Association between serum retinol-binding protein and lower limb atherosclerosis risk in type 2 diabetes mellitus

BACKGROUND Serum retinol-binding protein(RBP)is the primary transport protein of circulating vitamin A.RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis.Several studies have indicated that serum RBP participates in the progression of diabetes and diabetes-related complications.However,the impact of serum RBP on lower limb atherosclerosis has not been determined in individuals with type 2 diabetes mellitus(T2DM).AIM To determine the association between serum RBP and lower limb atherosclerosis in individuals with T2DM.METHODS This retrospective study enrolled 4428 eligible T2DM patients and divided the patients into non-lower limb atherosclerosis(n=1913)and lower limb atherosclerosis groups(n=2515)based on lower limb arterial ultrasonography results.At hospital admission,baseline serum RBP levels were assessed,and all subjects were categorized into three groups(Q1-Q3)based on RBP tertiles.Logistic regression,restricted cubic spline regression,subgroup analysis,and machine learning were used to assess the association between RBP levels and lower limb atherosclerosis risk.RESULTS Among 4428 individuals with T2DM,2515(56.80%)had lower limb atherosclerosis.Logistic analysis showed that lower limb atherosclerosis risk increased by 1%for every 1 unit rise in serum RBP level(odds ratio=1.01,95%confidence interval:1.00-1.02,P=0.004).Patients in the highest tertile group(Q3)had a higher lower limb atherosclerosis risk compared to the lowest tertile group(Q1)(odds ratio=1.36,95%confidence interval:1.12-1.67,P=0.002).The lower limb atherosclerosis risk gradually increased with an increase in RBP tertile(P for trend=0.005).Restricted cubic spline analysis indicated a linear correlation between serum RBP levels and lower limb atherosclerosis risk(non-linear P<0.05).Machine learning demonstrated the significance and diagnostic value of serum RBP in predicting lower limb atherosclerosis risk.CONCLUSION Elevated serum RBP levels correlate with an increased lower limb atherosclerosis risk in individuals with T2DM.

AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration

BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.

Anti-diabetic effects of cinnamaldehyde and berberine and their impacts on retinol-binding protein 4 expression in rats with type 2 diabetes mellitus

Background Retinol binding protein 4 （RBP4）, as an adipocyte secreted cytokine, was recently found to be inversely correlated with expression of glucose transporter 4 （GLUT4） in insulin resistance （IR） state and to have an intimate relationship with IR and type 2 diabetes mellitus （T2DM）. The present study aimed to evaluate the anti-diabetic efficacy of cinnamaldehyde （Cin）, berberine （Ber）, and metformin （Met） as well as their impacts on the RBP4-GLUT4 system. Methods Rat models of T2DM were established by combination of intraperitoneal injection of low-dose streptozotocin and high fat diet induction. Rats were divided into five groups： the control group, the diabetes group, the diabetes＋Ber group, the diabetes＋Cin group, and the diabetes＋Met group. Western blotting was used to detect the serum or tissue RBP4 and GLUT4 protein levels. Results After treatment for four weeks, both Cin and Ber displayed significant hypolipidemic, hypoglycemic, and insulin sensitizing functions （P 〈0.01） compared with the control group. Their effects on lowering fasting plasma glucose （FPG）, low density lipoprotein-cholesterol （LDL-C） and homeostasis model assessment of insulin resistance （HOMA-IR） seem even better than that of Met. Cin and Ber markedly lowered serum RBP4 levels and up-regulated the expression of tissue GLUT4 protein, and Cin seemed more notable in affecting these two proteins. Conclusions Both Cin and Ber display an exciting anti-diabetic efficacy in this study and may be of great value for the treatment of type 2 diabetes. Their mechanisms involve the RBP4-GLUT4 system, during which the serum RBP4 levels are lowered and the expression of tissue GLUT4 protein is up-regulated.

