甘草酸二铵治疗急性药物性肝损伤的疗效观察

目的:探讨甘草酸二铵治疗急性药物性肝损伤的疗效。方法:80例急性药物性肝损伤患者随机分为治疗组和对照组。治疗组予甘草酸二铵(甘利欣)注射液150mg加入5%葡萄糖溶液中静滴,每日1次。肝功能指标恢复正常或接近正常时改为口服甘利欣胶囊150mg,每日3次。对照组予门冬氨酸钾镁注射液40mL加入5%葡萄糖溶液中静滴,每日1次。肝功能指标恢复正常或接近正常时改为口服10mL,每日3次。两组治疗时间1月,1月后治疗无效者换用其他治疗。治疗前均停用怀疑引起急性药物性肝损伤的药物。观察症状、体征及肝功能改善情况。结果:两组症状体征均有改善,差别无统计学意义。治疗组显效率75%,总有效率95%;对照组显效率47.5%,总有效率77.5%;二者差异有统计学意义(P<0.01,P<0.05)。治疗组ALT复常时间(16.4±7.3)天,AST复常时间(17.3±6.9)天,ALP复常时间(19.5±8.7)天,TB复常时间(23.1±9.7)天;对照组ALT复常时间(23.6±8.5)天,AST复常时间(22.6±7.4)天,ALP复常时间(24.9±9.4)天,TB复常时间(28.4±5.3)天。二者差异有统计学意义(P<0.05)。结论:本研究结果表明,甘草酸二铵用于治疗急性药物性肝损伤有较好的疗效,且可缩短急性药物性肝损伤病程。     

甘草酸二铵注射液治疗急性荨麻疹的疗效观察

目的:观察甘草酸二铵注射液治疗急性荨麻疹的疗效和安全性。方法:将68例急性荨麻疹患者随机分为两组,A组给予甘草酸二铵注射液2mg/d,维生素C注射液3.0g/d,静脉滴注两周;B组给予10%葡萄糖酸钙注射液20ml/d,维生素C注射液3.0g/d,静脉滴注两周,口服氯雷他定胶囊10mg/d。结果:A、B两组有效率在14d时差异无统计学意义(P>0.05),分别为97.06%、94.12%,在7d时差异有统计学意义(P<0.05),分别为88.24%、67.65%。结论:甘草酸二铵注射液是治疗急性荨麻疹快速、安全、有效的药物。     

甘草酸二铵对动物血清胆碱酯酶的影响

目的 :研究甘草酸二铵 (diammoniumglycyrrhizinate ,DG)对小鼠和家兔外周血清胆碱酯酶的影响。 方法 :昆明种小鼠尾静脉注射甘草酸二铵 10～ 2 0mg·kg-1,家兔耳缘静脉注射甘草酸二铵 10～ 2 0mg·kg-1,静脉注射 30min后 ,采血测定血清胆碱酯酶活性。结果 :应用甘草酸二铵组的小鼠、家兔胆碱酯酶活性明显低于生理盐水组 ,但高于敌百虫组。结论 :甘草酸二铵可抑制血清胆碱酯酶活性 ,但抑制作用低于敌百虫组。     

甘草酸二铵注射液致急性喉头水肿1例

病例：患者,男,22岁。因“发热、咳嗽、咽痛7天”于2009年4月17日入院治疗。既往无饮酒及药物过敏史,有乙肝病史10余年。入院查体：体温39．8℃,     

甘草酸二铵致过敏反应1例

甘力欣是甘草酸二铰的商品名,主要成分为甘草甜素,是从甘草中分离出来的二铰盐,具有皮质激素的药理作用,而无     

甘草酸二铵致血压升高1例

患者,男,42岁。于2013年6月18日收入我院,主诉咳嗽、咯痰、盗汗,体检发现肺部阴影1月余未治疗。6月16日患者到市某医院行CT示：左上肺见小结节状、斑片状、索条状阴影;实验室检查示：ALT65．9U／L、AST212．4U／L、GGT1146．6U／L。门诊以：（1）左上肺继发型结核;（2）肝功能损害收入院。入院后查体：T36．5℃,P82次／min,R20次／min,BP120／80mmHg,B型超声示：脂肪肝。既往有饮酒史20年,平均5～6瓶啤酒／d;吸烟史25年,平均15—20支／d。     

