Search

To study the representative dose coefficients near nuclear facilities in the arid regions of Northwest China, a simplified anatomical model of Sphingonotus insects using computed tomography (CT) scanning is proposed. In addition, a voxel model created by using Photoshop and Python is used to assess the results of the simplified anatomical model. The dose coefficients of internal and external 90Sr and 137Cs irradiation on different organs of Sphingonotus insects in the environmental medium are calculated. To verify the feasibility of the proposed model, the results are compared with the dose coefficients reported in the International Commission on Radiological Protection (ICRP) Publication 108. Based on the simplified model adopted by ICRP to arrive at the results reported in Publication 108, the average value of dose coefficients of each organ of the insect is used to calculate the results presented in this paper. The dose coefficients of internal and external 90Sr irradiation for the simplified anatomical model of Sphingonotus were found to be 6.59×10-4 μGyh-1/Bqkg-1 and 6.74×10-4 μGyh-1/Bqkg-1, respectively. Meanwhile, the dose coefficients of internal and external 137Cs irradiation for the simplified anatomical model were 1.34×10-4 μGyh-1/Bqkg-1 and 4.40×10-3 μGyh-1/Bqkg-1, respectively. The dose coefficients were 7.87×10-4μGyh-1/Bqkg-1 and 6.74×10-4μGyh-1/Bqkg-1, respectively. The dose coefficients were 1.33×10-4μGyh-1/Bqkg-1 and 3.51×10-3μGyh-1/Bqkg-1, respectively. The dose coefficients of internal and external 90Sr radiation for reference insects as reported in the ICRP Publication 108 were 1.00×10-2 μGyh-1/Bqkg-1 and 3.90×10-10 μGyh-1/Bqkg-1, respectively. Moreover, the dose coefficients of internal and external 137Cs radiation in the ICRP Publication 108 were 3.20×10-3 μGyh-1/Bqkg-1 and 2.80×10-3 μGyh-1/Bqkg-1, respectively. The above data indicate that the dose coefficients of internal irradiation reported in the ICRP Publication 108 are larger than those calculated using the proposed dosiological model, whereas those of external irradiation in ICRP Publication 108 are smaller. This trend is probably related to the size of the organism, decay rate, and energy of radionuclides. The adoption of a simplified anatomical model, morphologically similar to the organism, and a voxel model, highly overlapping with the organism, in this study allows a visualization of the real exposure situation for the organism considered with high accuracy, proving the feasibility of the insect dosimetry model established in this study.

Objective To analyze the effect of Traditional Chinese Medicine(TCM) directional drug penetration therapy combined with elastic bandage compression dressing on relief of TCM syndrome in patients with ecthyma. Methods A total of 80 hospitalized patients with ecthyma were divided into two groups according their hospital admission sequence. In the control group(n=40), the ulcer wound was treated with elastic bandage after conventional dressing change. In the observation group(n=40), the ulcer wound was treated with directional drug penetration therapy for 15-20 minutes before dressing change, and then the ulcer wound was treated with elastic bandage after conventional dressing change. The improvement rate of ecthyma-related syndromes was measured and compared between the two groups. Results The total effective rate of syndromes relief was 97. 50%(39/40)in the observation group, which was significantly higher than 80. 00%(32/40)in the control group (P＜0. 05). Conclusion TCM directional drug penetration therapy combined with elastic bandage compression dressing has significant effect on relief of ecthyma-related clinical syndromes, and it is an easy-to-use, safe and painless TCM technique, which is worthy for clinical application. (目的 分析中医定向透药联合弹力绷带加压包扎对促进臁疮患者中医证候改善的效果。方法 根据入院时间顺序, 将住院治疗的80例臁疮患者分为两组。对照组40例患者溃疡创面采用常规换药后用弹力绷带加压包扎; 观察组40例患者在换药前进行定向透药治疗15~20 min, 溃疡创面采用常规换药后用弹力绷带加压包扎。比较两组患者臁疮相关中医证候的改善情况。结果 观察组中医证候改善总有效率97. 50%(39/40), 高于对照组的80. 00%(32/40), 差异有统计学意义(P＜0. 05)。结论 中医定向透药联合弹力绷带加压包扎能够促进臁疮患者中医证候改善, 且操作简便、安全、无痛苦, 适合临床推广使用。)

