The abnormal accumulation of neutrophil extracellular traps （NETs） can promote the initiation and progression of pancreatic cancer， which is considered a potential therapeutic target for this disease. The Miraculous Pivot·Inquiry About Statement （《灵枢·口问》） have recorded the concept of "defensive qi stagnation". Based on the recognition that the function of defensive qi is similar to the immune function of neutrophils， and combining traditional Chinese medicine theory with clinical practice， it is proposed that the abnormal accumulation of NETs may be a pathological product of "defensive qi stagnation"， with the spleen being the critical site of pathology. Further exploring the application strategy of cleaning spleen and restoring defensive qi method in pancreatic cancer treatment， it is proposed to employ three approaches such as dredging method to eliminate spleen stagnation and inhibit pancreatic cancer proliferation， cleaning method to remove spleen dampness and suppress the inflammatory micro-environment， and tonifying method to strengthen Weiqi and to improve the immune microenvironment， which aims to provide new insights for the clinical treatment of pancreatic cancer with traditional Chinese medicine.

Ying and wei qi is derived from the essence of water and grain， and is the basic material to maintain the normal life activities of the body. Ying and wei qi has the difference of nature of yin and yang or the clear and the turbid. When the relationship between ying and wei qi is out of order and in reverse disorder， it will lead to the occurrence of various diseases. Based on the analysis of the theory of "ying-wei disorder" in The Inner Canon of Yellow Emperor （《黄帝内经》）， this paper started from the perspective of the exuberance and debilitation， circulation and function of ying qi and wei qi， focused on the theoretical understanding that the change of deficiency and excess （"fall"） and the change of circulation （"move"）， and refined the core mechanism of "ying-wei disorder"， which is the depletion of ying qi and wei qi， stagnation of ying qi and wei qi， and disharmony of ying qi and wei qi， and finally summarized the syndrome identification and treatment method of supporting ying qi and assisting wei qi， promoting ying qi and moving wei qi， regulating ying qi and wei qi， and constructed the syndrome identification and treatment system for ying-wei disorder of malignant tumor in clinic.

Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.

A transcriptional regulatory network for wild-type and ATP7B-knockout HepG2 cells exposed to copper was constructed by bioinformatics methods to explore the potential mechanism of key transcription factors in the pathogenesis of hepatolenticular degeneration. The differentially expressed genes (DEGs) for wild-type and ATP7B-knockout HepG2 cell lines without copper and exposed to copper were collected from the gene expression omnibus (GEO) database. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed for DEGs induced by copper. The key functional modules and genes were identified based on the protein-protein interaction (PPI) network. Moreover, the enrichment analysis of genes in functional modules was performed. Finally, a transcriptional regulatory network was constructed to screen the core transcription factors. A total of 1 034 genes, including 509 down-regulated genes and 525 up-regulated genes, were selected as DEGs. The up-regulated and down-regulated functional modules based on PPI network included 3 785 and 3 931 genes, respectively. Genes in key functional modules were enriched in cell-substrate junction, chromosomal region, spliceosomal complex and ribosome. They were involved in mRNA processing, histone modification, RNA splicing, regulation of DNA metabolic process, protein phosphorylation and other biological processes. Moreover, they were correlated to transcriptional coregulator activity, DNA-binding transcription factor binding, ubiquitin-like protein ligase binding and other molecular functions. KEGG analysis showed that genes in key functional modules were significantly enriched in hepatitis B, MAPK signaling pathway, cellular senescence and apoptosis, neurotrophin signaling pathway and pathways of neurodegeneration-multiple diseases. The transcriptional regulatory network contained 11 differentially expressed transcription factors and 96 DEGs. Among them, U2AF1, NFRKB, FUS, MAX, SRSF1, CEBPA and RXRA were the core transcription factors, which may facilitate the study of the biological function of relevant molecules in transcriptional regulation of hepatolenticular degeneration.
Humans ; Transcriptome ; Gene Expression Profiling/methods* ; Hepatolenticular Degeneration/genetics* ; Copper ; Gene Regulatory Networks ; Computational Biology/methods* ; Transcription Factors/genetics* ; DNA ; DNA-Binding Proteins/genetics* ; Serine-Arginine Splicing Factors/genetics*

