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B cell dysfunction in chronic hepatitis B virus infection

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Liver Research 2021年第1期5卷 11-15页

作者： Lijie Ma Xuehua Sun Xiaoni Kong yueqiu gao Institute of Clinical Immunology Department of Liver DiseasesShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Chronic hepatitis B(CHB)remains a global health *** persistence of hepatitis B surface antigen(HBsAg)in the blood for longer than 6 months after the initial infection is a sign of *** therapeutic goal for the functional cure of CHB is the generation of antibodies against ***,the adaptive immune response of patients with CHB cannot generate an efficient antiviral *** previous studies have evaluated T cell function and T cell therapy specifically designed to counter hepatitis B virus(HBV)*** one of the major components of adaptive immunity,B cells also display dysfunctions in anti-HBsAg antibody(HBsAb)production and antigen *** with CHB have amplification of CD19^(+)CD10^(-)CD27^(-)CD21^(-)atypical memory B cell subsets and CD19^(+)CD24^(hi)CD38^(hi) regulatory B ***,no reviews have summarized specific B cell responses during CHB ***,in this study,we summarized B cell dysfunction during CHB progression and the potential mechanisms behind these dysfunctions to further our understanding of the mechanisms of adaptive immune response of B cells in the process of CHB development and help provide new methods and ideas for the treatment of CHB.

关键词： Chronic hepatitis B virus infection B cell dysfunction Hepatitis B surface antibody Atypical memory B cells(atMBCs) Antigen-presenting cells(APCs) Regulatory B cells(Bregs)

Therapeutic potential of traditional Chinese medicine for the treatment of NAFLD:A promising drug Potentilla discolor Bunge

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3529-3547页

作者： Longshan Ji Qian Li Yong He Xin Zhang Zhenhua Zhou Yating gao Miao Fang Zhuo Yu Robim M.Rodrigues yueqiu gao Man Li Laboratory of Cellular Immunity Institute of Clinical ImmunologyShanghai Key Laboratory of Traditional Chinese MedicineShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineKey Laboratory of Liver and Kidney Diseases(Shanghai University of Traditional Chinese Medicine)Ministry of EducationShanghai 201203China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China Department of Hepatopathy Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of in Vitro Toxicology and Dermato-Cosmetology Faculty of Medicine and PharmacyVrije Universiteit BrusselBrussels 1000Belgium

Nonalcoholic fatty liver disease(NAFLD)is characterized by excessive accumulation of hepatic lipids and metabolic stress-induced liver *** are currently no approved effective pharmacological treatments for *** Chinese medicine(TCM)has been used for centuries to treat patients with chronic liver diseases without clear disease types and *** recently,TCM has been shown to have unique advantages in the treatment of *** performed a systematic review of the medical literature published over the last two decades and found that many TCM formulas have been reported to be beneficial for the treatment of metabolic dysfunctions,including Potentilla discolor Bunge(PDB).PDB has a variety of active compounds,including flavonoids,terpenoids,organic acids,steroids and *** compounds have been shown to exhibit a series of beneficial effects for the treatment of NAFLD,including anti-oxidative and anti-inflammatory functions,improvement of lipid metabolism and reversal of insulin *** this review,we summarize potential therapeutic effects of TCM formulas for the treatment of NAFLD,focusing on the medicinal properties of natural active compounds from PDB and their underlying *** point out that PDB can be classified as a novel candidate for the treatment and prevention of NAFLD.

关键词： Nonalcoholic fatty liver disease(NAFLD) Traditional Chinese medicine Acupuncture Potentilla discolor Bunge(PDB) Natural active compounds Anti-oxidative Anti-inflammatory Lipid metabolism Insulin resistance Endoplasmic reticulum stress Intestinal microflora

CCL5 deficiency promotes liver repair by improving inflammation resolution and liver regeneration through M2 macrophage polarization

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Cellular & Molecular Immunology 2020年第7期17卷 753-764页

作者： Meng Li Xuehua Sun Jie Zhao Lei Xia Jichang Li Min Xu Bingrui Wang Han Guo Chang Yu yueqiu gao Hailong Wu Xiaoni Kong Qiang Xia Department of Liver Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Institute of Clinical Immunology Department of Liver DiseasesCentral LaboratoryShugang Hospital Affiliated to Shanghai University of Chinese Traditional MedicineShanghaiChina Shanghai Key Laboratory of Molecular Imaging Collaborative Research CenterShanghai University of Medicine&Health ScienceShanghaiChina

