DNA羟甲基化酶十-十一易位蛋白与5-羟甲基胞嘧啶在食管鳞癌组织的表达及其临床意义

目的探讨十-十一易位蛋白(TETs)和5-羟甲基胞嘧啶(5hmC)在食管鳞癌组织的表达及临床意义。方法随机选取2020年1月至2022年8月于郑州大学第一附属医院进行手术治疗的食管鳞癌患者癌组织和癌旁组织(距离癌组织2～3 cm)各10例, 采用高效液相-质谱联用法(LC-MS/MS)检测5hmC在食管鳞癌中的修饰水平;采用实时荧光定量聚合酶链反应(qRT-PCR)技术检测TETs mRNA在食管鳞癌中的表达;采用蛋白质印迹法(Western blot)检测TETs在食管鳞癌中的蛋白表达水平, 组间比较采用t检验。结果食管鳞癌组织中5hmC修饰水平显著高于食管癌癌旁组织[(0.21±0.03)%比(0.05±0.01)%, t=3.095, P<0.01]。TCGA数据库分析, 食管癌组织中TET1表达水平显著高于食管癌癌旁组织(1.48±0.08比0.22±0.05, t=5.032, P<0.01);TET2表达水平显著高于食管癌癌旁组织(6.12±0.32比2.86±0.45, t=11.035, P<0.05);TET3表达水平显著高于食管癌癌旁组织(3.69...     

胞嘧啶脱氨酶/5-氟胞嘧啶自杀基因治疗系统对恶性脑胶质瘤荷瘤裸鼠的抗肿瘤作用

目的 评判胞嘧啶脱氨酶/5-氟胞嘧啶(CD/5-FC)自杀基因治疗系统对恶性脑胶质瘤的抗肿瘤效果.方法 采用Lipofectamine2000TM脂质体介导方法将CD基因转染17251恶性胶质瘤细胞系,并接种于裸鼠前臂皮下,成瘤后腹腔注射5-FC(每13500mg/kg体重)10 d,观察荷瘤鼠肿瘤的生长情况,8周后比较转染组与对照组肿瘤的体积与重量,并进行病理形态学分析.结果 U251细胞获得CD基因的成功转染,5-FC用于不同组别荷瘤裸鼠,8周后转染组肿瘤体积(0.09±0.03)cm3和重量(0.28±0.11)g明显小于对照组(1.81±0.77)cm3和(1.63±0.80)g;形态学揭示转染组肿瘤细胞出现明显的凋亡与坏死.结论 裸鼠在体实验研究表明:CD/5-FC自杀基因治疗系统是治疗恶性脑胶质瘤行之有效的手段之一.     

尿毒症患者血浆5—羟色胺的变化及意义

尿毒症患者血浆５羟色胺的变化及意义汪昌树顾统元刘冰怀为探讨５羟色胺（５ＨＴ）与尿毒症的关系，我们观察２３例尿毒症血浆５ＨＴ及代谢产物５羟吲哚乙酸（５ＨＩＡＡ）含量变化，现将结果报道如下。材料与方法（１）观察对象：健康对照组５０例；肾炎组２...     

组织特异性胞嘧啶脱氨酶和5-氟胞嘧啶热化疗对裸鼠结肠癌肝脏转移的影响

目的 探讨组织特异性胞嘧啶脱氨酶/5-氟胞嘧啶(CD/5-FC)系统热化疗对裸鼠结肠癌肝脏转移的影响.方法 将45只裸鼠按随机数字表法分为3组:对照组、非热疗组、热疗组,每组15只.门静脉注射法建立结肠癌肝脏转移动物模型,3组分别给予不同的治疗方法.采用χ2检验和单因素方差分析3组肝脏肿瘤转移率、转移数目;观察各组病理学变化、肿瘤细胞凋亡指数;荧光定量RT-PCR和Westernblot检测肿瘤组织中CD基因的表达情况.结果 对照组、非热疗组、热疗组肝脏平均转移癌结节数目和转移率分别为(4.6±1.3)、(2.2±1.0)、(0.5±0.8)个和100.0%、60.0%、13.3%,3组比较差异有统计学意义(F=25.898,χ2=5.208,19.548,5.168,P<0.05);肿瘤细胞凋亡指数平均为4.6%、9.9%和17.4%.热疗组可见大量细胞空泡变性、坏死、溶解现象,有较多的凋亡小体形成.3组均可以检测到CD基因的表达.结论 组织特异性CD/5-FC系统热化疗对转CD基因结肠癌LoVo细胞裸鼠肝脏转移有明显的抑制作用.     

