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Type I interferon pathway in pediatric systemic lupus erythematosus

World Journal of Pediatrics 2024年第7期20卷 653-668页

作者： Yu Zhou Hong‑Mei Song Department of Pediatrics Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina State Key Laboratory of complex Severe and Rare Diseases Peking Union Medical College HospitalBeijingChina

Background The role of type I interferon(IFN-I)signaling in systemic lupus erythematosus(SLE)has been well ***,unanswered questions remain regarding the applicability of these findings to pediatric-onset *** aim of this review is to provide an overview of the novel discoveries on IFN-I signaling in pediatric-onset *** sources A literature search was conducted in the PubMed database using the following keywords:“pediatric systemic lupus erythematosus”and“type I interferon”.Results IFN-I signaling is increased in pediatric SLE,largely due to the presence of plasmacytoid dendritic cells and pathways such as cyclic GMP-AMP synthase–stimulator of interferon genes–TANK-binding kinase 1 and Toll-like receptor(TLR)4/*** extracellular traps and oxidative DNA damage further stimulate IFN-I *** variants in IFN-I-related genes,such as IFN-regulatory factor 5 and tyrosine kinase 2,are linked to SLE susceptibility in pediatric *** addition,type I interferonopathies,characterized by sustained IFN-I activation,can mimic SLE symptoms and are thus important to *** on interferonopathies also contribute to exploring the pathogenesis of *** IFN-I activation is crucial for SLE diagnosis and *** IFNstimulated gene expression and serum IFN-α2 levels are common *** cytometry markers such as CD169 and galectin-9 are promising ***-IFN therapies,such as sifalimumab and anifrolumab,show promise in adult patients with SLE,but their efficacy in pediatric patients requires further *** kinase inhibitors are another treatment option for severe pediatric SLE *** This review presents an overview of the IFN-I pathway in pediatric *** the intricate relationship between IFN-I and pediatric SLE may help to identify potential diagnostic markers and targeted therapies,paving the way for improved patient care and outcomes.

关键词： Interferonopathies Pediatric systemic lupus erythematosus Type I interferon

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Semaphorin 3C (Sema3C) reshapes stromal microenvironment to promote hepatocellular carcinoma progression

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3429-3448页

作者： Hao Peng Meng Yang Kun Feng Qingpeng Lv Yewei Zhang Medical School Southeast UniversityNanjing 210009China Department of Ultrasound State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of MedicalSciencesPeking Union Medical CollegeBeijing 100730China Hepatopancreatobiliary Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210009China

More than 90% of hepatocellular carcinoma(HCC)cases develop in the presence of fibrosis or cirrhosis,making the tumor microenvironment(TME)of HCC distinctive due to the intricate interplay between cancer-associated fibroblasts(CAFs)and cancer stem cells(CSCs),which collectively regulate HCC ***,the mechanisms through which CSCs orchestrate the dynamics of the tumor stroma during HCC development remain *** study unveils a significant upregulation of Sema3C in fibrotic liver,HCC tissues,peripheral blood of HCC patients,as well as sorafenib-resistant tissues and cells,with its overexpression correlating with the acquisition of stemness properties in *** further identify NRP1 and ITGB1 as pivotal functional receptors of Sema3C,activating downstream AKT/Gli1/c-Myc signaling pathways to bolster HCC self-renewal and tumor ***,HCCcells-derived Sema3Cfacilitated extracellular matrix(ECM)contraction and collagen deposition in vivo,while also promoting the proliferation and activation of hepatic stellate cells(HSCs).Mechanistically,Sema3C interacted with NRP1 and ITGB1 in HSCs,activating downstream NF-kB signaling,thereby stimulating the release of IL-6 and upregulating HMGCR expression,consequently enhancing cholesterol synthesis in ***,CAF-secreted TGF-β1 activates AP1 signaling to augment Sema3C expression in HCC cells,establishing a positive feedback loop that accelerates HCC ***,blockade of Sema3C effectively inhibits tumor growth and sensitizes HCC cells to sorafenib in *** sum,our findings spotlight Sema3C as a novel biomarker facilitating the crosstalk between CsCs and stroma during hepatocarcinogenesis,thereby offering a promising avenue for enhancing treatment efficacy and overcoming drug resistance in HCC.

