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Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation

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ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 3916-3930页

作者： Mou, Zezhong Chen, Yiling Hu, Jinzhong Hu, Yun Zou, Lujia Chen, Xinan Liu, Shenghua Yin, Qiuping Gong, Jian Li, Shuchen Mao, Shanhua Xu, Chenyang Jiang, Haowen Fudan Univ Huashan Hosp Dept Urol Shanghai 200040 Peoples R China Fudan Univ Fudan Inst Urol Shanghai 200040 Peoples R China Fudan Univ Natl Clin Res Ctr Aging & Med Shanghai 200040 Peoples R China

Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： Icaritin Neutrophil Neutrophil extracellular trap PADI2 Urothelial cancer

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Clinical efficacy and prognosis analysis of different treatment regimens in patients with uncomplicated brucellosis

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China Medical Abstracts(Internal Medicine) 2024年第1期41卷 24-25页

作者：袁关敏 Dept Infect Dis Natl Infect Dis Med CenterShanghai Key Lab Infect Dis&Biosafety Emerg ResponseHuashan HospFudan UnivShanghai 200040

Objective To analyze the efficacy and prognosis of different treatment regimens in patients with uncomplicated brucellosis,and to provide guidance for clinical *** The patients diagnosed with brucellosis in the Sixth ... 详细信息

关键词： regimen patients prognosis

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Outcome of contralateral C7 nerve transferring to median nerve

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Chinese Medical Journal 2013年第20期126卷 3865-3868页

作者： Gao Kai-ming Lao Jie Zhao Xin Gu Yu-dong huashan hosp Dept Hand Surg Shanghai 200040 Peoples R China

Background Contralateral C7 （cC7） transfer had been widely used in many organizations in the world, but the outcomes were significantly different. So the purpose of the study was to evaluate the outcome of patients ... 详细信息

关键词： brachial plexus contralateral C7 foIlow-up median nerve

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Quantitative evaluation of acute renal failure in rabbits with contrast-enhanced ultrasound

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Chinese Medical Journal 2012年第4期125卷 652-656页

作者： Dong Yi Wang Wen-ping Cao Jia-ying Fan Pei-li Lin Xi-yuan Fudan Univ Zhongshan Hosp Dept Ultrasound Shanghai 200032 Peoples R China Fudan Univ Huashan Hosp Dept Ultrasound Shanghai 200040 Peoples R China

Background Assessment of perfusion in the early period of acute renal failure （ARF） is important,and can not be made by conventional *** aim of this study was to prospectively test in a rabbit ARF model whether real-time contrast-enhanced ultrasound （CEUS） can quantitatively evaluate the hemodynamic changes of renal cortex in the early *** The model of ARF was induced in 30 healthy New Zealand white rabbits （2.5-3.0 kg）,by intramuscular injection of 50% glycerin solution （12 ml/kg）.CEUS were performed on right kidneys before,6 and 24 hours after glycerin *** quantitative indexes were measured in renal cortex using QLAB *** between different stages were performed using paired t *** sensitivity of CEUS in diagnosing ARF was compared with blood serum urea nitrogen （BUN）,serum creatinine （SCr） level and color Doppler flow imaging （CDFI）.Results Among quantitative indexes,time to peak （TTP） and area under curve （AUC） increased significantly from （5.86±2.57） seconds and （124.4±46.7） dB.s before glycerin injection to （7.66±2.05） seconds and （288.1±64.9） dB.s 6 hours after injection （P 〈0.05）.Slope rate of ascending curve （A） and descending curve （α） decreased slightly from （3.00±1.22） dB/s and （0.19±0.15） 1/s to （2.80±1.45） dB.s and （0.09±0.02） 1/s （P 〈0.05）.Twenty-four hours later,only AUC increased significantly from （124.4±46.7） dB.s to （466.2±52.2） dB.s （P〈0.05）.Conclusion Quantitative indexes of CEUS might be useful in predicting the hemodynamic changes of renal cortex in the early six hours of ARF model.

