Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

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.

Clinical Observation of Recombinant Bovine Basic Fibroblast Growth Factor Eye Gel Combined with Tobramycin Dexamethasone Eye Drops in the Treatment of Dry Eye Syndrome in Patients after Cataract Surgery

Objective:To evaluate the therapeutic effect of recombinant bovine basic fibroblast growth factor(rbFGF)eye gel combined with tobramycin-dexamethasone(TOB-Dex)eye drops on dry eye syndrome(DES)after cataract surgery.Methods:86 patients with DES after cataract surgery,admitted from November 2021 to November 2023,were randomly divided into groups.The observation group included 43 patients treated with rbFGF eye gel combined with TOB-Dex eye drops.The reference group included 43 patients treated with TOB-Dex eye drops alone.Multiple indicators,including total effective rate and clinical symptom scores,were compared between the two groups.Results:The total effective rate in the observation group was higher than in the reference group(P<0.05).Before treatment,there were no differences in clinical symptom scores,serum factors,or disease severity scores between the two groups(P>0.05).Three weeks after treatment,the observation group had lower clinical symptom scores,serum factors,and disease severity scores compared to the reference group(P<0.05).The adverse reaction rate in the observation group was lower than in the reference group(P<0.05).Conclusion:rbFGF eye gel combined with TOB-Dex eye drops can improve the clinical efficacy for patients with DES after cataract surgery,alleviate disease symptoms,reduce inflammatory responses,and have fewer adverse reactions.

Overexpression of fibroblast growth factor 13 ameliorates amyloid-β-induced neuronal damage

Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ_(1-42))-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.

Fibroblast growth factor 15,induced by elevated bile acids,mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy

BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are elevated after bariatric surgery.However,it is unclear whether the increase in FGF15/19 is induced by BAs.Moreover,it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery.AIM To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy(SG).METHODS By calculating and comparing the changes of body weight after SG with SHAM group,we examined the weight-loss effect of SG.The oral glucose tolerance test(OGTT)test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG.By detecting the glycogen content,expression and activity of glycogen synthase as well as the glucose-6-phosphatase(G6Pase)and phosphoenolpyruvate carboxykinase(Pepck),we evaluated the hepatic glycogen content and gluconeogenesis activity.We examined the levels of total BA(TBA)together with the farnesoid X receptor(FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery.Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4(FGFR4)with its corresponding signal pathways involved in glucose metabolism were detected.RESULTS After surgery,food intake and body weight gain of SG group was decreased compare with the SHAM group.The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG,while the expression of the key enzyme for hepatic gluconeogenesis:G6Pase and Pepck,were depressed.TBA levels in serum and portal vein were both elevated after SG,the FXR-agonistic BA subspecies:Chenodeoxycholic acid(CDCA),lithocholic acid(LCA)in serum and CDCA,DCA,LCA in portal vein were all higher in SG group than that in SHAM group.Consequently,the ileal expression of FXR and FGF15 were also advanced in SG group.Moreover,the hepatic expression of FGFR4 was stimulated in SG-operated rats.As a result,the activity of its corresponding pathway for glycogen synthesis:FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated,while the corresponding pathway for hepatic gluconeogenesis:FGFR4-cAMP regulatory element-binding protein-peroxisome proliferator-activated receptorγcoactivator-1αpathway was suppressed.CONCLUSION Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR.Furthermore,the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.

Depletion of gut microbiota facilitates fibroblast growth factor 21-mediated protection against acute pancreatitis in diabetic mice