组织特异性胞嘧啶脱氨酶和5-氟胞嘧啶热化疗对裸鼠结肠癌肝脏转移的影响

Objective To investigate the effects of tissue specific cytosine deaminase/5-fluorocytosine (CD/5-FC) thermotherapy on hepatic metastasis of colonic carcinoma in nude mice. Methods Forty-five nude mice were randomly divided into control group, 5-FC group and 5-FC thermotherapy group according to the random number table (15 mice in each group). Mice models of hepatic metastasis of colonic carcinoma were established by portal vein injection of LoVo/CEACD cells. The hepatic metastasis rate and number of metastatic nodules of the 3 groups were compared by ehi-square test and one-way ANOVA. The pathological changes in tumor tissues and apoptotic index of tumor cells were observed. The expression of the CD gene in tumor tissues was detected by fluorescent quantitative RT-PCR and Western blot. Results The number of metastatic nodules and liver metas-tasis rate were 4.6±1.3 and 100.0% in control group, 2.2±1.0 and 60.0% in 5-FC group, 0.5±0.8 and 13.3% in 5-FC thermotherapy group, with statistical difference among the 3 groups (F=25.898, χ2=5.208, 19.548, 5.168, P<0.05). The mean apoptotic indexes of tumor cells of the 3 groups were 4.6%, 9.9% and 17.4%, respectively. Vacuolar degeneration, cell necrosis, cytolysis and apoptotic bodies were mostly observed in the 5-FC thermotherapy group. The expression of CD gene in tumor tissue was detected in all the groups. Conclusion Tissue specific CD/5-FC thermotherapy has inhibitory effects on the hepatic metastasis of LoVo cells transfected with CD gene.     

组织特异性胞嘧啶脱氨酶和5-氟胞嘧啶热化疗对裸鼠结肠癌肝脏转移的影响

Objective To investigate the effects of tissue specific cytosine deaminase/5-fluorocytosine (CD/5-FC) thermotherapy on hepatic metastasis of colonic carcinoma in nude mice. Methods Forty-five nude mice were randomly divided into control group, 5-FC group and 5-FC thermotherapy group according to the random number table (15 mice in each group). Mice models of hepatic metastasis of colonic carcinoma were established by portal vein injection of LoVo/CEACD cells. The hepatic metastasis rate and number of metastatic nodules of the 3 groups were compared by ehi-square test and one-way ANOVA. The pathological changes in tumor tissues and apoptotic index of tumor cells were observed. The expression of the CD gene in tumor tissues was detected by fluorescent quantitative RT-PCR and Western blot. Results The number of metastatic nodules and liver metas-tasis rate were 4.6±1.3 and 100.0% in control group, 2.2±1.0 and 60.0% in 5-FC group, 0.5±0.8 and 13.3% in 5-FC thermotherapy group, with statistical difference among the 3 groups (F=25.898, χ2=5.208, 19.548, 5.168, P<0.05). The mean apoptotic indexes of tumor cells of the 3 groups were 4.6%, 9.9% and 17.4%, respectively. Vacuolar degeneration, cell necrosis, cytolysis and apoptotic bodies were mostly observed in the 5-FC thermotherapy group. The expression of CD gene in tumor tissue was detected in all the groups. Conclusion Tissue specific CD/5-FC thermotherapy has inhibitory effects on the hepatic metastasis of LoVo cells transfected with CD gene.     

