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Objective Because of their rarity, it is not known whether isocitrate dehydrogenase 2 (IDH2) mutations are related to olfactory neuroblastoma. We investigated relationships between IDH2 mutations, clinicopathological parameters, and prognosis for olfactory neuroblastoma to establish a molecular classification based on IDH2 mutations. Materials and methods An 82-patient cohort was retrospectively screened by immunohistochemistry using a mutation-specific IDH2 antibody and by real-time PCR for IDH2 mutations. We also determined immunohistochemically the expression of chromogranin A, synaptophysin, neuron-specific enolase, CD56, S100, and Ki67. Results The two methods for detection of IDH2 mutations had high consistency. Mutation of IDH2 detected by real-time PCR was correlated with higher Kadish stage, Hyams grade, and Ki67 proliferation index. Mutation of IDH2 was negatively correlated with expression of chromogranin A, synaptophysin, CD56, and S100. Kaplan-Meier analysis showed that an IDH2 mutation, high Hyams grade, and Ki67 index were associated with poor overall survival. Hyams grade and IDH2 mutation were independent prognostic factors in multivariable analysis. Conclusions Immunohistochemistry was a reliable method to assess the mutation status of IDH2. Tumors with IDH2 mutations represented a distinct subset with aggressive behavior and poor prognosis. The gene status of IDH2 can be a major molecular classification criterion in olfactory neuroblastoma.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is still an enormous threat to global health and the economy. Although China has adopted effective measures to control the outbreak, there is still a risk of local transmission from imported cases. Meanwhile, considering the high mortality rate and rapid spread of the disease, a safe and effective vaccine is urgently needed to control the pandemic. With COVID-19 vaccines becoming available to the population, it has become important to know about their acceptance in the population. This is important to enable high vaccination coverage rates and reflects the demand within the general population. An cross-sectional survey was conducted during October 2020 in Shanghai using a well-designed questionnaire, which aimed to evaluate the acceptability of COVID-19 vaccines and to identify the factors affecting its acceptability among working-age adults in Shanghai, China. We found that the acceptability of COVID-19 vaccines was high in work-age adults in Shanghai, China. The factors affecting the acceptability of vaccination identified in this study can provide guides to increase COVID-19 vaccine acceptability in future.

The aim of this study was to evaluate the efficacy of atorvastatin plus disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). METHODS We queried the PubMed, Embase, Web of Science, and the CENTRAL (Cochrane Central Register of Controlled Trials) databases for this study. The pooled efficacy was evaluated using standardized mean differences. The inverse of the variance model was used for data pooling. RESULTS Based on the search, we identified 9 randomized controlled trials. The trials included 258 patients in the atorvastatin plus DMARD groups and 246 patients in the DMARD alone groups. The primary outcome was the change from baseline in the 2018 (209:228 Disease Activity Score in 28 Joints). Based on the Disease Activity Score in 28 Joints, disease activity in RA patients decreased significantly in patients given atorvastatin plus DMARD compared with patients given DMARD alone (standardized mean difference, -2.46; 95% confidence interval, -3.98 to -0.95; p = 0.0015; I2 = 97%; p < 0.01). Subgroup analysis did not identify any confounding factors, and no publication bias was detected in the meta-analysis. CONCLUSIONS The result supports that atorvastatin could be added to DMARDs to treat patients with RA.

Zhimin Geng,* Yijing Tao,* Fenglei Zheng, Linlin Wu, Ying Wang, Yujia Wang, Yameng Sun, Songling Fu, Wei Wang, Chunhong Xie, Yiying Zhang, Fangqi Gong Department of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangqi GongDepartment of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of ChinaTel/Fax +86 571 86670008Email gongfangqi@zju.edu.cnBackground: Kawasaki disease (KD) is characterized by a disorder of immune response, and its etiology remains unknown. Monocyte is an important member of the body’s innate immune system; however its role in KD is still elusive due to its ambiguous heterogeneity and complex functions. We aim to comprehensively delineate monocyte heterogeneity in healthy and KD infants and to reveal the underlying mechanism for KD.Methods: Peripheral monocytes were enriched from peripheral blood samples of two healthy infants and two KD infants. scRNA-seq was performed to acquire the transcriptomic atlas of monocytes. Bio-information analysis was utilized to identify monocyte subsets and explore their functions and differentiation states. SELL+CD14+CD16- monocytes were validated using flow cytometry.Results: Three monocyte subsets were identified in healthy infants, including CD14+CD16- monocytes, CD14+CD16+ monocytes, and CD14LowCD16+ monocytes. Cell trajectory analysis revealed that the three monocyte subsets represent a linear differentiation, and possess different biological functions. Furthermore, SELL+CD14+CD16- monocytes, which were poorly differentiated and relating to neutrophil activation, were found to be expanded in KD.Conclusion: Our findings provide a valuable resource for deciphering the monocyte heterogeneity in healthy infants and uncover the altered monocyte subsets in KD patients, suggesting potential biomarkers for KD diagnosis and treatment.Keywords: Kawasaki disease, monocyte subsets, scRNA-seq

Emerging evidence suggests that the gut microbiota may interact with the host brain and play pivotal roles in the pathogenesis of neuropsychiatric disorders. However, the mechanism underlying reciprocal interactions along the microbiota-gut-brain axis in depression remains unclear. In this study, a murine model of chronic restraint stress (CRS) was established to investigate the metabolic signaling of tryptophan (Trp) neurotransmission at the intestinal and central levels in depression. The results showed that CRS mice displayed depression- and anxiety-like behaviors. Additionally, kynurenine (Kyn) and its metabolites, an important Trp metabolic pathway, were strongly activated in the brain. Intriguingly, the Kyn toxic signaling was exacerbated in the gut, especially in the colon. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme responsible for Kyn metabolic pathway initiation, was significantly upregulated in the brain and gut in CRS mice compared with control mice, promoting transfer of Trp metabolic pathway to Kyn signaling. Additionally, administration of IDO inhibitor, 1-methyl-tryptophan (1-MT), partially rescued CRS-induced depression- and anxiety-like changes. Moreover, the enhanced intestinal permeability mediated by CRS allowed toxic metabolites to “leak” into the bloodstream. The microbiome profiles of CRS mice displayed obviously altered taxonomic composition and negative correlations were observed between Enterorhabdus, Parabacteroides and Kyn levels in the brain. Reciprocal crosstalk between the brain and gut was further validated by citalopram treatment, IDO inhibitor and microbiota intervention, which counteracted depression-like behavior, Kyn metabolic signaling and microbiota composition in CRS mice. Meanwhile, Parabacteroides treatment affected Trp metabolism in mouse hippocampus, manifesting as elevated concentration of 5-HT as well as ratio of 5-HT to Trp. These results suggest that long-term stress disrupts Kyn metabolism and endocrine function along the gut-brain axis, accompanied by the disrupted homeostasis of certain microbiota, which collectively contribute to the development of depression-like behavior.

