Quantification of the breakpoint cluster region rearrangement for clinical monitoring in Philadelphia chromosome-positive chronic myeloid leukemia

The purpose of this report was to evaluate scintigraphy analysis of Southern blot hybridization as a method to quantify the breakpoint cluster region (BCR) rearrangement of Philadelphia chromosome (Ph)+ chronic myelogenous leukemia (CML). Cytogenetic and molecular studies performed simultaneously on 474 bone marrow and/or blood samples from 300 patients treated with alpha-interferon-based therapy were compared. Molecular results were expressed as the percentage of rearranged BCR bands versus the total scintigraphic signal. The percentage of Ph+ metaphases was calculated on 25 metaphases. The results of molecular studies obtained on both peripheral blood and bone marrow samples were identical. The rank correlation between the BCR quantification and the percentage of Ph positivity in 465 samples was excellent (r = .78). However, of 99 samples with a normal karyotype, 24% had a BCR rearrangement. Of 86 samples with no BCR rearrangement, 13% showed a Ph chromosome. Of 49 samples with partial cytogenetic remission (Ph+ metaphases, 1% to 34%), 23% had no BCR rearrangement. In samples with a minor or no cytogenetic response (Ph+ metaphases, > 34%), BCR analysis overestimated the degree of response in 73 of 326 samples (22%). Nevertheless, survival analysis by BCR quantification level showed statistically better outcome for patients in complete or partial molecular response (P < .01). Molecular quantification of BCR was useful in monitoring the course of Ph+ CML. This method, which can be used on peripheral blood, detected residual disease not shown by cytogenetic analysis and was prognostically relevant as a measure of disease suppression.     

Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.     

乳腺浸润性导管癌超声影像特征分析

 目的 分析超声各特征性影像表现在乳腺浸润性导管癌中的诊断价值。方法 选取解放军总医院第六医学中心 2018-01至2019-12两年内收治的 135例乳腺浸润性导管癌患者纳入本研究,分析乳腺浸润性导管癌的超声影像特征、体检自检发现率以及淋巴结转移与病变大小、位置的相关性。结果 (1)单因素分析显示:形态不规则(91.11%)、边界不清楚(64.44％)、血流信号(44.44％)、微钙化(37.78%)、纵横比＞1(17.78％)、后方回声衰减(15.56％)超声诊断指标,与浸润性导管癌的诊断具有相关性;(2)与其他三个象限相比较,内上象限浸润性导管癌更容易被患者自检发现,占自检发现病例的34.93%;(3)内上象限及外上象限的浸润性导管癌更容易发生淋巴结转移(转移率为:内上:25.53%,内下:0.00%,外上:64.70%,外下:11.76%);(4)对＜3 cm的浸润性导管癌,其大小与腋窝淋巴结的转移没有相关性。结论 超声表现以形态不规则在乳腺浸润性导管癌中的发生率最高,且在早期病变中即表现出来;乳腺病变的自检检出率、乳腺癌淋巴转移率均与乳腺病变的大小和位置密切相关。     

The use of bisphosphonates in children: review of the literature and guidelines for dental management

Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long‐term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.     

基于层次分析法（AHP）的保健食品原料评价体系构建及分析

目的建立保健食品原料评价体系(Functional Food Crude Materials Evaluation System,FUFMES),为保健食品原料目录排名提供科学依据与技术保障。方法首先,利用文献调研和多轮专家访谈方法筛选FUFMES的指标并确定其层级关系;第二,使用层次分析法(Analytic Hierarchy Process,AHP)计算指标权重,具体方法是依据专家打分构建判断矩阵,利用R语言进行一致性检验与最大特征根检验,得出各级指标权重;第三,使用极值法计算原料的单个指标值;第四,利用线性加权综合法得到每种原料的评价指数并据此进行排名;最后,将获得的分析结果与专家评价结果进行比较。结果 FUFMES包括6个一级指标、39个二级指标、11个三级指标。利用FUFMES对9种保健食品原料进行评价,获得的评价指数依次是:西洋参(0.49)、人参(0.48)、银杏叶(0.21)、灵芝孢子粉(0.08)、鱼油(0.06)、螺旋藻(0.03)、辅酶Q10(0.02)、褪黑素(0.01)、大蒜油(-0.03)。基于该评价指数的排名结果与专家评价结果显示了较高一致性。结论构建了科学、完整的FUFMES,FUFMES将成为保健食品原料目录评价与排名的有力工具,为推进保健食品原料备案制提供科学依据与技术保障。     

未净化Z:ZCLA长爪沙鼠封闭群繁育及遗传稳定性分析

目的 分析未净化Z:ZCLA长爪沙鼠封闭群繁育和生长指标,并利用直接测序法分析其遗传稳定性.方法 随机选择40对Z:ZCLA长爪沙鼠,记录其繁殖胎次、产子数等指标,分析其仔鼠的生长发育情况.遗传稳定性分析选择Z:ZCLA长爪沙鼠非同胞、非亲代个体33只,提取肝脏基因组DNA,PCR扩增D-Loop序列,产物纯化后双向测序,测序结果与Z:ZCLA长爪沙鼠标准序列比对.结果 Z:ZCLA长爪沙鼠每胎产仔7只,胎间隔多在20～60d间,雄性体重高于雌性.遗传稳定性分析检测发现33只Z:ZCLA长爪沙鼠序列与标准序列完全一致.结论 Z:ZCLA长爪沙鼠群体内未发现遗传多态性,说明该群体具有较好的遗传稳定性.     

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.     

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。     

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...