The Role of Immune Cells in Chronic HBV Infection

Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses are important factors that determine whether HBV infection is cleared or persists. After infection, viral replication occurs inside hepatocytes, and the secretion of infectious virions can take place at high rates for decades. Consequently, HBV DNA and viral proteins, like HBV early antigen (HBeAg) and HBV surface antigen (HBsAg), can be easily detected in serum. Chronic infection with HBV is the result of an ineffective antiviral immune response towards the virus. In this review, we discuss the role of immune cells in chronic HBV infection.     

Evaluating semantic similarity between Chinese biomedical terms through multiple ontologies with score normalization: An initial study

BackgroundSemantic similarity estimation significantly promotes the understanding of natural language resources and supports medical decision making. Previous studies have investigated semantic similarity and relatedness estimation between biomedical terms through resources in English, such as SNOMED-CT or UMLS. However, very limited studies focused on the Chinese language, and technology on natural language processing and text mining of medical documents in China is urgently needed. Due to the lack of a complete and publicly available biomedical ontology in China, we only have access to several modest-sized ontologies with no overlaps. Although all these ontologies do not constitute a complete coverage of biomedicine, their coverage of their respective domains is acceptable. In this paper, semantic similarity estimations between Chinese biomedical terms using these multiple non-overlapping ontologies were explored as an initial study.MethodsTypical path-based and information content (IC)-based similarity measures were applied on these ontologies. From the analysis of the computed similarity scores, heterogeneity in the statistical distributions of scores derived from multiple ontologies was discovered. This heterogeneity hampers the comparability of scores and the overall accuracy of similarity estimation. This problem was addressed through a novel language-independent method by combining semantic similarity estimation and score normalization. A reference standard was also created in this study.ResultsCompared with the existing task-independent normalization methods, the newly developed method exhibited superior performance on most IC-based similarity measures. The accuracy of semantic similarity estimation was enhanced through score normalization. This enhancement resulted from the mitigation of heterogeneity in the similarity scores derived from multiple ontologies.ConclusionWe demonstrated the potential necessity of score normalization when estimating semantic similarity using ontology-based measures. The results of this study can also be extended to other language systems to implement semantic similarity estimation in biomedicine.     

Effect of an extraction solvent on the antioxidant quality of Pinus densiflora needle extract

Pinus densiflora needle extract (PDNE) is widely reported to have many pharmacological activities including antioxidant potential. However, the solvent system used for extraction greatly affects its antioxidant quality. Hence, in the present study, we investigated the effect of a different ratio (vol/vol) of ethanol to water (0–100%) in the extraction of PDNE with potent antioxidant capacity. The chemical assays, 2,2-diphenyl-1 picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), were conducted to assess the antioxidant potential of PDNE. Subsequently, the cytoprotective effect of PDNE was determined using tert-butyl hydroperoxide (TBHP)-challenged HepG2 cellular model. The needle extracts from 40% ethanol (PDNE-40) showed greater radical scavenging activity followed by 60%, 20%, 80%, 0% and 100% ethanol extracts. EC₅₀ value of the most active extract, PDNE-40, was 8.56 ± 0.51 μg/mL, relative to 1.34 ± 0.28 μg/mL of the standard trolox (for ABTS radical), and 75.96 ± 11.60 μg/mL, relative to 4.83 ± 0.26 μg/mL of the standard trolox (for DPPH radical). Either PDNE-20 or PDNE-40 pretreatment remarkably decreased the levels of reactive oxygen species (ROS), lipid peroxides and protein carbonyls in TBHP-challenged HepG2 cells. In addition, both PDNE-20 and PDNE-40 significantly reversed the decreased ratio of reduced (GSH) to oxidized (GSSG) glutathione. Moreover, these two extracts showed a significant inhibitory effect on TBHP-induced nuclear damage and loss of cell viability. In summary, the inclusion of 40% ethanol in water for extraction of Pinus densiflora needle greatly increases the antioxidant quality of the extract.     

Proposed mechanisms for the extracellular release of PD-L1 by the anticancer saponin platycodin D

Platycodin D (PTD) is an oleanane-type terpenoid saponin, isolated from the plant Platycodon grandiflorus. PTD displays multiple pharmacological effects, notably significant anticancer activities in vitro and in vivo. Recently, PTD was shown to trigger the extracellular release of the immunologic checkpoint glycoprotein PD-L1. The reduction of PD-L1 expression at the surface of cancer cells leads to interleukin-2 secretion and T cells activation. In the present review, we have analyzed the potential origin of this atypical PTD-induced PD-L1 release to propose a mechanistic explanation. For that, we considered all published scientific information, as well as the physicochemical characteristics of the natural product (a modeling analysis of PTD and the related saponin β -escin is provided). On this basis, we raise the hypothesis that the capacity of PTD to induce PD-L1 extracellular release derives from two main mechanisms: (i) a drug-promoted shedding of membrane PD-L1 by metalloproteases or more likely, (ii) a cholesterol binding-related effect, that would lead to perturbation of membrane raft domains, limiting the recruitment of proteins like TLR4. The drug-induced membrane effects (frequently observed with saponin drugs), associated with a production of interferon-γ,can favor the release of proteins like PD-L1 into membrane vesicles. Our analysis supports the hypothesis that PTD is a cholesterol-dependent lipid raft-modulating agent able to promote the formation of PD-L1 containing extracellular vesicles. The anticancer potential of PTD and its capacity to modulate the functioning of the PD-1/PD-L1 checkpoint should be further considered.     

