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Comprehensive newborn screening for severe combined immunodefciency,X‑linked agammaglobulinemia,and spinal muscular atrophy:the Chinese experience

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World Journal of Pediatrics 2024年第12期20卷 1270-1282页

作者： Chi Chen Chao Zhang Ding-Wen Wu Bing-Yi Wang Rui Xiao Xiao-Lei Huang Xin Yang Zhi-Gang Gao Ru-Lai Yang Department of Genetics and Metabolism Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouChina National Engineering Laboratory for Key Technology of Birth Defect Control and Prevention Screening and Diagnostic R and D CenterHangzhouChina

Background Newborn screening(NBS)for severe combined immunodefciency(SCID),X-linked agammaglobulinemia(XLA),and spinal muscular atrophy(SMA)enables early diagnosis and intervention,signifcantly improving patient *** in real-time polymerase chain reaction(PCR)technology have been instrumental in facilitating their inclusion in NBS *** We employed multiplex real-time PCR to simultaneously detect T-cell receptor excision circles(TRECs),kappadeleting recombination excision circles(KRECs),and the absence of the survival motor neuron(SMN)1 gene in dried blood spots from 103,240 newborns in Zhejiang Province,China,between July 2021 and December *** Of all the samples,122 were requested further *** fow cytometry evaluation and/or genetic diagnostics,we identifed one patient with SCID,two patients with XLA,nine patients with SMA[one of whom also had Wiskott–Aldrich Syndrome(WAS)],and eight patients with other medical *** positive predictive values(PPVs)of NBS for SCID,XLA,and SMA were 2.44%,2.78%,and 100%,*** estimated prevalence rates in the Chinese population were 1 in 103,240 for SCID,1 in 51,620 for XLA,and 1 in 11,471 for *** This study represents the frst large-scale screening in China's Mainland using a TREC/KREC/SMN1 multiplex assay,providing valuable epidemiological *** fndings suggest that this multiplex assay is an efective screening method for SCID,XLA,and SMA,potentially supporting the universal implementation of NBS programs across China.

关键词： Genetic diagnosis Newborn screening Severe combined immunodefciency Spinal muscular atrophy X-linked agammaglobulinemia

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Regulatory mechanisms of dopamine metabolism in a marine Meyerozyma guilliermondii GXDK6 under NaCl stress as revealed by integrative multi-omics analysis

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Synthetic and Systems Biotechnology 2024年第1期9卷 115-126页

作者： Huijie Sun Huashan Bai Yonghong Hu Sheng He Ruihang Wei Duotao Meng Qiong Jiang Hongping Pan Peihong Shen Qian Ou Chengjian Jiang State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources Guangxi Research Center for Microbial and Enzyme Engineering TechnologyCollege of Life Science and TechnologyGuangxi UniversityNanning530004China Guangxi Key Laboratory for Green Processing of Sugar Resources College of Biological and Chemical EngineeringGuangxi University of Science and TechnologyLiuzhou545006China Guangxi Key Laboratory of Birth Defects Research and Prevention Guangxi Key Laboratory of Reproductive Health and Birth Defect PreventionGuangxi Zhuang Autonomous Region Women and Children Health Care HospitalNanning530033China College of Food Science and Light Industry Nanjing Tech UniversityNo.30South Puzhu RoadNanjing211816China

Dopamine can be used to treat depression,myocardial infarction,and other ***,few reports are available on the de novo microbial synthesis of dopamine from low-cost *** this study,integrated omics technology was used to explore the dopamine metabolism of a novel marine multi-stress-tolerant aromatic yeast Meyerozyma guilliermondii ***6 was found to have the ability to biosynthesize dopamine when using glucose as the substrate.14 key genes for the biosynthesis of dopamine were identified by whole genome-wide *** and proteomic data showed that the expression levels of gene AAT2 encoding aspartate aminotransferase(regulating dopamine anabolism)were upregulated,while gene AO-I encoding copper amine oxidase(involved in dopamine catabolism)were downregulated under 10%NaCl stress compared with non-NaCl stress,thereby contributing to biosynthesis of ***,the amount of dopamine under 10%NaCl stress was 2.51-fold higher than that of zero NaCl,which was consistent with the multi-omics ***-time fluorescence quantitative PCR(RT-qPCR)and high-performance liquid chromatography(HPLC)results confirmed the metabolic model of ***,by overexpressing AAT2,AST enzyme activity was increased by 24.89%,the expression of genes related to dopamine metabolism was enhanced,and dopamine production was increased by 56.36%in recombinant *** conclusion,Meyerozyma guilliermondii GXDK6 could utilize low-cost carbon source to synthesize dopamine,and NaCl stress promoted the biosynthesis of dopamine.

