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In this work, a platinum-nickel based nanozyme is prepared and used as a coreaction accelerator in the luminol-H 2 O 2 electrochemiluminescence (ECL) system to construct an ECL biosensor for dimethyl phthalate (DMP) detection. The PtNi/NC nanozyme possesses dispersed metal active sites, and the synergistic effect of Pt and Ni endows it with excellent catalytic performance, which effectively converts H 2 O 2 into more superoxide anions, and then significantly enhances the ECL intensity of the luminol system. The ECL mechanism is investigated by combining cyclic voltammetry and ECL with different types of free radical scavengers. Simultaneously, an "off-on" biosensor is constructed by integrating 3D DNA walker with enzyme-free recycling amplification for ultrasensitive detection of DMP. The biosensor based on PtNi/NC nanozyme mediated luminol-H 2 O 2 system and 3D DNA walker exhibits a linear range of 1 × 10 -16 to 1 × 10 -6  M with a detection limit of 4.3 × 10 -17  M (S/N = 3), and displays good stability and specificity. This study demonstrates the advantages of PtNi/NC nanozyme in enhancing the luminol-H 2 O 2 ECL system, providing new strategy for designing efficient ECL emitter and offering a new method for detecting phthalate esters., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The nuclear-encoded mitochondrial protein Tu translation elongation factor, mitochondrial (TUFM) is well-known for its role in mitochondrial protein translation. Originally discovered in yeast, TUFM demonstrates significant evolutionary conservation from prokaryotes to eukaryotes. Dysregulation of TUFM has been associated with mitochondrial disorders. Although early hypothesis suggests that TUFM is localized within mitochondria, recent studies identify its presence in the cytoplasm, with this subcellular distribution being linked to distinct functions of TUFM. Significantly, in addition to its established function in mitochondrial protein quality control, recent research indicates a broader involvement of TUFM in the regulation of programmed cell death processes (e.g., autophagy, apoptosis, necroptosis, and pyroptosis) and its diverse roles in viral infection, cancer, and other disease conditions. This review seeks to offer a current summary of TUFM's biological functions and its complex regulatory mechanisms in human health and disease. Insight into these intricate pathways controlled by TUFM may lead to the potential development of targeted therapies for a range of human diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Pang, Kang, Li, Jiang and Zhou.)

The aim of this study is to investigate the application performance of rapid copy number variation sequencing (rCNV-seq) technology for the detection of chromosomal abnormalities during prenatal diagnosis. Samples were collected from 424 pregnant women who were at high-risk for noninvasive prenatal screening in Kunming Maternal and Child Care Hospital from January 2018 to May 2022. rCNV-seq technique was used to detect fetal chromosome abnormalities and compare the results with that of chromosomal karyotype analysis. The Result showed that 330 (77.83%, 330/424) cases indicated chromosomal abnormalities among 424 high-risk pregnant women who underwent rCNV-seq. Moreover, 94 (22.17%, 94/424) cases were discovered to have copy number variations. Among the 330 fetuses with chromosomal abnormalities, common autosomal aneuploidy was observed in 203 cases (47.87%, 203/424) and sex chromosome aneuploidy was observed in 91 cases (21.46%, 91/424). Moreover, the abnormalities in multiple chromosomes were discovered in 33 cases (7.78%, 33/424), and the rare autosomal aneuploidy was observed in 3 cases (0.71%, 3/424). There were 63 fetuses (14.86%, 63/424) with pathogenic CNVs among the 94 fetuses with variable copy numbers. Of the 245 pregnant women who voluntarily selected G-band karyotyping, 1 fetus with copy number variation had normal karyotype results, and the remaining women were consistent with rCNV-seq. Our study revealed that rCNV-seq has higher accuracy in detecting common trisomy and can also detect chromosomal microdeletions or microduplications that cannot be detected by G-banding karyotype analysis. There is no effective treatment for chromosomal diseases, so it is particularly important to prevent chromosomal diseases through genetic counseling and prenatal diagnosis of chromosomal diseases., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

With the emergence of targeted inhibition strategies for Hedgehog signaling in cancer, multiple Hedgehog signaling pathway-related biomarkers have become the focus of research. SsGSEA algorithm was employed to analyze the Hedgehog pathway scores of samples in TCGA-HNSC dataset and divide them into two groups. Weighted co-expression network analysis was performed to identify modules strongly associated with the Hedgehog pathway. Differentially up-regulated genes in tumor samples in comparison to the normal ones were screened by Limma, in which genes belonging to modules strongly related to Hedgehog pathway were further filtered by LASSO reduction and multivariate Cox regression analysis to develop a model. ESTIMATE and CIBERSORT were served to characterize the tumor microenvironment (TME). TIDE assessed immunotherapy response. Hedgehog pathway activity was significantly higher in head and neck squamous cell carcinoma (HNSCC) tissues than in normal tissues and was correlated with HNSCC survival, glycan, cofactors and vitamins, drug metabolism, and matrix scores. Six genes (SLC2A3, EFNB2, OAF, COX4I2, MT2A and TXNRD1) were captured to form a Hedgehog associated 6-gene signature, and the resulting risk score was an independent indicator of HNSCC prognosis. It was significantly positively correlated with stromal score, metabolism, angiogenesis and inflammatory response. Patients in low-risk group with a low TIDE score had higher immunotherapy sensitivity relative to those in high-risk group. This study revealed novel findings of the Hedgehog pathway in HNSCC progression and opened up a Hedgehog pathology-related signature to help identify risk factors contributing to HNSCC progression and help predict immunotherapy outcomes., (© 2024. The Author(s).)

Background: Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability., Methods: We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells., Results: Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells., Limitations: Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants., Conclusions: Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS., (© 2024. The Author(s).)

Fe 2 O 3 is one of the most important lithium storage materials and has attracted increasing interest owing to its good capacity in theory, abundant reserves, and better security. The utilization of Fe 2 O 3 materials is hampered by their inferior cycle performance, low rate performance, and restricted composite variety. Herein, the heterostructure of Fe 2 O 3 @SnO 2 with hexahedral structure was manufactured by two- step hydrothermal strategy, while the SnO 2 nanopillars were epitaxially grown in six faces, not in the twelve edges of hexahedral Fe 2 O 3 cubes, which comes from maximizing lattice matching on the six surfaces of Fe 2 O 3 . Furthermore, the experimental results prove that the hexahedral Fe 2 O 3 @SnO 2 heterostructure exhibits remarkably enhanced electrochemical reversibility and reaction kinetics and delivers an impressive initial discharge capacity (1742 mA h g -1 at 4 A g -1 ), great rate performance (565 mA h g -1 at 5 A g -1 ), and stable long-term durability (661 mA h g -1 after 4000 cycles at 4 A g -1 ) as an anode for LIBs. The result of the finite element mechanical simulation further indicates that the SnO 2 nanopillars grow on the six surfaces but not on the twelve edges of the hexahedral Fe 2 O 3 cube, which would provide great rate performance and long-term stability. This study underlines the merits of the heterostructure and offers a useful design routine for superior electrode materials in LIBs.