Despite the diverse etiologies of drug-induced liver injury(DILI),innate immunity activation is a common feature involved in DILI ***,the involvement of innate immunity regulation in inflammation resolution and liver regeneration in DILI remains ***,we identified the chemokine CCL5 as a central mediator of innate immunity regulation in the pathogenesis of ***,we showed that serum and hepatic CCL5 levels are elevated in both DILI patients and an APAP-induced liver injury(AILI)mouse ***,both nonparenchymal cells and stressed hepatocytes are cell sources of CCL5 induction in response to liver *** experiments showed that CCL5 deficiency has no effect on the early phase of AILI but promotes liver repair in the late phase mainly by promoting inflammation resolution and liver regeneration,which are associated with an increased number of hepatic M2 ***,CCL5 can directly activate M1 polarization and impede M2 polarization through the CCR1-and CCR5-mediated activation of the MAPK and NF-κB *** then showed that CCL5 inhibition mediated by either a CCL5-neutralizing antibody or the antagonist Met-CCL5 can greatly alleviate liver injury and improve survival in an AILI mouse *** data demonstrate CCL5 induction during DILI,identify CCL5 as a novel innate immunity regulator in macrophage polarization,and suggest that CCL5 blockage is a promising therapeutic strategy for the treatment of DILI.

关键词： CCL5 APAP macrophage polarization acute liver injury

Chemical characters and protective effect of Baqi Lingmao formula(巴芪灵猫方) on experimental liver injury

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Journal of Traditional Chinese Medicine 2021年第6期41卷 862-874页

作者： LIU Lulu CHEN Yanxu LIU Lulu LI Man XU Rui QU Wensheng YIN Jiye ZHANG Xin ZHOU Zhenhua gao Yating NIE Dan SHAN Junjie gao yueqiu Institute of Chinese Materia Medica Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Institute of Pharmacology and Toxicology Academy of Military Medical SciencesAcademy of Military SciencesBeijing 100850China

OBJECTIVE:To investigate the chemical characters of water-extract of Baqi Lingmao formula(巴芪灵猫方,BQLM formula)and its effects on anti-liver injury in model mice and live ***:BQLM formula was composed of ten herbal *** determined the contents of alkaloids,saponins,phenolic acids and flavonoid in BQLM formula by UV *** active components of alkaloids and phenolic acids in BQLM formula were identified by HPLC *** anti-hepatic injury effects of BQLM formula were investigated with concanavalin A(Con A)-induced hepatitis model of mice,human liver LO2 and Hep G2.2.15 ***:BQLM formula(2 and 10 g/kg,orally)significantly improved the damages of liver tissues and functions caused by Con A in mice,reduced the infiltration of inflammatory cells into liver and inhibited the inflammatory cytokine secretion of interferon-γ,tumor necrosis factor-αand *** formula simultaneously decreased the levels of alanine aminotransferase and aspartate aminotransferase of liver and serum,and recovered the superoxide dismutase and catalase activities of liver to normal levels in Con A-induced hepatic-injury *** serum of BQLM formula group stimulated the human liver LO2 cell proliferation in ***,BQLM formula obviously promoted the proliferation of normal hepatocytes(LO2 cells)and inhibited the hepatocytes death induced by Con *** also significantly inhibited the proliferation of Hep G2.2.15 cells and decreased the secretion of HBs Ag and HBe Ag in ***:BQLM formula has anti-inflammation and anti-hepatitis virus Beffects,and is capable of improving liver injury in vivo and in vitro.

关键词： hepatitis B,chronic concanavalin A injury hepatocytes Baqi Lingmao formula

基于补肾健脾解毒法运用药对治疗慢性乙型病毒性肝炎经验举隅

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中华中医药杂志 2024年第6期39卷 2949-2952页

作者：张雪高月求上海中医药大学附属曙光医院上海201203

探讨高月求教授治疗慢性乙型病毒性肝炎的临床经验,其从事中西医结合治疗肝病30余年,善治慢性乙型病毒性肝炎,认为该病主要的发病机制是正虚为本,湿热疫毒为标,临床治疗大法主要包括两个方面,一是补益脾肾,一是清化湿浊,并基于补肾健脾... 详细信息

探讨高月求教授治疗慢性乙型病毒性肝炎的临床经验,其从事中西医结合治疗肝病30余年,善治慢性乙型病毒性肝炎,认为该病主要的发病机制是正虚为本,湿热疫毒为标,临床治疗大法主要包括两个方面,一是补益脾肾,一是清化湿浊,并基于补肾健脾解毒的治法治则创立临床基础方,在其基础上,应用对药进行加减治疗,故就其治疗慢性乙型病毒性肝炎的常用临床经验方及其对药举之一二。

关键词：高月求慢性乙型病毒性肝炎本虚标实补肾健脾解毒法药对

光激化学发光免疫检测法测定TSH功能灵敏度的评价

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检验医学 2011年第6期26卷 379-382页

作者：金磊周伟高月求上海中医药大学附属曙光医院上海200021

目的采用光激化学发光免疫技术(LiCA)测定促甲状腺激素(TSH)项目的功能灵敏度。方法制备系列低浓度的TSH样本,使用LiCA对其进行检测。将待测样本分成10个批次,选用3个批号的TSH检测试剂,并进行3次校准,最终以批间变异系数(CV)=20%确定TS... 详细信息

