复杂性尿道狭窄及并发症诊治的实验研究与临床运用

复杂性尿道狭窄或闭锁的处理一直是泌尿外科最棘手的难题之一,尤其是对初次或再次治疗失败后的复杂性超长段尿道狭窄或闭锁(＞ 14 cm)患者的治疗,作者在治疗复杂性尿道狭窄及其并发症中取得了一系列的原创性成果.与国内外的同类研究比较,主要有以下发现和创新点.①在国际上首次提出并证实结肠黏膜可作为尿道替代物;临床治疗55例超长段尿道狭窄(平均15.2 cm)的结果提示结肠黏膜具有材源丰富、易于剥离、抗感染力强、皱缩率低等优点,适于14 cm以上尿道的重建,尤其是多次治疗失败的复杂性超长段尿道狭窄.②在国际上首次建立新型分期手术治疗复杂性超长段狭窄或闭锁,临床应用11例,疗效显著,为难治性前后尿道间长段狭窄或闭锁提供了一个新的思路.③在国际上首次阐述舌黏膜尿道重建的病理学特征及转归,建立大面积舌黏膜取材新技术;在国内率先开展舌黏膜尿道成形术,样本量为国内外最大.④在国际上首次建立了尿道压客观量化指标(90 cmH2O或较基础压提高40 ～50 cmH2O),用于评估球部尿道悬吊术中尿道压力.从而提高了手术成功率,减少了并发症,取得了显著治疗效果.该系列研究成果先后获省部科技进步一等奖和多项二等奖.     

柠檬酸对分化型甲状腺癌患者首次131I治疗后唾液腺功能的保护作用

目的：探讨柠檬酸对术后首次行¹³¹I治疗（简称清甲治疗）的分化型甲状腺癌（DTC）患者唾液腺功能的影响,阐明柠檬酸对¹³¹I治疗的甲状腺癌患者唾液腺功能的保护作用。方法：经患者知情同意,随机选择准备首次行¹³¹I治疗的68例甲状腺乳头状癌患者,随机分为对照组和柠檬酸组,每组34例。对照组患者无特殊准备,柠檬酸组患者于¹³¹I治疗前1周及治疗后3周内每天含柠檬酸1 min（0.2 g/次）后吐出。2组患者分别于¹³¹I治疗前24 h及¹³¹I治疗后3个月行2次^99mTcO^4-唾液腺显像检查,计算第15分钟摄取指数（15 min UI）和排泌分数（SR）,评估唾液腺功能。结果：与¹³¹I治疗前比较,对照组患者¹³¹I治疗后右侧腮腺和双侧颌下腺15 min UI差异无统计学意义（P>0.05）,左侧腮腺15 min UI降低（P<0.05）;与¹³¹I治疗前比较,柠檬酸组患者¹³¹I治疗后双侧腮腺及双侧颌下腺15 min UI差异无统计学意义（P>0.05）;与对照组比较,柠檬酸组患者¹³¹I治疗前后双侧腮腺和双侧颌下腺15 min UI差异均无统计学意义（P>0.05）。与¹³¹I治疗前比较,对照组患者双侧腮腺治疗后SR降低（P<0.05）,双侧颌下腺SR差异无统计学意义（P>0.05）,柠檬酸组患者双侧腮腺和双侧颌下腺治疗后SR差异无统计学意义（P>0.05）;与对照组¹³¹I治疗后比较,柠檬酸组患者双侧腮腺SR升高（P<0.05）,双侧颌下腺SR差异无统计学意义（P>0.05）。结论：DTC患者术后首次¹³¹I治疗后唾液腺排泌功能可能受损,短期口含柠檬酸对唾液腺具有保护作用,可以减轻唾液腺的放射性损伤。     

Substrate for endothelial prostacyclin production in the presence of platelets exposed to collagen is derived from the platelets rather than the endothelium

Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation and exposure of subendothelium, fibrillar collagen in suspension was coinjected with the platelets. In this model, neither the passage of platelets alone nor collagen alone stimulated prostacyclin (PGI2) production by the HUVECs. Platelets activated by coinjection with collagen released thromboxane A2 (TXA2), and this was associated with the simultaneous production of PGI2 by the HUVECs. By means of double-isotope experiments with [3H]arachidonic acid (AA) incorporated into platelets and [14C]-AA into HUVECs, it was shown that all the PGI2 generated was derived from platelet AA and/or endoperoxides. This interpretation was strengthened by the finding that PGI2 production was not prevented by treatment of HUVECs with indomethacin followed by perfusion with collagen-stimulated platelets. AA metabolites in double-isotope label experiments were further characterized by reverse-phase chromatography, and it was shown that both cyclooxygenase and lipoxygenase products of the HUVECs were derived from platelet membrane lipid. Thrombin regularly produced transient PGI2 release, but showed rapid tachyphylaxis. Platelet-derived compounds including ADP, ATP, and platelet-activating factor (PAF) did not produce PGI2 release by HUVECs in this system. Thus, the transfer of AA and metabolites from collagen- stimulated platelets is likely to be the mechanism for PGI2 production in the context of minor degrees of endothelial desquamation.     

Parental origin of mutation and the risk of breast cancer in a prospective study of women with a BRCA1 or BRCA2 mutation

The objective is to estimate the risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation, according to parental origin of mutation. We conducted a cohort study of women with a BRCA1 mutation (n = 1523) or BRCA2 mutation (n = 369) who had not been diagnosed with breast or ovarian cancer. For each woman, the pedigree was reviewed and the origin of the mutation was assigned as probable paternal or maternal. The hazard ratio (HR) for developing breast cancer in the follow‐up period was estimated for women with a paternal mutation compared to a maternal mutation. The risk of breast cancer was modestly higher in women with a paternal BRCA1 mutation compared to women with a maternal BRCA1 mutation (HR = 1.46; 95% CI = 0.99–2.16) but the difference was not significant (p = 0.06). The parental mutation origin did not affect the risk in women with a BRCA2 mutation. Our results are consistent with the hypothesis that there is an increased risk of breast cancer among women with a paternally inherited BRCA1 mutation compared to a maternally inherited mutation. However, the data are not sufficiently compelling to justify different screening recommendations for the two subgroups.     

To tell or not to tell – what to do about p.C282Y heterozygotes identified by HFE screening

Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild‐type homozygous (CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening.     

基于UPLC-Q-TOF-MS对蒙药苏格木勒-3水提物化学成分的研究

目的：对蒙药苏格木勒-3水提物进行化学成分研究,构建较为全面的化学成分谱,为苏格木勒-3水提物有效物质基础研究奠定基础。方法：采用超高液相色谱串联四级杆飞行时间质谱（UPLC-Q-TOF-MS）技术,使用ESI离子源,通过mzCloud与mzVoult软件以及质谱裂解规律,并结合对照品及相关文献资料比对进行定性分析。结果：经过分析,从蒙药苏格木勒-3水提物中共鉴定出42个成分,主要包括氨基酸、酚酸类、黄酮类、内酯类、生物碱类及其他类等6类成分,并对各成分的药材来源进行归属。结论：本研究全面、快速、准确地分析了蒙药苏格木勒-3水提物的化学成分,为其药效物质基础和质量控制等研究奠定了基础。     

Molecular heterogeneity in acute leukemia lineage switch

Six cases of acute leukemia that underwent lineage switch from acute lymphocytic leukemia to acute myelogenous leukemia are reported. The mean age of the patients was 24 years, time to conversion was 36 months, and survival after conversion was only 3 months. Of the three cases which showed abnormal metaphases at both diagnosis and conversion, two (cases 2, 5) showed related cytogenetic abnormalities, and the third showed (case 3) independent chromosomal changes. Molecular analysis for immunoglobulin heavy chain and T-cell receptor beta chain genes showed that five of the six cases had rearrangement of at least one of these lymphoid associated genes at conversion to acute myelogenous leukemia. The single case (case 3) in which there were no lymphoid gene rearrangements at conversion was also the only case in which independent karyotypic abnormalities at diagnosis and conversion were demonstrated. Our findings suggest that lineage switch can represent either relapse of the original clone with heterogeneity at the molecular level or the emergence of a second new leukemic clone without molecular heterogeneity.     

