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Knocking down TRPM2 expression reduces cell injury and NLRP3 inflammasome activation in PC12 cells subjected to oxygen-glucose deprivation

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Neural Regeneration Research 2020年第11期15卷 2154-2161页

作者： Tao Pan Qiu-Jiao Zhu Li-Xiao Xu Xin Ding Jian-Qin Li Bin sun Jun Hua Xing Feng Department of Neonatology Children’s Hospital Affiliated to Suzhou UniversitySuzhouJiangsu ProvinceChina Department of Critical Care Medicine Children’s Hospital Affiliated to Suzhou UniversitySuzhouJiangsu ProvinceChina Institute of Pediatrics Children’s Hospital Affiliated to Suzhou UniversitySuzhouJiangsu ProvinceChina Blood section Children’s Hospital Affiliated to Suzhou UniversitySuzhouJiangsu ProvinceChina

Transient receptor potential melastatin 2(TRPM2) is an important ion channel that represents a potential target for treating injury caused by cerebral ischemia. However, it is unclear whether reducing TRPM2 expression can help repair cerebral injury, and if so what the mechanism underlying this process involves. This study investigated the protective effect of reducing TRPM2 expression on pheochromocytoma(PC12) cells injured by oxygen-glucose deprivation(OGD). PC12 cells were transfected with plasmid encoding TRPM2 shRNAs, then subjected to OGD by incubation in glucose-free medium under hypoxic conditions for 8 hours, after which the cells were allowed to reoxygenate for 24 hours. Apoptotic cells, mitochondrial membrane potentials, reactive oxygen species levels, and cellular calcium levels were detected using flow cytometry. The relative expression of C-X-C motif chemokine ligand 2(CXCL2), NACHT, LRR, and PYD domain–containing protein 3(NALP3), and caspase-1 were detected using fluorescence-based quantitative reverse transcription-polymerase chain reaction and western blotting. The rates of apoptosis, mitochondrial membrane potentials, reactive oxygen species levels, and cellular calcium levels in the TRPM2-shRNA + OGD group were lower than those observed in the OGD group. Taken together, these results suggest that TRPM2 knockdown reduces OGD-induced neuronal injury, potentially by inhibiting apoptosis and reducing oxidative stress levels, mitochondrial membrane potentials, intracellular calcium concentrations, and NLRP3 inflammasome activation.

关键词： apoptosis calcium caspase-1 NLRP3 mitochondrial impairment oxidative stress oxygen-glucose deprivation PC12 shRNA TRPM2

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Diagnosis and treatment of syncope in pediatric patients: a new guideline

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science Bulletin 2019年第6期64卷 357-358页

作者： Wenrui Xu Tianyou Wang Department of Pediatrics Peking University First Hospital Hematology Oncology Center Beijing Children's Hospital Capital Medical UniversityNational Center for Children's Health

syncope is a common emergency of children and adolescents. The reoccurrence of syncope seriously affects children's physical and mental health. The pathogenesis, etiology, diagnosis and treatment of pediatric syncope differ from those in adults. Most pediatric syncope is relatively transient and benign in nature. But cardiac syncope, although the incidence is relatively low as compared with the neurally-mediated syncope (NMs), poses high risks of sudden death and needs to be quickly identified and managed.

关键词： common emergency diagnosis and treatment quickly identified and managed

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Myricetin alleviates ovalbumin-induced allergic rhinitis in mice by regulating Th1/Th2 balance

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Asian Pacific Journal of Tropical Biomedicine 2023年第7期13卷 306-314页

作者： Ya-Nan shi Jin-Zhu su Juan Wang Jiang-Qiao Geng Department of Otolaryngology Sanya Women and Children's HospitalSanya572000China Department of Otolaryngology Hebei Children’s HospitalShijiazhuang050031China

