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Zhi-Jun Shen, Miao Liu, Jun-Xia Zhang, Yu Huang, Ying Kong, Shi-Guo Liu Department of Clinical Laboratory, Hubei Third People´s Hospital Affiliated to Jianghan University, Wuhan, 430033, People’s Republic of ChinaCorrespondence: Shi-Guo Liu, Department of Clinical Laboratory, Hubei Third People´s Hospital Affiliated to Jianghan University, No. 26, Zhongshan Road, Wuhan, Qiaokou District, People’s Republic of China, Email llsgg518@163.comBackground: Although observational studies have reported a correlation between vitamin D deficiency and type 2 diabetes mellitus (T2DM), epidemiological evidence on the risk of obese subjects suffering T2DM due to a vitamin D deficiency is limited. Therefore, we investigated the correlation between T2DM and serum vitamin D, lipids, blood pressure, insulin indexes in an obese population.Methods: A total of 1440 participants including 450 healthy controls and 990 obese subjects, 470 without T2DM and 520 with T2DM. Serum vitamin D levels were measured, and the association between low levels and T2DM in obese subjects was examined using multinomial and linear regression analyses.Results: Of the participants, 35% had deficient or insufficient vitamin D levels (ie, < 20 ng/mL). Compared with healthy controls, obese subjects, particularly those with T2DM had lower vitamin D levels. Multinomial logistic regression analysis showed that obese subjects with T2DM had a gradually increasing risk for desirable (RO = 1.41, 95% CI 1.06– 1.93, P = 0.027), insufficient (RO = 1.83, 95% CI 1.27– 2.84, P < 0.001), or deficient ((RO = 2.14, 95% CI 1.15– 3.75, P = 0.014) vitamin D levels. In obese subjects with T2DM, vitamin D levels correlated inversely with the risk indicators for diabetes, such as the levels of HbA1c (β = − 0.16, P = 0.002), fasting insulin (Fins; β = − 0.31, P = 0.008), and HOMA-IR (β = − 0.19, P < 0.001). In obese subjects without T2DM, vitamin D was associated negatively with the risk of having T2DM at five-year follow-up (relative risk = 0.93, 95% CI 0.79– 0.97, P = 0.037).Conclusion: This study demonstrates that low vitamin D levels correlate with the presence of T2DM in the obese population. This finding indicates that hypovitaminosis D may be a potential biological vulnerability factor for the development of T2DM in obese subjects.Keywords: vitamins, T2DM, obesity, biomarker

Abstract: The purpose of this study was to prepare a fully human anti-VEGF (vascular endothelial growth factor) monoclonal antibody with anti-tumor activity from five-feature mice which express human immunoglobin loci. Four hybridomas secreting mAb stably were isolated successfully. Some characters such as isotypes, cross-reactivity, inhibition on the binding of hVEGF to VEGFR-2, dissociation constants and the idiotypic characteristic were determined. Proliferation of T24 and Ls-174-T cell line and nude mice bearing human colorectal cancer were used to evaluate therapeutic effects and safety of this mAb. Pharmacokinetics data shows the half life of this mAb was about 5 days after a single intravenous injection. These results suggest the fully human anti-VEGF mAb maybe safe and efficient for cancer treatment. [Copyright &y& Elsevier]

Background: The International Classification of Functioning, Disability and Health (ICF) is the worldwide terminology system for measuring health and disability at both individual and population levels. However, the underlying challenges remain in achieving widespread adoption and implementation of ICF within healthcare contexts, including the unequal interval scale of the ICF Likert-type qualifier system ranging from 0 to 4, a lack of consensus on conceptualization and grading criteria of ICF items, and an excessive number of ICF items associated with each disease. The utilization of item response theory (IRT) for ICF studies demonstrated potential benefits in addressing these issues. Here, a review attempted to provide clarification of two predominant needs (sufficiency and efficiency) and two dimensions of scoring principles (stratification and assignment principles) in the ICF., Methods: A literature search was conducted on the PubMed database, and 44 relative articles were selected. On this basis, this review was undertaken to track the research progress of the ICF based on the parameter IRT method, typically the Rasch model., Results: This review outlined the classification of Item response model (IRM) for ICF studies and summarized existing IRT-based ICF research paradigms. Moreover, this review identified blind spots regarding assignment principles and the difficulty parameter in current ICF-based IRT studies. The Mokken scale analysis (MSA), as a non-parametric IRT method, was introduced as a data shaping tool for parametric IRM. The pipeline of the ICF-based MSA-Rasch modeling might advance the understanding of ICF clinical application and shed light on a new paradigm of questionnaire design., Conclusion: The advent of ICF-oriented IRM algorithms may advance the comprehension of ICF clinical application and pave the way for a new paradigm for IRT-derived ICF questionnaires, namely the parsimonious ICF core set. Additionally, the Wright map holds promise in facilitating insight into rehabilitation trajectories and personalizing rehabilitation goals., (© 2025 John Wiley & Sons Ltd.)

Degenerative musculoskeletal diseases are a class of diseases related to the gradual structural and functional deterioration of muscles, joints, and bones, including osteoarthritis (OA), osteoporosis (OP), sarcopenia (SP), and intervertebral disc degeneration (IDD). As the proportion of aging people around the world increases, degenerative musculoskeletal diseases not only have a multifaceted impact on patients, but also impose a huge burden on the medical industry in various countries. Therefore, it is crucial to find key regulatory factors and potential therapeutic targets. Recent studies have shown that irisin plays an important role in degenerative musculoskeletal diseases, suggesting that it may become a key molecule in the prevention and treatment of degenerative diseases of the musculoskeletal system. Therefore, this review provides a comprehensive description of the release and basic functions of irisin, and summarizes the role of irisin in OA, OP, SP, and IDD from a cellular and tissue perspective, providing comprehensive basis for clinical application. In addition, we summarized the many roles of irisin as a key information molecule in bone-muscle-adipose crosstalk and a regulatory molecule involved in inflammation, senescence, and cell death, and proposed the interesting possibility of irisin in degenerative musculoskeletal diseases., Competing Interests: Declaration of Competing Interest All authors confirmed no declarations of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Ratiometric fluorescence detection is endowed with higher accuracy than single fluorescence signal assay. In this work, we construct a ratiometric fluorescence probe for the facile quantification of sulfadimethoxine (SDM) in foods. By wrapping N-doped carbon dots (N-CDs) and gold nanoclusters (AuNCs) into zeolitic imidazolate framework-8 (ZIF-8), the nanocomposite of N-CDs/AuNCs@ZIF-8 is facilely prepared and emits two fluorescence including 475 nm from N-CDs and 650 nm from AuNCs. Since bovine serum albumin (BSA) is the stabilizer of AuNCs, SDM can form a complex with BSA, resulting in the fluorescence quenching of AuNCs at 650 nm by a static quenching mechanism. In contrast, SDM has a rare influence on the fluorescence of N-CDs (475 nm). As a result, the use of the probe of N-CDs/AuNCs@ZIF-8 for SDM detection enables simultaneous measurement of response signal and reference signal. Under the optimal condition, the SDM assay based on the probe has a good linear relationship within 10 to 2 × 10 6  ng/mL and the limit of detection (LOD) is low to 1.064 ng/mL. In addition, the fluorescent probe shows good reliability for the detection of SDM in practical food samples., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Background: Neonatal respiratory distress syndrome (NRDS) is one of the most common diseases in neonatal intensive care units, with an incidence rate of about 7% among infants. Additionally, it is a leading cause of neonatal death in hospitals in China. The main mechanism of the disease is hypoxemia and hypercapnia caused by lack of surfactant., Aim: To explore the effect of pulmonary surfactant (PS) combined with noninvasive positive pressure ventilation on keratin-14 (KRT-14) and endothelin-1 (ET-1) levels in peripheral blood and the effectiveness in treating NRDS., Methods: Altogether 137 neonates with respiratory distress syndrome treated in our hospital from April 2019 to July 2021 were included. Of these, 64 control cases were treated with noninvasive positive pressure ventilation and 73 observation cases were treated with PS combined with noninvasive positive pressure ventilation. The expression of KRT-14 and ET-1 in the two groups was compared. The deaths, complications, and PaO 2 , PaCO 2 , and PaO 2 /FiO 2 blood gas indexes in the two groups were compared. Receiver operating characteristic curve (ROC) analysis was used to determine the diagnostic value of KRT-14 and ET-1 in the treatment of NRDS., Results: The observation group had a significantly higher effectiveness rate than the control group. There was no significant difference between the two groups in terms of neonatal mortality and adverse reactions, such as bronchial dysplasia, cyanosis, and shortness of breath . After treatment, the levels of PaO 2 and PaO 2 /FiO 2 in both groups were significantly higher than before treatment, while the level of PaCO 2 was significantly lower. After treatment, the observation group had significantly higher levels of PaO 2 and PaO 2 /FiO 2 than the control group, while PaCO 2 was notably lower in the observation group. After treatment, the KRT-14 and ET-1 levels in both groups were significantly decreased compared with the pre-treatment levels. The observation group had a reduction of KRT-14 and ET-1 levels than the control group. ROC curve analysis showed that the area under the curve (AUC) of KRT-14 was 0.791, and the AUC of ET-1 was 0.816., Conclusion: Combining PS with noninvasive positive pressure ventilation significantly improved the effectiveness of NRDS therapy. KRT-14 and ET-1 levels may have potential as therapeutic and diagnostic indicators., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied., Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations., Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006)., Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Given the complex etiology, multidimensional impact, and widespread prevalence of low back pain (LBP), it is crucial to prioritize intervention targets based on understanding the relationships between functional impairments in patients. This prioritization maximizes the physical and psychological benefits for patients, and graph modeling holds promise in achieving these objectives., Aim: The aim of this study was establishing a graphical model of functioning variables for LBP based on the International Classification of Functioning, Disability, and Health (ICF) to identify the most influential items (i.e., functioning variables) on the physical and mental well-being of patients. Exploring feasible intervention measures by understanding the dysfunction correlations among these variables., Design: Cross-sectional survey., Setting: Nine hospitals in Jiangsu Province, China., Population: Three hundred and six persons with LBP aged ≥18 years., Methods: All patients were assessed using the Comprehensive ICF Core Sets for LBP. The scoring system was converted to dichotomous data, with 1 indicating dysfunction and 0 indicating no dysfunction. In the graphical model, network parameters and the results of Item Response Theory modeling (as detailed in our other article) were used to determine the importance of items, while partial correlations were utilized to estimate the dysfunction correlations between functioning variables., Results: 1) A total of 56 ICF items were located in the backbone structure of LBP, among which d430 (Lifting and carrying objects) occupied the most central position, followed by b126 (Temperament and personality functions). 2) In the main component of backbone structure, d430 has moderate dysfunction correlation with looking after one's health (0.6027), social norms, practices and ideologies (0.597), stability of joint functions (0.5759), and emotional functions (0.4078). b126 has moderate dysfunction correlation with basic interpersonal interactions (0.6595)., Conclusions: d430 and b126 significantly impact the physical and mental well-being of LBP patients. To improve d430, maintaining exercise habits, reducing working hours, enhancing lumbar stability, and overcoming fear-related emotions are recommended. Similarly, improving b126 can be achieved through enhancing interpersonal relationships., Clinical Rehabilitation Impact: Through the identification of crucial functioning variables and the associated dysfunctional correlation relationships, graphical model of Comprehensive ICF Core Set for LBP can offer healthcare decision-makers valuable insights into potential treatment targets and pathways aimed at improving the condition of LBP patients.

