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.

Over-expression of fibroblast growth factor receptor 3 in human hepatocellular carcinoma

AIM: To describe the significant over-expression of fibroblast growth factor receptor 3 (FGFR3), which is a signal transduction and cell proliferation related gene in hepatocellular carcinoma (HCC).METHODS: Following DNA microarray, Northern blot and quantitative real-time PCR were employed to confirm FGFR3 expression difference in HCC tissues and surrounding non-neoplastic liver tissue. FGFR3 expression levels were further determined by immunohistochemical study in 43 cases of HCC.RESULTS: Northern blot results showed the significant over-expression of FGFR3 in HCC tissues, which was consistent with that from DNA microarray. Quantitative real-time PCR demonstrated that the mean ratio of FGFR3 mRNA to glyceraldehyde-3-phosphate dehydrogenase (GADPH) mRNA in HCC tissue was 0.250, whereas the ratio in non-neoplastic liver tissue was 0.014. Statistical analyses of 43 cases of HCC revealed that HCC scored higher than the matched non-neoplastic liver tissues.Examination of clinicopathological features revealed a strong correlation of over-expression of FGFR3 with poor tumor differentiation and high nuclear grade.CONCLUSION: Over-expression of FGFR3 may play an important role in liver carcinogenesis. FGFR3 may be an ideal candidate as a molecular marker in the diagnosis of HCC and a potential therapeutic target.

Noggin versus basic fibroblast growth factor on the differentiation of human embryonic stem cells

The difference between Noggin and basic fibroblast growth factor for the neural precursor differen- tiation from human embryonic stem cells has not been studied. In this study, 100 tJg/L Noggin or 20 IJg/L basic fibroblast growth factor in serum-free neural induction medium was used to differen- tiate human embryonic stem cells H14 into neural precursors using monolayer differentiation. Two weeks after induction, significantly higher numbers of neural rosettes formed in the Noggin-induced group than the basic fibroblast growth factor-induced group, as detected by phase contrast micro- scope. Immunofluorescence staining revealed expression levels of Nestin, [3-111 Tubulin and Sox-1 were higher in the induced cells and reverse-transcription PCR showed induced cells expressed Nestin, Sox-1 and Neurofilament mRNA. Protein and mRNA expression in the Noggin-induced group was increased compared with the basic fibroblast growth factor-induced group. Noggin has a greater effect than basic fibroblast growth factor on the induction of human embryonic stem cell differentiation into neural precursors by monolayer differentiation, as Noggin accelerates and in- creases the differentiation of neural precursors.

EFFECTS OF TRANSFORMING GROWTH FACTOR β AND RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN 2 ON HUMAN PERIODONTAL LIGAMENT FIBROBLASTS

Objective To evaluate the effects of transforming growth factor β(TGF-β) and recombinant human bone morphogenetic protein 2 (rhBMP2) on human periodontal ligament fibroblasts (HPDLFs). Methods HPDLFs were done primary culture to detect the distinct concentrations of TGF-P and rhBMF2 on its proliferation, alkaline phosphatase (ALP) activity, osteocalcin (OC) synthesis and formation of the minerali-zed nodules, respectively. Results TGF-β (5～100ng/ml) significantly stimulated the proliferation of HPDLFs. The ALP activity of HPDLFs was evaluated evidently by 5ng/ml TGF-β. TGF-β( 0. 5 ～ 100ng/ml) had no effects on OC synthesis and formation of the mineralized nodules of HPDLFs. rhBMP2 (0. 25～2mg/ ml) had no remarkable effect on the proliferation of HPDLFs. The ALP activity, OC synthesis and forma-tion of the mineralized nodules of HPDLFs were significantly stimulated by 0. 5～ 2mg /ml rhBMP2. Conclusion The effects of TGF-β and rhBMP2 on HPDLFs are dose-dependent. TGF-P can stimulate HPDLFs to express the early marker of osteoblastic phenotype, and it lacks the ability to promote maturation of the osteogenic phenotype. rhBMP2 can not only stimulate the expression but also promote the maturation of osteoblas-tic phenotype of HPDLFs.

Role of Fibroblast Growth Factor 19 in Maintaining Nutrient Homeostasis and Disease

Fibroblast growth factor 19 （FGF19） is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. FGF19 plays a key role in coordination of liver bile acid biosynthesis and gallbladder motility, and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentration and reducing body weight.

