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Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

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Science China(Life Sciences) 2024年第1期67卷 113-121页

作者： Hui Zhu Taishun Li Peizhen Xu Lijun Ding Xianghong Zhu Bin Wang Xiaoqiu Tang Juan Li Pengfeng Zhu huiyan Wang Chenyan Dai Haixiang sun Jianwu Dai Yali Hu Department of Obstetrics and Gynecology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Biostatistics Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Gynecology Changzhou Maternal and Child Health Care HospitalChangzhou Medical CenterNanjing Medical UniversityChangzhou 213004China Clinical Center for Stem Cell Research Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Hematology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100190China

Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively

关键词： intrauterine adhesion Asherman’s syndrome uterine infertility autologous bone marrow stem cells transplantation endometrial regeneration ongoing pregnancy rate

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Research on Reimbursement Management of Innovative Drugs Abroad and Its Enlightenment to China

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Asian Journal of Social Pharmacy 2024年第1期19卷 1-8页

作者： Yu Hanshuang Huang Xianqin Wang huiyan sun Lihua School of Business Administration Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Peking UniversityBeijing 100191China

Objective To analyze the reimbursement policies of innovative drugs in some developed countries,and to provide reference for future reimbursement management in China.Methods Literature research method was used to study the policies related to the reimbursement management of innovative drugs in Germany,France and Japan,and their successful experience was summarized.Results and Conclusion China should establish an open and transparent value evaluation standard to improve the medical insurance reimbursement management of innovative drugs.Besides,the value of innovative drugs should be taken as an important basis for reimbursement decisions,and an independent third-party value evaluation agency must be established.

关键词： innovative drug medical insurance reimbursement

Metabolic reprogramming in cancer: the bridge that connects intracellular stresses and cancer behaviors

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National Science Review 2020年第8期7卷 1270-1273页

作者： Yi Zhou huiyan sun Ying Xu Cancer Systems Biology Center The China-Japan Union Hospital Department of Biochemistry and Molecular Biology University of Georgia School of Artificial Intelligence Jilin University

Extensive changes in cellular metabolisms have been observed in cancer. They are probably induced by the same intracellular stressor, persistent off-balance in intracellular p H across possibly all adult cancers. It is these altered metabolisms that gives rise to a variety of cancerous behaviors such as continuous cell division, metastasis and drug resistance.

关键词： IRON

The antioxidant trolox inhibits aging and enhances prostaglandin E-2 secretion in mesenchymal stem cells

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BIOCELL 2023年第2期47卷 385-392页

作者： XIAOXU ZHANG LIN ZHANG LIN DU huiyan sun XIA ZHAO YANG sun WEI WANG LISHENG WANG Laboratory of Molecular Diagnosis and Regenerative Medicine Medical Research CenterThe Affiliated Hospital of Qingdao UniversityQingdao266000China Department of Hematology The Affiliated Hospital of Qingdao UniversityQingdao266000China School of Nursing Jilin UniversityChangchun130000China Yanda Medical Research Institute Hebei Yanda HospitalSanhe065201China

Mesenchymal stem cells(MSCs)have been widely used in regenerative medicine and clinical therapy due to their capabilities of proliferation,differentiation,and immune regulation.However,during in vitro expansion,MSCs are prone to aging,which largely limits their application.Prostaglandin E-2(PGE-2)is a key effector secreted by MSCs to exert immunomodulatory effects.By screening the compound library for PGE-2 secretion,the antioxidant trolox was verified as a stimulator of MSCs to secrete PGE-2.The effect of antioxidant trolox on biological characteristics of MSCS,including aging,proliferation,and gene expression,was examined.The results demonstrated that trolox can resist aging,promote proliferation,and enhance PGE-2 secretion of MSCs without affecting their surface marker expression.Furthermore,trolox treatment up-regulates miR-17-92 clusters in MSCs and may contribute to its anti-aging effects.Thus,trolox addition might be beneficial for MSCs expansion and their application.

