中期因子在相关疾病发病机制和治疗中的研究进展

中期因子(Midkine,MK),是一种分泌型肝素结合性生长因子,具有促进细胞有丝分裂、诱导细胞恶化、促进微血管生成、抑制细胞凋亡、促进炎症介质趋化、促纤溶等功能特点;经研究发现,当机体处于健康状态时中期因子除了肾脏及小肠上皮少量表达,其他部位极少表达,但机体出现疾病时,中期因子在体内的表达明显增多,如在多种恶性肿瘤、动脉粥样硬化、各类炎症、糖尿病肾病、高血压及COPD等疾病中均监测到中期因子的高表达,进一步研究发现上述疾病的发生发展与中期因子的功能特点密切相关;近年有学者利用MK在疾病发生发展中的功能特点对疾病进行治疗,特别是MK在肿瘤领域的治疗已成为研究热点,本文结合国内外的最新研究现状就MK与相关疾病的发病机制及治疗作一简要概述,并提出进一步研究的设想。     

CD80、CD86在鼻咽癌中的表达及其临床病理意义

目的:研究CD80、CD86在鼻咽癌中的表达变化及其临床病理意义。方法:选择2014年10月至2018年10月本院接诊的鼻咽癌确诊患者64例纳入研究,依据鼻咽癌复发情况分复发组(n=30)和未复发组(n=34);同期选取正常鼻粘膜活检组织33例作为正常对照组,采用SP免疫组化法检测鼻咽癌患者癌组织或正常鼻粘膜活检组织CD80、CD86蛋白的表达,并经Spearman相关性分析法分析CD80、CD86蛋白表达与鼻咽癌恶化程度的相关性。结果:鼻咽癌的癌组织CD80、CD86蛋白均呈高表达,阳性表达主要定位于细胞膜、细胞质,与肿瘤临床TNM分期、淋巴结转移均显著相关(P0.05)。复发组、未复发组肿瘤组织中的mRNA(ARD1、Ptch1、Survivin)表达显著高于对照组,且复发组高于未复发组,差异有统计学意义(P0.05)。Spearman相关性分析显示CD80、CD86蛋白表达与鼻咽癌细胞侵袭能力呈显著正相关(r=0.403、0.547,P0.05)。结论:鼻咽癌的癌组织内CD80、CD86蛋白均呈高表达,与鼻咽癌的临床分期、淋巴结转移及放疗预后关系密切,可能作鼻咽癌临床诊治及预后评估的重要参考指标。     

中老年健康体检人群多项肿瘤标志物筛查结果及与年龄和性别的关系分析

摘要 目的：研究中老年健康体检人群多项肿瘤标志物（TM）筛查结果,分析其与年龄和性别的关系。方法：将自2017年6月至2019年12月于我院接受健康体检的600例中老年体检者纳入研究,分别以流式荧光发光法检测甲胎蛋白（AFP）、癌胚抗原（CEA）、糖类抗原-153（CA-153）、糖类抗原-125（CA-125）水平,并分析不同性别、年龄的体检者上述TM阳性率情况,分析各项TM阳性率检出疾病情况。结果：600例体检者AFP、CEA、CA-153、CA-125水平分别为（17.48±3.84）ng/mL、（4.54±1.19）ng/mL、（29.23±7.10）U/mL、（30.65±6.39）U/mL,阳性率分别为1.67%、4.00%、3.33%、3.83%。男性体检者CEA及CA-153阳性率均高于女性,而CA-125阳性率低于女性（P＜0.05）;男性与女性AFP阳性率对比不明显（P＞0.05）。81～89岁体检者的AFP、CEA、CA-153、CA-125阳性率均高于其他年龄段体检者（P＜0.05）。AFP、CEA、CA-153、CA-125阳性体检者恶性肿瘤检出率较低。结论：AFP、CEA、CA-153、CA-125表达升高,可能是中老年人群肿瘤发生、发展的早期预警,应予以高度重视,且和年龄、性别关系密切。中老年人群定期体检能够早期发现疾病并治疗,防止疾病继续恶化,保证身心健康。     

