Objective: To investigate the methylation status of the RUNX family transcription factor 3 ( RUNX3)promoter and its mRNA expression in sepsis patients , and to analyze their relationship with the prognosis of sepsis. Methods: Differentially expressed genes related to sepsis , including RUNX3 , were identified from multiple datasets obtained from the gene expression omnibus (GEO) database. The gene expression and methylation sites were validated. A total of 120 patients with sepsis were included. Clinical data were recorded , and blood samples were collected at enrollment. Relative expression levels of RUNX3 in blood samples and promoter methylation status were detected using qPCR and methylation⁃specific PCR ( MSP) , respectively. Pearson correlation coefficients were used to analyze the correlation between RUNX3 levels in patient blood and clinical indicators. Kaplan⁃Meier analysis was performed to plot survival curves , and Cox proportional hazards regression analysis was conducted to identify factors affecting the prognosis of sepsis patients. Results: Data set analysis revealed that RUNX3 was a differentially methylated gene associated with the prognosis of sepsis. The mRNA expression level of RUNX3 was lower in the non-survivor group compared to the survivor group (P < 0. 05) , and the methylation ratio of RUNX3 was higher in the non-survivor group than in the survivor group (P < 0. 05) . In sepsis patients , RUNX3 mRNA expression levels were negatively correlated with interleukin-6 ( IL-6) , procalcitonin ( PCT) , C-reactive protein ( CRP) , acute physiology and chronic health evaluation ( APACHE Ⅱ ) score , and sequential organ failure assessment ( SOFA) score. Kaplan-Meier analysis showed that the 28-day survival rate in the methylated group was lower than that in the unmethylated group ( P < 0. 05) . Cox regression analysis results indicated that RUNX3 promoter methylation was an independent risk factor for predicting the 28-day prognosis of sepsis patients. Conclusion In sepsis patients , the mRNA levels of RUNX3 were reduced , and the degree of promoter methylation was higher. RUNX3 promoter methylation was an independent risk factor for the 28-day prognosis of sepsis patients and could serve as a prognostic biomarker for sepsis.

Portal vein thrombosis (PVT) is one of the most common complications of liver cirrhosis. The formation of PVT can increase the mortality rate of cirrhotic patients and adversely affect the successful implementation and prognosis of liver transplantation. A hypercoagulable state is a unique mechanism underlying PVT formation in cirrhotic patients. In recent years, the pathogenesis of PVT has gradually been elucidated, with specific mechanisms including the following aspects: systemic and local inflammatory responses lead to vascular endothelial cell dysfunction, thereby promoting the activation of the coagulation system; abnormal activation of the monocyte-macrophage system exacerbates local inflammation, enhancing platelet adhesion and aggregation, and facilitating thrombus formation; an imbalance between the coagulation and fibrinolytic systems results in a sustained hypercoagulable state; and intestinal microbiota dysbiosis induces inflammation and metabolic disturbances, thereby increasing the risk of PVT. This article summarizes the latest research progress on these key mechanisms and their interactions, providing new insights into the molecular and cellular mechanisms of PVT. It also offers directions for the early diagnosis of PVT and the exploration of novel intervention strategies in the future.

