Effect of recombinant human interleukin-11 on expressions of interleukin-11 receptorα-chain and glycoprotein 130 in intestinal epithelium cell line-6 after neutron irradiation

AIM： To explore the effect of recombinant human interleukin-11 （rhIL-11） on the expressions of interleukin-11 receptor α-chain （IL-11Rα） and an additional signal transducer glycoprotein 130 （gp130） in intestinal epithelium cell line-6 （IEC-6） after neutron irradiation. METHODS： Cultured IEC-6 cells were exposed to 4.0Gy neutron and treated with 100 ng/mL rhIL-11 12 h prior to or immediately after irradiation. The apoptosis and necrosis rates and expressions of IL-11Rα and gp130 were observed by flow cytometry, immunohistochemistry, Western blot and image analysis. RESULTS： The apoptosis rate of IEC-6 cells was increased by irradiation at 6 h （P 〈 0.01）, IL-11 stimulation resulted in a decreased apoptosis rate in irradiated IEC-6 cells （P 〈 0.05）. In normal control IEC-6 cells, intense immunoreactivity of IL-11Rα was located within the cell membrane and cytoplasm. The level of IL-11Rα expression significantly decreased at 6 h after irradiation （P 〈 0.01） and restored at 24 h after irradiation. In IEC-6 cells treated with both radiation and rhIL-11, the level of IL- 11Rα expression was higher than that of irradiated cells （P 〈 0.05）. When it came to gp130 protein, it was located in the cytoplasm of IEC-6 cells. After irradiation, we found a progressive decrease in the expression of gp130 protein （P 〈 0.05） in 48 hours post-radiation, while in rhIL-11-stimulated cells, it came back to normal level at 24 h after irradiation and decreased at 48 h, but was still higher than that of only irradiated cells （P 〈 0.05）. CONCLUSION： rhIL-11 can protect IEC-6 cells from neutron irradiation. The protective effect of rhIL-11 might be connected with its ability to up-regulate the expressions of specific ligand-binding subunit IL-11Rα and signal-transducing subunit gp130.

Mucin 1 and interleukin-11 protein expression and inflammatory reactions in the intestinal mucosa of necrotizing enterocolitis children after surgery

BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.

Recombinant human interleukin-11 for treatment of chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer

Objective： To evaluate the efficacy and safety of recombinant human interleukin-11 （rhIL-11） for the chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer. Methods： It was an opened and non-randomized controlled clinical study. When the platelet counts was under 75 × 10^9/L after chemotherapy, rhlL-11 was administered 25 μg/（kg·d） as a daily SC injection last for 7-14 days, or discontinued when platelet counts 〉 100 × 10^9/L. Results： Seventysix patients were enrolled into this study. The treatment group and the control group had thirty-eight cases, respectively. The mean recovery time to PLT ≥ 100 × 10^9/L was 8.1 days in treatment group, while in control group was 12.2 days （P 〈 0.01）. Moreover, the mean recovery time from PLT 〈_ 50 × 10^9/L to 〉 100 × 10^9/L was 8.9 days in treatment group, while in control group was 12.9 days （P 〈 0.05）. There was a statistical difference between the two groups. Major side effects included edema, fever, articular muscle soreness, but they were all mild and well tolerable. Conclusion： rhIL-11 can be safely and effectively used for the treatment of chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer.

Expression of Interleukin-11 and Interleukin-11 receptor a in human colorectal adenocarcinoma; Immunohistochemical analyses and correlation with clinicopathological factors

AIM： There is strong evidence that interleukin-11 （IL-11） is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11 receptor （IL-11R） has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma. METHODS： To elucidate the involvement of IL-11 and IL-11Rα in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry and Western blotting. RESULTS： Among 115 cases of adenocarcinoma, 100 cases （87.0%） showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases （75.6%） were positive for the IL-11Ra. Six cases （54.5%） and four cases （36.4%） of 11 adenomas were positive for IL-11 and IL-11Ra, respectively. The expression of IL- 11Ra correlated with the histological differentiation （P=0.033503）, the depth of tumor invasion （P= 0.006395）, Dukes＇ classification （P= 0.015648） and lymphatic invasion （P= 0.003865）. However, the expression of IL- 11Rα was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Rα proteins. CONCLUSION： IL-11 and IL-11Rα are highly expressed in human colorectal adenocarcinoma and the IL-11Rα expression is correlated with clinicopathological factors, These findings suggest that the expression of IL-11Rα is an important factor for the invasion of human colorectal adenocarcinoma.

