Author: "Qin Yu" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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1. Physical and in silico immunopeptidomic profiling of a cancer antigen prostatic acid phosphatase reveals targets enabling TCR isolation

Author: Mao, Zhiyuan, Nesterenko, Pavlo A, McLaughlin, Jami, Deng, Weixian, Sojo, Giselle Burton, Cheng, Donghui, Noguchi, Miyako, Chour, William, DeLucia, Diana C, Finton, Kathryn A, Qin, Yu, Obusan, Matthew B, Tran, Wendy, Wang, Liang, Bangayan, Nathanael J, Ta, Lisa, Chen, Chia-Chun, Seet, Christopher S, Crooks, Gay M, Phillips, John W, Heath, James R, Strong, Roland K, Lee, John K, Wohlschlegel, James A, and Witte, Owen N
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Research, Prevention, Vaccine Related, Immunization, Cancer, 2.1 Biological and endogenous factors, Aetiology, Acid Phosphatase, Antigens, Neoplasm, Epitopes, HLA-A Antigens, HLA-A2 Antigen, Humans, Leukocytes, Mononuclear, Neoplasms, Peptides, Receptors, Antigen, T-Cell, T cell receptor, prostate cancer, immunopeptidome, prostatic acid phosphatase, major histocompatibility complexes
Abstract: Tissue-specific antigens can serve as targets for adoptive T cell transfer-based cancer immunotherapy. Recognition of tumor by T cells is mediated by interaction between peptide-major histocompatibility complexes (pMHCs) and T cell receptors (TCRs). Revealing the identity of peptides bound to MHC is critical in discovering cognate TCRs and predicting potential toxicity. We performed multimodal immunopeptidomic analyses for human prostatic acid phosphatase (PAP), a well-recognized tissue antigen. Three physical methods, including mild acid elution, coimmunoprecipitation, and secreted MHC precipitation, were used to capture a thorough signature of PAP on HLA-A*02:01. Eleven PAP peptides that are potentially A*02:01-restricted were identified, including five predicted strong binders by NetMHCpan 4.0. Peripheral blood mononuclear cells (PBMCs) from more than 20 healthy donors were screened with the PAP peptides. Seven cognate TCRs were isolated which can recognize three distinct epitopes when expressed in PBMCs. One TCR shows reactivity toward cell lines expressing both full-length PAP and HLA-A*02:01. Our results show that a combined multimodal immunopeptidomic approach is productive in revealing target peptides and defining the cloned TCR sequences reactive with prostatic acid phosphatase epitopes.
Published: 2022

2. Droplet-based mRNA sequencing of fixed and permeabilized cells by CLInt-seq allows for antigen-specific TCR cloning

Author: Nesterenko, Pavlo A, McLaughlin, Jami, Cheng, Donghui, Bangayan, Nathanael J, Sojo, Giselle Burton, Seet, Christopher S, Qin, Yu, Mao, Zhiyuan, Obusan, Matthew B, Phillips, John W, and Witte, Owen N
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Vaccine Related, Prevention, Human Genome, HIV/AIDS, Biotechnology, Genetics, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, Underpinning research, Inflammatory and immune system, CD8-Positive T-Lymphocytes, Cloning, Molecular, Cytomegalovirus, Epitopes, Epstein-Barr Virus Infections, Forkhead Transcription Factors, Herpesvirus 4, Human, Humans, Interferon-gamma, RNA, Messenger, RNA-Seq, Receptors, Antigen, T-Cell, Single-Cell Analysis, T-Lymphocytes, Regulatory, Tumor Necrosis Factor-alpha, V(D)J Recombination, TCR, T cell receptor, T cells, single-cell sequencing, mRNA sequencing
Abstract: T cell receptors (TCRs) are generated by somatic recombination of V/D/J segments to produce up to 1015 unique sequences. Highly sensitive and specific techniques are required to isolate and identify the rare TCR sequences that respond to antigens of interest. Here, we describe the use of mRNA sequencing via cross-linker regulated intracellular phenotype (CLInt-Seq) for efficient recovery of antigen-specific TCRs in cells stained for combinations of intracellular proteins such as cytokines or transcription factors. This method enables high-throughput identification and isolation of low-frequency TCRs specific for any antigen. As a proof of principle, intracellular staining for TNFα and IFNγ identified cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-reactive TCRs with efficiencies similar to state-of-the-art peptide-MHC multimer methodology. In a separate experiment, regulatory T cells were profiled based on intracellular FOXP3 staining, demonstrating the ability to examine phenotypes based on transcription factors. We further optimized the intracellular staining conditions to use a chemically cleavable primary amine cross-linker compatible with current single-cell sequencing technology. CLInt-Seq for TNFα and IFNγ performed similarly to isolation with multimer staining for EBV-reactive TCRs. We anticipate CLInt-Seq will enable droplet-based single-cell mRNA analysis from any tissue where minor populations need to be isolated by intracellular markers.
Published: 2021

3. Epithelial membrane protein-2 (EMP2) promotes angiogenesis in glioblastoma multiforme

Author: Qin, Yu, Takahashi, Masamichi, Sheets, Kristopher, Soto, Horacio, Tsui, Jessica, Pelargos, Panayiotis, Antonios, Joseph P, Kasahara, Noriyuki, Yang, Isaac, Prins, Robert M, Braun, Jonathan, Gordon, Lynn K, and Wadehra, Madhuri
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Neurosciences, Brain Disorders, Biotechnology, Brain Cancer, Rare Diseases, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Animals, Antigens, CD34, Cell Line, Tumor, Cell Movement, Female, Gene Expression Regulation, Neoplastic, Glioblastoma, Green Fluorescent Proteins, Human Umbilical Vein Endothelial Cells, Humans, Immunoglobulin G, Membrane Glycoproteins, Mice, Mice, Nude, Microarray Analysis, Neovascularization, Pathologic, RNA, Small Interfering, Transfection, Vascular Endothelial Growth Factor A, Xenograft Model Antitumor Assays, GBM, EMP2, Angiogenesis, Immunotherapy, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and is associated with an extremely poor clinical prognosis. One pathologic hallmark of GBM is excessive vascularization with abnormal blood vessels. Extensive investigation of anti-angiogenic therapy as a treatment for recurrent GBM has been performed. Bevacizumab, a monoclonal anti-vascular endothelial growth factor A (VEGF-A), suggests a progression-free survival benefit but no overall survival benefit. Developing novel anti-angiogenic therapies are urgently needed in controlling GBM growth. In this study, we demonstrate tumor expression of epithelial membrane protein-2 (EMP2) promotes angiogenesis both in vitro and in vivo using cell lines from human GBM. Mechanistically, this pro-angiogenic effect of EMP2 was partially through upregulating tumor VEGF-A levels. A potential therapeutic effect of a systemic administration of anti-EMP2 IgG1 on intracranial xenografts was observed resulting in both significant reduction of tumor load and decreased tumor vasculature. These results suggest the potential for anti-EMP2 IgG1 as a promising novel anti-angiogenic therapy for GBM. Further investigation is needed to fully understand the molecular mechanisms how EMP2 modulates GBM pathogenesis and progression and to further characterize anti-EMP2 therapy in GBM.
Published: 2017

4. Induction of the mitochondria-mediated apoptosis in human esophageal cancer cells by DS2, a newly synthetic diterpenoid analog, is regulated by Bax and caused by generation of reactive oxygen species

Author: Ma, Yong-Cheng, Ke, Yu, Zi, Xiaolin, Zhao, Fei, Yuan, Lin, Zhu, Ying-Li, Fan, Xia-Xia, Zhao, Ning-Min, Li, Qiao-Yan, Qin, Yu-Hua, and Liu, Hong-Min
Subjects: Medical Biotechnology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Liver Disease, Complementary and Integrative Health, Cancer, Digestive Diseases, Underpinning research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, Antineoplastic Agents, Apoptosis, Cell Cycle Checkpoints, Cell Line, Tumor, Cell Proliferation, Cytochromes c, Diterpenes, Kaurane, Esophageal Neoplasms, Humans, Mitochondria, Reactive Oxygen Species, bcl-2-Associated X Protein, ent-kaurene diterpenoid derivative, esophageal squamous cell carcinoma, ROS, mitochondrion, Bax, Oncology and carcinogenesis
Abstract: Ent-kaurane diterpene compounds have attracted considerable attention in recent years due to its antitumor, antibacterial, and antiviral activities. However, the clinical development of natural kaurane diterpenes, for example, oridonin for cancer therapy has been hampered by its relatively moderate potency, limited bioavailability. Herein, we report a newly synthetic analog of natural ent-kaurane diterpene, DS2, which exhibits significantly improved activity of antiproliferation against various cancer cell lines relative to oridonin. DS2 treatment triggers the mitochondria-mediated apoptosis and cell cycle arrest in human esophageal cancer cell lines (EC9706, EC109). Interestingly, normal human esophageal epithelial cells (HEECs) and normal human liver cells (HL-7702) are both significantly more resistant to the growth inhibition by DS2 compared with esophageal cancer cells. The DS2-induced apoptosis in EC9706 cells correlated with the drop of mitochondrial membrane potential (MMP), release of cytochrome c into the cytosol and activation of caspase-9 and -3. The induction of proapoptotic proteins p21 and Bax were also observed in DS2-treated cells. The DS2-induced apoptosis was significantly attenuated by knockdown of Bax proteins. Meanwhile, the DS2 treatment caused generation of reactive oxygen species (ROS) in human esophageal cancer cells, but not in HEECs, which was attenuated by pretreatment with ROS scavenger N-acetylcysteine (NAC). More interestingly, the antioxidants pretreatment completely attenuated DS2 mediated loss of the MMP and apoptosis, as well as Bax expression and growth inhibition. In conclusion, the present study reveals that the mitochondria-mediated cell death by DS2 is associated with Bax regulation and ROS generation, and understanding the function and mechanism of DS2 will help us to design better anti-cancer drugs.
Published: 2016

5. BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas.

Author: Dai, Meng, Lu, Jian-Jun, Guo, Wei, Yu, Wendan, Wang, Qimin, Tang, Ranran, Tang, Zhipeng, Xiao, Yao, Li, Zhenglin, Sun, Wei, Sun, Xiuna, Qin, Yu, Huang, Wenlin, Deng, Wenbin, and Wu, Taihua
Subjects: BPTF, lung cancer, prognosis, tumor growth, Adenocarcinoma, Adenocarcinoma of Lung, Aged, Animals, Antigens, Nuclear, Apoptosis, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Cell Separation, Cell Survival, Female, Fibroblasts, Flow Cytometry, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Lung Neoplasms, MAP Kinase Signaling System, Male, Mice, Mice, Nude, Middle Aged, Neoplasm Transplantation, Nerve Tissue Proteins, Oligonucleotide Array Sequence Analysis, Phosphatidylinositol 3-Kinases, Prognosis, Proportional Hazards Models, RNA, Small Interfering, Signal Transduction, Transcription Factors
Abstract: BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers.
Published: 2015

