Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

2型糖尿病视网膜病变患者中医证型分布及其与血清炎症因子及脂联素水平的相关性研究

【目的】探讨2型糖尿病视网膜病变(type 2 diabetic retinopathy,T2DR)的中医证型分布及其与血清炎症因子、脂联素(APN)水平的相关性,为T2DR的中医辨证分型提供客观依据。【方法】采用横断面病例对照研究方法,选择2022年9月至2023年3月在江西省赣州市人民医院眼科诊断为T2DR的患者共42例84眼,观察T2DR患者眼底荧光血管造影(FFA)分期与中医辨证分型的关系,分析不同中医证型与血清炎症因子及APN水平的关系以及不同FFA分期的血清炎症因子及APN水平差异,探讨T2DR患者各变量与不同中医证型之间的相关性。【结果】(1)42例T2DR患者中,男性27例,女性15例,平均年龄为(54.0±12.0)岁;其中,肝肾亏虚、目络失养证14例(33.3%),阴精不足、燥热内生证15例(35.7%),气阴两虚、络脉瘀阻证9例(21.4%),阴阳两虚、血瘀痰凝证4例(9.5%),脾失健运、水湿阻滞证0例(0.0%)。(2)肝肾亏虚、目络失养证患者中双眼眼底FFA分期≥4期[增殖期糖尿病视网膜病变(PDR)]者占78.6%(11/14),阴精不足、燥热内生证患者占73.3%(11/15),气阴两虚、络脉瘀阻证患者和阴阳两虚、血瘀痰凝证患者均占100%(9/9;4/4),但组间比较,差异无统计学意义(P=0.272)。(3)42例T2DR患者中,有35例(83.3%)患者的肿瘤坏死因子α(TNF-α)、28例(68.3%)患者的C反应蛋白(CRP)、38例(90.5%)患者的糖化血红蛋白(HbA1c)水平均高于正常值;但不同FFA分期患者的血清炎症因子TNF-α、CRP、白细胞介素6(IL-6)、血管内皮生长因子(VEGF)及APN、HbA1c水平比较,差异均无统计学意义(P>0.05);同时,不同中医证型的血清APN、TNF-α、CRP、IL-6、VEGF水平比较,差异也均无统计学意义(P>0.05)。(4)相比肝肾亏虚、目络失养证患者,阴阳两虚、血瘀痰凝证患者的眼部病程较短,两者的相关性接近差异有统计学意义(r=-0.467,P=0.051);相比阴精不足、燥热内生证患者,阴阳两虚、血瘀痰凝证患者的CRP水平较高(r=0.592,P=0.010);相比气阴两虚、络脉瘀阻证患者,阴阳两虚、血瘀痰凝证患者的CRP水平较高(r=0.668,P=0.013)和糖尿病病程更长(r=0.629,P=0.021)。【结论】血清TNF-α及CRP在T2DR中有更高的表达;肝肾亏虚、目络失养证和阴精不足、燥热内生证为T2DR的常见证型;阴阳两虚、血瘀痰凝证与CRP密切相关,同时阴阳两虚、血瘀痰凝证型患者有更长的糖尿病病程。