组织特异性胞嘧啶脱氨酶和5-氟胞嘧啶热化疗对裸鼠结肠癌肝脏转移的影响

Objective To investigate the effects of tissue specific cytosine deaminase/5-fluorocytosine (CD/5-FC) thermotherapy on hepatic metastasis of colonic carcinoma in nude mice. Methods Forty-five nude mice were randomly divided into control group, 5-FC group and 5-FC thermotherapy group according to the random number table (15 mice in each group). Mice models of hepatic metastasis of colonic carcinoma were established by portal vein injection of LoVo/CEACD cells. The hepatic metastasis rate and number of metastatic nodules of the 3 groups were compared by ehi-square test and one-way ANOVA. The pathological changes in tumor tissues and apoptotic index of tumor cells were observed. The expression of the CD gene in tumor tissues was detected by fluorescent quantitative RT-PCR and Western blot. Results The number of metastatic nodules and liver metas-tasis rate were 4.6±1.3 and 100.0% in control group, 2.2±1.0 and 60.0% in 5-FC group, 0.5±0.8 and 13.3% in 5-FC thermotherapy group, with statistical difference among the 3 groups (F=25.898, χ2=5.208, 19.548, 5.168, P<0.05). The mean apoptotic indexes of tumor cells of the 3 groups were 4.6%, 9.9% and 17.4%, respectively. Vacuolar degeneration, cell necrosis, cytolysis and apoptotic bodies were mostly observed in the 5-FC thermotherapy group. The expression of CD gene in tumor tissue was detected in all the groups. Conclusion Tissue specific CD/5-FC thermotherapy has inhibitory effects on the hepatic metastasis of LoVo cells transfected with CD gene.     

组织特异性胞嘧啶脱氨酶和5-氟胞嘧啶热化疗对裸鼠结肠癌肝脏转移的影响

Objective To investigate the effects of tissue specific cytosine deaminase/5-fluorocytosine (CD/5-FC) thermotherapy on hepatic metastasis of colonic carcinoma in nude mice. Methods Forty-five nude mice were randomly divided into control group, 5-FC group and 5-FC thermotherapy group according to the random number table (15 mice in each group). Mice models of hepatic metastasis of colonic carcinoma were established by portal vein injection of LoVo/CEACD cells. The hepatic metastasis rate and number of metastatic nodules of the 3 groups were compared by ehi-square test and one-way ANOVA. The pathological changes in tumor tissues and apoptotic index of tumor cells were observed. The expression of the CD gene in tumor tissues was detected by fluorescent quantitative RT-PCR and Western blot. Results The number of metastatic nodules and liver metas-tasis rate were 4.6±1.3 and 100.0% in control group, 2.2±1.0 and 60.0% in 5-FC group, 0.5±0.8 and 13.3% in 5-FC thermotherapy group, with statistical difference among the 3 groups (F=25.898, χ2=5.208, 19.548, 5.168, P<0.05). The mean apoptotic indexes of tumor cells of the 3 groups were 4.6%, 9.9% and 17.4%, respectively. Vacuolar degeneration, cell necrosis, cytolysis and apoptotic bodies were mostly observed in the 5-FC thermotherapy group. The expression of CD gene in tumor tissue was detected in all the groups. Conclusion Tissue specific CD/5-FC thermotherapy has inhibitory effects on the hepatic metastasis of LoVo cells transfected with CD gene.     

组织特异性胞嘧啶脱氨酶和5-氟胞嘧啶热化疗对裸鼠结肠癌肝脏转移的影响

Objective To investigate the effects of tissue specific cytosine deaminase/5-fluorocytosine (CD/5-FC) thermotherapy on hepatic metastasis of colonic carcinoma in nude mice. Methods Forty-five nude mice were randomly divided into control group, 5-FC group and 5-FC thermotherapy group according to the random number table (15 mice in each group). Mice models of hepatic metastasis of colonic carcinoma were established by portal vein injection of LoVo/CEACD cells. The hepatic metastasis rate and number of metastatic nodules of the 3 groups were compared by ehi-square test and one-way ANOVA. The pathological changes in tumor tissues and apoptotic index of tumor cells were observed. The expression of the CD gene in tumor tissues was detected by fluorescent quantitative RT-PCR and Western blot. Results The number of metastatic nodules and liver metas-tasis rate were 4.6±1.3 and 100.0% in control group, 2.2±1.0 and 60.0% in 5-FC group, 0.5±0.8 and 13.3% in 5-FC thermotherapy group, with statistical difference among the 3 groups (F=25.898, χ2=5.208, 19.548, 5.168, P<0.05). The mean apoptotic indexes of tumor cells of the 3 groups were 4.6%, 9.9% and 17.4%, respectively. Vacuolar degeneration, cell necrosis, cytolysis and apoptotic bodies were mostly observed in the 5-FC thermotherapy group. The expression of CD gene in tumor tissue was detected in all the groups. Conclusion Tissue specific CD/5-FC thermotherapy has inhibitory effects on the hepatic metastasis of LoVo cells transfected with CD gene.     

