赛沃替尼治疗MET基因突变非小细胞肺癌的药物浓度与疗效和不良反应的关系

目的:探讨药物浓度与疗效和不良反应之间的关系,了解赛沃替尼治疗MET14外显子跳跃突变晚期非小细胞肺癌患者的疗效和安全性。方法:回顾性分析2018年4月至2019年9月北京大学肿瘤医院收治的携带MET14外显子跳跃突变,并且接受赛沃替尼治疗的16例局部晚期或转移性非小细胞肺癌患者的临床资料及其血浆药物浓度,评估赛沃替尼治疗的疗效和安全性,分析药物浓度与疗效及不良反应的相关性。随访患者的无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS),采用Kaplan-Meier法计算中位PFS和OS。结果:16例患者中男性9例(56.3%),年龄范围51~84岁。肺癌病理类型包括:腺癌11例,肉瘤样癌5例,鳞癌1例。赛沃替尼的客观缓解率为50.0%(8/16),疾病控制率达到87.5%(14/16)。评效达到部分缓解患者和未达到者相比,赛沃替尼的药物谷浓度分别为77.2 ng/mL和146.7 ng/mL(P=0.06)。治疗中出现过2级以上不良反应的患者和仅出现过1级不良反应者,其药物谷浓度分别为116.5 ng/mL和93.2 ng/mL(P=0.59)。所有患者的中位PFS为8.5个月,中位OS为14.1个月。结论:赛沃替尼治疗MET基因突变非小细胞肺癌的效果较好,不良反应可耐受。常规用药剂量下,赛沃替尼的血浆药物谷浓度与疗效可能存在一定负相关,但药物浓度与不良反应的程度无明显相关性。

新型4-苯氧基吡啶类c-Met激酶抑制剂的合成和抗肿瘤活性研究

为了发现新型高活性c-Met激酶抑制剂,以2-氨基-4-氯吡啶为原料,经醚化、酰化、烷基化、还原和酰化等多步反应,制备了6种未见文献报道的4-苯氧基吡啶类化合物,化合物结构经红外光谱、核磁共振氢谱和质谱确证.生物活性测试结果显示,6种化合物对MKN-45、A549、H460和HT-294种肿瘤细胞株具有很好的抗增殖活性,两种化合物对c-Met激酶具有很好的抑制活性.其中化合物7b抑制MKN-45、A549、H460和HT-29细胞株的IC 50值分别为1.89、5.14、0.74、0.60μmol/L.该化合物在1000 nmol/L和200 nmol/L的浓度下对c-Met激酶的抑制率分别为96.2%和82.8%,显示出了优异的抗肿瘤活性.

GNSS/MET观测的台风“烟花”对上海地区PWV的影响

利用上海5个GNSS/MET站2021-07-21~08-08的观测数据,使用GAMIT软件反演大气可降水量(PWV),研究台风“烟花”期间上海地区PWV与降雨量之间的关系及PWV的空间分布特征。结果表明,GNSS PWV与探空PWV之间相关系数大于0.9。降水生成前,PWV经历了3次波动性上升过程,降水生成时间比台风登陆时间早约60 h;降水持续期间,PWV剧烈变化时会造成降水量急升或急降;降水结束后,PWV逐渐下降至40 mm以下。台风登陆前,PWV基本在75 mm以上,PWV大于80 mm的区域主要分布于上海南部和中部;台风登陆后,PWV在80 mm以上,高值区可达90 mm;台风远离后,PWV下降至85 mm以下。PWV高值区向西北方向的扩大、推移与台风路径基本吻合。

Movement and Degradation of Metolachlor and Metribuzin in North Central Sand Region of Minnesota Under Irrigated Potato Production

Field studies were conducted to determine the dissipation and movement of metribuzin and metolachlor applied at conventional rates to a Verndale sandy loam (Udic Argiboroll) in north-central Minnesota under irrigated potato production in two years. The rapid dissipation of both metribuzin and metolachlor was found during the initial 10 to 15 days in both years) and more than 70% of the applied herbicide dissipated during this period. From 10 to 15 days after application up to the end of growing season in both years, the levels of both herbicides decreased slowly with time. Metolachlor dissipated at a slower rate than metribuzin in surface soil and could carry over to the next cropping season. Metribuzin and metolachlor were detected in only 6 and 1 of 154 soil samples in the first year and in 3 and 4 of 225 soil samples in the second year, taken from 15 to 75cm, respectively. Fifty to 67% of water samples from suction samplers at 135-cm depth contained detectable levels (>0.4μg L-1 ) of herbicides in both years. Under laboratory conditions degradation of both herbicides was much slower than their dissipation in field. Therefore, it appeared that leaching might be an important dissipation pathway for metribuzin and metolachlor under irrigated potato production.

