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Collagen triple helix repeat containing-1 promotes functional recovery of sweat glands by inducing adjacent microvascular network reconstruction in vivo

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Burns & Trauma 2022年第1期10卷 387-400页

作者： Xingyu Yuan xianlan duan Zhao Li Bin Yao Enhejirigala Wei Song Yi Kong Yuzhen Wang Fanliang Zhang Liting Liang Shijun Zhu Mengde Zhang Chao Zhang Sha Huang Xiaobing Fu School of Medicine Nankai University94 Wei Jin RoadTianjin 300071PR China Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department PLA General Hospital28 Fu Xing RoadBeijing 100853PR China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and RegenerationChinese PLA General Hospital and PLA Medical College51 Fu Cheng RoadBeijing 100048PR China Research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048PR China Academy of Medical Engineering and Translational Medicine Tianjin University92 Weijin RoadTianjin300072PR China College of Graduate Tianjin Medical UniversityTianjin 300070PR China Institute of Basic Medical Research Inner Mongolia Medical UniversityHohhot 010110Inner MongoliaPR China Department of Burn and Plastic Surgery Air Force Hospital of Chinese PLA Central Theater CommandDatong 037000ShanxiPR China

Background:Sweat glands(SGs)have low regenerative potential after severe burns or trauma and their regeneration or functional recovery still faces many obstacles.In practice,restoring SG function requires not only the structural integrity of the gland itself,but also its neighboring tissues,especially blood vessels.Collagen triple helix repeat containing-1(CTHRC1)was first identified in vascular repair,and increasing reports showed a close correlation between cutaneous appendage specification,patterning and regeneration.The purpose of the present study was to clarify the role of CTHRC1 in SGs and their adjacent microvessels and find therapeutic strategies to restore SG function.Methods:The SGs and their adjacent microvascular network of Cthrc^(1−/−)mice were first inves-tigated using sweat test,laser Doppler imaging,tissue clearing technique and transcriptome analysis.The effects of CTHRC1 on dermal microvascular endothelial cells(DMECs)were further explored with cell proliferation,DiI-labeled acetylated low-density lipoprotein uptake,tube for-mation and intercellular junction establishment assays.The effects of CTHRC1 on SG function restoration were finally confirmed by replenishing the protein into the paws of Cthrc(1−/−)mice.Results:CTHRC1 is a key regulator of SG function in mice.At the tissue level,Cthrc1 deletion resulted in the disorder and reduction of the microvascular network around SGs.At the molecular level,the knockout of Cthrc1 reduced the expression of vascular development genes and functional proteins in the dermal tissues.Furthermore,CTHRC1 administration considerably enhanced SG function by inducing adjacent vascular network reconstruction.Conclusions:CTHRC1 promotes the development,morphogenesis and function execution of SGs and their neighboring vasculature.Our study provides a novel target for the restoration or regeneration of SG function in vivo.

关键词： Collagen triple helix repeat containing-1 Sweat glands Microvascular network Dermalmicrovascular endothelial cells Reconstruction

Reciprocal interaction between vascular niche and sweat gland promotes sweat gland regeneration

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Bioactive Materials 2023年第3期21卷 340-357页

作者： Xingyu Yuan xianlan duan Enhejirigala Zhao Li Bin Yao Wei Song Yuzhen Wang Yi Kong Shijun Zhu Fanliang Zhang Liting Liang Mengde Zhang Chao Zhang Deling Kong Meifeng Zhu Sha Huang Xiaobing Fu School of Medicine Nankai University94 Weijin RoadTianjin300071PR China Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital28 Fuxing RoadBeijing100853PR China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and RegenerationChinese PLA General Hospital and PLA Medical College51 Fucheng RoadBeijing100048PR China College of Graduate Tianjin Medical UniversityTianjin300070PR China Institute of Basic Medical Research Inner Mongolia Medical UniversityHohhot010110Inner MongoliaPR China Academy of Medical Engineering and Translational Medicine Tianjin University92 Weijin RoadTianjin300072PR China Department of Burn and Plastic Surgery Air Force Hospital of Chinese PLA Central Theater CommandDatong037000ShanxiPR China College of Life Science State Key Laboratory of Medicinal Chemical BiologyKey Laboratory of Bioactive Materials of Ministry of EducationNankai University94 Weijin RoadTianjin300071PR China Research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing100048PR China