Rational design of monomer sequence for desired properties is challenging. This study investigates the effect of monomer distribution of double hydrophilic copolymers (DHCs) with electron-rich units on cluster triggered emission (CTE) capacity. By means of combining latent monomer strategy, reversible addition fragmentation chain transfer (RAFT) polymerization and selective hydrolysis technology, the random, pseudo di-block and the gradient DHCs consisting of pH-responsive polyacrylic acid (PAA) segments and thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) segments were successfully synthesized in a controlled manner. Moreover, the gradient DHCs showed a tremendously increased luminescent intensity due to the distinct hydrogen-bonding interaction compared to random and pseudo di-block DHCs. To the best of our knowledge, this is the first reported the direct correlation between luminescent intensity and sequence structure of non-conjugated polymer. Meanwhile, thermo and pH dual-responsive clusteroluminescence could be easily performed. This work demonstrates a novel and facile method to tailor the hydrogen-bonding for the stimuli-responsive light-emitting polymers., (© 2023 Wiley-VCH GmbH.)

Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with genetic and clinical heterogeneity. Owing to the advancement of sequencing technologies, an increasing number of ASD-related genes have been reported. We designed a targeted sequencing panel (TSP) for ASD based on next-generation sequencing (NGS) to provide clinical strategies for genetic testing of ASD and its subgroups. Methods: TSP comprised 568 ASD-related genes and analyzed both single nucleotide variations (SNVs) and copy number variations (CNVs). The Autism Diagnostic Observation Schedule (ADOS) and the Griffiths Mental Development Scales (GMDS) were performed with the consent of ASD parents. Additional medical information of the selected cases was recorded. Results: A total of 160 ASD children were enrolled in the cohort (male to female ratio 3.6:1). The total detection yield was 51.3% for TSP (82/160), among which SNVs and CNVs accounted for 45.6% (73/160) and 8.1% (13/160), respectively, with 4 children having both SNVs and CNV variants (2.5%). The detection rate of disease-associated variants in females (71.4%) was significantly higher than that in males (45.6%, p = 0.007). Pathogenic and likely pathogenic variants were detected in 16.9% (27/160) of the cases. SHANK3, KMT2A, and DLGAP2 were the most frequent variants among these patients. Eleven children had de novo SNVs, 2 of whom had de novo ASXL3 variants with mild global developmental delay (DD) and minor dysmorphic facial features besides autistic symptoms. Seventy-one children completed both ADOS and GMDS, of whom 51 had DD/intellectual disability (ID). In this subgroup of ASD children with DD/ID, we found that children with genetic abnormalities had lower language competence than those without positive genetic findings ( p = 0.028). There was no correlation between the severity of ASD and positive genetic findings. Conclusion: Our study revealed the potential of TSP, with lower cost and more efficient genetic diagnosis. We recommended that ASD children with DD or ID, especially those with lower language competence, undergo genetic testing. More precise clinical phenotypes may help in the decision-making of patients with genetic testing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Wang, Li, Mei, Zhou, Li, Li, Xu and Xu.)

Introduction: Fragile X syndrome (FXS) is a X-linked neurodevelopmental disorder (NDD). This study aims to investigate the incidence of FXS in Chinese children and analyze the comprehensive clinical characteristics of these FXS children., Methods: Children diagnosed with idiopathic NDD were recruited between 2016 and 2021 from the department of Child Health Care, Children's Hospital of Fudan University. We combined tetraplet-primed PCR-capillary electrophoresis and whole exome sequencing (WES)/panel or array-based comparative genomic hybridization (array-CGH) to identify the size of the CGG repeats and the mutations or copy number variations (CNVs) in the genome and in FMR1 . The clinical features of FXS children were analyzed according to pediatricians' recording, parental questionnaires, the results of examinations and follow-up., Results: The incidence of FXS in Chinese children with idiopathic NDD was 2.4% (42/1753) and in those with FXS, 2.38% had a deletion (1/42). Here, we present the clinical characteristics of 36 children with FXS. Overweight was observed in two boys. The average intelligence quotient (IQ)/development quotient (DQ) of all FXS patients was 48. The average ages of meaningful words and walking alone were 2 years and 10 months and 1 year and 7 months, respectively. The most frequent repetitive behavior was stimulated by hyperarousal to sensory stimulation. On social aspects, social withdrawal, social anxiety, and shyness accounted for 75%, 58%, and 56% of the total number of children, respectively. Approximately 60% of FXS children in this cohort were emotionally labile and prone to temper tantrums. Self-injury and aggression toward others could also be observed, at 19% and 28%, respectively. The most frequent behavioral problem was attention-deficit hyperactivity disorder (ADHD) seen in 64% and the most common facial features were a narrow and elongated face and large or prominent ears in 92% of patients., Discussion: Screening of FMR1 full mutation provides the possibility for patients' further medical supports and the clinical features of FXS children obtained in this study will increase the understanding and diagnosis of FXS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Mei, Hu, Li, Wang, Li, Zhang, Zhou, Zhu, Hagerman, Xu and Xu.)

Background: Acute coronary syndrome (ACS) and diabetes mellitus (DM) are the leading health risks for the elderly. Triglyceride-glucose (TyG) index is a novel and reliable indicator of insulin resistance (IR). This study aims to explore the relationship between the TyG index and all-cause mortality in oldest-old patients with ACS and DM., Methods: Seven hundred twenty hospitalized patients with ACS aged ≥ 80 years were enrolled, and 699 patients signed informed consent for the study. During the follow-up period, 37 were lost to follow-up, and the follow-up rate was 94.7%. 231 ACS patients with DM were selected for the study's analyses. Kaplan-Meier curve, Cox regression model and receiver operating characteristic (ROC) curve were used to analyze the association between the TyG index and all-cause mortality., Results: The mean age of participants was 81.58 ± 1.93 years, and 32.47% were women. Compared to TyG tertile 1, the Hazard Ratio (HR) [95% confidence interval (CI)] of all-cause mortality was 2.04 (1.09, 3.81) for TyG tertile 3 in the fully adjusted model. For the TyG index per standard deviation (SD) increment, the HR (95% CI) of all-cause mortality was 1.44 (1.13, 1.83). Further, the association between the TyG index and all-cause mortality was dose-response (P for trend = 0.026). ROC curve analyses indicated that the TyG index outperformed FBG and TG in the prediction of mortality risk and improved the prognostic value of the Gensini score combined with LVEF., Conclusion: The TyG index predicts the risk of all-cause mortality in the oldest-old ACS patients with DM., (© 2023. The Author(s).)

Introduction: Genetic landscape, disease characteristics, and clinical outcomes of young adults with myeloproliferative neoplasms (MPNs) were reported. However, data on patient-reported outcomes (PROs) in young adults with MPNs were rare., Methods: We conducted a multicenter, cross-sectional study to compare the PROs in respondents with thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) by age at survey, including the young group (18-40 years), middle-aged group (41-60 years), and elderly group (>60 years)., Results: Of the 1,664 respondents with MPNs, 349 (21.0%) were young including 244 (69.9%) with ET, 34 (9.7%) with PV, and 71 (20.3%) with MF. In multivariate analyses, the young groups with ET and MF were associated with the lowest MPN-10 scores among the 3 age groups; those with MF, highest proportion of reporting negative impact of disease and therapy on their daily life and work. The young groups with MPNs had the highest physical component summary scores but the lowest mental component summary scores in those with ET. The young groups with MPNs were most concerned about fertility; those with ET, treatment-related adverse events and long-term efficacy of treatment., Conclusions: We concluded that young adults with MPNs have different PROs compared with middle-aged and elderly patients., (© 2023 S. Karger AG, Basel.)

