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World Journal of Gastroenterology 2018年第27期24卷 2974-2983页

作者： yan-lan fang Hong Chen Chun-Lin Wang Li Liang Department of Pediatrics The First Affiliated Hospital College of Medicine Zhejiang University College of Medicine Zhejiang University

Nonalcoholic fatty liver disease(NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of conditions, ranging from fatty liver-which generally follows a benign, non-progressive clinical course-to non-alcoholic steatohepatitis, a subset of NAFLD that may progress to cirrhosis and end-stage liver disease or liver carcinoma. The underlying pathophysiological mechanism of "pediatric" NAFLD remains unclear, although it is strongly associated with obesity and insulin resistance. In this review we provide a general overview on the current understanding of NAFLD in children and adolescents, which underpins practice, enabling early diagnosis and appropriate therapeutic intervention for this life-threatening liver disease.

关键词： Non-alcoholic steatohepatitis Children Adolescents Pathogenesis Nonalcoholic fatty liver disease

A rabbit model of pediatric nonalcoholic steatohepatitis: The role of adiponectin

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World Journal of Gastroenterology 2009年第8期15卷 912-918页

作者： Jun-Fen Fu yan-lan fang Li Liang Chun-Lin Wang fang Hong Guan-Ping Dong Department of Endocrinology The Children's Hospital of Zhejiang University School of Medicine Hangzhou 310003 Zhejiang Province China

AIM： To create a rabbit model of pediatric nonalcoholic steatohepatitis （NASH） and to evaluate the role of adiponectin in the process. METHODS： Thirty-two specific pathogen-free male New Zealand rabbits were divided randomly into three groups：（1） the normal control group （n = 10） was fed with standard diet for 12 wk; （2） the model group A （n = 11）; and （3） model group B （n = 11） were fed with a highfat diet （standard diet ＋ 10% lard ＋ 2% cholesterol） for 8 and 12 wk, respectively. Hepatic histological changes were observed and biochemical parameters as well as serum levels of adiponectin, interleukin （IL）-6, IL-10 and tumor necrosis factor （TNF）-α were measured. RESULTS： Typical histological hepatic lesions of NASH were observed in both model groups described as liver steatosis, liver inflammatory infiltration, cytologic ballooning, perisinusoidal fibrosis and overall fibrosis. Compared with the normal control group, there were significant increases in model groups A and B in weight gain （1097.2 ± 72.3, 1360.5± 107.6 vs 928.0 ±58.1, P 〈 0.05, P 〈 0.01）, liver weight （93.81±6.64, 104.6±4.42 vs 54.4±1.71, P 〈 0.01）, Lg （ALT）（1.9±0.29, 1.84± 0.28 vs 1.60±0.17, P 〈 0.01）, and Lg （TG）（1.03 ±0.24, 1.16 ±0.33 vs 0.00 ±0.16, P 〈 0.01）. Weight gain was much more in model group B than in model group A （1360.5± 107.6 vs 1097.2 ±72.3, P 〈 0.05）. But, there was no significant difference between the two groups concerning the other indexes. Pro-inflammatory cytokines （IL-6 and TNF-α） increased in model group B compared with that of control and model group A （IL-6：1.86±0.21 vs 1.41 ±0.33, 1.38± 0.42, P 〈 0.01; TNF-α： 1.18±0.07 vs 0.66 ±0.08, 0.86 ±0.43, P 〈 0.01, P 〈 0.05）, whereas serum adiponectin and IL-10 decreased in model groups compared with that in the control （adiponectin： A： 21.87±4.84 and B： 21.48 ±4.60 vs 27.36 ±7.29, P 〈 0.05. IL-10： A： 1.72± 0.38 and B： 1.83 ±0.39 vs 2.26±0.24, P 〈 0.01）. Lg （TC） and the degree of liver fatty infiltration was an independent determi

关键词： Nonalcoholic steatohepatitis Pediatricanimal model Adiponectin Interleukin 6 Tumornecrosis factor

Rare mutation in MKRN3 in two twin sisters with central precocious puberty: Two case reports