Objective:To evaluate the effect of myricetin on ovalbumin(OVA)-induced allergic rhinitis in ***:Mice were sensitized and challenged using OVA(5%,500 mL)intraperitoneally and intranasally,respectively,on an alternative day for 14 days,followed by administration of myricetin(50,100,and 200 mg/kg)till day *** symptoms,biochemical parameters,protein expressions,and histopathology were ***:OVA-induced increased nasal symptoms including rubbing,sneezing,and discharge were significantly reduced by myricetin(100and 200 mg/kg)(Pso protected against histamine challenge and attenuated elevated serum immunoglobulin E(IgE;total and OVA-specific),total IgG1,andβ-hexosaminidase levels,as well as leukotriene C4 and interleukins levels in nasal lavage fluid(Pstern blot analysis showed that myricetin significantly upregulated the protein expression of T-box expressed in T cells,while downregulating the protein expression of GATA binding protein 3,NF-κB,and IκB-α(Pstopathological abberations in the nasal mucosa was markedly ameliorated by myricetin treatment(Psions:Myricetin exerts anti-allergic effects against OVAinduced allergic rhinitis via regulating Th1/Th2 balance.

关键词： Allergic rhinitis GATA3 Interleukins Myricetin Montelukast Ovalbumin Th1/Th2 balance

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MicroRNAs as controlled systems and controllers in non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第41期20卷 15079-15086页

作者： Nadia Panera Daniela Gnani Annalisa Crudele sara Ceccarelli Valerio Nobili Anna Alisi Hepato-Metabolic Disease Unit "Bambino Gesù" Children’s HospitalIRCCS Liver Research Unit "Bambino Gesù" Children’s HospitalIRCCS

Non-alcoholic fatty liver disease(NAFLD) is a multi-faceted condition including simple steatosis alone or associated with inflammation and ballooning(non-alcoholic steatohepatitis) and eventually *** NAFLD incidence has increased over the last twenty years becoming the most frequent chronic liver disease in industrialized ***,visceral adiposity,insulin resistance,and many other disorders that characterize metabolic syndrome are the major predisposing risk factors for ***,different factors,including genetic background,epigenetic mechanisms and environmental factors,such as diet and physical exercise,contribute to NAFLD development and *** lines of evidence demonstrate that specific microRNAs expression profiles are strongly associated with several pathological conditions including *** NAFLD,microRNA deregulation in response to intrinsic genetic or epigenetic factors or environmental factors contributes to metabolic *** this review we focused on microRNAs role both as controlled and controllers molecules in NAFLD development and/or their eventual value as non-invasive biomarkers of disease.

关键词： Liver steatosis Fibrosis Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis MicroRNAs

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Maternal Perfluorinated Compound Exposure and Risk of Early Pregnancy Loss: A Nested Case-control study

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Biomedical and Environmental sciences 2022年第2期35卷 174-179页

作者： MI Xin LIN shi Qi ZHANG Xiao Fen LI Jia Jia PEI Li Jun JIN Feng LIAO Qi XIE Li Min WEI Li Cong HAO Chan Juan ZHANG Ya Wei LI Wei shunyi Women’s and children’s hospital of Beijing children’s hospital Beijing 101300China Institute of Population Research/China Center on Population Health and Development Peking UniversityBeijing 100871China

Early pregnancy loss,defined as a nonviable intrauterine pregnancy occurring before 12 weeks of gestation,is estimated to affect 25%of clinically diagnosed pregnancies[1].several demographic,lifestyle,and environmental risk factors have been reported to associate with the risk of early pregnancy loss,yet the causes of most early pregnancy losses remain elusive;thus,further studies are *** compounds(PFCs)are a class of widespread environmental pollutants that can adversely affect human reproductive *** are inevitably exposed to PFCs through diet,water,air and dust.A wealth of epidemiological and toxicological research using a variety of animal models has warned of the persistence,bioaccumulation,and toxicity of PFCs[2].

