bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiling of CYP4Z1 and CYP1B1 Expression in Bladder Cancers
Authors: Al-saraireh Yousef , Alshammari Fatemah , Youssef Ahmed , Al-Sarayreh Sameeh , Almuhaisen Ghadeer , Alnawaiseh Nedal , Alrawashdeh Hamzeh , Al-Shuneigat Jehad
Published: December 2020

Bladder cancer is the tenth most common cancer worldwide, where its burden remains a challenge and needs new novel therapies. Several reports indicate expression of CYP4Z1 and CYP1B1 in many tumours. Their expressions are associated with a poor prognosis, and therefore proposed as promising biomarkers or targets for anticancer therapy. By using immunohistochemistry, expression of CYP4Z1 and CYP1B1 was evaluated in a panel of different types of bladder cancer, and the enzymes’ relation to histopathological features were assessed. Results showed an increased expression of CYP4Z1 (54.3%) and CYP1B1 (76.9%) in the majority of bladder cancers compared to weak or lack of expression of both enzymes in normal tissues. Their expressions were significantly associated with tumour grade and stage where the expressions were markedly increased in a high grade and advanced stage of the disease ( p < 0.05). Additionally, CYP1B1 expression was also associated with TNM staging ( p < 0.05) and its expression was increased in patients with lymph node metastasis. The expression profiles of CYP4Z1 and CYP1B1 suggest that both enzymes have the potential to be biomarkers or targets for novel anticancer therapy for bladder cancer. Nevertheless, further studies are needed to better delineate whether these enzymes are druggable targets.
Proton-Pump Inhibitor vs. H2-Receptor Blocker Use and Overall Risk of CKD Progression
Authors: Cholin Liza , Ashour Tarek , Mehdi Ali , Taliercio Jonathan , Daou Remy , Arrigain Susana , Schold Jesse , Thomas George , Nally Joseph , Nakhoul Nazih , Nakhoul Georges
Published: December 2020

Background: The relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy. Methods: Using our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR <60), with at least 2 PCP visits in the year prior. A Cox proportional hazards model was used to evaluate the relationship between medication groups and overall mortality, while competing risks regression models were used to determine the risk of ESKD with death as a competing risk.Results: 25,455 patients met inclusion criteria and were stratified according to medication group: no antacid therapy (15,961), PPI use (8,646), or H2B use (848). At 4 years, the cumulative incidence of ESKD with death as a competing risk was 2.0% (95% CI: 1.7, 2.4), 1.5% (0.8, 2.8), and 1.6%(1.4, 1.9) among PPI, H2B, and no medication respectively (P=0.22). The cumulative incidence of death with ESKD as a competing risk was 17.6% (95% CI: 16.6, 18.6), 16.7% (13.7, 19.8), and 17.3% (16.6, 18.0) (P=0.71).Conclusions: Use of PPI in a CKD population was not associated with increased mortality or progression to ESKD when compared to H2 blocker and to no acid suppressing therapy.
Spatial Heterogeneity of Soil Moisture in Red Beds Area and the Associated Driving Factors
Authors: Yan Ping , Lin Kairong , Yu Chenxi , Yan Luobin , Tu Xinjun , Zhuang Luwen
Published: December 2020

Soil moisture is one of key factors which influence crop growth and ecological environment construction. Knowledge on the spatial heterogeneity of soil moisture and the associate driving factors is of great importance for water resources allocation and ecological environment management. The present study investigated the spatial heterogeneity of soil moisture under four land-use types (cropland, forestland, grassland and bare land) in the ecologically degraded of a red beds area which located in the Nanxiong basin, China. Geostatistical and classic statistical methods were used to analyze the spatial variance of soil moisture. In addition, the driving factors which affect the spatial variance were discussed. The geostatistical analysis showed that the Gaussian model is the optimal regression model of semi-variance functions for all these four land-use types, among which the model of cropland and forestland had better fitting results comparing with other land-use types. Moreover, the soil moisture in bare land exhibited intermediate spatial autocorrelation, which was affected by structural and random factors. Using a cross validation method, we found that the precision of the ordinary kriging interpolation (OK) method was better than the inverse distance weighting interpolation (IDW) method, and the OK method more accurately reflected the spatial distribution of soil moisture in all these four land-use types. Furthermore, the spatial heterogeneity of soil moisture was mainly affected by the natural and anthropogenic factors such as structural characteristics of the soil, soil texture, vegetation covered on the surface of the land, local climate, land-use types, and human intervention, among which human intervention is the most important factor.
Identification of Genes Targeted in South African Merino and Afrino Sheep Populations Under Long-Term Selection for Reproduction and Body Weight
Authors: Snyman Margaretha , Süllwald Sunika , Olivier Willem , Visser Carina
Published: December 2020

