First multi-target QSAR model for predicting the cytotoxicity of acrylic acid-based dental monomers

ObjectiveAcrylic acid derivatives are frequently used as dental monomers and their cytotoxicity towards various cell lines is well documented. This study aims to probe the structural and physicochemical attributes responsible for higher toxicity of dental monomers, using quantitative structure-activity relationships (QSAR) modeling approaches.MethodsA regression-based linear single-target QSAR (st-QSAR) model was developed with a comparatively small dataset containing 39 compounds, the cytotoxicity of which has been assessed over the Hela S3 cell line. By contrast, a classification-based multi-target QSAR model was developed with 138 compounds, the cytotoxicity of which has been reported against 18 different cell lines. Both models were set up following rigorous validation protocols confirming their statistical significance and robustness.ResultsThe performance of the linear mt-QSAR model, developed with various feature selection and post-selection similarity searching-based schemes, superseded that of all non-linear models produced with six machine learning methods by hyperparameter optimization. The final derived st-QSAR and mt-QSAR linear models are shown to be highly predictive, as well as revealing the crucial structural and physicochemical factors responsible for higher cytotoxicity of the dental monomers.SignificanceThis study is the first attempt on unveiling the cytotoxicity of dental monomers over several cell lines by means of a single multi-target QSAR model. Further, such a model is ready to get widespread applicability in the screening of new monomers, judging from its almost accurate predictions over diverse experimental assay conditions.     

胃超声检查在伴类神经症症状病人中的应用及其临床意义

目的 探讨胃超声在类神经症患者中的应用及临床意义。方法 所有病人均经超声和胃镜检查,并将结果进行分析对比。结果 实验组溃疡发生率高于对照组,胃超声检查结果与胃镜基本相符。结论 伴类神经症症状的患者是溃疡的高发人群,胃超声检查方便,无痛苦,有临床应用价值。     

补肾健骨胶囊高效液相色谱指纹图谱及主成分分析

目的：建立补肾健骨胶囊的高效液相色谱法(HPLC)指纹图谱,并进行主成分分析。方法：采用HPLC,色谱柱为Thermo-Hypersil GOLD^TM-C18(250 mm×4.6 mm×5μm),流动相为乙腈-0.2%磷酸水溶液(梯度洗脱),流速为1.0 mL/min,检测波长为235 nm,柱温为30℃,进样量为10μL。根据15批样品的HPLC检测图谱,采用国家药典委员会《中药色谱指纹图谱相似度评价系统》(2012年版)进行相似度评价和共有峰的确定,并采用Minitab17.0软件进行主成分分析。结果：补肾健骨胶囊指纹图谱共标出13个共有峰,并指认了其中3个共有峰,分别为莫诺苷、马钱苷、淫羊藿苷;15批样品的相似度均大于0.9,各批次样品之间有良好的相似性。经主成分分析,共提取出2个主成分,方差累计贡献率为92.3%,样品中1、2、4、6、8、13号共有峰(特别是13号共有峰)对应成分的含量变化是导致样品质量差异的重要原因。结论：所建HPLC指纹图谱及主成分分析结果可为补肾健骨胶囊的质量评价提供参考。     

