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Qiang Fu Le Xu Yiwei Wang Qi Jiang Zheng Liu Junyu Zhang Quan Zhou Han Zeng Shanyou Tong Tao Wang Yangyang Qi Baoying Hu Hangcheng Fu Huyang Xie Lin Zhou Yuan Chang Yu Zhu Bo Dai Jiejie Xu 《European urology》2019,75(5):752-763
Background
Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.Objective
To seek a potential therapeutic target in glutamine-addicted ccRCC.Design, setting, and participants
Tumors from ccRCC patients from a Shanghai cohort and ccRCC tumor data from The Cancer Genome Atlas (TCGA) cohort were analyzed. In vivo and in vitro studies were conducted with fresh human ccRCC tumors and murine tumor cells.Outcome measurements and statistical analysis
Immune cell numbers and functions were analyzed by flow cytometry. Glutamine and cytokine concentrations were determined. Survival was compared between different subpopulations of patients using Kaplan-Meier and Cox regression analyses.Results and limitations
We found that in ccRCC, high interleukin (IL)-23 expression was significantly associated with poor survival in both TCGA (overall survival [OS] hazard ratio [HR] = 2.04, cancer-specific survival [CSS] HR = 2.95; all p < 0.001) and Shanghai (OS HR = 2.07, CSS HR = 3.92; all p < 0.001) cohorts. IL-23 blockade prolongs the survival of tumor-bearing mice, promotes T-cell cytotoxicity in in vitro cultures of human ccRCC tumors, and augments the therapeutic benefits of anti-PD-1 antibodies. Mechanistically, glutamine consumption by ccRCC tumor cells results in the local deprivation of extracellular glutamine, which induces IL-23 secretion by tumor-infiltrating macrophages via the activation of hypoxia-inducible factor 1α (HIF1α). IL-23 activates regulatory T-cell proliferation and promotes IL-10 and transforming growth factor β expression, thereby suppressing tumor cell killing by cytotoxic lymphocytes. The positive correlations between glutamine metabolism, IL-23 levels, and Treg responses are confirmed in both TCGA cohort and tumors from Shanghai ccRCC patients. Study limitations include the unclear impacts of glutamine deprivation and IL-23 on other immune cells.Conclusions
Macrophage-secreted IL-23 enhanced Treg functions in glutamine-addicted tumors; thus, IL-23 is a promising target for immunotherapy in ccRCC.Patient summary
In this study, we analyzed the immune components in glutamine-addicted clear cell renal cell carcinoma (ccRCC) tumors from two patient cohorts and conducted both in vitro and in vivo studies. We found that ccRCC tumor cell-intrinsic glutamine metabolism orchestrates immune evasion via interleukin (IL)-23, and IL-23–high patients had significantly poorer survival than IL-23–low patients. IL-23 should thus be considered a therapeutic target in ccRCC, either alone or in combination with immune checkpoint inhibitors. 相似文献996.
Binghu Jiang Dongmei He Liwen Zhang Min Ye 《Journal of neuroradiology. Journal de neuroradiologie》2019,46(2):117-123
Background and purpose
It is not conclusive that magnetic resonance (MR)-based carotid atherosclerotic plaque assessment identifies high-risk features associated with cerebrovascular events. We aimed to systematically summarize the association of MR imaging (MRI)-determined intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and thinning/rupture of the fibrous cap (TRFC) with subsequent ischemic events.Materials and methods
We performed a comprehensive literature search evaluating the association of MRI-based carotid plaque composition with ischemic outcomes. We included cohort studies examining IPH, LRNC, or TRFC with mean follow-up of ≥ 6 months and an outcome measure of ipsilateral ischemic events. A meta-analysis was done according to the Cochrane guideline.Results
We identified 13 studies including 1.150 patients and 1.208 analyzed carotid arteries, with mean follow-up of 21.1 months. The hazard ratios (HR) for IPH, LRNC, and TRFC as predictors of subsequent ischemic events were 4.41 (95% CI: 2.87, 6.79), 3.00 (95% CI: 1.51, 5.95), and 5.94 (95% CI: 2.66, 13.28), respectively. The predictive value of carotid plaque MRI for ischemic events was acceptable, with sensitivity of 0.80 (95% CI: 0.66, 0.90) and specificity of 0.63 (95% CI: 0.57, 0.68). However, it was limited to confirm or exclude future ischemic events in clinical context, with positive likelihood ratio (LR) of 2.2 (95% CI: 1.9, 2.5) and negative LR of 0.31 (95% CI: 0.18, 0.55). No statistically significant heterogeneity or publication bias was observed.Conclusion
The presence of IPH, LRNC, and TRFC determined by MRI is associated with increased risk of future ischemic events, but its predictive value is moderate and should not be used for confirmation or exclusion of future ischemic events in clinical context. 相似文献997.