Background: Reproductive performance and body weight are of the utmost economic importance in determining the efficiency of sheep production. Simultaneous selection for increased reproductive performance and early growth traits is a common strategy in many flocks, but ambiguous results regarding the relationship between reproduction and body weight have been reported. The objective of this study was to perform a genome-wide association study (GWAS) in two South African Merino flocks and an Afrino sheep flock that were selected for both reproduction and body weight over decades. The GWAS aimed to identify SNPs associated with genes affecting the traits number of lambs born (NLB), number of lambs weaned (NLW), total weight of lamb weaned (TWW) and body weight (BW) and thus to ascertain which genes were targeted through directional selection.Results: In the GWAS, 16 SNP markers associated with reproductive traits were identified among the three populations, while 15 SNPs were associated with body weight. These SNPs were linked respectively to 26 and 21 documented genes in the sheep genome. Most of these genes were previously associated in literature with reproduction related, as well as with growth related traits in various farm animal species. This study, supported by results from previous studies performed on sheep and cattle, identified the following genes that warrant further investigation as to their functions and processes relating to growth and reproduction in sheep: MAP7D1, TRAPPC3, THRAP3, TRMP8, SPP2, HDAC9, ZFHX3, SIX6, C14orf39, TAF4B, TRSP1 EYA2, RBMS3, STL38L, BSPH1, LIG1, CABP5 and ELSPBP1. Conclusions: Long-term selection in the flocks for both body weight and reproductive traits, and especially on the composite trait TWW, have favoured genes with pleiotropic effects influencing both groups of traits. SNPs associated with these pleiotropic genes were detected in the association analyses for the various traits.
Serum and Urine ANGPTL8 Expression Levels are Associated with Hyperlipidemia and Proteinuria in Primary Nephrotic Syndrome
Authors: Gao Xia , Liu Qingju , Kang Chengdong , Cui Weijing , Xu Zichuan , Zhong Fu
Published: December 2020

Background: This study aimed to investigate the expression characteristics of ANGPTL8 in patients with primary nephrotic syndrome and its possible correlationwith hyperlipidemia and proteinuria.Methods: ANGPTL8 levels were determined using Enzyme‑linked immunosorbentassay in 133 subjects with PNS, and 60 subjects with healthy controls.Results: Subjects with primary nephrotic syndrome had higher levels of serum andurine ANGPTL8 than healthy controls subjects (P < 0.001). In primary nephroticsyndrome patients, serum ANGPTL8 was positively correlated with cholesterol (r =0.209, P < 0.05) and triglycerides (r = 0.412, P < 0.001), while no correlation with24hUTP. Urine ANGPTL8 was positively correlated with high density lipoprotein-cholesterol (r = 0.181, P < 0.05), while urine ANGPTL8 was significantly negativelycorrelated with creatinine (r = -0.323, P<0.001) and 24hUTP (r = -0.268, P = 0.002).Interestingly, urine ANGPTL8 concentrations were different between membranousnephropathy and mesangial proliferative glomerulonephritis pathological types.Conclusions: Serum and urine ANGPTL8 levels in primary nephrotic syndromepatients were correlated with blood lipid levels and proteinuria, respectively, suggestingthat ANGPTL8 may play a role in the development of primary nephrotic syndromehyperlipidemia and proteinuria.
The Effect of WKYMVm Peptide on Promoting mBMSCs Secrete Exosomes to Make M2 Macrophages Polarization Through FPR2 Pathway
Authors: Zhao Wenbo , Hu Junxian , He QingYi
Published: December 2020

Background: When the multicystic vesicles (precursor of exosomes) are formed in cells, there are two results. One is to be decomposed by lysosomes and the other one is to become exosomes which are transported out through transmembrane. On the other hand, M2 macrophages can promote the formation of local vascularization and provide necessary support for the repair of bone defects. In order to provide a new idea for the treatment of bone defects, the purpose of our study is to investigate the effect of WKYMVm peptide on the secretion of exosomes from murine bone marrow-derived MSCs （mBMSCs） and the effect of exosomes on the polarization of M2 macrophages. Methods: WKYMVm peptide was used to activate the Formyl Peptide Receptor 2 (FPR2) pathway in mBMSCs. At first, we used CCK-8 kit to detect the cytotoxic effect of WKYMVm Peptide on mBMSCs. Secondly, we used western blotting and Quantitative real-time Polymerase Chain Reaction （Qrt-PCR） to detect the expression of Interferon Stimulated Gene 15 （ISG15） and Transcription Factor EB （TFEB） in mBMSCs. Thirdly, we used exosomes extraction kit and western blotting to detect the content of exosomes secreted by mBMSCs. Finally, we used the immunofluorescence and western blotting to count the number of M2 macrophages polarization.Results: We firstly found that WKYMVm peptide had no toxic effect on mBMSCs at the concentration of 1μmol/L. Secondly, we found that when the FPR2 pathway was activated by WKYMVm peptide in mBMSCs, the expression of ISG15 and TFEB were decreased, leaded to the secretion of exosomes increased. Finally, we proved that the exosomes secreted by mBMSCs could promote the polarization of M2 macrophages. Moreover, all these effects can be blocked by WRWWWW (WRW4) peptide, an inhibitor of FPR2 pathway.Conclusion: Our findings demonstrated the potential value of WKYMVm peptide in promoting the secretion of exosomes by mBMSCs and eventually leading to M2 macrophages polarization. We believed that our study could provide a research basis for the clinical treatment of bone defects.
Treatment of Unstable Distal Clavicle Fractures (Neer type IIb): A Modified System using a Miniature Locking Plate with a Single Button
Authors: Ying Hua , Wang Jihuan , Sun Yuehua , Dai Kerong , Yu Chao , Yang Fei
Published: December 2020

