bluuebunny/crossref_metadata_2025 huggingface dataset:
A Retrospective Analysis of the Efficacy and Safety of Anlotinib in the Treatment of Advanced Sarcoma
Authors: Yan Qiang , Du Xinhui , Guo Liangyu , Yao Weitao
Published: May 2021

Background: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. Previous research has demonstrated the efficacy of anlotinib in the treatment of advanced sarcomas. However, there are few relevant clinical studies, and the efficacy of anlotinib varies among sarcomas of different subtypes. Therefore, more clinical studies are needed to explore the efficacy of anlotinib in different subtypes of sarcomas. This study assessed the efficacy and safety of anlotinib monotherapy in the treatment of advanced sarcoma. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and February 2021 were retrospectively analyzed, including 5 cases of osteosarcoma and 40 cases of soft tissue sarcoma(STS). According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, we evaluated objective response rates (ORR) and disease control rates (DCR) at 3 months, as well as overall ORR and DCR, and calculated progression-free survival(PFS), and then evaluated treatment-related adverse events (AEs). Results: 44 patients were evaluated for efficacy and 45 for treatment-related AES. The ORR and DCR after 3 months were 6.82% and 81.82% respectively. At the end of follow-up, the overall ORR was 2.27%, the total DCR was 27.27%, and the median progression-free survival (m-PFS) was 5.71 months. Among them, the m-PFS of alveolar soft tissue sarcoma (ASPS) was 8.07 months, which was significantly longer than that of other subtypes of sarcoma (P=0.025). The most common adverse events were hypothyroidism (increased TSH) (17.8%), anemia (15.6%), fatigue (11.1%), loss of appetite (11.1%), decreased liver function (11.1%), leukopenia (8.9%) and hand-foot syndrome (8.9%). After treatment, 5 patients developed grade 3 AES, including decreased liver function (4.4%), hypertension (2.2%), proteinuria (2.2%), fatigue (2.2%), and loss of appetite (2.2%). One patient had severe myelosuppression and a significant decrease in white blood cells and platelets. It is worth noting that the PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (P < 0.05). Conclusion: Anlotinib is effective in the treatment of sarcoma, especially in ASPS, Synovial sarcoma (SS) and Fibrosarcoma (FS), and its toxicity is controllable. In addition, the occurrence of hand-foot syndrome after treatment may be related to a good prognosis. However, large sample and prospective studies are needed to confirm it.
Research on the Correlation Mechanism of Psychological Contract Violation and Physicians’ Behaviour Options (EVLN) in Tertiary Public Hospitals: An Empirical Study in Beijing, China
Authors: Hu Lujia , Zhu Junli , Zhang Yao , Chen Yun , Jia Yufei
Published: May 2021

Background: With the continuous deepening of the new medical reform, the hospital management system has changed, and there have been corresponding changes at the organisational and individual levels. As the main body of medical services, how to effectively motivate physicians is an important issue for hospital management. Purpose: the purpose of this research was to investigate the correlation mechanism between psychological contract violation and the EVLN behavior of physicians in tertiary public hospitals and explore new ideas for encouraging physicians, and provides governance and intervention strategies for management in hospitals. Methodology: Based on related theories such as psychological contract, this research used the stratified cluster sampling method to survey a total of 321 physicians in four public hospitals in Beijing, established an Excel database, and used Stata15.0 to construct regression models to analyse the correlation mechanism between psychological contract violation and the EVLN behavior of physicians in tertiary public hospitals. Findings: Psychological contract violation has a positive effect on exit behavior and neglect behavior, and a negative effect on voice behavior and loyalty behavior. Organisational justice has a mediating effect on the direct correlation mechanism models. Practice Implications: Our results suggest that it is necessary to pay attention to the psychological contract violation of physicians, build a good psychological contract relationship between public hospitals and physicians, and make full use of the role of organisational justice to promote positive behaviors of physicians, and moreover to prevent and curb negative behaviors of physicians.
[6]-Paradol Suppresses Proliferation and Metastases of Pancreatic Cancer by Decreasing EGFR and Inactivating PI3K/AKT Signaling
Authors: Jiang Xueyi , Wang Jie , Chen Peng , He Zhiwei , Xu Jian , Chen Yankun , Liu Xinyuan , Jiang Jianxin
Published: May 2021

Background: The underlying mechanism behind the tumorigenesis and progression of pancreatic cancer is not clear, and treatment failure is generally caused by early metastasis, recurrence, drug resistance and vascular invasion. Exploring novel therapeutic regimens is necessary to overcome drug resistance and improve patients outcomes.Methods: Functional assays were performed to investigated the role of 6-Paradol in proliferation and metastasis in vitro and vivo. The interaction between EGFR and 6-P was tested by KEGG enrichment analysis and molecular docking analysis. qRT-PCR was performed to detected the mRNA expression of EGFR in 6-P treated groups. Involvement of the PI3K/AKT pathway was measured by western blotting.Results: 6-P significantly suppressed pancreatic cancer cell proliferation and metastasis. KEGG enrichment analysis and molecular docking analysis suggested that there was an interaction between EGFR and 6-P. In addition, 6-P obviously decreased EGFR protein expression levels but did not change the mRNA of EGFR. 6-P could induce degradation of EGFR through decreasing the protein stability of EGFR and enhancing the ubiquitin-mediated proteasome-dependent degradation,6-P-mediated EGFR degradation led to inactivating PI3K/AKT signaling pathway. However, Ectopic expression of EGFR protein resulted in resistance to 6-P-mediated inactivity of PI3K/AKT signaling and inhibition of malignant phenotype. Inversely, erlotinib could enhance the 6-P-mediated anticancer activity. Conclusion: Our data indicated that 6-P/EGFR/PI3K/AKT signaling axis might become one of the supplemental therapeutic strategies for pancreatic cancer.
Risk Factors associated with Fetal and Pregnancy Complications in Palestine
Authors: Al-Aqqad Sana ’ , Al-Natour Nihal , Al-Tell Mariam
Published: May 2021

