Background: Gastric cancer (GC) is one of the most malignant and lethal cancers worldwide. Multiple microRNAs (miRNAs) have been identified as key regulators in the progression of GC. However, the underlying pathogenesis that miRNAs govern GC malignancy remains uncertain. Here, we identified a novel miR-585-5p as a key regulator in GC development.Methods: The expression of miR-585-5p in the context of GC tissue was detected by in situ hybridization for GC tissue microarray and assessed by H-scoring. The gain- and loss-of-function analyses comprised of Cell Counting Kit-8 assay and Transwell invasion and migration assay. The expression of downstream microphthalmia-associated transcription factor (MITF), cyclic AMP-responsive element-binding protein 1 (CREB1) and mitogen-activated protein kinase 1 (MAPK1) were examined by Immunohistochemistry, quantitative real-time PCR and western blot. The direct regulation between miR-585-5p and MITF/CREB1/MAPK1 were predicted by bioinformatic analysis and screened by luciferase reporter assay. The direct transcriptional activation of CREB1 on MITF was verified by luciferase reporter assay, chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSAs). The interaction between MAPK1 and MITF was confirmed by co-immunoprecipitation (Co-IP) and immunofluorescent double-labelled staining.Results: MiR-585-5p is progressively downregulated in GC tissues and low miR-585-5p levels were strongly associated with poor clinical outcomes. Further gain- and loss-of-function analyses showed that miR-585-5p possesses strong anti-proliferative and anti-metastatic capacities in GC. Follow-up studies indicated that miR-585-5p targets the downstream molecules CREB1 and MAPK1 to regulate the transcriptional and post-translational regulation of MITF, respectively, thus controlling its expression and cancer-promoting activity. MiR-585-5p directly and negatively regulates MITF together with CREB1 and MAPK1. According to bioinformatic analysis, promotor reporter gene assays, ChIP and EMSAs, CREB1 binds to the promotor region to enhance transcriptional expression of MITF. Co-IP and immunofluorescent double-labelled staining confirmed interaction between MAPK1 and MITF. Protein immunoprecipitation revealed that MAPK1 enhances MITF activity via phosphorylation (Ser73). MiR-585-5p can not only inhibit MITF expression directly, but also hinder MITF expression and pro-cancerous activity in a CREB1-/MAPK1-dependent manner indirectly.Conclusions: In conclusion, this study uncovered miR-585-5p impedes gastric cancer proliferation and metastasis by orchestrating the interactions among CREB1, MAPK1 and MITF.

Background: The transjugular intrahepatic portal collateral-systemic shunt (transcollateral TIPS) is used to treat portal hypertension-related complications in patients with cavernous transformation of the portal vein (CTPV) and whose main portal vein cannot be recanalized. It is still not clear whether transcollateral TIPS can be as effective as portal vein recanalization–transjugular intrahepatic portosystemic shunt (PVR–TIPS). This study aimed to evaluate the efficacy and safety of transcollateral TIPS in the treatment of refractory variceal bleeding with CTPV. Methods: Patients with refractory variceal bleeding caused by CTPV were selected from the database of consecutive patients treated with TIPS in Xijing Hospital from January 2015 to March 2022. They were divided into the transcollateral TIPS group and the PVR–TIPS group. The rebleeding rate, overall survival, shunt dysfunction, overt hepatic encephalopathy (OHE) and operation-related complications were analyzed. Results: A total of 192 patients were enrolled, including 21 patients with transcollateral TIPS and 171 patients with PVR–TIPS. Compared with the patients with PVR–TIPS, the patients with transcollateral TIPS had more noncirrhosis (52.4 vs. 19.9%, p = 0.002), underwent fewer splenectomies (14.3 vs. 40.9%, p = 0.018), and had more extensive thromboses (38.1 vs. 15.2%, p = 0.026). There were no differences in rebleeding, survival, shunt dysfunction, or operation-related complication rates between the transcollateral TIPS and PVR–TIPS groups. However, the OHE rate was significantly lower in the transcollateral TIPS group (9.5 vs. 35.1%, p = 0.018). Conclusion: Transcollateral TIPS is an effective treatment for CTPV with refractory variceal bleeding.

Lecithin cholesterol acyltransferase (LCAT) is a crucial enzyme in high-density lipoprotein (HDL) metabolism that is often dysregulated in cancers, affecting tumor growth and therapy response. We extensively studied LCAT expression in various malignancies, linking it to clinical outcomes and genetic/epigenetic alterations. We analyzed LCAT expression in multiple cancers and used the Cox regression model to correlate it with patient survival metrics, including overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). We also examined the copy number variations (CNVs), single-nucleotide variations (SNVs), DNA methylation, and N6-methyladenosine (m6A) modifications of LCAT and their connections to tumor immune responses and drug sensitivity. LCAT expression varies among cancers and correlates with patient outcomes. Low expression is linked to poor prognosis in low-grade glioma (LGG) and liver hepatocellular carcinoma (LIHC), while high expression is associated with better outcomes in adrenocortical carcinoma (ACC) and colon adenocarcinoma (COAD). In kidney renal papillary cell carcinoma (KIRP) and uterine corpus endometrial carcinoma (UCEC), LCAT CNV and methylation levels are prognostic markers. LCAT interacts with m6A modifiers and immune molecules, suggesting a role in immune evasion and as a biomarker for immunotherapy response. LCAT expression correlates with chemotherapeutic drug IC50 values, indicating potential for predicting treatment response. In ACC and COAD, LCAT may promote tumor growth, while in LGG and LIHC, it may inhibit progression. LCAT expression and activity regulation could be a new cancer therapy target. As a key molecule linking lipid metabolism, immune modulation, and tumor progression, the potential of LCAT in cancer therapy is significant. Our findings provide new insights into the role of LCAT in cancer biology and support the development of personalized treatment strategies.