Background: Distal clavicle fractures were common in shoulder injuries. This study described the novel fixation technique using a miniature locking plate with a single button and reported its clinical outcomes obtained in patients with distal clavicle fractures associated with coracoclavicular ligaments disruption. Methods: Seven patients with distal clavicle fractures were included with a follow-up period of 12 months. All patients were diagnosed type IIb fractures according to the Neer classification. Distal clavicle fracture was fixed with a miniature locking plate and coracoclavicular ligaments were reconstructed using a single button. Functional outcomes were assessed at the final follow-up visit.Results: At 1-year follow-up, all patients had achieved radiographic union. There were no cases of nonunion or osteolysis. Mean Constant score at final follow-up was 88±5.13 (range, 78-93). Mean DASH score was 19.17±7.70 (range, 11.67-25). Mean UCLA score was 30±2.52 (range, 25-33).Conclusions: Internal fixation using a miniature locking plate and coracoclavicular reconstruction with a single button were reliable surgical techniques for restoring stability in patients with Neer type IIb distal clavicle fractures.
Prognostic Value of Preoperative Circulating Tumor Cell Counts in Patients with UICC-Stage I-IV Colorectal Cancer
Authors: Abdalla Thaer , Meiners Jan , König Alexandra , Melling Nathaniel , Karstens Karl , Gorges Tobias , Riethdorf Sabine , Izbicki Jakob , Pantel Klaus , Reeh Matthias
Published: December 2020

The detection of CTCs in peripheral blood is one of the most promising approaches to identify disseminated disease in colorectal cancer (CRC). This study aims to evaluate the prognostic relevance of preoperative CTCs using the Cellsearch® system (CS)in patients, who underwent resection with curative intent of different stages of colorectal cancer (UICC I-IV). CTC analysis was performed in 68 CRC patients at UICC stages I-IV immediately before surgery. Data were correlated with clinicopathological parameters and patient outcomes. One or more CTCs/7.5 mL were detected in 45.6% (31/68) of patients. CTCs were detected in all stages of the Union of International Cancer Control (UICC), in stage I (1/4, 25%), in stage II (4/12, 33.3%), in stage III (5/19, 26.3%) in stage IV (21/33, 63.6%).The detection of CTCs was associated to the UICC stage (p = 0.035) and to the presence of distant overt metastases (p = 0.014). The presence of ≥ 1 CTCs/ 7.5 ml correlated significantly with shorter progression-free (p = 0.013) and overall survival (p = 0.014). Multivariate analyses showed that preoperative CTCs are an independent prognostic indicator for overall survival (HR, 2.68; 95% CI, 1.05–6.92 7; p = 0.039, ≥ 1 CTC). In conclusion, detection of CTCs is an independent and strong prognostic factor in CRC, which might improve the identification of high-risk patients in future clinical trials.
Alternative Splicing of RNF180 Genes in Different Species Based on Comparative Genomics Analysis
Authors: Zhang Yuhao , Zhou Quan , Li Hao , Yuan Yuan , Sun Li-ping
Published: December 2020

Alternative splicing (AS) influences gene regulation, cell differentiation, and tissue development and is involved in many human diseases. The ring finger protein 180 (RNF180), a tumor suppressor gene, has four transcripts and seven predicted transcripts. However, the role of alternatively spliced products in the function and regulation of the RNF180 gene remain unknown. We used a comparative genomics approach to investigate RNF180 AS in different species. Conserved coding sequences, alternative splicing expression profiles and intron sequences were compared, and evolutionary selection pressure analyses of exons were performed. We found that the RNF180 zinc finger structure, which was related to major ubiquitination functions, was highly conserved and exon 5 was absent in many species. Comparisons with the corresponding intron revealed that exon 5 possessed high similarity. In exon pressure selection analysis, exon 6 was in the purifying selection, which corresponded to the zinc finger domain, while exons 7 and 8 faced positive selection evolution. Finally, there were multiple alternatively spliced forms of RNF180 in four transcripts. These results suggested that complex alternative splicing of the RNF180 gene occurred in multiple species. Partial splicing variants had evolutionarily conserved regions and functional region deletions.
Transcriptome Profile of the Sinoatrial Ring Reveals Conserved and Novel Genetic Programs of the Zebrafish Pacemaker
Authors: Minhas Rashid , Loeffler-Wirth Henry , Siddiqui Yusra , Obrebski Tomasz , Vhashist Shikha , Nahia Karim Abu , Paterek Aleksandra , Brzozowska Angelika , Bugajski Lukasz , Piwocka Katarzyna , Korzh Vladimir , Binder Hans , Winata Cecilia Lanny
Published: December 2020

Background: Sinoatrial Node (SAN) is part of the cardiac conduction system, which controls the rhythmic contraction of the vertebrate heart. The SAN consists of a specialized pacemaker cell population that has the potential to generate electrical impulses. Although the SAN pacemaker has been extensively studied in mammalian and teleost models, including the zebrafish, their molecular nature remains inadequately comprehended. Results: To characterize the molecular profile of the SAR and elucidate the mechanism of pacemaker function, we utilized the zebrafish transgenic line sqet33mi59BEt to isolate cells of the sinoatrial ring (SAR) of developing zebrafish embryos and profiled their transcriptome. Our analyses identified novel candidate genes and well-known conserved signaling pathways involved in pacemaker development. We show that, compared to the rest of the heart, the zebrafish SAR overexpresses several mammalian SAN pacemaker signature genes, which include hcn4 as well as those encoding calcium- and potassium-gated channels. Moreover, genes encoding components of the BMP and Wnt signaling pathways, as well as members of the Tbx family, which have previously been implicated in pacemaker development, were also overexpressed in the SAR. Among SAR-overexpressed genes, 24 had human homologues implicated in 104 different ClinVar phenotype entries related to various forms of congenital heart diseases, which suggest the relevance of our transcriptomics resource to studying human heart conditions. Finally, functional analyses of three SAR-overexpressed genes, pard6a, prom2, and atp1a1a.2, uncovered their novel role in heart development and physiology. Conclusion: Our results established conserved aspects between zebrafish and mammalian pacemaker function and revealed novel factors implicated in maintaining cardiac rhythm. The transcriptome data generated in this study represents a unique and valuable resource for the study of pacemaker function and associated heart diseases.
In Situ Observations of Ions and Magnetic Field Around Phobos: The Mass Spectrum Analyzer (MSA) for the Martian Moons eXploration (MMX) Mission
Authors: Yokota Shoichiro , Terada Naoki , Matsuoka Ayako , Murata Naofumi , Saito Yoshifumi , Delcourt Dominique , Futaana Yoshifumi , Seki Kanako , Schaible Micah J , Asamura Kazushi , Kasahara Satoshi , Nakagawa Hiromu , Nishino Masaki N , Nomura Reiko , Keika Kunihiro , Harada Yuki , Imajo Shun
Published: December 2020

