Objective: To investigate the implementation and evaluate the effectiveness of health management services for patients with type 2 diabetes mellitus (T2DM) in Urumqi City from 2017 to 2021, so as to provide the reference for enhancing T2DM patients management. Methods: Data on the rates of record establishment, health management and standardized management for T2DM patients, and blood glucose control rate in managed patients in Urumqi City from 2017 to 2021 were collected through the quarterly reports on basic public health service management from the Weining Health Platform System. The trends in the four management indicators, and the differences between urban and rural areas were analyzed. Results: The rates of record establishment, health management and blood glucose control rate in managed patients in Urumqi City were 46.94%, 38.37% and 59.92%, respectively, showing upward trends from 2017 to 2021 (all P<0.05). The rate of standardized management was 75.89%, showing a downward trend (P<0.05). The rate of record establishment was higher in urban areas than in rural areas (47.76% vs. 40.56%, P<0.05). The rates of standardized management and blood glucose control in managed patients were lower in urban areas than in rural areas (75.18% vs. 81.46%, 58.93% vs. 67.64%, both P<0.05). The rate of health management was 38.39% in urban areas and 38.24% in rural areas, with no statistically significant difference (P>0.05). The trends in the rates of record establishment, health management and standardized management in both urban and rural areas were consistent with those in the overall population. Conclusions From 2017 to 2021, the rates of record establishment, health management and blood glucose control in managed patients in Urumqi City showed upward trends, while the rate of standardized management exhibited a downward trend. There were urban-rural differences in the rates of record establishment, standardized management and blood glucose control in managed patients.

Based on the traditional Chinese medicine(TCM) theory of "kidney-brain interaction", a two-sample Mendelian randomization(MR) analysis was conducted to investigate the causal effects of chronic kidney disease(CKD) on Alzheimer's disease(AD) and analyze the potential mechanisms of kidney-tonifying and essence-replenishing TCM to improve AD. From the perspective that CKD is closely related to the core pathogenesis of AD, namely "kidney deficiency, essence loss, and marrow reduction", genome-wide association study(GWAS) data was used, with the inverse variance weighting(IVW) method as the main approach to reveal the causal association between CKD and AD. Sensitivity analysis was conducted to evaluate the robustness of the results. To further investigate the causal effects of CKD on AD, two different AD datasets were used as outcomes, and the urinary albumin-to-creatinine ratio(UACR) data was used as the exposure for a supplementary analysis. On this basis, the modern scientific mechanism of the kidney-tonifying and essence-replenishing method for improving AD was further explored. The IVW analysis show that CKD(ieu-b-2: OR=1.084, 95%CI[1.011, 1.163], P=0.024; ieu-b-5067: OR=1.001, 95%CI[1.000, 1.001], P=0.002) and UACR(ieu-b-2: OR=1.247, 95%CI[1.021, 1.522], P=0.031; ieu-b-5067: OR=1.001, 95%CI[1.000, 1.003], P=0.015) both have significant causal effects on AD in different datasets, with CKD increasing the risk of AD. The sensitivity analysis further confirmed the reliability of the results. Genetic studies have shown that CKD has a significant causal effect on AD, suggesting that controlling CKD is an important intervention measure for preventing and treating AD. Therefore, further research on CKD's role in AD is crucial in clinical practice. The research enriches the theoretical implication of "kidney-brain interaction", deepens the understanding of AD' etiology, and provides further insights and directions for the prevention and treatment of AD with TCM, specifically from a kidney-based perspective.
Humans ; Alzheimer Disease/genetics* ; Renal Insufficiency, Chronic/genetics* ; Kidney/metabolism* ; Brain/physiopathology* ; Genome-Wide Association Study ; Medicine, Chinese Traditional ; Mendelian Randomization Analysis