The purposes of this study are to explore the function and regulatory mechanism of a novel lncRNA MYC-Induced Long non-coding RNA (MINCR) in osteoarthritis (OA). The expression of lncRNA MINCR, miR-146a-5p, and bone morphogenetic protein receptor 2 (BMPR2), Sry-type high-mobility-group box 9 (SOX9), collagen type II alpha 1 (COL2A1), Aggrecan, metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), Matrix metalloproteinase 3 (MMP3), MMP13, COL2A1, and Aggrecan were determined using quantitative real-time PCR (qRT-PCR), western blot, immunohistochemistry (IHC) and immunofluorescence (IF) in vitro and in vivo . And distribution and expression of MINCR were examined by fluorescence in situ hybridization (FISH). Cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EdU) staining, Annexin V-FITC/Propidium Iodide (PI), and Terminal Deoxynucleotidyl transferase-mediated dUTP Nick-End Labeling (TUNEL) staining in vitro and in vivo . The anterior cruciate ligament transection (ACLT) rat model was constructed to analyze the MINCR/miR-146a-5p/BMPR2 axis in vivo . The cartilage degeneration was determined by pathological staining with Hematoxylin and Eosin (H&E) and Safranin O staining. The binding relationship between MINCR and miR-146a-5p, and between miR-146a-5p and BMPR2 were determined by a dual-luciferase reporter gene, RNA Immunoprecipitation (RIP) assay, and RNA-pull down assays. Here, MINCR and BMPR2 were downregulated whereas miR-146a-5p was upregulated in OA cartilage tissues compared with control as well as IL-1β-induced chondrocytes compared with normal chondrocytes. Function experiments indicated that MINCR upregulation promoted cell proliferation and inhibited apoptosis and extracellular matrix (ECM)-degeneration. We also proved the binding relationship between MINCR and miR-146a-5p, and the BMPR2 acted as a target of miR-146a-5p. Mechanism analysis using rescue experiments in vitro and in vivo , MINCR silencing reversed the effects of miR-146a-5p downregulation in OA. Overexpression of miR-146a-5p also reversed the function of BMPR2 overexpression in OA. These data indicated that MINCR prevented OA progression via targeting miR-146a-5p to promote BMPR2 expression.

Purpose: To explore predictors for readmission within 6 months of ACS patients, and to build a prediction model, and generate a nomogram., Methods: The retrospective cohort study included 498 patients with ACS in the Second Medical Center of the Chinese People's Liberation Army General Hospital between January 2016 and March 2019. Univariate and multivariate logistic regression with odds ratios (OR) and two-sided 95% confidence interval (CI) analysis were used to investigate predictors for readmission within 6 months. The cohort was randomly divided into training cohort to develop a prediction model, and the validation cohort to validate the model. The receiver operating characteristic curve (ROC) and the calibration curve was used to assess discriminative power and calibration., Results: Eighty-three ACS patients were readmitted within six months, with a readmission rate of 16.67%. Predictors included ACS type, treatment, hypertension, SUA, length of stay, statins, and adverse events occurred during hospitalization were used to form a six-month readmission prediction model for readmission within 6 months in ACS patients. The area under the curve (AUC) of the model was 0.788 (95%CI: 0.735-0.878) and 0.775 (95%CI: 0.686-0.865) in the training cohort and the validation cohort, respectively. Calibration curves showed the good calibration of the prediction model. Decision-curve analyses and clinical impact curve also demonstrated that it was clinically valuable., Conclusion: We used seven readily available predictors to develop a prediction model for readmission within six months after treatment in ACS patients, which could be used to identify high-risk patients for ACS readmission., (© 2022. The Author(s).)

Objective: Motor impairments are prevalent in children with autism spectrum disorder (ASD) and persistent across age. Our current study was designed to investigate motor deficits in Chinese toddlers with ASD and to explore the relationships between motor deficits and social communication skills., Methods: For this cross-sectional study, we recruited a total of 210 Chinese toddlers with ASD aged between 18 and 36 months in the study during December 2017 to December 2020. Griffiths Developmental Scales-Chinese (GDS-C), Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Communication and Symbolic Behavior Scales Developmental Profile-Infant-Toddler Checklist (CSBS-DP-ITC) were administered in these toddlers to evaluate their development, social communicative skills, and autism severity. We compared the developmental and social communicational profiles of ASD toddlers in different gross and fine motor subgroups, and explored potential associated factors. The univariate generalized linear model tested the relationship of fine and gross motor skills and social communicative skills., Results: The prevalence of gross and fine motor deficits were 59.5 and 82.5%, respectively, which are almost equivalent in boys and girls. The motor impairments tended to be more severe with age in toddlers. After adjusting for age, sex, non-verbal development quotient (DQ) and restricted, repetitive behaviors, severer gross motor impairments were significantly related to higher comparison score of ADOS-2 and higher social composite score of CSBS-DP-ITC, without interactions with other variables. Meanwhile, lower fine motor skills were associated with more deficits of social communication and higher severity of ASD, also depending on non-verbal DQ. In the lower non-verbal DQ subgroup, both fine motor deficits and restricted repetitive behaviors (RRBs) might have effects on autism symptomology., Conclusion: Motor impairments are common in Chinese toddlers with ASD. Toddlers with weaker gross and fine motor skills have greater deficits in social communicative skills. Gross motor impairment might be an independent predictor of the severity of autism and social communication skills, while the effect of fine motor deficits might be affected by non-verbal DQ and RRBs of toddlers with ASD. We provide further justification for the inclusion of motor impairments in the early intervention for toddlers with ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Xu, Li, Zhang, Li, Dong, Wang, Lu, Zhu and Xu.)

Background: Type 2 diabetes (T2DM) is a major risk factor for myocardial infarction. Thrombus aspiration was considered a good way to deal with coronary thrombus in the treatment of acute myocardial infarction. However, recent studies have found that routine thrombus aspiration is not beneficial. This study is designed to investigate whether intracoronary artery retrograde thrombolysis (ICART) is more effective than thrombus aspiration or percutaneous transluminal coronary angioplasty (PTCA) in improving myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI)., Methods/design: IntraCoronary Artery Retrograde Thrombolysis (ICART) vs. thrombus aspiration or PTCA in STEMI trial is a single-center, prospective, randomized open-label trial with blinded evaluation of endpoints. A total of 286 patients with STEMI undergoing PPCI are randomly assigned to two groups: ICART and thrombus aspiration or PTCA. The primary endpoint is the incidence of >70% ST-segment elevation resolution. Secondary outcomes include distal embolization, myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, and in-hospital bleeding., Discussion: The ICART trial is the first randomized clinical trial (RCT) to date to verify the effect of ICART vs. thrombus aspiration or PTCA on myocardial perfusion in patients with STEMI undergoing PPCI., Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR1900023849]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Wang, Li, Zhou, Guo, Zhang, Guo, Wang, Liu, Zhao, Zhao and Tian.)

Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function variants in the MECP2 gene, currently with no cure. Neuroimaging is an important tool for obtaining non-invasive structural and functional information about the in vivo brain. Multiple approaches to magnetic resonance imaging (MRI) scans have been utilized effectively in RTT patients to understand the possible pathological basis. This study combined developmental evaluations with clinical severity, T1-weighted imaging, and diffusion tensor imaging, aiming to explore the structural alterations in cohorts of young girls with RTT, idiopathic autism spectrum disorder (ASD), or typical development. Voxel-based morphometry (VBM) was used to determine the voxel-wised volumetric characteristics of gray matter, while tract-based spatial statistics (SPSS) was used to obtain voxel-wised properties of white matter. Finally, a correlation analysis between the brain structural alterations and the clinical evaluations was performed. In the RTT group, VBM revealed decreased gray matter volume in the insula, frontal cortex, calcarine, and limbic/paralimbic regions; TBSS demonstrated decreased fractional anisotropy (FA) and increased mean diffusivity (MD) mainly in the corpus callosum and other projection and association fibers such as superior longitudinal fasciculus and corona radiata. The social impairment quotient and clinical severity were associated with these morphometric alterations. This monogenic study with an early stage of RTT may provide some valuable guidance for understanding the disease pathogenesis. At the same time, the pediatric-adjusted analytic pipelines for VBM and TBSS were introduced for significant improvement over classical approaches for MRI scans in children., Competing Interests: The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer YY declared a shared parent affiliation with the authors to the handling editor at the time of review., (Copyright © 2022 Li, Mei, Li, Hu, Zhou, Zhang, Qiao, Xu and Xu.)

Background: Mutations in the STAMBP gene, which encodes a deubiquitinating isopeptidase called STAM-binding protein, are related to global developmental delay, microcephaly, and capillary malformation. Owing to the limited number of reported cases, the functional and phenotypic characteristics of STAMBP variants require further elucidation., Materials and Methods: Whole exome sequencing was performed on a patient presenting with a neurodevelopmental disorder. Novel compound heterozygous mutations in STAMBP [c.843_844del (p.C282Wfs*11) and c.920G > A (p.G307E)] were identified and validated using Sanger sequencing. A 3D human cortical organoid model was used to investigate the function of STAMBP and the pathogenicity of the novel mutation (c.920G > A, p.G307E)., Results: The patient was presented with global developmental delay, autism spectrum disorder, microcephaly, epilepsy, and dysmorphic facial features but without apparent capillary malformation on the skin and organs. Cortical organoids with STAMBP knockout (KO) showed significantly lower proliferation of neural stem cells (NSCs), leading to smaller organoids that are characteristic of microcephaly. Furthermore, STAMBP disruption did not affect apoptosis in early cortical organoids. After re-expressing wild-type STAMBP, STAMBP G 307 E , and STAMBP T 313 I (a known pathogenic mutation) within STAMBP KO organoids, only STAMBP WT rescued the impaired proliferation of STAMBP deficient organoids, but not STAMBP G 307 E and STAMBP T 313 I ., Conclusion: Our findings demonstrate that the clinical phenotype of STAMBP mutations is highly variable, and patients with different STAMBP mutations show differences in the severity of symptoms. The STAMBP missense mutation identified here is a novel pathogenic mutation that impairs the proliferation of NSCs in human brain development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Li, Huang, Li, Xu, Xu, Chen, Wang, Deng, Zhu, Feng and Xu.)

Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder in which genetics play a major role. Molecular diagnosis may lead to a more accurate prognosis, improved clinical management, and potential treatment of the condition. Both copy number variations (CNVs) and single nucleotide variations (SNVs) have been reported to contribute to the genetic etiology of ASD. The effectiveness and validity of clinical targeted panel sequencing (CTPS) designed to analyze both CNVs and SNVs can be evaluated in different ASD cohorts. CTPS was performed on 573 patients with the diagnosis of ASD. Medical records of positive CTPS cases were further reviewed and analyzed. Additional medical examinations were performed for a group of selective cases. Positive molecular findings were confirmed by orthogonal methods. The overall positive rate was 19.16% (109/569) in our cohort. About 13.89% (79/569) and 4.40% (25/569) of cases had SNVs only and CNVs only findings, respectively, while 0.9% (5/569) of cases had both SNV and CNV findings. For cases with SNVs findings, the SHANK3 gene has the greatest number of reportable variants, followed by gene MYT1L . Patients with MYT1L variants share common and specific clinical characteristics. We found a child with compound heterozygous SLC26A4 variants had an enlarged vestibular aqueduct syndrome and autistic phenotype. Our results showed that CTPS is an effective molecular diagnostic tool for ASD. Thorough clinical and genetic evaluation of ASD can lead to more accurate diagnosis and better management of the condition.

Objective: Early screening contributes to the early detection of children with autism spectrum disorder (ASD). We conducted a longitudinal ASD screening study in a large community setting. The study was designed to investigate the diagnostic rate of ASD screening and determine the effectiveness of ASD screening model in a community-based sample., Methods: We enrolled children who attended 18- and 24-month well-child care visits in Shanghai Xuhui District. Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) and Binomial Observation Test (BOT) were selected as screening instruments. Screen-positive children were referred to a tertiary diagnostic center for comprehensive ASD diagnostic evaluation. Screen-negative children received well-child checkups and follow-up every 3-6 months until age three and were referred if they were suspected of having ASD., Results: A total of 11,190 toddlers were screened, and 36 screen-positive toddlers were diagnosed with ASD. The mean age at diagnosis for these children was 23.1 ± 4.55 months, diagnosed 20 months earlier than ASD children not screened. The diagnostic rate of ASD was 0.32% (95% CI: 0.23-0.45%) in this community-based sample. In addition, 12 screen-negative children were diagnosed with ASD during subsequent well-child visit and follow-up. The average diagnostic rate of ASD rose to 0.43% (95% CI: 0.32-0.57%) when toddlers were followed up to 3 years old. The positive predictive values (PPVs) of M-CHAT-R/F, M-CHAT-R high risk, and BOT for ASD were 0.31, 0.43, and 0.38 respectively., Conclusion: Our findings provide reliable data for estimating the rate of ASD detection and identifying the validity of community-based screening model. M-CHAT-R/F combined with BOT can be an effective tool for early detection of ASD. This community-based screening model is worth replicating., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhou, Xu, Li, Lv, Zhu, Dong, Li, Wang, Tang and Xu.)

MiRNAs are a class of small non-coding RNAs (ncRNAs) responsible for post-transcriptional regulation of target genes. Accumulating evidence indicates that miRNAs are implicated in the progression of cardiac hypertrophy. Therefore, understanding the molecular mechanisms how these miRNAs regulate cardiac hypertrophy is useful for diagnosis and monitoring of disease progression. In this study, to investigate the effect of miR-27a-3p, we established an in vitro cardiac hypertrophy model by treating H9c2 cardiomyocytes with angiotensin II (Ang II) and an in vivo model through the chronic infusion of Ang II into mice. As revealed by our experimental results, miR-27a-3p expression was significantly increased in clinical samples, animal and cell models of cardiac hypertrophy. Inhibiting miR-27a-3p mitigated cardiac hypertrophy phenotype induced by Ang II. Additionally, our work identified NOVA1 (neuro-oncological ventral antigen 1) as a downstream target of miR-27a-3p. miR-27a-3p overexpression reduced NOVA1 protein level and mRNA expression. Consistently, NOVA1 silencing promoted cardiac hypertrophy phenotype induced by Ang II. In summary, these results suggest that the upregulation of miR-27a-3p may serve as a diagnostic factor for cardiac hypertrophy, and miR-27a-3p upregulation promotes cardiac hypertrophy by targeting NOVA1.

