血清M-CSF、sTNFRⅠ在宫颈上皮内瘤变与宫颈癌鉴别诊断中的作用

目的:探究血清巨噬细胞集落刺激因子(M-CSF)、可溶性肿瘤坏死因子受体Ⅰ(sTNFRⅠ)在宫颈上皮内瘤变(CIN)与宫颈癌鉴别诊断中的作用。方法:选取217例宫颈癌患者(宫颈癌组)及231例CIN患者[CINⅠ级109例(CINⅠ组)、CINⅡ级72例(CINⅡ组)、CINⅢ级50例(CINⅢ组)]为研究对象。比较各组患者血清巨噬细胞集落剌激因子(M-CSF)、可溶性肿瘤坏死因子受体Ⅰ(sTNFRⅠ)水平,分析各指标与CIN分级及宫颈癌病理特征的关系,判断各指标对CIN及宫颈癌的诊断价值。结果:各组患者血清M-CSF、sTNFRⅠ水平比较:CINⅠ组<CINⅡ组<CINⅢ组<宫颈癌组,差异均有统计学意义(P<0.05)。CIN患者血清M-CSF、sTNFRⅠ水平与CIN分级呈正相关(P<0.05)。宫颈癌患者血清M-CSF、sTNFRⅠ水平随FIGO分期的升高而升高;肿瘤低、中分化患者血清M-CSF、sTNFRⅠ水平高于肿瘤高分化患者;存在淋巴结转移患者血清M-CSF、sTNFRⅠ水平高于未出现淋巴结转移患者(P<0.05)。血清M-CSF、sTNFRⅠ水平联合检测鉴别CIN及宫颈癌的曲线下面积(AUC)大于各指标单独检测(P<0.05)。血清M-CSF、sTNFRⅠ水平升高是影响CIN进展为宫颈癌的危险因素(P<0.05)。结论:宫颈癌患者血清M-CSF、sTNFRⅠ高于CIN患者,血清指标联合检测对宫颈癌及CIN具有鉴别价值,且各指标变化与宫颈癌病理特征有关。

Overexpression of insulin-like growth factor-Ⅰ receptor as a pertinent biomarker for hepatocytes malignant transformation

AIM:To investigate the dynamic features of insulinlike growth factor-Ⅰreceptor(IGF-ⅠR)expression in rat hepatocarcinogenesis,and the relationship between IGF-ⅠR and hepatocytes malignant transformation at mRNA or protein level.METHODS:Hepatoma models were made by inducing with 2-fluorenylacetamide(2-FAA)on male SpragueDawley rats.Morphological changes of hepatocytes were observed by pathological Hematoxylin and eosin staining,the dynamic expressions of liver and serum IGF-ⅠR were quantitatively analyzed by an enzymelinked immunosorbent assay.The distribution of hepatic IGF-ⅠR was located by immunohistochemistry.The fragments of IGF-ⅠR gene were amplified by reverse transcription-polymerase chain reaction,and confirmed by sequencing.RESULTS:Rat hepatocytes after induced by 2-FAA were changed dynamically from granule-like degeneration,precancerous to hepatoma formation with the progressing increasing of hepatic mRNA or IGF-ⅠR expression.The incidences of liver IGF-ⅠR,IGF-ⅠR mRNA,specific IGF-ⅠR concentration(ng/mg wet liver),and serum IGF-ⅠR level(ng/mL)were 0.0%,0.0%,0.63±0.17,and 1.33±0.47 in the control;50.0%,61.1%,0.65±0.2,and 1.51±0.46 in the degeneration;88.9%,100%,0.66±0.14,and 1.92±0.29 in the precancerosis;and 100%,100%,0.96±0.09,and2.43±0.57 in the cancerous group,respectively.IGF-ⅠR expression in the cancerous group was significantly higher(P<0.01)than that in any of other groups at mRNA or protein level.The closely positive IGF-ⅠR relationship was found between livers and sera(r=0.91,t=14.222,P<0.01),respectively.CONCLUSION:IGF-ⅠR expression may participate in rat hepatocarcinogenesis and its abnormality should be an early marker for hepatocytes malignant transformation.