Objective:To explore the impact of changes of myocardial infarct size on left ventricular adverse remodeling in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI).Methods:This was a prospective cohort study. The STEMI patients who underwent primary PCI in the First Medical Center of the Chinese People′s Liberation Army General Hospital, Beijing Anzhen Hospital, Hainan Hospital of the Chinese People′s Liberation Army General Hospital and Guangxi Yulin First People Hospital from January 1, 2017 to January 1, 2022 were enrolled. Cardiac magnetic resonance (CMR) was performed to dynamically assess the myocardial infarct size and calculate the rate of infarct size change between the acute phase (5 to 7 days post-primary PCI) and 6-month follow-up. The endpoint was left ventricular adverse remodeling which was defined as an increase of more than 20% in left ventricular end-diastolic volume (LVEDV) assessed by CMR at 6 months after primary PCI compared with LVEDV at 1 week after primary PCI. Based on serial CMR assessments, the patients were divided into left ventricular adverse remodeling group and non-remodeling group. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of infarct size change for left ventricular adverse remodeling, and according to the optimal cutoff value, improved infarct size was defined as a decrease of >20% in the infarct size measured by CMR at 6 months after primary PCI compared with infarct size at 1 week after primary PCI. Multivariate logistic regression analysis was performed to identify the protective factors and risk factors for left ventricular adverse remodeling.Results:A total of 267 patients were enrolled, aged (58±11) years, with 234 males (87.6%). And 73 cases in the left ventricular remodeling group and 194 cases in the non-remodeling group. Infarct size assessed by CMR at 6 months after primary PCI decreased significantly compared with infarct size at 1 week after primary PCI in the left ventricular remodeling group ((23±13)% vs. (27±12)%, P=0.004), the same as in the non-remodeling group ((18±10)% vs. (23±10)%, P<0.001). The area under the ROC curve for the rate of infarct size change in predicting left ventricular remodeling was 0.735 (95% CI 0.670-0.799, P<0.001), a 20% reduction was the optimal cut-off value. Compared to the patients with non-improved infarct size, the incidence of left ventricular adverse remodeling was significantly lower in the patients with improved infarct size (18% (24/133) vs. 37% (49/134), P=0.001). Multivariate logistic regression analysis showed that improvement in IS was a protective factor for left ventricular adverse remodeling ( OR=0.376, 95% CI 0.236-0.721, P=0.002). Conclusion:Patients with STEMI who experience obvious reduction in infarct size after primary PCI have a significantly reduced risk of left ventricular adverse remodeling.

Objective:To explore the impact of changes of myocardial infarct size on left ventricular adverse remodeling in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI).Methods:This was a prospective cohort study. The STEMI patients who underwent primary PCI in the First Medical Center of the Chinese People′s Liberation Army General Hospital, Beijing Anzhen Hospital, Hainan Hospital of the Chinese People′s Liberation Army General Hospital and Guangxi Yulin First People Hospital from January 1, 2017 to January 1, 2022 were enrolled. Cardiac magnetic resonance (CMR) was performed to dynamically assess the myocardial infarct size and calculate the rate of infarct size change between the acute phase (5 to 7 days post-primary PCI) and 6-month follow-up. The endpoint was left ventricular adverse remodeling which was defined as an increase of more than 20% in left ventricular end-diastolic volume (LVEDV) assessed by CMR at 6 months after primary PCI compared with LVEDV at 1 week after primary PCI. Based on serial CMR assessments, the patients were divided into left ventricular adverse remodeling group and non-remodeling group. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of infarct size change for left ventricular adverse remodeling, and according to the optimal cutoff value, improved infarct size was defined as a decrease of >20% in the infarct size measured by CMR at 6 months after primary PCI compared with infarct size at 1 week after primary PCI. Multivariate logistic regression analysis was performed to identify the protective factors and risk factors for left ventricular adverse remodeling.Results:A total of 267 patients were enrolled, aged (58±11) years, with 234 males (87.6%). And 73 cases in the left ventricular remodeling group and 194 cases in the non-remodeling group. Infarct size assessed by CMR at 6 months after primary PCI decreased significantly compared with infarct size at 1 week after primary PCI in the left ventricular remodeling group ((23±13)% vs. (27±12)%, P=0.004), the same as in the non-remodeling group ((18±10)% vs. (23±10)%, P<0.001). The area under the ROC curve for the rate of infarct size change in predicting left ventricular remodeling was 0.735 (95% CI 0.670-0.799, P<0.001), a 20% reduction was the optimal cut-off value. Compared to the patients with non-improved infarct size, the incidence of left ventricular adverse remodeling was significantly lower in the patients with improved infarct size (18% (24/133) vs. 37% (49/134), P=0.001). Multivariate logistic regression analysis showed that improvement in IS was a protective factor for left ventricular adverse remodeling ( OR=0.376, 95% CI 0.236-0.721, P=0.002). Conclusion:Patients with STEMI who experience obvious reduction in infarct size after primary PCI have a significantly reduced risk of left ventricular adverse remodeling.

