Objectives:This study aimed to elucidate the incidence,clinical characteristics and prognosis of ST-elevation during radiofrequency catheter ablation for atrial fibrillation(AF). Methods:Consecutive patients who underwent radiofrequency catheter ablation for AF in Tongren Municipal People's Hospital,Qixingguan District People's Hospital of Bijie City and Guizhou Provincial People's Hospital from January 2021 to August 2023 were enrolled in this study.All patients underwent CARTO three-dimensional electroanatomical mapping and radiofrequency ablation via atrial septal approach under local anesthesia.The ST-elevation of electrocardiogram was analyzed.Follow-up was performed at 1,3,6,and 12 months after radiofrequency ablation.AF recurrence and duration,use of antiarrhythmic drugs,and incidence of death,thromboembolism,bleeding,and perioperative complications were evaluated. Results:ST-elevation was observed in 5 out of 798 patients(0.62%).ST-elevation occurred after transseptal puncture in three patients and during PentaRay multielectrode mapping in two patients.Blood pressure was significantly increased in three patients with transient ST-elevation(<20 min)and hemodynamic collapse occurred in two patients with persistent ST-elevation(>20 min).Catheter ablation of AF was completed in 4 patients,1 patient suffered severe hemodynamic disorders during radiofrequency catheter ablation,and the procedure was stopped immediately,this patient died from multiple organ system failure on the fifth day after failed radiofrequency catheter ablation,and the other 4 patients had no perioperative complications.The mean follow-up was(6±3)months,only 1 patient developed short atrial tachycardia,and the other patients had no recurrent atrial fibrillation and palpitation. Conclusions:Transient or persistent ST elevation can occur in patients during AF ablation.Early detection and rapid management are needed to prevent severe hemodynamic instability and cardiogenic death.

Public health emergencies pose severe challenges to the public health sector and emergency management work in hospitals.Enhancing the emergency management capabilities in general hospitals is of great significance in promoting high-quality development of hospitals,improving the government's public governance system,alleviating social panic,and other aspects.However,there are the practical dilemmas of insufficient monitoring and early warning,imperfect guarantee systems,and lack of technological innovation in emergency management in general hospitals.The emergency management capabilities in general hospitals can be improved through normalized monitoring and disposal,standing facility and material teams,information-based power systems,and standardization of technical support,further promoting the innovation and development of the emergency management system in general hospitals.

Objective:To explore the function of MDM2 and its relationship with p53 at the cellular level during H 2O 2 induced oxidative damage. Methods:MLE-12 HALI cell models were established using 0.5 mmol/L H 2O 2, and were divided into three groups: normal control group, H 2O 2 injury group, H 2O 2+MDM2 overexpressed group, and H 2O 2+MDM2 shRNA group. Infection of MLE-12 cells with adenovirus vector overexpressing and silencing MDM2; Using immunoprecipitation (Co-IP) to analyze the interaction between MDM2 and p53; Western blotting was used to detect the protein expression levels of MDM2, p53, Bcl-2, Bax, and cleared caspase-3 after HALI modeling; Measure the apoptosis rate of cells in each group. Results:After transcriptome sequencing,the p53 signaling pathway closely related to HALI. Compared with the normal group, the expression of MDM2 in the H 2O 2 injury group was lower ( P<0.05); Compared with the H 2O 2 injury group, overexpression of MDM2 resulted in a decrease in the apoptosis rate of MLE-12 cells ( P<0.05), a decrease in the expression levels of p53, Bax, and cleared caspase-3 proteins, and an upregulation of MDM2 and Bcl-2 protein expression ( P<0.05). Compared with the H 2O 2 injury group, when MDM2 was silenced, the cell apoptosis rate increased ( P<0.05), and the expression levels of p53, Bax, and cleared caspase-3 proteins were upregulated, while the expression levels of MDM2 and Bcl-2 proteins decreased ( P<0.05). Co-IP experiments showed that MDM2 binds to p53 protein. Conclusions:MDM2 can exert a protective effect on HALI by inhibiting MLE-12 cell apoptosis through the p53/Bcl-2/Bax axis.

MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.

