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Phase I trial of human umbilical cord-derived mesenchymal stem cells for treatment of severe bronchopulmonary dysplasia

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Genes & Diseases 2023年第2期10卷 521-530页

作者： yunqiu xia Tingyuan Lang Yuqin Niu xian Wu Ou Zhou Jihong Dai Lei Bao Ke Yang Lin Zou Zhou Fu Gang Geng Department of Dermatology Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Department of Gynecologic Oncology School of MedicineChongqing University Cancer HospitalChongqing UniversityChongqing 400030China The First Affiliated Hospital School of MedicineShihezi UniversityShiheziXinjiang 832008China Department of Respiratory Medicine West China Second University HospitalSichuan UniversityChengduSichuan 610041China Department of Respiratory Medicine Children's Hospital of Chongqing Medical UniversityChongqing 400014China Department of Neonatology Children's Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Engineering Technology Research Center of Stem Cell Therapy Children's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Clinical Molecular Medicine Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Severe bronchopulmonary dysplasia(BPD)is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system;no effective pharmacotherapy for this disease exists,and mortality remains high.Based on the evidence from previous preclinical studies and phase I clinical trials,this study aims to test the safety of intravenous application of a single dose of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)in patients with severe BPD.The Mesenchymal Stem cells for Bronchopulmonary Dysplasia Treatment(MSBDT)trial is a single center,open-label,dose-escalation phase I clinical trial.Severe BPD patients were enrolled in Children Hospital of Chongqing Medical University,Chongqing,China.The first six patients were treated with low-dose hUC-MSCs(1×10^(6) cells/kg)and the next seven patients were treated with high-dose hUC-MSCs(5×10^(6) cells/kg).This study is registered with ClinicalTrials.gov,number NCT03558334.No prespecified infusion-associated adverse events,immediate complication,respiratory or cardiovascular compromise were observed during infusion and 24 h after infusion.No significant changes in safety laboratory values were observed.One death event occurred in the low-dose group on study day 10,and one death event occurred in the high-dose group on study day 24,while,after review in detail,the two cases are not believed to be infusion-associated events.In conclusion,intravenous application of a single dose of hUC-MSCs was tolerated in thirteen patients with severe BPD.

关键词： Bronchopulmonary dysplasia Dose escalation Human umbilical cord-derived mesenchymal stem cells Intravenous treatment Phase I trial

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Development of a molecular feature-based survival prediction model of ovarian cancer using the deep neural network

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Genes & Diseases 2023年第4期10卷 1190-1193页

作者： Tingyuan Lang Muyao Yang yunqiu xia Jingshu Liu Yunzhe Li Lingling Yang Chenxi Cui Yunran Hu Yang Luo Dongling Zou Lei Zhou Zhou Fu Qi Zhou Department of Gynecologic Oncology Chongqing University Cancer Hospital&Chongqing Cancer Institute&Chongqing Cancer HospitalChongqing 400030China Reproductive Medicine Center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400042China Bioengineering College of Chongqing University Chongqing 400044China Department of Dermatology Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical Disorders Chongqing Engineering Research Center of Stem Cell TherapyChildren’s Hospital of Chongqing Medical UniversityChongqingChina Department of Gynaecology and Obstetrics Reproductive Medicine CenterThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400030China School of Medicine Chongqing UniversityChongqing 400044China Department of Pharmacy Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China School of Basic Medicine and Clinical Pharmacy China Pharmaceutical UniversityNanjing 210009Jiangsu ProvinceChina Center of Smart Laboratory and Molecular Medicine School of MedicineChongqing UniversityChongqing 400044China Centre for Eye and Vision Research School of OptometryThe Hong Kong Polytechnic UniversityHong Kong SARChina Centre for Eye and Vision Research Department of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHong Kong SARChina Centre for Eye and Vision Research Research Centre for SHARP Vision(RCSV)The Hong Kong Polytechnic UniversityHong Kong SARChina Department of Respiratory Children’s Hospital of Chongqing Medical University&National Clinical Research Center for Child Health and Disorders&Ministry of Education Key Laboratory of Child Development and DisordersChongqing 400044China

Ovarian cancer(OC)is one of the most lethal gynecologic cancer worldwide,and survival prediction is meaningful for personalized treatment.^(1)The survival outcome of cancer patients mainly depended on the malignancy of the primary tumor which is tightly linked with the expression profile of the molecular features.^(2)Therefore,in this study,we developed a molecular feature-based survival prediction model of OC using a deep neural network(DNN).