Payam Sajedi Lydia Chelala Joel Nunez-Gonalez Carolyn Cronin Steven Kittner Jiachen Zhuo Yang Zhang Dheeraj Gandhi Prashant Raghavan 《Journal of neuroradiology. Journal de neuroradiologie》2019,46(2):136-140
Background and purpose
Carotid webs are intraluminal filling defects at the carotid bulb which are considered rare, though possibly underappreciated entities with recent studies demonstrating a likely casual association with ischemic stroke. The purpose of the study is to describe our recent experience with clinical and imaging manifestations of carotid webs.Materials and methods
A retrospective review of CTA neck studies in all adult patients presenting to our institution during the 19-month study interval was performed to determine the presence of carotid webs. Subsequent chart review of these patients with webs was performed to assess their clinical history and to obtain demographic detail.Results
A total of 14 patients were identified with carotid webs in the study population. The mean age of patients with webs was 42.1?years (range: 28–54), consisting mostly of African Americans (86%) and females (64%). Ten (71%) of web patients had a history of ischemic stroke, each ipsilateral to the side of web, and at least four of these patients had recurrent ischemic stroke.Conclusion
We provide one of the largest sample sizes of webs gathered in a single study. Given its association with ischemic stroke, carotid webs should be assessed for in all patients presenting with ischemic stroke, especially younger African Americans. 相似文献998.
Jiantao Li Lin Han Hao Zhang Zhe Zhao Xiuyun Su Jianfeng Zhou Chen Li Peng Yin Ming Hao Kun Wang Gaoxiang Xu Lihai Zhang Licheng Zhang Peifu Tang 《Injury》2019,50(3):648-656
Objectives
Using finite element analysis and biomechanical tests, the biomechanical behaviors of Medial Sustainable Nail (MSN) and Proximal Femoral Nail Antirotation (PFNA) were compared for the fixation of fracture type of AO/OTA 31-A2.3.Methods
Finite element software Abaqus 6.14 was used to conduct axial loading of 2100?N and we analyzed the von Mises stress distribution and the model displacement of two implant models. Biomechanical tests were separately conducted in the axial stiffness test and axial cyclical loading test on a mechanical testing machine.Results
The results indicate that von Mises stress of MSN was lower than that of PFNA, and the model displacement in the MSN group was lower than that in the PFNA group. In the axial stiffness tests, MSN group was stiffer than PFNA construct. With respect to the axial load to ultimate failure, the PFNA construct exhibited higher loads exceeding 4000?N while the MSN construct withstood 3313.8?±?92.8?N. Specifically, F10mm was 2178.6?±?133.2?N of the MSN group and 1822.6?±?93.1?N of the PFNA group (P?=?0.001). Additionally, X2100N was 9.8?±?0.5?mm of the MSN group and 11.7?±?0.7?mm of the PFNA group (P?=?0.002). The MSN group exhibited superior performances in terms of the mean value of the vertical displacement, frontal rotation angle, and lateral rotation angle.Conclusions
The results indicated that the MSN construct might exhibit a better biomechanical performance when compared with that of the PFNA in reducing displacement and anti-varus in fracture type of AO/OTA 31-A2.3. 相似文献999.