The incorporation of vasculature is known to be effective in tissue or organ functional regeneration.However,a vague understanding of the interaction between epidermal appendages and their vascular niches is a foremost obstacle to obtaining sweat gland(SG)-specific vasculature units.Here,we map their precise anatomical con-nections and report that the interplay between SG cells(SGCs)and the surrounding vascular niche is key for glandular development and homeostasis maintenance.To replicate this interplay in vitro,we used three-dimensional(3D)bioprinting to generate reproducible SGC spheroids from differentiated adipose-derived mesenchymal stem cells(ADSCs).With dermal microvascular endothelial cells(DMECs),sacrificial templates made from poly(ε-caprolactone)(PCL)were fabricated to pattern the vascular niche.This interplay model promoted physiologically relevant vascularized glandular morphogenesis in vitro and in vivo.We identified a reciprocal regulatory mechanism for promoting SGs regeneration via contact-independent cell communication and direct cell-cell interactions between SGs and the vasculature.We envision the successful use of our approach for vascularized organ regeneration in the near future.

关键词： Vascular niche 3D bioprinting Sweat gland-vasculature interaction model ECM scaffold Sweat gland regeneration

Using bioprinting and spheroid culture to create a skin model with sweat glands and hair follicles

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Burns & Trauma 2021年第1期9卷 475-487页

作者： Yijie Zhang Enhejirigala Bin Yao Zhao Li Wei Song Jianjun Li Dongzhen Zhu Yuzhen Wang xianlan duan Xingyu Yuan Sha Huang Xiaobing Fu Research Center for Tissue Repair and Regeneration Medical Innovation Research Department and the Fourth Medical CenterChinese PLA General Hospital and PLA Medical CollegeBeijing 100048China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and RegenerationChinese PLA General Hospital and PLA Medical CollegeBeijing 100853China Research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048China College of Graduate Tianjin Medical UniversityTianjin 300070China Institute of Basic Medical Research Inner Mongolia Medical UniversityHohhot 010110Inner MongoliaChina The Shenzhen Key Laboratory of Health Sciences and Technology Graduate School at ShenzhenTsinghua UniversityShenzhen 518055GuangdongChina Department of General Surgery the Sixth Medical CenterChinese PLA General HospitalBeijing 100048China Department of Burn and Plastic Surgery Air Force Hospital of Chinese PLA Central Theater CommandDatong 037000ShanxiChina School of Medicine Nankai UniversityTianjin 300071China

Background:Sweat glands(SGs)and hair follicles(HFs)are two important cutaneous appendages that play crucial roles in homeostatic maintenance and thermoregulation,and their interaction is involved in wound healing.SGs can be regenerated from mesenchymal stem cell-laden 3D bioprinted scaffolds,based on our previous studies,whereas regeneration of HFs could not be achieved in the same model.Due to the lack of an in vitro model,the underlying molecular mechanism of the interaction between SGs and HFs in regeneration could not be fully understood.The purpose of the present study was to establish an in vitro model of skin constructs with SGs and HFs and explore the interaction between these two appendages in regeneration.Methods:To investigate the interaction effects between SGs and HFs during their regeneration processes,a combined model was created by seeding HF spheroids on 3D printed SG scaffolds.The interaction between SG scaffolds and HF spheroids was detected using RNA expression and immunofluorescence staining.The effects of microenvironmental cues on SG and HF regeneration were analysed by altering seed cell types and plantar dermis homogenate in the scaffold.Results:According to this model,we overcame the difficulties in simultaneously inducing SG and HF regeneration and explored the interaction effects between SG scaffolds and HF spheroids.Surprisingly,HF spheroids promoted both SG and HF differentiation in SG scaffolds,while SG scaffolds promoted SG differentiation but had little effect on HF potency in HF spheroids.Specifically,microenvironmental factors(plantar dermis homogenate)in SG scaffolds effectively promoted SG and HF genesis in HF spheroids,no matter what the seed cell type in SG scaffolds was,and the promotion effects were persistent.Conclusions:Our approach elucidated a new model for SG and HF formation in vitro and provided an applicable platform to investigate the interaction between SGs and HFs in vitro.This platform might facilitate 3D skin constructs with multiple appendages and unveil the

