Tests of linkage and/or association of TGF-β1 and COL1A1 genes with bone mass

Transforming growth factor beta 1 (TGF-1) is involved in bone metabolism and collagen type I alpha 1 (COL1A1) is the most abundant protein of bone matrix. Both have been considered as candidate genes for osteoporosis. In this study, we employed the transmission disequilibrium test (TDT) to examine the relationship between each of the two genes with bone mineral density (BMD) and bone mineral content (BMC) at the spine and hip in a sample of 1668 subjects from 387 Caucasian nuclear families. For the TGF-1 gene, three SNPs, SNP1, SNP2, and SNP4 (located in exon 1, intron 4 and intron 5, respectively) were tested and the minor allele frequencies were 30.9%, 2.1% and 27.0%, respectively. All eight possible haplotypes (TGF1–8) were observed. For the COL1A1 gene, the minor allele frequencies of SNP5, SNP6 and SNP8 (located in exon 1, intron 1, and exon 45, respectively) were 15.2%, 18.7%, 2.0%, respectively, and only six of eight potential haplotypes (COL1–6) were obtained. In the whole sample, total associations were observed between haplotype COL5 with spine BMD (P=0.027), haplotypes COL3 and TGF4 with hip BMC (P=0.002, 0.003, respectively). Within-family associations were found for spine BMD at haplotypes TGF4 (P=0.027) in female offspring families and TGF3 (P=0.021) in male offspring families. Further studies with denser markers and larger sample size are required to eventually define the relationship between these two genes with bone mass at the spine and hip.     

积雪草甙对兔耳增生性瘢痕TGF-β1 mRNA表达的影响

目的：通过建立兔耳腹侧增生性瘢痕的模型,探讨积雪草甙（Asiaticoside,hd）对TGF-β1 mRNA表达的影响。方法：新西兰大白兔20只（喂养过程中死亡4只）,在兔耳腹侧制备直径为1cm、深达软骨膜的圆形瘢痕93个,随机分为4组：空白对照组、得宝松组、低浓度积雪草甙组（25mg／m1）、高浓度积雪草甙组（50mg／m1）,分别于瘢痕制备3天后局部应用相应药物,2周后取材,分别测量瘢痕组织TGF-β1 mRNA的表达量。结果：积雪草甙组与空白对照组相比,TGF-β1 mRNA表达量明显降低,有明显统计学差异（P〈0．01）;积雪草甙与阳性对照组相比,二者mRNA表达量无统计学差异（P〉0．05）;积雪草甙组之间,高浓度组与低浓度组相比有统计学差异（P（0．05）。结论：较高浓度积雪草甙注射液局部注射可以减少增生性瘢痕TGF-β1mRNA的表达。     

经单鼻孔蝶窦入路显微手术切除垂体腺瘤

目的探讨经单鼻孔蝶窦入路显微手术切除垂体腺瘤的手术方法。方法回顾性分析46例垂体腺瘤患者的临床资料,均采用经单鼻孔蝶窦入路显微手术切除肿瘤。术前行高分辨率CT鞍区薄层扫描及MRI检查,充分了解蝶窦的气化程度、蝶窦分隔和鞍底隆突的解剖学特点。结果44例术中依靠蝶窦相关解剖标志,准确定位蝶窦及鞍底,2例出现偏差。肿瘤全切33例,大部分切除9例,部分切除3例,1例因海绵间窦出血终止手术,无手术死亡。术后一过性尿崩症12例,予药物治疗3～7d后好转 脑脊液漏4例,2例保守治疗治愈,1例予腰大池置管引流后治愈,1例再次经蝶入路修补鞍底后治愈。46例平均随访8个月（3个月～2年）,3例复发。结论单鼻孔蝶窦入路显微手术切除垂体腺瘤是一种安全有效的微侵袭手术方法 熟悉相关解剖标志,准确定位是手术成功的关键。     

腹腔镜在外科急腹症诊治中的应用

目的:探讨腹腔镜技术在外科急腹症中的诊断与治疗价值。方法:回顾性分析了20例腹腔镜外科急腹症探查及疗效。结果:20例经腹腔镜探查全部明确诊断,17例免除开腹手术,所有病例均恢复顺利,无术后并发症及死亡。结论:急诊腹腔镜探查可以提高急腹症的确诊率,降低阴性剖腹探查率。     

Use of ascorbate-rich dialysate to attenuate oxidative stress in maintenance hemodialysis patients