PURPOSE To retrospectively evaluate the efficacy and safety of computed tomography (CT)-guided microwave ablation (MWA) combined with percutaneous vertebroplasty (PVP) as a treatment for painful high thoracic vertebral metastases (T1-T4). MATERIALS AND METHODS In this retrospective study, 23 adult patients (33 high thoracic vertebral metastases) with moderate to severe pain were treated with CT-guided MWA and PVP. The procedural effectiveness was evaluated using a Visual Analog Scale (VAS), daily morphine consumption, and the Oswestry Disability Index (ODI) before and immediately after the procedure and during follow-up. RESULTS Technical success was achieved in all patients. The mean pre-procedure VAS score and morphine doses were 6.7 ± 1.7 (5-10) and 105.2 ± 32.7 (30-150) mg, respectively. The mean VAS scores and daily morphine doses at 24 h and 1, 4, 12, and 24 weeks post-operatively were 3.2 ± 1.4 and 41.3 ± 9.6 mg; 1.8 ± 1.0 and 31.5 ± 12.2 mg; 1.4 ± 1.3 and 19.6 ± 12.4 mg; 1.1 ± 0.8 and 14.5 ± 9.6 mg; and 1.0 ± 0.7 and 13.9 ± 9.3 mg, respectively (all p

PURPOSE: This study aims to evaluate the safety and effectiveness of the percutaneous cryoablation for subcapsular hepatocellular carcinoma (HCC). METHODS: A total of 57 patients with subcapsular (

Background Retinopathy of prematurity (ROP) continues to be a major cause of visual impairment and blindness in premature infants and children. Objectives To investigate the incidence of severe ROP receiving treatment in extremely preterm (EP) infants in China over time. The risk factors for ROP treatment were also assessed. Methods This was a multicentre retrospective study and a subanalysis of baseline data from the "Outcomes of EP infants in China 2010-2019" study. This study was conducted in 68 tertiary neonatal care centres from 31 provinces of China. Infants with a gestational age of 230 -276 weeks and admitted to a neonatal unit within the first 72 h of life between 2010 and 2019 were enrolled. Incidence of ROP was analysed in infants who survived to 32 weeks postmenstrual age and screened for ROP. Multivariable modified Poisson regression models were used to identify risk factors for ROP treatment. Results Among 7295 eligible infants, 4701 (64.5%) survived to 32 weeks postmenstrual age and met ROP screening criteria. Of the 3756 infants who screened and with ROP data, 2320 (61.8%) developed ROP of any stage. The overall incidence of ROP treatment was 12.6%, decreasing from 45.5% at 23 weeks to 8.3% at 27 weeks. During the 10-year period, the incidence of ROP treatment did not change, although the incidence of any ROP increased over time. Independent risk factors associated with ROP treatment included lower gestational age, small for gestational age, multiple birth, severe intraventricular haemorrhage, patent ductus arteriosus and supplemental oxygen duration. Conclusions The incidence of EP infants receiving ROP treatment showed no change during this 10-year period in China. Prevention of prematurity and foetal growth restriction, judicious use of oxygen and reducing comorbidities are promising factors that may reduce the incidence of ROP needing treatment in these high-risk infants.

Multiple myeloma (MM) is a malignancy of plasma cells that leads to marrow failure and bone lesions. Numerous studies have verified the link between long non‑coding RNAs (lncRNAs) and MM. The present study aimed to examine the role and underlying mechanism of differentiation antagonizing non‑protein coding RNA (DANCR) in MM cells. The relative expression levels of DANCR, microRNA (miR)‑135b‑5p and Krüppel‑like factor 9 (KLF9) were examined using reverse transcription‑quantitative PCR. Cell viability was assessed using the MTT assay, while relative cell migration and invasion were evaluated using Transwell assays. Moreover, the dual‑luciferase reporter assay was used to examine the interplay between DANCR, miR‑135b‑5p and KLF9. Western blotting was performed to determine the expression level of KLF9. It was found that lncRNA DANCR and KLF9 were downregulated, while miR‑135b‑5p was upregulated in the serum of patients with MM and in MM cells compared with the controls. Overexpressing DANCR or knocking down miR‑135b‑5p reduced the viability of the MM cells, as well as restrained MM cells from migrating and invading. Furthermore, DANCR directly targeted miR‑135b‑5p and was negatively correlated with miR‑135b‑5p. It was also found that KLF9 was targeted by miR‑135b‑5p and was inversely correlated with miR‑135b‑5p expression. The impact of lncRNA DANCR‑mediated suppression on cell viability, invasion and migration was partially abolished by short hairpin RNA KLF9 or miR‑135b‑5p mimics transfection in MM cells. Thus, it was suggested that lncRNA DANCR repressed the viability, migration and invasion of MM cells by sponging miR‑135b‑5p to target KLF9.