BACKGROUND Fibroblast growth factor 21(FGF21),primarily secreted by the pancreas,liver,and adipose tissues,plays a pivotal role in regulating glucose and lipid metabolism.Acute pancreatitis(AP)is a common inflammatory disease with specific clinical manifestations.Many patients with diabetes present with concurrent inflammatory symptoms.Diabetes exacerbates intestinal permeability and intestinal inflammation,thus leading to the progression to AP.Our previous study indicated that FGF21 significantly attenuated susceptibility to AP in mice.AIM To investigate the potential protective role of FGF21 against AP in diabetic mice.METHODS In the present study,a mouse model of AP was established in diabetic(db)/db diabetic mice through ceruletide injections.Thereafter,the protective effects of recombinant FGF21 protein against AP were evaluated,with an emphasis on examining serum amylase(AMS)levels and pancreatic and intestinal inflammatory cytokines[interleukin(IL)-6,tumor necrosis factor-alpha(TNF-),and intestinal IL-1β].Additionally,the impact of this treatment on the histopathologic changes of the pancreas and small intestinal was examined to elucidate the role of FGF21 in diabetic mice with AP.An antibiotic(Abx)cocktail was administered in combination with FGF21 therapy to investigate whether the effect of FGF21 on AP in diabetic mice with AP was mediated through the modulation of the gut microbiota. Subsequently, thePhylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), a bioinformaticssoftware package, was used to predict different pathways between the groups and to explore the potentialmechanisms by which the gut microbiota influenced the protective effect of FGF21.RESULTSThe results indicated that FGF21 notably diminished the levels of serum AMS (944.5 ± 15.9 vs 1732 ± 83.9, P < 0.01)and inflammatory factors including IL-6 (0.2400 ± 0.55 vs 1.233 ± 0.053, P < 0.01), TNF- (0.7067 ± 0.22 vs 1.433 ±0.051, P < 0.01), and IL-1β (1.377 ± 0.069 vs 0.3328 ± 0.02542, P < 0.01) in diabetic mice with AP. Moreover, notablesigns of recovery were observed in the pancreatic structure of the mice. The histologic evidence of inflammation inthe small intestine, including edema and villous damage, was significantly alleviated. FGF21 also significantlyaltered the composition of the gut microbiota, reestablishing the Bacteroidetes/Firmicutes ratio. Upon treatment withan Abx cocktail to deplete the gut microbiota, the FGF21 + Abx group showed lower levels of serum AMS (0.9328 ±0.075 vs 0.2249 ± 0.023, P < 0.01) and inflammatory factors (1.083 ± 0.12 vs 0.2799 ± 0.032, p < 0.01) than the FGF21group. Furthermore, the FGF21 + Abx group exhibited diminished injury to the pancreatic and small intestinaltissues, accompanied by a significant decrease in blood glucose levels (17.50 ± 1.1 vs 9.817 ± 0.69 mmol/L, P <0.001). These findings underscored the superior protective effects of the combination therapy involving an Abxcocktail with FGF21 over the FGF21 treatment alone in diabetic mice with AP. The gut microbiota compositionacross different groups was further characterized, and a differential expression analysis of gene functions wasundertaken using the PICRUSt2 prediction method. These findings suggested that FGF21 could potentially confertherapeutic effects on diabetic mice with AP by modulating the sulfate reduction I pathway and the superpathwayof n-acetylceramide degradation in the gut microbiota.CONCLUSION This study reveals the potential of FGF21 in improving pancreatic and intestinal damage recovery, reducing bloodglucose levels, and reshaping gut microbiota composition in diabetic mice with AP. Notably, the protective effectsof FGF21 are augmented when combined with the Abx cocktail.

Effect of basic fibroblast growth factor(bFGF) on the treatment of exposure of the orbital implants

