PURPOSE: Lung adenocarcinoma (LA) is one of the major types of lung cancer. MicroRNAs (miRNAs) play an essential role in regulating responses of natural killer (NK) cells to cancer malignancy. However, the mechanism of miR-218-5p involved in the killing effect of NK cells to LA cells remains poorly understood. MATERIALS AND METHODS: The expression of miR-218-5p was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Serine hydroxymethyl transferase 1 (SHMT1) level was detected by qRT-PCR or western blots. Cytokines production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The killing effect of NK cells to LA cells was investigated using lactate dehydrogenase cytotoxicity assay kit. The interaction of miR-218-5p and SHMT1 was probed by luciferase activity assay. Xenograft model was established to investigate the killing effect of NK cells in vivo. RESULTS: miR-218-5p was enhanced and SHMT1 was inhibited in NK cells of LA patients, whereas stimulation of interleukin-2 (IL-2) reversed their abundances. Addition of miR-218-5p reduced IL-2-induced cytokines expression and cytotoxicity in NK-92 against LA cells. Moreover, SHMT1 was negatively regulated by miR-218-5p and attenuated miR-218-5p-mediated effect on cytotoxicity, IFN-γ and TNF-α secretion in IL-2-activated NK cells. In addition, miR-218-5p exhaustion inhibited tumor growth by promoting killing effect of NK cells. CONCLUSION: miR-218-5p suppresses the killing effect of NK cells to LA cells by targeting SHMT1, providing a potential target for LA treatment by ameliorating NK cells function.
Adenocarcinoma ; Blotting, Western ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Heterografts ; Homicide ; Humans ; Interleukin-2 ; Killer Cells, Natural ; L-Lactate Dehydrogenase ; Luciferases ; Lung Neoplasms ; Lung ; MicroRNAs ; Necrosis ; Real-Time Polymerase Chain Reaction ; Serine ; Transferases

Objective To establish a mouse model of liver aging induced by irradiation combined with hepatectomy.Methods A model was established via single irradiation combined with hepatectomy.The survival rate,body weight,liver index and liver function of the mice were detected.The expressions of senescence-associated secretory phenotype factors in serum were detected with enzyme-linked immunosorbent assay(ELISA)and flow cytometry.The mRNA levels of senescence-associated secretory phenotype factors and telomerase in liver tissue were detected by real-time quantitative PCR(qPCR).The expressions of cyclin dependent kinase inhibitor 1A(CDKN1A)and cyclin dependent kinase inhibitor 2A(CDKN2A)were determined by Western blotting.ELISA was used to calculate senescence-associated β-galactosidase(SA-β-Gal)and lipofuscin levels.Tissue malondialdehyde levels were measured using the thiobarbituric acid(TBA)method.The size of hepatocyte nuclei and lipid accumulation were detected by hematoxylin-eosin(HE)stainingand oil-red-O while triglyceride levels in the liver were studied with the weighing method.Results After irradiation combined with hepatectomy,the body weight of mice was significantly reduced,the liver index was not significantly affected,but the transaminase level was significantly increased.The levels of SA-β-Gal and lipofuscin increased while telomerase activity decreased significantly,and the nucleus size increased.The expressions of cyclin dependent protein kinase inhibitors CDKN1A and CDKN2A increased.The levels of senescence-associated secretory phenotype factors were significantly increased.Hepatic lipid deposition and oxidative damage were aggravated.Conclusion A mouse model of liver aging induced by irradiation combined with hepatectomy has been established.

Atrial fibrillation (AF) is one of the most common arrhythmias, associated with high morbidity, mortality, and healthcare costs, and it places a significant burden on both individuals and society. Anti-arrhythmic drugs are the most commonly used strategy for treating AF. However, drug therapy faces challenges because of its limited efficacy and potential side effects. Catheter ablation is widely used as an alternative treatment for AF. Nevertheless, because the mechanism of AF is not fully understood, the recurrence rate after ablation remains high. In addition, the outcomes of ablation can vary significantly between medical institutions and patients, especially for persistent AF. Therefore, the issue of which ablation strategy is optimal is still far from settled. Computational modeling has the advantages of repeatable operation, low cost, freedom from risk, and complete control, and is a useful tool for not only predicting the results of different ablation strategies on the same model but also finding optimal personalized ablation targets for clinical reference and even guidance. This review summarizes three-dimensional computational modeling simulations of catheter ablation for AF, from the early-stage attempts such as Maze III or circumferential pulmonary vein isolation to the latest advances based on personalized substrate-guided ablation. Finally, we summarize current developments and challenges and provide our perspectives and suggestions for future directions.

ObjectiveTo investigate the clinical and epidemiological features of patients with bacterial liver abscess during the outbreak of coronavirus disease 2019 （COVID－19） in Changchun， China. MethodsA retrospective analysis was performed for 37 411 patients who were discharged from The First Hospital of Jilin University from March 1 to June 30 in 2022， and finally 135 patients with bacterial liver abscess were included for analysis. Related clinical data were collected to summarize their clinical features， and these patients were compared with the patients with bacterial liver abscess in 2019－2021 in terms of disease onset and pathogen. The Kruskal－Wallis H test was used for comparison of continuous data between multiple groups， and the chi－square test was used for comparison of categorical data between multiple groups. ResultsThe patients with bacterial liver abscess accounted for 0.36% of the patients admitted to our hospital during the same period of time， which showed varying degrees of increase compared with the previous years （χ²=32.081， P<0.001）. The 135 patients with bacterial liver abscess had a mean hospital stay of 11 （6－18） days， which was longer than that in the previous years （H=9.223， P=0.026）. The patients with bacterial liver abscess had higher levels of white blood cell count and C－reactive protein （CRP） than the previous years （H=14.150 and 8.736， P=0.003 and 0.033）. Among the 135 patients， 69 （51.11%） received blood culture， and the results showed sterile growth （59.42%）， Klebsiella pneumoniae （30.43%）， Escherichia coli （4.35%）， Bacteroides fragilis （1.45%）， Enterococcus faecium （1.45%）， Staphylococcus epidermidis （1.45%）， and Klebsiella oxytoca （1.45%）. Among the 135 patients， 90 （66.67%） received pus culture， and the results showed Klebsiella pneumoniae （72.22%）， sterile growth （14.44%）， Escherichia coli （4.44%）， Enterococcus faecium （2.22%）， Pseudomonas aeruginosa （2.22%）， Acinetobacter baumannii （1.11%）， Klebsiella aerogenes （1.11%）， Klebsiella oxytoca （1.11%）， and Enterococcus casseliflavus （1.11%）. Of all 135 patients， 127 （94.07%） were improved and cured after anti－infective therapy and ultrasound－guided abscess puncture and drainage， and 3 patients （2.22%） died during hospitalization. ConclusionDuring the outbreak of COVID－19 in Changchun， there are increases in the number of patients with liver abscess in our hospital， the length of hospital stay， and the levels of white blood cell count and CRP， with Klebsiella pneumoniae as the main pathogen， and most patients are improved after treatment.