利多卡因经气管内给药和静脉给药对全麻苏醒期患者镇静镇痛效果、血流动力学和呛咳反应的影响

摘要 目的：探讨利多卡因经气管内给药和静脉给药对全麻苏醒期患者镇静镇痛效果、血流动力学和呛咳反应的影响。方法：选取2018年3月~2019年8月于我院在气管内全麻下完成泌尿外科、腹部外科并预计于术后可以迅速拔除气管导管的患者63例,上述患者根据随机数字表法分为A组（n=31）和B组（n=32）,A组患者给予利多卡因静脉给药,B组患者给予利多卡因经气管内给药,比较两组患者苏醒时间、拔管时间、镇静镇痛效果、血流动力学及呛咳反应。结果：两组苏醒时间、拔管时间组间比较差异无统计学意义（P>0.05）。两组插管时、拔管时、拔管后10 min心率（HR）、收缩压（SBP）、舒张压（DBP）均呈先升高后降低趋势,且B组插管时、拔管时、拔管后10 min的HR、SBP、DBP均低于A组（P<0.05）。两组拔管时、拔管后10 min组内及组间镇静-躁动评分(SAS)比较差异无统计学意义（P>0.05）;两组拔管后10 min疼痛视觉模拟量表(VAS)评分高于拔管时,但B组低于A组（P<0.05）。B组患者插管时、拔管时呛咳反应发生率均低于A组（P<0.05）。结论：与静脉给药相比,全麻苏醒期患者给予利多卡因经气管内给药,镇静镇痛效果确切,可减轻血流波动,降低插管时、拔管时呛咳反应发生率。     

Relationship between body condition score loss and mRNA of genes related to fatty acid metabolism and the endocannabinoid system in adipose tissue of periparturient cows

The endocannabinoid system (ECS) controls feed intake and energy balance in nonruminants. Recent studies suggested that dietary management alters the expression of members of the ECS in the liver and endometrium of dairy cows. The aim of this study was to determine the relationship between body condition score (BCS) loss and the mRNA abundance of genes related to fatty acid metabolism and the ECS in the subcutaneous adipose tissue (AT) of dairy cows. The BCS was determined in multiparous (3.2 ± 0.5 lactations) Holstein cows at −21 and 42 days relative to calving (designated as d = 0). Cows were grouped into three categories according to BCS loss between both assessments as follows: (1) lost ≤0.25 unit (n = 8, low BCS loss (LBL)), (2) lost between 0.5 and 0.75 units (n = 8, moderate BCS loss (MBL)) and (3) lost ≥1 unit (n = 8, high BCS loss (HBL)). Concentrations of haptoglobin and non-esterified fatty acids (NEFAs) were determined in plasma. Real-time PCR was used to determine mRNA abundance of key genes related to fatty acid metabolism, inflammation and ECS in AT. Milk yield (kg/day) between week 2 and 6 post-calving was greater in the LBL group (49.4 ± 0.75) compared to MBL (47.9 ± 0.56) and HBL (47.4 ± 0.62) groups (P < 0.05). The overall mean plasma haptoglobin and NEFA concentrations were greater in MBL and HBL groups compared with the LBL group (P < 0.05). The mRNA abundance of TNF-α, Interleukin-6 (IL-6) and IL-1β was greatest at 21 and 42 days post-calving in HBL, intermediate in MBL and lowest in LBL groups, respectively. Cows in the HBL group had the greatest AT gene expression for carnitine palmitoyltransferase 1A, hormone sensitive lipase and adipose triglyceride lipase at 21 and 42 days post-calving (P < 0.05). Overall, mRNA abundance for very long chain acyl-CoA dehydrogenase and peroxisome proliferator-activated receptor gamma, which are related to NEFA oxidation, were greater in MBL and HBL groups compared to the LBL group at 42 days post-calving. However, mRNA abundance of fatty acid amide hydrolase was lower at 21 and 42 days post-calving in HBL cows than in LBL cows (P < 0.05). In summary, results showed a positive association between increased degree of BCS loss, inflammation and activation of the ECS network in AT of dairy cows. Findings suggest that the ECS might play an important role in fatty acid metabolism, development of inflammation and cow’s adaptation to onset of lactation.     

An on-lattice agent-based Monte Carlo model simulating the growth kinetics of multicellular tumor spheroids

PurposeTo develop an on-lattice agent-based model describing the growth of multicellular tumor spheroids using simple Monte Carlo tools.MethodsCells are situated on the vertices of a cubic grid. Different cell states (proliferative, hypoxic or dead) and cell evolution rules, driven by 10 parameters, and the effects of the culture medium are included. About twenty spheroids of MCF-7 human breast cancer were cultivated and the experimental data were used for tuning the model parameters.ResultsSimulated spheroids showed adequate sizes of the necrotic nuclei and of the hypoxic and proliferative cell phases as a function of the growth time, mimicking the overall characteristics of the experimental spheroids. The relation between the radii of the necrotic nucleus and the whole spheroid obtained in the simulations was similar to the experimental one and the number of cells, as a function of the spheroid volume, was well reproduced. The statistical variability of the Monte Carlo model described the whole volume range observed for the experimental spheroids. Assuming that the model parameters vary within Gaussian distributions it was obtained a sample of spheroids that reproduced much better the experimental findings.ConclusionsThe model developed allows describing the growth of in vitro multicellular spheroids and the experimental variability can be well reproduced. Its flexibility permits to vary both the agents involved and the rules that govern the spheroid growth. More general situations, such as, e. g., tumor vascularization, radiotherapy effects on solid tumors, or the validity of the tumor growth mathematical models can be studied.     