c-MET在非小细胞肺癌中的研究现状

非小细胞肺癌(NSCLC)是一种异质性疾病,可由许多基因突变驱动发生。间质–上皮细胞转化因子(MET)是继表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)等之后的又一热门研究靶点。MET异常已被证实在多种致癌中,促进肿瘤侵袭、血管生成和转移。c-MET不仅是独立的肺癌驱动因子,也是介导其他驱动基因靶向治疗耐药的副驱动因子。目前,针对c-Met通路的治疗策略主要包括单克隆抗体和靶向MET基因的小分子TKIs。作者对MET改变的NSCLC的研究现状及治疗进展进行综述。

免疫联合化疗逆转MET D1228E合并EGFR L858R介导的MET 14外显子跳跃突变肺腺癌耐药

1例间质-上皮细胞转化因子(MET)14外显子跳跃突变的Ⅳ期肺腺癌患者服用MET酪氨酸激酶抑制剂(TKI)赛沃替尼8.5个月后疾病进展(PD),耐药基因检测提示出现新的MET 19外显子D1228E及表皮生长因子受体(EGFR)21外显子L858R错义突变。遂将治疗方案改为EGFR-TKI奥希替尼联合克唑替尼治疗,23天后临床症状加重,复查CT提示PD。经多学科诊疗(MDT)讨论,将三线治疗方案改为以铂类为基础的化疗联合免疫治疗,期间最佳疗效评价为部分缓解(PR),无进展生存期为6.4个月。目前,对于MET-TKIs耐药后新发二次突变合并EGFR突变的患者尚无标准治疗方案,本案例为此类患者提供了一种可供参考的后续治疗方案。

幽门螺杆菌对肝癌HepG2细胞C‐Met基因表达的影响

目的研究幽门螺杆菌(Hp)对肝癌HepG2细胞原癌基因C-Met表达的影响。方法将Hp与HepG2细胞共同培养,设置空白对照组、Hp组、C-Met抑制剂空白组和C-Met抑制剂Hp组,每组设副孔5个,采用CCK8试剂盒检测HepG2细胞增殖活性,采用Western blot和qPCR方法检测C-Met原癌基因蛋白和mRNA表达水平。结果相较于空白对照组,Hp处理组HepG2细胞增殖活性升高且与时间呈正相关,而C-Met抑制剂可以抑制HepG2细胞的增殖活性。同时,Hp组HepG2细胞C-Met基因蛋白和mRNA表达水平均上调,C-Met抑制剂组则显著下调。相较于Hp共培养12 h,共培养24 h C-Met蛋白和mRNA表达水平均上调。结论Hp促进HepG2细胞的增殖可能与其提高原癌基因C-Met的蛋白及其mRNA表达水平有关,为后续更深入研究肝癌发生发展的复杂机制提供了理论依据。

黄芪建中汤对脾胃虚寒证胃溃疡大鼠炎症因子及HGF/c-Met信号通路的影响

目的观察黄芪建中汤对脾胃虚寒证胃溃疡大鼠炎症因子及HGF/c-Met信号通路的影响。方法将60只大鼠随机分为4组,即正常组、模型组、黄芪建中汤组[黄芪建中汤6.8 g/(kg·d)]、奥美拉唑组[奥美拉唑肠溶胶囊4.2 mg/(kg·d)],每组15只大鼠。正常组除外,其他组采用耗气破气法结合饥饱失常法进行大鼠脾胃虚寒证模型造模,再采用冰醋酸法建立大鼠胃溃疡模型。比较各组大鼠体质量、溃疡指数;HE染色观察大鼠胃组织病理学变化;采用酶联免疫吸附法检测血清中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)含量;免疫组化法检测胃组织中肝细胞生长因子(HGF)、肝细胞生长因子受体(c-Met)表达;荧光定量PCR检测胃组织HGF、c-Met m RNA水平。结果与正常组相比,模型组大鼠体质量降低,溃疡指数升高,IL-6、IL-1β、TNF-α含量升高,HGF升高,HGF、c-Met m RNA升高(P<0.05);与模型组相比,黄芪建中汤组和奥美拉唑组大鼠体质量升高,溃疡指数降低,IL-6、IL-1β、TNF-α降低,HGF升高,HGF、c-Met mRNA升高(P<0.05)。结论黄芪建中汤可以通过抑制炎症因子、调节HGF/c-Met通路的表达促进胃黏膜修复。