关键词： Skin regeneration Sweat glands Hair follicle 3D bioprinting Spheroid culture Skin constructs

自身免疫糖尿病患者外周血单个核细胞miR-142和miR-143表达的研究

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中华内分泌代谢杂志 2019年第8期35卷 690-696页

作者：谢志国李蒙禹俞海波段仙兰黄干周智广中南大学湘雅二医院代谢内分泌科、国家代谢性疾病临床医学研究中心、糖尿病免疫学教育部重点实验室长沙410011

目的探讨自身免疫糖尿病患者(ADM),包括经典1型糖尿病(T1DM)和成人隐匿性自身免疫糖尿病(LADA),以及2型糖尿病患者(T2DM)和健康对照外周血单个核细胞(PBMC)的microRNA(miRNA)表达水平。方法收集2015年1月至2016年12月在中南大学湘雅二... 详细信息

目的探讨自身免疫糖尿病患者(ADM),包括经典1型糖尿病(T1DM)和成人隐匿性自身免疫糖尿病(LADA),以及2型糖尿病患者(T2DM)和健康对照外周血单个核细胞(PBMC)的microRNA(miRNA)表达水平。方法收集2015年1月至2016年12月在中南大学湘雅二医院就诊的糖尿病患者及健康体检中心体检的健康对照人群,研究对象分为两批,分别进行高通量测序初筛差异表达的miRNA,以及对miR-142和miR-143的表达进行实时定量聚合酶链反应(RT-qPCR)验证。结果(1)T1DM患者、LADA患者、T2DM患者以及健康对照的PBMC中miRNA的表达存在差异;(2)与T2DM患者和健康对照相比,LADA和T1DM患者PBMC中的miR-142-5p表达下调,而miR-143-3p表达上调;(3)RT-qPCR验证实验显示,miR-142-5p在LADA患者中表达水平较T2DM患者显著下调。miR-143-3p在T1DM患者和LADA患者中表达量较T2DM患者和健康对照有升高趋势,但差异无统计学意义。结论(1)T1DM患者、LADA患者、T2DM患者以及健康对照的PBMC中miRNA的表达存在差异;(2)miR-142-5p和miR-143-3p的异常表达可能通过影响细胞凋亡和免疫细胞分化参与ADM发生发展。

关键词：自身免疫糖尿病外周血单个核细胞微小核糖核酸

体外艾塞那肽对1型糖尿病患者外周血单个核细胞的免疫调节作用

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中华糖尿病杂志 2017年第10期9卷 617-621页

作者：李霞雷康俞海波段仙兰彭亚妮周智广中南大学湘雅二医院内分泌代谢科中南大学糖尿病免疫学教育部重点实验室国家代谢性疾病临床医学研究中心长沙410011

目的探讨体外艾塞那肽（Exendin-4）对1型糖尿病（T1DM）患者外周血单个核细胞（PBMC）的免疫调节作用.方法通过密度梯度离心法分离11例T1DM患者外周血PBMC,体外研究Exendin-4对PBMC的作用.通过Western blotting检测胰高血糖素样肽1... 详细信息