Objectives: Hepatic hydrothorax (HH) is a predictor of poor survival in cirrhosis patients. However, whether HH increases the mortality risk of cirrhosis patients treated with transjugular intrahepatic portosystemic shunt (TIPS) is unknown. Our objective was to evaluate the influence of HH on the survival of cirrhosis patients after TIPS. Methods: Cirrhosis patients with portal hypertension complications were selected from a prospective database of consecutive patients treated with TIPS in Xijing Hospital from January 2015 to June 2021. Cirrhosis patients with HH were treated as the experimental group. A control group of cirrhosis patients without HH was created using propensity score matching. Survival after TIPS and the related risk factors were analysed. Results: There were 1292 cirrhosis patients with portal hypertension complications treated with TIPS, among whom 255 patients had HH. Compared with patients without HH, patients with HH had worse liver function (MELD, 12 vs. 10, p < 0.001), but no difference in survival after TIPS was observed. After propensity score matching, 243 patients with HH and 243 patients without HH were enrolled. There was no difference in cumulative survival between patients with and without HH. Cox regression analysis showed that HH was not associated with survival after TIPS, and main portal vein thrombosis (> 50%) was a prognostic factor of long-term survival after TIPS in cirrhosis patients (hazard ratio, 1.386; 95% CI, 1.030–1.865, p = 0.031). Conclusion: Hepatic hydrothorax does not increase the risk of death after TIPS in cirrhosis patients. Key Points: • Hepatic hydrothorax is a decompensated event of cirrhosis and increases the risk of death. • Hepatic hydrothorax is associated with worse liver function. • Hepatic hydrothorax does not increase the mortality of cirrhosis treated with TIPS.

Objective: Decompression sickness (DCS) causes serious brain hypoxic- ischemic injury. This experiment was designed to observe whether hyperbaric oxygen (HBO2) pretreatment played a neuroprotective effect in decompression sickness rat models and to explore the mechanism of protective effects. Methods: Sprague-Dawley (SD) male rats were pretreated with HBO2 and then underwent decompression to establish the DCS rat model. Antioxidant capacities were evaluated by detecting peroxides (GPx), superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in brains. The levels of metal elements manganese (Mn), zinc (Zn), iron (Fe) and magnesium (Mg) in brain tissues were assessed by flame atomic absorption spectrometry. Necrosis and apoptosis of neurons were assessed by H-E staining and immunohistochemical staining. Results: HBO2 pretreatment reduced the degree of necrosis and apoptosis in brain tissues of decompression sickness rat models. In addition, HBO2 pretreatment increased GPx, SOD and CAT activities and reduced MDA accumulation. It also increased the content of Mn, Zn, Fe and Mg in brain tissue, which are all related to free radical metabolism. Conclusion: These results suggested that HBO2 pretreatment has protective effects on brain injury of rats with decompression sickness. The mechanism of the protective effects may be related to reducing oxidative damage by affecting metal elements in vivo.

Hypoxic pulmonary hypertension (HPH) serves as a crucial link in the pathogenesis of chronic high-altitude diseases and chronic obstructive pulmonary disease (COPD), and ultimately may lead to right heart failure. Hypoxia triggers immune responses and inflammatory processes, which contribute to vascular remodeling and elevated pulmonary artery pressure. NLRX1, a member of the Nod-like receptor family, plays a significant regulatory role in immunity, antioxidation, and apoptosis. However, its role in the occurrence and development of HPH remains unknown. Wild type (WT) C57BL/6 mice and NLRX1 knockout (NLRX1−/−) Mice were subjected to intermittent chronic hypoxia for 6 weeks to establish a hypoxic pulmonary hypertension model that is similar to the moderate pulmonary hypertension (PH) induced by hypoxia in humans. Subsequently, data on hemodynamics and pulmonary pathomorphology were collected. Additionally, bone marrow derived macrophages (BMDMs) were cultured to determine the effects of up-regulating and down-regulating NLRX1 on cell function under hypoxia exposure. Western blotting or reverse transcription polymerase chain reaction (RT-PCR) was utilized to detect changes in inflammation factors and oxidative stress-related indicators in rat lung tissue and cultured BMDMs. Hypoxia downregulates the expression of NLRX1 in the lung tissues of mice and bone marrow-derived macrophages (BMDM). Chronic hypoxia significantly increases right ventricular systolic pressure (RVSP), the ratio of right ventricle weight to left ventricle plus septum weight (RV/LV + S), and the medial width of pulmonary arterioles in NLRX1-knockout (NLRX1−/−) mice. NLRX1 mediates the hemodynamic response and right ventricular hypertrophy in mice with hypoxic pulmonary hypertension. The deficiency of NLRX1 upregulates inflammatory mediators by activating nuclear factor-κB (NF-κB) and simultaneously promotes oxidative stress and the activation of nuclear factor E2-related factor 2 (Nrf2). The activator NX-13 of NLRX1 can reduce the production of inflammatory cytokines in BMDMs stimulated by hypoxia and mitigate oxidative stress. NLRX1 may suppress hypoxia-induced lung inflammation and alleviate hypoxia-induced pulmonary hypertension through its anti-inflammatory and antioxidant properties. Therefore, targeted up-regulation of NLRX1 may offer a new strategy for the treatment of HPH.