基于转录组测序探究C-MET表达在非小细胞肺癌中的免疫调控机制

目的通过转录组测序技术分析C-MET表达在非小细胞肺癌中的免疫调控机制。方法使用siRNA分子干扰技术将C-MET高表达肺腺癌细胞株(H1993)、肺鳞癌细胞株(EBC-1)的C-MET表达沉默,利用转录组测序技术检测C-MET沉默前后细胞差异表达的基因(DEGs),通过生物信息学分析挖掘出C-MET可能参与调控的免疫微环境信号通路及相关基因。最后使用人免疫细胞与H1993、EBC-1共培养技术验证C-MET对免疫因子(INF-γ、INF-β、CXCL-10)的影响。结果通过转录组测序技术共检测到505个DEGs,其中H1993的C-MET调控前后表达差异组的表达差异基因共有38个,上调的差异表达基因有24个,下调的差异表达基因有14个。EBC-1的C-MET调控前后表达差异组的表达差异基因共有467个,上调的差异表达基因有347个,下调的差异表达基因121个。差异基因的KEGG分析表明,C-MET表达可能通过白细胞介素(IL-17)信号通路、白细胞分化、细胞因子受体活性、细胞周期、细胞因子-细胞因子受体相互作用参与免疫细胞调节因子的调控。使用肺癌细胞与人免疫细胞共同培养技术验证C-MET对免疫因子分泌的影响,Rt-qPCR检测结果提示:与C-MET高表达组共培养的PBMC中干扰素(INF-γ)的m RNA转录水平是低表达组的77倍、CXCL-10的mRNA转录水平是低表达组的1.6倍,INF-β的mRNA转录水平是低表达组的2倍。结论C-MET表达可能通过IL-17信号通路、白细胞分化、细胞因子受体活性通路参与肿瘤周围免疫微环境调控。

Reduced Rates of Metribuzin and Time of Hilling Controlled Weeds in Potato

The current emphasis on reducing herbicide applications has led to an increase in alternative weed control measures. Field experiment was conducted in the spring of 2014 to examine the effect of hilling-time and reduced-rates of metribuzin and their combinations on weed infestation in potato, and to determine their impact on potato yield. Metribuzin at 0.35, 0.56, or 0.75 kg ai/ha with or without hilling 6, 7, and 8 weeks after planting (WAP) were used. Weed count, weed control visual rating, weed dry weight, potato plant height, number of shoots and leaves, root dry weight, and potato yield were collected. Results showed that metribuzin, at all tested rates, with or without hilling significantly reduced weed infestation after 50, 70, and 110 days after planting (DAP) compared to the check. Best results were obtained by a combination of metribuzin at all tested rates with hilling 6, 7, and 8 WAP. The results suggest that long season weed control and high marketable yield could be achieved by metribuzin at 0.35 kg ai/ha (53% reduction in metribuzin) supplemented with hilling (6 WAP). None of the treatments was toxic to potato plants compared to the hand-weeded plots.

Triazinone herbicide metribuzin induced acute liver injury: A study of animal model

Objective: To evaluate the acute toxicity effect of metribuzin at low dose on liver of mother rabbits and its fetus.Methods: Pregnant female rabbitsOryctolagus cuniculus were divided into three groups (n=5). The first group of non-treated pregnancy rabbits served as control;the second group of pregnancy rabbits were treated with 1/100 LD50 of metribuzin and the third group of pregnancy rabbits were treated with 1/50 LD50 of metribuzin. Metribuzin was added in their drinking water for 60 d before and during pregnancy. Levels of liver malondialdehyde, liver glutathione S transferase, serum glutamic oxaloacetic transaminase and serum glutamic-pyruvic transaminase were determined. Liver reduced glutathione level was also determined by a colorimetric method. And hepatic homogenate was analyzed by HPLC analysis to determine the existence of traces of metribuzin.Results: Results revealed a significant increase in level of liver malondialdehyde, glutathione S transferase, serum glutamic oxalacetic transaminase and serum glutamic-pyruvic transaminase activities in mother and fetuses rabbits of both metribuzin treatment groups as compared to the control group. However the level of reduced glutathione was decreased in mother and fetuses rabbits of both groups treated with metribuzin compared to control group. Also, the results obtained by HPLC technique showed the presence of trace metribuzin in liver cells of mothers and fetuses rabbits of the both metribuzin treated groups.Conclusions: In conclusion, this study shows that exposure to metribuzin at low concentrations causes a acute toxicity in liver of mother rabbits and its fetus, also the trace of the metribuzin detected in the liver is the origin of possible malformation of the fetuses or abortion of the rabbits.

