PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer.Inetetamab is a novel anti-HER2 drug,and its efficacy and safety in gastric cancer have not yet been reported.AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin(SOX)regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer.METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroeso-phageal junction adenocarcinoma were randomly divided into two groups:One group received inetetamab combined with the SOX regimen,and the other group received trastuzumab combined with the SOX regimen.After 4-6 cycles,patients with stable disease received maintenance therapy.The primary endpoints were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were the objective response rate,disease control rate,and adverse events(AEs).RESULTS Thirty-seven patients completed the trial,with 18 patients in the inetetamab group and 19 patients in the trastuzumab group.In the inetetamab group,the median PFS was 8.5 months,whereas it was 7.3 months in the trastuzumab group(P=0.046);this difference was significant.The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months(P=0.33),and the objective response rate was 50%vs 42%(P=0.63),respectively;these differences were not significant.Common AEs included leukopenia,thrombocytopenia,nausea,and vomiting.The incidence rates of grade≥3 AEs were 56%in the inetetamab group and 47%in the trastuzumab group(P=0.63),with no significant difference.CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer,inetetamab and trastuzumab showed comparable efficacy.The inetetamab group showed superior PFS,and both groups had good safety.

BIRC3 induces the phosphoinositide 3-kinase-Akt pathway activation to promote trastuzumab resistance in human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2(HER2)-positive gastric cancer.However,the emergence of resistance to trastuzumab poses significant challenges.AIM To identify the key genes associated with trastuzumab resistance.These results provide a basis for the development of interventions to address drug resistance and improve patient outcomes.METHODS High-throughput sequencing and bioinformatics were used to identify the differentially expressed pivotal gene BIRC3 and delineate its potential function and pathway regulation.Tumor samples were collected from patients with HER2-positive gastric cancer to evaluate the correlation between BIRC3 expression and trastuzumab resistance.We established gastric cancer cell lines with both highly expressed and suppressed levels of BIRC3,followed by comprehensive in vitro and in vivo experiments to confirm the involvement of BIRC3 in trastuzumab resistance and to elucidate its underlying mechanisms.RESULTS In patients with HER2-positive gastric cancer,there is a significant correlation between elevated BIRC3 expression in tumor tissues and higher T stage,tumor node metastasis stage,as well as poor overall survival and progressionfree survival.BIRC3 is highly expressed in trastuzumab-resistant gastric cancer cell lines,where it inhibits tumor cell apoptosis and enhances trastuzumab resistance by promoting the phosphorylation and activation of the phosphoinositide 3-kinase-Akt(PI3K-AKT)pathway in HER2-positive gastric cancer cells,both in vivo and in vitro.CONCLUSION This study revealed a robust association between high BIRC3 expression and an unfavorable prognosis in patients with HER2-positive gastric cancer.Thus,the high expression of BIRC3 stimulated PI3K-AKT phosphorylation and activation,stimulating the proliferation of HER2-positive tumor cells and suppressing apoptosis,ultimately leading to trastuzumab resistance.

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.

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.

Human epidermal growth factor receptor 2 expression level and combined positive score can evaluate efficacy of advanced gastric cancer

BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.

