Publications by authors named "Yanbo Yang"

65 Publications

Glycoprotein B Antibodies Completely Neutralize EBV Infection of B Cells.

Front Immunol 2022 27;13:920467. Epub 2022 May 27.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China.

The Epstein-Barr virus (EBV) is the first reported oncogenic herpesvirus that establishes persistent infection in B lymphocytes in 95% of adults worldwide. Glycoprotein B (gB) plays a predominant role in the fusion of the viral envelope with the host cell membrane. Hence, it is of great significance to isolate gB-specific fusion-inhibiting neutralizing antibodies (NAbs). AMMO5 is the only gB NAb but fails to antagonize B-cell infection. It is essential to isolate potent NAbs that can completely block EBV infection of B cells. Using hybridoma technology and neutralization assay, we isolate two gB NAbs 8A9 and 8C12 that are capable of completely neutralizing B-cell infection . In addition, 8A9 shows cross-reactivity with rhesus lymphocryptovirus (rhLCV) gB. Competitive binding experiments demonstrate that 8A9 and 8C12 recognize novel epitopes that are different from the AMMO5 epitope. The epitopes of 8A9 and 8C12 are mapped to gB D-II, and the AMMO5 epitope is located precisely at gB aa 410-419. We find that 8A9 and 8C12 significantly inhibit gB-derived membrane fusion using a virus-free fusion assay. In summary, this study identifies two gB-specific NAbs that potently block EBV infection of B cells. Our work highlights the importance of gB D-II as a predominant neutralizing epitope, and aids in the rational design of therapeutics or vaccines based on gB.
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http://dx.doi.org/10.3389/fimmu.2022.920467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197244PMC
May 2022

Oesophageal reconstruction with a reversed gastric conduit for a complex oesophageal cancer patient: a case report.

Authors:
Yanbo Yang Lin Ma

BMC Surg 2022 Jun 11;22(1):225. Epub 2022 Jun 11.

Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Sichuan, 610041, Chengdu, People's Republic of China.

Background: The gastric conduit is the best replacement organ for oesophageal reconstruction, but a reversed gastric conduit (RGC) is rare. Oesophageal reconstruction for oesophageal cancer patients with a previous history of complicated gastrointestinal surgery is rather difficult. Here, we report a case in which oesophageal reconstruction was successfully managed using RGC based solely on the left gastroepiploic artery supply.

Case Presentation: A 69-year-old man with oesophageal cancer had a history of endoscopic intestinal polypectomy and pylorus-preserving pancreaticoduodenectomy (PPPD). The right gastroepiploic artery and right gastric artery had been completely severed. The only supply artery that could be used for the gastric conduit was just the left gastroepiploic artery. Because of the complex history of abdominal surgery, we had no choice but to use the RGC to complete the oesophageal reconstruction, in which the gastric conduit was passed reversely through the hiatus to the oesophageal bed and layered end-to-side manual intrathoracic anastomosis with the esophagus. The patient had transient feeding problems with postoperative delayed thoracic stomach emptying but no anastomotic stenosis or thoracic stomach fistula. He was satisfied with his life and had no long-term complications. There was no significant effect on gut physiological function, and RGC could work normally.

Conclusions: Oesophageal reconstruction with RGC is a feasible procedure for complex oesophageal carcinoma that can simplify complicated surgical procedures, has less influence on gut function, is less invasive, and is safe.
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http://dx.doi.org/10.1186/s12893-022-01630-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188175PMC
June 2022

Effects of urbanization on woody plant phylogenetic diversity and its associations with landscape features in the high latitude northern hemisphere region, Northeast China.

Sci Total Environ 2022 Sep 23;838(Pt 2):156192. Epub 2022 May 23.

Key Laboratory of Forest Plant Ecology (MOE), College of Chemistry, Chemistry Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China; Urban Forests and Wetland Group, Northeast Institute of Geography and Agroecology, Changchun 130102, China. Electronic address:

Urbanization is one of the primary drivers of terrestrial modification, with marked biological homogenization worldwide but relatively poor knowledge of woody phylogenetic diversity. Here, we investigated 943 plots, about 93,000 woody plants from 130 species in Northeast China, and calculated six phylogenetic diversity indexes, and urbanization landscape metrics; the responses of phylogenetic diversity to urbanization and its coupling relationship with landscape features were explored at 25 km × 25 km, 50 km × 50 km and 75 km × 75 km grid scales. We found that urbanization had enhanced the evolutionary distinctiveness of woody plants, characterizing as increasing Faith phylogenetic diversity (FPD) and their mean pairwise distance (MPD) while decreasing the mean nearest taxon distance (MNTD); these trends were independent of landscape scales and gymnosperm inclusion or not. As indicated by increasing SesMPD (Standardized MPD), the dominant role of community assemblage changed from environmental filtering in low urbanization intensity (UI) to competitive exclusion in high UI regions. Artificial surface area (ASA) and its percentage, SHAPE_F (Shape index of forest), and PD_F (Patch density of forest) had a threshold effect on phylogenetic diversity. ASA%, GDP (gross domestic product), and population density were the most potent predictors for the variations of phylogenetic diversity, and GDP contributed the most (42.9%). A higher GDP accompanied a higher FPD, SesPD (Standardized FPD), and SesMNTD (Standardized MNTD); higher PD_F and lower SHAPE_F were associated with higher MNTD, MPD, and SesMPD. In conclusion, urbanization strongly modifies woody plant phylogenetic diversity. Identifying the threshold effects and significant factors for phylogenetic variations allows biodiversity assessment and conservation through proper landscape configuration under the urbanization context.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156192DOI Listing
September 2022

Pyroptosis-Related Gene Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Glioma.

Front Cell Dev Biol 2022 25;10:862493. Epub 2022 Apr 25.

Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, China.

