Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

ObjectiveTo explore the clinical efficacy of Gouteng prescription in treating the patients with primary hypertension with anxiety disorder due to yang hyperactivity and heat toxin and the impact of the formula on the balance of inflammatory cytokines. MethodA total of 98 patients diagnosed with primary hypertension and anxiety disorder were randomized into control and observation groups. On the basis of conventional western medicine treatment for hypertension， the control group （47 patients） was treated with Shugan Jieyu capsules for 8 weeks， while the treatment group （51 patients） with Gouteng prescription for 8 weeks. The two groups were compared in terms of the blood pressure level， 24-hour blood pressure variability， Hamilton anxiety scale （HAMA） score， Pittsburgh sleep quality index （PSQI） score， quality of life （SF-36 scale） score， traditional Chinese medicine （TCM） syndrome score and efficacy， incidence of adverse reactions， and the levels of interleukin （IL）-1β， IL-6， IL-10， and IL-4 in the serum of peripheral blood. ResultThe final trial was completed with 95 patients， including 46 in the control group and 49 in the observation group. The treatment in both groups lowered the blood pressure and blood pressure variability （P<0.05， P<0.01）. The observation group outperformed the control group in recovering the systolic blood pressure （SBP）， 24-hour mean systolic blood pressure （24 h SBP）， 24-hour systolic blood pressure variability （24 h SBPV）， and 24-hour diastolic blood pressure variability （24 h DBPV） （P<0.05）. After treatment， the HAMA and PSQI scores in both groups decreased （P<0.05， P<0.01）， and the observation group had lower HAMA and PSQI scores than the control group （P<0.05）. Compared with those before treatment， the SF-36 scores in both groups increased （P<0.05， P<0.01）. After treatment， the observation group had higher scores of physiological function （PF）， bodily pain （BP）， social function （SF）， role-emotional （RE）， and mental health （MH） indicators than the control group （P<0.05）. After treatment， the TCM syndrome scores in both groups decreased （P<0.05， P<0.01）， and the observation group had lower score than the control group （P<0.05）. The total response rate regarding TCM syndrome in the observation group was 85.71% （42/49）， which was higher than that （63.04%， 29/46） in the control group （χ²=6.621， P<0.05）. The treatment in both groups lowered the levels of pro-inflammatory cytokines （IL-1β， IL-6） and elevated the levels of anti-inflammatory cytokines （IL-10， IL-4） （P<0.05， P<0.01）， and the changes were more obvious in the observation group than in the control group （P<0.05）. There were no adverse events during the research process. ConclusionGouteng prescription can recover the blood pressure level， reduce blood pressure variability， suppress anxiety state， improve sleep and quality of life， decrease TCM syndrome score， increase total response rate， lower serum IL-1β and IL-6 levels， and elevate serum IL-10 and IL-4 levels in the patients with primary hypertension complicated with anxiety disorder due to yang hyperactivity and heat toxin. It may exert the effects by regulating the balance of pro-inflammatory and anti-inflammatory cytokines.

ObjectiveTo explore the material basis and molecular mechanism of Linggui Qihua prescription （LGQH） against myocardial fibrosis in heart failure with preserved ejection fraction （HFpEF）. MethodLiquid chromatography-mass spectrometry （LC-MS） was used to qualitatively analyze the active components of LGQH. AutoDock software was employed for molecular docking between the active components of LGQH and target proteins including α-smooth muscle actin （α-SMA）， type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， matrix metalloproteinase-9 （MMP-9）， and tissue inhibitor of metalloproteinase-1 （TIMP-1）. In vivo experiments were conducted on 40 spontaneously hypertensive rats （SHRs） aged 4 weeks， which were divided into an HFpEF group， an Entresto group （0.018 g·kg^-1）， and low- and high-dose LGQH groups （3.87， 7.74 g·kg^-1）. A high-fat， high-salt， and high-sugar diet was administered for 16 weeks along with intraperitoneal injection of streptozotocin solution for 8 weeks to establish an HFpEF model in rats. The blank group consisted of 10 Wistar Kyoto （WKY） rats and 10 SHRs. After successful modeling， the WKY， SHR， and HFpEF groups were given equal volumes of normal saline， while the other three groups received predetermined interventions. Daily oral gavage was performed for 6 weeks. After intervention， echocardiography was conducted to measure left ventricular （LV） anterior wall thickness （LVAWd）， LV posterior wall thickness （LVPWd）， LV internal diameter at end-diastole （LVIDd）， LV ejection fraction （LVEF）， isovolumic relaxation time （IVRT）， early diastolic peak velocity of mitral valve inflow （E）， and early diastolic mitral annular velocity （e'）. The E/e' ratio was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum atrial natriuretic peptide （ANP）， B-type natriuretic peptide （BNP）， and galectin-3 （Gal-3）. Myocardial fibrosis was observed through Masson staining of pathological sections， and collagen volume fraction （CVF） and perivascular fibrosis ratio （PFR） were calculated. Real-time polymerase chain reaction （PCR） and Western blot were employed to detect LV myocardial mRNA and protein expression of α-SMA， ColⅠ， ColⅢ， MMP-9， and TIMP-1. ResultLC-MS identified 13 active components in LGQH. Molecular docking indicated stable binding of the 13 compounds with five target proteins. In vivo experiments showed that compared with the blank group， the HFpEF group had significantly increased LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR. LV myocardial α-SMA， ColⅠ， and ColⅢ mRNA and protein expression was significantly upregulated， while MMP-9/TIMP-1 mRNA and protein ratios were significantly downregulated （P<0.05， P<0.01）. Compared with the HFpEF group， LGQH might dose-dependently reduce LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR， downregulated myocardial α-SMA， ColⅠ， ColⅢ mRNA expression， α-SMA， and ColⅠ protein expression， and upregulated MMP-9/TIMP-1 mRNA and protein expression （P<0.05， P<0.01）. ConclusionLGQH contains multiple active components and may inhibit myocardial fibrosis in HFpEF rats. It may further alleviate LV hypertrophy， dilation， and diastolic dysfunction， making it an effective Chinese medicinal prescription for treating HFpEF.

