Barley Protein LFBEP-C1 from Lactiplantibacillus plantarum dy-1 Fermented Barley Extracts by Inhibiting Lipid Accumulation in a Caenorhabditis elegans Model

Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test.Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism.Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.

In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke

In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1(PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.e B-GFAP-sh PTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-sh PTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway

Objective Keshan disease(KD)is a myocardial mitochondrial disease closely related to insufficient selenium(Se)and protein intake.PTEN induced putative kinase 1(PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body.This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury.Methods A low Se and low protein animal model was established.One hundred Wistar rats were randomly divided into 5 groups(control group,low Se group,low protein group,low Se+low protein group,and corn from KD area group).The JC-1 method was used to detect the mitochondrial membrane potential(MMP).ELISA was used to detect serum creatine kinase MB(CK-MB),cardiac troponin I(cTnI),and mitochondrial-glutamicoxalacetic transaminase(M-GOT)levels.RT-PCR and Western blot analysis were used to detect the expression of PINK1,Parkin,sequestome 1(P62),and microtubule-associated proteins1A/1B light chain 3B(MAP1LC3B).Results The MMP was significantly decreased and the activity of CK-MB,cTnI,and M-GOT significantly increased in each experimental group(low Se group,low protein group,low Se+low protein group and corn from KD area group)compared with the control group(P<0.05 for all).The mRNA and protein expression levels of PINK1,Parkin and MAP1LC3B were profoundly increased,and those of P62 markedly decreased in the experimental groups compared with the control group(P<0.05 for all).Conclusion Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

C-reactive protein to albumin ratio predict responses to programmed cell death-1 inhibitors in hepatocellular carcinoma patients

BACKGROUND Over the years,programmed cell death-1(PD-1)inhibitors have been routinely used for hepatocellular carcinoma(HCC)treatment and yielded improved survival outcomes.Nonetheless,significant heterogeneity surrounds the outcomes of most studies.Therefore,it is critical to search for biomarkers that predict the efficacy of PD-1 inhibitors in patients with HCC.AIM To investigate the role of the C-reactive protein to albumin ratio(CAR)in evaluating the efficacy of PD-1 inhibitors for HCC.METHODS The clinical data of 160 patients with HCC treated with PD-1 inhibitors from January 2018 to November 2022 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed.RESULTS The optimal cut-off value for CAR based on progression-free survival(PFS)was determined to be 1.20 using x-tile software.Cox proportional risk model was used to determine the factors affecting prognosis.Eastern Cooperative Oncology Group performance status[hazard ratio(HR)=1.754,95%confidence interval(95%CI)=1.045-2.944,P=0.033],CAR(HR=2.118,95%CI=1.057-4.243,P=0.034)and tumor number(HR=2.932,95%CI=1.246-6.897,P=0.014)were independent prognostic factors for overall survival.CAR(HR=2.730,95%CI=1.502-4.961,P=0.001),tumor number(HR=1.584,95%CI=1.003-2.500,P=0.048)and neutrophil to lymphocyte ratio(HR=1.120,95%CI=1.022-1.228,P=0.015)were independent prognostic factors for PFS.Two nomograms were constructed based on independent prognostic factors.The C-index index and calibration plots confirmed that the nomogram is a reliable risk prediction tool.The ROC curve and decision curve analysis confirmed that the nomogram has a good predictive effect as well as a net clinical benefit.CONCLUSION Overall,we reveal that the CAR is a potential predictor of short-and long-term prognosis in patients with HCC treated with PD-1 inhibitors.If further verified,CAR-based nomogram may increase the number of markers that predict individualized prognosis.

Polycytosine RNA-binding protein 1 regulates osteoblast function via a ferroptosis pathway in type 2 diabetic osteoporosis

BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.

AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

Molecular Docking Studies of Botanical Beverage Mix Berries (LIFEGREENTM) against Breast Cancer Cells from Targeted Protein 1QQG, 7B5Q & 7B5O & Uterine Fibroid from Targeted Protein 2AYR, 6T41 & 3GRF

Fibroids, also called leiomyomas or myomas, are communal tumors of the muscle or uterine wall that affect about 20% of females who are of reproductive age. They can look as if singly or in clusters, and they often cease to grow after menopause. Fibroids can be classified as intramural, sub serosal, pedunculated, or submucosal based on where they are positioned in the uterus. Although fibroids are benign, they can grow quickly and cause a range of symptoms, such as pelvic pressure, heavy menstrual flow, and infertility. As a result, fibroids are a main reason behind hysterectomy surgeries. The majority of cases of breast cancer are ductal and lobular cancers, making it the second utmost common cancer in women international. Gene mutations like those in BRCA1 or BRCA2 knowingly raise the risk of breast and other cancers, typically with an earlier cancer onset. Cancer risk is influenced by a complex interplay of genetic abnormalities, environmental factors, and lifestyle selections. Further research into these relations is domineering. Although they are common in uterine leiomyomas, especially multiple leiomyomas, MED12 mutations do not significantly correlate with tumor size. These mutations have also been noticed in smooth muscle tumors and leiomyosarcomas, two other types of uterine cancer. The identification of MED12 mutations as the sole genetic abnormality originates in leiomyomas raises the opportunity of a role in the genesis of cancer. 10% - 15% of women who are of reproductive age have endometriosis, which grants serious difficulties because of its chronic nature and range of clinical symptoms. Even after effective surgeries, issues reoccur often, adding to the enormous financial burden. The effects of MED12 mutations have been experiential in recent studies examining the molecular causes of endometriosis-associated infertility, which have shown anomalies in cellular connections and signaling cascades. Computational techniques were used in this study to investigate LifeGreenTM’s potential to prevent uterine fibroids and breast cancer. The efficacy of LifeGreenTM as a preventive measure or a treatment for common gynecological matters was examined and modeled. We investigated the mechanisms underlying LifeGreenTM’s benefits in the treatment of uterine fibroids and breast cancer using computational techniques. Our research contributes to our understanding of its potential therapeutic benefits for women’s health.

血清MCP-1、TRAF-6水平在脓毒症严重程度和急性肾损伤评估的作用

目的探讨血清单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子受体相关因子-6(TRAF-6)水平在脓毒症严重程度和急性肾损伤评估中的作用。方法回顾性分析2021年6月至2022年6月在新疆维吾尔自治区人民医院重症医学科接受治疗的110例脓毒症患者的病例资料,依据脓毒症相关急性肾损伤发生情况分为发生组(50例)、未发生组(60例)。统计分析两组患者基线资料、血清MCP-1、TRAF-6水平,并分析脓毒症患者血清MCP-1、TRAF-6水平与序贯多器官功能障碍(SOFA)评分、急性生理和慢性健康Ⅱ(APACHEⅡ)评分的相关性,多因素Logistic回归分析脓毒症相关急性肾损伤影响因素。结果110例患者中,脓毒症相关急性肾损伤发生50例,未发生60例,发生率为45.45%。发生组患者的高血压、肺部感染比例均高于未发生组(P<0.05),SOFA评分、APACHEⅡ评分均高于未发生组(P<0.05),氧合指数低于未发生组(P<0.05),肾小球滤过率(eGFR)、血肌酐(SCr)、尿素氮(BUN)水平均高于未发生组(P<0.05),动脉血乳酸水平高于未发生组(P<0.05),但两组患者的性别、年龄、糖尿病比例的差异无统计学意义(P>0.05)。发生组患者的血清MCP-1、TRAF-6水平均高于未发生组(P<0.05)。脓毒症患者血清MCP-1、TRAF-6水平与SOFA评分、APACHEⅡ评分均呈显著的正相关关系(P<0.05)。多因素Logistic回归分析显示,脓毒症相关急性肾损伤影响因素包括高血压、肺部感染、SOFA评分、APACHEⅡ评分、肾小球滤过率(eGFR)、动脉血乳酸、MCP-1、TRAF-6(P<0.05),不包括氧合指数、尿素氮(BUN)、SCr(P>0.05)。结论血清MCP-1、TRAF-6水平和脓毒症严重程度和关系密切,可作为急性肾损伤的诊断参考指标。