关键词： Sema hepatocellular thereby

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Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 393-398页

作者： Mei-Zi Li Tao Guo Yun-Lu Feng Sheng-Yu Zhang Xiao-Yin Bai Xi Wu Kai Xu Ai-Ming Yang Department of Gastroenterology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China Department of Radiology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is ***,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is *** study aimed to demonstrate and identify predictors of DM control under the influence of ***:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM *** incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM *** the 52 patients with DM,CST was administered in 48 *** logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control ***:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP *** exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

关键词： Type 1 autoimmune pancreatitis Diabetes mellitus Corticosteroid therapy Predictive factor Pancreatic atrophy

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Resection of polyps involving the appendiceal orifice by combined endo-laparoscopic surgery: Two case reports

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1948-1952页

作者： Yue-Yi Zhang Jun-Yang Lu Qiang Wang Ai-Ming Yang Department of Gastroenterology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

BACKGROUND The management of polyps involving the appendiceal orifice(AO)presents notable *** resection is frequently hindered by operational complexities,a heightened risk of incomplete removal,and an elevated risk of procedural complications,including ***,surgical resection may entail unnecessary excision of intestinal segments,leading to potential *** SUMMARY Here,we reported two patients who presented with polyps deeply situated within the AO,with indistinct boundaries making it challenging to ensure completeness using traditional endoscopic *** overcome these challenges,we em-ployed combined endo-laparoscopic surgery(CELS),achieving curative resection without postoperative *** The application of CELS in managing polyps involving the AO is emerging as a safe and effective treatment modality.

关键词： Polyps Laterally spreading tumor Appendiceal orifice Endoscopic resection Combined endo-laparoscopic surgery Case report

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The pathogenic mechanism of syndactyly type V identified in aHoxd13Q50R knock-in mice

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Bone Research 2024年第2期12卷 349-360页

作者： Han Wang Xiumin Chen Xiaolu Meng Yixuan Cao Shirui Han Keqiang Liu Ximeng Zhao Xiuli Zhao Xue Zhang McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Complex Severe and Rare DiseasesDepartment of Medical GeneticsInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Department of Orthopedics State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifthmetacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) ofHOXD13 in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlyingpathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed togenerate a Hoxd13Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly andpartial syndactyly between digits 2-4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in *** on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limbdevelopment, we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud atE10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibitednotable disparities in mRNA level between the Hoxd13Q50R homozygotes and the wild-type. These genes are known to be involvedin various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopicexpression of Shh and Fgf8, in conjunction with the down-regulation of Bmp2, results in a failure of patterning along both theanterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascadeultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations inhomozygous mice. These findings suggest that abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may beresponsible for the manifestation of human SDTY5.

关键词： BMP2 mechanism finding

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Fever assessment in children under five: Are we following the guidelines?

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World Journal of Clinical Pediatrics 2024年第1期13卷 62-72页

作者： Hasan M Isa Ahmed J Isa Murtadha A Alnasheet Mahmood M Mansoor Department of Pediatrics Salmaniya Medical ComplexManama 26671Bahrain Department of Pediatrics Arabian Gulf UniversityManama 26671Bahrain Department of General Surgery Salmaniya Medical ComplexManama 26671Bahrain

BACKGROUND Fever is a common cause of medical consultation and hospital admission,particularly among ***,the United Kingdom’s National Institute for Health and Care Excellence(NICE)updated its guidelines for assessing fever in children under five years of *** efficient assessment and management of children with fever are crucial for improving patient *** To evaluate fever assessment in hospitalized children and to assess its adherence with the NICE Fever in under 5s *** We conducted a retrospective cohort review of the electronic medical records of children under five years of age at the Department of Pediatrics,Salmaniya Medical complex,Bahrain,between June and July *** data,vital signs during the first 48 h of admission,route of temperature measurement,and indications for admission were *** was defined according to the NICE *** children were divided into five groups according to their age(0-3 months,>3-6 months,>6-12 months,>12-36 months,and>36-60 months).Patients with and without fever were compared in terms of demography,indication for admission,route of temperature measurement,and other vital *** with the NICE Fever in the under 5s guideline was *** compliance was defined as>95%,partial compliance as 70%-95%,and minimal compliance as≤69%.Pearson’sχ^(2),Student’s t test,the Mann-Whitney U test,and Spearman’s correlation coefficient(rs)were used for *** Of the 136 patients reviewed,80(58.8%)were *** median age at admission was 14.2[interquartile range(IQR):1.7-44.4]months,with the most common age group being 36-60 ***-six(26.4%)patients had fever,and 100(73.6%)were *** commonest age group for febrile patients(>12-36 months)was older than the commonest age group for afebrile patients(0-3 months)(P=0.027).The median weight was 8.3(IQR:4.0-13.3)*** with fever had higher weight than those without fever[10.2(IQR:7.3-13.0)vs 7

关键词： Fever Pediatrics Admission patterns Temperature measurement Guidelines Bahrain

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Immunosuppression and phenotypic plasticity in an atlas of human hepatocholangiocarcinoma

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 586-603,I0002-I0014页

作者： Yiran Li Ziyu Xun Junyu Long Huishan Sun Xu Yang Yanyu Wang Yunchao Wang Jingnan Xue Nan Zhang Junwei Zhang Jin Bian Jie Shi Xiaobo Yang Hanping Wang Haitao Zhao State Key Laboratory of complex Severe and Rare Diseases Department of Liver SurgeryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical College(CAMS&PUMC)BeijingChina Division of Pulmonary and Critical Care Medicine State Key Laboratory of Complex Severe and Rare DiseasesChinese Academy of Medical Sciences and Peking Union Medical College(CAMS&PUMC)BeijingChina

