Variation in Expression of Insulin-like Growth Factors( IGFs) System Genes in Ovarian and Uterine Tissues of Aging Rats

Variations in expression of insulin-like growth factors （IGFs） system genes in rat ovarian and uterine tissues were investigated by real-time quantitative PCR amplification using RT2 ProfilerTM PCR Array Rat Insulin Signaling Pathway （PARN-030A） chips. According to results of gene detection, a total of 15 differeutially expressed genes were screened in ovarian tissues, including 3 upregulated genes and 10 downregulated genes; a total of 22 differentially expressed genes were screened in uterine tissues, including 5 upregulated genes and 17 downregulated genes. These differentially expressed genes might be related to the insulin resistance.

Clinical Evaluation of Platelet Rich Growth Factors (PRGFS) in Treatment of Temporomandibular Joint Disc Displacement—Study Report

Objective: The aim of the study was to evaluate the effect of platelet rich growth factors (PRGFs) in treatment of temporomandibular joint disc displacement. Materials and Methods: The study subjects included 8 females having bilateral anterior disc displacement with reduction and 1 female having bilateral anterior disc displacement without reduction with the age range between 20 - 35 years. The process of obtaining PRGFs was carried out following the Anitua Technique. Results: Clinical parameters of Interincisal distance, Lateral excursion of mandible using digital caliper in millimeters and Visual Analogue Scale (VAS 0/10) for pain intensity score were used. All of these parameters were running through the intervals of two, four, and eight weeks till the end of the follow-up period at twenty-six weeks (six months). The participated patients showed the clinical improvement in the different clinical statuses such as interincisal distance;lateral excursion of mandible and Pain Score. Conclusion: the study reported early efficacy of PRGFs after the arthrocentesis of the joint in treatment of TMJ disc displacement, and according to our results, the injection of PRGFs could be a possible alternative treatment for patients who did not respond to standard treatment.

Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia

After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain 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.

Exploring the mechanistic role of epidermal growth factor receptor activation in non-cancer kidney disease

The epidermal growth factor receptor(EGFR)is a transmembrane glycoprotein that plays a crucial role in signal transduction and cellular responses.This review explores the function of EGFR in kidney physiology and its implications for various kidney diseases.EGFR signaling is essential for kidney function and repair mechanisms,and its dysregulation significantly impacts both acute and chronic kidney conditions.The review discusses the normal distribution of EGFR in kidney tubular segments,the mechanism of its activation and inhibition,and the therapeutic potential of EGFR-targeting antagonists and ligands.Additionally,it explores the pathophysiological characteristics observed in rodent models of kidney diseases through pharmacological and genetic inhibition of EGFR,highlighting therapeutic challenges and limitations such as species differences,variability in disease models,and potential adverse effects.Overall,the findings underscore the multifaceted role of EGFR in kidney diseases,influencing inflammation,fibrosis,and tissue injury.This complex involvement suggests that targeting EGFR may be a beneficial therapeutic strategy for managing these conditions,potentially mitigating inflammation and fibrosis while promoting tissue repair.

Overall survival with frontline vs subsequent anti-epidermal growth factor receptor therapies in unresectable,RAS/BRAF wild-type,leftsided metastatic colorectal cancer

BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.

Coaxial electrohydrodynamic printing of core–shell microfibrous scaffolds with layer-specific growth factors release for enthesis regeneration

The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues.Herein,a tri-layered core–shell microfibrous scaffold with layer-specific growth factors(GFs)release is developed using coaxial electrohydrodynamic(EHD)printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair.Stromal cell-derived factor-1(SDF-1)is loaded in the shell,while basic fibroblast GF,transforming GF-beta,and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner.Correspondingly,the tri-layered microfibrous scaffolds have a core–shell fiber size of(25.7±5.1)μm,with a pore size sequentially increasing from(81.5±4.6)μm to(173.3±6.9)μm,and to(388.9±6.9μm)for the tenogenic,chondrogenic,and osteogenic instructive layers.A rapid release of embedded GFs is observed within the first 2 d,followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks.The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte,chondrocyte,and osteocyte phenotypes in vitro.When implanted in vivo,the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients.Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.