Activated carbon (AC) electrodes applied in capacitive deionization (CDI) are usually prepared by coating activated materials on current collector, accompanying with low mass loading, poor areal salt adsorption capacity (SACA) and undesired volumetric salt adsorption capacity (SACV). Herein, we report preparation of free-standing AC electrodes by a simple mold-casting method. Unlike conventional coating methods, activated materials were well-dispersed together with binders to obtain a uniform suspension and then submitted for mold-casting preparation of electrodes. This new strategy helps to produce rational structure for porous free-standing AC electrodes by alleviating the blocking effect of pores. Obtained electrodes not only exhibit pretty good electrical conductivity and hydrophilicity, but also show excellent mechanical stability and water tolerance. The electrodes deliver both high SACA of 0.49 mg/cm2 and SACV of 2.48 mg/cm3. By virtue of the free-standing feature, a CDI device comprising 6 as-made units was built for demonstration, which exhibits a promising SACV of 2.01 mg/cm3 in NaCl aqueous solution. This work not only offers a simple method to prepare free-standing AC electrodes with extraordinary high mass loading (55 mg/cm2) and excellent salt adsorption capacity, but also provides good opportunity for large-scale application of CDI technology by substantially improving packing volumetric density.

Rationale: It is unclear whether removing the danger-associated molecular patterns (DAMPs) of gut lymph (GL) in the rats of gut ischemia-reperfusion injury (GIRI) model may reduce the distant organ lung injury.Objective: To determine whether oXiris gut lymph purification (GLP) may remove the DAMPs of GL in the rats’ model of acute lung injury (ALI) caused by GIRI.Methods: The experimental rats were divided into four groups: Sham group, GIRI group, GIRI + gut lymph drainage (GLD) group, and GIRI + GLP group. After successful modeling, the lung tissue samples of rats in each group were taken for hematoxylin-eosin (HE) staining and detection of expression levels of apoptotic indexes. The level of DAMPs was detected in blood and lymph. We observed its microstructure of type II alveolar epithelial cells (AECⅡ), and detected the expression level of apoptosis indexes.Measurements and Main Results: GIRI-induced destruction of alveolar structure, thickened alveolar walls, inflammatory cell infiltration emerged in the GIRI group, HMGB-1 and IL-6 levels significantly increased, and HSP70 and IL-10 levels reduced in lymph and serum. Compared with GIRI group, the lung tissue damage in GIRI + GLP group significantly improved, the expression level of HMGB-1 and IL-6 in the lymph and serum reduced, and HSP70 and IL-10 increased. The organelle structure of AECII in GIRI + GLP group was significantly improved compared with the GIRI group. Conclusions: oXiris GLP blocks the key link between DAMPs and mononuclear phagocyte system to inhibit inflammation and cell apoptosis, thereby reducing ALI induced by GIRI.

Glycation plays a pathogenic role in many age-related degenerative pathological conditions, such as diabetes, end-stage renal diseases, and cardiovascular diseases. Mass spectrometry-based qualitative and quantitative analysis methods have been greatly developed and contribute to our understanding of protein glycation. However, it is still challenging to sensitively and accurately quantify endogenous glycated proteome in biological samples. Herein, we proposed an integrated and robust quantitative strategy for comprehensive profiling of early-stage glycated proteome. In this strategy, a filter-assisted sample preparation method was applied to reduce sample loss and improve reproducibility of sample preparation, contributing to high-throughput analysis and accurate quantification of endogenous glycated proteins with low abundance. Standard glycated peptides were spiked and performed the subsequent process together with complex samples both in label-free quantification and multiple reaction monitoring (MRM) analysis, contributing to the improvement of quantitative accuracy. In parallel, a novel approach was developed for the synthesis of heavy isotope-labeled glycated peptides used in MRM analysis. By this way, a total of 1128 endogenous glycated peptides corresponding to 203 serum proteins were identified from 60 runs of 10 pairs of hemodialysis patients with and without cardiovascular complications, and 234 glycated peptides corresponding to 63 proteins existed in >70% runs, among which 17 peptides were discovered to be differentially glycated (P 1.5 or

Background Numerous long non-coding RNAs (lncRNAs) are reported to affect the progression of multiple myeloma (MM). This study is aimed to explore the role and downstream mechanism of lncRNA LINC01003 in MM. Materials and methods Xenograft tumor assay was used to assess the function of LINC01003 in MM in vivo. The mRNA expression levels of LINC01003, miR-33a-5p, and PIM1 were determined by quantitative real-time polymerase chain reaction. Cell viability was examined by MTT assay. Relative protein levels of apoptosis-related factors (Bcl-2 and Bax) and proviral integration site of the Moloney leukemia virus kinase 1 (PIM1) were detected via western blot. Adhesion-related proteins were measured by Enzyme-linked immunosorbent assay was used to determine the levels of adhesion-related proteins. Besides, the target relation among LINC01003, miR-33a-5p and PIM1 was tested via dual-luciferase reporter assay. Results Low expression of LINC01003 was observed in MM cell lines and peripheral blood samples of MM patients. Both LINC01003 up-regulation and miR-33a-5p down-regulation repressed cell viability and adhesion, and promoted apoptosis of MM cells. Moreover, LINC01003 suppressed the growth of xenograft tumor in mice. We then identified miR-33a-5p as a downstream target of LINC01003, and confirmed that PIM1 was a direct target gene of miR-33a-5p. Both high expression of miR-33a-5p and low expression of PIM1 reversed the suppressive effects of LINC01003 overexpression on cell adhesion and viability, and the promoting effect on apoptosis in MM cells. Conclusion LINC01003 functioned as a sponge of miR-33a-5p to inhibit the development MM by regulating PIM1 expression.

Aims Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease to cause end-stage kidney disease. This study investigated the difference in urinary exosomal circular RNA(circRNA) expression profiles between patients with IgAN and healthy controls (HCs), for better understanding of gene regulation in exosomes of IgAN patients. Methods A pairwise comparison of urinary circRNA expression profiles between IgAN patients and HCs was performed using methods, including high-throughput sequencing and quantitative polymerase chain reaction. Moreover, the potential functions of differentially expressed circRNAs(DECs) in IgAN were investigated by Gene Ontology (GO) enrichment analysis; Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis; and the circRNA-miRNA-mRNA network. Results We identified 450 upregulated and 26 downregulated circRNAs in the IgAN patients. GO analysis showed that these enriched circRNAs might regulate primary miRNA processing, the ability of angiotensin receptor binding, and stress fiber function. KEGG analysis suggested these DECs may be closely associated with the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K-Akt)signaling pathways. Network analysis revealed the relationship between circRNAs and their target genes. Conclusions The identified DECs may be useful for both research on molecular etiology of IgAN and development of potentially novel non-invasive biomarkers of IgAN.