Discovery of a novel selective water-soluble SMAD3 inhibitor as an antitumor agent

Targeting the SMAD3 protein is an attractive therapeutic strategy for treating cancer, as it avoids the potential toxicities due to targeting the TGF-β signaling pathway upstream. Compound SIS3 was the first selective SMAD3 inhibitor developed that had acceptable activity, but its poor water solubility limited its development. Here, a series of SIS3 analogs was created to investigate the structure–activity relationship for inhibiting the activation of SMAD3. On the basis of this SAR, further optimization generated a water-soluble compound, 16d, which was capable of effectively blocking SMAD3 activation in vitro and had similar NK cell-mediated anticancer effects in vivo to its parent SIS3. This study not only provided a preferable lead compound, 16d, for further drug discovery or a potential tool to study SMAD3 biology, but also proved the effectiveness of our strategy for water-solubility driven optimization.     

淇县宋庄东周墓殉人颅骨的形态学

河南省鹤壁市的淇县宋庄东周墓地的多座墓葬不仅出土大量青铜礼乐器和陶器,而且存在人殉现象,宋庄墓地的发现为探讨东周时期豫北地区考古学文化与政治格局提供了重要线索。为了分析宋庄墓地东周墓葬人殉的种系来源,本文对其中保存较好的7例女性人殉颅骨进行了形态学分析。淇县宋庄组与仰韶文化的宝鸡组和大汶口、龙山文化的呈子组均具有较大相似性,与青铜时代的毛饮合并B组、西村周组和双楼组也较为接近。初步认为,淇县宋庄女性人殉与东周时期的豫北和晋地传统居民在体质特征存在一定的区别,而与周人畿内和郑韩故城及其以西以北地区的中原文化居民有更多的亲缘关系。     

成都市温江区不同栽植年限园林植物土壤动物群落特征

对成都市温江区不同栽植年限园林植物土壤动物群落特征进行调查分析,4次取样共捕获土壤动物10258只,隶属26目78科。不同园林植物土壤动物类群数存在显著差异,基本以红花檵木、银杏样地最高,结缕草样地最低,各栽植年限土壤动物类群数均低于周边农田和撂荒地;桂花样地土壤动物类群数、个体数受季节变化影响较小,其余样地土壤动物个体数具有明显的季节动态,而类群数随季节变化不显著;土壤动物多样性指数受园林植物种类及栽植年限影响,银杏样地土壤动物密度-类群指数(DG)及Margalef丰富度指数(D)和结缕草样地土壤动物Shannon多样性指数(H)及D指数均随栽植年限增加而显著降低,桂花样地土壤动物DG指数、D指数则随栽植年限增加显著升高,红花檵木样地土壤动物多样性各指数随栽植年限增加未表现规律性变化,其中土壤动物DG、D、H指数各栽植年限基本以桂花样地最低;聚类及典型关联分析(CCA)表明,园林植物种类对样地生境的影响大于栽植年限,土壤动物对不同生境因子响应不同,其中速效P、土壤pH对土壤动物影响较大。土壤动物群落特征受园林植物种类、栽植年限及栽培管理方式的影响,而过度人为干扰、单一植物连栽会对土壤动物产生不利影响,并可能导致土壤地力衰退。     

多学科协作诊治模式下的营养干预在老年骨折患者围术期的应用

目的研究多学科协作诊治模式(MDT)下的营养干预对围术期老年骨折患者的干预效果。方法选取新疆维吾尔自治区人民医院骨科2018年9月至2019年9月收治的42例行常规治疗的围术期老年患者作为非MDT组,选取同期43例实施MDT模式并给予营养干预的围术期老年患者作为MDT组,比较两组患者术后基本情况、并发症发生情况及恢复情况。结果术后MDT组患者总蛋白、白蛋白水平均高于非MDT组,NRS2002评分、CRP、IL-6水平均低于非MDT组,差异均有统计学意义(t=-3.679 6、-4.138 8、9.073 3、-6.669 5、-4.500 2,P=0.000 4、0.000 1、0.000 1、0.000 1、0.000 1)。MDT组患者住院时间少于非MDT组,差异有统计学意义(髋关节置换术:t=2.154 8,P=0.034 1;膝关节置换术:t=2.491 9,P=0.018 9)。MDT组患者肠道功能恢复情况明显优于非MDT组,差异有统计学意义(χ~2=10.512 1,P=0.001 2)。结论 MDT模式下的营养干预能够有效促进老年骨折患者的术后康复,有利于预防并发症的发生。