Objective: To evaluate the efficacy and the indication of basic fibroblast growth factor (bFGF) in the treatment of exposure of orbital implants. Design: Retrospective and observational case series. Methods: We reviewed 41 patients (41 eyes) suffering exposure of orbital implants from Jan. 2000 to June 2006. The study group patients with mild exposure received com-bined treatment with bFGF and antibiotic drops, and while the control group patients with mild exposure were treated with anti-biotic drops only. The study group patients with moderate and severe exposure received combined treatment with bFGF and antibiotic drops, and after 2 months they were subjected to amniotic membrane transplantation, while the control group patients with moderate and severe exposure underwent amniotic membrane transplantation after using antibiotic drops. Observation of the growth of conjunctival epithelium and comparison of the healing rate of the two groups. Results: The healing rates of the mild, moderate and severe exposure study group were 100% and 92.3%. The healing rates of the mild, moderate and severe exposure control group were 55.6% and 66.7% respectively. The difference of the healing rates of the mild exposure study group and the control group was significant (P=0.033). And the difference of the healing rates of the moderate and severe exposure study group and the control group was not significant (P=0.167). Conclusion: bFGF may promote obviously the healing of orbital implant exposure, particularly it can be the first choice for the treatment of mild degree exposure. For the moderate and severe cases, it can be administered before surgical repair to enhance neovascularization and will tend to increase the success rate of surgical repair.

Usefulness of Basic Fibroblast Growth Factor (bFGF) Loaded Dissolving Microneedles for Local Therapy of Skin Wounds

Purpose: The usefulness of dissolving microneedles (DMs) for local skin therapy by basic fibroblast growth factor (bFGF) was studied in rats. Methods: We prepared four kinds of bFGF-loaded DMs, approximately 500 μm length and 300 μm diameter at the bottom. Long-term stability and dissolution studies were performed by HPLC method. Pharmacokinetic and pharmacological evaluations were performed after administration of bFGF loaded DMs to rats. Results: The bFGF contents were 2.15 ± 0.07, 1.07 ± 0.04, 0.56 ± 0.07 and 0.12 ± 0.03 μg. The 100.2 ± 3.4%, 100.2 ± 3.3%, 99.3 ± 1.4% and 100.4 ± 3.0% of bFGF were recovered after 1, 3 and 6 months and 1 year incubation at 40°C. The bFGF was released from DMs within 5 min. In a pharmacokinetic study using 2.0 and 1.0 μg bFGF-loaded DMs, no systemic exposure of bFGF was detected. The initial bFGF concentrations in the rat skin tissue after administration of bFGF-loaded DMs to the hair-removed rat abdominal skin were 510.2 ± 20.1 ng/g wet weight for 2 μg bFGF DMs and 264.2 ± 56.5 ng/g wet weight for 1 μg DMs, declining slowly thereafter to 226.3 ± 33.5 and 105.1 ± 27.4 ng/g wet weight at 6 hr after administration. Good dose-dependency was observed. Pharmacological evaluation of bFGF-loaded DMs of 2.0, 1.0, 0.5, and 0.1 μg, in the wound healing rat model, all used DMs, but 0.1 μg DMs, showed good healing effects. Considered collectively, these results suggest the usefulness of bFGF-loaded DMs for local therapy of skin wound disease.

Effects of basic fibroblast growth factor on ischemic gut and liver injuries

AIMS To explore the possible effects of basic fibrob- last growth factor (bFGF) on ischemic gut and liver in- juries after trauma. METHODS Animal model of super mesenteric artery (SMA) occlusion was used in this study. Seventy-two Wistar rats were divided into three groups of 24 rats each. Each animal in group 1 (bFGF treated) was in- jected with 4 μg of bFGF in 0.15 ml of normal saline solution containing 0.1%(w/v) heparin through the jugular vein at the onset of reperfusion. Animals in group 2 (saline treated) received the same vehicle, but without bFGF. Group 3 (sham-operated) ani- mals were treated with the same operations,but without SMA occlusion. Liver function parameters, serum TNFα,bacterial examination and pathological study were used to evaluate the results. RESULTS In group 1,the amounts of ALT and AST and serum TNFα were reduced significantly at 6,24 and 48 hours as compared with group 2. Bacterial ex- amination showed that the bacterial translocation from gut to liver,spleen and MLN in group 1 was much lower than that in group 2. The pathological results support the concept of significant protecting effects of bFGF. CONCLUSIONS Venous administration of bFGF may help reduce gut and liver injuries after ischemia and reperfusion. Its mechanism of action may involve the mitogenic and non-mitogenic effects of bFGF.