Objective To study the effect of microRNA-192(miR-192)on the proliferation,migration and invasion ability of colorectal cancer(CC)cell lines.Methods Group A(SW1116 CC transfected with physio-logical saline),group B(SW1116 CC transfected with miR-192 mimics)and group C(SW1116 CC transfected with miR-192 inhibitor)were set up,respectively.Cell proliferation was detected by MTT assay,cell apoptosis was detected by flow cytometry,cell migration ability was detected by scratch assay,and cell invasion ability was detected by Transwell assay.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the mRNA expression levels of miR-192 and WNT family member 2B(WNT2B)in each group.Results The survival rate and monoclonal number of SW1116 CC cells in group B were(57.32± 6.19)％and(284.59±15.08),which were lower than(76.21±8.23)％and(601.47±23.16)in group A and(89.52±10.62)％and(2 150.68±34.79)in group C,while the apoptosis rate in group B was(20.52± 2.52)％,which was higher than(13.78±1.62)％in group A and(11.62±1.41)％in group C.The survival rate and number of monoclonal formation of SW1116 CC cells in group C were higher than those in group A,while the apoptosis rate was lower than that in group A(all P＜0.05).The scratch width of SW1116 CC cells in group B was(785.10±46.18)mm,which was higher than(601.32±33.21)mm in group A and(326.99± 17.48)mm in group C,while the scratch width in group C was lower than that in group A.The number of per-forating cells in group B was(624.67±19.05),which was lower than(875.23±27.30)in group A and(1 204.17±34.59)in group C,and the number of perforating cells in group C was higher than that in group A(all P＜0.05).The relative expression level of miR-192 mRNA in SW1116 CC cells in group B was(3.01± 0.26),which was higher than(1.87±0.20)in group A and(0.97±0.23)in group C,and the relative expres-sion level of miR-192 mRNA in group C was lower than that in group A.The expression level of WNT2B mR-NA in group B was(2.16±0.26),which was lower than(4.11±0.50)in group A and(6.08±0.72)in group C,and the expression level of WNT2B mRNA in group C was higher than that in group A(all P＜0.05).Con-clusion miR-192 could inhibit the malignant evolution of CC,and one of its main mechanisms may be related to the regulation of WNT2B expression.

ObjectiveTo investigate the induction of ferroptosis by polyphyllin Ⅱ （PPⅡ） in hepatocellular carcinoma HepG2 cells and its underlying mechanism. MethodThe effect of PPⅡ （0， 1.5， 3.0， 4.5， 6.0， 9.0， 18.0 mg·L^-1） on the in vitro proliferation of HepG2 cells was assessed using the methyl thiazolyl tetrazolium （MTT） assay. Colony formation ability of HepG2 cells was evaluated through a colony formation assay. Cell migration ability was assessed via a scratch assay. Lactate dehydrogenase （LDH） content in HepG2 cells was measured using a kit. Reactive oxygen species （ROS） levels in HepG2 cells were observed using a fluorescence inverted microscope. Malondialdehyde （MDA）， glutathione （GSH）， and free Fe²⁺ content in HepG2 cells were detected using respective kits. The mitochondrial ultrastructure in HepG2 cells was observed by transmission electron microscopy. The expression of ferroptosis-related proteins p53， solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， and transferrin receptor 1 （TFR1） in HepG2 cells was detected using Western blot. ResultCompared with the control group， the PPⅡ treatment groups showed significantly decreased survival rate of HepG2 cells in a dose-dependent manner （P<0.01）， significantly reduced number of cell colonies （P<0.01）， significantly shortened scratch healing distance， inverse correlation of the migration distance with drug concentration （P<0.01）， significantly increased LDH leakage in cells （P<0.01）， significantly enhanced relative fluorescence intensity of intracellular ROS， and significantly increased accumulation of lipid peroxide MDA （P<0.01）， decreased intracellular GSH content with increasing drug concentration （P<0.01）， and significantly enhanced fluorescence intensity of FeRhoNox-1 in cells （P<0.01）. Moreover， cells exhibited vacuolation， and mitochondria showed significant shrinkage with reduced or even disappeared cristae. Compared with the results in the control group， the expression of p53， ACSL4， and TFR1 proteins significantly increased， while the expression of SLC7A11 and GPX4 proteins significantly decreased in the PPⅡ treatment groups （P<0.05）. ConclusionIn summary， PPⅡ induces ferroptosis in HepG2 cells by regulating the p53/SLC7A11/GPX4 signaling axis， promoting ACSL4 expression and Fe³⁺ uptake， leading to an imbalance in the antioxidant system.