血管生成素样蛋白4通过调节成纤维细胞和内皮细胞功能影响糖尿病足进程

背景:研究表明,血管因素对糖尿病足的发生具有重要影响。目的:探讨血管生成素样蛋白4在糖尿病足形成中的重要作用。方法:①对糖尿病足患者的基因表达谱数据进行生物信息学分析,找到关键基因。收集糖尿病足患者以及无糖尿病健康人的皮肤标本进行苏木精-伊红染色、免疫组化染色以及qRT-PCR实验,检测血管生成素样蛋白4表达情况。②培养人永生化皮肤成纤维细胞系和原代人脐静脉内皮细胞,将2种细胞分别分为对照组和外源性补充血管生成素样蛋白4组,通过划痕实验以及CCK-8实验分别检测成纤维细胞的迁移能力和增殖能力,通过Ki67实验检测内皮细胞的增殖能力。结果与结论:①生信分析发现,血管生成素样蛋白4基因的下调可能是导致糖尿病足形成的关键基因。②苏木精-伊红染色结果显示,与正常皮肤相比,血管生成素样蛋白在糖尿病足皮肤内弱表达,且其mRNA水平相对表达量降低(P<0.01)。③划痕实验结果显示,与对照组相比,血管生成素样蛋白4组成纤维细胞迁移能力明显增强;CCK-8细胞增殖实验显示,血管生成素样蛋白4组成纤维细胞的吸光度值在24,48 h均高于对照组(P<0.01,P<0.001);提示血管生成素样蛋白4可增强高糖处理的成纤维细胞迁移及增殖能力。④Ki67实验结果显示,与对照组相比,血管生成素样蛋白4组内皮细胞Ki67阳性细胞数目明显多于对照组;CCK-8细胞增殖实验显示,血管生成素样蛋白4组内皮细胞的吸光度值在24,48 h均高于对照组(P<0.05,P<0.001)。(5)以上结果均提示血管生成素样蛋白4可增强高糖处理内皮细胞的增殖能力。

ANGPTL4 TSP-1及CyPA与脑卒中后癫痫患者认知功能的关系

目的探讨血管生成素样蛋白4(ANGPTL4)、凝血酶敏感蛋白-1(TSP-1)、亲环素A(CyPA与脑卒中后癫痫患者认知功能的关系。方法选取2021-01—2022-12河南大学第一附属医院神经内科收治的100例脑卒中后癫痫病例进行观察,按简易精神状态量表(MMSE)划分认知障碍标准将患者分为认知障碍组(50例)和认知正常组(50例),应用酶联免疫吸附试验(ELISA)检测2组患者的血清ANGPTL4、TSP-1、CyPA水平,MMSE量表测评2组患者的认知功能。结果与认知正常组比较,认知障碍组患者MMSE评分降低,ANGPTL4、TSP-1、CyPA水平升高(P<0.05);与轻度认知障碍患者比较,中度认知障碍患者血清ANGPTL4、TSP-1、CyPA水平升高(P<0.05);与中度认知障碍患者比较,重度认知障碍患者血清ANGPTL4、TSP-1、CyPA水平升高(P<0.05)。在脑卒中后癫痫患者中,血清ANGPTL4、TSP-1、Cy PA与MMSE评分各维度均呈负相关(P<0.05)。结论脑卒中后癫痫会降低MMSE评分,提高患者血清ANGPTL4、TSP-1、CyPA水平。ANGPTL4、TSP-1、CyPA水平越高,患者认知功能障碍越严重。

肝细胞肝癌组织MCM4蛋白表达及其与临床病理特征的关系

目的探究肝细胞肝癌组织微小染色体维持蛋白4(MCM4)蛋白表达及其与临床病理特征的关系。方法选取2021年1月至2022年2月河南大学附属郑州颐和医院收治的102例行手术切除的肝细胞肝癌患者作为研究对象,采用免疫组织化学法检测癌组织与切缘正常组织MCM4蛋白表达,比较癌组织和切缘正常组织MCM4蛋白阳性表达率;比较不同临床病理特征患者癌组织MCM4蛋白阳性表达率;随访1 a分析癌组织MCM4蛋白表达与生存的关系;采用Kaplan-Meier法进行生存分析,并通过log-rank进行显著性检验。结果肝细胞肝癌组织MCM4蛋白阳性表达率高于切缘正常组织(P<0.05);乙型肝炎表面抗原(HBsAg)阳性、肿瘤淋巴结转移(TNM)分期Ⅲa期、低/未分化、肿瘤最大径≥5 cm、甲胎蛋白(AFP)≥400μg·L^(-1)、有微血管侵犯、有肝硬化患者癌组织MCM4蛋白阳性表达率分别高于HBsAg阴性、TNM分期I~Ⅱ期、高/中分化、肿瘤最大径<5 cm、AFP<400μg·L^(-1)、无微血管侵犯、无肝硬化患者,差异均有统计学意义(P<0.05);随访1 a,患者生存率为78.79%,HBsAg阳性、TNM分期Ⅲa期、低/未分化、AFP≥400μg·L^(-1)、有肝硬化、MCM4蛋白阳性表达均为肝癌患者死亡的危险因素(HR=4.026、5.767、6.430、6.874、4.496、7.588,P<0.05);癌组织MCM4蛋白阳性表达患者1 a生存率低于阴性表达患者(P<0.05)。结论肝细胞肝癌组织MCM4蛋白阳性表达率高于切缘正常组织,癌组织MCM4蛋白表达与HBsAg、TNM分期、分化程度、肿瘤大小、AFP水平、微血管侵犯、肝硬化有关,且癌组织MCM4蛋白阳性表达可降低患者生存率。

