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Background: With growing evidence that immune cells contribute greatly in tumor progression, identifying their role in tumor prognosis and therapy is crucial. Our aim is to comprehensively characterize tumor infiltration immune cells in BLCA and identify valuable immune cells and gene model related to prognosis and therapy in BLCA. Methods: Firstly, after comparing the relationship between the abundance of infiltrating immune cells and prognosis, CD8+T cell was selected to establish the risk model, which was constructed based on five key genes(GNLY, LHFPL6, APOL6, LRP1, and UBA7). Then ROC curve was drawn to demonstrate the risk model own high prognosis predictive value in BLCA. Results: Our results of correlation analysis showed that riskscore were negatively correlated with several steps of the tumor immune cycle, such as infiltration of tumor tissue T cells, and positively correlated with the fourth step of the cancer immune cycle. Furthermore, riskscore was negatively correlated with the expression of CD8,CD274,IFNG, Merck18, and several common immune checkpoint (TIGIT, CTLA4, HAVCR2 LAG3, PDCD). Moreover, tumor exclusion score and Tumor Immune Dysfunction and Exclusion (TIDE) score were higher in high-score group than that in low-score group. Importantly, riskscore was negatively correlated with the enrichment score of immunotherapy-related pathways, and the therapeutic benefit of low-score group was greater than that in high-score group. A total of 171 chemotherapy and targeted drugs were identified, of which the high-score group were more sensitive to 82 drugs and the low-score group were more sensitive to the other 89 drugs. Among the commonly used chemotherapy drugs for BLCA, such as cisplatin and doxorubicin, the IC50 in low-score group was smaller and more sensitive. Subsequently, immunohistochemistry was used to make a verification on the risk model. Finally, we explored the relationship between APOL6 expression and clinicopathological characteristics and found that the expression of APOL6 was positively correlated with tumor grade. Conclusions: Our results confirmed that the tumor infiltration CD8+T cells played a crucial role in the prognosis and therapy of BLCA,which may provide us a new inspiration and direction in prognosic prediction and therapy of bladder cancer in future.

Background: Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by inflammatory infiltration and dysfunction of the salivary and lacrimal glands. This research aimed to explore the disease pathogenesis and improve the diagnosis and treatment of pSS by mining inflammatory biomarkers. Methods: Five pSS-related datasets were retrieved from the Gene Expression Omnibus (GEO) database. Inflammatory biomarkers were determined by Least absolute shrinkage and selection operator (LASSO) and support vector machines recursive feature elimination (SVM-RFE). Single sample gene set enrichment analysis (ssGSEA) was implemented to profile the infiltration levels of immune cells. The expression of biomarkers in clinical samples was verified by Real-Time Quantitative PCR. Results: Four genes (LY6E, EIF2AK2, IL15, and CXCL10) were confirmed as inflammatory biomarkers in pSS. Functional enrichment suggested that the biomarkers were involved inimmune and inflammation-related pathways. Immune infiltration analysis revealed that biomarkers were notably connected with some differential immune cells between pSS and control. Also, the RT-qPCR results of clinical samples further affirmed the results of the public database. Conclusion: Four inflammatory biomarkers (LY6E, EIF2AK2, IL15, and CXCL10) were defined and regulatory mechanisms and targeted drugs were investigated in pSS, which provided a basis for understanding the pathogenesis and improving clinical diagnosis and treatment for the disease.

Background: Over the last decade, there has been an increasing number of clinical and laboratory evidence supporting associations between Polycystic ovary syndrome (PCOS) and periodontitis, but few studies have been conducted on the underlying mechanisms of the two diseases through the transcriptomic approach. In this study, gene co-expression networks between PCOS and periodontitis were analyzed by bioinformatics tools. Methods: PCOS and periodontitis expression data were downloaded from the GEO database, and the differentially expressed genes (DEGs) were identified. After obtaining Intersected genes, GO and KEGG pathway enrichment analysis and random forest (RF) algorithm were used to screen hub genes in PCOS and periodontitis. The functions of the hub genes were analyzed by GSEA, and the correlations between hub genes and immune infiltration in two diseases were examined. Furthermore, a TF-ceRNA regulatory network of hub genes was constructed. Results: There were 1,661 DEGs in PCOS and 701 DEGs in periodontitis compared to the controls. After overlapping, 66 intersected genes were shown to be involved in PCOS and periodontitis, and were mainly enriched in immune and inflammation-related biological processes and pathways. 40 common genes were selected from the PPI network constructed by STRING. The RF algorithm demonstrated that ACSL5, NLRP12, CCRL2, and CEACAM3 were hub genes in PCOS and periodontitis, and the GSEA result revealed their close relationship with the antigen processing and presentation, and chemokine signaling pathway. Moreover, the data showed that those 4 hub genes may serve as diagnostic genes for PCOS and periodontitis. Conclusion: This study identified ACSL5, NLRP12, CCRL2, and CEACAM3 as the diagnostic genes at the intersection of PCOS and periodontitis, and establish a ceRNA network, which could provide a molecular basis for future experimental studies on the association between PCOS and periodontitis.