钙调神经磷酸酶对钙化细胞Ⅰ型三磷酸肌醇受体表达的影响

目的探讨大鼠血管平滑肌细胞钙化过程中钙调神经磷酸酶对Ⅰ型三磷酸肌醇受体蛋白和mRNA表达的影响。方法大鼠胸主动脉血管平滑肌细胞经传代培养后随机分为对照组、钙化组和环孢素A组,采用磷酸二氢钠诱导大鼠动脉血管平滑肌细胞钙化。应用免疫印迹法及实时荧光定量RT-PCR法测定钙调神经磷酸酶B亚基、Ⅰ型三磷酸肌醇受体的表达变化,同时测定Ca2+浓度及碱性磷酸酶、钙调神经磷酸酶活性。结果与对照组比较,钙化组钙调神经磷酸酶B亚基、Ⅰ型三磷酸肌醇受体蛋白和mRNA表达显著增加(P<0.01);与钙化组比较,环孢素A组钙调神经磷酸酶B亚基、Ⅰ型三磷酸肌醇受体蛋白和mRNA表达显著降低(P<0.01)。钙化组Ca2+浓度、钙调神经磷酸酶活性、碱性磷酸酶活性较对照组显著增高(P<0.01);环孢素A组碱性磷酸酶活性、Ca2+浓度较钙化组显著增加(P<0.05或P<0.01),钙调神经磷酸酶活性较钙化组显著降低(P<0.01)。结论钙调神经磷酸酶能够增强钙化细胞中Ⅰ型三磷酸肌醇受体mRNA和蛋白的表达。

转化生长因子β受体Ⅰ在红藻氨酸致癫痫大鼠额叶和海马的表达

目的研究转化生长因子β受体Ⅰ(TβRⅠ)蛋白在红藻氨酸(KA)致癫痫大鼠额叶及海马组织的表达,以探讨TβRⅠ与癫痫的关系。方法雄性SD大鼠随机分成对照组(10只)和模型组(50只),模型组再分为致痫后6h、12h、24h、72h、1w共5个亚组;采用红藻氨酸侧脑室注射建立颞叶癫痫动物模型,用Western Bloting技术在不同时间点检测致痫大鼠额叶及海马组织中TβRⅠ蛋白的表达情况。结果模型组大鼠致痫后额叶及海马组织中TβRⅠ蛋白表达较对照组明显增高,于72h达高峰,1w后逐渐降低;海马组织中TβRⅠ蛋白表达比额叶更明显(P<0.05)。结论 TβRⅠ蛋白在致痫后的额叶和海马组织中大量表达,表明TβRⅠ参与了癫痫早期的发病机制。

Establishment and expression of recombinant human glial cell linederived neurotrophic factor and TNF α receptor in human neural stem cells

Objective:To investigate the interference and expression of human glial cell line-derived neurotrophic factor(hCDNF) and soluble TNF alpha(sTMFRⅠ) receptor genes in neural stem cells and to evaluate the roles of these proteins in the genetic treatment of spinal cord injury.Methods:Full-length of GDNF cDNA(538 bp) and sTMFRⅠcDNA(504 bp) were inserted into the early 1 region of adenovirus genomic DNA respectively and were immediated by the human cytomegalovirus(gene promoter/enhancer). These adenoviruses were propagated in HEK293 cells via homologous recombination for 7-10 days in vivo,then they were used to infect human neural stem ceils.The infection and expression of gene were tested under immunofluorescence.ELISA and Westem-blot after 48 hours.Results:Almost all the cultured cells showed the nestin immunofluorescence positive staining,which was the characteristics of neural stem cell.A great quantity of EGFP and KFP were observed in neural stem cells,which indicated the expression of GDNF and sTMFRⅠ.After transfection of GDNF and sTMFRⅠgenes,many neural stem cells show GFAP and tubulin immunofluorescence positive staining,which meant that most neural stem cells differentiated into neuron at that condition.Conclusions:The infective efficiency of adenovirus is greatly acceptable to neural stem cell,thus adenovirus provide a useful vector for exogenous GDNF and sTMFRⅠgenes expressing in neural stem cells,which is useful for differentiation of neural stem cell.