Gliomas are the most common primary tumors in the central nervous system with a bad prognosis. Pyroptosis, an inflammatory form of regulated cell death, plays a vital role in the progression and occurrence of tumors. However, the value of pyroptosis related genes (PRGs) in glioma remains poorly understood. This study aims to construct a PRGs signature risk model and explore the correlation with clinical characteristics, prognosis, tumor microenviroment (TME), and immune checkpoints. RNA sequencing profiles and the relevant clinical data were obtained from the Chinese Glioma Genome Atlas (CGGA), the Cancer Genome Atlas (TCGA), the Repository of Molecular Brain Neoplasia Data (REMBRANDT), and the Genotype-Tissue Expression Project (GTEx-Brain). Then, the differentially expressed pyroptosis related genes (PRGs) were identified, and the least absolute shrinkage and selection operator (LASSO) and mutiCox regression model was generated using the TCGA-train dataset. Then the expression of mRNA and protein levels of PRGs signature was detected through qPCR and human protein atlas (HPA). Further, the predictive ability of the PRGs-signature, prognostic analysis, and stratification analysis were utilized and validated using TCGA-test, CGGA, and REMBRANDT datasets. Subsequently, we constructed the nomogram by combining the PRGs signature and other key clinical features. Moreover, we used gene set enrichment analysis (GSEA), GO, KEGG, the tumor immune dysfunction and exclusion (TIDE) single-sample GSEA (ssGSEA), and Immunophenoscore (IPS) to determine the relationship between PRGs and TME, immune infiltration, and predict the response of immune therapy in glioma. A four-gene PRGs signature (CASP4, CASP9, GSDMC, IL1A) was identified and stratified patients into low- or high-risk group. Survival analysis, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group than in the low-risk group. Correlation analysis showed that the risk score was correlated with poor disease features. Furthermore, GSEA and immune infiltrating and IPS analysis showed that the PRGs signature could potentially predict the TME, immune infiltration, and immune response in glioma. The newly identified four-gene PRGs signature is effective in diagnosis and could robustly predict the prognosis of glioma, and its impact on the TME and immune cell infiltrations may provide further guidance for immunotherapy.
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http://dx.doi.org/10.3389/fcell.2022.862493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081442PMC
April 2022

Hirudin Regulates Vascular Function in Chronic Renal Failure through Modulating Macrophage Polarization.

Biomed Res Int 2022 19;2022:6043698. Epub 2022 Apr 19.

Department of Nephrology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, Jiangsu 222000, China.

Excessive inflammation is responsible for arteriovenous fistula (AVF) failure, which determines the therapeutic effect of chronic renal failure (CRF). Macrophage polarization is of great significance in the inflammatory response. Hirudin (Hiru) has been reported to possess a definite anti-inflammatory effect. This study is to uncover the impacts of Hiru on classically (M1)/alternatively (M2) macrophage polarization in the CRF rat model and rat vascular smooth muscle cells (VSMCs). After the CRF rat model was administrated with different concentrations of Hiru, blood urea nitrogen (BUN) and serum creatinine (Scr) levels were tested. H&E staining was to detect vascular injury, and IHC assay was to analyze inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) expressions in vascular tissues. Levels of inflammatory factors were examined by ELISA. Besides, western blot was to estimate the levels of marker proteins related to macrophage, proliferation, and apoptosis. CCK-8 was to measure cell viability. We discovered that Hiru alleviated renal function injury and vascular injury, exacerbated VSMC hyperplasia, and stimulated the differentiation and activation of M1 macrophage towards M2 macrophage in vivo. Moreover, after treatment with lipopolysaccharide (LPS)/IFN-gamma (IFN-), the increased M1/M2 ratio and enhanced levels of inflammatory factors were observed. Furthermore, Hiru boosted the proliferation and ameliorated the inflammatory response and apoptosis of rat VSMCs during the process of coincubation of M1-conditioned medium (CM). Collectively, Hiru played a protective role against vascular injury in CRF directly or through its influence on M1 macrophage polarization and inflammation.
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http://dx.doi.org/10.1155/2022/6043698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042600PMC
May 2022

Quercetin regulates vascular endothelium function in chronic renal failure via modulation of Eph/Cav-1 signaling.

Drug Dev Res 2022 Apr 25. Epub 2022 Apr 25.

Department of Nephrology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, Jiangsu, China.

Arteriovenous fistula (AVF) is frequently believed to be the best vascular access for chronic renal failure (CRF) patients. Vascular endothelial cell dysfunction has been implicated in AVF maturation. Quercetin (Quer) is a natural polyphenolic compound widely used in traditional Chinese medicine. We aimed to uncover the impacts of Quer on vascular endothelial cells in a CRF rat model and human umbilical vein endothelial cells (HUVECs) stimulated by lipopolysaccharide (LPS) and serum from rat with CRF. Blood urea nitrogen and serum creatinine levels were tested in CRF rat model after administration of Quer. H&E staining was used to estimate endothelial damage. Nitric oxide (NO), endothelial NO synthase (eNOS), EPH receptor B4 (EphB4), EphrinB2, and p-caveolin-1 (p-Cav-1) levels in the serum were examined by enzyme-linked immunosorbent assay. Western blot was employed to analyze the expressions of eNOS, phosphorylated (p)-eNOS, EphB4, and Cav-1 in arterial tissues and HUVECs. Cell counting kit-8 was applied for assessing cell proliferation. TUNEL (terminal-deoxynucleotidyl transferase-mediated nick end labeling) assay was employed to estimate cell apoptosis. Results showed that Quer ameliorated renal function impairment and endothelial injury in vivo. Meanwhile, Quer boosted the proliferation and suppressed the apoptosis of HUVECs stimulated by LPS and serum from rat with CRF. Additionally, Quer elevated NO and eNOS levels, upregulated p-eNOS expression but downregulated EphB4, EphrinB2, and p-Cav-1 expressions. Moreover, EphB4 inhibitor had the similar effect as Quer treatment in HUVECs stimulated by LPS and serum from rat with CRF. Collectively, Quer might effectively regulate vascular function to prevent AVF failure in CRF via modulation of Eph/Cav-1 signaling.
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http://dx.doi.org/10.1002/ddr.21940DOI Listing
April 2022

Different Monoclonal Antibodies in Myasthenia Gravis: A Bayesian Network Meta-Analysis.

Front Pharmacol 2021 18;12:790834. Epub 2022 Jan 18.

Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.

Myasthenia gravis (MG) is a common autoimmune disease with acquired neuromuscular transmission disorders. Recently, monoclonal antibodies have been shown to successfully treat a variety of diseases. In this meta-analysis, an appropriate search strategy was used to search eligible randomized controlled trials (RCTs) on different monoclonal antibodies to treat patients with MG published up to September 2021 from the embase, PubMed, and Cochrane Library. We assessed the average difference or odds ratio between each drug and placebo and summarized them as the average and 95% confidence interval (CI), respectively. In indicators of efficacy, patients receiving eculizumab (MD, -1.9; 95% CI, -3.2-0.76) had decreases in MG-ADL scores compared to placebo. In addition, only eculizumab (MD, -3.1; 95% CI, -4.7-1.5) and efgartigimod (MD, -1.4; 95% CI, -2.1-0.68) showed a significant difference from placebo in the amount of reduction in QMG scores, while neither of the other two monoclonal antibodies was statistically significant. With regard to the safety of monoclonal antibody therapy, there was no significant difference in the probability of AE in subjects treated with any of the four monoclonal antibodies compared to placebo. eculizumab was effective in reducing MG-ADL scores and QMG scores in myasthenia gravis. Meanwhile, eculizumab also caused fewer AE. As an emerging therapy, monoclonal antibodies are prospective in the treatment of MG. However, more researches are required to be invested in the future as the results obtained from small sample sizes are not reliable enough.
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http://dx.doi.org/10.3389/fphar.2021.790834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804097PMC
January 2022

The efficacy and safety of dual orexin receptor antagonists in primary insomnia: A systematic review and network meta-analysis.