血清AQP4、HMGB1、FGL2水平联合颅内压和脑组织氧分压监测在创伤性脑损伤患者预后中的价值

目的探讨血清通道蛋白4(AQP4)、高迁移率族蛋白B1(HMGB1)、纤维蛋白原样蛋白2(FGL2)水平联合颅内压和脑组织氧分压(PbtO_(2))监测在创伤性脑损伤(TBI)患者预后中的价值。方法选取2022年5月—2024年5月上海交通大学附属第六人民医院南院/上海市奉贤区中心医院重症医学科诊治的TBI患者128例为研究对象,根据患者治疗后随访3个月预后情况,将其分为预后不良组(n=38)、预后良好组(n=90)。采用ELISA法检测血清AQP4、HMGB1、FGL2水平;Spearman法分析TBI不同预后患者颅内压、PbtO_(2)、血清AQP4、HMGB1、FGL2与格拉斯哥昏迷量表(GCS)评分的相关性;运用ROC曲线分析颅内压、PbtO_(2)联合血清AQP4、HMGB1、FGL2对TBI患者预后的预测价值。结果预后不良组患者颅内压高于预后良好组,GCS评分、PbtO_(2)值显著低于预后良好组(t/P=7.491/<0.001、9.882/<0.001、7.215/<0.001)。预后不良组血清AQP4、HMGB1、FGL2水平明显高于预后良好组(t/P=7.106/<0.001、7.642/<0.001、7.383/<0.001);患者PbtO_(2)与GCS评分呈显著正相关(r/P=0.523/<0.001),而颅内压、血清AQP4、HMGB1、FGL2与GCS评分呈显著负相关(r/P=-0.515/<0.001、-0.492/<0.001、-0.617/<0.001、-0.569/<0.001);血清AQP4、HMGB1、FGL2、颅内压、PbtO_(2)及五者联合预测TBI患者预后的曲线下面积(AUC)分别为0.882、0.876、0.817、0.825、0.756、0.969,五者联合优于各自单独预测TBI患者预后的价值(Z/P=2.803/0.005、2.769/0.006、3.543/<0.001、3.269/0.001、3.956/<0.001)。结论TBI患者颅内压、血清AQP4、HMGB1、FGL2水平显著升高,PbtO_(2)显著降低,与患者预后有着紧密联系,联合检测对TBI患者预后有更高的预测价值。

Retinol-binding protein, acute phase reactants and Helicobacter pylori infection in patients with gastric adenocarcinoma

AIM： To determine the serum levels of c-reactive protein （CRP）, transferrin （TRF）, a2-macroglobulin （A2M）, ceruloplasmin （CER）, al-acid glycoprotein （AAG）, prealbumin （P-ALB） and retinol-binding protein （RBP） in gastric carcinoma patients and to explore their possible correlation with underlying Helicobacter pylori （H pylon） infection. METHODS： We measured the serum levels of CRP, TRF, A2M, CER, AAG, P-ALB, and RBP in 153 preoperative patients （93 males; mean age： 63.1±11.3 years） with non-cardia gastric adenocarcinoma and 19 healthy subjects. RESULTS： The levels of CRP, CER, RBP, and AAG in cancer patients were significantly higher than those in healthy controls （P〈0.0001）, while no difference was found regarding the TRF, P-ALB, and A2M levels. Cancer patients with H py/ori infection had significantly lower RBP values compared to non-infected ones （P〈0.0001） and also higher values of CRP and AAG （P = 0.09 andP = 0.08, respectively）. CONCLUSION： High serum levels of CRP, CER and AAG in cancer patients do not seem to be related to H pylori infection. Retinol-binding protein seems to discriminate between infected and non-infected patients with gastric carcinoma. Further studies are needed to explore if it is directly involved in the pathogenesis of the disease or is merely an epiphenomenon.