人促肾上腺皮质激素释放因子Ⅰ型受体EC1片段在原核系统中的可溶性表达

目的:研究人促肾上腺皮质激素释放因子Ⅰ型受体(hCRFR1)EC1区蛋白片段在原核表达系统中可溶性表达的影响因素。方法:以pcDNA3.1-hCRFR1全长质粒为模板,PCR扩增EC1区分别编码118和88个氨基酸残基(分别对应融合蛋白GST-EC1118和GST-EC188)的片段,将其插入pGEX-4T2载体,转化大肠杆菌BL21(DE3),用IPTG诱导目标蛋白表达;采用GSTrap FF亲和纯化柱对目标蛋白进行纯化,并用Western印迹证实。结果:与GST-EC1118相比,GST-EC188可溶性表达增加,为下一步hCRFR1相关研究的开展奠定了基础。结论:hCRFR1的EC1区M1～N19及N108～V118两个片段影响该区域在原核系统中表达的可溶性,推测可能与富含疏水性氨基酸有关。

Scavenger receptor BI: A multi-purpose player in cholesterol and steroid metabolism

Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a multi-purpose player in cholesterol and steroid metabolism because it has distinct roles in reverse cholesterol transport, adrenal steroidogenesis, and platelet function.

清胰化积汤联合介入化疗栓塞治疗晚期胰腺癌临床研究

目的:探讨清胰化积汤联合介入化疗栓塞治疗晚期胰腺癌的疗效及对患者血清免疫抑制酸性蛋白(IAP)、碱性纤维母细胞生长因子(bFGF)及可溶性肿瘤坏死因子受体Ⅰ(sTNFRⅠ)的影响。方法:92例晚期胰腺癌患者,以随机数字表法分为研究组和对照组,各46例。对照组接受介入化疗栓塞,研究组在对照组的基础上接受清胰化积汤治疗,两组治疗时间均为8周。对比两组中医症候积分、糖类抗原199(CA_(199))、癌胚抗原(CEA)、自然杀伤T细胞(NKT)、IAP、bFGF、sTNFRⅠ、卡氏功能状态(KPS)评分、生活质量评分表(QOL)、不良反应及临床疗效,记录两组生存情况。结果:治疗后两组中医症候积分均降低,研究组降低更明显(P<0.05)。治疗后两组CA_(199)、CEA均降低,且研究组更低(P<0.05);治疗后两组NKT均升高,研究组升高更明显(P<0.05);治疗后两组IAP、bFGF、sTNFRⅠ均降低,且研究组更低(P<0.05)。治疗后两组KPS评分、QOL评分均升高,且研究组更高(P<0.05);两组Ⅰ-Ⅳ级肝肾功能损害、胃肠道反应、骨髓抑制发生率比较差异无统计学意义(P>0.05)。研究组生存率高于对照组(P<0.05);研究组总有效率较对照组高(P<0.05)。结论:清胰化积汤联合介入化疗栓塞治疗晚期胰腺癌可改善患者临床症状、肿瘤标志物水平与免疫功能,提高患者生活质量,且安全性与预后良好。

Epigallocatechin-3-gallate exerts antihypertensive effects and improves endothelial function in spontaneously hypertensive rats

Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.