Sleep Med Rev 2022 02 26;61:101573. Epub 2021 Nov 26.

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China. Electronic address:

The efficacy and safety of dual orexin receptor antagonists (DORAs) for primary insomnia have been well verified in several large randomized controlled trials (RCTs) over the past several decades. However, there have been few systematic comparisons of different DORAs, and the best DORA for insomniacs has remained unclear. Here, Medline, Embase, Cochrane library, and clinicaltrials.gov were searched for RCTs (through December 31, 2020) to evaluate different DORAs versus a placebo. We pooled data from 13 RCTs. DORAs were superior to the placebo in all efficacy outcomes except the subjective number of awakenings (P = 0.90), but also showed higher risks of somnolence, abnormal dreams, fatigue, and dry mouth (somnolence: P < 0.00001; abnormal dreams: P = 0.03; fatigue: P = 0.001; dry mouth: P = 0.007). No statistical differences were found between any two of the DORAs in terms of primary efficacy outcomes. However, lemborexant yielded the three-highest surfaces under the curve ranking area (SUCRA) values (78.25%, 96.25% and 89.13%). Taken together, we conclude that DORAs are superior to the placebo in terms of efficacy and safety measures.
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http://dx.doi.org/10.1016/j.smrv.2021.101573DOI Listing
February 2022

Shelterbelt farmland-afforestation induced SOC accrual with higher temperature stability: Cross-sites 1 m soil profiles analysis in NE China.

Sci Total Environ 2022 Mar 27;814:151942. Epub 2021 Nov 27.

Key Laboratory of Forest Plant Ecology (Ministry of Education), Heilongjiang Provincial Key Laboratory of ecological utilization of Forestry-based active substances, College of Chemistry, Chemistry Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China; Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China. Electronic address:

Shelterbelt farmland afforestation has been well-reported in its wind-break and climate regulation function, but less is on underground-soil organic carbon (SOC) sequestration and environmental stability. In this paper, we collected 180 soil samples from soil depths of 1 m (0-20, 20-40, 40-60, 60-80, 80-100 cm) in the farmland and neighbor shelterbelts in Songnen Plain, northeastern China. The sample plots covered six regions in the study area. SOC concentration and respiration decomposition rate, Q (temperature sensitivity), H (humidity sensitivity) were determined in the laboratory cultivation. Soil properties (N, P, K, electrical conductivity-EC, pH) and geographic-climate factors (multiple-year mean annual temperature and precipitation, MAT&MAP; temperature and precipitation during sampling month, MT &MP) were used to reveal the underlying reason for the changes in soil carbon sequestration. The results showed no significant difference in SOC respirational decomposition rate between farmland and shelterbelt forests but a 15.8% higher SOC concentration in shelterbelt forests (p < 0.05). The poplar shelterbelts reduced the Q value by 15.4% (p < 0.05), with deeper soils a more significant reduction in Q. With soil moisture increases, both shelterbelt forests and farmland showed an obvious respiration pattern of first-increasing-then-decreasing. No significant H (linear gradients) differences were found in farmland and shelterbelt forests. Partitioning of the RDA ordination-based variation showed that SOC stability (H and Q) of farmland was more affected by geo-climate. In contrast, the SOC stability of shelterbelt forests was greatly influenced by soil properties. Our findings manifest that the above-mentioned SOC changes can improve shelterbelt forest carbon sequestration function by prolonging the SOC lifespan in soil by at least 7% and SOC concentration by >15%. This should be included in the future to assess the underground soil carbon impact of Three-North shelterbelts in China and provide data supports for the estimation of similar forest stands in other parts of the world.
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http://dx.doi.org/10.1016/j.scitotenv.2021.151942DOI Listing
March 2022

Primary solid pulmonary mucosa-associated lymphoid tissue lymphoma mimicking lung cancer.

Asian J Surg 2022 Jan 23;45(1):506-507. Epub 2021 Nov 23.

Department of Thoracic Surgery, West China Hospital, Sichuan University, PR China; Chest Oncology Institute, West China Hospital, Sichuan University, PR China; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.11.026DOI Listing
January 2022

Different Catechol-O-Methyl Transferase Inhibitors in Parkinson's Disease: A Bayesian Network Meta-Analysis.

Front Neurol 2021 24;12:707723. Epub 2021 Sep 24.

Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.

Parkinson's disease (PD) is a common, chronic, progressive, debilitating neurodegenerative disease. The current levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced PD. Therefore, a theoretical reference for treatment is urgently needed. In this study, an appropriate search strategy was used to screen eligible studies on different drugs to treat patients with PD from the Embase, PubMed, and Cochrane Library. The publication dates were from January 1990 to June 2021. We integrated eligible randomized controlled trials, and statistical analysis was performed on three kinds of effectiveness outcomes and two types of safety outcomes. We assessed the average difference or odds ratio between each drug and placebo and summarized them as the average and 95% confidence interval (CI), respectively. In terms of efficacy, entacapone (mean difference [MD], 0.64 h; 95% CI, 0.29-1.0), opicapone (MD, 0.92 h; 95% CI, 0.35-1.5), and tolcapone (MD, 3.2 h; 95% CI, 2.1-4.2) increased patients' total ON-time compared to placebo. Tolcapone (MD, -100 mg; 95% CI -160 to -45) reduced the total daily dose of levodopa therapy. None of these three drugs was found to have statistical significance in mean change from baseline in UPDRS part III scores when compared with others. In terms of safety, tolcapone (MD, 3.8; 95% CI, 2.1-6.8), opicapone (MD, 3.7; 95% CI, 2-7.2), and entacapone (MD, 2.2; 95% CI, 1.5-3.3) increased the number of cases of dyskinesia compared to placebo. Entacapone (MD, 1.7; 95% CI, 1.3-2.2) and tolcapone (MD, 4.3; 95% CI, 1.3-15) were more likely to cause adverse events than placebo. In conclusion, opicapone showed higher efficiency and fewer safety problems in five indicators we selected when compared with the other two drugs.
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http://dx.doi.org/10.3389/fneur.2021.707723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497751PMC
September 2021

Animal-eRNAdb: a comprehensive animal enhancer RNA database.

Nucleic Acids Res 2022 01;50(D1):D46-D53

Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P.R. China.

