Objective:To analyze and identify the expression profiles of oxidative stress-related genes and circular RNAs(circRNAs)in ricin toxin(RT)-induced pyroptosis of mouse mononuclear macrophages(RAW264.7)using transcriptome sequencing and bioinformatics technology,and to preliminarily analyze their potential functions.Methods:The macrophages(RAW264.7 cells)were treated with RT to establish a cell pyroptosis model and divided into control group,40 μg·L-1 RT group,and 80 ng/mL RT group.Transmission electron microscope(TEM)was used to observe the morphology of the RAW264.7 cells in various groups;Western blotting method was used to detect the expression levels of the pyroptosis pathway-related proteins in the cells in various groups;80 μg·L-1 RT was selected for subsequent experiments.Transcriptome sequencing(RNA-Seq)was performed to obtain the circRNA and mRNA expression profiles in the RAW264.7 cells in control group and RT-treated group,followed by bioinformatics analysis.Results:Compared with control group,the cells in 40 and 80 μg·L-1 RT groups underwent morphological changes;the cells in RT groups showed obvious pyroptosis-like morphological changes,characterized by significant swelling of dying cells and the appearance of characteristic large bubbles on the plasma membrane.Compared with control group,the expression level of gasdermin DN-terminal fragment(GSDMD-N)protein in 40 and 80 μg·L-1 RT groups was increased(P<0.05);compared with 40 μg·L-1 RT group,the expression level of GSDMD-N protein in the cells in 80 μg·L-1 RT group was increased(P<0.05);therefore,the subsequent experiments used the RT concentration of 80 μg·L-1.A total of 2930 differentially expressed messenger RNAs(mRNAs)and 24 differentially expressed circRNAs were identified.The constructed circRNA-microRNA(miRNA)-mRNA competing endogenous RNA(ceRNA)regulatory network consisted of 7 circRNAs,12 miRNAs and 13 mRNAs.Gene Ontology(GO)functional enrichment analysis showed that in biological process(BP),the functions regulated by differentially expressed genes mainly included immune response and oxidative stress response;in cellular component(CC),differentially expressed genes were mainly localized to the external side of plasma membrane and cell leading edge;in molecular function(MF),they were mainly involved in transporter transmembrane activity and hormone receptor binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis showed that differentially expressed genes were mainly enriched in Toll-like receptor signaling pathway,Forkhead box O(FoxO)signaling pathway and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.In the protein-protein interaction(PPI)network,the top 10 hub genes with the highest connectivity were screened by CytoHubba,including matrix metalloproteinase 9(MMP9),superoxide dismutase 2(SOD2),and v-src sarcoma viral oncogene homolog(Src).Conclusion:The expression profiles of oxidative stress-related genes and circRNAs in RAW264.7 cells are altered after RT treatment.The screened differentially expressed circRNAs and mRNAs may serve as potential targets to regulate RT-induced pyroptosis in RAW264.7 cells through oxidative stress pathways.

Objective:To identify latent profile types of self-acceptance among newly diagnosed young and middle-aged patients with type 2 diabetes mellitus (T2DM), and to analyze the influencing factors.Methods:A convenience sampling method was used to recruit 162 patients with T2DM who visited the Department of Endocrinology at the First Affiliated Hospital of Zhengzhou University between March 2023 and August 2024. A general information questionnaire was used to collect demographic and clinical data. The Acceptance and Action Diabetes Questionnaire (AADQ), Type 2 Diabetes Stigma Assessment Scale (DSAS-2), Diabetes Knowledge Test 2 (DKT2), and e-Health Literacy Scale (eHEALS) were used to assess self-acceptance, diabetes-related stigma, diabetes knowledge, and electronic health literacy, respectively. Latent profile analysis (LPA) was performed to identify categories of self-acceptance based on AADQ scores. Logistic regression analysis was conducted to examine the influencing factors of self-acceptance profiles in young and middle-aged patients with T2DM. A total of 162 questionnaires were distributed, and 157 valid responses were collected, with an effective response rate of 96.91% (157/162) .Results:The mean AADQ score of the 157 patients was (46.64±10.34), ranging from 20 to 63, with a mean item score of (4.24±1.16). Three latent profile categories of self-acceptance were identified: the "high avoidance-low self-acceptance group" (28.66%, 45/157), the "moderate self-acceptance group" (47.13%, 74/157), and the "low avoidance-high self-acceptance group" (24.20%, 38/157). Logistic regression analysis showed that age, body mass index (BMI), diabetes-related stigma, diabetes knowledge, and electronic health literacy were significant influencing factors of self-acceptance profiles in young and middle-aged patients with T2DM ( P<0.05) . Conclusions:The level of self-acceptance in newly diagnosed young and middle-aged patients with type 2 diabetes mellitus remains suboptimal. Particular attention should be paid to patients who are younger, have a BMI below 24.0 kg/m 2, experience high levels of diabetes-related stigma, and have low levels of diabetes knowledge and electronic health literacy. Targeted education and management should be implemented based on patient characteristics.