敲除背根神经节Fcgr1减弱类风湿关节炎模型大鼠NF-κB/NLRP3通路活化

目的探讨外周神经元FcγRⅠ调控类风湿关节炎疼痛的机制。方法利用野生型SD大鼠和条件敲除Fcgr1大鼠建立类风湿关节炎模型。设野生型大鼠对照组(control组)、野生型大鼠类风湿关节炎(RA)组和条件敲除Fcgr1大鼠类风湿关节炎(CKO+RA)组,每组7只。用痛觉行为学检测各组大鼠建模前第3、1 d,建模后第3、5、7、9 d机械痛阈值和热痛阈值变化,用荧光原位杂交实验检测条件敲除Fcgr1大鼠背根神经节(DRG)中是否表达Fcgr1 mRNA,用免疫荧光实验检测大鼠DRG中pNF-κB(p65)、NLRP3、IL-1β和IL-18表达和脊髓背角(SDH)胶质细胞活化。结果与control组比较,RA组和(CKO+RA)组大鼠机械和热疼痛阈值均降低,(CKO+RA)组大鼠机械和热疼痛阈值比RA组大鼠明显提高(P<0.05);与RA组大鼠相比,(CKO+RA)组大鼠DRG中pNF-κB(p65)、NLRP3、IL-1β和IL-18表达明显下调(P<0.05);SDH中GFAP和Iba1表达降低(P<0.05)。结论DRG神经元FcγRⅠ可能通过NF-κB/NLRP3通路促进神经元炎性细胞因子IL-1β和IL-18合成释放,引起SDH胶质细胞活化,参与类风湿关节炎疼痛。

溃疡组织中转化生长因子-β异构体与其受体含量的变化及其对创面修复的影响

目的 :观察转化生长因子 β的 3种异构体 (TGFβ1 、β2 、β3 )和其受体 (TGFβR )在溃疡和正常皮肤的表达特征及其对创面修复的影响。方法 :2 4份被测标本中包括不同类型的溃疡中心组织及其对应的溃疡边缘和周围正常皮肤组织各 8份 ,用免疫组织化学方法和常规病理技术确定 TGFβ1 、β2 、β3 和 TGFβR 的 4种蛋白在溃疡和正常皮肤组织中的定位和表达量的变化规律。结果 :在正常皮肤组织中 ,TGFβ2 、β3 细胞因子的阳性信号主要见于表皮基底层细胞、汗腺和毛囊细胞的胞浆和胞外基质中 ,TGFβR 蛋白则主要定位于表皮细胞和血管内皮细胞的细胞膜上。在溃疡组织中 ,TGFβ1 因子存在于巨噬细胞和部分成纤维细胞内 ,TGFβ2 、β3 分布于肉芽组织中几乎所有类型的细胞内 ,而 TGFβR 在组织内分布与对照相比没有明显变化。从正常皮肤到溃疡组织 ,TGFβ1 含量逐渐下降 ,而 TGFβ2 、β3 的蛋白表达呈升高趋势 ,而 TGFβR 的含量几乎没有改变。结论 :在溃疡组织中 ,TGFβ1 含量下降 ,TGFβ2 、β3 蛋白表达增强 ,这可能与溃疡形成密切相关 ;而 TGFβR 蛋白及其下游的信号传递蛋白是否参与溃疡的形成 。

老年心力衰竭患者血清肿瘤坏死因子及其受体的临床价值研究

目的 研究老年患者血清肿瘤坏死因子及其受体水平与心力衰竭之间的关系。方法 应用双抗夹心酶联免疫吸附法 (EL ISA)法测定 112例老年心力衰竭患者及 6 0例健康老年人的血清肿瘤坏死因子 (TNF) -α和可溶性肿瘤坏死因子受体 (STNFR )水平 ,同时采用心脏超声测定其左室舒张末直径 (L VEDd)和左室射血分数 (L VEF)。结果 血清 TNF- α和 STNFR 水平与原发病无关 ,而与心功能状态有关 ,且随心功能分级增高而升高。血清 TNF- α和 STNFR 水平与 L VEDd呈正相关 ,与 L VEF呈负相关。结论 在老年心力衰竭患者中 ,肿瘤坏死因子及其受体与心功能密切相关 ,其参与并加速了心力衰竭的发生和发展。