PURPOSE To evaluate the efficacy and safety of combined microwave ablation (MWA) and osteoplasty as a palliative therapy for painful bone metastases. MATERIALS AND METHODS As an extension of a previous limited single-center study, a retrospective review was conducted for 147 patients (77 male, 70 female) with painful bone metastases who underwent MWA combined with osteoplasty. In total, 102 (69.4%), 41 (27.9%), and 4 (2.7%) patients had spinal metastases, extraspinal metastases, and both, respectively. Treatment efficacy was determined by comparing visual analog scale (VAS) scores, daily morphine equivalent opioid consumption, and Oswestry disability index (ODI) scores before treatment and during the follow-up period (mean follow-up, 9.8 months; range 3-16). RESULTS The mean VAS score significantly declined from 6.4 ± 2.3 before treatment to 3.2 ± 2.1, 1.9 ± 1.6, 1.8 ± 1.6, 1.8 ± 1.6, and 1.9 ± 1.6 at 24 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after treatment, respectively (P < .01). Furthermore, the mean daily morphine equivalent opioid consumption was significantly reduced from 81.5 ± 32.8 mg before treatment to 40.0 ± 20.6, 32.4 ± 10.2, 26.4 ± 10.0, 21.5 ± 8.3, and 19.3 ± 7.4 mg. The mean ODI score also declined after treatment (P < .0001). Major complications occurred in 4 of 147 patients, with 1 pathologic fracture, 1 nerve injury, and 2 mild skin infections. Minor cement leakages were observed at 69 sites (32.8%). CONCLUSIONS MWA combined with osteoplasty is an effective and safe treatment for painful bone metastases.

Elabela, also known as Toddler or Apela, is a recently discovered hormonal peptide containing 32 amino acids. Elabela is a ligand of the apelin receptor (APJ). APJ is a G protein-coupled receptor widely expressed throughout body, and together with its cognate ligand, apelin, it plays an important role in various physiological processes including cardiovascular functions, angiogenesis and fluid homeostasis. Elabela also participates in embryonic development and pathophysiological processes in adulthood. Elabela is highly expressed in undifferentiated embryonic stem cells and regulates endoderm differentiation and cardiovascular system development. During differentiation, Elabela is highly expressed in pluripotent stem cells and in adult renal collecting ducts and loops, where it functions to maintain water and sodium homeostasis. Other studies have also shown that Elabela plays a crucial role in the pathogenesis of kidney diseases. This review addresses the role of Elabela in kidney diseases including renal ischemia/reperfusion injury, hypertensive nephropathy, diabetic nephropathy, and cardiorenal syndrome.

Catheter-related blood-stream infections (CRBSIs) are the most common healthcare-associated blood-stream infections. They can be diagnosed by either semi-quantitative or quantitative methods, which may differ in diagnostic accuracy. A meta-analysis was undertaken to compare the diagnostic accuracy of semi-quantitative and quantitative methods for CRBSI. A systematic search of Medline, Scopus, Cochrane and Embase databases up to January 2020 was performed and subjected to a QUADAS (quality assessment of diagnostic accuracy studies 2) tool to evaluate the risk of bias among studies. The pooled sensitivity and specificity of the methods were determined and heterogeneity was evaluated using the χ2 test and I2. Publication bias was assessed using a Funnel plot and the Egger's test. In total, 45 studies were analysed with data from 11 232 patients. The pooled sensitivity and specificity of semi-quantitative methods were 85% (95% CI 79–90%) and 84% (95% CI 79–88%), respectively; and for quantitative methods were 85% (95% CI 79–90%) and 95% (95% CI 91–97%). Considerable heterogeneity was statistically evident (P < 0.001) by both methods with a correspondingly symmetrical Funnel plot that was confirmed by a non-significant Deek's test. We conclude that both semi-quantitative and quantitative methods are highly useful for screening for CRBSI in patients and display high sensitivity and specificity. Quantitative methods, particularly paired quantitative cultures, had the highest sensitivity and specificity and can be used to identify CRBSI cases with a high degree of certainty.

ObjectivesTo compare the clinical characteristics between the rapid cohort and the normal cohort of erythrocyte sedimentation rate (ESR) in COVID-19 infections, analyze the variables with significant differences, and explore the influencing factors of rapid ESR.MethodsSelected a total of 80 patients with ESR detection during hospitalization were measured in 146 patients who received medical observation in concentrated isolation hospital in Guizhou province in China, collected and compared demographic information, epidemiological data, clinical symptoms, laboratory test data and CT image data during the observation between rapid cohort and normal group of ESR.ResultsBy comparison, the proportion of male in the rapid cohort was higher than female. The average age was more than 35 years old, with a large age gap. The proportion of severe and critical patients was more than 26.53% (13/49). However, in the normal cohort the proportion of female was more than male, and the average age was about 8 years lower than the rapid cohort, and the age gap was smaller. The proportion of severe and critical patients was 12.90%, which was less than half of the rapid group. In the two groups, the proportion of clustered cases accounted for more than 50%, and the average number of patients in one family was more than 3. The most common clinical symptoms were cough, sputum, fever, sore throat and weakness of limbs. There were significant differences in ALT, γ-GT and C-reactive protein between the rapid and normal cohort (PConclusionsIn this study, we found that ESR is related to Hemoglobin and C-reactive protein. (Funded by Science and Technology Department of Guizhou Province; Chinese ClinicalTrials.gov number, ChiCTR2000033346. opens in new tab.)