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World Journal of Clinical Cases 2021年第32期9卷 10018-10023页

作者： Li-Qiong Jiang yan-Qiong Zhou Ke Yuan Jian-fang Zhu yan-lan fang Chun-Lin Wang Department of Pediatrics The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in *** ring finger protein 3(MKRN3),a maternal imprinted gene with a highly conserved sequence,is the most common genetic etiology associated with *** 50 different mutations in MKRN3 have been found in *** SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 *** left hand bone age of both patients revealed advanced age(9 years).Pelvic B ultrasound indicated enlargement of the *** hormone(LH)releasing hormone testing confirmed *** sequencing detected the c.841C>T mutation in MKRN3,leading to a single base substitution,in the *** mutation was inherited from the father and paternal *** 3 mo of treatment with a gonadotropin-releasing hormone analog,levels of LH,follicle-stimulating hormone,and estradiol in the proband’s sister returned to normal *** Here,we report a rare mutation(c.841C>T)in MKRN3 in identical twin sisters with CPP.

关键词： Central precocious puberty MKRN3 Mutation Case report

Growth hormone ameliorates hepatopulmonary syndrome and nonalcoholic steatohepatitis secondary to hypopituitarism in a child:A case report

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World Journal of Clinical Cases 2022年第18期10卷 6211-6217页

作者： Xiao-Yuan Zhang Ke Yuan yan-lan fang Chun-Lin Wang Department of Pediatrics The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Craniopharyngioma is a benign tumor that usually develops in children;however,it is located in the center and close to sensitive structures,such as the pituitary gland and *** the hypothalamus plays a crucial role in the homeostasis of anterior pituitary hormone synthesis,damage to the hypothalamus leads to multiple pituitary hormone deficiencies and non-alcoholic fatty liver disease,including hepatopulmonary syndrome(HPS).HPS has limited treatment and poor *** SUMMARY A girl aged 13 years and 6 mo underwent surgery for craniopharyngioma 6 years *** craniotomy was performed with total resection via the corpus callosum approach,and the tumor at the base was approximately 3.5 cm×3.5 cm×4.0 *** 1 year postoperatively,she exhibited abdominal distension and weakness,and the laboratory tests revealed fatty liver ***,she had not visited the outpatient clinic for 2 *** years ago,she developed decreased activity endurance,severe cyanosis,chest tightness,wheezing,and intermittent and recurrent low fever after mild physical *** ultrasonography,liver biopsy,and contrast echocardiography of the right heart showed cirrhosis and multiple pituitary hormone deficiencies,indicating *** 1 year of treatment with recombinant human growth hormone,the liver function and oxygenation improved;she did not undergo liver *** Craniopharyngioma surgery can easily cause hypopituitarism,which can lead to nonalcoholic steatohepatitis and HPS in *** growth hormone therapy is important to improve the prognosis of these diseases.

关键词： Craniopharyngioma Nonalcoholic fatty liver disease Hypopituitarism Hepatopulmonary syndrome Growth hormone Children Case report

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

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World Journal of Gastroenterology 2007年第14期13卷 2104-2107页

作者： Jie Shao Lai Wei Hao Wang yan Sun lan-fang Zhang Jing Li Jian-Qiang Dong Department of Hepatic Disease People's Hospital Peking University Beijing 100034 China

AIM： To study the relationship between hepatitis B virus （HBV） DNA levels and liver histology in patients with chronic hepatitis B （CHB） and to determine the prevalence and characteristics of hepatitis B e antigen （HBeAg） negative patients.METHODS： A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg *** correlation between serum HBV DNA levels and liver damage （liver histology and biochemistry） was explored.RESULTS： Of the 213 patients with serum HBV DNA levels higher than 10^5 copies/mL, 178 （83.6%） were HBeAg positive, 35 （16.4%） were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse （ALT）,aspartate aminotrans-ferase （AST） in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT （r = 0.351, P = 0.042）. The grade （G） of liver disease correlated with ALT and AST （P 〈 0.05, r = 0.205, 0.327 respectively）in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G （P 〈 0.01, and r = 0.862, 0.802 respectively）. HBeAg negative patients were older （35 ± 9 years vs 30 ±9 years, P 〈 0.05 ） and had a longer history of HBV infection （8 ± 4 years vs 6 ± 4 years, P 〈 0.05） and a lower HBV DNA level than HBeAg positive patients （8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P 〈0.001）. There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.CONCLUSION： Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA more than 10^5 copies/*** to HB

