Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel–Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear.
Patients and Methods
Surgical specimens were recruited from 129 patients with sporadic ccRCC and 26 patients with VHL-associated hereditary ccRCC. The PD-L1 expression level was assessed using immunohistochemistry. Correlations between PD-L1 expression and clinicopathological features were analyzed.
Results
In sporadic ccRCC, the positive expression rate of PD-L1 was 47.3% (61/129). Positive PD-L1 expression was correlated with advanced tumor T stage (P = .011), higher Fuhrman nuclear grade (P = .022), poor disease-free survival (P = .037), and sex (P = .025). In the VHL-associated hereditary ccRCC, positive PD-L1 expression rate was 34.6% (9/26), lower than that in sporadic ccRCC. Positive PD-L1 was correlated with higher Fuhrman nuclear grade (P = .008), but not with sex, age, tumor stage, or the onset age of VHL-associated tumors.
Conclusion
Positive PD-L1 expression was correlated with the aggressive clinicopathological features in sporadic and VHL-associated hereditary ccRCC. Whether PD-L1 expression level in ccRCC is related to the effectiveness of programmed death-1/PD-L1 checkpoint inhibitor immunotherapy needs to be further investigated. 相似文献
Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear.
Objective
To investigate the potential role of CCL20 and the involvement of Th1/17 and Tc1/17 cells in the mechanism in vitiligo.
Methods
One hundred patients with vitiligo, and 20 healthy controls were included. The serum and blister fluid IL-17, IFN-γ, CCL20, and CXCL10 were studied using enzyme-linked immunosorbent assays. The numbers of Th1/17 cells and Tc1/17 cells in circulation were quantified using flow cytometry. CCR6 mRNA in peripheral blood mononuclear cells (PBMCs) was analyzed by real-time polymerase chain reaction and the protein level was confirmed by western blotting. CCR6 and CCL20 expression in lesions was analyzed by immunohistochemistry.
Results
The serum CCL20 level was significantly elevated in patients with vitiligo. The level of serum CCL20 was higher in active than in the stable stage, which correlated positively with the Vitiligo European Task Force spreading score and the Vitiligo Area Scoring Index score. Patients with active vitiligo had elevated numbers of circulating Th1/17 cells and Tc1/17 cells, and upregulated expression of CCR6 in PBMCs and lesions. After effective treatment, the level of CCL20 in sera and blister fluid was significantly decreased, as were the numbers of circulating Th1/17 cells and Tc1/17 cells.
Conclusion
CCL20 might be a vital biomarker of active vitiligo, and circulating Th1/17 and Tc1/17 cells are involved in the pathogenesis of vitiligo. 相似文献
Study overview. 83 patients with stage I lung adenocarcinoma were included in this study. Whole-exome sequencing was performed on surgical samples of these patients. Patients were further divided into 4 groups according to their TP53 mutational status. Tumor mutational burden, recurrence-free survival and overall survival were compared among different groups.
There is keen interest in many jurisdictions in finding ways to improve the way that research evidence informs policy. One possible mechanism for this is to embed academics within government agencies either as advisers or full staff members. Our commentary argues that, in addition to considering the role of academics in government as proposed by Glied and colleagues, we need to understand better how research and policy interactions function across policy sectors. We believe more comparative research is needed to understand if and why academics from certain disciplines are more likely to be recruited to work in some policy sectors rather than others. We caution against treating government as monolithic by advocating the same model for collaborative interaction between academics and government. Lastly, we contend that contextualized research is needed to illuminate important drivers of research and policy interactions before we can recommend what is likely to be more and less effective in different policy sectors. 相似文献
Due to its chemical complexity, proper quality control for a Chinese medical preparation (CMP) has been a great challenge. Choosing the appropriate quality markers (Q-markers) for quality control of CMP is an important work. Best of all, the chosen Q-markers are the main chemical compounds from the herbals as well as the active constituents of this CMP. Only in this way the established quality control system can really achieve the purpose of controlling the quality of CMP and ensuring the safely and effectively use of CMP. To achieve the purpose, network pharmacology combined with the contents of chemical compounds in the CMP has been used in this research. We took an anti-arrhythmic CMP, Shenxian-Shengmai oral liquid (SSOL), as an example. Firstly, UPLC-QTOF-MS/MS method was used to analyze the main components of SSOL. A total of 64 compounds were unambiguously or tentatively identified and 32 of them were further validated by reference compounds. Secondly, the network was constructed based on the identified compounds to predict the effective compounds related to cardiac arrhythmias. Based on the existing database and the operation method of topology, a method of double network analysis (DNAA) was proposed, from which 10 important targets in the pathway of arrhythmia were screened out, and 26 compounds had good antiarrhythmic activity. Based on the prediction results of network pharmacology along with the contents of the compounds in this CMP, ten representative compounds were chosen as the Q-markers for the quality control of SSOL. We find that five of these ten compounds, including danshensu, rosmarinic acid, salvianolic acid A, epimedin A and icariin, have antiarrhythmic activity. Then, the UPLC-DAD method was established as the control method for SSOL. 相似文献
Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C‐Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model. 相似文献
The effects of airborne particulate matter （PM） trace elements on health are widely concerned nowadays. Many achievements have been made while many unknowns exist. This article reports the recent research progresses, describes the effects of exposure to PM trace elements on health epidemiological evidence, toxicology findings, and raises some questions for future studies. 相似文献