Research progress of interleukin-11 in tumor

Interleukin-11 （IL-11） is a cytokine of IL-6 family that mediates signal transduction through a common signal transduction molecule glycoprotein 130gp130. JAK/STAT, Ras/Erk and PI3K-mediated pathways are involved in the IL-11 signaling pathway. IL-11 has traditionally been thought to be an anti-inflammatory cytokine that has a complex role in the body＇s immune response. Simultaneously, the activation of STAT3 by IL-11 provides a functional link to support the survival and growth of cancer cells. There is also evidence that IL-11 may play a role in promoting liver cancer through wound healing mechanisms. In recent years, studies have found that IL-11 could stimulate the development of tumors via promoting the proliferation and inhibiting the apoptosis of cancer cells, mediating the tolerance of cancer cells to radiotherapy and chemotherapy, and mediating the growth and survival of early microtransferred colonies. Sustained activation of JAK-STAT and PI3K-AKT signaling pathway, up-regulating the expression of IL-11 receptor and hypoxia microenvironment mediated by HIF-1a and AP-1 transcription factors are involved in the progression of cancer. Therefore, targeted therapies that treat the over expression of IL-11 or IL-11 receptors and IL-11 signaling pathway such as the JAK 1/2 and STAT3 inhibitor in cancer patients has the potential to completely relieve the tumor, which may provide us a new idea for the treatment of cancer.

Neutralization of interleukin-11 attenuates silica particles-induced pulmonary inflammation and fibrosis in vivo

Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11(IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines(i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins(i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α(IL-11Rα), Glycoprotein130(GP130), and phosphorylated extracellular signal-regulated kinase(p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.

^(11)C-PIB PET定性及半定量分析在鉴别诊断阿尔茨海默病中的价值

目的探讨通过11 C-匹兹堡化合物B(11 C-Pittsburgh compound B,11 C-PIB)正电子发射计算机断层显像(positron emission tomography,PET)定性及半定量分析脑内β-淀粉样蛋白(β-amyloid,Aβ)沉积程度,评价其对阿尔茨海默病(Alzheimer’s disease,AD)、轻度认知障碍(mild cognitive impairment,MCI)及非阿尔茨海默病所致认知障碍(non Alzheimer s disease induced cognitive impairment,NAD)的诊断及鉴别诊断价值。方法回顾性分析首都医科大学宣武医院神经内科2022年收治的AD患者(AD,n=36)、轻度认知障碍患者(MCI,n=20)、非AD所致认知障碍患者(NAD,n=19)及健康对照者(normal control,NC,n=10)作为研究对象。此85例受试者均行11 C-PIB PET显像,首先对脑内是否有Aβ沉积做阴性或阳性定性判断,再以脑干为参考脑区对大脑皮质额、顶、颞、枕叶Aβ沉积最大标准化摄取值比值(maximum standardized uptake value ratio,SUVRmax)半定量测量,并分析AD、MCI、NAD及NC组之间SUVRmax的差异。结果定性判断显示,AD组、NC组与其他各组之间差异有统计学意义,MCI组与NAD组之间差异无统计学意义。半定量分析显示,对于所有的脑区(额叶、顶叶、颞叶、枕叶),AD组的SUVRmax值都明显高于其他3个组,差异有统计学意义。在所有脑区中,NC组的SUVRmax数值最低,但SUVRmax在MCI组、NAD及NC组之间差异无统计学意义。结论11 C-PIB PET显像定性及半定量分析对诊断AD均有较高价值,半定量分析对AD及MCI有一定的鉴别意义。

