Chronic heart failure is the terminal stage of various cardiovascular diseases， and cardiomyocyte apoptosis is the turning point of decompensation. Studies have shown that traditional Chinese medicine （TCM） could regulate apoptosis-related signaling pathways and factors and inhibit or up-regulate the expression of apoptosis-related proteins. Thus， TCM can reduce cardiomyocyte apoptosis， protect the myocardial tissue and improve the cardiac function， demonstrating remarkable clinical effects. In recent years， the research on the treatment of chronic heart failure based on the inhibition of cardiomyocyte apoptosis is increasing and becomes the current research hotspot. On the basis of literature review， this paper discovers that TCM regulates apoptosis factors and multiple signaling pathways to inhibit apoptosis and inflammation and delay the progression of chronic heart failure through classical pathways such as the death receptor pathway， the mitochondrial pathway， and the endoplasmic reticulum pathway. At the same time， the studies in this field have the following problems： Repeated studies with shallow， simple， and fragmented contents， treating animal models with TCM prescriptions without syndrome differentiation， treating diseases with drugs at only one concentration which is insufficient to indicate efficacy， and lacking comprehensive， holistic， and systematic studies on the relationships of apoptosis with inflammatory responses， pyroptosis， ferroptosis， and autophagy. In the future， more scientific， reasonable， comprehensive， and feasible experimental schemes should be designed on the basis of comprehensively mastering the research progress in this field， and the communication and cooperation between researchers in different disciplines should be strengthened. The specific pathological mechanism of cardiomyocyte apoptosis in chronic heart failure and the signaling pathways， active components， and action targets of TCM in inhibiting cardiomyocyte apoptosis in chronic heart failure should be elucidated. Such efforts are expected to provide sufficient reference for the clinical treatment of chronic heart failure.

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

Objective To explore the mechanism of Glaucocalyxin A(GLA)in inhibiting ovalbumin(OVA)-induced airway remodeling in asthmatic mice through the topoisomerase Ⅱ α(TOP2A)/cyclin-dependent kinase 1(CDK1)signaling pathway.Methods Forty Balb/c mice were randomly divided into 5 groups:the control group,the model group,the low-dose GLA group,the high-dose GLA group and the Dexamethasone group,with 8 mice in each group.The effect of GLA on airway remodeling was examined by immunohistochemical staining,ELISA and other methods,and bioinformatics methods were used to predict new targets of GLA.The action targets of TOP2A were screened using the STRING database,and the interaction relationship between the two was verified by co-immunoprecipitation.In vitro,GLA and siRNA were used to interfere with interleukin-4(IL-4)-stimulated human airway epithelial cells BEAS-2B.The expressions of TOP2A,epidermal growth factor receptor(EGFR),Integrin β1,focal adhesion kinase(FAK),β-catenin,CDK1 and DRP1 were detected by Western Blot.Results GLA intervention could significantly reduce OVA-induced asthma airway remodeling,airway smooth muscle thickening,collagen deposition around the airway,the number of eosinophils in alveolar lavage fluid,the expression of pro-inflammatory cytokines such as IL-4,and the level of serum IgE.The new target of GLA screened out was TOP2A,which was highly expressed in the lung tissue of the asthma airway remodeling model.GLA intervention could down-regulate its expression.In vitro,intervention with GLA and si-TOP2A could significantly down-regulate the expressions of IL-4-induced TOP2A,EGFR,Integrin β1,FAK and β-catenin.Further studies have found that TOP2A had an interaction relationship with CDK1.si-TOP2A could downregulate the expression of CDK1,and knockdown of CDK1 could significantly down-regulate the expression of phosphorylated DRP1.Conclusion GLA may alleviate asthma airway remodeling by targeting the TOP2A/CDK1 signaling pathway,providing experimental evidence for the clinical diagnosis and treatment of asthma airway remodeling in asthma.