Objective:To analyze the clinical diagnosis, treatment ，and surgical timing of otogenic intracranial complications. Methods:The clinical data of 11 patients with intracranial complications with ear symptoms as the first manifestation in Department of Otorhinolaryngology Head and Neck Surgery, Qilu Hospital of Shandong University（Qingdao） from December 2014 to June 2022 were collected, including 8 males and 3 females, aged from 4 to 69 years. All patients had complete otoendoscopy, audiology, imaging and etiology examination, and the diagnosis and treatment plan was jointly developed through multidisciplinary consultation according to the critical degree of clinical symptoms and imaging changes. Among the 11 patients, 5 cases were treated with intracranial lesions first in neurosurgery department and middle ear lesions later in otolaryngology, 3 cases of meningitis, were treated with middle ear surgery after intracranial infection control, 1 case was treated with middle ear lesions and intracranial infection simultaneously, and 2 cases were treated with sigmoid sinus and transverse sinus thrombosis conservatively. They were followed up for 1-6 years. Descriptive statistical methods were used for analysis. Results:All the 11 patients had ear varying symptoms, including ear pain, pus discharge and hearing loss, etc, and then fever appeared, headache, disturbance of consciousness, facial paralysis and other intracranial complication. Otoendoscopy showed perforation of the relaxation of the tympanic membrane in 5 cases, major perforation of the tension in 3 cases, neoplasia in the ear canal in 1 case, bulging of the tympanic membrane in 1 case, and turbidity of the tympanic membrane in 1 case. There were 4 cases of conductive hearing loss, 4 cases of mixed hearing loss and 3 cases of total deafness. Imaging examination showed cholesteatoma of the middle ear complicated with temporal lobe brain abscess in 4 cases, cerebellar abscess in 2 cases, cholesteatoma of the middle ear complicated with intracranial infection in 3 cases, and sigmoid sinus thrombophlebitis in 2 cases. In the etiological examination, 2 cases of Streptococcus pneumoniae were cultured in the pus of brain abscess and cerebrospinal fluid, and 1 case was cultured in streptococcus vestibularis, Bacteroides uniformis and Proteus mirabilis respectively. During the follow-up, 1 patient died of cardiovascular disease 3 years after discharge, and the remaining 10 patients survived. There was no recurrence of intracranial and middle ear lesions. Sigmoid sinus and transverse sinus thrombosis were significantly improved. Conclusion:Brain abscess, intracranial infection and thrombophlebitis are the most common otogenic intracranial complications, and cholesteatoma of middle ear is the most common primary disease. Timely diagnosis, multidisciplinary collaboration, accurate grasp of the timing in the treatment of primary focal and complications have improved the cure rate of the disease.
Female ; Humans ; Male ; Brain Abscess/therapy* ; Cholesteatoma ; Deafness/etiology* ; Hearing Loss/etiology* ; Lateral Sinus Thrombosis/therapy* ; Retrospective Studies ; Thrombophlebitis/therapy* ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Cholesteatoma, Middle Ear/therapy* ; Central Nervous System Infections/therapy* ; Sinus Thrombosis, Intracranial/therapy* ; Ear Diseases/therapy*

OBJECTIVE To isolate and ide ntify the chemical constituents of the root of Ardisia virens and preliminarily evaluate the in vitro anti-inflammatory activity of the compounds. METHODS The ethyl acetate extraction part from 70％ ethanol extract of the root of A. virens were separated and purified by silica gel column chromatography ，ODS column chromatography ， etc. The structures of the compounds were identified according to physical and chemical properties and spectral data. The inflammation model of RAW 264.7 cells was induced by lipopolysaccharide ，and anti-inflammatory activity of the compound was investigated by MTT assay. RESULTS A total of 11 compounds were isolated from the ethyl acetate extraction part ，and were identified as cyclamiretin A （1），α-spinasterol （2），（3S，5R，6S，7E）-3，5，6-trihydroxy-7-megastigmen-9-one （3）， （+）-angelicoidenol（4），octadeca-dienoic acid- 2，3-dihydroxypropyl ester （5），α-linolenic acid （6），glycerol monooleate （7），5， 5′-（4，7-hexadecadlene-1，16-diyl）bisresorcinol（8），1-（3，5-dihydroxyphenyl）heptan-1-one（9），5-heptylresorcinol and （10） 5-n-nonylresorcinol（11）. The in vitro anti-inflammatory results showed that 80，40，20，10，5 μg/mL of compounds 2，8，9 and 10 could reduce the cell survival rate in different degrees. CONCLUSIONS Compounds 1-11 are isolated from this plant for the first time，and compound 8 is a new natural product. Compound 2，8，9 and 10 show certain anti-inflammatory activity in vitro .