血清L/A、NRG-1、Tie-2水平与首发精神分裂症患者临床症状严重程度的相关性

目的探讨血清瘦素与脂联素比值(L/A)、神经调节蛋白-1(NRG-1)、血管生成素受体酪氨酸激酶-2(Tie-2)水平与首发精神分裂症患者临床症状严重程度的相关性及对认知障碍的评估价值。方法选择2021年5月—2023年5月收治的首发精神分裂症103例为研究组,另选取同期正常健康体检志愿者103例为对照组。比较2组血清L/A、NRG-1、Tie-2水平,对比研究组认知障碍与认知正常患者临床症状[阳性和阴性症状量表(PANSS)、简明精神病评定量表(BPRS)评分]、血清L/A、NRG-1、Tie-2水平。分析血清L/A、NRG-1、Tie-2水平与临床症状严重程度的相关性及其联合检测对认知障碍的评估价值。结果研究组血清瘦素、L/A水平高于对照组,脂联素、NRG-1、Tie-2水平低于对照组(P<0.01)。研究组认知障碍患者PANSS各分量表评分及总分、BPRS量表各维度评分及总分、血清瘦素、L/A水平高于认知正常患者,脂联素、NRG-1、Tie-2水平低于认知正常患者(P<0.01)。血清L/A水平与PANSS各分量表评分及总分、BPRS量表各维度评分及总分呈正相关,NRG-1、Tie-2水平与PANSS各分量表评分及总分、BPRS量表各维度评分及总分呈负相关(P<0.01)。血清L/A、NRG-1、Tie-2评估认知障碍的曲线下面积(AUC)分别为0.764、0.708、0.755,最佳截断值分别为6.81、8.52 pg/mL、1962.62 pg/mL;血清L/A高表达、NRG-1、Tie-2低表达分别提示认知障碍发生风险增加5.237、6.172、4.538倍;L/A、NRG-1、Tie-2两两联合及三者联合评估认知障碍的AUC分别为0.882、0.868、0.876、0.932。结论血清L/A、NRG-1、Tie-2与首发精神分裂症患者临床症状严重程度显著相关,异常表达增加认知障碍发生风险,联合评估认知障碍的价值更为可靠。

Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer

The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.

补肾健脾方治疗2型糖尿病合并血脂异常患者的疗效及对脂联素的影响研究

【目的】探讨补肾健脾方(主要由黄芪、淫羊藿、山药、丹参、鹿角胶、沙苑子、制何首乌、黄精、葛根、大黄等中药组成)对脾肾两虚型2型糖尿病(T2DM)合并血脂异常患者临床疗效及脂联素(adiponectin,ADP)的影响。【方法】将90例脾肾两虚型T2DM合并血脂异常患者随机分为西药治疗组(简称西药组)、中药治疗组(简称中药组)、中西医结合治疗组(简称联合组),每组各30例。3组患者均给予常规降糖治疗,在此基础上,西药组给予阿托伐他汀钙片口服治疗,中药组给予补肾健脾方治疗,联合组给予阿托伐他汀钙片联合补肾健脾方治疗,疗程为8周。观察3组患者治疗前后中医证候积分、糖脂代谢指标、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)及血清ADP水平的变化情况,并评价3组患者的中医证候疗效。【结果】(1)疗效方面,治疗8周后,西药组、中药组、联合组患者的总有效率分别为66.67%(20/30)、90.00%(27/30)、93.33%(28/30),组间比较,中药组和联合组的中医证候疗效均明显优于西药组(P<0.05)。(2)中医证候积分方面,治疗后,3组患者的中医证候积分均较治疗前下降(P<0.01),且中药组和联合组对中医证候积分的下降幅度均优于西药组(P<0.05或P<0.01)。(3)脂代谢方面,治疗后,3组患者的总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平均较治疗前有不同程度的改善,其中TC、TG、LDL-C水平均较治疗前显著下降,HDL-C水平均较治疗前显著升高,差异均有统计学意义(P<0.05或P<0.01);组间比较,中药组对TC、LDL-C的下降幅度和对HDL-C的升高幅度均不及西药组和联合组(P<0.05或P<0.01)。(4)糖代谢方面,治疗后,中药组和联合组患者的空腹血糖(FPG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)、FINS、HOMA-IR水平均较治疗前显著下降(P<0.05或P<0.01),西药组患者仅FPG、2hPG、HOMA-IR水平较治疗前下降(P<0.05或P<0.01);组间比较,中药组和联合组患者对FPG、2hPG、HbA1c、FINS、HOMA-IR水平的下降幅度均明显优于西药组(P<0.05或P<0.01)。(5)脂肪激素方面,治疗后,3组患者的血清ADP水平均较治疗前显著升高(P<0.05或P<0.01),且中药组和联合组患者血清ADP水平的升高幅度均显著优于西药组(P<0.05)。【结论】补肾健脾方具有一定的调节脂质代谢作用,在改善脾肾两虚型T2DM合并血脂异常患者的临床症状、胰岛素抵抗,降低血糖,升高ADP水平等方面具有明显优势。