ObjectiveTo describe the efficacy of convalescent plasma transfusion for COVID-19 patients.MethodsThis is a retrospective study of 6 COVID-19 patients with convalescent plasma at Guizhou Provincial Jiangjunshan Hospital – a tertial hospital, in Guiyang, Guizhou, China, from January 29, to April 30, 2020; final data of follow-up was May 12, 2020. Through the review of the electronic medical records of Guizhou Jiangjunshan Hospital, clinical data of 6 patients were obtained. Three patients with worsening symptoms after empirical treatment with antivirals were transfused convalescent plasma therapy for the first treatment, while the other three severe or critical COVID-19 patients with rapid progression were transfused. The efficacy of convalescent plasma depends on the relief of symptoms, changes in laboratory indicators and chest imaging abnormalities.ResultsThe PaO2 / FiO2 and lymphocyte count of patients 1, 2 and 3 treated with convalescent plasma treatment for the first treatment period were changed from abnormal to normal. The levels of inflammation markers CRP and IL-6 of the patients decreased significantly. Chest imaging examination showed that the lung lesions gradually subsided. The relapsed patients (No. 4 and No. 6), after using convalescent plasma therapy, turned negative on two consecutive throat swab tests on Day 24 and Day 3, respectively.ConclusionsConvalescent plasma treatment of COVID-19 is beneficial for those patients with be difficult to turn to negative or re-positive RT-PCR.Key PointsConvalescent plasma treatment of COVID-19 is beneficial for those patients with be difficult to turn to negative or re-positive RT-PCR.

Aim: We aim to study clinically and pathologically whether narrow resection margin (1 cm) and narrow resection margin (

Perinatal exposure to bisphenol A (BPA) contributes to neurological disorders in offspring, but the underlying mechanisms are still poorly understood. The abnormal release of neuroactive metabolites in the tryptophan (TRP) and dopamine (DA) pathways is considered to be closely associated with some disorders. Thus, in this study, TRP and DA pathways in adult female mouse offspring were investigated when the pregnant mice were given either vehicle or BPA (2, 10, or 100 μg/kg/d) from day 6 of gestation until weaning. Then, the serum and brain samples of offspring were collected at 3, 6 and 9 months, and 12 neuroactive metabolites in the TRP and DA pathways were detected. The results showed that, in the TRP pathway, TRP levels decreased, whereas kynurenine (KYN) levels and TRP turnover increased in the brain. In the serum, TRP, KYN and 5-hydroxytryptamine (5-HT) levels decreased significantly. For the DA pathway, DA and DA metabolites, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA), reduced significantly in the brain and serum. DA turnover decreased dramatically in the brain but enhanced in the serum. The disturbance of these two metabolic pathways might be one of the potential mechanisms of BPA-induced neuropsychiatric disorders.

Excess androgen-induced obesity has become a public health problem, and its prevalence has increased substantially in recent years. Chemokine-like receptor 1 (CMKLR1), a receptor of chemerin secreted by adipose tissue, is linked to adipocyte differentiation, adipose tissue development, and obesity. However, the effect of CMKLR1 signaling on androgen-mediated adiposity in vivo remains unclear. Using CMKLR1-knockout mice, we constructed an androgen-excess female mouse model through 5α-dihydrotestosterone (DHT) treatment and an androgen-deficient male mouse model by orchidectomy (ORX). For mechanism investigation, we used 2-(α-Naphthoyl) ethyltrimethylammonium iodide (α-NETA), an antagonist of CMKLR1, to suppress CMKLR1 in vivo and wortmannin, a PI3K signaling antagonist, to treat brown adipose tissue (BAT) explant cultures in vitro . Furthermore, we used histological examination and quantitative PCR, as well as Western blot analysis, glucose tolerance tests, and biochemical analysis of serum, to describe the phenotypes and the changes in gene expression. We demonstrated that excess androgen in the female mice resulted in larger cells in the white adipose tissue (WAT) and the BAT, whereas androgen deprivation in the male mice induced a reduction in cell size. Both of these adipocyte size effects could be attenuated in the CMKLR1-knockout mice. CMKLR1 deficiency influenced the effect of androgen treatment on adipose tissue by regulating the mRNA expression of the androgen receptor (AR) and adipocyte markers (such as Fabp4 and Cidea). Moreover, suppression of CMKLR1 by α-NETA could also reduce the extent of the adipocyte cell enlargement caused by DHT. Furthermore, we found that DHT could reduce the levels of phosphorylated ERK (pERK) in the BAT, while CMKLR1 inactivation inhibited this effect, which had been induced by DHT, through the PI3K signaling pathway. These findings reveal an antiobesity role of CMKLR1 deficiency in regulating lipid accumulation, highlighting the scientific importance for the further development of small-molecule CMKLR1 antagonists as fundamental research tools and/or as potential drugs for use in the treatment of adiposity.

Background Esophageal squamous cell precursor lesions remain one of the most controversial topics in pathology and clinical management. Aims To analyze the dysregulation of human telomerase RNA component (hTERC) in esophageal squamous cell precursor lesions and the clinicopathological correlations with the characteristics of esophageal squamous cell precursor lesions. Methods Florescence in situ hybridization was performed to detect hTERC amplification in different gradings of esophageal squamous cell precursor lesions. With retrospective follow-up data, clinicopathological correlations between hTERC and esophageal squamous cell precursor lesions were subjected to logistic regression analysis. Results hTERC amplification gradually increased with upgrading of dysplasia, reaching the highest level in high-grade intraepithelial neoplasia, and there was a significant difference between the low-grade intraepithelial neoplasia group and the high-grade intraepithelial neoplasia group (P = 0.00). Logistic regression analysis showed that hTERC amplification was correlated with both dysplasia grading and ulcer characteristics of esophageal squamous cell precursor lesions (P