We explored variables associated with patient-reported outcomes (PROs) including symptom burden, impact on daily life and work, obstacles during therapy, satisfaction level with therapy, and health-related quality of life in 1500 respondents with myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) in a multicenter, cross-sectional study across China, a representative of the developing countries. In multivariate analyses, urban household registration and higher education level were significantly-associated with no symptoms at diagnosis in respondents with ET or MF. CALR mutation was significantly-associated with lower MPN-10 scores in respondents with MF. Higher MPN-10 scores were significantly-associated with negative impact on daily life and work as well as lower satisfaction level in respondents with ET, PV and MF. Receiving ruxolitinib was significantly-associated with high satisfaction and satisfaction in respondents with MF. In addition, other demographics and clinical variables were also impacting PROs.

SH3 and Multiple Ankyrin Repeat Domains 3 ( SHANK3 )-caused autism spectrum disorder (ASD) may present a unique opportunity to clarify the heterogeneous neuropathological mechanisms of ASD. However, the specificity and commonality of disrupted large-scale brain organization in SHANK3- deficient children remain largely unknown. The present study combined genetic tests, neurobehavioral evaluations, and magnetic resonance imaging, aiming to explore the disruptions of both local and networked cortical structural organization in ASD children with and without SHANK3 deficiency. Multiple surface morphological parameters such as cortical thickness (CT) and sulcus depth were estimated, and the graph theory was adopted to characterize the topological properties of structural covariance networks (SCNs). Finally, a correlation analysis between the alterations in brain morphological features and the neurobehavioral evaluations was performed. Compared with typically developed children, increased CT and reduced nodal degree were found in both ASD children with and without SHANK3 defects mainly in the lateral temporal cortex, prefrontal cortex (PFC), temporo-parietal junction (TPJ), superior temporal gyrus (STG), and limbic/paralimbic regions. Besides commonality, our findings showed some distinct abnormalities in ASD children with SHANK3 defects compared to those without. Locally, more changes in the STG and orbitofrontal cortex were exhibited in ASD children with SHANK3 defects, while more changes in the TPJ and inferior parietal lobe (IPL) in those without SHANK3 defects were observed. For the SCNs, a trend toward regular network topology was observed in ASD children with SHANK3 defects, but not in those without. In addition, ASD children with SHANK3 defects showed more alterations of nodal degrees in the anterior and posterior cingulate cortices and right insular, while there were more disruptions in the sensorimotor areas and the left insular and dorsomedial PFC in ASD without SHANK3 defects. Our findings indicate dissociable disruptions of local and networked brain morphological features in ASD children with and without SHANK3 deficiency. Moreover, this monogenic study may provide a valuable path for parsing the heterogeneity of brain disturbances in ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Liu, Huang, Li, Xu, Zhou, Hu, Zhang, Wang, Nie, Qiao, Yin and Xu.)

Background: Obesity is reported as closely correlated with the development of chronic kidney disease (CKD); however, whether causation exists is unknown, and controversy remains about whether the role of obesity is protective or destructive in CKD. In this study, we attempted to infer the causal relationship between life course adiposity and CKD, to provide a rationale for obesity management in CKD patients., Methods: A 2-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship of life course adiposity traits including body mass index (BMI), childhood BMI, body fat percentage (BF%), birth weight (BW), waist circumference, hip circumference, and waist-to-hip ratio (WHR) to CKD. Significant single nucleotide polymorphisms from genome-wide association study on human adiposity traits were utilized as exposure instruments, and summary statistics of CKD as the outcome. The causal relationship was evaluated by inverse variance weighted, MR Egger regression and weighted median methods, and further verified by extensive sensitivity analyses., Results: Genetically determined one standard deviation increase in adult BMI was associated with higher risk of CKD in all 4 MR methods. Other indexes including childhood BMI, body fat percentage, and waist/hip circumference were also shown to have a causal effect on the risk of CKD. The results were robust under all sensitivity analyses., Conclusions: There exists a causal effect of life course adiposity on the risk of CKD. A genetic predisposition to higher adult BMI may increase the risk of CKD.

SHANK3 deficiency represents one of the most replicated monogenic risk factors for autism spectrum disorder (ASD) and SHANK3 caused ASD presents a unique opportunity to understand the underlying neuropathological mechanisms of ASD. In this study, genetic tests, comprehensive clinical and neurobehavioral evaluations, as well as multimodal structural MRI using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were conducted in SHANK3 group (N = 14 with SHANK3 defects), ASD controls (N = 26 with idiopathic ASD without SHANK3 defects) and typically developing (TD) controls (N = 32). Phenotypically, we reported several new features in Chinese SHANK3 deficient children including anteverted nares, sensory stimulation seeking, dental abnormalities and hematological problems. In SHANK3 group, VBM revealed decreased grey matter volumes mainly in dorsal striatum, amygdala, hippocampus and parahippocampal gyrus; TBSS demonstrated decreased fractional anisotropy in multiple tracts involving projection, association and commissural fibers, including middle cerebral peduncle, corpus callosum, superior longitudinal fasciculus, corona radiata, external and internal capsule, and posterior thalamic radiation, etc. We report that the disrupted striatum centered brain structures are associated with SHANK3 deficient children. Study of subjects with monogenic cause offer specific insights into the neuroimaging studies of ASD. The discovery may support a path for future functional connectivity studies to allow for more in-depth understandings of the abnormal neural circuits and the underlying neuropathological mechanisms for ASD., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy. And probiotics may have the function of preventing colon cancer. The aim of this study was to investigate the inhibitory effects of a probiotic mixture on colorectal cancer and its potential mechanisms., Methods: The effects of the probiotic mixture on proliferation and metastasis of mouse colon cancer CT26 cells were assessed by probiotics and cells co-culture assay, Cell Counting Kit-8 assay, colony formation assay, wound-healing assay, as well as migration and invasion assays. And CT26 cells were also transplanted into BALB/c mice to construct transplanted tumor animal model. The mice were randomly divided into two groups, control group and probiotic mixture intragastric administration group, after injection 21 days the tumor size and infiltration of immune cells in the tumor or spleen tissues were analyzed by hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining., Results: The probiotic mixture significantly inhibited the proliferation, invasion, and migration ability of CT26 cells compare to the control cells (P<0.05). In the animal experiments, the tumor volume of mice that had been fed the probiotic mixture was significantly smaller than that of the control group (P<0.05). Compared with control mice, more apoptotic cells and infiltration of immune cells were showed in the tumor tissues of the mice treated with the probiotic mixture, and an increased number of CD8+ cells in the tumor and spleen tissues but no significant change in tissues., Conclusions: These results suggested that the probiotic mixture could inhibit the growth of CT26 tumors and induce an immune response in vivo . The probiotic mixture also inhibited the invasion, migration, and proliferation ability of CT26 cells in vitro ., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-20-573). The authors have no conflicts of interest to declare., (2020 Journal of Gastrointestinal Oncology. All rights reserved.)