Background: Complications observed during pregnancy affect both mother and fetus, and are more commonly observed among pregnant women from developing countries. The study aims to identify the most common pregnancy and fetal complications during pregnancy, and associated risk factors with these complications. Methods: A longitudinal study was conducted from September 2017 to July 2018 among pregnant women attending and registering in primary health care clinics of the Palestinian Ministry of Health in Nablus city. Data were collected through interviews and by reviewing medical records. Women were followed up during their regular visits to the primary health care clinics. Any complication affecting either the fetus or the mother during the pregnancy period was recorded. Binary logistic regression was used to identify independent risk factors for pregnancy and fetal complications. Results: A total of 380 pregnant women were included in the study. The most common complications seen among women during pregnancy were preterm labor (PTL) (11.3%), followed by an equal number of gestational diabetes (GDM) and pregnancies induce hypertension (PIH), i.e. (7.9%). Large for gestational age (LGA) (11.6 %) and small for gestational age (SGA) (10.5%) were the most commonly observed fetal complications. Pregnant women living in camps (O.R 2.35, 95% [CI] 1.02- 5.45), nulliparity (O.R 14.9, 95% [CI] 1.09-202.5) and low parity women (O.R 16.8, 95% [CI] 1.47- 192.5) were at higher risk of having pregnancy complications. However, lower risk was noticed between women with gravida 4 (O.R 0.11, 95% [CI] 0.03-0.47) compared to women having more than 6 pregnancies. Age younger than 41 years was a protective factor against fetal complications, while parity (≤ 6 parities) especially 4 to 6 parities (OR 36.17; 95% CI 4.88-268) and active smoking mothers (OR 1.25; 95% CI 1.0-3.07) were identified as risk factors that are associated with an increased risk of fetal complications. Conclusions: Fetal and pregnancy-related complications are prevalent among Palestinian pregnant women. Increasing the awareness and improving the understanding of the identified risk factors related to these complications among the public, and specifically, females may help to reduce the prevalence of these conditions and the associated risk of these complications.
Characterization of a Novel Tombusviridae Species Isolated From Paris polyphylla var. yunnanensis
Authors: Zhao Mingfu , Chen Lu , Anane Rex Frimpong , Wang Zhe , Chen Zeli , Gao Like , Wen Guosong
Published: May 2021

A novel virus, Paris virus 2 (ParV2), was isolated from diseased Paris polyphylla var. yunnanensis, and its complete genome sequence was determined and analyzed. ParV2 is a positive-sense single-stranded RNA (+ssRNA) virus with a genome size of 4118 nucleotides. The ParV2 genome contains six putative open reading frames (ORFs) that encode proteins with predicted molecular weights of 40.14, 100.26, 7.31, 7.85, 26.09, and 8.77 kDa. The first ORF (ORF1) of ParV2 encodes a putative protein of 40.14 kDa (p40, nt: 20-1096), whiles the second ORF (ORF2, 888 aa) containing the GDD motif encodes the highly conserved RNA-dependent RNA polymerase protein (RdRP, nt:20-2683, p100, 100.26 kDa) of viruses in the family Tombusviridae. Multiple sequence alignments analysis showed that the complete genome sequence of ParV2 shares 31.7-55.5% nucleotide sequence identities with viruses in the family Tombusviridae. Ginger chlorotic fleck-associated tombusvirus (GCFaV-1,Accession No.QKE30557) had the highest sequence identity (55.5%) with ParV2, and also shares 59.2% RdRp and 34.9% CP amino acid sequence identity with GCFaV-1.Sequence comparisons and phylogenetic analysis of RdRp suggested that ParV2 is a novel member of the family Tombusviridae, and its closest known relative is GCFaV-1.
Evolutionary Analysis of Transcriptional Regulation Mediated by Cdx2 in Rodents
Authors: Liang Weizheng , Li Guipeng , Cui Huanhuan , Wang Yukai , Wei Wencheng , Sun Siyue , Gan Diwen , Chen Rui , Yi Hongyang , Schaefke Bernhard , Hu Yuhui , Zhou Qi , Li Wei , Chen Wei
Published: May 2021