AIM Autophagy is a common process during development. Abnormal autophagy can impact cell apoptosis. Previous studies have shown that apoptosis is present during bronchopulmonary dysplasia (BPD). However, there is no consensus on the level of coexisting autophagy. This study was designed to investigate the role of autophagy and the effects of autophagy inducers in a BPD model. METHOD A total of 100 newborn Sprague-Dawley rats were randomly assigned to model and control groups. BPD models were established by hyperoxic induction(FiO2 0.80). Some of them were treated with autophagy-inducing agents. RESULT As compared to the control group, more autophagic bodies were found within Type II alveolar epithelial cells (AT-II cells) under transmission electron microscopy (TEM) in the model group at 3 d . These autophagic bodies were also accompanied by apoptotic bodies and expression of both bodies peaked at 7 d. As shown by TdT-mediated dUTP nick end labeling (TUNEL), there were more apoptotic cells in the model group than in the control group. Protein expression levels of LC3B-II, p62, Lamp1, and cleaved Caspase-3 increased with increased hyperoxic exposure time. No significant differences were observed in the mRNA expression levels of LC3B, p62, and Lamp1. After introducing an autophagy inducer, either rapamycin or lithium chloride, the radial alveolar count (RAC) value of BPD model group increased as compared with placebo group, the thickness of alveolar septum decreased, while apoptosis decreased. CONCLUSION Reduced autophagy resulting from blocked autophagy flow may be a key link in the pathogenesis of BPD. By enhancing repressed autophagy, apoptosis could be reduced and alveolar development improved.

Gpbar1 (TGR5), a G-protein-coupled bile acid membrane receptor, is well known for its roles in regulation of glucose metabolism and energy homeostasis. In the current work, we found that TGR5 activation by its ligand suppressed lipopolysaccharide (LPS)-induced proinflammatory gene expression in wild-type (WT) but not TGR5−/− mouse kidney. Furthermore, we found that TGR5 is a suppressor of kidney cancer cell proliferation and migration. We show that TGR5 activation antagonized NF-κB and STAT3 signaling pathways through suppressing the phosphorylation of IκBα, the translocation of p65 and the phosphorylation of STAT3. TGR5 overexpression with ligand treatment inhibited gene expression mediated by NF-κB and STAT3. These results suggest that TGR5 antagonizes kidney inflammation and kidney cancer cell proliferation and migration at least in part by inhibiting NF-κB and STAT3 signaling. These findings identify TGR5 may serve as an attractive therapeutic tool for human renal inflammation related diseases and cancer.

Objective: The objective of this study is to determine the frequency of no residual cancer tissue in the chemotherapy regression area (CRA) of hepatoblastoma after preoperative chemotherapy and to ...

Cutaneous T-cell lymphoma (CTCL) is associated with the downregulation of miR-337 expression, although the exact underlying mechanism is unknown. In the present work, we investigated the molecular mechanism and function of miR-337 in regulating CTCL cell viability and invasion. We observed that miR-337 expression was downregulated in both CTCL tumors and cell lines. Furthermore, CCK assay, BrdU incorporation assay, and flow cytometry revealed that transfection with the miR-337 mimic resulted in decreased proliferation and increased apoptotic levels in CTCL cells. Results of the Transwell migration assay indicated that the miR-337 mimic decreased CTCL cell invasion in vitro. Both bioinformatics prediction and the dual-luciferase reporter assay revealed that miR-337 targets the 3'-UTR of STAT3 for silencing. Overexpression of STAT3 counteracted the pro-apoptotic influence of miR-337 in CTCL cell lines and restored their invasion properties. The results thus indicate that the miR-337-STAT3 axis inhibits the proliferation of malignant T cells and that miR-337 may serve as a promising therapeutic target for CTCL.

Epidemiological studies have demonstrated that the general population’s exposure to bisphenol A (BPA) substitutes is ubiquitous. Bisphenol F (BPF), one of the main BPA substitutes, is increasingly replacing BPA in plastics for food and beverage applications. Accumulating evidence suggests that BPA exposure is associated with nonalcoholic fatty liver disease (NAFLD)-like changes. However, the potential effects of BPF on lipid homeostasis remain poorly understood. In the present study, an epidemiological analysis with LC-MS-MS revealed that the BPF concentrations in the serum of NAFLD patients were significantly higher than those in a control group. Supporting this result, using Oil Red O, BODIPY 493/503, LipidTox Deep Red staining and gas chromatography-time-of-flight mass spectrometry (TOF-MS) assays, we found that BPF exposure induced NAFLD-like changes, with obvious lipid droplet deposition, triglyceride (TG) and fatty acids increase in mouse livers. Meanwhile, lipid droplet deposition and TG increase induced by BPF were also observed in HepG2 cells, accompanied by autophagic flux blockade, including autophagosome accumulation and the decreased degradation of SQSTM1/p62. Using adenoviruses dual-reporter plasmid RFP-GFP-LC3, RFP-GFP-PLIN2 transfection, AO staining, and EGFR degradation assays, we demonstrated that BPF treatment impaired lysosomal degradative capacity, since BPF treatment obviously impaired lysosomal acidification, manifested as decreased lysosomal hydrolase cathepsin L (CTSL) and mature cathepsin D (CTSD) in HepG2 and mouse liver issues. Additionally, v-ATPase D, a multi-subunit enzyme that mediates acidification of eukaryotic intracellular organelles, significantly decreased after BPF exposure in both the vitro and in vivo studies. This study ascertained a novel mechanism involving dysfunctional of lysosomal degradative capacity induced by BPF, which contributes to lipophagic disorders and causes lipid droplet deposition. This work provides evidence that lysosomes may be a target organelle where BPF exerts its potential toxicity; therefore, novel intervention strategies targeting lysosome are promising for BPF-induced NAFLD-like changes.

While the activated carbon (AC) electrodes applied in the field of capacitive deionization (CDI) are mostly prepared by slurry-coating methods, they have long been suffering from the unideal electron transfer rates and exfoliation during long-term operation. Herein, we report an AC electrode modification method involving carbonizing less-conductive binders and in-situ grafting of carbon nanotubes (CNTs) on entire AC electrodes via a one-step vacuum chemical vapor deposition (CVD) process. The in-situ grafted CNTs showed a much more homogeneous distribution in AC electrodes, which functioned as conductive glue bridging the AC granules and intimately formed a solid and highly conductive carbon framework. The as-prepared AC electrode with grafted CNTs had a superior salt adsorption capacity of 15.6 mg NaCl g−1 with prominent long-term stability and increased current efficiency (by 70%) compared with traditional AC electrodes. The boosted CDI performance should be ascribed to the unique structure and electrical properties of the electrode. This work provides an efficient and facile alternative to preparing tuned AC electrodes for viable water treatment technologies, which is of great potential to be applied in many attractive fields such as catalysis, energy conversion and storage.