儿童慢性粒细胞白血病慢性期红细胞参数及血清bFGF、TGF-β1、VEGF表达变化分析

目的探究儿童慢性粒细胞白血病(CML)慢性期红细胞参数及血清碱性成纤维细胞生长因子(bFGF)、转化生长因子β1(TGF-β1)及血管内皮生长因子(VEGF)表达变化。方法前瞻性选取2020年1月至2023年1月在首都医科大学附属北京儿童医院进行治疗的54例CML慢性期患儿为研究组,另随机抽取46名同期在本院进行体检的健康儿童为健康对照组。研究组给予酪氨酸激酶抑制剂治疗。比较两组间红细胞参数及血清bFGF、TGF-β1、VEGF表达变化,并比较研究组治疗前后红细胞参数及血清bFGF、TGF-β1、VEGF表达水平。结果研究组的RBC、血红蛋白、红细胞压积(HCT)及平均红细胞血红蛋白浓度(MCHC)水平分别为(3.45±0.04)×10^(12)/L、(102.33±1.15)g/L、(32.03±0.61)%、322.15±2.58,均显著低于对照组[(4.98±0.03)×10^(12)/L、(149.78±1.88)g/L、(44.33±0.31)%、334.12±0.77],平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)及红细胞体积分布宽度(RDW)水平分别为(91.44±0.77)fL、(33.15±2.55)pg、(17.55±0.12)%,均显著高于对照组[(89.88±0.34)fL、(30.24±0.16)pg、(12.66±0.11)%],差异均有统计学意义(P<0.05)。研究组的血清bFGF、VEGF水平分别为(30.66±9.66)、(128.68±30.58)pg/mL,均显著高于对照组[(5.26±1.54)、(70.66±11.26)pg/mL],TGF-β1水平为(38.22±8.06)μg/L,显著低于对照组[(78.66±8.13)μg/L],差异均有统计学意义(P<0.05)。治疗后,研究组患儿的RBC、血红蛋白、HCT、MCV及MCH水平均较治疗前显著降低,MCHC及RDW水平均较治疗前显著升高,差异均有统计学意义(P<0.05)。研究组治疗后的血清bFGF、VEGF水平均较治疗前显著降低,TGF-β1水平较治疗前显著升高,差异均有统计学意义(P<0.05)。结论在儿童CML慢性期患儿中可见血细胞参数明显异常,血清bFGF、VEGF水平显著升高,TGF-β1水平显著降低。酪氨酸激酶抑制剂治疗CML慢性期能有效改善患儿红细胞形态及功能,抑制肿瘤细胞生长,临床疗效显著,值得临床推广使用。

外周血Lp-PLA2和FGF23水平变化与脑梗死后认知功能障碍的相关性

目的分析外周血脂蛋白相关磷脂酶A2(Lp-PLA2)、成纤维细胞生长因子23(FGF23)水平变化与脑梗死后患者认知功能障碍的相关性。方法选取2019-04—2022-12邯郸市中心医院收治的160例脑梗死患者为研究对象,根据患者是否发生认知功能障碍分为认知障碍组和非认知障碍组,对比2组基线资料及外周血Lp-PLA2、FGF23水平,并采用Logistic回归分析患者发生认知功能障碍的影响因素,采用Pearson相关性分析外周血Lp-PLA2、FGF23与简易智力状态评价量表(MMSE)评分的关系,采用ROC曲线评估外周血Lp-PLA2、FGF23对脑梗死后患者认知功能障碍的预测价值。结果160例脑梗死患者中,48例(30.00%)发生认知功能障碍。认知障碍组患者的平均年龄、高血压、糖尿病、吸烟、文化程度、MMSE评分及血清Lp-PLA2、FGF23水平等方面与非认知障碍组相比,差异有统计学意义(P<0.05)。Logistic回归分析显示,年龄、高血压、糖尿病、吸烟、文化程度低及血清Lp-PLA2、FGF23水平升高是影响脑梗死后认知功能障碍发生的独立危险因素(P<0.05)。Pearson相关性分析显示,脑梗死患者血清Lp-PLA2、FGF23水平与MMSE评分呈负相关(P<0.05)。ROC曲线显示,Lp-PLA2的曲线下面积为0.770,FGF23的曲线下面积为0.779,联合检测的曲线下面积为0.873(P<0.05),表示两者联合检测可作为评价脑梗死后认知功能障碍的有效指标。结论Lp-PLA2、FGF23在脑梗死后认知功能障碍患者血清中均呈高表达,二者联合检测有助于提高对脑梗死后认知功能障碍的预测价值。