Background: Differences in gene expression, which arises from divergence in cis-regulatory elements or alterations in transcription factors (TFs) binding specificity, are one of the most important causes of phenotypic diversity during evolution. On one hand, changes in the cis-elements located in the vicinity of target genes affect TF binding and/or local chromatin environment, thereby modulating gene expression in one-to-one manner. On the other hand, alterations in trans-factors influence the expression of their target genes in a more pleiotropic fashion. Although evolution of amino acid sequences is much slower than that of non-coding regulatory elements, particularly for the TF DNA binding domains (DBD)， it is still possible that changes in TF-DBD might have the potential to drive large phenotypic changes if the resulting effects have a net positive effect on the organism’s fitness. If so, species-specific changes in TF-DBD might be positively selected. So far, however, this possibility has been largely unexplored.Results: By protein sequence analysis, we observed high sequence conservation in the DNA binding domain (DBD) of the transcription factor Cdx2 across many vertebrates, whereas three amino acid changes were exclusively found in mouse Cdx2 (mCdx2), suggesting potential positive selection in the mouse lineage. Multi-omics analyses were then carried out to investigate the effects of these changes. Surprisingly, there were no significant functional differences between mCdx2 and its rat homologue (rCdx2), and none of the three amino acid changes had any impact on its function. Finally, we used rat-mouse allodiploid embryonic stem cells (RMES) to study the cis effects of Cdx2-mediated gene regulation between the two rodents. Interestingly, whereas Cdx2 binding is largely divergent between mouse and rat, the transcriptional effect induced by Cdx2 is conserved to a much larger extent.Conclusions: There were no significant functional differences between mCdx2 and its rat homologue (rCdx2), and none of the three amino acid changes had any impact on its function. Moreover, Cdx2 binding is largely divergent between mouse and rat, the transcriptional effect induced by Cdx2 is conserved to a much larger extent.
Neutrophil–Lymphocyte Ratio Predicts Overall Survival in Elderly Patients With Unresectable or Recurrent Gastric Cancer
Authors: Yamauchi Yoshiya , Sofuni Atsushi , Suzuki Yuka , Kurosawa Takashi , Iwasaki Kenichi , Tsuchida Akihiko , Itoi Takao
Published: May 2021

BackgroundThe relationship between various systemic inflammatory biomarkers and outcomes in patients with a variety of solid cancers has been reported. However, the relevance of these markers is unclear in elderly patients with unresectable or recurrent gastric cancer (GC). This retrospective study was conducted to identify specific factors associated with the survival of elderly patients with GC.Methods Patients with GC undergoing chemotherapy at our institution from April 2014 to April 2020 were included in the study. The patients were categorized into either the young group (Y group; aged <70 years) or the elderly group (E group; aged ≥70 years). The association between overall survival (OS) and pre-treatment values of systemic biomarkers, including the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio, and Glasgow prognostic score, was evaluated using the Kaplan–Meier method and log-rank test in each group. Univariate and multivariate analyses using Cox proportional hazards regression were used to investigate the prognostic factors associated with OS in each group.ResultsA total of 112 patients were eligible for inclusion in the analysis. The patients were categorized into the Y and E groups based on their age, and each group consisted of 56 patients. In both groups, high NLR and high Glasgow prognostic score were associated with poor OS (Y: p = 0.002 and p = 0.009; E: p < 0.001 and p = 0.045, respectively), whereas the platelet–lymphocyte ratio was not (Y: p = 0.296; E: p = 0.346). Univariate and multivariate Cox regression analyses revealed that poor performance status was correlated with poor OS in the Y group (hazard ratio: 2.56; 95% confidence interval: 1.02–6.43; p = 0.045). However, in the E group, NLR was the only independent prognostic factor of OS (hazard ratio: 4.22; 95% confidence interval: 1.69–10.56; p = 0.002). ConclusionsPoor performance status was an independent marker of poor prognosis in the Y group, whereas a high NLR was an independent marker in the E group. Thus, NLR may be a specific biomarker for predicting the OS of elderly patients with unresectable GC.
The Association Between Non-Suicidal Self-Injury of Adolescents and the COVID-19: The Lesson We Should Notice
Authors: Du Na , Ouyang Yingjie , Xiao Yu , Li Yunge
Published: May 2021

Background: Non-suicidal self-injury (NSSI) in psychiatric hospitalized adolescents keeps growing after the outbreak of COVID-19. This study aims to explore the relationship between the pandemic and the NSSI among adolescents, focusing on the underlying reasons. Methods: Through the retrospective analysis of medical record data retrieved from the electronic medical record system from January 2016 to March 2021, 609 medical records of adolescents were obtained. The main potential influencing factors were determined by the method of inductive content analysis. Results: Among the 609 adolescents, 420 subjects had NSSI, while 189 did not. We found the percentage of NSSI adolescents in 2016 was only 29.2% (7/24), reaching 34.5% (29/55) in 2017, 45.7% (42/92) in 2018, 61.3% (76/124) in 2019, 92.5% (196/212) in 2020, and 95.9% (70/73) in 2021. In the Binary logistic regression model, gender (OR=0.075), age (OR=1.215), single parent (OR=7.751) , experienced trauma (OR=2.214), social isolation (OR=8.313), body bully (OR=3.116), mobile phone overused (OR=4.199), committed suicide (OR=9.276), and before/after pandemic (OR=5.421) were significantly associated with NSSI. When comparing the differences in influencing factors between the pre-pandemic and the post-pandemic group, the results showed that experiencing trauma and suffering body bullying played less role in the appearance of NSSI, while the family constitution, relationship with parents, mobile phone use, and stressful learning have become the important factors. Conclusions: The pandemic has increased the risk of NSSI among adolescents and changed the influencing factors of this behavior. Tailored intervention gearing toward the changed risk factors should be formulated.
Revalorization of Sunflower Stalk Pitch As Feedstock for the Coproduction of Pectin and Glucose Using a Two-Step Dilute Acid Pretreatment Process
Authors: Zhang Qibo , Ma Xutong , Zhou Xin , Xu Yong
Published: May 2021

