ObjectiveTo investigate the effects of the combination of components from Tripterygii Radix et Rhizoma and Chuanxiong Rhizoma on rheumatoid arthritis fibroblast-like synoviocytes （RA-FLSs） and the underlying mechanism. MethodsRA-FLSs were grouped as follows： blank control， positive control （methotrexate）， Tripterygii Radix et Rhizoma components， Chuanxiong Rhizoma components， and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma. The cell-counting kit-8 （CCK-8） assay was employed to the cell proliferation， invasion， and apoptosis. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， reactive oxygen species （ROS）， and malondiadehyde （MDA） in cells were measured. Western blot was employed to determine the protein levels of nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB） p65， phosphorylated inhibitory subunit of NF-κBα （p-IκBα）， cysteinyl aspartate-specific protease-3 （Caspase-3）， and B-cell lymphoma 2 （Bcl-2）. Real-time PCR was employed to determine the mRNA levels of Nrf2， HO-1， and NF-κB p65. ResultsThe cells in the groups of positive control， Tripterygii Radix et Rhizoma components， Chuanxiong Rhizoma components， and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma were treated with 2.50 mg·L^-1 methotrexate， 0.20 mg·L^-1 triptolide + 0.20 mg·L^-1 celastrol， 5.00 mg·L^-1 ferulic acid + 20.00 mg·L^-1 ligustrazine， 0.20 mg·L^-1 triptolide + 0.20 mg·L^-1 celastrol + 5.00 mg·L^-1 ferulic acid + 20.00 mg·L^-1 ligustrazine， respectively. Compared with the blank control group， drug administration reduced the proliferation and invasion and increased the apoptosis of cells （P<0.01）， lowered the levels of TNF-α， IL-6， ROS， and MDA （P<0.01）， up-regulated the mRNA and protein levels of Caspase-3， Nrf2， and HO-1 （P<0.01）， and down-regulated the mRNA and protein levels of Bcl-2， NF-κB p65， and p-IκBα （P<0.01）. Compared with the Tripterygii Radix et Rhizoma components group， the combination of components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma inhibited the proliferation and invasion （P<0.05） and promoted the apoptosis of RA-FLSs， up-regulated the mRNA levels of Nrf2 and HO-1 and protein levels of Nrf2 and Caspase-3 （P<0.05）， and down-regulated the protein levels of NF-κB p65 and p-IκBα （P<0.05）. ConclusionThe combination of components from Chuanxiong Rhizoma and Tripterygii Radix et Rhizoma can inhibit the proliferation and invasion and promote the apoptosis of RA-FLSs and alleviate oxidative stress and inflammation by inhibiting the NF-κB signaling pathway， activating the Nrf2/HO-1 pathway， and regulating the expression of Bcl-2/Caspase-3.

Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML. Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR. Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05). Conclusion We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML. Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR. Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05). Conclusion We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML. Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR. Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05). Conclusion We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Objective:Healthy life expectancy (HLE), which combines life expectancy with health, is an essential comprehensive measure of life length and quality. This article aimed to systematically review the methods for defining and measuring HLE and describe application studies published, providing a reference for decision makers to select and develop methods suitable for China's conditions to measure HLE.Methods:Seven Chinese and English literature databases were searched up to May 7, 2022, and several related reviews and bibliography were manually retrieved. Systematic reviews and empirical research were included concerning HLE indicators and measurement of HLE. Information including the study area, type of the study, study population, HLE index, measurement method, data sources, and results from application studies published in the last five years were extracted. The evolution of the definition of HLE, the scope of different indicators, the measurement scale of health, and measurement methods, were all collected. Results of the empirical research related to measurement methods of indicators were summarized. The study followed the scoping review framework and was written according to the PRISMA-ScR statement.Results:A total of 84 articles were included, including 13 reviews, 17 original studies related to HLE index definition, ten original studies related to index measurement, and 44 empirical studies conducted in the past five years. There were as many as 20 indicators related to HLE, and each scale had its emphasis. A total of ten methods measuring HLE were identified, which vary in the definition of health, whether using weight, and the data type. The most commonly used indicators in the past five years were disability-free life expectancy and HLE. For the method of HLE calculation, Sullivan's method was mainly used for cross-sectional data, and the multistate life table was mainly used for longitudinal data.Conclusions:There are various definitions and measurement methods of HLE, but none are suitable for all scenarios. To summarize the HLE concept, health evaluation techniques, measurement methods, and application studies published worldwide can provide a reference for the localization of HLE measurement in China.