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.

Discrete Choice Analysis of Temporal Factors on Social Network Growth

Social networks like Facebook, X (Twitter), and LinkedIn provide an interaction and communication environment for users to generate and share content, allowing for the observation of social behaviours in the digital world. These networks can be viewed as a collection of nodes and edges, where users and their interactions are represented as nodes and the connections between them as edges. Understanding the factors that contribute to the formation of these edges is important for studying network structure and processes. This knowledge can be applied to various areas such as identifying communities, recommending friends, and targeting online advertisements. Several factors, including node popularity and friends-of-friends relationships, influence edge formation and network growth. This research focuses on the temporal activity of nodes and its impact on edge formation. Specifically, the study examines how the minimum age of friends-of-friends edges and the average age of all edges connected to potential target nodes influence the formation of network edges. Discrete choice analysis is used to analyse the combined effect of these temporal factors and other well-known attributes like node degree (i.e., the number of connections a node has) and network distance between nodes. The findings reveal that temporal properties have a similar impact as network proximity in predicting the creation of links. By incorporating temporal features into the models, the accuracy of link prediction can be further improved.

Skeletal myoblast based delivery of angiogenic growth factors:a comparison between angiopoietin-1 and VEGF gene delivery for therapeutic angiogenesis in the heart

Objectives This study investigated the efficacy of human skeletal myoblasts (SkM) mediated either human vascular endothelial growth factor-165 (hVEGF165) or angiopoietin-1 (Ang-1) on vascular development and myocardial regional perfusion. Methods A porcine heart model of chronic infarction was created in 28 female swine by coronary artery ligation. The animals were randomized into: (1) group-1, DMEM injected (n=6), (2) group-2, Ad-null transduced SkM transplanted (n=6), (3) group-3, Ad-hVEGF165 transduced SkM transplanted (n=8), and (4) group-4, Ad-Ang-1 transduced SkM (n=8). Three weeks later, 5 ml DMEM containing 3×108 SkM carrying exogenous genes were intramyocardially injected into 20 sites in left ventricle in groups-2, -3 and -4. Animals in group-1 were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted at 2, 6 and 12 weeks after transplantation for histological studies. Results Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density based on Von Willebrand factor-VIII (vWF-VIII) at low power field (×100) was 57.13±11.85 in group-3 at 6 weeks and declined to 32.1±5.21 at 12 weeks, while it was 39.9±10.26 at 6 weeks and increased to 45.14±6.54 at 12 weeks in group-4. The mature blood vessel index was highest in group- 4 at 6 and 12 weeks after transplantation. The regional blood flow in the center and peri-infarct area was significantly increased in animals of groups-3 and -4. Conclusions SkM carrying either hVEGF165 or Ang-1 induced neovascularization with increased blood flow. Ang-1 overexpression resulted in mature and stable blood vessel formation and may be a more potent arteriogenic inducer for neovascularization.

Effects of Environmental Factors on Tomato Growth

[Objective] This study was conducted to evaluate the effects of environmental factors on the biological characteristics of tomatoes.[Method] The growth traits such as plant height,stem diameter,leaf shape index of tomato plants grown under different environmental conditions（temperature,light and soil moisture content）were measured and compared.[Result] The effect of light on tomatoes was higher than that of soil moisture in high-temperature environment（30 ℃ or higher）;while the speed of tomato plant growth and fruit development were improved by low light.The synthesis of chlorophyll was influenced by soil moisture and light,and greater impact of soil water content on the synthesis of chlorophyll was observed.Among the three treatments,the chlorophyll content of all the three tomato cultivars was in a descending order as follows：control〉 shading treatment〉 drought treatment.[Conclusion] This study will provide references for the control of temperature,light and soil water in tomato cultivation.

