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。     

Tribological Behavior of Aluminum Hybrid Nanocomposites Reinforced with Alumina and Graphene Oxide

Due to rapid technological advancements, the demand for lightweight materials with improved tribo-mechanical properties is continuously growing. The development of composite materials is one of the routes taken by researchers to meet these target properties. Aluminum (Al) is one of the most suitable materials used for developing composites for a wide range of applications because of its light weight, high conductivity, and high specific strength. In this study, aluminum hybrid nanocomposites with alumina (10 Vol% Al₂O₃) and varying loadings of graphene oxide (0.25, 0.5 and 1 wt% GO) were fabricated using the spark plasma sintering technique. The tribological properties of the developed hybrid composites were evaluated by conducting ball-on-disk wear tests at a normal load of 3N, with a sliding speed of 0.1 m/s, and for a sliding distance of 100 m. A 440C hardened stainless steel ball with a diameter of 6.3 mm and a hardness of 62 RC was used as a counterface. Scanning electron microscopy (SEM), elemental X-ray dispersive analysis (EDS), and optical profilometry were used to ascertain the involved wear mechanisms. The results revealed that Al-10 Vol%Vol% Al₂O₃-0.25 wt% GO hybrid nanocomposite showed an increase of 48% in the hardness, a reduction of 55% in the specific wear rate, and a reduction of 5% in COF compared with pure aluminum.     

Dendrimers as novel systems for delivery of neuropharmaceuticals to the brain

Most of the newly developed drugs fails to achieve sufficient bioavailability in to brain due to low water solubility and low permeability. Drug delivery systems are one method for achieving entry of molecules to their desired site of action within the body. Dendrimers are the customizable nanopolymers with uniform and well-defined particle size and shape. Dendrimers are of eminent interest for biomedical applications because of their ability to cross cell membranes. This potential pharmaceutical delivery system crosses the blood brain barrier (BBB) and other important target points. The high level of control over the dendritic architecture (size, branching density, surface functionality) make dendrimers ideal carriers in the field of brain drug delivery of anticancer, antiinflammatory, and antimicrobial agents. Examples of dendrimers such as poly(amidoamine) (PAMAM), poly(propylene imine) (PPI) and polyether-copolyester (PEPE), Glyco, PEGylated, peptide and pH dendrimers are of outmost significance. These dendrimers carry the drug molecules by physical interactions (encapsulation) or through chemical bonding (prodrug approach), while pH sensitive dendrimers are able to deliver drug molecules by alteration of ionic exchange in the brain microenvironment at the tumor site. Techniques employing dendrimers could be especially useful for drugs targeting to Alzheimer's and Prion's diseases. The present review should be of value to scientists who wish to work on the dendrimers for the delivery of molecules into the brain by systemic dosing.     

Prognostic value of positive T wave in lead aVR in patients with non‐ST segment myocardial infarction

Background

Lead aVR provides prognostic information in various settings in patients with ischemia. We aim to investigate the role of a positive T wave in lead aVR in non‐ST segment myocardial infarction (NSTEMI).

Methods

In a prospective cohort study, we included 400 patients with NSTEMI. Presentation electrocardiogram (ECG) was investigated for presence of a positive T wave as well as ST segment elevation (STE) in aVR and study variables were compared. Predictors of primary outcome defined as hospital major adverse cardiovascular events (MACE) and secondary outcome, defined as three‐vessel coronary disease and/or left main coronary artery stenosis (3VD/LMCA) stenosis in angiography, were determined in multivariate logistic regression analysis.

Results

Patients with a positive T wave in aVR were significantly older and were more likely to be female. Left ventricular ejection fraction was significantly lower in patients of positive T group. Positive T group was more likely to have 3VD/LMCA stenosis (58.3% vs. 19.8%, p < .001). The prevalence of a positive T wave in aVR was significantly higher in MACE group (54.9 % vs. 24.8%, p < .001). However, in multivariate analysis, it was not an independent predictor of MACE (OR: 1.083 95% CI: [0.496–2.365], p: .841). Though, it was independently associated with presence of 3VD/LMCA stenosis (OR: 3.747 95% CI: [2.058–6.822], p < .001).

Conclusion

Though positive T wave in lead aVR was more common in patients with MACE; it was not an independent predictor. Additionally, a positive T wave in aVR was an independent predictor of 3VD/LMCA stenosis in NSTEMI.