Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

Taking the Department of Obstetrics and Gynecology as an example, this paper expounds a series of practices of online education, in the process from pre-course training, platform selection, curriculum design, to student evaluation, etc. From that, we can provide a reference for carrying out online teaching in response to the epidemic for clinical medical colleges which have not been exposed to the online course. Furthermore, it is a new attempt to explore a way to make a change of the traditional teaching method and deepen the reform of clinical teaching in our hospital after the epidemic, not only in professional medical education, but also in the popularization of medical knowledge.

Objective:To evaluate the retinal differentiation ability of human induced pluripotent stem cells (hiPSCs) from various somatic cell sources.Methods:The hiPSCs lines BC1- green fluorescent protein (GFP) and Gibco obtained by blood cell reprogramming and the hiPSCs line UE017 obtained by urine cell reprogramming were used to induce retinal differentiation.The morphogenesis and development of retina were recorded with an optical microscope, and the expression of specific molecular markers of various cell subclasses in the retina was detected by immunofluorescence, and the efficiency of retinal differentiation of different cell lines was analyzed and compared.Results:All three hiPSC lines derived from blood and urine cells were able to be induced into three-dimensional (3D) retinal organoids, including neuroretina and retinal pigment epithelial cells.Retinal organoids simulated the development process of retina in vivo and gradually differentiated into all cell subtypes of retina, including retinal ganglion cells, photoreceptor cells, amacrine cells, horizontal cells, bipolar cells, Müller cells, and even formed lamellar structures.However, in terms of the efficiency of acquiring retinal organoids, the hiPSCs derived from blood were more efficient than those derived from urine. Conclusions:hiPSCs from both blood and urine somatic cells can differentiate into 3D retinal organoids, including all subtypes of retinal cells.The differentiation efficiency among lines is different.

Objective:To establish a fluorescent reporter human induced pluripotent stem cell line (hiPSCs) for monitoring the expression of visual system homeobox 2 ( VSX2). Methods:VSX2_small guide RNA (sgRNA) was inserted into vector PX459 to construct knockout plasmid, and the P2A-eGFP knock-in donor plasmid was conducted at the same time.The two plasmids were transfected into BC1-hiPSCs.Single cell clones were generated after treatment of puromycin.Correct insertion was confirmed by PCR and Sanger sequencing.The isogenicity of the parental and the reporter hiPSCs was confirmed by STR analysis and karyotyping.Pluripotency capacity of the reporter hiPSCs was analysed by reverse trascription PCR and immunofluorescence.Three-germ-layer formation experiment was carried out to analyse the multi-lineage differentiation ability of the reporter hiPSCs.The reporter hiPSCs were further differentiated to obtain three-dimension (3D) retinal organoids, and immunofluorescence was used to identify the co-localization of the enhanced green fluorescent protein (eGFP) and VSX2.Results:A VSX2 eGFP reporter hiPSC clone was successfully obtained by CRISPR/Cas9 technology, which was consistent with the parental hiPSCs (BC1-hiPSCs) in morphology, without any chromosomal aberrations or cell line cross-contamination.Reverse transcription PCR assay and immunofluorescence showed obvious positive expressions of iPSCs markers in BC1- VSX2 eGFP-iPSCs, including NANOG, OCT4, SOX2, DNMT3B and GDF3 mRNA as well as NANOG, OCT4, SSEA4 and TRA-1-60 protein.The α-fetoprotein (AFP), α-smooth muscle actin (α-SMA) and neuronal class Ⅲ β-tubulin (TUJ1) were expressed in endoderm, mesoderm and ectoderm, respeetively, derived from BC1- VSX2 eGFP-iPSCs, and eGFP and VSX2 were co-stained in the neural retinal layer of 3D retinal organoids derived from BC1- VSX2 eGFP-iPSCs by immunofluorescence. Conclusions:VSX2 fluorescent reporter hiPSCs is successfully generated, which can monitor the temporal and spatial expression changes of VSX2 protein in real time, providing a powerful tool for evaluation of retina development mechanism and cell therapy.