Purpose: To develop a deep learning model to accurately detect anterior cruciate ligament (ACL) ruptures on magnetic resonance imaging (MRI) and to evaluate its effect on the diagnostic accuracy and efficiency of clinicians., Methods: A training dataset was built from MRIs acquired from January 2017 to June 2021, including patients with knee symptoms, irrespective of ACL ruptures. An external validation dataset was built from MRIs acquired from January 2021 to June 2022, including patients who underwent knee arthroscopy or arthroplasty. Patients with fractures or prior knee surgeries were excluded in both datasets. Subsequently, a deep learning model was developed and validated using these datasets. Clinicians of varying expertise levels in sports medicine and radiology were recruited, and their capacities in diagnosing ACL injuries in terms of accuracy and diagnosing time were evaluated both with and without artificial intelligence (AI) assistance., Results: A deep learning model was developed based on the training dataset of 22,767 MRIs from 5 centers and verified with external validation dataset of 4,086 MRIs from 6 centers. The model achieved an area under the receiver operating characteristic curve of 0.987 and a sensitivity and specificity of 95.1%. Thirty-eight clinicians from 25 centers were recruited to diagnose 3,800 MRIs. The AI assistance significantly improved the accuracy of all clinicians, exceeding 96%. Additionally, a notable reduction in diagnostic time was observed. The most significant improvements in accuracy and time efficiency were observed in the trainee groups, suggesting that AI support is particularly beneficial for clinicians with moderately limited diagnostic expertise., Conclusions: This deep learning model demonstrated expert-level diagnostic performance for ACL ruptures, serving as a valuable tool to assist clinicians of various specialties and experience levels in making accurate and efficient diagnoses., Level of Evidence: Level III, retrospective comparative case series., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Dichlorvos (DDVP), as a highly effective insecticide, is widely used in agricultural production. However, DDVP residue in foodstuffs adversely affects human health. Conventional instrumental analysis can provide highly sensitive and accurate detection of DDVP, while the need of bulky and expensive equipment limits their application in resource-poor areas and on-site detection. Therefore, the development of easily portable sensing platforms for convenient, rapid and sensitive quantification of DDVP is very essential for ensuring food safety., Result: A portable colorimetric sensing platform for rapid and sensitive quantification of DDVP is developed based on nanozyme-participated highly efficient chromogenic catalysis. The Fe-Mn bimetallic oxide (FeMnOx) nanozyme possesses excellently oxidase-like activity and can efficiently catalyze oxidation of 3, 3', 5, 5'-tetramethylbenzidine (TMB) into a blue oxide with a very low Michaelis constant (K m ) of 0.0522 mM. The nanozyme-catalyzed chromogenic reaction can be mediated by DDVP via inhibiting the acetylcholinesterase (AChE) activity. Thus, trace DDVP concentration-dependent color evolution is achieved and DDVP can be sensitively detected by spectrophotometry. Furthermore, a smartphone-integrated 3D-printed miniature lightbox is fabricated as the colorimetric signal acquisition and processing device. Based on the FeMnOx nanozyme and smartphone-integrated lightbox system, the portable colorimetric sensing platform of DDVP is obtained and it has a wide linear range from 1 to 3000 ng mL -1 with a low limit of detection (LOD) of 0.267 ng mL -1 for DDVP quantification., Significance: This represents a new portable colorimetric sensing platform that can perform detection of DDVP in foodstuffs with simplicity, sensitivity, and low cost. The work not only offers an alternative to rapid and sensitive detection of DDVP, but also provides a new insight for the development of advanced sensors by the combination of nanozyme, 3D-printing and information technologies., 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.)

As a common raw material of industrial products, bisphenol A (BPA) is widely used in the production of food contact materials, and there is a high risk of exposure in food. However, BPA is a well-known endocrine disruptor and poses a serious threat to human health. Herein, a fluorescent sensing platform of BPA based on enzymatic oxidation-mediated fluorescence quenching of silicon nanoparticles (SiNPs) is established and used to the detection of BPA in food species. The SiNPs are prepared with a facile one-step synthesis and emit bright green fluorescence. BPA can be oxidized by horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ) to form a product which can quench the fluorescence of SiNPs through electron transfer. There is a good linear relationship between the fluorescence intensity and BPA concentration in the range of 1-100 μM. Therefore, a fluorometry of BPA is established with a low limit of detection (LOD) of 0.69 μM. This method has been applied to the determination of BPA in mineral drinking water, orange juice, and milk with satisfactory results. The fluorescent sensor of BPA based on SiNPs has favorable application foreground in the field of food safety analysis., 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 Elsevier B.V. All rights reserved.)

