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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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Whole exome sequencing and functional validation identify CAPN1 variants as a cause of Chinese moyamoya disease

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Genes & Diseases 2024年第4期11卷 35-38页

作者： Yue Wang Zhengxing Zou Zhibin Yang Zhengshan Zhang jun Xu Fangbin Hao Juan Shen Cong Han Wanyang Liu Lian duan Department of Nutrition and Food Hygiene School of Public HealthChina Medical UniversityShenyangLiaoning 110122China Division of Pneumoconiosis School of Public HealthChina Medical UniversityShenyangLiaoning 110122China Department of Neurosurgery The Fifth Medical CentreChinese PLA General Hospital(Former 307th Hospital of the PLA)Beijing 100071China

Moyamoyadisease(MMD,MIM607151)is a rarevascular condition that has high recurrence,mortality,and disability rates,and an effective treatment for this disease is currently lacking.The main symptoms of affected children and adults include ischemic and hemorrhagic strokes,with an age of onset that follows a bimodal distribution trend at approximately 5 and 40 years of age.

关键词： mortality Whole modal

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Pentacoordinate Phosphoranes as Versatile Reagents in Fluoroalkylation Reactions

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CCS Chemistry 2024年第1期6卷 165-176页

作者： huanhuan Song Weihao Li Xiaoying Wang Kaiteng Wang Jingwen Li Shuai Liu Pin Gao Xin-hua duan Jinbo Hu Mingyou Hu School of Chemistry Engineering Research Center of Energy Storage Materials and DevicesMinistry of EducationXi’an Key Laboratory of Sustainable Energy Material ChemistryXi’an Jiaotong UniversityXi’an 710049 Key Laboratory of Organofluorine Chemistry Center for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200032

A general method for the synthesis of bench-stable bis(difluoromethyl)pentacoordinate phosphoranes has been developed.The reaction is rapid,operationally simple,and easily scalable.The pentacoordinate phosphoranes can generate both difluoromethyl radical(·CF_(2)H)and difluorocarbene(:CF_(2))intermediates.Thus,a variety of fluoroalkylation transformations havebeen achieved by·CF_(2)H,such asoxidativedifluoromethylation of electron-deficient heterocycles,nickel/photoredox dual-catalyzed difluoromethylation of aryl bromides,and photoredox difluoromethylation of alkenes,or by:CF_(2),such as gem-difluorocyclopropanation of alkenes,base-promoted difluoromethylation of heteroatom nucleophiles,Pd-catalyzed difluoromethylation of arylboronic acids,and Cu-mediated trifluoromethylation of aryl iodides(via:CF_(2) and recombined CF_(3)-).These fluoroalkylation methods have been successfully applied to late-stage fluoroalkylation of drugs and drug-like molecules.

关键词： pentacoordinate phosphorane difluoromethyl radical difluorocarbene difluoromethylation fluoroalkylation

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Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice

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World Journal of Stem Cells 2024年第5期16卷 575-590页

作者： Han duan Ning Tao Lin Lv Kai-Xin Yan Yong-Gang You Zhuang Mao Chang-Yao Wang Xue Li Jia-Yan Jin Chu-Tse Wu hua Wang School of Life Sciences Hebei UniversityBaoding 071002Hebei ProvinceChina Beijing Institute of Radiation Medicine Beijing 100850China Department of Cardiology The Sixth Medical CentreChinese People’s Liberation Army General HospitalBeijing 100037China Department of Orthopaedics The Fourth Medical CentreChinese People’s Liberation Army General HospitalBeijing 100853China Third Cadet Regiment School of Basic Medical ScienceAir Force Medical UniversityXi’an 710032Shaanxi ProvinceChina

BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regul

关键词： Atherosclerosis Apolipoprotein E-knockout mice Cell therapy Dental pulp stem cells Hepatocyte growth factor

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TRIM21-dependent ultrasmall chiral gold nanoparticles for preventing microglia senescence against Alzheimer's disease

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Science China Chemistry 2024年第4期67卷 1360-1372页