Neuroprotective effects of acteoside in a glaucoma mouse model by targeting Serta domain-containing protein 4

AIM:To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice.METHODS:Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice.After acteoside administration in DBA/2J mice,anterior segment observation,intraocular pressure(IOP)monitoring,electrophysiology examination,and hematoxylin and eosin staining were used to analyze any potential effects.Immunohistochemistry(IHC)assays were used to verify the proteomics results.Furthermore,retinal ganglion cell 5(RGC5)cell proliferation was assessed with cell counting kit-8(CCK-8)assays.Serta domain-containing protein 4(Sertad4)mRNA and protein expression levels were measured by qRT-PCR and Western blot analysis,respectively.RESULTS:Proteomics analysis suggested that Sertad4 was the most significantly differentially expressed protein.Compared with the saline group,the acteoside treatment group showed decreased IOP,improved N1-P1 wave amplitudes,thicker retina,and larger numbers of cells in the ganglion cell layer(GCL).The IHC results showed that Sertad4 expression levels in DBA/2J mice treated with acteoside were significantly lower than in the saline group.Acteoside treatment could improve RGC5 cell survival and reduce the Sertad4 mRNA and protein expression levels after glutamate injury.CONCLUSION:Sertad4 is differentially expressed in DBA/2J mice.Acteoside can protect RGCs from damage,possibly through the downregulation of Sertad4,and has a potential use in glaucoma treatment.

Application of urinary N-acetyl-β-D-glucosaminidase combined with serum retinol-binding protein in early detection of diabetic nephropathy

BACKGROUND Diabetic nephropathy(DN)is a microangiopathy of type 2 diabetes mellitus(T2DM),which can damage the kidney through various ways and mechanisms due to the nature of the disease,involving the renal interstitium and glomeruli.However,in the early stage of the disease,patients only showed kidney volume increase and glomerular hyperthyroidism,and typical symptoms that are difficult to arouse individual attention were noticed.AIM To observe the expression of serum retinol-binding protein(RBP)and urinary Nacetyl-β-D-glucosaminidase(NAG)in patients with DN,and to analyze their value in disease prediction,so as to provide new targets for early diagnosis and treatment of DN.METHODS The baseline data of 50 T2DM patients treated in our hospital between January 2021 and December 2022 were retrospectively reviewed and included in group A.The baseline data of 50 patients with type 2 DN admitted to our hospital during the same period were collected and included in group B.The baseline data and serum RBP and urine NAG expression were compared between the two groups to analyze their value in the early prediction of DN.RESULTS There was no significant difference in age,gender,duration of diabetes,combined hyperlipidemia and combined hypertension between the two groups(P>0.05);the expression of urinary NAG and serum RBP in group B was higher than that in group A,and the difference was statistically significant(P<0.05);a multiple logistic regression model was established,and the results showed that urinary NAG and serum RBP were related to the presence or absence of injury in diabetic patients,and overexpression of urinary NAG and serum RBP may be risk factors for renal injury in T2DM patients(OR>1,P<0.05);receiver operating curve curve was plotted,and the results showed that the area under the curve of urinary NAG and serum RBP expression alone and in combination for predicting DN was>0.80,and the predictive value was satisfactory;bivariate Spearman linear correlation analysis showed that there was a positive correlation between urinary NAG and serum RBP expression in patients with DN(r=0.566,P=0.000).CONCLUSION The increased expression of urinary NAG and serum RBP may be the risk factors leading to the progression of T2DM to DN.The possibility of DN can be considered in patients with urinary NAG and serum RBP overexpression by examining the expression of urinary NAG and serum RBP in patients with T2DM in clinical practice.