BACKGROUND: Oxidative stress exists in uremic milieu, particularly in maintenance hemodialysis (MHD) patients, and accounts for certain long-term complications. Yet little is known about whether supplementation of ascorbic acid (vitamin C, or vitC) via extracorporeal circuit has substantial effects on minifying oxidative impairment. SUBJECTS AND METHODS: The entire experiment consisted of three sections: 1) Practicing ascorbate dialysate among 8 MHD patients in a single dialysis session, compared with a conventional hemodialysis session and another one with intravenous injection of vitC. In each session, oxidative stress markers--namely, plasma total ascorbic acid (TAA), ratio of dehydroascorbic acid (DHAA) to TAA (DHAA/TAA), vitamin E (vitE), and malondialdehyde (MDA)--in both plasma and erythrocytes were measured. 2) A relatively long-term application of ascorbate dialysate in 12 of 23 MHD patients, who were randomly allocated to experimental group (n = 12), and control group (n = 11). Oxidative stress markers and main hematological and biochemical indices were determined at the beginning and end of the period. 3) Application of ascorbate dialysate in 10 MHD patients with intravenous iron treatment, performed in similar procedures as section 1. In addition to determining the aforementioned oxidative stress markers, area under the curve (AUC0-180 min) of ratio of plasma MDA to cholesterol (MDA:Cho) was calculated to evaluate the extent of lipoperoxidation. RESULTS: 1) Plasma TAA gradually decreased during dialysis, whereas a mild increase appeared in MDA. A protruding TAA concentration peak, as well as an extreme DHAA/TAA reduction, followed the injection of vitC, but soon a precipitous fall in DHAA/TAA ensued. Stable plasma TAA and slightly raised vitE were observed when applying ascorbate dialysate. 2) Plasma TAA augmented (27.4 +/- 13.3 vs. 16.8 +/- 9.5 mg/dL, P < .05) and plasma low-density lipoprotein (oxLDL) became two-thirds of baseline data (32.6 +/- 25.2 vs. 83.8 +/- 56.5 micromol/L, P < .05) in the experimental group, whereas oxLDL in the control group reduced quantitatively but not significantly in statistics. (3) As iron sucrose was infused, the decline of TAA and ascending of MDA would be abated not only by intravenous drop of vitC, but also by ascorbate dialysate; however, TAA or MDA curve manifested totally distinguished in the two modalities. AUC0-180 min in ascorbate dialysate group was significantly less than that in control group (400.25 +/- 28.54 vs. 487.25 +/- 109.82). CONCLUSION: Plasma ascorbic acid diminished a great deal during hemodialysis, and at the same time oxidative stress formed and intensified, which will be exacerbated by a remedy of frequent intravenous iron. Ascorbate supplementation, by means of either infusion or extracorporeal circuit, can lessen the loss and therefore attenuate oxidative stress. The latter pattern takes the advantage of retaining the approximate internal balance instead of exquisite change in vivo due to administration of intravenous vitC.     

The characteristics of tolerogenic plasmacytoid dendritic cells stimulated with interleukin-3

This study focused on whether bone marrow would differentiate tolerogenic dendritic cells (DCs) by comparing interleukin-3 (IL-3) DCs (induced by IL-3+IL-4) with GM-CSF DCs (induced by GM-CSF+IL-4, generating myeloid DCs). Mouse bone marrow progenitors were induced in vitro to differentiate into DCs by exposure to IL-3. The morphology and yields of IL-3 DCs and GM-CSF DCs were compared by scanning electron microscopy and laser scanning confocal microscopy. Immunohistochemistry and flow cytometer (FCM) were used to identify immune phenotypes. The results showed that IL-3 DCs and GM-CSF DCs both expressed the specific marker DEC-205 with about 80% and 70% purity, respectively. IL-3 DCs had similar morphology as plasma cells, but a different immune phenotype, namely, CD80(-), CD86(-), CD14(-), and MHC class II(+). IL-3 DCs remained in the costimulatory molecule-deficient state when TNF-alpha was supplemented into the culture. We therefore propose that IL-3 induces a high purity and yield of DCs from bone marrow. Since IL-3 DCs possess a tolerogenic phenotype (MHC class II(+), B7(-)), they may induce alloantigen-specific hyporesponsiveness in vitro.     

阻断炎症介质的信号转导对极限肝切除术后大鼠肝内细胞因子表达的影响

目的 探讨炎症介质特异性阻断剂AG490对极限肝切除术后大鼠细胞因子信号转导及肝内细胞因子表达的影响。方法 将90％肝切除大鼠38只分为对照组(n=10)和AG490组(n=28),后术中至术后36h内每12h腹腔内注射AG490(1mg／kg),其间检测肝组织中磷酸化Janus激酶2(Jak2)和信号转导与转录激活子3(Stat3)蛋白水平,并测定剩余肝中白细胞介素6(IL-6)和白细胞介素10(IL-10)的表达。结果 应用AG490后,术后8h和12h细胞因子信号蛋白Jak2和Stat3磷酸化显下降并递次改变,大鼠肝脏中IL-6表达、IL-6／IL-10比值下降,而IL-10的表达增高。结论 阻断Jak2与Stat3细胞因子信号通路能使剩余肝内促炎细胞因子表达下降和抗炎细胞因子表达升高,减轻极限肝切除术后大鼠体内炎症反应。     