Analysis on Characters and Growth Factors of academicians of Agriculture Faculty of Chinese Academy of Engineering

The research analyzed birthplace, work site and Work unit, discipline, agri- cultural product variety, current age, and selected age, as well as internal and exter- nal factors for growth, which providers references for exploring development of high- level agricultural S＆T talents and formulation of relevant policies.

Growth and Influencing Factors of Three Native Tree Species in Coastal Casuarina equisetifolia Plantation

[Objective] The aim was to study the growth and environment factors of three native tree species（Thespesia lampas,Calophyllum inophyllum and Hernandia sonora）in Hainan in coastal Casuarina equisetifolia plantation.[Method] The coastal sandy soil was treated by adding wood chips,bagasse and the control without adding anything in the plant pits.The growth of three native tree species planted for one year was analyzed.[Result] ① One year later,the survival rate showed an order of T.lampasH.sonoraC.inophyllum;the net increase of basal diameter showed an order of H.sonoraT.lampasC.inophyllum;while the net increase of plant height showed an order of T.lampasC.inophyllumH.sonora.The difference of survival rate between T.lampas and C.inophyllum was extremely significant,the difference of survival rate between H.sonora and C.inophyllum was significant,but the survival rate between T.lampas and H.sonora showed no significant difference.The difference on net growth of plant height among T.lampas,C.inophyllum and H.sonora was extremely significant,and the different on the net growth of basal diameter between T.lampas and C.inophyllum was significant.② Among different soil treatments,the survival rate of three native tree species in the treatment by adding wood chips,bagasse were higher than the treatment without adding anything,and the difference of survival rate of T.lampas between the treatment by adding wood chips,bagasse and the treatment without adding anything was extremely significant,but the treatment by adding wood chips and bagasse had not significant difference.③ The growth of three native tree species showed some correlation with environment factors（∣r∣0.3）.The survival rate of T.lampas showed higher correlation with soil pH value and soil moisture,and the basal diameter and height of T.lampas showed some correlation with soil pH value and soil temperature.The survival rate of C.inophyllum showed higher correlation with soil pH value,soil temperature and light intensity,while the basal diameter and height of C.inophyllum showed some correlation with soil temperature.The survival rate of H.sonora showed higher correlation with soil salinity and soil temperature,while the basal diameter and height of H.sonora showed some correlation with soil temperature.The basal diameter and height of three native tree species had higher correlation（r0.5）,which had reached a significant level.[Conclusion] In the one-year growth period in C.equisetifolia forest,the native tree species of T.lampas grew best and it was the most potential forest species mixed with C.equisetifolia.

颅内动脉瘤术后患者血清VEGFs、MMPs表达水平特征及对预后的预测效能

目的探讨颅内动脉瘤术后患者血清血管内皮生长因子(VEGFs)、基质金属蛋白酶(MMPs)水平特征及对预后的预测效能。方法选取2021年12月—2023年12月就诊于新疆维吾尔自治区人民医院神经外科的颅内动脉瘤术后患者121例作为研究对象,根据术后1个月预后情况将患者分为预后良好组(n=92)和预后不良组(n=29)。采用化学发光免疫测定法检测2组患者血清VEGFs、MMPs表达谱水平;Spearman相关性分析血清VEGFs、MMPs水平与颅内动脉瘤术后患者预后不良的相关性;Logistic回归分析颅内动脉瘤术后患者预后不良的危险因素;绘制受试者工作特征(ROC)曲线分析血清VEGFs、MMPs水平预测颅内动脉瘤术后患者预后不良的价值。结果预后不良组患者血清VEGF-1、VEGF-2、MMP-1、MMP-2、MMP-9水平均显著高于预后良好组患者(t/P=4.455/<0.001、3.982/<0.001、4.848/<0.001、5.702/<0.001、5.144/<0.001);血清VEGF-1、VEGF-2、MMP-1、MMP-2、MMP-9水平均与颅内动脉瘤术后患者预后不良呈显著正相关(r/P=0.338/<0.001、0.361/<0.001、0.383/<0.001、0.386/<0.001、0.331/<0.001);血清VEGF-1、VEGF-2、MMP-1、MMP-2、MMP-9水平升高均是颅内动脉瘤术后患者预后不良的独立危险因素[OR(95%CI)=1.142(1.011~1.372)、1.126(1.004~1.276)、1.027(1.002~1.052)、1.029(1.006~1.052)、1.026(1.006~1.047)];血清VEGF-1、VEGF-2、MMP-1、MMP-2、MMP-9水平独立及联合预测颅内动脉瘤术后患者预后不良的AUC分别为0.729、0.744、0.759、0.761、0.724、0.890,联合预测的效能大于各指标独立预测效能(Z/P=4.344/<0.001、4.185/<0.001、4.013/<0.001、4.010/<0.001、4.350/<0.001)。结论颅内动脉瘤术后患者血清VEGFs、MMPs表达水平与预后不良具有密切相关性。基于上述指标的联合预测模型对颅内动脉瘤术后患者不良预后有较高预测价值。