组织特异性胞嘧啶脱氨酶和5-氟胞嘧啶热化疗对裸鼠结肠癌肝脏转移的影响

Objective To investigate the effects of tissue specific cytosine deaminase/5-fluorocytosine (CD/5-FC) thermotherapy on hepatic metastasis of colonic carcinoma in nude mice. Methods Forty-five nude mice were randomly divided into control group, 5-FC group and 5-FC thermotherapy group according to the random number table (15 mice in each group). Mice models of hepatic metastasis of colonic carcinoma were established by portal vein injection of LoVo/CEACD cells. The hepatic metastasis rate and number of metastatic nodules of the 3 groups were compared by ehi-square test and one-way ANOVA. The pathological changes in tumor tissues and apoptotic index of tumor cells were observed. The expression of the CD gene in tumor tissues was detected by fluorescent quantitative RT-PCR and Western blot. Results The number of metastatic nodules and liver metas-tasis rate were 4.6±1.3 and 100.0% in control group, 2.2±1.0 and 60.0% in 5-FC group, 0.5±0.8 and 13.3% in 5-FC thermotherapy group, with statistical difference among the 3 groups (F=25.898, χ2=5.208, 19.548, 5.168, P<0.05). The mean apoptotic indexes of tumor cells of the 3 groups were 4.6%, 9.9% and 17.4%, respectively. Vacuolar degeneration, cell necrosis, cytolysis and apoptotic bodies were mostly observed in the 5-FC thermotherapy group. The expression of CD gene in tumor tissue was detected in all the groups. Conclusion Tissue specific CD/5-FC thermotherapy has inhibitory effects on the hepatic metastasis of LoVo cells transfected with CD gene.     

Genome-wide analysis of DNA 5-hmC in peripheral blood of uremia by hMeDIP-chip

Background: Treatment of uremia is now dominated by dialysis; in some cases, patients are treated with dialysis for decades, but overall outcomes are disappointing. A number of studies have confirmed the relevance of several experimental insights to the pathogenesis of uremia, but the specific biomarkers of uremia have not been fully elucidated. To date, our knowledge about the alterations in DNA 5-hydroxymethylcytosine (5-hmC) in uremia is unclear, to investigate the role of DNA 5-hmC in the onset of uremia, we performed hMeDIP-chip between the uremia patients and the normal controls from the experiment to identify differentially expressed 5-hmC in uremia-associated samples. Methods: Extract genomic DNA, using hMeDIP-chip technology of Active Motif companies for the analysis of genome-wide DNA 5-hmC, and quantitative real-time PCR confirmation to identify differentially expressed 5-hmC level in uremia-associated samples. Results: There were 1875 genes in gene Promoter, which displayed significant 5-hmC differences in uremia patients compared with normal controls. Among these genes, 960 genes displayed increased 5-hmC and 915 genes decreased 5-hmC. 4063 genes in CpG Islands displayed significant 5-hmC differences in uremia patients compared with normal controls. Among these genes, 1780 genes displayed increased 5-hmC and 2283 genes decreased 5-hmC. Three positive genes, HMGCR, THBD, and STAT3 were confirmed by quantitative real-time PCR. Conclusion: Our studies indicate the significant alterations of 5-hmC. There is a correlation of gene modification 5-hmC in uremia patients. Such novel findings show the significance of 5-hmC as a potential biomarker or promising target for epigenetic-based uremia therapies.     