关键词： Dopamine biosynthesis Multi-omics analysis NaCl stress Meyerozyma guilliermondii

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Autologous cord blood mononuclear cells for preventing preterm complications in very preterm monozygotic twins: the first-in-human randomized, placebo-controlled, double-blinded phase I trial and long term follow-up outcomes

Autologous cord blood mononuclear cells for preventing prete...

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第二十次中国暨国际生物物理大会

作者： Zhuxiao.Ren Fang.Xu Jingjun.Pei Wei.Wei Shumei.Yang Jiangxue.Han Liling.Yang Qi.Zhang Gengying.Liu Liu.Yang Zhipeng.Liu Qiuping.Li Feng Zhichun Jie.Yang National Engineering Laboratory for Birth defects prevention and control of key technology

One-sentence summary This first-in-human randomized, placebo-controlled, double-blinded phase I clinical trial showed autologous cord blood mononuclear cells(ACBMNCs) infusion early after birth was feasible, safe and may alleviate preterm complications via a potent immunomodulatory *** Persistent inflammation is the common main contributor to the pathogenesis of preterm complications. Immunomodulation effect was an important mechanism underlying the beneficial results of stem cell therapy. We conducted a randomized, placebo-controlled, double-blinded phase I trial to establish whether autologous cord blood mononuclear cells(ACBMNCs) infusion was feasible, safe and may improve outcomes in very preterm monozygotic twins(VPMTs), and we assessed the immunoregulation effects via multi-omics approaches. Eight pairs of VPMTs received intravenous ACBMNCs or placebo within 24 hours after birth. ACBMNCs treatment was safely conducted, well tolerated, and led to a reduction trend in preterm complications. We found significant increase in Treg proportion, decreased inflammatory cytokines level, induced transcriptional up-regulation of processes facilitating Treg differentiation in immune cells, improved diversity and favorable components of lung microbiota after ACBMNCs infusion. Our findings nominated intravenous ACBMNCs intervention as a potent immunomodulatory and protective therapy for alleviating preterm complications.

关键词： very preterm monozygotic twins autologous cord blood mononuclear cells safety feasibility immunomodulation outcomes

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Improving chitosan-based composite membrane by introducing a novel hybrid functional nano-hydroxyapatite with carboxymethyl cellulose and phytic acid

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Frontiers of Chemical Science and engineering 2024年第6期18卷 1-15页

作者： Liuyun Jiang Yingjun Ma Shuo Tang Yuqing Wang Yan Zhang Shengpei Su Xiang Hu Jun He National&Local Joint Engineering Laboratory for New Petro-chemical Materials and Fine Utilization of Resources Key Laboratory of Chemical Biology&Traditional Chinese Medicine Research(Ministry of Education)College of Chemistry and Chemical EngineeringHunan Normal UniversityChangsha 410081China State Key Laboratory Developmental Biology of Freshwater Fish School of Life ScienceHunan Normal UniversityChangsha 410081China Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control Changsha Hospital for Matemal&Child Health Care Aiffiliated to Hunan Normal UniversityChangsha 410081China

A functional hybrid nano-hydroxyapatite(carboxymethyl cellulose-phytic acid-n-HA,CMC-PA-n-HA)was prepared by adding CMC and *** results of Fourier transformation infrared spectra,X-ray diffraction,thermal gravimetric analysis and dispersion experiments indicated that the addition of CMC and PA affected the morphology,crystallinity and crystal size of hybrid n-HA,and CMC endowed hybrid n-HA with excellent *** electron microscope results showed that CMC-PA-n-HA nanoparticle could be uniformly dispersed in chitosan(CS)matrix to obtain composite membrane by casting technology,so that the highest tensile strength of CMC-PA-n-HA/CS composite membrane was 69.64%and 144.45%higher than that of CS membrane and n-HA/CS composite membrane,*** angle test showed that CMC-PA-n-HA effectively improved hydrophilicity of the CS *** simulated body fluid immersion results indicated that the CMC-PA-n-HA/CS composite membrane not only exhibited good degradability but also promoted bone-like apatite *** cell proliferation experiments proved that the introduction of PA made the composite membrane have better cell adhesion and proliferation *** tests demonstrated that PA could effectively improve the antibacterial properties of the composite membrane,which is expected to be applied as guide bone tissue regeneration membrane.