目的探讨体外艾塞那肽（Exendin-4）对1型糖尿病（T1DM）患者外周血单个核细胞（PBMC）的免疫调节作用.方法通过密度梯度离心法分离11例T1DM患者外周血PBMC,体外研究Exendin-4对PBMC的作用.通过Western blotting检测胰高血糖素样肽1受体（GLP-1R）的表达情况;根据检测PBMC中环磷酸腺苷（cAMP）的浓度设置不同Exendin浓度干预组（0、10、100 nmol/L）及拮抗剂组[50 nmol/L Exendin 9（39）＋100 nmol/L Exendin-4];实时荧光定量聚合酶链反应（PCR）和细胞因子微球检测技术分别测定Exendin-4干预前后细胞因子[白细胞介素（IL）10、肿瘤坏死因子（TNF）α]在胞内和上清中的变化情况.两组间比较采用t检验,多组间比较采用方差分析.结果（1）T1DM患者PBMC表达GLP-1R,与对照组（0 nmol/L）相比,100 nmol/L Exendin-4干预组GLP-1R表达显著上升（1.97±0.24比1;t=13.89,P〈0.05）,此种效应能够被GLP-1R阻断剂Exendin-9（39）阻断（0.56±0.10比1, t=15.68,P〈0.05）.（2）与对照组相比,1、10、100 nmol/L浓度Exendin-4对T1DM患者PBMC活力无明显影响（F=0.362、0.393、0.374,均P〉0.05）.（3）与对照组相比,10、100 nmol/L Exendin-4上调PBMC中cAMP水平（7.51±0.01比2.56±0.01,17.21±0.04比2.56±0.01,t=19.71、32.89,P〈0.05）.（4）与对照组相比,Exendin-4显著下调PBMC细胞中TNF-α mRNA及上清液中TNF-α水平（F=5.54、5.12,P〈0.05）,此种效应能够被GLP-1R阻断剂Exendin-9（39）阻断（F=5.43、5.97,P〈0.05）;同时Exendin-4可上调上清液中IL-10水平（F=5.95、6.01,P〈0.05）.结论 Exendin-4可上调IL-10的分泌,下调TNF-α的分泌,提示其可能抑制炎症反应.

关键词：艾塞那肽糖尿病 1型胰高血糖素样肽1受体免疫调节

外周T细胞淋巴瘤患者血清代谢产物与临床特征的相关性分析

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陆军军医大学学报 2024年第4期46卷 352-358页

作者：段一硕饶军夏菁马娜丫蔺诗佳李甫唐书翰周沙曾韫璟李炘檑黄德智李琼刘帮洞赵先兰魏锦张曦川北医学院附属医院血液内科南充637002 陆军军医大学(第三军医大学)第二附属医院血液病医学中心全军临床重点专科创伤与化学中毒全国重点实验室重庆市临床重点专科血液病与微环境重庆市重点实验室重庆400037 金凤实验室重庆401329

目的观察外周T细胞淋巴瘤患者血清能量代谢产物的变化,从能量代谢角度寻找监测外周T细胞淋巴瘤的血清生物标志物。方法收集2020年11月至2021年12月在陆军军医大学第二附属医院血液病医学中心诊治的16例外周T细胞淋巴瘤初诊患者,并招... 详细信息

目的观察外周T细胞淋巴瘤患者血清能量代谢产物的变化,从能量代谢角度寻找监测外周T细胞淋巴瘤的血清生物标志物。方法收集2020年11月至2021年12月在陆军军医大学第二附属医院血液病医学中心诊治的16例外周T细胞淋巴瘤初诊患者,并招募同期10名健康志愿者作为对照。采用选择性反应/多反应监测技术(selected/multiple reaction monitoring, SRM/MRM)检测其血清中能量相关代谢产物的差异,并结合其临床资料,包括病史、影像学、实验室检查等进行回顾性分析。结果与健康对照相比,外周T细胞淋巴瘤患者血清中能量代谢相关产物水平表达谱存在差异,其中环磷腺苷、琥珀酸、柠檬酸和顺乌头酸含量显著降低(P<0.05),6-磷酸葡萄糖水平升高(P<0.05),且患者血清中的柠檬酸和琥珀酸水平与疾病危险度分级(低危、中危、高危)和临床分期呈负相关(P<0.05),同时,苹果酸和柠檬酸水平与患者中期疗效评估结果[完全缓解/部分缓解(CR/PR)或疾病稳定(SD)]呈明显负相关(P<0.05)。对于结外NK/T细胞淋巴瘤患者(n=10),与健康对照相比,其血清中环磷腺苷、琥珀酸、柠檬酸、异柠檬酸和顺乌头酸含量亦有显著降低(P<0.05),其中柠檬酸与琥珀酸的水平与结外NK/T细胞淋巴瘤患者的临床分期呈负相关(P<0.05),与中期疗效评估(CD/PR或SD)呈明显相关性(P<0.05);对于血管免疫母细胞性T细胞淋巴瘤患者(n=6),与健康对照相比,其血清中环磷腺苷、柠檬酸和琥珀酸的含量明显降低,而6-磷酸葡萄糖的含量明显升高(P<0.05),其中琥珀酸水平分别与患者临床分期和危险度分级都表现出明显的负相关(P<0.05)。结论外周T细胞淋巴瘤患者与健康对照人群在血清代谢产物水平上共鉴定出5个差异代谢产物,其中琥珀酸、柠檬酸有希望成为血清生物标志物。

