A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma

Background: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumor derived from the adrenal cortex. Because of its highly aggressive nature, the prognosis of patients with adrenocortical carcinoma is not impressive. Hypoxia exists in the vast majority of solid tumors and contributes to invasion, metastasis, and drug resistance. This study aimed to reveal the role of hypoxia in Adrenocortical carcinoma and develop a hypoxia risk score (HRS) for Adrenocortical carcinoma prognostic prediction.Methods: Hypoxia-related genes were obtained from the Molecular Signatures Database. The training cohorts of patients with adrenocortical carcinoma were downloaded from The Cancer Genome Atlas, while another three validation cohorts with comprehensive survival data were collected from the Gene Expression Omnibus. In addition, we constructed a hypoxia classifier using a random survival forest model. Moreover, we explored the relationship between the hypoxia risk score and immunophenotype in adrenocortical carcinoma to evaluate the efficacy of immune check inhibitors (ICI) therapy and prognosis of patients.Results: HRS and tumor stage were identified as independent prognostic factors. HRS was negatively correlated with immune cycle activity, immune cell infiltration, and the T cell inflammatory score. Therefore, we considered the low hypoxia risk score group as the inflammatory immunophenotype, whereas the high HRS group was a non-inflammatory immunophenotype. In addition, the HRS was negatively related to the expression of common immune checkpoint molecules such as PD-L1, CD200, CTLA-4, and TIGIT, suggesting that patients with a lower hypoxia risk score respond better to immunotherapy.Conclusion: We developed and validated a novel hypoxia risk score to predict the immunophenotype and response of patients with adrenocortical carcinoma to immune check inhibitors therapy. These findings not only provide fresh prognostic indicators for adrenocortical carcinoma but also offer several promising treatment targets for this disease

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial

Background: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792. Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial (vol 26, 46, 2022)

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Advances in the study of the correlation between vitamin D-24-hydroxylase and thyroid carcinoma

Thyroid carcinoma(TC) is the most common malignant tumor of endocrine system. Patients with vitamin D deficiency have an increased risk of TC. Vitamin D-24-hydroxylase (CYP24A1) is main inactivating enzyme of active vitamin D which may inhibit the antiproliferative effect of vitamin D and promote the development of TC by inactivating 1,25-dihydroxyvitamin D3

Characterizing the Mechanism of Serotonin Alleviates Rice Resistance to Brown Planthopper <i>Nilaparvata lugens</i> (Homoptera: Delphacidae) Nymphs

Serotonin is a well-known secondary metabolite that plays an important role in many growth and developmental processes, as well as biotic and abiotic stress responses of plants. Yet, whether serotonin biosynthesis regulates the resistance of rice to the brown planthopper (BPH) Nilaparvata lugens and its underling mechanisms have not been entirely investigated. In this study, we found that expression levels of four serotonin biosynthesis gene, OsTDC1, OsTDC2, OsTDC3, and OsT5H, and the serotonin content were significantly induced by BPH nymph infestation. The rice seedlings pretreated with serotonin were more attractive to BPH nymphs and promoted their feeding behavior as indicated by increased honeydew excretion. In addition, serotonin application to artificial diets increased the survival rates of BPH nymphs in a dose-dependent manner compared to the controls. Moreover, the exogenous serotonin application to rice seedlings increased the average injury scale and functional plant loss indices caused by BPH nymph infestation. Moreover, supplemented serotonin enhanced soluble sugar and free amino acid contents, as well as the activities of SOD, POD, and PPO, but repressed the production of flavonoids. Our findings illustrated that serotonin plays a negative role in the regulation of rice resistance to BPH nymphs probably by modulating contents of soluble sugars, free amino acids, and flavonoids

Prediction of silicon-based room temperature quantum spin Hall insulator via orbital mixing

The search for realistic materials capable of supporting the room temperature quantum spin Hall (QSH) effect remains a challenge, especially when compatibility with the current electronics industry is required. We report a theoretical prediction to identify halogenated silicon films as excellent candidates, which demonstrate high stability, flexibility, and tunable spin-orbit coupling (SOC) gaps up to ∼0.5 eV under minimal strain below 3%. The extraordinary SOC strength is mainly contributed by the p-orbital of heavy halogen atoms hybridized with the px,y-orbitals of Si scaffold, and thus can be easily manipulated by strain (being ∼100 times more effective than in silicene) or substrate. Not only the instability problem of silicene for real applications is solved, but also it provides a new strategy to drastically enhance SOC of light-element scaffolds by orbital hybridization. The silicon-based QSH insulator is most promising for developing next-generation, low-power consumption nanoelectronics and spintronics at ambient conditions