尿毒症患者外周血单个核细胞超保守区域转录表达水平的分析

目的 尿毒症是由于肾衰竭致使代谢产物和其他有毒物质在体内蓄积而引起的一种自身中毒综合征,超保守区域转录子(transcribed ultra-conserved regions,T-UCRs)是lncRNA重要组成部分,转录自人类基因组中481个极度保守区域,希望分析尿毒症外周血单个核细胞的超保守区域转录表达水平,从而发现尿毒症潜在的诊断和预后的生物标志物.方法 本研究采用T-UCRs芯片技术分析了15例尿毒症患者和15例健康对照组的外周血单个核细胞的超保守区域转录表达水平,并且用实时荧光定量PCR技术验证了尿毒症患者与健康对照组表达差异最显著的基因的表达水平.结果 对比尿毒症患者与健康对照组,通过芯片筛选出T UCRs发现21个T-UCRs表达水平上调,49个T-UCRs表达水平下调,在表达上调和下调的T-UCRs中,对应的超保守区域uc.458-表达水平最显著(P-2.47524E-24;FC=3118.5361),其相关基因为RBFOX2.结论 通过GO分析以及验证后发现uc.458-可能是尿毒症潜在的生物标志物,RBFOX2可能是尿毒症潜在的关键基因.     

透析中心夜间血液透析治疗尿毒症患者的疗效及安全性分析

目的 探讨与分析透析中心夜间血液透析对尿毒症患者的临床治疗效果及安全性,评价血液透析对尿毒症患者营养状况的影响.方法 将2013年1月到2014年5月于本院接受治疗的80例尿毒症患者作为研究对象,随机将其分为对照组与观察组各40例,针对对照组给予常规血液透析治疗方案,对观察组则选用夜间血液透析治疗方案,治疗半年后,对两组患者的营养状况进行评分,并对比观察两组患者的临床治疗效果.结果 ①在完成6个月的血液透析治疗后,观察组患者在治疗后其上臂周径[(30.4±5.5)cm]显著高于治疗前期,同时显著优于对照组[(27.2±4.6)cm](t=4.326,P＜0.05),同时体重、皮褶厚度、握力等均得到不同程度的改善;②完成6个月的透析治疗,观察组患者的血液生化指标,包括血浆白蛋白、血钙等指标均有所提升,甲状旁腺激素与血磷均有所降低,其中以血磷降低更为明显,显著低于对照组,组间对比差异显著(t =6.264,P＜0.05).结论 夜间血液透析对比常规透析方式来说能够明显提升患者的营养需求量,提升治疗效果,保障治疗安全性,提高患者营养状况的目的,值得临床推广应用.     

胰岛素拮抗在尿毒症高血压发生中的作用

目的 研究胰岛素拮抗在尿毒症高血压发生中的作用。方法 采用口服葡萄糖耐量试验方法检测29例伴高血压(CRF-H)和21例无高血压(CRF-NH)尿毒症患者空腹及糖负荷后各时点血糖及胰岛素水平,计算其胰岛素敏感指数(ISI)、机体糖利用率(M)、糖及胰岛素反应曲线下面积(AUCG、AUCINS),同时测定其血浆肾素(PRA)、血管紧张素Ⅱ(AT Ⅱ)水平,并与12例正常人相比较,分析上述诸变量与尿毒症高血压的关系。结果 (1)尿毒症组较正常组糖负荷后血糖、胰岛素水平及AUCG、AUCINS显著增高,ISI、M显著低下;与CRF-NH组相比,CRF-H组糖负荷后30＇、60＇、120＇血糖水平及AUCG、糖负荷后120＇胰岛素水平及AUCINS显著增高,ISI、M显著低下,胰岛素拮抗和糖耐量异常发生率显著增加;(2)胰岛素拮抗组动脉血压值和高血压发生率显著高于非胰岛素拮抗组;动脉血压与AUCG、AUCINS呈显著正相关,与ISI、M呈显著负相关;(3)PRA、ATⅡ水平在二组尿毒症患者间无差异;(4)多因素相关分析显示AUCG、AUCINS是独立于年龄、性别、肥胖、肾衰程度、血浆肾素血管紧张素活性的影响尿毒症动脉血压的主要因素。结论 胰岛素拮抗、高胰岛素血症、糖耐量异常或高血糖可能是尿毒症高血压的重要发生机制。     