肺癌术中血癌胚抗原mRNA的检测及意义

目的探讨肺癌术中有无肿瘤细胞的血行播散及其规律。方法对52例肺癌、5例肺部良性病变手术患者,于开胸时、结扎肺静脉时及结扎后1h取外周静脉血,结扎肺静脉时取肺静脉血,采用巢式逆转录聚合酶链反应(RTPCR)技术检测血中癌胚抗原(CEA)mRNA的表达量(以经内参照校正的紫外灯光下灰度值表示)。取人腺癌细胞系A549作阳性对照并检测该方法的灵敏度。结果CEAmRNA检测阳性率开胸时为31%(16/52),结扎肺静脉时外周血与肺静脉血、结扎肺静脉后1h外周静脉血均为54%(28/52),且病例一致。开胸时的CEAmRNA表达水平最低95±20,结扎肺静脉时肺静脉血最高126±22,结扎肺静脉时外周静脉血与结扎肺静脉后1h的外周静脉间差异无统计学意义(P>0.05)。CEAmRNA的术中阳性率,鳞癌患者为64%(14/22),腺癌患者为47%(14/30),阳性率与肿瘤性质无关(χ2=1.47,P>0.05);中央型肺癌的术中阳性率(80%,20/25)显著高于周围型肺癌(30%,8/27)(χ2=16.81,P=0.000);TNM分期Ⅰ、Ⅱ、Ⅲ、Ⅳ期者阳性率分别为32%(8/25),55%(6/11),93%(14/15)和0(0/1),分期较晚者显著高于分期较早者(χ2=17.93,P=0.000)。5例阴性对照均为阴性。经检验该方法的灵敏度为1×10-6。结论肺癌术中的确存在血行播散,结扎肺静脉的早晚可能对瘤细胞播散量有较大影响;中央型肺癌和     

子痫前期患者oxLDL、8-isoprostane、MDA和MIF的检测及意义

目的探讨子痫前期患者氧化低密度脂蛋白(oxidatively modified low density lipoprotein,oxLDL)、8-异前列腺素(8-isoprostane)、丙二醛(malondialdehyde,MDA)和巨噬细胞移动抑制因子(macrophage migration inhibition factor,MIF)的检测及其临床意义。方法选择子痫前期患者49例,其中轻度子痫前期患者(轻度子痫前期组)26例,重度子痫前期患者(重度子痫前期组)者23例。选择接受剖宫产术的正常妊娠晚期孕妇(对照组)30例。检测3组胎盘组织中MIF mRNA的表达水平及血浆oxLDL、8-isoprostane、MDA的水平,并对轻度、重度子痫前期2组血浆oxLDL水平与胎盘组织中MIF mRNA表达水平的相关性进行分析。结果与对照组比较,轻度、重度子痫前期2组血浆oxLDL、8-isoprostane、MDA水平及胎盘组织中MIF mRNA表达水平均明显升高(均P<0.01);与轻度子痫前期组比较,重度子痫前期组血浆oxLDL、8-isoprostane、MDA水平及胎盘组织中MIF mRNA表达水平均显著升高(均P<0.01)。轻度、重度子痫前期2组血浆oxLDL水平与胎盘组织中MIF mRNA表达水平均呈正相关(r=0.85、0.87,均P<0.05)。结论子痫前期患者胎盘组织中MIF及血浆oxLDL、8-isoprostane、MDA的过度表达,可能参与子痫前期的发生发展。     

ERCC1、XPD、XPC单核苷酸多态性与局部晚期宫颈癌新辅助化疗敏感性的相关性

目的：探讨DNA修复切除修复交叉互补基因1（ERCC1）、人类着色性干皮病D组基因（XPD）、人类着色性干皮病C组基因（XPC）基因多态性与局部晚期宫颈癌（LACC）铂类为基础的新辅助化疗（NACT）敏感性的关系。方法：经病理学确诊的LACC患者114例,所有病例化疗前抽取静脉血并提取DNA,采用聚合酶链式反应-限制性片段长度多态性分析（PCR-RFLP）技术检测单核苷酸多态性（SNPs）,比较不同基因型与NACT疗效的关系。结果：携带ERCC1 Asn118Asn C/T基因型的化疗敏感率高于C/C基因型,差异有统计学意义（P＜0.05）,携带C/T基因型化疗敏感性比C/C基因型增加4.48倍（OR=4.480;95%CI=1.436～13.976）。携带XPD Lys751Gln A/A基因型化疗敏感性高于A/C基因型,但差异无统计学意义（P＞0.05）。XPC Lys939Gln基因型与化疗敏感性差异无统计学意义（P＞0.05）。结论：ERCC1 Asn118Asn多态性可以预测以铂类为基础的LACC患者化疗疗效。