Enhancer RNAs (eRNAs) are a class of non-coding RNAs transcribed from enhancers. As the markers of active enhancers, eRNAs play important roles in gene regulation and are associated with various complex traits and characteristics. With increasing attention to eRNAs, numerous eRNAs have been identified in different human tissues. However, the expression landscape, regulatory network and potential functions of eRNAs in animals have not been fully elucidated. Here, we systematically characterized 185 177 eRNAs from 5085 samples across 10 species by mapping the RNA sequencing data to the regions of known enhancers. To explore their potential functions based on evolutionary conservation, we investigated the sequence similarity of eRNAs among multiple species. In addition, we identified the possible associations between eRNAs and transcription factors (TFs) or nearby genes to decipher their possible regulators and target genes, as well as characterized trait-related eRNAs to explore their potential functions in biological processes. Based on these findings, we further developed Animal-eRNAdb (http://gong_lab.hzau.edu.cn/Animal-eRNAdb/), a user-friendly database for data searching, browsing and downloading. With the comprehensive characterization of eRNAs in various tissues of different species, Animal-eRNAdb may greatly facilitate the exploration of functions and mechanisms of eRNAs.
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http://dx.doi.org/10.1093/nar/gkab832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728245PMC
January 2022

Optimal Dose of Erenumab for Preventive Treatment of Episodic Migraine: A Systematic Review and Meta-Analysis.

Curr Neuropharmacol 2022 ;20(2):460-470

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China.

Background: Erenumab is a novel monoclonal calcitonin gene-related peptide receptor antibody that is used for the preventive treatment of migraine.

Objectives: This study aimed to evaluate the overall safety, efficacy, and dose-response relationship of erenumab in patients with episodic migraine and patients with prior migraine treatment failures.

Methods: We searched randomized clinical trials on PUBMED, EMBASE database, and Cochrane Library database. A pair-wise meta-analysis and Bayesian network analysis were performed.

Results: For efficacy outcomes, the network meta-analysis suggests that in comparison to erenumab 70 mg, participants who received erenumab 140 mg reported a significant decrease in monthly acute Migraine-Specific Medication Days (MSMD) and 50% increase in response rate, and erenumab was most likely to be ranked first for Monthly Migraine Days (MMD), MSMD, and 50% response rate. For safety outcomes, the network meta-analysis has found no significant difference between the 70 mg group and the 140 mg group measured by adverse events and serious adverse events. In the 140 mg erenumab group, a significant decreased in MMD and MSMD and 50% and 75% increased in response rate were reported in patients with ≥ 2 treatment failures compared to placebo. For safety outcomes, no significant difference was found between the 140 mg erenumab group and the placebo group.

Conclusion: Erenumab was effective in patients with episodic migraine. A total of 140 mg erenumab was associated with better efficacy outcomes without any increased risk for developing adverse events compared to 70 mg erenumab. Furthermore, 140 mg erenumab was effective in patients with prior migraine treatment failures.
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http://dx.doi.org/10.2174/1570159X19666210823104916DOI Listing
March 2022

Hydroxysafflor Yellow A inhibits the viability and migration of vascular smooth muscle cells induced by serum from rats with chronic renal failure via inactivation of the PI3K/Akt signaling pathway.

Exp Ther Med 2021 Aug 8;22(2):850. Epub 2021 Jun 8.

Department of Nephrology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, Jiangsu 222000, P.R. China.

It has been reported that the viability and migration of vascular smooth muscle cells contributes to arteriovenous fistula stenosis. Hydroxysafflor Yellow A (HSYA) has been demonstrated to inhibit the viability and migration of VSMCs by regulating Akt signaling. The present study aimed to investigate the role of HSYA on the viability and migration of human umbilical vein smooth muscle cells (HUVSMCs) following stimulation using serum from rats with chronic renal failure (CRF), and to determine the effects of HSYA on PI3K/Akt signaling. Wistar rats were randomly divided into two groups, control and CRF groups. Serum from each group was collected to stimulate the HUVSMCs. Cell Counting Kit-8 and wound healing assays were performed to assess cell viability and migration, respectively. Flow cytometry analysis was performed to assess apoptosis, and western blot analysis was performed to detect protein expression levels of PI3K and Akt. Nitric oxide (NO) production was measured using the Nitrate/Nitrite assay kit. The results demonstrated that serum from CRF rats significantly enhanced cell viability, migration and apoptosis, the effects of which were reversed following treatment with HSYA. In addition, CRF serum decreased NO and endothelial NO synthase expression, whilst increasing the protein expression levels of PI3K and phosphorylated-Akt in HUVSMCs. Notably, treatment with HSYA markedly restored NO production and inactivated the PI3K/Akt signaling pathway. Furthermore, the PI3K/Akt inhibitor, AMG511, exerted similar effects to HSYA. Taken together, the results of the present study suggest that HSYA suppresses cell viability and migration in the presence of CRF serum by inactivating the PI3K/Akt signaling pathway.
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http://dx.doi.org/10.3892/etm.2021.10282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210222PMC
August 2021

A systematic comparison of normalization methods for eQTL analysis.

Brief Bioinform 2021 11;22(6)

Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P. R. China.

Expression quantitative trait loci (eQTL) analysis has been widely used in interpreting disease-associated loci through correlating genetic variant loci with the expression of specific genes. RNA-sequencing (RNA-Seq), which can quantify gene expression at the genome-wide level, is often used in eQTL identification. Since different normalization methods of gene expression have substantial impacts on RNA-seq downstream analysis, it is of great necessity to systematically compare the effects of these methods on eQTL identification. Here, by using RNA-seq and genotype data of four different cancers in The Cancer Genome Atlas (TCGA) database, we comprehensively evaluated the effect of eight commonly used normalization methods on eQTL identification. Our results showed that the application of different methods could cause 20-30% differences in the final results of eQTL identification. Among these methods, COUNT, Median of Ratio (MED) and Trimmed Mean of M-values (TMM) generated similar results for identifying eQTLs, while Fragments Per Kilobase Million (FPKM) or RANK produced more differential results compared with other methods. Based on the accuracy and receiver operating characteristic (ROC) curve, the TMM method was found to be the optimal method for normalizing gene expression data in eQTLs analysis. In addition, we also evaluated the performance of different pairwise combinations of these methods. As a result, compared with single normalization methods, the combination of methods can not only identify more cis-eQTLs, but also improve the performance of the ROC curve. Overall, this study provides a comprehensive comparison of normalization methods for identifying eQTLs from RNA-seq data, and proposes some practical recommendations for diverse scenarios.
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http://dx.doi.org/10.1093/bib/bbab193DOI Listing
November 2021

Structure characterization, antioxidant and emulsifying capacities of exopolysaccharide derived from Pantoea alhagi NX-11.

Carbohydr Polym 2021 Jun 27;261:117872. Epub 2021 Feb 27.

Hubei Sanning Chemical Industry CO., Ltd, Yichang, 443200, China.