血清HMGB1、CCL20、HSP27水平与慢性牙周炎患者牙周病变程度的相关性分析

目的探讨血清高迁移率族蛋白1(HMGB1)、CC趋化因子配体20(CCL20)、热休克蛋白27(HSP27)水平与慢性牙周炎(CP)患者牙周病变程度的相关性。方法选取2021年9月至2023年8月在新乡医学院第一附属医院诊治的60例CP患者纳入观察组,根据1∶1原则,另选取同期牙周健康者60例纳入对照组。比较两组及不同牙周病变程度CP患者血清HMGB1、CCL20、HSP27水平,分析各指标水平与CP牙周病变程度的相关性及联合诊断价值,并分析不同血清水平患者发生CP的危险度。结果观察组血清HMGB1、CCL20、HSP27水平高于对照组(P<0.05);不同牙周病变程度CP患者血清HMGB1、CCL20、HSP27水平比较:轻度<中度<重度,且各指标水平与牙周病变程度均呈正相关(P<0.05);入院时HMGB1、CCL20、HSP27水平联合诊断CP的曲线下面积(AUC)为0.905,最佳诊断敏感度为91.67%,特异度为88.33%,约登指数0.800,且各指标高水平患者发生CP的危险度是低水平的1.105倍、1.034倍、1.105倍(P<0.05)。结论HMGB1、CCL20、HSP27在CP患者血清中呈异常高表达,各指标水平与牙周病变程度均呈正相关,且联合检测对CP具有较高诊断价值,可作为临床诊断CP、评估牙周病变程度的有效指标。

OGDHL、FHL1在非小细胞肺癌组织中的表达及其临床意义

目的分析OGDHL、4个半LIM结构域蛋白1(FHL1)在非小细胞肺癌组织中的表达水平及其临床意义。方法选取80例非小细胞肺癌患者癌组织标本、癌旁组织标本(距肿瘤边缘4cm处),采用免疫组织化学染色法检测所有标本组织中OGDHL、FHL1表达水平。采用χ^(2)检验分析OGDHL、FHL1表达与患者病理特征的关系,采用Kaplan-Meier生存曲线分析OGDHL、FHL1表达与患者预后的关系,多因素Cox回归模型分析非小细胞肺癌患者预后的影响因素。结果非小细胞肺癌患者癌组织OGDHL高表达率明显低于癌旁组织(35.00%vs 62.50%,P<0.05),FHL1高表达率明显高于癌旁组织(67.50%vs 40.00%,P<0.05)。OGDHL、FHL1表达水平与非小细胞肺癌患者TNM分期、淋巴结转移、分化程度密切相关(P<0.05)。OGDHL高表达患者术后5年总生存率为82.14%,低表达患者术后5年总生存率为36.54%,两者比较差异有统计学意义(P<0.05);FHL1高表达患者术后5年总生存率为40.74%,低表达患者术后5年总生存率为76.92%,两者比较差异有统计学意义(P<0.05)。单因素分析得出,TNM分期、淋巴结转移、分化程度、OGDHL表达、FHL1表达均与非小细胞肺癌患者预后密切相关(P<0.05)。TNMⅢ期、淋巴结转移、低分化、OGDHL低表达、FHL1高表达均为影响非小细胞肺癌患者预后的独立危险因素(P<0.05)。结论非小细胞肺癌患者癌组织中OGDHL蛋白呈低表达,FHL1蛋白呈高表达,两者表达水平与非小细胞肺癌患者的临床病理特征及预后密切相关,能够作为评估患者预后的有效指标。