Evaluation of natural dyes for human spermatozoa morphology assessment

Dye extracts from plants have been valuable not only for the economy but also environmental sustainability. There have been many reports on the utilization of natural dyes extracted from various sources for staining of biological tissues. This study aimed to investigate the extraction of natural dye from black rice (Oryza Sativa), butterfly pea (Clitoria ternatea), fresh roselle (Hibiscus sabdariffa), and mulberry (Morus alba) to stain of human spermatozoa for morphology assessment. The results showed that black rice extracted from solvents C containing 5?ml of absolute ethanol, 10?g of potassium alum and 100?ml of distilled water is the best dye for human spermatozoa evaluation comparable to the rapid PAP and Dip quick® stain. Effectiveness of the process was found with black rice extract stain by using 2 steps for 15?min. There were no statistically significant differences in the parameters of head, midpiece, tail and background for human sperm morphology assessment comparable to rapid PAP and Dip quick® stain (p?>?0.05) unless the midpiece compartment when compare to rapid PAP. This finding suggests that the black rice extracted has potential for use as an alternative dye for human spermatozoa morphology evaluation. The usefulness of black rice extracts will decrease the expense for purchasing synthetic dyes and reduce their adverse effects on human and environment.     

Preparing an annotated gold standard corpus to share with extramural investigators for de-identification research

ObjectiveThe current study aims to fill the gap in available healthcare de-identification resources by creating a new sharable dataset with realistic Protected Health Information (PHI) without reducing the value of the data for de-identification research. By releasing the annotated gold standard corpus with Data Use Agreement we would like to encourage other Computational Linguists to experiment with our data and develop new machine learning models for de-identification. This paper describes: (1) the modifications required by the Institutional Review Board before sharing the de-identification gold standard corpus; (2) our efforts to keep the PHI as realistic as possible; (3) and the tests to show the effectiveness of these efforts in preserving the value of the modified data set for machine learning model development.Materials and methodsIn a previous study we built an original de-identification gold standard corpus annotated with true Protected Health Information (PHI) from 3503 randomly selected clinical notes for the 22 most frequent clinical note types of our institution. In the current study we modified the original gold standard corpus to make it suitable for external sharing by replacing HIPAA-specified PHI with newly generated realistic PHI. Finally, we evaluated the research value of this new dataset by comparing the performance of an existing published in-house de-identification system, when trained on the new de-identification gold standard corpus, with the performance of the same system, when trained on the original corpus. We assessed the potential benefits of using the new de-identification gold standard corpus to identify PHI in the i2b2 and PhysioNet datasets that were released by other groups for de-identification research. We also measured the effectiveness of the i2b2 and PhysioNet de-identification gold standard corpora in identifying PHI in our original clinical notes.ResultsPerformance of the de-identification system using the new gold standard corpus as a training set was very close to training on the original corpus (92.56 vs. 93.48 overall F-measures). Best i2b2/PhysioNet/CCHMC cross-training performances were obtained when training on the new shared CCHMC gold standard corpus, although performances were still lower than corpus-specific trainings.Discussion and conclusionWe successfully modified a de-identification dataset for external sharing while preserving the de-identification research value of the modified gold standard corpus with limited drop in machine learning de-identification performance.     

近3年国家自然科学基金对于肺癌领域的资助情况分析

目的分析2018—2020年度国家自然科学基金（NSFC）对肺癌领域的资助情况。 方法以"肺癌"或者"肺恶性肿瘤"为关键词检索既往3年NSFC的申请和资助情况，并进行整理与分析。 结果近3年肺癌领域NSFC共资助了751项，其中青年项目348项，面上项目330项，两种项目类型在年龄、职称、身份分布方面存在较大的差异。 结论肺癌领域是NSFC资助的热点之一，竞争非常激烈，申请人需不断增强自身实力。     

PHLEBOTOMINE FAUNA (DIPTERA: PSYCHODIDAE) IN AN AREA OF FISHING TOURISM IN CENTRAL-WESTERN BRAZIL

The aim of this study was to identify behavioral aspects of the sandfly fauna of a fishing tourism area in the municipality of Bonito (MS). Monthly captures were undertaken from December 2009 to November 2010, using automatic CDC type light traps, from 18h00 to 06h00, in a forested area, a savannah area, peridomiciles and animal shelters near peridomiciliary areas. Nyssomyia whitmani was the most frequent out of a total of 6,699 specimens collected, belonging to 16 species, followed by Psathyromyia bigeniculata and Lutzomyia longipalpis, found in all the environments investigated, though in their greatest numbers in the animal shelters. Ny. whitmani exhibited its highest frequencies during the dry months, coincident with the fishing season, when the risk of transmission of cutaneous leishmaniasis for tourists and inhabitants increases. Noteworthy was the finding of two species naturally infected by flagellates: Ny. whitmani and Pa. bigeniculata. The local population and visiting tourists should be warned of the threat posed by leishmaniasis and the health authorities alerted to the need for adopting environmental sanitary measures, especially regarding such animal shelters as they seem to provide favorable conditions to the proliferation, maintenance and breeding opportunities of phlebotomines.