甘草酸二铵对肝炎病人血清氢化可的松的影响

目的：观察甘草酸二铵对血清氧化可的松木水平的影响，方法：慢性肝病７０例，男性４９例，女性２１例，年龄３２±ｓ９ａ；分成３组，ＣＰＨ组１７例，ＣＡＨ组４１例，ＬＣ组１２例，均给甘草酸二铵１５０ｍｇ，加入１０％葡萄糖液２５０ｍＬ中ｉｖ，ｇｔｔ，ｑｄ，连续１５ｄ，并于使用前１ｄ及用药后ｄ１５晨８时抽血备测，另设正常对照组（健康男性１６例，女性９例，年龄２３±８ａ，不用药）２５例。结果：治疗前血清氢化的     

甘草酸二铵脂质复合物肠溶胶囊与甘草酸二铵胶囊对照治疗慢性乙型肝炎60例

目的:评价甘草酸二铵脂质复合物肠溶胶囊(甘平)治疗慢性乙型肝炎的临床疗效及安全性。方法:采用随机、盲法、平行对照的方法。60例伴有谷丙转氨酶(ALT)升高的慢性乙型肝炎患者分成试验组和甘草酸二铵胶囊对照组各30例。两组剂量均为:第1～10周450 mg·d-1,tid;第11周300 mg·d-1,tid;第12周150 mg·d-1,tid;疗程均为12周,停药后随访4周。观察两组的临床症状、血生化指标及不良反应。结果:试验组的总有效率显著高于对照组(73．3％vs 50．0％,P<0．01)。与对照组相比,试验组在给药4,8,12周时的ALT和谷草转氨酶(AST)降低更明显(P<0．01)。两组均无明显的不良反应。结论:甘草酸二铵脂质复合物肠溶胶囊对幔性乙型肝炎患者安全有效,降低ALT和AST的作用优于甘草酸二铵胶囊。     

孕三烯酮联用甘草酸二铵对肝功能的影响

目的 观察孕三烯酮联用甘草酸二铵治疗子宫内膜异位症时对肝功能的影响. 方法 将96例子宫内膜异位症患者,随机分为两组,每组48例. 两组均于手术后1周开始服孕三烯酮胶囊（每粒2.5 mg）,每次1粒,每周2次,连用3个月; 治疗组在服孕三烯酮的同时,加服甘草酸二铵胶囊（每粒50 mg）,每次3粒,tid. 3个月后比较肝功能的变化. 结果 治疗组丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、γ-谷氨酰转肽酶（γ-GT）、总胆红素（T-BiL）变化较少,只有5例轻度异常; 对照组有16例轻度异常,6例中重度异常（后停止服药）. 结论 甘草酸二铵可以减轻孕三烯酮的肝损伤,值得临床推广.     

甘草酸二铵注射液致过敏性休克1例

患者,男,38岁,农民,既往无过敏史,因"反复乏力1年,加重半月",于2010年9月3日就诊。经检查,拟诊为"慢性乙型肝炎",ALT 125u·L^-1。予以5%葡萄糖注射液250ml+甘草酸二铵注射液（甘利欣,江苏正大天晴药业股份有限公司,批号:1008042）30ml ivd。50滴/min,静滴约8min时,患者突然出现胸闷气促,呼吸困难,面部潮红,双手     