脑梗死继发癫痫患者血清NRG1、VILIP-1水平及临床意义

目的检测脑梗死继发癫痫患者的血清神经调节蛋白1(NRG1)、视锥蛋白样蛋白-1(VILIP-1)水平并探讨其临床意义。方法选取2019年1月至2023年4月期间安阳市第三人民医院收治的100例脑梗死继发癫痫患者作为研究组,并依照发病时间分为早发型癫痫组(n=53)和晚发型癫痫组(n=47)。选取同期脑梗死未继发癫痫患者60例作为对照组。比较早发型癫痫组和晚发型癫痫组患者的血清NRG1、VILIP-1水平以及研究组和对照组患者的临床资料,采用Pearson相关分析血清NRG1与VILIP-1的关系,采用多因素Logistic回归分析脑梗死继发癫痫的影响因素,绘制受试者工作特征曲线(ROC)分析NRG1、VILIP-1对脑梗死继发癫痫的预测价值。结果早发型癫痫患者的血清NRG1、VILIP-1水平分别为(23.72±3.47)pg/mL、(627.49±72.29)pg/mL,明显高于晚发型癫痫的(20.38±3.60)pg/mL、(572.52±61.49)pg/mL,差异均有统计学意义(P<0.05);研究组患者入院时的美国国立卫生研究院卒中量表(NIHSS)评分、血清神经元特异性烯醇化酶(NSE)、NRG1、VILIP-1、同型半胱氨酸(Hcy)水平分别为(12.58±2.86)分、(8.87±1.54)k U/L、(22.15±3.53)pg/mL、(601.65±67.21)pg/mL、(31.53±4.08)μmol/L,明显高于对照组的(11.66±2.12)分、(7.76±1.67)k U/L、(18.72±2.83)pg/mL、(542.74±61.71)pg/mL、(31.53±4.08)μmol/L,而脑源性神经生长因子(BDNF)为(4.18±0.89)μg/mL,明显低于对照组的(5.02±1.10)μg/mL,差异均有统计学意义(P<0.05);Pearson相关分析结果显示,血清NRG1与VILIP-1表达水平呈正相关(r=0.553,P<0.05);多因素Logistic回归分析结果显示,NSE、NRG1、VILIP-1、Hcy均是脑梗死继发癫痫的危险因素(P<0.05),BDNF是脑梗死继发癫痫的保护因素(P<0.05);ROC分析结果显示,血清NRG1、VILIP-1预测脑梗死继发癫痫的AUC分别为0.844、0.768,NRG1联合VILIP-1预测的AUC为0.883,两者联合预测脑梗死继发癫痫的AUC优于NRG1(Z_(两者联合-NRG1)=2.058)、VILIP-1(Z_(两者联合-VILIP-1)=3.820)单独指标(P<0.05)。结论脑梗死继发癫痫患者血清NRG1、VILIP-1水平异常高表达,是患者脑梗死后继发癫痫的危险因素,两者联合检测对预测脑梗死后继发癫痫具有较高的临床价值。

血清长链非编码RNA肌动蛋白纤维相关蛋白1-反义RNA1水平与钙化性主动脉瓣狭窄病人左心室功能的相关性研究

目的 分析血清长链非编码RNA(lncRNA)肌动蛋白纤维相关蛋白1-反义RNA1(AFAP1-AS1)表达水平与钙化性主动脉瓣狭窄(CAS)病人左心室收缩及舒张功能的相关性。方法 于2020年1月至2021年12月,选取中国中医科学院广安门医院就诊的CAS病人129例作为CAS组[左心室射血分数(LVEF)≥50%],同期该院健康志愿者130例作为对照组。收集病人人口学资料、超声及实验室生化指标,检测血清lncRNA AFAP1-AS1表达。受试者操作特征曲线(ROC曲线)分析血清lncRNA AFAP1-AS1诊断CAS效能。结果 对照组血清lncRNA AFAP1-AS1表达水平(1.15±0.18)低于CAS组(1.58±0.30)(P<0.001)。轻度狭窄者血清lncRNA AFAP1-AS1表达水平(1.37±0.26)低于中、重度狭窄者,而中度狭窄者lncRNA AFAP1-AS1表达水平(1.59±0.30)低于重度狭窄者(1.79±0.34)(P<0.001)。ROC结果显示,血清lncRNA AFAP1-AS1诊断CAS、重度狭窄的曲线下面积分别为0.86[95%CI:(0.82,0.91)]、0.88[95%CI:(0.82,0.94)]。CAS组AVA水平低于对照组(P<0.001),左室舒张末期内径(LVEDD)、左室舒张末期容积(LVEDV)、室间隔厚度(IVST)、左室后壁厚度(LVPWT)、左房前后径(LAD)、主动脉瓣平均压差(PGmean)、主动脉瓣峰值流速(Vmax)水平高于对照组(均P<0.001)。相关性分析显示,血清lncRNA AFAP1-AS1与LVEDD、Vmax、二尖瓣口舒张早期血流速度峰值(E峰)、二尖瓣口舒张晚期血流速度峰值(A峰)、LVEDV、PGmean、LVESD呈正相关(r=0.60、0.66、0.72、0.68、0.56、0.57、0.50,均P<0.001),与LVEF、AVA呈负相关(r=-0.78、-0.62,均P<0.001)。结论 CAS病人血清lncRNA AFAP1-AS1表达水平升高,与CAS病情严重程度以及左心室舒张、收缩功能有关,并可作为无创血清标志物辅助临床诊断CAS。