Herbicidal Activity of Chlorimuron-ethyl （107 g/kg） Associated with Metribuzin （643 g/kg） on Sugar Cane Weeds and Its Effects on Soil Agrochemical Properties, in Burkina Faso

The efficiency and selectivity of chlorimuron-ethyl （107 g/kg） associated with metribuzin （643 g/kg）, against weeds which causes big damages to sugar cane, have been studied on the sugar cane field of Beregadougou. The experimental design was a Latin rectangle with eight treatments in four replications including an untreated control, manual weeding, a control product （Trifloxysulfuron-sdium 1.85% ＋ Ametryn 73.15%） and five rates of chlorimuron-ethyl associated with metribuzin. Weeds counting and weighing their dry biomass have been done using 0.25 m2 quadrants to determine their biological efficiencies. The soil nitrogen nitrate and assimilable phosphorus contents were evaluated on a spectrophotometer, those of available potassium on a flame photometer. The biological efficiency coefficients of this herbicide, varied from 12.41% to 100%, according to their dry biomass. High rates, phytotoxics, showed the best coefficients. At the sugar cane complete maturation, the higher rates of imposter led to an accumulation of nitrogen nitrate content and lower available phosphorus and potassium contents, compared to the untreated control. The rate of 1.20 kg/ha became the dose to apply against weeds and less toxic to the soil.

斜刺动痛穴结合MET运动针法治疗Ⅰ~Ⅲ级膝骨关节炎的临床研究

目的 针对Ⅰ~Ⅲ级膝骨关节炎患者接受斜刺动痛穴结合MET运动针法治疗的临床效果展开分析与探讨。方法 选择2021年1月—2023年3月本院收治的60例膝骨关节炎患者为研究对象,按就诊顺序编号,并通过随机数字表法划分为治疗组(30例)、对照组(30例)。两组基础治疗方案相同,治疗组配合斜刺动痛穴结合MET运动针法治疗,对照组配合电针疗法治疗,针对两组治疗效果展开对照分析。结果 治疗前,两组骨关节指数对比差异无统计学意义(P>0.05);治疗后,治疗组各骨关节指数均低于对照组(P<0.05)。治疗组临床总疗效、关节积液总疗效、滑膜厚度总疗效、生活质量评分均高于对照组(P<0.05)。结论 使用斜刺动痛穴结合MET运动针法的治疗方案,有助于将Ⅰ~Ⅲ级膝骨关节炎患者临床疗效显著提升,并改善其生活质量,患者各项临床指标优化效果良好,值得普及。

Effects of Vitamin C and NADH on in Vitro Proliferative Function of Human Lymphocytes Exposed to Pesticides （Mancozeb and Metribuzin）

Antioxidants such as vitamin C and NADH can protect against pesticide adverse effects on immune function. The aim of this work was to study the in vitro effects of vitamin C and NADH on the proliferative responses of human lymphocytes exposed to pesticides （Mancozeb fungicide and Metribuzin herbicide） and on Thl and Th2 cytokine secretion. Their possible protective role on intracellular stress oxidative induced by pesticides was also investigated. Peripheral blood lymphocytes were isolated using differential centrifugation on a density gradient of Histopaque. They were cultured with mitogen concanavalin A （Con A）, Mancozeb and Metribuzin （50 μM） in the presence or the absence of vitamin C （50 μM） or NADH （50 μM）. Proliferation （MTT assay）, IL-2, INFγ and IL-4 （Elisa kits）, oxidative markers （intracellular superoxide anion, hydroperoxides, carbonyl proteins, GSH, catalase and SOD） were determined, The results showed that pesticides were immunosuppressive and decreased cytokine secretion with a shift away from to Thl phenotype. These immunomodulatory properties were accompanied by an increase in lymphocyte intracellular oxidative stress. The presence of vitamin C or NADH, in the medium, exhibited protective effects in human lymphocytes by inhibiting pesticide---induced lymphocyte proliferation suppression, inflammatory status and oxidative stress generation. In conclusion, vitamin C and NADH can result in a safe and effective method to reduce pesticide adverse effects and help to restore immune function.