Objective To investigate the intervention effect of nursing based on shared decision making (SDM) in maintenance period of comprehensive detumescence therapy (CDT)for lower-extremity lymphedema, and to investigate its influence on patient self-management skills. Methods Totally 27 patients were randomly divided into two groups on even or odd numbers according to the order of hospitalization: control group (n=14) included the patients with odd numbers and observation group (n=13) included the patients with even numbers. In the control group, lymphedema therapist implemented CDT for lower-extremity lymphedema, 10 days as a course of treatment, two consecutive courses. Self-identification of symptoms and signs of lymphedema and basic routine nursing measures were carried out during hospitalization. Before discharge, patients were educated with knowledge about skin care, lymphatic drainage, use of pressure gradient socks and functional exercise during the maintenance period of CDT treatment. In addition to routine care, nursing interventions based on a five-step process of shared decision making were carried out in the observation group during hospitalization and within 3 months after discharge. The patient self-management skills and satisfaction with nursing service were evaluated at discharge time, 1 month and 3 months after discharge. Results Scores of Self-management Behavior Assessment Scale and Newcastle Satisfaction with Nursing Scale (NSNS) decreased at 1 month and 3 months after discharge, and scores of the observation group were significantly higher than those of the control group(P＜0. 01). Conclusion The application of SDM-based nursing interventions in maintenance period of CDT for lower-extremity lymphedema is effective to improve patient satisfaction, enhance the ability of home self-management and compliance, reduce the occurrence of recurrence and complications, and improve the quality of life of patients. (目的 探讨共享决策模护理模式在下肢淋巴水肿患者综合消肿治疗(CDT)维持期中的干预效果, 以及对患者自我管理能力的影响。方法 根据患者入院时间顺序单双号, 单号14例患者纳入对照组, 由淋巴水肿治疗师实施下肢淋巴水肿CDT治疗, 10 d为1个疗程, 连续2个疗程。住院期间落实患者自我识别淋巴水肿的症状、体征和基本的常规护理措施, 出院前对患者进行CDT治疗维持期的皮肤护理、淋巴引流和压力梯度袜使用及功能锻炼的指导。双号13例患者纳入观察组, 观察组实在对照组常规护理的基础上, 采用共享决策护理模式进行干预, 实施基于共享决策5步骤的护理干预过程至出院后3个月。分别在出院时、出院后1个月和3个月, 对患者进行自我管理行为和护理满意度进行评估。结果 出院1个月和3个月后, 两组自我管理行为量表评分和纽卡斯尔护理满意度量表(NSNS)评分均较出院时升高, 且观察组得分优于对照组, 差异有统计学意义(P＜0. 01)。结论 共享决策护理模式应用于下肢淋巴水肿患者CDT治疗维持期中, 能提高护理满意度, 增强患者居家自我管理的能力和依从性, 降低复发和并发症的发生风险, 从而提高患者的生活质量。)

Antiangiogenic therapy targeting VEGF‐A has become the standard of first‐line therapy for non‐small cell lung cancer (NSCLC). However, its clinical response rate is still less than 50%, and most patients eventually develop resistance, even when using combination therapy with chemotherapy. The major cause of resistance is the activation of complex bypass signals that induce angiogenesis and tumor progression. Therefore, exploring novel proangiogenic mechanisms and developing promising targets for combination therapy are crucial for improving the efficacy of antiangiogenic therapy. Immunoglobulin‐like transcript (ILT) 4 is a classic immunosuppressive molecule that inhibits myeloid cell activation. Recent studies have shown that tumor cell‐derived ILT4 drives tumor progression via the induction of malignant biologies and creation of an immunosuppressive microenvironment. However, whether and how ILT4 participates in NSCLC angiogenesis remain elusive. Herein, we found that enriched ILT4 in NSCLC is positively correlated with high microvessel density, advanced disease, and poor overall survival. Tumor cell‐derived ILT4 induced angiogenesis both in vitro and in vivo and tumor progression and metastasis in vivo. Mechanistically, ILT4 was upregulated by its ligand angiopoietin‐like protein 2 (ANGPTL2). Their interaction subsequently activated the ERK1/2 signaling pathway to increase the secretion of the proangiogenic factors VEGF‐A and MMP‐9, which are responsible for NSCLC angiogenesis. Our study explored a novel mechanism for ILT4‐induced tumor progression and provided a potential target for antiangiogenic therapy in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Although RET‐tyrosine kinase inhibitors (RET‐TKIs) are the preferred first‐line therapy for advanced RET‐arranged NSCLC, most patients cannot afford them. In this population, bevacizumab, immunotherapy, and chemotherapy are the most commonly used regimens. However, the optimal scheme beyond RET‐TKIs has not been defined in the first‐line setting. Methods: This retrospective study included 86 stage IV NSCLC patients harboring RET rearrangement from six cancer centers between May 2017 and October 2022. RET‐TKIs, chemotherapy, or one of the combination therapies (including immune checkpoint inhibitor (ICI) combined with chemotherapy (I + C), bevacizumab combined with chemotherapy (B + C), ICI and bevacizumab combined with chemotherapy (I + B + C)), were used as the first‐line therapeutics. The clinical outcomes and safety were evaluated. Results: Fourteen of the 86 patients received RET‐TKIs, 57 received combination therapies, and 15 received chemotherapy alone. Their medium PFS (mPFS) were 16.92 months (95% CI: 5.9–27.9 months), 8.7 months (95% CI: 6.5–11.0 months), and 5.55 months (95% CI: 2.4–8.7 months) respectively. Among all the combination schemes, B + C (p = 0.007) or I + B + C (p = 0.025) gave beneficial PFS compared with chemotherapy, while I + C treatment (p = 0.169) generated comparable PFS with chemotherapy. In addition, I + B + C treatment had a numerically longer mPFS (12.21 months) compared with B + C (8.74 months) or I + C (7.89 months) schemes. In terms of safety, I + B + C treatment led to the highest frequency of hematological toxicity (50%) and vomiting (75%), but no ≥G3 adverse effect was observed. Conclusions: I + B + C might be a preferred option beyond RET‐TKIs in the first‐line therapy of RET‐arranged NSCLC. Combination with Bevacizumab rather than with ICIs offered favorable survival compared with chemotherapy alone. [ABSTRACT FROM AUTHOR]