Effect of charge at an amino acid of basic fibroblast growth factor on its mitogenic activity

The amino acid at the 119th position of human basic fibroblast growth factor(hbFGF),lysine(K119),is a critical component for its mitogenic activity.However,little is known about the effects of the characteristics of this residue including charge on the mitogenic activity of hbFGF.Herein,this basic residue was replaced with neutral glutamine residue and acidic glutamic acid residue to construct mutants hbFGF^(K119Q) and hbFGF^(K119E),respectively.The mutants were produced by BL21(DE3)/pET3c expression system...

The change of basic fibroblast growth factor and effect of prostacyclin in lung injury

In this study,the changes in activity and mRNA transcript of basic fibroblast growth fac-tor(bFGF)in lung injury and the effect of prostacyclin on the treatment of lung injury wereinvestigated.The result of the experiment revealed that there were not any bioactive bFGF andbFGF mRNA in the lung tissue of normal dogs.bFGF activity and bFGF mRNA were detectedonly in the injured lung tissue.Prostacyclin could slightly elevate the activity of bFGF andsignificantly elevate the level of bFGF mRNA.The findings suggest that(1)the level of bFGF in-creased after lung injury.(2)Prostacyclin could influence the expression of bFGF.(3)bFGF couldplay an important role in the repair of injury lung tissue.

Basic fibroblast growth factor increases the numbe of endogenous neural stem cells and inhibits the expression of amino methyl isoxazole propionic acid receptors in amyotrophic lateral sclerosis mice

This study aimed to investigate the number of amino methyl isoxazole propionic acid （AMPA） receptors and production of endogenous neural stem cells in the SOD1 G93AG1H transgenic mouse model of amyotrophic lateral sclerosis, at postnatal day 60 following administration of basic fibroblast growth factor （FGF-2）. A radioligand binding assay and immunohistochemistry were used to estimate the number of AMPA receptors and endogenous neural stem cells respectively. Results showed that the number of AMPA receptors and endogenous neural stem cells in the brain stem and sensorimotor cortex were significantly increased, while motor function was significantly decreased at postnatal days 90 and 120. After administration of FGF-2 into mice, numbers of endogenous neural stem cells increased, while expression of AMPA receptors decreased, whilst motor functions were recovered. At postnatal day 120, the number of AMPA receptors was negatively correlated with the number of endogenous neural stem cells in model mice and FGF-2-treated mice. Our experimental findings indicate that FGF-2 can inhibit AMPA receptors and increase the number of endogenous neural stem cells, thus repairing neural injury in amyotrophic lateral sclerosis mice.

Exogenous acid fibroblast growth factor inhibits ischemia-reperfusion-induced damage in intestinal epithelium via regulating P53 and P21WAF-1 expression

AIM： To detect the effect of acid fibroblast growth factor （aFGF） on P53 and P21WAF-1 expression in rat intestine after ischemia-reperfusion （I-R） injury in order to explore the protective mechanisms of aFGF. METHODS： Hale rats were randomly divided into four groups, namely intestinal ischemia-reperfusion group （R）, aFGF treatment group （A）, intestinal ischemia group （I）, and sham-operated control group （C）. In group I, the animals were killed after 45 min of superior mesenteric artery （SHA） occlusion. In groups R and A, the rats sustained for 45 min of SHA occlusion and were treated with normal saline （0.15 mL） and aFGF （20 μg/kg, 0.15 mL）, then sustained at various times for up to 48 h after reperfusion. In group C, SHA was separated, but without occlusion. Apoptosis in intestinal villi was determined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling technique （TUNEL）. Intestinal tissue samples were taken not only for RT- PCR to detect P53 and P21WAF-1 gene expression, but also for immunohistochemical analysis to detect P53 and P21WAF-1 protein expression and distribution. RESULTS： In histopathological study, ameliorated intestinal structures were observed at 2, 6, and 12 h after reperfusion in A group compared to R group. The apoptotic rates were （41.17±3.49）%, （42.83±5.23）%, and （53.33±6.92）% at 2, 6, and 12 h after reperfusion, respectively in A group, which were apparently lower than those in R group at their matched time points （50.67±6.95）%, （54.17±7.86）%, and （64.33±6.47）%, respectively, （P〈0.05））. The protein contents of P53 and P21WAF-1 were both significantly decreased in A group compared to R group （P〈0.05） at 2-12 h after reperfusion, while the mRNA levels of P53 and P21VVAF-1 in A group were obviously lower than those in R group at 6-12 h after reperfusion （P〈0.05）. CONCLUSION： P53 and P21WAF-1 protein accumulations are associated with intestinal barrier injury induced by I-R insult, while intravenous aFGF can alleviate apoptosis of rat intestinal cells by inhibiting P53 and P21WAF-1 protein expression.