Objective To explore the mechanism of Glaucocalyxin A(GLA)in inhibiting ovalbumin(OVA)-induced airway remodeling in asthmatic mice through the topoisomerase Ⅱ α(TOP2A)/cyclin-dependent kinase 1(CDK1)signaling pathway.Methods Forty Balb/c mice were randomly divided into 5 groups:the control group,the model group,the low-dose GLA group,the high-dose GLA group and the Dexamethasone group,with 8 mice in each group.The effect of GLA on airway remodeling was examined by immunohistochemical staining,ELISA and other methods,and bioinformatics methods were used to predict new targets of GLA.The action targets of TOP2A were screened using the STRING database,and the interaction relationship between the two was verified by co-immunoprecipitation.In vitro,GLA and siRNA were used to interfere with interleukin-4(IL-4)-stimulated human airway epithelial cells BEAS-2B.The expressions of TOP2A,epidermal growth factor receptor(EGFR),Integrin β1,focal adhesion kinase(FAK),β-catenin,CDK1 and DRP1 were detected by Western Blot.Results GLA intervention could significantly reduce OVA-induced asthma airway remodeling,airway smooth muscle thickening,collagen deposition around the airway,the number of eosinophils in alveolar lavage fluid,the expression of pro-inflammatory cytokines such as IL-4,and the level of serum IgE.The new target of GLA screened out was TOP2A,which was highly expressed in the lung tissue of the asthma airway remodeling model.GLA intervention could down-regulate its expression.In vitro,intervention with GLA and si-TOP2A could significantly down-regulate the expressions of IL-4-induced TOP2A,EGFR,Integrin β1,FAK and β-catenin.Further studies have found that TOP2A had an interaction relationship with CDK1.si-TOP2A could downregulate the expression of CDK1,and knockdown of CDK1 could significantly down-regulate the expression of phosphorylated DRP1.Conclusion GLA may alleviate asthma airway remodeling by targeting the TOP2A/CDK1 signaling pathway,providing experimental evidence for the clinical diagnosis and treatment of asthma airway remodeling in asthma.

Objective To investigate the cancer death and distribution characteristics of residents in Cixian County. Methods In accordance with the norms of cancer registration, cancer death data from 2013 to 2017 in Cixian were collected and analyzed, and the crude cancer death rate, age-standardized mortality rates by the Chinese standard population (ASMRC), age-standardized mortality rates by the global standard population (ASMRW). Results From January 1st, 2013, to December 31st, 2017, 6 490 cases of cancer death were recorded. The average annual crude mortality rate was 202.88/100 000, ASMRC was 186.49/100 000, and the ASMRW was 189.02/100 000. The top 10 male mortality cancers were esophageal cancer, stomach cancer, trachea, bronchus and lung cancer, liver cancer, rectal cancer, cerebral nervous system cancer, colon cancer, leukemia, pancreatic cancer, and bladder cancer in order. The top 10 female mortality cancers were esophageal cancer, trachea, bronchus and lung cancer, stomach cancer, liver cancer, breast cancer, cervical cancer, colon cancer, brain, nervous system cancer, rectal cancer, and ovarian cancer. The age of death increased considerably from the age of 40 years. It increased with the increase in age and reached the peak at the age of 85 years. Conclusion Upper gastrointestinal cancer and lung cancer were the main cancers that threatened the residents of Cixian County from 2013 to 2017. Screening and comprehensive prevention of high-risk groups are still the main targets of cancer prevention and control.

