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Objective: To investigate the relationship among the gut microbiome, serum metabolomic profile and RNA m6A methylation in patients with sepsis-associated encephalopathy (SAE), 16S rDNA technology, metabolomics and gene expression validation were applied. Methods: Serum and feces were collected from patients with and without (SAE group and non-SAE group, respectively, n = 20). The expression of serum markers and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA), and blood clinical indicators were detected using a double antibody sandwich immunochemiluminescence method. The expression of RNA m6A regulator were checked by Q-RTPCR. The gut microbiome was analyzed by 16S rDNA sequencing and the metabolite profile was revealed by liquid chromatography-mass spectrometry (LC-MS/MS). Results: In the SAE group, the IL-6, ICAM-5 and METTL3 levels were significantly more than those in the non-SAE group, while the FTO levels were significantly decreased in the SAE group. The diversity was decreased in the SAE gut microbiome, as characterized by a profound increase in commensals of the Acinetobacter , Methanobrevibacter , and Syner-01 genera , a decrease in [ Eubacterium ]_ hallii _group, while depletion of opportunistic organisms of the Anaerofilum , Catenibacterium , and Senegalimassilia genera were observed in both groups. The abundance of Acinetobacter was positively correlated with the expression of METTL3. The changes between the intestinal flora and the metabolite profile showed a significant correlation. Sphingorhabdus was negatively correlated with 2-ketobutyric acid, 9-decenoic acid, and l-leucine, and positively correlated with Glycyl-Valine [Eubacterium]_hallii _group was positively correlated with 2-methoxy-3-methylpyazine, acetaminophen, and synephrine acetonide. Conclusion: The gut microbiota diversity was decreased. The serum metabolites and expression of RNA m6A regulators in PBMC were significantly changed in the SAE group compared to the non-SAE group. The results revealed that serum and fecal biomarkers could be used for SAE screening. [ABSTRACT FROM AUTHOR]

Longitudinal studies have highlighted allogeneic natural killer (NK) cell-based cytotherapy for cancer immunosurveillance and immunotherapy, yet the deficiency of systematic and detailed comparison of NK cells from candidate sources including umbilical cord blood (UC) and bone marrow (BM) largely hinders the large-scale application. Herein, we isolated resident NK cells (rUC-NK, rBM-NK) from mononuclear cells (MNC), and analyzed the corresponding expanded NK cell counterparts (eUC-NK, eBM-NK). Then, the eUC-NK and eBM-NK were turned to multifaceted bioinformatics from the aspects of gene expression profiling and genetic variations. The percentages of total or activated NK cells in rBM-NK group were approximate 2-fold higher over those in the rUC-NK group, respectively. Instead, the proportion of total NK cells in eUC-NK was higher than that in the eBM-NK group, and in particular, the CD25 + memory-like NK cell subset. Furthermore, eUC-NK and eBM-NK manifested multidimensional similarities and diversities in gene expression pattern and genetic spectrum, whereas both eUC-NK and eBM-NK exhibited effective tumor killing capacity. Collectively, we dissected the cellular and transcriptomic signatures of NK cells generated from UC-MNC and BM-MNC, which supplied new literature for further exploring the characteristics of the indicated NK cells and would benefit the clinical application for cancer immunotherapy in future., Competing Interests: None., (AJCR Copyright © 2023.)

Objective: To investigate the relationship among the gut microbiome, serum metabolomic profile and RNA m6A methylation in patients with sepsis-associated encephalopathy (SAE), 16S rDNA technology, metabolomics and gene expression validation were applied. Methods: Serum and feces were collected from patients with and without (SAE group and non-SAE group, respectively, n = 20). The expression of serum markers and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA), and blood clinical indicators were detected using a double antibody sandwich immunochemiluminescence method. The expression of RNA m 6 A regulator were checked by Q-RTPCR. The gut microbiome was analyzed by 16S rDNA sequencing and the metabolite profile was revealed by liquid chromatography-mass spectrometry (LC-MS/MS). Results: In the SAE group, the IL-6, ICAM-5 and METTL3 levels were significantly more than those in the non-SAE group, while the FTO levels were significantly decreased in the SAE group. The diversity was decreased in the SAE gut microbiome, as characterized by a profound increase in commensals of the Acinetobacter , Methanobrevibacter , and Syner-01 genera , a decrease in [ Eubacterium ]_ hallii _group, while depletion of opportunistic organisms of the Anaerofilum , Catenibacterium , and Senegalimassilia genera were observed in both groups. The abundance of Acinetobacter was positively correlated with the expression of METTL3. The changes between the intestinal flora and the metabolite profile showed a significant correlation. Sphingorhabdus was negatively correlated with 2-ketobutyric acid, 9-decenoic acid, and l-leucine, and positively correlated with Glycyl-Valine [Eubacterium]_hallii _group was positively correlated with 2-methoxy-3-methylpyazine, acetaminophen, and synephrine acetonide. Conclusion: The gut microbiota diversity was decreased. The serum metabolites and expression of RNA m6A regulators in PBMC were significantly changed in the SAE group compared to the non-SAE group. The results revealed that serum and fecal biomarkers could be used for SAE screening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wang, Chen and Chen.)