Background and Objectives: Haemophilia comprises a continuum of blood disorders that often include joint and muscular dysfunction, which may lead to a constellation of activity limitations and participation restrictions. However, there is scant research incorporating functional assessment scales into the common language provided by the International Classification of Functioning, Disability and Health (ICF). This study aims to identify the ICF categories to include in an item bank of functioning aspects relevant for haemophilia., Design and Methods: A systematic search was carried out in July 2021 based on the PubMed MEDLINE, CLINICAL, and Cochrane databases for qualified articles, investigating haemophilia-specific scales and the scales recommended by the World Federation of Haemophilia (WFH) linked to ICF categories between 2001 and 2021. Well-trained healthcare professionals in the haemophilia field and ICF evaluation conducted group discussions to determine the ICF items for haemophilia., Results: A total of 112 out of 176 items measuring function were collected for the haemophilia ICF item bank, including 32 items for body function (b), 45 items for activity and participation (d), 27 items for environmental factors (e), and 8 items for body structure(s)., Interpretation and Conclusions: We recommend that future haemophilia research use the haemophilia-specific ICF item bank, which could capture a whole spectrum of functional measurements and facilitate multidisciplinary and worldwide communication. This study also indicates that further development and analysis of the psychometric properties of the 112 haemophilia-related ICF items is warranted.

Background: Despite the growing interest of the item response theory (IRT) in assessment of person abilities and functioning difficulties in screening tools, there is scarcity of research using IRT on ICF-based tools for persons with low back pain (LBP)., Aim: To generate and validate a parsimonious core set of ICF (PCSI) for LBP based on the IRT modelling., Design: A cross-sectional study., Setting: Nine hospitals in Jiangsu Province, China., Population: We recruited patients with LBP., Methods: All participants completed the 78 items of the comprehensive ICF Core Set for LBP. The five-point scoring system was converted to dichotomous data with 1 as functioning/independent and 0 as impairment/dependent. Psychometric properties of the data were examined using Mokken Scale analysis and parametric item response modelling., Results: This study recruited 306 participants (185 females and 121 males) with LBP. The overall median age of the study participants was 50.28 (95% CI 23.34; 82.05) years. We constructed a three-parameter logistic model with 28 ICF categories (8 of body function, 18 of activities and participation, and two of body structures). The internal consistency was good with Cronbach's alpha = 0.927 and latent class reliability coefficient (LCRC) = 0.955. The model was validated by significant correlations (P<0.001) of its estimated person abilities with the Oswestry Disability Index (ODI, r=-0.41), the Roland-Morris Disability Questionnaire (RMDQ, r=-0.57), the Physical Component Summary (PCS, r=0.63), and the Mental Component Summary (MCS, r = 0.46) of 12-Item Short Form Survey (SF-12). The person abilities and item difficulties were integrated into a Wright map that offered a background for making individualized clinical decisions., Conclusions: The PCSI of LBP with 28 categories has good construct validity and internal consistency, and is a convenient instrument for assessing functioning among persons with LBP. The IRT model provided theoretical and algorithmic support for deriving a simplified model for functioning assessment hence serving a basis for formulating rehabilitation plans in clinical practice and research., Clinical Rehabilitation Impact: A parsimonious core set of ICF (PCSI) for LBP based on the IRT modelling provides a background for making individualized clinical decisions based on item difficulties.

Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are associated with various complex human diseases. They can serve as disease biomarkers and hold considerable promise for the prevention and treatment of various diseases. The traditional random walk algorithms generally exclude the effect of non-neighboring nodes on random walking. In order to overcome the issue, the neighborhood constraint (NC) approach is proposed in this study for regulating the direction of the random walk by computing the effects of both neighboring nodes and non-neighboring nodes. Then the association matrix is updated by matrix multiplication for minimizing the effect of the false negative data. The heterogeneous lncRNA-disease network is finally analyzed using an unbalanced random walk method for predicting the potential lncRNA-disease associations. The LUNCRW model is therefore developed for predicting potential lncRNA-disease associations. The area under the curve (AUC) values of the LUNCRW model in leave-one-out cross-validation and five-fold cross-validation were 0.951 and 0.9486 ± 0.0011, respectively. Data from published case studies on three diseases, including squamous cell carcinoma, hepatocellular carcinoma, and renal cell carcinoma, confirmed the predictive potential of the LUNCRW model. Altogether, the findings indicated that the performance of the LUNCRW method is superior to that of existing methods in predicting potential lncRNA-disease associations., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2023. Published by Elsevier Inc.)

Background: Incorporating artificial intelligence (AI) into clinics brings the risk of automation bias, which potentially misleads the clinician's decision-making. The purpose of this study was to propose a potential strategy to mitigate automation bias., Methods: This was a laboratory study with a randomized cross-over design. The diagnosis of anterior cruciate ligament (ACL) rupture, a common injury, on magnetic resonance imaging (MRI) was used as an example. Forty clinicians were invited to diagnose 200 ACLs with and without AI assistance. The AI's correcting and misleading (automation bias) effects on the clinicians' decision-making processes were analyzed. An ordinal logistic regression model was employed to predict the correcting and misleading probabilities of the AI. We further proposed an AI suppression strategy that retracted AI diagnoses with a higher misleading probability and provided AI diagnoses with a higher correcting probability., Results: The AI significantly increased clinicians' accuracy from 87.2%±13.1% to 96.4%±1.9% (P < .001). However, the clinicians' errors in the AI-assisted round were associated with automation bias, accounting for 45.5% of the total mistakes. The automation bias was found to affect clinicians of all levels of expertise. Using a logistic regression model, we identified an AI output zone with higher probability to generate misleading diagnoses. The proposed AI suppression strategy was estimated to decrease clinicians' automation bias by 41.7%., Conclusion: Although AI improved clinicians' diagnostic performance, automation bias was a serious problem that should be addressed in clinical practice. The proposed AI suppression strategy is a practical method for decreasing automation bias., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

One of the highly attractive research directions in the electrochemiluminescence (ECL) field is how to regulate and improve ECL efficiency. Quantum dots (QDs) are highly promising ECL materials due to their adjustable luminescence size and strong luminous efficiency. MoS 2 NSs@QDs, an ECL emitter, is synthesized via hydrothermal methods, and its ECL mechanism is investigated using cyclic voltammetry and ECL-potential curves. Then, a stable and vertical attachment of a triplex DNA (tsDNA) probe to the MoS 2 nanosheets (NSs) is applied to the electrode. Next, an innovative ECL sensor is courageously empoldered for precise and ultrasensitive detection of target miRNA-199a through the agency of ECL-resonance energy transfer (RET) strategy and a dextrous target-initiated catalytic three-arm DNA junction assembly (CTDJA) based on a toehold strand displacement reaction (TSDR) signal amplification approach. Impressively, the ingenious system not only precisely regulates the distance between energy donor-acceptor pairs leave energy less loss and more ECL-RET efficiency, but also simplifies the operational procedure and verifies the feasibility of this self-assembly process without human intervention. This study can expand MoS 2 NSs@QDs utilization in ECL biosensing applications, and the proposed nucleic acid amplification strategy can become a miracle cure for ultrasensitive detecting diverse biomarkers, which helps researchers to better study the tumor mechanism, thereby unambiguously increasing cancer cure rates and reducing the risk of recurrence.

Objective: To investigate the morphology and immunohistochemical (IHC) expression of pseudostratified ependymal tubules in ovarian mature teratoma (MT). Methods: Five cases of ovarian MT with pseudostratified ependymal tubules were collected from Shenzhen Hospital(Futian) of Guangzhou University of Chinese Medicine and the Eighth Affiliated Hospital of Sun Yat-sen University from March 2019 to March 2022. In addition, 15 cases of ovarian MT with monolayer ependymal epithelium from Shenzhen Hospital (Futian) of Guangzhou University of Chinese medicine and seven cases of immature teratoma (IMT) from Hainan Provincial People's Hospital from March 2019 to March 2022 were collected as control. The morphologic characteristics and immunophenotypes of pseudostratified ependymal tubules, monolayer ependymal epithelium, and primitive neural epithelial tubules were observed and compared by H&E stain and IHC expression pattern of genes related to the differentiation status of neuroepithelium, namely SALL4, Glypican3, nestin, SOX2, Foxj1, and Ki-67. Results: Mean age of the five patients of ovarian MT with pseudostratified ependymal tubules was 26 years (range from 19 to 31 years). Two tumors were located in the left ovary and three in the right. All five cases were excised, and clinical follow-up was available (mean follow-up 1.5 years; range 0.5 to 3 years). No recurrence was noted in any cases. The pseudostratified ependymal tubules of ovarian MT, which were lined with columnar or oval epithelia up to 4-6 layers, were morphologically similar to the primitive neuroepithelial tubules of IMT and different from monolayer ependymal epithelium of ovarian MT. By immunohistochemistry, SALL4 and Glypican3 were negative, Foxj1 was positive and Ki-67 index was lower in the pseudostratified ependymal tubules and the monolayer ependymal epithelium of ovarian MT. However, the primitive neuroepithelial tubules of IMT showed variably expression of SALL4 and Glypican3, were negative for Foxj1 and high Ki-67 index. All the above three groups expressed nestin and SOX2. Conclusions: The pseudostratified ependymal tubules of ovarian MT, which have morphological similarities to the primitive neuroepithelial tubules of IMT, are similar to the monolayer ependymal epithelia of the MT in immunophenotype. IHC assessment of Foxj1 and Ki-67 is helpful to differentiate the pseudostratified ependymal tubules of ovarian MT from the primitive neuroepithelial tubules of IMT.