PRODUCTION 1N PICHIA PA STORIS AND CHARACTERIZATION OF GENETIC ENGINEERED CHIMERIC HBV／HEV VIRUS-LIKE PARTICLES

Objective To investigate the presentation of a neutralization epitope-containing peptide antigen of hepatitis E virus (HEV)on chimeric virus-like particles (VLPs) of hepatitis B surface antigen (HBsAg). Methods The gene fi-agment corresponding to amino acids (aa) 551-607 (HEnAg) of HEV capsid protein, which contains the only neutralization epitope identified to date, was fused via a synthetic glycine linker in flame with the gene of HBsAg. The resulted fusion gene was then integrated through transformation into the genome of Pichiapastoris under the control of a methanol-induced alcohol oxidase 1 (A OXI) promoter and expressed intraceUularly. The expression products in the soluble cell extracts were characterized by Western blot, ELISA, CsCI density gradient analysis, and electron microscopic visualization. Results The novel fusion protein incorporating HBsAg and the neutralization epitope-containing HEnAg was expressed successfully in Pichiapastoris with an expected molecular weight of approximately 32 kD. It was found to possess the ability to assemble into chimeric HBV/HEV VLPs with immunological, physical and morphological characteristics akin to HBsAg particles. Not only did the chimeric VLPs show high activity levels in a HBsAg particle-specific ELISA but they were also strongly immunoreactive with hepatitis E (HE) positive human serum in a HEV specific ELISA, indicating that HEnAg peptide fragments were exposed on VLP surfaces and would be expected to be readily accessible by cells and molecules of the immune system. Similarity between chimeric VLPs to highly immunogenic HBsAg particles may confer good immunogenicity on surface-displayed HEnAg. Conclusion The chimeric HBV/HEV VLPs produced in this study may have potential to be a recombinant HBV/HEV bivalent vaccine candidate.     

妇科止带片的体外溶出度比较

目的 比较不同生产厂家妇科止带片的体外溶出情况,为临床用药提供参考.方法 参照日本“药品品质再评价”在溶出度中所拟定的模拟人体消化道内体液的4种溶出介质及溶出度实验条件的规定,考察了不同药厂妇科止带片在4种溶出介质中的体外溶出情况,并进行了比较.结果 7家药厂的妇科止带片只有1家的在4种溶出介质中的溶出状况均较好,且在60 min时,在溶出介质Ⅰ、Ⅳ条件下的累积溶出百分率大于65％,在溶出介质Ⅱ、Ⅲ条件下的累积溶出百分率大于80％;其他药厂的妇科止带片在4种溶出介质中的溶出状况不尽相同.在溶出介质Ⅱ、Ⅲ的条件下,7家药厂的妇科止带片在60 rmin时的累积溶出百分率均大于65％,综合比较,在溶出介质Ⅲ条件下的溶出状况较佳.结论 不同厂家生产的妇科止带片的体外溶出差异较大;其质量水平差异显著.     

四妙君逸软膏成分的HPLC指纹图谱研究

摘 要 目的：建立四妙君逸软膏HPLC指纹图谱分析方法,为制定其质量控制标准提供依据。 方法: 建立了分析四妙君逸软膏中主要成分的HPLC指纹图谱分离条件,即：色谱柱Ultimate C₁₈-ODS柱（250 mm×4.6 mm,5 μm）;流动相为乙腈-0.1%磷酸水;流速：1.0 ml·min^-1;检测波长：280 nm ;柱温：35℃,并且对色谱图中的共有峰进行了归属分析。结果: 在筛选的最佳分离条件下进行梯度洗脱,四妙君逸软膏中各组分分离效果较好,可得到最优的指纹图谱;经方法学考察表明,所建立的HPLC指纹图谱分析方法精密度、稳定性、重复性均良好,指纹图谱清晰、可辨、易分析;初步确定四妙君逸软膏与四味药材指纹图谱共有峰之间的关系,为四妙君逸软膏的质量控制提供了重要依据。结论:四妙君逸软膏HPLC指纹图谱分析方法可作为质量控制的一项指标,供制订成品质量标准参考。     

不同介质中利培酮口溶膜剂溶出曲线相似性比较

摘 要 目的：考察不同溶出介质对利培酮口溶膜剂溶出度的影响,为其制剂质量判断提供依据。方法: 分别考察自制利培酮口溶膜剂和参比制剂在水、0.1 mol·L^-1 盐酸溶液、pH 4.5醋酸 醋酸钠缓冲液、pH 6.8磷酸盐缓冲液4种溶出介质中的体外溶出行为,以HPLC法进行测定,并采用溶出相似（f2）因子法评价自制制剂和参比制剂溶出曲线的相似性。结果: 在4种介质中,自制制剂与参比制剂的f2因子均大于50。结论: 自制制剂与参比制剂在4种介质中的溶出行为相似,表明该制剂的处方工艺稳定可行。     