6. Ku80 cooperates with CBP to promote COX-2 expression and tumor growth

Author: Xiao, Yao, Wang, Jingshu, Qin, Yu, Xuan, Yang, Jia, Yunlu, Hu, Wenxian, Yu, Wendan, Dai, Meng, Li, Zhenglin, Yi, Canhui, Zhao, Shilei, Li, Mei, Du, Sha, Cheng, Wei, Xiao, Xiangsheng, Chen, Yiming, Wu, Taihua, Meng, Songshu, Yuan, Yuhui, Liu, Quentin, Huang, Wenlin, Guo, Wei, Wang, Shusen, and Deng, Wuguo
Subjects: Cancer, Rare Diseases, Genetics, Lung, Lung Cancer, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Adenocarcinoma, Adenocarcinoma of Lung, Animals, Antigens, Nuclear, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cyclooxygenase 2, DNA-Binding Proteins, Disease Progression, Heterografts, Humans, Ku Autoantigen, Lung Neoplasms, Mice, Promoter Regions, Genetic, RNA, Small Interfering, Random Allocation, Transfection, Ku80, CBP, COX-2, lung cancer, Oncology and Carcinogenesis
Abstract: Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer.
Published: 2015

7. Epithelial Membrane Protein-2 (EMP2) Activates Src Protein and Is a Novel Therapeutic Target for Glioblastoma*

Author: Qin, Yu, Fu, Maoyong, Takahashi, Masamichi, Iwanami, Akio, Kuga, Daisuke, Rao, Rajiv G, Sudhakar, Deepthi, Huang, Tiffany, Kiyohara, Meagan, Torres, Kathleen, Dillard, Christen, Inagaki, Akihito, Kasahara, Noriyuki, Goodglick, Lee, Braun, Jonathan, Mischel, Paul S, Gordon, Lynn K, and Wadehra, Madhuri
Subjects: Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Biotechnology, Brain Disorders, Rare Diseases, Brain Cancer, Neurosciences, Cancer, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Aetiology, Development of treatments and therapeutic interventions, Animals, Cell Line, Tumor, Cell Proliferation, Enzyme Activation, Female, Focal Adhesion Kinase 1, Gene Expression Regulation, Neoplastic, Glioblastoma, Humans, Membrane Glycoproteins, Mice, Molecular Targeted Therapy, Phenotype, src-Family Kinases, Cell Invasion, Immunotherapy, Tetraspanins, Tumor Marker, EMP2, Chemical Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract: Despite recent advances in molecular classification, surgery, radiotherapy, and targeted therapies, the clinical outcome of patients with malignant brain tumors remains extremely poor. In this study, we have identified the tetraspan protein epithelial membrane protein-2 (EMP2) as a potential target for glioblastoma (GBM) killing. EMP2 had low or undetectable expression in normal brain but was highly expressed in GBM as 95% of patients showed some expression of the protein. In GBM cells, EMP2 enhanced tumor growth in vivo in part by up-regulating αvβ3 integrin surface expression, activating focal adhesion kinase and Src kinases, and promoting cell migration and invasion. Consistent with these findings, EMP2 expression significantly correlated with activated Src kinase in patient samples and promoted tumor cell invasion using intracranial mouse models. As a proof of principle to determine whether EMP2 could serve as a target for therapy, cells were treated using specific anti-EMP2 antibody reagents. These reagents were effective in killing GBM cells in vitro and in reducing tumor load in subcutaneous mouse models. These results support the role of EMP2 in the pathogenesis of GBM and suggest that anti-EMP2 treatment may be a novel therapeutic treatment.
Published: 2014

8. INFRARED THERMOGRAPHY–BASED BODY-SURFACE THERMAL INHOMOGENEITY MONITORING TO ASSESS THE SEVERITY OF HYPOPERFUSION IN CRITICALLY ILL PATIENTS

Author: Jing-Chao, Luo, Jia-Dong, Zhang, Qin-Yu, Zhao, Huan, Wang, Guo-Wei, Tu, Ming-Hao, Luo, Dan-Lei, Huang, Ji-Yang, Zhang, Wei, Lu, Fei, Gao, and Zhe, Luo
Subjects: Intensive Care Units, Thermography, Critical Illness, Area Under Curve, Emergency Medicine, Humans, Prospective Studies, Critical Care and Intensive Care Medicine
Abstract: Background: Uneven body-surface thermal distribution is a manifestation of hypoperfusion and can be quantified by infrared thermography. Our aim was to investigate whether body-surface thermal inhomogeneity could accurately evaluate the severity of patients at risk of hypoperfusion. Methods: This was a prospective cohort study in which infrared thermography images were taken from unilateral legs of critically ill patients at high risk of hypoperfusion in a cardiac surgical intensive care unit. For each patient, five body-surface thermal inhomogeneity parameters, including standard deviation (SD), kurtosis, skewness, entropy, and low-temperature area rate (LTAR), were calculated. Demographic, clinical, and thermal characteristics of deceased and living patients were compared. The risk of mortality and capillary refill time (CRT) were chosen as the primary outcome and benchmarking parameter for hypoperfusion, respectively. The area under the receiver operating characteristic curve (AUROC) was used to evaluate predictive accuracy. Results: Three hundred seventy-three patients were included, and 55 (14.7%) died during hospital stay. Of inhomogeneity parameters, SD (0.738) and LTAR (0.768) had similar AUROC to CRT (0.757) for assessing mortality risk. Besides, there was a tendency for LTAR (1%-3%-7%) and SD (0.81°C-0.88°C-0.94°C) to increase in normotensive, hypotensive, and shock patients. These thermal parameters are associated with CRT, lactate, and blood pressure. The AUROC of a combined prediction incorporating three thermal inhomogeneity parameters (SD, kurtosis, and entropy) was considerably higher at 0.866. Conclusions: Body-surface thermal inhomogeneity provided a noninvasive and accurate assessment of the severity of critically ill patients at high risk of hypoperfusion.
Published: 2022

9. Emotion Context Insensitivity is generalized in individuals with major depressive disorder but not in those with subclinical depression

Author: Ching-Wen, Sun, Chao, Yan, Qin-Yu, Lv, Ya-Jing, Wang, Wen-Yi, Xiao, Yi, Wang, Zheng-Hui, Yi, and Ji-Kun, Wang
Subjects: Depressive Disorder, Major, Psychiatry and Mental health, Clinical Psychology, Anhedonia, Reward, Depression, Emotions, Humans
Abstract: Depressed individuals experience deficits in emotional reactivity. One well-established theory is the Emotion Context Insensitivity (ECI) theory. To better understand impairments in emotional reactivity, we investigated whether the ECI theory is applicable to anticipatory, consummatory, and remembered affect, in both clinical and subclinical depression.Participants were divided into four groups: Major Depressive Disorder Group (MDD, N = 60), Control Group for MDD (ControlThe MDD group was more insensitive to both monetary reward and loss across most types of affect than was the control group. Compared with the controls, the SD group exhibited lower reactivity in anticipatory positive affect but enhanced reactivity in consummatory positive, anticipatory, and remembered negative affect.Emotional affect was evaluated by subjective ratings, which may lack objectivity. Additionally, laboratory settings and monetary rewards used in this study may cause the results less generalized to daily life and to other types of rewards.The pattern of emotional reactivity in the MDD group was partly consistent with the ECI theory, whereas the SD group showed greater arousal and instability of emotional reactions. These different patterns could facilitate the understanding of emotional reactivity and develop further treatments across the course of depression.
Published: 2022

10. Short‐chain fatty acids affect the development of inflammatory bowel disease through intestinal barrier, immunology, and microbiota: A promising therapy?

Author: Kaixin Peng, Suhong Xia, Siqi Xiao, and Qin Yu
Subjects: Inflammation, Hepatology, Microbiota, Gastroenterology, Humans, Intestinal Mucosa, Fatty Acids, Volatile, Inflammatory Bowel Diseases, Gastrointestinal Microbiome
Abstract: Intestinal metabolites are attracting increasing interest, especially more and more studies have found they are closely related to diseases. Microbial fermentation of indigestible dietary fibers in the gut produces short chain fatty acids (SCFAs) as the main product. SCFAs can exert influences on the integrity of the intestinal epithelial and mucosal barrier, immune reactions, and the diversity of microbiota in humans. Thus, alteration in SCFAs may affect inflammatory bowel disease (IBD). In IBD, SCFAs are involved in the main pathogenic process and play an important role in the development of intestinal inflammation. Although many studies have proved that pretreatment with SCFAs can effectively ameliorate inflammation in the gut, the mechanisms are not fully understood. In this review, we describe the relationship between SCFAs and IBD from the aspects of defense barrier, immune effects, and microbial alterations. We also summarize the effects of SCFAs on comorbidities in IBD via the gut-brain, gut-liver, and gut-lung axis, and we give an overview of the prospects of their clinical application. A better understanding of the relevance of SCFAs in IBD may reveal novel targets for future study.
Published: 2022

11. Cancer Incidence in Migrants in Australia: Patterns of Three Infection-Related Cancers

Author: Xue Qin Yu, Susan Yuill, Eleonora Feletto, Megan Smith, and Peter Baade
Subjects: Transients and Migrants, Oncology, Risk Factors, Epidemiology, Incidence, Australia, Humans, Uterine Cervical Neoplasms, Female
Abstract: Background: Australia provides an ideal population-base for cancer migration studies because of its multicultural society and high-quality cancer registrations. Among migrant groups there is considerable variability in the incidence of infection-related cancers; thus, the patterns of three such cancers were examined among migrant groups relative to Australian-born residents. Methods: Using national incidence data for cancers of the stomach, liver, and cervix diagnosed during 2005 to 2014, incidence rates were compared for selected migrant groups with the Australian-born population using incidence rate ratios (IRR), from a negative binomial regression model. Results: Wide variations in incidence between countries/regions of birth were observed for all three cancers (P < 0.0001). The patterns were similar for cancers of the stomach and liver, in that migrants from countries/regions with higher incidence rates maintained an increased risk in Australia, with the highest being among South American migrants (IRR = 2.35) for stomach cancer and among Vietnamese migrants (5.44) for liver cancer. In contrast, incidence rates of cervical cancer were lower for many migrant groups, with women from Southern Asia (0.39) and North Africa (0.42) having the lowest rates. The rate of cervical cancer was higher in migrants from New Zealand, Philippines, and Polynesia. Conclusions: Several Australian migrant groups were found to experience a disproportionate burden of infection-related cancers; further studies of associated risk factors may inform the design of effective interventions to mediate these disparities. Impact: By identifying these migrant groups, it is hoped that these results will motivate and inform prevention or early detection activities for these migrant groups. See related commentary Dee and Gomez, p. 1251
Published: 2022

12. Effectiveness and safety of Danmu extract syrup for acute upper respiratory tract infection in children: A real‐world, prospective cohort study

Author: Linan Zeng, Hailong Li, Chuan Zhang, Deying Kang, Guanjian Liu, Xihong Li, Lina Chen, Min Zeng, Liang Huang, Peipei Xu, Shiyin Feng, Qin Yu, Hanmin Liu, and Lingli Zhang
Subjects: China, Health Policy, Humans, Prospective Studies, General Medicine, Child, Respiratory Tract Infections, Drugs, Chinese Herbal
Abstract: To evaluate the effectiveness and safety of Danmu Extract Syrup for the treatment of acute upper respiratory tract infection (AURI) in children.In this prospective cohort study, we enrolled children with AURI in the pediatric outpatient department and emergency department of West China Second Hospital. According to the treatment, they were divided into two groups: Danmu Extract Syrup Group (Danmu Group) and Xiaoer Chiqiao Granule Group (Chiqiao Group). The primary outcome was time to symptom remission, and the secondary outcomes were defervescence time, relief time, admission rate, and adherence. We used restricted mean survival time (RMST) to quantify the treatment effects and test noninferiority for primary outcome. Propensity score matching (PSM) was used to adjust confounding. Subgroup analysis and sensitivity analysis were used to verify the robustness of results.We enrolled 1036 children with AURI, including 516 in Danmu Group and 520 in Chiqiao Group. After PSM, no significant difference was observed in the baseline characteristics of the two groups. The primary results showed that the RMST difference was -3 h (95% CI: -15.1 to 9.1) and the upper limit of the 95% CI was less than the noninferiority margin of 11 h. There was no statistical difference in the secondary outcomes except for defervescence between the two groups. The results of safety analysis showed that the incidence of adverse events occurred is 4.1% in Danmu Group, which was lower than the incidence of Chiqiao Group (6.9%).This study indicated that Danmu extract syrup is noninferiority to Chiqiao Granule for AURI in children.
Published: 2022

