我院2017-2019年深部抗真菌药物利用分析

目的:分析评价某三甲专科医院2017-2019深部抗真菌药物的临床使用情况,为深部抗真菌药物的合理规范使用提供参考.方法:利用信息系统,采用金额排序法和用药频度排序法对某三甲专科医院2017-2019年深部抗真菌药物进行统计分析.结果:2017-2019年该院深部抗真菌药物销售金额及所占比例有逐步下降趋势,使用频度排在...     

外环境湿度和换气次数对独立通风笼盒微环境湿度和氨浓度的影响

目的：评估在独立通风笼盒（IVC）所处环境不同湿度条件下,IVC 不同换气次数时,大、小鼠 IVC 微环境湿度和氨浓度的变化。方法屏障环境内,以7 d 为换笼周期,分别设定室内环境低湿（40％）、中湿（50％）、高湿（60％）,IVC 换气次数为40次/h、60次/h 时,对3个品牌大、小鼠 IVC 微环境进行测定,观察笼盒内湿度和氨浓度的变化。结果当室内环境为低湿条件,小鼠和大鼠 IVC 换气次数设置为40次/h 时;当室内环境为中湿条件,小鼠换气次数设置为40次/h、大鼠换气次数设置为60次/h 时;当室内环境为高湿条件,小鼠换气次数设置为60次/h 时,笼盒内微环境均基本能够满足 GB14925-2010对湿度和氨浓度的要求。而在高湿情况下,即使大鼠 IVC换气次数置为60次/h 也不能满足要求。结论室内环境湿度和 IVC 换气次数是影响 IVC 微环境的关键指标,只有依据室内环境条件合理设置 IVC 换气次数才能较好地维护 IVC 微环境和达到有效管理的目的。     

肾交感神经刺激对全身交感神经系统的影响

目的：评价肾交感神经刺激(Renal sympathetic nerves stimulation,RSNS)对全身交感神经系统的影响。方法12只成年杂种犬随机分为两组：假手术组(Sham组,n=6)和肾交感神经刺激组(RSNS组,n=6)。RSNS组经左肾动脉外膜给予持续2 h高频电刺激,刺激参数：频率20 Hz,脉宽0.1 ms,刺激强度随血压进行调整,以保持血压较刺激前升高10%;假手术组在左肾动脉附近寻找一处体表皮肤给予以同样2 h高频电刺激。分别于基础状态和2 h刺激末检测血压(BP)、心率(HR)、心率变异性(HRV)和血清去甲肾上腺素（NE）浓度。结果与基础状态比较,Sham组成年杂种犬2 h末BR、HR、交感神经活性和血清去甲肾上腺素浓度比较差异均无统计学意义(P>0.05)。与基础状态比较,RSNS可以明显提高成年杂种犬BR、交感神经活性和血清去甲肾上腺素浓度,差异有统计学意义(P<0.05)。结论肾交感神经刺激可以明显提高全身交感神经系统活性。     

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.     

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。