Is handling unbalanced datasets for machine learning uplifts system performance?: A case of diabetic prediction

Background and aimsHealthcare is a sensitive sector, and addressing the class imbalance in the healthcare domain is a time-consuming task for machine learning-based systems due to the vast amount of data. This study looks into the impact of socioeconomic disparities on the healthcare data of diabetic patients to make accurate disease predictions.MethodsThis study proposed a systematic approach of Closest Distance Ranking and Principal Component Analysis to deal with the unbalanced dataset. A typical machine learning technique was used to analyze the proposed approach. The data set of pregnant diabetic women is analysed for accurate detection.ResultsThe results of the case are analysed using sensitivity, which demonstrates that the minority class's lack of information makes it impossible to forecast the results. On the other hand, the unbalanced dataset was treated using the proposed technique and evaluated with the machine learning algorithm which significantly increased the performance of the system.ConclusionThe performance of the machine learning-based system was significantly enhanced by the unbalanced dataset which was processed with the proposed technique and evaluated with the machine learning algorithm. For the first time, an unbalanced dataset was treated with a combination of Closest Distance Ranking and Principal Component Analysis.     

In Vivo Estimation of Flexor Digitorum Superficialis Tendon Displacement with Speckle Tracking on 2-D Ultrasound Images Using Laplacian,Gaussian and Rayleigh Techniques

This study applies 2-D speckle tracking using B-scan ultrasound imaging to estimate the instantaneous and total displacement of the middle flexor digitorum superficialis (FDS) tendon proximal to the wrist. This is achieved by performing the study with human patients, during regular carpal tunnel surgeries. B-Scan images were collected with a 12-MHz transducer placed proximal to the wrist, while a video microscope simultaneously imaged the exposed flexor tendons in the palm as a reference for validation. The accuracy of the proposed speckle-based tracking method is compared using log-compressed Rayleigh (Fisher-Tippet)-, Gaussian (sum of squared differences)- and Laplacian (sum of absolute differences)-based statistics as similarity measures. Overall, tracking was successful and the Rayleigh technique performed better than the Laplacian or Gaussian technique. One goal of this research was to non-invasively monitor FDS tendon displacement in the wrist for the purposes of controlling a prosthetic device. An additional goal was to obtain pre- and post-operative clinical information.     

Representation of Lesion Similarity by Use of Multidimensional Scaling for Breast Masses on Mammograms

Presentation of similar reference images can be useful for diagnosis of new lesions. A similarity map which can visually present the overview of the relationship between the lesions with different types may provide the supplemental information to the reference images. A new method for constructing the similarity map by multidimensional scaling (MDS) for breast masses on mammograms was investigated. Nine pathologic types were included; three regions of interests each from the nine groups were employed in this study. Subjective similarity ratings by expert readers were obtained for all possible 351 pairs of masses. Using the average ratings, MDS similarity map was created. Each axis of the MDS configuration was fitted by the linear model with 13 image features to reconstruct the similarity map. Dissimilarity based on the distance in the reconstructed space was determined and compared with the subjective rating. The MDS map consistently represented the similarity between cysts and fibroadenomas, invasive lobular carcinomas and scirrhous carcinomas, and ductal carcinomas in situ, solid–tubular carcinomas, and papillotubular carcinomas with the experts’ data. The correlation between the average subjective ratings and the dissimilarities based on the distance in the reconstructed feature space was much greater (−0.87) than that of the dissimilarities based on the distance in the conventional feature space (−0.65). The new similarity map by MDS can be useful for visualizing the relationship between breast masses with different pathologic types. It has potential usefulness in selecting the similarity measures and providing the supplemental information.