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Protective effect of N-acetylcysteine against lipopolysaccharide injury in hepatocytes of neonatal mice

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Frontiers of Medicine 2008年第2期2卷 182-185页

作者： Lin WANG Jianbo XU Yuan TIAN heshui wu Yalan LIU Department of Pediatrics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of General Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

The present study provides supportive evid-ence for the effective prevention and treatment of lipopo-lysaccharide(LPS)-induced hepatocyte injury in neonatal mice by N-acetylcysteine(NAC).Hepatocytes of neonatal mice were obtained through collagenase digestion of the liver.The hepatocytes were treated either with LPS(10 mg/mL)alone or with NAC(5 mmol/L)for 1 h before the addition of LPS(10 mg/mL).After LPS treatment,12 wells of the cultured hepatocytes and supernatants were harvested at 0,6,and 12 h,respectively.Levels of alanine aminotransferase(ALT)and nitric oxide(NO)in the supernatant were biochemically quantified and reverse transcription-polymerase chain reaction(RT-PCR)was performed to detect the expression of inducible nitric oxide synthase(iNOS)mRNA after different treatments.At 0 h following the treatment of primary cultured hepa-tocytes with LPS,the levels of ALT,NO and iNOS mRNA in the supernatant were(21.1±4.78)u/L,(1.6±0.31)mmol/L and 0.17±0.023,respectively;at 6 h,(59.8±8.59)u/L,(6.6±0.81)mmol/L,and 0.71±0.091;and at 12 h,(89.6±15.30)u/L,(7.8±1.01)mmol/L,and 0.71±0.097.The levels of ALT,NO and iNOS mRNA at 6 and 12 h increased significantly,compared to those at 0 h(P<0.01).In contrast to LPS treatment alone,pre-treatment with NAC before LPS addition significantly reduced the levels of ALT,NO and iNOS mRNA in the supernatant at 6 h to(40.8±7.30)u/L,(3.2±0.71)mmol/L,and 0.41±0.060;and at 12 h to(55.4±5.48)u/L,(4.0±0.71)mmol/L,and 0.40¡0.067,respectively(P<0.01).However,the levels of ALT,NO and iNOS mRNA at 0 h did not change significantly with both treat-ment approaches.NAC has protective effects in hepato-cytes of neonatal mice against LPS-induced injury as shown by the reduced levels of ALT,NO and iNOS mRNA when primary hepatocytes were treated with NAC prior to LPS stimulation.We postulate that NAC exhibits its protective function by inhibiting LPS-induced transcription of iNOS,resulting in decreased levels of NO.

关键词： N-acetylcysteine endotoxin hepatocytes nitric oxide inducible nitric oxide synthase

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翻译后修饰在胰腺癌中的研究现状及展望

中华实验外科杂志 2024年第1期41卷 7-11页

作者：秦耕读吴河水华中科技大学同济医学院附属协和医院胰腺外科武汉430022

胰腺癌恶性程度极高,尽管近年来胰腺癌的诊治有较大进展,晚期胰腺癌患者生存期明显延长,但5年生存率仍较低,因此迫切需要更有效的治疗手段,特别是针对胰腺癌信号通路中关键分子的调控可能是治愈胰腺癌的希望所在。蛋白质翻译后修饰是调... 详细信息

胰腺癌恶性程度极高,尽管近年来胰腺癌的诊治有较大进展,晚期胰腺癌患者生存期明显延长,但5年生存率仍较低,因此迫切需要更有效的治疗手段,特别是针对胰腺癌信号通路中关键分子的调控可能是治愈胰腺癌的希望所在。蛋白质翻译后修饰是调控蛋白质结构及功能的重要方式之一,通过对不同的功能基团进行加工、转运及与底物蛋白结合,影响底物蛋白的理化性质、空间构象和结合能力,从而在定位、稳定性及活性等多个方面调控底物蛋白。研究结果显示翻译后修饰在调控胰腺癌增殖、侵袭、凋亡、细胞周期、放化疗抵抗等多个方面均发挥重要作用,进一步研究其在胰腺癌发生发展中的作用,并针对性地进行干预有可能为胰腺癌治疗提供有效治疗方法。本文重点阐述翻译后修饰在胰腺癌中的作用研究现状,并展望其临床应用前景。

