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Background: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant condition caused by shortened D4Z4 repeat units in the subtelomeric region of 4q35, always on the 4qA haplotype, or due to variants in the SMCHD1 gene leading to hypomethylation of the D4Z4 macrosatellite DNA repeats., Methods: To explore the potential genetic basis for suspected FSHD presenting with early onset in two siblings without evident family history of the disorder, whole genome sequencing (WGS) and optical genome mapping (OGM) were conducted on the affected individuals and their parents., Results: The two siblings manifested severe and early-onset clinical features consistent with FSHD, initiating with facial muscle weakness that progressively spread downward since the age of four months. OGM disclosed a reduced number of D4Z4 repeat units within the subtelomeric region of 4q35 in both affected siblings. This finding was pivotal in establishing the diagnosis of FSHD1 in the two brothers. The analysis also revealed that their clinically asymptomatic mother harbored the pathogenic D4Z4 repeat configuration (4qA) at a 50% frequency, indicating her mosaic carrier status. Additionally, WGS and Sanger sequencing identified a paternal origin variant c.695_699del (p.Val232Glyfs*7) in the DNAJB6 gene in both siblings., Conclusion: The application of advanced genomic methodologies has proven instrumental in unraveling the intricacies of genetic diseases that challenge traditional diagnostic paradigms. Specifically, this study highlights the effectiveness of OGM in diagnosing FSHD1 and confirming D4Z4 repeat reduction, particularly in cases involving parental mosaicism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Few data are available on metastatic colorectal cancer (mCRC) treated with late-line regorafenib monotherapy or combined with other therapies. This study thus aimed to examine regorafenib combined with immune checkpoint inhibitors (ICIs) compared with regorafenib monotherapy in patients with advanced CRC., Methods: This single-center retrospective cohort study included patients with advanced CRC who experienced recurrence and progression after standard first- and second-line treatments treatment from November 2018 to December 2021. The patients received regorafenib plus ICIs or regorafenib monotherapy. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST). Overall survival (OS) and progression-free survival (PFS) were analyzed via multivariate analysis., Results: The combined group and the monotherapy group included 30 and 43 patients, respectively. The median OS (13.7 vs . 10.1 months; P=0.10) and PFS (4 vs . 3.6 months; P=0.32) were not significantly different between the two groups. In males, the median OS was significantly longer in the combined group compared with the monotherapy group (not reached vs . 8.03 months; P=0.02), but the median PFS showed no significant difference (7.23 vs . 3.90 months; P=0.16). There was no significant difference in OS (P=0.71) or PFS (P=0.89) in females. Eastern Cooperative Oncology Group performance status (ECOG PS) 1 [ vs . 0; hazard ratio (HR) =3.13, 95% confidence interval (CI): 1.61-6.10; P<0.001] was independently associated with PFS. ECOG PS 1 ( vs . 0; HR =3.63, 95% CI: 1.54-8.56; P=0.003) and combined therapy ( vs . monotherapy; HR =0.47, 95% CI: 0.22-0.99; P=0.048) were associated with OS., Conclusions: Regorafenib combined with ICIs led to numerically longer PFS and significantly prolonged OS in patients with mCRC compared to regorafenib monotherapy, especially in male patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-468/coif). J.M.P. reports honoraria and support for attending meetings and travel from MSD, Bristol-Myers Squibb, and Merck. The other authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Objective: This study was conducted to identify the factors (especially parental involvement, academic self-efficacy, and depression) associated with academic performance among Chinese K-12 students during the COVID-19 pandemic., Methods: This cross-sectional study used data from the 2020 China Family Panel Studies (CFPS). The CFPS was conducted from July to December 2020 during the COVID-19 pandemic. A multistage probability sample proportional to size was used for the survey. The final sample consisted of 1747 K-12 students. This study used the 14-item Chinese Parental Involvement and Support Scale, the Responsibility Scale, and the 8-item Center for Epidemiologic Studies Depression Scale to measure parental involvement, academic self-efficacy, and depression, respectively. An ordered probit regression and structural equation models were employed to analyze the factors associated with academic performance. A multiple imputation technique was applied to compute missing values in selected variables., Results: We found that parental involvement and academic self-efficacy were positively associated with good academic performance. In contrast, depression was negatively associated with good academic performance. Moreover, academic stress, male, rural residency, middle school, family size, high income, online gaming daily, reading, and intelligence quotient were statistically significant predictors on academic performance., Conclusion: The empirical findings suggested that parental involvement and academic self-efficacy were positively and significantly associated with good academic performance. However, depression was negatively and significantly associated with good academic performance. These results showed that policymakers and practitioners can help improve academic success and address educational inequalities among K-12 students by implementing a series of reforms., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Kang et al.)

Background: The Chinese central government launched the third phase of health system reforms in 2009. After a decade since the initiation of the reform, the health system has witnessed noteworthy gains. However, there is no concurrent improvement in public satisfaction with the health system. This study analysed various factors that influence public satisfaction with the system and examined whether perceived quality of care affects public satisfaction., Methods: A longitudinal nationally representative survey was used for this study. We used five waves of China Family Panel Studies (CFPS) survey data. The final sample consisted of 145 843 observations. A two-way fixed-effects ordered logistic model was used for the analysis., Results: The results indicate that perceived good quality of care was positively associated with public satisfaction in health system regardless of rural-urban residence. Older adults and individuals with more than 3 years of college education were less likely to be satisfied with the system in rural areas. Personal income and the density of medical professionals in the geographic area tend to improve public satisfaction in rural areas. Having medical insurance coverage and fair or good self-rated health improved the probability of reporting public satisfaction in urban areas. Married people and individuals who lived in the West region were less likely to be satisfied with the health system in urban areas., Conclusions: Knowledge and skills of healthcare providers or physical quality of facilities are not sufficient in improving public satisfaction in the health system. Policymakers need to identify options to influence the important factors that affect public perception of the system. This analysis identified several policy-amenable factors to improve public perception of the health system in rural and urban China., (© 2023. The Author(s).)

Purpose: Medical care delay or avoidance increases morbidity and mortality risk and is costly for the national healthcare system. The objective of this study was to identify factors associated with medical care delay or avoidance among Chinese adults during the COVID-19 pandemic., Materials and Methods: A cross-sectional analysis was conducted using data from the 2020 China Family Panel Study (CFPS). The CFPS was conducted from July to December 2020 during the COVID-19 pandemic. The final sample included 4369 adults. A logistic regression model was employed to identify the factors associated with medical care delay or avoidance., Results: The empirical results indicate that regardless of rural-urban residence, older adults and adults with chronic conditions were less likely to delay or avoid medical care during the pandemic. However, individuals who had completed more than three years of college showed a higher likelihood of delaying or avoiding medical care. In urban areas, larger family sizes, greater general trust in physicians, and higher provider structural quality were associated with a decreased probability of delaying or avoiding medical care during the pandemic. In contrast, employed adults were more likely to delay or avoid medical care. In rural areas, current smokers were more likely to delay or avoid medical care during the pandemic., Conclusion: This study has identified several factors affecting medical care delay or avoidance, some of which are amenable to policy changes. Policymakers can help improve the utilization of health facilities and patient health outcomes by implementing a series of reforms., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2023 Kang et al.)