血清DKK1、FGF19联合CT在原发性肝癌患者介入治疗疗效评估中的应用价值

目的探讨血清Dickkopf-1(DKK1)、成纤维细胞生长因子19(FGF19)联合计算机断层扫描(CT)对原发性肝癌(PHC)患者经导管动脉栓塞化疗(TACE)的疗效评估价值。方法分别纳入2022年1月-2023年2月本院136例PHC患者,TACE治疗2个月后依据疗效分为灭活组(59例)与残留组(77例)。双抗体夹心法检测血清DKK1、FGF19水平,并对患者进行CT扫描。ROC曲线获取血清DKK1、FGF19诊断PHC患者TACE治疗后疗效的最佳截断值。以数字减影血管造影检查(DSA)为金标准,探讨血清DKK1、FGF19联合CT扫描对TACE治疗后疗效的诊断价值。采用Kappa检验分析血清DKK1、FGF19联合CT诊断PHC疗效与DSA结果一致性。结果残留组患者血清DKK1、FGF19水平分别为(2.41±0.33)ng/mL、(206.72±21.60)pg/mL,明显高于灭活组的(1.87±0.29)ng/mL、(169.57±18.45)pg/mL,差异有统计学意义(P<0.05)。ROC曲线显示,血清DKK1、FGF19水平诊断PHC患者TACE治疗后疗效的曲线下面积分别为0.925、0.916,敏感度为83.12%、84.42%,特异度为91.52%、94.92%。CT扫描评估PHC患者TACE治疗疗效与DSA结果一致性高,Kappa值=0.766(P<0.05)。血清DKK1、FGF19联合CT扫描诊断疗效的准确度为93.38%,敏感度、特异度为96.10%、89.83%,且联合检测的敏感度明显优于单独DKK1、FGF19、CT扫描(P<0.05)。结论血清DKK1、FGF19联合CT扫描对PHC患者TACE治疗后疗效有一定诊断价值。

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。

乳腺癌组织中bFGF、Ki-67及ADAM15表达情况及与其临床病理特征的相关性分析

目的 探讨乳腺癌组织中碱性成纤维细胞生长因子(bFGF)、Ki-67及去整合素金属蛋白酶15(ADAM15)表达情况及其与临床病理特征的关系。方法 选取87例乳腺癌患者作为研究对象,均行手术治疗,采集肿瘤标本及癌旁标本行免疫组化染色检查,比较肿瘤组织及癌旁组织内bFGF、Ki-67及ADAM15表达情况,并分析bFGF、Ki-67及ADAM15表达与其临床病理特征的关系。结果 肿瘤组织内bFGF、Ki-67及ADAM15阳性率高于癌旁组织,差异有统计学意义(P<0.05);bFGF阳性组肿瘤Ⅲ~Ⅳ期、有淋巴结转移、肿瘤直径≥3 cm占比高于bFGF阴性组,差异有统计学意义(P<0.05);Ki-67阳性组肿瘤Ⅲ~Ⅳ期、有淋巴结转移、肿瘤直径≥3 cm占比高于Ki-67阴性组,差异有统计学意义(P<0.05);ADAM15阳性组肿瘤Ⅲ~Ⅳ期、有淋巴结转移、肿瘤直径≥3 cm占比高于ADAM15阴性组,差异有统计学意义(P<0.05)。结论 bFGF、Ki-67及ADAM15在乳腺癌组织内存在较高阳性表达,且与肿瘤分期、淋巴结转移及肿瘤直径存在密切关系,或可作为完善乳腺癌治疗方案的新靶点。

