TopoⅡα和Ki67在浸润性乳腺癌中的表达及其临床意义

目的 探讨TopoⅡα、Ki67在浸润性乳腺癌中的表达及其与乳腺癌患者一般临床病理特征之间的关系。方法 回顾性分析接受手术治疗的78例乳腺癌病例资料,采用免疫组化方法检测TopoⅡα及Ki67的表达情况,并分析两种蛋白与患者一般临床病理特征的关系。结果 TopoⅡα蛋白阳性率48.72%(38/78),Ki67蛋白表达阳性率66.67%(52/78),TopoⅡα与Ki67均阳性表达率38.46%(30/78)。TopoⅡα与乳腺癌患者的年龄、肿块大小、雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(HER-2)均无明显相关(P>0.05),与Ki67的表达及淋巴结转移组数有关(P<0.05)。Ki67的表达与乳腺癌患者的年龄、肿块大小、ER、HER-2均无明显相关(P>0.05),与淋巴结转移数及孕激素受体PR相关(P<0.05)。TopoⅡα、Ki67共表达与肿瘤组织大小及淋巴结转移组数相关(P<0.05),而与年龄、ER、PR等无关(P>0.05)。多因素logistic回归分析显示,淋巴结转移组数(P=0.007,OR=1.781,95%CI:1.175~2.700)是TopoⅡα阳性表达的独立预测因子,淋巴结转移组数(P=0.032,OR=1.730,95%CI:1.049~2.855)及PR蛋白表达状态(P=0.000,OR=0.126,95%CI:0.039~0.402)是Ki-67阳性表达的独立预测因子,淋巴结转移组数(P=0.005,OR=1.819,95%CI:1.198~2.762)是TopoⅡα及Ki-67共表达的独立预测因子。结论 TopoⅡα与Ki67均可作为可反映肿瘤细胞的增殖活性的指标,联合检测两者表达水平可以为乳腺癌预后判断提供参考。     

缺氧诱导因子-1α与特异AT序列结合蛋白1在胃癌组织中的表达及临床意义

目的 探讨缺氧诱导因子-1α(HIF-1α)与特异AT序列结合蛋白1(SATB1)蛋白在胃癌及癌旁组织中的表达情况及相关性,为胃癌的诊断和预后提供参考依据。方法 采用免疫组化SP法检测42例胃癌组织、42例配对癌旁组织(距癌组织边缘＞5 cm)中HIF-1α和SATB1蛋白的表达,分析胃癌组织中HIF-1α和SATB1蛋白表达与胃癌临床病理因素的相关性,并分析HIF-1α和SATB-1蛋白表达之间的相关性。结果 HIF-1α和SATB1在胃癌组织中的表达均明显高于癌旁正常组织,差异有统计学意义(P＜0.05);HIF-1α与SATB1蛋白的表达与浸润深度、临床分期、淋巴结是否转移相关(P＜0.05),与患者的性别、年龄、分化程度及肿瘤大小无关(P>0.05)。胃癌组织中HIF-1α与SATB-1蛋白表达呈正相关(r=21.63,P=0.00)。结论 胃癌组织中HIF-1α和SATB1蛋白的高表达预示胃癌恶性程度高,临床分期较晚,可能存在淋巴结转移。HIF-1α和SATB1蛋白具有协同作用,对临床诊治有重要指导意义。     