血清FGF2和FGFR1对子痫前期患者不良妊娠结局的预测价值

目的 探讨血清成纤维细胞生长因子2(FGF2)和成纤维细胞生长因子受体1(FGFR1)与子痫前期(PE)患者妊娠结局的关系。方法 选取2021年1月—2022年12月河南省妇幼保健院PE患者82例(PE组)和健康孕妇82名(健康对照组)。收集所有研究对象的临床资料,并检测血清FGF2和FGFR1水平。根据PE患者的妊娠结局分为结局良好组(44例)和结局不良组(38例)。采用Pearson相关分析评估PE患者血清FGF2与FGFR1的相关性。采用Logistic回归分析评估PE患者发生不良妊娠结局的影响因素。采用受试者工作特征(ROC)曲线评价血清FGF2和FGFR1判断PE患者发生不良妊娠结局的效能。结果 PE组血清FGF2和FGFR1水平均低于健康对照组(P<0.05)。结局不良组血清FGF2和FGFR1水平均低于结局良好组(P<0.05),早发型PE和重度PE所占比例高于结局良好组(P<0.05),其他临床资料2个组之间差异均无统计学意义(P>0.05)。PE患者血清FGF2与FGFR1呈正相关(r=0.524,P<0.05)。早发型PE、重度PE是PE患者发生不良妊娠结局的危险因素[比值比(OR)值分别为3.682、4.029,95%可信区间(CI)分别为1.054~12.858、1.086~14.951,P<0.05],FGF2、FGFR1升高为保护因素(OR值分别为0.491、0.586,95%CI分别为0.293~0.822、0.382~0.898,P<0.05)。血清FGF2、FGFR1单项检测和联合检测判断PE患者发生不良妊娠结局的曲线下面积(AUC)分别为0.81、0.82、0.92。结论 PE患者血清FGF2和FGFR1水平显著降低,2项指标联合检测对PE患者发生不良妊娠结局有较高的预测效能。

FGF2和BMP-2对Ⅲ、Ⅳ型慢性骨髓炎患者病灶清除联合封闭负压引流治疗预后的预测价值

目的探讨成纤维细胞生长因子2(FGF2)和骨形态发生蛋白-2(BMP-2)对Ⅲ、Ⅳ型慢性骨髓炎患者病灶清除联合封闭负压引流治疗预后的预测价值。方法前瞻性选取2020年1月—2021年12月在新疆医科大学第一附属医院住院治疗的105例Ⅲ、Ⅳ型慢性骨髓炎患者作为研究对象,均接受病灶清除联合封闭负压引流治疗,按不同治疗预后分为疗效好组75例(71.4%)和疗效差组30例(28.6%)。比较两组患者的临床资料、血清炎症因子、FGF2及BMP-2表达水平;采用多因素Logistic回归分析影响患者预后的独立危险因素,分析FGF2及BMP-2与预后的关系;构建相关列线图模型,绘制受试者工作特征(ROC)曲线和决策曲线,分析FGF2、BMP-2及联合预测模型的预测效能和净收益率。结果疗效差组Ⅳ型Cierny-Mader分型及窦道形成患者占比高于疗效好组(P<0.05)。疗效差组患者术前红细胞沉降率(ESR)、C反应蛋白(CRP)及肿瘤坏死因子-α(TNF-α)水平均高于疗效好组(P<0.05),疗效差组患者术前FGF2及BMP-2水平均低于疗效好组(P<0.05)。多因素Logistic回归分析结果显示,Cierny-Mader分型[O^R=5.036(95%CI:1.369,9.894)]、窦道形成[O^R=2.987(95%CI:1.156,7.247)]、FGF2[O^R=0.446(95%CI:0.129,0.735)]和BMP-2[O^R=0.485(95%CI:0.212,0.738)]为影响Ⅲ、Ⅳ型慢性骨髓炎患者预后的危险因素(P<0.05)。基于FGF2、BMP-2构建预测预后的列线图模型,校准曲线显示,Ⅲ、Ⅳ型慢性骨髓炎患者治疗疗效的预测值与实际观测值十分接近;ROC曲线分析结果显示,Cierny-Mader分型、窦道形成、FGF2及BMP-2预测预后的曲线下面积分别为0.783(95%CI:0.754,0.875)、0.752(95%CI:0.761,0.893)、0.823(95%CI:0.789,0.885)及0.811(95%CI:0.797,0.875),FGF2及BMP-2的最佳截断值分别为18.9 ng/L和113.5 ng/L,4者联合预测的曲线下面积为0.952(95%CI:0.896,0.991);决策曲线分析结果显示,Cierny-Mader分型、窦道形成、FGF2及BMP-2预测预后均具有良好的净收益率,并且联合预测的总体净收益率高于单一指标。结论基于Cierny-Mader分型、窦道形成、FGF2及BMP-24个指标构建的列线图模型能准确预测Ⅲ、Ⅳ型慢性骨髓炎患者病灶清除联合封闭负压引流治疗预后。

