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Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis:a nationwide retrospective study in China

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World Journal of Pediatrics 2024年第5期20卷 506-516页

作者： Li-Wen Tan Jun-Li Wan Chun-hua Zhu Hong Xu Zheng-Kun Xia Li-Zhi Chen Xiao-Chuan Wu Fang Wang Xiao-Rong Liu Cheng-Guang Zhao Xiao-Zhong Li Jian-hua Mao Xiao-Wen Wang Wen-Yan huang Yu-Hong Li Jian-Jiang zhang Shi-Pin Feng Jun Yang Jiao-Jiao Liu Chun-Lin Gao Li-Ping Rong Lan-Jun Shuai Ke Xu He-Jia zhang Qiu Li ai-hua zhang Mo Wang Department of Nephrology Children’s Hospital of Chongqing Medical UniversityZhongshan 2nd Rd.136Chongqing400014China Ministry of Education Key Laboratory of Child Development and Disorders National 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 UniversityChongqingChina Chongqing Key Laboratory of Pediatrics Children’s Hospital of Chongqing Medical UniversityChongqingChina Department of Nephrology Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing210008China Department of Nephrology Children’s Hospital of Fudan UniversityNational Paediatric Medical Center of ChinaShanghaiChina Department of Pediatrics Jinling HospitalNanjing Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalThe First School of Clinical MedicineSouthern Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalMedical School of Nanjing UniversityNanjingChina Department of Pediatric Nephrology and Rheumatology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina Department of Pediatrics The Second Xiangya Hospital of Central South UniversityChangshaChina Department of Pediatrics Peking University First HospitalBeijingChina Department of Nephrology Beijing Children’s HospitalCapital Medical UniversityBeijing100045China National Center for Children’s Health BeijingChina Department of Pediatrics Shengjing Hospital of China Medical UniversityShenyangChina Department of Nephrology and Immunology Children’s Hospital of Soochow UniversitySuzhouChina Department of Nephrology Children HospitalZhejiang University School of MedicineHangzhouChina Department of Nephrology Wuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanChina Department of Nephrology and Rheumatology Shanghai Children’s HospitalSchool

Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.Methods Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively.The risk factors and predictive model of end-stage renal disease(ESRD)in AAV were explored.Results Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 months.The eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal biopsy.Based on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive model.The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external validation.Conclusions Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into ESRD.The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.

关键词： Antineutrophil cytoplasmic antibody End-stage renal disease Glomerulonephritis Pediatric nephrology Vasculitis

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MiR-29b expression is altered in crescent formation of HSPN and accelerates AngⅡ-induced mesangial cell activation

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World Journal of Pediatrics 2020年第2期16卷 201-212页

作者： Shan Cheng Chun-hua Zhu ai-hua zhang Song-Ming huang Department of Infectious Disease Children's Hospital of Nanjing Medical University72 Guangzhou RoadNanjing 210008China Department of Nephrology Children's Hospital of Nanjing Medical University72 Guangzhou RoadNanjing 210008China

Background MicroRNA-29b(miR-29b)has been suggested to possess pro-inflammatory activity,which can partially be explained by the repression of tumor necrosis factor alpha protein three antibody(TNFaiP3).Meanwhile,it also promotes thyroid cell proliferation via Smad signaling pathways.The present study aimed to elucidate the role of miR-29b in Henoch Sch(o)nlein purpura nephritis(HSPN)and its underlying molecular mechanism in angiotensinⅡ(AngⅡ)-induced human glomerular mesangial cell(HGMC)activation.Methods We evaluated miR-29b expression in 35 HSPN renal tissues based on crescent formation,glomerular sclerosis,interstitial fibrosis,thrombosis formation and capillary loop necrosis.Meanwhile,HGMCs were cultured,treated with AngⅡand then transfected with LV-hsa-miR-29b-1 to induce miR-29b overexpression or LV-hsa-miR-29b-3p-inhibition to inhibit miR-29b expression.Finally,we examined the effects of miR-29b on cell proliferation and release of inflammatory mediators.Results We observed that miR-29b expression was significantly higher in the crescent group than in the no crescent group.MiR-29b overexpression induced the release of intercellular adhesion molecule-1,interleukin-1β(IL-1β),IL-6,IL-8,the increase of CyclinA2,CyclinD 1,and cell proliferation.It also could inhibit the expressions of TNFaiP3 and NF-kappa-B-repressing factor(NKRF).Correspondingly,miR-29b inhibition produced the opposite effects and increased the expression of TNFaiP3 and NKRF.Conclusion MiR-29b expression is altered in crescent formation of HSPN and accelerates AngⅡ-induced mesangial cell proliferation and release of inflammatory mediators.