Urban fringe areas, characterized by relatively larger community sizes and lower population densities compared to central areas, may lead to variations in walkability as well as gender differences, such as safety perception. While objective measurements have received considerable attention, further research is needed to comprehensively assess subjective perceptions of walking in the urban periphery. As a case study, we evaluated survey responses of community perceptions of "Imageability", "Enclosure", "Human scale", "Complexity" and "Safety" of Shanghai's five new towns, comparing these with responses from the central area in terms of gender difference, and analyzed influencing factors and prediction performance of machine learning (ML) models. We developed a TrueSkill-based rating system to dynamically collect audits of street view images (SVIs) from professional students and used the result to integrate with Geographic Information Systems (GIS), Computer Vision (CV), Clustering analysis, and ML algorithm for further investigation. Results show that most of the new towns' communities are perceived as moderately walkable or higher, with the city center's community exhibiting the best walkability perceptions in general. Male and female perceptions of the "Human scale" and the factors that affect it differ little, but there are significant disparities in the other four perceptions. The best-performing ML models were effective at variable explanations and generalizations, with Random Forest Regression (RFR) performing better on more perception predictions. Responses also suggest that certain street design factors, such as street openness, can positively influence walkability perceptions of women and could be prioritized in new town development and urban renewal for more inclusive and walkable cities. [ABSTRACT FROM AUTHOR]

To solve the problem of low classification accuracy caused by differences in object types, shapes, and scales in SAS images, an object classification method based on a deformable residual network and transfer learning is proposed. First, a lightweight deformable convolution module DSDCN was designed by adding offsets to a traditional convolution, to adapt to objects with different shapes in SAS images, and the depthwise separable convolution was used to optimize the module. Second, a deformable residual network was designed with the DSDCN, which combined the traditional depth features with deformable features for object representation and improved the robustness of the model. Furthermore, the network was trained by the transfer learning method to save training time and prevent model overfitting. The model was trained and validated on the acquired SAS images. Compared with other existing state-of-the art models, the classification accuracy in this study improved by an average of 6.83% and had an advantage in the amount of computation, which is 108 M. On the deformation dataset, this method improved the accuracy, recall, and F1 scores by an average of 5.3%, 5.6%, and 5.8%, respectively. In the ablation experiments of the DSDCN module, the classification accuracy of the model with the addition of the DSDCN module improved by 5.18%. In addition, the training method of transfer learning also led to an improvement in model classification performance, reflected in the classification accuracy, which increased by 7.4%. [ABSTRACT FROM AUTHOR]

The relationship between cancer and iron metabolism has received more attention, but there is less research on nutritional support to improve the nutritional and inflammatory status of cancer patients by regulating iron metabolism. A survey was conducted involving 90 patients with lung cancer. The control group was given routine hospitalization diet and the oral nutrition supplement (ONS) group was given oral nutrient solution on the basis of routine hospitalization diet. It lasted for 2 weeks. The changes of iron metabolism, nutritional status, and inflammatory indicators of the two groups were compared. After 2 weeks of intervention, the levels of ALB and PA in the ONS group were increased than that in the control group (P <.05), the inflammation was significantly decreased in the ONS group (P <.05), and the levels of Hb, SI, and TIBC in the ONS group were higher than that in the control group, while the SF was significantly reduced (P <.05). ONS could improve iron metabolism, nutritional status, and inflammatory levels. We speculate that the decrease in inflammation may be due to the changes of iron metabolism, thereby improving nutritional status. It may become a new target for tumor treatment. [ABSTRACT FROM AUTHOR]

In order to improve the accuracy of underwater object classification, according to the characteristics of sonar images, a classification method based on depthwise separable convolution feature fusion is proposed. Firstly, Markov segmentation is used to segment the highlight and shadow regions of the object to avoid the loss of information caused by simultaneous segmentation. Secondly, depthwise separable convolution is used to learn the deep information of images for feature extraction, which produces less network computation. Thirdly, features of highlight and shadow regions are fused by the parallel network structure, and pyramid pooling is added to extract the multi-scale information. Finally, the full connection layers are used to achieve object classification through the Softmax function. Experiments are conducted on simulated and real data. Results show that the method proposed in this paper achieve superior performance compared with other models, and it also has certain flexibility. [ABSTRACT FROM AUTHOR]