子痫前期患者胎盘中EG-VEGF及其PROKR1和PROKR2的表达情况

目的探讨子痫前期(PE)患者血清、胎盘中内分泌腺源性血管内皮生长因子(EG-VEGF)、前动力蛋白1(PROK1)、前动力蛋白2(PROK2)的表达情况及其临床意义。方法选取2019年1月至2022年1月该院收治的100例PE患者作为研究组,依据病情严重程度分为轻度组和重度组,各50例。同时,选取同期行剖宫产手术的50例健康孕妇作为对照组。比较两组临床指标[γ-谷氨酰转移酶(GGT)、乳酸脱氢酶(LDH)、尿酸(UA)、收缩压、舒张压、血小板计数、新生儿体重、螺旋动脉管壁厚度、螺旋动脉管腔面积、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、尿素氮(BUN)]。对比分析不同组、不同病情严重程度患者血清、胎盘组织中EG-VEGF、PROKR1、PROKR2 mRNA水平。采用免疫组化法检测两组胎盘组织中EG-VEGF、PROKR1、PROKR2阳性表达率,分析研究组血清各指标与临床特征、病情严重程度相关性,以及检测不同新生儿结局的孕妇血清中各指标水平。采用受试者工作特征(ROC)曲线分析血清各指标水平对PE的诊断价值。结果与对照组比较,研究组收缩压、舒张压、血小板计数、螺旋动脉管壁厚度升高,GGT、LDH、UA、ALT、AST、MDA水平升高,新生儿体重、螺旋动脉管腔面积降低,BUN、SOD水平降低,差异均有统计学意义(P<0.05)。与对照组比较,研究组血清、胎盘组织中EG-VEGF、PROKR1、PROKR2 mRNA水平降低(P<0.05),且其水平与新生儿体重、螺旋动脉管腔面积、BUN、SOD呈正相关,而与收缩压、舒张压、螺旋动脉管壁厚度、GGT、LDH、ALT、MDA、病情严重程度呈负相关(P<0.05)。研究组EG-VEGF、PROKR1、PROKR2阳性表达率低于对照组(P<0.05);研究组发生新生儿不良结局的孕妇血清中EG-VEGF、PROKR1、PROKR2水平低于对照组(P<0.05)。EG-VEGF、PROKR1、PROKR2联合诊断PE的曲线下面积大于单项诊断(P<0.05)。结论PE患者血清、胎盘中EG-VEGF、PROKR1、PROKR2呈低表达,且与临床特征、病情严重程度、新生儿不良结局存在相关性,联合检测其水平可提高PE的诊断效能。