Background: Sunflower stalk pith, residue from the processing of sunflower, is rich in pectin and cellulose, thereby acting as an economic raw material for the acquisition of these compounds. In order to increase the commercial value of sunflower processing industry, a two-step sequential dilute sulfuric acid treatment combined with subsequent enzymatic hydrolysis was conducted on spent sunflower stalk pith to obtain the value-added products, pectin and glucose. Results: In this study, pectin was firstly extracted with a mild condition to avoid pectin degradation, which conducted at 95℃ with a pH of 2.0 for 2 h, and approximately 0.12 g/g of pectin could be recovered. Then the remaining solids followed by extracted pectin were subjected to the reinforced treatment process with 0.75% H2SO4 at 150 oC for 30 min to further improving enzymatic hydrolysis efficiency. Moreover, a fed-batch enzymatic hydrolysis was successfully performed with a solid 16% content, the glucose titer reached 103.1 g/L with a yield of 83.6 %.Conclusion: Finally, approximately 140 g pectin and 260 g glucose were produced from 1 kg of raw sunflower stalk pith using the integrated biorefinery process. This work put forward a two-step dilute acid pretreatment combined with enzymatic hydrolysis method to produce pectin and glucose from sunflower spent waste.
The Relationship of the Efficiency of Energy Conversion Into Growth as an Indicator for the Determination of the Optimal Dosage for Mutation Breeding With the Appearance of Chromosomal Bridges, Ring Chromosomes, Micronuclei and Incomplete Mitosis After Gamma Irradiation of Kernels of Triticum Turgidum Ssp. Durum L. Cultivar Orania
Authors: VON WELL EBEN , FOSSEY ANNABEL , BOOYSE MARDÉ
Published: May 2021

BackgroundA 50% growth reduction of seedling height (GR50) after acute gamma irradiation of dormant kernels is widely used as a measure of irradiation damage to obtain the ideal irradiation dosage for mutation breeding. It became clear in recent years that the GR50 is not sensitive enough to predict the ideal gamma irradiation dosage for mutation breeding and it predicts a value that is higher than ideal. The study aim was to determine whether root, shoot and seedling growth on the one side and the efficiency of energy conversion into growth on the other are measuring different growth retardation effects of gamma irradiation that are the result of DNA damage (bridges, ring chromosomes, micronuclei, incomplete mitosis) in Triticum turgidum ssp. durum. If the efficiency of energy conversion into growth is measuring different effects, the usefulness of efficiency of energy conversion into growth to predict the optimal dosage for mutation breeding will be investigated. ResultsThe kernels were gamma irradiated from 50 - 350 Gy using a 60Cobalt source. The kernels were left to germinate and grow for a period of 132 hours for the shoot and root growth and the efficiency of energy conversion into growth determination and for a period of 47.5 hours for the determination of the number of bridges, ring chromosomes, micronuclei and incomplete mitosis. The control differed highly significantly from 50 Gy and higher dosages and from 250 Gy and higher dosages for root and shoot growth respectively and from 250 Gy for the efficiency of energy conversion into growth. There was a highly significant increase in the number of bridges and micronuclei between 50 Gy and 150 Gy together with the higher irradiation dosages and only from 250 Gy for the ring chromosomes and interphase cells with incomplete mitosis. Root and seedling growth on the one hand and the efficiency of energy conversion into growth on the other were found to be measuring different effects of gamma irradiation on plant growth. ConclusionThe optimal dosage for mutation breeding was determined by making use of the efficiency of energy conversion into growth.
Multi-omic Analysis of Familial Adenomatous Polyposis Reveals Molecular Pathways and Polyclonal Spreading Associated with Early Tumorigenesis
Authors: Snyder Michael , Horning Aaron , Esplin Edward , Wu Si , Hanson Casey , Bararpour Nasim , Nevins Stephanie , Jiang Lihua , Contrepoi Kevin , Lee Hayan , Guha Tuhin , Hu Zheng , Laquindanum Rozelle , Mills Meredith , Chaib Hassan , Chiu Roxanne , Jian Ruiqi , Chan Joanne , Ellenberger Mathew , Khan Aziz , Michael Basil , Bahmani Bahareh , Esplin Glen , Shen Jeanne , Lancaster Samuel , Ladabaum Uri , Kundaje Anshul , Longacre Teri , Greenleaf William , Curtis Christina , Ford James , Becker Winston
Published: May 2021

Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected patients, leading to colorectal cancer (CRC), and is an ideal model to study early transition to CRC. We performed deep multi-omic profiling of 135 normal mucosal, benign and dysplastic polyps and adenocarcinoma samples from 6 FAP patients who consented to broad data sharing. Whole genome sequencing indicates that spatially separated polyps from the same donor harbor numerous mutations in common, but evolve independently, consistent with a model of polyclonal origin and spreading. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during early hyperplasia, dysplasia and cancer formation. These involve processes such as cell proliferation, immune response, alterations in metabolism (including amino acids, lipids), hormones, and extracellular matrix proteins. Interestingly, activation of the arachidonic acid pathway was found to occur early in hyperplasia; this pathway is targeted by aspirin/NSAIDs, a common preventative treatment of FAP patients. Overall, our results reveal key genomic, cellular and molecular events during the earliest steps in cancer formation and potential mechanisms of pharmaceutical prophylaxis.
Efficacy and Safety of Intra-Articular Hyaluronic Acid Injection (NRD101 / SUVENYL®) in Patients With Knee Osteoarthritis: a Multicenter, Randomized, Double-blind, Parallel, Active Control, Non-Inferiority Clinical Study
Authors: Wang Haoyang , Wang Wei , Xu Yongsheng , Li Jianan , Liu Kang , Kobayashi Ryota , Matsuda Yuya , Zhou Zongke , Weng Xisheng
Published: May 2021