血清PDGF、OPN水平与原发性肝癌TACE治疗预后的关系

目的探讨血清血小板源性生长因子(PDGF)、骨桥蛋白(OPN)水平与原发性肝癌(PLC)患者经导管动脉化疗栓塞术(TACE)治疗预后的关系。方法选取2021年10月至2023年5月南阳市中心医院收治的110例PLC患者作为研究对象进行前瞻性研究,检测所有患者入院时的血清PDGF、OPN水平。所有患者均行TACE治疗,于患者出院后随访1年,根据预后情况将其分为预后不良组和预后良好组。比较两组患者的基线资料及血清PDGF、OPN水平;采用多因素Logistic回归分析PLC患者TACE治疗预后的影响因素;绘制受试者工作特征(ROC)曲线分析PDGF、OPN对PLC患者TACE治疗预后的预测价值;绘制决策曲线评估PDGF、OPN预测PLC患者TACE治疗预后的临床收益情况。结果108例PLC患者完成1年随访,将29例预后不良者纳入预后不良组,79例预后良好者纳入预后良好组。预后不良组患者的肿瘤最大直径、甲胎蛋白(AFP)、PDGF、OPN分别为(4.91±0.86)mm、(494.74±100.09)μg/L、(429.28±92.30)pg/m L、(115.82±20.45)ng/m L,明显高于预后良好组的(4.20±0.82)mm、(411.15±88.10)μg/L、(350.46±74.93)pg/mL、(97.37±16.53)ng/mL,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,肿瘤最大直径、AFP、PDGF、OPN均是PLC患者TACE治疗后预后不良的危险因素(P<0.05)。绘制ROC曲线结果显示,血清PDGF、OPN单独及两者联合检测预测PLC患者TACE治疗后预后不良的曲线下面积(AUC)分别为0.739、0.768、0.844,联合预测的AUC明显高于单独预测(P<0.05);绘制决策曲线结果显示,在阈值0.10~0.57、0.81~0.97范围内,PDGF、OPN联合预测PLC患者TACE治疗后预后不良的净收益率明显优于单一指标,且在高风险阈值0.10~0.70、0.75~0.97范围内,联合预测净收益率>0,净收益率最大值为0.269。结论血清PDGF、OPN与PLC患者TACE治疗后预后有关,用于预测预后有一定价值,且联合两项指标可提高预测效能。