circRNA SIPA1L1修饰牙髓干细胞来源外泌体促血管生成能力的机制

目的 探究环状RNA(circRNA)信号诱导增殖相关蛋白1样蛋白1(SIPA1L1)修饰的人牙髓干细胞(hDPSC)来源外泌体(Exo)对人脐静脉内皮细胞(HUVEC)血管生成能力的影响及机制。方法 从牙髓组织分离培养hDPSC,将circSIPA1L1过表达质粒载体转染至hDPSC后,分离Exo并进行鉴定。将HUVEC分为对照组、hDPSC Exo组、circSIPA1L1-hDPSC Exo组,培养48 h后,Matrigel基质胶血管形成实验检测血管形成能力,qRT-PCR和Western blot测定血管内皮细胞生长因子(VEGF)、血管内皮细胞生长因子受体2(VEGFR2)、胎盘生长因子(PGF)的表达水平。结果 从未转染的hDPSC与转染circSIPA1L1的hDPSC中成功分离出Exo,且相较于h DPSC来源的Exo,转染circSIPA1L1的hDPSC来源的Exo中circSIPA1L1相对表达量显著上调(P <0.05)。与hDPSC Exo组比较,circSIPA1L1-hDPSC Exo组HUVEC的管样结构形成数目显著增加(P <0.05),VEGF、VEGFR2、PGF mRNA与蛋白相对表达量也显著上调(P<0.05)。结论 circRNA SIPA1L1修饰hDPSC来源的Exo能够促进血管生成,其机制可能与上调VEGF、VEGFR2、PGF的表达水平有关。

中晚期宫颈癌患者血清HE4、TK1、DCLK1水平变化及其与化疗效果的关系

目的 分析中晚期宫颈癌患者血清人附睾蛋白4(HE4)、胸苷激酶1(TK1)、双皮质素样激酶1(DCLK1)变化及其与化疗效果的关系。方法 收集2020年1月至2023年1月于郑州大学第一附属医院接受化疗的215例中晚期宫颈癌患者的病历资料,根据纳入患者的化疗效果将其分为良好组和不良组,其中良好组疗效评估结果为完全缓解(CR)与部分缓解(PR),共173例,不良组疗效评估结果为稳定(SD)与进展(PD),共42例。比较两组血清HE4、TK1、DCLK1水平等临床资料,分析中晚期宫颈癌患者血清HE4、TK1、DCLK1水平与化疗效果的关系。结果 良好组临床分期为Ⅱ期比例、高分化比例、无淋巴结转移比例均高于不良组,肿瘤最大直径以及血清HE4、TK1、DCLK1水平均低于不良组,差异均有统计学意义(P<0.05);经logistic多因素分析显示,肿瘤的临床分期达到Ⅳ期、分化程度为中低分化、淋巴结转移以及血清HE4、TK1、DCLK1水平升高均为影响中晚期宫颈癌患者化疗效果的独立因素(P<0.05);经Spearman相关性分析显示,中晚期宫颈癌患者临床分期、淋巴结转移以及血清HE4、TK1、DCLK1水平与其化疗效果成负相关,分化程度与其化疗效果成正相关(P<0.05)。结论 中晚期宫颈癌患者临床分期越晚、分化程度越差、临床转移以及HE4、TK1、DCLK1水平越高,越不利于患者的化疗,上述指标对其预后均具有一定预测价值。

NRG1、HER3在前列腺癌组织中的表达及其与临床病理特征和预后的关系

目的研究前列腺癌(PC)组织中神经调节蛋白1(NRG1)、人表皮生长因子受体3(HER3)表达与临床病理特征及预后的关系。方法选取2015年2月—2020年2月吉林省人民医院泌尿外科诊治PC患者96例,免疫组织化学检测组织中NRG1、HER3表达;Kaplan-Meier曲线(Log-Rank检验)比较不同NRG1、HER3表达对PC患者预后的影响;COX回归分析PC患者预后的影响因素。结果PC癌组织中NRG1、HER3阳性率分别为78.13%(75/96)、75.00%(72/96),高于癌旁组织6.25%(6/96)、8.33%(8/96)(χ^(2)/P=101.670/<0.001,87.771/<0.001)。TNM分期Ⅲ期、Gleason评分>7分及术前PSA水平≥20μg/L患者癌组织中NRG1、HER3阳性率大于TNM分期Ⅰ~Ⅱ期、Gleason评分≤7分及术前PSA水平<20μg/L(χ^(2)/P=6.181/0.013,8.533/0.003;7.731/0.005,6.769/0.009;6.508/0.011,7.376/0.007)。NRG1阳性组、HER3阳性组3年累积无进展生存率分别低于NRG1阴性组、HER3阴性组(χ^(2)/P=4.267/0.039,5.499/0.019)。TNM分期Ⅲ期、Gleason评分>7分、术前PSA≥20μg/L、NRG1阳性,HER3阳性是影响PC患者预后的独立危险因素[OR(95%CI)=1.448(1.118~1.875),1.401(1.138~1.724),1.353(1.059~1.728),1.338(1.057~1.692),1.293(1.014~1.649)]。结论PC癌组织中NRG1、HER3表达升高,与PC不良临床病理特征相关,是新的评估PC预后的肿瘤标志物。