纳米多级孔SAPO-11分子筛制备及其催化2-甲基萘烷基化反应

SAPO-11分子筛作为微孔沸石,通常粒径大,而粒径小的SAPO-11分子筛具有较短的孔道,更有利于分子的扩散使SAPO-11分子筛具有更高的催化活性,但存在稳定性较差的缺点,如何在水热法基础上进一步合成纳米多级孔SAPO-11分子筛极具挑战。在水热合成SAPO-11分子筛基础上,通过对前驱体凝胶进行老化处理制备纳米多级孔SAPO-11分子筛。其中,在80℃用搅拌老化制备的SAPO-11分子筛有最小晶体尺寸,通过SEM可知通过搅拌老化制备的S11-80℃-stirring分子筛呈现一种均匀纳米棒状结构,这些纳米棒的直径约500~700 nm,长度约2~4μm。通过N_(2)吸附-脱附曲线及孔径分布图可知经过老化处理的SAPO-11分子筛较传统SAPO-11都具有更大的比表面积,搅拌老化与静置老化制备的分子筛相比而言具有更大的微孔比表面积与孔体积。且通过NH_(3)-TPD对SAPO-11分子筛酸性性质进行表征,所有老化处理合成的SAPO-11分子筛酸量都有所下降。2-甲基萘(2-MN)主要来源于煤焦油,可用于制备2,6-二甲基萘(2,6-DMN),用于合成高端聚酯,为此将上述纳米多级孔SAPO-11分子筛用于催化2-甲基萘烷基化反应,结果表明使用老化处理制备的纳米多级孔SAPO-11分子筛有77.8%的2-MN初始转化率,20.4%的初始选择性,2,6-DMN、2,7-DMN的物质的量比为1.13,反应第4小时有最高2,6-DMN选择性39.9%,通过系列表征揭示了纳米多级孔SAPO-11分子筛择形催化催化机理。

小晶粒ZSM-11分子筛的合成及其正辛烷催化裂化反应性能

采用传统水热合成法,以聚丙烯酰胺(PAM)为介孔模板剂,动态晶化合成小晶粒多级孔ZSM-11分子筛。并采用预晶化液法以减少有机模板剂的用量,降低合成成本。通过X射线衍射仪、低温N_(2)物理吸附、扫描电子显微镜和化学吸附仪等多种手段对合成样品进行了系统表征。考察了介孔模板剂的用量对合成小晶粒ZSM-11分子筛颗粒尺寸的影响及其催化裂化反应性能的影响。研究发现,在合成凝胶中加入聚丙烯酰胺并不会改变ZSM-11的拓扑结构,但会显著影响分子筛的形貌、孔结构及分子筛的酸性。合成的ZSM-11晶粒尺寸大幅度减小,同时出现介孔结构,样品的酸量和酸强度均增加。在正辛烷催化裂化微反评价中小晶粒ZSM-11分子筛表现出更高的活性稳定性、更少的氢转移反应和更高的丙烯收率。

ST段抬高型心肌梗死患者血清转化生长因子11、补体C1q/肿瘤坏死因子相关蛋白5的表达及临床意义

目的 探讨转化生长因子11(transforming growth factor 11,GDF11)、补体C1q/肿瘤坏死因子相关蛋白5(complement C1q/tumor necrosis factor-related protein 5,CTRP5)在ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者血清中的表达及诊断价值。方法 选取2019年3月到2021年2月石家庄市第三医院收治的60例STEMI患者为心肌梗死组,另选取同期健康体检者50名为对照组。检测两组受试者血清GDF11、CTRP5的表达水平。采用Pearson相关性分析对STEMI患者血清中GDF11和CTRP5表达水平及二者与高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、血糖(blood glucose,GLU)、白细胞计数(white blood cell count,WBC)、中性粒细胞计数(neutrophil count,NEUT)、单核细胞计数(monocyte count,MONO)及超敏C反应蛋白(hypersensitive C reactive protein,hs-CRP)、高敏心肌肌钙蛋白T(high-sensitivity cardiac troponin T,hs-cTnT)、肌酸激酶同工酶(creatine kinase isoenzymes,CK-MB)浓度及预后不良事件的相关性进行分析。采用受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清中GDF11和CTRP5对STEMI患者的诊断价值。结果 心肌梗死组患者的血清GDF11(1.42±0.35 vs. 0.99±0.18,t=7.860,P<0.05)和CTRP5(1.49±0.43 vs. 1.01±0.22,t=7.148,P<0.05)表达水平高于对照组,差异有统计学意义。相关性分析结果显示,心肌梗死组血清GDF11和CTRP5表达水平呈正相关(r=0.550,P<0.05),GDF11和CTRP5表达水平与HDL-C呈负相关(r=-0.548,-0.592,P<0.05),与GLU(r=0.447,0.534,P<0.05)、WBC(r=0.653,0.502,P<0.05)、NEUT(r=0.562,0.578,P<0.05)、MONO(r=0.439,0.423,P<0.05)、hs-CRP(r=0.513,0.542,P<0.05)、hs-cTnT(r=0.513,0.524,P<0.05)、CK-MB(r=0.630,0.417,P<0.05)及预后不良事件(r=0.557,0.529,P<0.05)呈正相关。GDF11和CTRP5联合诊断STEMI的ROC曲线下面积大于GDF11、CTRP5单独诊断(Z=2.424、2.507,P<0.05)。结论 GDF11和CTRP5在STEMI患者血清中表达水平升高,两者联合对STEMI具有较高的诊断价值。