CD133和Ki-67在神经母细胞瘤中的表达及其与预后的关系

目的 探讨小儿神经母细胞瘤（NB）组织中CD133和Ki-67蛋白的表达与肿瘤发展及预后的关系。方法 选取2010年1月至2017年1月在安徽省立医院进行NB手术治疗患儿81例,手术中留取肿瘤组织,采用免疫组化染色法检测瘤组织中的CD133和Ki-67蛋白的阳性率,分析CD133和Ki-67表达水平的相关性,及其表达水平与NB患者年龄、性别以及肿瘤分期、分化程度和肿瘤转移情况等临床病理参数的关系;手术后电话随访患儿生存情况,共随访到67例,失访14例。通过Kaplan-Merier法建立生存曲线,分析CD133蛋白表达水平与患儿生存时间的关系。结果 在81例NB患儿病理组织中CD133阳性率为56.8%,Ki-67阳性率为59.3%,CD133与Ki-67表达呈正相关（r=0.188,P=0.001）;在I期和Ⅱ期NB中CD133和Ki-67的表达水平显著低于Ⅲ、IV及IV-S期（P=0.0014,P=0.0009）;在肿瘤细胞未分化的患儿中CD133和Ki-67阳性率显著高于分化程度高的患儿（P=0.0013,P=0.0009）;在发生肿瘤转移的患儿中CD133和Ki-67阳性率显著高于未发生转移的病例（P=0.0013,P=0.0009）;CD133和Ki-67的阳性率与性别和年龄无相关性（P>0.05）。CD133阳性患儿生存率低于阴性患儿（Log rank=53.80,P=0.001）。结论 CD133和Ki-67在NB组织中均有较高的阳性率,两者的表达呈正相关,表达水平与NB的发展和预后相关。     

HER-2和Ki67在激素依赖性乳腺癌中的表达及其临床意义

目的 探讨激素依赖性乳腺癌中人表皮生长因子-2（HER-2）、增殖细胞核抗原Ki67的表达与临床病理因素的关系及临床意义。方法 选取安徽医科大学附属六安医院2012年10月至2016年10月接受标准手术治疗的激素依赖性乳腺癌患者术后组织标本,采用免疫组化En Vision二步法检测93例激素依赖性乳腺癌组织标本HER-2和Ki67表达情况,免疫组化结果为HER-2（++）标本给予FISH检测进一步验证HER-2表达,分析HER-2和Ki67表达与临床病理因素的关系。结果 HER-2和Ki67阳性表达率分别为22.58%（21/93）和67.74%（63/93）,两者共同阳性表达率为20.43%（19/93）,不同年龄、淋巴结有无转移、不同临床分期组间HER-2阳性表达率差异无统计学意义（P>0.05）,不同肿瘤直径组间HER-2阳性表达率差异有统计学意义（P<0.05）;不同年龄、不同肿瘤直径、淋巴结有无转移、不同临床分期组间的Ki67阳性表达率差异无统计学意义（P>0.05）;HER-2和Ki67共同阳性表达率在不同肿瘤直径组间差异有统计学意义（P<0.05）,在不同年龄、淋巴结有无转移、不同临床分期组间差异无统计学意义（P>0.05）。结论 HER-2和Ki67可用作判断激素依赖性乳腺癌生物学行为的标志物。     

肿瘤并发病原菌感染患者NLR的临床意义

目的 探讨肿瘤患者外周血象中性粒细胞与淋巴细胞数比值（NLR）对肿瘤并发病原菌感染的诊断价值。方法 回顾分析中科院合肥物质研究院肿瘤医院2014年4月至2016年1月收治的43例伴病原菌感染肿瘤患者（感染组）和43例无病原菌感染患者（非感染组）资料,统计学分析两组与健康对照组患者白细胞数（WBC）、中性粒细胞数（NEUT）、淋巴细胞数（LYMPH）、NLR、血红蛋白（Hb）及血清白蛋白（ALB）指标差异及其相关性;采用logistic二分类回归分析肿瘤并发病原菌感染危险因素;ROC曲线分析NLR对肿瘤并发病原菌感染诊断价值。结果 感染组患者的NLR高于非感染组及对照组且非感染组高于对照组,差异均有统计学意义（P=0.000）;感染组WBC及NEUT数均高于非感染组及对照组（P=0.000、P=0.001）但非感染组与对照组比较,差异无统计学意义（P=0.240、P=0.666）;感染组LYMPH、ALB及Hb均低于非感染组及对照组（P=0.000、P=0.000、P=0.003）且非感染组低于对照组（P=0.000、P=0.000、P=0.000）;肿瘤组NLR与其ALB、Hb、淋巴细胞呈负相关（r=-0.530、r=-0.216、r=-0.740,P=0.000、P=0.046、P=0.000）,与中性粒细胞正相关（r=0.604,P=0.000）;logistic回归显示,NLR升高及ALB降低是肿瘤患者合并病原菌感染独立危险因素（P=0.001、P=0.023）。ROC曲线显示,NLR的曲线下面积（AUC）为0.864（P=0.000）,当NLR取值为4.19、4.62时,NLR诊断感染敏感性为88.39%,83.7%,特异性为69.77%、74.4%,诊断价值最大;NEUT的AUC为0.647（P=0.018）;WBC对感染无诊断价值（P=0.237）。结论 NLR对肿瘤患者发生病原菌感染具有较好诊断效能;NLR与ALB、Hb有相关性。     