2型糖尿病患者血清C1q肿瘤坏死因子相关蛋白5、脂联素水平与颈动脉粥样硬化关系研究

目的:探讨2型糖尿病(T2DM)患者血清C1q肿瘤坏死因子相关蛋白5(CTRP5)、脂联素(APN)水平与颈动脉粥样硬化(CAS)的关系。方法:选择T2DM患者96例为观察组,选择体检健康者108例为对照组。采用酶联免疫吸附(ELISA)法检测血清CTRP5、APN水平。根据超声检查将T2DM患者分为CAS组和无CAS组,并比较两组一般资料及血清生化指标。分析T2DM患者发生CAS的影响因素,并进行相关性分析。结果:观察组血清CTRP5水平高于对照组,APN水平低于对照组(均P<0.05)。T2DM患者中,40例出现CAS,56例无CAS。CAS组患者年龄、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、CTRP5水平较无CAS组升高,APN水平较无CAS组下降(均P<0.05)。HbA1c、TG、LDL-C、CTRP5为CAS发生的独立危险因素,APN是CAS的独立保护因素(均P<0.05)。血清CTRP5与HbA1c、TG、LDL-C水平呈正相关,血清APN与HbA1c、TG、LDL-C水平呈负相关(均P<0.05)。结论:T2DM患者发生CAS后CTRP5水平升高,APN水平下降,CTRP5为CAS发生的独立危险因素,APN为CAS发生的独立保护因素。

芪地糖肾颗粒对2型糖尿病大鼠胰岛素抵抗、脂代谢及AdipoR1、AMPK蛋白的影响

目的:探究芪地糖肾颗粒对2型糖尿病大鼠胰岛素抵抗、脂代谢以及脂联素受体1(AdipoR1)、腺苷酸激活蛋白激酶(AMPK)蛋白等相关指标的影响。方法:取50只健康大鼠,分为健康组,模型组,低、中、高剂量组,除健康组外均建立糖尿病模型。建模后低、中、高剂量组分别灌胃芪地糖肾颗粒1.31、2.62、5.24 g/kg;健康组、模型组给予等量0.9%氯化钠溶液灌胃,1次/d,均干预30 d。采用ELISA检测血清高密度脂蛋白胆固醇(HDL-C)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG),酶联免疫法测定空腹血糖(FBG),放免法测定空腹胰岛素(FINS),免疫印迹与PCR分别检测脂联素受体1(AdipoR1)、腺苷酸激活蛋白激酶(AMPK)蛋白、肾小管间质p38激活丝裂原活化蛋白激酶(p38MAPK)。结果:与健康组比较,模型组大鼠血清中HDL-C及AdipoR1、AMPK、p38MAPK蛋白/mRNA降低,LDL-C、TC、TG、FBC、FINS均升高(P<0.05);与模型组比较,低剂量组大鼠血清中HDL-C及AdipoR1、AMPK、p38MAPK蛋白/mRNA升高,LDL-C、TC、TG及FBC、FINS均降低(P<0.05);与低剂量组比较,中剂量组大鼠血清中HDL-C及AdipoR1、AMPK、p38MAPK蛋白/mRNA升高,LDL-C、TC、TG及FBC、FINS均降低(P<0.05);与中剂量组比较,高剂量组大鼠血清中HDL-C及AdipoR1、AMPK、p38MAPK蛋白/mRNA升高,LDL-C、TC、TG及FBC、FINS均降低(P<0.05)。结论:芪地糖肾颗粒可改善2型糖尿病的脂质代谢及胰岛素抵抗,可能与提高AdipoR1、AMPK、p38MAPK表达相关。