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。

经钻孔引流术治疗慢性硬膜下血肿患者血清TSP1、TSP2、bFGF、VEGF、S-100β水平变化及其临床意义

目的探讨经钻孔引流术治疗慢性硬膜下血肿患者血清血小板反应蛋白1(TSP1)、血小板反应蛋白2(TSP2)、碱性成纤维细胞生长因子(bFGF)、血管内皮生长因子(VEGF)、中枢神经特异蛋白(S-100β)水平变化及其临床意义。方法选取江苏省中医院2019年1月~2023年6月收治的慢性硬膜下血肿患者142例作为病例组,均进行钻孔引流术;另选取同期健康体检人员146例作为健康对照组,比较两组不同脑损伤、手术前后、不同复发情况的血清TSP1、TSP2、bFGF、VEGF、S-100β水平,分析血清TSP1、TSP2、bFGF、VEGF、S-100β水平与慢性硬膜下血肿患者脑损伤程度的相关性。结果与健康对照组比较,病例组血清TSP1、TSP2、bFGF、VEGF、S-100β水平均相对更高;与轻度脑损伤组进行比较,中度脑损伤组、重度脑损伤组血清TSP1、TSP2、bFGF、VEGF、S-100β水平均相对更高,且重度脑损伤组高于中度脑损伤组;与术前进行比较,术后7 d慢性硬膜下血肿患者血清TSP1、TSP2、bFGF、VEGF、S-100β水平均相对较低;与复发组进行比较,未复发组血清TSP1、TSP2、bFGF、VEGF、S-100β水平均相对较低(P<0.05)。Pearson相关分析结果显示,慢性硬膜下血肿患者血清TSP1、TSP2、bFGF、VEGF、S-100β水平与GCS评分均呈负相关关系(r=-0.655、-0.674、-0.711、-0.689、-0.705,P<0.05)。结论慢性硬膜下血肿患者经钻孔引流术后血清TSP1、TSP2、bFGF、VEGF、S-100β水平均降低,并与患者脑损伤程度、转归具有高度相关性,临床上可通过检测慢性硬膜下血肿患者上述各项血清学指标的变化情况,以便及时判断慢性硬膜下血肿患者的脑损伤程度。

血清维生素D结合蛋白、FGF23、Klotho与乳腺癌骨转移的相关性分析

目的骨转移是乳腺癌常见的并发症之一,严重影响患者的生存和预后。本研究旨在探究血清维生素D结合蛋白(vitamin D⁃binding protein,VDBP)、成纤维细胞生长因子23(fibroblast growth factor 23,FGF23)和Klotho蛋白在乳腺癌骨转移中的表达及临床意义。方法收集95例来自本院2019⁃08⁃01至2021⁃08⁃01的女性乳腺癌患者作为研究对象,经影像学和组织病理学方式诊断是否发生骨转移,将患者分为骨转移组36例,非骨转移组59例。分析两组患者的临床病理特征;采集患者外周血样本,通过ELISA对血清中VDBP、FGF23和Klotho进行定量分析;使用Spearman相关分析进行指标间的关联性分析;Logistic回归分析乳腺癌发生骨转移的影响因素;ROC曲线分析血清VDBP、FGF23和Klotho水平预测乳腺癌发生骨转移的价值。结果骨转移和非骨转移乳腺癌病理分级比较有统计学意义(P<0.05)。骨转移和非骨转移乳腺癌患者血清中VDBP、FGF23及Klotho的水平依次为:(80.35±29.34)和(115.18±48.69)ng/mL、(658.35±201.19)和(405.36±154.42)pg/mL以及(155.82±40.29)和(229.35±72.46)pg/mL,两组比较差异有统计学意义(P<0.05)。Spearman相关性分析显示,骨转移乳腺癌患者血清中VDBP水平与乳腺癌病理分级相关(P<0.05);FGF23和Klotho水平与病理分级、是否骨痛以及转移部位有关(P<0.05)。VDBP、FGF23和Klotho水平均为乳腺癌骨转移发生的独立影响因素(P<0.05)。ROC曲线结果显示,VDBP、FGF23及Klotho预测乳腺癌患者发生骨转移的曲线下面积依次为:0.733、0.806、0.761,最佳截断值为:81.56 ng/mL、573.501 pg/mL和201.193 pg/mL;3个指标联合诊断的曲线下面积为0.820,高于单一指标诊断的曲线下面积。结论血清VDBP、FGF23及Klotho水平可作为乳腺癌骨转移的参考指标,在乳腺癌骨转移的临床诊断上具有一定应用前景。