Pantoea alhagi exopolysaccharides (PAPS) have been shown to enhance crop resistance to abiotic stress. However, physicochemical properties and structure of PAPS have not yet been analyzed. In this study, two PAPSs, named PAPS1 and PAPS2, were isolated and purified from the P. alhagi NX-11. The results showed PAPS1 and PAPS2 were composed of glucose, galactose, glucuronic acid, glucosamine and mannose with average molecular weight of 1.326 × 10 Da and 1.959 × 10 Da, respectively. Moreover, the structure of PAPS1 and PAPS2 was investigated by FT-IR and NMR analysis. PAPS1 was identified to have the backbone structure of →4)-β-D-GlcpA-(1→2)-α-D-Galp-(1→3)-β-D-Galp-(1→3)-β-D-GlcpN- (1→3)-α-D-Galp-(1→3)-β-D-Galp-(1→. PAPS2 had the backbone structure of →4)-β-D-GlcpA-(1→2)-α-D-Galp-(1→3)-β-D-Glcp-(1→3)-β-D-GlcpN-(1→3)-α-D-Galp-(1→3)-α-D-GlcpN-(1→. In addition, PAPS1 and PAPS2 had moderate antioxidant and emulsifying capacities. Overall, the structure analysis of PAPS may point out the direction for the subsequent study of PAPS-mediated microbial and plant interactions, and further exploration of the application of PAPS.
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http://dx.doi.org/10.1016/j.carbpol.2021.117872DOI Listing
June 2021

Ozanimod for Treatment of Relapsing-Remitting Multiple Sclerosis in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Front Pharmacol 2020 20;11:589146. Epub 2020 Nov 20.

Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.

Ozanimod has been approved for use in the treatment of relapsing forms of multiple sclerosis by the United States FDA. As a novel, orally available sphingosine 1-phosphate receptor modulator, ozanimod selectively binds to S1P1 and S1P5 receptor with high affinity, minimizing safety concerns caused by S1P receptor activation. e systematically searched PUBMED, EMBASE database, and Cochrane Library database to identify randomized controlled trials (RCTs) from inception to June 28, 2020. Trials were considered eligible if they 1) were randomized clinical trials (RCTs); 2) enrolled adult participants diagnosed with Relapsing-remitting MS; 3) compared ozanimod with placebo or any other approved DMDs that evaluated in phase III or phase II clinical trials; 4) enrolled over 100 participants; 5) provided any available information for predefined primary or secondary outcomes. 2917 participants from three high-quality, multi-centered randomized clinical trials were pooled in our analysis. We found that using ozanimod was significantly associated with the reduction of the annualized relapse rate during the treatment period (RR, -0.10 [95% CI, -0.15, -0.06]). Also, the decreased number of gadolinium-enhancing lesions at the end of the trial was relative to the treatment of ozanimod (ozanimod, 0.29; control, 0.65; RR, -0.20 [95% CI, -0.34, -0.06]). Compared with patients in the control group, the number of new or enlarging T2 lesions over the treatment period decreased in patients treated with ozanimod (ozanimod, 1.82; control, 3.55; RR, -1.12 [95% CI, -1.52, -0.71]). As to the safety endpoints, patients in the ozanimod group reported a lower rate of adverse events (ozanimod, 66.03%; control, 77.07%; RR, 0.64 [95% CI, 0.43, 0.95]). Similar incidence of infection-related TEAEs was found across treatment groups (nasopharyngitis: ozanimod, 11.19%; control, 9.83%; RR, 1.10 [95% CI, 0.77-1.57]; urinary-tract infection: ozanimod, 3.81%; control, 2.97%; RR, 1.29 [95% CI, 0.83-2.00]). No case of macular edema was noted as well as second-degree, type 2, or third-degree atrioventricular block. As for the subgroup analysis, compared with 0.5 mg ozanimod, 1 mg ozanimod is related with a significant reduction of the annualized relapse rate during the treatment period (1 mg ozanimod, 0.18; 0.5 mg ozanimod, 0.24; RR, 0.05 [95% CI, 0.01, 0.09])and a decreased number of new or enlarging T2 lesions over the treatment period (1 mg ozanimod,1.58; 0.5 mg ozanimod, 2.05; RR, 0.49 [95% CI, 0.19, 0.79]). No significant difference in causing adverse events between 1 and 0.5 mg was found. Our meta-analysis found that, with favorable safety performance, the use of ozanimod as a treatment of relapsing-remitting multiple sclerosis in adults was associated with a significant reduction of the annualized relapse rate during the treatment period, decreased number of gadolinium-enhancing lesions at the end of the trial, and lowered number of new or enlarging T2 lesions over the treatment period. Ozanimod 1 mg outperformed 0.5 mg dose in efficacy without increasing the risk of adverse events.
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http://dx.doi.org/10.3389/fphar.2020.589146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919188PMC
November 2020

Thymic Squamous Cell Carcinoma: A Population-Based Surveillance, Epidemiology, and End Result Analysis.

Front Oncol 2020 22;10:592023. Epub 2020 Dec 22.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Objectives: Thymic squamous cell carcinoma (TSCC) is a rare neoplasm that has been sparsely cited in the literature. The aim of this study was to determine disease characteristics and prognostic factors of patients in a Surveillance, Epidemiology, and End Results (SEER) analysis.

Methods: Cases from 1990-2016 were retrieved from the SEER database and demographics, treatments, and survival outcomes were analyzed.

Results: The TSCC accounted for 72.4% of the thymic carcinomas and 7.2% of thymic tumors. The 276 patients (165 men) selected for analysis had a median age of 65 (24-85) years, and 201 patients were diagnosed with Masaoka-Koga stage III/IV. The median survival of TSCC was 59 months with a 49.0% 5-year OS rate, a better prognosis than lymphoepithelioma-like carcinoma (32.1%) and undifferentiated carcinoma (33.3%). Multivariate analysis revealed the Masaoka-Koga stage (p = 0.003) and surgical types (complete resection, incomplete resection, and none; p < 0.001) were determinants of survival. Complete resection had the best prognosis with a 72.7% 5-year OS rate. Chemotherapy was an independent protective factor (HR = 0.555, 95% CI 0.347-0.886; p = 0.014) though poor survival was showed in univariate analysis. And the survival benefit of chemotherapy was validated in PSM analysis (3-year OS rate was 77.7% with chemotherapy 52.8% without chemotherapy; p = 0.014).

Conclusions: TSCC was frequently diagnosed in older patients with advanced Masaoka-Koga stage and had more favorable survival than other subtypes of thymic carcinomas. Complete resection is the preferred treatment. Masaoka-Koga stage and chemotherapy had a strong association with prognosis.
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http://dx.doi.org/10.3389/fonc.2020.592023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783386PMC
December 2020

Different Targets of Monoclonal Antibodies in Neuromyelitis Optica Spectrum Disorders: A Meta-Analysis Evidenced From Randomized Controlled Trials.