Objective:To evaluate the predictive value of mechanical power (MP) on the risk of in-hospital mortality in critical ill patients in emergency department.Methods:A total of 105 critical ill patients with invasive mechanical ventilation in the Department of Emergency of Second Affiliated Hospital of Guangzhou Medical University between December 1, 2017 and October 31, 2020 were retrospectively analyzed. Based on the clinical prognosis, the patients were divided into the in-hospital survival group (80 patients) and the in-hospital death group (25 patients). The clinical data and ventilator parameters were recorded, and the MP of the two groups was calculated in order to assess the predictive efficacy of MP on in-hospital death.Results:Compared to the in-hospital death group, the oxygenation index PaO 2/FiO 2 was significantly higher (271 mmHg vs. 217 mmHg, P=0.020) and blood lactate (1.59 mmol/L vs. 2.56 mmol/L, P<0.001) and procalcitonin (0.31 ng/mL vs. 3.55 ng/mL, P=0.028), minute ventilation (7.03 L/min vs.8.32 mmol/L, P=0.013), MP (14.37 J/min vs. 16.12 J/min, P=0.041), SOFA score (5 vs. 8, P=0.001) and APACHE II score (16 vs. 22, P=0.041) were significantly lower in the in-hospital survival group. Multivariate Logistic regression analysis showed that PaO 2/FiO 2( OR=1.015, P=0.044), MP ( OR=1.813, P=0.039) and SOFA score( OR=2.651, P=0.010) were independent risk factors for predicting hospital mortality in patients with mechanical ventilation. The areas under the ROC curves (AUC) were 0.62, 0.63 and 0.75, respectively. Moreover, the MP combined with SOFA score for predicting in-hospital death was significantly higher than that of MP alone (0.77 vs. 0.63, P<0.05). Conclusions:MP is associated with in-hospital death in patients with invasive mechanical ventilation in emergency department. MP combined with SOFA score can enhance its predictive efficacy

Objective:To analyze the clinical characteristics of Chlamydia psittaci pneumonia in the elderly, and factor related to the disease severity. Methods:Clinical data of 32 elderly patients with Chlamydia pneumoniae pneumonia admitted in the First People′s Hospital of Xiaoshan District from January 2019 to January 2021 were retrospectively analyzed. The patients were diagnosed by the second generation sequencing using bronchoalveolar lavage fluid (BALF) samples. There were 17 patients in moderate group and 15 patients in severe group; the liver function, muscle enzymes, imaging and lymphocyte subsets of the two groups were compared. Results:There were no significant differences in the age, gender and basic diseases, bird contact history, flaccid fever and dry cough symptoms between two groups, while there were significant differences in mental symptoms and gastrointestinal symptoms between the two groups ( P=0.032, 0.018). There were significant differences in ALT , AST, LDH , CK , CK-MB, CRP, BNP , troponin-T and PCT between the two groups (all P<0.001). The increase of leukocytes was not significant in both groups. The moderate group was dominated by single lobe involvement, while the severe group was dominated by multi lobe involvement and pleural effusion ( P=0.043, 0.015, 0.023). The total lymphocytes, T lymphocytes, CD4 + T cells, CD8 + T cells, CD4 +/CD8 + ratio, NK cells, B cells, CD4 +CD8 + double positive T cells decreased in both groups, while those in the severe group decrease more markedly ( P<0.05). CD4 -CD8 - double negative T cells were higher in the severe group than those in the moderate group ( P<0.001). CD4 +/CD8 + ratio and CD4 -CD8 - double negative T cells were correlated with severity index PSI and CURB-65 ( P<0.05). Conclusions:The liver function, muscle enzyme, lymphocyte immune function in patients with Chlamydia psittaci pneumonia are impaired, which were more markedly in severe patients. The multileaf infiltration and increased procalcitonin may indicate the severe pneumonia. CD4 +/CD8 + ratio and CD4 -CD8 - double negative T cells are correlated with the severity of pneumonia.