作者： Meiru Lu Changlong Hao Liguang Xu Feng Yu Jiwei Jiang Yanli Wang jun Xu hua Kuang Chuanlai Xu Maozhong Sun International Joint Research Laboratory for Biointerface and Biodetection State Key Laboratory of Food Science and ResourcesSchool of Food Science and TechnologyJiangnan UniversityWuxi 214122China Institute of Life Sciences Jiangsu UniversityZhenjiang 212013China Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China National Clinical Research Center for Neurological Diseases Beijing 100070China

Tripartite motif 21(TRIM21)is an E3 ubiquitin ligase that shows great promise for protein degradation through ubiquitination.Here,ultrasmall chiral gold nanoparticles(D-or L-NPs)modified by D-or L-glutathione ligands were fabricated.After conjugated with an NLR family pyrin domain-containing protein 3(NLRP3)antibody(D-NP-a NLRP3 or L-NP-a NLRP3),DNP-a NLRP3 showed effective delivery efficiency of the antibody into microglia and prevented Aβ-mediated microglia senescence,and p16^(ink4a),a marker of senescence,in the microglia was reduced by 90.3%±7.8% while L-NP-a NLRP3 decreased by 48.01%±3.1%.Mechanistic investigations revealed that the D-NP-a NLRP3((1.5±0.3)×10^(7)M^(-1))exhibited sixteen-fold larger binding affinity to transmembrane glycoprotein SLC3A2 than L-type((9.5±2.7)×10^(5)M^(-1)),which led to a high efficiency of antibody delivery and TRIM21-dependent NLRP3 degradation.Notably,the blood-brain barrier(BBB)-crossing ability of chiral NP-a NLRP3 as well as NLRP3 degradation was demonstrated in vivo.The APP/PS1 Alzheimer's disease(AD)model mice experiments exhibited a reduction of 89.7%±6.8% for the NLRP3 protein and 84.2±7.5% for p16^(ink4a)following the intravenous administration of D-NP-a NLRP3 once a week for 60 days.Furthermore,the levels of the AD markers Aβ and phosphorylatedTau in the brains were reduced by 86.2%±8.2% and 81.6%±9.1%;these were 2.1-fold and 1.9-fold higher than those treated with L-NP-a NLRP3,respectively.The studies provide a method to rescue AD-like pathologies and prevent senescence.

关键词： chiral gold nanoparticles amyloid-β NLRP3 TRIM21 senescence Alzheimer's disease

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Novel MIP gene mutation causes autosomal-dominant congenital cataract

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 454-465页

作者： Jing-Lan Ni hua-Ming Wen Xiao-Sheng huang Qian-Wen Li Jia-Min Cai Bao-Jian Fan jun Zhao The Second Clinical Medical College Jinan UniversityShenzhen 518020Guangdong ProvinceChina Department of Ophthalmology Dongguan Chang’an HospitalDongguan 523843Guangdong ProvinceChina Shenzhen Eye Hospital Affiliated to Jinan University Shenzhen Eye InstituteShenzhen 518040Guangdong ProvinceChina Department of Oral&Maxillofacial Surgery Shenzhen Stomatology Hospital Affiliated to Shenzhen UniversityShenzhen 518040Guangdong ProvinceChina Department of Neurosurgery Massachusetts General Hospital and Harvard Medical SchoolBoston 02114MassachusettsUSA Department of Ophthalmology Shenzhen People’s Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020Guangdong ProvinceChina

●AIM:To identify disease-causative mutations in families with congenital cataract.●METHODS:Two Chinese families with autosomaldominant congenital cataract(ADCC)were recruited and underwent comprehensive eye examinations.Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family.Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis.The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis.Major intrinsic protein(MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos.Zebrafish embryonic lens phenotypes were screened using confocal microscopy.●RESULTS:A novel heterozygous mutation(c.85G>A;p.G29R)in the MIP gene was identified in the proband of one family.A known heterozygous mutation(c.97C>T;p.R33C;rs864309693)in MIP was found in the proband of another family.In-silico prediction indicated that the novel mutation might affect the MIP protein function.Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP.●CONCLUSION:Two missense mutations in the MIP gene in Chinese cataract families are identified,and one of which is novel.These findings expand the genetic spectrum of MIP mutations associated with cataracts.The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