Within the context of mounting competition faced by Hollywood movies in the global cinema market, particularly in emerging markets, this paper examines the influence of review disagreements and cultural capital on the cultural discount of imported Hollywood blockbusters in China's movie market. Using a dataset of 652 movies from the U.S. spanning 1994-2019, we find that review disagreements between U.S. and Chinese consumers exacerbate the cultural discount on imported Hollywood movies in China. However, cultural capital, measured by the accumulated revenue of specific imported movie genres in China, effectively mitigates this discount. We also observe a reduction in the discount for movie genres with fewer language barriers. Accounting for endogeneity due to reverse causality and selection bias, we identify a significant structural break in 2012. In the post-2012 era, collaboration involving China's censorship, quota rules, and film-production laws has improved the market mechanism and cultural capital accumulation, enhancing the performance of imported Hollywood movies in China. Minority movies, characterized by being less mainstream and commercial, are more sensitive to review disagreements, while cultural capital plays a greater role in mitigating the discount for mainstream Hollywood movies. These findings have significant implications for professionals involved in the distribution and screening of Hollywood movies in China., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Understanding the factors that affected academic performance of students during the COVID-19 pandemic will help design effective interventions for improving students' academic performance during emergency situations as well as during regular academic environment. This cross-sectional study aimed to identify the factors that explain academic performance of students in China during the pandemic., Methods: Data on college students from the 2020 China Family Panel Studies were used, and the final sample consisted of 728 students. Ordered probit regression models were estimated to explain students' relative performance in the semester when the in-person classes were suspended by using various student and household-related variables and characteristics. To compute missing values in selected variables, a multiple imputation technique was applied., Results: The odds of poor academic performance declined with higher Internet use for academic purposes, but Internet use for entertainment increased the probability of being in the poor academic performance. College students who spent more time studying on college work were less likely to have poor academic performance., Discussion: This study identified the factors (Internet use and study time) associated with academic performance among Chinese college students during the COVID-19 pandemic. These results can be used to design policies to improve educational outcomes and to address educational inequalities., 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 Li, Kang, Miles and Khan.)

Ultrawide-bandgap semiconductors, possessing bandgaps distinctly larger than the 3.4 eV of GaN, have emerged as a promising class capable of achieving deep ultraviolet (UV) light detection. Based on first-principles calculations, we propose an unexplored two-dimensional (2D) InTeClO 3 layered system with ultrawide bandgaps ranging from 4.34 eV of bulk to 4.54 eV of monolayer. Our calculations demonstrate that 2D InTeClO 3 monolayer can be exfoliated from its bulk counterpart and maintain good thermal and dynamic stability at room temperature. The ultrawide bandgaps may be modulated by the small in-plane strains and layer thickness in a certain range. Furthermore, the 2D InTeClO 3 monolayer shows promising electron transport behavior and strong optical absorption capacity in the deep UV range. A two-probe InTeClO 3 -based photodetection device has been constructed for evaluating the photocurrent. Remarkably, the effective photocurrent (5.7 A m -2 at photon energy of 4.2 eV) generation under polarized light has been observed in such a photodetector. Our results indicate that 2D InTeClO 3 systems have strong photoresponse capacity in the deep UV region, accompanying the remarkable polarization sensitivity and high extinction ratio. These distinctive characteristics highlight the promising application prospects of InTeClO 3 materials in the field of deep UV optoelectronics.

Two-dimensional (2D) ferroelectric tunnel junctions (FTJs) have great potential in the design of non-volatile memory devices due to the tunneling electroresistance (TER) effect and the fact that it is not constrained by critical thickness. Incorporation of 2D ferroelectric materials in realistic FTJs inevitably involves the contacts to the traditional three-dimensional (3D) metals. However, how to design the FTJs by combining the 2D ferroelectric materials with the 3D metals still needs to be studied. In this work, we design a vertical 3D FTJ by adopting the 3D metal Au as the left and right electrodes and the 2D ferroelectric material In2Se3 together with h-BN as the central scattering region. By density functional theory combined with the non-equilibrium Green's function (NEGF) method, we demonstrate that the h-BN intercalation with a large bandgap plays the role of good "insulator," which breaks the symmetry of the left and right electrodes. As a result, we obtain the TER ratio of about 170%, and it can be further improved to about 1200% if two layers of In2Se3 (2L-In2Se3) are adopted as the tunneling barrier layer. Our results provide another way for the design and application of ferroelectric memory devices based on 2D ferroelectric materials., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Rationale: KBG syndrome (KBGS, OMIM: 148050), a rare genetic disorder, is clinically characterized by megalodontia, short stature, skeletal abnormalities, and nervous system manifestations. In the study, we explore the clinical and genetic characteristics of one neonate suffering KBGS caused by ANKRD11 gene mutation., Patient Concerns: The proband, a female, was born prematurely at 31 + 2 weeks. There were repeated infections and abdominal distension in the first month after birth, and the platelets could not rise to normal. Head ultrasound showed intracranial brain injury and intracranial hemorrhage., Diagnoses: Sequencing revealed that there was a heterozygous mutation in exon 9 of the ANKRD11 gene (NM&#95;013275.5) for the child, c.1896&#95;1897delTA (p.H632Qfs*30), which was a de novo mutation and has not been reported. Combining clinical features and genetic results, the proband was diagnosed as KBGS., Interventions and Outcomes: The brain sonography on day 4 after birth showed brain injury and intracranial hemorrhage. Therefore, 140 mg of bovine lung surfactant was administered through endotracheal intubation in addition to ventilator-assisted ventilation. Antibiotic treatment was also given till the inflammatory indicators of the infant returned to normal levels. The following-up of 1-year-6-month showed that the language, motion and height of development is slight falling behind the children of the same age., Lessons: This is the first case of KBGS was diagnosed in the neonatal period, which provides a reference for the child to receive timely and correct treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Gestational duration has a significant impact on eye diseases. A large number of evidences suggest that cytokines are associated with gestational duration and eye diseases. However, the causal relationships among cytokines, maternal gestational impairment and offspring eye diseases remain unclear., Methods: We performed lifecourse-network Mendelian randomization (MR) to explore the causal relationships between maternal gestational duration (from the Early Growth Genetics (EGG) Consortium and the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) study, N = 84,689), neonatal/adult cytokines (from the NHGRI-EBI Catalog, N = 764/4,618), and adult eye diseases (from FinnGen consotium, N = 309,154) using summary-level data from large genome-wide association studies. Multiplicative random effects inverse variance weighted (IVW) and multivariable-IVW methods were the main analysis methods, and the other 15 pleiotropy-robust methods, weak IV-robust methods, and outliers-robust methods were used as auxiliary methods., Results: Maternal gestational age (early preterm birth, preterm birth, gestational duration, and post-term birth) had a causal relationship with 42 eye diseases. Four neonatal cytokines, Tumor Necrosis Factor-α(TNF-α), IL10, GROA, and CTACK, as well as four adult cytokines, CTACK, IL10, IL12p70 and IL6 are mediators in the causal relationships between early preterm birth and preterm birth in eight eye diseases. However, after adjusting for these mediators, a null direct causal effect of early preterm birth and preterm birth on eight eye diseases was found. In addition, there was no mediator in the causal relationship between gestational duration and post-term birth to eye diseases., Conclusion: The effects of maternal gestational duration on offspring eye diseases through cytokines are long-term and life-course effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease (VEO-IBD) type 28 child with atypical clinical manifestations., Methods: A VEO-IBD type 28 child with atypical clinical manifestations admitted to the Department of Neonatology, Children's Hospital Affiliated to Shandong University on November 5, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis., Results: The child, a 50-day-old male, had manifested bronchitis, ulcerative stomatitis, eczema and slightly loose stool. High-throughput sequencing revealed that he has harbored compound heterozygous variants of the IL-10RA gene, namely c.299T>G (p.V100G) and c.301C>T (p.R101W), which were inherited from his father and mother, respectively. Bioinformatic analysis showed that both variants have been recorded in the HGMD database, though the c.299T>G variant has not been included in the gnomAD, 1000 Genomes, ExAC and ESP6500 databases, while the c.301C>T variant has a low population frequency. Both variants were predicted to be deleterious by the online software including SIFT, PolyPhen-2 and Mutation Taster. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PS3+PM2&#95;Supporting+PP3)., Conclusion: The c.299T>G and c.301C>T variants of the IL-10RA gene probably underlay the VEO-IBD type 28 in this child. Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.

