Rt-PA静脉溶栓治疗急性脑梗死的疗效及对血清IL-6，IL-17及VEGF水平的影响

目的:探讨重组组织纤溶酶原激活剂(Rt-PA)静脉溶栓治疗急性脑梗死的疗效及对血清白介素-6(IL-6)、IL-17及血管内皮生长因子(VEGF)水平的影响。方法:选择2014年8月至2016年8月我院接诊的86例急性脑梗死患者,通过随机数表法分为观察组(n=43)和对照组(n=43)。对照组给予常规治疗,观察组在对照组基础上进行Rt-PA静脉溶栓。比较两组的治疗效果、不良反应的发生情况、治疗前后美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数、血清IL-6、IL-17及VEGF水平的变化。结果:治疗14 d后,观察组NIHSS评分显著低于对照组,Barthel指数明显高于对照组(P0.05);观察组在治疗后1 d、3 d、7 d、14 d时血清IL-6、IL-17水平均显著低于对照组(P0.05),治疗后1 d、3 d、7 d时血清VEGF水平明显高于对照组,治疗后14 d时血清VEGF水平显著低于对照组(P0.05)。观察组治疗后总有效率显著高于对照组(P0.05)。结论:在急性脑梗死患者中早期采用Rt-PA治疗的效果显著,可有效促进神经功能恢复,且安全性高,可能与其降低血清IL-6、IL-17、VEGF水平有关。     

胆管癌组织白介素-6、环氧合酶-2和血管内皮生长因子的表达及临床意义

目的:探讨胆管癌组织白介素-6(IL-6)、环氧合酶-2(COX-2)和血管内皮生长因子(VEGF)的表达及临床意义。方法:将手术切除并经病理诊断确诊的胆管癌石蜡包埋标本80例纳为胆管癌组,另取癌旁正常胆管组织作为对照组,采用免疫组织化学SP法检测两组组织中IL-6、COX-2、VEGF的表达情况并做比较,分析胆管癌组织中VEGF、COX-2、IL-6阳性表达与临床病理特征关系,采用Spearman等级相关分析胆管癌组织中VEGF、COX-2、IL-6表达的相关性。结果:胆管癌组的VEGF、COX-2、IL-6阳性表达率均显著高于对照组,组间比较差异有统计学意义(P0.05)。胆管癌组织中VEGF、COX-2、IL-6阳性表达率与有无淋巴结转移、TNM分期、分化程度有关(P0.05),而与性别、年龄、肿瘤直径无关(P0.05),其中有淋巴结转移、TNM分期Ⅲ～Ⅳ期、低分化程度的胆管癌患者的VEGF、COX-2、IL-6阳性表达率高于无淋巴结转移、TNM分期Ⅰ～Ⅱ期、中高分化程度的胆管癌患者(P0.05)。Spearman等级相关分析显示,胆管癌组织中VEGF与COX-2、IL-6呈正相关(P0.05),COX-2与IL-6也呈正相关(P0.05)。结论:胆管癌组织IL-6、COX-2、VEGF均呈现高表达,并与胆管癌的生长、转移密切相关,检测IL-6、COX-2和VEGF有助于判断胆管癌疾病进展。     

Autologous Bone-Marrow Mesenchymal Stem Cell Implantation and Endothelial Function in a Rabbit Ischemic Limb Model

Background

The purpose of this study was to determine whether autologous mesenchymal stem cells (MSCs) implantation improves endothelial dysfunction in a rabbit ischemic limb model.

Methods

We evaluated the effect of MSC implantation on limb blood flow (LBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted (n = 20) or saline was injected as a control group (n = 20). LBF was measured using an electromagnetic flowmeter. A total of 10⁶ MSCs were implanted into each ischemic limb.

Results

Histological sections of ischemic muscle showed that capillary index (capillary/muscle fiber) was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of N^G-nitro-L-arginine, a nitric oxide synthase inhibitor, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar.

Conclusions

These findings suggest that MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.     