青少年抑郁障碍患者血清FGF2和BDNF表达与病情程度及CI的关系

目的探讨青少年抑郁障碍患者血清成纤维细胞生长因子2(FGF2)和脑源性神经生长因子(BDNF)表达与病情程度及认知功能障碍(CI)的关系。方法选取2021年1月至2022年8月在本院治疗的88例青少年抑郁障碍患者(观察组)为研究对象,根据病情程度将其分为轻度组、中度组、重度组,根据是否发生CI将其分为非CI组和CI组,另选取同期入院体检的88例健康志愿者作为对照组。采用酶联免疫吸附法(ELISA)检测血清FGF2、BDNF水平。结果重度组血清FGF2、BDNF水平低于中度组和轻度组,重度组HAMD-17评分高于中度组和轻度组(P<0.05)。血清FGF2、BDNF二者联合诊断青少年发生重度抑郁障碍、发生CI均优于单独诊断(P<0.05)。结论血清FGF2、BDNF水平随青少年抑郁障碍患者疾病严重程度加重而降低,且与CI发生相关,可能作为病情程度和CI发生的预测指标。

连接蛋白2和FGF23在房颤介导心肌病兔心房组织中的表达

目的 探究连接蛋白2(JP2)和成纤维细胞生长因子23(FGF23)在房颤介导心肌病(AMC)兔中的表达规律。方法 通过左心房快速起搏法建立心房颤动(AF)模型,4周后行超声心动图检查,射血分数下降>10%纳入AMC组,否则为AF组,对照组只植入起搏器不起搏。最终成功建立AF动物模型11只,其中AF组6只,AMC组5只,对照组6只。超声心动图检测左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)等指标,酶联免疫吸附法(ELISA)检测血清JP2和FGF23水平。处死动物后,取心房组织,Western blot和RT-qPCR检测JP2和FGF23蛋白及mRNA表达。结果 与对照组相比,AMC组左房内径、右房内径、右室内径增大,LVEF降低,与AF组相比,AMC组LVEF降低,主动脉增宽,右室扩大。与对照组相比,AF组左房心肌细胞FGF23(P<0.001)、JP2(P<0.01)的表达均明显增加,而AMC组JP2表达降低(P<0.001)。与AF组相比,AMC组FGF23和JP2的表达下降。与对照组相比,AF组FGF23和JP2血浆浓度升高,AMC组FGF23水平升高。与AF组相比,AMC组FGF23和JP2血浆浓度偏低。结论 在AMC兔模型中,FGF23表达增加,JP2表达下降。

