Androgen deprivation therapy (ADT) is a cornerstone treatment for locally advanced or metastatic prostate cancer (PCa). However, its potential effects on the tumor immune microenvironment (TIM) of PCa patients and the underlying mechanism remain largely unclear. To explore the effects of ADT on PCa TIM, RNA sequencing was performed on six paired pre-ADT biopsy and post-ADT PCa lesions, and five paired paracancerous benign tissues from patients receiving neoadjuvant ADT with locally advanced PCa. Bioinformatics methods including ESTIMATE and ssGSEA were used to evaluate the stromal immune score and immune cell infiltration in PCa and paracancerous tissues. Weighted correlation network analysis was used to screen hub genes in the ADT-induced immune remodeling process. The results showed differences exist between PCa and paracancerous tissues in response to ADT. Compared with paracancerous tissues, the immune remodeling effect of ADT in PCa was more intense. ZFP36, JUNB, and SOCS3 served as hub genes in the ADT-induced immune remodeling process and were associated with PSA recurrent-free survival in the TCGA and our neoadjuvant ADT cohort. To investigate the joint action of the above three hub genes, an immune signature score was constructed. The results showed that immune signature score-based immune subtypes reveal the heterogeneity of the immune microenvironment of PCa and showed significant differences in patient prognosis, tumor immune infiltration, mutation burden, and landscape.
This paper developed a GIS-based spatial multi-index model for the large basinscale flood risk assessment. In terms of the risk definition proposed by the IPCC, the flood risk in the Yangtze River Basin (YRB) was classified into the indexes of hazard, vulnerability, and exposure. The model systematically accounts for various flood risk indicators related to the YRB economic, social and ecological environment. Based on the ArcGIS's robust data space analysis and processing capabilities, these flood risk indicators were superimposed and analyzed to generate the integrated flood risk spatial distribution map across the YRB. The modelling results were verified reasonably well using the observed YRB floods in 1998, 2008, and 2016. We found that 24.90% of the study area was found to be of very high and high risk in 1998, while these areas in the YRB fell to 15. 95% and 17.61% in 2008 and 2016, respectively. We believe that the GIS-based spatial multi-index model can be applied to other areas, where the basinscale flood risk assessment is desired, and also contribute to further scientific research on flood forecasting and mitigation.
Background Climate heterogeneity not only indirectly shapes the genetic structures of plant populations, but also drives adaptive divergence by impacting demographic dynamics. The variable localized climates and topographic complexity of the Taihang Mountains make them a major natural boundary in Northern China that influences the divergence of organisms distributed across this region. Opisthopappus is an endemic genus of the Taihang Mountains that includes only two spatially partitioned species Opisthopappus longilobus and Opisthopappus taihangensis. For this study, the mechanisms behind the genetic variations in Opisthopappus populations were investigated. Results Using SNP and InDel data coupled with geographic and climatic information, significant genetic differentiation was found to exist either between Opisthopappus populations or two species. All studied populations were divided into two genetic groups with the differentiation of haplotypes between the groups. At approximately 17.44 Ma of the early Miocene, O. taihangensis differentiated from O. longilobus under differing precipitation regimes due to the intensification of the Asian monsoon. Subsequently, intraspecific divergence might be induced by the dramatic climatic transformation from the mid- to late Miocene. During the Pleistocene period, the rapid uplift of the Taihang Mountains coupled with violent climatic oscillations would further promote the diversity of the two species. Following the development of the Taihang Mountains, its complex topography created geographical and ecological heterogeneity, which could lead to spatiotemporal isolation between the Opisthopappus populations. Thus the adaptive divergence might occur within these intraspecific populations in the localized heterogeneous environment of the Taihang Mountains. Conclusions The localized environmental events through the integration of small-scale spatial effects impacted the demographic history and differentiation mechanism of Opisthopappus species in the Taihang Mountains. The results provide useful information for us to understand the ecology and evolution of organisms in the mountainous environment from population and species perspective.
ObjectiveTo assess the efficacy and safety of green-light laser photoselective vaporisation of the prostate (PVP) compared with transurethral resection of the prostate (TURP) for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).DesignSystematic review and meta-analysis, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement.Data sourcesPubMed, EMBASE, the Cochrane Library until October 2018.Eligibility criteriaRandomised controlled trials and prospective studies comparing the safety and efficacy of PVP versus TURP for LUTS manifesting through BPH.Data extraction and synthesisPerioperative parameters, complications rates and functional outcomes including treatment-related adverse events such as International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), postvoid residual (PVR), quality of life (QoL) and International Index of Erectile Function (IIEF).Results22 publications consisting of 2665 patients were analysed. Pooled analysis revealed PVP is associated with reduced blood loss, transfusion, clot retention, TUR syndrome, capsular perforation, catheterisation time and hospitalisation, but also with a higher reintervention rate and longer intervention duration (all p<0.05). No significant difference in IPSS, Qmax, QoL, PVR or IIEF at 3, 24, 36 or 60 months was identified. There was a significant difference in QoL at 6 months (MD=−0.08; 95% CI −0.13 to −0.02; p=0.007), and IPSS (MD = −0.10; 95% CI −0.15 to −0.05; p<0.0001) and Qmax (MD=0.62; 95% CI 0.06 to 1.19; p=0.03) at 12 months, although these differences were not clinically relevant.ConclusionPVP is an effective alternative, holding additional safety benefits. PVP has equivalent long-term IPSS, Qmax, QoL, PVR, IIEF efficacy and fewer complications. The main drawbacks are dysuria and reintervention, although both can be managed with non-invasive techniques. The additional shortcoming is that PVP does not acquire histological tissue examination which removes an opportunity to identify prostate cancer.
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