关键词： Cell proliferation Crescent Inflammation MiR-29b

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Chinmedomics: A Powerful Approach Integrating Metabolomics with Serum Pharmacochemistry to Evaluate the Efficacy of Traditional Chinese Medicine

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Engineering 2019年第1期5卷 60-68页

作者： ai-hua zhang Hui Sun Guang-Li Yan Ying Han Qi-Qi Zhao Xi-Jun Wang National Chinmedomics Research Center & Sino-America Chinmedomics Technology Collaboration Center & National TCM Key Laboratory of Serum Pharmacochemistry & Laboratory of Metabolomics Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine Harbin 150040 China

Evaluation of the efficacy of traditional Chinese medicines (TCMs) is an important prerequisite for discovering effective substances, lead compounds, and quality markers (Q markers). At present, there is an urgent need to develop a biological language that can act as abridge for the scientific elaboration of the efficacy of TCMs, and to further highlight the significant value of TCM. Chinese medicinal syndromes and formulae are two essential parts of TCM that directly relate to its efficacy. Syndromes and formulae have been taken as the research objects. The serum pharmacochemistry of the TCM approach with metabolomics were integrated to establish an innovative chinmedomics strategy, which is able to explore syndrome biomarkers and evaluate TCM efficacy in order to discover effective substances from TCMs. A great deal of concrete work in chinmedomics has already performed to bridge the gap between Chinese and Western medicine, and to provide a powerful approach to enhance the scientific value of TCM theory and clinical practice. This article summarizes the application of chinmedomics in identifying the candidate biomarkers of a syndrome and revealing the efficacy of the related formula. We also highlight the discovery of lead compounds and Q markers from TCMs.

关键词： Chinmedomics Serum pharmacochemistry of TCM Efficacy Metabolomics Syndrome Biomarkers Quality markers

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Bibliometric analysis of literature regarding ostomy research based on the Web of Science database

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Frontiers of Nursing 2018年第3期5卷 193-198页

作者： Lan Gao Xiu-Zhen Cao ying zhang Tai-Fang Liu ai-hua zhang Taishan Medical University Tai'anShandong 271016China Tai'an City Central Hospital Tai'anShandong 271000China

Objective： To analyze the literature status and research hotspots of Science Citation Index （SCI）-related ostomy in the world and to provide references for scientific research and clinical work in the stoma care field. Methods： Based on the Web of Science core database and its own analysis function, HistCite analysis software and Excel were used to study the published research about ostomy patients. Results： A total of 1,262 articles were published between 1910 and 2016 with the authors from 48 countries and regions, 1,347 research institutions, published in 321 journals, with 4,048 first authors and coauthors; globally, there was a trend of slow growth in the number of authors every year. The study in the USA was absolutely in the lead position, and Canada and Turkey were more active. China＇s circulation volume was the 15th in the world. The periodical that published most often was the Journal of Wound Ostomy and Continence Nursing. The most interdisciplinary surgical studies were surgery and nursing, where these should be considered important. The most prolific author in the field was ＂Grant＂, and the highest cited article was entitled as ＂Living with a stoma： a review of the literature＂. Conclusions： The related research of global stoma is constantly developing. The research hotspot is nursing before and after stoma surgery. China and the USA are leading countries in research. They should follow the recent trend to improve the depth and breadth of the research in the field.