冠心病患者血清bFGF、sTLT-1水平与支架置入术后再狭窄的关系

目的探讨冠心病患者血清碱性成纤维细胞生长因子(bFGF)、可溶性髓样细胞触发受体样转录因子1(sTLT-1)水平与支架置入术后支架内再狭窄(ISR)的关系。方法收集2020年1月至2022年3月收治的冠心病行支架置入术患者450例。根据术后1年复查是否发生ISR分为ISR组(41例)、非ISR组(409例)。比较ISR组与非ISR组一般资料、实验室相关指标、血清bFGF、sTLT-1水平;Pearson法分析冠心病支架置入术后ISR患者血清bFGF、sTLT-1水平的相关性;Logistic回归分析冠心病患者支架置入术后发生ISR的影响因素;ROC曲线分析血清bFGF、sTLT-1水平诊断冠心病患者支架置入术后发生ISR的临床价值。结果ISR组狭窄程度、植入支架数量、术前Gensini评分、血清sTLT-1、CRP水平显著高于非ISR组,支架直径、血清bFGF、CysC水平显著低于非ISR组(P<0.05);Ⅲ级组血清bFGF水平显著高于Ⅳ级组(P<0.05),Ⅲ级组血清sTLT-1水平显著低于Ⅳ级组(P<0.05);冠心病支架置入术后发生ISR的患者血清bFGF与sTLT-1水平呈负相关(R=-0.648,P<0.001);sTLT-1、CRP是冠心病患者支架置入术后发生ISR的危险因素,bFGF、CysC是保护因素(P<0.05);血清bFGF、sTLT-1两者联合诊断冠心病患者支架置入术后发生ISR的AUC为0.901,优于各自单独诊断(Z二者联合-bFGF=3.086、Z二者联合-sTLT-1=2.754,P=0.002、P=0.030),联合诊断的敏感度为89.80%,特异性为76.12%。结论冠心病支架置入术后发生ISR的患者血清bFGF水平下调,sTLT-1水平上调,二者均是ISR的影响因素,且联合诊断冠心病患者支架置入术后ISR的发生具有较高效能。