经腹次全子宫切除术治疗子宫肌瘤的临床效果及对血清VEGF，IL-6，IL-8水平的影响

目的:探讨经腹次全子宫切除术治疗子宫肌瘤的临床效果及对血清血管内皮生长因子(VEGF)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)水平的影响。方法:选择我院2014年2月~2016年2月收治的106例子宫肌瘤患者,参照抽签法分作对照组与研究组。对照组采用经腹全子宫切除术治疗,研究组采用经腹次全子宫切除术治疗。比较两组的手术时间,出血量,肛门排气时间,住院时间,手术前后VEGF、IL-6、IL-8、促卵泡生成素(FSH)、雌二醇(E2)、抗苗勒管激素(AMH)水平的变化及并发症的发生情况。结果:研究组的手术时间、出血量、肛门排气时间、住院时间均明显短于对照组(P0.05)。手术前,两组血清VEGF、IL-6、IL-8、FSH、E2、AMH水平比较差异无统计学意义(P0.05);手术后,研究组血清IL-6、IL-8、E2、AMH水平明显低于对照组(P0.05),血清FSH水平明显高于对照组,差异具有统计学意义(P0.05),两组血清VEGF水平比较差异无统计学意义(P0.05)。研究组并发症的发生率显著低于对照组(P0.05)。结论:采用经腹次全子宫切除术治疗子宫肌瘤患者可起到与经腹全子宫切除术相似的应用效果,但经腹次全子宫切除术对机体形成的创伤较小,利于术后卵巢功能的恢复,可能与其降低患者术后血清IL-6、IL-8、VEGF水平有关。     

Angiogenesis gene expression in murine endothelial cells during post-pneumonectomy lung growth

Background

Human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) attenuate hyperoxic neonatal lung injury primarily through anti-inflammatory effects. We hypothesized that intratracheal transplantation of human UCB-derived MSCs could attenuate Escherichia coli (E. coli)-induced acute lung injury (ALI) in mice by suppressing the inflammatory response.

Methods

Eight-week-old male ICR mice were randomized to control or ALI groups. ALI was induced by intratracheal E. coli instillation. Three-hours after E. coli instillation, MSCs, fibroblasts or phosphate-buffered saline were intratracheally administered randomly and survival was analyzed for 7 days post-injury. Lung histology including injury scores, myeloperoxidase (MPO) activity, and protein levels of interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and macrophage inflammatory protein (MIP)-2 as well as the wet-dry lung ratio and bacterial counts from blood and bronchoalveolar lavage (BAL) were evaluated at 1, 3, and 7 days post-injury. Levels of inflammatory cytokines in the lung were also profiled using protein macroarrays at day 3 post-injury which showed peak inflammation.

Results

MSC transplantation increased survival and attenuated lung injuries in ALI mice, as evidenced by decreased injury scores on day 3 post-injury and reduced lung inflammation including increased MPO activity and protein levels of IL-1α, IL-1β, IL-6, TNF-α, and MIP-2 on day 3 and 7 post-injury. Inflammatory cytokine profiles in the lungs at day 3 post-injury were attenuated by MSC transplantation. MSCs also reduced the elevated lung water content at day 3 post-injury and bacterial counts in blood and BAL on day 7 post-injury.

Conclusions

Intratracheal transplantation of UCB-derived MSCs attenuates E. coli-induced ALI primarily by down-modulating the inflammatory process and enhancing bacterial clearance.     