关键词： This research was supported by a grant from the Shanghai Leading Academic Discipline Project (No.B112). acute renal failure contrast-enhanced ultrasound quantification time-intensity curve

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CT volume measurement for prognostic evaluation of unresectable hepatocellular carcinoma after TACE

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World Journal of Gastroenterology 2010年第16期16卷 2038-2045页

作者： Zhang, Jia-Wen Feng, Xiao-Yuan Liu, Han-Qiu Yao, Zhen-Wei Yang, Yan-Mei Liu, Bin Yu, Yong-Qiang Fudan Univ Huashan Hosp Dept Radiol Shanghai 200040 Peoples R China Anhui Med Univ Affiliated Hosp 1 Dept Radiol Hefei 200040 Anhui Peoples R China

AIM:To analyze the value of computed tomography(CT) volume measurements for evaluation of the survival rate of unresectable hepatocellular carcinoma(HCC) patients after transcatheter arterial chemoembolization(TACE).METHODS:One hundred and sixty-six unresectable HCC patients after TACE were involved in this retrospective *** CT scan was performed for all patients before and 4 wk to 2 mo after TACE to def ine the morphologic features of HCC including its largest diameter,volume,product of the greatest axial dimension,tumor to liver volume ratio(TTLVR),and tumor shrinkage *** variables used in the study included gender,age,pattern of tumor growth,number of lesions,Child-Pugh classif ication of liver function,repeated TACE times,pre-or post-treatment α-fetoprotein(AFP) level,portal vein cancerous thrombus,tumor metastasis,degree of lipiodol retention within the tumor,and percutaneous ethanol *** correlation between survival time and clinical variables of patients or lesions was analyzed by combining morphologic features with the corresponding clinical and general data as input.A Cox proportional hazard model was used to analyze prognostic *** Kaplan-Meier method was used to calculate the cumulative survival ***? uence of the parameters on prognosis was analyzed by the log-rank ***:The overall 6,12,24,36 and 60 mo cumulative survival rates were 78.92%,49.85%,23.82%,15.60% and 8.92%,*** median survival time was 12 *** and multivariate analysis showed that only 4 parameters were the independent prognostic factors including TTLVR(χ2 = 14.328,P < 0.001),portal vein cancerous thrombus(χ2 = 5.643,P = 0.018),repeated TACE times(χ2 = 8.746,P = 0.003),and post-treatment serum AFP level(χ2 = 5.416,P = 0.020).When the TTLVR value was less than 70%,the survival time was inversely correlated with the TTLVR ***:CT volume measurement technique can predict the prognosis of unresectable HCC patients

关键词： Hepatocellular carcinoma Chemoembolization Tumor volume Computed tomography Prognosis

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Association between the polymorphisms of interleukin-4, the interleukin-4 receptor gene and asthma

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Chinese Medical Journal 2013年第15期126卷 2943-2951页

作者： ZHU Ning GONG Yi CHEN Xiao-dong ZHANG Jing LONG Feng HE Jian XIA Jing-wen DONG Liang Fudan Univ Allergy Res Lab Inst Resp Dis Shanghai 200040 Peoples R China Fudan Univ Dept Resp Dis Huashan Hosp Shanghai 200040 Peoples R China

Background Interleukin-4 （IL4） is one of the most important cytokines involved in a variety of allergic disorders, particularly, asthma. A number of genetic epidemiological studies have identified an association between the gene polymorphisms of IL4 and interleukin-4 receptor （IL4R） and asthma in different populations. However, these studies have been inconsistent and inconclusive. The aim of this study was to investigate the association between the single nucleotide polymorphism （SNP） of IL-4, IL-4R and asthma risk in case-controlled studies using meta-analysis. Method A genetic model-free approach was used to perform the meta-analysis. Asthma （atopy status nondefined）, nonatopic and atopic asthma subgroups were separately analyzed. Next, the ethnic subgroup was analyzed. Heterogeneity and publication bias were also explored. Results Only two polymorphisms of IL4 （rs2243250 and rs2070874） and four polymorphisms of IL4R （rs1801275, rs1805011, rs1805010, and rs1805015） were included in the meta-analysis. Polymorphisms rs2243250 and rs2070874 of IL-4 and rs1801275 and rs1805011 of IL4R were associated with asthma. The overall odds ratio （OR） of rs2243250 in the CC versus TT＋TC genotypes was 0.84 （95% CI： 0.75-0.94）, and the Z-test for the overall effect was 3.0 （P=0.003）. We obtained significant results from this polymorphism in the Caucasian ethnicity and adult groups. However, the overall OR of rs1801275 for the GG＋AG versus AA genotype was 1.16 （95% CI： 1.00-1.35）, and the Z-test for the overall effect was 1.87 （P=0.06）. Moreover, significant results were only obtained from the sub-group analysis in Asians （P=0.02）. In the rs1805011 polymorphism of IL4R, the overall OR for the CC ＋AC versus AA genotypes was 0.39 （95% CI： 0.16-0.95）, and the Z-test for the overall effect was 2.08 （P=0.04）. Conclusions Both the IL4 and IL4R polymorphisms were associated with asthma. The rs2243250 polymorphism of IL4 was more important in the white and adult groups. Individuals who ca