Two-dimensional (2D) ferroelectric materials have important application potential in device miniaturization due to their characteristics of only being a few atomic layers thick and non-volatility. How to design high-performance ferroelectric memory devices based on 2D ferroelectric materials has attracted extensive attention. In this work, based on the 2D organic ferroelectric material semi-hydroxylized graphane (SHLGA), which has in-plane ferroelectric polarization along three different directions, we construct a 2D organic ferroelectric tunnel junction (FTJ). By means of density functional theory (DFT) and the non-equilibrium Green's function (NEGF) method, we calculate the transport properties of the FTJ under different polarizations and obtain a giant tunnel electroresistance (TER) ratio of 7.55 × 10 4 %. We find that the mechanism behind the TER effect in the organic SHLGA is based on the unique built-in electric field. That is, among the three ferroelectric polarization directions, any two directions have an angle of 120°. As a result, the built-in electric fields along the transport direction of the FTJ under different ferroelectric polarization directions are different. Moreover, our study shows that the giant TER effect can also be achieved by utilizing the asymmetry of the polarization along the transport direction of the ferroelectric material itself, which provides another route for the design of 2D FTJs.

Abstract: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by pulmonary arterial remodeling mainly because of apoptosis resistance and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). Sildenafil is a phosphodiesterase-5 inhibitor. Some reports have shown that sildenafil exerts protective effects against PPHN. However, the function of sildenafil in PPHN and the underlying molecular mechanisms is not clear. Here, we revealed that sildenafil effectively suppressed hypoxia-induced PASMC proliferation and apoptosis inhibition ( P < 0.05). Also, sildenafil obviously reduced ventricular hypertrophy, and inhibited pulmonary vascular remodeling in the PPHN model ( P < 0.05). Moreover, sildenafil treatment significantly attenuated the induction of Notch3 and Hes1 induced by hypoxia treatment ( P < 0.05). Furthermore, overexpression of Notch3 abolished the reduction of PASMC proliferation and promotion of PASMC apoptosis induced by sildenafil under hypoxia ( P < 0.05), whereas knockdown of Notch3 had an opposite effect ( P < 0.05). Together, our study demonstrates that sildenafil shows a potential benefit against the development of PPHN by inhibiting Notch3 signaling, providing a strategy for treating PPHN in the future., Competing Interests: The author reports no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

This paper investigated the relationship between cultural distance, classroom silence, and the performance of culturally responsive and inclusive education (CRIE) using a survey of 1051 college students in Shanghai in 2022. We found a significantly positive association between migrant students' cultural distance and their perceived learning gains in class. Students' cultural distance increased their classroom silence as a form of protection but had no significant effect on their classroom silence as a sign of power. The classroom silence as protection decreased students' perceived learning gains. However, classroom silence as power could be used by both local and migrant students as a hold-up strategy to strengthen their influence in class discussions, which could improve their perceived learning gains. Teachers' CRIE played the most important role in migrant students' perceived learning gains, while the effectiveness of CRIE was also actually dependent on the different channels and mechanisms of cultural distance and classroom silence. A cautious identification of classroom silence will improve the effectiveness of CRIE. Suggestions are offered to lighten the practice of educators, administrators, and instructors who face classroom silence from subnational migrant students.

The corpse plant (Amorphophallus titanum) is so named because it produces a pungent, foul odor when flowering. Little is known about how the emitted volatiles change throughout the two-day flowering period. In this study, the comprehensive monitoring of the presence and change in volatile molecules during the female and the male flowering phases of A. titanum was conducted, and the plant temperature was monitored. A total of 422 volatile features were detected over the entire sampling period, of which 118 features were statistically significantly different between the pre-flowering and both flowering phases, and an additional 304 features were found present throughout the flowering period. A total of 45 molecules could be assigned putative names. The volatile profile of A. titanum changes over the two-day flowering period, with the S-containing molecules and aldehydes dominant in the female flowering phase, and the alcohols and hydrocarbons dominant in the male flowering phase. The two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOFMS) enabled us to identify 32 new molecules produced by A. titanum. Each of these molecules alone, and in combination, likely contribute to the different odors emitted during the flowering phase of A. titanum., (© 2023. The Author(s).)

Background: Necrotizing enterocolitis (NEC) is a disastrous gastrointestinal disease of newborns, and the mortality rate of infants with NEC is approximately 20%-30%. The exploration of pathogenic targets of NEC will be conducive to timely diagnosis of NEC., Methods: The whole transcriptome RNA sequencing was performed on NEC samples to reveal the expression of lncRNAs, circRNAs, miRNAs and mRNAs. Using differential expression analysis, cross analysis, target prediction, enrichment analysis, the pathogenic ceRNA network and target was found., Results: Preliminarily, 281 DEmRNAs, 21 DEmiRNAs, 253 DElncRNAs and 207 DEcircRNAs were identified in NEC samples compared with controls. After target prediction and cross analyses, a key ceRNA regulatory network was built including 2 lncRNAs, 4 circRNAs, 2 miRNAs and 20 mRNAs. These 20 mRNAs were significantly enriched in many carbohydrate metabolism related pathways. After cross analysis of hypoxia-, carbohydrate metabolism-related genes, and 20 core genes, one gene HK2 was finally obtained. Dendritic cells activated were significantly differentially infiltrated and negatively correlated with HK2 expression in NEC samples., Conclusions: The promising pathogenic hypoxia-related gene HK2 has been firstly identified in NEC, which might also involve in the carbohydrate metabolism in NEC., (© 2022. The Author(s).)

Phosphatidylinositol-4-kinase alpha (PI4KIIIα), encoded by the PI4KA gene, can synthesize phosphatidylinositol-4-phosphate (PI-4-P), which serves as a specific membrane marker and is instrumental in signal transduction. PI4KA mutations can cause autosomal recessive diseases involving neurological, intestinal, and immunological conditions (OMIM:619621, 616531, 619708). We detected sepsis, severe diarrhea, and decreased immunoglobulin levels in one neonate. Two novel compound heterozygous mutations, c.5846T>C (p.Leu1949Pro) and c.3453C>T (p.Gly1151=), were identified in the neonate from the father and the mother, respectively. Sanger sequencing and reverse transcription polymerase chain reaction (RT-PCR) for peripheral blood and minigene splicing assays showed a deletion of five bases (GTGAG) with the c.3453C>T variant at the mRNA level, which could result in a truncated protein (p.Gly1151GlyfsTer17). The missense mutation c.5846T>C (p.Leu1949Pro) kinase activity was measured, and little or no catalytic activity was detected. According to the clinical characteristics and gene mutations with functional verification, our pediatricians diagnosed the child with a combined immunodeficiency and intestinal disorder close to gastrointestinal defects and immunodeficiency syndrome 2 (GIDID2; OMIM: 619708). Medicines such as immunomodulators are prescribed to balance immune dysregulation. This study is the first report of a synonymous mutation in the PI4KA gene that influences alternative splicing. Our findings expand the mutation spectrum leading to PI4KIIIa deficiency-related diseases and provide exact information for genetic counseling., 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, Kang, Zhang, Bai, Pang, Liu, Zhang, Chen, Yu, Lv, Gao, Liu, Gai, Wang and Li.)