关键词： cancer prediction neural

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中国古典文学对服饰发展的影响

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纺织报告 2024年第5期43卷 75-77页

作者：夏云秋上饶幼儿师范高等专科学校江西上饶334000

服饰作为社会生活的外在表现,其形成与政治经济条件紧密相关。文学作品中对服饰的描写不仅能细腻刻画人物形象,还是展现作品主题、塑造人物性格和揭示人物命运的重要手段,反映了当时社会的审美观念、价值取向和生活方式,并为后人了解和... 详细信息

服饰作为社会生活的外在表现,其形成与政治经济条件紧密相关。文学作品中对服饰的描写不仅能细腻刻画人物形象,还是展现作品主题、塑造人物性格和揭示人物命运的重要手段,反映了当时社会的审美观念、价值取向和生活方式,并为后人了解和研究服饰文化提供了宝贵的资料。基于此,文章深度剖析了中国古典文学的内涵、核心要素及其释义,通过举例建安时期、唐代和清代的经典文学作品,探讨了中国古典文学对服饰演变的描述与影响,并详细阐释了中国古典文学中服饰审美观念的流变,旨在帮助大众更好地理解服饰文化的内涵与价值,更深入地感受文学作品的魅力。

关键词：古典文学服饰文化服饰发展

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Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice

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Genes & Diseases 2017年第4期4卷 204-214页

作者： Danyi Peng Daozhu Si Rong Zhang Jiang Liu Hao Gou yunqiu xia Daiyin Tian Jihong Dai Ke Yang Enmei Liu Yujun Shi Q.Richard Lu Lin Zou Zhou Fu Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityMinistry of Education Key Laboratory of Child Development and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing 400014China Department of Respiratory Medicine Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Centre for Clinical Molecular Medicine Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Engineering Research Centre of Stem Cell Therapy Chongqing 400014China Laboratory of Pathology West China HospitalSichuan UniversityChengdu 610041China Key Laboratory of Birth Defects and Related Diseases of Women and Children(Ministry of Education) State Key Laboratory of BiotherapyWest China Second HospitalSichuan UniversityChengdu 610041China

Alveolar epithelial cells(AECs)injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis(PF).Nevertheless,the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear.SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF,which is essential for kidney and heart fibrosis.We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II(ATII)cells.Moreover,we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice(SOSM4D/D)model,as well as a new SMARCA4-deleted alveolar type II(ATII)-like mle-12 cell line.We found that the bleomycin-induced PF was more aggressive in SOSM4D/D mice.Also,the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro.In addition,we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections.These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells,which might affect the progression of PF.

关键词： Cell proliferation Pulmonary fibrosis SMARCA4 Transgenic mice Type II alveolar epithelial cells

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Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway

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Chinese Journal of Integrative Medicine 2024年第1期30卷 34-41页

作者： QI Zhi-min WANG xia LIU xia ZHAO Juan Medical Examination Center Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Department of Gynaecology and Obstetrics Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Experimental Center for Teaching Hebei Medical UniversityShijiazhuang(050017)China

Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration(IC_(50)) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species(ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78(GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid(4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. Results: Asperuloside of 325, 650, and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells(P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions(P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis(P<0.05), and 650 μg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3,-4 and GRP78 protein expressions(P<0.05). Conclusion: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

关键词： asperuloside Chinese medicine cervical cancer endoplasmic reticulum stress mitochondrial damage apoptosis

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Pretreating and normalizing metabolomics data for statistical analysis