Objective To study the impacts of curcumin on the proliferation, migration and cisplatin (DDP) resistance of bladder cancer cells by regulating the liver kinase B1-AMP activated protein kinase-microtubule-associated protein 1 light chain 3 (LKB1-AMPK-LC3) signaling pathway. Methods Human bladder cancer cell line T24 was cultured in vitro, and its DDP resistant T24/DDP cells were induced by cisplatin (DDP). After treating T24 and T24/DDP cells with different concentrations of curcumin, the optimal concentration of curcumin was screened by MTT assay. T24 cells were randomly grouped into control group, curcumin group, metformin group, and combination group of curcumin and metformin. After treatment with curcumin and LKB1-AMPK activator metformin, the proliferation, autophagy, migration, and apoptosis of T24 cells in each group were detected by MTT assay, monodansylcadavrine (MDC) fluorescence staining, cell scratch assay, and flow cytometry, respectively. Western blot was used to detect the expression of proteins related to LKB1-AMPK-LC3 signaling pathway in T24 cells of each group. T24/DDP cells were randomly assigned into control group, curcumin group, metformin group, and combination group of curcumin and metformin. Cells were treated with curcumin and metformin according to grouping and treated with different concentrations of DDP simultaneously. Then, the effect of curcumin on the DDP resistance coefficient of T24/DDP cells was detected by MTT assay. T24/DDP cells were randomly grouped into control group, DDP group, combination groups of DDP and curcumin, DDP and metformin, DDP, curcumin and metformi. After treatment with DDP, curcumin, and metformin, the proliferation, autophagy, migration, apoptosis, drug resistance, and the expression of proteins related to LKB1-AMPK-LC3 signaling pathway in T24/DDP cells of each group were detected with the same methods. Results Compared with the control group, the activity of T24 cells, relative number of autophagosomes, migration rate, Phosphorylated-LKB1 (p-LKB1)/LKB1, Phosphorylated-AMPK (p-AMPK)/AMPK, LC3II/LC3I, and the DDP resistance coefficient of T24/DDP cells in the curcumin group were lower, and the apoptosis rate of T24 cells was higher; the changes in various indicators in the metformin group were opposite to those in the curcumin group. Compared with the curcumin group, the activity of T24 cells, relative number of autophagosomes, migration rate, p-LKB1/LKB1, p-AMPK/AMPK, LC3II/LC3I, and the DDP resistance coefficient of T24/DDP cells in the combination group of curcumin and metformin were higher, and the apoptosis rate of T24 cells was lower. Compared with the control group, there were no obvious changes in various indicators of T24/DDP cells in the DDP group. Compared with the control group and DDP group, the viability of T24/DDP cells, relative number of autophagosomes, migration rate, P-glycoprotein (P-gp) protein expression, p-LKB1/LKB1, p-AMPK/AMPK, and LC3II/LC3I in the combination group of DDP and curcumin were lower, and the apoptosis rate of T24/DDP cells was higher; the changes in the above indicators in the combination group of DDP and metformin were opposite to those in the combination group of DDP and curcumin. Compared with the combination group of DDP and curcumin, the viability of T24/DDP cells, relative number of autophagosomes, migration rate, P-gp protein expression, p-LKB1/LKB1, p-AMPK/AMPK, and LC3II/LC3I in the combination group of DDP, curcumin and metformin were higher, and the apoptosis rate of T24/DDP cells was lower. Conclusion Curcumin can reduce the activity of LKB1-AMPK-LC3 signaling pathway, thereby inhibiting autophagy, proliferation and migration of bladder cancer cells, promoting their apoptosis, and weakening their resistance to DDP.
Humans ; Cisplatin/pharmacology* ; Curcumin/pharmacology* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinases/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; Urinary Bladder Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/drug effects* ; AMP-Activated Protein Kinase Kinases ; Microtubule-Associated Proteins/metabolism* ; Apoptosis/drug effects* ; Antineoplastic Agents/pharmacology* ; Metformin/pharmacology* ; Autophagy/drug effects*