胃癌组织中TGF-β_1和TβR_1基因的表达及意义的研究

目的 :观察转化生长因子β1 (TGF-β1 )及其受体 I(TβR1 )基因在人类胃癌组织中的表达及其与胃癌病理生物学行为的关系。方法 :应用抗 TGF-β1 和 TβR1 多克隆抗体对 10 7例胃癌组织中的 TGF-β1 和 97例胃癌组织中的 TβR1 基因表达蛋白进行了 S- P免疫组织化学方法检测。结果 :TGF-β1 在胃癌组织中的阳性表达 (75 % )明显高于癌旁组织 (2 4.4% )及正常组织 (2 9.2 % ) ,差异非常显著 (P <0 .0 1) ;TRβ1 在胃癌组织中阳性表达 (19.6 % )明显低于癌旁组织 (79.6 % )和正常组织 (75 .6 % ) ,差异有显著性 (P <0 .0 5 )。结论 :TGF-β1 和 TβR1 基因的异常表达与胃癌的发展及恶性程度有关。

Biliary cholesterol secretion: More than a simple ABC

Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophysiological determinant of cholesterol gallstone formation. This review summarizes current knowledge on the origins of cholesterol secreted into the bile as well as the relevant processes and transporters involved. Next to the established ATP-binding cassette (ABC) transporters mediating the biliary secretion of bile acids (ABCB11), phospholipids (ABCB4) and cholesterol (ABCG5/G8), special attention is given to emerging proteins that modulate or mediate biliary cholesterol secretion. In this regard, the potential impact of the phosphatidylserine flippase ATPase class Ⅰ type 8B member 1, the Niemann Pick C1-like protein 1 that mediatescholesterol absorption and the high density lipoprotein cholesterol uptake receptor, scavenger receptor class B type Ⅰ, is discussed.

Overflow phenomenon in serum lutein after supplementation:a systematic review supported with SNPs analyses

Lutein,a type of carotenoids,is found to delay the onset and progression of age-related macular degeneration(AMD).Several lutein supplementation studies showed that after an initial increase,lutein serum levels demonstrated a subsequent decrease despite continuous supplementation.In this systematic literature review,this obscure phenomenon was tried to be explained.The subsequent drop in lutein levels was postulated due to down-regulation of lutein receptors scavenger receptor class B typeⅠ(SR-BI)in the gastrointestinal tract,upregulation of lutein degrading enzymeβ-carotene dioxygenase(BCDO2),or perhaps a combination of both.Some single nucleotides polymorphisms(SNPs)that could have influence on the occurrence of this phenomenon.To date,an exact scientific explanation for this phenomenon has not been established.Further research is needed to investigate this phenomenon in depth to reach an irrefutable explanation,giving that lutein is proven to be effective in delaying the onset and progression of AMD and its metabolism in the human body becomes of equal importance.

早期运动训练对心力衰竭大鼠心脏功能与尾动脉血压的影响及相关机制

目的探讨早期运动训练对心力衰竭大鼠心脏功能与尾动脉血压的影响及相关机制。方法采用结扎左冠状动脉前降支建立心力衰竭模型,将建模成功的45只大鼠按照随机数字表法分为模型组、药物组与训练+药物组,每组各15只。模型组灌胃0.9%氯化钠溶液,药物组予依普利酮灌胃,训练+药物组在药物治疗的基础上给予早期运动训练,所有大鼠均治疗观察8周。检测与比较3组大鼠心脏功能[左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVEDs)、射血分数(EF)]、尾动脉血压、脑钠肽(BNP)、C反应蛋白(CRP)与白细胞介素-6(IL-6)含量、心脏组织血管紧张素Ⅱ受体Ⅰ(ATⅠR)、血管生成素样蛋白2(ANGPTL2)、可溶性生长刺激表达基因2蛋白(sST2)蛋白相对表达水平。结果治疗后,药物组与训练+药物组大鼠的LVEDd、LVEDs、尾动脉血压均显著低于模型组,EF值显著高于模型组,差异均有统计学意义(P<0.05);且训练+药物组大鼠的LVEDd、LVEDs、尾动脉血压均显著低于药物组,EF值显著高于药物组,差异均有统计学意义(P<0.05)。药物组与训练+药物组大鼠的血清BNP、CRP、IL-6含量均低于模型组,差异均有统计学意义(P<0.05),且训练+药物组大鼠的血清BNP、CRP、IL-6含量低于药物组,差异均有统计学意义(P<0.05)。药物组与训练+药物组大鼠的心脏组织ATⅠR、ANGPTL2、sST2蛋白相对表达水平低于模型组,差异均有统计学意义(P<0.05),且训练+药物组大鼠心脏组织ATⅠR、ANGPTL2、sST2蛋白相对表达水平低于药物组,差异均有统计学意义(P<0.05)。结论早期运动训练在心力衰竭大鼠的应用能抑制ATⅠR蛋白与血清BNP、CRP、IL-6的表达,从而改善大鼠心脏功能与降低尾动脉血压。