Objective: To investigate the relationship between vitamin D binding protein gene rs2282679 A/C polymorphism with blood vitamin D levels., Methods: A total of 286 eligible subjects were selected from one university in Hebei Province. Serum 25-hydroxylated vitamin D levels were measured by liquid chromatography-mass spectrometry, and gene chip was used for genotyping of rs2282679 locus. Statistical analysis was performed using R software., Results: A total of 285 participants in the study completed the experiment, and result indicated that the distribution of the rs2282679 locus A/C polymorphism in the participants was consistent with the Hardy-Weinberg equilibrium. The genotype of rs2282679 was significantly associated with serum vitamin D insufficiency and deficiency(P=0. 031). Allele A was a risk factor for vitamin D insufficiency and deficiency. The OR value of allele C relative to A was 0. 65, and the genetic pattern of allele C relative to A was dominant(P=0. 03)., Conclusion: The vitamin D-binding protein gene rs2282679 was significantly associated with serum vitamin D insufficiency and deficiency in college students, and A-allele is a risk factor accounting for vitamin D insufficiency and deficiency in college students.

Background: Cinobufacin is a Chinese patent medicine widely used for breast cancer in China. However, no systematic review and meta-analysis have been published to validate its effects in breast cancer treatment. We, therefore, summarize the efficacy and safety of Cinobufacin combined with chemotherapy in order to provide rigid evidence for its clinical application., Methods: By searching multiple databases incepted to December 2019, the RCTs of breast cancer patients treated with Cinobufacin were screened according to the inclusion criteria, and the meta-analysis and sensitivity analysis were conducted using RevMan5.3., Results: A total of 1163 articles were retrieved, and 16 studies were included. The total sample size was 1331 cases, including 666 cases in the treatment group receiving Cinobufacin combined with chemotherapy and 665 cases in the control group receiving chemotherapy alone. Our study found that the ORR (overall response rate) (RR = 1.35, 95% CI: [1.23, 1.49], P < 0.00001), CBR (clinical benefit rate) (RR = 1.14, 95% CI: [1.08, 1.21], P < 0.00001), KPS scores (RR = 1.98, 95% CI: [1.45, 2.68], P < 0.0001), and pain relief rate (RR = 1.34, 95% CI: [1.01, 1.78] P =0.04 of the Cinobufacin combined with chemotherapy group were better than those of the chemotherapy group, and the difference was statistically significant. Our study also discovered that the tumor markers (CA125, CA153, and CEA) in the Cinobufacin combined with chemotherapy group were lower than those in the chemotherapy group, which heterogeneity was derived from the low-quality literature included in the study, but the results were robust. In addition, in terms of safety, we found that the incidences of gastrointestinal reactions (RR = 0.58, 95% CI: [0.48, 0.70], P < 0.00001), liver and kidney damage (RR = 0.57, 95% CI: [0.38, 0.84], P =0.004), and hair loss (RR = 0.61, 95% CI: [0.40, 0.92], P =0.02) in the Cinobufacin combined chemotherapy group were lower than those in the chemotherapy group, and the difference was statistically significant, but the incidences of peripheral neurotoxicity (RR = 0.69, 95% CI: [0.26, 1.85], P =0.46) and myelosuppression (RR = 0.78, 95% CI: [0.46, 1.34], P =0.37) in the combined group were similar to those of the chemotherapy group, and the difference was not statistically significant., Conclusions: Cinobufacin combined with chemotherapy can improve the clinical efficacy of breast cancer patients, enhance the quality of life of the patients, reduce the value of tumor markers such as CA125, CA153, and CEA, and lower the occurrence of adverse reactions such as gastrointestinal reactions, liver and kidney damage, and hair loss., Competing Interests: The authors declare that there are no conflicts of interest between them., (Copyright © 2020 Jing Xu et al.)

Background: Biqi capsule is a traditional Chinese medicine widely used as a complementary and alternative treatment for rheumatoid arthritis (RA). The objective is to understand the efficacy, safety and mechanism of Biqi combined with methotrexate (MTX) in RA., Methods: We present a randomized, controlled pilot trial on Biqi combined with MTX against patients with active RA. Seventy patients were randomized 1:1 to receive Biqi + MTX or Leflunomide (LEF) + MTX for 24 weeks, and were assessed at baseline, 4, 12 and 24 weeks. Serum and urine samples were collected for metabolomics., Results: Overall, 81.2% patients in Biqi group achieved ACR20 at 24 weeks. No statistically significant differences were observed in primary or secondary outcomes between the two groups. A better safety profile was observed for Biqi with significantly fewer adverse effects reported (11.4%) compared to LEF group (40%, P  < 0.05). Comparison between treatment responders and non-responders indicated a unique urine metabolic profile of enriched fatty acids and decreased acylcarnitines associated with Biqi responders, indicating a restored energy homeostasis in response to Biqi. The gene targets of these metabolites were significantly enriched in interleukin-4 and interleukin-13 pathways, implying that Biqi could ameliorate Th2-derived inflammatory response. Multivariate network analysis indicated that patient morning stiffness and SJC were key factors associated with metabolomics in Biqi-treated patients, whereas CRP was the main factor in LEF group. Therefore, Biqi and LEF likely work by influencing different patient clinical parameters., Conclusions: Our study suggests that Biqi capsule can be a promising alternative option in combination with MTX for RA treatment, and demonstrates the capability of using metabolomics to interrogate mechanism of action for traditional Chinese medicine. Trial registration This trial is registered with ChiCTR, No. ChiCTR-IPR-16009029. Registered August 15, 2016. http://www.chictr.org.cn/showprojen.aspx?proj=15034., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: H19, a well-known long non-coding RNA, is involved in carcinogenesis and progression of multiple cancers. Molecular epidemiological research suggests that polymorphisms in H19 are associated with an increased risk of cancer, but the results are inconsistent. Thus, we performed a meta-analysis to estimate the associations between H19 polymorphisms and cancer susceptibility., Methods: PubMed, Embase, and Web of Science databases were searched. Odds ratios with 95% confidence interval were applied to assess the association between H19 rs2107425, rs217727, rs2839698, rs2735971, rs3024270, and rs3741219 polymorphisms and cancer susceptibility in all 5 models. We also predicted the H19 secondary structure, as well as the generation and abolishment of miRNA binding sites on H19 through the selected SNPs., Results: Eighteen related studies, involving 17,090 patients and 23,532 control samples, were analyzed. The pooled data showed that rs2839698 polymorphism was significantly associated with an increased cancer susceptibility. As for rs217727 and rs3024270 polymorphisms, similarly increased risks were found in specific genetic models and stratified groups. However, significant decreases in cancer risk were observed for rs2107425 and rs2735971 in the total population, as well as in subgroup analyses. In addition, no significant associations were found in all 5 models for rs3741219 polymorphism. Furthermore, RNAfold prediction revealed that the centroid secondary structure was markedly altered in rs217727 and rs2735971. We also identified that rs217727 G>A and rs2839689 G>A alleles could create and destroy miRNA binding sites on H19., Conclusion: The results of our meta-analyses suggest that H19 polymorphisms may be associated with the risk of cancer development.