关键词：胰腺癌翻译后修饰磷酸化乙酰化

The relationship between activation of TLR4 and partial hepatic ischemia/reperfusion injury in mice

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Hepatobiliary & Pancreatic Diseases International 2006年第1期5卷 101-104页

作者： Lin Wang JianBo Xu heshui wu JinXiang Zhang JinHui Zhang Yuan Tian ChunYou Wang Department of Pediatrics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China. whs1898@***

BACKGROUND: Toil-like receptors (TLRs) are a group of evolutionarily conserved pattern recognition receptors involved in the activation of the immune system in response to various pathogens. In this study, we elucidated the relationship between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice. METHODS: BALB/c mice were used in a model of partial hepatic I/R injury, and the changes of TLR4 gene expression in ischemic liver lobes were detected with real-time polymerase chain reaction (RT-PCR). The levels of plasma ALT and endotoxin in the portal vein were measured. TLR4-deficient mice (C3H/Hej) and wild type mice (C3H/Heouj) were used in a model of I/R injury; liver function impairment and the level of serum TNF-α were observed. RESULTS: After one hour ischemia, the expression of TLR4 mRNA increased at the 1st, 3rd hour of reperfusion, indicating the value of △Ct(1st hour: 1.21±0.87vs. 5.85±1.07, t=13.72, P<0.01; 3rd hour: 0.85±0.92vs. 6.11±1.24, t=16.33, P<0.01). No endotoxemia developed in every group of mice. At the 3rd hour of reperfusion, the level of serum TNF-α was significantly higher than that of sham group (Hej: 152±43 pg/ml vs. 18±10pg/ml, t=5.26, P<0.01; Heouj: 249±52pg/ml vs. 25±13 pg/ml, t=7.24, P<0.01). At the 1st, 3rd hour reperfusion, the level of plasmid ALT in Hej mice was lower than that in Heouj mice (1st hour 662±106 U/Lvs. 1216±174 U/L, t=4.21, P<0.01; 3rd hour 1145±132U/L vs. 29584±187 U/L, t=13.72, P<0.01). The level of serum TNF-αwas lower than that in Heouj mice (1524.43 U/L vs. 2494±52 U/L, t=3.94, P<0.01) at the 3rd hour reperfusion. CONCLUSION: TLR4 activation causes partial hepatic I/R injury through release of TNF-α.

关键词： liver reperfusion injury toll-like receptor endotoxin

Headspace Solid-Phase Micro-Extraction Gas Chromatography/Mass Spectrometry(HS-SPME-GC/MS)-Based Untargeted Metabolomics Analysis for Comparing the Volatile Components from 12 Panax Herbal Medicines

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Phyton-International Journal of Experimental Botany 2022年第7期91卷 1353-1364页

作者： Simiao Wang Xiaohang Li Meiting Jiang Xinlong wu Yuying Zhao Meiyu Liu Xiaoyan Xu Huimin Wang Hongda Wang heshui Yu Wenzhi Yang State Key Laboratory of Component-Based Chinese Medicine&Tianjin Key Laboratory of TCM Chemistry and Analysis Tianjin University of Traditional Chinese MedicineTianjin301617China College of Pharmaceutical Engineering of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin301617China

Quality control of ginseng currently is mainly based on ginsenoside analysis,but rarely focuses on the volatile organic components.In the current work,an untargeted metabolomics approach,by headspace solid-phase micro-extraction gas chromatography/mass spectrometry(HS-SPME-GC/MS),was elaborated and further employed to holistically compare the compositional difference of the volatile components simultaneously from 12 Panax herbal medicines,which included P.ginseng(PG),P.quinquefolius(PQ),P.notoginseng(PN),red ginseng(PGR),P.ginseng leaf(PGL),P.quinquefolius leaf(PQL),P.notoginseng leaf(PNL),P.ginseng flower(PGF),P.quinquefolius flower(PQF),P.notoginseng flower(PNF),P.japonicus(PJ),and P.japonicus var.major(PJvm).Chromatographic separation was performed on an HP-5MS elastic quartz capillary column using helium as the carrier gas,enabling good resolution within 1 h.We were able to characterize totally 259 volatile compounds,including 82 terpenes(T),46 alcohols(Alc),29 ketones(K),25 aldehydes(Ald),21 esters(E),and the others.By analyzing 90 batches of ginseng samples based on the untargeted metabolomics workflows,236 differential ions were unveiled,and accordingly 36 differential volatile components were discovered.It is the first report that simultaneously compares the compositional difference of volatile components among 12 Panax herbal medicines,and useful information is provided for the quality control of ginseng aside from the well-known ginsenosides.