Objective:To study the value of autoregressive integrated moving average (ARIMA) and autoregressive (AR) models in predicting the daily number of ambulances in prehospital emergency medical services demand in Guangzhou.Methods:Matlab simulation software was used to analyze the emergency dispatching departure records in Guangzhou from January 1, 2021 to December 31, 2021. A time series for the number of ambulances per day was calculated. After identifying the time series prediction model, ARIMA(1,1,1), AR(4) and AR(7) models were obtained. These models were used to predict the number of ambulances per day. ARIMA(1,1,1) model divided the time series into the training set and test set. Prony method was used for parameter calculation, and the demands of number of ambulances of the next few months were forecasted. AR(4) and AR(7) models used uniformity coefficient to forecast the demands of number of ambulances on that very day.Results:ARIMA(1,1,1), AR(4) and AR(7) can effectively predict the number of ambulances per day. The prediction fitting error of ARIMA (1,1,1) decreased with the extension of prediction time. The mean absolute percentage error (MAPE) of forecast results of daily vehicle output of emergency dispatching within two months was less than 6% and the predicted results were almost within the 95% confidence interval. The residual analysis of the model verified that the model was significantly effective.Conclusions:ARIMA model can make a long-term within two months and effective prediction fitting of the daily vehicle output of emergency dispatching, and AR model can make a short-term and effective prediction of the daily vehicle output of emergency dispatching.

Objective:To investigate the effect of lipopolysaccharide (LPS) on primary neonatal rat cardiomyocytes (CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs).Methods:The hiPS-CMs and primary neonatal rat CMs were treated with different concentrations of LPS for 24 to 48 h. Then the cellular viability was analyzed by the xCELLigence RTCA Cardio system. The measurement of NPPB gene was studied by qRT-PCR and the gene expression analysis was performed by the qPCR array, in order to evaluate the cardiac inflammation effect induced by LPS.Results:The LPS exposure led to dysfunction in the primary neonatal rat CMs, which shown as an increase in beating rate and a decrease in contraction amplitude ( P<0.01), accompanied by an increased NPPB mRNA level ( P<0.01). There was no significant alteration in beating rate and the contraction amplitude in the corresponding concentration of the primary neonatal rat CMs ( P>0.05), as well as the NPPB mRNA level ( P>0.05). However, the expression of NPPB mRNA in hiPS-CMs was significantly different at a higher concentration of LPS (5 μg/mL~40 μg/mL) ( P<0.01), but the beating rate and the contraction amplitude showed no significant change, even the concentration of LPS up to 40 μg/mL ( P>0.05). Finally, the genes of C3, Gpnmb, Atf3, Il6r and Ly96 upregulated to 1.5 folds in the primary neonatal rat CMs. In comparison with primary neonatal rat CMs, the AK4, TOLLIP, SPP1, FABP1, IL6R, LY96 and C3 were over expression to 1.5 folds in the hiPS-CMs. Conclusions:In comparison with primary neonatal rat CMs, hiPS-CMs are markedly less injured by LPS and show a different pattern of inflammation gene expression.