The Mass Spectrum Analyzer (MSA) will perform in-situ observations of ions and magnetic fields around Phobos as part of the Martian Moons eXploration (MMX) mission to investigate the origin of the Martian moons and physical processes in the Martian environment. MSA consists of an ion energy mass spectrometer and two magnetometers which will measure velocity distribution functions and mass/charge distributions of low-energy ions and magnetic field vectors, respectively. For the MMX scientific objectives, MSA will observe solar wind ions, those scattered at the Phobos surface, water-related ions generated in the predicted Martian gas torus, secondary ions sputtered from Phobos, and escaping ions from the Martian atmosphere, while monitoring the surrounding magnetic field. MSA will be developed from previous instruments for space plasma missions such as Kaguya, Arase, and BepiColombo/Mio to contribute to the MMX scientific objectives.
lncRNA-RMST Functioned as a SOX2 Transcription Co-regulator to Regulate miR-1251 in the Progression of Hirschsprung's Disease
Authors: Zhou Lingling , Zhi Zhengke , Chen Pingfa , Du Chunxia , Wang Binyu , Fang Xiang , Tang Weibing , Li Hongxing
Published: December 2020

Background：Hirschsprung’s disease (HSCR) is a congenital colon disease characterized by the lack of ganglion cells which is closely related to impaired migration and proliferation of enteric neural crest cells (ENCCs). Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been authenticated as an important class of regulators of biological functions. In this study, a microarray analysis was conducted and found that Rhabdomyosarcoma 2-associated transcript (RMST), a newly defined lncRNA, was down-regulated in the stenotic segment of HSCR patients. MiR-1251 is transcribed from the intron region of RMST and was also low expressed in the aganglionic tract. This study aimed to clarify the roles they played in the occurrence of HSCR. Methods：qRT-PCR was applied to validate the mRNA expression of RMST, miR-1251, SOX2 and AHNAK, while western blotting was employed to evaluate the protein level of SOX2 and AHNAK in clinical samples and cells. CCK-8 and transwell assays were used to detect cell proliferation and migration after transfection. Chromatin immunoprecipitation (CHIP) was applied to confirm SOX2 could bind to the promoter region of miR-1251. RNA binding protein immunoprecipitation (RIP) was used to demonstrate the interaction between RMST and SOX2. Dul-luciferase reporter assay was performed to confirm miR-1251 could interact with AHNAK. Results: When the expression of RMST or miR-1251 was reduced, cell proliferation and migration was attenuated. However, RMST not to influence the expression of miR-1251 directly. Through bioinformatic analysis, transcription factor SOX2 was predicted to bind to the promoter region of miR-1251 which was confirmed by CHIP assay. We also demonstrated that RMST exerted as a co-regulator of SOX2 via RIP assay. AHNAK was predicted as the downstream gene of miR-1251 confirmed by the dual-luciferase reporter assay. Furtherly, rescue experiments showed RMST functioned as a transcription co-regulator of SOX2 to upregulate the expression of downstream gene AHNAK by strengthening the regulation of SOX2 on miR-1251 in HSCR.Conclusions: These findings uncovered the role of RMST/SOX2/miR-1251/AHNAK pathway during the development of Hirschsprung's disease and presented potential therapeutic targets for HSCR.
Tracking Progress in Anthropometric Failure Among Under-five Children in Ethiopia: A Geospatial and Multilevel Analysis.
Authors: Seboka Binyam Tariku , Hailegebreal Samuel , Yehualashet Delelegn Emwodew , Demeke Abel Desalegn
Published: December 2020