关键词：外周T细胞淋巴瘤结外NK/T细胞淋巴瘤血管免疫母细胞性T细胞淋巴瘤血清代谢组学生物标志物多反应监测

井冈山竹柏种群结构和分布格局及其群落特征分析

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植物资源与环境学报 2013年第2期22卷 92-97页

作者：邓贤兰肖平根吴杨段世华徐日华井冈山大学生命科学学院江西吉安343009 江西省永丰县林业局江西永丰331500

采用样方法对江西井冈山竹柏〔Nageia nagi(Thunb.)Kuntze〕种群的4个样地进行了调查,并据此分析了种群的年龄结构、分布格局及其群落区系特征和物种多样性。结果表明:根据株高和胸径可将种群分为6个径级,其中Ⅰ级幼苗和Ⅱ级幼树数量最... 详细信息

采用样方法对江西井冈山竹柏〔Nageia nagi(Thunb.)Kuntze〕种群的4个样地进行了调查,并据此分析了种群的年龄结构、分布格局及其群落区系特征和物种多样性。结果表明:根据株高和胸径可将种群分为6个径级,其中Ⅰ级幼苗和Ⅱ级幼树数量最多,比例分别达到33.33%和30.48%,种群的年龄结构为金字塔型。随径级增加种群生命期望值逐级递减、种群中的存活个体数逐渐减少;其中,Ⅰ级幼苗的死亡率最小、生命期望值最大,而Ⅵ级衰老株死亡率最大;种群存活曲线接近Deevey-Ⅱ型(直线型);种群的方差/均值比达到3.41,表明其分布格局为集群分布。该竹柏群落包含维管植物34科56属62种,其中,蕨类植物8科8属8种、裸子植物1科1属1种、被子植物25科47属53种,以木本植物占绝对优势。群落维管植物科、属的区系地理成分较复杂,但均具有明显的热带性质。群落各样地间的多样性指数差异较大,但均为Pielou指数较高,物种丰富度指数、Simpson指数和Shannon-Wiener指数均较低;群落不同层次的各项多样性指数差异明显,均为灌木层最高、乔木层最低,但乔木层的多样性变幅较大。研究结果显示:该竹柏种群为增长型种群,具有较强的自然更新能力,但物种多样性程度较低。

关键词：竹柏种群结构分布格局物种组成群落特征多样性指数

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孕晚期营养因素与子痫前期的病例-对照研究

卫生研究 2019年第2期48卷 232-237页

作者：窦伟峰赵先兰吕全军段丹丹陈改云付文君刘艳华王玲郑州大学公共卫生学院郑州450001 郑州大学第一附属医院郑州450001 洛阳新区人民医院洛阳471023

目的探讨孕晚期膳食摄入情况与子痫前期发生的关系。方法采用1∶1匹配的病例-对照研究,选择2016年3—12月在郑州大学第一附属医院产科住院分娩的子痫前期患者131例为病例组,按照年龄±3岁、孕周±2周,随机选取血压正常且没有蛋白尿的孕... 详细信息