基于水资源生态足迹的沿海11个省级行政区水资源可持续利用分析

基于水资源生态足迹模型,对中国沿海11个省级行政区2005—2020年水资源生态足迹、水资源生态承载力及水资源可持续利用进行分析。结果表明:①水资源生态足迹与水环境生态足迹变化趋势相似,总体呈“W”型变化轨迹,水环境生态足迹占比为3类水资源生态足迹账户中最高,表明水环境生态足迹是水资源生态足迹的主要产源;②4类淡水生态足迹中,农业用水生态足迹占总淡水生态足迹的比重最高,农业用水生态足迹远高于工业、生活和生态用水生态足迹(除上海外),表明农业用水生态足迹是淡水生态足迹的主要贡献类型;③受自然因素和社会因素的影响,水资源生态承载力波动明显,呈南高北低的分布格局;④水资源整体上处于生态赤字状态,仅广西在研究期内一直为水资源生态盈余,水资源负载指数呈增长趋势且整体在II级以上,表明水资源利用程度高,潜力小,开发利用较困难,万元GDP水资源生态足迹呈下降趋势,水资源利用效率不断提升,水资源可持续利用具有一定潜力。

川崎病患儿血清Cav-1、sLR11水平与冠状动脉病变严重程度的相关性分析

目的 分析川崎病(KD)患儿血清小窝蛋白-1(Cav-1)、可溶性低密度脂蛋白受体11(sLR11)与冠状动脉病变(CAL)严重程度的关系。方法 回顾性分析2021年2月至2022年10月于济源市人民医院儿科收治的153例KD合并CAL患儿的临床资料。依据KD患儿CAL病变程度分为单支病变组(n=54)、双支病变组(n=68)和多支病变组(n=31)。对比三组患儿临床资料、血清Cav-1、sLR11水平。Logistic多因素回归分析影响KD患儿CAL严重程度的相关因素。受试者工作特征曲线(ROC)分析血清Cav-1、sLR11对KD患儿CAL严重程度的预测价值。结果 单支病变组、双支病变组和多支病变组患儿发热持续时间、C反应蛋白(CRP)、血小板(PLT)计数、红细胞沉降率(ESR)、血清Cav-1、sLR11水平依次升高(P<0.05)。多因素分析结果显示治疗前发热持续时间(OR=1.772,95%CI:1.054~2.982,P=0.031)、血清Cav-1(OR=1.139,95%CI:1.080~1.201,P<0.01)及sLR11(OR=1.251,95%CI:1.105~1.417,P<0.01)均为影响KD患儿CAL严重程度的危险因素。ROC分析显示,血清Cav-1、sLR11两者联合预测KD患儿CAL严重程度的AUC为0.910(95%CI:0.854~0.951,P<0.01)。结论 血清Cav-1、sLR11两者联合对KD患儿CAL严重程度的预测效能较高。

脂肪乳氨基酸(17)葡萄糖(11%)注射液稳定性研究

目的为临床合理使用脂肪乳氨基酸(17)葡萄糖(11%)注射液(商品名卡文)提供依据。方法将卡文3个腔室液体混匀(样品S1);再分别添加电解质(氯化钾和氯化钠,样品S2),维生素(水溶性维生素及脂溶性维生素,样品S3),多种微量元素(样品S4),以及上述所有成分(样品S5)。分别于室温下放置0,4,8,12 h时测定混合液的pH、渗透压、不溶性微粒数,并考察乳剂粒径分布情况。结果样品S1-S5室温下放置12 h内外观无明显变化,pH为5.51~5.59;渗透压,S2为934~972 mOsmol/kg,S3为816~831 mOsmol/kg,S4为810~835 mOsmol/kg,S5为934~957 mOsmol/kg;不溶性微粒变化不明显;乳剂粒径分布集中在1~10 nm。结论在卡文中添加规定限度内的电解质、维生素和多种微量元素,对其pH、不溶性微粒、乳剂粒径等影响较小,但电解质对渗透压影响较大,应予以重视。