维格列汀联合二甲双胍治疗肥胖2型糖尿病患者的效果

目的:观察维格列汀联合二甲双胍治疗肥胖2型糖尿病患者的效果。方法:选取2021年1月至2023年1月该院收治的102例肥胖2型糖尿病患者进行前瞻性研究,按随机数字表法将其分为观察组和对照组各51例。对照组采用二甲双胍治疗,观察组在对照组基础上联合维格列汀治疗,比较两组治疗前后糖代谢指标[空腹血糖(FBG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)]水平、脂代谢指标[总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)]水平,脂联素和趋化素水平,临床疗效,以及治疗期间不良反应发生率。结果:治疗后,观察组FBG、2hPG、HbA1c、TC、TG、LDL-C水平均低于对照组,HDL-C水平高于对照组,差异有统计学意义(P<0.05);观察组脂联素水平高于对照组,趋化素水平低于对照组,差异均有统计学意义(P<0.05);观察组治疗总有效率为96.08%(49/51),高于对照组的74.51%(38/51),差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:维格列汀联合二甲双胍治疗肥胖2型糖尿病患者可提高治疗总有效率和脂联素水平,改善脂代谢指标水平,降低糖代谢指标和趋化素水平,效果优于单纯二甲双胍治疗。

利拉鲁肽对小切口阑尾切除术治疗急性阑尾炎合并T2DM患者血糖、脂联素及胰岛素的影响

目的探讨利拉鲁肽对急性阑尾炎合并2型糖尿病(Type 2 Diabetes Mellitus,T2DM)患者采用小切口阑尾切除术对血糖、脂联素及胰岛素的影响。方法选取2019年12月—2021年12月厦门前埔医院收治的96例急性阑尾炎合并T2DM患者为研究对象,采用随机抽签法分为对照组(n=48)、观察组(n=48)。两组均接受小切口阑尾切除术,对照组术后采用二甲双胍治疗,观察组术后采用利拉鲁肽治疗,两组患者的疗程均为2周。比较两组治疗前、治疗2周后空腹血糖(Fasting Plasma Glucose,FPG)、餐后2 h血糖(2-Hour Postprandial Glu-cose,2 hPG)、糖化血红蛋白(Glycosylated Hemoglobin A1c,HbA1c)、胰岛β细胞分泌指数(Homeostasis Model Assessment-β,HOMA-β)、空腹胰岛素(Fasting Insulin,FNIS)、胰岛素抵抗指数(Homeostatic Model Assess-ment for Insulin Resistance,HOMA-IR)水平。结果观察组治疗2周后的血糖指标及HOMA-IR水平均低于对照组,脂联素、HOMA-β、FNIS水平高于对照组,差异有统计学意义(P均<0.05)。结论利拉鲁肽能降低急性阑尾炎合并T2DM小切口阑尾切除术患者的血糖水平,提高脂联素水平,改善胰岛素分泌和抵抗。

Adiponectin Gene Variation -4522C/T Is Associated with Type 2 Diabetic Obesity and Insulin Resistance in Chinese

The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with CHD, 389 patients with T2DM, and 405 age and sex-matched healthy control subjects was carried out by means of PCR-RFLP approach. No significant difference in the genotype or allele frequencies was found, either between patients with CHD and control subjects, or between patients with T2DM and control subjects. However, in the subgroup analysis, an association of the TAr genotype and T allele with type 2 diabetes combined with obesity （BMI ≥ 25 kg/m2） was found （P = 0.014 and P = 0.034, respectively）. Also the homeostasis model assessment of insulin resistance （HOMA-IR） in T2DM patients with T/T genotype was significantly higher than that in T2DM patients carrying C allele （P = 0.0069）. The authors＇ findings for the first time demonstrated that SNP --4522 in the adiponectin gene was associated with T2DM that combined with obesity and higher insulin resistance index in patients with T2DM. This indicated that the variation might associate with an increased susceptibility to type 2 diabetic obesity and insulin resistance. But -4522C/T polymorphism did not contribute to the susceptibility of CHD.

