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Comparison of clinical features and outcomes of proliferative,fibrotic,and mixed subtypes of IgG4-related disease:A retrospective cohort study

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Chinese medical Journal 2024年第3期137卷 303-311页

作者： Linyi Peng Xinlu Zhang Jiaxin Zhou Jieqiong Li Zheng Liu Hui Lu Yu Peng Yunyun Fei Yan Zhao Xiaofeng Zeng Wen Zhang Department of Rheumatology and clinical Immunology Peking Union Medical College HospitalNational Clinical Research Center for Dermatologic and Immunologic DiseasesState Key Laboratory of Complex Severe and Rare DiseasesThe Ministry of Education Key LaboratoryBeijing 100730China Institute of clinical Medicine Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Background:Immunoglobulin G4-related disease(IgG4-RD)is a recently recognized immune-mediated disorder that can affect almost any organ in the human body.IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients’clinicopathological characteristics.This study aimed to compare the clinical manifestations,laboratory findings,and treatment outcomes of IgG4-RD among different subtypes.Methods:We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking union medical College Hospital from March 2011 to August 2021.The patients were divided into three groups according to their clinicopathological characteristics:proliferative,fibrotic,and mixed subtypes.We compared demographic features,clinical manifestations,organ involvement,laboratory tests,and treatment agents across three subtypes.We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants.Moreover,risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.Results:We classified the 622 patients into three groups consisting of 470 proliferative patients,55 fibrotic patients,and 97 mixed patients,respectively.We found that gender distribution,age,disease duration,and frequency of allergy history were significantly different among subgroups.In terms of organ involvement,submandibular and lacrimal glands were frequently involved in the proliferative subtype,while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype.The comparison of laboratory tests revealed that eosinophils(P=0.010),total IgE(P=0.006),high-sensitivity C-reactive protein(P<0.001),erythrocyte sedimentation rate(P<0.001),complement C4(P<0.001),IgG(P=0.001),IgG1(P<0.001),IgG4(P<0.001),and IgA(P<0.001),at baseline were significantly different among three subtypes.Compared with proliferative and mixed subtypes,the fibrotic subtype showed the lowest rate of relapse(log-rank P=0.014).Conclus

关键词： IgG4-related disease Proliferative subtype Fibrotic subtype clinical features Treatment outcome

Biological scaffold as potential platforms for stem cells:Current development and applications in wound healing

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World Journal of Stem Cells 2024年第4期16卷 334-352页

作者： Jie-Yu Xiang Lin Kang Zi-Ming Li Song-Lu Tseng Li-Quan Wang Tian-Hao Li Zhu-Jun Li Jiu-Zuo Huang Nan-Ze Yu Xiao Long Department of Plastic and Reconstructive Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Biomedical Engineering Facility Institute of Clinical MedicinePeking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100021China

Wound repair is a complex challenge for both clinical practitioners and researchers.Conventional approaches for wound repair have several limitations.Stem cell-based therapy has emerged as a novel strategy to address this issue,exhibiting significant potential for enhancing wound healing rates,improving wound quality,and promoting skin regeneration.However,the use of stem cells in skin regeneration presents several challenges.Recently,stem cells and biomaterials have been identified as crucial components of the wound-healing process.Combination therapy involving the development of biocompatible scaffolds,accompanying cells,multiple biological factors,and structures resembling the natural extracellular matrix(ECM)has gained considerable attention.Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells,providing them with an environment conducive to growth,similar to that of the ECM.These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing.This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing,emphasizing their capacity to facilitate stem cell adhesion,proliferation,differentiation,and paracrine functions.Additionally,we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

关键词： Stem-cell-based therapy Biological scaffolds Wound healing Extracellular matrix mimicry Cellular activities enhancement Scaffold characteristics

Progress in the generation of spinal cord organoids over the past decade and future perspectives

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Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： Gang Zhou Siyuan Pang Yongning Li Jun Gao Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of International medical Service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

Incidence and Mortality of Cancers in Female Genital Organs—China,2022

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China CDC weekly 2024年第10期6卷 195-202,I0003,I0004页