METS-IR与心血管疾病研究进展

随着生活水平提高,心血管疾病发病率及病死率逐年上升,已成为重要的公共卫生问题。胰岛素抵抗状态与心血管疾病发生及发展中的病理生理过程密切相关。深入研究二者之间的内在联系对于心血管疾病的早期预防、治疗和随访至关重要。传统的胰岛素抵抗检测方法操作繁琐、耗时,价格昂贵,不适合在医院开展,更无法在大规模人群中推广。胰岛素抵抗代谢评分(METS-IR)是一个新型的胰岛素抵抗预测指标,其反映胰岛素抵抗具有高效及简便的特点,并且METS-IR升高与心血管疾病发生及不良心血管预后具有正相关性。基于此,本文就METS-IR对常见心血管疾病的诊断及临床应用价值进行综述。

CTC、RON及c-Met在早期三阴性乳腺癌预后预测中的作用

目的 分析循环肿瘤细胞(CTC)、受体酪氨酸激酶(RON)及间质表皮转化因子(c-Met在早期三阴性乳腺癌(TNBC)预后预测中的作用。方法 分析2018年1月至2021年1月于郑州大学第一附属医院进行诊治的1 225例乳腺癌患者资料,根据纳入标准最终选取168例TNBC患者设为研究组,选取患者癌旁3 cm的组织为对照组,另选取同时期在本院进行健康体检者168名为健康组。根据患者治疗后的预后情况将研究组分为预后良好组(n=142)以及预后不良组(n=26)。比较研究组与健康组CTC的表达情况,比较研究组与对照组c-Met与RON的表达情况,采用多元Logistic回归分析影响TNBC预后的独立危险因素;并通过受试者工作特征曲线(ROC)分析c-Met、RON、CTC对TNBC患者预后的预测价值。结果 研究组CTC水平高于健康组,差异有统计学意义(P<0.05);研究组c-Met与RON阳性表达高于对照组,差异有统计学意义(P<0.05);预后良好组、预后不良组年龄、肿瘤直径比较差异无统计学意义(P>0.05),预后良好组、预后不良组腋窝淋巴结、体重指数、糖尿病、RON、c-Met、CTC比较,差异有统计学意义(P<0.05),经非条件多因素logistic回归模型分析显示,腋窝淋巴结转移、CTC阳性、RON阳性、c-Met阳性为TNBC患者预后的危险因素(P<0.05)。CTC、RON及c-Met单独检测以及三者联合检测AUC分别为0.764、0.778、0.776、0.857,其中三者联合检测AUC值最大。结论 联合检测RON、c-MET、CTC水平对TNBC患者预后具有一定的预测价值。

宫颈癌患者癌组织c-Met mRNA与NF-κB mRNA表达的关系及其对预后的影响

目的分析肝细胞生长因子受体原癌基因c-Met mRNA与核因子-κB(NF-κB)mRNA在宫颈癌发病中的关系及对宫颈癌患者预后的影响。方法选取本院宫颈癌患者89例作为癌变组,宫颈癌前病变患者89例作为癌前病变组,因子宫肌瘤行全子宫切除患者89例作为正常宫颈组。采用RT-PCR检测3组宫颈组织中c-Met、NF-κB mRNA相对表达量。采用Spearman/Pearson分析c-Met mRNA与NF-κB mRNA在宫颈癌发病中的关系。采用Kaplan-Meier曲线分析不同c-Met mRNA、NF-κB mRNA表达水平患者的3年生存率。结果宫颈组织中c-Met、NF-κB mRNA相对表达量,癌变组>癌前病变组>正常宫颈组(P<0.05)。癌前病变组、癌变组c-Met mRNA与NF-κB mRNA呈正相关(P<0.001)。c-Met高表达与NF-κB mRNA高表达在宫颈癌发病中呈正向交互作用(P<0.05)。c-Met、NF-κB mRNA与宫颈癌临床分期、淋巴结转移、脉管浸润呈正相关,与分化程度呈负相关(P<0.05)。癌变组c-Met、NF-κB mRNA高表达患者3年生存率低于低表达患者(P<0.05)。结论c-Met mRNA与NF-κB mRNA高表达在宫颈癌发病中呈正向交互作用,与临床分期、淋巴结转移、脉管浸润呈正相关,且宫颈癌患者3年生存率显著降低。