Quantitative trait loci identification reveals zinc finger protein CONSTANS-LIKE 4 as the key candidate gene of stigma color in watermelon(Citrullus lanatus)

Stigma color is a critical agronomic trait in watermelon that plays an important role in pollination.However,there are few reports on the regulation of stigma color in watermelon.In this study,a genetic analysis of the F2 population derived from ZXG1553(P1,with orange stigma)and W1-17(P2,with yellow stigma)indicated that stigma color is a quantitative trait and the orange stigma is recessive compared with the yellow stigma.Bulk segregant analysis sequencing(BSA-seq)revealed a 3.75 Mb segment on chromosome 6 that is related to stigma color.Also,a major stable effective QTL Clqsc6.1(QTL stigma color)was detected in two years between cleaved amplified polymorphic sequencing(CAPS)markers Chr06_8338913 and Chr06_9344593 spanning a~1.01 Mb interval that harbors 51 annotated genes.Cla97C06G117020(annotated as zinc finger protein CONSTANS-LIKE 4)was identified as the best candidate gene for the stigma color trait through RNA-seq,quantitative real-time PCR(qRT-PCR),and gene structure alignment analysis among the natural watermelon panel.The expression level of Cla97C06G117020 in the orange stigma accession was lower than in the yellow stigma accessions with a significant difference.A nonsynonymous SNP site of the Cla97C06G117020 coding region that causes amino acid variation was related to the stigma color variation among nine watermelon accessions according to their re-sequencing data.Stigma color formation is often related to carotenoids,and we also found that the expression trend of ClCHYB(annotated asβ-carotene hydroxylase)in the carotenoid metabolic pathway was consistent with Cla97C06G117020,and it was expressed in low amounts in the orange stigma accession.These data indicated that Cla97C06G117020 and ClCHYB may interact to form the stigma color.This study provides a theoretical basis for gene fine mapping and mechanisms for the regulation of stigma color in watermelon.

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

血清血管生成素样蛋白4、过氧化物酶体增殖物激活受体γ表达水平与急性缺血性脑卒中预后的关系

目的探究血清血管生成素样蛋白4(Angptl4)、过氧化物酶体增殖物激活受体γ(PPARγ)表达水平与急性缺血性脑卒中预后的关系。方法选取2020年2月至2022年6月沧州市中心医院收治的急性缺血性脑卒中病人100例作为观察组,依据美国国立卫生研究院卒中量表(NIHSS)评分评估病情严重程度,分为轻症组(n=33,NIHSS评分<6分)、中症组(n=39,6分≤NIHSS评分<14分)、重症组(n=28,NIHSS评分≥14分);根据治疗90 d后改良Rankin量表(mRs)评分评估预后,分为预后良好组(n=68,0~2分)、预后不良组(n=32,≥3分);另选取同期健康志愿者100例作为对照组。酶联免疫吸附试验(ELISA)检测血清Angptl4、PPARγ表达水平,并进行组间比较;多因素logistic回归分析急性缺血性脑卒中病人预后的影响因素;受试者操作特征曲线(ROC曲线)分析血清Angptl4、PPARγ对预后的评估价值。结果观察组血清Angptl4[(14.16±3.28)μg/L比(11.52±2.36)μg/L]、PPARγ[(38.54±9.63)ng/L比(26.68±7.48)ng/L]表达水平高于对照组(P<0.05);重症组血清Angptl4、PPARγ表达水平高于轻症组和中症组,且中症组高于轻症组(P<0.05);预后不良组年龄、Angptl4、PPARγ、高血压比例、糖尿病比例、入院时NIHSS评分均明显高于预后良好组(P<0.05);血清Angptl4、PPARγ、NIHSS评分为急性缺血性脑卒中病人预后的影响因素(P<0.05);血清Angptl4、PPARγ二者联合评估急性缺血性脑卒中病人预后的曲线下面积(AUC)为0.98。结论血清Angptl4、PPARγ表达水平较高的急性缺血性脑卒中病人病情较严重,预后较差,血清Angptl4、PPARγ为急性缺血性脑卒中病人预后影响因素,能较好地评估病人预后情况。