作者： Kexin Sun Bingfeng Han Hongmei Zeng Shaoming Wang Li Li Ru Chen Rongshou Zheng Wenqiang Wei National Central Cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Introduction:This study presented the incidence and mortality rates of cancers affecting the female genital organs in China,along with their trends spanning from 2010 to 2018.Methods:700 population-based cancer registries provided relevant cancer incidence and mortality data for the year 2018.Among these,106 registries had continuous monitoring data suitable for trend analysis from 2010 to 2018.We focused specifically on cancers affecting female genital organs(ICD10=C51-C54,C56)and projected their incidences and mortalities in China for 2022 based on data from 2018 and the trends observed from 2010 to 2018.Age-standardized incidence rate(ASIR)and mortality rate(ASMR)were calculated using Segi’s world standard population.Results:In 2022,there were an estimated 296,300 new cases and 104,900 deaths from female cancers in China.ASIRs for vulva(C51),vagina(C52),cervix uteri(C53),corpus uteri(C54),and ovary(C56)were 0.32,0.23,13.83,6.84,and 5.68 per 100,000 population.ASIRs for corpus uteri and ovary cancers were higher in urban areas.ASMRs for vulva,vagina,cervix,corpus uteri,and ovary cancers were 0.14,0.08,4.54,1.05,and 2.64 per 100,000 population,respectively.ASMR for ovarian cancer was higher in urban areas.ASIRs and ASMRs for most female genital organ cancers increased from 2010 to 2018,although the rate of increase for vulvar and cervical cancers in rural areas has slowed recently.Conclusions:Tailored cancer prevention and control programs specific to each region are necessary to address the growing disease burden.

关键词： ICD10 mortality organs

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military medical Research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

Comprehensive characterization of cell disulfidptosis in human cancers:An integrated pan-cancer analysis

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Genes & Diseases 2024年第4期11卷 5-8页

作者： Guo Zhao Yale Jiang Yuning Wang Shuhang Wang Ning Li clinical Trial Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Excessive accumulation of disulfide molecules,like cystine,can induce disulfide stress and high toxicity in cells,but the reduced form of nicotinamide adenine dinucleotide phosphate can reverse this process and mitiga... 详细信息

关键词： disulfide cancer characterization

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 393-398页

作者： Mei-Zi Li Tao Guo Yun-Lu Feng Sheng-Yu Zhang Xiao-Yin Bai Xi Wu Kai Xu Ai-Ming Yang Department of Gastroenterology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China Department of Radiology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

关键词： Type 1 autoimmune pancreatitis Diabetes mellitus Corticosteroid therapy Predictive factor Pancreatic atrophy

Pathogenesis of chronic enteropathy associated with the SLCO2A1 gene:Hypotheses and conundrums

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World Journal of Gastroenterology 2024年第19期30卷 2505-2511页

作者： Zhi-Xin Xie Yue Li Ai-Ming Yang Dong Wu Qiang Wang State Key Laboratory of Complex Severe and Rare Diseases Department of GastroenterologyPeking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China Department of clinical Medicine Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China

Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.

关键词： SLCO2A1 Prostaglandin E2 Chronic enteropathy associated with the SLCO2A1 gene Small intestine Macrophage

Efficacy and safety of transvaginal mesh repair in a cohort with a minimum of 10-year follow-up

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Science China(Life Sciences) 2024年第5期67卷 1061-1068页

作者： Zhibo Zhang Jianbin Guo Weijie Tian Ye Zhang Yuelun Zhang Tianshu Sun Jiali Duan Xinmiao Bao Yuan Wang Yang Ye Qianqian Gao Honghui Shi Abraham Nick Morse Juan Chen Lan Zhu Departmentof Obstetrics and Gynecology Peking Union MedicalCollege HospitalChinese Academyof Medical Sciences&Peking Union MedicalCollegeNational Clinical Research Center for Obstetricand Gynecologic DiseasesBeijing 100730China Department of Gynecology Guizhou Provincial People’s HospitalMedical College of Guizhou UniversityGuiyang 550002China Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China medical Research Center Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China medical Doctor Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Pathology Peking Union Medical College HospitalBeijing 100730China Tufts University School of Medicine Boston MA 02111USA

Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great importance globally.However,reports with follow-up>10 years are limited.Thus,this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up.Women with stageⅢ–Ⅳsymptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital.The main outcome measure was symptomatic failure.Secondary outcomes included anatomic failure,recurrence,patient satisfaction,complications,and reoperation.The Kaplan-Meier curve was used to estimate the cumulative failure rate.Of the 121 patients enrolled in the study,103(85.1%)completed a median follow-up of 11 years.The estimated probability rates of symptomatic and anatomic failure were 17.6%and 8.8%in 11 years,respectively.The estimated incidence of symptomatic failure increased by 8.2%between 5 and 11 years;however,the corresponding rate for anatomic failure was 3.7%.The most common complication was vaginal mesh exposure,and its estimated probability increased from 19.3%to 28.4%from 5 to 11 years,respectively.Office trimming resolved 80.0%of vaginal exposures.These patients did not report decreased overall satisfaction.Patients with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room(5.8%by 11 years)had lower satisfaction rates(P<0.01)and were defined as having severe mesh exposure.The rates of postoperative pain,reoperation,and Patient Global Impression of Improvement≥2 were 2.5%,3.3%,and 94.2%,respectively.The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall.Vaginal mesh exposure was common in women who were largely not sexually active;however,80%of the cases could be managed in the outpatient clinic,which did not affect patient satisfaction.

关键词： complication efficacy long-term follow-up pelvic organ prolapse safety transvaginal mesh