右美托咪定联合地佐辛在臂丛神经阻滞麻醉中的应用及对血清VEGF、IL-6、IL-10的影响

目的:右美托咪定联合地佐辛在臂丛神经阻滞麻醉中的应用及对血清VEGF(内皮细胞生长因子)、IL-6(白介素-6)、IL-10(白介素-10)的影响。方法:选择我院2016年10月至2017年12月94例上肢骨折内固定术患者作为本次研究对象,随机分为对照组和联合组,各47例。对照组于臂丛阻滞实施前10分钟持续泵注右美托咪定,联合组在此基础上辅助静脉推注地佐辛。随之在超声引导下行肌间沟臂丛神经阻滞对比分析两组患者臂丛神经麻醉前(T0),药物注射分钟后(T1),手术切皮(T2)、手术操作5分钟(T3)、手术操作30分钟(T4)和手术结束(T5)各时间点血流动力学、Ramsay镇静评分、VEGF、IL-6和IL-10水平。结果:联合组T1～T5时间MAP(血压)、HR(心率)均低于对照组(P0.05);两组SpO2(血氧饱和度)在各时间点比较差异无统计学意义(P0.05);联合组T1～T5时间点的Ramsay镇静评分明显优于观察组(P0.05);两组T1～T5时间点VEGF均上升,且联合组各时间点明显高于对照组(P0.05);术后24小时显示,联合组IL-6、IL-10水平显著低于对照组(P0.05);联合组麻醉起效时间明显短于对照组(P0.05),镇痛持续时间、感觉神经和运动神经阻滞的持续时间明显比对照组长(P0.05)。结论:在行上肢手术过程中,联合使用右美托咪定和地佐辛行臂丛神经阻滞麻醉镇痛效果明显,同时可有效刺激VEGF分泌,降低IL-6、IL-10炎症因子水平,加速患者术后恢复。     

Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components

Background aimsThe clinical use of human mesenchymal stromal cells (MSC) requires ex vivo expansion in media containing supplements such as fetal bovine serum or, alternatively, human platelet lysate (PL).MethodsPlatelet concentrates were frozen, quarantine stored, thawed and sterile filtered to obtain PL. PL content and its effect on fibroblast–colony-forming unit (CFU-F) formation, MSC proliferation and large-scale expansion were studied.ResultsPL contained high levels of basic fibroblast growth factor (bFGF), soluble CD40L (sCD40L), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), platelet-derived growth factor AA (PDGF-AA), platelet-derived growth factor AB/BB (PDGF-AB/BB), chemokine (C-C) ligand 5 (CCL5; RANTES) transforming growth factor-β1 (TGF-β1) and chemokine (C-X-C) ligand 1/2/3 (GRO), with low batch-to-batch variability, and most were stable for up to 14 days. Inhibition of PDGF-BB and bFGF decreased MSC proliferation by about 20% and 50%, respectively. The strongest inhibition (about 75%) was observed with a combination of anti-bFGF + anti-PDGF-BB and anti-bFGF + anti-TGF-β1 + anti-PDGF-BB. Interestingly, various combinations of recombinant PDGF-BB, bFGF and TGF-β1 were not sufficient to promote cell proliferation. PL from whole blood-derived pooled platelet concentrates and apheresis platelet concentrates did not differ significantly in their growth-promoting activity on MSC.ConclusionsPL enhances MSC proliferation and can be regarded as a safe tool for MSC expansion for clinical purposes. \in particular, PDGF-BB and bFGF are essential components for the growth-promoting effect of PL, but are not sufficient for MSC proliferation.     

IL-17和VEGF在慢性鼻-鼻窦炎患者鼻息肉组织中的表达及相关性研究

目的:探讨慢性鼻-鼻窦炎患者鼻息肉组织中白介素-17(IL-17)、血管内皮生长因子(VEGF)的表达,并分析IL-17、VEGF表达水平的相关性。方法:以我院2015年1月~2017年12月期间收治的慢性鼻-鼻窦炎患者95例为研究对象,按患者有无鼻息肉分为伴鼻息肉(观察1组)49例和不伴鼻息肉(观察2组)46例。另选取同期在我院进行治疗的鼻中隔偏曲患者40例为对照组。所有患者均进行鼻内镜手术治疗,并在术中取其较窄侧的鼻甲黏膜作为检测标本,采用免疫组化SP法检测各组织标本中的IL-17、VEGF的表达水平,并分析IL-17、VEGF表达水平的相关性。结果:观察1组患者IL-17、VEGF的阳性表达率分别为93.88%(46/49)、85.71%(42/49),均高于观察2组患者IL-17、VEGF的阳性表达率[76.09%(35/46)、65.22%(30/46)]以及对照组患者IL-17、VEGF的阳性表达率[5.00%(2/40)、2.50%(1/40)],差异均具有统计学意义(P0.05)。观察1组患者IL-17、VEGF的表达水平分别为(38.92±5.34)个/LP、(33.21±4.87)个/LP,均高于观察2组患者IL-17、VEGF的表达水平[(28.19±4.56)个/LP、(21.28±4.03)个/LP]以及对照组患者IL-17、VEGF的表达水平[(9.31±2.76)个/LP、(7.19±1.95)个/LP],差异均具有统计学意义(P0.05)。经Spearman相关性分析结果显示,观察1组患者、观察2组患者中,IL-17与VEGF的表达水平呈正相关性(P0.05)。结论:慢性鼻-鼻窦炎患者鼻息肉组织中IL-17、VEGF的表达显著升高,且IL-17与VEGF表达水平呈明显的正相关性,表明IL-17、VEGF可能共同参与鼻息肉的发生与发展过程。     