关键词： pregnancy viable Early

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systematic co-delivery of dual agonists to enhance cancer immunotherapy

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Nano Research 2022年第9期15卷 8326-8335页

作者： Xiangxia Li Guiyuan Chen Yangyi Wang Lanhong su Bo Chen Kecheng Wu Yun Xing Zechenxi song Ruike Dai Tianxin Liu Jiaao Zhao Zhe Xie Peijie Zhou Xiaoping Xia Yuanzeng Min Department of Chemistry University of Science and Technology of ChinaHefei 230026China The First Afffiliated hospital of UsTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Anhui Provincial children's hospital Hefei 230051China children's hospital of Fudan University Anhui hospital Hefei 230051China children's hospital of Anhui Medical University Hefei 230051China

In the tumor immunosuppressive microenvironment(TIME),antigen presenting cells(APCs)usually exhibit a tumor suppressor ***-like receptors(TLRs)agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells(DCs)*** combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic ***,we designed a lipid-coated mesoporous silica nanoparticle(MsNs@Lipo)for the co-delivery of TLR7/8 agonist resiquimod(R848)and TLR9 agonist CpG oligodeoxynucleotides(ODNs)(CpG@MsNs-R@L-M).R848 was firstly conjugated onto the nanoparticle via silane chemistry,which is acidic responsive drug ***,CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist *** in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of *** importantly,CpG@MsNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma *** mechanistic study demonstrated that CpG@MsNsR@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T *** was concluded that in comparison to single agonist,the codelivery of dual agonists,CpG and R848,can improve anti-tumor immune responses for cancer immunotherapy.

关键词： toll-like receptors(TLRs)agonists mesoporous silica nanoparticles(MsNs) drug delivery tumor immunosuppressive microenvironment(TIME) cancer immunotherapy

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A clinical study to determine the threshold of bronchodilator response for diagnosing asthma in Chinese children

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World Journal of Pediatrics 2019年第6期15卷 559-564页

作者： Xiao-Hui Kang Wan Wang Ling Cao children's hospital Affiliated to the Capital Institute of Pediatrics No.2 Ya bao RoadChaoyang DistrictBeijingChina shanxi Provincial children's hospital TaiyuanChina

Background There is few objective,clinically feasible and inexpensive test for diagnosing childhood *** want to find an ideal way to solve *** The control group was 301 non-asthmatic children,and the asthma group was 286 asthmatic *** asthmatic children were divided into three groups according to the severity of their ***-and post-bronchodilator spirometer tests were performed,and the main spirometer parameters were *** bronchodilator response(BDR)[BDR is used to determine the reversibility of airway obstruction by measuring the changes of forced expiratory volume in the first second(FEV1)before and after inhalation of bronchodilators]was then determined,and the optimal threshold of BDR for diagnosing childhood asthma was *** 301 non-asthmatic children and 286 asthmatic children participated in the study,the demographics were *** 1 for pre-bronchodilator of asthmatic children was significantly lower than that of non-asthmatic children(P≤0.01).BDR of non-asthmatic children was 3.30±3.85%.BDR of asthmatic children was 9.45±9.15%.There was no significant difference in BDR for patients with different severities of asthma within the *** had no statistical correlation with gender,age,height,weight in neither non-asthmatic children nor asthmatic *** the receiver-operating characteristic curve,a BDR threshold of≥7.5%offered an optimal balance in asthma diagnosis with a sensitivity rate of 50.7%and specificity rate of 87.7%.Meanwhile,with a BDR threshold of≥12%,the sensitivity rate was 28.7%and the specificity rate was 96.3%.Conclusion A BDR threshold of≥7.5%has more value in childhood asthma diagnosis as compared to≥12%.

关键词： Asthma diagnosis Bronchodilator response Threshold

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Gene mutations and clinical phenotypes in 15 Chinese children with cryopyrin-associated periodic syndrome(CAPs)

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science China(Life sciences) 2017年第12期60卷 1436-1444页

作者： Caifeng Li Xiaohua Tan Junmei Zhang shipeng Li Wenxiu Mo Tongxin Han Weiying Kuang Yifang Zhou Jianghong Deng Department of Rheumatology and Immunology Beijing Children's HospitalCapital Medical UniversityNational Center for Children"s HealthBeijing 100045China