法舒地尔对脓毒症所致急性肺损伤及肺组织中HMGB1表达的影响

目的观察法舒地尔对小鼠脓毒症所致急性肺损伤的影响及其使用与否对肺组织中HMGB1表达量的影响。方法将48只BALB-C小鼠随机分为对照组、盲肠结扎穿刺（CLP）组、法舒地尔预处理组,在6、24 h时间点取血、肺泡灌洗液及鼠肺用于结果分析。结果在6、24 h时间点,法舒地尔可以显著降低CLP所致的小鼠血清中TNF-α及HMGB1和肺泡灌洗液中蛋白浓度的增加。除此之外,法舒地尔预处理还可以逆转CLP诱导的小鼠肺组织病理形态改变。同时,法舒地尔能减少CLP所致小鼠肺组织中HMGB1 mRNA表达量的增加。结论法舒地尔能减轻CLP小鼠所致的肺损伤并降低肺组织中HMGB1的表达。     

Non-histone nuclear factor HMGB1 as a therapeutic target in colorectal cancer

Introduction: High-motility group box (HMGB)-1 is the focus of recent cancer research. HMGB1 plays a critical role in cancer development, progression, and metastasis by activation of cancer cells, enhancement of tumor angiogenesis, and suppression of host anti-cancer immunity. HMGB1 is a relevant target for cancer treatment.

Areas covered: This review aims to overview the biological feature and diverses role in cancer of HMGB1. HMGB1 is a non-histone chromosomal protein, a secretory protein binding to the receptor for advanced glycation end products in cancer cells and monocyte-lineage immune cells, and a DNA presenting chaperon for toll-like receptors. HMGB1 enhances proliferation, motility, invasion and survival of cancer cells. In contrast, HMGB1 induces apoptosis in monocyte-lineage immune cells and inhibits tumor-infiltrating macrophages and dendritic cells, lymph node sinus macrophages and liver Kupffer cells to attenuate anti-cancer immune responses and anti-metastatic organ defense. Then the novel techniques for inhibiting HMGB1 are reviewed.

Expert opinion: Various techniques targeting HMGB1 are subjected to trial. HMGB1 targeting is a potential therapeutic techniqueagainst cancer development, progression, and especially metastasis. Technical breakthroughs in application of HMGB1 targeting to human diseases are now urgently required.     

HMGB1/RAGE蛋白在食管鳞癌中的表达及临床意义

目的探讨HMGB1/RAGE蛋白在食管鳞癌中的表达及其对食管鳞癌预后判定的作用。方法以食管鳞癌旁正常组织40例为对照,免疫组化检测80例食管鳞癌组织HMGB1、RAGE蛋白的表达,分析HMGB1、RAGE表达与临床病理因素的关系及其对食管鳞癌预后的影响。结果HMGB1、RAGE蛋白在食管鳞癌组织和正常鳞状上皮的阳性表达率分别为47.5%vs17.5%和72.5%vs42.5%,差异均具有统计学意义;HMGB1、RAGE蛋白的阳性表达与食管鳞癌浸润深度、淋巴结转移及TNM分期正相关（P〈0.05）,与癌细胞分化程度负相关（r分别为-0.51、-0.242,P〈0.05）;HMGB1和RAGE之间的表达呈正相关（r=0.35,P=0.001）;HMGB1、RAGE蛋白阳性表达食管鳞癌患者预后较差,COX分析显示HMGB1蛋白为影响食管鳞癌预后的独立因素（HR=4.853,P=0.000）。结论HMGB1和RAGE蛋白的表达与食管鳞癌的临床病理学特征密切相关,HMGB1与其受体RAGE的结合可能参与了食管鳞癌的侵袭和转移,HMGB1可作为预测食管鳞癌预后的重要指标。     