Objective To analyze the distribution of platelet antibodies in hospitalized patients and explore the clinical significance of platelet antibody detection. Methods A total of 95 987 hospitalized patient cases from a tertiary hospital in Xi'an from April 1, 2021 to December 31, 2023 were collected. Platelet antibodies were detected by solid-phase agglutination method. Statistical analysis was performed on variables including gender, age, blood type, department, history of blood transfusion, pregnancy history, and disease type. Results Among 95 987 hospitalized patients, the positive rate of platelet antibody detection reached 4.35%. The positive rate of platelet antibodies in female hospitalized patients (5.29%) was higher than that in male patients (3.31%), and the difference was statistically significant (x²=224.124). The positive rate of platelet antibodies in those with pregnancy history (7.92%) was higher than that in those without pregnancy history (4.19%), and the difference was significant (x²=292.773). Similarly, the positive rate of platelet antibodies in those with transfusion history (7.79%) was higher than that in those without transfusion history (3.97%), and the difference was significant (x²=300.209). There was a significant correlation between the positive rate of platelet antibodies and the number of pregnancies (x²=91.061). Conclusion The positive rate of platelet antibodies in 95 987 inpatient cases was 4.35%. The positive rate of platelet antibodies had a close relationship with a history of blood transfusions and pregnancies, and it increased with the number of pregnancies. For patients with multiple transfusion histories and pregnancy histories, screening for platelet antibodies holds significant diagnostic value.
Humans ; Female ; Male ; Adult ; Middle Aged ; Blood Platelets/immunology* ; Inpatients ; Aged ; Pregnancy ; Young Adult ; Adolescent ; Aged, 80 and over ; Autoantibodies/blood*

Objective To investigate the expression and correlation of LY86-AS1 and KHDRBS2 in glioblastoma (GBM), and their impacts on the prognosis of patients and immune cell infiltration. Methods Based on the GSE50161 dataset from the Gene Expression Omnibus (GEO) database, LY86-AS1 and KHDRBS2, which are closely related to the development of GBM, were identified by WGCNA and differential expression analysis. The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to analyze the relationship between the expression of LY86-AS1 and KHDRBS2 and the prognosis of GBM patients. Multiple datasets were employed to analyze the correlation between the expression levels of LY86-AS1 and KHDRBS2 and its relationship with immune cell infiltration. Real-time quantitative PCR was used to verify the expression of LY86-AS1 and KHDRBS2 in GBM and normal brain tissues. The Human Protein Atlas (HPA) database was accessed to obtain the protein expression of KHDRBS2, and immunohistochemical staining was conducted to verify the protein expression of KHDRBS2. Results LY86-AS1 and KHDRBS2 were lowly expressed in GBM tissues and were closely related to the development of GBM, showing a significant positive correlation. Patients with low expression levels of LY86-AS1 and KHDRBS2 had a lower overall survival rate than those with high expression levels. LY86-AS1 was positively correlated with naive B cells, plasma cells, activated NK cells, M1 macrophages, activated mast cells and monocytes. KHDRBS2 was positively correlated with naive B cells, plasma cells, helper T cells, activated NK cells and monocytes. Conclusion The low expression levels of LY86-AS1 and KHDRBS2 in GBM, which is associated with poor prognosis, affect the tumor immune microenvironment and may serve as potential new biomarkers for the diagnosis of GBM and the prognosis assessment of patients.
Humans ; Glioblastoma/metabolism* ; Prognosis ; Brain Neoplasms/pathology* ; Gene Expression Regulation, Neoplastic ; RNA-Binding Proteins/metabolism*

Objective To investigate the clinical relevance and diagnostic or prognostic value of ST3β-galactoside α-2, 3-sialyltransferase 1 (ST3GAL1) in glioma and to confirm its role in promoting malignant phenotypes. Methods Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the correlation between ST3GAL1 expression levels in glioma and clinical parameters to evaluate its diagnostic and prognostic value. The impact of ST3GAL1 on malignant phenotypes of glioma cells-including proliferation, cell cycle progression, apoptosis, and invasion was further validated through ST3GAL1 knockdown experiments. Results The expression level of ST3GAL1 was significantly higher in glioma tissues compared to healthy brain tissues and showed a strong correlation with clinical characteristics of glioma patients. Survival analysis and receiver operating characteristic (ROC) curve demonstrated that ST3GAL1 could serve as a potential diagnostic and prognostic biomarker for glioma. Knockdown of ST3GAL1 suppressed proliferation, invasion, and migration capabilities of glioma cell lines, and induced G1-phase cell cycle arrest. Conclusion ST3GAL1 promotes malignant phenotypes in glioma and plays a critical role in its malignant progression, suggesting its potential as a biomarker for glioma diagnosis and prognosis.
Humans ; Sialyltransferases/metabolism* ; Glioma/diagnosis* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Brain Neoplasms/enzymology* ; beta-Galactoside alpha-2,3-Sialyltransferase ; Disease Progression ; Prognosis ; Cell Movement/genetics* ; Apoptosis/genetics* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism* ; Middle Aged

