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991.
992.

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   
993.
Objectives The aim of this study was to evaluate the reliability and validity of the Chinese version of the Stigma Scale for Chronic Illness (SSCI) in patients with stroke.

Methods In total, 220 patients with stroke were recruited to complete the scale. The reliability of the SSCI was evaluated using internal consistency and test–retest methods. Exploratory factor analysis (EFA) was conducted to identify domains of the SSCI. Convergent validity was determined by analyzing the correlation between SSCI scores, activities of daily living (ADL) and depression.

Results Construct validity was determined by factor analysis, extracting three factors with eigenvalues greater than 1, explaining 30.5%, 25.7%, and 8.5% of the variance, respectively, and accounting for 64.8% of the variance. All items had factor loadings above 0.40. The first factor comprised questions related to ‘self-stigma’ (items 1–13). The second (items 14–22) and third (items 23–24) factors aggregated questions related to ‘enacted stigma’. In terms of convergent validity, the SSCI total scale was moderately correlated to the Barthel Index (BI) and the Self-rating Depression Scale (SDS). Cronbach’s alpha value (internal reliability) for the total SSCI score was 0.949, and the intraclass correlation coefficient value (test-retest reliability) was 0.802.

Discussion The results provide initial evidence that the SSCI is a reliable and validated measure for evaluating stigma in stroke patients in China.  相似文献   

994.
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   
995.
996.
Macao, a special administrative region (SAR) of the People’s Republic of China, is located in southern China and shares the border with mainland China. It is the most densely populated region in the world, with a population of 667400 and a total land area of 32.9 square kilometers in 2019. Since the first case diagnosed on January 22, 2020, there was a total of 45 laboratory-confirmed coronavirus disease 2019 (COVID-19) cases in Macao, of which 43 patients (96%) were imported cases. To date, all patients had been discharged successfully from Centro Hospitalar Conde de São Januário, a designated hospital to manage all COVID-19 patients in Macao. Eventually, no patient died, and no local community outbreak was noted. This opinion review describes the underlying factors that could have contributed to the successful experience in Macao SAR, China, which include the following: (1) Early implementation of containment measures; (2) Large-scale quarantine using hotel rooms to reduce the risk of a local outbreak; and (3) Multidisciplinary co-operation and transparency of information to the public. Although the successful experience in Macao SAR, China, may not be generalized to other regions, it should not be unreasonable to be well prepared with sufficient logistic support to conduct timely containment and early detection of episodic cases to prevent the backsliding of COVID-19 outbreak.  相似文献   
997.
998.
999.
目前新型冠状病毒肺炎疫情防控形势严峻,各级医疗机构在做好新型冠状病毒肺炎防控的同时,还需提供优质安全的常规医疗服务。笔者旨在通过严格患者分类管理以及围术期标准预防,为需行外科治疗的患者,尤其是需行急诊外科治疗的患者提供优质安全的医疗服务,减少院内感染,为新型冠状病毒肺炎防控贡献一份力量。  相似文献   
1000.
目的探讨消毒隔离结合免疫及营养治疗在预防和治疗反复感染手足口病患儿中的作用。 方法收集初次就诊的手足口病患儿共400例,利用随机数字表将患者分为治疗组与对照组各200例,治疗组患儿定期给予消毒隔离健康教育及营养随访,再次患病后给予个体化营养支持治疗。对照组患儿仅在感染手足口病后给予常规治疗。比较两组患儿手足口病再发率和重症率等指标。 结果治疗组患儿平均退热时间为(1.7 ± 1.1)d、皮疹消退时间为(4.0 ± 1.3)d、平均住院天数为(5.6 ± 2.4)d、抗菌药物使用率为19%(38/200)、激素使用率为8%(16/200),均显著低于对照组,差异具有统计学意义(t = 10.028、8.677、8.353、20.650、11.312,P = 0.015、0.032、0.001、0.004、0.011)。治疗组患儿1年内再发率、重症率和并发症发生率分别为12%(24/200)、1%(2/200)和5%(10/200),显著低于对照组患儿,差异均有统计学意义(χ2 = 9.21、0.88、7.24,P = 0.010、0.002、0.007)。 结论健康教育、营养随访及个体化营养支持治疗可降低手足口病的再发率及重症率,改善临床结局。  相似文献   
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