血清VEGF、sFlt-1、IL-4水平与妊娠期高血压疾病患者预后的关系研究

摘要 目的：探讨血清血管内皮生长因子（VEGF）、可溶性Fms样酪氨酸激酶-1（sFlt-1）、白细胞介素-4（IL-4）水平与妊娠期高血压疾病（HDP）患者分类及妊娠结局的关系。方法：选取2019年7月～2021年1月我院收治的204例HDP患者（HDP组）,根据指南分类原则分为妊娠期高血压组（n=88）、子痫前期组（n=66）、子痫组（n=50）,根据妊娠结局分为结局不良组和结局良好组,另选取同期100名于我院产检健康孕产妇为对照组。采用单因素及多因素Logistic回归和受试者工作特征（ROC）曲线分析HDP患者妊娠结局不良的影响因素及血清VEGF、sFlt-1、IL-4水平对妊娠结局不良的预测价值。结果： 与对照组比较,HDP组血清VEGF、IL-4水平降低,sFlt-1水平升高（P＜0.05）。妊娠期高血压组、子痫前期组、子痫组血清VEGF、IL-4水平依次降低,sFlt-1水平依次升高（P＜0.05）。204例HDP患者妊娠结局不良发生率为29.90%（61/204）。单因素分析显示,妊娠结局不良与年龄、不同疾病分类、SBP、DBP、尿蛋白、VEGF、sFlt-1、IL-4有关（P＜0.05）。多因素Logistic回归分析显示,HDP患者妊娠结局不良的独立危险因素与独立保护因素分别为子痫、sFlt-1升高与VEGF、IL-4升高（P＜0.05）。血清VEGF、sFlt-1、IL-4水平单独与联合预测HDP患者妊娠结局不良的曲线下面积（AUC）分别为0.766、0.774、0.770、0.905,VEGF、sFlt-1、IL-4联合预测HDP患者妊娠结局不良的AUC最大。结论：HDP患者血清VEGF、IL-4水平降低,sFlt-1水平升高,与HDP分类和妊娠结局不良有关,VEGF、sFlt-1、IL-4联合对HDP患者妊娠结局不良的预测价值较高。     

脑出血大鼠血肿周围脑组织含水量与MMP-9、IL-6及TIMP-1表达水平的相关性研究

目的:研究脑出血(ICH)大鼠血肿周围脑组织含水量与基质金属蛋白酶-9(MMP-9)、白细胞介素-6(IL-6)及组织基质金属蛋白酶抑制剂-1(TIMP-1)表达水平的相关性。方法:84只健康成年雄性Wistar大鼠按随机数字表法分成观察组、假手术组以及对照组,每组28只。另将观察组分成ICH后1d亚组9只,3d亚组9只,7d亚组10只。观察组大鼠实施ICH模型的制备,假手术组的大鼠仅给予空针穿刺,对照组不进行模型制备。检测并对比各组血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1水平,对比观察组内不同亚组(ICH后1d、3d、7d)血肿周围的脑组织含水量、MMP-9、IL-6和TIMP-1水平,并分析ICH大鼠血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1表达水平的相关性。结果:观察组血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1水平均分别高于假手术组及对照组,差异均有统计学意义(P0.05)。观察组内3d和7d亚组血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1水平均分别高于1d亚组,但7d亚组低于3d亚组,差异均有统计学意义(P0.05)。根据Spearman相关性分析结果显示,ICH大鼠血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1表达水平均呈正相关(P0.05)。结论:ICH大鼠的血肿周围脑组织含水量与MMP-9、IL-6及TIMP-1表达水平均呈正相关,MMP-9、IL-6、TIMP-1在ICH后周围组织水肿的发生、发展中具有重要作用。     