Intestinal calcium binding protein in uremia

Summary In order to assess the usefulness of intestinal biopsies as indicators of end-organ responsiveness to vitamin D in uremic patients, calcium binding activity and calcium binding protein (CaBP) content were measured in intestinal biopsies from 12 uremic patients (glomerular filtration rate<5.0 ml/min) and 12 adult controls. Values for both were found to vary with the site of biopsy, highest values being obtained in the duodenal bulb, with lower values distally. Values for activity correlated with values for CaBP content in both normals and uremics and no difference was observed between groups. Levels of calcium binding activity and content of CaBP did not correlate with serum immunoreactive parathormone levels, but were directly related to circulating 25-hydroxycholecalciferol (25-OHD) levels. The data show that intestinal CaBP is normal in activity, quantity, and affinity for calcium in malabsorbing uremic patients, and are consistent with the hypothesis that calcium malabsorption in uremia is unrelated to deficiency of intestinal calcium binding protein.     

尿毒症继发性甲状旁腺功能亢进外科治疗的对比分析

目的 对比分析甲状旁腺全切除术(TPTX)及甲状旁腺全切除术联合甲状旁腺自体移植术(TPTX+AT)治疗尿毒症继发性甲状旁腺功能亢进(SHPT)的临床疗效.方法 收集2015年6月-2019年7月于成都医学院第一附属医院进行TPTX或TPTX+AT的SHPT的病例82例,根据手术方式分为TPTX组和TPTX+AT组.T...     

Bacterial translocation in experimental uremia

The aim of this study was to investigate whether or not experimental uremia would induce bacterial translocation. Forty male Wistar rats were randomized into two groups: uremic (n=20) and control (n=20). Under anesthesia, the upper and lower left renal poles and the marginal lateral parenchyma were excised in uremic group. Seven days later, in a second operation the whole right kidney was removed. In control animals, two sham operations with the same interval were performed. After 60 days from the first operation, the liver, spleen and the mesenteric lymph nodes (MLN) were excised and cultured. Blood samples were sent for biochemical analysis (BUN, creatinine, sodium and potassium) and cultured. Specimens of the jejunum (1 cm below the Treitz angle) and ileum (1 cm above the ileocecal valve) were collected and sent for histological examination and scored for the degree of inflammation of the mucosa using a classification proposed by Chiu et al. in 1970. Uremic rats presented higher BUN, creatinine and potassium than controls. Bacterial translocation was more frequent in uremic than in control animals (8/20 (40%) vs. 1/20 (5%); p=0.02). Translocation in uremic rats was observed mainly at the MLN (all eight cases). Both at the jejunum (uremic=3 [0–5] vs. control=2 [0–4]; p=0.04) and the ileum (uremic=2 [0–5] vs. control=0 [0–3]; p=0.01), inflammation score was higher in uremic rats than in controls. The intestinal mucosa barrier is impaired and bacterial translocation occurs in experimental uremia.     