脑小血管病患者外周血GPER30、NPAS4、FKBP5表达与认知功能障碍的相关性研究

目的探讨脑小血管病(CSVD)患者外周血G蛋白耦联雌激素受体30(GPER30)、神经元PAS结构域蛋白4(NPAS4)、FK506结合蛋白5(FKBP5)表达与认知功能障碍(CD)的相关性。方法前瞻性选取2022年1月至2023年12月郑州大学第二附属医院收治的227例CSVD患者,根据有无CD分为障碍组(n=66)与无障碍组(n=161)。比较两组患者的一般资料及外周血GPER30、NPAS4、FKBP5 m RNA表达水平,Logistic回归分析CSVD患者CD的影响因素,比较不同程度CD患者外周血GPER30、NPAS4、FKBP5 m RNA表达水平,采用Pearson法分析外周血GPER30、NPAS4、FKBP5 m RNA表达与蒙特利尔认知评估量表(Mo CA)评分的相关性。结果障碍组患者的年龄、病程分别为(72.49±5.68)岁、(2.69±0.78)年,明显高(长)于无障碍组的(67.51±7.04)岁、(2.31±0.62)年,差异均有统计学意义(P<0.05);障碍组患者的外周血GPER30 m RNA表达水平为1.02±0.17,明显低于无障碍组的1.66±0.31,NPAS4m RNA、FKBP5 m RNA表达水平分别为2.79±0.60、3.88±1.12,明显高于无障碍组的1.55±0.51、2.10±0.59,差异均有统计学意义(P<0.05);Logistic回归分析结果显示,年龄、病程、GPER30 m RNA、NPAS4 m RNA及FKBP5 m RNA均为CSVD患者CD的独立影响因素(P<0.05)。轻度组患者的外周血GPER30 m RNA表达水平为1.27±0.25,明显高于中重度组的0.70±0.12,NPAS4 m RNA、FKBP5 m RNA表达水平分别为2.31±0.58、3.19±1.07,明显低于中重度组的3.40±0.72、4.76±1.39,差异均有统计学意义(P<0.05);Pearson法分析结果显示,外周血GPER30 m RNA表达与CSVD患者Mo CA评分呈正相关(r=0.704,P<0.05),NPAS4 m RNA、FKBP5 m RNA与Mo CA评分呈负相关(r=-0.572、-0.542,P<0.05)。结论外周血GPER30、NPAS4、FKBP5是CSVD患者CD的独立相关因素,各指标表达水平与CD病情严重程度均具有一定相关性,可为临床判断CD、评估CD病情严重程度提供参考,以指导后续临床工作。

腹股沟疝患者血清高迁移率族蛋白B1和Toll样受体4水平变化及检测意义

目的:探讨腹股沟疝患者血清高迁移率族蛋白B1(HMGB1)和Toll样受体4(TLR4)水平变化及检测意义。方法:选取接受腹腔镜下全腹膜外疝修补术(TEP)的腹股沟疝患者256例为疾病组,另选取同期体检健康者213例为对照组。比较对照组和疾病组血清HMGB1和TLR4水平。术后进行随访,根据腹腔镜下TEP术后1年内复发情况将患者分为复发组(24例)和未复发组(232例)。比较复发组和未复发组临床资料及不同时间点血清HMGB1和TLR4水平。采用多因素Logistic回归分析腹股沟疝患者腹腔镜下TEP术后1年复发的影响因素。绘制受试者工作特征(ROC)曲线分析血清HMGB1和TLR4对腹股沟疝患者腹腔镜下TEP术后1年复发的预测价值。结果:疾病组术前血清HMGB1和TLR4水平高于对照组(均P<0.05)。术后7 d,两组血清HMGB1和TLR4水平较术前降低,且未复发组低于复发组(均P<0.05)。复发组合并糖尿病、高血压、疝环重度粘连、术后发生并发症、术后过早下床活动以及手术医生经验<3年的比例高于未复发组(均P<0.05)。术后7 d血清HMGB1、术后7 d血清TLR4、合并高血压、疝环粘连程度、术后并发症、手术医生经验为腹股沟疝患者腹腔镜下TEP术后1年复发的独立影响因素(均P<0.05)。术后7 d血清HMGB1、TLR4两者联合预测腹股沟疝患者腹腔镜下TEP术后1年复发的曲线下面积(AUC)高于单独预测的AUC(均P<0.05)。结论:腹股沟疝患者血清HMGB1和TLR4水平较高,两者联合对腹股沟疝患者腹腔镜下TEP术后1年复发具有一定预测价值。