脂联素、直接胆红素及甘油三酯对2型糖尿病患者大血管病变的诊断价值

目的探讨脂联素(APN)、直接胆红素(DB)、甘油三酯(TG)及三者联合对2型糖尿病(T2DM)患者大血管病变的诊断价值。方法选取120例T2DM患者,根据是否合并大血管病变将其分为T2DM组(62例)和T2DM+大血管病变组(58例)。比较两组的临床资料;采用非条件多因素逐步Logistic回归分析T2DM患者合并大血管病变的风险因素;绘制受试者工作特征(ROC)曲线评估APN、DB、TG及三者联合对T2DM患者合并大血管病变的诊断效能。结果非条件多因素逐步Logistic回归分析结果显示,HbA1c[OR=24.096(95%CI:6.419,90.453)]、LDL-C[OR=13.118(95%CI:2.202,78.134)]和TG[OR=7.019(95%CI:2.414,20.407)]是T2DM患者合并大血管病变的危险因素(P<0.05);HDL-C[OR=0.000(95%CI:0.000,0.011)]、APN[OR=0.504(95%CI:0.313,0.809)]和DB[OR=0.694(95%CI:0.581,0.829)]是T2DM患者合并大血管病变的保护因素(P<0.05)。ROC曲线分析结果显示,当APN≤5.870 nmol/mL时,诊断T2DM患者合并大血管病变的曲线下面积(AUC)为0.718,敏感性为70.7%(95%CI:0.571,0.815),特异性为61.3%(95%CI:0.480,0.713);当DB≤14.205 mol/L时,AUC为0.772,敏感性为74.1%(95%CI:0.607,0.844),特异性为71.0%(95%CI:0.579,0.814);当TG≥1.955 mol/L时,AUC为0.735,敏感性为72.4%(95%CI:0.589,0.830),特异性为69.4%(95%CI:0.562,0.801);三者联合诊断的AUC为0.881,敏感性为84.5%(95%CI:0.721,0.922),特异性为77.4%(95%CI:0.647,0.867)。结论APN、DB、TG可用于T2DM患者合并大血管病变的辅助诊断,且三者联合可进一步提升诊断效能。

2型糖尿病患者发生下肢动脉硬化闭塞症的危险因素分析

目的探讨2型糖尿病患者发生下肢动脉硬化闭塞症(LEAOD)的危险因素及与脂联素、胱抑素C、载脂蛋白A1(ApoA1)/ApoB比值的关系。方法选取山东中医药大学附属医院2018年1月至2021年1月收治的2型糖尿病患者120例,根据是否合并LEAOD将患者分为LEAOD组和非LEAOD组。比较2组临床资料,采用逐步Logistic回归分析方法分析2型糖尿病患者发生LEAOD的危险因素,采用Spearman相关性分析方法分析LEAOD发生风险与2型糖尿病患者血清脂联素、胱抑素C、ApoA1/ApoB比值的相关性。结果120例患者中,48例合并LEAOD(LEAOD组)、72例未合并LEAOD(非LEAOD组)。2组吸烟史、糖尿病周围神经病变(DPN)、脑梗死、高血压病、冠心病(冠状动脉粥样硬化性心脏病)比例及空腹血糖、糖化血红蛋白(HbA1c)、空腹C肽、三酰甘油、总胆固醇、低密度脂蛋白胆固醇(LDL-C)、脂蛋白a、血尿酸、血肌酐、脂联素、胱抑素C水平、ApoA1/ApoB比值比较差异均有统计学意义(均P<0.05)。逐步Logistic回归分析结果显示DPN(比值比=2.988,95%置信区间:1.335~6.688)、冠心病(比值比=2.513,95%置信区间:1.366~4.623)、HbA1c(比值比=2.617,95%置信区间:1.163~5.889)、LDL-C(比值比=2.478,95%置信区间:1.292~4.753)、脂联素(比值比=2.192,95%置信区间:1.014~4.739)、胱抑素C(比值比=2.431,95%置信区间:1.071~5.718)、ApoA1/ApoB比值(比值比=3.091,95%置信区间:1.376~6.944)是2型糖尿病患者发生LEAOD的独立危险因素(均P<0.05)。Spearman相关性分析结果显示2型糖尿病患者LEAOD的发生风险与血清脂联素、ApoA1/ApoB比值呈负相关,与胱抑素C呈正相关(均P<0.001)。结论DPN、冠心病、HbA1c、LDL-C、脂联素、胱抑素C、ApoA1/ApoB比值是2型糖尿病患者发生LEAOD的独立危险因素,LEAOD的发生风险与血清脂联素、ApoA1/ApoB比值呈负相关性,与胱抑素C呈正相关性。

