Objective To investigate the effects of dapagliflozin on the risk of malignant ventricular arrhythmia(MVA)during hospitalization in patients with acute myocardial infarction(AMI).Methods A retrospective study was conducted to select patients with AMI who underwent percutaneous coronary intervention(PCI)in the department of cardiology of the Third Affiliated Hospital of Nanjing Medical University between January 2018 and November 2023.Clinical datas collected during hospitalization included demographics(gender,age),baseline vital signs(systolic blood pressure,diastolic blood pressure,heart rate),comorbidities(hypertension,diabetes mellitus),body mass index(BMI),smoking,alcohol consumption,ST segment elevation myocardial infarction(STEMI),Killip class≥3,laboratory parameters[white blood cell count(WBC),neutrophil percentage(NEU%),serum creatinine(SCr)],procedural data(number of coronary stents implanted,culprit vessels being the left main coronary artery,left anterior descending artery,right coronary artery,left circumflex artery and intraoperative hypotension),medications[angiotensin converting enzyme inhibitor/angiotensinⅡreceptor blocker(ACEI/ARB),β-blockers,aspirin,ticagrelor,clopidogrel,platelet glycoproteinⅡb/Ⅲa receptor antagonists,Statin],and electrocardiogram characteristics[the number of cases frequent ventricular premature contractions(premature beats)and the number of cases of sinus rhythm].The study endpoint was the occurrence of MVA during hospitalization among enrolled patients.Patients were categorized into the MVA group and the non-MVA group based on the occurrence of MVA during their hospital stay.Differences in clinical characteristics between the two groups were compared.Univariate and multivariate Logistic regression analyses were employed to evaluate the impact of dapagliflozin use on the risk of MVA in patients with AMI.Results A total of 2 893 eligible AMI patients were enrolled and 145 patients(5.01%)experienced MVA during hospitalization.Compared with the MVA group,the proportion of patients taking dapagliflozin was higher in the non-MVA group[13.2%(363/2 748)vs.6.2%(9/145),P=0.014],the proportion of males was higher[74.3%(2 042/2 748)vs.66.9%(97/145),P=0.048],the age was younger(years:64.82±13.91 vs.69.78±14.07,P<0.001),the heart rate at admission was slower(beats/min:80.09±15.72 vs.84.31±20.92,P=0.002),the proportion of patients with Killip grade≥3 was lower[11.5%(317/2 748)vs.38.6%(56/145),P<0.001],the proportion of smoking patients was higher[48.0%(1 319/2 748)vs.33.8%(49/145),P<0.05],SCr level was lower(μmol/L:84.73±58.52 vs.102.87±59.47,P<0.001),and the proportion of patients taking ACEI/ARB and β-blockers was higher[64.9%(1 783/2 748)vs.49.0%(71/145),65.1%(1 788/2 748)vs.53.8%(78/145),both P<0.05],the rate of frequent premature ventricular beats was lower[1.0%(28/2 748)vs.11.7%(17/145),P<0.05],and the proportion of patients with intraoperative hypotension was lower[3.2%(86/2 748)vs.10.6%(15/145),P<0.05].After adjusting numerous confounding factors,multifactorial Logistic regression analysis showed that dapagliflozin may significantly reduced the risk of MVA in patients with AMI after PCI[odds ratio(OR)=0.417,95%confidence interval(95%CI)was 0.200-0.880,P=0.022].Subgroup analysis suggested that there were 1 042 AMI patients with diabetes mellitus,of whom 348 took dapagliflozin,and 8 patients(2.30%)had MVA.The risk of MVA was reduced in patients taking dapagliflozin(Log-Rank:χ2=11.983,P=0.001).Conclusion The use of dapagliflozin significantly reduced the risk of MVA during hospitalization in patients with AMI.