Objective:To analyze and screen the key genes of sepsis secondary to pulmonary infection by bioinformatics, and to provide theoretical basis for the basic research of the disease and find an ideal animal model program.Methods:Experiment 1 (bioinformatics analysis): gene expression data sets of pulmonary infection secondary sepsis patients and multiple sepsis animal models were screened by Gene Expression Omnibus (GEO) Database, and gene differences were analyzed by R software. Differential genes were analyzed by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Correlation analysis was conducted between differential genes and clinical symptoms in the data set of pulmonary infection secondary sepsis, and the correlation heat map between differential genes and clinical symptoms was drawn. Key genes were screened by weighted gene co-expression network analysis (WGCNA) and protein-protein interaction network analysis (PPIN) clustering. Experiment 2 (sepsis animal model preparation): male mice weighing 21-25 g were randomly divided into the key genes group and the control (Sham) group. And cecal ligation and puncture (CLP) was used to establish mouse sepsis model, while the mice in sham group were performed by exposure of cecum. And all the mice were scarified 24 hours after surgery to extract the total RNA from lung tissue, real time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA expression of key genes.Results:Experiment 1 (bioinformatics analysis): 319 differential genes were showed by GSE 134364 and GSE 65682 data set analysis of pulmonary infection secondary sepsis. And there was no genetic difference between community acquired pneumonia (CAP) and hospital acquired pneumonia (HAP) in patients with pulmonary infection secondary to sepsis. Obvious differences existed between differential genes in animal models, and there was no common differential gene. Differential genes in patients and animal models were similarly enriched in GO function, mainly in cell differentiation, regulation of cell process, and regulation of cellular response to stimuli, there were significant differences in pathway enrichment, among which, CLP animal models showed higher consistency with patients. The key genes obtained by WGCNA and PPIN analysis were MAPK14, NLRC4 and LCN2. Experiment 2 (sepsis animal model preparation): animal experiment results showed that the mRNA expressions of MAPK14, NLRC4 and LCN2 in lung tissue of CLP model mice were significantly up-regulated compared with the sham group.Conclusions:MAPK14, NLRC4 and LCN2 are key genes involved in the regulation of biological processes of pulmonary sepsis secondary to infection, and are potential research directions of this disease. What's more, CLP animal model can better reflect the biological characteristics of patients with pulmonary infection secondary sepsis, and is one of the ideal animal model schemes for pulmonary infection secondary sepsis.

To analyze the distribution of HPV infection subtypes and HPV vaccination intention in Liaoyang area. Methods A total of 3 612 women in Liaoyang area who underwent HPV screening at the Department of Gynecology and Obstetrics of Liaoyang Central Hospital from November 2017 to December 2019 were enrolled in this study. The HPV infection in the population was analyzed, and the differences in HPV infection and multiple HPV infection of people at different ages were compared. The influencing factors of vaccination willingness were analyzed. Results There were 576 patients with HPV infection, and the infection rate was 15.95%. The difference in HPV infection at different ages was statistically significant (χ²=9.261, P=0.000), and the difference in multiple HPV infections at different ages was statistically significant (P<0.05). Among low-risk infections, HPV55, HPV61, and HPV81 were the main subtypes, and among high-risk infections, HPV16, HPV51, HPV66, and HPV53 were the main subtypes. In the multivariate analysis, the HPV vaccination intention of people with lower age and lower monthly family income, college students and students with non-medical majors was significantly lower. Conclusion The high-risk types of HPV in Liaoyang area are mainly HPV16, HPV51, HPV66, and HPV53. It is recommended to focus on the intervention of young people, people with low family monthly income, college students and students with a non-medical major to reduce the incidence of cervical cancer.