Objective:To explore the mediating effect of chronic disease resource utilization between health promotion behaviors and disease control in patients with type 2 diabetes mellitus (T2DM) .Methods:Convenience sampling was used to select T2DM patients who attended the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Zhengzhou University from September 2023 to October 2024 for the study. The survey was conducted using the General Information Questionnaire, Chronic Illness Resources Survey (CIRS), Health Promoting Lifestyle Profile-Ⅱ (HPLP-Ⅱ), and Control Status Scale for Diabetes (CSSD). Pearson correlation was used to analyze the relationship between chronic disease resource utilization, health promotion behaviors, and disease control. Structural equation modeling and mediating effect validation were performed using AMOS 21.0.Results:A total of 310 questionnaires were distributed, 292 valid questionnaires were recovered, with a valid recovery rate of 94.19%. The CIRS, HPLP-Ⅱ, and CSSD scores of 292 patients were (53.45±12.83), (145.85±28.40), and (89.41±24.57), respectively. CIRS scores were positively correlated with HPLP-Ⅱ scores and CSSD scores ( P<0.05), and HPLP-Ⅱ scores were positively correlated with CSSD scores ( P<0.05), with statistically significant differences. Mediating effect analysis showed that health promotion behaviors had a direct positive effect on disease control ( P=0.001), and chronic disease resource utilization had a partial mediating effect between health promotion behaviors and disease control ( P=0.001), with statistically significant differences and mediating effect accounting for 26.88% of the total effect (0.157/0.584) . Conclusions:Chronic disease resource utilization, health promotion behaviors, and disease control among T2DM patients are suboptimal, and there is room for improvement. Chronic disease resource utilization has a partial mediating effect between health promotion behaviors and disease control, which may guide clinical nursing practice.

Objective:To identify latent profile types of self-acceptance among newly diagnosed young and middle-aged patients with type 2 diabetes mellitus (T2DM), and to analyze the influencing factors.Methods:A convenience sampling method was used to recruit 162 patients with T2DM who visited the Department of Endocrinology at the First Affiliated Hospital of Zhengzhou University between March 2023 and August 2024. A general information questionnaire was used to collect demographic and clinical data. The Acceptance and Action Diabetes Questionnaire (AADQ), Type 2 Diabetes Stigma Assessment Scale (DSAS-2), Diabetes Knowledge Test 2 (DKT2), and e-Health Literacy Scale (eHEALS) were used to assess self-acceptance, diabetes-related stigma, diabetes knowledge, and electronic health literacy, respectively. Latent profile analysis (LPA) was performed to identify categories of self-acceptance based on AADQ scores. Logistic regression analysis was conducted to examine the influencing factors of self-acceptance profiles in young and middle-aged patients with T2DM. A total of 162 questionnaires were distributed, and 157 valid responses were collected, with an effective response rate of 96.91% (157/162) .Results:The mean AADQ score of the 157 patients was (46.64±10.34), ranging from 20 to 63, with a mean item score of (4.24±1.16). Three latent profile categories of self-acceptance were identified: the "high avoidance-low self-acceptance group" (28.66%, 45/157), the "moderate self-acceptance group" (47.13%, 74/157), and the "low avoidance-high self-acceptance group" (24.20%, 38/157). Logistic regression analysis showed that age, body mass index (BMI), diabetes-related stigma, diabetes knowledge, and electronic health literacy were significant influencing factors of self-acceptance profiles in young and middle-aged patients with T2DM ( P<0.05) . Conclusions:The level of self-acceptance in newly diagnosed young and middle-aged patients with type 2 diabetes mellitus remains suboptimal. Particular attention should be paid to patients who are younger, have a BMI below 24.0 kg/m 2, experience high levels of diabetes-related stigma, and have low levels of diabetes knowledge and electronic health literacy. Targeted education and management should be implemented based on patient characteristics.