RP-HPLC法测定田七痛经胶囊中阿魏酸、藁本内酯、欧当归内酯A

目的 建立高效液相色谱法测定田七痛经胶囊中阿魏酸、藁本内酯、欧当归内酯A的方法。方法 选用Thermo Acclaim C₁₈色谱柱,Thermo SCIENTIFICSyncronis C₁₈色谱柱;检测波长为321、280 nm;体积流量1.0 mL/min;柱温35℃结果 阿魏酸、藁本内酯、欧当归内酯A的质量浓度与峰面积分别在1.12～112.30、1.33～132.60、0.96～95.50 μg/mL呈良好的线性关系;回归方程分别为Y=46 335 540 X+44 186.71（r=0.998）,Y=14 514 060 X+8 715.27（r=0.999）,Y= 22 031 250 X+16 472.10（r=0.999）。结论 该方法准确,简便,灵敏,可作为田七痛经胶囊质量控制的方法。     

胃癌组织中自噬相关蛋白与上皮间质转化的关系及意义★

目的 探讨胃癌组织中自噬蛋白微管相关蛋白轻链3B（LC3B）和上皮间质转化（EMT）标志物的表达及其临床意义。方法 随机选取2018年1月—2019年12月我院收治的胃癌患者术后癌组织110例和癌旁组织40例，采用免疫组织化学法检测LC3B、E-cadherin和vimentin的表达，并分析这些标志物与胃癌患者临床病理特征的关系。结果 与癌旁正常组织相比，胃癌组织中LC3B和vimentin蛋白表达水平显著升高，E-cadherin表达水平显著降低（P<0.05）；LC3B、E-cadherin和vimentin表达水平与肿瘤分化程度、T分期、TNM分期及淋巴结转移密切相关（P<0.05），与年龄、性别和肿瘤大小无关（P>0.05）；LC3B表达与vimentin呈正相关（r=0.320， P=0.001），与E-cadherin呈负相关（r=-0.484， P<0.001）。结论 胃癌组织中LC3B、vimentin表达上调，E-cadherin表达下调，且三者与肿瘤分化程度、T分期、TNM分期及淋巴结转移密切相关，可能作为预测胃癌的潜在生物标志物。     

HPLC同时测定不同产地番石榴叶药材中4种黄酮类成分含量

目的 建立同时测定不同产地番石榴叶药材中金丝桃苷、槲皮素-3-O-β-D-吡喃阿拉伯糖苷、槲皮素-3-O-α-L-呋喃阿拉伯糖苷、槲皮素含量的方法。方法 采用色谱柱为Agilent Eclipse XDB-C₁₈（4.6 mm×250 mm,5 μm）,流动相为甲醇-0.2%磷酸水（梯度洗脱）,流速为1 mL·min^-1,柱温为35℃,检测波长为360 nm,进样量10µL。结果 金丝桃苷、槲皮素-3-O-β-D-吡喃阿拉伯糖苷、槲皮素-3-O-α-L-呋喃阿拉伯糖苷、槲皮素检测进样量线性范围分别为0.155~3.100 μg （r=1.000 0）,0.159~3.182 μg （r=0.999 8）,0.180~3.601 μg （r=0.999 8）,0.007~0.135 μg （r=1.000 0）;精密度,稳定性,重复性试验的RSD<2.0%;加样回收率分别为100.32%（RSD=1.44%,n=6）,97.79%（RSD=1.11%,n=6）,100.73%（RSD=1.43%,n=6）,98.33%（RSD=1.48%,n=6）,10批不同产地的番石榴叶药材中4种黄酮类成分含量差异较大。结论 该方法简便、专属性强、准确度高、重复性好,可用于不同产地番石榴叶药材的质量控制。     

