Neuroblastoma with high ASPM reveals pronounced heterogeneity and poor prognosis.

OBJECTIVE: We explored the preliminary value of abnormal spindle-like microcephaly- associated (ASPM) protein in aiding precise risk sub-stratification, prediction of metabolic heterogeneity, and prognosis of neuroblastoma (NB). METHODS: This retrospective study enrolled newly diagnosed patients with NB who underwent positron emission tomography/computed tomography (PET/CT) before therapy, and tumor tissue was collected after surgery. Regression analysis was used to evaluate ASPM expression and risk stratification in patients with NB. The expression levels of ASPM, clinical information, and PET/CT text features were analyzed using univariate and multivariate survival analyses. Finally, a correlation analysis was used to explore the relationship between ASPM and tumor metabolic heterogeneity. RESULTS: There were 48 patients with NB in this study (35 boys and 13 girls); 22 patients progressed and 16 died. We found that the level of ASPM was highly associated with risk stratification (OR = 5.295, 95%IC: 1.348-41.722, p = 0.021). Patients with NB and high-risk stratification with high ASPM level had a lower 3-year progression-free survival (PFS) rate (14.28%) and 1-year PFS rate (57.14%) than those with low ASPM level (57.14% and 93.75%, respectively). Using univariate and multivariate survival analyses, this study revealed that ASPM and LDH were independent risk factors for both PFS and overall survival (OS), whales GLZLM_ZLNU was only a risk factor for PFS. CONCLUSION: ASPM holds promise as a novel biomarker for refining current risk stratification and predicting prognosis in neuroblastoma. Elevated levels of ASPM, LDH, and GLZLM_ZLNU may be associated with poorer survival outcomes in neuroblastoma patients.

The prognostic role of 18F-FDG PET/CT-based response evaluation in children with stage 4 neuroblastoma.

OBJECTIVES: To evaluate the association between metabolic response on 18F-FDG PET/CT and long-term survival in children with neuroblastoma (NB). METHODS: A total of 39 consecutive children with newly diagnosed stage 4 NB undergoing both 18F-FDG PET/CT imaging at baseline and after chemotherapy were retrospectively analyzed. The associations between metabolic parameters, including SUVmax of the lesion with the most intense 18F-FDG uptake at baseline (SUVb), after chemotherapy (SUVe), and the percentage change between SUVb and SUVe, and long-term survival were evaluated. RESULTS: With a median follow-up of 56 months, 22 patients who had achieved complete resolution on PET (no residual 18F-FDG uptake higher than the surrounding backgrounds) after chemotherapy had superior 5-year overall survival (OS) (73.6% vs. 39.0%, p = 0.044). SUVb > 6.9 indicated significantly poorer 5-year event-free survival (EFS) (12.5% vs. 59.3%, p = 0.005), as did SUVe > 1.2 (18.8% vs. 41.7%, p = 0.041). Children with SUVe > 1.2 had shorter 5-year OS (33.9% vs. 75.0%, p = 0.018). Multivariate analysis identified SUVe > 1.2 as an independent predictor for both EFS [hazard ratio (HR), 3.479, 95% CI, 1.381-8.761, p = 0.008] and OS (HR, 6.948, 95% CI, 1.663-29.025, p = 0.008), while SUVb > 6.9 was a predictor for EFS (HR, 2.889, 95% CI, 1.064-7.842, p = 0.037). Among 11 children with both SUVb > 6.9 and SUVe > 1.2, all experienced disease progression or relapse within 2 years since diagnosis. CONCLUSION: 18F-FDG PET/CT could be of useful to evaluate treatment response in children with stage 4 NB. CLINICAL RELEVANCE STATEMENT: 18F-FDG PET/CT after chemotherapy exhibits prognostic significance in neuroblastoma and holds potential as an alternative imaging modality for response evaluation, especially in cases with metaiodobenzylguanidine-nonavid or persistent avid disease. KEY POINTS: The prognostic value of chemotherapy response on 18F-FDG PET/CT in advanced neuroblastoma is unknown. Higher 18F-FDG uptake after chemotherapy was associated with worse long-term event-free survival and overall survival. 18F-FDG PET/CT after chemotherapy holds prognostic significance in children with stage 4 neuroblastoma.

The Theoretical Lineage and Evolutionary Logic of Research on the Environmental Behavior of Family Firms: A Literature Review.

Family firms research is becoming one of the most important and promising areas for theoretical innovation in management practice. Corporate environmental behavior has attracted widespread academic attention, but the research on the environmental behavior of family firms is obviously insufficient, and the relevant research results are still in a fragmented state. In this paper, we review and summarize the existing research on the environmental behavior of family firms from three aspects: the research dimensions, the influencing factors, and the influencing effects, and try to sort out the theoretical lineage and evolutionary logic of the environmental behavior of family firms. From the existing research results, the research on the influencing factors and effects of family firms' environmental behavior is at the stage of strife, and there is a lack of in-depth and systematic research on the mechanisms affecting the environmental behavior of family firms and the changes of their effects. In the future, we can explore how to apply or integrate multiple theories simultaneously for complementary explanations, so as to provide a reference for the government to formulate targeted policies to stimulate and regulate the environmental behaviors of family firms.