Roles of fibroblast growth factors in the treatment of diabetes

Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

中老年2型糖尿病患者血清FGF21水平与糖代谢、血清尿酸关系的研究

目的分析中老年2型糖尿病(T2DM)患者血清中成纤维细胞生长因子21(FGF21)与糖代谢、血清尿酸(SUA)的关系。方法随机选取2020年6月—2020年11月在兰州大学第一医院内分泌科住院治疗的245例平均年龄(58.64±9.80)岁T2DM患者(男性171例,女性74例)。收集所有研究对象的一般资料及生化指标,ELISA法检测血清FGF21水平,根据糖化血红蛋白水平(HbA1c)将患者分为3组:血糖控制达标组(HbA1c≤7%)、血糖控制较差组(7%<HbA1c≤10%)、血糖控制极差组(HbA1c>10%),比较各组之间血清FGF21水平的差异。其次根据血清FGF21水平的四分位数将T2DM患者分为4组:Q1[10.00,55.00]mmol/L、Q2[55.01,88.00]mmol/L、Q3[88.01,129.00]mmol/L、Q4[129.01,213.00]mmol/L组,比较各组患者生化指标之间的差异。Spearman相关分析血清FGF21与糖代谢、SUA水平的相关性。多元线性回归分析血清FGF21的独立影响因素。结果血糖控制极差组血清FGF21水平([81.48±43.29)mmol/L]显著低于血糖控制达标组(104.56±52.67)和血糖控制较差组[(97.64±48.28)mmol/L,P<0.05]。Q3组[(355.92±70.15)、Q4组SUA水平(365.49±81.45)mmol/L]显著高于Q1组[(322.92±77.35)mmol/L,均P<0.05]。Q4组HbA1c水平[7.55(6.70,9.10)%]显著低于Q1组[8.50(7.00,10.40)%]、Q2组[9.00(7.60,11.00)%]、Q3组[8.80(7.30,9.90)%]。SUA水平与血清FGF21水平呈正相关关系(r=0.183,P=0.004),与HbA1c水平、空腹血糖(FPG)呈负相关关系(r=-0.157,P=0.013;r=-0.133,P=0.038)。多元线性回归显示SUA与血清FGF21水平呈独立正相关关系[B=0.086,95%CI:[0.001,0.172],P=0.048]。结论中老年T2DM患者血清FGF21水平与SUA呈正相关关系,与HbA1c、FPG呈负相关关系,并且FGF21与SUA水平增加独立相关。高水平血清FGF21与中老年T2DM患者血糖控制达标有关,但是会增加高尿酸血症的风险。

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer

More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.

妊娠期高血压疾病患者孕晚期血清FGF2和VEGF表达与胎儿生长受限的相关性分析

目的探究妊娠期高血压(HDP)疾病患者孕晚期血清成纤维细胞生长因子2(FGF2)和血管内皮生长因子(VEGF)表达与胎儿生长受限(FGR)的相关性。方法收集2022年1月至2022年12月在我院分娩的60例孕晚期HDP并发FGR孕妇(FGR组)、60例HDP孕妇未发生FGR孕妇(HDP组)临床资料,并以同期60例健康孕产妇作为对照组。血清FGF2、VEGF水平测定使用酶联免疫吸附法(ELISA);比较HDP组、FGR组及对照组孕妇血清FGF2、VEGF水平;采用Logistic回归分析影响FGR发生的因素;Pearson相关性分析血清FGF2、VEGF水平与新生儿体质量间的关系;受试者工作特征曲线(ROC)探究血清FGF2、VEGF表达对FGR的预测效能。结果3组在年龄、孕周、BMI、分娩方式上差异无统计学意义(P>0.05),在收缩压、舒张压、新生儿体质量上差异有统计学意义(P<0.05);与对照组相比,HDP组、FGR组血清FGF2水平升高(P<0.05),VEGF水平降低(P<0.05),且FGR组孕妇血清FGF2水平高于HDP组(P<0.05),VEGF水平低于HDP组(P<0.05);Logistic回归分析显示,收缩压、舒张压、血清FGF2、VEGF水平均是孕晚期HDP孕妇发生FGR的独立影响因素(P<0.05);ROC曲线结果显示,FGF2、VEGF诊断HDP孕妇发生FGR的AUC分别为0.850、0.849,灵敏度分别为76.7%、86.7%,特异性分别为60.0%、60.0%,两者联合诊断孕晚期HDP孕妇发生FGR的AUC为0.933,灵敏度为88.3%,特异性为76.6%。结论发生FGR的孕晚期HDP孕妇血清FGF2水平升高,VEGF水平降低,两者为孕晚期HDP孕妇发生FGR的危险因素,且对FGR具有一定的预测价值。