目的采用光激化学发光免疫技术(LiCA)测定促甲状腺激素(TSH)项目的功能灵敏度。方法制备系列低浓度的TSH样本,使用LiCA对其进行检测。将待测样本分成10个批次,选用3个批号的TSH检测试剂,并进行3次校准,最终以批间变异系数(CV)=20%确定TSH项目的功能灵敏度,对其进行验证。结果 LiCA检测TSH项目的功能灵敏度验证值为0.018 mIU/L。结论 LiCA检测TSH项目的功能灵敏度能够达到美国国家临床生化学院(NCAB)的相关要求,有助于TSH项目实验室检测技术发展的需要。

关键词：促甲状腺激素功能灵敏度光激化学发光免疫技术

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慢性乙型肝炎的中医药防治策略

临床肝胆病杂志 2015年第1期31卷 35-37页

作者：高月求上海中医药大学附属曙光医院上海201203

中医药防治慢性乙型肝炎(CHB)积累了丰富经验,但尚存在一些不足之处,如随机对照的临床研究开展不够、客观化的疗效评价指标重视程度欠缺等。在今后的临床防治工作中,应紧密结合CHB免疫发病机制的研究进展,充分发挥中医药调整人体功能状... 详细信息

中医药防治慢性乙型肝炎(CHB)积累了丰富经验,但尚存在一些不足之处,如随机对照的临床研究开展不够、客观化的疗效评价指标重视程度欠缺等。在今后的临床防治工作中,应紧密结合CHB免疫发病机制的研究进展,充分发挥中医药调整人体功能状态包括免疫功能状态的特色和优势,开展中医药调控CHB免疫应答的临床研究和转化医学研究,进一步提高临床疗效;在总结临床实践经验时,除了注重患者的症状,还要积极应用生化学、病毒学、病理学等替代结局指标,以提高疗效评价的客观性;在临床研究中,尽可能采用随机对照的临床研究方法,以提高中医药临床疗效的公认性。充分发挥我国CHB防治的中西医结合优势,必将造福广大患者。

关键词：肝炎,乙型,慢性中药疗法

肝细胞线粒体自噬在非酒精性脂肪性肝病发病机制中的作用

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临床肝胆病杂志 2019年第12期35卷 2809-2811页

作者：周振华王灵台高月求上海中医药大学附属曙光医院肝病科

非酒精性脂肪性肝病已成为我国第一大慢性肝病和健康体检肝生化指标异常的首要原因。线粒体自噬可降解肝脏中功能受损的线粒体和错误折叠蛋白以调节细胞死亡,同时具有维持肝脏脂质代谢稳态的作用。脂肪组织分泌的脂联素与脂联素受体2结... 详细信息

非酒精性脂肪性肝病已成为我国第一大慢性肝病和健康体检肝生化指标异常的首要原因。线粒体自噬可降解肝脏中功能受损的线粒体和错误折叠蛋白以调节细胞死亡,同时具有维持肝脏脂质代谢稳态的作用。脂肪组织分泌的脂联素与脂联素受体2结合,可增加肝脏Kupffer细胞分泌自噬激动剂,诱导肝细胞线粒体自噬,促进脂质代谢,从而减轻肝脏炎症,为研发疗效显著和机制明确的非酒精性脂肪性肝病治疗药物提供了新思路。

关键词：非酒精性脂肪性肝病脂联素线粒体自噬

GC-MS定量测定山豆根非生物碱部分成分含量

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中国中药杂志 2011年第4期36卷 468-473页

作者：祝路齐心高月求赵爱华贾伟上海交通大学药学院上海200240 上海中医药大学附属曙光医院上海200021

目的:采用GC-MS定性、定量分析山豆根非生物碱中的部分化学物质组成和含量。方法:非生物碱部位样品经TMS衍生后,采用GC-MS法测定,通过NIST 2.0数据谱库检索,结合人工解析,鉴定各种化学成分。在此基础上,测定了各组分的含量。结果:从非... 详细信息

目的:采用GC-MS定性、定量分析山豆根非生物碱中的部分化学物质组成和含量。方法:非生物碱部位样品经TMS衍生后,采用GC-MS法测定,通过NIST 2.0数据谱库检索,结合人工解析,鉴定各种化学成分。在此基础上,测定了各组分的含量。结果:从非生物碱部位共鉴定了24个化合物,其中定量测定了19个化合物的含量,占总量的34.72%,其中5个糖类成分占22.62%,9个有机酸占11.81%,其他5个成分占0.29%。结论:该法简便、快速、灵敏度高、重复性好,为定性、定量测定植物中复杂初生代谢产物提供了一种有效方法。

关键词：山豆根非生物碱气相色谱-质谱联用