急性病毒性肝炎患者血清HDAC3和HDAC11表达与T细胞淋巴亚群的关系研究

目的 探究急性病毒性肝炎(AVH)患者血清组蛋白脱乙酰酶3(HDAC3)和组蛋白脱乙酰酶11(HDAC11)表达水平与T细胞淋巴亚群的关系。方法 选取2022年1月—2023年6月在秦皇岛市第三医院就诊的120例AVH患者作为研究对象(AVH组),并选择同期的120名体检健康者作为对照组。收集并比较两组的一般临床资料。检测两组血清中HDAC3、HDAC11、CD3^(+)、CD4^(+)和CD4^(+)/CD8^(+)水平。利用Pearson等级相关性分析AVH患者血清HDAC3、HDAC11水平与T细胞淋巴亚群的相关性。利用受试者工作特征(ROC)曲线分析血清HDAC3、HDAC11对诊断AVH的临床价值。结果 AVH组和对照组的年龄、性别和BMI无显著性差异(P>0.05)。与对照组相比,AVH组的丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素、三酰甘油、胆固醇、低密度胆固醇显著升高(P<0.05),而AVH组的高密度胆固醇显著降低(P<0.05)。AVH组患者的血清HDAC3和HDAC11表达水平均显著高于对照组(P<0.05),CD3^(+)、CD4^(+)和CD4^(+)/CD8^(+)均显著降低于对照组(P<0.05)。Pearson相关分析显示,AVH患者血清HDAC3水平与CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)均呈负相关(r=-0.458、-0.533、-0.462,均P<0.001),HDAC3表达水平与CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)均呈负相关(r=-0.473、-0.551、-0.422,均P<0.001)。ROC曲线显示,HDAC3、HDAC11及二者联合预测诊断AVH的曲线下面积(AUC)分别为0.921、0.941、0.988,血清HDAC3、HDAC11联合诊断AVH的临床应用价值高于单项指标诊断(Z_(二者联合-HDAC3)=3.672、P=0.000;Z_(二者联合-HDAC11)=3.078、P=0.002)。结论 AVH患者血清HDAC3和HDAC11表达水平升高,且与T淋巴细胞亚群存在相关性,HDAC3与HDAC11联合预测AVH的临床价值较高。

旱地春小麦新品种银春11号生产性能评价

为全面了解银春11号的生产特性,依据2016—2017年甘肃省旱地春小麦区域试验和2018年甘肃省旱地春小麦生产试验,对其丰产性、稳产性和适应性等进行了分析。结果表明,银春11号丰产性好,增产潜力大,2016、2017年的区域试验中,分别较对照品种西旱2号增产13.25%、9.90%;银春11号具有较好的高产稳产性,2016、2017年高稳系数分别为102.82、100.06,均高于对照品种西旱2号的90.90;银春11号具有广泛的适应性,2016、2017年适应度分别为80%、60%,在各试验点中增产点率为90%。综上,银春11号丰产性、稳产性较好,适应性较强,适宜在甘肃中部旱地春麦区栽培。