Introduction: The high co-occurrence of tobacco smoking and depression is a major public health concern during the novel coronavirus disease-2019 pandemic. However, no studies have dealt with missing values when assessing depression. Therefore, the present study aimed to examine the effect of tobacco smoking on depressive symptoms using a multiple imputation technique., Methods: This research was a longitudinal study using data from four waves of the China Health and Retirement Longitudinal Study conducted between 2011 and 2018, and the final sample consisted of 74,381 observations across all four waves of data collection. The present study employed a multiple imputation technique to deal with missing values, and a fixed effects logistic regression model was used for the analysis., Results: The results of fixed effects logistic regression showed that heavy smokers had 20% higher odds of suffering from depressive symptoms than those who never smoked. Compared to those who never smoked, for short-term and moderate-term quitters, the odds of suffering from depressive symptoms increased by 30% and 22%, respectively. The magnitudes of the odds ratios for of the variables short-term quitters, moderate-term quitters, and long-term quitters decreased in absolute terms with increasing time-gaps since quitting. The sub-group analysis for men and women found that heavy male smokers, short-term and moderate-term male quitters had higher odds of suffering from depressive symptoms than those who never smoked. However, associations between smoking status and depressive symptoms were not significant for women., Conclusions: The empirical findings suggested that among Chinese middle-aged and older adults, heavy smokers and short-term and moderate-term quitters have increased odds of suffering from depressive symptoms than those who never smoked. Moreover, former smokers reported that the probability of having depressive symptoms decreased with a longer duration since quitting. Nevertheless, the association between depressive symptoms and smoking among Chinese middle-aged and older adults is not straightforward and may vary according to gender. These results may have important implications that support the government in allocating more resources to smoking cessation programs to help middle-aged and older smokers, particularly in men., 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 Du, Wu, Kang, Zhao and Li.)

Neuroblastoma is a metastatic tumor almost exclusively plaguing young children. To provide an early warning for timely medical interference that may prevent such tragedies from happening, we mimic the biomolecular pathology of this disease and have obtained an assay without using costly biomolecules such as antibodies and enzymes but can still sensitively detect trace level metal ions and metastatic marker proteins in the cerebrospinal fluid of neuroblastoma-bearing children in a one-step and reagentless fashion. Specifically, a surface-tethered "open bridge"-like molecular machine is designed. This probe, after interacting with cupric ions, can form an electrochemically active peroxidase-like artificial enzyme. Its activity first opens the probe, freeing the Bcl-2-targeting sequence of the probe to adopt the most favorable conformation, forming a noncovalent complex with Bcl-2. Then, the peroxidase-like activity of the probe induces the formation a robust fluorescence covalent linkage with the target protein. This fluorescence and electrochemical dual detection allows an analytical performance not inferior to the commercially available methods, pointing to possible clinical application in the early screening of pediatric metastatic conditions in the near future.

Background: Septic shock is the most severe complication of sepsis, and is a major cause of childhood mortality, constituting a heavy public health burden., Methods: We analyzed the gene expression profiles of septic shock and control samples from the Gene Expression Omnibus (GEO). Four differentially expressed genes (DEGs) from survivor and control groups, non-survivor and control groups, and survivor and non-survivor groups were selected. We used data about these genes to establish a logistic regression model for predicting the survival of septic shock patients., Results: Leave-one-out cross validation and receiver operating characteristic (ROC) analysis indicated that this model had good accuracy. Differential expression and Gene Set Enrichment Analysis (GSEA) between septic shock patients stratified by prediction score indicated that the systemic lupus erythematosus pathway was activated, while the limonene and pinene degradation pathways were inactivated in the high score group., Conclusions: Our study provides a novel approach for the prediction of the severity of pathology in septic shock patients, which are significant for personalized treatment as well as prognostic assessment., (© 2021. The Author(s).)

Tunneling electroresistance (TER) is the change in tunneling resistance induced by ferroelectric polarization reversal in ferroelectric tunnel junctions (FTJs), and how to achieve a giant TER has always been a central topic in the study of FTJs. In this work, by considering the NaTiO3/BaTiO3/LaTiO3 junction with asymmetric polar interfaces as an example, we propose a novel scheme to realize a giant TER based on the reversible partial metallization of ferroelectric barrier upon the switching of ferroelectric polarization. Density functional theory calculations indicate that high on-state and low off-state conductances are obtained and the TER ratio is as high as 3.20 × 108% due to the reversible partial barrier metallization, which leads to a great difference in the effective tunneling barrier widths. The reversible partial barrier metallization, accompanied by the ferroelectric polarization reversal, is driven by the parallel or anti-parallel alignment of the depolarization electrical field of the ferroelectrical barrier and a strong built-in electrical field cooperatively contributed by the asymmetric polar interfaces and the difference in the work functions of the two leads. The findings suggest a feasible scheme for constructing promising high performance FTJ memory devices by combining both asymmetric polar interfaces and substantially different work functions.

Pediatric tuberculosis (TB) remains a global health crisis. Despite progress, pediatric patients remain difficult to diagnose, with approximately half of all childhood TB patients lacking bacterial confirmation. In this pilot study (n = 31), we identify a 4-compound breathprint and subsequent machine learning model that accurately classifies children with confirmed TB (n = 10) from children with another lower respiratory tract infection (LRTI) (n = 10) with a sensitivity of 80% and specificity of 100% observed across cross validation folds. Importantly, we demonstrate that the breathprint identified an additional nine of eleven patients who had unconfirmed clinical TB and whose symptoms improved while treated for TB. While more work is necessary to validate the utility of using patient breath to diagnose pediatric TB, it shows promise as a triage instrument or paired as part of an aggregate diagnostic scheme.

The effect of emotion on memory often leads to the trade-off: enhanced memory for emotional items comes at the cost of memory for background information. Although this effect is usually attributed to overt attention during encoding, Steinmetz and Kensinger (2013) proposed that such an effect might also be related to post-stimulus elaboration. Based on previous different viewpoints, we used the directed forgetting paradigm to further explore the effect of post-stimulus elaboration on the memory trade-off. In the meantime, we also tested the roles of background valence and item salience (high salient items were placed in the centre of backgrounds while low salient items were placed in the periphery of backgrounds) in modulating the memory trade-off. Our results showed that there was a memory trade-off when backgrounds were neutral, whereas this was no longer the case when backgrounds were negative. This indicated the memory trade-off might be affected by background valence. Meanwhile, we found post-stimulus elaboration contributed to selective memory enhancement for backgrounds, while item salience enhanced item memory performance in the memory trade-off. These findings suggest the emotion-induced memory trade-off may be a complex memory effect, which can be influenced by different factors to varying degrees.

Mastocytosis is an accumulation of clonal mast cells within tissues and it is most commonly caused by an activating mutation in the KIT gene. In this study, we report a neonatal case who presented with diffuse cutaneous mastocytosis (CM) at birth. In China, nine other cases of neonatal-onset CM have been reported in the literature since 2006. In those cases, diffuse CM and urticaria pigmentosa were the main symptoms, and mutations in exon 17 at codon 816 in KIT were identified.