BackgroundIntra-articular injection of hyaluronic acid (HA) has favorable effects on pain relief and knee function along with the low incidence of serious adverse reactions. Although various HA products are available for the treatment of knee osteoarthritis, it is still controversial whether differences in HA products have any clinically significant difference in efficacy and safety. In light of the above, the efficacy and safety of intra-articular injection of biological fermentation–derived high-molecular-weight HA (NRD101) was investigated in a double-blind comparative manner in Chinese patients with knee osteoarthritis.MethodA multicenter, prospective, randomized, double-blind, parallel, active control, non-inferiority study was conducted in Chinese patients with knee osteoarthritis. Patients were randomized to receive five consecutive weekly injections of either NRD101 or Artz (a non-crosslinked low-molecular-weight HA derived from combs of roosters) followed by 4 weeks follow-up. The primary efficacy endpoint was the change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) NRS pain subscale score at Week 5. Secondary efficacy endpoints included WOMAC stiffness and physical function subscale score, local pain, range of joint motion, and overall improvement.ResultsAmong 267 randomized patients, 259 patients completed the study. The change from baseline in WOMAC NRS pain subscale score at Week 5 was −2.98 ± 0.193 in the NRD101 group and −2.66 ± 0.194 in the Artz group, and the trial met the non-inferiority criteria. Efficacy in the NRD101 group tended to be consistently higher than in the Artz group for most items of WOMAC. Several subgroup analyses also showed differences between the two groups, tending to favor NRD101. Adverse events were seen in 26.0% (34/131) of patients in the NRD101 group and 38.3% (51/133) in the Artz group.ConclusionsNRD101 improved knee pain in Chinese patients with osteoarthritis after five consecutive weekly injections. NRD101 tended to be somewhat more effective than Artz. No new safety concerns were identified.Trial registration: JapicCTI, JapicCTI-173531. Registered 10 March 2017, https://www.clinicaltrials.jp/cti-user/trial/Search.jsp
Analysis of Co-Expression Module of Liver Metastasis Genes in Colorectal Cancer and Mining of Potential High-Expression Biomarkers
Authors: Wang Xuehu , Li Nie , Wang Yun , Yin Xiaoping , Zheng Yongchang
Published: May 2021

AimsThe Hub genes highly related to the disease were found from the gene co-expression module, and the potential high expression genes were analyzed to predict the liver metastasis of colorectal cancer, so as to provide reference for subsequent targeted therapy.MethodsIn this study, we used the public data set of GEO database (GSE50760) to analyze the gene co-expression of liver metastasis of colon cancer, primary colon cancer and normal colon tissue (54 cases) and 50 cases of clinical cases. The functional annotations based on GO database are enriched, and the functional annotations of five gene modules are obtained through the enrichment of biological processes. Then the data mining is carried out to find the sub-networks with high adjacency in the gene co-expression network. At the same time, these sub-networks are annotated to find oncogenes related to liver metastasis of colorectal cancer.ResultsThis experiment found that KRAS, APC, FBXW7, PIK3CA, TP53 were highly correlated with liver metastasis of colorectal cancer. Finally, two protein genes STAT1 and MAPK1 were found by MCODE, which may be highly correlated with liver metastasis of colorectal cancer. Two new genes with high expression proteins found in this experiment have potential cancer, which has not been reflected in previous studies.Conclusion﻿According to clinical data, KRAS, APC, FBXW7, PIK3CA, TP53 are related to colorectal cancer liver metastasis, and the analysis of the data set shows that STAT1 and MAPK1 are not only related to colorectal cancer liver metastasis oncogene but also related to clinically obtained genes.
A radical polymer for highly efficient solar evaporation and gas separation
Authors: Liu Wei , Yang Ming , Liu Jing , Yang Meijia , Li Jing , Lu Yanqiu , Japip Susilo , Chen Zhongxin , Wu Ji , Li Feng , Zhang Sui
Published: May 2021

The unique magnetic, electronic and optical features derived from their unpaired electrons have made radical polymers an attractive material platform for various applications. Here, we report solution-processable radical polymer membranes with multi-level porosities and study the impact of free radicals on important membrane separation processes including solar vapor generation, hydrogen separation and CO2 capture. The radical polymer is a supreme light absorber over the full solar irradiation range with sufficient water transport channels, leading to a highly efficient solar evaporation membrane. In addition, the radical polymer with micropores and adjustable functional groups are broad-spectrum gas separation membranes for both hydrogen separation and CO2 capture. First principle calculations indicate that the conjugated polymeric network bearing radicals is more chemically reactive with CO2, compared with H2, N2 and CH4. This is evidenced by a high CO2 permeability in gas separation membranes made of the conjugated radical polymer.
Larotinib in Patients with Advanced and Previously Treated Esophageal Squamous Cell Carcinoma with Epidermal Growth Factor Receptor Overexpression or Amplification: An Open-Label, Multicenter Phase 1b Study
Authors: Xu Jianming , Liu Lianke , Liu Rongrui , Bai Yuxian , Zheng Yulong , Zhang Shu , Li Ning , Yang Jianwei , Fan Qingxia , Wang Xiuwen , Zeng Shan , Zhang Yingjun , Zhang Weihong , Zhuang Yulei , Kang Ning , Zhou Qinghong , Jiang Yingzhi , Huang Yue , Sun Hongmei
Published: May 2021

PurposeLarotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This open-label, phase 1b study is aimed to evaluate the efficacy, safety of larotinib in patients with advanced esophageal squamous cell carcinoma (ESCC) with EGFR overexpression or amplification pretreated with one or more system regimens, and to recommend appropriate dose for its further study.MethodsPatients received larotinib orally at 3 doses (250, 300, 350 mg), once daily. Clinical response was evaluated every 8-weeks according to RECIST v1.1 criteria by both investigators and independent radiology review (IRC).Results81 patients were enrolled. The investigator-assessed overall response rate (ORR) was 13.7% (10/73), all responses were observed in the 350 mg group of which ORR up to 20.0% (10/50), with 10 of them having EGFR overexpression and 4 having EGFR amplification. Per IRC assessment, ORR for all patients and 350 mg group were 13.9% (10/72) and 16.3% (8/50). In the 350 mg group, median overall survival (OS) and progression-free survival (PFS) were 8.0 (95% CI, 4.9–10.2) months and 3.4 (95%CI, 2.4–3.7) months, respectively. The most common treatment-related adverse events (TRAEs) were diarrhea, rash and palmar-plantar erythrodysesthesia syndrome, elevated AST/ALT, vomiting, similarly with other EGFR TKIs.ConclusionLarotinib demonstrated promising antitumor activity and manageable safety profiles in patients with pre-treated advanced ESCC with EGFR overexpression or amplification, especially at the dose of 350 mg, which showed better efficacy and acceptable safety. A phase 3 study is underway on 350 mg larotinib in ESCC patients with EGFR overexpression.Trial registrationNCT03888092, registered on March 25, 2019, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03888092
Myogenesis of Siboglinum Fiordicum Sheds Light on Body Regionalisation in Beard Worms (Siboglinidae, Annelida)
Authors: Rimskaya-Korsakova Nadezhda Nikolaevna , Karaseva Nadezda , Pimenov Timofei , Rapp Hans Tore , Southward Eve , Temereva Elena , Worsaae Katrine
Published: May 2021

BackgroundMany annelids, including well-studied species such as Platynereis, show similar structured segments along their body axis (homonomous segmentation). However, numerous annelid species diverge from this pattern and exhibit specialised segments or body regions (heteronomous segmentation). Recent phylogenomic studies and paleontological findings suggest that a heteronomous body architecture may represent an ancestral condition in Annelida. To better understand the segmentation within heteronomous species we describe the myogenesis and mesodermal delineation of segments in Siboglinum fiordicum during development. ResultsEmploying confocal and transmission electron microscopy we show that the somatic circular musculature lies inside the longitudinal musculature and is predominantly developed at the anterior end of the larva. The longitudinal musculature consists of four separate strands at the ventral, dorsal, and ventrolateral body sides. Posteriorly, the longitudinal strands form a continuous layer. Our application of transmission electron microscopy allows us to describe the developmental order of the non-muscular septa. The first septum to form is supported by thick bundles of longitudinal muscles and separates the body into an anterior and a posterior region. The second group of septa to develop further divides the posterior body region (opisthosoma) and is supported by developing circular muscles. At the late larval stage, a septum reinforced by circular muscles divides the anterior body region into a forepart and a trunk segment. The remaining septa and their circular muscles form one by one at the very posterior end of the opisthosoma. Functionally, the prominent ventrolateral longitudinal muscles in the larva are proposed to drive the search movements of the head, while the anterior circular muscles and the posterior continuous layers of longitudinal muscles support the burrowing behaviour of the larva.ConclusionsThe heteronomous Siboglinum lacks the strict anterior to posterior sequence of segment formation as it is found in the most studied annelid species. Instead, the first septum divides the body into two body regions, before segments are layed down in first the posterior opisthosoma and then in the anterior body, respectively. Similar pattern of segment formation is described for the heteronomous chaetopterid Chaetopterus variopedatus and may represent an ancestral segmentation process in Annelida.
Shelf Life of Fresh Pistachio (Pistacia vera L.) upon Foliar Application of Sulfur as Pesticide
Authors: Nazoori Fatemeh , ZamaniBahramabadi Elaheh , Mirdehghan Seyed Hossein , Afrousheh Maryam
Published: May 2021

Application of sulfur as pesticide is a strategy in plant protection, but it is of great importance for a pesticide not to influence the quality of the product. In this study, movento (0.5 kg/1000 L), confidor (0.4 kg/1000 L) and refinery micronized (R) and mineral (M) sulfur (30 and 60 kg/1000 L in water) were sprayed on pistachio trees of cultivar ‘Ahmadaghaei’ twice (in middle May and after 50 days) for controlling the psylla. Pistachios were harvested in late September and stored in 4 °C for 25 and 50 days in order to evaluate the effect of pesticides on the quality of hulls and kernels. Weight, taste, aroma, appearance, respiration rate, firmness of hull and kernel, phenolic content of kernel, anthocyanin, chlorophyll, carotenoid, a*, b* and chroma of hull and kernel declined over time, while phenolic content of hull, L* and hue of hull and kernel displayed an increasing trend. Antioxidant activity of hulls and kernels and ethylene production remained stable over time. Chemical pesticides stimulated loss of weight and hull firmness. Refinery micronized sulfur at both concentrations caused higher wight loss, higher chlorophyll of hull and kernel, lower carotenoid of hull and kernel, higher L* and hue and lower a*, b* and chroma of hull and kernel (lighter and greener color). All sulfur treatments reduced firmness and antioxidant activity of hull and kernel, while elevated the respiration rate, hull phenolics and hull anthocyanin. R30 saved the taste and aroma after 50 days. R30 and M30 showed higher ethylene production.
Accuracy of Echocardiographic Estimates of Pulmonary Artery Pressures in Pulmonary Hypertension: Insights From the KARUM Hemodynamic Database
Authors: Venkateshvaran Ashwin , Seidova Natavan , Tureli Hande Oktay , Kjellström Barbro , Lund Lars H , Tossavainen Erik , Lindquist Per
Published: May 2021