13. Development and validation of a nomogram for primary duodenal carcinoma: a multicenter, population-based study

Author: Qin-Yu Yang, Chao-Tao Tang, Yun-Feng Huang, Dan-Ting Shao, and Xu Shu
Subjects: Male, China, Cancer Research, Kaplan-Meier Estimate, General Medicine, Middle Aged, Prognosis, Risk Assessment, United States, Nomograms, Oncology, Duodenal Neoplasms, Lymphatic Metastasis, Humans, Female, Neoplasm Grading, Neoplasm Staging, SEER Program
Abstract: Aim: This study aimed to develop a predictive model for patients with duodenal carcinoma. Methods: Duodenal carcinoma patients from the Surveillance, Epidemiology, and End Results database (2010–2015) and the First Affiliated Hospital of Nanchang University (2010–2021) were enrolled. A nomogram was constructed according to least absolute shrinkage and selection operator regression analysis, the Akaike information criterion approach and Cox regression analysis. Results: Five independent prognostic factors were significantly associated with the prognosis of the duodenal carcinoma patients. A nomogram was constructed with a C-index in the training and validation cohorts of 0.671 (95% CI: 0.578–0.716) and 0.662 (95% CI: 0.529–0.773), respectively. Conclusion: The established nomogram model provided visualization of the risk of each prognostic factor.
Published: 2022

14. Quantifying the absolute number of cancer deaths that would be avoided if cancers were diagnosed prior to progressing to distant metastasis, New South Wales, Australia 1985‐2014

Author: Xue Qin Yu, Paramita Dasgupta, and Peter Baade
Subjects: Adult, Aged, 80 and over, Cancer Research, Adolescent, Australia, Middle Aged, Cohort Studies, Young Adult, Oncology, Neoplasms, Humans, New South Wales, Aged, Neoplasm Staging
Abstract: Our study measures the impact of diagnosing cancers early before they metastasise on reducing the burden of cancer death. A cohort of 716 501 people aged 15 to 89 years diagnosed with a solid cancer in New South Wales, Australia, during 1985 to 2014 were followed-up to December 2015. Crude probabilities of cancer death by stage at diagnosis were calculated for all solid cancers combined and five individual cancers using flexible parametric relative survival models. These probabilities were used to estimate the number of avoided cancer deaths within 10 years of diagnosis in three 10-year diagnostic periods if all cases with known distant stage were instead diagnosed at an earlier stage. Cancers are known to be diagnosed at distant stage composed ~16% of all solid cancers diagnosed during 2005 to 2014. Assuming all these cases were instead diagnosed at regional stage, an annual average of 2064 cancer deaths would have been potentially avoided within 10 years of diagnosis. This equated to ~21% of modelled observed deaths. Alternatively, if half of all known distant cases diagnosed during 2005 to 2014 were diagnosed as regional and half as localised, the average number of deaths avoided per year would increase to 2677 (~28%). Estimates varied by diagnostic period, sex and cancer type, reflecting both the different stage distributions for the cancer types, and the respective survival differences between cancer stages. While prevention is the most effective pillar of cancer control, these findings quantify the potential benefits of diagnosing all cancer types when they are less advanced to reduce the burden of cancer mortality.
Published: 2022

15. Differential Survival Outcomes Between De Novo and Secondary Acute Promyelocytic Leukemia: An Updated Population-based study

Author: Yuan-Yuan Liu, Mengyu Jia, Yi Tao, Ya-Qin Yu, and Lu Gao
Subjects: Male, Acute promyelocytic leukemia, Cancer Research, medicine.medical_specialty, Prostate cancer, Breast cancer, Leukemia, Promyelocytic, Acute, immune system diseases, Internal medicine, medicine, Surveillance, Epidemiology, and End Results, Humans, neoplasms, Aged, Proportional hazards model, business.industry, Mortality rate, Hematology, Middle Aged, medicine.disease, Survival Analysis, Minimal residual disease, Treatment Outcome, Oncology, Marital status, business, SEER Program
Abstract: Background Whether the characteristics and outcome of secondary acute promyelocytic leukemia (s-APL) are similar to de no APL (dn-APL) remains unknown. Patients and Methods Using the SEER database, we identified 3877 patients with APL diagnosed from 2000 to 2014, including 465 s-APL and 3412 dn-APL. Results Compared with dn-APL, s-APL werecharacterized by older median age, and a higher early mortality rate. Multivariate Cox model showed s-APL, older age, earlier year of diagnosis, and male gender were independently associated with worse survival. Notably, s-APL had a significantly inferior survival regardless of gender, race, marital status, and year of diagnosis. However, the difference between the 2 cohorts was only evident in younger patients (≤ 65 years) but was lost in older patients (> 65 years). Additionally, the majority of index cancer type was breast and prostate in female and male s-APL, respectively. Latency Conclusions Inferior survival of s-APL points to the need for treatment improvement.
Published: 2022

16. MDA5 disease variant M854K prevents ATP-dependent structural discrimination of viral and cellular RNA

Author: Qin Yu, Yorgo Modis, Alba Herrero del Valle, Rahul Singh, Yu, Qin [0000-0001-9265-632X], Herrero Del Valle, Alba [0000-0001-8153-6146], Singh, Rahul [0000-0001-8397-0202], Modis, Yorgo [0000-0002-6084-0429], Apollo - University of Cambridge Repository, and Herrero del Valle, Alba [0000-0001-8153-6146]
Subjects: Models, Molecular, 82/29, Interferon-Induced Helicase, IFIH1, Protein Conformation, ATPase, viruses, General Physics and Astronomy, medicine.disease_cause, 631/45/173, 631/45/535/1258/1259, Adenosine Triphosphate, 0302 clinical medicine, ATP hydrolysis, Interferon, Adenosine Triphosphatases, 0303 health sciences, Mutation, Multidisciplinary, biology, Chemistry, 631/45/500, article, food and beverages, MDA5, Chronic inflammation, 3. Good health, Cell biology, RNA silencing, Enzyme mechanisms, RNA, Viral, Protein Binding, medicine.drug, Science, Allosteric regulation, Mutation, Missense, General Biochemistry, Genetics and Molecular Biology, 96/95, 03 medical and health sciences, medicine, Humans, 82/83, RNA, Double-Stranded, 030304 developmental biology, Inflammation, 631/250/262/2106/2518, Cryoelectron Microscopy, 101/28, fungi, RNA, General Chemistry, Immunity, Innate, HEK293 Cells, 631/250/256/2515, RIG-I-like receptors, biology.protein, Nucleic Acid Conformation, 030217 neurology & neurosurgery
Abstract: Our innate immune responses to viral RNA are vital defenses. Long cytosolic double-stranded RNA (dsRNA) is recognized by MDA5. The ATPase activity of MDA5 contributes to its dsRNA binding selectivity. Mutations that reduce RNA selectivity can cause autoinflammatory disease. Here, we show how the disease-associated MDA5 variant M854K perturbs MDA5-dsRNA recognition. M854K MDA5 constitutively activates interferon signaling in the absence of exogenous RNA. M854K MDA5 lacks ATPase activity and binds more stably to synthetic Alu:Alu dsRNA. CryoEM structures of MDA5-dsRNA filaments at different stages of ATP hydrolysis show that the K854 sidechain forms polar bonds that constrain the conformation of MDA5 subdomains, disrupting key steps in the ATPase cycle- RNA footprint expansion and helical twist modulation. The M854K mutation inhibits ATP-dependent RNA proofreading via an allosteric mechanism, allowing MDA5 to form signaling complexes on endogenous RNAs. This work provides insights on how MDA5 recognizes dsRNA in health and disease., MDA5 is the primary immune sensor for SARS-CoV-2 and many other viruses. Mutations in MDA5 can cause disease. Here the authors employ CryoEM and biochemical methods to show how steric constraints cause MDA5 to misrecognize endogenous RNA as viral RNA.
Published: 2021

17. Ultrasensitive detection of multiple cancer biomarkers by a triple cascade amplification strategy in combination with single particle inductively coupled plasma mass spectrometry

Author: Yan-Li, Zhu, Ji-Kai, Wang, Zeng-Ping, Chen, Yu-Jie, Zhao, and Ru-Qin, Yu
Subjects: Exonucleases, Neoplasms, Biomarkers, Tumor, Humans, Biosensing Techniques, alpha-Fetoproteins, DNA, Mass Spectrometry, Carcinoembryonic Antigen, Analytical Chemistry
Abstract: A versatile triple cascade amplification strategy was developed for ultrasensitive simultaneous detection of multiple cancer biomarkers using single particle inductively coupled plasma mass spectrometry (spICP-MS). The triple cascade amplification strategy consisted of an enhanced RecJ
Published: 2022

18. Management of granulomatous lobular mastitis

Author: Qian-Qian Yuan, Shu-Yuan Xiao, Omar Farouk, Yu-Tang Du, Fereshte Sheybani, Qing Ting Tan, Sami Akbulut, Kenan Cetin, Afsaneh Alikhassi, Rami Jalal Yaghan, Irmak Durur-Subasi, Fatih Altintoprak, Tae Ik Eom, Fatih Alper, Mustafa Hasbahceci, David Martínez-Ramos, Pelin Seher Oztekin, Ava Kwong, Cedric W. Pluguez-Turull, Kirstyn E. Brownson, Shirish Chandanwale, Mehran Habibi, Liu-Yi Lan, Rui Zhou, Xian-Tao Zeng, Jiao Bai, Jun-Wen Bai, Qiong-Rong Chen, Xing Chen, Xiao-Ming Zha, Wen-Jie Dai, Zhi-Jun Dai, Qin-Yu Feng, Qing-Jun Gao, Run-Fang Gao, Bao-San Han, Jin-Xuan Hou, Wei Hou, Hai-Ying Liao, Hong Luo, Zheng-Ren Liu, Jing-Hua Lu, Bin Luo, Xiao-Peng Ma, Jun Qian, Jian-Yong Qin, Wei Wei, Gang Wei, Li-Ying Xu, Hui-Chao Xue, Hua-Wei Yang, Wei-Ge Yang, Chao-Jie Zhang, Fan Zhang, Guan-Xin Zhang, Shao-Kun Zhang, Shu-Qun Zhang, Ye-Qiang Zhang, Yue-Peng Zhang, Sheng-Chu Zhang, Dai-Wei Zhao, Xiang-Min Zheng, Le-Wei Zheng, Gao-Ran Xu, Wen-Bo Zhou, Gao-Song Wu, and Graduate School
Subjects: Treatment, Consensus, Recurrence, Granulomatous lobular mastitis, Granulomatous mastitis, Diagnosis, Humans, Female, General Medicine, Breast, Idiopathic granulomatous mastitis, human activities
Abstract: Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM. Improving the Ability of Diagnosis and Treatment of Difficult Diseases
Published: 2022

19. Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: a 12-week randomized, double-blind, placebo-controlled trial