关键词： nano-hydroxyapatite chitosan dispersion guide bone tissue regeneration membrane

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Medication use in the neonatal intensive care unit in a tertiary hospital in China from 2020 to 2023

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Italian Journal of Pediatrics 2025年第1期51卷 1-9页

作者： Wang, Yi Song, Linhong Wang, Yanhua Li, Jun Xie, Yuanyuan Yan, Lei Zhou, Huixia Hu, Siqi Institute of Pediatrics Faculty of Pediatrics The Seventh Medical Center of PLA General Hospital Beijing China National Engineering Laboratory for Birth Defect Prevention and Control of Key Technology Beijing China Beijing Key Laboratory of Pediatric Organ Failure Beijing China Department of Pediatric Cardiac Surgery Faculty of Pediatrics The Seventh Medical Center of PLA General Hospital Beijing China Department of Pediatric Urology Faculty of Pediatrics The Seventh Medical Center of PLA General Hospital Beijing China

Background: The use of medication in the neonatal intensive care unit (NICU) is a complex field that requires special attention, as neonatal patients may have different sensitivities and responses to drugs than adults and older children. The administration of medication in the NICU must consider various factors, including the dosage of the medication, the route of administration, monitoring, and potential drug interactions. Methods: In this study, we conducted a retrospective analysis of medication use in the neonatal intensive care unit of 122 preterm infants treated in our hospital from 2020 to 2023. Results: Correlation analysis revealed that among perinatal clinical characteristics, birth weight was moderately positively correlated with gestational age, with a correlation coefficient greater than that of birth weight with the Apgar score. The top 3 medication types in the NICU were “vitamins, nutritional drugs, enzyme preparations and drugs that regulate water, electrolytes, and acid-base balance”, “blood hematopoietic system medications”, and “antimicrobial medications”. From 2020 to 2023, the most commonly used drugs in the NICU were vitamin AD (vitamin A and vitamin D) drops and calcium gluconate injections. In addition, we demonstrated that the most commonly prescribed off-label drugs were vitamins, water and electrolyte balance nutrition drugs, and blood circulation system drugs. Conclusions: Our retrospective study will not only help identify and evaluate interventions to reduce medication errors but also aid healthcare systems and providers in understanding, implementing, and enhancing these interventions to improve the safety and quality of care for newborns. Nonetheless, further research is needed to assess the relative cost-effectiveness of various medication safety interventions to facilitate their adoption and implementation in the decision-making process. © The Author(s) 2025.

关键词： Clinical pharmacology Neonatal intensive care unit Off-label drug Pharmacotherapy Trends over time

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Exploring the Efficacy of BMSC Transplantation via Various Pathways for Treating Cholestatic Liver Fibrosis in Mice

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Biomedical and Environmental Sciences 2025年第4期38卷 447-458页

作者： Junjie Ren Zixu Li Xinrui Shi Tingting Lyu Xiaonan Li Min Ge Qizhi Shuai Tingjuan Huang Department of Gastroenterology and Hepatology The First Hospital of Shanxi Medical UniversityTaiyuan 030001ShanxiChina Department of Academy of Medical Sciences Shanxi Medical UniversityTaiyuan 030001ShanxiChina Liver Research Center Beijing Friendship HospitalCapital Medical UniversityBeijing Key Laboratory of Translational Medicine on Liver CirrhosisNational Clinical Research Center for Digestive DiseaseBeijing 100050China Department of Cancer Radiotherapy Fifth Hospital of Shanxi Medical UniversityTaiyuan 030001ShanxiChina School of Clinical Medicine Medical CollegeHebei University of EngineeringHandan 056038HebeiChina Department of Biochemistry and Molecular Biology Shanxi Key Laboratory of Birth Defect and Cell RegenerationMOE Key Laboratory of Coal Environmental Pathogenicity and PreventionShanxi Medical UniversityTaiyuan 030001ShanxiChina Department of Hepatopancreatobiliary Surgery First Hospital of Shanxi Medical University Key Laboratory of Birth Defect and Cell RegenerationShanxi Medical UniversityTaiyuan 030001ShanxiChina

Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrowderived mesenchymal stem cells(BMSCs) against cholestatic liver fibrosis in *** BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells(HSCs).HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation(BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver *** BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore,BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell(HSC) activation and collagen fiber *** The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.

