Exosomal LINC00161 promotes angiogenesis and metastasis via regulating miR-590-3p/ROCK axis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a lethal malignancy with few effective options for therapeutic treatment in its advanced stages. While exosomal LINC00161 has been identified as a potential biomarker for HCC, its regulatory function and clinical values remain largely unknown. LINC00161 expressions in serum-derived exosomes from HCC patients and HCC cells were determined by qRT-PCR. The ability of proliferation, migration, and angiogenesis in HUVECs was assessed by MTT, Transwell, and tube formation. Luciferase reporter assay and AGO2-RIP assay were conducted to explore the interactions among LINC00161, miR-590-3p, and ROCK2. The level of ROCK signal-related proteins was examined by Western blotting and immunohistochemistry (IHC) assay. Subcutaneous tumor growth was observed in nude mice, in which in vivo metastasis was observed following tail vein injection of HCC cells. High levels of LINC00161 were detected in both serum-derived exosomes from HCC patients and the supernatants of HCC cell lines and were significantly associated with poor survival. Functional study demonstrated that exosomal LINC00161 derived from HCC-cells were significantly associated with enhanced proliferation, migration, and angiogenesis in HUVECs in vitro, all of which were effectively inhibited when LINC00161 was sliced with shRNA in HCC-cells. In vivo experiment showed that LINC00161 loss inhibited tumorigenesis and metastasis of HCC. Mechanistic study revealed that exosome-carried LINC00161 directly targeted miR-590-3p and induced its downstream target ROCK2, finally activating growth/metastasis-related signals in HCC. Exosome-carried LINC00161 promotes HCC tumorigenesis through inhibiting miR-590-3p to activate the ROCK2 signaling pathway, suggesting that LINC00161 may be used as potential targets to improve HCC treatment efficiency.

Most impactful predictors for hyperoxaemia in exacerbation of chronic obstructive pulmonary disease managed by Emergency Medical Services and Emergency Department.

INTRODUCTION: Hyperoxemia in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) leads to adverse outcomes. It remains prevalent in the pre-hospital Emergency Medical Services (EMS) and Emergency Department (ED). OBJECTIVE: To determine the key predictors for hyperoxemia in AECOPD in EMS and ED. METHODS: This was a prospective observational study of AECOPD patients in EMS and two EDs. Hyperoxemia was defined as PaO2 > 65 mm Hg (corresponds to SpO2 > 92%). We determined apriori candidate factors in Patient, Organization and Staff domains. Primary outcomes were the key predictors for hyperoxemia. Secondary outcomes were in-hospital mortality and mechanical ventilation rates in hyperoxemic versus non-hyperoxemic groups. We generated a logistic regression model for each domain. We reported the adjusted odds ratios (AORs), 95% CIs and p values. We selected the output factors using AOR ≥2.0 and ≥2.5 for modifiable and non-modifiable factors, respectively. These selected factors were fed into a final model with eventual factors selected based on: threshold AORs as stated above and/or 95% CIs including these AORs. RESULTS: Three hundred and twenty-six patients were analysed; 60.7% had hyperoxemia. We found three eventual modifiable factors; first, ED SpO2 > 95% [AOR 2.62 (95% CIs: 1.61-4.33); P < 0.001], EMS non-rebreathing mask [AOR 2.01 (95% CIs: 1.06-3.97); P = 0.04]; and ED nasal cannula [AOR 1.69 (95% CIs: 1.05-2.72); P = 0.03]. Secondary outcomes did not differ between groups. CONCLUSION: We identified three key modifiable predictors. We intend to conduct an interventional study using them to reduce hyperoxemia rate in AECOPD.

Autoantibodies against ß1-adrenergic receptor: response to induction therapy with bortezomib-containing regimens for multiple myeloma patients.

This study aims to investigate the predictive value of pre-chemotherapy ß1R-AABs by evaluating the response of newly diagnosed symptomatic multiple myeloma (MM) patients to their treatment with a bortezomib-containing regimen. Forty-five de novo MM patients and 50 normal controls (NCs) were prospectively enrolled in this study. Serum titers of ß1R-AABs were detected by ELISA. These 45 MM patients were divided into two groups (positive and negative groups) according to their ß1R-AABs. Follow-up examinations were performed on these patients during chemotherapy induction. The final analysis covered all 45 MM patients, including 19 patients who were positive for MM and 26 patients who were negative for MM. Multivariate analysis revealed that pre-chemotherapy ß1R-AABs are possibly independent predictors for less than very good partial response (VGPR) after the bortezomib-containing regimen treatment (odds ratio: 5.967, 95% confidence interval: 1.513-23.531; p = .011). This study demonstrates for the first time that the presence of ß1R-AABs is associated with MM. Pre-chemotherapy ß1R-AABs are independent predictors for less than VGPR in de novo MM patients after the bortezomib-containing regimen was administrated. Bortezomib might not significantly give rise to cardiac impairment in MM patients.