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Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase(G6PD)by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis

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Science China(Life Sciences) 2024年第8期67卷 1648-1665页

作者： Jie Gao Xiaoyi Shi Yaohui Sun Xudong Liu Feng Zhang Chengcheng Shi Xiao Yu Zhiping Yan Long Liu Shizhe Yu Jiacheng Zhang Xiaodan Zhang Shuijun Zhang Wenzhi Guo Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China henan diagnosis&treatment league for hepatopathy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China henan Innovative Research Group for Hepatobiliary&Pancreatic Surgery and Digestive Organ Transplantation Zhengzhou 450052China henan Organ Transplantation Quality Control Centre Zhengzhou 450052China henan Engineering Technology Research Center for Organ Transplantation Zhengzhou 450052China Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of General Surgery Huashan HospitalFudan University Shanghai 200040China Cancer Metastasis Institute Fudan UniversityShanghai 200040China

Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely ***,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 *** was to be frequently found(86.6%)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with *** overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt^(−/−))produced the opposite *** combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt^(−/−)promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing *** contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated ***,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of *** sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue ***,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed *** together,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.

关键词： HCC BHMT arginine methylation G6PD PPP metabolism

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Natural herbal medicine Lianhuaqingwen capsule anti-influenza A （H1N1） trial： a randomized, double blind, positive controlled clinical trial

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Chinese Medical Journal 2011年第18期124卷 2925-2933页

作者： DUAN Zhong-ping JIA Zhen-hua ZHANG Jian LIU Shuang CHEN Yu LIANG Lian-chun ZHANG Chang-qing ZHANG Zong SUN Yan ZHANG Shu-qin WANG Yong-yan WU Yi-ling Beijing You-An Hospital Capital Medical University Beijing 100069 China Key Research Centre of Collateral Disease of State Administration of Traditional Chinese Medicine Yiling Pharmaceutical Research Academy of Hebei Province Shijiazhuang Hebei 050035 China Kaifeng Infectious Disease Hospital Kaifeng Henan 415001 China Jinan Infectious Disease Hospital Jinan Shandong 250021 China henan Provincial Infectious Disease Hospital Zhengzhou Henan 450005 China Jilin Provincial hepatopathy Hospital Changchun Jilin 130061China China Academy of Chinese Medical Sciences Beijing 100700China

Background The 2009 influenza A （H1N1） virus infection is associated with the high risk of severe complications and is spreading more rapidly throughout the world than other reported seasonal influenzas. This study aimed to evaluate the efficacy and safety of the nature herbal medicine Lianhuaqingwen capsule （LHC） in patients infected with influenza A （H1N1） virus. Methods A total of 244 patients aged 16-65 years confirmed with influenza A （H1N1） virus infection by the real time RT-PCR were randomized to one of two treatment groups of 122 patients each. Each group assigned to receive either LHC or Oseltamivir for five days and observation for seven days. The patients were enrolled within 36 hours of illness onset if they had an axillary temperature of ≥37.4℃ and with at least one of the following symptoms： nasal obstruction, runny nose, cough, sore throat, fatigue, headache, myalgia, chills and sweating. The primary end point was the duration of illness. Results Of 244 patients, 240 （98.36%） patients with a median age 21 years completed the study between October 24, 2009 and November 23, 2009. There were no significant overall differences between LHC treated and Oseltamivir treated patients in the median duration of illness （LHC 69 hours vs. Oseltamivir 85 hours P 〉0.05） or the median duration of viral shedding （LHC 103 hours vs. Oseltamivir 96 hours, P 〉0.05）. However, it was worthwhile to note that LHC significantly reduced the severity of illness and the duration of symptoms including fever, cough, sore throat, and fatigue （P〈0.05）. Both study medications were well tolerated. No drug related serious adverse events occurred during the study. Conclusions Compared with Oseltamivir, LHC achieved a similar therapeutic effectiveness reduction of the duration of illness and duration of viral shedding. Therefore, LHC might be an alternative therapeutic measure for influenza A （H1N1） virus infections.

关键词： influenza A (H1N1 ) Lianhuaqingwen capsule clinical randomized controlled trial

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Development and validation of a CT-based radiomics model for differentiating pneumonia-like primary pulmonary lymphoma from infectious pneumonia: A multicenter study

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Chinese Medical Journal 2023年第10期136卷 1188-1197页

作者： Xinxin Yu Bing Kang Pei Nie Yan Deng Zixin Liu Ning Mao Yahui An Jingxu Xu Chencui Huang Yong Huang Yonggao Zhang Yang Hou Longjiang Zhang Zhanguo Sun Baosen Zhu Rongchao Shi Shuai Zhang Cong Sun Ximing Wang Department of Radiology Shandong Provincial HospitalShandong UniversityJinanShandong 250021China Department of Radiology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250021China Department of Radiology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266000China Department of Radiology Qilu HospitalShandong UniversityJinanShandong 250012China Department of Medicine Graduate SchoolKyung Hee UniversitySeoul 446701Republic of Korea Department of Radiology Yantai Yuhuangding HospitalAffiliated Hospital of Qingdao UniversityYantaiShandong 164000China Department of Research Collaboration R&D CenterBeijing Deepwise&League of PHD Technology Co.LtdBeijing 100080China Department of Radiology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117China Department of Radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Radiology Shengjing Hospital of China Medical UniversityShenyangLiaoning 110004China Department of Medical Imaging Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu 210002China Department of Radiology Affiliated Hospital of Jining Medical UniversityJiningShandong 272029China

Background:Pneumonia-like primary pulmonary lymphoma(PPL)was commonly misdiagnosed as infectious pneumonia,leading to delayed *** purpose of this study was to establish a computed tomography(CT)-based radiomics model to differentiate pneumonia-like PPL from infectious ***:In this retrospective study,79 patients with pneumonia-like PPL and 176 patients with infectious pneumonia from 12 medical centers were *** from center 1 to center 7 were assigned to the training or validation cohort,and the remaining patients from other centers were used as the external test *** features were extracted from CT images.A three-step procedure was applied for radiomics feature selection and radiomics signature building,including the inter-and intra-class correlation coefficients(ICCs),a one-way analysis of variance(ANOVA),and least absolute shrinkage and selection operator(LASSO).Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical factor *** radiologists reviewed the CT images for the external test *** of the radiomics model,clinical factor model,and each radiologist were assessed by receiver operating characteristic,and area under the curve(AUC)was ***:A total of 144 patients(44 with pneumonia-like PPL and 100 infectious pneumonia)were in the training cohort,38 patients(12 with pneumonia-like PPL and 26 infectious pneumonia)were in the validation cohort,and 73 patients(23 with pneumonia-like PPL and 50 infectious pneumonia)were in the external test ***-three radiomics features were selected to build the radiomics model,which yielded AUCs of 0.95(95%confidence interval[CI]:0.94-0.99),0.93(95%CI:0.85-0.98),and 0.94(95%CI:0.87-0.99)in the training,validation,and external test cohort,*** AUCs for the two readers and clinical factor model were 0.74(95%CI:0.63-0.83),0.72(95%CI:0.62-0.82),and 0.73(95%CI:0.62-0.

关键词： Primary pulmonary lymphoma Pneumonia Computed tomography Radiomics Differentiation

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