Colorectal cancer (CRC) is the third most common tumor in the world; however, the role and mechanism of endoplasmic reticulum (ER) stress in CRC metastasis remains largely unclear. Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) is a long non‑coding RNA (lncRNA), which has previously been associated with CRC metastasis. It has been suggested that ER stress pathways regulate lncRNA expression; however, the effect of ER stress on MALAT1 expression in cancer is unknown. The present study aimed to investigate the relationship between ER stress pathways, MALAT1 expression and cell migration in CRC cells. ER stress was induced by thapsigargin (TG); low dose TG induced the migration of HT29 and HCT116 cells, but not SW1116 and SW620 cells. This effect was associated with increased expression levels of MALAT1, as the knockdown of MALAT1 prevented TG‑induced cell migration. TG‑induced MALAT1 expression was associated with inositol‑requiring enzyme 1 (IRE1) expression and activation of the protein kinase R (PKR)‑like ER kinase (PERK) signaling pathway. X‑box‑binding protein 1 (XBP1) and activating transcription factor 4 (ATF4) binding sites were predicted to be located in the MALAT1 gene promoter regions and the expression of MALAT1 was positively associated with XBP1 and ATF4 expression levels in CRC tissue samples. Thus, these findings indicated that ER stress may promote the migration of CRC cells and contribute to the progression of CRC through the activation of the IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways. In conclusion, to the best of our knowledge, this study is the first report that lncRNA MALAT1 expression is regulated by the IRE1/XBP1 pathway in CRC.

Numerous studies have reported that temporal order perception is biased in neurological patients with extinction and neglect. These individuals tend to perceive two objectively simultaneous stimuli as occurring asynchronously, with the ipsilesional item being perceived as appearing prior to the contralesional item. Likewise, they report that two stimuli occurred simultaneously in situations where the contralesional item is presented substantially prior to the ipsilesional item. Therefore, they exhibit a biased point of subjective simultaneity (PSS). Here we demonstrate that the magnitude of this effect is modulated by the relative position of the stimuli with respect to the patient's trunk. This effect was only observed in patients who still exhibited neglect symptoms, and neither the pathological bias nor substantial modulation were observed in individuals who had recovered from neglect, those who never had neglect or neurologically healthy controls. Crucially, our design kept the retinal and head-centered coordinates of these stimuli constant, providing a pure measure for the influence of egocentric trunk position. This finding emphasizes the interaction of egocentric spatial position on the temporal symptoms observed in these individuals., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A widely debated question concerns whether or not spatial and nonspatial components of visual attention interact in attentional performance. Spatial neglect is a common consequence of brain injury where individuals fail to respond to stimuli presented on their contralesional side. It has been argued that, beyond the spatial bias, these individuals also tend to exhibit nonspatial perceptual deficits. Here we demonstrate that the "nonspatial" deficits affecting the temporal dynamics of attentional deployment are in fact modulated by spatial position. Specifically, we observed that the pathological attentional blink of chronic neglect is enhanced when stimuli are presented on the contralesional side of the trunk while keeping retinal and head-centered coordinates constant. We did not find this pattern in right brain-damaged patients without neglect or in patients who had recovered from neglect. Our work suggests that the nonspatial attentional deficits observed in neglect are heavily modulated by egocentric spatial position. This provides strong evidence against models that suggest independent modules for spatial and nonspatial attentional functions while also providing strong evidence that trunk position plays an important role in neglect.

Searching for effective biomarkers is one of the most challenging tasks in the research field of Autism Spectrum Disorder (ASD). Magnetic resonance imaging (MRI) provides a non-invasive and powerful tool for investigating changes in the structure, function, maturation, connectivity, and metabolism of the brain of children with ASD. Here, we review the more recent MRI studies in young children with ASD, aiming to provide candidate biomarkers for the diagnosis of childhood ASD. The review covers structural imaging methods, diffusion tensor imaging, resting-state functional MRI, and magnetic resonance spectroscopy. Future advances in neuroimaging techniques, as well as cross-disciplinary studies and large-scale collaborations will be needed for an integrated approach linking neuroimaging, genetics, and phenotypic data to allow the discovery of new, effective biomarkers.

The present study was designed to elucidate the key parameters associated with X-ray radiation induced oxidative stress and the effects of STS on X-ray-induced toxicity in H9c2 cardiomyocytes. Cytotoxicity of STS and radiation was assessed by MTT. Antioxidant activity was evaluated by SOD and MDA. Apoptosis was measured by the flow cytometry, Hoechst 33258, clonogenic survival assay, and western blot. It was found that the cell viability of H9c2 cells exposed to X-ray radiation was significantly decreased in a dose-dependent manner and was associated with cell cycle arrest at the G0/G1 phase as well as apoptosis. STS treatment significantly reversed the morphological changes, attenuated radiation-induced apoptosis, and improved the antioxidant activity in the H9c2 cells. STS significantly increased the Bcl-2 and Bcl-2/Bax levels and decreased the Bax and caspase-3 levels, compared with the cells treated with radiation alone. STS treatment also resulted in a significant increase in p38-MAPK activation. STS could protect the cells from X-ray-induced cell cycle arrest, oxidative stress, and apoptosis. Therefore, we suggest the STS could be useful for the treatment of radiation-induced cardiovascular injury., Competing Interests: The authors declare that they have no competing interests.

Objective: To observe the effect of compound Zhebei granules (CZBG) with chemotherapy in the treatment of refractory acute leukemia., Methods: In this multicenter, double-blind, placebo-controlled clinical trial, we used a central (online) randomization system to assign 235 patients to two treatment groups. A total of 118 patients received chemotherapy combined with CZBG (4 g, twice daily) and 117 patients received chemotherapy plus placebo. The clinical efficacy was evaluated at the end of one chemotherapeutic cycle., Results: In the full analysis set, in which deaths due to disease progression were regarded as inefficacy, the rates of complete remission (CR) and partial remission (CR + PR) were 32.35% and 50.00% , respectively, for the chemotherapy combined with CZBG group, and 23.08% and 35.58%, respectively, for the chemotherapy plus placebo group. There was a statistically significant difference between the two groups according to a χ2 test (P < 0.05). In the per protocol analysis set (PPS), the CR (33.67%), CR+PR (52.04%) response rates for the chemotherapy plus CZBG group were significantly different from the response rates of the control group (CR: 24.24% and CR+PR: 37.37%), respectively (P < 0.05)., Conclusion: CZBG plus chemotherapy can improve the clinical remission rate of refractory acute leukemia after one just one therapeutic cycle.

Objective: To investigate curative effect and importance of radiofrequency thermocoagulation onsemilunar ganglion of aged patients with recurrent trigeminal neuralgia., Method: 112 cases with recurrent trigeminal neuralgia were performed with radiofrequency thermocoagulation on semilunar ganglion by puncture through skin under local anesthesia., Result: The maintaining effective duration in 112 cases was 7.3 ± 1.3 years after primary therapy. After the first thermocoagulation, 89.28% (100/112) patients got the relief from pain immediately, 8 (7.14%) cases also recieved the same effect after twice treatment. However two cases (2.6%) had no effects. The total effective rate was 98.21%. During five follow-up years, VAS scores, dose of carbamazepine and satisfaction were better than those before the treatment. The effective rate was still over 57.5% within three years after the treatment. The recurrent risk increased obviously from 40 months after the treatment by Kaplan-Meier method., Conclusion: Semilunar ganglion of radiofrequency thermocoagulation was an ideal option for old-age patients with trigeminal neuralgia. It can be performed repeatedly.