Objectives: CRLF2 alterations are associated with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This study aimed to explore the clinical, biological, and outcome features of pediatric BCP-ALL with CRLF2 abnormalities., Methods: This study enrolled 630 childhood BCP-ALLs treated on CCLG-ALL 2008 or 2018 protocol. P2RY8-CRLF2 was determined by Sanger sequencing and CRLF2 expression was evaluated by qRT-PCR. The correlation between clinical, biological features and outcomes with P2RY8-CRLF2 or CRLF2 over-expression were analyzed., Results: P2RY8-CRLF2 and CRLF2 over-expression were found in 3.33% and 5.71% respectively. P2RY8-CRLF2 was associated with male, higher frequency of CD7 expression, high WBC and MRD before consolidation. CRLF2 over-expression showed ETV6-RUNX1 - , higher frequency of CD22, CD34, CD66c, CD86 expression, hyperdiploidy and high MRD at early treatment. The lower overall survival (OS) was found in patients with P2RY8-CRLF2 and confined only in IR group. Furthermore, adverse event-free survival and OS of P2RY8-CRLF2 were discovered comparing to those without known fusions or treated on CCLG-ALL 2008 protocol. However, P2RY8-CRLF2 was not confirmed as independent prognostic factors and no prognostic impact of CRLF2 over-expression was found., Conclusions: These findings indicate P2RY8-CRLF2 identifies a subset of patients with specific features and adverse outcomes that could be improved by risk-directed treatment., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Severe knee valgus/varus or complex multiplanar deformities are common in clinic. If not corrected in time, cartilage wear will be aggravated and initiate the osteoarthritis due to lower limb malalignment. Internal fixation is unable to correct severe complex deformities, especially when combined with lower limb discrepancy (LLD). Based on the self-designed digital six-axis external fixator Q spatial fixator (QSF), which can correct complex multiplanar deformities without changing structures, accuracy of correction can be improved significantly., Methods: This retrospective study included 24 patients who suffered from complex knee deformity with LLD treated by QSF and internal fixation at our institution from January 2018 to February 2021. All patients had a closing wedge distal femoral osteotomy with internal fixation for immediate correction and high tibia osteotomy with QSF fixation for postoperative progressive correction. Data of correction prescriptions were computed by software from postoperative CT scans., Results: Mean discrepancy length of operative side was 2.39 ± 1.04 cm (range 0.9-4.4 cm) preoperatively. The mean difference of lower limb was 0.32 ± 0.13 cm (range 0.11-0.58 cm) postoperatively. The length of limb correction had significant difference (p < 0.05). The mean MAD and HKA decreased significantly (p < 0.05), and the mean MPTA and LDFA increased significantly (p < 0.05). There were significant increase (p < 0.05) in the AKSS-O, AKSS-F and Tegner Activity Score. The lower limb alignment was corrected (p < 0.05). The mean time of removing external fixator was 112.8 ± 17.9 days (range 83-147 days)., Conclusions: Complex knee deformity with LLD can be treated by six-axis external fixator with internal fixation without total knee arthroplasty. Lower limb malalignment and discrepancy can be corrected precisely and effectively by this approach., (© 2023. The Author(s).)

Due to the extensive use of antibiotics, the resistance of microorganisms to antibiotics in the environment is increasing, and the problem of antibiotic resistance genes (ARGs) is becoming more and more severe, which seriously threatens ecological security and human health. In order to study the distribution characteristics of ARGs and the microbial community in different media in the coastal area of the Yangtze River Estuary, water and sediment samples from eight sites were collected through a field investigation. Two sulfonamide resistance genes ( [STBX]sul1 , sul2[STBZ] ) and six tetracycline resistance genes ( tetM , tetC , tetX , tetA , tetO , and tetQ ), one integrase gene intI[STBX]1[STBZ] , 16S rRNA gene, and the microbial community were detected and analyzed. The results showed that the detection rate of 10 resistance genes in the coastal area of the Yangtze River Estuary was 100%. [STBX]intI1[STBZ] was significantly positively correlated with various ARGs in the water samples. Proteobacteria and Bacteroidota were the dominant bacteria phyla in the water environment of the Yangtze River Estuary. Chloroplast was the main bacteria genus in water, and Chloroplast and Nitrospira were the main bacteria genera in sediment. In water, Nitrospirota was the common potential host of four tetracycline resistance genes ( tetX , tetA , tetO , and tetQ ). In sediments, Sva0485 was a potential host community shared by [STBX]sul1 and intI1[STBZ] . The distribution of the microbial community was an important factor affecting the migration and transformation of ARGs in the nearshore area of the Yangtze River Estuary.

Heteroatom doping was recently regarded as an effective method to tune the band gap and improve the separation and transfer of photogenerated electron-hole pairs in semiconductor photocatalysts. Herein, a novel S,F-codoped Bi 2 WO 6 (S,F-Bi 2 WO 6 ) with suitable oxygen vacancies was synthesized via the hydrothermal-calcination and post-sulfurization, for efficient Cr(VI) reduction and methyl orange (MO) degradation under visible light. The amount of surface oxygen vacancies could be controlled by adjusting the S/F ratio during the doping process, which modulated the band structure and photogenerated charge behavior of Bi 2 WO 6 . The optimal S 0.10 F-Bi 2 WO 6 exhibited an excellent photooxidation-reduction performance, which Cr(VI) reduction and MO degradation efficiencies were 1.6 and 2.6 times than those of the pristine Bi 2 WO 6 without oxygen vacancy under visible-light, respectively. The enhanced photooxidation-reduction performance was because the right amount of oxygen vacancies could effectively narrow the bandgap and improve the separation efficiency of electron-hole pairs. Thus, this work offered a mild and simply approach for preparing heteroatom doped Bi 2 WO 6 and a potential to be extended to the synthesis of other doped materials for environmental remediation., 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 © 2022 Elsevier Inc. All rights reserved.)

Background and Objectives: There is scant research investigating the user-friendly functional assessment tool conceptualized by the International Classification of Functioning, Disability and Health (ICF) among persons with haemophilia (PWH). This study aims to accomplish two goals: (1) quantifying comprehensive functioning measures of haemophilia through Item Response Theory (IRT); (2) discussing patient-centred care based on the Wright map of personal ability and item difficulty., Methods: A cross-sectional study was carried out in 70 PWH (mean age, 33.09 ± 11.04) via convenience sampling. All patients completed the 45 ICF categories of haemophilic-specific activity and participation. Psychometric properties of the categories were examined using Mokken scale analysis and parametric item response modelling., Results: We extracted a unidimensional scale with 31 categories, and constructed a Rasch model with good fitness. The Cronbach's α of the scale was .9713, with the Guttman's λ 2  = .9730, Molenaar Sijtsma ρ = .9802, and latent class reliability coefficient = .9769, indicating great internal reliability. The estimated individual social competence by the Rasch model was highly related to the index score of the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) (p < .001, r = .62), and had a moderate correlation (p < .001, r = .54) with the score of Haemophilia Activities List (HAL)., Conclusions: The ICF scale of haemophilic activity and participation with 31 categories (HAPPY-ICF) has good construct validity and internal consistency. The person-item threshold distribution map might be helpful in research and clinical practices for patient-oriented care., (© 2022 John Wiley & Sons Ltd.)