Objective:To explore the mediating effect of chronic disease resource utilization between health promotion behaviors and disease control in patients with type 2 diabetes mellitus (T2DM) .Methods:Convenience sampling was used to select T2DM patients who attended the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Zhengzhou University from September 2023 to October 2024 for the study. The survey was conducted using the General Information Questionnaire, Chronic Illness Resources Survey (CIRS), Health Promoting Lifestyle Profile-Ⅱ (HPLP-Ⅱ), and Control Status Scale for Diabetes (CSSD). Pearson correlation was used to analyze the relationship between chronic disease resource utilization, health promotion behaviors, and disease control. Structural equation modeling and mediating effect validation were performed using AMOS 21.0.Results:A total of 310 questionnaires were distributed, 292 valid questionnaires were recovered, with a valid recovery rate of 94.19%. The CIRS, HPLP-Ⅱ, and CSSD scores of 292 patients were (53.45±12.83), (145.85±28.40), and (89.41±24.57), respectively. CIRS scores were positively correlated with HPLP-Ⅱ scores and CSSD scores ( P<0.05), and HPLP-Ⅱ scores were positively correlated with CSSD scores ( P<0.05), with statistically significant differences. Mediating effect analysis showed that health promotion behaviors had a direct positive effect on disease control ( P=0.001), and chronic disease resource utilization had a partial mediating effect between health promotion behaviors and disease control ( P=0.001), with statistically significant differences and mediating effect accounting for 26.88% of the total effect (0.157/0.584) . Conclusions:Chronic disease resource utilization, health promotion behaviors, and disease control among T2DM patients are suboptimal, and there is room for improvement. Chronic disease resource utilization has a partial mediating effect between health promotion behaviors and disease control, which may guide clinical nursing practice.

Objective To investigate the protective effect and mechanism of J147 on the injury of human neuroblastoma cells(SH-SY5Y)induced by high glucose(HG).Methods We established HG-induced SH-SY5Y cell injury model.Then SH-SY5Y cells were divided into blank control(Con)group HG group,HG+J147 0.5 μmol/L(HG+J147 0.5)group,HG+J147 1 μmol/L(HG+J147 1)group,HG+J147 2 μmol/L(HG+J147 2)group,HG+PI3K/AKT inhibitor LY294002(LY)10 μmol/L(HG+LY)group,HG+ERK1/2 inhibitor U0126(U0)5 μmol/L(HG+U0)group,HG+J147 2 μmol/L+LY 10 μmol/L(HG+J147 2+LY)group,HG+J147 2 μmol/L+U0 5 μmol/L(HG+J147 2+U0)group.Cell viability was detected by MTS cell proliferation and toxicity detection kit;LDH activity was tested by lactate dehydrogenase kit;morphological changes of SH-SY5Y cells were evaluated by microscope;cell apoptosis was detected by flow cytometry;and apoptosis-related proteins(Bcl-2,Bax)and signaling pathway-related proteins(p-AKT,AKT,p-ERK1/2,ERK1/2,p-CREB,CREB,BDNF)were detected by Western blot.Results Compared with Con group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT,p-ERK/ERK,p-CREB/CREB and BDNF protein expressions decreased(P<0.01),while LDH activity and apoptosis rate increased in HG group(P<0.01).Compared with HG group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT,p-ERK/ERK,p-CREB/CREB and BDNF protein expressions increased(P<0.01),while LDH activity and apoptosis rate decreased in HG+J147 2 group(P<0.01).Compared with HG+J147 2 group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT and BDNF protein expression decreased(P<0.05 or P<0.01),while LDH activity and apoptosis rate increased(P<0.05 or P<0.01),the expression of p-ERK/ERK protein in HG+J147 2+LY group decreased(P<0.05),and the expression of p-CREB/CREB protein in HG+J147 2+U0 group decreased in HG+J147 2+LY and HG+J147 2+U0 groups(P<0.05).Conclusions J147 can alleviate HG-induced SH-SY5Y cell damage,and the mechanism may be related to the activation of PI3K/AKT and ERK1/2 signaling and the reduction of apoptosis.