M2型巨噬细胞来源外泌体调控HGF/c-Met通路参与多发性骨髓瘤细胞转移的作用研究

目的探究M2型巨噬细胞来源的外泌体对人多发性骨髓瘤细胞转移的影响及机制。方法在体外将THP-1细胞诱导分化成M0型和M2型巨噬细胞,实时荧光定量聚合酶反应(RT-qPCR)检测诱导后M2型巨噬细胞标志物血红蛋白清道夫受体(CD163)、白细胞介素-10(IL-10)、精氨酸酶-1(Arg-1)、转化生长因子-β1(TGF-β1)的表达水平,分离M2型巨噬细胞来源的外泌体;将RPMI-8226细胞分为对照组、M0-Exos组、M2-Exos组,Transwell小室法检测细胞迁移数目与侵袭数目,蛋白质印迹检测细胞中N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)、E-钙黏附蛋白(E-cadherin)及转录因子Snail的表达水平,并检测肝细胞生长因子(HGF)/c-Met相关蛋白的表达水平;接着将RPMI-8226细胞分为对照组、M2-Exos组、SU11274组、SU11274+M2-Exos组,Transwell小室法检测细胞迁移数目与侵袭数目,蛋白质印迹检测细胞中N-cadherin、Vimentin、E-cadherin及Snail表达水平。结果与M0型巨噬细胞比较,M2型巨噬细胞中CD163、IL-10、Arg-1、TGF-β1的mRNA表达水平均显著上调(P<0.05);从M2型巨噬细胞中分离的颗粒物中有CD9、CD63、TSG101、ALIX蛋白表达,由此判定该颗粒物为外泌体。与对照组比较,M2-Exos组细胞迁移与侵袭数目均显著增加(P<0.05),N-cadherin、Vimentin、Snail蛋白表达显著增加(P<0.05),E-cadherin蛋白表达显著减少(P<0.05),HGF蛋白表达及p-c-Met/c-Met比值也显著增加(P<0.05)。与M2-Exos组比较,SU11274+M2-Exos组细胞迁移与侵袭数目显著减少(P<0.05),N-cadherin、Vimentin、Snail蛋白表达显著减少(P<0.05),且E-cadherin蛋白表达显著增加(P<0.05)。结论M2型巨噬细胞来源的外泌体能够促进人多发性骨髓瘤细胞迁移、侵袭及EMT,加剧肿瘤细胞转移,该作用与调控HGF/c-Met通路有关。

Advances in MET tyrosine kinase inhibitors in gastric cancer

Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths globally.Because gastric cancer is highly heterogenous and comprised of different subtypes with distinct molecular and clinical characteristics,the management of gastric cancer calls for better-defined,biomarker-guided,molecular-based treatment strategies.MET is a receptor tyrosine kinase mediating important physiologic processes,such as embryogenesis,tissue regeneration,and wound healing.However,mounting evidence suggests that aberrant MET pathway activation contributes to tumour proliferation and metastasis in multiple cancer types,including gastric cancer,and is associated with poor patient outcomes.As such,MET-targeting therapies are being actively developed and promising progress has been demonstrated,especially with MET tyrosine kinase inhibitors.This review aims to briefly introduce the role of MET alterations in gastric cancer and summarize in detail the current progress of MET tyrosine kinase inhibitors in this disease area with a focus on savolitinib,tepotinib,capmatinib,and crizotinib.Building on current knowledge,this review further discusses existing challenges in MET alterations testing,possible resistance mechanisms to MET inhibitors,and future directions of MET-targeting therapies.

METS-IR与代谢性疾病的研究进展

代谢性疾病主要包括心血管疾病、糖尿病和非酒精性脂肪性肝病等,近年来已成为重要的公共卫生问题。相关研究证明,胰岛素抵抗(IR)在代谢性疾病发生和发展中有重要作用。胰岛素抵抗代谢评分(METS-IR)是评估IR的简易指标,同时其是常规检测易得到的无创数据。近年来,相关研究表明,METS-IR对冠心病、高血压、冠状动脉钙化、糖尿病、非酒精性脂肪性肝病等有重要预测价值。基于此,本文就METS-IR对代谢性疾病的诊断及临床应用价值进行综述。