血清几丁质酶-3样蛋白1与血液透析患者预后关系的研究

目的探讨血清几丁质酶-3样蛋白1(chitinase 3-like protein 1,CHI3L1)与血液透析患者全因死亡和心脑血管疾病死亡之间的关系。方法本研究为前瞻性队列研究,病例来自2014年9月北京大学第三医院肾内科维持性血液透析患者。测定基线血CHI3L1水平,并根据中位数将患者分为高CHI3L1组和低CHI3L1组,随访9年。用Kaplan-Meier生存分析高CHI3L1组和低CHI3L1组患者生存率的差异,用限制性立方样条(restricted cubic spline,RCS)曲线描述CHI3L1与全因死亡率的剂量反应关系,用多因素COX比例风险模型分析患者全因死亡或心脑血管疾病死亡的独立危险因素。结果共纳入109例患者,随访时间为80.0(38.2,113.2)个月。Kaplan-Meier生存分析显示高CHI3L1组患者全因死亡率高于低CHI3L1组(χ^(2)=4.720,P=0.030),2组患者心脑血管疾病死亡率无明显差异(χ^(2)=1.954,P=0.162)。当CHI3L1≥199.8 ng/ml时,全因死亡率随着CHI3L1水平的增加有明显增加(HR=1.747,95%CI:1.035~2.947,P=0.037)。COX回归分析结果显示:年龄增加(HR=1.029,95%CI:1.001~1.056,P=0.040)、长透析龄(HR=2.251,95%CI:1.310~3.868,P=0.003)、收缩压高(HR=1.022,95%CI:1.008~1.036,P=0.002)、血肌酐低(HR=0.135,95%CI:0.064~0.283,P<0.001)均为血液透析患者全因死亡的独立危险因素,多种因素校正后高CHI3L1仍然是患者全因死亡的独立危险因素(HR=1.963,95%CI:1.010~3.813,P=0.047)。结论高CHI3L1组患者全因死亡率高于低CHI3L1组患者,血CHI3L1可能是血液透析患者全因死亡的独立预测指标。

有氧运动通过Keap1Nrf2HO-1通路对睡眠障碍老年大鼠认知的改善机制

目的探究有氧运动通过Keap1Nrf2HO-1通路对睡眠障碍老年大鼠认知的改善机制。方法选用Wistar大鼠,60只,雌雄各半,将大鼠均分为4组,其中一组为空白组,其余分为模型组、给药组(根据每只大鼠的体重按照0.5 mg/kg进行艾司唑仑片灌胃给药)和有氧运动组,每组15只。结果与空白组比较,模型组逃避潜伏期延长(P<0.01),且伴随着明显的寻台次数较少、穿越原平台次数降低(P<0.01),大鼠在原平台停留的时间占总游泳时间的百分比降低(P<0.05);与模型组比较,给药组和有氧运动组逃避潜伏期缩短(P<0.01),且伴随着明显的寻台次数增加、穿越原平台次数增加(P<0.01),在原平台停留的时间占总游泳时间的百分比升高(P<0.05)。与空白组比较,模型组MDA水平升高,SOD活性降低(P<0.01),Keap1水平升高(P<0.01),Nrf2和HO-1水平降低(P<0.01);与模型组比较,给药组和有氧运动组MDA水平降低,SOD活性升高(P<0.01),Keap1水平降低,Nrf2和HO-1水平升高(P<0.01)。结论有氧运动能够有效缓解失眠障碍大鼠的认知功能,其机制原理可能与有氧运动通过改善睡眠障碍大鼠机体内海马组织的Keap1/Nrf2/HO-1蛋白表达水平从而产生抗氧化应急作用有关。