关键词： Headspace solid-phase micro-extraction gas chromatography/mass spectrometry Panax volatile component untargeted metabolomics

Guidelines for the diagnosis and treatment of acute pancreatitis in China (2021)

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Journal of Pancreatology 2021年第2期4卷 67-75页

作者： Fei Li Shouwang Cai Feng Cao Rufu Chen Deliang Fu Chunlin Ge Chunyi Hao Jihui Hao Heguang Huang Zhixiang Jian Gang Jin Ang Li Haimin Li Shengping Li Weiqin Li Yixiong Li Tingbo Liang Xubao Liu Wenhui Lou Yi Miao Yiping Mou Chenghong Peng Renyi Qin Chenghao Shao Bei Sun Guang Tan Xiaodong Tian Huaizhi Wang Lei Wang Wei Wang Weilin Wang Junmin Wei heshui wu Wenming wu Zheng wu Changqing Yan Yinmo Yang Xiaoyu Yin Xianjun Yu Chunhui Yuan Taiping Zhang Yupei Zhao on behalf of the Chinese Pancreatic Surgery Association Department of General Surgery Xuanwu HospitalCapital Medical UniversityBeijing Department of Hepatobiliary and Pancreatic Surgery the First Medical CenterChinese PLA General HospitalBeijing Pancreatic Center Guangdong Provincial People’s HospitalGuangzhouGuangdong Province Department of Pancreatic Surgery Huashan HospitalFudan UniversityShanghai Department of Pancreatic and Biliary Surgery The First Affiliated Hospital of China Medical UniversityShenyangLiaoning Province Department of Hepatopancreatobiliary Surgery Peking University Cancer HospitalBeijing Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalTianjin Department of General Surgery Fujian Medical University Union HospitalFuzhouFujian Province Department of General Surgery Guangdong Provincial People’s HospitalGuangzhouGuangdong Province Department of Hepatobiliary Pancreatic Surgery Changhai Hospital Affiliated to Navy Medical UniversityShanghai Department of Hepatobiliary Surgery Xijing HospitalFourth Military Medical UniversityXi’anShaanxi Province Department of Pancreatobiliary Surgery Sun Yat-sen University Cancer CenterGuangzhouGuangdong Province Department of General Surgery Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu Province Department of General Surgery Xiangya HospitalCentral South UniversityChangshaHunan Province Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of Medical CollegeZhejiang UniversityHangzhouZhejiang Province Department of Pancreatic Surgery West China HospitalSichuan UniversityChengduSichuan Province Department of General Surgery Zhongshan HospitalFudan UniversityShanghai Pancreas Center The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu Province Department of Gastrointestinal and Pancreatic Surgery Zhejiang Provincial People’s HospitalHangzhouZhejiang Province Department of General Surgery Pancreatic Disease CenterRuijin HospitalShanghai Jiao Tong University School of Med

Acute pancreatitis(AP)is a common acute abdominal condition of the digestive system.In recent years,treatment concepts,methods,and strategies for the diagnosis of AP have advanced,and this has played an important role in promoting the standardization of AP diagnosis and treatment and improving the treatment quality of AP patients.On the basis of previous guidelines and expert consensus,this guideline adopts an evidence-based,problem-based expression;synthesizes important clinical research data at home and abroad in the most recent 5 years;and forms 29 recommendations through multidisciplinary expert discussion,including diagnosis,treatment,and follow-up.It is expected to provide evidence support for the treatment of AP in the clinical setting in China.