血清GGT、NGF、Nf L对经奥沙利铂化疗的结直肠癌患者发生外周神经相关不良反应的诊断价值

目的 分析血清γ-谷氨酰转移酶(GGT)、神经生长因子(NGF)、神经丝轻链(NfL)水平对经奥沙利铂化疗的结直肠癌患者发生外周神经相关不良反应的诊断价值。方法 选取2021年8月至2023年8月在该院经奥沙利铂化疗且发生外周神经相关不良反应的104例结直肠癌患者作为研究组,另选取同期在该院经奥沙利铂化疗且未发生外周神经相关不良反应的104例结直肠癌患者为对照组。采用Spearman相关分析血清GGT、NGF、NfL水平与经奥沙利铂化疗的结直肠癌患者发生的外周神经不良反应评级的相关性。绘制受试者工作特征(ROC)曲线分析血清GGT、NGF、NfL对经奥沙利铂化疗的结直肠癌患者发生外周神经相关不良反应的诊断价值。结果 研究组血清GGT、NfL水平高于对照组,NGF水平低于对照组,差异均有统计学意义(P<0.05)。研究组中,外周神经相关不良反应Ⅰ级23例,Ⅱ级38例,Ⅲ级29例,Ⅳ级14例。不同外周神经不良反应评级患者血清GGT、NfL水平比较结果显示,Ⅳ级>Ⅲ级>Ⅱ级>Ⅰ级,任意两两间比较,差异均有统计学意义(P<0.05)。不同外周神经不良反应评级患者血清NGF水平比较结果显示,Ⅳ级<Ⅲ级<Ⅱ级<Ⅰ级,任意两两间比较,差异均有统计学意义(P<0.05)。Spearman相关分析结果显示,研究组血清GGT、NfL水平与外周神经不良反应评级呈正相关(r=0.688、0.627,P<0.05),NGF水平与外周神经不良反应评级呈负相关(r=-0.694,P<0.05)。ROC曲线分析结果显示,3项指标联合诊断经奥沙利铂化疗的结直肠癌患者发生外周神经相关不良反应的曲线下面积(AUC)大于GGT、NGF、NfL单独诊断的AUC(Z=2.302、2.098、2.482,P<0.05)。结论 经奥沙利铂化疗且发生外周神经相关不良反应的结直肠癌患者血清GGT、NfL水平显著升高,NGF水平显著降低,且3项指标联合对经奥沙利铂化疗的结直肠癌患者发生外周神经相关不良反应的诊断价值较高,有一定的临床意义。

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.

Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway

AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Diagnostic value of serum vascular endothelial growth factor and interleukin-17 in primary hepatocellular carcinoma

BACKGROUND Despite significant advancements in the medical treatment of primary hepato-cellular carcinoma(PHC)in recent years,enhancing therapeutic effects and im-proving prognosis remain substantial challenges worldwide.AIM To investigate the expression levels of serum vascular endothelial growth factor(VEGF)and interleukin(IL)-17 in patients with PHC and evaluate their diagnostic value while exploring their relationship with patients’clinical characteristics.METHODS The study included 50 patients with confirmed PHC who visited Wuhan Han-yang Hospital from January 2021 to January 2022,and 50 healthy individuals from the same period served as the control group.Serum VEGF and IL-17 levels in both groups were measured by Enzyme-Linked Immunosorbent Assay,and their diagnostic value was assessed using receiver operating characteristic(ROC)curves.Pearson correlation analysis was performed to examine the relationship between serum VEGF and IL-17 levels.Pathological data of the PHC patients were analyzed to determine the relationship between serum VEGF and IL-17 levels and pathological characteristics.RESULTS Serum VEGF and IL-17 levels were significantly higher in the study group com-pared to the control group(P<0.05).No significant association was observed between serum VEGF and IL-17 levels and gender,age,combined cirrhosis,tumor diameter,or degree of differentiation(P>0.05).However,there was a significant relationship between clinical TNM stage,tumor metastasis,and serum VEGF and IL-17 levels(P<0.05).Correlation analysis revealed a positive correlation between serum VEGF and IL-17(P<0.05).ROC analysis demonstrated that both serum VEGF and IL-17 had good diagnostic efficacy for PHC.CONCLUSION Serum VEGF and IL-17 levels were significantly higher in PHC patients compared to healthy individuals.Their levels were closely related to pathological features such as tumor metastasis and clinical TNM stage,and there was a significant positive correlation between VEGF and IL-17.These biomarkers may serve as valuable reference in-dicators for the early diagnosis and treatment guidance of PHC.