宫内炎症暴露对早产儿固有免疫应答的影响

目的探讨宫内炎症暴露对早产儿固有免疫应答的影响。方法 2013年6月至2014年6月出生、胎龄35周的早产儿47例纳入本研究。依据胎盘病理检查结果,将早产儿分为宫内炎症阳性组和阴性组。采用Ficoll密度梯度离心法和贴壁黏附法分别获得脐血单个核细胞以及单核细胞。用内毒素(LPS,100 ng/ml)刺激单个核细胞12 h后,流式细胞术(PCR)检测CD14+单核细胞HLA-DR的表达量以及CD3+CD4+/CD3+CD8+的比例。用LPS(100 ng/ml)刺激单核细胞6 h后,Real-Time PCR检测单核细胞IL-1β、IL-6、IL-10、TNF-αm RNA表达量的变化。ELISA检测脐血以及单核细胞培养上清液中IL-1β、IL-6、IL-10和TNF-α水平。结果宫内炎症阳性组脐血血浆IL-6水平高于宫内炎症阴性组,差异有统计学意义(P=0.001)。LPS刺激后,两组单核细胞IL-1β、IL-6、IL-10、TNF-αm RNA表达量及培养上清液中蛋白水平均显著升高,与刺激前比较差异均有统计学意义(P0.05);但两组间比较差异均无统计学意义(P0.05)。LPS刺激后,宫内炎症阳性组CD14+单核细胞HLA-DR表达量显著降低,而宫内炎症阴性组则显著升高,与刺激前比较差异均有统计学意义(P0.05);且阳性组HLA-DR表达量显著低于阴性组(P=0.002)。结论宫内炎症暴露并不影响早产儿脐血单核细胞对LPS的应答反应水平,但可抑制单核细胞激活后主要抗原递呈受体的表达。     

Search for intrafamilial transmission of hepatitis C virus in hemophilia patients

This study was performed to determine the risk of family members of anti-hepatitis C virus (HCV)-positive hemophilia patients (index patients) for infection with HCV compared with the risk of acquiring hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis A virus (HAV) infection. All index patients (n = 141) were found to be positive by first and second generation anti-HCV enzyme immunoassays (EIAs). Among their household contacts (n = 228), 224 were negative and 1 positive by both assays. Three contacts gave positive results in first generation anti-HCV EIA and negative results in second generation assay. This latter result was confirmed by further tests (neutralization test, synthetic peptides, and supplemental assay). Percent positivity for anti-HBc was about the same in non-sexual household contacts and sexual partners (13 of 109 [12%] and 7 of 54 [13%], respectively). Percent prevalence of anti-HBc was higher in contacts of index patients with chronic hepatitis B than in those of index patients who had recovered from that disease (6 of 20 [30%] and 14 of 133 [10%], respectively; P < .05). The HBV infection rate of contacts participating in controlled self-treatment was not higher than that of controls (3 of 57 [5%] and 10 of 98 [10%], respectively). Of 44 sexual partners, 5 (11%) were found to be positive for anti-HIV. Prevalence of anti-HAV matched with the age-related distribution in the German population. These findings suggest that intrafamilial transmission of HCV to family members of hemophilia patients is uncommon. In contacts of hemophilia patients, the risk of acquiring HBV infection seems to be as high in household contacts as in sexual contacts. Participation in controlled self-treatment does not appear to be an additional risk for HCV and HBV infection. There is no doubt that sexual transmission of HCV is less common than that of HBV and HIV.