Author: Ming-Huan, Zhu, Zhen-Jing, Liu, Qiong-Yue, Hu, Jia-Yu, Yang, Ying, Jin, Na, Zhu, Ying, Huang, Dian-Hong, Shi, Min-Jia, Liu, Hong-Yang, Tan, Lei, Zhao, Qin-Yu, Lv, Zheng-Hui, Yi, Feng-Chun, Wu, and Ze-Zhi, Li
Subjects: Cognition, Schizophrenia, Humans, General Medicine, Amisulpride, Sulpiride, Clozapine, Schizophrenia, Treatment-Resistant, Antipsychotic Agents
Abstract: Background Although clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purpose of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia (CTRS) patients. Methods A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride (amisulpride group) or clozapine plus placebo (placebo group). Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements, and electrocardiograms (ECG) were performed at baseline, at week 6, and week 12. Results Compared with the placebo group, amisulpride group had a lower PANSS total score, positive subscore, and general psychopathology subscore at week 6 and week 12 (PBonferroni PBonferroni P = 0.04), lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group (PBonferroni Conclusion This study indicates that amisulpride augmentation therapy has important clinical significance for treating CTRS to improve clinical symptoms and cognitive function with tolerability and safety. Trial registration Clinicaltrials.gov identifier- NCT03652974. Registered August 31, 2018, https://clinicaltrials.gov/ct2/show/NCT03652974
Published: 2022

20. MSCs enhances the protective effects of valsartan on attenuating the doxorubicin-induced myocardial injury via AngII/NOX/ROS/MAPK signaling pathway

Author: Qinfu Wang, Wencheng Tu, Qin Yu, Dong Cheng, Hainiang Liu, Ning Zhu, Haoren Wang, Weiyi Fang, and Libo Chen
Subjects: Aging, Cell Survival, MAP Kinase Signaling System, doxorubicin, valsartan, Downregulation and upregulation, polycyclic compounds, Animals, Humans, Myocytes, Cardiac, MTT assay, Viability assay, chemistry.chemical_classification, mesenchymal stem cells, Reactive oxygen species, Antibiotics, Antineoplastic, NADPH oxidase, biology, Chemistry, Mesenchymal stem cell, NOX4, ROS, Cell Biology, Cardiotoxicity, carbohydrates (lipids), Oxidative Stress, Apoptosis, MAPK signaling pathway, cardiovascular system, biology.protein, Cancer research, Reactive Oxygen Species, Signal Transduction, Research Paper
Abstract: Objective: To verify if AngII/NOX/ROS/MAPK signaling pathway is involved in Doxorubicin (DOX)-induced myocardial injury and if mesenchymal stem cells (MSCs) could enhance the protective effects of valsartan (Val) on attenuating DOX-induced injury in vitro. Methods: Reactive oxygen species (ROS) formation and the protein expression of AT1R, NOX2, NOX4, caspase-3, caspase-9 and MAPK signaling were assessed in H9c2 cardiomyocytes exposed to DOX for 24 h in the absence or presence of Val, NADPH oxidase inhibitor DPI or knockdown and overexpression of NADPH oxidase subunit: NOX2 and NOX4, co-culture with MSCs, respectively. Finally, MTT assay was used to determine the cell viability of H9c2 cells, MDA-MB-231 breast cancer cells and A549 pulmonary cancer cells under Val, DOX and Val+ DOX treatments. Results: DOX increased ROS formation and upregulated proteins expression of AT1R, NOX2, NOX4, caspase-3, caspase-9 and MAPK signaling including p-p38, p-JNK, p-ERK in H9c2 cells. These effects could be attenuated by Val, DPI, NOX2 siRNA and NOX4 siRNA. Meanwhile, overexpression of NOX2 and NOX4 could significantly increase DOX-induced ROS formation and further upregulate apoptotic protein expressions and protein expressions of MAPK signaling. MSCs on top of Val further enhanced the protective effects of Val on reducing the DOX-induced ROS formation and downregulating the expression of apoptotic proteins and MAPK signaling as compared with Val alone in DOX-treated H9c2 cells. Simultaneous Val and DOX treatment did not affect cell viability of DOX-treated MDA-MB-231 breast cancer cells or A549 pulmonary cancer cells but significantly improved cell viability of DOX-treated H9c2 cardiomyocytes. Conclusions: AT1R/NOX/ROS/MAPK signaling pathway is involved in DOX-induced cardiotoxicity. Val treatment significantly attenuated DOX-induced cardiotoxicity, without affecting the anti-tumor effect of DOX. MSCs enhance the protective effects of Val on reducing the DOX-induced toxicity in H9c2 cells.
Published: 2021

21. Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial

Author: Jun Liu, Dan-Dan Li, Wei Dong, Yu-Qi Liu, Yang Wu, Da-Xuan Tang, Fu-Chun Zhang, Meng Qiu, Qi Hua, Jing-Yu He, Jun Li, Bai Du, Ting-Hai Du, Lin-Lin Niu, Xue-Jun Jiang, Bo Cui, Jiang-Bin Chen, Yang-Gan Wang, Hai-Rong Wang, Qin Yu, Jing He, Yi-Lin Mao, Xiao-Fang Bin, Yue Deng, Yu-Dan Tian, Qing-Hua Han, Da-Jin Liu, Li-Qin Duan, Ming-Jun Zhao, Cui-Ying Zhang, Hai-Ying Dai, Ze-Hua Li, Ying Xiao, You-Zhi Hu, Xiao-Yu Huang, Kun Xing, Xin Jiang, Chao-Feng Liu, Jing An, Feng-Chun Li, Tao Tao, Jin-Fa Jiang, Ying Yang, Yao-Rong Dong, Lei Zhang, Guang Fu, Ying Li, Shu-Wei Huang, Li-Ping Dou, Lan-Jun Sun, Ying-Qiang Zhao, Jie Li, Yun Xia, Fan Liu, Wen-Jin He, Jian-Cong Tan, Yang Lin, Ya-Bin Zhou, Jian-Fei Yang, Guo-Qing Ma, Hui-Jun Chen, He-Ping Liu, Zong-Wu Liu, Jian-Xiong Liu, Xiao-Jia Luo, Xiao-Hong Bin, Ya-Nan Yu, Hai-Xia Dang, Bing Li, Fei Teng, Wang-Min Qiao, Xiao-Long Zhu, Bing-Wei Chen, Qi-Guang Chen, Chun-Ti Shen, Yong-Yan Wang, Yun-Dai Chen, and Zhong Wang
Subjects: Drug, Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, QH301-705.5, media_common.quotation_subject, Population, Cardiology, Drug development, Placebo, Article, law.invention, Injections, Angina, Young Adult, Clinical trials, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Target identification, Genetics, medicine, Humans, Angina, Stable, Biology (General), education, Adverse effect, media_common, Aged, education.field_of_study, business.industry, Cardiovascular Agents, Middle Aged, medicine.disease, Confidence interval, Clinical trial, Treatment Outcome, Gene Expression Regulation, Medicine, Female, business, Drugs, Chinese Herbal
Abstract: It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).
Published: 2021

22. MKRN1 Ubiquitylates p21 to Protect against Intermittent Hypoxia-Induced Myocardial Apoptosis

Author: Hui Yang, Yan Zhao, Xue Bai, Qin Yu, Jiayuan Pu, and Ying Jin
Subjects: rho GTP-Binding Proteins, Aging, Article Subject, Apoptosis, Nerve Tissue Proteins, Biochemistry, Rats, Sprague-Dawley, Mice, Downregulation and upregulation, Western blot, Ubiquitin, medicine, Animals, Humans, chemistry.chemical_classification, Reactive oxygen species, TUNEL assay, QH573-671, medicine.diagnostic_test, biology, Chemistry, Myocardium, Ubiquitination, Intermittent hypoxia, Cell Biology, General Medicine, Cell Hypoxia, Rats, Cell biology, Ribonucleoproteins, biology.protein, Immunohistochemistry, Cytology, Research Article
Abstract: Although chronic intermittent hypoxia- (IH-) induced myocardial apoptosis is an established pathophysiological process resulting in a poor prognosis for patients with obstructive sleep apnea syndrome, its underlying mechanism remains unclear. This study is aimed at exploring the role of makorin ring finger protein 1 (MKRN1) in IH-induced myocardial apoptosis and elucidating its molecular activity. First, the GSE2271 dataset was downloaded from the Gene Expression Omnibus database to identify the differentially expressed genes. Then, an SD rat model of IH, together with rat cardiomyocyte H9C2 and human cardiomyocyte AC16 IH models, was constructed. TUNEL, Western blot, and immunohistochemistry assays were used to detect cell apoptosis. Dihydroethidium staining was conducted to analyze the concentration of reactive oxygen species. In addition, RT-qPCR, Western blot, and immunohistochemistry were performed to measure the expression levels of MKRN1 and p21. The direct interaction between MKRN1 and p21 was determined using coimmunoprecipitation and ubiquitination analysis. MKRN1 expression was found to be downregulated in IH rat myocardial tissues as well as in H9C2 and AC16 cells. Upregulated expression of MKRN1 in H9C2 and AC16 cells alleviated the IH-induced reactive oxygen species production and cell apoptosis. Mechanistically, MKRN1 promoted p21 protein ubiquitination and the proteasome pathway degradation to negatively regulate p21 expression. Thus, MKRN1 regulates p21 ubiquitination to prevent IH-induced myocardial apoptosis.
Published: 2021

23. Monitoring frequency of interferon gamma release assay for tuberculosis surveillance following infliximab therapy in patients with<scp>Crohn's</scp>disease

Author: Qin-Yu Yang, Lin Zhang, Cheng-Dang Wang, Yi-Juan Liu, and Xu Ye
Subjects: History of tuberculosis, medicine.medical_specialty, Crohn's disease, Tuberculosis, Latent tuberculosis, biology, Tuberculin Test, business.industry, Gastroenterology, Interferon gamma release assay, medicine.disease, biology.organism_classification, Inflammatory bowel disease, Infliximab, Mycobacterium tuberculosis, Interferon-gamma, Crohn Disease, Internal medicine, medicine, Humans, business, Retrospective Studies, medicine.drug
Abstract: OBJECTIVE To characterize the pattern of positive conversion of interferon gamma release assay (IGRA) in patients with Crohn's disease (CD) during infliximab therapy in China, which has a high burden of tuberculosis. METHODS Eligible patients with CD who received serial IGRA screening during infliximab therapy from January 2015 to March 2020 were retrospectively included. The positive conversion rate of IGRA and the risk of subsequent tuberculosis of the patients were analyzed. RESULTS A total of 128 patients with CD were included, and the median time from the initiation of IFX treatment to positive conversion or the last follow-up test of IGRA was 43.6 weeks. At baseline 3.9% of the patients were positive for IGRA and received prophylactic anti-tuberculosis treatment. In the other 123 patients with negative IGRA at baseline, 6.5% had IGRA positive conversion during infliximab treatment, and one (12.5%) who was exposed to Mycobacterium tuberculosis was diagnosed as having active tuberculosis. The conversion rate at 40 weeks, 2 years and 3 years after treatment were 10.0% (6/60), 2.2% (1/46) and 5.9% (1/17), respectively. Age, sex, history of smoking and alcohol consumption, disease severity (Crohn's disease activity index score) and immunosuppressive therapy were not significantly associated with latent tuberculosis test conversion. CONCLUSIONS Positive conversion of IGRA occurs early during treatment with infliximab for CD and the monitoring frequency of IGRA should be appropriately increased at the early stage of treatment. Physicians should pay attention to patient's history of tuberculosis exposure and carry out surveillance in a timely fashion.
Published: 2021

24. A Multi-Center Study on the Negative Psychological Impact and Associated Factors in Chinese Healthcare Workers 1 Year After the COVID-19 Initial Outbreak

