Moreover, DNA damage transcript 4 (Ddit4) was identified as a direct and functional target of miR-222-3p. miR-222-3p is negatively regulated by Ddit4. The mutation of binding site of Ddit4 3'UTR abrogated the responsiveness of luciferase reporters to miR-222-3p and showed that Ddit4 expression partially attenuated the function of miR-222-3p. We preliminatively confirmed that low expression of miR-222-3p has reduced the expression of ß-catenin, TCF4 and other related genes in the Wnt/ß-catenin signaling pathway.Collectively, these results demonstrated that miR-222-3p regulates the Wnt/ß-catenin signaling pathway through Ddit4 inhibition in HT-22 cells, resulted in cell proliferation and apoptosis imbalance, and thus led to neural tube defects.

Establishment of pediatric reference intervals for complete blood count parameters in capillary blood in Beijing.

BACKGROUND: Reference intervals (RIs) are normal ranges of clinical indicators established from healthy subjects, and comparing test results with RIs is the first step for clinicians in differentiating between healthy and diseased subjects. Capillary blood is widely used in complete blood count (CBC) tests in children; however, capillary blood-based RIs for the CBC parameters are still lacking for all pediatric populations. The aim of this study was to establish capillary blood-based RIs for the CBC parameters in children aged 3 months to 18 years in Beijing. METHODS: A total of 6799 capillary blood specimens from children were collected, including 3832 males and 2967 females aged 3 months to 18 years, and CBC parameters were analyzed. Data analysis, RI calculations, and 90% confidence interval (CI) calculations were performed according to CLSI C28-A3 guidelines. RESULTS: Capillary blood RIs for 22 CBC parameters were established in children aged 3 months to 18 years. The levels of most red blood cell-related parameters increased with age and were generally higher in males than in females. White blood cell counts were relatively stable, with no obvious upward or downward trends from 3 months to 18 years of age. Platelet levels decreased within the first year and tended to be stable thereafter. Further validation with 458 healthy children illustrated that the verified results were within the established RIs with a 90%-100% proportion. CONCLUSION: We established capillary blood RIs for 22 CBC parameters in children across a broad age range in Beijing.

Effects of different doses of dexamethasone as local anesthetic adjuvant on brachial plexus block: A protocol for systematic review and meta analysis.

BACKGROUND: Dexamethasone has been widely used in brachial plexus block to enhance the effects of brachial plexus block. However, the clinical findings are not consistent with the dosage of dexamethasone prolonging local anesthetic nerve block. Therefore, the purpose of this study was to explore the effects of different doses of dexamethasone as local anesthetic adjuvant on brachial plexus block through network meta-analysis. METHODS: We searched PubMed, Web of Science, Cochrane Library, and Embase databases to collect all randomized controlled trials (RCTs) of different doses of dexamethasone as local anesthetic adjuvant on brachial plexus block until March 2021. Two researchers then independently screened articles, extracted data, and evaluated the quality of selected literatures. All data was processed by Stata 14.0 and WinBUGS 1.4.3.software. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: Our study is expected to provide high-quality evidence-based medicine advice for the effects of different doses of dexamethasone as local anesthetic adjuvant on brachial plexus block. ETHICS AND DISSEMINATION: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/PZ5WR.

Nkx2.1 downregulation is involved in brain abnormality induced by excess retinoic acid.

Abnormal development of central nervous system (CNS) caused by neural tube defects is not only a major contributor in the prevalence of stillbirths and neonatal deaths but also causes lifelong physical disability in surviving infants. Due to insufficient known investigated causes, CNS developmental abnormality has brought sever burden on health around the world. From previous results of high throughput transcriptome sequencing, we selected transcription factor Nkx2.1 as a candidate to investigate its role on brain abnormalities induced by excessive retinoic acid. The result of in situ hybridization showed that Nkx2.1 was mainly expressed in mouse brain. After the Nkx2.1 gene was silenced, retarded proliferation and accelerated apoptosis were found in mouse Neuro-2a (N2a) cells. Furthermore, our results indicated that the main components of sonic hedgehog (Shh) signaling pathway were affected in Nkx2.1-silenced cells, implying that Nkx2.1 plays an important role in the development of mouse brain by regulating Shh signaling pathway.

Exosome-encapsulated miR-6089 regulates inflammatory response via targeting TLR4.

Exosome-encapsulated microRNAs (miRNAs) have been identified as potential biomarkers in autoimmune diseases. However, little is known about the role of exosome-delivered miRNAs in rheumatoid arthritis (RA). In this study, we investigated the profile of specific exosomal miRNAs by microarray analysis of serum exosomes from three patients with RA and three healthy controls. Quantitative real-time PCR (qRT-PCR) was performed to validate the aberrantly expressed exosomal miRNAs. A total of 20 exosome-encapsulated miRNAs were identified to be differently expressed in the serum of patients with RA compared with controls. Interestingly, we found that exosome-encapsulated miR-6089 was significantly decreased after validation by qRT-PCR in serum exosomes from 76 patients with RA and 20 controls. Besides, miR-6089 could inhibit lipopolysaccharide (LPS)-induced cell proliferation and activation of macrophage-like THP-1 cells. TLR4 was a direct target for miR-6089. MiR-6089 regulated the generation of IL-6, IL-29, and TNF-α by targetedly controlling TLR4 signaling. In conclusion, exosome-encapsulated miR-6089 regulates LPS/TLR4-mediated inflammatory response, which may serve as a novel, promising biomarker in RA.

[Association of short-term efficacy for infliximab in rheumatoid arthritis with plasma concentration and anti-drug antibody].

OBJECTIVE: To investigate the correlation between peripheral concentration of infliximab (IFX) or anti-IFX antibody titers and short-term therapeutic effect of IFX in patients with active rheumatoid arthritis (RA).
 Methods: Twenty patients with active RA were treated with combination of methotrexate (MTX), leflunomide (LEF) with IFX, and the clinical and laboratory index and the side effects were recorded before and after IFX treatment. Twenty healthy subjects were chosen as a control group.
 Results: After 14-week treatment, patients were categorized into good, moderate or no responders according to EULAR remission criteria. There were no significant differences in peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels among the 3 groups, and there were no significant correlations among ΔDAS28-CRP, peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels.
 Conclusion: Peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels can not be used as reliable predictive index for short-term effect of IFX in active RA.

[Clinical effect of tocilizumab on patients with severe active rheumatoid arthritis].

OBJECTIVE: To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).
 Methods: Twelve patients with severe refractory RA were treated with tocilizumab. The clinical and laboratory indices and the side effects were recorded after treatment.
 Results: The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients, which were significantly improved after TCZ therapy (P<0.05), and no obvious adverse reactions were found.
 Conclusion: Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.