LOC102549726/miR-760-3p network is involved in the progression of ISO-induced pathological cardiomyocyte hypertrophy via endoplasmic reticulum stress.

Pathological cardiac hypertrophy (CH) is featured by myocyte enlargement and cardiac malfunction. Multiple signaling pathways have been implicated in diverse pathological and physiological processes in CH. However, the function of LOC102549726/miR-760-3p network in CH remains unclear. Here, we characterize the functional role of LOC102549726/miR-760-3p network in CH and delineate the underlying mechanism. The expression of LncRNA LOC102549726 and hypertrophic markers was significantly increased compared to the control, while the level of miR-760-3p was decreased. Next, we examined ER stress response in a hypertrophic cardiomyocyte model. The expression of ER stress markers was greatly enhanced after incubation with ISO. The hypertrophic reaction, ER stress response, and increased potassium and calcium ion channels were alleviated by genetic downregulation of LOC102549726. It has been demonstrated that LOC102549726 functions as a competitive endogenous RNA (ceRNA) of miR-760-3p. Overexpression of miR-760-3p decreased cell surface area and substantially mitigated ER stress response; protein levels of potassium and calcium channels were also significantly up-regulated compared to the NC control. In contrast, miR-760-3p inhibition increased cell size, aggravated CH and ER stress responses, and reduced ion channels. Collectively, in this study we demonstrated that the LOC102549726/miR-760-3p network was a crucial regulator of CH development. Ion channels mediate the ER stress response and may be a downstream sensor of the LOC102549726/miR-760-3p network. Therefore, these findings advance our understanding of pathological CH and provide new insights into therapeutic targets for cardiac remodeling.

Simultaneous removal of lead, manganese, and copper released from the copper tailings by a novel magnetic modified biosorbent.

Potentially toxic elements including lead (Pb), manganese (Mn), and copper (Cu) released from copper tailings would cause severe long-term environmental risks and potential threats to human health. To prevent these negative effects caused by the release of the metals, a novel magnetic carboxyl groups modified bagasse with high adsorption affinity and strong magnetism was synthesized through an in-situ precipitation method and used to simultaneously remove Pb, Mn, and Cu from the eluate of copper tailings. Results showed that release of Pb, Mn, and Cu from the copper tailings was pH, time, and particle size dependent, and maximum concentrations of them released in the eluate was 1.7, 1.9, and 4.1 mg L-1 under weak acid conditions. Batch adsorption experiment showed that the as-synthesized magnetic modified bagasse could selectively absorb Pb, Mn, and Cu from a complex solution with adsorption capacity of 137.3, 13.1, and 90.0 mg g-1, respectively. X-ray photoelectron spectroscopy (XPS) and energy dispersive spectroscopy-mapping (EDS-mapping) demonstrated that Pb, Mn, and Cu interacted with the magnetic modified biosorbent mainly through coordination and ion exchange. Column experiments showed that higher than 99.5% of the released Pb, Mn, and Cu could be simultaneously removed by the magnetic modified bagasse, and the maximum concentrations of them released in the eluate of the copper tailings were all decreased to lower than 0.01 mg L-1, which reached the discharge standards. After recycled by a magnet, the magnetic modified bagasse could be collected easily and used repeatedly. Because of the high efficiency and easy recovery, the used method had great practical application value in removal of potentially toxic elements released from metallic tailings.