关键词： congenital cataract major intrinsic protein missense mutation zebrafish model

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Laser powder bed fusion of NiTiFe shape memory alloy via premixed powder: microstructural evolution, mechanical and functional properties

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Rare Metals 2024年第5期43卷 2300-2316页

作者： Bo Yuan Jin-Guo Ge Liang Zhang Hong-jun Chen Long-Sha Wei Yu-Duo Zhou Run-hua Song Institute of Intelligent Manufacturing Technology Shenzhen Polytechnic School of Mechanical and Electrical Engineering Guilin University of Electronic Technology Guangdong Advanced Polymer Composite EngineeringTechnology Research Center Shenzhen Academy of Aerospace Technology Jihua Laboratory Testing Center Jihua Laboratory

High-cost pre-alloyed powder is the bottleneck problem that limits the widespread application of additivemanufactured shape memory alloys. In this work, the lowcost ternary NiTiFe shape memory alloy is fabricated by laser powder bed fusion (LPBF) technique via mechanically mixed pre-alloy NiTi powder and varying contents pure Fe powder (1, 2, 3 wt%). All NiTiFe alloys show a relative density of up to 99.8%by optimizing the LPBF processing parameters. Owing to the heterogeneous nucleation effect of micron-sized Fe particles, both grain refinement and texture weakening are generated in the NiTiFe alloys, accompanied by the reduction of dislocation density. For the room-temperature mechanical properties,the NiTi-3Fe alloy shows the highest microhardness of HV370, but the fracture strength and elongation reduce to1701 MPa and 23%simultaneously. The evolution of mechanical properties is attributed to the high internal defects, low dislocation density and the incoherent oxide.Moreover, the NiTi-3Fe alloy shows the quasi-linear superelasticity behavior; the superelastic recoverable strain of NiTi-1Fe and NiTi-2Fe decreased with the increase in Fe content. This study provided a new-fangled insight for the development of multi-component NiTi-based shape memory alloys by additive manufacturing.

关键词： Additive manufacturing Shape memory alloy Metal matrix composite Microstructure Mechanical properties

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New insights into mechanisms and interventions of locoregional therapies for hepatocellular carcinoma

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Chinese Journal of Cancer Research 2024年第2期36卷 167-194页

作者： Hanyuan Liu Chunmei Wang Ruiqiang Wang Hengsong Cao Yongfang Cao Tian huang Zhengqing Lu hua Xiao Mengcheng Hu Hanjin Wang jun Zhao Department of General surgery Nanjing First HospitalNanjing Medical UniversityNanjing 210019China Department of Oncology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China School of Public Health China Medical UniversityShenyang 110122China Hepatobiliary/Liver Transplantation Center the First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Living Donor TransplantationChinese Academy of Medical SciencesNanjing 210024China Department of Gastroenterology the Affiliated Jiangning Hospital of Nanjing Medical UniversityNanjing 211103China Department of Nuclear Medicine the Affiliated Changzhou Second People's Hospital of Nanjing Medical UniversityChangzhou 213001China

Hepatocellular carcinoma(HCC) is responsible for a significant number of cancer-related deaths worldwide and its incidence is increasing. Locoregional treatments, which are precision procedures guided by imaging to specifically target liver tumors, play a critical role in the management of a substantial portion of HCC cases. These therapies have become an essential element of the HCC treatment landscape, with transarterial chemoembolization(TACE)being the treatment of choice for patients with intermediate to advanced stages of the disease. Other locoregional therapies, like radiofrequency ablation, are highly effective for small, early-stage HCC. Nevertheless, the advent of targeted immunotherapy has challenged these established treatments. Tyrosine kinase inhibitors(TKIs) and immune checkpoint inhibitors(ICIs) have shown remarkable efficacy in clinical settings. However, their specific uses and the development of resistance in subsequent treatments have led clinicians to reevaluate the future direction of HCC therapy. This review concentrates on the distinct features of both systemic and novel locoregional therapies. We investigate their effects on the tumor microenvironment at the molecular level and discuss how targeted immunotherapy can be effectively integrated with locoregional therapies. We also examine research findings from retrospective studies and randomized controlled trials on various combined treatment regimens, assessing their validity to determine the future evolution of locoregional therapies within the framework of personalized, comprehensive treatment.