关键词： Hepatitis B virus Hepatitis B virus DNA Chronic hepatitis B Liver histology

Novel deletion mutation in Bruton’s tyrosine kinase results in X-linked agammaglobulinemia:A case report

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World Journal of Clinical Cases 2020年第17期8卷 3859-3866页

作者： Xiao-Mei Hu Ke Yuan Hong Chen Chun Chen yan-lan fang Jian-fang Zhu Li Liang Chun-Lin Wang Department of Pediatrics The First Affiliated Hospital of Zhejiang UniversityHangzhou 310003Zhejiang ProvinceChina

BACKGROUND X-linked agammaglobulinemia is a primary immunodeficiency disease caused by gene mutations of Bruton’s tyrosine kinase(BTK).We found a new mutation point and summarized the correlation analysis and performed a literature *** SUMMARY The proband was a 5-year-old *** was admitted to our hospital due to a recurrent cough and a fever that had persisted for a *** had a history of multiple respiratory infections and *** was no immunodeficiency or recurrent infection history among his family *** was characterized as follows:Immunoglobulin(Ig)A,90.0 mg/dL(90-450 mg/dL);IgG,20.0 mg/dL(800-1800 mg/dL);and IgM,18.0 mg/dL(60-280 mg/dL).Notably,the assessment of IgG subtypes revealed the following very low levels:Subtype 1,0.26 g/L(3.62-12.28 g/L);subtype 2,0.10 g/L(0.57-2.9 g/L);subtype 3,0.009 g/L(0.129-0.789 g/L);and subtype 4,0.003 g/L(0.013-1.446 g/L).Cellular immunological test results were as follows:CD3,74.6%(50%-84.0%);CD4,47.3%(27.0%-51.0%);and CD8,24.9%(15.0%-44.0%).A de novo hemizygous deletion in BTK was detected:c.902_c.904delAAG/*** levels of the mutant BTK were similar to those of the wild-type gene,though overexpression resulted in markedly reduced levels of mutant BTK(9.49%±1.58%),relative to the wildtype BTK(75.8%±2.98%,P<0.01).CONCLUSION This case of X-linked agammaglobulinemia was attributed to a de novo hemizygous deletion mutation in BTK(c.902_c.904delAAG/p.E301del).The mutation resulted in markedly reduced BTK protein stability in vitro.

关键词： Agammaglobulinemia Bruton’s tyrosine kinase Mutation Immunodeficiency Case report

Engineered Cancer Nanovaccines:A New Frontier in Cancer Therapy

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Nano-Micro Letters 2025年第2期17卷 134-168页

作者： Yijie Wang Congrui Liu Chao fang Qiuxia Peng Wen Qin Xuebing yan Kun Zhang Central Laboratory and Department of Medical Ultrasound Sichuan Academy of Medical SciencesSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaNo.32West Second SectionFirst Ring RoadChengdu 610072People’s Republic of China Department of Stomatology and Central Laboratory School of MedicineShanghai Tenth People’s HospitalTongji UniversityNO.301 Yan‑Chang‑Zhong RoadShanghai 200072People’s Republic of China Jiangsu Provincial Innovation and Practice Base for Postdoctors Suining People’s HospitalAffiliated Hospital of Xuzhou Medical UniversityNo.2Bayi West RoadSuiningXu Zhou 221000Jiangsu ProvincePeople’s Republic of China