寻常型银屑病患者血清IL-17、IL-18、VEGF的表达及与病情严重程度的相关性研究

目的:探讨寻常型银屑病患者血清白介素17(IL-17)、白介素18(IL-18)、血管内皮生长因子(VEGF)的表达及与病情严重程度的相关性。方法:选取2015年8月到2017年4月在我院接受治疗的寻常型银屑病患者86例为研究组,另选取同期在我院体检结果为健康的志愿者40例作为健康对照组,并根据临床症状和病情变化对研究组患者进行分组,其中进行期银屑病组32例,静止期银屑病组24例,退行期银屑病组30例。对比研究组和健康对照组血清中IL-17、IL-18、VEGF水平,对比不同严重程度的寻常型银屑病患者血清中IL-17、IL-18、VEGF水平和PASI评分,采用Spearman相关性分析IL-17、IL-18、VEGF的表达与PASI评分的相关性。结果:研究组患者血清中的IL-17、IL-18、VEGF水平显著高于健康对照组(P0.05),进行期银屑病组患者血清中IL-17、IL-18、VEGF水平和PASI评分显著高于静止期银屑病组和退行期银屑病组,静止期银屑病组患者血清中IL-17、IL-18、VEGF水平和PASI评分显著高于退行期银屑病组(P0.05),Spearman相关性分析结果显示,研究组患者血清中IL-17、IL-18、VEGF水平与PASI评分均呈正相关(P0.05)。结论:寻常型银屑病患者血清中IL-17、IL-18、VEGF水平异常升高,且其水平与病情严重程度有关,对上述三种指标进行监测有助于临床治疗寻常型银屑病。     

Mesenchymal stem cells as a gene therapy carrier for treatment of fibrosarcoma

Background aimsCell-based gene therapy is an alternative to viral and non-viral gene therapy. Emerging evidence suggests that mesenchymal stem cells (MSC) are able to migrate to sites of tissue injury and have immunosuppressive properties that may be useful in targeted gene therapy for sustained specific tissue engraftment.MethodsIn this study, we injected intravenously (i.v.) 1 × 10⁶ MSC, isolated from green fluorescent protein (GFP) transgenic rats, into Rif-1 fibrosarcoma-bearing C3H/HeN mice. The MSC had been infected using a lentiviral vector to express stably the luciferase reporter gene (MSC-GFP-luci). An in vivo imaging system (IVIS 200) and Western blotting techniques were used to detect the distribution of MSC-GFP-luci in tumor-bearing animals.ResultsWe observed that xenogenic MSC selectively migrated to the tumor site, proliferated and expressed the exogenous gene in subcutaneous fibrosarcoma transplants. No MSC distribution was detected in other organs, such as the liver, spleen, colon and kidney. We further showed that the FGF2/FGFR pathways may play a role in the directional movement of MSC to the Rif-1 fibrosarcoma. We performed in vitro co-culture and in vivo tumor growth analysis, showing that MSC did not affect the proliferation of Rif-1 cells and fibrosarcoma growth compared with an untreated control group. Finally, we demonstrated that the xenogenic MSC stably expressing inducible nitric oxide synthase (iNOS) protein transferred by a lentivirus-based system had a significant inhibitory effect on the growth of Rif-1 tumors compared with MSC alone and the non-treatment control group.ConclusionsiNOS delivered by genetically modified iNOS-MSC showed a significant anti-tumor effect both in vitro and in vivo. MSC may be used as a target gene delivery vehicle for the treatment of fibrosarcoma and other tumors.     