The leukemic stem cell marker CD44, has been reported to have prognostic significance in hematological malignancies. The present study therefore aimed to evaluate whether the expression levels of CD44 and the associated pathway components are associated with the survival rate of elderly patients with refractory acute myeloid leukemia (AML). A total of 20 elderly patients diagnosed with refractory AML were divided into two groups, following induction chemotherapy: Complete remission (CR, n=9) and non-remission (NR. n=11). Bone marrow biopsy specimens were collected, expression levels of CD44, phosphatase and tensin homolog (PTEN), mammalian target of rapamycin (mTOR) and nuclear factor-κB (NF-κB) were analyzed by immunohistochemistry and the captured images were analyzed in a blinded manner using Image Pro Plus software, version 6.0. The overall survival rates (OS) of the patients were then analyzed with log rank, and the correlation between CD44, PTEN, mTOR and NF-κB expression levels and patients survival rates were statistically analyzed using Pearson's method. Significant differences were observed between the CR and NR groups for PTEN (P=0.025) and CD44 (P=0.020) expression levels. Positive CD44 expression was significantly correlated with poor overall survival, with a hazard ratio of 6.281 (95% CI, 1.78-22.12; P=0.0042). The mean OS was 4.00 months for patients that demonstrated positive CD44 expression, compared with 9.27 months for patients that demonstrated negative CD44 expression. A tendency towards reduced survival rates was also observed in patients negative for PTEN expression, when compared with that of PTEN-positive patients. The mean OS was 4.81 months in PTEN-negative patients vs. 8.8 months in PTEN-positive patients, with a hazard ratio of 2.689 (95%CI, 0.89-8.08; P=0.078). Patients that exhibited PTEN-positive and CD44-negative expression, survived significantly longer than patients that demonstrated PTEN-negative and CD44-positive expression (mean OS, 9.86 vs 2.67 months; hazard ratio=0.037; 95% CI, 0.006-0.222, P=0.0006). The expression levels of NF-κB and mTOR were slightly increased in the NR group compared with those of the CR group, although no significant differences were identified. PTEN and CD44 expression levels demonstrated trends towards negative correlation. In conclusion, the expression levels of CD44 and PTEN may be useful markers to predict the prognosis of elderly patients with refractory AML.

Objective: This study was conducted to research the prognostic utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP), compare the utility of the Seattle Heart Failure Score (SHFS) with NT-proBNP, develop a risk-evaluation model based on NT-proBNP, assess the associations of NT-proBNP with patient characteristics, and screen for decisive factors of NT-proBNP in Chinese elderly with chronic heart failure (CHF)., Patients and Methods: There were 306 patients (≥60 years) with CHF chosen as study subjects. Each one received an assessment of NT-proBNP on serum. The end point was all-cause mortality during a mean follow-up period of 471 days., Results: Subjects had a median age of 85 (60-100) years, a median NT-proBNP of 1,743.4 pg/mL, and a median SHFS of 1.87. During the follow-up period, 104 deaths occurred. NT-proBNP was significantly related to mortality (odds ratio 1.603, 95% confidence interval 1.407-1.826; P<0.001) and the significance persisted after full adjustment (odds ratio 1.282, 95% confidence interval 1.103-1.489; P=0.001). Age, New York Heart Association class IV CHF, plasma albumin, and neutrophils/lymphocytes were also independent predictors for mortality (P<0.05 for all). NT-proBNP and the SHFS showed similar predictive capacities (0.736 versus 0.796, P=0.105). The addition of NT-proBNP to the SHFS (0.818 versus 0.796, P=0.168) generated marginal growth in the c-statistic. The model based on NT-proBNP consisting of all selected predictors in this study, including age, New York Heart Association class IV CHF, plasma albumin, neutrophils/lymphocytes, and NT-proBNP, had a moderately higher c-statistic compared with the SHFS (0.846 versus 0.796, P=0.066). NT-proBNP was bound with the SHFS (r=0.500, P<0.001). Characteristics regarding general condition, inflammation, and cardiac and renal function were the decisive factors of NT-proBNP (P<0.05 for all)., Conclusion: As a comprehensive representation of the patient characteristics described earlier, NT-proBNP values provided significant prognostic power similar to the SHFS in Chinese elderly with CHF. A novel model based on NT-proBNP could offer help for risk stratification.

The brain transforms sensory input to motor coordinates to accommodate for changes of posture and gaze direction. Neurophysiological and neuropsychological evidence supports the existence of multiple representations of space. A debated issue regards whether objects that we see are encoded in egocentric frames only or also maintain an object-centered frame of reference. Previous clinical studies were unable to discriminate between these models as the stimuli used to determine object-based (allocentric) biases are contaminated by body-centered (egocentric) effects. To address this, we used stimuli where allocentric side was elicited by gestalt configuration rather than egocentric location. We then displayed these stimuli at different egocentric positions allowing us to independently measure the effects of allocentric position, egocentric position as well as their interaction. In a group of stroke patients with neglect we demonstrate that allocentric biases are modulated as a function of egocentric position. These findings help adjudicate between the different models of space representation, demonstrating that specific allocentric deficits not only exist but also often co-exist with egocentric biases., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Adopting the emerging technology of printed electronics in manufacturing novel ultrathin flat panel displays attracts both academic and industrial interests because of the challenge in the device physics and the potential of reducing production costs. Here we produce all-solution processed polymer light-emitting diode displays by solution-depositing the cathode and utilizing a multifunctional buffer layer between the cathode and the organic layers. The use of ink-jetted conducting nanoparticles as the cathode yields high-resolution cathode patterns without any mechanical stress on the organic layers. The buffer layer, which offers the functions of solvent-proof electron injection and proper affinity, is fabricated by mixing the water/alcohol-soluble polymer and a curable epoxy adhesive. Our 1.5-inch polymer light-emitting diode displays are fabricated without any dead pixels or dead lines. The all-solution process eliminates the need for high vacuum for thermal evaporation of the cathode, which paves the way to industrial roll-to-roll manufacturing of flat panel displays.

Background: To explore the significance of lung biopsy through CT-guided percutaneous paracentesis in the diagnosis of space-occupying lesions of the lung., Methods: Thirty-five patients with space occupying lesions of the lung underwent lung biopsy through CT-guided percutaneous paracentesis and DLTRA-CUT 16G, 18G or 20G soft-tissue-cutting biopsy needles and PICKER IQ computerized tomograph were used., Results: Of the 35 patients, 26 were confirmed by pathological examination to suffer from primary malignant tumor, 1 from metastatic carcinoma, 3 from tuberculosis and 3 from inflammatory pseudotumor. No definite diagnosis was made in two patients. The diagnostic rate was 94.3%. After operation, minor pneumothorax occurred in 5 cases and traces of blood in sputum in 2 cases, however, they didn't need any treatment., Conclusions: Lung biopsy through CT-guided percutaneous paracentesis is a safe and practical technique and may be widely used in hospitals if conditions permit.