The aim of our study is to explore the features of clinical manifestations and genetic mutations in Chinese CAPs patients. Fifteen confirmed patients with CAPs were enrolled. The onset time ranges from 2 days after birth to 6 years and 1 month. Recurrent urticaria rash(93.3%) with fever(100%) were two dominant characteristics of these patients that were presented as either acute or chronic process. systemic involvements were found in all patients except for one with only rash and fever. The top three symptoms were fever(100%), rash(93.3%) and myalgia(76%). Other clinical manifestations include arthritis(11 cases), lung involvement(seven cases), optical dysfunction(seven cases), nerve deafness(six cases), nervous system involvement(five cases), hepatomegaly, splenomegaly and lymphadenectasis(five cases). Also, four patients had heart involvement and one patient suffered kidney involvement. The laboratory inflammation index such as leukocyte counts, platelet counts, erythrocyte sedimentation rate(EsR), C-reactive protein(CRP), serum amyloid A(sAA) and fibrinogen(FIB) increased significantly at initial stage, but decreased after therapy. As for gene mutation detection, Twelve out of 15 patients were confirmed with mutation in NLRP3, including 11 mutant site: c1789 A>G, c.1703 T>A, c.913 G>A, c.1710 G>C, c.1057 G >T, c.2335 C>T, c.932 T>C,c.296 G>C, c.663 C>T, t.1702 T>A, 299 G>A. Mutation sites c.1703 T>A, c.2335 C>T, c.296 G>C, c.663 C>T, and 299 G>A were newly identified. The association between gene mutation and clinical manifestation shows that D305 N was highly associated with severe organs involvements, and therefore, the time of therapy and regimen were critical for the prognosis of disease. As the largest cohort study of Chinese CAPs patients, we confirmed that all patients presented typical clinical manifestations, identified five new mutation sites on NLRP3 and analyzed the correlation between the genotypes and phenotypes. We also raise concerns for one case

关键词： CAPs genetic mutation clinical phenotTpe NLRP3

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Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature

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World Journal of Gastroenterology 2018年第35期24卷 4086-4092页

作者： Hui-Hui Wang Fei-Qiu Wen Dong-Ling Dai Jian-she Wang Jing Zhao Kenneth DR setchell Li-Na shi shao-Ming Zhou si-Xi Liu Qing-Hua Yang Gastroenterology Department Shenzhen Children’s Hospital Center for Pediatric Liver Diseases Children’s Hospital of Fudan University Department of Pathology and Laboratory Medicine Cincinnati Children’s Hospital Medical Center My Genostics Incorporation Konggang Industrial Park

steroid 5β-reductase [aldo-keto reductase family 1 member D1(AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307(p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid(UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid(CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.

关键词： Aldo-keto reductase family 1 member D1 Cholestasis Congenital bile acid synthesis defect Gene mutation

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World Journal of Clinical Cases 2021年第13期9卷 3070-3078页

作者： Qiao-Feng Ye Guang-Fei Wang Yi-Xue Wang Guo-Ping Lu Zhi-Ping Li Department of Clinical Pharmacy National Children's Medical CenterChildren's Hospital of Fudan UniversityShanghai 201102China Department of Pediatric Intensive Care Unit National Children's Medical CenterChildren's Hospital of Fudan UniversityShanghai 201102China

BACKGROUND Vancomycin is often used as an anti-infective drug in patients receiving antitumor *** are concerns about its adverse drug reactions during treatment,such as nephrotoxicity,ototoxicity,hypersensitivity reactions,***,potential convulsion related to high plasma concentrations of vancomycin in children receiving chemotherapy has not been *** sUMMARY A 3.9-year-old pediatric patient with neuroblastoma receiving vancomycin to treat post-chemotherapy infection developed an unexpected *** other potential disease conditions could explain the occurrence of the *** subsequently measured overly high plasma concentrations of vancomycin could possibly provide a clue to the occurrence of this *** peak and trough plasma concentrations of vancomycin were 59.5 mg/L and 38.6 mg/L,respectively,which were much higher than the safe *** with the Bayesian approach using MwPharm software showed that the area under the concentration-time curve over 24 h was 1086.6 mg·h/***,vancomycin was immediately stopped and teicoplanin was administered instead combined with meropenem and fluconazole as the anti-infective treatment *** Unexpected convulsion occurring in a patient after chemotherapy is probably due to toxicity caused by abnormal pharmacokinetics of *** evaluation and close therapeutic drug monitoring should be conducted to determine the underlying etiology and to take the necessary action as soon as possible.

关键词： Vancomycin Neuroblastoma Convulsion children Adverse drug reaction Case report

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