Background Under-nutrition is a major public health concern among under-five children in many developing countries. This work evaluated the overall prevalence of under-nutrition by using a composite index of anthropometric failure (CIAF), which helps in the detection of children with multiple anthropometric failures. Additionally, this study provides a Spatio-temporal distribution and associated factors of childhood anthropometric failures across time.Methods Secondary data was obtained from the Ethiopian Demographic and Health Survey for the survey 2005, 2011, and 2016 years. Data included 23,864 samples of children between the ages of 0-59 months, which is a nationally representative sample in Ethiopia. Analytical methods used in this paper include multivariate multilevel logistic regression to identify associated factors and Getis-Ord spatial statistical tool to identify high and low hotspots areas of anthropometric failures. ResultThe prevalence obtained with CIAF in 2005, 2011, and 2016 was, 53.5%, 51%, and 46.2% of children were suffering from under-nutrition respectively. The spatial analysis revealed areas that are at a higher risk of anthropometric failures consistently were found in northern parts of the country, largely in the Amhara, Tigray, and Afar regions. Multilevel logistic regression analysis showed that the risk of anthropometric failure was higher among older children, had low birth weight, had a mother with low BMI, was in a rural area, had mothers and fathers without formal education. Conclusion In addition to identifying wasted, stunted, and overweight children, CIAF also identified children with multiple conditions, which are generally neglected in most nutritional surveys. As revealed by this composite index, the prevalence of anthropometric failure remains considerably high and its spatial distribution also significantly varied across the regions in the country. The identified socio-demographic characteristics and districts at an increased likelihood of anthropometric failure can inform localized intervention and prevention strategies to improve the nutritional status and healthcare of children in Ethiopia.
Protective Effects of Sodium Butyrate on Rotavirus Inducing Endoplasmic Reticulum Stress-Mediated Apoptosis Via PERK-eIF2α Signaling Pathway in IPEC-J2 Cells
Authors: Zhao Ye , Hu Ningming , Jiang Qin , Zhu Li , Zhang Ming , Jiang Jun , Xiong Manyi , Yang Mingxian , Yang Jiandong , Shen Linyuan , Zhang Shunhua , Niu Lili , Chen Lei , Chen Daiwen
Published: December 2020

Background: Rotavirus (RV) is an important pathogens that causes severe gastroenteritis in infants and young animals. Endoplasmic reticulum (ER) stress and subsequent apoptosis played pivotal role in virus infection. However, the protective mechanisms of intestinal damage caused by RV are poorly defined, especially the molecular pathways related to enterocytes apoptosis. Thus, the aim of this study was to investigate the protective effect and mechanism of sodium butyrate (SB) on RV-induced apoptosis of IPEC-J2 cells. Results: The RV infection led to significant cell apoptosis, increased the expression levels of ER stress (ERS) markers, phosphorylated protein kinase-like ER kinase (PERK), phosphorylated eukaryotic initiation factor 2 alpha (eIF2α), caspase9, and caspase3. Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis. The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78 (GRP78), PERK, and eIF2α. In addition, SB treatment restrained the ERS-mediated apoptotic pathway, as indicated by downregulation of C/EBP homologous protein (CHOP), as well as decreased cleaved caspase 9 and 3. Furthermore, siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis. Conclusion: Taken together, these findings revealed that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis via PERK-eIF2α signaling pathway in a GPR109a-dependent manner, which provide new ideas for the prevention and control of RV.
Spectral Computed Tomography Findings of Peripheral Lung Adenocarcinoma and Peripheral Squamous Cell Carcinoma
Authors: Deng Liangna , Zhang Guojing , Lin Xiaoqiang , Jing Mengyuan , Han Tao , Zhang Bin , Zhou Junlin
Published: December 2020

Background: To investigate the spectral computed tomography (CT) findings of peripheral adenocarcinoma (P-AC) and peripheral squamous cell carcinoma (P-SCC) in lung. Methods: In this retrospective study, A total of 273 patients (150 patients with P-AC and 123 patients with P-SCC) confirmed by surgery and pathology who underwent chest contrast enhanced CT scan with GSI mode, including arterial phase (AP) and venous phase (VP). During two phases, The CT40keV, CT70keV, CT100keV values, iodine concentration (IC), water concentration (WC), effective atomic number (Zeff) were measured and the slope of the spectral curve (K) was calculated. Differences between two groups were compared using two-sample t-test, Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was also calculated to calculate diagnostic efficacies.Results: There was significant difference in gender between the two groups (P < 0.05), No significant difference between other clinical features and symptoms (P > 0.05). For AP and VP, the CT40keV, CT70keV, K70keV, IC and Zeff of P-AC were significantly higher than those of P-SCC (P<0.05), but there was no significant difference in WC and CT100keV between the two groups. ROC curve analysis showed that the combination of all quantitative parameters in AP and VP had the best diagnostic performance, with the area under the curve, sensitivity and specificity of 92%, 88%, and 84%, respectively.Conclusions: Spectral CT can provide reference for the differentiation of P-AC and P-SCC.
Massive hemothorax Caused by Intercostal Artery Pseudoaneurysm: A Case Report.
Authors: Liu Caiyang , Ran Ran , Li Xiaoliang , Liu Gaohua , Wang Chuanxi , Li Ji
Published: December 2020

Background: Intercostal artery pseudoaneurysm is rare and at the risk of rupture. The aetiology is always reported to be iatrogenic and traumatic injury. Embolisation is the most common therapeutic method. Here, we report a case of spontaneous intercostal artery pseudoaneurysm and cured by combining covered stent grafting and surgical management.Case presentation:A 60-year-old man complained of acute right back pain for 5 hours. Computed tomography showed right massive hemothorax and a giant mass with distinct feeding vessel originated from the thoracic aorta within the right hemithorax. Thoracocentesis was performed, and then a covered stent was positioned across the origin of the feeding vessel. The patient was diagnosed with intercostal artery pseudoaneurysm. Finally, we successfully resected the pseudoaneurysm and ligated the proximal part of the artery. Histologic examination have proved the diagnosis. The postoperative course was uneventful, and the patient was discharged on postoperative day 10. There is no recurrence reported during follow-up.Conclusions: Spontaneous intercostal artery pseudoaneurysm is extremly rare. Delayed hemothorax due to rupture of the pseudoaneurysm may occur years after the formation. Early diagnosis is important and a combined treatment of endovascular intervention and surgical management is feasible, especially for the case of ruptured large tumour-like mass presentation of the pseudoaneurysm.
Risk factors for Takotsubo Syndrome Following Cardiac Surgery: A Case–Control Study
Authors: Kim Yun Seok , Lim Ju Yong
Published: December 2020