Genome-wide physical protein-protein interaction(PPI)mapping remains a major chal-lenge for current technologies.Here,we reported a high-efficiency BiFC-seq method,yeast-enhanced green fluorescent protein-based bimolecular fluorescence complementation(yEGFP-BiFC)coupled with next-generation DNA sequencing,for interactome mapping.We first applied yEGFP-BiFC method to systematically investigate an intraviral network of the Ebola virus.Two-thirds(9/14)of known interactions of EBOV were recaptured,and five novel interactions were discovered.Next,we used the BiFC-seq method to map the interactome of the tumor protein p53.We identified 97 interactors of p53,more than three-quarters of which were novel.Furthermore,in a more complex background,we screened potential interactors by pooling two BiFC libraries together and revealed a network of 229 interactions among 205 proteins.These results show that BiFC-seq is a highly sensitive,rapid,and economical method for genome-wide interactome map-ping.

The accumulation of various types of drug informatics data and computational approaches for drug repositioning can accelerate pharmaceutical research and development. How-ever, the integration of multi-dimensional drug data for precision repositioning remains a pressing challenge. Here, we propose a systematic framework named PIMD to predict drug therapeutic properties by integrating multi-dimensional data for drug repositioning. In PIMD, drug similarity networks (DSNs) based on chemical, pharmacological, and clinical data are fused into an integrated DSN (iDSN) composed of many clusters. Rather than simple fusion, PIMD offers a systematic way to annotate clusters. Unexpected drugs within clusters and drug pairs with a high iDSN similarity score are therefore identified to predict novel therapeutic uses. PIMD provides new insights into the universality, individuality, and complementarity of different drug properties by evaluating the con-tribution of each property data. To test the performance of PIMD, we use chemical, pharmacolog-ical, and clinical properties to generate an iDSN. Analyses of the contributions of each drug property indicate that this iDSN was driven by all data types and performs better than other DSNs. Within the top 20 recommended drug pairs, 7 drugs have been reported to be repurposed. The source code for PIMD is available at https://github.com/Sepstar/PIMD/.

Advances in biological and medical technologies have been providing us explosive volumes of biological and physiological data, such as medical images, electroencephalography, genomic and protein sequences. Learning from these data facilitates the understanding of human health and disease. Developed from artificial neural networks, deep learning-based algorithms show great promise in extracting features and learning patterns from complex data. The aim of this paper is to provide an overview of deep learning techniques and some of the state-of-the-art applications in the biomedical field. We first introduce the development of artificial neural network and deep learning. We then describe two main components of deep learning, i.e., deep learning architectures and model optimization. Subsequently, some examples are demonstrated for deep learning applications, including medical image classification, genomic sequence analysis, as well as protein structure classification and prediction. Finally, we offer our perspectives for the future directions in the field of deep learning.
Algorithms ; Computational Biology ; methods ; Diagnostic Imaging ; Genomics ; methods ; Humans ; Image Interpretation, Computer-Assisted ; methods ; Machine Learning ; Neural Networks (Computer) ; Protein Structure, Secondary ; Proteins ; metabolism

OBJECTIVE:To systematically evaluate therapeutic efficacy and safety of pitavastatin comparison of atorvastatin in the treatment of primary hypedipemia in Chinese adults,and to provide evidence-based reference for clinic.METHODS:Retrieved from The Cochrane Library,PubMed,Chinese Journal Full-text Database,Wanfang database,and manually search Google Scholar,Baidu academic search engine,randomized controlled trials (RCTs) about pitavastatin (trial group) vs.atorvastatin (control group) in the treatment of primary hyperlipemia in Chinese adults were collected.After literature screening,data extraction,quality evaluation of included studies with modified Jadad scale,Meta-analysis of the levels of total cholesterol (TC),low density lipoprotein cholesterol (LDL-C),triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C),response rate and the incidence of ADR was conducted by using Rev Man 5.3 statistical software.RESULTS:A total of 5 RCTs were included,involving 456 patients.Results of Meta-analysis showed that the decrease of TC level [MD=0.09,95％CI(0.01,0.16),P=0.03] in trial group was more better than control group,while the increase of HDL-C level [MD=0.08,95％ CI (0.01,0.14),P=0.03] and the decrease of the TG level [MD=-0.13,95％ CI (-0.20,-0.06),P=0.000 4] in trial group were worse than control group,with statistical significance.There was no statistical difference in the decrease of LDL-C[MD=-0.01,95％ CI (-0.13,0.10),P=0.84],response rate [OR=0.75,95％CI (0.15,3.66),P=0.72] or the incidence of ADR [OR=0.68,95 ％ CI (0.44,1.05),P=0.08] between 2 groups.CONCLUSIONS:Pitavastatin has better therapeutic efficacy in decreasing TC,but its therapeutic efficacy in decreasing LDL-C is similar to that of atorvastatin;its therapeutic efficacy in decreasing TG and increasing HDL-C is worse than that of atorvastatin.The safety of them is equivalent.

