Objectives: The coronavirus disease (COVID-19) pandemic has caused a large number of deaths. Some patients with severe or critical COVID-19 have been observed to have elevated bilirubin levels. Studies on the association of bilirubin level and mortality in patients with COVID-19 are limited. This study aimed to examine the role of bilirubin levels in COVID-19 severity and mortality. Methods: A retrospective cohort study was conducted in patients hospitalized with COVID-19 in Leishenshan Hospital in Wuhan, China. Cox regression analyses and logistic regression analyses were conducted to investigate the risks for mortality and disease severity, respectively. Kaplan–Meier analyses with log-rank tests were performed to assess the association between bilirubin level and survival. Results: In total, 1,788 patients with COVID-19 were included in the analysis. 5.8% (4/69) of patients in the elevated serum total bilirubin (STB) group died, compared to 0.6% (11/1,719) of patients in the non-elevated STB group. The median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the elevated STB group were 29 U/L [interquartile range (IQR): 16–45 U/L] and 22 U/L (IQR: 13–37 U /L), respectively, which were significantly higher than the median ALT (median: 23, IQR: 15–37) and AST (median: 20, IQR: 16–26) activities in the non-elevated STB group (both p < 0.05). Patients with an elevated STB level showed increased mortality [hazard ratio (HR): 9.45, P = 0.002], elevated conjugated bilirubin (CB) levels (HR: 4.38, P = 0.03), and an elevated ratio of CB to unconjugated bilirubin (UCB, CB/UCB) (HR: 2.49, P = 0.01). CB/UCB was positively correlated with disease severity (odds ratio: 2.21, P = 0.01). Conclusions: COVID-19 patients with elevated STB and CB levels had a higher mortality, and CB/UCB was predictive of disease severity and mortality. Thus, it is necessary to pay special attention to COVID-19 patients with elevated bilirubin levels in clinical management.

As hyperprolactinemia is observed in patients with bromocriptine‑resistant prolactinoma, prolactin (PRL) has been implicated in the development of bromocriptine resistance. Since PRL primarily mediates cell survival and drug resistance via the Janus kinase‑2 (JAK2)/signal transducer and activator of transcription 5A (STAT5) signaling pathway, the STAT5 inhibitor, pimozide, may inhibit cell proliferation and reverse bromocriptine resistance in prolactinoma cells. In the present study, compared with bromocriptine or pimozide alone, the combination of pimozide and bromocriptine exerted enhanced reduction in cell growth and proliferation, and increased apoptosis and cell cycle arrest in bromocriptine‑resistant prolactinoma cells. A reduction in phospho‑STAT5, cyclin D1 and B‑cell lymphoma extra‑large (Bcl‑xL) expression levels were observed in cells treated with the combination of drugs. In addition, pimozide suppressed spheroid formation of human pituitary adenoma stem‑like cells, and reduced the protein expression of the cancer stem cell markers, CD133 and nestin. Pimozide did not exert any additional antitumor activity in STAT5‑knockdown primary culture cells of human bromocriptine‑resistant prolactinomas. Furthermore, Pimozide combined with bromocriptine treatment significantly reduced human prolactinoma xenograft growth. Western blot and immunohistochemical analyses also demonstrated significant inhibition of cell proliferation and stem cell marker proteins in vivo. Collectively, these data indicated that pimozide treatment reduced prolactinoma growth by targeting both proliferating cells and stem cells, at least in part, by inhibiting the STAT5/Bcl‑xL and STAT5/cyclin D1 signaling pathways.

Recent studies have reported that gene amplified in squamous cell carcinoma 1 (GASC1) is involved in the progression of several types of cancer. However, whether GASC1 promotes glioma progression remains unknown. Therefore, the present study aimed to investigate the effect of GASC1 exposure on glioma tumorigenesis. The western blot demonstrated that grade III and IV glioma tissues exhibited a higher mRNA and protein expression of GASC1. Moreover, CD133+ U87 or U251 cells from magnetic cell separation exhibited a higher GASC1 expression. Invasion Transwell assay, clonogenic assay and wound healing assay have shown that GASC1 inhibition using a pharmacological inhibitor and specific short hairpin (sh)RNA suppressed the invasive, migratory and tumorsphere forming abilities of primary culture human glioma cells. Furthermore, GASC1‑knockdown decreased notch receptor (Notch) responsive protein hes family bHLH transcription factor 1 (Hes1) signaling. GASC1 inhibition reduced notch receptor 1 (NOTCH1) expression, and a NOTCH1 inhibitor enhanced the effects of GASC1 inhibition on the CD133+ U87 or U251 cell tumorsphere forming ability, while NOTCH1 overexpression abrogated these effects. In addition, the GASC1 inhibitor caffeic acid and/or the NOTCH1 inhibitor DAPT (a γ‑Secretase Inhibitor), efficiently suppressed the human glioma xenograft tumors. Thus, the present results demonstrated the importance of GASC1 in the progression of glioma and identified that GASC1 promotes glioma progression, at least in part, by enhancing NOTCH signaling, suggesting that GASC1/NOTCH1 signaling may be a potential therapeutic target for glioma treatment.

Objective: This study aims to identify the predictors of postoperative hydrocephalus in patients with posterior fossa tumors (PFTs) and guide the management of perioperative hydrocephalus.Methods: We performed a single-institution, retrospective analysis of patients who underwent resection of PFTs in our department over a 10-year period (2011–2021). A total of 682 adult patients met the inclusion criteria and were divided into either a prophylactic external ventricular drainage (EVD) group or a nonprophylactic-EVD group. We analyzed data for the nonprophylactic-EVD group by univariate and multivariate analyses to identify predictors of postoperative acute hydrocephalus. We also analyzed all cases by univariate and multivariate analyses to determine the predictors of postoperative ventriculoperitoneal (VP) shunt placement.Results: Tumor infiltrating the midbrain aqueduct [P = 0.001; odds ratio (OR) = 9.8], postoperative hemorrhage (P < 0.001; OR = 66.7), and subtotal resection (P = 0.006; OR = 9.3) were independent risk factors for postoperative EVD. Tumor infiltrating the ventricular system (P < 0.001; OR = 58.5) and postoperative hemorrhage (P < 0.001; OR = 28.1) were independent risk factors for postoperative VP shunt placement.Conclusions: These findings may help promote more aggressive monitoring and earlier interventions for postoperative hydrocephalus in patients with PFTs.

Intracranial aneurysms (IAs) are benign cerebrovascular maladies characterized by wall dilatation in the intracranial arteries. Nevertheless, spontaneous aneurysmal rupture can cause a life-threatening spontaneous subarachnoid hemorrhage (SAH). Emerging evidence indicates potential associations between gut dysbiosis and IAs pathogenesis, though the relationship with IA rupture remains unclear. This research analyzed 124 fecal samples for microbiomics and 160 for metabolomics, with the discovery and validation sets established for cross-validation. We identified differential gut microbiota and metabolites associated with ruptured intracranial aneurysms (RIAs) and developed a superior risk assessment model. Subsequent integrative analyses and validation revealed a significant link between disrupted unsaturated fatty acid and essential amino acid metabolic pathways and IA rupture, driven by alterations in gut microbiota. This study underscores the potential association between the gut-brain axis and IA rupture, while also highlighting gut microbiota dysbiosis as a potential risk factor for IA rupture and providing biomarkers for assessment.