关键词： Acute pancreatitis Diagnosis Follow-up Guideline Treatment

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胰腺癌靶向治疗的研究现状和展望

中华实验外科杂志 2023年第1期40卷 5-7页

作者：孙岩吴河水华中科技大学同济医学院附属协和医院胰腺外科武汉430022

胰腺癌是侵袭性和致命性均极高的消化系统恶性肿瘤,近年来,吉西他滨联合白蛋白紫杉醇是不可切除胰腺癌治疗的主要方案,但其改善预后的效果并不显著,因此需要探索新的治疗方案来提升患者的生存率。研究表明,基因突变和细胞信号传导通路... 详细信息

胰腺癌是侵袭性和致命性均极高的消化系统恶性肿瘤,近年来,吉西他滨联合白蛋白紫杉醇是不可切除胰腺癌治疗的主要方案,但其改善预后的效果并不显著,因此需要探索新的治疗方案来提升患者的生存率。研究表明,基因突变和细胞信号传导通路异常是驱动胰腺癌发生发展的重要因素,如果能够识别这些异常的靶点并针对这些靶点设计药物,对于改善胰腺癌预后具有重要意义。同时,不同的胰腺癌患者可能有其特定的基因改变,这为患者的个性化治疗提供了理论基础,有希望进一步延长患者的生存时间。本文阐述了胰腺癌靶向治疗的研究现状,并展望其临床应用前景。

关键词：胰腺癌基因突变细胞信号传导通路靶向治疗耐药

Guidelines for the diagnosis and treatment of pancreatic cancer in China (2021)

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Journal of Pancreatology 2021年第2期4卷 49-66页

作者： Yinmo Yang Xueli Bai Dapeng Bian Shouwang Cai Rufu Chen Feng Cao Menghua Dai Chihua Fang Deliang Fu Chunlin Ge Xiaochao Guo Chunyi Hao Jihui Hao Heguang Huang Zhixiang Jian Gang Jin Fei Li Haimin Li Shengping Li Weiqin Li Yixiong Li Hongzhen Li Tingbo Liang Xubao Liu Wenhui Lou Yi Miao Yiping Mou Chenghong Peng Renyi Qin Chenghao Shao Bei Sun Guang Tan Xiaodong Tian Huaizhi Wang Lei Wang Wei Wang Weilin Wang Junmin Wei heshui wu Wenming wu Zheng wu Jingyong Xu Changqing Yan Xiaoyu Yin Xianjun Yu Chunhui Yuan Taiping Zhang Jixin Zhang Jun Zhou Yupei Zhao on behalf of the Chinese Pancreatic Surgery Association Department of General Surgery Peking University First HospitalBeijing Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of Medical CollegeZhejiang UniversityHangzhouZhejiang Province Departments of Endoscopy Peking University First HospitalBeijing Institute of Hepatobiliary Surgery of PLA Chinese PLA General HospitalBeijing Department of Pancreatobiliary Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong Province Department of General Surgery Xuanwu HospitalCapital Medical UniversityBeijing Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing Department of Hepatobiliary Surgery Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong Province Department of Pancreatic Surgery Huashan Hospital Fudan UniversityShanghai Department of General Surgery The First Affiliated Hospital of China Medical UniversityShenyangLiaoning Province Department of Imaging Peking University First HospitalBeijing Department of Hepato-Pancreato-Biliary Surgery Peking University Cancer Hospital&InstituteBeijing Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalTianjin Department of General Surgery Fujian Medical University Union HospitalFuzhouFujian Province Department of General Surgery Guangdong Provincial People’s HospitalGuangzhouGuangdong Province Department of Hepatobiliary Pancreatic Surgery Changhai Hospital Affiliated to Navy Medical UniversityShanghai Department of Hepatobiliary Surgery Xijing HospitalFourth Military Medical UniversityXi’anShaanxi Province Department of Pancreatobiliary Surgery Sun Yat-sen University Cancer CenterGuangzhouGuangdong Province Department of General Surgery Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu Province Department of General Surgery Xiangya HospitalCentral South UniversityChangshaHunan Province Department of Radiation Oncology Peking University First H

The incidence of pancreatic cancer has been rising worldwide,and its clinical diagnosis and treatment remain a great challenge.To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years,Chinese Pancreatic Association,the Chinese Society of Surgery,Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China(2014)after reviewing evidence-based and problem-oriented literature published during 2015-2021,mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer,conversion strategies for locally advanced pancreatic cancer,treatment of pancreatic cancer with oligo metastasis,adjuvant and neoadjuvant therapy,standardized processing of surgical specimens and evaluation of surgical margin status,systemic treatment for unresectable pancreatic cancer,genetic testing,as well as postoperative follow up of patients with pancreatic cancer.Forty recommendation items were finally proposed based on the above issues,and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation,Assessment,Development,and Evaluation system.This guideline aims to standardize the clinical diagnosis and therapy,especially surgical treatment of pancreatic cancer in China,and further improve the prognosis of patients with pancreatic cancer.