The oral toilet cleaners poisoning can result in devastating gastrointestinal tract injuries with the risk of perforation and/or hemorrhage, and sometimes potentially fatal systemic complications and sequelas. It should be given positive treatment. In this paper, six cases of acute toilet cleaners poisoning were analyzed, and the clinical characteristics and treatment effect were summarized, so as to improve the understanding, diagnosis and treatment level of the disease.

Dual-mode sensing with a two-signal read-out is conducive to the improvement of detection accuracy. Herein, a fluorescent and scattering dual-mode chemosensor for tetracycline (TC) is proposed based on a carbon dot@cerium-guanosine monophosphate (CD@GMP-Ce) coordination polymer network. The inexpensive CD@GMP-Ce was prepared by exploiting the adaptive inclusion capability of coordination polymers and possessed remarkable fluorescence and strong Rayleigh scattering. The functional CD@GMP-Ce demonstrated fluorescence and scattering, the two optical-signal responses to TC simultaneously. Based on TC-specific fluorescence and scattering decline, the dual-mode detection of TC was established and the probe's detection limits were 43 nM in the fluorescence mode and 77 nM in the scattering mode, respectively. Furthermore, the potential application of the dual-mode sensor was verified by measuring TC in milk and tap-water samples. The study not only provides a new perspective for the development of assay methods for TC but also expands the applications of cerium coordination polymers.

Aim: To evaluate the association between SLCO1B1 polymorphisms and elimination/toxicities of high-dose methotrexate (MTX). Methods: SLCO1B1 rs11045879 and rs4149056 polymorphisms were retrospectively genotyped in 301 children with newly diagnosed acute lymphoblastic leukemia. MTX concentration, doses of leucovorin rescue and toxicities were recorded. Results: SLCO1B1 rs11045879C carriers (CC + CT) had higher plasma MTX levels at 96 hr, and longer MTX elimination time. The number of leucovorin rescue doses in rs4149056C carriers (CC + CT) was more than those in TT ones. Moreover, SLCO1B1 polymorphisms were associated with HDMTX toxicities including thrombocytopenia, renal toxicity and anal mucositis, but not associated with MTX level at other time points or delayed elimination. Conclusions: Our data demonstrate that genotyping of SLCO1B1 might be useful to optimize MTX therapy.

Objective: To establish a rat model for laryngeal precancerous lesions histologically and pathologically comparable to the human counterpart. Methods: Thirty-six Wistar rats were randomly divided into experimental group and control group, with 18 rats in each group, and 1% 4-nitroquinoline-1-oxide (4NQO) solution and saline were respectively applied to the laryngeal mucosas of rats in two groups. During subsequent 20 weeks, the changes of laryngeal mucosas were regularly observed with naked eyes and endoscope and lesions were determined by histology. SPSS 22.0 software was used for statistical analysis. Results: The food intake, water intake and body weight of the rats in the experimental group were lower than those in the control group, with statistically significant differences (all P< 0.05). White plaque, superficial ulcer, erosion and miliary particles were present in the larynxes of rats in the experimental group, with histological manifestations of atypical hyperplasia or carcinoma in situ, and normal epitheliums were shown in the control group. The number of Ki67 positive cells in the laryngeal mucosas of rats in the experimental group at the 4 th, 8 th, 12 th, 16 th, and 20 th weeks were 13.5±2.4, 35.6±5.8, 53.4±8.3, 78.8±11.6, 80.6±12.4, respectively, no Ki67 positive cells were found in the control group at individual time points, and the differences were statistically significant ( t =9.74, 10.63, 11.14, 11.77, 11.26, respectively, all P <0.01). Conclusion: 4NQO can credibly cause rats laryngeal precancerous lesions, which morphologically and histologically mimic laryngeal carcinnogenesis. This method is practical, easy and reliable to prepare the animal model of laryngeal precancerous lesions.

Numerous epidemiological studies have shown a close relationship between outdoor air pollution and increased risks for cancer, infection, and cardiopulmonary diseases. However, very few studies have investigated the potential health effects of coexposure to airborne particulate matter (PM) and bioaerosols through the transmission of infectious agents, particularly under the current circumstances of the coronavirus disease 2019 pandemic. In this study, we aimed to identify urinary metabolite biomarkers that might serve as clinically predictive or diagnostic standards for relevant diseases in a real-time manner. We performed an unbiased gas/liquid chromatography-mass spectroscopy (GC/LC-MS) approach to detect urinary metabolites in 92 samples from young healthy individuals collected at three different time points after exposure to clean air, polluted ambient, or purified air, as well as two additional time points after air repollution or repurification. Subsequently, we compared the metabolomic profiles between the two time points using an integrated analysis, along with Kyoto Encyclopedia of Genes and Genomes-enriched pathway and time-series analysis. We identified 33 and 155 differential metabolites (DMs) associated with PM and bioaerosol exposure using GC/LC-MS and follow-up analyses, respectively. Our findings suggest that 16-dehydroprogesterone and 4-hydroxyphenylethanol in urine samples may serve as potential biomarkers to predict or diagnose PM- or bioaerosol-related diseases, respectively. The results indicated apparent differences between PM- and bioaerosol-associated DMs at five different time points and revealed dynamic alterations in the urinary metabolic profiles of young healthy humans with cyclic exposure to clean and polluted air environments. Our findings will help in investigating the detrimental health effects of short-term coexposure to airborne PM and bioaerosols in a real-time manner and improve clinically predictive or diagnostic strategies for preventing air pollution-related diseases., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

NOTCH1 / FBXW7 mutation is common in T-cell acute lymphoblastic leukemia (T-ALL), but controversy looms on its prognostic significance. We screened 98 pediatric T-ALL patients treated on minimal residual disease (MRD) risk-directed CCLG-ALL 2008 protocol. NOTCH1 / FBXW7 mutations were analyzed by Sanger sequencing, and MRD was evaluated by flow cytometry. In overall, 51.02 and 8.75% of patients harbored NOTCH1 and FBXW7 mutations respectively. More favorable 10-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were seen in NOTCH1 mut patients ( NOTCH1 mut vs. NOTCH1 wt , OS, 82.7 ± 5.6% vs. 62.4 ± 7.4%, p  = .020; EFS, 80.9 ± 5.8 vs. 48.4 ± 7.8%, p  = .001; DFS, 82.9 ± 5.6 vs. 52.9 ± 7.7%, p  = .001). NOTCH1 gene status and MRD post-induction were identified as independent prognostic factors. A combination of NOTCH1 gene status and MRD could distinguish patients with NOTCH1 mutations and MRD < 1 × 10 -4 with 100% OS, EFS, and DFS. These results indicated NOTCH1 mutation predicted a favorable outcome in pediatric T-ALL and may be considered a risk stratification factor.

Objective: To compare the immunogenicity of three kinds immunization programs with poliovirus vaccine. Methods: Healthy infants aged 2 months or over were selected and divided into three groups by complete randomization method. Basic immunization with Sabin inactivated poliovirus vaccine(sIPV) and bivalent oral poliovirus vaccine(bOPV) were completed. Three kinds of basic immunization procedures were 1sIPV+2bOPV,2sIPV+1bOPV and 3sIPV, respectively.Two qualified serums that before basic immunization and 28-42 days later were collected, and measured the poliovirus neutralizing antibody with microcell neutralization method. To compare the difference by analysis of variance, rank test and χ 2 test. Results: After the basic immunization, 205 subjects of the positive conversion rate of poliovirus neutralizing antibodies of types Ⅰ, Ⅱ and Ⅲwere all higher than 97.00%, and the positive rates were all higher than 98.00%, the geometric mean titer (GMT) of neutralizing antibody was significantly higher than that before basic immunization in three groups.There were significant differences in the positive rate and GMT before and after basic immunization of typeⅠ, Ⅱand Ⅲ in the three ( P <0.05). The highest GMT in three groups after basic immunization were all typeⅠ, followed by type Ⅲ, and the lowest in type Ⅱ. The GMT of type Ⅱin 2sIPV+1bOPV and 3sIPV groups were both higher than that in sIPV+2bOPV group. Conclution: After three kinds of basic immunization, the poliovirus neutralizing antibodies of serum were all at high levels in three groups, which could form an effective immune barrier against poliovirus. The immunogenicity of three kinds of basic immunization programs were all well, but there were certain differences of neutralizing antibodies among three kinds basic immunization programs. The immunogenicity in 2sIPV+1bOPV and 3sIPV groups against typeⅡpoliovirus were better than that in 1sIPV+2bOPV group.