关键词： Locoregional therapies transarterial chemoembolization hepatocellular carcinoma immunotherapy tumor microenvironment

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Icariin ameliorates viral myocarditis by inhibiting TLR4-mediated ferroptosis

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Asian Pacific Journal of Tropical Biomedicine 2024年第3期14卷 106-114,I0002-I0005页

作者： Wei Luo Yi Lu jun-hua Deng Peng Liu Yan huang Wan-Xi Liu Chun-Li huang Laboratory of the Atherosclerosis and Ischemic Cardiovascular Diseases Department of CardiologyAffiliated Hospital of Youjiang Medical University for NationalitiesYoujiang Medical University for NationalitiesBaiseGuangxi 533000China Department of Critical Care Medicine Affiliated Hospital of Youjiang Medical University for NationalitiesBaiseGuangxi 533000China Department of Respiratory and Critical Care Medicine Affiliated Hospital of Youjiang Medical University for NationalitiesBaiseGuangxi 533000China Postgraduate School of Youjiang Medical University for Nationalities BaiseGuangxi 533000China Department of Neonatology Affiliated Hospital of Youjiang Medical University for NationalitiesBaiseGuangxi 533000China Department of Nephrology People’s Hospital of PubeiQinzhouGuangxi 535300China Urban Community Health Service Center of Youjiang District BaiseGuangxi 533000China

Objective:To explore the mechanism by which icariin alleviates viral myocarditis.Methods:CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability,inflammation,and apoptosis.Moreover,the effects of icariin on ferroptosis and TLR4 signaling were assessed.After AC16 cells were transfected with TLR4 overexpression plasmids,the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated.Results:Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α,IL-1β,IL-6,and IL-18.Flow cytometry revealed that icariin decreased apoptosis rate,and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes.Additionally,it suppressed ferroptosis including lipid peroxidation and ferrous ion,as well as the TLR4 signaling.However,TLR4 overexpression abrogated the modulatory effects of icariin.Conclusions:Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis.Further animal study is needed to verify its efficacy.

关键词： Viral myocarditis CVB3 TLR4 Ferroptosis Icariin

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Cyclic Dinucleotide Self-Assembled Nanoparticles as a Carrier-Free Delivery Platform for STING-Mediated Cancer Immunotherapy

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CCS Chemistry 2024年第1期6卷 177-195页

作者： Lang Zhao Shao-hua Zhuo Tian-Yang Wang jun-jun Wu Jing-Yun Su Wen-Hao Li Bo-Dou Zhang Yan-Mei Li Key Lab of Bioorganic Phosphorus Chemistry&Chemical Biology Department of ChemistryTsinghua UniversityBeijing 100084 Beijing Institute for Brain Disorders Beijing 100069 Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084

Cyclic dinucleotides(CDNs)are natural agonists of the stimulator of interferon genes(STING),which is an attractive immunotherapy target.Currently,CDNs and their derivatives are being investigated clinically.However,the poor bioavailability of exogenous CDNs has limited their application in immunotherapy.Although nanocarriers are widely used for cytosolic delivery of CDNs,their loading capacity is insufficient,and their complicated composition and purification process raises bio-compatibility concerns.Herein,we report a super-simplified CDN self-assembly strategy for carrier-free delivery of CDNs.In the presence of excess K^(+),CDNs form oligomers which further self-assemble with divalent metal ions(such as Mn^(2+))to form nanoparticles(NPs)in aqueous solution.We demonstrate that the self-assembled CDN NPs promote cellular uptake of CDNs and enhance tumor immunogenicity by remodeling the tumor microenvironment,inducing immunogenic tumor cell death and increasing tumorinfiltrating lymphocytes,which is conducive to the generation of tumor neoantigen-specific T-cell responses.We also demonstrate that the use of CDN NPs alone or in combination with immune checkpoint blockades inhibits tumor growth,highlighting the fact that CDN NPs are a potent platform for cancer immunotherapy.

关键词： cyclic dinucleotide STING carrierfree delivery tumor immunogenicity cancer immunotherapy

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