Author: Maria Jose Gonzalez Mendez, Li Ma, Ruben Alvarado, Jorge Ramirez, Kun-Peng Xu, Hui-Fang Xu, Shao-Kai Zhang, Mohamed S. Bangura, Ying Yang, Yan-Qin Yu, Xi Zhang, Wenjun Wang, Xiaofen Gu, Li Li, Didier Sama Salah, and Youlin Qiao
Subjects: China, Cross-Sectional Studies, Health (social science), Health Personnel, Public Health, Environmental and Occupational Health, COVID-19, Humans, Female, Pandemics, Disease Outbreaks
Abstract: Objectives: The study aimed at analyzing the prevalence of five psychological outcomes (depression, anxiety, stress, post-traumatic stress disorder (PTSD), and suicidal ideation) among Chinese healthcare workers (HCWs), and measured the total possible negative psychological impact 1 year after the COVID-19 initial outbreak.Methods: A cross-sectional nationwide multi-center study was performed between November 2020 and March 2021 in China. A self-report questionnaire was applied, and three psychological scales were used. Binary logistic regression was performed to analyze the risk factors associated with each psychological outcome.Results: The findings demonstrated that the COVID-19 pandemic had a negative psychological impact on HCWs, which was still evident 1 year after the initial outbreak. Nurses showed higher depression and anxiety than other HCWs. Female gender, passive coping, long working hours, having a chronic disease, and experiencing violence, among other factors, were all risk factors for psychological impairment.Conclusion: Developing and promoting programs to improve mental health among HCWs, and identifying those who might need psychological support is still relevant 1 year after the initial outbreak.
Published: 2022
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25. Intestinal microbiota modulates pancreatic carcinogenesis through intratumoral natural killer cells

Author: Qin Yu, Rachel C. Newsome, Mark Beveridge, Maria C. Hernandez, Raad Z. Gharaibeh, Christian Jobin, and Ryan M. Thomas
Subjects: Homeodomain Proteins, Microbiology (medical), Carcinogenesis, Gastroenterology, Microbiology, Gastrointestinal Microbiome, Killer Cells, Natural, Mice, Inbred C57BL, Pancreatic Neoplasms, Mice, Infectious Diseases, Animals, Humans, Carcinoma, Pancreatic Ductal
Abstract: Preclinical data demonstrate that the gut microbiota can promote pancreatic ductal adenocarcinoma (PDAC), but mechanisms remain unclear. We hypothesized that intestinal microbiota alters anti-tumor innate immunity response to facilitate PDAC progression. Human PDAC L3.6pl cells were heterotopically implanted into
Published: 2022

26. Total RNA sequencing of

Author: Jing, Wang, Qin-Yu, Gou, Geng-Yan, Luo, Xin, Hou, Guodong, Liang, and Mang, Shi
Subjects: Mammals, Phlebovirus, Bacteria, Sequence Analysis, RNA, Phlebotomus, Animals, Eukaryota, Humans, RNA, Psychodidae
Published: 2022

27. The presence of living endometrial cells in ovarian endometriotic cyst fluid may contribute to the recurrence of endometriosis after surgical excision of endometriomas

Author: Xinxin, Xu, Yichen, Chen, Qin, Yu, Jianzhang, Wang, Ping, Xu, Libo, Zhu, Qiong, Xu, Jing, Zhang, Shuling, Cui, Kewen, Yu, Tiantian, Li, Xinyue, Guo, and Xinmei, Zhang
Subjects: Endometrium, Oncology, Cysts, Gene Expression Profiling, Endometriosis, Animals, Humans, Obstetrics and Gynecology, Female, Laparoscopy
Abstract: Background Many factors can affect the recurrence of endometriosis after surgery, however, whether endometriotic cyst fluid contributes to endometriosis recurrence after surgical excision of ovarian endometriomas remains unclear. The objective of this study was to determine the presence of endometrial cells in ovarian endometriosis cyst fluid and the potential differences between these cells and those in the cyst wall. Methods Samples of cyst fluid (n = 39) and drainage fluid (n = 14) were collected from patients with ovarian endometriomas undergoing laparoscopic surgery. Drainage fluid from 14 patients without endometriosis was used as a control. The presence of endometrial cells in cyst fluid and drainage fluid was determined by cell culture in vitro and immunostaining. In addition, cyst fluid endometrial fragments and viscosity were analysed by transcriptome sequencing analysis and apparent diffusion coefficients, respectively. An animal model was used to confirm the ability of endometrial cells in cyst fluid to form new lesions. Results We found endometrium-like tissues in 71.8% (28/39) of cyst fluid and 71.4% (10/14) of drainage fluid samples by histopathological examination, and the presence of endometrioid tissue in cyst fluid was related to the viscosity of the cyst fluid. The living endometrial cells in cyst fluid and drainage fluid were confirmed by cell culture in vitro and immunostaining. Moreover, the adhesion ability of endometrial fragments in cyst fluid was significantly higher than that of ectopic tissues in the cyst wall (P Conclusions The existence of living endometrial cells with high adhesion ability in ovarian endometriotic cyst fluid may contribute to the recurrence of endometriosis after surgical excision of endometriomas due to cyst fluid outflow during the surgical procedure.
Published: 2022

28. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author: Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly 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Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider 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Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, 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Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020

29. Bioequivalence of 2 Aripiprazole Orally Disintegrating Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions

Author: Jin Xiang, Mao-Zhi Liang, Xueyan Wang, Linchuan Liao, Yuqi Zhu, Shiqing Shu, Songfan Li, Qin Yu, Nan Xu, Rui Yan, and Feng Nan
Subjects: Male, China, Drug Compounding, Aripiprazole, Cmax, Administration, Oral, Pharmaceutical Science, Bioequivalence, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Animal science, Pharmacokinetics, medicine, Humans, Pharmacology (medical), Cross-Over Studies, business.industry, Fasting, Middle Aged, Crossover study, Healthy Volunteers, Confidence interval, Therapeutic Equivalency, Tolerability, Area Under Curve, 030220 oncology & carcinogenesis, Female, Geometric mean, business, Tablets, medicine.drug
Abstract: To assess the bioequivalence of 2 formulations of aripiprazole orally disintegrating tablets and to monitor their safety and tolerability in Chinese subjects, a single-site, open-label, randomized, 2-preparation, single-dose, 2-period crossover design was conducted. All 60 subjects were randomly divided into the fasting group and the fed group. Blood samples were collected at scheduled times after a single oral dose of orodispersible tablets containing 10 mg of aripiprazole. In the fasting state, the geometric mean ratios (90% confidence intervals [CIs]) of the test/reference formulation were 92.22%-100.20% for the area under the concentration-time curve (AUC) from time zero to the last measured concentration (AUC0-t ), 91.73%-100.14% for the AUC from administration to infinite time (AUC0-∞ ), and 98.52%-112.52% for the maximum plasma concentration (Cmax ). In the fed state, AUC0-t , AUC0-∞ , and Cmax were 92.23%-100.20%, 91.73%-100.14%, and 95.91%-105.13%, respectively. The 90%CIs of the test/reference AUC ratio and Cmax ratio were within the acceptance range of 80.00%-125.00% for bioequivalence. Neither the maximum peak plasma concentration (tmax ) nor the terminal elimination half-life (t1/2 ) showed any significant difference. No serious adverse events) were encountered during the study. The test and reference formulations were bioequivalent under both fasting and fed conditions and were found to be safe and tolerated.
Published: 2021

30. Measuring the global, regional, and national burden of multiple myeloma from 1990 to 2019

Author: Qin Yu, Guoqing Wei, Kejia Hu, Yongxian Hu, He Huang, Linghui Zhou, Linqin Wang, and Yue Huang
Subjects: Burden of disease, Male, Cancer Research, Population ageing, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Age Distribution, Risk Factors, Multiple myeloma, Disability adjusted life-years, Genetics, medicine, Humans, 030212 general & internal medicine, Mortality, Sex Distribution, RC254-282, Aged, Aged, 80 and over, business.industry, Incidence (epidemiology), Mortality rate, Research, Incidence, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, medicine.disease, Global burden of disease, Death, Oncology, 030220 oncology & carcinogenesis, Western europe, Female, Quality-Adjusted Life Years, business, Demography
Abstract: Background Multiple myeloma (MM) is a major health concern. Understanding the different burden and tendency of MM in different regions is crucial for formulating specific local strategies. Therefore, we evaluated the epidemiologic patterns and explored the risk factors for MM death. Methods Data on MM were collected from the 2019 Global Burden of Disease study. We used incidence, mortality, and disability adjusted life-years to estimate the global, regional, and national burden of MM. Results In 2019, there were 155,688 (95% UI, 136,585 – 172,577) MM cases worldwide, of which 84,516 (54.3%, 70,924 – 94,910) were of men. The age-standardized incidence rate (ASIR) was 1.72/100,000 persons (95% UI, 1.59–1.93) in 1990 and 1.92/100,000 persons (95% UI, 1.68–2.12) in 2019. The number of MM deaths increased 1.19-fold from 51,862 (95% UI, 47,710–58,979) in 1990 to 113,474 (95% UI, 99,527 – 121,735) in 2019; the age-standardized death rate (ASDR) was 1.42/100,000 persons (95% UI, 1.24–1.52) in 2019. In recent 15 years, ASDR showed a steady tendency for men, and a downward tendency for women. Countries with high social-demographic indexes exhibited a higher ASIR and ASDR. Australasia, North America, and Western Europe had the highest ASIR and ASDR, with 46.3% incident cases and 41.8% death cases. Monaco had the highest ASIR and ASDR, which was almost half as high as the second highest country Barbados. In addition, United Arab Emirates and Qatar had the largest growth multiple in ASIR and ASDR, which was twice the third country Djibouti. Conclusions Globally, incident and death MM cases have more than doubled over the past 30 years. The increasing global burden may continue with population aging, whereas mortality may continue to decrease with the progression of medical technology. The global burden pattern of MM was diverse, therefore specific local strategies based on different burden patterns for MM are necessary.
Published: 2021

31. Solid fuel, secondhand smoke, and lung cancer mortality: a prospective cohort of 323,794 Chinese never-smokers

Author: Elvin S. Cheng, Ka Hung Chan, Marianne Weber, Julia Steinberg, Jane Young, Karen Canfell, and Xue Qin Yu
Subjects: Adult, Cohort Studies, Pulmonary and Respiratory Medicine, China, Smokers, Lung Neoplasms, Risk Factors, Humans, Tobacco Smoke Pollution, Prospective Studies, Critical Care and Intensive Care Medicine
Abstract: Rationale: Household air pollution and secondhand tobacco smoke are known carcinogens for lung cancer, but large-scale estimates of the relationship with lung cancer mortality are lacking. Objectives: Using the large-scale cohort China Kadoorie Biobank, we prospectively investigated associations between these two risk factors and lung cancer death among never-smokers. Methods: The Biobank recruited 512,715 adults aged 30–79 years from 10 regions in China during 2004–2008. Self-reported never-smoking participants were followed up to December 31, 2016, with linkage to mortality data. Total duration of exposure to household air pollution was calculated from self-reported domestic solid fuel use. Exposure to secondhand tobacco smoke was ascertained using exposure at home and/or other places. Hazard ratios and 95% confidence intervals for associations between these two exposures and lung cancer death were estimated using Cox regression, adjusting for key confounders. Measurements and Main Results: There were 979 lung cancer deaths among 323,794 never-smoking participants without a previous cancer diagnosis during 10.2 years of follow-up. There was a log-linear positive association between exposure to household air pollution and lung cancer death, with a 4% increased risk per 5-year increment of exposure (hazard ratio = 1.04; 95% confidence interval = 1.01–1.06; P trend = 0.0034), and participants with 40.1–50.0 years of exposure had the highest risk compared with the never-exposed (hazard ratio = 1.53; 95% confidence interval = 1.13–2.07). The association was largely consistent across various subgroups. No significant association was found between secondhand smoke and lung cancer death. Conclusions: This cohort study provides new prospective evidence suggesting that domestic solid fuel use is associated with lung cancer death among never-smokers.
Published: 2022