Humerus is the long bone second-most commonly affected by metastases. An impending pathologic humeral fracture requires rigid surgical stabilization to prevent it from fully fracturing. In the present study, we report a case of a 71-year-old male patient with a visual analog score of 10 (indicating extreme pain) and an impending pathologic fracture that allowed for combined treatment with percutaneous microwave ablation and simultaneous injection of bone cement during Kirschner wire insertion. The procedure was performed successfully with no complications. The patient reported pain relief and improved quality of life and functional status 1 day, 7 days, 1 month, and 2 months after his procedure.

Circular RNA (circRNA) belongs to the non-coding RNA family and is involved in various human cancers, such as lung cancer and colorectal cancer. Nevertheless, whether circRNA expression is related to chronic lymphocytic leukemia (CLL) progression remains largely unclear. In our study, we investigated the role of circ-CBFB in CLL. We found that circ-CBFB was markedly overexpressed in CLL cells compared to normal controls. Furthermore, we found that circ-CBFB could serve as a diagnostic and prognostic biomarker for CLL patients. We also explored the physiological function of circ-CBFB. We found that circ-CBFB knockdown significantly suppressed CLL cell proliferation, arrested cell cycle progression, and induced cellular apoptosis. In terms of its mechanism, we identified circ-CBFB as a sponge of miR-607, which targeted FZD3. By inhibiting miR-607 availability, circ-CBFB promoted FZD3 expression, leading to the activation of the Wnt/β-catenin pathway and consequent CLL progression. Taken together, our findings revealed that the circ-CBFB/miR-607/FZD3/Wnt/β-catenin regulatory signaling cascade contributes to CLL progression.

Vitamin D and its receptor have a protective effect on epithelial barriers in various tissues. Low levels of vitamin D are associated with numerous pulmonary diseases, including acute lung injury (ALI) and acute respiratory distress syndrome. The present study investigated whether the vitamin D/vitamin D receptor (VDR) pathway may ameliorate lipopolysaccharide (LPS)-induced ALI through maintaining the integrity of the alveolar epithelial barrier. This was investigated by exposing wild-type (WT) and VDR knockout C57BL/6J mice to LPS, then comparing the healthy and LPS-treated mice lungs and bronchoalveolar lavage fluid (BALF). More specifically, lung histology, mRNA levels of proinflammatory cytokines and chemokines, and protein expression levels of tight junction proteins were determined. In addition, a vitamin D analog (paricalcitol) was administered to WT mice in order to investigate the effect of vitamin D on the alveolar epithelial barrier following exposure to LPS. VDR knockout mice exhibited severe lung injuries (P

We report here an approach to redirecting somatic cell fate under chemically defined conditions without transcription factors. We start by converting mouse embryonic fibroblasts to epithelial-like cells with chemicals and growth factors. Subsequent cell fate mapping reveals a robust induction of SOX17 in the resulting epithelial-like cells that can be further reprogrammed to endodermal progenitor cells. Interestingly, these cells can self-renew in vitro and further differentiate into albumin-producing hepatocytes that can rescue mice from acute liver injury. Our results demonstrate a rational approach to convert mouse embryonic fibroblasts to hepatocytes and suggest that this mechanism-driven approach may be generalized for other cells.

Novel clay–polymer composite hydrogels with high water content (up to 98 wt %) are developed, in which mechanical properties are reinforced by the formation of multiple ion-pairs between the polymer chains and clay nanosheets (CNS). When a small amount of guanidinium-pendant methacrylamide (0.1–0.2 wt %) is copolymerized with a neutral monomer (0.5–2.0 wt %) in an aqueous dispersion of CNS (1.0–3.0 wt %), a self-standing hydrogel with satisfactory mechanical toughness and elasticity results, despite its high water content (95–98 wt %). The mechanical properties and swelling behaviors of the hydrogels can be tuned by the amount of the guanidinium-pendant acrylamide. A systematic study indicates that the ion pairs, formed between the guanidinium groups in the polymer chains and the oxyanions on the surfaces of the CNS, serve as crosslinking points in the three-dimensional network developed in these hydrogels. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 839–847

This study aimed to investigate the prevalence of resistance to second-line antituberculosis (anti-TB) drugs and its association with resistance-related mutations in Mycobacterium tuberculosis isolated in China. In the present study, we collected 380 isolates from a population-based study in China and tested the drug susceptibility to first- and selected second-line drugs. These results were compared with polymorphisms in the DNA sequences of genes associated with drug resistance and MIC values of the studied second-line drugs. Of 43 multidrug-resistant M. tuberculosis isolates, 13 showed resistance to fluoroquinolones or injectable second-line drugs (preextensively drug-resistant TB [pre-XDR-TB]), and 4 were resistant to both and thus defined as extensively drug-resistant TB (XDR-TB). Age and previous TB therapy, including use of second-line drugs, were two independent factors associated with increased resistance to both first- and second-line drugs. Molecular analysis identified the most frequent mutations in the resistance-associated genes: D94G in gyrA (29.1%) and A1401G in rrs (30.8%). Meanwhile, all 4 XDR-TB isolates had a mutation in gyrA , and 3 of them carried the A1401G mutation in rrs . Mutations in gyrA and rrs were associated with high-level resistance to fluoroquinolones and the second-line injectable drugs. In addition to the identification of resistance-associated mutations and development of a rapid molecular test to diagnose the second-line drug resistance, it should be a priority to strictly regulate the administration of second-line drugs to maintain their efficacy to treat multidrug-resistant TB.