关键词： Mesenchymal stem cells(MSCs) Trolox Antioxidation Prostaglandin E-2

Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection

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Biophysics Reports 2024年第1期10卷 15-21页

作者： Qinggang Hao Rui Dong Weiyu Bai Dong Chang Xinyi Yao Yingru Zhang Huangying Xu huiyan Li Xiang Kui Feng Wang Yan Wang Chengqin Wang Yujie Lei Yan Chen Junling Shen Lei Sang Yan Bai Jianwei sun Center for Life Sciences Yunnan Key Laboratory of Cell Metabolism and Diseases State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan School of Life Sciences Yunnan University Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province Yan'an Hospital Affiliated to Kunming Medical University Shandong Provincial Key Laboratory of Animal Resistance Biology Collaborative Innovation Center of Cell Biology in Universities of Shandong Center for Cell Structure and Function Institute of Biomedical Science College of Life Sciences Shandong Normal University Department of Pathology The Second Affiliated Hospital of Kunming Medical University State Key Laboratory of Bioactive Molecules and Druggability Assessment Institute of Genomic Medicine College of Pharmacy Jinan University Department of Pathology School of Basic Medicine Qingdao University Department of Thoracic Surgery Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study, we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of in vivo screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improves our understanding of the metastasis mechanisms, but also provides potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.

关键词： Melanoma Lung metastasis model Gene screening Tail vein injection

Suppression of cell pyroptosis by omeprazole through PDE4-mediated autophagy in gastric epithelial cells

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BIOCELL 2023年第12期47卷 2709-2719页

作者： LIPING YE huiyan sun XINHUA LIANG WENXU PAN LI XIANG WENJUN DU LANLAN GENG WANFU XU SITANG GONG Department of Pediatrics The First School of Clinical Medicine of Jinan UniversityThe First Affiliated HospitalJinan UniversityGuangzhouChina Department of Gastroenterology Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhouChina Department of Gastroenterology Guangdong Provincial Clinical Research Center for Child HealthGuangzhou Medical UniversityGuangzhouChina Department of Nephrology Zhuhai Maternal and Child Health HospitalZhuhaiChina

Helicobacter pylori is a risk factor for the development of peptic ulcers with autophagy dysfunction.Omeprazole was widely known as the first-line regimen for H.pylori-associated gastritis.Objectives:The objective of this work was to assess the role of omeprazole on cell pyroptosis and autophagy.Methods:The clinical samples were collected.Quantitative polymerase chain reaction,western blotting,enzyme linked immunosorbent assay,and immunofluorescence(IF)analysis were conducted to reveal the mechanism of omeprazole on cell pyroptosis and autophagy.Results:The results revealed that omeprazole could decrease cell pyroptosis,which was attributed to the downregulation of cleaved caspase-1 expression,resulting in the inhibition of gasdermin E and interleukin-18/1βmaturation and secretion as well as the resolution of inflammation.Mechanistically,omeprazole treatment led to drastic downregulation of mammalian target of rapamycin(mTOR)activity was observed in BGC823 cells,leading to enhanced autophagy characterized by increased LC3II expression,which further reduced cell pyroptosis.This omeprazole-mediated phenomenon was enhanced after phosphodiesterase-4(PDE4)inhibitor dipyridamole(DIP)treatment.In addition,activation of mTOR by MHY1485 could rescue the suppression of cell pyroptosis induced by omeprazole.Most importantly,IF analysis suggested that phosphorylation of mTOR and PDE4 activity and caspase-1 were enhanced in H.pylori-infected gastric mucosa.Conclusion:These findings indicate that omeprazole suppresses cell pyroptosis through PDE4-mediated autophagy in gastric epithelial cells,and DIP enhanced the omeprazole-mediated inhibition of cell pyroptosis,implying that DIP is an alternative combined therapy strategy in improving the treatment of patients with H.pylori infection.

关键词： Omeprazole Autophagy Dipyridamole mTOR Cell pyroptosis

Warburg Effects in Cancer and Normal Proliferating Cells:Two Tales of the Same Name

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Genomics, Proteomics & Bioinformatics 2019年第3期17卷 273-286页