BACKGROUND: Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intestinal injury model for sepsis. METHODS: Stable passaged organoids were constructed and pre-treated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury. The LPS-induced sepsis model was used as a reference. We used quantitative real-time polymerase chain reaction to evaluate the RNA levels of inflammatory factors and antimicrobial peptides. Enzyme-linked immunosorbent assay was used to evaluate the protein levels, hematoxylin and eosin staining was used to evaluate the pathology of the small intestine of mice, and immunohistochemistry and immunofluorescence were used to evaluate the intestinal epithelial barrier function. Perkin Elmer Operetta™ was used to obtain high-resolution images of three-dimensional organoids. RESULTS: An LPS concentration >150 μg/mL after 24 h was identified to cause organoid growth restriction. The fluorescence intensity of zonula occludens-1 and occludins at LPS concentrations >100 μg/mL decreased significantly after 24 h. After LPS stimulation for 8 h, the RNA expression levels of interleukin (IL)-1α, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, IL-6, and regenerating islet-derived protein 3 alpha, beta, and gamma increased. These results resembled those of intestinal epithelial layer alterations in a mouse sepsis model. For IL-10, the RNA expression level increased only when the LPS level >200 μg/mL for 24 h. CONCLUSIONS This study provides the primary intestinal in vitro model to study the effects of LPS-induced intestinal injury resembling sepsis. This model provides a platform for immune associated mechanism exploration and effective drug screening.
Mice ; Animals ; Lipopolysaccharides/toxicity* ; Sepsis ; Intestinal Diseases ; Tumor Necrosis Factor-alpha ; Disease Models, Animal ; Organoids ; RNA

Background::Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods::Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4-knockdown ( Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Results::CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. Conclusion::ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.

Objective:To investigate the clinic effect of r-MHT and hematoma aspiration on the traumatic intracerebral hematoma.Methods:89 cases with traumatic intracerebral hematoma were given hematoma aspiration,47 of them were given r-MHT and hematoma aspiration,the clinic effect on the 1st,7th,14th day after treatment were evaluated by NIHSS,the hematoma volume before treatment on the 1st,7th,14th day after treatment were counted by Dotian formula.Results:The effective rate of treatment group was 93.6％,which was significantly higher than that of the control group (P＜0.05).The NIHSS score of treatment group was significantly higher than that of the control group(P＜0.05) on the 1 st day,1st,2nd week after treatment (P＜0.05).Conclusion:r-MHT and hematoma aspiration couldn effectively reduce the brain damage,improve the patient's neurological fumction in treating traumatic intracerebral hematoma.

As a new form of medical practice,narrative medicine has been paid much attention since it was put forward.In the view of "narrative ability",narrative medicine has a strong oriental temperament.In the literature and art tradition of our country,which has existed thousands of years ago,disease and narrative of medicine has always been an important topic.Oriental physician group,represented by Confucian doctor,has the strongest narrative ability.Medical temperament and quality,represented by narrative,can connect the western and eastern medical traditions and medical culture and become the starting point of modern Chinese medical spirit,which combines western medical technology and oriental culture.

OBJECTIVE:To observe the success rate and safety of diphenhydramine combined with prednisone in the preven-tion of iodine-containing contrast agent allergic reactions. METHODS:1 day before surgery,42 patients with positive iodine aller-gy test was given 40 mg Prednisone tablet,orally,3 times a day,50 mg diphenhydramine was given by intramuscular injection and 1 ml iodine contrast by intravenous injection(allergy test performed again)1 h before surgery. After all patients used iodine con-trast in 15 min,vascular interventional treatment was conducted if there was no bronchospasm,angioedema,leather ball sample itchy rash,hypotension,itching and other allergic reactions. Prevention success rate were observed,and the incidence of adverse re-actions was recorded. RESULTS:Prevention success rate was 90.48%,the incidence of adverse reactions was 7.14%,and it self-improved after stopping drugs. CONCLUSIONS:Diphenhydramine combined with prednisone has high success rate in the pre-vention of iodine-containing contrast agent allergic reactions,with good safety.

OBJECTIVETo screen novel miRNAs targeting EZH2 3' untranslated region (UTR) in recombinational MCF-7 breast cancer cells over-expressing EZH2 3' UTR and quantitative analyze the expressions of the screened miRNA in breast cancer cells and tissues.

METHODSA lentiviral library was transfected into the recombinant cell line MCF-7. The cells were screened with cytotoxic agents before extraction of the genome for amplification of the miRNA precursors using PCR. The screened miRNAs were identified with sequence analysis and their expressions were analyzed quantitatively with real-time PCR in breast cancer cells and tissues.

RESULTSSeven miRNAs were screened from the recombinant MCF-7 cells, namely miR-15b, miR-16-2, miR-181b2, miR-217, miR-224, miR-329-1, and miR-487b, all of which failed to be predicted by bioinformatics software. Real-time PCR showed that miR-217, miR-329-1, and miR-487b were over-expressed in MCF-7 cells, and the expression of miR-15b and miR-16-2 was significantly increased in cancer tissues compared with the adjacent tissues (P<0.05).

CONCLUSIONNovel targeted miRNAs that can not be predicted by bioinformatics software were successfully screened from MCF-7 breast cancer cells over-expressing EZH2 3' UTR. These miRNAs are expressed differentially between normal breast cells and breast cancer tissues.

3' Untranslated Regions ; Breast Neoplasms ; genetics ; Cell Line, Tumor ; Enhancer of Zeste Homolog 2 Protein ; Female ; Gene Expression Profiling ; Humans ; Lentivirus ; genetics ; MicroRNAs ; genetics ; Polycomb Repressive Complex 2 ; genetics