Tear cytokines and chemokines in patients with Demodex blepharitis

PurposeThe purpose of the study is to evaluate the causes of inflammation in Demodex-induced blepharitis by analyzing cytokine levels in lacrimal fluid.MethodsFifteen Demodex blepharitis patients were selected for assessment of tear cytokine concentrations. Fifteen Demodex-free blepharitis patients and 15 subjects with no ocular symptoms were selected as control groups. Minimally stimulated tear samples (20 μl) were collected from each eye and analyzed using a Luminex® 200? Total System for detection of IL-1β, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), and macrophage inflammatory protein-1 beta (MIP-1β).ResultsThe concentration of IL-17 in tears was significantly higher in the Demodex blepharitis group than in the Demodex-free blepharitis group. Tear IL-7 and IL-12 levels show serial increases for these three groups (p < 0.05). There were no significant differences in the other cytokines levels between both blepharitis groups. We confirmed that elevated cytokines normalized after treatments.ConclusionsInfestation of Demodex mites induces change of tear cytokine levels, IL-17 especially, which cause inflammation of the lid margin and ocular surface. These findings might increase our understanding of the mechanism of ocular discomfort and telangiectasias frequently found in Demodex blepharitis patients.     

膝骨关节炎患者关节液和滑膜中IL-6、MMP-13、VEGF的表达及与病情进展的关系

目的:研究膝骨关节炎(KOA)患者关节液和滑膜中白细胞介素-6(IL-6)、基质金属蛋白酶-13(MMP-13)、血管内皮生长因子(VEGF)的表达及与病情进展的关系。方法:选择自2017年1月到2017年6月在我院就诊的KOA患者30例进行研究,其中维吾尔族和汉族各15例,分别记为维吾尔族组和汉族组。另选同期在我院接受骨折修复和截肢等手术治疗的10例无骨关节炎的患者作为对照组。对比各组IL-6、MMP-13及VEGF水平以及关节软骨中水通道蛋白3(AQP3)阳性表达率,对比维吾尔族组和汉族组软骨不同区域内AQP3阳性表达,分析KOA患者关节液和滑膜中IL-6、MMP-13、VEGF及关节软骨中AQP3的阳性表达与病情进展的相关性。结果:维吾尔族组和汉族组关节液和滑膜中IL-6、MMP-13及VEGF水平均分别高于对照组,差异均有统计学意义(均P0.05)。维吾尔族组和汉族组关节软骨中AQP3阳性表达率均分别明显高于对照组,且维吾尔族组明显高于汉族组,差异均有统计学意义(均P0.05)。维吾尔族组和汉族组浅层软骨磨损严重区的AQP3阳性表达率明显高于软骨深层区和软骨下骨区,差异均有统计学意义(均P0.05)。Spearman相关性分析显示,KOA患者关节液和滑膜中IL-6、MMP-13、VEGF及关节软骨中AQP3的阳性表达与病情进展均呈正相关(均P0.05)。结论:KOA患者关节液和滑膜中IL-6、MMP-13、VEGF水平及关节软骨中AQP3阳性表达均异常升高,以上指标参与了病情的进展,且AQP3阳性表达高低还与民族有关,临床上可考虑将这些指标作为监测KOA患者病情的靶点。     

Adoptive transfer of mesenchymal stromal cells accelerates intestinal epithelium recovery of irradiated mice in an interleukin-6-dependent manner