Zhang Di Tang Xiaojing Gao Yuan Yu Hongjing Wen Bin Fu Lili Song Shuwei Mei Changlin 《中华肾脏病杂志》2019,35(4):288-294
Objective To screen Oxalobacter formigenes (OxF) from fresh feces of healthy adults, and study its effect on the the prevention of calcium oxalate kidney stones. Methods OxF was screened and cultured from fresh feces of healthy adults. The rat model of calcium oxalate stone was established by esophageal gavage of 0.8% of ethylene glycol. Rats were divided into a control group and four groups of rats with ethylene glycol-induced calcium oxalate kidney stones according to random number table. Three groups were treated with 106 CFU, 107 CFU, 108 CFU viable OxF every day, respectively, for 4 weeks. The blood and 24-hour urine samples were collected to detect the serum creatinine, urea nitrogen, serum and urine calcium, phosphorus, magnesium and urine oxalate every week. At the end of the 4th week, the rats were sacrificed and the kidney tissues were stained with HE and Yasue. The deposition and content of calcium oxalate crystals were observed under a light microscope. Results The bacteria strain isolated from fresh feces of healthy adults was 100% as same as the known ATCC35274 bacteria strain, which means the strain screened is OxF. Among the 5 groups, there were no significant differences in body weight, Scr, BUN, serum calcium, blood magnesium, blood phosphorus, urinary magnesium and urinary phosphorus. The 24-hour urinary calcium excretion in the model group was significantly lower than that of the control group (P<0.05). After intervention with OxF solution, the 24-hour urinary calcium excretion in the 108 CFU OxF group was significantly higher than that in the model group (P<0.05), while there was no significant difference between the other intervention groups and the model. The oxalic acid excretion of 106 CFU OxF group and 107 CFU OxF group was lower than that of the model, but the difference did not reach statistical significance (P>0.05). The 24 h oxalic acid excretion in the 108 CFU OxF group was significantly lower than that of the model at the end of first week (P<0.05), and continued to decrease for the next 3 weeks. After 4 weeks of intervention, no crystal formation was observed in the control group under the deflection microscope, but a large amount of calcium oxalate crystals were formed in the renal cortex and renal medulla. The crystals were piled up and connected to each other. Yasue staining coincided with the calcium oxalate crystal in the same part of the kidneys. Compared with the model, there was no significant change in the score of calcium oxalate crystal in the kidneys of 106 CFU OxF group and 107 CFU OxF group, while the score of calcium oxalate crystal in the kidneys of 108 CFU OxF group was significantly lower (P<0.05). Conclusions OxF are successively screened from healthy adults. Daily administration of 108 CFU OxF can safely and effectively reduce the urinary oxalic acid excretion, prevent the formation of calcium oxalate crystals and inhibit the formation of stones in kidneys of rats. 相似文献
1000.
Zhang Sufeng Wu Buyun Yan Wenyan Liu Kang Xu Xueqiang Yu Xiangbao Zhu Yamei Xu Xianrong Xing Changying Mao Huijuan 《中华肾脏病杂志》2019,35(7):507-514
Objective To investigate the predictive value of nutritional and fluid status measured by bioelectrical impedance methods for the prognosis of acute kidney injury (AKI) patients undergoing continuous renal replacement therapy (CRRT). Methods Patients with severe AKI received CRRT in the First Affiliated Hospital of Nanjing Medical University from September 2016 to September 2018 were enrolled, and divided into death group and survival group according to 28-day survival. Cox regression was used to analyze the association between 28-day survival and lean tissue index (LTI), fat tissue index (FTI), the ratio of extracellular water (ECW) and body cell mass (BCM) (ECW/BCM), and overhydration (OH), respectively. Results A total of 156 patients were included, including 101 males and 55 females. The age was (62.7±15.4) years, with sequential organ failure assessment (SOFA) score of 9.9±3.9. The 28-day mortality rate was 46.2%. The pre-CRRT OH values in the 28-day survival group and death group were 2.95(1.80, 5.50) L and 4.20(2.95, 5.70) L(P=0.016), and ECW/BCM values were 1.00(0.76, 1.18) and 1.07(0.88, 1.25) (P=0.033), respectively. Univariate Cox regression analysis showed that pre-CRRT high OH values (HR=1.08, 95%CI 1.00-1.17, P=0.040) and high ECW/BCM values (HR=3.02, 95%CI 1.46-6.22, P=0.003) were associated with 28-day death. The changes of OH values (HR=0.83, 95%CI 0.72-0.95, P=0.008) and ECW/BCM values (HR=6.79, 95%CI 1.72-26.82, P=0.006) between pre-CRRT and the 7th day after CRRT initiation were significantly associated with 28-day mortality in patients who survived 7 days after CRRT initiation. After adjusting for age, gender, and SOFA scores, multivariate Cox regression analysis showed that the high OH value (HR=1.16, 95%CI 1.06-1.27, P=0.002) and the high ECW/BCM value (HR=2.80, 95%CI 1.30-6.06, P=0.003) before CRRT, the change of OH value (HR=0.82, 95%CI 0.72-0.95, P=0.008) and ECW/BCM value (HR=2.79, 95%CI 1.30-5.98, P=0.009) between the 7th day after CRRT initiation and pre-CRRT, were independently associated with 28-day death, while LTI (HR=0.93, 95%CI 0.86-1.02, P=0.113) and FTI (HR=0.98, 95%CI 0.92-1.04, P=0.475) before CRRT were uncorrelated with 28-day death. Conclusions In bioelectrical impedance analysis, the high OH value and high ECW/BCM value before CRRT are associated with 28-day mortality in patients with AKI, while the nutritional indicators LTI and FTI before CRRT are not significantly related. The correction of fluid overload by CRRT within 7 days may reduce the risk of 28-day mortality. 相似文献