At present, a large number of studies have reported that hydrogen has antioxidant functions and prevents oxidative stress damage. However, it is not clear whether hydrogen can prolong longevity based on these effects. Therefore, we studied and explored the antiaging potential of exogenous hydrogen and its ability to extend longevity using Caenorhabditis elegans (C. elegans) as an animal model. Our results showed that the lifespans of the N2, sod-3 and sod-5 mutant strains were extended by approximately 22.7%, 9.5%, and 8.7%, respectively, after hydrogen treatment, but hydrogen had no effect on the lifespans of the daf-2 and daf-16 mutant strains. Meanwhile, the level of reactive oxygen species (ROS) in the hydrogen treatment group was significantly lower than that in the control group. At the transcript level, the expression of age-1 and let-363 was obviously decreased, while the expression of ins-18 was increased at the same time point (14 d). Compared with the control group, paraquat (PQ) could reduce the lifespan of the N2 and sod-5 mutant strains. Importantly, the longevity of these mutant strains recovered to normal levels when the animals were treated with exogenous hydrogen. According to these results, the lifespan of C. elegans is closely related to oxidative stress and can be significantly prolonged by reducing oxidative stress damage. Taken together, our data showed that hydrogen is a valuable antioxidant that can significantly reduce the body's ROS levels and extend the lifespan of C. elegans. This study also laid a foundation for the subsequent application of hydrogen in antiaging studies. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) and vascular endothelial growth factor-A (VEGF-A) may play important roles in the process of tumor progression and tumor angiogenesis. The aim of the present study was to examine the co-expression of IMP3 and VEGF-A in primary human non-small cell lung cancer (NSCLC), to investigate the association between these two expression levels and determine the clinicopathological implications, including changes to microvessel density (MVD), and to assess the prognostic value of co-expression. Using immunohistochemical staining, the expression of IMP3, VEGF-A and CD34 expression was detected in 128 primary NSCLC tissue samples. According to the expression of IMP3 and VEGF-A, the cases were divided into four groups. Next, the clinicopathological features, MVD and survival time were investigated across the different groups. The immunohistochemical analyses demonstrated that there was a significant correlation between IMP3 and VEGF-A expression in NSCLC (r=0.181; P=0.041). Co-expression of IMP3 and VEGF-A was significantly associated with larger primary tumor size (P=0.016), poorer differentiation (P=0.014), more advanced Tumor-Node-Metastasis stage (P=0.012), increased MVD (P=0.004) and positive lymph node metastasis (P=0.002). Survival analysis demonstrated that cases with IMP3 and VEGF-A double-positive staining were significantly associated with lower survival rates compared with cases with double-negative staining (P=0.039). In the early NSCLC (I–IIa) subgroup, the mean survival time of the double-positive staining group was significantly shorter compared with that of the double-negative staining group (P=0.015). Co-expression of IMP3 and VEGF-A was associated with angiogenesis and a poorer prognosis in NSCLC, and may therefore play a critical role in NSCLC progression. [ABSTRACT FROM AUTHOR]

Abstract Chromatin spatial organization is essential for transcriptional modulation and stabilization. The pattern of DNA distal interplay form the multiple topological associating domains (TADs), and further assemble the functional compartmentalization with open and expression-active chromatin ("A" compartments) or closed and expression-inactive chromatin ("B" compartments) in genome, whose boundaries were defined by the high enrichment of CCCTC-binding factor (CTCF). Nevertheless, As a potential therapeutic strategy, changing the local chromatin architecture via adding or removing the CTCF binding sites in situ to regulate the transcription activity of genes within one TAD in cancer cells is poorly explored. In present study, we observed that the metallothionein (MT) family were all remarkably decreased in HCC of TCGA database, and MT genes family were located within a TAD of 1.2 Mb at 16q13 in order, and CTCF binding sites were distributed at the both sites of MT gene clusters. Furthermore, CRISPR/Cas9 was employed to destroy the CTCF binding sites at the vicinity of the MT family in human liver hepatocellular carcinoma (HCC) cell lines Huh-7 and HepG2. And the presence of up-regulated transcription of MTs were observed in Huh-7 and HepG2 cells compared to normal liver CRL-12461 cells. Moreover, the presence of the varying DNA interplay as well as H3K4me3 and H3K9me3 modification on different MT genes were observed after CTCF binding domain destruction compared to the control using chromosome conformation capture (3C) and chromatin immunoprecipitation (ChIP). Our results determined a potential way to regulate the transcription of a series of genes via changing the local genomic organization for diseases treatment. Highlights • CTCF controls the transcription activity of metallothionein family. • CTCF binding sites affect the local chromatin organization. • Editing CTCF binding sites by CRISPR/Cas9 is a way for cancer treatment. [ABSTRACT FROM AUTHOR]