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Deficiency, stasis, water and toxin are of great significance in the pathogenesis and pathologic evolution of chronic heart failure (CHF). Based on "deficiency, blood stasis, water and toxin", the pathogenesis and treatment of CHF were discussed in this article. It was found that in the pathogenesis, deficiency--deficiency of heart qi and deficiency of heart yang were the origin of the disease, and blood stasis, water and toxin were the markers of the disease. Among them, blood stasis was the central pathological link, and also an important mechanism that could aggravate the disease and cause a vicious cycle; water-phlegm and water dampness were the basic pathological products; toxin-heat toxin, water toxin, and stasis toxin were the final results of disease progress and product accumulation. In terms of treatment, CHF can be divided into four stages: early, middle, late and end. In the early stage, tonifying qi and regulating heart can be used for the treatment of root cause, and promoting blood circulation and water can be used for the treatment of symptoms; tonifying qi and yin and reinforcing the healthy qi, reducing blood stasis, purging turbid, and eliminating pathogenic factors can be used in the middle stage; reducing blood stasis and removing toxic materials should be used in the late stage, supplemented with warming yang and increasing urine excretion; astringing yang,generating body fluids, tonifying qi and yang should be used in the end stage. At the same time of treating by stages, attention should be paid to adhering to a holistic concept and dialectical treatment; pay attention to timing and flexible medication; adopting a combination of Chinese and Western approaches and integrating them.

ObjectiveTo observe the difference in the efficacy of three kinds of traditional Chinese medicine （TCM） injections on rat model of heart failure induced by transverse aortic constriction （TAC）， explore the TCM syndrome of the model based on the theory of correspondence of prescription and syndrome， and reveal the biological basis of prescription-syndrome from the perspective of metabolism. MethodRats were treated with TAC for modeling and were divided into Shenmai injection group （6.0 mL·kg^-1）， model group， Danhong injection group （6.0 mL·kg^-1）， Shenfu injection group （6.0 mL·kg^-1） and trimetazidine group （10 mg·kg^-1）， and sham operation group was set up as control. After drug intervention for 15 days， echocardiography， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and myocardial histopathological staining were performed for each group， so as to compare the efficacy to select the effective injection. Colorimetry was used to detect the serum glucolipid metabolism after the intervention of the effective injection， and ultra high performance liquid chromatography-mass spectrometry was used to observe the metabolites and related metabolic pathways in myocardial tissue. ResultCompared with the sham operation group， the left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （FS） in the model group decreased （P<0.01）， while the left ventricular end-diastolic diameter （LVIDd）， left ventricular internal diameter at end-systole （LVIDs） and NT-proBNP level increased （P<0.01）. Compared with model group， LVEF and FS increased （P<0.01）， LVIDd， LVIDs and NT-proBNP level decreased （P<0.05， P<0.01） in Danhong injection group， NT-proBNP level in Shenfu injection group decreased （P<0.05）， LVIDd and NT-proBNP level increased （P<0.05， P<0.01） in Shenmai injection group， in trimetazidine group， LVEF and FS increased （P<0.01）， while LVIDs and NT-proBNP level decreased （P<0.05， P<0.01）. Serum glucose， low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels in Danhong injection group and trimetazidine group were adjusted by callbacks （P<0.01， P<0.05）. There were the callback of 9 myocardial metabolites in Danhong injection group， including glycine， serine and threonine metabolism， glyoxylate and dicarboxylate metabolism， glycerol phospholipid metabolism. There were the callback of 10 myocardial metabolites in trimetazidine group， including glycerol phospholipid metabolism. ConclusionThe efficacy of Danhong injection on heart failure model induced by TAC is significant and superior to Shenfu injection and Shenmai injection， suggesting that the model is closely related to heart-blood stasis. The biological mechanism of Danhong injection interfering with the model involves regulating the metabolic disorder of lipid， glucose， amino acid and butyric acid.