血清FGF21和SIRT3水平对慢性心力衰竭患者病情及预后评估的价值

目的:对慢性心力衰竭(congestive heartfailure,CHF)患者的病情及预后进行早期评估有助于降低其病死率,改善其预后。本研究旨在探索CHF患者血清成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)和沉默信息调节因子2相关酶3(silent information regulator factor 2 related enzyme 3,SIRT3)水平及其在患者病情及预后评估中的应用价值。方法:选取2021年1月至2022年6月确诊的164例CHF患者作为疾病组,选择同期160例健康体检者作为对照组。采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清FGF21和SIRT3水平,采用多普勒超声仪检测患者左室重量指数(left ventricular weight index,LVMI)、左心室舒张期末内径(left ventricular end-diastolic internal diameter,LVEDD)、左房内径(left atrium diameter,LAD)、左室射血分数(left ventricular ejection fractions,LVEF);Pearson相关性分析血清FGF21、SIRT3分别与LVMI、LVEDD、LAD的相关性;采用受试者操作特征(receiver operator characteristic,ROC)曲线分析血清FGF21和SIRT3对CHF患者预后的诊断价值,采用Kaplan-Meier法分析FGF21和SIRT3与CHF患者预后的关系。结果:与对照组比较,疾病组LVMI、LVEDD、LAD及FGF21水平均升高,SIRT3水平降低(均P<0.05);不同心功能分级患者血清FGF21和SIRT3水平差异均有统计学意义(均P<0.05);FGF21水平与LVMI、LVEDD、LAD呈正相关,SIRT3水平与LVMI、LVEDD、LAD和FGF21水平呈负相关(均P<0.05);FGF21和SIRT3联合诊断CHF患者预后的曲线下面积(area under the curve,AUC)显著大于FGF21单独诊断的AUC(Z=2.645,P=0.008)及SIRT3单独诊断的AUC(Z=2.738,P=0.006),FGF21高表达组生存率低于低表达组(χ^(2)=8.257,P=0.004),SIRT3高表达组生存率高于低表达组(χ^(2)=15.305,P<0.001)。结论:CHF患者血清FGF21水平升高,SIRT3水平降低,FGF21与SIRT3联合在CHF病情及预后评估中具有较高的应用价值。

2型糖尿病合并脑梗死患者血清FGF21、RAGE、DKK1表达情况及其意义

目的探讨2型糖尿病(T2DM)合并脑梗死患者血清成纤维细胞生长因子(FGF)21、晚期糖基化终末产物受体(RAGE)及Dickkopf-1蛋白(DKK1)表达情况及其意义。方法前瞻性选取2021年6月至2023年6月于中部战区总医院治疗T2DM合并脑梗死患者300例纳入试验组,选择同期于本院接受治疗的T2DM患者300例纳入T2DM组,选择同期于本院进行体检的健康者300名纳入对照组。检测并比较3组血清FGF21、RAGE、DKK1表达水平;分析血清FGF21、RAGE、DKK1对T2DM合并脑梗死的诊断价值;分析不同预后T2DM合并脑梗死患者临床资料和血清FGF21、RAGE、DKK1表达水平;分析血清FGF21、RAGE、DKK1与T2DM合并脑梗死预后的相关性;采用多因素Logistic回归分析分析血清FGF21、RAGE、DKK1对T2DM合并脑梗死预后的预测价值。结果试验组血清FGF21、RAGE、DKK1表达水平分别为(3.45±0.36)ng/L、(789.74±80.57)μg/mL、(98.76±9.92)ng/mL,均大于T2DM组[(2.68±0.29)ng/L、(578.06±59.84)μg/mL、(44.76±4.65)ng/mL]及对照组[(1.52±0.17)ng/L、(289.75±30.38)μg/mL、(24.95±2.64)ng/mL],差异均有统计学意义(P<0.05)。经受试者工作特征(ROC)曲线分析,血清FGF21、RAGE及DKK1联合诊断T2DM合并脑梗死的临床价值高于血清FGF21、RAGE及DKK1单一诊断的临床价值。预后不良患者和预后良好患者的性别构成比、年龄、体重指数、随机血糖比较,差异均无统计学意义(P>0.05);预后不良患者的糖化血红蛋白(HbA1c)、FGF21、RAGE、DKK1分别为(8.42±0.86)%、(3.89±0.40)ng/L、(865.64±89.43)μg/mL、(125.64±14.26)ng/mL,均大于预后良好患者[(7.04±0.73)%、(3.11±0.33)ng/L、(735.08±75.07)μg/mL、(83.64±8.61)ng/mL],差异均有统计学意义(P<0.05)。经Spearman相关分析,血清FGF21、RAGE、DKK1与T2DM合并脑梗死预后均呈负相关(r=-0.624、-0.553、-0.726,P<0.05)。经Logistic回归分析,结果显示HbA1c、FGF21、RAGE、DKK1均为影响T2DM合并脑梗死预后的独立危险因素(P<0.05)。结论血清FGF21、RAGE、DKK1联合诊断T2DM合并脑梗死具有较高的诊断及预后价值,可将其应用于T2DM合并脑梗死患者的临床诊断及预后评价。