Acute lung injury (ALI) severely impairs gas exchange and results in high mortality. Insulin-like growth factor binding protein 3 (IGFBP-3) plays a crucial role in diverse lung diseases;however, the expression and function of IGFBP-3 in ALI remain unclear. In the present study, mice were injected with lipopolysaccharide to establish ALI, and IGF and IGFBP3 expression was measured using ELISA, western blotting, and immunohistochemical staining. Mice with ALI were then treated with recombinant human IGFBP-3 (rhIGFBP-3), and treatment was evaluated using survival analysis, histological staining analysis, and inflammatory cytokine expression in lung tissues and bronchoalveolar lavage fluid (BALF). The expression of NF-κB and VEGF was also measured using western blotting and ELISA in ALI mice. Our results demonstrated the upregulation of IGF expression in lung tissues and BALF of ALI mice, accompanied by downregulation of IGFBP-3. Administration of rhIGFBP-3 prolonged the survival time and attenuated LPS-induced lung injury. The expression of TNF-α, IL-6, IL-1β, and IFN-γ both in lung tissues and BALF decreased after rhIGFBP-3 treatment, whereas IL-10 expression increased. These results suggest that rhIGFBP-3 inhibits the expression of NF-κB and VEGF in lung tissues. Collectively, our study demonstrates a protective role of rhIGFBP-3 in ALI by regulation of lung inflammation., Competing Interests: None., (IJCEP Copyright © 2020.)

Objective: This study evaluated change in caesarean section rate with reform of birth planning policy in China from one-child to two-child policy., Methods: Study data were collected from patient-level hospital records of 59,668 pregnant women who visited three major urban hospitals in Jiangsu Province and Inner Mongolia Autonomous Region of China between January 2012 and December 2016. A segmented logistic regression approach was developed to evaluate the changes in caesarean section rate in these regions with the launch of China's new partial and universal two-child policies in January 2014 and January 2016, respectively., Results: Jiangsu Province had a significantly lower non-emergency caesarean rate (Jiangsu 8.15% vs Inner Mongolia 34.03%, p < 0.001) and a much lower percentage of minority population (Jiangsu 6.99% vs Inner Mongolia 21.76%, p < 0.001) than Inner Mongolia Autonomous Region. In Jiangsu Province, no change in caesarean section rate was detected with the two-child policies (all p -values > 0.05), although the unadjusted trend change (0.038, 95% confidence interval or CI: [0.016, 0.060], p < 0.001) in log odds after the implementation of the partial two-child policy was statistically significant. In Inner Mongolia Autonomous Region, an immediate jump in caesarean section rate was discovered by the segmented logistic regression with the implementation of both the partial (unadjusted level change 0.297, CI: [0.105, 0.489], p = 0.002) and universal two-child policies (unadjusted level change 1.945, CI: [1.277, 2.614], p < 0.001); but the rate reverted to the previous level thereafter. Ethnicity, maternal age, maternal reproduction history, insurance coverage type, infant weight, and infant gender were the significant factors associated with caesarean section rate (for odds ratios, all p -values < 0.05). However, the significance of infant gender may stem from the large sample size of the study and is not clinically meaningful., Conclusion: Change in caesarean section rate was not observed with the launch of two-child policy in China., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Kang et al.)

Objective: To assess the rural-urban disparity in caesarean section rates using electronic health records from hospitals located in the Province of Inner Mongolia, which is a minority area in Northeastern China., Methods: The study examined the electronic health records of women that gave birth in three major public hospitals between January 2012 and December 2016. Multinomial regression analyses were used to estimate rural-urban disparities in caesarean section rates., Results: Data from 61 903 women were examined. Caesarean section rates increased slightly over the study period and the rate was significantly higher in rural compared with urban hospitals (48% versus 38%). This disparity consistently increased over time. Multinomial regression analyses showed that maternal age, ethnicity, health insurance type, employment status, reproductive history and the newborn's sex were significant risk factors associated with caesarean section rate. Furthermore, stratified analysis of first-time pregnancies, minorities and different age groups showed that the odds of undergoing an emergency caesarean section was lower in the rural hospital, but the odds of undergoing a planned caesarean section was higher in the rural hospital., Conclusions: Caesarean section rates have increased in rural areas and the disparity in rural-urban areas has increased substantially over the years.

Using first-principles density functional theory combined with non-equilibrium Green's function method, we investigate the spin-dependent current generated by photogalvanic effect (PGE) in photoelectric devices based on zigzag silicence nanoribbons with unsymmetrical sp 2 -sp 3 hydrogen passivated edges (H-2H ZSiNRs) and C s symmetry. Due to their unique atomic structures and spin-semiconductor properties, we find that the flow direction of different spin channels, spin polarization and magnitude of the photocurrent can be efficiently controlled by tuning the photon energy ([Formula: see text]) or polarization/helicity angle ([Formula: see text]) of the incident polarized light. Interestingly, at certain polarization/helicity angles or certain photon energy, 100% spin polarized current can be achieved by either linearly or elliptically polarized light. Further, robust pure spin current without an accompanying charge current can be achieved by the irradiation of linearly and elliptically polarized light when the two leads are in antiparallel magnetic configuration and [Formula: see text], [Formula: see text] and [Formula: see text]. Most importantly, without suffering from Schottky barriers or tunnel barriers at metal-semiconductor interfaces, the generated pure spin current or fully spin polarized current in such a purely two-dimensional device with PGE is several orders of magnitude larger than those achieved in metal/semiconductor/metal structures. These numerical results suggest that the asymmetrically sp 2 -sp 3 terminated ZSiNRs are promising materials for construction of novel photoinduced pure spin current and fully spin polarized current generators, which will be of great significance in future spintronic applications.

Background: Our objective was to study the phenotype of and molecular genetic mechanisms underlying congenital protein C (PC) deficiency in Chinese neonates. We report the case of a neonate who presented 4 h after birth with purpura fulminans of the skin and thrombosis in the kidney. We also carried out a through literature review to study the genotype and phenotype, relevance, diagnosis, management, and prognosis of neonates with congenital PC deficiency in China., Case Presentation and Literature Review: Following a septic work-up and check of PC and protein S (PS) levels that showed PC deficiency, we investigated the patient's and her parents' genotypes. Our patient was found to have a plasma PC level of 0.8%. Molecular testing revealed a compound heterozygous mutation of the PROC gene: From the father, a c.&#95;262 G > T p. ASP88Tyr mutation in exon 4; from the mother, a C. 400 + 5G mutation in intron 5 that had been previously reported as likely pathogenic. Both parents were found to have heterozygous mutations for PC deficiency. In China, 5 other cases of congenital PC deficiency in the neonatal period were reported in the literature. In those cases, purpura fulminans and thrombosis were the main symptoms, and homozygous or compound heterozygous mutations of the PROC gene were identified., Conclusion: Congenital PC deficiency should be ruled out for neonates presenting with purpura fulminans and thrombosis., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Ferroelectric tunnel junctions (FTJs) composed by sandwiching a thin ferroelectric layer between two leads have attracted great interest for their potential applications in nonvolatile memories due to the tunnel electroresistance (TER) effect. So far, almost all FTJs studied focus on adopting three dimensional (3D) ferroelectric materials as the tunnel barrier. Recently, many two-dimensional (2D) ferroelectric materials with in-plane or out-of-plane spontaneous polarization have been theoretically proposed or even fabricated, providing a new type of candidate as the tunnel barrier in FTJs. However, very little has been known about whether such 2D ferroelectric materials may lead to an excellent TER effect. In this work, using first-principles calculations, we demonstrate that a giant TER effect of around 623%, which is comparable to 3D FTJs, can be realized through the ferroelectric tunnel junction constructed with the 2D ferroelectric materials BiP and B/N-doped graphene. The analysis of the effective potential and electronic structure indicates that the large TER ratio arises from the unsymmetrical screening effects of the B/N-doped vertical van der Waals graphene/BiP leads. Our findings demonstrate the great potential of novel application of 2D ferroelectric BiP in FTJs.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) especially aspirin has been gained increasing attention due to its potential therapy against to lung cancer. Previous investigations have showed different findings in this issue. We studied the safety profile and efficacy of NSAIDs in treating lung cancer., Method: Embase, Pubmed, and Cochrane Library databases were searched from January 2011 to February 2019. We identified the studies meeting a priori inclusion criteria and it also conducted a secondary review. This meta-analysis of 5 prospective studies was launched to evaluate the effect of NSAIDs for patients with lung cancer on the hazard risk (HR). We used the Random-Effect Model to assess pooled HR and between-study heterogeneity. Application of subgroup analysis, meta-regression, as well as sensitivity analysis was to pinpoint the exact sources of the observed heterogeneity., Results: 5 Prospective Cohorts Studies, including 6017 patients with lung cancer were recruited in the final meta-analysis. In general, using of NSAIDs especially aspirin is not associated with mortality of lung cancer: pooled hazard ratio (HR) of 0.88 [95% confidence intervals (CI): 0.73-1.05] with low heterogeneity (Q = 6.95; I = 42.4%, P = .139). Egger (P = .665) and Begg (P = 1.000) test also showed little trial error in this meta-analysis., Conclusion: NSAIDs did not increase the risk of mortality in patients with lung cancer.

