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Purpose@#Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) has become the first-line treatment for advanced renal cell carcinoma, despite the lack of prognostic biomarkers. Cyclin-dependent kinase 5 (CDK5) affects the tumor microenvironment, which may influence the efficacy of TKI+IO. @*Materials and Methods@#Two cohorts from our center (Zhongshan Metastatic Renal Cell Carcinoma [ZS-MRCC] cohort, Zhongshan High-risk Localized Renal Cell Carcinoma [ZS-HRRCC] cohort) and one cohort from a clinical trial (JAVELIN-101) were enrolled. The expression of CDK5 of each sample was determined by RNA sequencing. Immune infiltration and T cell function were evaluated by flow cytometry and immunohistochemistry. Response and progression-free survival (PFS) were set as primary endpoints. @*Results@#Patients of low CDK5 expression showed higher objective response rate (60.0% vs. 23.3%) and longer PFS in both cohorts (ZS-MRCC cohort, p=0.014; JAVELIN-101 cohort, p=0.040). CDK5 expression was enhanced in non-responders (p < 0.05). In the ZS-HRRCC cohort, CDK5 was associated with decreased tumor-infiltrating CD8+ T cells, which was proved by immunohistochemistry (p < 0.05) and flow cytometry (Spearman’s ρ=–0.49, p < 0.001). In the high CDK5 subgroup, CD8+ T cells revealed a dysfunction phenotype with decreased granzyme B, and more regulatory T cells were identified. A predictive score was further constructed by random forest, involving CDK5 and T cell exhaustion features. The RFscore was also validated in both cohorts. By utilizing the model, more patients might be distinguished from the overall cohort. Additionally, only in the low RFscore did TKI+IO outperform TKI monotherapy. @*Conclusion@#High-CDK5 expression was associated with immunosuppression and TKI+IO resistance. RFscore based on CDK5 may be utilized as a biomarker to determine the optimal treatment strategy.
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Objective To investigate the prognostic value of preoperative neutrophil lymphocyte ratio (NLR) in patients with gastrointestinal stromal tumors (GIST).Methods The clinical-pathological data from 85 GIST cases were collected from the Second Affiliated Hospital of Wenzhou Medical University and retrospectively analyzed from June 2009 to December 2013.According to the exclusion criteria,79 cases were enrolled.Preoperative neutrophil and lymphocyte count was collected and NLR was calculated.According to the receiver operating characteristic (ROC) curve of NLR,GIST patients were divided into low NLR group (NLR ＜ 2.30) and high NLR group (NLR ≥ 2.30).Clinic-pathological features and five year disease free survival (DFS) were compared between the two groups.Results There was a statistical significant difference in tumor size and tumor risk between high NLR group and low NLR group (respectively,x2 =9.517,12.411,all P ＜ 0.05).Univariate analysis showed that the five year disease free survival rate of low NLR and high NLR group were 78％ and 32％ (x2 =18.749,P =0.000).By multivariate analysis a high NLR was identified as an independent risk factor of poorer prognosis for patients with GISTs (RR:3.516,95％CI:1.453-8.506,P=0.005).Conclusion A high preoperative NLR is an independent risk factor for the prognosis of GISTs.
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Objective To improve the selection of flying cadets of the Air Force of People′s Liberation Army of China ( PLAAF) by analyzing the differences of medical identification of lumbar spondylolysis between PLAAF and the US Air Force ( USAF) .Methods Flight crew who had been checked for lumbar spondylolysis during hospitalization at the Air Force General Hospital between 2013 and 2015 were chosen.The results of their medical identification were compaired according to PLAAF and USAF Medical Standards Directory, and their differences and possible reasons were analyzed accordingly.Results The qualified rate of PLAAF was about 85%, which was very close to the standards of USAF, but the difference was not of any statistical significance(P>0.05).Conclusion The standards of our medical identification of lumbar spondylolysis was similar to those of USAF, suggesting that the selection of flying cadets can be improved.
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Objective To improve and determine the Medical Standards Directory of the Air Force of People′s Libera-tion Army of China( PLAAF) by analyzing the differences in lumbar spondylolysis and scoliosis between PLAAF and the US Air Force( USAF) .Methods All candidates of flying cadets participating in the final radiographic selection between 2013 and 2015 were chosen.They were judged to be qualified or not according to PLAAF and USAF Medical Standards Directory. Results The average morbility of lumbar spondylolysis and scoliosis in PLAAF was 47%and 30.3%respectively.Arnong those who were eliminated in China,86.0%and 92.5%could be regarded as qualified according to the standard of USAF in 2015.The difference was statistically significant (P<0.01).Conclusion Our selection standards for lumbar spondylol-ysis and scoliosis should be improved based on this study.
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<p><b>OBJECTIVE</b>To determine and analyze plasma ammonia concentration difference of the portal vein system and ramifications of rabbits and consequently guide selection of the portal vein in transjugular intrahepatic portosystemic shunt (TIPS) so that reduce shunt-induced hepatic encephalopathic incidence. To evaluate clinical significance of transjugular intrahepatic left branch of portal vein portosystemic shunt (TILPS) and to analyse hemodynamics of both branches of the portal vein and to observe long-term results in the prevention of encephalopathy.</p><p><b>METHODS</b>Blood samples in different portal vein branches of rabbits were collected and the plasma ammonia concentration was assayed and compared. The left branch of portal vein was used as the puncture site to perform TILPS and to keep away from the right branch of portal vein blood that contains nutrition and toxin.</p><p><b>RESULTS</b>Plasma ammonia content was superior in the mesenteric vein and higher than the portal vein branch, the splenic vein, and the vena cava. The right portal vein was above the left. Encephalopathy did not occur in all patients within 3 months. Of the 341 patients undergoing TILPS, encephalopathy occurred in only 5 patients (1.47%) and shunt abnormalities in 19 patients (5.57%) verified by venography during overall follow-up period.</p><p><b>CONCLUSIONS</b>Selective left branch of the portal vein portosystemic shunt can decrease encephalopathy obviously and protect liver function.</p>
Subject(s)
Adult , Aged , Animals , Female , Humans , Male , Middle Aged , Rabbits , Ammonia , Blood , Follow-Up Studies , Hepatic Encephalopathy , Blood , Portal Vein , General Surgery , Portasystemic Shunt, Transjugular Intrahepatic , Treatment OutcomeABSTRACT
Purpose:To assess the security and efficacy of mechanical recanalization and stenting of lilac arteries with complete occlusions without preceding thrombolytic therapy. Materials and methods:During a 3-year period,Eighteen consecutive patients underwent mechanical reeanalization and stenting for complete occlusion of the iliac artery.The method involved recanalizition with a guide wire and a catheter advanced as a while unit through the occluded segment(snowplow technique).Results The occluded segments were successfully traversed and dilated and 32 stents were placed in 18 patients.The mean ankle-brachial index (BAI)increased from 0.39?0.33 before the procedure to 0.86?0.13 after the procedure(P