Background:Hepatocholangiocarcinoma(H-ChC)has the clinicopathological features of both hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)and is a more aggressive subtype of primary hepatic carcinoma than HCC or ***:We sequenced 91,112 single-cell transcriptomes from 16 human samples to elucidate the molecular mechanisms underlying the coexistence of HCC and iCCA components in ***:We observed two molecular subtypes of H-ChC at the whole-transcriptome level(CHP and CIP),where a metabolically active tumour cell subpopulation enriched in CHP was characterized by a cellular pre-differentiation *** define the heterogeneity of tumours and their associated microenvironments,we observe greater tumour diversity in H-ChC than HCC and iCCA.H-ChC exhibits weaker immune cell infiltration and greater CD8+exhausted T cell(Tex)dysfunction than HCC and *** we defined two broad cell states of 6,852 CD8+Tex cells:GZMK+CD8+Tex cells and terminal CD8+Tex ***+CD8+Tex cells exhibited higher infiltration of after treatment in H-ChC,the effector scores and expression of the immune checkpoints of them greatly increased after immunotherapy,which indicated that H-ChC might be more sensitive than HCC or iCCA to ***:In this paper,H-ChC was explored,hoping to contribute to the study of mixed tumours in other cancers.

关键词： Hepatocholangiocarcinoma(H-ChC) biphenotypic plasticity CD8+Tex cells immunosuppression

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Pathogenesis of chronic enteropathy associated with the SLCO2A1 gene:Hypotheses and conundrums

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World Journal of Gastroenterology 2024年第19期30卷 2505-2511页

作者： Zhi-Xin Xie Yue Li Ai-Ming Yang Dong Wu Qiang Wang State Key Laboratory of complex Severe and Rare Diseases Department of GastroenterologyPeking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China Department of Clinical Medicine Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China

Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein *** review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)*** have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal *** effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of *** the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.

关键词： SLCO2A1 Prostaglandin E2 Chronic enteropathy associated with the SLCO2A1 gene Small intestine Macrophage

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Magnetic resonance imaging of knees:a novel approach to predict recombinant human growth hormone therapy response in short-stature children in late puberty

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World Journal of Pediatrics 2024年第7期20卷 723-734页

作者： Xi Bai Zhi‑Bo Zhou Xiao‑Yuan Guo Yi‑Ling He Yue‑Lun Zhang Feng‑Dan Wang Feng Feng Hong‑Bo Yang Shi Chen Feng‑Ying Gong Hui‑Juan Zhu Hui Pan Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina Key Laboratory of Endocrinology of National Health Commission Department of EndocrinologyState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Medical Research Center Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Radiology Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina

Background There is no appropriate tool to predict recombinant human growth hormone(rhGH)response before therapy initiation in short-stature children in late *** current study aimed to explore the associations between magnetic resonance imaging(MRI)stages of the knee growth plates and rhGH response in short-stature children in late *** In this prospective cohort study,short-stature children in late puberty were treated with rhGH and followed up for 6 *** proposed a novel knee MRI staging system according to the growth plate states of distal femurs or proximal tibias and divided the participants into three groups:unclosed growth plate group,marginally closed growth plate group,and nearly closed growth plate *** primary outcomes were height gain and growth velocity(GV),which were assessed three months *** Fifty participants were enrolled,including 23 boys and 27 *** and height gain after 6 months of rhGH therapy decreased successively in the three groups with an increased degree of growth plate fusion,especially when grouped by proximal tibias(GV_(1-3 mon)from 9.38 to 6.08 to 4.56 cm/year,GV_(4-6 mon)from 6.75 to 4.92 to 3.25 cm/year,and height gain from 4.03 to 2.75 to 1.95 cm,all P<0.001).Moreover,the MRI stages of growth plates independently served as a significant variable for GV and height gain after therapy,especially when grouped by proximal tibias(all P<0.01).Conclusion The MRI staging method is expected to be an effective tool for predicting rhGH response before therapy initiation in short-stature children in late puberty.

关键词： Growth hormone Growth velocity Late puberty Magnetic resonance imaging Short stature

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Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 25-35页

作者： Zhuanzhuan Mu Xin Zhang Dongquan Liang Jugao Fang Ge Chen Wenting Guo Di Sun Yuqing Sun Zhentian Kai Lisha Huang Jun Liang Yansong Lin Department of Nuclear Medicine State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine Beijing 100730China Pepperdine University Graduate School of Education and Psychology Los Angeles 90045USA Department of Head and Neck Surgery Affiliated Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Central Laboratory State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Department of Bioinformatics Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Medicine Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Oncology Peking University International HospitalBeijing 102206China

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively ***: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low ***: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

关键词： Differentiated thyroid cancer distant metastases genetic alterations RAI refractoriness molecular risk stratification

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