扩张型心肌病患者的血清分泌型卷曲相关蛋白4水平及其临床预后预测价值分析

目的:分析扩张型心肌病(DCM)患者的血清分泌型卷曲相关蛋白4(SFRP4)水平及其临床预后预测价值。方法:连续入选2017年1月至2019年1月就诊于复旦大学附属中山医院心内科并确诊为DCM的患者259例为DCM组,另选取本院体检中心同时期进行健康体检,没有心力衰竭病史、超声心动图检查左心室射血分数正常且N末端B型利钠肽原(NT-proBNP)水平正常的84名体检者为对照组。采用酶联免疫吸附试验(ELISA)法检测血清SFRP4水平,分析SFRP4水平与DCM的相关性及其对DCM患者的预后预测价值。结果:与对照组相比,DCM组患者血清SFRP4水平明显升高[(28.54±10.25)ng/ml vs.(52.70±19.74)ng/ml,P<0.05]。随机将具有预后数据的234例DCM患者按2∶1的比例分为训练集(n=156)与验证集(n=78)。训练集进行多因素Logistic回归分析显示,血清SFRP4水平与全因死亡独立相关(OR=1.06,95%CI:1.03~1.10,P<0.001)。进一步评估模型预测效果,训练集与验证集受试者工作特征(ROC)曲线(曲线下面积均>0.8)、校准曲线和决策曲线分析均表明包含血清SFRP4水平用于构建预测模型对DCM患者的全因死亡预测具有较好的价值。Kaplan-Meier生存曲线分析显示,中位随访33.5(11.0,49.0)个月,血清SFRP4≥75百分位水平DCM患者的无事件累积生存率显著低于血清SFRP4<75百分位水平DCM患者(16.57%vs.28.81%,P=0.02)。结论:DCM患者血清SFRP4水平显著升高,SFRP4水平对于DCM的预后预测具有潜在的临床价值。

输尿管软镜钬激光碎石术后尿路感染患者血清sTREM-1、RBP4、HBD-3水平变化及检测意义

目的:探讨输尿管软镜钬激光碎石术(FURL)后尿路感染(UTI)患者血清可溶性髓样细胞触发受体-1(sTREM-1)、视黄醇结合蛋白4(RBP4)、人β-防御素-3(HBD-3)水平变化及检测意义。方法:选取行FURL患者183例,根据患者术后是否发生UTI分为UTI组(98例)和非UTI组(85例)。比较两组临床资料及血清sTREM-1、RBP4、HBD-3水平。采用多因素Logistic回归分析患者FURL术后发生UTI的影响因素。分析血清sTREM-1、RBP4、HBD-3对患者FURL术后发生UTI的预测价值。结果:UTI组有泌尿道手术史、导尿管留置时间≥7 d、抗菌药物种类>3种患者比例高于非UTI组(均P<0.05)。UTI组血清sTREM-1、RBP4、HBD-3水平高于非UTI组(均P<0.05)。泌尿道手术史、导尿管留置时间、抗菌药物种类及血清sTREM-1、RBP4、HBD-3是患者FURL术后发生UTI的影响因素(均P<0.05)。血清sTREM-1、RBP4、HBD-3水平与患者泌尿道手术史、导尿管留置时间及抗菌药物种类呈正相关(均P<0.05)。血清sTREM-1、RBP4、HBD-3联合预测患者FURL术后发生UTI的曲线下面积(AUC)为0.894,高于三者独立预测的AUC(均P<0.05)。结论:FURL术后UTI患者血清sTREM-1、RBP4、HBD-3水平升高,三者联合对FURL术后发生UTI具有较高的预测价值。

血清CKAP4、CTRP9对维持性血液透析患者发生血管钙化的预测价值

目的分析细胞骨架相关蛋白4(CKAP4)、补体C1q肿瘤坏死因子相关蛋白9(CTRP9)对维持性血液透析(MHD)患者发生血管钙化的预测价值。方法选取2021年4月至2023年6月该院收治的132例MHD患者作为研究对象,根据血管钙化总评分将其分为钙化组、非钙化组,另选取同期在该院体检的62例健康人群作为对照组。比较钙化组、非钙化组、对照组一般资料及血清CKAP4、CTRP9水平,比较钙化组和非钙化组临床资料。采用Pearson相关分析MHD患者血清CKAP4、CTRP9水平与钙磷代谢相关指标的相关性。采用多因素Logistic回归分析MHD患者发生血管钙化的影响因素。绘制受试者工作特征(ROC)曲线分析MHD患者发生血管钙化的预测价值。结果非钙化组和钙化组患者血清CKAP4、CTRP9水平低于对照组,且钙化组低于非钙化组,差异均有统计学意义(P<0.05)。钙化组血钙、血磷、甲状旁腺激素(PTH)水平高于非钙化组,差异均有统计学意义(P<0.05)。Pearson相关分析结果显示,MHD患者血清CKAP4、CTRP9水平与血钙、血磷、PTH水平呈负相关(P<0.05)。多因素Logistic回归分析结果显示,血清CKAP4、CTRP9水平降低是MHD患者发生血管钙化的危险因素(P<0.05)。ROC曲线分析结果显示,血清CKAP4、CTRP9联合预测患者发生血管钙化的曲线下面积大于各项指标单独预测(Z_(2项联合-CKAP4)=2.307、P=0.021;Z_(2项联合-CTRP9)=2.484、P=0.013)。结论MHD患者血清CKAP4、CTRP9水平明显降低,2项指标联合对MHD患者发生血管钙化的预测价值高于单项指标。