Adverse outcome pathways (AOP) have been proposed as a new method to improve the ecological risk assessment of pollutants, but it requires quantitation linkage between exposure, biomarker response and toxicity of pollutants. A toxicokinetic and toxicodynamic (TK-TD) model was used to quantify AOP of the toxicity of Cd and Pb to zebrafish, including the quantitative relationship between Cd and Pb accumulation in gill and oxidative damage level based on ROS or MDA, and LC 50 values at different times. Significant relationships were found between the oxidative damage level characterized by ROS and MDA content and Cd or Pb accumulation in gill (R 2  > 0.60), and the TK model could better simulate the Pb accumulation in the gills (R 2  > 0.60) than Cd. The increasing of Cd or Pb concentrations induced the generation of ROS and the formation of ROS initiated the fluctuation of MDA level in the cells as compared to controls (p < 0.05). For the individual level effect, the Damage Assessment Model (DAM) could successfully explain the change of LC 50-ROS and LC 50-MDA values at different times (R 2  > 0.99). Our findings suggested that the TK-TD model based on ROS and MDA could be used as a quantitative AOP to predict toxicity of metals to zebrafish., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Sepsis represents a complex disease with the dysregulated inflammatory response. The purpose of this study is to explore the role of interleukin 17 (IL-17, also known as IL-17A) in the occurrence and development of pediatric sepsis., Methods: We established the sepsis neonatal rat model with the method of intraperitoneal injection of Escherichia coli (E coli). At each target time point, we got the blood from heart after anesthetizing animals, and the lung and liver tissues were fixed in formalin. Immunohistochemistry and enzyme-linked immunosorbent assay assay was used to analyze the expression of IL-17A in the lung/liver and plasma respectively. A public data set of neonatal sepsis gene microarray was used to verify our result, and explore main functions of IL-17A in sepsis., Results: The expression levels of IL-17A in the plasma, lung and liver gradually increased with the extension of the experimental time in sepsis group, and were significantly higher than control group at 4 hours after injection of E coli (P < 0.01). In our study, we found the levels of IL-17A mRNA in pediatric sepsis group were significantly higher than control group, which is consistent with the neonatal rat septicemia model. In addition, through the functional (GO) enrichment analysis, we found the genes associated with IL-17A in pediatric sepsis are mainly enriched in the functions of immune response and cell membrane formation., Conclusion: IL-17A might be a potential therapeutic target for pediatric sepsis., (© 2018 Wiley Periodicals, Inc.)

Objective: To explore the genetic basis for a neonate with bloody stool and thrombocytopenia., Methods: Clinical data of the neonate was collected. Peripheral venous blood samples were extracted from the neonate and his parents. Next generation sequencing through target capturing was carried out to detect potential mutations of genes associated with thrombocytopenia. Suspected mutation was validated by Sanger sequencing., Results: The 14-day-old male neonate was admitted to hospital for bloody stool for 8 days, decreased platelet count and reduced platelet volume. His liver function and blood coagulation were both normal. Genetic testing revealed a novel deletional mutation in c.1221delG (G407fsX444) of the WAS gene in the patient, which was inherited from his mother., Conclusion: The c.1221delG (G407fsX444) mutation of the WAS gene probably underlies the X-linked thrombocytopenia in the proband. Next generation sequencing can facilitate the diagnose and genetic counseling of such diseases.

Aquaporin-9 (AQP9) is an aquaglyceroporin that biophysically conducts water, glycerol, and other small solutes. AQP9 is expressed in hepatocytes on the sinusoidal surfaces of hepatocyte plates in the liver, where it is considered responsible for the glycerol uptake in gluconeogenesis. However, limited information is available on the expression and regulating mechanism of AQP9 in different hyperglycemia models. Thus, this study examined the expression patterns of AQP9 and mitogen-activated protein kinase (MAPK) in Types 1 and 2 diabetes mellitus (DM) to clarify the roles and regulating mechanism of AQP9 in gluconeogenesis. Compared with the control group, the AQP9 expression significantly increased in both Types 1 and 2 DM, and the increased expression was associated with the activation of phosphorylated JNK (p-JNK) and the inhibition of phosphorylated p38 (p-p38). By contrast, phosphorylated ERK remained stable in the liver with Type 1 or 2 DM. These effects could be reversed by insulin treatment. That is, insulin downregulated AQP9 by inhibiting p-JNK and activating p-p38. The upregulation of AQP9 could be involved in gluconeogenesis and co-regulated by the JNK and p38 MAPK pathway in both Types 1 and 2 DM., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

The joint toxicity of chemical mixtures has emerged as a popular topic, particularly on the additive and potential synergistic actions of environmental mixtures. We investigated the 24h toxicity of Cu-Zn, Cu-Cd, and Cu-Pb and 96h toxicity of Cd-Pb binary mixtures on the survival of zebrafish larvae. Joint toxicity was predicted and compared using the concentration addition (CA) and independent action (IA) models with different assumptions in the toxic action mode in toxicodynamic processes through single and binary metal mixture tests. Results showed that the CA and IA models presented varying predictive abilities for different metal combinations. For the Cu-Cd and Cd-Pb mixtures, the CA model simulated the observed survival rates better than the IA model. By contrast, the IA model simulated the observed survival rates better than the CA model for the Cu-Zn and Cu-Pb mixtures. These findings revealed that the toxic action mode may depend on the combinations and concentrations of tested metal mixtures. Statistical analysis of the antagonistic or synergistic interactions indicated that synergistic interactions were observed for the Cu-Cd and Cu-Pb mixtures, non-interactions were observed for the Cd-Pb mixtures, and slight antagonistic interactions for the Cu-Zn mixtures. These results illustrated that the CA and IA models are consistent in specifying the interaction patterns of binary metal mixtures., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Vav1 play key roles in the progression of human cancer. However, the role of Vav1 in gastric cancer (GC) remains to be elucidated. The present study aimed to investigate the potential relevance of the clinicopathological characteristics and prognostic significance of Vav1 in GC patients., Methods: The protein expression of Vav1 was analyzed by immunohistochemistry in formalin-fixed samples obtained from 105 GC patients., Results: Positive Vav1 expression was correlated with larger tumor size and more lymph node metastasis ( P <0.05) in GC tissues. Serosal invasion (hazard ratio [HR] = 2.764, P = 0.007), lymph node metastasis (HR = 1.298, P = 0.002) and Vav1 expression (HR = 0.436, P = 0.006) were identified as independent factors of the overall survival (OS) of GC patients. For advanced GC patients, lymph node metastasis (HR = 1.310, P = 0.003) and Vav1 expression (HR = 0.443, P = 0.010) were the independent prognostic factors of OS., Conclusion: Vav1 performs important functions in the aggressiveness of GC, and Vav1 may serve as a novel prognostic factor in GC., Competing Interests: None., (IJCEP Copyright © 2018.)