Objective:To analyze the sepsis related long non-coding RNA (lncRNA) and mRNA expression profiles based on Gene Expression Omnibus (GEO) datasets and bioinformatic analysis, and to analyze the sepsis-associated competing endogenous RNA (ceRNA) network based on microRNA (miRNA) database.Methods:The sepsis-related lncRNA dataset was downloaded from the GEO database, and the differential expression analysis was conducted by Bioconductor on the sepsis dataset to obtain differentially expressed lncRNA (DElncRNA) and differentially expressed mRNA (DEmRNA), and cluster heat map was drawn. miRNA combined with DElncRNA were predicted by miRcode. mRNA targeted by miRNA was simultaneously met by three databases: TargetScan, miRDB, and mirTarBase. The interaction relationship of lncRNA-miRNA-mRNA was obtained. The regulatory network visualization software CytoScape was used to draw ceRNA networks. DEmRNA in the ceRNA networks were imported into the Search Tool for the Retrieval of Interacting Genes Database (STRING) online database to draw the protein-protein interaction (PPI) map. The gene ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEmRNA were performed.Results:Dataset GSE89376 and GSE145227 were found from GEO database. Difference analysis showed there were 14 DElncRNA and 359 DEmRNA in the elderly group of GSE89376; 8 DElncRNA and 153 DEmRNA in the adult group of GSE89376; 1 232 DElncRNA and 1 224 DEmRNA in the children group of GSE145227. Clustering heatmap showed that there were significant differences in the expression of lncRNA and mRNA between the sepsis group and the control group. The ceRNA networks were constructed with miRNA. Several DElncRNA and multiple DEmRNA participated in the ceRNA network of sepsis. The PPI diagram demonstrated that several genes encoding proteins interacted with each other and form a multi-node interaction network with multiple genes encoding proteins. Functional annotation and enrichment analysis demonstrated that there might be a crosstalk mechanism on functionally related genes such as nuclear receptor activity, ligand-activated transcription factor activity, and steroid hormone receptor activity, and played a role in the occurrence and development of diseases through forkhead box transcription factor O (FoxO) signaling pathway, Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway, p53 signaling pathway, and phosphateidylinositol 3-kinase (PI3K)/Akt signaling pathway.Conclusion:Through sepsis-related lncRNA-miRNA-mRNA ceRNA network and combining with KEGG pathway analysis, there were several lncRNA and mRNA participating in the ceRNA network related sepsis, which played an important role in several signal pathways.

Objective:To explore the role of bedside cardiopulmonary ultrasound in the evaluation of non-invasive positive pressure ventilation (NPPV) in patients with cardiaogenic pulmonary edema in emergency department.Methods:The clinical data and characteristics of bedside rapid cardiopulmonary ultrasound in patients withcardiaogenic pulmonary edema treated with NPPV in the emergency department were retrospectively analyzed. The following ultrasound parameters, including lung ultrasound score, the ratio of lung consolidation, diameter of inferior vena cava, left ventricular ejection fraction (LVEF), the mitral annular systolic displacement (MAPSE) and tricuspid annular systolic displacement (TAPSE), the peak Doppler velocities of the early diastolic mitral (E), the tissue velocity imaging of left ventricular and right ventricular (Sm), the tissue Doppler of the early diastolic velocity of the mitral annulus (e’), the average E/e’ ratio of left ventricular, systolic pulmonary artery pressure (SPAP) and the ratio of atrial fibrillation,, were determined. All of the parameters combined with clinical parameters were compared between the non-invasive ventilation success group and non-invasive ventilation failure group. Univariate and multivariate logistic regression analysis were used to screen out the risk factors by taking the failure of NPPV treatment as the dependent variable. The area under the receiver operating characteristic (ROC) curve was used to analyze the predictive value of the indicators above.Results:A total of 66 patients, included 44 (66.%) of NPPV success and 22 (33.3%) of NPPV failure revealed by bedside cardiopulmonary ultrasound. In comparison with the NPPV success group, the lung ultrasound score, ratio of lung consolidation, E/e’ of LV , SPAP, the ratio of right ventricular dysfunction, the ratio of atrial fibrillation and the level of Ccr were significantly evaluated, but the Sm of right ventricular and PaO2/FiO2 were significantly lower in the NPPV failure group (all P< 0.05). There were no differences in LVEF, MAPSE, TPASE, diameter of inferior vena cava and the Sm of left ventricular between groups (all P> 0.05). Multivariate logistic regression analysis showed that lung ultrasound score, E/e’ and SPAP were independent predictors of NPPV failure in patients with cardiaogenic pulmonary edema. The AUCs of lung ultrasound score, E/e’ of LV and SPAP for predicting NPPV failure was 0.802, 0.783 and 0.852, respectively. . Conclusions:The lung ultrasound score, right ventricular diastolic function and SPAP evaluated by bedside cardiopulmonary ultrasound could provide predictive values for the non-invasive positive ventilation failure in patients with cardiaogenic pulmonary edema.

Clinical practice guideline (CPG) for pain management of osteoarthritis in China contains 14 recommendations in treating patients with symptomatic osteoarthritis (OA) who are considering pharmaceutical and non-pharmaceutical treatments. Compared with the other consensus on diagnosis and treatment for OA, this clinical practice guideline (CPG) proposed by Chinese Orthopedics Association has some advantages in terms of methodology selection and recommendation. Therefore, it is necessary for us to interpret this CPG to speed up the understanding and application of the CPG. The ultimate aim were: to strengthen the normative and understanding of non-surgical or surgical treatment of OA; to enhance the understanding this CPG for clinicians to treat OA; to speed up the development of guideline methodologies in our country; to provide methodological guidance for the development of CPG based on the current situation in our country.