Vaccinations are essential for preventing and treating disease,especially cancer nanovaccines,which have gained considerable interest recently for their strong anti-tumor immune *** can prompt the immune system to generate antibodies and activate various immune cells,leading to a response against tumor tissues and reducing the negative effects and recurrence risks of traditional chemotherapy and *** enhance the flexibility and targeting of vaccines,nanovaccines utilize nanotechnology to encapsulate or carry antigens at the nanoscale level,enabling more controlled and precise drug delivery to enhance immune *** nanovaccines function by encapsulating tumor-specific antigens or tumor-associated antigens within *** small size of these nanomaterials allows for precise targeting of T cells,dendritic cells,or cancer cells,thereby eliciting a more potent anti-tumor *** this paper,we focus on the classification of carriers for cancer nanovaccines,the roles of different target cells,and clinically tested cancer nanovaccines,discussing strategies for effectively inducing cytotoxic T lymphocytes responses and optimizing antigen presentation,while also looking ahead to the translational challenges of moving from animal experiments to clinical trials.

关键词： Cancer nanovaccines Immunotherapy Nanobiotechnology Immune targets Signaling pathway

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High Fe‑Loading Single‑Atom Catalyst Boosts ROS Production by Density Effect for Efficient Antibacterial Therapy

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Nano-Micro Letters 2025年第2期17卷 187-203页

作者： Si Chen fang Huang Lijie Mao Zhimin Zhang Han Lin Qixin yan Xiangyu Lu Jianlin Shi Department of Cardiology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200092People’s Republic of China Shanghai Institute of Ceramics Chinese Academy of SciencesShanghai 200050People’s Republic of China Shanghai Frontiers Science Center of Nanocatalytic Medicine School of MedicineTongji UniversityShanghai 200092People’s Republic of China

The current single-atom catalysts(SACs)for medicine still suffer from the limited active site ***,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with *** constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial ***,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading ***,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/*** addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)*** in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound *** work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.

关键词： Nanocatalytic medicine Single-atom catalysts Reactive oxygen species(ROS) High metal loading Oxidase catalysis

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Trinuclear gold-catalyzed site-selective alkylation of peptides

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Science China Chemistry 2025年第1期68卷 249-256页

作者： Qing-Yun fang Chengyihan Gu Yinghan Chen Wencheng yan Yong Liang Weipeng Li Chengjian Zhu Jie Han Jin Xie State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (Chem BIC) School of Chemistry and Chemical Engineering Nanjing University Green Catalysis Center College of Chemistry Zhengzhou University State Key Laboratory of Natural Medicines China Pharmaceutical University

Selective modification of peptides has always been a challenging issue. The selective alkylation of peptides can alter the biological activity and physical properties of molecules, and it has gained significant research interest. We herein disclose an intriguing gold-catalyzed alkylation of peptides using bench-stable unactivated alkyl bromides under photoredox catalysis. A wide range of structurally diverse primary, secondary and tertiary alkyl bromides serve as effective coupling partners to precisely connect with the α-C(sp3)–H in glycine residue of peptides. This protocol demonstrates an exceptionally broad scope for alkyl halides and excellent tolerance for a wide range of useful functional groups. A series of relay transformations to construct cyclic peptides, to proceed click reaction and to realize peptide fluorescence labeling further enhance its synthetic practicality. In addition, mechanistic studies and density functional theory(DFT) calculations reveal an inner-sphere and subsequent outersphere single electron transfer(SET) mechanism.

关键词： gold catalysis peptide alkylation C-C coupling radical

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BOPPPS模式下的EGAP有效教学实践

教育教学论坛 2020年第27期 218-219页

作者：蓝艳芳广西民族大学外国语学院广西南宁530006

高校的通用学术英语是我国大学英语新一轮教学改革的方向。然而现有的通用学术英语教学面临费时低效的困境。基于以有效教学著称的BOPPPS模型,以通用学术英语课程中的英文概要写作为例,探讨BOPPPS模型在构建有效通用学术英语教学模式中... 详细信息

高校的通用学术英语是我国大学英语新一轮教学改革的方向。然而现有的通用学术英语教学面临费时低效的困境。基于以有效教学著称的BOPPPS模型,以通用学术英语课程中的英文概要写作为例,探讨BOPPPS模型在构建有效通用学术英语教学模式中的运用,以期为通用学术英语有效教学模式,提供新的思路与借鉴。

关键词： BOPPPS 通用学术英语有效教学模式

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