Establishment and Application of Hepatitis B Virus Persistent Replication Model in IFNAR^(-/-) Mouse

Summary： The type I interferon and IFNAR play an important role in hepatitis B virus （HBV） infection and anti-HBV therapy. However, its mechanism of action is still poorly understood. To gain more in- sights into the role of type I interferon and type I interferon receptor （IFNAR） in HBV infection, we established an HBV persistent replication IFNAR knockout （IFNAR-/-） mouse model and preliminarily applied this model. At first, the progeny of IFNAR-/- mouse was reproduced. Then hydrodynamic injec- tion with pAAV/HBV1.2 plasmid was conducted to establish the persistent HBV replication IFNAR-/- mouse model. At last, we applied this model to evaluate the effect of nucleoside analogues entecavir （ETV） on HBV replication. It was found that there was no difference in the serum HBsAg and HBeAg levels and HBcAg expression in the liver tissue between the ETV treated groups and normal saline （NS） treated group, but the serum HBV DNA levels were significantly suppressed 10, 25, 40 and 55 days af- ter the ETV treatment [P=0.035, P=0.00, P=0.149 and P=-0.084, IFNAR knockout （KO） control group vs. C57BL/6 ETV groups, respectively; P=0.081, P=0.001, P=0.243 and P=-0.147, IFNAR KO control group vs. IFNAR KO ETV groups, respectively]. Interestingly, there was no difference in serum HBV DNA levels between the ETV treated IFNAR/- and C57BL/6 mice. This result suggests that HBV sup- pression during ETV treatments doesn＇t depend on type Ⅰinterferon and IFNAR. Collectively, persis- tent HBV replication IFNAR/ mouse model that we established is a useful and convenient tool to detect the function of the type Ⅰ interferon and IFNAR in HBV infection and anti-HBV treatments.

产妇血清、宫颈分泌物MCP-1、sTNFRⅠ、HMGB1与感染性早产的关系

目的探究产妇血清、宫颈分泌物单核细胞趋化蛋白-1、可溶性肿瘤坏死因子受体Ⅰ、高迁移率蛋白1与感染性早产的关系。方法选取2017年1月1日-2019年8月31日某院142例产妇作为研究对象,根据是否发生绒毛膜羊膜炎分为感染组(37例)、非感染组(105例)。比较2组血清、宫颈分泌物MCP-1、sTNFRⅠ、HMGB1水平,分析各指标在血清与宫颈分泌物之间相关性,采用受试者工作特征曲线分析上述指标对感染性产妇的诊断价值,并对比感染性早产、感染性足月产产妇血清、宫颈分泌物MCP-1、sTNFRⅠ、HMGB1水平,分析各指标与感染性早产的关系。结果感染组血清、宫颈分泌物MCP-1、sTNFRⅠ、HMGB1水平高于非感染组(P<0.05);血清MCP-1、sTNFRⅠ、HMGB1水平与宫颈分泌物各指标水平存在正相关关系(P<0.05);血清、宫颈分泌物各指标中,宫颈分泌物sTNFRⅠ诊断感染性产妇的曲线下面积(AUC)高达0.808,高于血清sTNFRⅠ及血清、宫颈分泌物MCP-1、HMGB1,其截断值下诊断敏感度为62.16%,特异度为96.24%;感染性早产的发生与血清、宫颈分泌物MCP-1、sTNFRⅠ、HMGB1关系密切(P<0.05)。结论发生绒毛膜羊膜炎的产妇血清、宫颈分泌物MCP-1、sTNFRⅠ、HMGB1水平均呈异常高表达状态,可作为诊断感染性产妇的生物学指标,同时与感染性早产的发生密切相关,有助于临床预防感染性早产,改善母婴预后。

Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers on lymphangiogenesis of gastric cancer in a nude mouse model

Background Angiotensin-converting enzyme inhibitors （ACEI） and angiotensin II type 1 receptor blockers （ARB） can inhibit tumor growth by inhibition of angiogenesis. This study was designed to study the anticancer effects of ACEI and ARB on tumor growth and lymphangiogenesis in an implanted gastric cancer mouse model. Methods A model of gastric cancer was established by subcutaneously inoculating human gastric cancer cell line SGC-7901 into 60 nude mice. One week later, all mice were randomly divided into 5 groups. A control group received physiologic saline once daily for 21 days. Mice in the 4 treatment groups received one of the following agents by gavage once daily for 21 days： perindopril, 2 mg/kg; captopril, 5 mg/kg; Iosartan, 50 mg/kg; or valsartan, 40 mg/kg. Twenty-one days after treatment, all the mice were sacrificed and the tumors were removed. Tumor sections were processed, and immunohistochemical methods were used to observe the expressions of vascular endothelial growth factor C （VEGF-C）, matrix metalloproteinase 7 （MMP-7）, and lymphatic microvessel density （LMVD）. Results Tumor volume was significantly inhibited in all ACEI and ARB groups, compared with the control group （all P 〈0,01）. LMVD in the ACEI and ARB groups was also significantly lower than that of the control group （all P 〈0.01）. In the ACEI groups, the expressions of VEGF-C and MMP-7 were both significantly decreased, compared with the control group （all P 〈0.05）. In the ARB groups, expression of VEGF-C was significantly decreased compared with the control group （all P 〈0.05）. However, no significant difference was found in the expression of MMP-7 between ARB groups and the control group. Conclusion In a mouse model, ACEI and ARB might inhibit gastric cancer tumor growth by suppressing lymphangiogenesis.

肿瘤坏死因子α对小鼠胰岛内皮细胞表达胰岛素样生长因子结合蛋白7的影响

目的研究肿瘤坏死因子α(TNF-α)对小鼠胰岛内皮(MS1)细胞胰岛素样生长因子结合蛋白7(IGFBP7)的mRNA和蛋白水平的影响,并探讨其机制。方法采用可溶性TNF受体Ⅰ(sTNFRⅠ)(50ng/ml)和不同浓度TNF-α(0、10、50、100、200、500ng/ml)作用MS1细胞,再收集TNF-α(100ng/ml)作用MS1细胞12h后的培养液,直接或加入sTNFRⅠ(50ng/ml)后培养新鲜的MS1细胞,采用RTPCR和Western blot检测各组MS1细胞中IGFBP7的mRNA和蛋白水平。结果与0ng/ml TNF-α组相比,100、200、500ng/ml TNF-α均可使MS1细胞中IGFBP7mRNA和蛋白水平升高(P<0.05),其中500ng/ml TNF-α组最高(P<0.05);TNF-α(100ng/ml)作用MS1细胞12h后的培养液可明显提高IGFBP7的mRNA和蛋白水平(P<0.05),但该效应可被sTNFRⅠ(50ng/ml)完全抑制(P<0.05)。结论TNF-α可能是在转录水平促进MS1细胞IGFBP7表达的。