Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

The efficacy mechanism of the alcoholic extract of Gnaphalium affine was investigated by observing its influence on oxidative stress and intestinal flora in rats modeled for chronic obstructive pulmonary disease(COPD). UPLC-MS was used to evaluate the quality of the alcoholic extract of G. affine, and 72 rats were randomly divided into six groups, with COPD models established in five groups by cigarette smoke combined with airway drip lipopolysaccharide, and the rats were given the positive drug of Danlong Oral Solution, as well as low-, medium-, and high-doses alcoholic extract of G. affine, respectively. After two weeks of continuous gastric gavage, the body weights and general morphology observations were performed; HE staining and Masson staining were used to verify the effects of the alcoholic extract of G. affine on alveolar inflammation and collagen deposition area in COPD rats; the oxidative stress indexes CAT and GSH in serum and SOD and MDA in lung tissue of the rats were measured, and the mRNA expression of HO-1, Nrf2, and NQO1 were determined by qRT-PCR. The protein expressions of HO-1, Nrf2, and NQO1 were determined by the Western blot method, and the mechanism by which the alcoholic extract of G. affine affected oxidative stress in COPD rats was explored. Finally, the influence of G. affine on the changes in intestinal flora caused by COPD was studied by 16S rRNA sequencing. The results showed that a total of 121 chemical components were identified by UPLC-MS, including 70 positive and 51 negative ion modes. In animal experiments, it was found that the alcoholic extracts of G. affine were able to reduce the percentage of collagen deposition, affect the oxidative stress indexes such as CAT, GSH, SOD, MDA, as well as the mRNA and protein expression of Nrf2, HO-1, and NQO1. The 16S rRNA sequencing results showed an increase in the level of Lactobacillales and a decrease in the level of Desulfovibrio and Desulfovibrionales, suggesting that the alcoholic extracts of G. affine could reverse the changes in intestinal flora caused by COPD. In conclusion, the alcoholic extracts of G. affine may exert anti-COPD effects by affecting the oxidative stress pathway and modulating the changes in intestinal flora.
Animals ; Oxidative Stress/drug effects* ; Pulmonary Disease, Chronic Obstructive/genetics* ; Rats ; Male ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Lung/metabolism*

Objective:To investigate the effectiveness and safety of domestic upper gastrointestinal endoscopic ultrasound (EUS).Methods:A total of 160 patients undergoing EUS at Shengjing Hospital of China Medical University (Center1) and Shenzhen People's Hospital (Center 2) from March to July 2021 were randomly selected by stratified blocked randomization, and were treated with SonoScape EG-UG5T (the test group) or Fujifilm EG-580UT (the control group). The primary outcome was the ultrasound image quality excellence rate, and the comparison was verified by non-inferiority. The secondary outcomes were the endoscopic image quality excellence rate, the operational performance excellence rate, and the system stability evaluation. The safety evaluation was based on the occurrence of intraoperative and postoperative adverse events in the subjects.Results:In the intention-to-treat analysis set (ITT), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (77/77), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.8%). In the per protocol analysis set (PPS), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (75/75), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.9%). The lower limit of the confidence interval of ultrasound image quality excellence rate of both data sets was greater than the non-inferiority threshold value of -8%, which inferred that the non-inferiority hypothesis of the test machine non-inferior to the control machine was valid. The endoscopic image quality excellence rate and the operational performance excellence rate of the test group and the control group was 100.0% in both the ITT and PPS analyses, and there was no statistically significant difference between the two groups ( P=1.000). The system instability event rate was 0.0% (0/78) in the test group and 3.9% (3/77) in the control group ( P=0.120). No adverse event occurred in either group. Conclusion:The domestic upper gastrointestinal endoscopic ultrasound is standard-compliant for clinical application under normal conditions in terms of effectiveness, safety, and stability.

Objective:To explore mechanism of regulation of proliferation,migration,invasion and expressions of immune factors of ovarian cancer SKOV3 cells by circSKA3/miR-3163/disintegrin-metalloproteinase 9(ADAM9)gene axis.Methods:qRT-PCR was used to detect circSKA3 and miR-3163 expressions in ovarian cancer tissues and paracancerous tissues.Western blot was used to detect ADAM9 protein level in tissues.SKOV3 cells were selected for cell experiment in vitro,and divided into sh-NC group,sh-circSKA3 group,miR-NC group,miR-3163 group,sh-circSKA3+anti-miR-3163 group,sh-circSKA3+pcDNA-ADAM9 group.circSKA3 and miR-3163 expressions in SKOV3 cells were detected by qRT-PCR.CCK-8,scratch test and Transwell were used to detect cell proliferation activity,migration and invasion ability.ELISA was used to detect expressions of TNF-α,IL-6 and IL-10.Double luciferase report experiment verified targeting relationship between circSKA3 with miR-3163,miR-3163 and ADAM9.Western blot was used to detect levels of ADAM9,matrix metalloproteinase-2(MMP-2)and MMP-9 in SKOV3 cells.Results:Com-pared with paracancerous tissues,circ-SKA3 and ADAM9 expressions were increased,and miR-3163 expression was decreased in ovarian cancer tissues(P<0.05).Compared with sh-NC group/miR-NC group,sh-circSKA3 group/miR-3163 group showed decreased cell proliferative activity and healing rate,decreased number of invasive cells,MMP-2,MMP-9 proteins and TNF-α and IL-6 expres-sions were decreased,expression of IL-10 was increased(P<0.05).circSKA3 could targeting regulate expression of miR-3163,and miR-3163 could targeting bind to ADAM9(P<0.05).Compared with sh-circSKA3 group,cell proliferation activity and scratch healing rate in sh-circSKA3+anti-miR-3163 and sh-circSKA3+pcDNA-ADAM9 groups were increased,number of invasive cells was in-creased,MMP-2,MMP-9 protein and TNF-α,IL-6 expressions were increased,while expression of IL-10 was decreased(P<0.05).Conclusion:Silencing circSKA3 expression can reduce expression of ADAM9 by up-regulating miR-3163 expression,inhibit ovarian cancer cell proliferation,migration and invasion,and regulate immune factor expression.