A simple organic molecule, 2-(9H-carbazol-9-yl)ethanol (CZEO), displays both mechanoluminescence (ML) and photo-induced room-temperature phosphorescence (RTP). The D–A type dimer formed in the crystals was found to play a crucial role in the light-stimulated luminescent response, responsible for the turn-on RTP and turn-off ML switching of CZEO. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC), a prevalent gynecologic tumor, is a great threat to women. We aimed to explore miR-142's effects on EC and the relevant mechanisms. Cell proliferation was evaluated with MTT, cell counting, and colony formation assay. MRNA abundances of miR-142 and cyclin D1 (CCND1) were examined with quantitative real-time PCR. CCND1 protein level in cells was analyzed with Western blot. miR-142's downstream target was identified with targetscan and luciferase reporter assay. Nude mice were injected subcutaneously with Ishikawa (ISK) cells transfected with or without miR-142 mimics. Ki-67 and CCND1 expressions in tumors of xenograft mice were analyzed with immunohistochemical assay. miR-142 was expressed at a lower level in human EC tumor samples than matched normal tissues, and its mRNA level in EC patients without metastasis was higher than that in patients with metastatic EC. Additionally, low-level miR-142 was closely linked with the poor prognosis of EC patients. miR-142 restricted ISK and HEC-1A cell proliferation. Targetscan and luciferase reporter assay proved the target relationship between miR-142 and CCND1. Moreover, high-level CCND1 was positively correlated with the poor prognosis of EC patients. Besides, miR-142 mimics restricted tumor growth in ISK xenografted mice, as well as inhibited the expression of Ki67 and CCND1 in excised tumors. miR-142 restricted EC proliferation by targeting CCND1. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) is essential in regulation of cancer cell and cancer stem cells (CSCs) behaviour. Linc00662 is a newly identified human lung cancer related lncRNA. In this study, we aimed to explore the function of Linc00662 in human lung cancer. The expression level of Linc00662 was analysed by quantitative real-time PCR. Cell metastasis and invasive ability were detected by transwell and scratch wound healing assays. The stemness of CSCs was shown by tumorsphere formation assay and flow cytometry. The interaction between Linc00662 and Lin28 was confirmed by RNA immunoprecipitation and RNA pulldown assay. Overexpression of Linc00662 promoted the poor prognosis of lung cancer. Cell invasion, metastasis and CSCs stemness in H1299 and A549 could be influenced by Linc00662. Linc00662 had direct interaction with Lin28, and the Linc00662 function was dependent on Lin28. We demonstrate that overexpression of Linc00662 enhances lung cancer cell metastasis and CSC stemness by interacting with Lin28 in human lung cancer, which could be utilized as a potential diagnostic and therapeutic target for lung cancer patients. [ABSTRACT FROM AUTHOR]

We intended to clarify the role of sphingosine kinase 1 (SPHK1) in gastric cancer (GC) using both in vitro and in vivo assays. The study was designed to identify novel therapeutic targets for GC treatment. Differential analysis was utilized to dissect two gene expression omnibus series (GSE49515 and GSE79973) microarray data form Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) dataset. MRNA and protein expressions were determined by quantitative polymerase chain reaction and Western blot, respectively. GC cell growth was measured by MTT assays and verified by in vivo analysis. Cell cycle and cell apoptosis were detected via flow cytometer observation. Cell migration and invasion were assessed by wound healing assays and Transwell assays. The targeting relationship between miRNA and SPHK1/S1PR1 was identified via dual‐luciferase assay. Twenty‐four common differentially expressed genes were screened out from two gene expression omnibus series (GSE49515 and GSE79973), among which SPHK1 was chosen for its higher fold change. We found elevated SPHK1 expression in GC tissues and cells, along with an increased concentration of SPHK1‐generated sphingosine‐1‐phosphate (S1P) in both GC serum and tissue. SPHK1 knockdown significantly suppressed cell proliferation, migration, and invasion of MKN1 and KATO3 cells. It also blocked cell cycle and induced apoptosis in MKN1 and KATO3 cells. Silencing of SPHK1 also refrained tumor growth and inhibited S1P level. MiR‐330‐3p directly targeted SPHK1 and S1PR1. Overexpressed miR‐330‐3p in MKN1 cells repressed SPHK1 and S1PR1 expressions like their chemical inhibitors‐SPHK1 inhibitors (FTY720) and S1PR1 inhibitors (VPC23019), and acted anti‐tumor both in vitro and in vivo. Our study provides evidence that SPHK1 was promotive for GC tumor growth and cell biological behaviors, and that miR‐330‐3p targeted 3′‐UTR of SPHK1 and inhibited its expression. SPHK1 was expected to become a new molecular marker and miR‐330‐3p a novel therapeutic target for GC. © 2018 IUBMB Life, 70(11):1164–1176, 2018 [ABSTRACT FROM AUTHOR]

