Although previous studies suggest that myeloid zinc-finger 1 (MZF-1) is a multifaceted transcription factor that may function as either an oncogene or a tumor suppressor, the molecular bases determining its different traits remain elusive. Increasing evidence suggests that disorders in iron metabolism affect tumorigenesis and tumor behaviors, and that excess tumor iron stimulates tumor progression through various mechanisms such as enhancing DNA replication and energy metabolism. Ferroportin (FPN) is the only known iron exporter in mammalian cells, and it determines global iron egress out of cells. FPN reduction leads to decreased iron efflux and increased intracellular iron that consequentially aggravates the oncogenic effects of iron. MZF-1 was recently identified as a transcription factor that regulates FPN expression. Thus far, however, the molecular mechanisms underlying the MZF-1-FPN signaling in cancers are largely unknown. Here, we found a significant reduction of FPN levels in prostate tumors relative to adjacent tissues, and demonstrated a crucial role of FPN in tumor growth through controlling tumor iron concentration. Inhibition of MZF-1 expression led to reduced FPN concentration, coupled with resultant intracellular iron retention, increased iron-related cellular activities and enhanced tumor cell growth. In contrast, increase of MZF-1 expression restrained tumor cell growth by promoting FPN-driven iron egress. Importantly, we demonstrated that AP4 and c-Myb jointly modulated MZF-1 transcription, and that miR-492 was also directly involved in regulating MZF-1 concentration through binding to the 3' untranslated regions of its mRNA. These results correlate with reduced AP4 and c-Myb expression and elevated miR-492 expression found in prostate tumors as compared with adjacent tissues that resulted in diminished MZF-1 and FPN. Moreover, we demonstrated that alterations of AP4, c-Myb and miR-492 levels significantly affected tumor cell growth. Targeting molecules within the MZF-1-FPN signaling thus appears to be a promising approach to restrain prostate cancer.

Background:In patients with hepatocellular carcinoma (HCC), the prognostic role of tumor-infiltrating lymphocytes (TILs) for survival is still controversial. A meta-analysis was performed to investigate the prognostic effect of TILs in HCC.Methods:We identify studies from PubMed, Embase, and the Cochrane Library to evaluate the prognostic value of TILs in patients with HCC. A meta-analysis was conducted to estimate overall survival and disease-free survival. The hazard ratio (HR) and 95% confidence interval (CI) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials.Results:A total of 7905 patients from 46 observational studies were enrolled. For TILs subsets, the density of CD8+, FOXP3+, CD3+, and Granzyme B+ lymphocytes was significantly associated with improved survival (P < .05). The density of FOXP3+ TILs in intratumor (IT) was the most significant prognostic marker (pooled HR = 1.894; 95% CI = 1.659–2.164; P < .001). Patients with high infiltration of CD8+ TILs in IT (pooled HR = 0.676; 95% CI = 0.540–0.845; P = .001) or in margin of tumor (MT) (pooled HR = 0.577; 95% CI = 0.437–0.760; P < .001) had better OS. The pooled analysis revealed that high density of Granzyme B+ T-lymphocytes in IT was statistically significant associated with better OS (pooled HR = 0.621; 95% CI = 0.516–0.748; P < .001) and DFS (pooled HR = 0.678; 95% CI = 0.563–0.815; P < .001). It was interesting that high density of CD3+ in IT foreboded worse OS (pooled HR = 1.008; 95% CI = 1.000–1.015; P = .037), but better DFS (pooled HR = 0.596; 95% CI = 0.374–0.948; P = .029).Conclusion:Our findings suggested that some TIL subsets could serve as prognostic biomarkers in HCC. High-quality randomized controlled trials are needed to determine if these TILs could serve as targets for immunotherapy in HCC.