损伤相关分子模式HMGB1在前列腺炎症中的作用

高迁移率族蛋白1(High mobility group protein, HMGB1)作为炎症反应的关键调节分子,能够通过其下游受体晚期糖基化终末产物受体(RAGE)、Toll样受体(TLR)等来发挥促炎等作用。大量研究表明前列腺炎症为前列腺早期疾病发展提供了免疫微环境,促进前列腺上皮细胞增生,作用于前列腺间质内的免疫细胞,促进免疫细胞分泌促炎因子白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)等。本文全面综述了高迁移率族蛋白1及其下游受体在前列腺相关疾病中的作用关系,为前列腺炎和前列腺癌相关免疫疾病的转化治疗提供一种参考。     

HMGB1, TLR and RAGE: a functional tripod that leads to diabetic inflammation

Introduction: Despite advances in treatment of diabetes mellitus, its prevalence continues to rise globally. Medications available are unable to control the vascular complications. Proposals for new therapeutic targets must take into account the hyperglycemia-induced signaling pathways that give rise to the inflammatory profile of the disease.

Areas covered: How high-mobility-group box-1 (HMGB1) protein, acting as an activator of Toll-like receptors (TLR) and receptors for advanced glycation end products (RAGE), creates a functional tripod that contributes to increased production of pro-inflammatory mediators, and sustains the chronic inflammatory state associated with diabetes. The interaction of TLR2 and TRL4 with host-derived ligands, which links diabetic complications with the innate immune response, and the activation of RAGE, which induces a cascade of metabolic responses, leading to the production and secretion of pro-inflammatory cytokines.

Expert opinion: Considering the involvement of the innate immune system, in association with the role of HMGB1 as an activator of TLR and RAGE, diabetes should be considered and treated as a metabolic and immunological disease, triggered by hyperglycemia. HMGB1 plays a central role in mediating injury and inflammation, and interactions involving HMGB1–TLR–RAGE constitute a tripod that trigger NF-κB activation. Blockade or downregulation of HMGB1, and/or control of the inflammatory tripod, represent a promising therapeutic approach for the treatment of diabetes.     

乌司他丁降低HMGB1表达并减轻失血性休克后大鼠肺损伤的影响

目的 探讨蛋白酶抑制剂乌司他丁对失血性休克后急性肺损伤及HMGB1水平的影响.方法 将54只SD雄性大鼠随即分为三组：正常对照组、生理盐水＋休克组、乌司他丁＋休克组.大鼠提前5分钟经股静脉注射给药后放血休克90分钟,分别在造模完成后3小时、6小时、12小时处死测量其动脉血PaCO2、PaO2、血乳酸、干湿重比法测量肺组织含水率、western blot法检测肺组织HMGB1表达,HE染色观察病理变化.结果 休克后动脉血PCO2、血乳酸、肺组织含水率及HMGB1表达均明显增高,PaO2明显降低,肺组织间质水肿、炎性细胞浸润明显,提示急性肺损伤的发生,而乌司他丁＋休克组的动脉血PaCO2、PaO2、血乳酸、干湿重比法测量肺组织含水率及HMGB1较生理盐水＋休克组明显改善.结论 乌司他丁减轻肺部炎症反应抑制失血性休克所致的急性肺损伤从而改善肺功能,其机制可能与降低肺组织HMGB1表达有关.     

马来酸二乙酯对半乳糖胺/脂多糖致小鼠急性肝损伤发生中核转录因子表达的影响

目的　耗竭肝脏还原型谷胱甘肽 (GSH)导致氧化还原失平衡后 ,是否可通过改变库普弗细胞核转录因子表达而影响肝损伤发生。方法　给小鼠注射马来酸二乙酯 (DEM) ,耗竭 GSH。结果　马来酸二乙酯在一定程度上 ,抑制了半乳糖胺 /脂多糖 (Galn/ L PS)诱导胞质 IκBα的降解和核 NF- κBp6 5的表达。结论　 DEM可能是通过抑制 IκBα降解 ,影响 NF-κBp6 5易位入核 ,从而抑制肿瘤坏死因子 (TNF) -α释放 ,减轻肝损伤     