Objective:To investigate the changes in the expression levels of long non-coding ribonucleic acids (lncRNAs) in human lymphocytes induced by low-dose ionizing radiation (LDIR) and the potential of lncRNAs as radiation biomarkers.Methods:Human immortalized lymphocytes (AHH-1) were irradiated with 0, 0.05, and 0.1 Gy of γ-rays at 24 h to extract RNAs for whole transcriptome sequencing. The sequencing was performed based on the 0, 0.05, and 0.1 Gy groups. The differentially expressed lncRNAs induced by LDIR were identified. The molecular functions, biological processes, and signaling pathway enrichment of differentially expressed genes were analyzed through the Gene Ontology (GO) analysis. Candidate lncRNAs were preliminarily validated using the qRT-PCR method. AHH-1 cells were irradiated with 0, 0.02, 0.05, 0.075, 0.1, and 0.2 Gy to extract the total RNAs at 4, 24, 48, 72, 96, and 120 h. The dose-response relationship of candidate lncRNAs was detected and analyzed. Peripheral blood sampled from eight healthy persons was irradiated with 0, 0.02, 0.05, 0.075, 0.1, and 0.2 Gy in vitro, followed by culturing for 24 h and 48 h to further verify the changes in the expression levels of radiation-responsive lncRNAs at the cellular level. Results:A total of 44 lncRNAs that were significantly up- or down-regulated after 0.05 and 0.1 Gy irradiation were initially identified through transcriptome sequencing. Among them, lncRNAs with over two-fold differential expression included SNHG1, SNHG15, NEAT1, and PRC1-AS1. At the cellular level, compared to 0 Gy, the relative expression level of PRC1-AS1 after 4 h to 48 h of γ-ray irradiation, was significantly elevated at 0.05, 0.075, and 0.1 Gy( t= -3.11 to 1.23, P < 0.05). In contrast, the relative expression level of NEAT1 was significantly up-regulated in a dose range of 0.02 to 0.1 Gy ( t=-2.47 to 2.10, P < 0.05). At the level of human peripheral blood, the relative expression levels of PRC1-AS1 and NEAT1 were significantly increased at 24 h after 0 to 0.2 Gy irradiation ( t=-3.79 to -1.96, P < 0.05). Conclusion:The PRC1-AS1 and NEAT1 with significant changes in expression levels serve as potential LDIR biomarkers.

China emerges as a major country in nuclear energy development and the application of nuclear and radiologic technology. The diagnosis and treatment of acute radiation syndrom (ARS) caused by external irradiation represent a core function in the country′s medical rescue of nuclear and radiological emergencies. Clinically, ARS manifests hematopoietic, gastrointestinal, cutaneous, and central nervous system syndromes, with specific clinical manifestations, signs, severity, and prognosis strongly correlated with radiation dose. China has established a number of national and provincial centers for treating radiation-induced damage. Nevertheless, most medical staff have limited experience in ARS treatment. This consensus presents a summary of recent experience in treating ARS of China. In combination with recommendations from international organizations such as the World Health Organization (WHO), this consensus proposes key evidence of critical clinical issues of ARS, covering all links in the rescue of external irradiation-induced ARS. Initially, clinical diagnosis, syndromes, and severe degrees should be determined based on clinical symptoms and dose estimates. It is necessary to normalize clinical treatment measures for hematopoietic recovery, gastrointestinal injury treatment, infection control, symptomatic treatment, and multi-organ function preservation. To this end, this consensus offers cautions. This consensus provides principles of treatment with traditional Chinese medicine, psychological intervention, and follow-up. Additionally, it highlights multidisciplinary collaboration. It is recommended that this consensus be applied in relevant treatment centers.

Salmonellosis represents a global epidemic, and the emergence of extensively drug-resistant (XDR) Salmonella and its sustained transmission worldwide constitutes a significant public health concern. Flagellum-mediated motility serves as a crucial virulence trait of Salmonella that guides the pathogen toward the epithelial surface, enhancing gut colonization. Artemisia argyit essential oil, a traditional herb extract, demonstrates efficacy in treating inflammation-related symptoms and diseases; however, its effects on flagellum assembly and expression mechanisms in anti-Salmonella activity remain inadequately explored. This study aimed to elucidate the mechanism by which Artemisia argyit essential oil addresses Salmonella infections. Network pharmacological analysis revealed that Traditional Chinese Medicine (TCM) Artemisia argyit exhibited anti-Salmonella infection potential and inhibited flagellum-dependent motility. The application of Artemisia argyit essential oil induced notable motility defects through the downregulation of flagellar and fimbriae expression. Moreover, it significantly reduced Salmonella-infected cell damage by interfering with flagellum-mediated Salmonella colonization. In vivo studies demonstrated that Artemisia argyit essential oil administration effectively alleviated Salmonella infection symptoms by reducing bacterial loads, inhibiting interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) production, and diminishing pathological injury. Gas chromatography-mass spectrometry (GC-MS) analysis identified forty-three compounds in Artemisia argyit essential oil, with their corresponding targets and active ingredients predicted. Investigation of an in vivo model of Salmonella infection using the active ingredient demonstrated that alpha-cedrene ameliorated Salmonella infection. These findings suggest the potential application of Artemisia argyit essential oil in controlling Salmonella, the predominant food-borne pathogen.
Artemisia/chemistry* ; Oils, Volatile/chemistry* ; Animals ; Flagella/drug effects* ; Salmonella Infections/microbiology* ; Humans ; Mice ; Anti-Bacterial Agents/pharmacology* ; Salmonella/pathogenicity*