BACKGROUND. Accurate assessment of pulmonary artery (PA) pressures is integral to diagnosis, follow-up and therapy selection in pulmonary hypertension (PH). Despite wide utilization, the accuracy of echocardiography to estimate PA pressures has been debated. We aimed to evaluate echocardiographic accuracy to estimate right heart catheterization (RHC) based PA pressures in a large, dual-centre hemodynamic database. METHODS. Consecutive PH referrals that underwent comprehensive echocardiography within 3 hours of clinically indicated right heart catheterization were enrolled. Subjects with absent or severe, free-flowing tricuspid regurgitation (TR) were excluded. Accuracy was defined as mean bias between echocardiographic and invasive measurements on Bland-Altman analysis for the cohort and estimate difference within ±10mmHg of invasive measurements for individual diagnosis. RESULTS. In 419 subjects, echocardiographic PA systolic and mean pressures demonstrated minimal bias with invasive measurements (+2.4 and +1.9mmHg respectively) but displayed wide limits of agreement (-20 to +25 and -14 to +18mmHg respectively) and frequently misclassified subjects. Recommendation-based right atrial pressure (RAP) demonstrated poor precision and was falsely elevated in 32% of individual cases. Applying a fixed, median RAP to echocardiographic estimates resulted in relatively lower bias between modalities when assessing PA systolic (+1.4mmHg; 95% limits of agreement +25 to –22mmHg) and PA mean pressures (+1.4mmHg; 95% limits of agreement +19 to -16mmHg).CONCLUSIONS. Echocardiography accurately represents invasive PA pressures for population studies but may be misleading for individual diagnosis owing to modest precision and frequent misclassification. Recommendation-based estimates of RAPmean may not necessarily contribute to greater accuracy of PA pressure estimates.
Upregulation of the ErbB family by EZH2 in hepatocellular carcinoma confers resistance to FGFR inhibitor
Authors: Prawira Aldo , Le Thi Bich Uyen , Ho Rebecca Zhi Wen , Huynh Hung
Published: May 2021

Purpose

Hepatocellular carcinoma (HCC), the most common manifestation of liver cancer, is one of the leading causes of cancer-related mortality worldwide with limited treatment options. Infigratinib, a pan-FGFR inhibitor, has shown a potent antitumour effect in HCC. However, drug resistance is often observed in long term treatment. In this study, we examined the potential feedback mechanism(s) leading to infigratinib and explored a combination therapy to overcome resistance in HCC.
Methods

Patient-derived xenograft (PDX) tumours were subcutaneously implanted into SCID mice and were subsequently treated with infigratinib. Tumour growth was monitored over time, and tumour samples were subjected to immunohistochemistry and Western blotting. For drug combination studies, mice were treated with infigratinib and/or varlitinib. Gene overexpression and knockdown studies were conducted to investigate the relationship between EZH2 and ErbB activity in infigratinib resistance.
Results

Infigratinib-resistant tumours exhibited higher levels of p-ErbB2 and p-ErbB3, concomitant with an increase in EZH2 expression. Gene overexpression and knockdown studies revealed that EZH2 directly regulates the levels of p-ErbB2 and p-ErbB3 in acquired resistance to infigratinib. The addition of varlitinib effectively overcame infigratinib resistance and prolonged the antitumour response, with minimal toxicity.
Conclusion

The upregulation of the ErbB family by EZH2 appears to contribute to infigratinib resistance. The combination of infigratinib and varlitinib showed a potent antitumour effect and did not result in additional toxicity, warranting further clinical investigation.
Hypoxia Pre-Challenged Glioma-Derived Exosomes Promote Recovery From Spinal Cord Injury by Inducing M2 Macrophage Polarization via Modulating MicroRNA-1246/TERF2IP and Let-7b/TERF2IP Signaling Pathway
Authors: Zhi Zhongzheng , Zhang Chenglin , Wang Yingjie , Kang Jian , Yuan Wei , Liu Jingdong , Wu Furong , Xu Guanghui
Published: May 2021

Background: Hypoxic GLIOMA derived exosomes may induce M2 macrophage polarization by upregulating TERF2IP expression. Furthermore, M2 macrophage polarization was found to be associated with accelerated SCI recovery by suppressing inflammatory response. The underlying mechanism of the therapeutic role of hypoxic GLIOMA derived exosomes in SCI recovery remains to be explored.Methods: Electron microscopy and Western blot were used to characterize U251 derived exosomes. Quantitative real-time PCR was performed to measure the mRNA expression of target genes, and Western blot and IHC were used to evaluate the protein expression of target genes. ELISA was performed to examine the levels of cytokines. Luciferase assay was carried out to explore the inhibitory role of miR-1246/let-7b in the expression of TERF2IP. TUNEL was performed to evaluate the apoptosis of spinal cord cells in SCI rats. Results: Hypoxic U251 derived exosomes significantly enhanced the expression of CD163, IL-10, IL-1RA, TGFB1, and CCL2 as well as the proportion of CD11b+/CD163+ cells while suppressing the expression of TNFa in U937 cells. Furthermore, the expression of miR-1246 and let-7b was remarkably elevated by Hypoxic U251 derived exosomes, while the expression of TERF2IP was inhibited. Luciferase assay demonstrated that miR-1246/let-7b effectively suppressed the expression of TERF2IP through binding to its 3’ UTR. In an SCI rat model, hypoxic U251 derived exosomes notably promoted the survival and functional recovery of left hindlimb by up-regulating IL-10, miR-1246, and let-7b expression while down-regulating TNFa/TERF2IP expression and attenuating apoptosis of spinal cord cells.Conclusion: The findings of this study demonstrated that glioma derived exosomes upregulated the expression of miR-1246 and let-7b to suppress the expression of TERF2IP to induce M2 macrophage polarization. The promoted M2 macrophage polarization suppressed inflammatory response to accelerate the recovery from SCI.
Association Between Visual Impairment and Income Change: A Longitudinal Follow-up Study With a National Health Screening Cohort
Authors: Choi Hyo Geun , Lee Min Joung , Baek Sung Uk
Published: May 2021