关键词： Web of Science ostomy stoma literature measurement nursing

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Pharmacokinetics Applications of Traditional Chinese Medicines

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World Journal of Traditional Chinese Medicine 2016年第1期2卷 42-47页

作者： Qiu-Ju Li ai-hua zhang Hui Sun Xi-Jun Wang National TCM Key Lab of Serum Pharmacochemistry Key Laboratory of Metabolomics and Chinmedomics Department of Pharmaceutical AnalysisHeilongjiang University of Chinese Medicine

Traditional Chinese medicine(TCM) has been widely used in many oriental countries for thousands of years and played an indispensable role in the prevention and treatment of diseases, especially the complicated and chronic ones. It is a very complex mixture containing hundreds or thousands of different components. Pharmacokinetic study on active constituents in TCM preparations is a good way for us to explain and predict a variety of events related to the efficacy and toxicity of TCM. In the drug discovery phases, pharmacokinetics is a key to guide medicinal chemists in the optimization process of a chemical series and to assist pharmacologists to design in vivo studies.To explore the potentially bioactive components in TCM, it is necessary to further study the in vivo pharmacokinetic characteristics of multiple absorbed components and find out the optical time-course behavior to providing more substantial research for new leads in drug discovery. Pharmacokinetics screening method could provide a reliable means of prospecting natural products in the search for new leads in drug discovery. This review summarizes the research progress of PK on TCM in the search for suitable lead compounds in recent years.

关键词： Traditional Chinese medicine Pharmacokinetics Drug discovery Active constituents

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Use of off-label nephrology-related drugs in hospitalized pediatric patients: a retrospective study

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世界儿科杂志:英文版 2016年第2期12卷 236-242页

作者： Marchella Yasinta Ruo-Chen Che Cai-Yu Hu Xiang-Hui Du Gui-Xia Ding Song-Ming huang Ying Chen ai-hua zhang Department of Nephrology Nanjing Children's Hospital Affiliated to Nanjing Medical UniversityNanjingChina Jiangsu Key Laboratory of Pediatrics NanjingChina

Background: The information about the use of off-labeldrugs in pediatric nephrology is still lacking, which leadsto increased adverse reactions and medical disputes. Weretrospectively analyzed the use of off-label drugs in thein-patient ward of the nephrology department of NanjingChildren's Hospital, China in order to provide morecomplete information about the use of drugs for children.Methods: Proportional stratified random samplingwas applied to select patients with renal diseases aged 1month to 18 years, who were admitted to the hospital fromOctober 1, 2012 to September 30, 2013. All nephrologyrelateddrugs prescribed in the hospitalization period andtake-home drugs prescribed on discharge were recordedand evaluated as off-label drugs or not from threedifferent perspectives: person-time, prescription, anddrug category.Results: From 385 person-times of patients with 1424prescriptions, according to the ratio between off-labeldrugs and person-times, drug prescriptions, and drugproducts, the rates of off-label drugs were 40.78%, 16.64%,and 31.43%, respectively. Low-molecular-weight heparin,alfacalcidol and diltiazem were the most commonly usedoff-label drugs. Infants and younger children were thehigh-risk population of off-label drug use. The high rateoff-label nephrology-related drug use in children wasmainly related to lacking clinical research into drugs inchildren and the pace of drug label's revision, which cannotfollow the development of medical science.Conclusions: Approximaely half of pediatric patientswith renal diseases are usually prescribed with off-labelnephrology-related drugs. Analyzing the off-label conditionsfrom different perspectives may lead to various results.More clinical research into drugs for infants and youngerchildren is needed so as to update drug descriptions.