LECT2、FGF21水平在T2DM伴NAFLD患者中的变化及其临床意义

目的探讨血清白细胞衍生趋化因子2(leukocyte cell derived chemotaxin 2,LECT2)、成纤维细胞生长因子21(fibroblast growth factor 21,FGF-21)在2型糖尿病(diabetes mellitus type 2,T2DM)伴非酒精性脂肪性肝病(non-alchoholic fatty liver disease,NAFLD)患者中的变化及临床意义。方法选取中国人民解放军西部战区总医院2019年10月~2021年10月收治的T2DM患者142例,按是否合并NAFLD分为伴NAFLD组(68例)与无NAFLD组(74例),收集患者临床指标,采用酶联免疫吸附法检测LECT2、FGF-21水平。比较两组临床指标差异,分析LECT2、FGF-21水平与其他临床指标的相关性,采用Logistic回归分析T2DM伴NAFLD的独立影响因素;采用ROC曲线分析各变量预测T2DM伴NAFLD的效能。结果伴NAFLD组BMI、WHR、SBP、DBP、FPG、FINS、FCP、HbAlc、HOMA-IR、TC、TG、LDL-C、ALT、AST、GGT、LECT2、FGF21高于无NAFLD组,HOMA-β、HDL-C低于无NAFLD组(P<0.05);相关分析显示,LECT2与BMI、WHR、FPG、FINS、FCP、HbAlc、HOMA-IR、TC、GGT存在正相关,与HOMA-β、HDL-C存在负相关(P<0.05);FGF21与FPG、FINS、FCP、HbAlc、HOMA-IR、TC、TG存在正相关,与HOMA-β、HDL-C存在负相关(P<0.05);Logistic分析,结果显示,HOMA-IR、HDL-C、LECT2、FGF21是T2DM伴NAFLD的独立影响因素(P<0.05);ROC曲线分析显示,LECT2、FGF21预测T2DM伴NAFLD的最佳截断值为30.72 ng/ml、138.66 ng/L,灵敏度为72.61%、71.36%,特异度为72.54%、73.75%,AUC值为0.732、0.753(P<0.001),两项指标联合检测灵敏度为85.72%、特异度为87.44%,AUC值为0.863(P<0.001)。结论LECT2、FGF-21与胰岛素抵抗及血脂水平存在相关,可作为预测T2DM伴NAFLD的指标。