腺相关病毒感染GDF11对2型糖尿病大鼠血管损伤的保护作用

目的探讨腺相关病毒感染上调体内生长和分化因子11(GDF11)表达水平对2型糖尿病大鼠(T2DM)主动脉损伤的影响。方法随机选取9周龄雄性SD大鼠,采用高糖高脂饲料加小剂量链脲佐菌素(STZ)联合诱导,建立T2DM模型。正常大鼠和糖尿病模型大鼠随机分为5组:空白对照组(Control组)、阴性病毒对照组(NC组)、GDF11腺相关病毒组(GDF11组)、糖尿病组(DM组)、糖尿病+GDF11腺相关病毒组(DM+GDF11组)。喂养8周后,检测大鼠血清中胰岛素(INS)、晚期糖基化终末产物(AGES)、重组生长转化因子11(GDF11)、总胆固醇(T-CHO)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、不对称二甲基精氨酸(ADMA)、丙二醛(MDA)浓度;采用过碘酸雪夫氏染色(PAS染色)观察糖原沉积部位,苏木精-伊红染色(HE)观察血管损伤情况,扫描电镜观察血管内皮细胞和血管弹性纤维损伤情况,蛋白印迹和免疫组化检测血管损伤相关蛋白的表达水平。结果在动物实验中与Control组相比,生化指标提示:DM组大鼠血清中AGES、T-CHO、TG、LDL-C和MDA浓度升高(P<0.05),INS、GDF11、HDL-C、ADMA显著低于Control组(P<0.05),DM+GDF11组AGES和HDL-C与DM组无明显差异,T-CHO、TG、LDL-C和MDA相比较DM组降低(P<0.05),INS、GDF11和ADMA相比较DM组升高(P<0.05)。病理染色提示:DM组PAS染色提示糖原颗粒在主动脉内皮及内皮下沉积,HE染色观察到主动脉中膜增厚,内皮细胞及弹性纤维断裂走形不规则,电镜观察到DM组血管内皮损伤,弹性纤维断裂,DM+GDF11组这些变化有所减轻。蛋白印迹和免疫组化表示内皮细胞相关蛋白在DM组中表达下降(P<0.05),间充质标志物在DM组中表达升高(P<0.05),DM+GDF11组中这些蛋白有所回调,且差异有统计学意义(P<0.05)。结论提高体内GDF11表达水平可以改善糖尿病导致的主动脉血管损伤,推断可能与其抑制内皮间充质转化保护血管内皮细胞的功能从而改善血管损伤有关。

^(68)Ga-PSMA-11 PET/CT前列腺癌假阳性病灶的病理学特点

目的基于前列腺癌根治术后标本病理大切片探究^(68)Ga-前列腺特异性膜抗原(PSMA)-11配体正电子发射/计算机断层扫描(PET/CT)前列腺癌假阳性病灶的病理特点,以期更准确地评估前列腺组织的恶性程度,避免过度诊断和不必要的治疗。方法回顾性分析2018年1月—2022年12月于南京大学医学院附属鼓楼医院行前列腺癌根治术并且术后标本制作病理大切片的77例患者的临床资料,患者术前均进行^(68)Ga-PSMA-11 PET/CT检查。2名核医学科医生盲于病理大切片对^(68)Ga-PSMA-11 PET/CT影像进行诊断,2名病理科医生盲于影像结果对病理大切片进行诊断。通过匹配影像和病理大切片来明确^(68)Ga-PSMA-11 PET/CT上前列腺内假阳性病灶,并与相应的真阴性病灶对比以明确其病理特点。采用Fisher精确检验对假阳性病灶和真阴性病灶的病理类型进行比较。结果经影像和病理大切片相互匹配后,确诊出21处(16.3%)假阳性病灶,其病理类型分别为:16处(76.2%)单纯性萎缩伴囊肿形成、3处(14.3%)前列腺增生、2处(9.5%)前列腺炎症。相应圈选的21处真阴性病灶的病理类型分别为:13处(61.9%)正常腺体结构、5处(23.8%)前列腺增生、3处(14.3%)单纯性萎缩伴囊肿形成。经Fisher精确检验发现,单纯性萎缩伴囊肿形成在假阳性病灶与其在真阴性病灶病理类型中占比的差异有统计学意义(76.2%vs.14.3%,P<0.001)。结论单纯性萎缩伴囊肿形成可能是^(68)Ga-PSMA-11 PET/CT在前列腺癌假阳性病灶中的一个特征性病理类型。