32. Species discrimination in Schima (Theaceae): Next-generation super-barcodes meet evolutionary complexity

Author: Xiang‐Qin Yu, Yin‐Zi Jiang, Ryan A. Folk, Jian‐Li Zhao, Chao‐Nan Fu, Liang Fang, Hua Peng, Jun‐Bo Yang, and Shi‐Xiong Yang
Subjects: DNA, Plant, Species Specificity, Theaceae, Genome, Plastid, Genetics, DNA Barcoding, Taxonomic, Humans, Sequence Analysis, DNA, Plants, DNA, Ribosomal, Ecology, Evolution, Behavior and Systematics, Phylogeny, Biotechnology
Abstract: Plastid genome and nuclear ribosomal DNA (nrDNA) arrays, proposed recently as "super-barcodes," might provide additional discriminatory power and overcome the limitations of traditional barcoding loci, yet super-barcodes need to be tested for their effectiveness in more plant groups. Morphological homoplasy among Schima species makes the genus a model for testing the efficacy of super-barcodes. In this study, we generated multiple data sets comprising standard DNA barcodes (matK, rbcL, trnH-psbA, nrITS) and super-barcodes (plastid genome, nrDNA arrays) across 58 individuals from 12 out of 13 species of Schima from China. No samples were correctly assigned to species using standard DNA barcodes and nrDNA arrays, while only 27.27% of species with multiple accessions were distinguished using the plastid genome and its partitioned data sets-the lowest estimated rate of super-barcode success in the literature so far. For Schima and other taxa with similarly recently divergence and low levels of genetic variation, incomplete lineage sorting, hybridization or taxonomic oversplitting are all possible causes of the failure. Taken together, our study suggests that by no means are super-barcodes immune to the challenges imposed by evolutionary complexity. We therefore call for developing multilocus nuclear markers for species discrimination in plant groups.
Published: 2022

33. Nobiletin Inhibits Hypoxia-Induced Placental Damage via Modulating P53 Signaling Pathway

Author: Meng-Ling Zhang, Qian Yang, Yan-Di Zhu, Ya-Di Zhang, Rui Zhang, Jian Liu, Xiao-Yan Zhao, Qin-Yu Dang, Dong-Xu Huang, Ming-Yuan Zhang, Yu-Chen Wei, Zhuo Hu, Xia-Xia Cai, Li-Fang Gao, Yang Shan, and Huan-Ling Yu
Subjects: Nutrition and Dietetics, Placenta, Nobiletin, placenta, hypoxia, RUPP, P53 signaling pathway, Flavones, Rats, Rats, Sprague-Dawley, Pre-Eclampsia, Ischemia, Pregnancy, Animals, Humans, Female, Tumor Suppressor Protein p53, Hypoxia, Food Science, Signal Transduction
Abstract: In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague–Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.
Published: 2022
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34. Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis

Author: Bingchen, Lang, Lu, Han, Linan, Zeng, Qianqian, Zhang, Shouming, Chen, Liang, Huang, Zhijun, Jia, Qin, Yu, and Lingli, Zhang
Subjects: Pediatrics, Perinatology and Child Health, Acetylcholinesterase, Neuromuscular Blockade, Humans, Child, Sugammadex, Neuromuscular Nondepolarizing Agents, Randomized Controlled Trials as Topic
Abstract: Background A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. Methods PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. Results Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. Conclusion Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.
Published: 2022

35. Acceptance of the COVID-19 vaccine based on the health belief model: a multicenter national survey among medical care workers in China

Author: Hao Wang, Yi-Man Huang, Xiao-You Su, Wei-Jun Xiao, Ming-Yu Si, Wen-Jun Wang, Xiao-Fen Gu, Li Ma, Li Li, Shao-Kai Zhang, Chun-Xia Yang, Yan-Qin Yu, and You-Lin Qiao
Subjects: Pharmacology, China, Health Knowledge, Attitudes, Practice, COVID-19 Vaccines, Influenza Vaccines, Surveys and Questionnaires, Immunology, Influenza, Human, Vaccination, Immunology and Allergy, COVID-19, Humans, Patient Acceptance of Health Care
Abstract: Vaccine uptake rate is crucial for herd immunity. Medical care workers (MCWs) can serve as ambassadors of COVID-19 vaccine acceptance. This study aimed to assess MCWs' willingness to receive the COVID-19 vaccine, and to explore the factors affecting COVID-19 vaccination acceptance. A multicenter study among medical care workers was conducted in seven selected hospitals from seven geographical territories of China, and data were collected on sociodemographic characteristics, vaccine hesitancy, and health beliefs on COVID-19 vaccination among participants. Univariate and multivariate logistic regression models were performed to explore the correlations between individual factors and the acceptance of the COVID-19 vaccine. Among the 2681 subjects, 82.5% of the participants were willing to accept the COVID-19 vaccination. Multivariate regression analyses revealed that individuals with more cues to action about the vaccination, higher level of confidence about the vaccine, and higher level of trust in the recommendations of COVID-19 vaccine from the government and the healthcare system were more likely to get the COVID-19 vaccine. In contrast, subjects with higher level of perceived barriers and complacency were less likely to accept the COVID-19 vaccine. Overall, MCWs in China showed a high willingness to get the COVID-19 vaccine. The governmental recommendation is an important driver and lead of vaccination. Relevant institutions could increase MCWs' willingness to COVID-19 vaccines by increasing MCWs' perception of confidence about COVID-19 vaccines and cues to action through various strategies and channels. Meanwhile, it can also provide evidence in similar circumstances in the future to develop vaccine promotion strategies.
Published: 2022

36. ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity

Author: Fu-Hui Xiao, Qin Yu, Zhi-Li Deng, Ke Yang, Yunshuang Ye, Ming-Xia Ge, Dongjing Yan, Hao-Tian Wang, Xiao-Qiong Chen, Li-Qin Yang, Bin-Yu Yang, Rong Lin, Wen Zhang, Xing-Li Yang, Lei Dong, Yonghan He, Jumin Zhou, Wang-Wei Cai, Ji Li, and Qing-Peng Kong
Subjects: Healthy Aging, Proto-Oncogene Protein c-ets-1, Multidisciplinary, Humans, Female, Child, Promoter Regions, Genetic, Ribosomes, Transcription Factors
Abstract: Adaptation to reduced energy production during aging is a fundamental issue for maintaining healthspan or prolonging life span. Currently, however, the underlying mechanism in long-lived people remains poorly understood. Here, we analyzed transcriptomes of 185 long-lived individuals (LLIs) and 86 spouses of their children from two independent Chinese longevity cohorts and found that the ribosome pathway was significantly down-regulated in LLIs. We found that the down-regulation is likely controlled by ETS1 (ETS proto-oncogene 1), a transcription factor down-regulated in LLIs and positively coexpressed with most ribosomal protein genes (RPGs). Functional assays showed that ETS1 can bind to RPG promoters, while ETS1 knockdown reduces RPG expression and alleviates cellular senescence in human dermal fibroblast (HDF) and embryonic lung fibroblast (IMR-90) cells. As protein synthesis/turnover in ribosomes is an energy-intensive cellular process, the decline in ribosomal biogenesis governed by ETS1 in certain female LLIs may serve as an alternative mechanism to achieve energy-saving and healthy aging.
Published: 2022

37. [Emission of Methane from a Key Lake in the Eastern Route of the South-to-North Water Transfer Project and the Corresponding Driving Factors]

Author: Jun-Yu, Zhu, Kai, Peng, Yu-Yang, Li, Xiao-Qin, Yu, Hui-Min, Chen, Lei, Zhou, Yong-Qiang, Zhou, and Yan-Qing, Ding
Subjects: Lakes, Spectrometry, Fluorescence, Humans, Water, Dissolved Organic Matter, Methane
Abstract: Lakes play an important role in the biogeochemical cycling of dissolved organic matter (DOM) and the emission of methane (CH
Published: 2022

38. CRS-related coagulopathy in BCMA targeted CAR-T therapy: a retrospective analysis in a phase I/II clinical trial

Author: He Huang, Qin Yu, Huijun Xu, Guoqing Wei, Mi Shao, Xinyi Teng, Xin Guo, Alex Hongsheng Chang, Yongxian Hu, and Jiazhen Cui
Subjects: medicine.medical_specialty, medicine.medical_treatment, Immunotherapy, Adoptive, Gastroenterology, 03 medical and health sciences, Tissue factor, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Coagulopathy, Humans, B-Cell Maturation Antigen, Multiple myeloma, Coagulation Disorder, Retrospective Studies, Transplantation, Chemotherapy, Factor XII, Receptors, Chimeric Antigen, business.industry, Factor X, Hematology, Blood Coagulation Disorders, medicine.disease, Cytokine release syndrome, chemistry, 030220 oncology & carcinogenesis, Cytokine Release Syndrome, Multiple Myeloma, business, 030215 immunology
Abstract: Chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) has shown promising effects in the treatment of patients with refractory/relapsed multiple myeloma (R/R MM) patients. In this retrospective analysis of phase I/II clinical trial (ChiCTR1800017404), 37 patients with R/R MM received their first BCMA-targeted CAR T-cells following lymphodepletion chemotherapy. The response rate was high (97%), while accompanied by a high incidence of adverse events including coagulation dysfunction. Of 37 patients, all (100%) had cytokine release syndrome (CRS) and 34 (91%) developed at least one abnormal coagulation parameter. The values of coagulation parameters were positively correlated with the severity of CRS as well as with the levels of some cytokines, such as interleukin (IL)-6, IL-10, and interferon (IFN)-γ, etc. Furthermore, levels of the plasma tissue factor (TF), Factor X (FX), Factor XII (FXII), and P-selectin also showed a positive correlation with severity of CRS as well as some specific cytokines, which indicates that these factors are likely to play important roles in CRS-related coagulopathy. Our study suggests that there exists relationship in some extent between coagulation disorder and CRS. Moreover, coagulation dysfunction can be managed with daily monitoring and early intervention despite high incidence.
Published: 2021

39. Implications of the microbiome in the development and treatment of pancreatic cancer: Thinking outside of the box by looking inside the gut

Author: Qin Yu, Ryan M. Thomas, and Christian Jobin
Subjects: 0301 basic medicine, Cancer Research, Pancreatic ductal adenocarcinoma, Carcinogenesis, GF, germ free, Review Article, medicine.disease_cause, Bioinformatics, lcsh:RC254-282, SPF, specific pathogen free, 03 medical and health sciences, 0302 clinical medicine, Immune system, Pancreatic cancer, medicine, Humans, Microbiome, Pancreas, Carcinogen, business.industry, Microbiota, Disease Management, Cancer, POPF, postoperative pancreatic fistula, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, medicine.disease, Combined Modality Therapy, PDAC, Pancreatic ductal adenocarcinoma, WT, wild-type, Gastrointestinal Microbiome, Pancreatic Neoplasms, Oncobiome, Natural history, Cell Transformation, Neoplastic, Treatment Outcome, 030104 developmental biology, Bacterial Translocation, 030220 oncology & carcinogenesis, qPCR, quantitative polymerase chain reaction, Disease Susceptibility, business, Biomarkers, Carcinoma, Pancreatic Ductal
Abstract: Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related death in the United States. As one of the most lethal cancer types, the prognosis for patients diagnosed with pancreatic cancer remains dismal and novel investigations are urgently needed. Evidence for an association of microbes with pancreatic cancer risk, development, treatment response, and post-treatment survivorship is rapidly developing. Herein, we provide an overview on the role of the microbiome as it relates to the natural history of pancreatic cancer, including host immune interactions, alterations in metabolism, direct carcinogenic effect, and its role in treatment response.
Published: 2021