血清成纤维细胞生长因子21和脂肪酸结合蛋白4检测对急性ST段抬高型心肌梗死患者经皮冠状动脉介入治疗术后心力衰竭的预测价值

目的探究血清成纤维细胞生长因子21(FGF21)和脂肪酸结合蛋白4(FABP4)检测对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后心力衰竭的预测价值。方法选取2020年9月至2022年9月内蒙古医科大学附属医院接诊的113例STEMI患者为研究对象,依据PCI术后1年是否发生心力衰竭(心衰),将其分为心衰组(n=32)和非心衰组(n=81)。应用ELISA法测定血清FGF21、FABP4表达水平,比较两组血清FGF21、FABP4水平,多因素logistic回归分析影响STEMI患者PCI术后发生心力衰竭的相关因素,ROC曲线评估血清FGF21、FABP4水平对STEMI患者PCI术后心力衰竭发生的预测价值。结果心衰组心率次数、C反应蛋白(CRP)、心肌肌钙蛋白(cTnI)、N末端B型利钠肽原(BNP)、利尿剂使用比例均显著高于非心衰组,左心室射血分数(LVEF)显著低于非心衰组(P<0.05)。心衰组血清FGF21、FABP4表达水平均明显高于非心衰组[(228.37±33.07)ng/L比(185.68±25.52)ng/L、(34.26±5.51)ng/ml比(26.87±4.67)ng/ml,t=7.345、7.195,P<0.05]。血清FGF21(95%CI 1.371~8.191)、FABP4(95%CI 1.176~4.090)及发病到至导丝通过时间(95%CI 1.058~8.157)是影响STEMI患者PCI术后发生心力衰竭的危险因素(OR>1,P<0.05),LVEF(95%CI 0.473~0.913)是保护因素(OR<1,P<0.05)。血清FGF21、FABP4单独及二者联合预测STEMI患者PCI术后发生心力衰竭的曲线下面积(AUC)分别为0.828、0.856、0.934,二者联合优于单一(Z二者联合-FGF21=1.971、Z二者联合-FABP4=2.417,P=0.048、P=0.015)。结论STEMI患者PCI术后发生心力衰竭血清FGF21、FABP4水平均明显升高,二者联合对STEMI患者PCI术后发生心力衰竭的风险具有更高的预测价值。

枇杷叶三萜酸联合重组人表皮生长因子对激素依赖性皮炎豚鼠皮肤屏障功能的修复及免疫失衡的影响

目的 观察枇杷叶三萜酸(TAL)联合重组人表皮生长因子(rh-EGF)对激素依赖性皮炎(HDD)豚鼠模型皮肤屏障功能修复及免疫失衡的影响。方法 选取40只无特定病原(SPF)级豚鼠,随机分为对照组、模型组、rh-EGF组、TAL组和联合组,每组各8只。除对照组外,其他各组涂抹0.05%卤米松乳膏,连续45 d,构建HDD模型。构建成功后,rh-EGF组涂抹rh-EGF凝胶,TAL组涂抹TAL溶液,联合组涂抹TAL和rh-EGF凝胶,对照组和模型组涂抹生理盐水,共15 d。记录各组临床症状并打分;检测经皮水分丢失(TEWL)、角质层含水量(WCSC)和皮脂量(SC);HE染色观察各组豚鼠皮肤组织病理变化;采用酶联免疫吸附测定(ELISA)法检测总免疫球蛋白E(IgE)、白细胞介素-4(IL-4)、干扰素-γ(IFN-γ)水平。结果 与对照组比较,模型组症状明显、皮肤组织损坏严重,TEWL增加,WCSC和SC减少;免疫因子Ig E和IL-4水平升高、IFN-γ水平降低(P<0.05)。与模型组比较,rh-EGF组、TAL组和联合组用药后临床症状减轻、皮肤组织损伤不明显;TEWL减少,WCSC和SC增加,免疫因子IgE和IL-4水平降低、IFN-γ水平升高(P<0.05)。且联合组与rh-EGF组和TAL组比较,作用效果更加明显(P<0.05)。TAL组和联合组各指标比较,差异无统计学意义(P>0.05)。结论 TAL联合rh-EGF可有效缓解HDD豚鼠的临床症状,改善皮肤细胞损伤,修复皮肤屏障功能,提升免疫能力。