探讨血清Perilipin-2联合尿Netrin-4预测2型糖尿病患者糖尿病肾病的临床价值

目的探讨血清脂滴包被蛋白2(Perilipin-2)联合尿液轴突导向因子4(Netrin-4)预测2型糖尿病(T2DM)患者糖尿病肾病(DN)的临床价值。方法采用横断面研究,选取2020年7月至2023年7月期间西安大兴医院收治的208例T2DM病患者作为研究对象,依据尿白蛋白排泄率(UAER)将患者分为单纯T2DM组和DN组。单纯T2DM组(UAER<30 mg/24 h):男74例、女56例,年龄(56.18±7.38)岁,体重指数(22.73±4.37)kg/m2。DN组(30 mg/24 h≤UAER<300 mg/24 h):男42例、女36例,年龄(57.02±7.13)岁,体重指数(23.68±4.29)kg/m2。选取同期入院健康体检者120名作为健康对照组。检测所有研究对象血清Perilipin-2,尿Netrin-4含量。采用t检验、χ^(2)检验进行统计分析,受试者操作特征曲线(ROC)评估血清Perilipin-2联合尿Netrin-4预测T2DM患者DN的临床价值,多因素logistic回归分析探讨DN的相关因素。结果单纯T2DM组、DN组血清Perilipin-2水平分别为(12.52±3.37)μg/L、(20.84±3.42)μg/L,均高于健康对照组[(5.13±2.15)μg/L],且DN组高于单纯T2DM组,3组比较,差异有统计学意义(F=15.14,P<0.05)。单纯T2DM组、DN组尿Netrin-4水平分别为(63.93±8.72)μg/L、(41.32±7.04)μg/L,均低于健康对照组[(98.64±15.37)μg/L],且DN组低于单纯T2DM组,3组比较,差异有统计学意义(F=37.03,P<0.05)。血清Perilipin-2、尿Netrin-4对T2DM患者发生DN的曲线下面积(AUC)分别为0.739[95%置信区间(CI)0.694~0.789]、0.835(95%CI 0.791~0.884),两者联合预测的AUC为0.903(95%CI 0.858~0.954)。DN组二级及以上高血压史人数高于单纯T2DM组(χ2=11.68,P<0.05);多因素logistic逐步回归分析显示,二级及以上高血压史(OR=3.232,95%CI 1.499~6.968)、血清Perilipin-2(OR=4.252,95%CI 1.752~10.267)、尿Netrin-4(OR=5.145,95%CI 1.985~13.337)均是T2DM患者发生DN的影响因素(均P<0.05)。结论血清Perilipin-2、尿Netrin-4可作为预测T2DM患者DN发生的生物标志物,且二者联合检测能提高临床诊断价值。

Fe_(3)O_(4)磁性纳米材料在医学领域中的研究进展

随着纳米科技的发展,磁性纳米材料尤其是四氧化三铁(Fe_(3)O_(4))纳米材料在医学领域的应用日益凸显其重要价值。Fe_(3)O_(4)磁性纳米材料(magnetic nanoparticles,MNPs)因具备独特的磁学性质、优良的生物相容性以及便捷的表面功能化能力而备受科研人员青睐。该材料在外加磁场作用下能够迅速定向移动,且由于其纳米级尺寸带来的高比表面积和表面能,有利于药物分子、生物分子的高效吸附和偶联。此外,Fe_(3)O_(4)MNPs稳定的化学性质和低生物毒性使得其在医疗应用上表现出巨大潜力。在医学研究中,Fe_(3)O_(4)MNPs被广泛应用于多个领域并取得显著成果。本文就Fe_(3)O_(4)MNPs在药物载体、肿瘤热疗、血液净化、酶催化治疗、核磁共振成像、蛋白质与核酸的分离提纯、细胞分离以及免疫分析等方面的研究进展进行综述,并展望未来可能的发展路径与技术创新点。