40. How Well Have Projected Lung Cancer Rates Predicted the Actual Observed Rates?

Author: Xue Qin Yu, Dianne L. O'Connell, Karen Canfell, Julia Steinberg, Qingwei Luo, and Michael Caruana
Subjects: Adult, Male, 0301 basic medicine, Lung Neoplasms, Population, Global Health, World health, 03 medical and health sciences, Age Distribution, age-period, 0302 clinical medicine, Predictive Value of Tests, Humans, Medicine, Registries, Sex Distribution, Lung cancer, education, Aged, cohort model, Statistical projections, education.field_of_study, Models, Statistical, business.industry, Incidence, Mortality rate, Incidence (epidemiology), Cancer, General Medicine, Middle Aged, medicine.disease, Survival Rate, 030104 developmental biology, mortality rates, generalized linear model, 030220 oncology & carcinogenesis, Percentage difference, Female, incidence rates, business, Research Article, Demography
Abstract: Background While many past studies have constructed projections of future lung cancer rates, little is known about their consistency with the corresponding observed data for the time period covered by the projections. The aim of this study was to assess the agreement between previously published lung cancer incidence and/or mortality rate projections and observed rates. Methods Published studies were included in the current study if they projected future lung cancer rates for at least 10 years beyond the period for which rates were used to obtain the projections, and if more recent observed rates for comparison covered a minimum of 10 years from the beginning of the projection period. Projected lung cancer incidence and/or mortality rates from these included studies were extracted from the publications. Observed rates were obtained from cancer registries or the World Health Organization's Mortality Database. Agreement between projected and observed rates was assessed and the relative difference (RD) for each projected rate was calculated as the percentage difference between the projected and observed rates. Results A total of 59 projections reported in 14 studies were included. Nine studies provided projections for 20 years or more. RDs were higher for those projections in which the lung cancer rates peaked during the projection period, and RDs increased substantially with the length of the projection period. When lung cancer rates peaked during the projection period, methods incorporating smoking data were generally more successful at predicting the trend reversal than those which did not incorporate smoking data. Mean RDs for 15-year projections comparing methods with or without smoking data were 12.7% versus 48.0% for males and 8.2% versus 42.3% for females. Conclusions The agreement between projected and observed lung cancer rates is dependent on the trends in the observed rates and characteristics of the population, particularly trends in smoking.
Published: 2021

41. Recepteur d'origine nantais contributes to the development of endometriosis via promoting epithelial‐mesenchymal transition of a endometrial epithelial cells

Author: Gen Zou, Qin Yu, Xinmei Zhang, Xinxin Xu, Libo Zhu, Jianzhang Wang, Xuan Che, Tiantian Li, Xinyue Guo, Shaojie Ding, and Yangying Peng
Subjects: endometriosis, 0301 basic medicine, MAPK/ERK pathway, Epithelial-Mesenchymal Transition, Endometriosis, recepteur d'origine nantais, migration, Receptor tyrosine kinase, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Humans, Medicine, Epithelial–mesenchymal transition, Protein kinase A, Protein kinase B, Gene knockdown, epithelial‐mesenchymal transition, biology, Transition (genetics), business.industry, Receptor Protein-Tyrosine Kinases, Epithelial Cells, Original Articles, Cell Biology, invasion, medicine.disease, Immunohistochemistry, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Molecular Medicine, Female, Original Article, Disease Susceptibility, Mitogen-Activated Protein Kinases, business, Proto-Oncogene Proteins c-akt, Biomarkers, Signal Transduction
Abstract: Endometriosis is a benign, chronic inflammatory disease that commonly occurs in reproductive‐aged women. Epithelial‐mesenchymal transition (EMT) of endometrial epithelial cells plays an important role in the development of endometriosis. Recepteur d'origine nantais (RON), a receptor tyrosine kinase, has been reported to promote EMT and progression in tumours. However, whether and how RON mediates the EMT and endometriosis development is not known. Here, we found that RON activation could improve the migratory and invasive capabilities, change cellular morphologies, and decrease expression of E‐cadherin and increase expression of N‐cadherin in endometrial epithelial cells. Inhibition or knockdown of RON expression suppressed the migration and invasion of endometrial epithelial cells. Our studies also indicated that RON played its part in endometrial epithelial cells through protein kinase B (Akt) and mitogen‐activated protein kinase (MAPK) pathways. Treatment with a RON inhibitor could decrease the number of ectopic lesions in a mouse model of endometriosis and mediate expression of EMT markers in endometriotic lesions. These data suggest that RON contributed to endometriosis development by promoting EMT of endometrial epithelial cells. Therefore, RON may be a new therapeutic target for endometriosis.
Published: 2021

42. Free CA125 promotes ovarian cancer cell migration and tumor metastasis by binding Mesothelin to reduce DKK1 expression and activate the SGK3/FOXO3 pathway

Author: Chen Xu, Qin Yu, Qianyu Huo, Lunhui Huang, Huijing Bao, Yanhong Shao, and Yunde Liu
Subjects: endocrine system diseases, MSLN, Protein Serine-Threonine Kinases, Applied Microbiology and Biotechnology, Metastasis, CA125, 03 medical and health sciences, Ovarian tumor, Cell Movement, Cell Line, Tumor, medicine, Humans, Mesothelin, Neoplasm Metastasis, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Ovarian Neoplasms, therapy, 0303 health sciences, biology, DKK1, business.industry, Carcinoma, Forkhead Box Protein O3, Membrane Proteins, Cell migration, Cell Biology, medicine.disease, female genital diseases and pregnancy complications, ovarian cancer, Apoptosis, CA-125 Antigen, biology.protein, Cancer research, Intercellular Signaling Peptides and Proteins, Female, Signal transduction, Ovarian cancer, business, Research Paper, Developmental Biology
Abstract: Objective: CA125/MUC16 is an O-glycosylated protein that is expressed on the surfaces of ovarian epithelial cells. This molecule is a widely used tumor-associated marker for diagnosis of ovarian cancer. Recently, CA125 was shown to be involved in ovarian cancer metastasis. The purpose of this study was to investigate the mechanism of CA125 during ovarian cancer metastasis. Methods: We analyzed the Oncomine and CSIOVDB databases to determine the expression levels of DKK1 in ovarian cancer. DKK1 expression levels were upregulated or downregulated and applied with CA125 to Transwell and Western blot assays to ascertain the underlying mechanism by which CA125 stimulates cell migration via the SGK3/FOXO3 pathway. Anti-mesothelin antibodies (anti-MSLN) were used to block CA125 stimulation. Then the expression levels of DKK1were tested by enzyme-linked immunosorbent assay (ELISA) to eliminate the blocking effect of anti-MSLN to CA125 stimulation. Xenograft mouse models were used to detect the effects of CA125 and anti-MSLN on ovarian cancer metastasis in vivo. Results: DKK1 levels were downregulated in ovarian tumor tissues according to the analyses of two databases and significantly correlated with FIGO stage, grade and disease-free survival in ovarian cancer patients. DKK1 levels were downregulated by CA125 stimulation in vitro. Overexpression of DKK1 reversed the ability of exogenous CA125 to mediate cell migration by activating the SGK3/FOXO3 signaling pathway. Anti-MSLN abrogated the DKK1 reduction and increased the apoptosis of ovarian cancer cells. The use of anti-MSLN in xenograft mouse models significantly reduced tumor growth and metastasis accelerated by CA125. Conclusions: These experiments revealed that the SGK3/FOXO3 pathway was activated, wherein decreased expression of DKK1 was caused by CA125, which fuels ovarian cancer cell migration. Mesothelin is a potential therapeutic target for the treatment of ovarian cancer metastasis.
Published: 2021

43. Elevated expression of IGFL1 indicates unfavorable prognosis in lung adenocarcinoma through promotion of cell proliferation and inhibition of apoptosis

Author: Zhuo, Wang, Xiaoqin, Liang, Xiaojun, Wang, and Qin, Yu
Subjects: Gene Expression Regulation, Neoplastic, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Humans, Adenocarcinoma of Lung, Apoptosis, General Medicine, Prognosis, Cell Proliferation, Pathology and Forensic Medicine
Abstract: Non-small cell lung cancer (NSCLC) is one of the principal causes of death worldwide. The disease is often diagnosed late, at the stage of metastasis, which leads to a poor prognosis. With currently available treatment, most patients experience relapse and drug resistance. This study aimed to determine the potential role of insulin growth factor-like family member 1 (IGFL1) in lung adenocarcinoma (LUAD). We analyzed the expression of IGFL1 using TIMER, UALCAN, and GEPIA. The association of IGFL1 expression with symptoms and overall survival (OS) in LUAD patients was evaluated using a tissue microarray (TMA). Moreover, A549 and H1299 cells with selective IGFL1 knockdown were used to observe their proliferation and apoptosis in vitro. From the TIMER, UALCAN and GEPIA databases, we found that IGFL1 was upregulated in LUAD (p0.001). The level of promoter methylation in IGFL1 was significantly downregulated in LUAD and patient groups with different gender. Similar results were obtained in UALCAN. The semi-quantitative analysis revealed that IGFL1 expression is correlated with TNM stage (p0.001) and tumor size (p0.001) in TMA. High levels of IGFL1 expression were associated with poor OS (p0.05). Functional tests in A549 and H1299 cells showed that knocking down the expression of IGFL1 inhibited proliferation and enhanced apoptosis. Our study revealed the potential utility of IGFL1 as a predictive biomarker, which may play a biological role by regulating the proliferation and apoptosis of tumor cells.
Published: 2021

44. Ferroptosis: A Novel Mechanism of Artemisinin and its Derivatives in Cancer Therapy

Author: Botian Ran, Chunsong Huo, Ji Chen, Linshen He, Wanhong Liu, Shunqin Zhu, Yuanpeng Li, Yonghao Li, and Qin Yu
Subjects: Programmed cell death, Cell cycle checkpoint, Antineoplastic Agents, 01 natural sciences, Biochemistry, Antimalarials, 03 medical and health sciences, Neoplasms, Drug Discovery, medicine, Ferroptosis, Humans, Doxorubicin, 0101 mathematics, Artemisinin, Cytotoxicity, 030304 developmental biology, Pharmacology, 0303 health sciences, Chemistry, Organic Chemistry, Autophagy, Cancer, medicine.disease, Artemisinins, 010101 applied mathematics, Cancer cell, Cancer research, Molecular Medicine, medicine.drug
Abstract: Background: Artemisinin is a sesquiterpene lactone compound with a special peroxide bridge that is tightly linked to the cytotoxicity involved in fighting malaria and cancer. Artemisinin and its derivatives (ARTs) are considered to be potential anticancer drugs that promote cancer cell apoptosis, induce cell cycle arrest and autophagy, inhibit cancer cell invasion and migration. Additionally, ARTs significantly increase intracellular Reactive Oxygen Species (ROS) in cancer cells, which result in ferroptosis, a new form of cell death, depending on the ferritin concentration. Ferroptosis is regarded as a cancer suppressor and as well as considered a new mechanism for cancer therapy. Methods: The anticancer activities of ARTs and reference molecules were compared by literature search and analysis. The latest research progress on ferroptosis was described, with a special focus on the molecular mechanism of artemisinin-induced ferroptosis. Results: Artemisinin derivatives, artemisinin-derived dimers, hybrids and artemisinin-transferrin conjugates, could significantly improve anticancer activity, and their IC50 values are lower than those of reference molecules such as doxorubicin and paclitaxel. The biological activities of linkers in dimers and hybrids are important in the drug design processes. ARTs induce ferroptosis mainly by triggering intracellular ROS production, promoting the lysosomal degradation of ferritin and regulating the System Xc-/Gpx4 axis. Interestingly, ARTs also stimulate the feedback inhibition pathway. Conclusion: Artemisinin and its derivatives could be used in the future as cancer therapies with broader applications due to their induction of ferroptosis. Meanwhile, more attention should be paid to the development of novel artemisinin-related drugs based on the mechanism of artemisinininduced ferroptosis.
Published: 2020