Glucosidases are an indispensable class of enzymes in the sugar metabolism of organisms. To investigate the biological functions and expression patterns of α-glucosidases (AGLUs) and β-glucosidases (BGLUs), we identified the two family members in the genome of melon (Cucumis melo). The number, location on chromosomes, gene structure, subcellular localization, conserved motifs, and phylogenetic relationship of the two family members were analyzed. Based on the cis-acting elements in the promoter region and protein interaction models, their functions were preliminarily predicted. Furthermore, the gene expression of the two family members was determined by qRT-PCR. The results showed that the melon genome contained five AGLU family members on five chromosomes, and all of the five members were located in the extracellular matrix, with the amino acid sequence lengths ranging from 899 aa to 1 060 aa. The melon genome carried 18 BGLU family members on 8 chromosomes, and all the members were located in the cell membrane or cytoplasm, with the amino acid lengths ranging from 151 aa to 576 aa. The qRT-PCR results showed that the expression of about 50% of the genes was down-regulated upon cold stress. CmAGLU5 and CmBGLU7 may be key members of the two families, respectively, in response to cold stress. The expression of all members of the two families was up-regulated under abscisic acid (ABA), high salt, and drought stress. In the AGLU family, CmAGLU3 was the key gene in response to ABA and high salt stress, while CmAGLU4 was the key gene in response to drought stress. In the BGLU family, CmBGLU18 was the key gene in response to ABA, while CmBGLU6 was the key gene in response to high salt and drought stress.
beta-Glucosidase/metabolism* ; Phylogeny ; alpha-Glucosidases/metabolism* ; Gene Expression Regulation, Plant ; Cucurbitaceae/enzymology* ; Multigene Family ; Cucumis melo/enzymology* ; Stress, Physiological

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

OBJECTIVE: To investigate the role of telomerase reverse transcriptase (TERT) in alleviating doxorubicin (DOX)-induced cardiotoxicity. METHODS: (1) Cell experiments: rat H9c2 cardiomyocytes were divided into control group (CON group), null adenovirus transfection group (NC group), TERT overexpression adenovirus transfection group (TERT group), DOX group (treated with 1 μmol/L DOX for 12 hours), DOX+NC group, and DOX+TERT group (null adenovirus or TERT overexpression adenovirus were transfected for 24 hours and then treated with 1 μmol/L DOX for 12 hours). The mRNA expression of TERT in cardiomyocytes was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The level of mitochondrial membrane potential was detected by immunofluorescence. The expression levels of intracellular Bax, Bcl-2, microtubule-associated protein 1 light chain 3 (LC3) and p62 were detected by Western blotting. (2) Animal experiments: male C57BL/6 mice were randomly divided into a sham operation group (Sham group), DOX group (acute cardiotoxicity model was constructed by intraperitoneal injection of DOX 15 mg/kg), DOX+NC group and DOX+TERT group (modeled after transfection with airborne adenovirus or TERT overexpression adenovirus for 7 days). After 7 days of modeling, the area of myocardial fibrosis was detected by Sirius scarlet staining, and cardiac function was detected by echocardiography. RESULTS: (1) Cellular experiments: the mRNA expression level of TERT was significantly higher in the TERT group compared with the CON and NC groups. Compared with the CON group, the TERT mRNA expression level of cardiomyocytes in the DOX group and the DOX+NC group were significantly lower, the level of mitochondrial membrane potential was significantly lower, the protein expressions of Bax and LC3 were significantly increased, and the protein expressions of Bcl-2 and p62 were significantly decreased. No significant differences were found between the DOX group and DOX+NC group. Compared with the DOX group and DOX+NC group, the TERT mRNA expression level was increased in the DOX+TERT group (relative expression: 1.02±0.10 vs. 0.61±0.05, 0.54±0.03, both P < 0.05), the level of mitochondrial membrane potential was significantly increased (1.14±0.05 vs. 0.96±0.01, 0.96±0.01, both P < 0.05), the protein expressions of Bax and LC3 were significantly decreased, and the protein expressions of Bcl-2 and p62 were significantly increased (Bax/β-actin: 0.88±0.01 vs. 1.31±0.02, 1.26±0.01; LC3-II/I: 2.16±0.05 vs. 2.64±0.06, 2.58±0.02; Bcl-2/β-actin: 0.65±0.01 vs. 0.40±0.01, 0.41±0.01; p62/β-actin: 0.45±0.01 vs. 0.23±0.02, 0.29±0.01; all P < 0.05). (2) Animal experiments: compared with the Sham group, the percentage of myocardial fibrosis area was significantly increased and left ventricular ejection fraction (LVEF) and fractional shortening (FS) were significantly decreased in the DOX group and DOX+NC group. Compared with the DOX group and DOX+NC group, the percentage of myocardial fibrotic area was significantly decreased in the DOX+TERT group (%: 2.33±0.06 vs. 3.76±0.07, 3.87±0.06, both P < 0.05), and the LVEF and FS were significantly increased [LVEF (%): 67.00±1.14 vs. 54.60±1.57, 53.40±2.18; FS (%): 38.60±0.51 vs. 30.60±1.10, 30.00±0.71; all P < 0.05]. CONCLUSION Up-regulation of TERT expression can inhibit DOX-induced cardiomyocyte autophagy and apoptosis, attenuate DOX-induced myocardial fibrosis in mice, improve cardiac function, and thus alleviate DOX-induced cardiotoxicity.
Animals ; Doxorubicin/toxicity* ; Telomerase/metabolism* ; Myocytes, Cardiac/metabolism* ; Rats ; Male ; Cardiotoxicity ; Mice, Inbred C57BL ; Mice ; Membrane Potential, Mitochondrial ; Adenoviridae ; bcl-2-Associated X Protein/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Transfection ; Apoptosis