Front Neurol 2020 17;11:604445. Epub 2020 Dec 17.

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.

Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune inflammatory disorder of the central nervous system, often leads to vision loss or paralysis. This meta-analysis focused on the assessment of the monoclonal antibody therapy in NMOSD and compared different targets of monoclonal antibodies with each other in terms of efficacy and safety outcomes. We searched through the databases of MEDLINE, EMBASE, Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov for randomized controlled trials (RCTs) evaluating monoclonal antibody therapy in NMOSD up to April 2020. We identified seven randomized controlled trials (RCTs), including 775 patients (monoclonal antibody group, = 485 and placebo group, = 290). Monoclonal antibody therapy decreased relapse risk (RR 0.33, 95% CI 0.21-0.52, < 0.00001), annualized relapse rate (ARR) (mean -0.28, 95% CI -0.35-0.20, < 0.00001), expanded disability status scale score (EDSS) (mean -0.19, 95% CI -0.32-0.07, = 0.002) and serious adverse events (RR 0.78, 95% CI 0.61-1.00, = 0.05). However, we did not observe any significant difference in terms of adverse events or mortality. Further, the subgroup analysis demonstrated that the anti-complement protein C5 monoclonal antibody (eculizumab) might have a lower relapse risk (RR 0.07, 95% CI 0.02-0.23, < 0.0001) in the AQP4 seropositive patients, and anti-interleukin-6 receptor monoclonal antibodies (satralizumab and tocilizumab) showed decreased EDSS score (mean -0.17, 95% CI -0.31-0.02, = 0.02) more effectively than other monoclonal antibodies. Monoclonal antibodies were effective and safe in NMOSD. Different targets of monoclonal antibodies might have their own advantages.
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http://dx.doi.org/10.3389/fneur.2020.604445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773932PMC
December 2020

A new scoring system for predicting extent of resection in medial sphenoid wing meningiomas based on three-dimensional multimodality fusion imaging.

Chin Neurosurg J 2020 Nov 2;6(1):35. Epub 2020 Nov 2.

Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China.

Background: Three-dimensional (3D) fusion imaging has been proved to be a promising neurosurgical tool for presurgical evaluation of tumor removal. We aim to develop a scoring system based on this new tool to predict the resection grade of medial sphenoid wing meningiomas (mSWM) intuitively.

Methods: We included 46 patients treated for mSWM from 2014 to 2019 to evaluate their tumors' location, volume, cavernous sinus involvement, vascular encasement, and bone invasion by 3D multimodality fusion imaging. A scoring system based on the significant parameters detected by statistical analysis was created and evaluated.

Results: The tumor volumes ranged from 0.8 cm to 171.9 cm. A total of 39 (84.8%) patients had arterial involvement. Cavernous sinus (CS) involvement was observed in 23 patients (50.0%) and bone invasion was noted in 10 patients (21.7%). Simpson I resection was achieved in 10 patients (21.7%) and Simpson II resection was achieved in 17 patients (37.0%). Fifteen patients (32.6%) underwent Simpson III resection and 4 patients (8.7%) underwent Simpson IV resections. A scoring system was created. The score ranged from 1 to 10 and the mean score of our patients was 5.3 ± 2.8. Strong positive monotonic correlation existed between the score and resection grade (R = 0.772, P < 0.001). The scoring system had good predictive capacity with an accuracy of 69.60%.

Conclusions: We described a scoring system that enabled neurosurgeons to predict extent of resection and outcomes for mSWM preoperatively with 3D multimodality fusion imaging.

Trial Registration: Retrospectively registered.
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http://dx.doi.org/10.1186/s41016-020-00214-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604967PMC
November 2020

COVID-19 Associated Ischemic Stroke and Hemorrhagic Stroke: Incidence, Potential Pathological Mechanism, and Management.

Front Neurol 2020 27;11:571996. Epub 2020 Oct 27.

Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.

The outbreak of the novel coronavirus infectious disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has rapidly spread around the world. Increasing evidence has suggested that patients with COVID-19 may present neurological symptoms, and cerebrovascular diseases are one of the most frequent comorbidities. The markedly elevated D-dimer levels in patients with acute ischemic stroke suggests that SARS-CoV-2 infection may induce an inflammatory response and trigger a hypercoagulation state, thus leading to acute ischemic stroke. Cardioembolism and atherosclerosis in patients with COVID-19 infection may also increase the risk of ischemic stroke. The reduction of the angiotensin-converting enzyme II (ACE2) caused by SARS-CoV-2 binding to the ACE2 receptor can lead to abnormally elevated blood pressure and increase the risk of hemorrhagic stroke. Additionally, the cytokine storm induced by the immune response against the viral infection increases the risk of acute stroke. The management for COVID-19 patients with stroke is not only based on the traditional guidelines, but also based on the experience and new instructions from healthcare workers worldwide who are combatting COVID-19.
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http://dx.doi.org/10.3389/fneur.2020.571996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652923PMC
October 2020

Tranexamic Acid Inhibits Hematoma Expansion in Intracerebral Hemorrhage and Traumatic Brain Injury. Does Blood Pressure Play a Potential Role? A Meta-Analysis from Randmized Controlled Trials.

J Stroke Cerebrovasc Dis 2021 Jan 7;30(1):105436. Epub 2020 Nov 7.

Department of Neurosurgery& Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China. Electronic address:

Background: Tranexamic acid (TXA) is an antifibrinolytic agent, which has shown an effect on reducing blood loss in many diseases. Many studies focus on the effect of TXA on cerebral hemorrhage, however, whether TXA can inhibit hematoma expansion is still controversial. Our meta-analysis performed a quantitative analysis to evaluate the efficacy of TXA for the hematoma expansion in spontaneous and traumatic intracranial hematoma.

Method: Pubmed (MEDLINE), Embase, and Cochrane Library were searched from January 2001 to May 2020 for randomized controlled trials (RCTs).

Result: We pooled 3102 patients from 7 RCTs to evaluate the efficacy of TXA for hematoma expansion. Hematoma expansion (HE) rate and hematoma volume (HV) change from baseline were used to analyze. We found that TXA led to a significant reduction in HE rate (P = 0.002) and HV change (P = 0.03) compared with the placebo. Patients with moderate or serious hypertension benefit more from TXA. (HE rate: P = 0.02, HV change: P = 0.04) TXA tends to have a better efficacy on HV change in intracerebral hemorrhage (ICH). (P = 0.06) CONCLUSIONS: TXA showed good efficacy for hematoma expansion in spontaneous and traumatic intracranial hemorrhage. Patients with moderate/severe hypertension and ICH may be more suitable for TXA administration in inhibiting hematoma expansion .
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105436DOI Listing
January 2021

Plant-ImputeDB: an integrated multiple plant reference panel database for genotype imputation.