目的探讨孕晚期膳食摄入情况与子痫前期发生的关系。方法采用1∶1匹配的病例-对照研究,选择2016年3—12月在郑州大学第一附属医院产科住院分娩的子痫前期患者131例为病例组,按照年龄±3岁、孕周±2周,随机选取血压正常且没有蛋白尿的孕妇131例为对照组。通过食物频率问卷(FFQ)及自制孕期健康危险因素调查问卷,调查研究对象近3个月的膳食摄入情况,并计算平均每天各种营养素的摄入量,采用条件Logistic回归对统计结果进行分析。结果多因素条件Logistic回归发现,病例组的孕前体质指数(OR=1.18,95%CI 1.08～2.82)和孕期增重(OR=1.51,95%CI 1.15～1.97)均高于对照组,该组孕妇红黄色水果(OR=0.76,95%CI 0.60～0.98)的摄入量、以及膳食中维生素C(OR=0.57,95%CI 0.33～0.99)和叶酸(OR=0.36,95%CI 0.18～0.72)摄入量均低于对照组,两组之间的差异有统计学意义(P<0.05)。结论过高的孕前体质指数和孕期增重过多是子痫前期的危险因素,妊娠期适当增加红黄色水果的摄入有利于预防子痫前期的发生,维生素C和叶酸的摄入可能是子痫前期的保护因素。

关键词：子痫前期膳食营养素孕妇病例-对照研究

腹主动脉球囊封堵联合剖宫产术治疗凶险性前置胎盘的安全性随访研究

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中华介入放射学电子杂志 2021年第1期9卷 36-40页

作者：王艳丽蒋天段旭华赵毅徐苗焦德超韩新巍陈志敏刘传赵先兰王晓娟储勤军郑州大学第一附属医院放射介入科河南郑州450052 河南省人民医院放射科华中阜外医院放射科郑州大学华中阜外医院河南郑州450003 郑州大学第一附属医院产科河南郑州450003 郑州大学第一附属医院麻醉科河南郑州450003

目的探讨腹主动脉球囊封堵联合剖宫产术治疗凶险性前置胎盘的安全性和有效性,评估其对患者生育功能和新生儿健康状况的影响。方法回顾性分析2013年1月至2019年1月我院收治的1018例凶险性前置胎盘患者的临床资料。所有患者均接受腹主动... 详细信息

目的探讨腹主动脉球囊封堵联合剖宫产术治疗凶险性前置胎盘的安全性和有效性,评估其对患者生育功能和新生儿健康状况的影响。方法回顾性分析2013年1月至2019年1月我院收治的1018例凶险性前置胎盘患者的临床资料。所有患者均接受腹主动脉球囊封堵联合剖宫产术治疗。本研究旨在通过分析1018例患者的手术时间、术中出血量、输血量、术中和术后并发症、术后恢复情况以及胎儿射线暴露时间和剂量、新生儿Apgar评分等评估腹主动脉球囊封堵联合剖宫产术治疗凶险性前置胎盘的安全性和有效性。结果所有1018例患者中,940例仅接受腹主动脉球囊封堵术,78例因术后活动性出血紧急行子宫动脉栓塞术,所有患者均成功保全子宫,除8例发生右侧股动脉血栓、3例发生右下肢肌间静脉血栓外,其余患者术后均未发生下肢动静脉血栓、肾功能不全、晚期产后出血、异位栓塞、脊髓及周围神经损害及盆腔感染等严重并发症。平均手术时间(57.6±17.3)min。平均术中出血量(590±570)mL。126例(12.38%,126/1018)给予输血治疗,平均输血量(630±450)mL。1018例平均住院天数(6.4±4.2)d,胎儿射线暴露平均时间为(5.1±1.4)s,平均剂量为(4.0±2.6)mGy。新生儿Apgar评分,1 min为(9.2±0.4)分,5 min为(9.6±0.3)分。随访至2019年5月31日,38例失访,137例处于哺乳期,843例月经复潮。除38例失访外,余982名存活新生儿(其中2例双胞胎)出生后42 d门诊随访检查均未见异常。结论腹主动脉球囊封堵联合剖宫产术治疗凶险性前置胎盘,能够降低子宫切除风险,减少术中出血量,对孕妇和新生儿无不良影响,是一种安全、有效的治疗方法。

关键词：凶险性前置胎盘腹主动脉球囊剖宫产安全性