As the coronavirus disease 2019 pandemic causes a general concern regarding the overall mental health of employees worldwide, policymakers across nations are taking precautions for curtailing and scaling down dispersion of the coronavirus. In this study, we conceptualized a framework capturing recurring troublesome elements of mental states such as depression and general anxiety, assessing them by applying standard clinical inventory. The study explores the extent to which danger control and fear control under the Extended Parallel Processing Model (EPPM) threat impact job insecurity, with uncertainty phenomenon causing afflicting effect on the experiential nature of depression heightened by anxiety. With the aim to explore the job insecurity relationship with anxiety and depression, and measure the impact of EPPM threat, an empirical study was conducted in the United States on a sample of 347 white collar employees. Demographic data, EPPM threat, job insecurity, anxiety, and depression data were collected via a standardized questionnaire during the coronavirus disease 2019 (COVID-19) pandemic. The questionnaire consisting of multi-item scales was distributed online. All the scale items were evaluated on a 5-point Likert scale. SEM software AMOS version 23 was used to perform confirmatory factor analysis with maximum likelihood estimation. In the structural model, relationships between the threat of COVID-19, job insecurity, anxiety, and depression were assessed. The findings of the study suggest that job insecurity has a significant impact on depression and anxiety, whereas the threat of COVID-19 has a significant impact on depression. Mediating effects of job insecurity and EPPM threat impact on anxiety were not established in the study. The study contributes to the apprehension of the repercussions of major environmental disruptions on normal human functioning, and it investigates the effects of self-reported protective behaviors on risk perception. The study also explains the underlying mechanisms of coping behavior as possible antecedents to mental disorders. When subjected to stressful events, heightened psychological arousal causes physical and psychological challenges of affected employees to manifest as behavioral issues.

ObjectivePituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Due to the rarity of PSIS, clinical data are limited, especially in Chinese people. Herein, we analyzed the clinical characteristics of patients diagnosed with PSIS from our center over 10 years.Patients and MethodsWe retrospectively analyzed the clinical manifestations and laboratory and MRI findings in 55 patients with PSIS.ResultsOf the 55 patients with PSIS, 48 (87.3%) were male. The average age was 19.7±6.7 years and there was no familial case. A history of breech delivery was documented in 40 of 45 patients (88.9%) and 19 of 55 patients (34.5%) had a history of dystocia. Short stature was found in 47 of 55 patients (85.5%) and bone age delayed 7.26±5.37 years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone, gonadotropins, corticotropin, and thyrotropin were 100%, 95.8%, 81.8%, 76.3%, respectively. Hyperprolactinemia was found in 36.4% of patients. Three or more pituitary hormone deficiencies were found in 92.7% of the patients. All patients had normal posterior pituitary function and absent pituitary stalk on imaging. The average height of anterior pituitary was 28 mm, documented anterior pituitary hypoplasia. Midline abnormalities were presented in 9.1% of patients.ConclusionsThe clinical features of our Chinese PSIS patients seem to be different from other reported patients in regarding to the higher degree of hypopituitarism and lower prevalence of midline defects. In addition, our patients were older at the time of case detection and the bone age was markedly delayed. We also had no cases of familial PSIS.

Background:In patients with hepatocellular carcinoma (HCC), the clinicopathologic and prognostic roles of tumor-infiltrating CD8+ T cells for survival are still controversial. A meta-analysis was performed to resolve this issue.Methods:We identified studies from PubMed, Embase, and the Cochrane Library to evaluate the clinicopathologic and prognostic value of tumor-infiltrating CD8+ T cells in patients with HCC. A meta-analysis was conducted to estimate clinicopathologic characteristics, overall survival (OS), and disease-free survival. The hazard ratio (HR) and 95% confidence interval (CI) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials.Results:A total of 3509 patients from 21 observational studies were enrolled. The meta-analysis revealed that high levels of intratumoral CD8+ tumor-infiltrating lymphocytes (TILs) were associated with better OS (OS; HR = 0.676, P = .001) and disease-free survival (disease-free survival [DFS]; HR = 0.712, P = .002). The pooled analysis also demonstrated high density of infiltration of CD8+ TILs in margin of tumor (MT) was statistically significant associated with better OS (HR = 0.577; P <.001). Moreover, the patients with low CD8+ TILs infiltration had negative HBSAg (OR = 1.67, P = .02), large tumor size (OR = 1.74, P <.01), and later TNM stage (OR = 1.70, P <.01).Conclusions:Our findings suggested that low levels of CD8+ TILs predict large tumor size, later TNM stage and might be a promising prognostic factor of HCC especially for Asian patients. High-quality randomized controlled trials are needed to determine if CD8+ TILs could serve as targets for immunotherapy in hepatocellular carcinoma.