Excessive metal exposure has been recognized as one of the detrimental factors for brain damage. However, the potential adverse effects induced by heavy metals on monoamine neurotransmitter pathways remains poorly understood. Our study aimed to investigate the possible association between metal exposure and neurotransmitter metabolism. By a cross-sectional investigation, 224 electroplating workers and 213 non-electroplating exposure workers were recruited in the exposure and control groups. Metal exposure levels were analyzed using inductively-coupled plasma mass spectrometry and monoamine neurotransmitter pathway metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in human urine samples. Multivariate linear regression model was used to assess the dose-response relationships of urinary metals and neurotransmitter pathway metabolites. Significant dose-dependent trends of urinary vanadium quartiles with all metabolites were observed, and the trends demonstrated significance after multiple testing correction. It also showed that urinary chromium levels were significantly associated with decreased serotonin level and cadmium was positively associated with norepinephrine and epinephrine. In addition, arsenic was positively associated with tryptophan, serotonin, dopamine and norepinephrine. Iron was positively associated with increased homovanillic acid (HVA) and epinephrine while nickel was negatively associated with increased epinephrine levels. Zinc was positively related to tryptophan, kynurenin (KYN), 5-hydroxyindole acetic acid (5-HIAA), dopamine, HVA and norepinephrine. There was no significant association between urinary copper with any other metabolites after adjusting of multiple metal models. Metal exposure may be associated with neurotransmitter metabolism disturbances. The present work is expected to provide some support in the prevention and management of metal-associated neurological diseases.

Wireless Capsule Endoscope (WCE) enables developing actively controlled capsule for potential complex surgeries, imaging, and new medicine tests. These tasks of WCE need safe, efficient, and precise 3D localization techniques. In this paper, a new application of the magnetic resonance coupling (MRC) technique, which has been widely developed for efficient wireless power transfer, is introduced. It is proposed that the distance dependent signal strength in a MRC system can be beneficially used for 3D localization. The new 3D-MRC localization system consists of three orthogonal emitting coils which are powered by a battery in the capsule, and three pairs of orthogonal receiving coils which are placed outside human body. The distances between the WCE and the receiving coils can be estimated with good accuracy by studying the signal strengths in individual receiving coils. The proposed new 3D-MRC localization system also exhibits higher efficiency when compared with traditional magnetic induction method for 3D localization due to the use of MRC.

This study introduced the protease inhibitor-encoding gene sporamin from sweet potato together with the wound-responsive promoter pMSPOA into the Chinese cabbage (Brassica campestris ssp. chinensis var. parachinensis) through Agrobacterium tumefaciens-mediated transformation. Transgenic lines were confirmed via PCR detection of both the sporamin and hygromycin gene fragments in the cloning vector. The expression level of sporamin in the different lines was determined using RT-PCR analysis. Leaves from four individual transgenic lines including T0-2, T0-3, T0-4 and T0-5, possessing higher levels of sporamin than control plants, were then used to conduct insect feeding studies. Second instar larvae of diamondback moth (Plutella xylostella L.) were used in feeding assays. All four transgenic lines demonstrated high levels of resistance against diamondback based on average body weight of total incubated larvae following feeding assays and amount of leaf damage.

To develop PEGylated multi-walled carbon nanotubes as a sustained release drug delivery system. Oxaliplatin was incorporated into inner cavity of PEGylated multi-walled carbon nanotubes (MWCNT-PEG) using nano-extraction. Oxaliplatin release rates from MWCNT-PEG-Oxaliplatin were investigated using dialysis tubing. Cytotoxicity of oxaliplatin, MWCNT-Oxaliplatin and MWCNT-PEG-Oxaliplatin were evaluated in HT29 cell by MTT assay, Pt-DNA adducts formation, γ-H2AX formation and cell apoptosis assay. Loading of oxaliplatin into MWCNT-PEG was ~43.6%. Sustained release occurred to MWCNT-PEG-Oxaliplatin, with only 34% of oxaliplatin released into medium within 6 h. In MTT assay, MWCNT-PEG-Oxaliplatin showed slightly decreased cytotoxic effect when cell viability was assessed at 12 and 24 h. A drastic increase of cytotoxicity was found when cell viability was assessed at 48 and 96 h. Pt-DNA adducts formation, γ-H2AX formation and cell apoptosis assay results showed the same trend as the MTT assay, suggesting sustained-release for MWCNT-Oxaliplatin and MWCNT-PEG-Oxaliplatin formulations. PEGylated multi-walled carbon nanotubes can be used as sustained release drug delivery system, thus remarkably improving cytotoxicity of oxaliplatin on HT-29 cells.

Highly crystalline and well-dispersed TiO2 nanorods have been prepared by well-controlled solvothermal reactions and applied to fabricate inorganic/polymer hybrid ultraviolet photodetectors. The incorporation of TiO2 nanorods could substantially improve device performance because of the widespread interface area between two components and yield a very promising device performance of high ultraviolet photo-to-dark current ratio of nearly three orders of magnitude with short response time of less than 200 ms. The proposed method provides a new route for fabricating low-cost, environmentally friendly hybrid bulk heterojunction ultraviolet photodetectors.

Lysine (K)-specific demethylase 4B (KDM4B) is a histone H3K9 demethylase and is reported to activate gene transcription through regulation of chromatin structures. Previous research has revealed that KDM4B plays special regulatory roles in colorectal, prostate and gastric cancers. However, its physiological role in pancreatic cancer remains largely unknown. In the present study, it is demonstrated KDM4B plays a crucial in epithelial-mesenchymal transition (EMT) in pancreatic cancer. siRNA mediated silencing of KDM4B inhibits cell migration, invasion and EMT. Moreover, KDM4B was demonstrated to epigenetically regulate the expression of ZEB1 in the TGF-β-induced EMT process. In tumor tissues of pancreatic cancer patient, the protein level of KDM4B was positively correlated with ZEB1. In conclusion, our results suggested that KDM4B is a key mediator in EMT process, and may serve as an important prognostic marker and therapeutic target for the metastatic progression of human pancreatic cancer.