复方桐叶烧伤油联合重组人碱性成纤维细胞生长因子凝胶治疗喉癌术后咽漏的疗效研究

目的研究喉癌术后咽漏患者应用复方桐叶烧伤油联合重组人碱性成纤维细胞生长因子凝胶(rh-bFGF)治疗的疗效。方法选取2018年1月至2022年12月本院收治的行喉癌切除术后咽漏患者60例,采用随机数字表法分为治疗组和对照组,每组30例。治疗组使用复方桐叶烧伤油联合rh-bFGF纱条进行局部换药,对照组仅使用rh-bFGF纱条进行局部换药。评估咽漏疗效、治愈时间和费用。结果治疗组患者显效率[46.67%(14/30)]、总有效率[96.67%(29/30)]与对照组[30.00%(9/30)和86.67%(26/30)]比较,差异均无统计学意义(P>0.05)。治疗组患者治疗后血清白细胞介素6水平[(16.56±4.26)pg/L]均低于治疗前[(53.96±6.28)pg/L]与对照组[(24.35±3.61)pg/L],术后住院费用[(57817.7±2203.7)元]明显少于对照组[(61915.5±1972.9)元],住院时间[(19.27±2.35)d]明显短于对照组[(24.77±2.16)d],差异均有统计学意义(P<0.05)。结论复方桐叶烧伤油联合rh-bFGF治疗喉癌术后咽漏效果与常规使用rh-bFGF相当,可促进愈合,减轻炎症反应,且与常规使用rh-bFGF比较,可缩短住院时间和费用,具有较好的临床获益,值得推广应用。

附子理中汤通过FXR-FGF15通路影响非酒精性脂肪肝胆汁酸代谢

目的探讨附子理中汤对非酒精性脂肪性肝病(NAFLD)大鼠胆汁酸(TBA)代谢和肝脏损伤的影响及其机制。方法采用脂肪乳灌胃大鼠,连续4周,构建NAFLD动物模型。造模后用附子理中汤和阳性药物干预治疗,将大鼠分为对照组、模型组、附子理中汤组和阳性药物组。HE染色观察肝脏的病理变化,生化分析法检测高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、游离脂肪酸(NEFA)的含量,Western blot检测回肠组织中法尼酯X受体(FXR)、成纤维细胞生长因子15(FGF15)的蛋白表达和肝脏组织中FXR的蛋白表达,RT-PCR检测回肠组织中FXR、FGF15的mRNA表达和肝脏组织中FXR的mRNA表达,ELISA检测肝组织TBA水平。结果与对照组比较,模型组大鼠肝脏出现严重病理损伤,血清中HDL-C含量下降,LDL-C和NEFA含量增加(均P<0.01),大鼠肝脏组织中FXR蛋白、mRNA表达和回肠组织中FXR、FGF15的蛋白、mRNA表达上升(均P<0.01),肝组织中TBA水平下降(P<0.01)。与模型组比较,附子理中汤组和阳性药物组大鼠肝脏病理损伤缓解,HDL-C含量增加,LDL-C和NEFA含量下降(均P<0.05),大鼠肝组织中FXR蛋白、mRNA表达和回肠组织中FXR、FGF15蛋白、mRNA表达下降(P<0.05),肝组织中TBA水平增加(P<0.01)。结论附子理中汤治疗可通过激活回肠FXR-FGF15信号,增加肝脏TBA代谢,缓解NAFLD引起的肝损伤。

Expression and effect of basic fibroblast growth factor on human cataract lens epithelial cells