山西地区60例2型糖尿病肾病患者血清Adiponectin水平分析

山西地区患者,血清adiponectin水平,糖尿病肾病(DN)组较单纯糖尿病组显著升高;白蛋白尿组血清adiponectin水平较正常对照组、单纯糖尿病组、早期DN组显著升高。Adiponectin水平与尿白蛋白排泄率呈正相关,与腰臀比呈负相关。DN大量白蛋白尿期血清脂联素水平显著升高。

IL-8、脂联素、Hcy在T2DM合并甲状腺功能亢进患者中的表达及相关性研究

目的 探讨2型糖尿病(T2DM)合并甲状腺功能亢进(以下简称甲亢)患者血清白细胞介素-8(IL-8)、脂联素(APN)、同型半胱氨酸(Hcy)水平,分析其与T2DM合并甲亢的关系。方法 选择2019年3月至2021年6月我院收治的39例T2DM合并甲亢患者(甲亢组),130例单纯T2DM患者(T2DM组)和60例体检志愿者(对照组),检测血清IL-8、APN、Hcy、糖脂代谢以及甲状腺激素水平。分析IL-8、APN、Hcy与甲状腺激素的相关性以及IL-8、APN、Hcy鉴别诊断T2DM合并甲亢的价值。结果 甲亢组血清三酰甘油(TG)、总胆固醇(TC)、空腹血糖(FPG),空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)、游离三碘甲状腺激素(FT3)、游离甲状腺素(FT4)、IL-8、APN水平高于T2DM组(P<0.05),血清促甲状腺激素(TSH)、Hcy水平低于T2DM组(P<0.05)。甲亢组血清IL-8、APN水平与TSH呈负相关(P<0.05),与FT3、FT4呈正相关(P<0.05);Hcy与TSH呈正相关(P<0.05),与FT3、FT4呈负相关(P<0.05)。IL-8、APN、Hcy鉴别T2DM合并甲亢的曲线下面积为0.672、0.671、0.688,联合3项指标鉴别T2DM合并甲亢的曲线下面积为0.898,高于单独指标诊断(Z=4.918、5.372、3.722,P<0.05)。结论 T2DM患者合并甲亢患者血清IL-8、APN水平升高,Hcy水平降低,IL-8、APN增高,Hcy水平降低与T2DM患者甲状腺功能亢进有关,可作为T2DM合并甲亢的评估指标。