关键词： interleukin-4 interleuMn-4 receptor asthma gene polymorphism case-controlled study meta-analysis

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Comparison of gene expression between normalcolon mucosa and colon carcinoma by means of messenger RNA differential display

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World Journal of Gastroenterology 1999年第6期5卷 533-534页

作者： Wang L Lu W Chen YG Zhou XM Gu JR Shanghai Med Univ Dept Gastroenterol Huashan Hosp Shanghai 200040 Peoples R China Shanghai Canc Inst Natl Lab Oncogene & Related Genes Shanghai 200032 Peoples R China

INTRODUCTIONMessenger RNA differential display technique, developed by Dr. Liang in 1992[1], is a powerful new tool for identifying and cloning differentially expressed genes in a certain type of cell line, tissue or a special developing stage. Using this method, large amounts of molecular biological information can be obtained easily and quickly. In our study, this technique was used to compare genes expressed differentially between normal colon mucosa and colon carcinomas, in order to understand the molecular biological basis of colon cancer.

关键词： colonic mucosa colonic neoplasms RNA, messenger gene expression

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Comparison of clinical features of autoimmune encephalitis with viral encephalitis in patients with limbic encephalitis syndrome

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China Medical Abstracts (Internal Medicine) 2017年第3期 187-188页

作者：邓波 Dept Neurol Huashan HospFudan Univ

Objective To investigate the frequency of autoimmune encephalitis(AE)in limbic encephalitis(LE)syndrome and compare its clinical features with viral *** Patients diagnosed with LE syndrome who admitted to huashan hospital from December2015 to June 2016 were enrolled and screened for autoantibodies associated with AE(anti-N-methyl-D-aspar-

关键词： Comparison of clinical features of autoimmune encephalitis with viral encephalitis in patients with limbic encephalitis syndrome

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Mechanism of salvianolate regulating activity of NLR family pyrin domain containing 3 inflammasome in treatment of mice with colitis

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China Medical Abstracts (Internal Medicine) 2017年第4期 220-221页

作者：蒋晓芸 Dept Gastroenterol Huashan HospFudan Univ

Objective To study the role of salvianolate in the treatment of inflammation of intestinal mucosa by colitis mice *** A total of 60 C57BL/6J mice were divided into acute control group,acute model group,acute interventional group,chronic control group,chronic model group and chronic interventional group with 10 mice in each *** sodium sulfate

关键词： NLR Mechanism of salvianolate regulating activity of NLR family pyrin domain containing 3 inflammasome in treatment of mice with colitis

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Efficacy of low dose and short-term rifaximin on irritable bowel syndrome related with small intestinal bacterial overgrowth

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China Medical Abstracts (Internal Medicine) 2020年第1期 48-49页

作者：陈坚 Dept Gastroenterol Huashan HospFudan Univ

Objective To investigate the efficacy of low dose and short-term oral rifaximin in patients with small intestinal bacterial overgrowth (SIBO) related irritable bowel syndrome (IBS).Methods From June 2017 to June 2018,... 详细信息

关键词： IBS Efficacy of low dose and short-term rifaximin on irritable bowel syndrome related with small intestinal bacterial overgrowth

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