高通量透析和血液透析滤过在尿毒症患者中应用的疗效及安全性的Meta分析

目的比较高通量血液透析(HFHD)和血液透析滤过(HDF)治疗慢性肾脏病尿毒症患者的疗效和安全性。方法计算机检索Cochrane图书馆、PubMed、EMBASE、CNKI、万方数据库、CBM数据库,使用随机对照试验(RCT)比较HFHD和HDF对尿毒症患者的疗效。根据纳入和排除标准,两名系统评估员独立进行数据提取和质量评价,并使用RevMan5.3软件进行荟萃分析。结果共纳入12项研究,829例患者。Meta分析显示,对于慢性肾衰竭尿毒症患者,与HDF相比,HFHD对血肌酐(Scr)(MD=-43.77,95%CI:-84.92^-2.63,P=0.04)、血磷(P)(MD=-0.39,95%CI:-0.64^-0.14,P=0.002)以及β2-微球蛋白(β2-MG)(MD=-5.86,95%CI:-10.79^-0.92,P=0.02)等代谢废物的清除方面,效果更佳,但在血钙(Ca)(MD=0.07,95%CI:-0.08~0.21,P=0.37)的恢复和甲状旁腺激素(PTH)(SMD=0.73,95%CI:-3.45~4.90,P=0.73)及尿素氮(BUN)(MD=-2.99,95%CI:-6.84~0.85,P=0.13)的清除方面两者差异无统计学意义。在不良反应方面,HFHD可使得血压异常(RR=0.33,95%CI:0.12~0.88,P=0.03)等具有更低的发生率;而对于皮肤瘙痒(RR=0.48,95%CI:0.23~1.00,P=0.05)、肌肉痉挛(RR=0.72,95%CI:0.35~1.49,P=0.37)的发生率两者差异无统计学意义。结论慢性肾脏病尿毒症患者,经HFHD治疗可明显提高Scr、P、β2-MG等物质的透析效率,降低血压异常这一不良反应的发生率,但对Ca、BUN及PTH等因素的治疗效果无明显提高,并且不能减少皮肤瘙痒、肌肉痉挛等不良反应的发生。然而,这一结论还有待于大规模、高质量的RCT的验证。     

小剂量重组人红细胞生成素在尿毒症患者的药物动力学和药效学观察

目的观察小剂量重组人红细胞生成素治疗尿毒症贫血的药物动力学和疗效及对血压的影响，探索更为有效、安全的用药方案。方法红细胞生成素测定采用酶联法。起始剂量２０Ｕ／ｋｇ每日静脉注射，维持Ｈｃｔ３０％～３５％。结果５例尿毒症未透析患者静脉和皮下注射２０Ｕ·ｋｇ－１／ｄ后，１／２消除速率常数（ｋｅ）分别为１４３±７０和７０±３１小时（Ｐ＜００１），平均驻留时间（ＭＲＴ）分别为２０３±４８和８０±２４小时（Ｐ＜００１）；皮下注射后生物利用度（Ｆ）为２３６％±８２％。４７例尿毒症患者治疗２周后Ｈｃｔ显著升高，贫血纠正期总剂量仅为常规剂量（１００Ｕ／ｋｇ每周３次）皮下及静脉组的５５％～６０％和７１％～７１３％（Ｐ＜００１），血压升高发病率显著低于常规剂量组（８５％和２０９％，Ｐ＜００５）。结论本药小剂量每日静脉注射能显著提高对贫血的疗效，降低高血压发生率。     

Estimation of plasma very low density lipoprotein-cholesterol levels in uremia

Background. In investigations of plasma lipids and lipoproteins, very low density lipoprotein (VLDL)-cholesterol is often calculated from the level of plasma triacylglycerols (in mmol/l) divided by 2.2. This is then used to calculate low density lipoprotein (LDL)-cholesterol. This approach to quantifying lipoprotein levels is invalid for hypertriglyceridemic subjects and patients with type III or remnant hyperlipoproteinemia. It may also not give accurate results for subjects with other forms of dyslipoproteinemia, including patients with uremia or chronic renal failure. In the present study, a simple ultracentrifugation procedure was used to separate VLDL from normal and uremic plasma samples. The levels of VLDL-cholesterol were measured directly and compared with the calculated values. Methods. Fasted blood samples were collected from 31 control subjects and 99 uremic patients and analyzed for total, free, and high density lipoprotein (HDL)-cholesterol. An aliquot from each plasma was used to prepare VLDL by a single preparative ultracentrifuge spin, using a Beckman type 25 rotor. Total cholesterol was measured in the VLDL samples and compared with the values calculated from the plasma triacylglycerol levels. Results. Measurement of VLDL-cholesterol after preparative ultracentrifugation in the type 25 rotor was reproducible. There were significant correlations between the measured and the calculated VLDL-cholesterol levels for both groups of plasma samples. However, calculated values were consistently 20%–40% higher than the measured values in both groups. Conclusions. The simple method for direct measurement of VLDL-cholesterol described here is easy and reproducible, and avoids overestimation of this parameter in uremic plasma samples. Received: June 20, 2001 / Accepted: November 7, 2001