Background: Takotsubo syndrome following cardiac surgery is a rare occurrence. However, early diagnosis is essential to prevent treatment which could increase the left ventricular outflow tract pressure gradient in patients with Takotsubo syndrome, and lead to cardiogenic shock. Therefore, our study aimed to identify the incidence of Takotsubo syndrome after cardiopulmonary bypass and the associated risk factors and prognosis.Methods: We retrospectively studied 5,773 patients who underwent cardiopulmonary bypass between February 2007 and July 2017. Among these, Takotsubo syndrome was diagnosed in 52 (0.9%). To evaluate the risk factors for Takotsubo syndrome, 104 of the remaining 5,721 patient were randomly selected as the control group (1:2 ratio). Univariate and multivariate logistic regression analyses were used for risk factor analysis. Results: Majority of patients (69.2%) in the Takotsubo syndrome group underwent mitral valve surgery, compared to 32.7% in the control group. The following risk factors of Takotsubo syndrome were identified: atrio-ventricular valve surgery (odds ratio (OR),10.5; 95% confidence interval (CI), 2.6-42.5; P=0.001); and the immediate postoperative use of epinephrine (OR, 3.3; 95%CI, 1.0-10.7; P=0.05) and dobutamine (OR, 4.8; 95%CI, 1.72-13.3; P=0.003). Hypertension was a significant protective factor against Takotsubo syndrome following cardiac surgery (OR, 0.22; 95%CI, 0.06-0.73; P=0.01).Conclusions: Takotsubo syndrome following cardiac surgery is rare. Immediate postoperative use of epinephrine and doputamine, as well as atrio-ventricular valve surgery were factors associated with the development of Takotsubo syndrome.
Postoperative Chemotherapy after Pneumonectomy in PIIB-PIIIB Non-Small-Cell Lung Cancer: A Safe Treatment but Lack of Survival Benefits
Authors: Wu Haoxuan , Zhang Yang , Luo Xiaoyang , Zhang Yawei , Xiang Jiaqing , Sun Yihua , Hu Hong
Published: December 2020

Background. Few reports have focused on postoperative chemotherapy (POCT) in stage pIIB-pIIIB non-small-cell lung cancer (NSCLC) patients after pneumonectomy. The safety and survival benefits of POCT have not been thoroughly evaluated among these patients. Methods. Records of patients who underwent pneumonectomy for stage pIIB-pIIIB NSCLC at a single institution between Jan. 2008 and Dec. 2016 were retrospectively reviewed.Results. Among the 169 patients included, 143 cases received R0 resection and survived over 90 days postoperatively. Among these, 98 cases received POCT (Chem(+) cohort), and 45 cases did not (Chem(-) cohort). The 5-year rate of non-cancer specific death (death caused by reasons other than cancer) after pneumonectomy was 7% in all patients, 11.1% in the Chem(-) cohort and 5.5% in the Chem(+) cohort. The recurrence rate had a tendency to decrease after POCT (HR=0.95, P=0.883), both in the local recurrence and distant recurrence (HR=0.58, P=0.290; HR=0.85, P=0.645), but the change did not reach statistical significance. pTNM stage and pleural invasion were independent factors associated with the recurrence rate (HR=1.91, P=0.003; HR=1.65, P=0.027). Cancer-specific survival (CSS) was not reduced by POCT (HR=1.27, P=0.614), neither in the N2 station negative group (N2(-) group) (HR=0.55, P=0.474), nor in the N2 station positive group (N2(+) group) (P=1.64; P=0.482).Conclusions. POCT after pneumonectomy is safe among carefully selected patients in pIIB-pIIIB NSCLC. Patients who achieved R0 resection probably benefit from POCT in terms of recurrence, but not in cancer-specific survival, particularly in stage pIIIA/pIIIB-N2 patients.
HDL Inhibited Atherosclerosis Induced by Radiation Injury
Authors: Xie Jin , Zhu Ke , Wang Qingya , Zhao Pei , Pan Lihua , Hui Jie
Published: December 2020

Background- HDL inhibits atherosclerosis development from radiation damage, nonetheless, the underlying mechanism is yet to be defined.Methods-This study used radiation patients along with cultured mouse aortic endothelial cells (MAECs) to investigate the process. Firstly, 158 patients from the oncology department of Jingzhou hospital who received radiation after neck cancers participated, and their arterial function was monitored by B ultrasound. Similarly, HDL and other blood lipid indexes were also tested. Then, MAECs were isolated and cultured and passed through MTT assay to test the HDL protective role on UVB radiation along with western blotting to test some apoptosis protein expression and possible molecules.Results-Firstly, those patients with high HDL levels were less likely to develop atherosclerosis, with statistical differences. We observed that MAECs treated with UVB were damaged significantly however HDL reversed the cell damage in a dose-depended manner. In the meantime, the apoptosis process was assessed and found that HDL inhibited the apoptosis caused by UVB. Western blotting results showed that HDL enhanced phosphatidylinositol 3-kinase (PI3K) in addition to Akt phosphorylation in MAECs.Conclusion-These results suggest that HDL protected UVB-mediated apoptosis by activation of a mechanism involving PI3K/Akt signaling pathway.
Robotic low anterior resection for rectal cancer with side-to-end anastomosis in a patient with anal stenosis
Authors: Tajima Yosuke , Hanai Tsunekazu , Katsuno Hidetoshi , Masumori Koji , Koide Yoshikazu , Ashida Keigo , Matsuoka Hiroshi , Hiro Junichiro , Endo Tomoyoshi , Kamiya Tadahiro , Chong Yongchol , Maeda Kotaro , Uyama Ichiro
Published: December 2020