The estuarine planktonic copepods have a wide geographical distribution and commendable tolerance to various kinds of contaminants. The primary aim of the present study was to contrast the impacts of model POPs (TBBPA and HBCD) on three common estuarine planktonic copepods (Oithona similis, Acartia pacifica and Pseudodiaptomus inopinus) and establish a protocol for the assessment of acute toxicity of marine organic pollutants. We first quantified the 96h-LC50 (0.566, 0.04 and 0.257 mg/L of TBBPA to the three subjects above respectively and 0.314 mg/L of HBCD to P. inopinus; all reported concentrations are nominal values). In the sub-lethal toxicity tests, it was turned out that the effects of copepods exposed to TBBPA could product different influences on the energy ingestion and metabolism. Different type of pollutions, meanwhile, could also bring varying degree effect on the target copepods. In general, the indicators (the rate of oxygen consumption, ammonia excretion, food ingestion and filtration) in higher concentration groups showed marked significant difference compared with controls as well a dose-effect relationship. The study also extended the research on the joint toxicity of TBBPA and HBCD based on the survival rate of P.inopinus. Whether 1:1 concentration or 1:1 toxic level, the research showed synergy effect relative to single exposure conditions. The result indicated that current single ecological testing used for environmental protection activities may underestimate the risk for copepods. It was also demonstrated that short-term sub-lethal experiment could be a standard to evaluate the sensitivity of copepods to POPs. [ABSTRACT FROM AUTHOR]

Zinc-dependent histone deacetylases (HDACs) play a critical role in transcriptional repression and gene silencing, and are among the most attractive targets for the development of new therapeutics against cancer and various other diseases. Two HDAC inhibitors have been approved by FDA as anti-cancer drugs: one is SAHA whose hydroxamate is directly bound to zinc, the other is FK228 whose active form may use thiol as the zinc binding group. In spite of extensive studies, it remains to be ambiguous regarding how thiol and hydroxamate are bound to the zinc active site of HDACs. In this work, our computational approaches center on Born-Oppenheimer ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics with umbrella sampling, which allow for modeling of the zinc active site with reasonable accuracy while properly including dynamics and effects of protein environment. Meanwhile, an improved short-long effective function (SLEF2) to describe non-bonded interactions between zinc and other atoms has been employed in initial MM equilibrations. Our ab initio QM/MM MD simulations have confirmed that hydroxamate is neutral when it is bound to HDAC8, and found that thiol is deprotonated when directly bound to zinc in the HDAC active site. By comparing thiol and hydroxamate, our results elucidated the differences in their binding environment in the HDAC active sites, and emphasized the importance of the linker design to achieve more specific binding toward class IIa HDACs. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Epithelial protein lost in neoplasm (EPLIN) has been implicated as a suppressor of cancer progression. The current study explored EPLIN expression in clinical gastric cancer and its association with chemotherapy resistance. EPLIN transcript expression, in conjunction with patient clinicopathological information and responsiveness to neoadjuvant chemotherapy (NAC), was explored in two gastric cancer cohorts collected from the Beijing Cancer Hospital. Kaplan-Meier survival analysis was undertaken to explore EPLIN association with patient survival. Reduced EPLIN expression was associated with significant or near significant reductions of overall, disease-free, first progression or post-progression survival in the larger host cohort and Kaplan Meier plotter datasets. In the larger cohort EPLIN expression was significantly higher in the combined T1 + T2 gastric cancer group compared to the T3 + T4 group and identified to be an independent prognostic factor of disease-free survival and overall survival by multivariate analysis. In the smaller, NAC cohort, EPLIN expression was found to be significantly lower in tumour tissues than in paratumour tissues. EPLIN expression was significantly associated with responsiveness to chemotherapy which contributes to overall survival. Together, EPLIN appears to be a prognostic factor and may be associated with patient sensitivity to NAC. [ABSTRACT FROM AUTHOR]

Yohimbine is an indole alkaloid from the leaves and bark of the Pausinystalia johimbe tree that has acquired an enviable reputation in treating erectile dysfunction. This report presents four simultaneous severe poisoning/death cases caused by yohimbine. The test samples comprised the venous blood of four middle-aged men (aged 47-65) who were suspected of poisoning; one of the men died due to ineffective rescue. Ethanol concentration determination and toxicological routine screening were performed using gas chromatography with flame ionization detection (GC-FID) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A specific LC-MS/MS method was developed to quantify yohimbine, which showed concentrations of 459, 249, and 301ng/mL in three poisoned blood samples and concentrations as high as 5631ng/mL in the deceased. Moreover, the deceased's autopsy ruled out death from trauma and previous illness, and no other common toxic components were detected in his blood. Therefore, yohimbine poisoning appears to be the most likely cause of death. As a type of alkaloid that can be employed in the treatment of clinical diseases and additives for supplements, the danger of yohimbine should be of widespread concern in society. [ABSTRACT FROM AUTHOR]