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Genes & Diseases 2024年第3期11卷 188-205页

作者： Jun Sun Yinglin xia Division of Gastroenterology and Hepatology Department of MedicineDepartment of Microbiology/ImmunologyUIC Cancer CenterUniversity of Illinois ChicagoJesse Brown VA Medical Center Chicago(537)ChicagoIL 60612USA Division of Gastroenterology and Hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA

Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological samples.Metabolomics is emerging as a powerful tool generally for pre-cision medicine.Particularly,integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and disease.However,metabo-lomics data are very complicated.Preprocessing/pretreating and normalizing procedures on metabolomics data are usually required before statistical analysis.In this review article,we comprehensively review various methods that are used to preprocess and pretreat metabolo-mics data,including MS-based data and NMR-based data preprocessing,dealing with zero and/or missing values and detecting outliers,data normalization,data centering and scaling,data transformation.We discuss the advantages and limitations of each method.The choice for a suitable preprocessing method is determined by the biological hypothesis,the characteristics of the data set,and the selected statistical data analysis method.We then provide the perspective of their applications in the microbiome and metabolome research.

关键词： Data centering and scaling Data normalization Data transformation Missing values MS-Baseddata preprocessing NMRData preprocessing Outliers Preprocessing/pretreatment

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P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

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Neural Regeneration Research 2024年第8期19卷 1849-1856页

作者： Meihui He Mingfang xia Qian Yang Xingyi Chen Haibo Li xiaobo xia Eye Center of xiangya Hospital Central South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

关键词： Achaetescute complex-like 1a(Ascl1a) metabolomics Müller glia p-aminobenzoic acid(PABA) retina regeneration zebrafish

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Regional features of pollen R-values in China

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Science China Earth Sciences 2024年第1期67卷 295-308页

作者： Jie xia Jian NI College of Life Sciences Zhejiang Normal UniversityJinhua 321004China Jinhua Mountain Observation and Research Station for Subtropical Forest Ecosystems Jinhua 321004China

Establishing a quantitative relationship between modern pollen and vegetation remains a pivotal but intricate pursuit within the field of Quaternary palynology.The R-value,a well-established and traditional metric characterized by its simplicity and direct applicability,serves to calibrate the nonlinear disparities between surface pollen and modern vegetation.This study entails the construction of a comprehensive pollen R-value dataset for China derived from R-values published between 1987 and 2021.The dataset,compiled after rigorous screening,calibration,and standardization processes,encompasses 898 modern pollen sampling sites and 2115 pollen R-value data entries,encapsulating 152 pollen taxa spanning 65 families and 113 genera.Synthesizing the extracted R-values yielded the following insights:(1)A macrospatial analysis validates previously established knowledge at a site-specific scale.Evidently,pollen R-value variations across China are statistically significant.Approximately two-thirds of pollen taxa exhibit underrepresentation(e.g.,Taxodiaceae,Corylus,Nitraria,Tamarix,Cyperaceae,Poaceae,and Fabaceae),while the remaining one-third display overrepresentation(e.g.,Pinus,Picea,Betula,Ephedra,Chenopodiaceae,and Artemisia).The degree of underrepresentation surpasses that of overrepresentation,and the representation patterns of Castanea,Quercus,Polygonaceae,and Asteraceae are contingent upon vegetation types.(2)Pollen R-values follow distinct spatial distribution patterns within China.In the woody vegetation region of eastern China,R-values progressively decline from north to south,correlating with rising temperatures and precipitation.Conversely,in herbaceous vegetation regions of northern and western China,R-values decrease from east to west and from northeast to southwest,corresponding to increased aridity.Nevertheless,pollen R-values manifest variation contingent on pollen taxa,vegetation types,and climatic regions,even differing for the same taxa across varying vegetation types and climatic conditions.This hi

关键词： Pollen R-value Modern pollen-vegetation relationship Regional pattern Variability Paleovegetation reconstruction

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“Buckets effect”in the kinetics of electrocatalytic reactions