关键词： Bone marrow mesenchymal stem cells Portal vein Tail vein Cholestatic hepatic fibrosis Administration route

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A multicenter prospective study of next-generation sequencing-based newborn screening for monogenic genetic diseases in China

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World Journal of Pediatrics 2023年第7期19卷 663-673页

作者： Ru-Lai Yang Gu-Ling Qian Ding-Wen Wu Jing-Kun Miao Xue Yang Ben-Qing Wu Ya-Qiong Yan Hai-Bo Li Xin-Mei Mao Jun He Huan Shen Hui Zou Shu-Yuan Xue Xiao-Ze Li Ting-Ting Niu Rui Xiao Zheng-Yan Zhao National Clinical Research Center for Child Health Children's HospitalZhejiang University School of MedicineHangzhouChina Chongqing Health Center for Women and Children Neonatal Screening CenterChongqingChina Guiyang Maternal and Child Health Hospital GuiyangChina University of the Chinese Academy of Science Shenzhen HospitalShenzhen 518000GuangdongChina Shanxi Children's Hospital Shanxi Maternal and Child Health Hospital TaiyuanShanxiChina The Central Laboratory of Birth Defects Prevention and Control Ningbo Women and Children's HospitalNingbo 315012ZhejiangChina Maternal and Child Health Hospital of Ningxia Hui Autonomous Region YinchuanChina Changsha Maternal and Child Health Hospital ChangshaHunanChina Yunnan Maternal and Child Health Hospital KunmingYunanChina Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University JinanShandongChina Urumqi Maternal and Child Health Care Hospital Xinjiang Uygur Autonomous RegionUrumqi CityChina Medical Genetic Center Changzhi Maternal and Child Health Care HospitalChangzhiShanxiChina Maternal and Child Health Care Hospital of Shandong Province JinanShandongChina National Engineering Laboratory for Key Technology of Birth Defect Control and Prevention Screening and Diagnostic R and D CenterHangzhouChina

Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn *** develop-ment of next-generation sequencing(NGS)technology provides new opportunities to expand current newborn screening *** We designed a a newborn genetic screening(NBGS)panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with *** this panel,a large-scale,multicenter,prospective multidisease analysis was conducted on dried blood spot(DBS)profiles from 21,442 neonates *** We presented the positive detection rate and carrier frequency of diseases and related variants in different regions;and 168(0.78%)positive cases were ***-6-Phosphate Dehydrogenase deficiency(G6PDD)and phenylketonuria(PKU)had higher prevalence rates,which were significantly different in different *** positive detection of G6PD variants was quite common in south China,whereas PAH variants were most commonly identified in north *** addi-tion,NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants,which were normal in conventional NBS,but were confirmed later as abnormal in repeated biochemical testing after *** percent of high-frequency gene carriers and 60%of high-frequency variant carriers had obvious regional *** the premise that there was no significant difference in birth weight and gestational age,the biochemical indicators of SLC22A5 c.1400C>G and ACADSB c.1165A>G carriers were significantly different from those of *** We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS *** data also showed that the prevalence of diseases has significant regional charac-teristics,which provides a theoretical basis for screening diseases in di

关键词： Monogenic genetic diseases Newborn screening Next-generation sequencing Monogenic genetic diseases Regional features

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Treatment of SMA type 1 infants using a single-dose AAV9-mediated gene therapy via intrathecal injection of GC101:An open-label,single-arm study

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Chinese Medical Journal 2024年第16期137卷 1976-1978页

作者： Xiuwei Ma Lu Zhuang Wenhao Ma Jun Li Xiaodong Wang Zhongqiu Li Xinyang Jiang Yongxia Wang Ying Du Yingqian Zhang Fang He Zhiming Zhu Shaopeng Du Juan Xu Ruijie Gu Yanping Zhang Shan Zhang Ting Li Xiao Yang Sheng Zhang Lina Zhu Qiuping Li Xiaoyan Dong Xiaobing Wu Zhichun Feng Department of Neurodevelopment Faculty of PediatricsThe Seventh Medical Center of Chinese PLA General HospitalBeijing 100700China National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology Beijing 100700China Research and Development Division Genecradle Therapeutics Inc.Beijing 100176China Medical Division Genecradle Therapeutics Inc.Beijing 100176China Department of Pharmacy Medical Supplies Center of Chinese PLA General HospitalBeijing 100700China Beijing Key Laboratory of Pediatric Organ Failure Beijing 100700China

Spinal muscular atrophy(SMA),a neurodegenerative disorder caused by mutations in survival motor neuron 1(SMN1)resulting in reduced expression of the survival motor neuron(SMN)protein,is inherited in an autosomal recessive *** type 1 is the most frequent subtype of SMA characterized by onset before 6 months of life,inability to achieve independent sitting,and rapidly progressive respiratory and bulbar deterioration,causing a mortality of>90%before 2 years of age.[1]Currently,there have been two lifelong splice-modifying therapies(nusinersen and risdiplam),and a single-dose gene replacement therapy via intravenous onasemnogene abeparvovec for SMA type 1 patients.