Background: Delta-like ligand 3 (DLL3) is one of the NOTCH family of ligands, which plays a pro- or anti-carcinogenic role in some cancers. But the role of DLL3 in colon adenocarcinoma (COAD) has not been studied in depth. Materials and methods: First, we used Kaplan-Meier (K-M) curve to evaluate the effect of DLL3 on the prognosis of COAD in The Cancer Genome Atlas (TCGA), which was further validated in clinical samples for immunohistochemistry. Then we screened for differentially expressed genes (DEGs) of DLL3 by analyzing datasets of COAD samples from Gene Expression Omnibus (GEO) and TCGA. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and Gene Set Enrichment Analysis (GSEA) were conducted to explore the underlying mechanisms of DLL3-related in the development and prognosis of COAD. On the basis of DLL3-related signature genes, a prognostic model and a nomogram were constructed. Finally, CIBERSORT was applied to assess the proportion of immune cell types in COAD sample. Results: Survival analysis showed a significant difference in overall survival between high- and low-expression group ( p = 0.0092), with COAD patients in the high-group having poorer 5-year survival rate. Gene functional enrichment analysis revealed that DLL3-related DEGs were mainly enriched in tumor- and immunity-related signaling pathways, containing AMPK pathway and mitophagy-animal. The comparison of COAD tumor and normal, DLL3 high- and low-expression groups by GSEA found that AMPK signaling pathway and mitophagy-animal were inhibited. Nomogram constructed from DLL3-related signature genes had a good predictive effect on the prognosis of COAD. We found the highest correlation between DLL3 and interstitial dendritic cell (iDC), natural killer (NK) cell and Interstitial dendritic cell (Tem). DLL3 was also revealed to be diagnostic for COAD. In clinical sample, we identified higher DLL3 expression in colon cancer tissue than in adjacent control ( p < 0.0001) and in metastasis than in primary lesion ( p = 0.0056). DLL3 expression was associated with stage and high DLL3 expression was observed to predict poorer overall survival ( p = 0.004). Conclusion: It suggested that DLL3 may offer prognostic value and therapeutic potential for individualized treatment of COAD, and that it may has a diagnostic role in COAD., 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 Xiang, Gong, Liu, Zhang, Li, Wang, Lv and Sun.)

Objective: To compare the effect of different techniques on serum immunoglobulin A and interleukin-10 in patients with high simple anal fistula., Methods: .The cross-sectional study was conducted at Dongyang People's Hospital, Weishan, China, from January 2019 to April 2021, and comprised patients with high simple anal fistula who were randomly and equally divided into Group A getting treatment with modified ligation of intersphincteric fistula tract, and Group B getting treatment with incision-thread-drawing method. Serum immunoglobulin A and interleukin-10 as well as the Wexner score were compared between the groups. Data was analysed using SPSS 25., Results: Of the 140 patients, there were 70(50%) in each of the two groups. There were 125(89.2%) male subjects overall. The mean age in Group A was 38.91±8.91 years, while in Group B it was 38.20±8.51. Mean hospital stay in Group A was shorter than that in Group B (p<0.001). Mean serum immunoglobulin A and interleukin-10 values were not significantly different at baseline, but on day 7 post-surgery, the difference was significant between the groups (p<0.05). Likewise, Wexner score was significantly different at 3 months post-surgery (p<0.05). There was no significant difference in the incidence of postoperative complications between the groups (p=0.730)., Conclusions: The modified ligation of intersphincteric fistula tract method was found to be a better option in the management of patients with high simple anal fistula.