The ROX index as a predictor of high-flow nasal cannula outcome in pneumonia patients with acute hypoxemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: The respiratory rate-oxygenation (ROX) index has been increasingly applied to predict the outcome of high-flow nasal cannula (HFNC) in pneumonia patients with acute hypoxemic respiratory failure (AHRF). However, its diagnostic accuracy for the HFNC outcome has not yet been systematically assessed. This meta-analysis sought to evaluate the predictive performance of the ROC index for the successful weaning from HFNC in pneumonia patients with AHRF. METHODS: A literature search was conducted on electronic databases through February 12, 2022, to retrieve studies that investigated the diagnostic accuracy of the ROC index for the outcome of HFNC application in pneumonia patients with AHRF. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy due to the varied cutoff values of the index. We observed the distribution of the cutoff values and estimated the optimal threshold with corresponding 95% confidential interval (CI). RESULTS: Thirteen observational studies comprising 1751 patients were included, of whom 1003 (57.3%) successfully weaned from HFNC. The ROC index exhibits good performance for predicting the successful weaning from HFNC in pneumonia patients with AHRF, with an AUHSROC of 0.81 (95% CI 0.77-0.84), a pooled sensitivity of 0.71 (95% CI 0.64-0.78), and a pooled specificity of 0.78 (95% CI 0.70-0.84). The cutoff values of the ROX index were nearly conically symmetrically distributed; most data were centered between 4.5 and 6.0, and the mean and median values were 4.8 (95% CI 4.2-5.4) and 5.3 (95% CI 4.2-5.5), respectively. Moreover, the AUHSROC in the subgroup of measurement within 6 h after commencing HFNC was comparable to that in the subgroup of measurement during 6-12 h. The stratified analyses also suggested that the ROC index was a reliable predictor of HFNC success in pneumonia patients with coronavirus disease 2019. CONCLUSIONS: In pneumonia patients with AHRF, the ROX index measured within 12 h after HFNC initiation is a good predictor of successful weaning from HFNC. The range of 4.2-5.4 may represent the optimal confidence interval for the prediction of HFNC outcome.

Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis.

BACKGROUND: Immune checkpoint inhibitors, which are a milestone in anti-cancer therapy, have been applied in the treatment of multiple malignancies. Real-world data have suggested that smoking status may be associated with the efficacy of anti-PD-1/PD-L1 therapy. Hereby, to evaluate "smoking benefit or not", we included numerous high-quality randomized controlled clinical trials (RCTs) without any restriction on category. METHODS: A systematic search of online database was performed from July 2010 to July 2019. Eligible studies included phase II/III RCTs comparing PD-1/PD-L1 inhibitors with chemotherapy in the treatment of multiple carcinomas and contained subgroup analysis of smoking status. Then, related hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) were pooled. RESULTS: In the initial meta-analysis, compared with chemotherapy, the OS of non-smokers (HR, 0.81; 95% CI, 0.67-0.98) and smokers (HR, 0.77; 95% CI, 0.71-0.83) were significantly prolonged with PD-1/PD-L1 inhibitors. Outcomes from subgroup analysis showed that in anti-PD-1/PD-L1 monotherapy groups, non-smokers showed no significant improvement in OS (HR, 0.94; 95% CI, 0.83-1.06), while the OS of smokers was significantly prolonged (HR, 0.79; 95% CI, 0.74-0.85); in groups of PD-1/PD-L1 inhibitors combined with chemotherapy, the OS of non-smokers (HR, 0.45; 95% CI, 0.28-0.71) and smokers (HR, 0.72; 95% CI, 0.61-0.85) were significantly prolonged. Combined ipilimumab and chemotherapy showed no significance in both groups. CONCLUSION: Smokers benefit from either anti-PD-1/PD-L1 monotherapy or the combined regimen compared with chemotherapy. Considering cost-effectiveness, monotherapy was recommended to smokers. For non-smokers, only the combined regimen was feasible in non-small cell lung cancer.

Septic shock due to community-acquired Pseudomonas aeruginosa necrotizing fasciitis: A case report and literature review.

Necrotizing fasciitis is a rare but fatal infection, characterized by the rapid progression of necrosis of the fascia, skin, soft tissue and muscle. The most common bacteria associated with necrotizing fasciitis is group A streptococcus, although other pathogens have also been implicated. In the present study, a case of community-acquired necrotizing fasciitis, complicated with septic shock and multiple organ dysfunction syndromes due to Pseudomonas aeruginosa, is presented. Despite intensive medical treatment, the condition of the patient deteriorated rapidly and the patient subsequently succumbed to multiple organ failure. In view of the rapid progression and high mortality rate of this disease, early surgery, as well as novel therapeutic approaches for septic shock are required to improve the outcome for patients.