Gliomas are one of the most common types of brain cancers. Numerous efforts have been devoted to studying the mechanisms of glioma genesis and identifying biomarkers for diagnosis and treatment. To help further investigations, we present a comprehensive database named GliomaDB. GliomaDB includes 21,086 samples from 4303 patients and integrates genomic, transcriptomic, epigenomic, clinical, and gene-drug association data regarding glioblastoma multiforme (GBM) and low-grade glioma (LGG) from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Chinese Glioma Genome Atlas (CGGA), the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), the US Food and Drug Administration (FDA), and PharmGKB. GliomaDB offers a user-friendly interface for two main types of functionalities. The first comprises queries of (i) somatic mutations, (ii) gene expression, (iii) microRNA (miRNA) expression, and (iv) DNA methylation. In addition, queries can be executed at the gene, region, and base level. Second, GliomaDB allows users to perform survival analysis, coexpression network visualization, multi-omics data visualization, and targeted drug recommendations based on personalized variations. GliomaDB bridges the gap between glioma genomics big data and the delivery of integrated information for end users, thus enabling both researchers and clinicians to effectively use publicly available data and empowering the progression of precision medicine in glioma. GliomaDB is freely accessible at http://bigd.big.ac.cn/gliomaDB.

Objective To explore the effects of self-management education on sharp instruments operation behavior of nursing staff. Methods Form January to June 2017, 231 nurses were given the self-management education on sharp instruments operation. The general self-efficacy, the self-management ability and the accuracy of sharp instruments operation behavior of nurses were compared before and after the education. Results After the self-management education, the general self-efficacy, the total score of self-management ability in sharp instruments operation, the control operation, the emotion management, the operation information management, occupational health management, the operation environment management and the accuracy of sharp instruments operation behavior of nurses also improved apparently than before, and the differences were statistically significant (P< 0.05). Conclusions The self-management education can improve the self-management ability and the accuracy of sharp instruments operation behavior of nurses.

Objective To observe the effect of sinomenine (SIN) on the expression of cyclooxygenase (COX2),alpha-7 nicotinic acetylcholine receptor(α7nAChR) and adenosine receptor(A2A) in A549 cells,and to explore the relative mechanism for cell proliferation.Methods The effect of SIN and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on the proliferation of A549 cells was determined by methyl thiazolyl tetrazolium (MTT) assay.The effect of SIN and NNK on the migration of A549 cells was detected by cell wound scratch assay.The effect of SIN and NNK on COX2 expression in A549 cells was determined by Western blotting method.The effect of SIN and NNK on the expression of α7nAChR and A2A mRNA and protein was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting method.Results NNK increased the proliferation and migration of A549 cells,while SIN inhibited the proliferation and migration of A549 cells.COX2 expression level was increased in NNK group but was decreased in SIN group.The expression levels of α7nAChR and A2A were up-regulated in NNK group but were down-regulated in SIN group.Conclusion SIN plays a role in inhibiting the proliferation and migration of A549 cells by suppressing COX2 expression.SIN has an inhibitory effect on the expression of α7nAChR and A2A.

ObjectiveTo study the effects of quality control circle (QCC) activities on improving the revisiting rate in discharged patients with chronic hepatitis B,so as to supervise patients to return visit regularly and improve medical compliance.Methods To investigate the revisiting situation of chronic hepatitis B patients discharged from infection department from January to March 2016 through QCC activities,in which the causes of the missing revisits were analyzed,and goals for improvement and corresponding measurements were set up. Corresponding measures were taken from April to October,2016. Statistical analysis was made to compare the revisiting rate before and after QCC activities.Results After taken the measures,the revisiting rate of discharged chronic hepatitis B patients was raised from 30.56% to 63.22%.Conclusions QCC activity can improve the revisiting rate and satisfaction of discharged patients with chronic hepatitis B.