Objective:To explore the mechanism of Ma-Xing Shi-Gan decoction combined with Xiao-Chai-Hu decoction (hereinafter referred to as " Sanyang combined treatment" ) in alleviating colon injury in mice infected with influenza virus by transcriptome sequencing technique.Methods:The mouse model of colonic injury caused by influenza virus was induced by intranasal drip of influenza A virus H1N1 suspension. The mice were divided into Control group, Model group, and Sanyang combined treatment (SCT) group. Model group and SCT group were fed with PBS and Ma-Xing Shi-Gan decoction combined with Xiao-Chai-Hu decoction respectively. Seven days later, the colon tissues of each group were taken, the colon length and pathological damage were observed, and the transcriptome was sequenced to screen the significantly different genes between the SCT group and model group for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis(GSEA).Results:After the therapy with SCT, the length of the colon of mice was significantly improved and the pathological injury of the colon was reduced. There are 92 differentially expressed genes between the SCT group and the model group. GO analysis indicated that the differential genes were enriched in biological processes such as regulation of cytokine and chemokine production, inflammatory response, defense response, immune response, regulation of NF-κB inducing kinase(NIK)/Nuclear factor-κB(NF-κB) signal and Mitogen-activated protein kinase(MAPK) cascade, as well as cell components related to intestinal barrier such as brush border membrane, brush border and microvilli. KEGG analysis indicated that the differential genes were enriched in Toll-like receptor signaling pathway, intestinal immune network for IgA production, complement and coagulation cascade, and Peroxisome proliferator-activated receptor(PPAR) signaling pathway. GSEA indicated that the intestinal immune network for IgA production, PPAR signaling pathway, propionic acid metabolism and butyrate metabolism were significantly up-regulated after the intervention with SCT, while apoptosis and MAPK signaling pathway were significantly down-regulated.Conclusions:Sanyang combined therapy can protect the intestinal tract of mice infected with influenza virus mainly through immunity, inflammation and metabolism pathways.

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

Objective To study the clinical value of amplitude integrated EEG(aEEG),EEG reactivity,EEG patterns,and Glasgow Coma Scale(GCS) scores of predicting the prognosis in comatose patients with severe traumatic brain injury.Methods Sixty-four hospitalized comatose patients with severe traumatic brain injury were evaluated by aEEG,EEG reactivity,EEG patterns and GCS and followed up for one year to observe the prognosis of the patients.Results Accuracy of aEEG,EEG reactivity,EEG patterns and GCS in predicting outcomes of comatose patients with severe traumatic brain injury correctly classified as 73.4％,68.8％,73.4％,64.1％ respectively.The accuracy of GCS in evaluating the prognosis of comatose patients with severe traumatic brain injury was lower than that of the other three methods (P＜0.05).There were positive correlations among aEEG,EEG reactivity,EEG patterns,and GCS (r=0.574-0.843,P＜ 0.05).There were positive correlations between aEEG,EEG reactivity,EEG patterns,GCS and the patients' prognosis(r=0.647,0.609,0.621,0.532,P＜ 0.05).Conclusion As a new electroencephalographic technique,aEEG combined with EEG reactivity,EEG patterns,and GCS can be effectively used to evaluate the prognosis of STBI coma patients,which has a certain clinical value.

Objective To evaluate the significance of serum 8-hydroxy-deoxyguanosine acid ( 8-OHdG) in the diagnosis of nonalcoholic steatohepatitis ( NASH).Methods Patients or healthy subjects were enrolled at the Second Hospital of Tianjin Medical University and the Second People ′s Hospital of Tianjin from May 2013 to December 2015.A total of 41 patients with nonalcoholic fatty liver disease were enrolled in the study , including 20 nonalcoholic simple fatty liver ( NAFL) patients and 21 NASH patients whose diagnosis were proven by liver biopsy.The other 32 healthy subjects were studied as controls.Serum 8-OHdG, ALT, AST and GGT were tested.Nonalcoholic fatty liver disease activity score ( NAS ) and expression of 8-OHdG in liver was investigated between NAFL patients and NASH patients.The correlations between serum 8-OHdG and serum ALT , AST, GGT, and 8-OHdG in liver tissue in NASH group were investigated.In addition , the receiver operating characteristic ( ROC) curve analyses for ALT and 8-OHdG levels were performed in NAFL patients and NASH patients , and the cut-off value was determined.Results Serum 8-OHdG values in healthy controls , NAFL and NASH patients were (0.19 ±0.16) μg/L, (0.22 ±0.16) μg/L, (0.42 ±0.21) μg/L respectively.The serum 8-OHdG and serum ALT, GGT and 8-OHdG in liver tissue were all positively correlated in NASH group with respective correlation coefficient r values as 0.454 7, 0.382 9, and 0.497 6.AUC of 8-OHdG was 0.901 with cut-off value 0.39 μg/L.Its sensitivity was 88.3%and specificity was 81.5%, which were higher than those of ALT.Conclusion The value of serum 8-OHdG would be used as a marker for the diagnosis of NASH.