Background: This study aimed to better understand the prognostic effect of multiple genetic markers and identify more subpopulations at ultra high risk of poor outcome in bone marrow (BM) metastatic neuroblastoma (NB)., Methods: We screened the MYCN, 1p36 and 11q23 loss of heterozygosity (LOH) statuses of 154 patients by interphase fluorescence in situ hybridization of BM cells. The clinical characteristics of patients with the three markers and their associations with prognosis were analysed., Results: MYCN amplification and LOH at 1p36 and 11q23 were identified in 16.2%, 33.1% and 30.5% of patients, respectively. There were strong associations between MYCN amplification and 1p36 LOH as well as 11q23 LOH. Both MYCN amplification and 1p36 LOH were strongly associated with high levels of lactate dehydrogenase (LDH) and neuron-specific enolase, more than 3 metastatic organs, and more events. 11q23 LOH occurred mainly in patients older than 18 months, and those who had high LDH levels. In univariate analysis, patients with MYCN amplification had poorer prognosis than those without. Patients with 1p36 LOH had a 3-year event-free survival (EFS) and overall survival lower than those without. 11q23 LOH was associated with poorer EFS only for patients without MYCN amplification. In a multivariate model, MYCN amplification was independently associated with decreased EFS in all cohorts. 11q23 LOH was an independent prognostic factor for patients without MYCN amplification, whereas 1p36 LOH was not an independent marker regardless of MYCN amplification. Compared with all cohorts, patients with both MYCN amplification and 1p36 LOH had the worst outcome and clinical features., Conclusions: Patients with both MYCN amplification and 1p36LOH had the worst survival rate, indicating an ultra high-risk group. Our results may be applied in clinical practice for accurate risk stratification in future studies., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Ten new triterpenoids, including nine 9,10- seco -cycloartanes ( 1 - 9 ) and one 9,19-cyclolanostane ( 10 ), as well as one sesquiterpenoid ( 11 ) and four known compounds ( 12 - 15 ), were extracted and purified from the whole plant of the Chinese liverwort Lepidozia reptans . Multiple techniques (NMR, HRESIMS, IR, and X-ray crystallographic analysis) were applied to determine the structures of the isolated compounds. Bioassay determinations showed that compound 7 , which contains an α,β-unsaturated carbonyl moiety in its structure, inhibited the growth of a panel of cancer cell lines with IC 50 values ranging from 4.2 ± 0.2 to 5.7 ± 0.5 μM. Further investigation revealed that compound 7 induces PC-3 cell death via mitochondrial-related apoptosis.

Paratuberculosis a contagious and chronic disease in domestic and wild ruminants, is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Typical clinical signs include intractable diarrhea, progressive emaciation, proliferative enteropathy, and mesenteric lymphadenitis. Paratuberculosis is endemic to many parts of the world and responsible for considerable economic losses. In this study, different types of paratuberculosis and MAP in sheep and goats were investigated in Inner Mongolia, a northern province in China contiguous with two countries and eight other provinces. A total of 4434 serum samples were collected from six cities in the western, central, and eastern regions of Inner Mongolia and analyzed using the ELISA test. In addition, tissue samples were collected from seven animals that were suspected to be infected with MAP. Finally, these tissues samples were analyzed by histopathological examination followed by polymerase chain reaction (PCR), IS1311 PCR-restriction enzyme analysis (PCR-REA), and a sequence analysis of five genes. Among all 4434 ruminant serum samples collected from the six cities in the western, central, and eastern regions of Inner Mongolia, 7.60% (337/4434) measured positive for the MAP antibody. The proportions of positive MAP antibody results for serum samples collected in the western, central, and eastern regions were 5.10% (105/2058), 6.63% (85/1282), and 13.44% (147/1094), respectively. For the seven suspected infected animals selected from the herd with the highest rate of positivity, the gross pathology and histopathology of the necropsied animals were found to be consistent with the pathological features of paratuberculosis. The PCR analysis further confirmed the diagnosis of paratuberculosis. The rest of the results demonstrated that herds of sheep and goats in Inner Mongolia were infected with both MAP type II and type III. To the best of our knowledge, this is the first study of the two subtypes of MAP strains in sheep and goats in Inner Mongolia., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate the effect of AMD3100 treatment to cholangiocarcinoma by analyzing the relationship between them, and provide experimental evidence for whether AMD3100 can become a clinical treatment drug for cholangiocarcinoma., Materials and Methods: Cholangiocarcinoma RBE cell lines were used in this study. MTT cell proliferation test was used for evaluating the effect of gemcitabine and AMD3100 to cell. CXCR4, N-cadherin, VEGF-C and MMP-9 were detect by RT-PCR and western. Transwell was used for evaluating the invasion effect., Results: We demonstrated that as the concentration of gemcitabine increasing from 0.33, 3.33 to 33.33 uM, the cell survival rate was 76.65%, 71.40%, 52.25%, respectively. RT-PCR and Western blot that gemcitabine could affect the expression of CXCR4 protein and the level of mRNA transcription in a dose-dependent manner. N-cadherin VEGF-C, MMP-9 mRNA transcription level showed a significant upward trend in gemcitabine group. In Transwell test, the number of cells in the gemcitabine group was significantly higher than that in the no-medication group ( p  < .05), the AMD3100 group and the combination group of gemcitabine and AMD3100, the difference between the no-medication group and the AMD3100 monotherapy group was not significant, and the combination group was between them., Conclusions: This study showed that gemcitabine significantly inhibited the growth of cholangiocarcinoma RBE cells in a dose-dependent manner, and gemcitabine can affect the expression of CXCR4, N-cadherin, VEGF-C, MMP-9 protein and mRNA. Cell invasion and metastasis-related factors decreased after AMD3100 combined with gemcitabine.

Objective: To investigate the differential expression of long non-coding RNA (lncRNA) in placental tissues of women with preeclampsia (PE) and the effect of MIR210HG on the biological function of HTR8/SVneo cells. Methods: A total of 39 cases of PE women (PE group) and 39 cases of normal pregnant women (CTL group) admitted to the Affiliated Hospital of Qingdao University from July 2018 to July 2019 were collected. (1) Transcriptome sequencing (RNA-seq) was used to analyze the differentially expressed lncRNAs in the placental tissues of the two groups. (2) The expression level of MIR210HG, one of the differentially expressed lncRNAs, in the placental tissues of the two groups was detected by real-time quantitative PCR. And the correlations between the expression level of MIR210HG and systolic blood pressure, diastolic blood pressure and neonatal birth weight were analyzed. (3) The constructed small interfering RNA and negative control (NC) RNA were transfected into the HTR8/SVneo cells. The cells were divided into MIR210HG knockdown (KD) group and NC group. The effects of living cell counting (CCK-8) and transwell assay on the proliferation and migration of HTR8/SVneo cells were detected. (4) RNA interacting with MIR210HG was predicted using the Encyclopedia of RNA Interactomes (ENCORI) database. Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Gene and Genomes (KEGG) and BioCarta pathway enrichment analysis were performed. Results: (1) A total of 26 significantly differentially expressed lncRNAs were found by RNA-seq, among which 21 lncRNAs were up-regulated and 5 lncRNAs were down-regulated. (2) The relative expression level of MIR210HG in the PE group was significantly higher than that in the CTL group (9.30±1.90 and 1.10±0.20, respectively; t =4.425, P <0.01). The relative expression level of MIR210HG had positive linear correlation with systolic blood pressure ( r 2 =0.234, P <0.05) and diastolic blood pressure ( r 2 =0.190, P <0.05), but had a negative linear correlation with newborn birth weight ( r 2 =0.157, P <0.05). (3) Compared with the NC group, the proliferation and migration ability of HTR8/SVneo cells in the KD group were increased (all P <0.05). (4) A total of 38 RNAs that might interact with MIR210HG were predicted by ENCORI database. GO functional annotation analysis showed that MIR210HG might be involved in the functions of 27 pathways, including the regulation of production of molecular mediator of immune response, etc; KEGG pathway analysis showed that MIR210HG might be involved in the function of 8 pathways including allograft rejection, etc; Biocarta pathway analysis showed that MIR210HG may be involved in the functions of 8 pathways, including the eukaryotic initiation factor (eIF) pathway, etc. Conclusion: The expression of MIR210HG is up-regulated in the placental tissue of PE women, and MIR210HG might be a regulator of the biological behavior of trophoblast cells.