Objective: To investigate the efficacy of intravenous combined with aerosol inhalation of polymyxin B for the treatment of pneumonia caused by multidrug-resistant Gram-negative (G - ) bacteria., Methods: A observational study was conducted. The clinical data of 45 patients with pneumonia due to multidrug-resistant G - bacteria admitted to intensive care unit of Fujian Medical University Union Hospital from January to October in 2020 were analyzed. According to the different use methods of polymyxin B, 25 patients who received single intravenous drip (the first dose was 2.0 mg/kg, then 1.25 mg/kg, once every 12 hours) from January to April in 2020 were enrolled in the routine group, and 20 patients who received intravenous drip combined with aerosol inhalation (25 mg once every 12 hours, sputum in the airway was sucked and then sprayed aerosol) from May to October in 2020 were enrolled in the combination group. After the treatment course of polymyxin B, the total bacterial clearance rate, total clinical efficiency rate, recovery time of body temperature, time of bacterial clearance and the change of serum procalcitonin (PCT) level before and after treatment were compared between the two groups. Moreover, the incidence of adverse reactions during treatment in the two groups was observed., Results: The results of sputum culture in the routine group were Acinetobacter baumannii in 13 patients, Klebsiella pneumoniae in 5 patients, Pseudomonas aeruginosa in 6 patients, Enterobacter cloacae in 1 patient; the sputum culture results of the combination group showed that there were 5 patients of Acinetobacter baumannii, 9 Klebsiella pneumoniae and 6 Pseudomonas aeruginosa. There was no significant difference in the results of sputum culture between the two groups (P > 0.05). The total bacterial clearance rate and the total clinical efficiency rate of the combination group were significantly higher than those in the routine group (total bacterial clearance rate: 70.0% vs. 40.0%, total clinical efficiency rate: 75.0% vs. 40.0%, both P < 0.05). The recovery time of body temperature and the time of bacterial clearance of the combination group were significantly shorter than those in the routine group [recovery time of body temperature (days): 6.0±3.9 vs. 10.2±7.3, time of bacterial clearance (days): 6.1±5.2 vs. 11.5±6.8, both P < 0.05]. No significant difference was found in serum PCT level before treatment between the two group. There was no significant difference in serum PCT level before and after treatment in the routine group [μg/L: 0.85 (0.44, 2.87) vs. 1.43 (0.76, 5.30), P > 0.05]. The serum PCT level after treatment in the combination group was significantly lower than that before treatment [μg/L: 0.27 (0.10, 0.70) vs. 0.91 (0.32, 3.53), P < 0.05], and it was significantly lower than that in the routine group [μg/L: 0.27 (0.10, 0.70) vs. 0.85 (0.44, 2.87), P < 0.01]. The incidence of renal toxicity of polymyxin B between the combination group and the routine group was not significantly different (5.0% vs. 4.0%, P > 0.05)., Conclusions: The efficacy of intravenous combined with aerosol inhalation of polymyxin B for the treatment of pneumonia due to multidrug-resistant G - bacteria is better than that of intravenous drip of polymyxin B only. The aerosolized polymyxin B will not increase the risk of renal injury.

Several somatic copy number variations (CNVs) have been identified in papillary thyroid cancer (PTC). However, the functional roles of CNVs and the genes responsible for the roles of CNVs are largely unknown. In this study, we identified a novel long noncoding RNA (lncRNA) CNALPTC1 (copy number amplified long noncoding RNA in papillary thyroid cancer 1). The genomic copy number of CNALPTC1 is amplified and CNALPTC1 expression level is up-regulated in PTC. Increased expression of CNALPTC1 is associated with aggressive clinicopathological characteristics. Gain-of-function and loss-of-function assays revealed that CNALPTC1 promotes proliferation and migration of PTC cells, and inhibits apoptosis of PTC cells. Mechanistically, we found that CNALPTC1 physically associates to miR-30 family and down-regulates miR-30 expression. Furthermore, CNALPTC1 up-regulates the expression of miR-30 targets, such as BCL9, SNAI1, and VIM. The mutation of miR-30 binding site on CNALPTC1 or overexpression of miR-30 abrogates the oncogenic roles of CNALPTC1 in PTC. Collectively, our results suggested that the copy number amplified lncRNA CNALPTC1 promotes PTC progression via sponging miR-30 family. Our data also implied that CNALPTC1 may be a novel therapeutic target for PTC., Competing Interests: None.