作者： huiyan sun Liang Chen Sha Cao Yanchun Liang Ying Xu The China-Japan Union Hospital Jilin UniversityChangchun 130033China MOE Key Laboratory of Symbolic Computation and Knowledge Engineering College of Computer Science and TechnologyJilin UniversityChangchun 130012China Computational Systems Biology Lab Department of Biochemistry and Molecular Biology and Institute of BioinformaticsUniversity of GeorgiaAthensGA 30602USA Faculty of Health Sciences University of MacaoTaipaMacao SAR 999078China Department of Biostatistics School of MedicineIndiana UniversityIndianapolisIN 46202USA Zhuhai Laboratory of MOE Key Laboratory of Symbolic Computation and Knowledge Engineering Zhuhai College of Jilin UniversityZhuhai 519041China

It has been observed that both cancer tissue cells and normal proliferating cells(NPCs)have the Warburg effect.Our goal here is to demonstrate that they do this for different reasons.To accomplish this,we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO.Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect,to raise the intracellular pH from 6.8 to 7.2 and to prepare for cell division energetically.Once cell cycle starts,the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release,to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral.The cells go back to the normal respirationbased ATP production once the cell division phase ends.In comparison,cancer cells have reached their intracellular pH at 7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed.Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters.Co-expression analyses suggest that lactic acid secretion is regulated by external,non-pH related signals.Overall,our data strongly suggest that the two cell types have the Warburg effect for very different reasons.

关键词： Cancer Warburg effect Fenton reaction Cell proliferation pH homeostasis

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Assessment of cognitive dysfunction in traumatic brain injury patients:a review

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Forensic Sciences Research 2017年第4期2卷 174-179页

作者： huiyan sun Chengliang Luo Xiping Chen Luyang Tao School of Biology&Basic Medical Science Soochow UniversitySuzhouChina Affiliated Hospital Chifeng UniversityInner MongoliaChina

Traumatic brain injury(TBI)is one of the major causes of human mortality and morbidity in the world.Brain injury could affect the core of a person’s being–their thinking,memory,personality and behaviour.Electrophysiological markers from the human electroencephalogram and brain imaging provide a rich source of data which helps to elucidate specific processing impairments in TBI patients.To assess the cognitive and social function in traumatic brain injury patients,this review will focus on some of methods for assessing the disabling cognitive and social function deficits induced by TBI.There are many new technologies available to address TBI and recognition related questions.Integration of the various techniques will help to facilitate our comprehending of TBI,cognitive function and social function,and improve treatment and rehabilitation.

关键词： Forensic science traumatic brain injury event-related potential,P300 cognitive impairment

Fenton reactions drive nucleotide and ATP syntheses in cancer

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Journal of Molecular Cell Biology 2018年第5期10卷 448-459页

作者： huiyan sun Chi Zhang Sha Cao Tao Sheng Ning Dong Ying Xu College of Computer Science and Technology Jilin University Changchun China Computational Systems Biology Lab Department of Biochemistry and Molecular Biology and institute of Bioinformatics University of Georgia GA USA School of Public Health Jilin University Changchun China The First Hospital of Jilin University Changchun China

我们在场 14 癌症的织物 transcriptomic 数据的计算研究打字到地址：什么可以驾驶癌症房间分割？我们到由 Fenton 反应的细胞内部的 pH 的那坚持的混乱的分析点可能在癌症开发的根。明确地，我们统计上证明了 Fenton 反应发生在癌症 cy... 详细信息

我们在场 14 癌症的织物 transcriptomic 数据的计算研究打字到地址：什么可以驾驶癌症房间分割？我们到由 Fenton 反应的细胞内部的 pH 的那坚持的混乱的分析点可能在癌症开发的根。明确地，我们统计上证明了 Fenton 反应发生在癌症 cytosol，越过所有 14 癌症的线粒体打字，基于经由 Michaelis-Menten 方程综合的癌症组织基因表示数据。另外，我们证明了在疾病房间的 cytosol 的(i) Fenton 反应将连续地房间由产生网质子通过综合的联合使 pH 稳定，对哪个作出回应增加他们的 pH 对哪个 glycolytic ATP 并且由核苷酸综合体消费他们，它可以驱使房间分割连续地综合的核苷酸根除；并且(ii ) 在线粒体的 Fenton 反应与最终来自 H 2 O 2, 大部分从有免疫力的房间发源。一个模型被开发连接这些到癌症开发，在一些变化可以被选择以 Fenton 反应支配的率便于房间分割的地方。

关键词： Fenton 核苷酸 ATP 综合体癌症反应驾驶 H2O2