Nucleic Acids Res 2021 01;49(D1):D1480-D1488

Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P.R. China.

Genotype imputation is a process that estimates missing genotypes in terms of the haplotypes and genotypes in a reference panel. It can effectively increase the density of single nucleotide polymorphisms (SNPs), boost the power to identify genetic association and promote the combination of genetic studies. However, there has been a lack of high-quality reference panels for most plants, which greatly hinders the application of genotype imputation. Here, we developed Plant-ImputeDB (http://gong_lab.hzau.edu.cn/Plant_imputeDB/), a comprehensive database with reference panels of 12 plant species for online genotype imputation, SNP and block search and free download. By integrating genotype data and whole-genome resequencing data of plants from various studies and databases, the current Plant-ImputeDB provides high-quality reference panels of 12 plant species, including ∼69.9 million SNPs from 34 244 samples. It also provides an easy-to-use online tool with the option of two popular tools specifically designed for genotype imputation. In addition, Plant-ImputeDB accepts submissions of different types of genomic variations, and provides free and open access to all publicly available data in support of related research worldwide. In general, Plant-ImputeDB may serve as an important resource for plant genotype imputation and greatly facilitate the research on plant genetic research.
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http://dx.doi.org/10.1093/nar/gkaa953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779032PMC
January 2021

Monthly versus quarterly fremanezumab for the prevention of migraine: a systemic review and meta-analysis from randomized controlled trials.

Naunyn Schmiedebergs Arch Pharmacol 2021 04 2;394(4):819-828. Epub 2020 Nov 2.

Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China.

Fremanezumab (TEV-48125) is a novel therapeutic drug for migraine prevention. Previous randomized controlled trials have proved the efficacy of fremanezumab; however, no systematic review has been performed to compare the differences between monthly and quarterly administration of fremanezumab. This meta-analysis aims to probe into the safety and efficacy of monthly fremanezumab for the prevention of migraine versus quarterly fremanezumab. We searched Pubmed, Embased, and Cochrane Library from December 1999 to December 2019 for randomized controlled trials (RCTs). Our meta-analysis finally pooled three RCTs with 1884 patients. We combined 1884 patients from three randomized controlled trials; the primary endpoint was mean monthly migraine days, from baseline to week 12. We concluded that the monthly administration of fremanezumab brought about a significant reduction in migraine days versus quarterly fremanezumab (P = 0.0008). Besides, monthly and quarterly fremanezumab have the same risk with mild and severe adverse events (P = 0.50; P = 0.39). Monthly administration of fremanezumab shows better outcomes for preventing migraines than quarterly fremanezumab and will not let to more adverse events. Patients with episodic migraine (EM) benefit more from monthly fremanezumab than patients with chronic migraine (CM).
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http://dx.doi.org/10.1007/s00210-020-02009-7DOI Listing
April 2021

Grading Characteristics of Texaco Gasification Fine Slag: Quality Distinction and Selective Distribution of Trace Elements.

ACS Omega 2020 Oct 9;5(41):26883-26893. Epub 2020 Oct 9.

School of Chemical & Environmental Engineering, China University of Mining and Technology (Beijing), D11, Xueyuan Road, Haidian District, Beijing 100083, China.

Aiming at hard-to-reuse gasification fine slag, a new process of treating gasification fine slag by classification was presented. The screening treatment was carried out based on ensuring the original particle size composition of fine slag, and it was divided into six particle size ranges as follows: +0.5, 0.3-0.5, 0.125-0.3, 0.074-0.125, 0.045-0.074, and -0.045 mm. The physical properties of different size range samples were examined by elemental analysis, X-ray diffraction, X-ray fluorescence, cold field emission scanning electron microscopy, and energy-dispersive spectrometry. The results showed that the carbon content of the median section (0.125-0.3 mm) fine slag had significant improvement compared with the other section fine slag. The carbon distribution of the +0.125 mm fine slag was concentrated, while the carbon distribution of -0.125 mm was dispersed and closely mixed with minerals. The content of trace elements Cr, Mn, Ni, V, Cd, Pb, and Mo was determined by inductively coupled plasma-mass spectrometry, and the correlation between minerals and trace elements of different particle size-graded fine slag was evaluated by Pearson correlation analysis. The results suggested that high vaporization temperature and metallic oxide forms of trace elements had a strong correlation with feldspar.
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http://dx.doi.org/10.1021/acsomega.0c04126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581257PMC
October 2020

Therapeutic Effect of Aerobic Exercise for Adolescents After Mild Traumatic Brain Injury and Sport-Related Concussion: A Meta-Analysis from Randomized Controlled Trials.

World Neurosurg 2021 02 1;146:e22-e29. Epub 2020 Oct 1.

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. Electronic address:

Background: We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials from January 1980 to April 2018 for adolescents with mild traumatic brain injury (mTBI) to explore the value of aerobic exercise in sport-related concussion (SRC) and mTBI treatment.

Methods: A meta-analysis for the postconcussion symptom scale (PCSS) score and time to recovery was performed with STATA software.

Results: We found that aerobic exercise versus usual treatment significantly decreased the PCSS score (weighted mean difference = 6.51, 95% confidence interval: 0.29, 12.72; P = 0.040), as well as the time to recovery (weighted mean difference = -3.87; 95% confidence interval: -6.50, -1.23; P = 0.004). However, aerobic exercise showed no significant improvement in immediate postconcussion assessment and cognitive testing (P = 0.471/0.129/0.648/0.800, respectively, in verbal memory, visual memory, visual motor speed, and reaction time).

Conclusions: Compared with usual treatment, aerobic exercise promoted mTBI adolescents' recovery, assessed by PCSS and time to recovery. However, aerobic exercise may not help with neurocognitive function recovery.
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http://dx.doi.org/10.1016/j.wneu.2020.09.143DOI Listing
February 2021

Animal-APAdb: a comprehensive animal alternative polyadenylation database.

Nucleic Acids Res 2021 01;49(D1):D47-D54

Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P.R. China.