The cellular and molecular components of the tumor immune microenvironment (TIME) and their information exchange processes significantly influence the trends of anti-tumor immunity. In recent years, numerous studies have begun to evaluate TIME in the context of previous cancer treatment strategies. This review will systematically summarize the compositional characteristics of TIME and, based on this foundation, explore the impact of current cancer therapies on the remodeling of TIME, aiming to provide new insights for the development of innovative immune combination therapies that can convert TIME into an anti-tumor profile.
Tumor Microenvironment/immunology* ; Humans ; Neoplasms/therapy* ; Immunotherapy/methods* ; Animals

Objective To investigate the gene expression and regulatory mechanisms of mouse embryonic fibroblasts (MEFs) under inflammatory conditions, aiming to elucidate the role of MEFs in inflammatory responses and provide a foundation for discovering anti-inflammatory drugs that act by modulating MEF function. Methods MEFs cultured in vitro were divided into the following groups: lipopolysaccharides (LPS)-treated group, inflammatory conditioned medium (CM)-treated group, and control group, which were treated with LPS, CM, and equal volume solvent, respectively. Transcriptome sequencing was used to analyze the effects of two stimuli on gene expression profile of MEFs. Real time fluorescence quantitative PCR (RT-qPCR) was employed to verify the transcription levels of highly expressed genes of MEFs induced by CM. ELISA was performed to determine the concentrations of cytokines in cell supernatants. Finally, the regulatory effects of CM on the activation of signaling pathways in MEFs were analyzed by immunoblotting. Results Transcriptome analysis showed that both LPS and CM induced the transcription of a large number of genes in MEFs. Compared with LPS, CM potentiated the mRNA transcription of some acute phase proteins, inflammatory cytokines, chemokines, matrix metalloproteinases (MMP), prostaglandin synthetases, and colony-stimulating factors. The transcriptome analysis was verified by RT-qPCR. The results of ELISA showed that CM treatment significantly increased the secretion of interleukin 6 (IL-6), C-C motif chemokine ligand (CCL2), and C-X-C motif chemokine ligand (CXCL1) by MEFs compared with LPS. Mechanism study showed that both LPS and CM induced the phosphorylation of nuclear factor-κB p65 (NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), extracellular regulated protein kinases 1/2 (ERK1/2), and TANK-binding kinase (TBK) in MEFs, and CM strongly stimulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in MEFs. Conclusion Both LPS and CM can induce transcription and protein secretion of various inflammation-related genes in MEFs. CM can partly enhance LPS-induced activation of MEFs, and the mechanism may be related to the enhancement effect of CM on the activation STAT3 signaling pathway.
Animals ; Fibroblasts/immunology* ; Mice ; Lipopolysaccharides/pharmacology* ; Inflammation/metabolism* ; Signal Transduction/drug effects* ; Gene Expression Regulation/drug effects* ; Cytokines/genetics* ; Culture Media, Conditioned/pharmacology* ; Cells, Cultured

Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

In hypoxic-ischemic brain damage (HIBD), the programmed cell death known as ferroptosis is significantly activated. Microglial cells demonstrate a high level of sensitivity to iron accumulation. Understanding how to regulate the dual role of microglia and transforming the microglial ferroptosis to a moderate and controllable process has considerable implications for the targeted treatment in HIBD. This paper serves as an overview of microglia-mediated ferroptosis in HIBD as a disease model. We discuss various aspects centered around microglia, including pathophysiological mechanisms, polarization and functions of microglia, molecular mechanisms of ferroptosis, signaling pathways, and therapeutic strategies. The review aims to provide a reference for studies of ferroptosis in microglia.
Microglia/physiology* ; Ferroptosis/physiology* ; Humans ; Animals ; Hypoxia-Ischemia, Brain/pathology* ; Signal Transduction