45. Regulation of human sphingomyelin synthase 1 translation through its 5′‐untranslated region

Author: Gabriella Luciano, Chiara Luberto, Brecken Shenandoah Esper, Sitapriya Moorthi, Foysal Daian, Navid Ashrafi, and Gui-Qin Yu
Subjects: Five prime untranslated region, RNA biology, Fusion Proteins, bcr-abl, Biophysics, Transferases (Other Substituted Phosphate Groups), Nerve Tissue Proteins, Biochemistry, mRNA secondary structures, 5′ UTR, 03 medical and health sciences, sphingomyelin synthase 1, Structural Biology, Transcription (biology), Sphingomyelin synthase, Upstream open reading frame, Translational regulation, Genetics, Humans, RNA, Messenger, Molecular Biology, Gene, Research Articles, 030304 developmental biology, 0303 health sciences, Messenger RNA, Reporter gene, biology, 030302 biochemistry & molecular biology, Membrane Proteins, Cell Biology, SGMS1, translational regulation, Cell biology, Gene Expression Regulation, Neoplastic, Protein Biosynthesis, biology.protein, Nucleic Acid Conformation, Transcription Initiation Site, 5' Untranslated Regions, HeLa Cells, Research Article
Abstract: Bcr‐abl1 oncogene causes a shift in the transcription start site of the SMS1 gene (SGMS1) encoding the sphingomyelin (SM) synthesizing enzyme, sphingomyelin synthase 1 (SMS1). This results in an mRNA with a significantly shorter 5′‐UTR, called 7‐SGMS1, which is translated more efficiently than another transcript (IIb‐SGMS1) with a longer 5′UTR in Bcr‐abl1‐positive cells. Here, we determine the effects of these alternative 5′UTRs on SMS1 translation and investigate the key features underlying such regulation. First, the presence of the longer IIb 5′UTR is sufficient to greatly impair translation of a reporter gene. Deletion of the upstream open reading frame (−164 nt) or of the predicted stem‐loops in the 5′UTR of IIb‐SGMS1 has minimal effects on SGMS1 translation. Conversely, deletion of nucleotides −310 to −132 enhanced transcription of IIb‐SGMS1 to reach that of 7‐SGMS1. We thus suggest that regulatory features within nucleotides −310 and −132 modulate IIb‐SGMS1 translation efficiency.
Published: 2020

46. Diversity of α‐tubulin transcripts in Lolium rigidum

Author: Qin Yu, Zhizhan Chu, Eric L. Patterson, Heping Han, Stephen B. Powles, and Jinyi Chen
Subjects: 0106 biological sciences, Gene isoform, Lolium rigidum, Mutant, ved/biology.organism_classification_rank.species, Biology, medicine.disease_cause, 01 natural sciences, Tubulin, Complementary DNA, Lolium, medicine, Humans, Gene family, Genetics, Mutation, Herbicides, ved/biology, Point mutation, General Medicine, 010602 entomology, Insect Science, biology.protein, Agronomy and Crop Science, Herbicide Resistance, 010606 plant biology & botany
Abstract: Background Tubulin, the target site of dinitroaniline herbicides, is encoded by small gene families in plants. To better characterize the mechanisms of target-site resistance to dinitroaniline herbicides in the globally important weedy species Lolium rigidum, attempts were made to amplify and sequence α-tubulin transcripts. Results Four α-tubulin isoforms (TUA1, TUA2, TUA3 and TUA4) were identified in L. rigidum. Variations in the number and sequence of transcripts encoding these α-tubulin proteins were found in individuals from the two L. rigidum populations examined. Within and among populations, differences in the 5'- and 3'-untranslated regions of cDNA in TUA3 and TUA4 were identified. Furthermore, a novel double mutation, Arg-390-Cys+Asp-442-Glu, in the TUA3 transcript was identified and has the potential to confer dinitroaniline resistance. Conclusion This research reveals the complexity of the α-tubulin gene family in individuals/populations of the cross-pollinated weedy species L. rigidum, and highlights the need for better understanding of the molecular architecture of tubulin gene families for detecting resistance point mutations. Although TUA4 is a commonly expressed α-tubulin isoform containing most frequently reported resistance mutations, other mutant tubulin isoforms may also have a role in conferring dinitroaniline resistance.
Published: 2020

47. Tracheal development after left pulmonary artery reimplantation: an individual study

Author: Xiaoyang Hong, Xiaohong Liu, Zhe Zhao, Zhichun Feng, Hui Wang, Gang Wang, Ruijie Li, Jun Li, Gengxu Zhou, Qin Yu, and Jiangheng Guan
Subjects: Male, medicine.medical_specialty, Respiratory distress syndrome, medicine.medical_treatment, lcsh:Medicine, 030204 cardiovascular system & hematology, Pulmonary Artery, Paediatric research, Article, Sling (weapon), 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Survivors, Child, lcsh:Science, Survival analysis, Retrospective Studies, Multidisciplinary, business.industry, lcsh:R, Infant, Newborn, Infant, Retrospective cohort study, Left pulmonary artery, Pulmonary artery sling, medicine.disease, Survival Analysis, Surgery, Trachea, Treatment Outcome, 030228 respiratory system, Respiratory failure, Echocardiography, Child, Preschool, Replantation, lcsh:Q, business, Tomography, X-Ray Computed, Cohort study, Follow-Up Studies
Abstract: Pulmonary artery sling (PA sling) often presents as a life-threatening condition requiring urgent surgical correction. We reported 32 cases of PA sling in children who were followed up postoperatively in the past 6 years. All patients with PA slings who were admitted to the hospital from January 2012 to December 2017 and underwent surgery were retrospectively analyzed. The mean age of the 32 patients at repair was 16.97 months (range, 15 days to 128 months). Six patients required ventilator assistance for respiratory failure. All children underwent left pulmonary artery (LPA) reimplantation (n = 32), and 3 patients needed reimplantation slide tracheoplasty (n = 3) due to ventilation weaning failure. Four patients died, 27 patients survived until discharge, and 18 patients were followed up. Pulmonary computed tomography imaging and echocardiography were performed in 18 patients who were followed up. After LPA reimplantation, the tracheal carina area was significantly enlarged compared to that preoperation (p = 0.0002). In this follow-up cohort study, 75% of the patients who underwent LPA reimplantation survived until discharge. The survivors had subsequently well-developed pulmonary arteries and tracheas.
Published: 2020

48. Impact of Maternal Age on Singleton Birthweight in Frozen Embryo Transfer Cycles

Author: Zhe-xin Ni, Kun-ming Wan, Zhi-hao Zhou, Yan-ping Kuang, and Chao-qin Yu
Subjects: Adult, Male, Pregnancy, Endocrinology, Diabetes and Metabolism, Infant, Newborn, Birth Weight, Humans, Premature Birth, Female, Embryo Transfer, Maternal Age, Retrospective Studies
Abstract: BackgroundPrevious studies have investigated the effect of maternal age on assisted reproductive technology success rates. However, little is known about the relationship between maternal age and neonatal birthweight in frozen embryo transfer (FET) cycles. Whether maternal age influences singleton birthweight in FET cycles remains to be elucidated.MethodsThis study was conducted at a tertiary care center, involving singleton live births born to women undergoing frozen–thawed embryo transfer during the period from January 2010 to December 2017. A total of 12,565 women who fulfilled the inclusion criteria were enrolled and grouped into four groups according to the maternal age: ResultsThe highest proportions of low birthweight (LBW, 4.1%), high birthweight (1.2%), preterm birth (PTB, 5.9%), and very PTB (0.9%) were found in the group over 40 years old, but no significant difference was observed among the four groups. Additionally, the 35–39-year-old group had the highest rate of very LBW (0.6%), whereas the 30–34-year-old group had the lowest rate of small for gestational age (SGA, 2.7%). However, multivariate analyses revealed that neonatal outcomes including PTB, LBW, and SGA were similar between the different maternal age groups.ConclusionGrouping with different maternal age was not associated with mean birthweight and Z-scores of singletons resulting from FET.
Published: 2022
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49. Identification of cerebrospinal fluid metabolites as biomarkers for neurobrucellosis by liquid chromatography-mass spectrometry approach

Author: Hao Yang, Zhenfei Wang, Shujun Shi, Qin Yu, Meiling Liu, and Zhelin Zhang
Subjects: Discriminant Analysis, Humans, Metabolomics, Bioengineering, General Medicine, Applied Microbiology and Biotechnology, Biomarkers, Mass Spectrometry, Biotechnology, Chromatography, Liquid
Abstract: Neurobrucellosis is the most morbid form in brucellosis disease. Metabolomics is an emerging method which intends to explore the global alterations of various metabolites in samples. We aimed to identify metabolites in cerebrospinal fluid (CSF) as biomarkers that were potentially unique for neurobrucellosis. CSF samples from 25 neurobrucellosis patients and 25 normal controls (uninfected patients with hydrocephalus) were collected for metabolite detection using liquid chromatography-mass spectrometry (LC-MS) approach. Inflammatory cytokines in CSF were measured with Enzyme-linked immunosorbent assay (ELISA). The base peak chromatogram in CSF samples showed that small-molecule metabolites were well separated. Principal Component Analysis (PCA) analysis exhibited the examined samples were arranged in two main clusters in accordance with their group. Projection to Latent Structures Discriminant Analysis (PLS-DA) revealed there was a noticeable separation between neurobrucellosis and normal groups. Orthogonal Partial Least-Squares-Discriminant Analysis (OPLS-DA) could responsibly illuminate the differences between neurobrucellosis and normal controls. Neurobrucellosis showed a total of 155 differentiated metabolites. Prominent potential biomarkers including 30 metabolites were then selected out, regarded as more capable of distinguishing neurobrucellosis. TNF-α and IL-6 in CSF were remarkably increased in neurobrucellosis. We presented the heatmaps and correlation analyses among the identified 30 potential biomarkers. In conclusion, this study showed that CSF metabolomics based on LC-MS could distinguish neurobrucellosis patients from normal controls. Our data offered perspectives for diagnosis and treatment for neurobrucellosis.
Published: 2022

50. Comment on: 'Effect of intraoperative subhypnotic infusion of propofol on postoperative nausea and vomiting: A retrospective analysis'

Author: Qin Yu, Jie Zhang, and Yong Xin Liang
Subjects: Anesthesiology and Pain Medicine, Double-Blind Method, Vomiting, Postoperative Nausea and Vomiting, Antiemetics, Humans, Propofol, Retrospective Studies
Published: 2022

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