Objective: To investigate the effect of exposure to particulate matter ≤10 μm in aerodynamic diameter (PM₁₀) on sperm quality in different stages of sperm development. Methods: This cross-sectional study included 1 827 patients attending the reproductive medicine center in Renmin Hospital of Wuhan University during April 2013 to January 2015. Air pollution data from January 2013 to January 2015 was obtained from the database of Wuhan Municipal Environmental Protection Bureau. The generalized linear model was employed to assess the association between each exposure variables and sperm parameters for several exposure windows (0-9, 10-14, 15-69, 70-90, 0-90 days before sampling) . Results: The average levels of PM₁₀ was (116.2±71.6) μg/m³ during the research period. Sperm volume was (75.4±49.1) ×10⁶/ml in sample population, (29.4±16.2) % in progressive motility and (51.8±21.6) % in total motility. Exposure to PM₁₀ was inversely associated with sperm concentration (β:-0.319; 95%CI:-0.529,-0.046) during 70-90 lag days. PM₁₀ exposure during the 0-90 lag days was significantly associated with progressive motility (β:-0.312; 95%CI:-0.527,-0.097) and total motility (β:-0.347; 95%CI:-0.636,-0.059) after adjusted for age, education level, BMI, smoking, abstinence time, temperature, humidity and season. Conclusion Exposure to PM₁₀ was associated with statistically significant decrements in sperm concentration and motility, and the adverse impact on sperm concentration was significantly in early phases of spermatogenesis.

Objective To explore the role of the DACT2 gene in the occurrence and development of renal cell carcinoma(RCC).Methods The samples of RCC tissues and corresponding tumor-adjacent tissues after radical operation and normal kidney tissues were collected.The methylation specific PCR (MSP) and real time fluorescence reverse transcriptase-PCR (RT-PCR) methods were adopted to detect the methylation status and mRNA expression of DACT2.The streptavidin-peroxidase (SP) method labeled by immunohistochemistry peroxidase was used to examine the expression of β-catenin protein.Then the relationship between DACT2 gene methylation status and mRNA expression with the clinicopathologic characteristics was analyzed.The relationship between DACT2 gene methylation with mRNA and β-catenin expression was analysed,as well.Results The DACT2 mRNA relative expression level in RCC tissues was 0.427±0.025,which was significantly lower than (0.801±0.047) in tumor-adjacent tissues and (0.872±0.022) in normal tissue,the positive rate of DACT2 gene methylation in RCC tissues was 45.76%,which was significantly higher than 6.78% in tumor-adjacent tissues and 5.08% in normal tissues,the difference was statistically significant (P<0.05),while the difference between tumor-adjacent tissues and normal tissues had no statistical significance (P>0.05).The DACT2 gene mRNA expression level in RCC tissues and promoter area methylation occurrence rate had no obvious correlation with the clinical data such as patients age,gender,tumor size,clinical stage and Fuhrman grade (P>0.05).The DACT2 gene mRNA relative level in the methylation group was lower than that in the non-methylation group,the difference was statistically significant (P<0.05).The expression rate of β-catenin protein in cytoplasma in RCC tissues was higher than that in the tumor-adjacent tissues and normal tissues,the difference was statistically significant (P<0.05),moreover,DACT2 gen methylation had a positive correlation with β-catenin protein expression (r=0.324,P=0.012).Conclusion The decrease of DACT2 gene promoter area methylation and mRNA relative expression level may participate in the RCC occurrence,but has no relationship with RCC clinical progression.Methylation occurred in DACT2 gene promoter area may be one of reasons causing mRNA relative expression decrase.DACT2 gene methylation occurrence in RCC tissue might be related to the high expression of β-catenin.