A total of 15 batches of the substance reference of Guizhi Jia Gegen Decoction(GZGGD) were prepared and the characteristic fingerprints of them were established. Furthermore, the similarity of the fingerprints and peak attributes were explored. The extraction rate, and the content and the transfer rate ranges of the index components, puerarin, paeoniflorin, liquiritin, and ammonium glycyrrhizate were determined for the analysis of the quality value transfer. The result demonstrated that the fingerprints of the 15 batches of the samples showed high similarity(>0.99). A total of 15 characteristic peaks were identified from the fingerprints, with 10 for Puerariae Lobatae Radix, 1 for Cinnamomi Ramulus, 2 for Paeoniae Radix Alba, and 2 for Glycyrrhizae Radix et Rhizoma. The content of puerarin was 11.05-18.35 mg·g~(-1) and the average transfer rate was 21.27%-39.49%. The corresponding figures were 7.95-10.90 mg·g~(-1) and 23.28%-43.23% for paeoniflorin, 3.25-4.95 mg·g~(-1) and 32.31%-61.27% for ammonium glycyrrhizate, and 3.65-5.80 mg·g~(-1) and 14.57%-27.05% for liquiritin. The extraction rate of the 15 batches of samples was in the range of 16.85%-21.78%. In this paper, the quality value transfer of the substance reference of GZGGD was analyzed based on characteristic fingerprint, content of index components, and the extraction rate. This study is expected to lay a basis for the quality control and further development of GZGGD.
Ammonium Compounds ; Benchmarking ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Paeonia

Objective: To analyze the influencing factors of healthy life expectancy (HLE). Methods: Seven Chinese and English databases were used for the retrieval of related literatures published by May 7, 2022 to identify influencing factors of HLE, including diseases and injuries and their risk factors. Based on the ecological model of health determinants, this study classifies the risk factors of diseases and injuries into five levels: personal characteristics, individual behavior and lifestyle, social network, living and working conditions, and macroscopic socio-economic, cultural and environmental conditions. Contents of research area, HLE indicators, research population, influencing factors, data sources and results were extracted. The frequencies of reported documents of different HLE indicators and influencing factors of different dimensions were visualized by using evidence map, and the empirical studies of four authoritative English medical journals and Chinese core medical journals were further compared and described. Results: A total of 90 studies were selected, in which 26 were conducted in China (28.9%). Fifty-three studies are about diseases and injuries in the first dimension, and all of them have studied non-communicable diseases, accounting for the highest proportion (58.9%). There were 77 studies about the analysis on the determinants of health at five levels by an ecological model, all the studies reported multi-level results. Among them, 53 studies reported personal characteristics (58.9%), 47 studies reported individual behavior and lifestyle (52.2%), 10 studies reported social networks (11.1%), 35 studies reported living and working environment (38.9%), 8 studies reported social economy, culture status and environment condition (8.9%). The literatures about HLE published by 4 authoritative English medical journals and 21 Chinese core medical journals in recent three years were selected. Non-communicable diseases and personal characteristics were the top two most commonly studied factors of HLE, and 11 (52.3%) and 12 (57.1%) studies reported these two kinds of factors respectively. The most important factor contributing to the global disability-adjusted life years of non-communicable diseases was individual behavior and lifestyle, which was the most changeable factor. Conclusions: In recent three years, studies involving influencing factors of HLE were mainly non-communicable diseases and personal characteristics. In the future, individual behavior, lifestyle and working environment should be strengthened.
Humans ; Noncommunicable Diseases ; Healthy Life Expectancy ; Life Style ; Asian People ; Risk Factors

Objective:To investigate the role of receptor-interacting protein kinse3 (RIPK3)-mediated necroptosis in diabetic mellitus-caused abolition of cardioprotection induced by sevoflurane postconditioning in rats.Methods:Eighty rats with diabetes mellitus, aged 4-5 weeks, weighing 90-100 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (group Sham), myocardial ischemia-reperfusion (I/R) group (group I/R), sevoflurane postconditioning group (group SP) and sevoflurane postconditiong plus RIPK3 inhibitor GSK-872 group (group GSK). Myocardial I/R was induced by 40 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.In group SP, 2.4% sevoflurane was inhaled for 15 min at the beginning of reperfusion.In group GSK, GSK-872 3.3 mg/kg (dissolved in normal saline) was intraperitoneally injected at 24 and 2 h before surgery, and the other treatments were similar to those previously described in group SP.After 120 min of reperfusion, blood samples from the abdominal aorta were collected for determination of concentrations of serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB). Myocardial tissues were taken for determination of percentage of myocardial infarct size (by TTC staining) and expression of RIPK3, phospho-Ca 2+ -calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ) and phospho-mixed lineage kinase domain-like protein (p-MLKL) (by Western blot), and the ultrastructure of myocardium was observed by transmission electron microscopy. Results:Compared with group Sham, the serum LDH and CK-MB concentrations and percentage of myocardial infarct size were significantly increased, the expression of RIPK3, p-MLKL and p-CaMKⅡ in myocardial tissues was up-regulated ( P<0.05), and the damage to cardiomyocytes was severe in group I/R.Compared with group I/R, no significant change was found in the parameters mentioned above in group SP ( P>0.05). Compared with group SP, the serum LDH and CK-MB concentrations and percentage of myocardial infarct size were significantly decreased, the expression of RIPK3, p-MLKL and p-CaMKⅡ in myocardial tissues was down-regulated ( P<0.05), and the damage to cardiomyocytes was reduced in group GSK. Conclusion:The mechanism of diabetic mellitus-caused abolition of cardioprotection induced by sevoflurane postconditioning is related to excessive activation of RIPK3-mediated necroptosis in rats.