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IntroductionInfluenza susceptibility difference is a widely existing trait that has great practical significance for the accurate prevention and control of influenza.MethodsHere, we focused on the human susceptibility to the seasonal influenza A/H3N2 of healthy adults at baseline level. Whole blood expression data for influenza A/H3N2 susceptibility from GEO were collected firstly (30 symptomatic and 19 asymptomatic). Then to explore the differences at baseline, a suite of systems biology approaches - the differential expression analysis, co-expression network analysis, and immune cell frequencies analysis were utilized.ResultsWe found the baseline condition, especially immune condition between symptomatic and asymptomatic, was different. Co-expression module that is positively related to asymptomatic is also related to immune cell type of naïve B cell. Function enrichment analysis showed significantly correlation with “B cell receptor signaling pathway”, “immune response−activating cell surface receptor signaling pathway” and so on. Also, modules that are positively related to symptomatic are also correlated to immune cell type of neutrophils, with function enrichment analysis showing significantly correlations with “response to bacterium”, “inflammatory response”, “cAMP−dependent protein kinase complex” and so on. Responses of symptomatic and asymptomatic hosts after virus exposure show differences on resisting the virus, with more effective frontline defense for asymptomatic hosts. A prediction model was also built based on only baseline transcription information to differentiate symptomatic and asymptomatic population with accuracy of 0.79.DiscussionThe results not only improve our understanding of the immune system and influenza susceptibility, but also provide a new direction for precise and targeted prevention and therapy of influenza.

Immunotherapies, especially the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors, have revolutionized the therapeutic strategies of various cancers. As for colorectal cancer (CRC), the current clinical application of PD-1/PD-L1 inhibitors are mainly used according to the mutation pattern, which is categorized into deficient mismatch repair (dMMR)/high levels of microsatellite instability (MSI-H) and proficient mismatch repair (pMMR), or non-high levels of microsatellite instability (non-MSI-H). PD-1/PD-L1 inhibitors have been proven to have favorable outcomes against dMMR/MSI-H CRC because of more T-cell infiltration into tumor tissues. Nevertheless, the effectiveness of PD-1/PD-L1 inhibitors in pMMR/non-MSI-H CRC is still uncertain. Because of the quite-lower proportion of dMMR/MSI-H in CRC, PD-1/PD-L1 inhibitors have been reported to combine with other antitumor treatments including chemotherapy, radiotherapy, and targeted therapy for better therapeutic effect in recent clinical trials. Neoadjuvant therapy, mainly including chemotherapy and radiotherapy, not only can reduce clinical stage but also benefit from local control, which can improve clinical symptoms and the quality of life. Adding immunotherapy into neoadjuvant therapy may change the treatment strategy of primary resectable or some metastatic CRC. In this review, we focus on the development of neoadjuvant anti-PD-1/PD-L1 therapy and discuss the future perspectives in CRC.

BackgroundHormones and immune imbalance are critical factors in polycystic ovary syndrome (PCOS). The alternation of immune microenvironment of oocytes may play a significant role in infertility of PCOS patients.ObjectiveThis study explores the role of follicular fluid microenvironment change in inflammatory pathways activation of granulosa cells (GCs) in PCOS women infertility.MethodsWe enrolled 27 PCOS patients and 30 controls aged 22 to 38 years who underwent IVF and collected their luteinized granulosa cells (LGCs). Meanwhile, a granulosa-like tumor cell line (KGN) as a cell-model assisted this study. Key inflammatory markers in human ovarian GCs and follicular fluid were detected by RT-qPCR, Western blotting, or ELISA. The KGN cells were treated with follicle supernatant mixed with normal medium to simulate the microenvironment of GCs in PCOS patients, and the inflammation indicators were observed. The assembly of NLRP3 inflammasomes was detected by immunofluorescence techniques. Dihydroethidium assay and EdU proliferation assay were used to detect ROS and cell proliferation by flow cytometry.ResultsCompared with normal controls (n = 19), IL-1β (P = 0.0005) and IL-18 (P = 0.021) in the follicular fluid of PCOS patients (n = 20) were significantly increased. The NF-κB pathway was activated, and NLRP3 inflammasome was formatted in ovarian GCs of PCOS patients. We also found that inflammation of KGN cells was activated with LPS irritation or stimulated by follicular fluid from PCOS patients. Finally, we found that intracellular inflammation process damaged mitochondrial structure and function, which induced oxidative stress, affected cellular metabolism, and impaired cell proliferation.ConclusionInflammatory microenvironment alteration in the follicular fluid of PCOS patients leads to activated inflammatory pathway in GCs, serving as a crucial factor that causes adverse symptoms in patients. This study provides a novel mechanism in the inflammatory process of PCOS.

PurposeThis study aimed to investigate the profiles of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in peripheral blood samples collected from polycystic ovary syndrome (PCOS) patients. In addition, an in-depth bioinformatics analysis regarding the lncRNA-mRNA co-expression network was performed.MethodsHigh-throughput sequencing was used to measure the profiles of mRNAs and lncRNAs expressed in the peripheral blood samples isolated from six patients (three patients with PCOS and three normal women). In addition, five differentially expressed lncRNAs were chosen to validate the results of high-throughput sequencing by quantitative RT-PCR (qRT-PCR). Furthermore, a lncRNA-mRNA co-expression network was constructed using the Cytoscape software.ResultsA total of 14,276 differentially expressed mRNAs and 4,048 differentially expressed lncRNAs were obtained from the RNA-seq analysis of PCOS patients and healthy controls (adjusted q-value < 0.05, Fold change >2.0).The qRT-PCR results were consistent with the data obtained through high-throughput sequencing. Gene ontology (GO) and KEGG pathway analyses showed that the differentially expressed mRNAs were enriched in the chemokine signaling pathway. In addition, the analysis of the lncRNA-mRNA co-expression network of the chemokine signaling pathway showed the involvement of 6 mRNAs and 42 lncRNAs.ConclusionClusters of mRNAs and lncRNAs were aberrantly expressed in the peripheral blood of PCOS patients compared with the controls. In addition, several pairs of lncRNA-mRNAs in the chemokine signaling pathway may be related to PCOS genetically.