OBJECTIVE: To detect the expression of basic fibroblast growth factor (bFGF) in human ocular tissues, and to assess the effect of bFGF on the proliferation of human cataract lens epithelial cells (LECs) and its correlation with age. METHODS: Enucleated eyes were subjected to immunostaining for bFGF protein. Human cataract LECs were cultured in vitro, and treated with bFGF for 48 hr. Proliferation was estimated by the positive area ratio of proliferating cell nuclear antigen (PCNA) in immunohistochemistry. RESULTS: bFGF protein was found in various human ocular tissues. bFGF stimulated human cataract LEC proliferation, and there was an age-related decrease in responsiveness of human cataract LECs to bFGF (P

牛磺熊去氧胆酸通过调节内质网应激抑制转化生长因子β1所诱导的心肌成纤维细胞纤维化

目的探讨牛磺熊去氧胆酸(TUDCA)对转化生长因子β1(TGF-β1)所诱导的心肌成纤维细胞(CFs)活化的作用及相关机制,为TUDCA治疗糖尿病心肌纤维化提供新的治疗目标。方法提取原代SD乳鼠CFs和心肌细胞,通过免疫荧光法鉴定CFs的纯度。分别将高糖培养下的CFs用不同时间的TGF-β1干预,用Western blot检测内质网应激(ERS)通路相关蛋白和纤维化指标的表达,探讨TGF-β1对CFs活化及ERS相关通路的影响。用Western blot检测CFs和心肌细胞内同型半胱氨酸内质网应激泛素样结构域1(Herpud1)的表达情况。通过沉默Herpud1的表达及用Transwell和Western blot检测沉默Herpud1后CFs纤维化指标的表达,探讨Herpud1在TGF-β1诱导的CFs活化中的作用。用CCK-8检测不同浓度的TUDCA处理下CFs的活力。用免疫荧光和Western blot检测TUDCA对TGF-β1诱导的CFs中Herpud1、葡萄糖调节蛋白78(GRP78)、转录激活因子6(ATF6)、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)和Ⅰ型胶原蛋白(CollagenⅠ)表达的影响。为进一步明确Herpud1在TUDCA抑制CFs活化中的作用,用Western blot检测过表达Herpud1后相关蛋白的表达情况。结果在成功构建CFs纤维化模型的基础上,TGF-β1能够诱导CFs活化及ERS通路相关蛋白的表达;Herpud1在CFs中的表达高于心肌细胞;敲除Herpud1可抑制TGF-β1所诱导的CFs活化;TUDCA能显著降低TGF-β1诱导的CFs中GRP78、ATF6、α-SMA、Vimentin和CollagenⅠ的表达水平;此外,过表达Herpud1还可逆转TUDCA对TGF-β1诱导的CFs活化的抑制。结论下调Herpud1基因的表达是TUDCA抑制TGF-β1诱导的CFs纤维化的机制之一。

大隐静脉高位结扎联合泡沫硬化剂注射术+外用重组人酸性成纤维细胞生长因子治疗重度静脉曲张合并溃疡患者的临床疗效

目的探讨大隐静脉高位结扎联合泡沫硬化剂注射术+外用重组人酸性成纤维细胞生长因子治疗重度静脉曲张合并溃疡患者的临床疗效。方法收集2018年1月至2023年6月解放军联勤保障部队第九〇〇医院收治的60例大隐静脉曲张患者的临床资料,按照治疗方式的不同将其分为对照组(n=30)与观察组(n=30),两组患者均采用大隐静脉高位结扎联合泡沫硬化剂注射术,对照组溃疡创面采用碘伏和生理盐水常规换药,观察组溃疡创面采用外用重组人酸性成纤维细胞生长因子治疗。比较两组患者手术时间、术中出血量、住院时间、住院费用、术后并发症的发生情况、治疗前后溃疡面积、溃疡愈合时间、疼痛数字评价量表(NRS)评分以及患者对诊疗过程的满意度。结果观察组患者住院时间短于对照组患者,差异有统计学意义(P﹤0.05)。术后第7天,两组患者溃疡面积均小于本组术前,且观察组患者溃疡面积小于对照组患者,差异均有统计学意义(P﹤0.05)。观察组患者溃疡愈合时间短于对照组患者,差异有统计学意义(P﹤0.05)。术后第14天,两组患者NRS评分均低于本组术前,且观察组患者NRS评分低于对照组患者,差异均有统计学意义(P﹤0.05)。观察组患者满意度评分高于对照组患者,差异有统计学意义(P﹤0.05)。结论大隐静脉高位结扎联合泡沫硬化剂注射术+外用重组人酸性成纤维细胞生长因子可显著促进下肢静脉性溃疡创面的愈合,明显缩短溃疡愈合时间、住院时间,缓解患者下肢疼痛程度,提高患者的诊疗满意度,值得在临床上进一步推广应用。