Prolonged androgen deprivation therapy (ADT) in patients with prostate cancer can eventually lead to the development of castration-resistant prostate cancer (CRPC). Once CRPC occurs, the patient's prognosis will be extremely poor. This study explored the time to progression and the predictability of risk factors for CRPC progression based on clinical information and laboratory indicators. Among 159 prostate cancer patients initially treated with ADT, 90 patients were screened for inclusion. Patients progressed to CRPC after endocrine therapy enrolled in Group B, and others enrolled in Group A. Within Group B, they were divided into B1 and B2 Group Based on progression to CRPC within 18 months or not. Multi-factor logistic regression analysis showed that the time to PSA nadir (TTN) (P = 0.031) and serum lactate dehydrogenase (LDH) (P = 0.013) were significantly different between Group A and B. TTN (P

Tianshui is located in a geomorphologic transitional zone with well-developed tectonics. Two historical earthquakes with magnitudes greater than 7.0 have occurred in Tianshui and its surrounding areas. The strata consist of primarily loess and mudstone, and geological disasters frequently occur. The Zhoujiashan landslide is a historical earthquake landslide that is currently relatively stable. To study its deformation and stability under the combined effect of rainfall and earthquake motion, the landslide was analyzed via field investigations, shaking table tests, and numerical calculations. The fastest responses were those of the pore water pressure and volume water content in the 0.3-m-depth range under rainfall conditions. The rainfall infiltration depth is limited to approximately 2 m and has a minimal impact on the overall stability of the slope. The response to earthquake accelerations increases with increasing elevation, and earthquakes have a significant amplification effect on structures with an inherent period of 0.2–0.4 s. Under 0.1-g and 0.3-g earthquake conditions, the slope deforms and the safety factor decreases but the landslide does not suffer overall failure. Under the 0.6-g earthquake condition, the slope liquefies, leading to the overall failure of the slope. The location of the liquefaction zone in the numerical calculation is in agreement with the actual situation. Under the 0.6-g earthquake condition, the overall failure mechanism of the slope is vibration liquefaction at the sliding surface.

Objective: We assessed the correlation between lactate dehydrogenase(LDH) to phosphate ratio and the prognosis of microsurgically clipping for ruptured intracranial aneurysm (rIA) in this study, to test the hypothesis that serum LDH to phosphate ratio could be a predictor for the outcome of microsurgically clipping for rIA. Methods: The rIA patients between 2012 and 2018 were retrospectively collected. Age, sex, Hunt-Hess(H-H) grade, Fisher grade, smoking, drink, medical history, aneurysm location, hydrocephalus, laboratory data including serum LDH, phosphate and LDH to phosphate ratio, related complication and the outcomes in 3 months were recorded. Results: A total of 1608 rIA patients in our institution were collected, and 856 patients treated by microsurgical clipping were enrolled. A significantly higher LDH- phosphate ratio on admission was observed in patients with poor outcome at 3 months (median±SD, 200.175±107.290 for mRS 0–2 vs 323.826±219.075 for mRS score 3–6; P Conclusions: LDH to phosphate ratio was a potential biomarker and could predict the unfavorable outcome of microsurgically clipping for rIA in 3 months. However, the detailed mechanism remain unclear and the conclusion needs be further confirmed by large-scale randomized clinical trials.

Background and PurposeIn this study, the therapeutic effect of Mel-incubated ADSCs on CCl4-induced hepatic fibrosis was investigated. MethodsThe experiment was arranged into ADSCS group, ADSCS + Mel group, Model group and Control group with 10 mice in each group. The other three groups of mice were intraperitoneally injected with 8% CCl4, and the control group was injected with the same dose of PBS twice a week for 4 weeks. From the fifth week, ADSCs group and ADSCs + Mel group mice were injected with 1×106 cells/1 ml PBS dose of ADSCs and 50 μM Mel pretreated ADSCs into tail vein, respectively, twice a week for 2 weeks, and mice in the control and model groups were injected with the same dose of PBS. Samples were tested after six weeks. ResultsIn model group, severe histomathological changes were observed in liver, including severe vacuolation, nuclear fragmentation and liver fibrosis, and these changes were ameliorated by Mel pretreated ADSCs. At the same time, RT-qPCR results showed that Mel-induced ADSCs significantly inhibited the expression of pro-apoptotic genes (Caspase-8, Bax and Caspase-3), and promoted the expression of anti-apoptotic gene (Bcl-2). Immunohistochemical results showed that a large number of MMP-9, TGF-β, MMP-2 yellow-stained positive cells were found in the liver tissues of the model group, while the expression of positive cells was blocked by Mel-induced ADSCs. Conclusion and ImplicationsADSCs pretreated with Mel significantly improved CCl4-induced liver fibrosis, which provides a reference for clinical treatment of liver injury with mesenchymal stem cells.

Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including in population-trials as surrogate subjects in vivo. PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS). We have built a biobank of carcinoma PDX-derived organoids (PDXOs) by converting an existing PDX library and confirmed high degree of similarities between PDXOs and parental PDXs in genomics, histopathology and pharmacology, suggesting “biological equivalence or interchangeability” between the two. Here we demonstrate the applications of PDXO biobank for HTS “matrix” screening for both lead compounds and indications, immune cell co-cultures for immune-therapies and engineering enables in vitro/in vivo imaging. This large biobank of matched pairs of PDXs/PDXOs across different cancers could become powerful tools for the future cancer drug discovery.