Glioma is the most common and lethal central nervous system tumors. Temozolomide (TMZ) is an effective drug for malignant glioma, however, the intracellular and molecular mechanisms behind this anti-cancer effect have yet to be fully understood. The aim of the present study was to determine whether TMZ inhibits proliferation, invasion of glioma cells in vitro and whether these effects can be mediated through modulation of aquaporin 4 (AQP4) and phosphorylation of the MAPK pathway. The viability of U87 and U251 human glioma cells was evaluated using MTT assay. The cell cycle distribution was detected with flow cytometry. Migration ability and invasion ability were tested by scratch assays and transwell assays, respectively. The levels of AQP4 and MAPK were measured using immunoblot analyses. Our results showed that TMZ inhibited proliferation, migration and invasion, and induced G2/M arrest in U87 and U251 glioma cell lines. These changes were associated with a decrease in the levels of AQP4 expression as well as activation phosphorylated level of p38. Treatment with a p38 chemical activator (anisomycin) resulted in similar effects as TMZ treatment on glioma cells. And p38 chemical inhibitor (SB203580) could block these effects in glioma treated with TMZ, suggesting a direct up-regulation of the p38 signaling pathway. Therefore, we identified that TMZ might have therapeutic potential for controlling proliferation, invasion of malignant glioma by inhibiting AQP4 expression through activation of p38 signal transduction pathway. J. Cell. Biochem. 118: 4905-4913, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

This study aimed to elucidate how miR-27a-3p modulates the Wnt/β-catenin signaling pathway to promote colorectal cancer (CRC) progression. Our results showed that the expression of miR-27a-3p was up-regulated in CRC and closely associated with histological differentiation, clinical stage, distant metastasis and CRC patients' survival. miR-27a-3p mimic suppressed apoptosis and promoted proliferation, migration, invasion of CRC cells in vitro and in vivo . Whereas miR-27a-3p inhibitor promoted apoptosis and suppressed proliferation, migration, invasion of CRC cells in vitro and in vivo . Furthermore, RXRα was the target gene of miR-27a-3p in CRC. miR-27a-3p expression negatively correlated with RXRα expression in CRC tissues. The underlining mechanism study showed that miR-27a-3p/RXRα/Wnt/β-catenin signaling pathway is involved in CRC progression. In conclusion, our findings first demonstrate that miR-27a-3p is a prognostic and/or potential therapeutic biomarker for CRC patients and RXRα as miR-27a-3p targeting gene plays an important role in activation of the Wnt/β-catenin pathway during CRC progression., Competing Interests: CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.

Objective: This study aimed to investigate mRNA and protein expression levels of RABEX-5 and matrix metalloproteinase-9 (MMP-9), their mutual correlation, and biological behavior in gastric cancer (GC) patients., Methods: The expression levels of RABEX-5 and MMP-9 were determined by real-time quantitative PCR and Western blotting in cell lines, GC tissues, and adjacent normal tissues. In addition, RABEX-5 and MMP-9 expression was analyzed by immunohistochemistry in formalin-fixed tissues from 113 GC patients., Results: The mRNA and protein expression levels of RABEX-5 and MMP-9 in GC cell lines and GC tissues were higher than those in normal gastric mucosa cell line and adjacent normal tissues. RABEX-5 expression and MMP-9 expression in GC tissues were significantly and positively correlated. In addition, the size of tumor (p<0.001), Lauren's classification (p=0.009), and N stage (p<0.001) were identified as the relative factors of RABEX-5 expression, whereas the expression of MMP-9 was correlated with N stage (p=0.003). The results of the multivariate analysis revealed that the independent predictive factors of overall survival were T stage (hazard ratio (HR)=2.382; p=0.028), N stage (HR=1.755; p<0.001), RABEX-5 expression (HR=0.452; p=0.004), and MMP-9 expression (HR=0.561; p=0.032)., Conclusions: RABEX-5 and MMP-9 expression levels were elevated in GC tissues and were associated with tumor invasion, metastasis, and prognosis. Therefore, they may be promising prognostic indicators of survival in GC patients.

Multi-source and multi-frequency emission method can make full use of the valuable and short flight time in frequency domain semi-airborne electromagnetic (FSAEM) exploration, which has potential to investigate the deep earth structure in complex terrain region. Because several sources are adjacent in multi-source emission method, the interaction of different sources should be considered carefully. An equivalent circuit model of dual-source is established in this paper to assess the interaction between two individual sources, where the parameters are given with the typical values based on the practical instrument system and its application. By simulating the output current of two sources in different cases, the influence from the adjacent source is observed clearly. The current waveforms show that the mutual resistance causes the fluctuation and drift in another source and that the mutual inductance causes transient peaks. A field test with dual-source was conducted to certify the existence of interaction between adjacent sources. The simulation of output current also shows that current errors at low frequency are mainly caused by the mutual resistance while those at high frequency are mainly due to the mutual inductance. Increasing the distance between neighboring sources is a proposed measure to reduce the emission signal errors with designed ones. The feasible distance is discussed in the end. This study gives a useful guidance to lay multi sources to meet the requirement of measurement accuracy in FSAEM survey.

Purpose: To develop and evaluate a novel method of generalized auto-calibrating partially parallel acquisition (GRAPPA) with spatially varying calibration of self-constraint for parallel magnetic resonance imaging (MRI) reconstruction., Theory and Methods: The conventional GRAPPA independently estimates each missing sample with adjacent acquired data over multiple coils, thereby ignoring correlations inside missing data. Self-constrained methods can exploit correlations inside missing data by imposing linear dependence within full neighborhood kernels and showing improved reconstruction compared with GRAPPA. However, self-constraint kernels are currently calibrated by using auto-calibration signals. Thus, they may be suboptimal for reconstructing outer k-space because of spatially varying correlations. This study proposes a novel GRAPPA method with separate self-constraints (SSC-GRAPPA). In this method, the spatially varying self-constraint coefficients are adaptively calibrated by separately exploiting correlations inside missing and acquired data in the outer k-space. Both phantom and in vivo imaging experiments were conducted with retrospective undersampling to evaluate the performance of the proposed method., Results: Compared with GRAPPA and self-constrained GRAPPA, the proposed SSC-GRAPPA generates images with reduced artifacts and noise., Conclusion: The proposed method provides an effective and efficient approach to improve parallel MRI reconstruction, and has potential to benefit routine clinical practice in the future., (© 2014 Wiley Periodicals, Inc.)

Here we confirmed that metastasis-associated in colon cancer 1 (MACC1) and β-catenin expression were higher in colorectal cancer (CRC) cells and tissues than those in normal colonic epithelial cell line and adjacent non-tumour colorectal mucosa (ANM) tissues, respectively. MACC1 expression was significantly related to histological differentiation (p<0.001), UICC stage (p=0.029), T classification (p=0.017), and N classification (p=0.023). Cox regression analysis demonstrated that high MACC1/abnormal β-catenin expression was the strongest independent prognostic indicator for reduced overall survival in CRC patients. Significant positive correlation between MACC1 expression and abnormal β-catenin expression was found in CRC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, colony formation, and tumorigenesis, both in vitro and in vivo, but induced apoptosis in CRC cells. Further MACC1 over-expression increased Met, β-catenin, and its downstream genes including c-Myc, cyclin D1, and MMP9 expression, and its upstream gene phos-GSK3β (Ser9) expression. In addition, MACC1 increased vimentin and suppressed E-cadherin in HCT116 cells. Silencing of MACC1 reversed all these changes. Our results firstly suggest that MACC1 plays an important role in carcinogenesis and progression of CRC through β-catenin signaling pathway and mesenchymal-epithelial transition.