Background aimsApoptosis of radiosensitive cells in the bone marrow and gut is a serious, at times life-threatening, complication arising from radiation exposure.MethodsWe investigated whether adoptive transfer of allogeneic bone marrow-derived mesenchymal stromal cells (MSC) could exert cytoprotective and life-sparing effects in a mouse model of sublethal total body irradiation (TBI).ResultsWe demonstrated that a single intraperitoneal injection of C57Bl/6 MSC given to major histocompatibility complex (MHC)-mismatched Balb/c mice within 24 h of sublethal TBI significantly reduced mortality in a dose-dependent manner. Histologic analysis and Ki67 immunostaining of jejunum sections collected 3 and 6 days post-TBI indicated that MSC protected the gastrointestinal epithelium from TBI-induced damage and significantly accelerated recovery of the gut by stimulating proliferation of the crypt cell pool. Using interleukin-6^–/– (IL-6) MSC, we demonstrated that IL-6 expressed by MSC played a role in gastrointestinal epithelium regeneration.ConclusionsOur results suggest that allogeneic MHC-mismatched MSC may be exploited to reduce gastrointestinal complications and mortality arising from ionizing radiation exposure.     

不同剂量瑞舒伐他汀钙治疗脑梗死患者的临床疗效及机制研究

目的:探讨不同剂量瑞舒伐他汀钙治疗脑梗死患者的临床疗效,并分析其疗效机制。方法:将2015年2月至2018年2月医院诊治的脑梗死患者84例按随机数字表法分为观察组(42例)及对照组(42例)。所有患者入院后均给予降血压、降血糖、稳定颅内压以及改善微循环等基本治疗,在此基础上,对照组口服瑞舒伐他汀钙10 mg/d,观察组口服瑞舒伐他汀钙20 mg/d,两组疗程均为14 d。比较两组疗效、治疗前后美国国立卫生研究所卒中量表(NIHSS)评分以及日常生活能力量表(Barthel指数)变化,并比较两组血清白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、高迁移率族蛋白-1(HMGB1)和超敏C反应蛋白(hs-CRP)水平,分析血清HMGB1、IL-6、IL-8和hs-CRP之间的相关性,记录两组患者治疗过程中不良反应发生情况。结果:观察组治疗总有效率为95.24%(40/42),明显高于对照组的80.95%(34/42)(P0.05)。两组治疗后NIHSS评分均低于治疗前,Barthel指数高于治疗前,同时,观察组NIHSS评分降低程度大于对照组,Barthel指数升高程度大于对照组(P0.05)。治疗后两组患者血清IL-6、IL-8、HMGB1、hs-CRP明显降低,且观察组血清IL-6、IL-8、HMGB1、hs-CRP明显低于对照组(P0.05)。Person相关性分析表明患者血清HMGB1与IL-6、IL-8、hs-CRP呈正相关(r=0.306,0.428,0.367,均P0.05),IL-6与IL-8、hs-CRP呈正相关(r=0.327,0.385,P0.05),IL-8与hs-CRP亦呈正相关(r=0.430,P0.05)。治疗期间两组不良反应发生率比较无统计学差异(P0.05)。结论:高剂量瑞舒伐他汀钙治疗脑梗死能够促进神经功能恢复,提高日常生活能力,临床疗效显著,其机制可能与降低脑梗死急性期炎症反应有关。     

Mesenchymal stromal cells alone or expressing interferon-β suppress pancreatic tumors in vivo,an effect countered by anti-inflammatory treatment

Background aimsBecause of the inflammatory nature and extensive stromal compartment in pancreatic tumors, we investigated the role of mesenchymal stromal cells (MSC) to engraft selectively in pancreatic carcinomas and serve as anti-tumor drug delivery vehicles to control pancreatic cancer progression.MethodsHuman pancreatic carcinoma cells, PANC-1, expressing renilla luciferase were orthotopically implanted into SCID mice and allowed to develop for 10 days. Firefly luciferase-transduced MSC or MSC expressing interferon (IFN)-β were then injected intraperitoneally weekly for 3 weeks. Mice were monitored by bioluminescent imaging for expression of renilla (PANC-1) and firefly (MSC) luciferase.ResultsMSC selectively homed to sites of primary and metastatic pancreatic tumors and inhibited tumor growth (P = 0.032). The production of IFN-β within the tumor site by MSC–IFN-β further suppressed tumor growth (P = 0.0000083). Prior studies indicated that MSC home to sites of inflammation; therefore, we sought to alter the tumor microenvironment through treatment with a potent anti-inflammatory agent. After treatment, inflammation-associated mediators were effectively down-regulated, including NFκB, vascular endothelial growth factor (VEGF) and interleukin (IL)-6 as well as chemokines involved in MSC migration (CCL3 and CCL25). Treatment with the anti-inflammatory agent CDDO-Me before and after MSC–IFN-β injections resulted in reduction of MSC in the tumors and reversed the positive effect of tumor inhibition by MSC–IFN-β alone (P = 0.041).ConclusionsThese results suggest that MSC exhibit innate anti-tumor effects against PANC-1 cells and can serve as delivery vehicles for IFN-β for the treatment of pancreatic cancer. However, these beneficial effects may be lost in therapies combining MSC with anti-inflammatory agents.     