Background: Nivolumab combined with chemotherapy has been shown to improve prognosis in patients with untreated, human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer (GC) and programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥5. However, the available first-line treatment options for advanced GC are limited. Analysis of efficacy and safety of other programmed cell death protein 1 (PD-1) antibodies combined with chemotherapy may provide alternative treatment options., Methods: This retrospective study included patients with untreated, HER2-negative, unresectable locally advanced, or metastatic GC or gastroesophageal junction (GEJ) cancer who received either camrelizumab combined with oxaliplatin plus S-1 (SOX)/capecitabine plus oxaliplatin (CapeOX) or SOX/CapOX alone between November 2020 and April 2022. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety were evaluated., Results: This study included 49 patients in camrelizumab plus chemotherapy group and 54 in chemotherapy group. The baseline clinical characteristics beyond Epstein-Barr virus (EBV) status and PD-L1 CPS had no difference between combination group and chemotherapy group. ORR and DCR were significantly higher in combination therapy group than in chemotherapy group (59.18% vs. 38.89%, P=0.048; 83.67% vs. 62.96%, P=0.018). The median PFS in combination group was significantly longer than chemotherapy group [10.03 vs. 6.24 months, hazard ratio (HR) 0.603, 95% confidence interval (CI): 0.368-0.989, P=0.045]. The OS was not mature at the time of the OS analysis, with 40% patients died. Subgroup analyses showed that PFS was longer in patients with PD-L1 CPS ≥1 compared with CPS <1 and in patients with a neutrophil-lymphocyte ratio (NLR) <2.38 compared with ≥2.38. The most common grade 3-4 treatment-related adverse events (TRAEs) were granulocytopenia (57% in combination group vs. 54% in chemotherapy group), anemia (39% vs. 33%, respectively), and thrombocytopenia (39% vs. 33%, respectively). The proportion of reactive cutaneous capillary endothelial proliferation (RCCEP, 73% vs. 0%) was higher in combination group relative to chemotherapy group; all were grades 1-2., Conclusions: Among patients treated with camrelizumab combined with chemotherapy, the clinical outcomes were superior to those patients treated with chemotherapy. However, these promising findings need to be confirmed in future clinical trials., 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-22-1229/coif). All authors report that this work was supported by the Wu Jieping Medical Foundation of China (No. 320.6750.2020-02-45). The authors have no other conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Hypoxia-mediated tumor progression is a major problem in colorectal cancer (CRC). MicroRNA (miR)-200b-3p can attenuate tumorigenesis in CRC, while exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) can promote cancer progression. Nevertheless, the function of exosomal miR-200b-3p derived from CAFs in CRC remains unclear. In this study, CAFs and normal fibroblasts (NFs) were isolated from CRC and adjacent normal tissues. Next, exosomes were isolated from the supernatants of CAFs cultured under normoxia and hypoxia. Cell viability was tested using the cell counting kit-8 assay, and flow cytometry was used to assess cell apoptosis. Cell invasion and migration were evaluated using the transwell assay. Dual-luciferase was used to investigate the relationship between miR-200b-3p and high-mobility group box 3 (HMBG3). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the miR-200b-3p and HMBG3 level. Our results found that the miR-200b-3p level was sharply reduced in CRC tissues compared to adjacent normal tissues. Additionally, the miR-200b-3p level was reduced in exosomes derived from hypoxic CAFs compared to exosomes derived from CAFs under normoxia. Exosomes derived from hypoxic CAFs weakened the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. However, hypoxic CAFs-derived exosomes with upregulated miR-200b-3p increased the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. In addition, HMBG3 was identified as the downstream target of miR-200b-3p in CRC cells, and its overexpression partially reversed the anti-tumor effect of the miR-200b-3p agomir on CRC via the mediation of the β-catenin/c-Myc axis. Furthermore, compared to exosomes derived from normoxia CAFs, exosomes derived from hypoxic CAFs weakened the therapeutic effects of 5-FU on CRC in vivo via the upregulation of HMGB3 levels. Collectively, the loss of exosomal miR-200b-3p in hypoxia CAFs reduced the sensitivity to 5-FU in CRC by targeting HMGB3. Thus, our research outlines a novel method for the treatment of CRC., 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 Yuan, Chen, Chai, Gong, Wan, Zheng, Hu, Guo, Gao, Dai, Yu and Tu.)

The construction industry in China is characterized by higher safety risk, and construction workers' unsafe behaviors are one of the main causes of construction safety accidents, thus, designing scientific mechanisms that motivate and cultivate the construction workers to adopt safety behaviors becomes the key to the construction safety problem. Existing studies have examined some of the factors leading to workers' safety behavior (WSB) at the social, organizational, and individual levels, but ignore investigating the impact of co-workers' guanxi (CWG) on WSB. Thus, this research utilized exploratory factor analysis, confirmatory factor analysis, and structural equation modeling to examine the impact of CWG on WSB, and the mediating role of group identification (GI) in the relationship between CWG and WSB. Results show that CWG can directly or indirectly influence WSB, GI can exert a partial mediating effect on the relationship between CWG and GI. The research results enrich the research on c guanxi and causation of WSB, and provide a reference for project managers to carry out relationship-related safety management and industry regulations., 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 Chen, Gong, Li and Shi.)

Colorectal cancer is one of the common malignant tumors in the digestive system, with high incidence and mortality rate. Therefore, there is an urgent need to identify and develop new molecular targets for colorectal cancer treatment. Previous studies have pointed out the important role of HMGB3 in tumors, and how it works in colorectal cancer needs to be studied in depth. In this study, we found that HMGB3 was highly expressed in COAD in the cBioPortal and GEPIA2 databases. Kaplan-Meier analysis showed that compared with patients with lower HMGB3 levels, patients with higher HMGB3 levels had poorer OS ( p = 0.001). We also found a correlation between HMGB3 expression and immune infiltration of CRC. To investigate the mechanism of HMGB3 knockdown-mediated colorectal cancer inhibition, we detected a downregulation of N-cadherin, Vimentin and β-catenin proteins after knockdown of HMGB3. Taken together, HMGB3 can be an effective target for CRC treatment in the future, and we have reason to believe that HMGB3 will be of greater value in more tumors in the near future., 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 Gong, Guo, Yuan, Hu, Chai, Zheng, Wan and Tu.)

MicroRNAs (miRNAs/miRs), non‑coding single‑stranded RNAs of length 18‑24 nucleotides, can modulate gene expression through post‑transcriptional control. As such, they can influence tumor proliferation, apoptosis, invasion, metastasis as well as chemotherapy resistance by regulating certain downstream genes. In this context, miR‑200b‑3p, one particular member of the miR‑200 family, possesses the ability to suppress tumor progression. However, many studies have suggested that, in certain cases, this miRNA may also promote the development of some tumors due to differences in the microenvironments and molecular backgrounds of different cancers. This review summarizes previous studies on the involvement of miR‑200b‑3p in tumors, including the underlying mechanism.