To investigate miR-378a-3p and miR-378a-5p expression and their relationships with the clinicopathological features of colorectal cancer (CRC). Our results showed that miR-378a-3p and miR-378a-5p expression were dramatically lower in CRC cell lines and tissues than that in adjacent normal colorectal mucosal tissues, respectively. MiR-378a-3p and miR-378a-5p expression were significantly associated with histological differentiation and TNM stage, respectively. CRC patients with low miR-378a-3p and miR-378a-5p expression had a significantly shorter survival time than those patients with high miR-378a-3p and miR-378a-5p expression (p<0.001, p<0.001), respectively. Univariate and multivariable Cox regression analysis showed that tumour size, TNM stage, miR-378a-3p expression and miR-378a-5p expression were independent prognostic factors for CRC patients. Ectopic miR-378a-3p or miR-378a-5p expression inhibited cellular proliferation and colony formation, induced apoptosis and G1-phase cell cycle arrest in CRC cells, but had no effect on migration and invasion of CRC cells. Furthermore, miR-378a-3p over-expression or down-regulation could inhibit or enhance insulin-like growth factor 1 receptor (IGF1R) expression in CRC cells. There was a significantly negative correlation between IGF1R protein expression and miR-378a-3p expression in CRC tissues. MiR-378a-3p over-expression or down-regulation suppressed or enhanced phosphorylated-ERK1/2 protein level, but had no effect on phosphorylated-Akt protein level. In conclusion, miR-378a-3p and miR-378a-5p expression might play an important role as tumour suppressor gene in the initial stage of carcinogenesis of CRC., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To investigate p53 and hepatoma-derived growth factor (HDGF) expression and their association with clinicopathological features of Ewing family tumour (EFT)., Experimental Design: A total of 108 cases of EFT were retrospectively analysed. p53 and HDGF expression were detected using immunohistochemistry, and the relationships between p53 expression and HDGF expression and clinicopathological features of EFT were analysed. Kaplan-Meier curves were applied to estimate overall survival, log-rank test was used to assess prognostic relevance of p53 expression with overall survival and Cox regression model was performed to evaluate HRs., Results: p53 expression and high HDGF expression was found in 17 (15.7%) and 55 (50.9%) patients, respectively. p53 expression was significantly associated with metastatic stage at initial diagnosis (p=0.007) and tumour venous/nerve invasion (p=0.023). A significant positive correlation was found between p53 expression and HDGF expression in EFT (p=0.022). p53 expression was an independent prognostic factor for overall survival of patients with EFT (p<0.001). Patients with p53-positive/high HDGF expression had a significantly shorter overall survival than those with p53-positive/low HDGF expression or p53-negative/high HDGF expression or p53-negative/low HDGF expression. We first constructed a novel molecular staging system by combining p53 expression and HDGF expression, which significantly improved prognostic stratification for patients with EFT., Conclusions: p53 expression was an independent prognostic factor for patients with EFT. Combining p53 expression and HDGF expression significantly improved prognostic stratification for patients with EFT.

Accuracy of interpolation coefficients fitting to the auto-calibrating signal data is crucial for k-space-based parallel reconstruction. Both conventional generalized autocalibrating partially parallel acquisitions (GRAPPA) reconstruction that utilizes linear interpolation function and nonlinear GRAPPA (NLGRAPPA) reconstruction with polynomial kernel function are sensitive to interpolation window and often cannot consistently produce good results for overall acceleration factors. In this study, sparse multi-kernel learning is conducted within the framework of least squares support vector regression to fit interpolation coefficients as well as to reconstruct images robustly under different subsampling patterns and coil datasets. The kernel combination weights and interpolation coefficients are adaptively determined by efficient semi-infinite linear programming techniques. Experimental results on phantom and in vivo data indicate that the proposed method can automatically achieve an optimized compromise between noise suppression and residual artifacts for various sampling schemes. Compared with NLGRAPPA, our method is significantly less sensitive to the interpolation window and kernel parameters., (© 2013.)

We sought to investigate the clinicopathological significance and biological function of hepatoma-derived growth factor (HDGF) in Ewing's sarcoma. Our results showed that HDGF expression is up-regulated in Ewing's sarcoma. Nuclear HDGF expression is significantly associated with tumour volume (p < 0.001), metastases at diagnosis (p < 0.001), low overall survival rate (p < 0.001) and low disease-free survival rate (p < 0.001). HDGF knock-down results in significant reduction of Ewing's sarcoma cell growth, proliferation and enhances tumourigenesis, both in vitro and in vivo. Meanwhile, HDGF knock-down causes cell cycle arrest and enhanced sensitization to serum starvation-induced apoptosis. Furthermore, recombinant HDGF promotes proliferation and colony formation of Ewing's sarcoma cells. Ninety-eight candidate HDGF downstream genes were identified in Ewing's sarcoma cells using cDNA microarray analysis. In addition, we found that HDGF knock-down inhibited FLI1 expression in Ewing's sarcoma cells at the mRNA and protein levels. Our findings suggest that HDGF exhibits oncogenic properties and may be a novel prognostic factor in Ewing's sarcoma. Targeting HDGF might be a potential therapeutic strategy for Ewing's sarcoma., (Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Objective: The phase information of magnetic resonance (MR) phase image can be used in many MR imaging techniques, but phase wrapping of the images often results in inaccurate phase information and phase unwrapping is essential for MR imaging techniques. In this paper we analyze the causes of errors in phase unwrapping with the commonly used Goldstein Brunch-cut algorithm and propose an improved algorithm. During the unwrapping process, masking, filtering, dipole- remover preprocessor, and the Prim algorithm of the minimum spanning tree were introduced to optimize the residues essential for the Goldstein Brunch-cut algorithm. Experimental results showed that the residues, branch-cuts and continuous unwrapped phase surface were efficiently reduced and the quality of MR phase images was obviously improved with the proposed method.

The present study was aimed at investigating the expression of metastasis-associated in colon cancer 1 (MACC1) in nasopharyngeal carcinoma (NPC), its relationship with β-catenin, Met expression and the clinicopathological features of NPC, and its roles in carcinogenesis of NPC. Our results showed that MACC1 expression was higher in NPC cells and tissues than that in normal nasopharyngeal cells and chronic inflammation of the nasopharynx tissues, respectively. MACC1 expression was closely related to the clinical stage (p = 0.005) and the N classification (p<0.05) of NPC. Significant correlations between MACC1 expression and Met expression (p = 0.003), MACC1 expression and β-catenin abnormal expression (p = 0.033) were found in NPC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in NPC cells compared with the control group. Furthermore, MACC1 down-regulation inhibited phosphorylated-Akt (Ser473) and β-catenin expression in NPC cells, but phosphorylated-Erk1/2 expression was not altered. Further study showed that phosphotidylinsitol-3-kinase inhibitor downregulated β-catenin and Met expression in NPC cells. There was a significant relationship between MACC1 expression and phosphorylated-Akt expression (p = 0.03), β-catenin abnormal expression and phosphorylated-Akt expression (p = 0.012) in NPC tissue, respectively. In addition, Epstein Barr virus-encoded oncogene latent membrane protein 1 upregulated MACC1 expression in NPC cells. Our results firstly suggest that MACC1 plays an important role in carcinogenesis of NPC through Akt/β-catenin signaling pathway. Targeting MACC1 may be a novel therapeutic strategy for NPC.