血清FGF23对2型糖尿病患者冠状动脉钙化的预测价值

目的评估血清全段成纤维细胞生长因子(FGF23)对2型糖尿病患者冠状动脉钙化的预测价值。方法选择2022年1月至2023年1月门诊及住院的2型糖尿病患者共86例为2型糖尿病患者组,选择年龄、性别匹配的80例健康体检者为对照组。比较两组患者的临床资料,血压、血脂、肾功能、钙磷代谢指标,血清FGF23及冠状动脉钙化发生率等。分析血清FGF23及碱性磷酸酶(AKP)对2型糖尿病患者冠状动脉钙化的预测价值。结果2型糖尿病患者组的糖化血红蛋白(HbA1c)、血清FGF23、收缩压(SBP)、舒张压(DBP)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三脂(TG)、尿蛋白肌酐比值(UACR)、血磷、钙磷乘积、AKP以及冠状动脉钙化发生率均明显高于对照组,高密度脂蛋白胆固醇(HDL-C)低于对照组,差异均有统计学意义(t分别=6.32、5.12、3.65、4.25、5.78、2.47、3.45、5.12、2.45、2.47、3.89,χ^(2)=3.46,t=-2.46,P均<0.05)。多元线性回归分析,logFGF23与吸烟、血磷、AKP、UACR、冠状动脉钙化有相关性(t分别=9.02、5.69、6.35、7.65、12.89,P均<0.05)。受试者工作特征曲线(ROC)结果显示,血清FGF23预测2型糖尿病患者合并冠状动脉钙化的曲线下面积为0.70(95%CI 0.62~0.78),当检测的截点为305.52 pg/mL时,其灵敏度及特异度分别为76.73%及68.12%。血清AKP预测2型糖尿病患者合并冠状动脉钙化的曲线下面积为0.62(95%CI 0.55~0.70),当检测的截点为67.15 mmol/L,其灵敏度及特异度分别为66.52%及58.26%。结论2型糖尿病患者有更高的血清FGF23水平,血清FGF23对2型糖尿病患者合并冠状动脉钙化具有较好的预测价值。

四妙勇安汤联合自粘性软聚硅酮有边型泡沫敷料对Wagner 1—2级糖尿病足肢端血流动力学、EGF及血清FGF21、CTRP9的影响

目的:观察四妙勇安汤联合自粘性软聚硅酮有边型泡沫敷料对Wagner 1—2级糖尿病足肢端血流动力学、表皮生长因子(EGF)及血清成纤维细胞生长因子-21(FGF21)、C1q肿瘤坏死因子相关蛋白9(CTRP9)的影响。方法:选择2020年2月至2023年6月该院收治的Wagner 1—2级糖尿病足患者102例,分组方式为随机数字表法。对照组51例患者给予自粘性软聚硅酮有边型泡沫敷料治疗,观察组51例患者给予四妙勇安汤联合自粘性软聚硅酮有边型泡沫敷料治疗。比较两组患者的临床疗效,治疗前后测量患者的创面面积、病灶处皮肤温度,检测足背部经皮氧分压,记录视觉模拟评分(VAS),检测患者足背动脉血流速度、血管内径,测量足背部微血管基础血流灌注量,检测血清EGF、淀粉样蛋白A(SAA)、FGF-21、CTRP9和脂蛋白相关磷脂酶A2(Lp-PLA2)水平。结果:观察组患者的总有效率为96.08%(49/51),高于对照组的80.39%(41/51),差异有统计学意义(P<0.05)。治疗后,观察组患者的VAS评分低于对照组,创面面积小于对照组,皮肤温度、经皮氧分压高于对照组,差异均有统计学意义(P<0.05)。治疗后,观察组患者足背动脉血流速度较对照组快,血管内径、微血管基础血流灌注量较对照组大,FGF21水平较对照组降低,CTRP9、EGF水平较对照组升高,SAA、Lp-PLA2水平较对照组降低,差异均有统计学意义(P<0.05)。结论:四妙勇安汤联合自粘性软聚硅酮有边型泡沫敷料治疗Wagner 1—2级糖尿病足患者,可抑制机体炎症,提升EGF水平,调节FGF-21、CTRP9水平,改善肢端动脉血流动力学及微血管循环,促进创面愈合,缓解创面疼痛,提升皮肤温度、经皮氧分压,提高临床疗效。