瑞舒伐他汀辅助治疗2型糖尿病患者应用价值分析

目的 探讨瑞舒伐他汀联合常规降糖方案对2型糖尿病(Type 2 diabetes mellitus,T2DM)患者血糖控制效果及脂联素(APN)、视黄醇结合蛋白4(RBP-4)血清表达的影响。方法 选取2019年6月至2021年6月濮阳市安阳地区医院T2DM患者98例,依据随机数字表法分为研究组与对照组,各49例。对照组采取常规降糖方案(二甲双胍、阿卡波糖),研究组在对照组基础上加用瑞舒伐他汀。统计和比较两组治疗前后血糖指标[空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)]、胰岛素抵抗[胰岛素抵抗指数(HOMA-IR)、空腹胰岛素(FINS)]、血脂指标[低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、总胆固醇(TC)、甘油三酯(TG)]、APN及RBP-4血清表达水平、血管内皮功能[一氧化氮(NO)、内皮素-1(ET-1)]和不良反应的差别。结果 治疗后研究组HbA1c、FPG、2 h PG低于对照组,差异有统计学意义(t=7.589、4.833、5.777,P<0.05);治疗后研究组HOMA-IR、FINS低于对照组,差异有统计学意义(t=5.450、4.898,P<0.05);治疗后研究组LDL-C、TC、TG水平低于对照组,HDL-C水平高于对照组,差异有统计学意义(t=2.821、3.108、4.582、3.919,P<0.05);治疗后研究组APN水平高于对照组,RBP-4水平低于对照组,差异有统计学意义(t=4.919、3.732,P<0.05);治疗后研究组ET-1水平低于对照组,NO水平高于对照组,差异有统计学意义(t=3.026、4.392,P<0.05);研究组不良反应发生率(12.24%)与对照组(8.16%)间差异无统计学意义(P>0.05)。结论 瑞舒伐他汀联合常规降糖方案(二甲双胍、阿卡波糖)治疗T2DM患者,可调节血清APN、RBP-4水平,改善血脂指标与血管内皮功能,减轻胰岛素抵抗,提高血糖控制效果,且安全性高。

Adiponectin and its association with insulin resistance and type 2 diabetes

Adiponectin is an adipokine, which is expressed in adipose tissue and is thought to play an important role in glucose metabolism. Hypoadiponectinemia can cause reduction of fatty acid oxidation, decreased glucose uptake in skeletal muscle cells, and increased gluconeogenesis in hepatic cells. The level of plasma glucose can be increased. On the other hand, the decrease of fatty acid oxidation increases the level of free fatty acid （FFA）, which increases the insulin resistance, and then decreases the glucose uptake, which ultimately causes increased plasma glucose and type 2 diabetes （T2D）. This review describes the process from hypoadiponectinemia to T2D and the genesis of hypoadiponectinemia at a molecular level.

Roles of adipocyte derived hormone adiponectin and resistin in insulin resistance of type 2 diabetes

AIM： To detect plasma levels of new adipocyte derived hormone adiponectin and resistin in type 2 diabetes patients and to explore their potential roles in insulin resistance in type 2 diabetes. METHODS： According to the body mass index （BMI）, 60 type 2 diabetes patients were divided into two groups, one group was non-obese diabetes patients with BMI 〈 25Kg/M^2 （30 cases） and the other group was obese diabetes patients with BMI 〉25Kg/M^2 （30 cases）. There were 28 healthy persons in the control group. EUSA technique was employed to determine the plasma adiponectin and resistin concentrations. The fasting blood glucose, insulin and blood lipid were detected respectively by electrocheminescence immunoassay and immunoturbidimetric assay. Insulin resistance index and insulin sensitive index were calculated by the homeostasis model assessment （HOMO）. RESULTS： The levels of plasma adiponectin were decreased significantly in diabetes group compared to that in control group （non-obese： 8.58±0.86, obese： 6.22±1.34 vs 10.53±1.47 P〈0.05）; moreover, adiponectin concentration in obese diabetes group was significantly decreased compared to that in non-obese diabetes group （6.22±1.34 vs 8.58±0.86, P〈 0.05）. The levels of plasma resistin were increased significantly in diabetes group compared to that in control group （obese： 18.64 ± 4.65, non-obese： 24.05±9.07 vs 14.16±5.25, P〈0.05,P〈0.05）; furthermore, the levels of resistin in obese diabetes group were increased significantly compared to that in non-obese diabetes group （P〈 0.05）. Plasma adiponectin was correlated negatively with BMI, blood glucose, insulin resistance index and triglyceride （respectively, r=-0.55, P〈0.01; r=-0.51, P〈0.05; r=-0.52, P〈 0.05： r=-0.39, P〈 0.05）, while it was positively correlated with insulin sensitive index （r=0.45, P〈0.05）. Conversely, plasma resistin correlated positively with BMI, blood glucose, triglyceride and insulin resistance index （respectively, r=0.40, P〈 0.05; r= 0.52, P〈0.05; r= 0.46, P〈 0.01; r= 0.27, P〈 0.05）, and negatively correlated with insulin sensitive index （r=-0.32, P〈 0.05）. CONCLUSION： Plasma adiponectin and resistin are associatecl with the disorder of metabolism of glucose and lipid in diabetes. The relationship between these hormone and insulin sensitivity suggests that they may take part in the development of insulin resistance of type 2 diabetes.