Objective:To systematically evaluate the clinical outcomes of hemihepatic inflow occlusion(HHO)and total hepatic inflow occlusion(THO)in liver resection surgery.Method:Re-trieve the Cochrane Library,PubMed,EMbase,Ovid,Web of Science,CNKI,and WanFang Data databases,and search for journal articles published from January 1,2000 to January 31,2023,on randomized controlled trials(RCTs)comparing the effects of HHO and THO in liver resection.At the same time,two researchers independently screened literature based on inclusion and exclusion cri-teria,conducted meta-analysis using RevMan 5.4 and State17PM software.Result:Fifteen RCTs were ultimately included,including 624 patients.The meta-analysis results showed that HHO re-duced serum AST(MD=-104.75,95％CI:-134.45-75.06,P＜0.05),ALT(MD=-155.37,95％CI:-182.90-127.85,P＜0.05),and TBIL(MD=-6.28,95％CI:-8.07-4.48,P＜0.05)on postoperative days 1,3,and 7 Compared to THO,the elevation of blood levels and reduction of intraoperative bleeding(MD=-66.21,95％CI:-116.49-15.94,P＜0.05)were superior.THO is superior to HHO in shortening surgical time(MD=13.94,95％CI:4.77-23.12,P＜0.05).There was no significant differ-ence between the two methods in hospital stay,hospital death rate and complication rate(P＞0.05).Conclusion:compared with THO,the application of HHO in hepatectomy has less damage to liver function and less intraoperative bleeding,but the two methods have the similar effect in terms of hospitalization time,hospital mortality rate and complication rate.

Objective:To systematically evaluate the clinical outcomes of hemihepatic inflow occlusion(HHO)and total hepatic inflow occlusion(THO)in liver resection surgery.Method:Re-trieve the Cochrane Library,PubMed,EMbase,Ovid,Web of Science,CNKI,and WanFang Data databases,and search for journal articles published from January 1,2000 to January 31,2023,on randomized controlled trials(RCTs)comparing the effects of HHO and THO in liver resection.At the same time,two researchers independently screened literature based on inclusion and exclusion cri-teria,conducted meta-analysis using RevMan 5.4 and State17PM software.Result:Fifteen RCTs were ultimately included,including 624 patients.The meta-analysis results showed that HHO re-duced serum AST(MD=-104.75,95％CI:-134.45-75.06,P＜0.05),ALT(MD=-155.37,95％CI:-182.90-127.85,P＜0.05),and TBIL(MD=-6.28,95％CI:-8.07-4.48,P＜0.05)on postoperative days 1,3,and 7 Compared to THO,the elevation of blood levels and reduction of intraoperative bleeding(MD=-66.21,95％CI:-116.49-15.94,P＜0.05)were superior.THO is superior to HHO in shortening surgical time(MD=13.94,95％CI:4.77-23.12,P＜0.05).There was no significant differ-ence between the two methods in hospital stay,hospital death rate and complication rate(P＞0.05).Conclusion:compared with THO,the application of HHO in hepatectomy has less damage to liver function and less intraoperative bleeding,but the two methods have the similar effect in terms of hospitalization time,hospital mortality rate and complication rate.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.
Animals ; Mice ; Endothelial Cells ; Toll-Like Receptor 2 ; Macrophages ; Apoptosis ; Atherosclerosis ; Myocytes, Smooth Muscle ; MicroRNAs

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Six new (1-6) and seven known depsidones (7-13) were isolated from the culture of an ant (Monomorium chinensis)-derived fungus Spiromastix sp. MY-1. Their structures were elucidated by extensive spectroscopic analysis including high resolution MS, 1D and 2D NMR data. The new bromide depsidones were obtained through supplementing potassium bromide in the fermentation medium of Spiromastix sp. MY-1. All isolated compounds showed various bioactivities against the tested phytopathogenic bacteria. Particularly, new bromide compound 4, named spiromastixone S, exhibited the strongest activity against Xanthomonas oryzae pv. oryzae with a MIC value of 5.2 μmol·^-1.
Animals ; Anti-Bacterial Agents ; Ants ; Bromides ; Depsides ; Fungi ; Lactones ; Microbial Sensitivity Tests ; Molecular Structure