关键词： kidney off-label drug pediatrics

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Metabolomics Deciphering Therapeutic Effects and Mechanism of Traditional Chinese Medicines

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World Journal of Traditional Chinese Medicine 2016年第3期2卷 17-24页

作者： Wei-Wei Ma ai-hua zhang Hui Sun Xiang-Cai Meng Xi-Jun Wang National TCM Key Laboratory of Serum Pharmacochemistry Sino-America Chinmedomics Technology Cooperation CenterResearch Center of Chinmedomics(State Administration of TCM)Department of Pharmaceutical AnalysisHeilongjiang University of Chinese Medicine School of Pharmacy Heilongjiang University of Chinese Medicine

Traditional Chinese medicine(TCM),an ancient medical system,has the advantages of multi-targeting and multi-ingredient preparations,and is different from modern pharmacology.However,because of the complexity of TCM and the limitation of present investigation method,the research for deciphering the scientific basis and systematic features of TCM is difficult to go further.Metabolomics has a significant increased study in recent years and enables mapping of early biochemical changes in disease and hence provides an opportunity to develop predictive biomarkers.Moreover,its method and design resemble those of traditional Chinese medicine.Therefore,it can provide useful tools for exploring essence of TCM,and will help to in-depth understand Chinese medicine syndromes.In this mini-paper,particular attention will be paid to the past successes in applications of robust metabolomics to contribute to small metabolites discovery in TCM development.

关键词： Metabolomics Biomarkers Metabolites Traditional Chinese medicine Syndromes

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A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome

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Engineering 2021年第9期7卷 1293-1305页

作者： Hui Xiong ai-hua zhang Ya-Jing Guo Xiao-Hang Zhou Hui Sun Le Yang Heng Fang Guang-Li Yan Xi-Jun Wang National Chinmedomics Research Center&National TCM Key Laboratory of Serum Pharmacochemistry Department of Pharmaceutical AnalysisHeilongjiang University of Chinese MedicineHarbin 150040China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacao 999078China National Engineering Laboratory for the Development of Southwestern Endangered Medicinal Materials Guangxi Botanical Garden of Medicinal PlantNanning 530023China

A herbal prescription in traditional Chinese medicine(TCM)has great complexity,with multiple components and multiple targets,making it extremely challenging to determine its bioactive compounds.Yinchenhao Tang(YCHT)has been extensively used for the treatment of jaundice disease.Although many studies have examined the efficacy and active ingredients of YCHT,there is still a lack of an in-depth systematic analysis of its effective components,mechanisms,and potential targets—especially one based on clinical patients.This study established an innovative strategy for discovering the potential targets and active compounds of YCHT based on an integrated clinical and animal experiment platform.The serum metabolic profiles and constituents of YCHT in vivo were determined by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry(UPLC-Q-ToF-MS)-based metabolomics combined with a serum pharmacochemistry method.Moreover,a compound–target–pathway network was constructed and analyzed by network pharmacology and ingenuity pathway analysis(IPA).We found that eight active components could modulate five key targets.These key targets were further verified by enzyme-linked immunosorbent assay(ELISA),which indicated that YCHT exerts therapeutic effects by targeting cholesterol 7a-hydroxylase(CYP7A1),multidrug-resistance-associated protein 2(ABCC2),multidrug-resistance-associated protein 3(ABCC3),uridine diphosphate glucuronosyl transferase 1A1(UGT1A1),and farnesoid X receptor(FXR),and by regulating metabolic pathways including primary bile acid biosynthesis,porphyrin and chlorophyll metabolism,and biliary secretion.Eight main effective compounds were discovered and correlated with the key targets and pathways.In this way,we demonstrate that this integrated strategy can be successfully applied for the effective discovery of the active compounds and therapeutic targets of an herbal prescription.

关键词： Efficacy Bioactive compound Small molecule Targets Herbal medicine Metabolomics

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Analysis of Factors Associated with Death in Maintenance Hemodialysis Patients： A Multicenter Study in China

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Chinese Medical Journal 2017年第8期130卷 885-891页