Five diverse 1D supramolecular chains, {[4-pmntd]} n (1), {H 2 [4-pmntd]•2Br - } n (2), {H 2 [4-pmntd]•2NO 3 - } n (3), {H 2 [4-pmntd]•2ClO 4 - } n (4), {H 2 [4-pmntd]•2BF 4 - } n (5), (where 4-pmntd was N,N'-bis (4-pyridylmethyl)naphthalene diimide) were synthesized and characterized by X-ray single-crystal structure analysis, IR spectroscopy, elemental analyses, thermogravimetric analyses, fluorescence detection. The anions effect construction of their 1D chain structural diversity through different π interactions. Compound 1 through the adjacent pyridine rings parallel π∙∙∙π interactions formed 1D linear chain structure. Compound 2 through Br - anion∙∙∙π interactions and halogenbond interactions formed 1D zigzag chain structure. Compound 3 through lone pair∙∙∙π interactions of naphthalene diimide and the adjacent carboxyl group formed 1D stairway chain structure. Compound 4 through ClO 4 - anion∙∙∙π interactions formed 1D ribbon chain structure. Compound 5 through parallel π∙∙∙π interactions of the adjacent naphthalene diimide planes and pyridine rings formed 1D ladder chain structure. The five compounds' fluorescence properties and thermal stabilities were investigated. The compound 2 solution could fluorescence detection for iodide anion via fluorescence quenching., 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 © 2021 Elsevier B.V. All rights reserved.)

Oral lichen planus (OLP), defined as a potential for malignant transformation, is a chronic inflammatory disease in which abnormal angiogenesis serves a role in the malignant changes of the disease. OLP-associated fibroblasts (OLP-MFs), derived from the stroma of OLP tissues, are characterized by the presence of myofibroblasts and contribute to the secretion of pro-inflammatory cytokines, which may be involved in the molecular pathogenesis of OLP. However, the associated mechanisms of angiogenesis in OLP remain unknown. The present study aimed to verify the expression of intercellular adhesion molecular 1, vascular cell adhesion molecule 1, VEGF and CD34 in OLP, and to investigate whether IL-6 secreted by OLP-MFs promoted OLP angiogenesis and the effect of its corresponding antibody inhibition. The results of the experiments demonstrated that inflammation was present and OLP upregulated the secretion of IL-6 by OLP stromal fibroblasts, thereby enhancing OLP angiogenesis. Anti-IL-6 receptor antibody inhibited OLP-stroma IL-6 signaling and suppressed OLP angiogenesis. The antibody inhibited the inflammatory response by inhibiting the secretion of inflammatory factors, including IL-6, to suppress angiogenesis and reduce disease progression, thus indicating that this could be a potential target to develop a treatment for OLP., (Copyright: © Xu et al.)

Gallbladder carcinoma (GBC) is one of the most common fatal biliary tract tumors in the world. Its 3-year survival rate is 30% and the recurrence rate remains very high. miR-365 was downregulated in numerous tumors and worked as tumor suppressor gene. However, the role of miR-365 in GBC was unclear. In this study, our results found that the expression of miR-365 in GBC tissues was reduced rather than that in non-cancerous tissues. miR-365 overexpression inhibited the proliferation, metastasis and expansion of GBC CSCs. Mechanically, bioinformatic and luciferase reporter analysis identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as a direct target of miR-365. Overexpression of miR-365 in GBC cells reduced the RAC1 mRNA and protein expression. The special RAC1 inhibitor EHop-106 abolished the discrepancy of growth, metastasis and self-renewal ability between miR-365-overexpression GBC cells and their control cells, which further demonstrated that RAC1 was involved in miR-365-disrupted GBC cells growth, metastasis and self-renewal. More importantly, reduced expression of miR-365 was a predictor of poor prognosis of GBC patients. In conclusion, miR-365 inhibited GBC cell growth, metastasis and self-renewal capacity by directly targeting RAC1, and may therefore prove to be a novel prognosis biomarker for GBC patients.

• Smart usage of single molecule photobleaching technology and dual-color fluorescence colocalization is of critical importance for exploiting the sensing platform. Here, we provide the detailed protocols related to the article "A split aptamer sensing platform for highly sensitive detection of theophylline based on dual-color fluorescence colocalization and single molecule photobleaching" (published online by Biosensors and Bioelectronics) (Liu et al., 2020). The protocols contain: (1) how to clean the slides; (2) how to prepare the probe and detection sample; (3) Single molecule imaging; 4) Data processing by using the Image J. Finally, we used a simple model to confirm the feasibility of the method for integrating dual-color fluorescence colocalization and single molecule photobleaching technology on the theophylline sensing platform. • A simple, ultrasensitive method for the detection of theophylline. • The method is easily comprehensible. • Both strategy formulation and data processing are simple, learnability, and highly reproducible., 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., (© 2020 The Authors. Published by Elsevier B.V.)

Objective: To explore the feasibility of fast and accurate osteotomy using a new angle adjustable osteotomy guide (AAOG) in closing wedge distal femoral osteotomy(CWDFO). Methods: The clinical data of 14 patients (17 knees) with valgus knee treated with CWDFO at Department of Integrated Chinese and Western Medicine Orthopedics, Honghui Hospital, Xi'an Jiaotong University from January 2018 to July 2019 were analyzed retrospectively. There were 3 males and 11 females, aging (41.4±16.4) years (range: 18 to 56 years). The body mass index was (23.5±3.5) kg/m(2) (range: 18.1 to 28.9 kg/m(2)). The guide pins were placed with the assistance of the self-designed AAOG. Before the surgery, Solidworks software was used to calculate the correction angle and the osteotomy radius accurately. The osteotomy guide was adjusted according to these two parameters. During the surgery, the adjusted osteotomy guide was placed to the surface of bone closely and the guide pins were drilled into the bone through the guide holes. The position of the guide pins was confirmed under fluoroscopy. The osteotomy was finished under guide of pins and fixed with Tomofix plate (Synthes). The times and duration of placement of the guide pins, the times of X-ray examination, the planned and actual thickness of the osteotomy wedge, the top and bottom area of the osteotomy wedge, the posterior distal femoral angle(PDFA), the correction of the weight line, and the American Knee Society Score(AKSS) and Tegner scores were collected and compared by paired t test or Kruskal-Wallis non-parametric test. Healing time after osteotomy and complications were recorded. Results: The guide pins were successfully placed once in 10 knees, adjusted once in 5 knees and twice in 2 knees. The time spent in placing all the 6 pins was 82.4 seconds (range: 51 to 125 seconds), and the times of X-ray examination was 1.5 times (range: 1 to 5 times). The top and bottom areas of the osteotomy wedge were (5.52±0.52)cm(2) and (5.36±0.49)cm(2). PDFA was (85.2±2.6)° preoperatively and (85.5±1.4)° postoperatively ( t=- 0.401, P> 0.05). The thickness of the osteotomy was (11.3±1.9)mm according to the preoperative plan, and the actual thickness was (8.1±1.7)mm. All the patients were followed up for 6 months after surgery and AKSS and Tegner scores improved significantly (all P< 0.05). The correction of the weight lines was within the ideal range. Fractures of the hinge point occurred in 3 knees. All of the osseous healing without complications. Conclusion: The new osteotomy guide helps to place the guide pins rapidly and precisely according to the preoperative planning, which should be widely used in clinical applications with promising outcomes.