炎调方通过PD-1/PD-L1通路抑制脓毒症大鼠T淋巴细胞衰竭的实验研究

目的研究炎调方对脓毒症大鼠T淋巴细胞及T淋巴细胞表面表面程序性死亡蛋白(PD-1)、程序性死亡蛋白配体(PD-L1)表达的影响。方法SD大鼠(雄性)分为正常组、假手术组、模型组和炎调方组。盲肠结扎穿孔(CLP)制备脓毒症大鼠模型,于造模后12、24、48、72 h采集外周血处死大鼠(每个时间点各5只大鼠),采用流式细胞分析法测定CD3^(+)、CD4^(+)、CD8^(+)比例;双抗体夹心酶联免疫吸附法(ELISA)测定CD4^(+)及CD8^(+)表面PD-1、PD-L1表达水平。结果白介素-6(IL-6)在脓毒症模型组12 h分泌达到高峰后逐渐下降,降钙素原(PCT)在模型组24 h达到高峰后逐渐下降;炎调方组在12 h降低IL-6的水平(P<0.05),24 h时明显降低IL-6、PCT的水平(P<0.01)。模型组CD3^(+)、CD4^(+)、CD8^(+)比例早期分泌开始减少,48 h分泌达最低点(P<0.01);炎调方组在48 h时可升高CD3^(+)、CD4^(+)、CD8^(+)比例,提高CD4^(+)/CD8^(+)的比值而具体调节T细胞活化和增殖的功能。模型组CD4^(+)、CD8^(+)表面PD-1、PD-L1表达水平早期24 h即表达增多(P<0.01),72 h表达最多;炎调方组24 h时即可抑制PD-1、PD-L1的表达水平而具体改善T细胞衰竭的作用。CD4^(+)的比例与CD4^(+)表面PD-1、PD-L1的表达呈负相关(P<0.01);CD8^(+)比例与CD8^(+)表面PD-1、PD-L1的表达呈负相关(P<0.01)。结论脓毒症早期48 h内即出现了T细胞活化和增殖的功能衰竭引起的T细胞免疫抑制。炎调方能在脓毒症早期改善T细胞活化和增殖的功能,其机制可能与抑制PD-1/P-L1通路有关。

依达拉奉右莰醇联合丁苯酞氯化钠注射液对急性脑梗死患者血清单核细胞趋化蛋白-1、内皮素-1表达的影响

目的探讨依达拉奉右莰醇联合丁苯酞氯化钠注射液对急性脑梗死患者血清单核细胞趋化蛋白-1(MCP-1)、内皮素-1(ET-1)表达及动脉粥样硬化斑块的影响。方法选取河北省邯郸市中医院2020年12月至2022年8月收治的急性脑梗死患者140例,按随机数字表法分为联合组和对照组,各70例。两组患者均予丁苯酞氯化钠注射液,联合组患者加用依达拉奉右莰醇注射液,均治疗14 d。结果联合组总有效率为91.43%,显著高于对照组的68.57%(P<0.05)。治疗后,两组患者的颈动脉内中膜厚度、斑块面积、美国国立卫生研究院卒中量表(NIHSS)评分、改良Rankin量表(MRS)评分及血清MCP-1、ET-1、丙二醛、超氧化物歧化酶水平均显著降低(P<0.05),且联合组均显著低于对照组(P<0.05);联合组和对照组患者治疗期间不良反应发生率相当(12.86%比14.29%,P>0.05)。结论依达拉奉右莰醇联合丁苯酞氯化钠注射液治疗急性脑梗死的临床疗效良好,可有效改善患者的神经功能缺损情况、颈动脉粥样硬化斑块稳定性及内皮功能,降低氧化应激水平,提高生活质量,且安全性良好。