关键词： Diagnosis Guideline Multidisciplinary team Pancreatic cancer Treatment

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胰腺癌新辅助治疗的适应证的选择与疗效评估

中华医学杂志 2021年第10期101卷 716-721页

作者：勾善淼吴河水华中科技大学同济医学院附属协和医院胰腺外科武汉430022

胰腺癌恶性程度较高、预后较差。虽然手术切除仍是目前唯一能够治愈胰腺癌的方法,但伴随着胰腺癌辅助治疗的进展,其治疗模式已由“手术优先”向“多学科协作”转变。新辅助治疗已被证实可提高交界性可切除和局部进展期胰腺癌的R0切除率... 详细信息

胰腺癌恶性程度较高、预后较差。虽然手术切除仍是目前唯一能够治愈胰腺癌的方法,但伴随着胰腺癌辅助治疗的进展,其治疗模式已由“手术优先”向“多学科协作”转变。新辅助治疗已被证实可提高交界性可切除和局部进展期胰腺癌的R0切除率并改善患者预后,这些患者应给予新辅助治疗已成共识,但胰腺癌新辅助化疗方案的选择、放射治疗的地位、新辅助治疗后影像学与病理学评估等方面仍存较大争议。

关键词：胰腺肿瘤新辅助治疗放射治疗影像学评估病理学评估

Consensus of clinical diagnosis and treatment for non-functional pancreatic neuroendocrine neoplasms with diameter<2 cm

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Journal of Pancreatology 2023年第3期6卷 87-95页

作者： wu Wenming Cai Shouwang Chen Rufu Fu Deliang Ge Chunlin Hao Chunyi Hao Jihui Huang Heguang Jian Zhixiang Jin Gang Li Fei Li Haimin Li Shengping Li Weiqin LiYixiong Liang Tingbo Liu Xubao Lou Wenhui Miao Yi Mou Yiping Peng Chenghong Qin Renyi Shao Chenghao Sun Bei Tan Guang Wang Huaizhi Wang Lei Wang Wei Wang Weilin Wei Junmin wu heshui wu Zheng Yan Changqing Yang Yinmo Yin Xiaoyu Yu Xianjun Yuan Chunhui Zhao Yupei Department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Department of Hepatobiliary Surgery PLA General HospitalBeijing 100853China Department of General Surgery Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Pancreatic Surgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China Department of Hepatobiliary and Pancreatic Surgery Hunnan Division of The First Hospital of China Medical UniversityShenyang 110167China Department of Hepato-Pancreato-Biliary Surgery Peking University Cancer Hospital&InstituteBeijing 100142China Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of General Surgery Fujian Medical University Union HospitalFuzhou 350001China Department of General Surgery Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510000China Department of Hepatobiliary Pancreatic Surgery Changhai Hospital Affiliated to Navy Medical University(Second Military Medical University)Shanghai 200433China Department of General Surgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Hepatobiliary Surgery Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Hepatobiliary and Pancreatic Surgery Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China Department of Critical Care Medicine Jinling HospitalMedical School of Nanjing UniversityNanjing 210002China Department of General Surgery Xiangya HospitalCentral South UniversityChangsha 410008China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department

In clinical practice,pancreatic neuroendocrine neoplasms(pNENs)with a diameter smaller than 2 cm are commonly referred to as small pNENs.Due to their generally favorable biological characteristics,the diagnosis and treatment of small pNENs differ from other pNENs and are somewhat controversial.In response to this,the Chinese Pancreatic Surgery Association,Chinese Society of Surgery,Chinese Medical Association have developed a consensus on the diagnosis and treatment of small pNENs,which is based on evidence-based medicine and expert opinions.This consensus covers various topics,including concepts,disease assessment,treatment selection,follow-up,and other relevant aspects.

关键词： 2 cm Clinical diagnosis Non-functional pancreatic neuroendocrine neoplasms Treatment