Objective:To investigate the changes in the expression levels of long non-coding ribonucleic acids (lncRNAs) in human lymphocytes induced by low-dose ionizing radiation (LDIR) and the potential of lncRNAs as radiation biomarkers.Methods:Human immortalized lymphocytes (AHH-1) were irradiated with 0, 0.05, and 0.1 Gy of γ-rays at 24 h to extract RNAs for whole transcriptome sequencing. The sequencing was performed based on the 0, 0.05, and 0.1 Gy groups. The differentially expressed lncRNAs induced by LDIR were identified. The molecular functions, biological processes, and signaling pathway enrichment of differentially expressed genes were analyzed through the Gene Ontology (GO) analysis. Candidate lncRNAs were preliminarily validated using the qRT-PCR method. AHH-1 cells were irradiated with 0, 0.02, 0.05, 0.075, 0.1, and 0.2 Gy to extract the total RNAs at 4, 24, 48, 72, 96, and 120 h. The dose-response relationship of candidate lncRNAs was detected and analyzed. Peripheral blood sampled from eight healthy persons was irradiated with 0, 0.02, 0.05, 0.075, 0.1, and 0.2 Gy in vitro, followed by culturing for 24 h and 48 h to further verify the changes in the expression levels of radiation-responsive lncRNAs at the cellular level. Results:A total of 44 lncRNAs that were significantly up- or down-regulated after 0.05 and 0.1 Gy irradiation were initially identified through transcriptome sequencing. Among them, lncRNAs with over two-fold differential expression included SNHG1, SNHG15, NEAT1, and PRC1-AS1. At the cellular level, compared to 0 Gy, the relative expression level of PRC1-AS1 after 4 h to 48 h of γ-ray irradiation, was significantly elevated at 0.05, 0.075, and 0.1 Gy( t= -3.11 to 1.23, P < 0.05). In contrast, the relative expression level of NEAT1 was significantly up-regulated in a dose range of 0.02 to 0.1 Gy ( t=-2.47 to 2.10, P < 0.05). At the level of human peripheral blood, the relative expression levels of PRC1-AS1 and NEAT1 were significantly increased at 24 h after 0 to 0.2 Gy irradiation ( t=-3.79 to -1.96, P < 0.05). Conclusion:The PRC1-AS1 and NEAT1 with significant changes in expression levels serve as potential LDIR biomarkers.