急性脑梗死神经功能缺损患者血清VEGF、TXA2、FGF4表达及其与预后的关联

目的 探讨急性脑梗死(ACI)神经功能缺损患者血清血管内皮生长因子(VEGF)、血栓素A2(TXA2)、成纤维细胞生长因子4(FGF4)水平的表达及其与预后的关联。方法 回顾性纳入2022年4月至2022年9月沧州市中心医院收治的ACI患者103例作为研究对象,采用美国国立卫生研究所卒中量表(NIHSS)评估患者神经功能缺损程度,根据严重程度分为3组,即轻度组(≤4分,n=28)、中度组(5~15分,n=59)、重度组(>15分,n=16),比较3组血清VEGF、TXA2、FGF4水平。同时,随访3个月,根据预后情况再分为两组,即预后良好组(改良Rankin量表≤2分,n=71)、预后不良组(改良Rankin量表>2分,n=32)。经单因素和多因素Logistic回归分析影响预后危险因素;采用Pearson法分析NIHSS评分与血清VEGF、TXA2、FGF4水平的相关性;采用受试者操作特征(ROC)曲线分析血清VEGF、TXA2、FGF4水平预测效能。结果 重度组血清VEGF、TXA2、FGF4水平分别为(364.67±40.11)、(312.11±36.01)、(351.51±57.48) pg/mL,均高于轻度组[(142.16±22.12)、(155.21±24.16)、(207.49±37.79) pg/mL]、中度组[(188.24±25.97)、(202.13±29.31)、(257.94±46.12) pg/mL],且中度组血清VEGF、TXA2、FGF4水平均高于轻度组,差异均有统计学意义(P<0.05)。预后良好组与预后不良组患者的饮酒史、吸烟史、糖尿病史、冠心病史、梗死部位比较,差异均无统计学意义(P>0.05);预后不良组患者的年龄大于预后良好组,入院时NIHSS评分、血清VEGF、TXA2、FGF4水平均高于预后良好组,差异均有统计学意义(P<0.05)。经多因素Logistic回归分析提示,NIHSS评分、血清VEGF、TXA2、FGF4水平是ACI患者预后的影响因素(P<0.05)。经Pearson法分析,NIHSS评分与血清VEGF、TXA2、FGF4水平均呈正相关(r=0.789、0.768、0.760,P<0.001)。ROC曲线提示,血清VEGF、TXA2、FGF4水平评估ACI预后的AUC(敏感度、特异度)分别为0.819(87.3%、81.2%)、0.872(100.0%、81.2%)、0.856(88.7%、84.4%),3者联合评估预后的AUC(敏感度、特异度)为0.962(100.0%、90.6%)。结论 随着ACI患者的神经功能缺损加重,血清VEGF、TXA2、FGF4水平呈增高趋势,3者与ACI神经功能缺损程度有关,且3项联合能够较好预测预后不良风险。

首发精神分裂症患者血清sTfR、FGF22水平与临床症状的关系及其诊断价值

目的探讨首发精神分裂症(FES)患者血清可溶性转铁蛋白受体(sTfR)及成纤维细胞生长因子22(FGF22)表达情况,分析二者与FES患者临床症状的关系并进行诊断价值分析。方法选取2021年3月至2023年2月在该院确诊的97例FES患者作为FES组,同期选取来该院体检的96例健康志愿者作为对照组。采用免疫透射比浊法检测sTfR水平,酶联免疫吸附试验(ELISA)检测FGF22水平,Spearman法分析FES患者血清中sTfR及FGF22水平与阳性与阴性病症量表(PANSS)评分及威斯康辛卡片分类测验(WCST)结果的相关性,受试者工作特征(ROC)曲线分析sTfR及FGF22水平对FES的临床诊断价值。结果两组在性别、年龄、体质量指数、受教育年限、饮酒史及吸烟史方面差异均无统计学意义(P>0.05),与对照组比较,FES组血清sTfR及FGF22水平均下降(P<0.05)。sTfR单独诊断FES的曲线下面积(AUC)为0.835,最佳截断值为4.606 mg/L,FGF22单独诊断FES的AUC为0.772,最佳截断值为208.333μg/L,二者联合诊断的AUC(0.921)大于sTfR单独诊断的AUC(Z=2.613,P=0.009)及FGF22单独诊断的AUC(Z=5.140,P<0.001);sTfR高水平组及FGF22高水平组的PANSS阳性症状评分、阴性症状评分、病理症状评分、总评分、WCST持续性错误数、错误应答数分别低于sTfR低水平组及FGF22低水平组(P<0.05),而WCST完成分类数、WCST正确应答数分别高于sTfR低水平组及FGF22低水平组(P<0.05);FES组中sTfR、FGF22水平与PANSS阳性症状评分、阴性症状评分、病理症状评分、总评分、WCST持续性错误数、WCST错误应答数均呈负相关(P<0.05),与WCST完成分类数及WCST正确应答数均呈正相关(P<0.05)。结论FES患者血清sTfR及FGF22水平下降,联合检测sTfR及FGF22水平对于FES的临床诊断具有重要意义。