β-珠蛋白生成障碍性贫血患者血清FABP4,FGF19水平表达及与预后的关系

目的研究β-珠蛋白生成障碍性贫血(beta-thalassaemia,β-TM)患者血清脂肪酸结合蛋白4(fatty acidbindingprotein 4,FABP4)、纤维细胞生长因子19(fibroblast growth factor 19,FGF19)表达及其与预后的关系。方法选取2018年1月~2020年8月重庆大学附属黔江医院诊治的112例β-珠蛋白生成障碍性贫血患者为病例组,选取同期体检的60例健康人为对照组。采用酶联免疫吸附实验(ELISA)检测血清FABP4和FGF19水平。Logistic回归模型分析β-珠蛋白生成障碍性贫血患者预后影响因素。受试者工作特征(ROC)曲线分析血清FABP4和FGF19对β-珠蛋白生成障碍性贫血患者预后的预测价值。结果病例组患者血清FABP4(67.13±11.35μg/L)水平高于对照组(22.01±4.16μg/L),血清FGF19(104.24±21.46 ng/L)水平低于对照组(218.01±36.79 ng/L),差异均具有统计学意义(t=29.708,25.620,均P<0.05)。轻型组、中间型组及重型组患者血清FABP4水平(54.20±12.63μg/L,66.83±10.5μg/L,79.72±11.05μg/L)依次升高,而FGF19水平(122.53±22.36 ng/L,103.16±20.37 ng/L,86.53±18.14 ng/L)依次降低,差异具有统计学意义(F=39.701,24.231,均P<0.05)。相比于生存组,死亡组患者血清FGF19(62.80±22.09 ng/L vs 110.16±20.69 ng/L),血红蛋白、杂合子基因型比例(βCD17/βN,βCD41-42/βN)较低,而血清FABP4(116.69±12.30 ng/L vs 60.05±10.17 ng/L),铁蛋白及心脏增大比例较高,差异具有统计学意义(t/χ^(2)=4.436~18.981,均P<0.05)。FGF19(OR=0.634,95%CI:0.451~0.891)是β-珠蛋白生成障碍性贫血患者预后的独立保护因素(P<0.001),血清FABP4(OR=1.840,95%CI:1.193~2.838)为预后独立危险因素(P<0.001)。血清FABP4,FGF19联合对β-珠蛋白生成障碍性贫血患者预后评估的曲线下面积(95%CI)为0.897(0.853~0.951),大于单指标检测0.842(0.801~0.879)和0.814(0.762~0.858),差异具有统计学意义(Z=4.864,5.270,P=0.002,0.001)。结论β-珠蛋白生成障碍性贫血患者血清FABP4升高,FGF19降低。血清FABP4,FGF19联合检测对β-珠蛋白生成障碍性贫血患者预后具有较高的预测价值。

新生血管形成过程中miR-296-5p对FGF23的调控作用

目的研究miR-296-5p通过调节成纤维细胞生长因子23(FGF23)在新生血管生成过程中发挥的调控作用。方法用血管内皮生长因子(VEGF)诱导人脐静脉内皮细胞(HUVECs),构建模拟新生血管形成的体外模型,通过RT-qPCR比较对照组与新生血管组中miR-296-5p的表达水平。通过细胞转染构建miR-296-5p高表达组、miR-296-5p低表达组以及对照组细胞,比较3组细胞的迁移和成管能力,并通过蛋白免疫印迹实验比较3组FGF23的表达水平。结果与未经处理的对照组相比,VEGF诱导的新生血管组中miR-296-5p的表达水平显著增加(P<0.001)。与对照组比较,miR-296-5p低表达组的迁移距离和成管数均降低(P<0.001和P<0.05);而miR-296-5p高表达组的迁移距离和成管数均增加(P<0.001和P<0.01)。与对照组比较,miR-296-5p低表达组的FGF23表达水平明显降低(P<0.01);而miR-296-5p高表达组FGF23表达水平明显升高(P<0.01)。结论miR-296-5p可通过上调FGF23的表达促进新生血管生成。