BackgroundColorectal anastomosis using the double stapling technique (DST) has become a standard procedure. However, DST is difficult to perform in patients with anal stenosis because a circular stapler cannot be inserted into the rectum through the anus. Thus, an alternative procedure is required for colorectal anastomosis.Case presentationA 78-year-old woman presented with bloody stool. Colonoscopy and computed tomography revealed advanced low rectal cancer without lymph node or distant metastasis. We initially planned to perform low anterior resection using a double-stapling technique or transanal hand-sewn anastomosis but this would have been too difficult due to anal stenosis and fibrosis caused by a Milligan-Morgan hemorrhoidectomy performed 20 years earlier. The patient had never experienced defecation problems and declined a stoma. Therefore, we inserted an anvil into the rectal stump and fixed it robotically with a purse-string suture followed by insertion of the shaft of the circular stapler from the sigmoidal side. In this way, side-to-end anastomosis was accomplished laparoscopically. The distance from the anus to the anastomosis was 5 cm. The patient was discharged with no anastomotic leakage. Robotic assistance proved extremely useful for low anterior resection with side-to-end anastomosis.ConclusionPerforming side-to-end anastomosis with robotic assistance was extremely useful in this patient with rectal cancer and anal stenosis.
Clinicopathological Characteristics and Differential Diagnosis of Signet-ring Cell Carcinoma of Gastric Pit Epithelium
Authors: Zhang Zhi-Shang , Deng Wei-Yi , Huang Si-Lin , Yang Bin-Feng , Zhu Fang-Heng , Jiang Bo , Wang Su-Nan , Wang Yang-Kun
Published: December 2020

Background:To investigate the clinicopathological characteristics, immunophenotype and differential diagnosis of signet-ring cell carcinoma of gastric pit epithelium. Methods Seven cases of signet-ring cell carcinoma of gastric pit epithelium were studied by histomorphology observation, special staining, immunohistochemical staining and follow-up. Results At the initial stage, the glands proliferated and expanded, and the cells morphologically transformed into signet ring-like atypical cells and then formed clonal hyperplastic signet-ring cell carcinoma, which expanded laterally along the gastric pit, with a length of 3–6 mm. Erosion or mucosal ulcers can be formed on the surface, and the atrophy of fundus or pylorus glands leads to local depression of gastric mucosa. PAS was positive by special staining. Immunophenotype testing included MUC5AC, CKpan, CK20, CEA, villin and CDX2 with positive expression. In cytology, five cell morphologies could be seen: classic, immature, high proliferation, non-nucleus vacuole and degeneration. Three out of seven cases were accompanied by Helicobacter pylori (Hp) infection, accounting for 42.9% of the cases. Conclusion The signet-ring cell carcinoma of gastric pit epithelium originates from the proliferative region of the gastric fundus and the neck of gastric gland, which grows laterally along the gastric pit and is easy to be missed and misdiagnosed. Attention should be paid to the differential diagnosis, and the recognition level of signet-ring cell carcinoma of gastric pit epithelium should be improved.
A Clinical Study on Bone Defect Reconstruction and Functional Recovery in Benign Bone Tumors of the Lower Extremity, Treated by Bone Marrow Mesenchymal Stem Cell Rapid Screening–enrichment–composite System
Authors: Wang Lei , Luo Dinghao , Wu Junxiang , Xie Kai , Guo Yu , Gan Yaokai , Wu Wen , Hao Yongqiang
Published: December 2020

Background: With the development of medical technology, credible options for defect reconstructions after the resection of benign bone tumors of the lower extremities has become a high priority. As the current reconstructive methods commonly used in clinical practice have some flaws, new methods of reconstruction need to be explored. We aimed to prepare a new kind of bioactive scaffold for the repair of bone defects through a stem cell rapid screening–enrichment–composite technology system developed by our team. Furthermore, we aimed to investigate the curative effects of these bioactive scaffolds. Methods: Firstly, cell count, trypan blue exclusion rate and ALP staining were used to evaluate changes in enrichment efficiency, cell activity and osteogenic ability before and after enrichment. Then, the scaffolds were placed under the skin of nude mice to verify their osteogenic effects in vivo. Finally, the scaffolds were used for the reconstruction of bone defects after operations for benign bone tumors in a patient’s lower limb. The healing status of the defect site at 1 and 3 months was assessed by X-ray and the Musculoskeletal Tumor Society (MSTS) score was applied to reflect the recovery of patient limb function. Results: The system effectively enriched stem cells without affecting the activity and osteogenic abilities of the bone marrow mesenchymal stem cells (BMSCs). Meanwhile, the bioactive scaffolds obtained better osteogenic effects. In patients, the active scaffolds showed better bone integration and healing status, and the patients also obtained higher MSTS scores at 1 and 3 months after surgery. Conclusion: As a new technique, the rapid screening–enrichment–composite technology of stem cells demonstrates a better therapeutic effect in the reconstruction of bone defects after surgery for benign bone tumors of the lower extremities, which will further improve patient prognosis.
General Characteristics and Reasons for the Discontinuation of Drug Clinical Trials in Mainland China
Authors: Huo Ben-nian , Ai Mao-lin , Jia Yun-tao , LIU Yao , Yin Nan-ge , Song Lin
Published: December 2020

