Organic and Inorganic Mercury in Biological Samples of Flouresecent Lamp Industries Workers and Health Risks

Objective The present study aims to investigate the concentrations of Hg and its aspects methyl mercury(Me-Hg) and inorganic mercury(I-Hg) in the biological samples(BSs) of fluorescent lamp industries workers(FLIWs).Methodology Different BSs including red blood cells(RBCs),plasma,urine,hair and nails were collected from the workers exposed to Hg and unexposed persons were selected as control group to measure both the T-Hg concentration as well as its species in different biological samples through quantitative analysis.Health data was collected through questionnaire survey.Results The mean concentrations of T-Hg(31.9 μg/L),Me-Hg(27.7 μg/L),and I-Hg(5.36 μg/L) in RBCs were found significantly(P 0.001) higher among the workers(n = 40) as compared to the control group(n = 40).Similarly the mean Hg concentrations in plasma,urine,hair and nails were also significantly higher among the workers than the control group.The statistical relation between Hg concentration and demographic characteristics observed that workers experience and fish consumption has increased the Hg concentration while age,weight and smoking found no significant effect on Hg concentration in the BSs.Conclusion The study observed that the workers were highly exposed to high concentration of Hg and they are at a high health risk.     

EMA对药用辅料右旋糖酐新的安全性评价

欧洲药品局（EMA）于2018年11月发布了"人用药品辅料右旋糖酐的包装说明书资料"，该文件引用大量文献全面评价了右旋糖酐的安全性，特别指出含有右旋糖酐辅料的注射和吸入制剂的疫苗与药品，应在说明书中描述有关其过敏反应信息的新要求。介绍该文件的主要内容，期望对我国这类药品说明书的撰写和监管有所帮助。     

Use of autofluorescence and fluorescent probes as a potential diagnostic tool for oral cancer: A systematic review

IntroductionThe prognosis of patients with Oral squamous cell carcinoma (OSCC) are directly related to the stage of development of the tumor at the time of diagnosis, but it is estimated an average delay in diagnosis of 2–5 months. New non-invasive techniques for the early diagnosis of OSCC are being developed, such as methodologies to detect spectral changes of tumor cells. We conducted a systematic review to analyze the potential use of autofluorescence and/or fluorescent probes for OSCC diagnosis.Material and MethodsFour databases (PubMed, Scopus, Embase and Web of Science) were used as research sources. Protocol was registered with PROSPERO. It was included studies that evaluated tissue autofluorescence and/or used fluorescent probes as a method of diagnosing and/or treatment of oral cancer in humans.ResultsForty-five studies were selected for this systematic review, of which 28 dealt only with autofluorescence, 18 on fluorescent probes and 1 evaluated both methods. The VELscope® was the most used device for autofluorescence, exhibiting sensitivity (33%–100%) and specificity (12%–88.6%). 5-Aminolevulinic acid (5-ALA) was the most used fluorescent probe, exhibiting high sensitivity (90%–100%) and specificity (51.3%–96%). Hypericin, rhodamine 6 G, rhodamine 610, porphyrin and γ-glutamyl hydroxymethyl rhodamine green have also been reported.ConclusionThus, the autofluorescence and fluorescent probes can provide an accurate diagnosis of oral cancer, assisting the dentist during daily clinical activity, but it is not yet possible to suggest that this method may replace histopathological examination.     

Using arterial spin labeling blood flow and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma from lymphoid hyperplasia

To investigate the feasibility of arterial spin labeling (ASL) blood flow (BF) and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPLH).Sixty-three stage T1 NPC patients and benign NPLH patients underwent ASL on a 3.0-T magnetic resonance imaging system. BF histogram parameters were derived automatically, including the mean, median, maximum, minimum, kurtosis, skewness, and variance. Absolute values were obtained for skewness and kurtosis (absolute value of skewness [AVS] and absolute value of kurtosis [AVK], respectively). The Mann–Whitney U test, receiver operating characteristic curve, and multiple logistic regression models were used for statistical analysis.The mean, maximum, and variance of ASL BF values were significantly higher in early-stage NPC than in NPLH (all P < 0.0001), while the median and AVK values of early-stage NPC were also significantly higher than those of NPLH (all P < 0.001). No significant difference was found between the minimum and AVS values in early-stage NPC compared with NPLH (P = 0.125 and P = 0.084, respectively). The area under the curve (AUC) of the maximum was significantly higher than those of the mean and median (P < 0.05). The AUC of variance was significantly higher than those of the other parameters (all P < 0.05). Multivariate analysis showed that variance was the only independent predictor of outcome (P < 0.05).ASL BF and its histogram analysis could distinguish early-stage NPC from NPLH, and the variance value was a unique independent predictor.     