The present study aimed to investigate the expression of cyclin-dependent kinase 6 (CDK6) and microRNA-126-5p (miR-126-5p) in esophageal cancer tissues and cells, and their effect on esophageal cancer cell proliferation and invasion, and to explore the potential molecular mechanisms. The relative expression levels of CDK6 and miR-126-5p in esophageal cancer tissue, paracancerous tissue, and HEEC and EC109 cells were determined and compared using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A miR-126-5p overexpression vector was constructed and a stable EC109 cell line expressing miR-126-5p was established. The EC109 cell line was transfected with a CDK6 small interfering RNA sequence. The rate of cell proliferation was determined using the WST-8 method, and cell invasion was determined using a Transwell assay. In addition, the relative expression levels of genes were determined using RT-qPCR; the relative expression levels of proteins were determined by western blot analysis; the binding sites of CDK6 and miR-126-5p were analyzed using TargetScan software; and the interaction of CDK6 and miR-126-5p was verified using dual-fluorescence reporter gene expression. Esophageal tissues and EC109 cells expressed higher levels of CDK6 but significantly lower levels of miR-126-5p compared with adjacent tissues and HEEC cells, and their correlation coefficient between esophageal tissues and matched adjacent tissues was -7.526. The overexpression of miR-126-5p and CDK6 knockdown in the EC109 cell line inhibited cell proliferation and invasion compared with the control and NC (negative control) groups. miR-126-5p overexpression reduced the relative expression level of CDK6, and CDK6 knockdown by siRNA increased the expression of miR-126-5p. miR-126-5p regulated CDK6 expression by binding to the 3'-untranslated region of its mRNA. Overexpression miR-126-5p inhibited the proliferation and migration of esophageal cancer cells by targeting CDK6 and negatively regulating its expression. These findings contribute to the understanding of the underlying molecular mechanism of esophageal cancer., (© 2020 American Association for Anatomy.)

CtBP is a known corepressor abundantly expressed in cancer and regulates genes involved in cancer initiation, progression, and metastasis. This study aimed to investigate the prognostic significance of CTBP2 expression in a cohort of pediatric patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL). It further evaluated the role of combined CTBP2 and CASP8AP2 expression in risk of relapse of BCP-ALL. The expression of CTBP2 mRNA was retrospectively detected by a qRT-PCR approach in bone marrow samples from 104 children with newly diagnosed BCP-ALL. CASP8AP2 was assessed simultaneously in the 100 patients included in this study. The receiver operating characteristic (ROC) curve analysis determined the cut off levels for CTBP2 and CASP8AP2 expression with good predictive significance for relapse of BCP-ALL. Patients with low CTBP2 expression had inferior relapse-free survival (RFS) and event-free survival (EFS) when compared to patients with high- CTBP2 expression. The expression level of CTBP2 was significantly associated with CASP8AP2 expression ( r  = 0.449, P  < 0.001). Patients were stratified into three groups according to the combined evaluation of the two gene expression, and patients with simultaneous low-expression had the worst outcome (6-year RFS: 64.6%±12.8%, P  < 0.001). Multivariate analysis demonstrated the expression of CTBP2 and CASP8AP2 , minimal residual disease (MRD) at day 33 remained as independent prognostic factors for RFS. Based on the final Cox hazards model, we proposed an algorithm to calculate the risk index, which was more precise for predicting relapse. In conclusion, low expression of CTBP2 and CASP8AP2 correlated with poor outcome and predicted risk of relapse in pediatric BCP-ALL.

A new split aptamer sensing platform is developed for highly sensitive and selective detection of theophylline based on single molecule photobleaching (SMPB) technique. The sensing system contains two probes. One is formed by one streptavidin and four biotinylated RNA fragments labelled with fluorescein isothiocyanate (FITC). Each biotinylated RNA fragment contains two repeating aptamer fragments. The other probe is the complementary aptamer fragment labelled with Cy5 dye. The existence of theophylline can trigger the first probe to bind as many as eight Cy5-labelled probes. The average combined number depends on the theophylline concentration and can be measured by SMPB technique. In the sensing system, the dual-color fluorescence colocalization is performed by the red fluorophore (Cy5) and green fluorophore (FITC), in which the red fluorophore is utilized for quantitative counting of photobleaching steps, while the green fluorophore serves as a counting reference to increase detection efficiency. On basis of the principle, an ultra-sensitive sensing platform of theophylline is created with a low limit of detection (LOD) of 0.092 nM. This work provides not only a highly sensitive method for theophylline detection but also a novel perspective for the applications of SMPB technology to construct biosensors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Development of selective and sensitive methods for on-site assay of tetracycline (TC) is of great significance for public health and food safety. Herein, a valid ratiometric fluorescence strategy using g-C 3 N 4 nanosheets coupled with Eu 3+ is designed for the assay of TC. In this strategy, both Eu 3+ and g-C 3 N 4 nanosheets serve as the recognition units of TC. The blue fluorescence of g-C 3 N 4 nanosheets can be quenched by TC via the inner filter effect (IFE); meanwhile, the red fluorescence of Eu 3+ can be enhanced by TC through the antenna effect (AE). The synergistic effect of AE and IFE caused by TC makes the developed ratiometric fluorescent sensor display a wide linear range for TC from 0.25 to 80 μM with a detection limit of 6.5 nM and a significant fluorescence color evolution from blue to red. Given its simplicity, free-label, excellent selectivity, high sensitivity, and recognizable color change, point-of-care testing systems, including smartphones and test paper-based assays, are developed for the visual sensing of TC. The integration of smartphones and test paper on a ratiometric fluorescent sensor greatly reduces the detection cost and time, providing a promising method for the qualitative discernment and semi-quantitative assay of TC on-site. Moreover, the potential application of the approach is also verified by detecting TC in milk.

Low expression levels of CREB‑binding protein (CREBBP) have been demonstrated to be associated with high minimal residual disease at the end of induction therapy and adverse long‑term outcomes in pediatric patients with acute lymphoblastic leukemia (ALL). However, the effect of low CREBBP expression on the prognosis of ALL has not yet been investigated. In the present study, CREBBP was downregulated and overexpressed in ALL cell lines (Jurkat and Reh). Sensitivity to chemotherapy and cell proliferation activity was determined via a Cell Counting Kit‑8 assay. Cell cycle analysis was performed using flow cytometry. Immunofluorescence confocal microscopy and co‑immunoprecipitation (Co‑IP) assays were performed to determine the interaction between CREBBP and E2F transcription factor 3a (E2F3a). The binding of CREBBP to downstream gene caspase 8 associated protein 2 (CASP8AP2) promoters was assessed using a chromatin immunoprecipitation assay, and mRNA expression levels were detected via reverse transcription‑quantitative PCR. Western blot analysis was performed to detect protein expression of CREBBP, E2F3a and CASP8AP2. Downregulation of CREBBP increased the IC50 value of daunorubicin; however, no significant affects were observed on the IC50 values of vincristine and L‑asparaginase. Furthermore, downregulation of CREBBP notably inhibited leukemia cell proliferation, accumulated cells in the G0/G1 phase and decreased cell proportions in the S and G2/M phases. Co‑IP analysis demonstrated that CREBBP interacted with E2F3a, a transcription factor involved in G1/S transition. Immunofluorescence confocal microscopy indicated co‑localization of CREBBP and E2F3a at the cell nucleus. Furthermore, E2F3a protein expression decreased in CREBBP RNA interference treated Jurkat and Reh cells. CASP8AP2, a target gene of E2F3a, was also identified to be a downstream gene of CREBBP. In addition, decreased IC50 value and cell proportions in the G0/G1 phase, accelerated cell proliferation and upregulated E2F3a and CASP8AP2 expression were exhibited in CREBBP overexpressed cells. Taken together, the results of the present study suggested that CREBBP downregulation affects proliferation and cell cycle progression in leukemia cells, potentially via the interaction and regulation of E2F3a, resulting in chemotherapy resistance. Thus, targeting CREBBP may be a therapeutic strategy for treating pediatric patients with ALL.

Ascorbic acid (AA) is an important diet-derived antioxidant to human body. Thus, efficient and accurate detection of AA is of considerable significance in food analysis. Herein, smartphone assisted colorimetric and fluorescent triple-channel signal sensor has been developed for AA monitoring based on oxidase-like CoOOH nanoflakes. CoOOH nanoflakes can efficiently catalyze the oxidation of p-phenylenediamine (p-PD) into reddish brown p-PDox. The carbon dots (C-dots) are further introduced, of which the fluorescence can be quenched by p-PDox. However, in the presence of AA, the CoOOH nanoflakes is reduced and thus collapsed. As a result, the oxidation of p-PD is restrained, and thus the fluorescence of C-dots keeps strong. Based on AA induced light color, low absorbance, and strong fluorescence, triple-channel signal sensor has been proposed for AA determination. The AA assay shows a dynamic response range from 0.5 to 10 μM with a detection limit of 0.09 μM. The method assay allows detection of AA in real samples such as fruit juices. Combination with portable smartphone, the developed sensor is potential for AA determination in resource-poor settings., 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 © 2020 Elsevier B.V. All rights reserved.)