Background: Although discontinuation is common in clinical trials, no study has been conducted to analyse the current situation and reasons for the suspension or discontinuation of drug clinical trials in China. This study aims to analyse the general characteristics and reasons for the discontinuation of registered clinical trials in mainland China and to identify the associated factors.Methods: Trials with a status of terminated or stopped in the Drug Trial Registration and Information Publication Platform before March 31, 2020, were classified as discontinued trials and included in the analysis. Information related to researchers, studied drugs, the trials and the reasons for discontinuation were recorded. Fisher’s exact and χ2 tests were used to examine the associations of trial characteristics with different issues related to trial discontinuation. Results: Three hundred and twelve discontinued trials were included in this study. The studied drugs were mainly chemical drugs [229 (73.4%)]. The indications of the studied drugs were mainly neoplasms [77 (24.7%)]. The study type was mainly bioequivalence studies [97 (31.1%)]. More than half [177 (56.7%)] of the trials were discontinued because of trial issues, among which the main causes were negative results [69 (22.1%)], protocol issues [41 (13.1%)], and poor recruitment [35 (11.2%)]. Ninety-five (30.4%), 15 (4.8%) and 26 (8.3%) trials were discontinued because of sponsor issues, research centre issues and administration issues, respectively. Study design, blinding status, number of centres, planned sample size and whether participants had been enrolled may have been associated with one to three of the issues related to trial discontinuation.Conclusions: Discontinuation of clinical trials was commonly due to trial issues, sponsor issues, research centre issues and administration issues, such as negative results, and protocol issues. Study design, the number of centres, and sample size may be related to the discontinuation of trials. Careful study designs, smart business decisions, sufficient preparation of supplies such as the research drugs, and whether research centres have enough availability and patients are factors that should be considered before conducting trials.
Inkjet-Printed Wide Range and Highly Linear Signal Processed Systematic Humidity Sensor Array Based on Methylene Blue and Graphene Nanocomposite
Authors: Khan Muhammad Umair , Hassan Gul , Shaukat Rayyan Ali , Saqib Qazi Muhammad , Chougale Mahesh , Kim Jungmin , Bae Jinho
Published: December 2020

This paper proposes a signal processed systematic humidity sensor 3×3 array with all range and highly linear humidity response based on different particle size nanocomposite inks and different interspaces of interdigital electrodes (IDEs) (300, 200, and 100 µm). The fabricated sensors are patterned through a commercial inkjet printer by utilizing nanocomposites of methylene blue and graphene with three different particle sizes of bulk Graphene Flakes (BGF), Graphene Flakes (GF), and Graphene Quantum Dots (GQD), which are employed as an active layer on three types of IDEs with different interspaces of 300, 200, and 100 µm. From 3×3 sensor array, all range linear function (0-100% RH) is achieved by applying linear combination method of nine sensors in signal processing field, where weights for linear combination are required, which are estimated by the least square solution. The humidity sensing array shows a fast response time (Tres) of 0.2 sec and recovery time (Trec) of 0.4 sec. From the results, the proposed humidity sensor array opens a new gateway for a wide range of humidity sensing applications with a linear function.
Mitochondrial DNA Variants in Autism Spectrum Disorder: A Systematic Review
Authors: Xiaoli Liao , Yamin Li
Published: December 2020

Objectives The present review aimed to systematically characterize existing literature regarding the involvement of mtDNA variants in the pathophysiology of ASD. Methods A systematic search of publications in three online databases plus a manual search of reference lists of included articles was performed to collate potentially eligible literature. The study selection and data extraction were conducted by two independent authors, and the discrepancies in each step were settled through discussions.Results From 1874 resulting searched articles, 28 studies remained for this review. These included studies involving 3 studies reported ancient haplogroup variants, 16 studies reported point mutations, 7 studies reported copy number variants, and 8 studies reported deletions, with point mutation being the most common type of disease-related variants.Conclusions Findings generated from this review support mtDNA variants as important contributory components in susceptibility to ASD, since most variants have yet been mapped to specific loci, and the exact pathogenic mechanism remains to be determined.
Gene mutations in the PI3K/Akt signaling pathway were related to immune thrombocytopenia pathogenesis
Authors: Sun Ruijie , Liu Shu-Yan , Zhang Xiao-Mei , Zhu Jing-Jing , Yuan Dai , Shan Ning-Ning
Published: December 2020

Immune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. In this research, we conducted an in-depth genomic analysis of a cohort of patients and elucidate molecular features associated with disease pathogenesis of ITP. High-molecular-weight genomic DNA was extracted from freshly frozen BMBMCs (bone marrow blood mononuclear cell) in 20 active ITP patients. After this, the samples were subjected to molecular genetic analysis by whole-exome sequencing technique (WES) then, confirmed by sanger sequencing method. The enriched signaling pathway analysis and cellular processes associated with the mutated genes was performed with gene mapping to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results of this study showed that there were 3998 missense mutations involving 2269 genes in more than 10 individuals. Unique genetic variants including PTEN, INSR and COCH were the most associated with the pathogenesis of ITP. Functional analysis revealed these mutation genes mainly affect Phosphatidylinositol 3 kinase/serine/threonine kinase B (PI3K/Akt) signaling pathways (signal transduction) and platelet activation (immune system). Our finding further demonstrates the functional connections between these variant genes and ITP. Although the substantial mechanism and the impact of genetic variation are required further investigation, the application of next generation sequencing in ITP in this paper is a valuable method to reveal the genetic susceptibility.