SPE-HPLC测定风湿骨痛片中6种生物碱类物质的含量

目的 建立SPE-HPLC同时检测风湿骨痛片中6种生物碱类物质含量的方法。方法 采用Welch XB-C₁₈（4.6 mm×250 mm,5 μm）色谱柱,以含乙腈-四氢呋喃（25：15）溶液为流动相A,以0.05%醋酸铵溶液为流动相B进行梯度洗脱,流速为1.0 mL·min^-1,检测波长为235 nm,柱温为30℃,进样量为10 μL。结果 6种生物碱在优化条件下均可有效分离,苯甲酰新乌头原碱、苯甲酰乌头原碱、苯甲酰次乌头原碱、新乌头碱、次乌头碱和乌头碱分别在162.4~8 121 ng（r=1.000 0）、24.96~1 248 ng（r=1.000 0）、58.03~2 902 ng（r=1.000 0）、17.26~863.0 ng（r=1.000 0）、20.16~1 008 ng（r=1.000 0）和19.90~995.0 ng（r=1.000 0）内有良好的线性关系,平均回收率为88%~98%,RSD为1.8%~2.4%。结论 该方法准确、可靠,适用于风湿骨痛片中生物碱类物质含量的分析。     

检测血清抗PLA2受体抗体在特发性膜性肾病中的意义

目的 探讨特发性膜性肾病（IMN）患者血清抗PLA2受体（PLA2R）抗体与尿蛋白谱的变化情况及临床意义。方法 回顾性分析2015年11月至2016年5月安徽医科大学第一附属医院肾内科行肾脏活检并确诊IMN患者60例的临床资料,比较血清抗PLA2R抗体阳性与阴性患者尿蛋白谱的差异。结果 血清抗PLA2R抗体阳性组患者的血清清蛋白低于阴性组（P<0.05）,24 h 尿蛋白定量高于阴性组（P<0.05）。血清抗PLA2R抗体阳性组患者尿蛋白谱中尿白蛋白（A1b）/肌酐、总蛋白/肌酐和转铁蛋白/肌酐值均明显高于阴性组（P<0.05）;尿视黄醇结合蛋白（RBP）/肌酐、N-乙酰-β-D-氨基葡萄糖苷酶（NAG）/肌酐、IgG/肌酐、α1微球蛋白（α1-MG）/肌酐、β2微球蛋白（β2-MG）/肌酐、胱抑素C/肌酐和纤维蛋白原降解产物（FDP）/肌酐与阴性组比较,差异无统计学意义（P>0.05）。IMN患者24 h尿蛋白定量分别与尿A1b/肌酐（r=0.43, P=0.001）、尿总蛋白/肌酐（r=0.56,P=0.001）及尿转铁蛋白（TRF）/肌酐（r=0.46, P=0.00）呈正相关。结论 IMN患者血清抗PLA2R抗体阳性与阴性的尿蛋白谱存在差异,阳性患者的尿蛋白含量更高。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Hyperkalaemia in patients in hospital

A survey of all laboratory blood specimens with a plasma potassium concentration greater than or equal to 5.5 mmol/L was conducted over a three month period. Of 331 specimens with hyperkalaemia, 71 were excluded because the specimens was haemolysed, old or contaminated. The laboratory served a population of 348,561 and during this time measured the plasma potassium on 25,016 occasions. Sixty-six outpatients and 20 neonates were not evaluated. The survey was undertaken on 86 of 102 inpatients (46 males), 48 of whom were over 66 years of age. Fifty-seven patients were admitted under a medical service and 29 under a surgical service. Fifty-nine had a single episode of hyperkalaemia. Thirty-two underwent a surgical procedure. The commonest contributing factor was impaired renal function which was present in 71 (83%) patients. Although a definitive causative role for drugs could be identified in only five patients, in 52 (60%) patients drugs were a contributing factor (potassium supplements 24, ACE inhibitors 16, nonsteroidal antiinflammatory drugs 12). Thirty-five of the 86 (41%) patients died during their hospital admission. Nineteen of the 35 deaths occurred within three days of the hyperkalaemia being recorded. A normal plasma potassium was eventually documented in 50 of the 86 patients. Of the remaining 36 patients, 25 (69%) subsequently died. In general the treatment of patients with hyperkalaemia focused on identifying and treating the underlying cause. Hyperkalaemia must always be considered seriously and regard given to the overall clinical status of the patient, with particular attention to drug therapy, renal and cardiac function, acid base status and the possibility of sepsis.