Assessing the impact of land surface temperature on urban net primary productivity increment based on geographically weighted regression model.

Urbanization had a huge impact on the regional ecosystem net primary productivity (NPP). Although the urban heat island (UHI) caused by urbanization has been found to have a certain promoting effect on urban vegetation NPP, the factors on the impact still are not identified. In this study, the impact of urbanization on NPP was divided into direct impact (NPPdir) and indirect impact (NPPind), taking Kunming city as a case study area. Then, the spatial heterogeneity impact of land surface temperature (LST) on NPPind was analyzed based on the geographically weighted regression (GWR) model. The results indicated that NPP, LST, NPPdir and NPPind in 2001, 2009 and 2018 had significant spatial autocorrelation in Kunming based on spatial analytical model. LST had a positive impact on NPPind in the central area of Kunming. The positively correlation areas of LST on NPPind increased by 4.56%, and the NPPind caused by the UHI effect increased by an average of 4.423 gC m-2 from 2009 to 2018. GWR model can reveal significant spatial heterogeneity in the impacts of LST on NPPind. Overall, our findings indicated that LST has a certain role in promoting urban NPP.

A Cross-Species Reactive TIGIT-Blocking Antibody Fc Dependently Confers Potent Antitumor Effects.

The T cell immunoreceptor with Ig and ITIM domains (TIGIT) has been shown to exert inhibitory roles in antitumor immune responses. In this study, we report the development of a human mAb, T4, which recognizes both human and mouse TIGIT and blocks the interaction of TIGIT with its ligand CD155 in both species. The T4 Ab targets the segment connecting F and G strands of TIGIT's extracellular IgV domain, and we show in studies with mouse tumor models that the T4 Ab exerts strong antitumor activity and induces durable immune memory against various tumor types. Mechanistically, we demonstrate that the T4 Ab's antitumor effects are mediated via multiple immunological impacts, including a CD8+ T immune response and Fc-mediated effector functions, through NK cells that cause significant reduction in the frequency of intratumoral T regulatory cells (Tregs). Notably, this Treg reduction apparently activates additional antitumor CD8+ T cell responses, targeting tumor-shared Ags that are normally cryptic or suppressed by Tregs, thus conferring cross-tumor immune memory. Subsequent engineering for Fc variants of the T4 Ab with enhanced Fc-mediated effector functions yielded yet further improvements in antitumor efficacy. Thus, beyond demonstrating the T4 Ab as a promising candidate for the development of cancer immunotherapies, our study illustrates how the therapeutic efficacy of an anti-TIGIT Ab can be improved by enhancing Fc-mediated immune effector functions. Our insights about the multiple mechanisms of action of the T4 Ab and its Fc variants should help in developing new strategies that can realize the full clinical potential of anti-TIGIT Ab therapies.

[Clinical observation on therapeutic effect of three-step acupuncture for the secondary prevention of ischemic cerebral apoplexy].

OBJECTIVE: To observe the therapeutic effect and safety of three-step acupuncture for the secondary prevention of ischemic cerebral apoplexy. METHODS: One hundred and twenty cases of first-episode ischemic cerebral apoplexy were randomly divided into an observation group and a control group according to the visiting sequence, 60 cases in each group. Both groups were treated on the basis of the routine treatment, the observation group was treated with three-step acupuncture combined with oral administration of Aspirin for six months. The threestep acupuncture includs scalp acupuncture, body point acupuncture and rehabilitation training. The control group was treated with oral administration of Aspirin alone. Six-month follow-up was done in two groups. Then the recurrence rate of ischemic cerebral apoplexy, the improvement of neurologic impairment, activity of daily living and TCM symptom scores and the safety of three-step acupuncture between two groups were compared. RESULTS: The recurrence rate was 10.2% (5/49) in observation group, and 16.7% (9/54) in control group. There was no significant difference between two groups (P > 0.05). The observation group was superior to the control group in improving the scores of the neurologic impairment, activity of daily living and TCM symptom (P < 0.01, P < 0.001). There was no severe adverse reaction in two groups except 2 cases of gastrointestinal reaction caused by oral administration of Aspirin in control group. CONCLUSION: Three-step acupuncture has a certain therapeutic effect for both treatment and the secondary prevention of ischemic cerebral apoplexy, and it is one of the safe and effective methods for treating and preventing ischemic cerebral apoplexy in clinic.