China emerges as a major country in nuclear energy development and the application of nuclear and radiologic technology. The diagnosis and treatment of acute radiation syndrom (ARS) caused by external irradiation represent a core function in the country′s medical rescue of nuclear and radiological emergencies. Clinically, ARS manifests hematopoietic, gastrointestinal, cutaneous, and central nervous system syndromes, with specific clinical manifestations, signs, severity, and prognosis strongly correlated with radiation dose. China has established a number of national and provincial centers for treating radiation-induced damage. Nevertheless, most medical staff have limited experience in ARS treatment. This consensus presents a summary of recent experience in treating ARS of China. In combination with recommendations from international organizations such as the World Health Organization (WHO), this consensus proposes key evidence of critical clinical issues of ARS, covering all links in the rescue of external irradiation-induced ARS. Initially, clinical diagnosis, syndromes, and severe degrees should be determined based on clinical symptoms and dose estimates. It is necessary to normalize clinical treatment measures for hematopoietic recovery, gastrointestinal injury treatment, infection control, symptomatic treatment, and multi-organ function preservation. To this end, this consensus offers cautions. This consensus provides principles of treatment with traditional Chinese medicine, psychological intervention, and follow-up. Additionally, it highlights multidisciplinary collaboration. It is recommended that this consensus be applied in relevant treatment centers.

Objective To investigate the effects of dapagliflozin on the risk of malignant ventricular arrhythmia(MVA)during hospitalization in patients with acute myocardial infarction(AMI).Methods A retrospective study was conducted to select patients with AMI who underwent percutaneous coronary intervention(PCI)in the department of cardiology of the Third Affiliated Hospital of Nanjing Medical University between January 2018 and November 2023.Clinical datas collected during hospitalization included demographics(gender,age),baseline vital signs(systolic blood pressure,diastolic blood pressure,heart rate),comorbidities(hypertension,diabetes mellitus),body mass index(BMI),smoking,alcohol consumption,ST segment elevation myocardial infarction(STEMI),Killip class≥3,laboratory parameters[white blood cell count(WBC),neutrophil percentage(NEU%),serum creatinine(SCr)],procedural data(number of coronary stents implanted,culprit vessels being the left main coronary artery,left anterior descending artery,right coronary artery,left circumflex artery and intraoperative hypotension),medications[angiotensin converting enzyme inhibitor/angiotensinⅡreceptor blocker(ACEI/ARB),β-blockers,aspirin,ticagrelor,clopidogrel,platelet glycoproteinⅡb/Ⅲa receptor antagonists,Statin],and electrocardiogram characteristics[the number of cases frequent ventricular premature contractions(premature beats)and the number of cases of sinus rhythm].The study endpoint was the occurrence of MVA during hospitalization among enrolled patients.Patients were categorized into the MVA group and the non-MVA group based on the occurrence of MVA during their hospital stay.Differences in clinical characteristics between the two groups were compared.Univariate and multivariate Logistic regression analyses were employed to evaluate the impact of dapagliflozin use on the risk of MVA in patients with AMI.Results A total of 2 893 eligible AMI patients were enrolled and 145 patients(5.01%)experienced MVA during hospitalization.Compared with the MVA group,the proportion of patients taking dapagliflozin was higher in the non-MVA group[13.2%(363/2 748)vs.6.2%(9/145),P=0.014],the proportion of males was higher[74.3%(2 042/2 748)vs.66.9%(97/145),P=0.048],the age was younger(years:64.82±13.91 vs.69.78±14.07,P<0.001),the heart rate at admission was slower(beats/min:80.09±15.72 vs.84.31±20.92,P=0.002),the proportion of patients with Killip grade≥3 was lower[11.5%(317/2 748)vs.38.6%(56/145),P<0.001],the proportion of smoking patients was higher[48.0%(1 319/2 748)vs.33.8%(49/145),P<0.05],SCr level was lower(μmol/L:84.73±58.52 vs.102.87±59.47,P<0.001),and the proportion of patients taking ACEI/ARB and β-blockers was higher[64.9%(1 783/2 748)vs.49.0%(71/145),65.1%(1 788/2 748)vs.53.8%(78/145),both P<0.05],the rate of frequent premature ventricular beats was lower[1.0%(28/2 748)vs.11.7%(17/145),P<0.05],and the proportion of patients with intraoperative hypotension was lower[3.2%(86/2 748)vs.10.6%(15/145),P<0.05].After adjusting numerous confounding factors,multifactorial Logistic regression analysis showed that dapagliflozin may significantly reduced the risk of MVA in patients with AMI after PCI[odds ratio(OR)=0.417,95%confidence interval(95%CI)was 0.200-0.880,P=0.022].Subgroup analysis suggested that there were 1 042 AMI patients with diabetes mellitus,of whom 348 took dapagliflozin,and 8 patients(2.30%)had MVA.The risk of MVA was reduced in patients taking dapagliflozin(Log-Rank:χ2=11.983,P=0.001).Conclusion The use of dapagliflozin significantly reduced the risk of MVA during hospitalization in patients with AMI.