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Journal of Energy Chemistry 2024年第2期89卷 388-396,I0010页

作者： Haowen Cui Yan-xia Chen Hefei National Laboratory for Physical Sciences at Microscale Department of Chemical PhysicsUniversity of Science and Technology of ChinaHefei 230026AnhuiChina

In this study,we systematically investigated the effect of proton concentration on the kinetics of the oxygen reduction reaction(ORR)on Pt(111)in acidic solutions.Experimental results demonstrate a rectangular hyperbolic relationship,i.e.,the ORR current excluding the effect of other variables increases with proton concentration and then tends to a constant value.We consider that this is caused by the limitation of ORR kinetics by the trace oxygen concentration in the solution,which determines the upper limit of ORR kinetics.A model of effective concentration is further proposed for rectangular hyperbolic relationships:when the reactant concentration is high enough to reach a critical saturation concentration,the effective reactant concentration will become a constant value.This could be due to the limited concentration of a certain reactant for reactions involving more than one reactant or the limited number of active sites available on the catalyst.Our study provides new insights into the kinetics of electrocatalytic reactions,and it is important for the proper evaluation of catalyst activity and the study of structureperformance relationships.

关键词： Oxygen reduction reaction Kinetics Zero order Rectangular hyperbolic relationship pH effect

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Differences in insomnia-related self-reported outcomes among elderly hospitalized patients

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World Journal of Psychiatry 2024年第5期14卷 686-694页

作者： xia Ding Ling-xia Qi Dong-Yun Sun Department of Gangzha General Medical Center The Affiliated Hospital of Nantong UniversityNantong 226000Jiangsu ProvinceChina Department of Anesthesiology and Surgery The Affiliated Hospital of Nantong UniversityNantong 226000Jiangsu ProvinceChina Department of Ophthalmic Surgery Room The Affiliated Hospital of Nantong UniversityNantong 226000Jiangsu ProvinceChina

Insomnia is among the most common sleep disorders worldwide.Insomnia in older adults is a social and public health problem.Insomnia affects the physical and mental health of elderly hospitalized patients and can aggravate or induce physical illnesses.Understanding subjective feelings and providing reasonable and standardized care for elderly hospitalized patients with insomnia are urgent issues.AIM To explore the differences in self-reported outcomes associated with insomnia among elderly hospitalized patients.METHODS One hundred patients admitted to the geriatric unit of our hospital between June 2021 and December 2021 were included in this study.Self-reported symptoms were assessed using the Athens Insomnia Scale(AIS),Generalized Anxiety Disorder Scale-7(GAD-7),Geriatric Depression Scale-15(GDS-15),Memorial University of Newfoundland Scale of Happiness(MUNSH),Barthel Index Evaluation(BI),Morse Fall Scale(MFS),Mini-Mental State Examination,and the Short Form 36 Health Survey Questionnaire(SF-36).Correlation coefficients were used to analyze the correlation between sleep quality and self-reported symptoms.Effects of insomnia was analyzed using Logistic regression analysis.RESULTS Nineteen patients with AIS≥6 were included in the insomnia group,and the incidence of insomnia was 19%(19/100).The remaining 81 patients were assigned to the non-insomnia group.There were significant differences between the two groups in the GDA-7,GDS-15,MUNSH,BI,MFS,and SF-36 items(P<0.05).Patients in the insomnia group were more likely to experience anxiety,depression,and other mental illnesses,as well as difficulties with everyday tasks and a greater risk of falling(P<0.05).Subjective well-being and quality of life were poorer in the insomnia group than in the control group.The AIS scores positively correlated with the GAD-7,GDS-15,and MFS scores in elderly hospitalized patients with insomnia(P<0.05).Logistic regression analysis showed that GDS-15≥5 was an independent risk factor for insomnia in elderly hospitalized patients(P<0.05).C

关键词： Elderly hospitalized patients Insomnia Self-reported outcomes Symptoms Subjective feelings Correlation

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