塞来昔布治疗类风湿性关节炎的临床疗效及其对血清CRP、RF水平的影响

目的:研究塞来昔布治疗类风湿性关节炎的临床评价及其对患者血清C反应蛋白(CRP)、类风湿因子(RF)水平的影响。方法:选取2014年9月至2015年8月本院收治的84例类风湿关节炎患者,按照随机数字法分为观察组和对照组,每组42例。对照组采取常规方案进行治疗,观察组患者在对照组治疗基础上加以塞来昔布进行治疗。比较两组患者治疗前和治疗后CRP、RF、白介素-1(IL-1)、白介素-6(IL-6)水平的变化、临床疗效和不良反应的发生情况。结果:治疗后,观察组患者的总有效率、患者的自评疗效总有效率均显著高于对照组(P0.05)。治疗前,两组患者血清CRP、RF、IL-1、IL-1、IL-6水平比较差异无统计学意义(P0.05);治疗后,两组患者血清CRP、RF、IL-1、IL-1、IL-6水平均较治疗前显著降低(P0.05),且观察组的血清CRP、RF、IL-1、IL-1、IL-6水平显著低于对照组(P0.05)。此外,观察组的不良反应率显著低于对照组(P0.05)。结论:塞来昔布能显著提高类风湿性关节炎患者的临床疗效,且安全性较高,可能与其有效降低血清CRP、RF水平有关。     

Protein profiling of anastomosed facial nerve treated with mesenchymal stromal cells

Background aimsThe types of proteins released from mesenchymal stromal cells (MSC) are still unclear. Our aim was to compare apoptosis scores and the expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), neural cell adhesion molecule (NCAM)-1,matrix metalloproteinase (MMP)-1A, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-1/MMP-1A ratio, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), neurotrophin (NT)-3, NT-4, glial cell-derived neurotropic factor (GDNF), leukemia inhibitory factor (LIF), basic fibroblast growth factor (FGF)-2, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)-α and transforming growth factor (TGF)-β1 in anastomosed facial nerves that had been treated with or without MSC.MethodsIn seven rats, the buccal branch of the right facial nerve was transected, anastomosed and treated with MSC (anastomosed + MSC group). The left buccal branch was anastomosed only (anastomosed-only group). The left mandibular branch served as an intact nerve group. On days 18–20, the distal segments of the branches were examined in terms of expression of the mentioned proteins and apoptosis scores using polymerase chain reaction (PCR) and terminal deoxynucleotidyl transferase-mediated digoxigenin-UTP nick end labeling (TUNEL) assays.ResultsMSC application significantly increased CNTF, PDGF-α, LIF, TGF-β1, BDNF and NT-3 expression (P < 0.05). MAG expression slightly decreased whereas NCAM-1, MMP-1A and FGF-2 slightly increased(P > 0.05). Changes in other proteins and apoptosis scores were not significant.ConclusionsThese results suggest that MSC increases expression of CNTF, PDGF-α, LIF,TGF-β1, BDNF and NT-3. MAG, NCAM-1, MMP-1A and FGF-2 expressions were slightly changed in this stage of nerve regeneration. The comparison of apoptotic activity was not conclusive. Overall, it appears that MSC might have differential effects on the mentioned tissue-related proteins and trophic/growth factors.