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Background: Early neurological deterioration, a common complication in patients with intracerebral hemorrhage, is associated with poor outcomes. Despite the fact that the prevalence and predictors of early neurological impairment are widely addressed, few studies have consolidated these findings. This study aimed to systematically investigate the prevalence and predictors of early neurological deterioration. Methods: The PubMed, Embase, Cochrane Library, CIHNAL, and Web of Science databases were systematically searched for relevant studies from the inception to December 2023. The data were extracted using a predefined worksheet. Quality assessment was conducted using the Newcastle–Ottawa Scale. Two reviewers independently performed the study selection, data extraction, and quality appraisal. The pooled effect size and 95% confidence intervals were calculated using the STATA 17.0 software package. Results: In total, 32 studies and 5,014 patients were included in this meta-analysis. The prevalence of early neurological deterioration was 23% (95% CI 21–26%, p < 0.01). The initial NIHSS score (OR = 1.24, 95% CI 1.17, 1.30, p < 0.01), hematoma volume (OR = 1.07, 95% CI 1.06, 1.09, p < 0.01), intraventricular hemorrhage (OR = 3.50, 95% CI 1.64, 7.47, p < 0.01), intraventricular extension (OR = 3.95, 95% CI 1.96, 7.99, p < 0.01), hematoma expansion (OR = 9.77, 95% CI 4.43, 17.40, p < 0.01), and computed tomographic angiography spot sign (OR = 5.77, 95% CI 1.53, 20.23, p = 0.01) were predictors of early neurological deterioration. The funnel plot and Egger's test revealed significant publication bias (p < 0.001). Conclusions: This meta-analysis revealed a pooled prevalence of early neurological deterioration of 23% in patients with intracerebral hemorrhage. The initial NIHSS score, hematoma volume, intraventricular hemorrhage, intraventricular expansion, hematoma expansion, and spot sign enhanced the probability of early neurological deterioration. These findings provide healthcare providers with an evidence-based basis for detecting and managing early neurological deterioration in patients with intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) or tumor-initiating cells (TICs) are thought to be the main drivers for disease progression and treatment resistance across various cancer types. Identifying and targeting these rare cancer cells, however, remains challenging with respect to therapeutic benefit. Here, we report the enrichment of LGR5 expressing cells, a well-recognized stem cell marker, in mouse liver tumors, and the upregulation of LGR5 expression in human hepatocellular carcinoma. Isolated LGR5 expressing cells from mouse liver tumors are superior in initiating organoids and forming tumors upon engraftment, featuring candidate TICs. These cells are resistant to conventional treatment including sorafenib and 5-FU. Importantly, LGR5 lineage ablation significantly inhibits organoid initiation and tumor growth. The combination of LGR5 ablation with 5-FU, but not sorafenib, further augments the therapeutic efficacy in vivo. Thus, we have identified the LGR5+ compartment as an important TIC population, representing a viable therapeutic target for combating liver cancer. Cancer stem cells (CSCs) are thought to be the main drivers for disease progression and treatment resistance in liver cancer. This study identifies the LGR5+ compartment as an important CSC population, representing a viable therapeutic target for combating liver cancer. [ABSTRACT FROM AUTHOR]

Abstract: Interferons (IFNs) with antiviral and immune-stimulatory functions have been widely used in prevention and treatment of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 1 (STAT1) is a key element of the IFN signaling, and the function of STAT1 is critically determined by its phosphorylation state. This study aims to understand the functions of phosphorylated (p-) and unphosphorylated (u-) STAT1 in HCC. We found that u-STAT1 is significantly elevated in patient HCC tumor tissues and predominantly expressed in cytoplasm; while p-STAT1 is absent. Loss of u-STAT1 potently arrested cell cycle and inhibited cell growth in HCC cells. Induction of p-STAT1 by IFN-α treatment effectively triggers the expression of interferon-stimulated genes (ISGs), but has moderate effect on HCC cell growth. Interestingly, both u-STAT1 and p-STAT1 are induced by IFN-α, through with distinct time-dependent process. Furthermore, the ISG induction patterns mediated by p-STAT1 and u-STAT1 are also distinct. Importantly, artificial blocking of the induction of u-STAT1, but not p-STAT1, sensitizes HCC cells to treatment of IFNs. Therefore, p-STAT1 and u-STAT1 exert dichotomal functions and coordinately regulate the responsiveness to IFN treatment in HCC.Key Messages: STAT1 is upregulated and predominantly presented as u-STAT1 in HCC, while p-STAT1 is absent.U-STAT1 sustains but p-STAT1 inhibits HCC growth.The dynamic change of phosphorylation state of STAT1 control the responsiveness to IFN treatment. [ABSTRACT FROM AUTHOR]

Three sequencing batch reactors (M1, M2, and M3) were set up to investigate the influence of different lengths of starvation time (3, 5, and 7 h) on aerobic granulation in the perspective of quorum sensing (QS). Autoinducer-2 (AI-2) level was quantified to evaluate the QS ability of aerobic granules. The results indicated that AI-2 level increased steadily during a cycle of sequencing batch reactors, suggesting that starvation was closely related to AI-2 secretion. In the long-term operation, aerobic granules cultivated using a prolonged starvation period had a better integrity and a higher level of cell adhesiveness despite a slower formation speed. With the extension of the starvation period, the total amount of extracellular polymeric substances (EPS) displayed an increasing tendency. EPS with large molecular weight (MW) also reached a higher level using a prolonged starvation period. However, a higher level of AI-2 and cell adhesiveness was observed in M2, which might be related to more stable granules. The results implied that the starvation period could trigger AI-2 secretion and promoted the production of large MW EPS, leading to cell adhesiveness enhancement and granule formation. Therefore, a combination of different starvation periods was proposed in this study in order to improve aerobic granulation. [ABSTRACT FROM AUTHOR]

Purpose: The potent anticancer efficacy of oncolytic viruses has been verified in Clinic in recent years. Cisplatin (DDP) is one of most common chemotherapeutic drugs, but is accompanied by side effects and drug resistance. Our previous studies have shown the strategy of cancer -targeting gene-viro-therapy (CTGVT) mediated by the oncolytic virus ZD55 containing the XAF1 cDNA (ZD55-XAF1), which exhibited potent antitumor effects in various tumor cells and no apparent toxicities on normal cells. In the study, the CTGVT strategy is broadened by combining DDP with ZD55-XAF1 for growth inhibition of hepatocellular carcinoma (HCC) cells. Methods: The transgenic expression was evaluated by both in vitro and in vivo experiments, and the enhanced inhibitory effect of ZD55-XAF1 combined with cisplatin was assessed in HCC cells. The cytotoxicity on normal liver cells was evaluated by MTT assay and apoptotic cell staining. Activation of caspase-9 and PARP for apoptosis was further detected by Western blot analysis. The in vivo antitumor efficacy of combination treatment with cisplatin and ZD55-XAF1 was estimated in an HCC xenograft mouse model. Results: We found that the combination of ZD55-XAF1 and cisplatin showed enhanced inhibitory effects on the proliferation of HCC cells in vitro and tumor growth in mice. Furthermore, the combined treatment of ZD55-XAF1 and DDP decreases the chemotherapy dose needed to achieve the same inhibitory effect without overlapping toxicities on normal liver cells and induces tumor cell apoptosis via the activation of caspase-9/PARP pathway. Conclusion: Thus, these data suggest that the chemo-gene-viro-therapeutic strategy by combining ZD55-XAF1 and DDP reveals a novel therapeutic strategy for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]