TP患者应用IL-11联合重组人血小板生成素治疗的临床疗效及安全性

目的:探讨血小板减少症(TP)患者应用白细胞介素(IL)-11联合重组人血小板生成素注射液治疗的临床疗效及安全性。方法:选取2022年8月至2023年8月在漯河医学高等专科学校第二附属医院接受治疗的150例TP患者,随机均分为常规组与联合组,每组各纳入75例。常规组给予应用IL-11治疗,联合组在常规组的基础上联合应用重组人血小板生成素输注治疗。观察两组患者治疗期间血小板计数的变化,比较血小板计数达标时间;治疗14 d,观察血清学检测指标的变化;出院前统计两组患者不良反应发生情况并比较。结果:治疗3 d、7 d、14 d时,联合组患者血小板计数均高于常规组;联合组患者血小板计数恢复至≥50×10^(9)·L^(-1)时间、≥70×10^(9)·L^(-1)时间、≥100×10^(9)·L^(-1)时间均短于常规组;治疗14 d时,联合组血清促血小板生成素(TPO)、IL-6、肿瘤坏死因子-α(TNF-α)水平均低于常规组,差异均具有统计学意义(P<0.05)。两组患者不良反应总发生率的差异无统计学意义(P>0.05)。结论:IL-11联合重组人血小板生素注射液治疗TP可获得理想的临床疗效,能有效缩短血小板达标时间,且联合方案安全性可靠。

生长分化因子11激活PI3K/Akt信号途径促进糖尿病小鼠ADSCs体外矿化的研究

目的探讨生长分化因子11(GDF11)对糖尿病小鼠来源的脂肪间充质干细胞(ADSCs)成骨分化的影响及信号机制。方法分离、培养糖尿病小鼠ADSCs。流式细胞术检测GDF11对ADSCs增殖的影响。成骨诱导培养后,检测碱性磷酸酶(ALP)活性,实时荧光定量PCR(qPCR)检测成骨相关基因的表达,Western blot检测PI3K、Akt的磷酸化水平。结果GDF11不影响ADSCs增殖,呈浓度依赖性地增强ALP活性,且具有饱和性;显著上调Runx2[(2.41±0.19)vs.(1.00±0.11)]、Osx[(1.41±0.21)vs.(1.00±0.10)]和ALP[(1.42±0.20)vs.(1.00±0.09)]的表达(P<0.05);明显提高PI3K[(2.84±0.19)vs.(1.00±0.11)]和Akt[(4.58±0.20)vs.(1.00±0.19)]的磷酸化水平(P<0.05)。而且,GDF11促进糖尿病小鼠ADSC s成骨分化的作用被PI3K抑制剂LY294002部分减弱。结论GDF11促进糖尿病小鼠ADSCs骨向分化,其作用机制可能与激活PI3K/Akt信号通路有关。

利用酵母双杂交筛选菠萝AcSWEET11的互作蛋白

SWEET(sugars will eventually be exported transporter)基因在植物开花过程中具有重要的作用,但AcSWEET11在菠萝成花中的作用机制尚不清楚。通过鉴定成花过程中与AcSWEET11的互作蛋白,为菠萝成花机制的解析奠定基础。本研究利用共转化的方法在菠萝成花过程的cDNA膜文库中筛选AcSWEET11的互作蛋白,分析候选蛋白的表达量。结果表明,pBT3-STE-AcSWEET11+pPR3-N对NMY51酵母细胞无毒性,但有自激活活性。进一步研究结果显示,在TDO/3?AT培养基和QDO培养基上自激活受到抑制。利用该系统筛选到了81个阳性克隆,经测序鉴定出48个与AcSWEET11互作的候选蛋白,包括E3 ubiquitin-protein ligase RING1-like、Trehalose-phosphate synthase 7、Cytochrome P450、TranscriptionfactorLUX等。GO和KEGG分析结果显示,48个蛋白主要分布在细胞进程、代谢过程、刺激反应和催化活性等生物过程,参与脂类代谢、氨基酸代谢和碳水化合物代谢、信号转导和运输与分解代谢等新陈代谢途径。Trehalose-phosphate synthase 7(XP_020105459.1)、Protein TIFY 3-like(XP_020082835.1)、40S ribosomal protein S27(XP_020092770.1)、Heterogeneous nuclear ribonucleoprotein 1-like(XP_020112516.1)等4个基因与AcSWEET11表达趋势一致,在菠萝成花过程中下调表达;Dihydrolipoyl dehydrogenase 2(XP_020113798.1)、Putative lipid-transfer protein DIR1(XP_020086640.1)、clathrin assembly protein At4g32285(XP_020108161.1)等3个基因在菠萝成花过程中上调表达。这些结果表明,AcSWEET11可能通过与Trehalose-phosphatesynthase7等蛋白发生互作,参与菠萝成花过程。本研究进一步丰富了AcSWEET11的蛋白互作网络,为AcSWEET11在菠萝成花中的调控机制的解析奠定基础。