We evaluated the influence of visual impairment (VI) on income change using the longitudinal database of a Korean National Health Insurance Service cohort. A total of 5,292 participants ≥ 40 years old and registered as visually impaired persons were selected at a 1:4 ratio with 45,081 controls matched for age, sex, and income level. The income level of both the VI and control groups increased over time. In the VI group, the income levels 3, 4 and 5 years were higher than the initial value, while the income levels from 1 through 5 years were increased each year in the control group. The rate of change in income between time and VI were significant. In the subgroup analysis considering age, sex, and severity of VI, the rate of change in income were significant in < 65 years old subgroups. Regarding the severity of VI, a significant interaction was found for the mild-to-moderate VI subgroup. Although both the VI and control groups showed increased income levels over 5 years, the degree of income increase in the VI group was relatively lower than that in the control group. This finding was prominent in the middle-age subgroup. These results strongly suggested that VI induced an income inequality.
Cadmium(II) Capture Using Amino Functionalized Hydrogel with Double Network Interpenetrating Structure: Adsorption Behavior Study
Authors: Liu Sihua , Wang Haifei , Hu Jue , Li Yue , zhou guiyin
Published: May 2021

Heavy metal pollution caused by the indiscriminate disposal of toxic heavy metal wastewater has become one of the serious water environmental issues. In this study, a novel NH2-PAA/Alginate hydrogel with double network interpenetrating structure was constructed with alginate, acrylic acid, and other raw materials. Characterized by SEM, this hydrogel shows a three-dimensional porous structure, which would be useful in adsorption process for its high diffusion coefficient. The results of adsorption experimental show that the NH2-PAA/Alginate possessed the well adsorption capacity when pH above 3.5, the maximum adsorption capacity calculated by Langmuir was 176.5 mg/g, the adsorption equilibrium can be achieved within 150 min. In addition, the NH2-PAA/Alginate has good recycling ability and stability. The results of XPS analysis reveal that the Cd(II) exchanged with Ca(II) and then coordinated with amino and hydroxyl groups in NH2-PAA/Alginate. The NH2-PAA/Alginate hydrogel can deal with all kinds of heavy metal ions and is a potential material for heavy metal adsorption.
Anti-inflammatory effects of DhHP-6 in LPS-induced RAW264.7 macrophages and carrageenan-induced air pouch model in rat
Authors: Meng Fanwei , Ke Junfeng , Xu Jia , Li Jinze , Wang Liping
Published: May 2021

DhHP-6 (Deuterohemin-Ala-His-Thr-Val-Glu-Lys) is a novel peptide mimic of peroxidases that was previously designed in our laboratory. Here, we explored the anti-inflammatory potential of DhHP-6 against lipopolysaccharide(LPS)stimulated inflammatory response in RAW264.7 cells and carrageenan-induced air pouch model rats. DhHP-6 treatment dramatically attenuated the production of nitric oxide (NO), IL-6, andTNF-α in LPS induced RAW264.7 cells. Also, it blocked phosphorylation and degradation of IκBα and suppressed the nuclear translocation of p65. DhHP-6 (0.2, 0.6, and 2.0 mg/kg) significantly reduced the levels of total proteins and WBC counts in the exudates of the air pouch model rats. Moreover, MDA contents in the plasma of rats were reduced and SOD activities were enhanced in the DhHP-6-treatment group. Our results strongly show the effectiveness of DhHP-6 as an anti-inflammatory agent. The mechanism could be related to the reduction of Reactive oxygen species(ROS), inhibition of NF-κB nuclear translocation, and reduction of pro-inflammatory cytokines.
Meissner Effect: History of Development and Novel Aspects
Authors: Kozhevnikov Vladimir
Published: May 2021

The discovery of the Meissner (Meissner–Ochsenfeld) effect in 1933 was an incontestable turning point in the history of superconductivity. First, it demonstrated that superconductivity is an unknown before equilibrium state of matter, thus allowing to use the power of thermodynamics for its study. This provided a justification for the two-fluid model of Gorter and Casimir, a seminal thermodynamic theory founded on a postulate of zero entropy of the superconducting (S) component of conduction electrons. Second, the Meissner effect demonstrated that, apart from zero electric resistivity, the S phase is also characterized by zero magnetic induction. The latter property is used as a basic postulate in the theory of F. and H. London, which underlies the understanding of electromagnetic properties of superconductors. Here the experimental and theoretical aspects of the Meissner effect are reviewed. The reader will see that, in spite of almost nine decades age, the London theory still contains questions, the answers to which can lead to a revision of the standard picture of the Meissner state (MS) and, if so, of other equilibrium superconducting states. An attempt is made to take a fresh look at electrodynamics of the MS and try to work out with the issues associated with this the most important state of all superconductors. It is shown that the concept of Cooper's pairing along with the Bohr–Sommerfeld quantization condition allows one to construct a semi-classical theoretical model consistently addressing properties of the MS and beyond, including non-equilibrium properties of superconductors caused by the total current. As follows from the model, the three “big zeros” of superconductivity (zero resistance, zero induction and zero entropy) have equal weight and grow from a single root: quantization of the angular momentum of paired electrons. The model predicts some yet unknown effects. If confirmed, they can help in studies of microscopic properties of all superconductors. Preliminary experimental results suggesting the need to revise the standard picture of the MS are presented.