含重组人碱性成纤维细胞生长因子和重组人骨形态发生蛋白-2骨水泥在骨质疏松性腰椎压缩性骨折治疗的应用价值

目的:探讨含重组人碱性成纤维细胞生长因子(recombinant human basic fibroblast growth factor,rhbFGF)和重组人骨形态发生蛋白-2(recombinant human bone morphogenetic protein-2,rhBMP-2)骨水泥在骨质疏松性腰椎压缩性骨折(osteoporotic vertebral compression fracture,OVCF)患者经皮椎体后凸成形术(percutaneous kyphoplasty,PKP)治疗的应用价值。方法:回顾性分析2018年1月至2021年1月收治的103例行PKP手术治疗的OVCF患者,男40例,女63例;年龄61~78(65.72±3.29)岁。受伤原因:滑倒33例,跌倒42例,提重物受伤28例。根据填充骨水泥不同分为3组:磷酸钙组34例,男14例,女20例,年龄(65.1±3.3)岁,填充磷酸钙骨水泥;rhBMP-2组34例,男12例,女22例,年龄(64.8±3.2)岁,填充含rhBMP-2的骨水泥;rhbFGF+rhBMP-2组35例,男14例,女21例,年龄(65.1±3.6)岁,填充含rhbFGF和rhBMP-2的骨水泥。比较3组Oswestry功能障碍指数(Oswestry dysfunction index,ODI)、骨密度、椎体前缘丢失高度、伤椎前缘压缩率、疼痛视觉模拟评分(visual simulation score,VAS)及再骨折发生率。结果:所有患者获得12个月随访。3组术后ODI、VAS呈下降(P<0.001),骨密度增高(P<0.001),椎体前缘丢失高度、伤椎前缘压缩率呈先下降后缓慢上升趋势(P<0.001),rhbFGF+rhBMP-2组术后第1、6、12个月ODI、VAS均低于rhBMP-2组和磷酸钙组(P<0.05),术后第6、12个月骨密度大于rhBMP-2组和磷酸钙组(P<0.05)。rhbFGF+rhBMP-2组术后第6、12个月椎体前缘丢失高度、伤椎前缘压缩率均低于rhBMP-2组和磷酸钙组(P<0.05)。3组再骨折发生率比较差异无统计学意义(P>0.05)。结论:含rhbFGF和rhBMP-2骨水泥可更有效地增加OVCF患者骨密度,获得术后满意的临床和放射学效果,显著改善临床症状。

桦木酸通过Wnt/β-catenin信号通路调控瘢痕疙瘩成纤维细胞增殖、侵袭和胶原合成

目的研究桦木酸(betulinic acid,BA)对瘢痕疙瘩成纤维细胞增殖、侵袭和胶原合成的影响并探讨分子作用机制。方法收集临床切除的瘢痕疙瘩组织,采取组织块贴壁法分离培养成纤维细胞。细胞分为3组:空白对照组、二甲基亚砜(dimethyl sulfoxide,DMSO)处理组(溶剂对照组)和BA处理组。细胞计数试剂盒-8(cell counting kit-8,CCK-8)法检测细胞生长。5-乙炔基-2’-脱氧尿苷(5-ethynyl-2’-deoxyuridine,EdU)法检测细胞增殖。流式细胞术检测细胞凋亡。Transwell法测细胞侵袭。荧光素酶报告基因实验检测Wnt/β-catenin信号通路活性。实时定量PCR(real-time quantitative PCR,RT-qPCR)检测c-myc和cyclin D1 mRNA表达。Western blot检测Ⅰ型胶原(Collagen typeⅠ,ColⅠ)、β-catenin、c-myc和cyclin D1蛋白表达。结果与空白对照组和DMSO处理组相比,BA处理组瘢痕疙瘩成纤维细胞增殖降低,细胞凋亡率上升,细胞侵袭水平下降,胶原合成减少,差异有统计学意义(P<0.05)。与空白对照组和DMSO处理组相比,BA处理组瘢痕疙瘩成纤维细胞中Wnt/β-catenin信号通路活性降低,β-catenin、c-myc和cyclin D1表达水平减少,差异有统计学意义(P<0.05)。结论桦木酸通过下调Wnt/β-catenin信号通路抑制瘢痕疙瘩成纤维细胞增殖、侵袭和胶原合成。