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism that recognizes different polyadenylation signals on transcripts, resulting in transcripts with different lengths of 3' untranslated regions and thereby influencing a series of biological processes. Recent studies have highlighted the important roles of APA in human. However, APA profiles in other animals have not been fully recognized, and there is no database that provides comprehensive APA information for other animals except human. Here, by using the RNA sequencing data collected from public databases, we systematically characterized the APA profiles in 9244 samples of 18 species. In total, we identified 342 952 APA events with a median of 17 020 per species using the DaPars2 algorithm, and 315 691 APA events with a median of 17 953 per species using the QAPA algorithm in these 18 species, respectively. In addition, we predicted the polyadenylation sites (PAS) and motifs near PAS of these species. We further developed Animal-APAdb, a user-friendly database (http://gong_lab.hzau.edu.cn/Animal-APAdb/) for data searching, browsing and downloading. With comprehensive information of APA events in different tissues of different species, Animal-APAdb may greatly facilitate the exploration of animal APA patterns and novel mechanisms, gene expression regulation and APA evolution across tissues and species.
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http://dx.doi.org/10.1093/nar/gkaa778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779049PMC
January 2021

ROS1-fusion protein induces PD-L1 expression via MEK-ERK activation in non-small cell lung cancer.

Oncoimmunology 2020 05 6;9(1):1758003. Epub 2020 May 6.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Introduction: Despite some of the oncogenic driver mutations that have been associated with increased expression of programmed death-ligand 1 (PD-L1), the correlation between PD-L1 expression and ROS1 fusion in NSCLC cells, especially for those with Crizotinib resistance has not been fully addressed.

Materials And Methods: The expression of PD-L1 in 30 primary NSCLC tumors with/without ROS1-fusion protein was evaluated by immunohistochemical (IHC) analysis. To assess the correlation between ROS1 fusion and PD-L1 expression, we down-regulated ROS1 with RNA interference or specific inhibitor (Crizotinib) in ROS1-fusion positive NSCLC cell line HCC78; or up-regulate ROS1-fusion gene in an immortalized human bronchial epithelial cell line (HBE). Mouse xenograft models were also used to determine the effect of ROS1 expression on PD-L1 expression . Crizotinib-resistant cell line was generated for measuring the association between Crizotinib resistance and PD-L1 expression.

Results: ROS1-rearrangement in primary NSCLC tumor was significantly associated with up-regulated PD-L1 expression. PD-L1 expression was significantly up-regulated in bronchial epithelial cells after forced expression of ROS1 fusion and was eliminated when HCC78 xenograft mouse models were treated with Crizotinib. We found PD-L1 expression was modulated by MEK-ERK pathway signaling in both parental and Crizotinib-resistant NSCLC cells with ROS1 fusion.

Conclusions: The correlation between ROS1-fusion and PD-L1 overexpression suggested that PD-L1/PD-1 blockade could be the second-line treatment option for the Crizotinib-resistant NSCLC with rearrangement.
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http://dx.doi.org/10.1080/2162402X.2020.1758003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458663PMC
May 2020

Sex differences in traumatic brain injury: a multi-dimensional exploration in genes, hormones, cells, individuals, and society.

Chin Neurosurg J 2019 4;5:24. Epub 2019 Oct 4.

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Jiangsu Province, 188 Shizi Street, Suzhou, 215006 China.

Traumatic brain injury (TBI) is exceptionally prevalent in society and often imposes a massive burden on patients' families and poor prognosis. The evidence reviewed here suggests that gender can influence clinical outcomes of TBI in many aspects, ranges from patients' mortality and short-term outcome to their long-term outcome, as well as the incidence of cognitive impairment. We mainly focused on the causes and mechanisms underlying the differences between male and female after TBI, from both biological and sociological views. As it turns out that multiple factors contribute to the gender differences after TBI, not merely the perspective of gender and sex hormones. Centered on this, we discussed how female steroid hormones exert neuroprotective effects through the anti-inflammatory and antioxidant mechanism, along with the cognitive impairment and the social integration problems it caused. As to the treatment, both instant and long-term treatment of TBI requires adjustments according to gender. A further study with more focus on this topic is therefore suggested to provide better treatment options for these patients.
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http://dx.doi.org/10.1186/s41016-019-0173-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398330PMC
October 2019

Lasmiditan for Acute Treatment of Migraine in Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

CNS Drugs 2020 10;34(10):1015-1024

Department of Neurosurgery and Brain, Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.

Background: The US Food and Drug Administration has approved orally administered 100-mg and 200-mg doses of lasmiditan for the acute treatment of migraine, with or without aura. Having a unique mechanism of action, lasmiditan is the first and only Food and Drug Administration-approved serotonin 5-HT receptor agonist.

Objective: The objective of this study was to systematically evaluate the efficacy and safety of lasmiditan for the acute treatment of migraine in adult patients.

Methods: We systematically searched PUBMED, EMBASE, and Cochrane Library databases. Any relevant articles published before 3 March, 2020 were collected. Inclusion criteria were: (1) randomized clinical trials; (2) enrolled adult participants diagnosed with migraine; (3) compared lasmiditan at 100 mg or 200 mg with placebo; (4) enrolled more than 100 participants; and (5) provided any available data for predefined primary or secondary outcomes.

Results: Three high-quality, multi-centered randomized clinical trials with 4506 patients in total were included. We found that the use of lasmiditan was related to a significantly increased rate of pain freedom at 2 h post-dose with 31.60% patients achieving freedom of pain in the lasmiditan group compared with 17.55% patients in the placebo group (relative risk [RR] 1.80 [95% confidence interval (CI) 1.34-2.42]), with no significant heterogeneity. In addition, lasmiditan is reported to significantly increase the rate of absence of the most bothersome symptoms at 2 h compared with the placebo group with no significant heterogeneity (lasmiditan, 42.82%; placebo, 30.38%; RR 1.44 [95% CI 1.03-2.01], I = 0%). With regard to the safety endpoints, compared with the placebo group, participants in the lasmiditan group had a higher rate of fatigue, paresthesia, and somnolence (fatigue: lasmiditan, 1.94%; placebo, 0.24%; RR 7.96 [95% CI 0.4-158.86]; paresthesia: lasmiditan, 6.91%; placebo, 1.56%; RR 4.46 [95% CI 1.54-12.93], somnolence: lasmiditan, 5.9%; placebo, 2.15%; RR 2.76 [95% CI, 1.49-5.11]) with low heterogeneity. A subgroup analysis demonstrated that without safety differences, participants who received the 200-mg dose had a higher percentage of freedom of pain at 2 h and sustained pain relief at 2-24 h compared with the 100-mg dose (freedom of pain at 2 h: lasmiditan, 34.53%; placebo, 28.67%; RR 1.2 [95% CI 1.04-1.38]; lasmiditan, 20.62%; placebo, 16.33%; RR 1.26 [95% CI 1.19-1.34]), with low heterogeneity for both outcomes (I = 0%).

Conclusions: In this meta-analysis, the use of lasmiditan as an acute treatment for episodic migraine in adults led to a greater percentage of freedom of pain and the absence of the most bothersome symptoms at 2 h post-dose. Lasmiditan 200 mg had superior efficacy to 100-mg dose without a significantly increased risk for adverse events.
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http://dx.doi.org/10.1007/s40263-020-00753-1DOI Listing
October 2020
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