Effect of Exercise on the Expression of Adiponectin mRNA and GLUT4 mRNA in Type 2 Diabetic Rats

Summary: To investigate the impact of exercise on the expression of adiponectin and GLUT4 mRNA in type 2 diabetic rats, type 2 diabetic rat model was made. The diabetic rats were treated with swimming training for 8 weeks. The expression of adiponectin mRNA in perirenal fat and GLUT4 mRNA in skeletal muscles were assessed by reverse transcription polymerase chain reaction (RT-PCR) and the levels of blood glucose, serum insulin, and blood lipid were measured. Our results showed that the expression of adiponectin mRNA and GLUT4 mRNA in diabetic model group was decreased by 45 % (P<0.01), 43 % (P<0.01) respectively. The gene expression of adiponectin and GLUT4 was increased significantly in swimming group (P<0.05 and P<0.01, respectively). Compared with the model group, fasting insulin, TG, TC and FFA were decreased significantly in the training group (P<0.05 or P<0.01) as compared with model group. It is concluded that exercise can promote the expression of adiponectin mRNA and GLUT4 mRNA in type 2 diabetic rats, which may be one of the mechanisms responsible for the amelioration of insulin resistance in the rats.

Gasdermin D-mediated hepatocyte pyroptosis expands inflammatory responses that aggravate acute liver failure by upregulating monocyte chemotactic protein 1/CC chemokine receptor-2 to recruit macrophages

BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(shRNA)was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1)and its receptor CC chemokine receptor-2(CCR2)in vitro.For in vivo experiments,we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALF patients and a hepatocyte injury model increased significantly.The level of GSDMD-N protein increased most obviously(P<0.001).In vitro,downregulation of GSDMD by shRNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P<0.01).In vivo,GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P<0.001).Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1βand IL-18,GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death.However,this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF,recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses.GSDMD knockout can reduce hepatocyte death and inflammatory responses,thus alleviating ALF.

Human epidermal growth factor receptor-2 gene amplification in gastric cancer using tissue microarray technology

AIM:To assess human epidermal growth factor receptor-2 (HER2)-status in gastric cancer and matched lymph node metastases by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH).METHODS:120 cases of primary gastric carcinomas and 45 matched lymph node metastases from patients with full clinicopathological features were mounted onto multiple-punch and single-punch tissue microarrays,respectively,and examined for HER2 overexpression and gene amplification by IHC and CISH.RESULTS:Twenty-four tumors (20%) expressed HER2 immunohistochemically.An IHC score of ≥ 2+ was observed in 20 tumors (16.6%).HER2 amplification was detected by CISH in 19 tumors (15.8%) and in their matched lymph node metastases.A high concordancerate was found between HER2 positivity (as detected by IHC) and HER2 gene amplification (as detected by CISH),since 19 of the 20 IHC positive cases were amplified (95%).All amplified cases had 2+ or 3+ IHC results.Amplification was associated with intestinal phenotype (P < 0.05).No association with grading,staging or survival was found.CONCLUSION:In gastric cancer,HER2 amplification is the main mechanism for HER2 protein overexpression and is preserved in lymph node metastases.