关键词： injection mortality muscular

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An Exploration into the Safe and Precise In Vivo Fluorescence Visualization of Uteroplacental Circulation in the NIR-II Window

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ACS applied materials & interfaces 2025年第22期17卷 2025 May 23页

作者： Junyan Zheng Yanyun Ying Jin Li Xiaoming Yu Jiayi Li Jiani Jin Yuhuang Zhang Zhongmin Xu Hao Jin Zhe Feng Jun Qian Dan Zhang Institute of Medical Genetics and Development Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital Zhejiang University School of Medicine Zhejiang 310006 China. State Key Laboratory of Extreme Photonics and Instrumentation International Research Center for Advanced Photonics Centre for Optical and Electromagnetic Research College of Optical Science and Engineering Zhejiang University Zhejiang 310058 China. State Key Laboratory Breeding Base of Green-Chemical Synthesis Technology Institute of Green Petroleum Processing and Light Hydrocarbon Conversion College of Chemical Engineering Zhejiang University of Technology Hangzhou Zhejiang 310014 China. Key Laboratory of Safety Evaluation of Medical Devices of Zhejiang Province Hangzhou 310018 China. Zhejiang Provincial Birth Defect Control and Prevention Research Center Hangzhou 310006 China.

The uteroplacental circulation is essential for maintaining normal placental physiology and ensuring fetal development. Imaging this circulation is crucial for a comprehensive understanding of its physiological characteristics and associated pathological processes. Fluorescence imaging in the second near-infrared window (NIR-II, 900-1880 nm) offers significant advantages, including high resolution and deep tissue penetration, facilitating more accurate in vivo assessments. In this study, we employed nanoparticles composed of organic fluorescent dyes with NIR-II emission for precise imaging of the uteroplacental circulation. This approach enabled visualization of the uterine artery and placental blood perfusion in pregnant mice with high resolution. We successfully examined the developmental status across different pregnancy stages and assessed pathological alterations associated with inflammation-induced injury. Furthermore, the maternal and fetal safety of the nanoparticles was validated through comprehensive evaluations. These investigations present a novel approach for studying the formation and development of uteroplacental circulation, as well as related pathological conditions.

关键词： NIR-II fluorescence imaging maternal and fetal safety nanoparticle placenta uteroplacental circulation

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Caffeine Exposure Causes Immune Dysfunction and Intrauterine Growth Restriction Retardation in Rats

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Biomedical and Environmental Sciences 2022年第2期35卷 170-173页

作者： ZHANG Wen Zhong SUN Na Na HU Yang CAO Yu Amber Sheeks Department of Safety Engineering North China Institute of Science&TechnologySanhe 065201HebeiChina Key Laboratory of Food Risk Assessment Ministry of Health China National Center for Food Safety Risk AssessmentBeijing 100021China Center for Public Health Surveillance and Information Service Chinese Center for Disease Control and PreventionBeijing 102206China Muskingum University OH 43762USA

This study was conducted to assess the effects of caffeine on the dam and the physical development of rat *** Sprague-Dawley rats(20 per dose group)were administered caffeine by gavage at 0(control),5,20,and 80 mg/kg body weight(bw)daily from gestational day 6 through lactation using caffeine dissolved in *** developmental toxicity of caffeine was *** in the 80 mg/kg bw group exhibited splenic *** litter weights were significantly lower in the 20 and 80 mg/kg bw groups than the untreated control(P<0.05),with a greater reduction in the higher dose *** number of female offspring was reduced in the 20 and 80 mg/kg bw groups(P<0.05).Some of the offspring were eaten by the dam following birth,which accounted for half of the litters in the 80 mg/kg bw group(P<0.05).Offspring body weight in the 80 mg/kg bw group was lower than that in the control during the lactation period(P<0.05).Exposure to caffeine during pregnancy can cause maternal immune dysfunction and intrauterine growth restriction retardation(IUGR);the developmental toxicity of caffeine varied with gender,as females were more sensitive than *** no observed adverse effect level was 5 mg/kg bw based on the IUGR.

关键词： Immune weights offspring

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