Development and function of tissue resident macrophages in mice

Macrophages are important for tissue development, homeostasis as well as immune response upon injury or infection. For a long time they were only seen as one uniform group of phagocytes with a common origin and similar functions. However, this view has been challenged in the last decade and revealed a complex diversity of tissue resident macrophages. Here, we want to present the current view on macrophage development and tissue specification and we will discuss differences as well as common patterns between heterogeneous macrophage subpopulations.     

Recent advances in construction of small molecule-based fluorophore-drug conjugates

As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs’ transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

SA脂质体介导GFP／bFGF基因在豚鼠耳蜗中的表达

目的 :观察天然碱性脂 (Stearylamine,SA)脂质体介导绿色荧光蛋白 /碱性成纤维细胞生长因子(GFP/bFGF)基因于不同时间段豚鼠耳蜗中的表达 ,为进一步研究耳聋的基因治疗提供实验基础。方法 :取豚鼠 1 6只 ,分成 4组 ,每组 4只。其中 3只右耳圆窗内注入SA -GFP/bFGF复合物 ,1只同法注入生理盐水作为对照。分别于术后第 2、7、1 4、2 1天取材。在荧光显微镜下观察GFP的表达 ,用免疫组化法检测bFGF的转导情况。结果 :荧光显微镜下见双侧耳蜗于术后第 2天开始部分细胞发出绿色荧光 ,第 7天达到高峰 ,支持细胞及内外毛细胞均显荧光 ,细胞轮廓清晰 ;第 1 4天开始减弱 ,第 2 1天消失。免疫组化染色显示 ,除血管纹外 ,耳蜗各回Corti器、螺旋韧带、螺旋缘及螺旋神经节细胞均有高浓度的表达产物 ,对照动物呈阴性表达。结论 :SA脂质体介导的GFP/bFGF基因单耳给药双侧耳蜗均有高效表达 ,为进一步研究基因治疗耳聋提供了可能。     

幕上星形细胞肿瘤Ki-67抗原表达及其预后作用

目的 探讨Ki-67抗原在幕上星形细胞肿瘤中的表达及其预后作用。方法 使用S-P免疫组化方法检测82例原发性幕上星形细胞肿瘤标本中Ki-67抗原的表达。单因素使用Kaplan-Meier法,多因素分析使用COX比例风险模型进行预后分析。结果Ki-67 指数在组织学分级GradeⅡ、Ⅲ、Ⅳ中分别为2.86%±1.57%,6.72%±3.95%,8.16%±3.92%(P<0.01)。单因素及多因素分析均提示Ki-67指数是独立的预后因素。在GradeⅡ中,Ki-67指数>2.5%与Grade Ⅲ中Ki-67指数≤2.5%的患者生存期差异无显著性(P>0.05);在GradeⅣ中,Ki-67指数≤2.5%与>2.5%的患者生存期有显著性差异(P<0.01)。结论 Ki-67指数随着各病理级别增高而增高;Ki-67指数>2.5%提示预后较差。在同一病理级别中,Ki-67指数不同,其预后有显著性差异。而部分不同病理级别的患者,随着Ki-67指数的不同,其生存期却无显著差异。联合组织病理检查及Ki-67指数检测有助于更精确地判断预后。     

日本血吸虫酚氧化酶的组化定位研究

目的观察酚氧化酶(phenol oxidase,PO)在日本血吸虫成虫的组织学分布.方法酚氧化酶组化方法:将42 d虫龄的日本血吸虫活成虫置含25 mmol/L邻苯二酚的磷酸盐缓冲液(pH 6.8)中,37℃孵育30 min后,转移虫体至载玻片上,吸去虫体表面液体,将其中一部分虫体置Olym-pus显微镜下观察酚氧化酶在虫体的组织学分布.荧光组织化学方法:经上述过程处理后,在另一部分虫体上滴加2滴含0.05%戊巴比妥钠的PBS溶液,然后置Leica荧光显微镜下观察酚氧化酶在虫体的组织学分布.结果酶组织化学方法显示,日本血吸虫酚氧化酶仅分布于雌虫卵黄腺及子宫内虫卵卵壳表面,呈现棕褐色显色反应;雌虫卵巢和雄虫均未发现酚氧化酶活性.然而,荧光组织化学方法显示,酚氧化酶除主要分布于雌虫卵黄腺及子宫内虫卵卵壳表面,呈现强荧光外,还少量分布于雄虫体壁表层,呈现弱荧光反应.结论不仅日本血吸虫雌虫含有酚氧化酶活性,而且雄虫也含酚氧化酶活性,只不过其含量少、活性低.荧光组织化学方法能更灵敏地显示日本血吸虫酚氧化酶活性,更适用于日本血吸虫酚氧化酶的组织学定位.