作者： Kang-Kang Song De-Long Zhao Yuan-Da Wang Yong Wang Xue-Feng Sun Li-Ning Miao Zhao-Hui Ni Hong-Li Lin Fu-You Liu Ying Li Ya-Ni He Nian-Song Wang Cai-Li Wang ai-hua zhang Meng-hua Chen Xiao-Ping Yang Yue-Yi Deng Feng-Min Shao Shu-Xia Fu Jing-ai Fang Guang-Yan Cai Xiang-Mei Chen Department of Nephrology Chinese PLA General Hospital Chinese PLA Institute of Nephrology State Key Laboratory of Kidney Diseases National Clinica Research Center for Kidney Diseases Beijing 100853 China Department of Nephrology The Second Hospital of Jilin University Changchun Jilin 130041 China Department of Nephrology Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai Peritoneal Dialysis Research Center Shanghai 200127 China Department of Nephrology First Affiliated Hospital of Dalian Medical University Dalian Liaoning 116011 China Department of Nephrology The Second Xiangya Hospital of Central South University Changsha Hunan 410011 China Department of Nephrology Third Hospital of Hebei Medical University Kidney Disease Research Center of Hebei Province Shijiazhuang Hebei 050081 China Department of Nephrology Institute of Surgery Research Daping Hospital Third Military Medical University Chongqing 400042 China Department of Nephrology Shanghai Jiao Tong University Affiliated The Sixth People's Hospital Shanghai 200233 China Department of Nephrology First Affiliated Hospital of Baotou Medical College Baotou Inner Mongolia 014040 China Department of Nephrology Peking University Third Hospital Beijing 100191 China Department of Nephrology General Hospital of Ningxia Medical University Yinchuan Ningxia 750004 China Department of Nephrology The First Affiliated Hospital of Shihezi University School of Medicine Shihezi Xinjiang 832008 China Department of Nephrology Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai 200032 China Department of Nephrology Henan Provincial People's Hospital Zhengzhou Henan 450003 China Department of Nephrology The Second Hospital of Hebei Medical University Shijiazhuang Hebei 050000 China Department of Nephrology First Hospital of Shanxi Medical University Taiyuan Shanxi 030001 China

Background： Patients on hemodialysis have a high-mortality risk. Tiffs study analyzed factors associated with death in patients on maintenance hemodialysis （MHD）. While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to iliad the characteristics of patients preceding death.Methods： Participants were selected from 16 blood purification centers in China from January 2012 to December 2014, Patients＇ data were collected retrospectively. Based on survival status, the participants were divided into two groups： survival group and the death group. Logistic regression analysis was performed to determine/＇actors associated with all-cause mortality.

关键词： Hemodialysis Mortality： Risk Factors

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Chinmedomics:Newer Theory and Application

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Chinese Herbal Medicines 2016年第4期8卷 299-307页

作者： Xi-jun Wang ai-hua zhang Hui Sun Guang-li Yan Key Laboratory of Metabolomics Department of Pharmaceutical AnalysisNational TCM Key Laboratory of Serum PharmacochemistryChinmedomics Research Center of State Administration of TCMSino-America Chinmedomics Technology Cooperation CenterHeilongjiang University of Chinese Medicine

The scientific interpretation of the effectiveness of traditional Chinese medicine（TCM） is a communication channel between Chinese medicine and modern medicine. The evaluation of TCM efficacy is an important prerequisite for discovering active constituents. Therefore, there is an urgent need to establish a biological language for scientific explanation of the effectiveness of TCM, and modern scientists can further accept the significant value of TCM theory and its clinical practice. The syndrome and corresponding formulation are two important parts in TCM, and they are directly related to the effectiveness of TCM. Our team has taken syndrome and formulation as the research objects, integrated serum pharm-chemistry of TCM with metabolomics technology, developed a new platform termed Chinmedomics, which is capable of evaluating effectiveness of TCM and discovering the syndrome biomarkers as well as the effective substances. The correlation between the endogenous biomarkers of syndrome and exogenous constituents of formulation is analyzed to find the highly associated compounds as the effective substances, and further clarifying their activities, and may discover lead compounds. This effective strategy could speed the drug discovery from natural resources. This article systematically introduced the establishment and application of Chinmedomics theory, in order to provide references for studies on TCM, and some characteristic examples are presented to highlight the application of this new strategy for discovering the potential active constituents of TCM.

关键词： active constituents biomarkers Chinmedomics effectiveness traditional Chinese medicine

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