HMGB1 increases RAGE expression in vascular smooth muscle cells via ERK and p-38 MAPK-dependent pathways

The increased expression of receptors for advanced glycation end-product (RAGE) is known as a key player in the progression of vascular remodeling. However, the precise signal pathways regulating RAGE expression in vascular smooth muscle cells (VSMCs) in the injured vasculatures are unclear. Given the importance of mitogen-activated protein kinase (MAPK) signaling in cell proliferation, we investigated the importance of MAPK signaling in high-mobility group box 1 (HMGB1)-induced RAGE expression in VSMCs. In HMGB1 (100 ng/ml)-stimulated human VSMCs, the expression of RAGE mRNA and protein was increased in association with an increase in AGE-induced VSMC proliferation. The HMGB1-induced RAGE expression was attenuated in cells pretreated with inhibitors for ERK (PD98059, 10 μM) and p38 MAPK (SB203580, 10 μM) as well as in cells deficient in ERK and p38 MAPK using siRNAs, but not in cells deficient of JNK signaling. In cells stimulated with HMGB1, the phosphorylation of ERK, JNK, and p38 MAPK was increased. This increase in ERK and p38 MAPK phosphorylation was inhibited by p38 MAPK and ERK inhibitors, respectively, but not by JNK inhibitor. Moreover, AGE-induced VSMC proliferation in HMGB1-stimulated cells was attenuated in cells treated with ERK and p38 MAPK inhibitors. Taken together, our results indicate that ERK and p38 MAPK signaling are involved in RAGE expression in HMGB1-stimulated VSMCs. Thus, the ERK/p38 MAPK-RAGE signaling axis in VSMCs was suggested as a potential therapeutic target for vascular remodeling in the injured vasculatures.     

大面积脑梗死并急性肾功能衰竭对预后的影响

目的：探讨大面积脑梗死高死亡率原因及防治对策。方法：对７２例大面积脑梗死临床资料进行分析。结果：梗死灶越大病死率越高，急性肾功能衰竭（ＡＲＦ）发生率也越高；有并发症者病死率显著高于无并发症者（Ｐ〈０．０１）。ＡＲＦ居并发症首位，有４４．４％患者并发ＡＲＦ，死亡病例中有６０．５％并发ＡＲＦ；并发ＡＲＦ者病死率（７５％）明显高于无ＡＲＦ者（３５％）（Ｐ〈０．０１）。结论：大面积脑梗死死亡原因主要为脑疝     

Anti-inflammatory activities of oleanolic acid on HMGB1 activated HUVECs

As a late mediator of inflammation, high mobility group box 1 (HMGB1) protein up-regulates pro-inflammatory cytokines in several inflammatory diseases. Further, high plasma levels of HMGB1 correlate with poor prognosis and increased mortality in patients with severe inflammation. Oleanolic acid (OA), a triterpenoid known for its anti-inflammatory and anti-cancer properties, is commonly present in several medicinal plants but the effects of OA on HMGB1-mediated pro-inflammatory responses of human endothelial cells is not well-studied. In this study, we investigated this question by monitoring the effect of OA on lipopolysaccharide (LPS)-mediated release of HMGB1 and the HMGB1-mediated modulation of inflammatory responses in human umbilical vein endothelial cells (HUVECs). OA potently inhibited the release of HMGB1 by HUVECs as well as down-regulated HMGB1-dependent adhesion and migration of the monocytic cell line THP-1 to activated HUVECs. OA also down-regulated the cell surface expression of the receptor of HMGB1, thereby inhibiting HMGB1-dependent pro-inflammatory responses by inhibiting activation of nuclear factor-κB (NF-κB) and production of tumor necrosis factor-α (TNF-α) by HMGB1. Given these results, OA showed anti-inflammatory activities and could be a candidate as a therapeutic agent for various inflammatory diseases through the inhibition of the HMGB1 signaling pathway.