Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Asthma, a chronic inflammatory airway disease with a high global prevalence, has a complex pathogenesis, in which airway remodeling plays a key role in the chronicity of the disease. Airway remodeling involves a series of pathophysiological changes, including airway epithelial damage, proliferation of mucous glands and goblet cells, subepithelial fibrosis, proliferation and migration of airway smooth muscle cells, and epithelial-mesenchymal transition. These complex pathological changes significantly increase airway resistance and responsiveness, forming an important pathological basis for refractory asthma. Currently, the regulatory mechanisms of airway remodeling focus on signaling pathways and regulatory targets. The signaling pathways include phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor-κB(NF-κB), transforming growth factor-β1(TGF-β1)/Smads, and mitogen-activated protein kinase(MAPK). The regulatory targets include microRNAs(miRNAs), competing endogenous RNAs(ceRNAs), long non-coding RNAs(lncRNAs), and circular RNAs(circRNAs). Key proteins involved in these processes include TGF-β1, silencing information regulator 2-related enzyme 1(SIRT1), chitinase 3-like protein 1(YKL-40), and adenosine deaminase-metalloproteinase 33(ADAM33). In recent years, the potential of traditional Chinese medicine in the treatment of asthma has become increasingly evident. Its active ingredients, extracts, and complexes can inhibit airway remodeling in asthma through multiple pathways, demonstrating a variety of effects, including anti-inflammatory actions, inhibition of smooth muscle cell proliferation and migration, regulation of epithelial-mesenchymal transition, attenuation of fibrosis and basement membrane thickening, reduction of mucus secretion, inhibition of vascular remodeling, modulation of immune imbalance, and antioxidative stress. This paper aims to provide an in-depth analysis of the pathogenesis and therapeutic targets of asthma, offering theoretical support and innovative strategies for clinical research and drug development in the treatment of asthma.
Asthma/pathology* ; Humans ; Airway Remodeling/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; Transforming Growth Factor beta1/metabolism*

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:To explore the correlation between color Doppler ultrasound, Cyfra21-1, Fer and malignant ovarian lesions and the value of combined model identification.Methods:A total of 108 patients with suspected ovarian cancer admitted to our hospital from Jan. 2021 to Dec. 2023 were selected as subjects. All patients were tested by color Doppler ultrasound, Cyfra21-1 and Fer, and were divided into malignant group (61 cases) and benign group (47 cases) according to the pathological test results. The baseline data, ultrasound parameters, Cyfra21-1 and Fer levels of the two groups were compared, and multivariate regression analysis was performed to establish a multi-factor combined model, and ROC curve was used to evaluate the differential efficacy of the combined model.Results:There was no significant difference in baseline data such as age and course of disease between the two groups ( P>0.05). In the malignant group, the lesion diameter was (7.66±1.24) cm, with solid echo detection in 37 cases and inner wall with nipple detection in 38 cases. In the benign group, the lesion diameter was (5.14±1.03) cm, with solid echo detection in 18 cases and inner wall with nipple detection in 17 cases. In the malignant group, PS was (22.94±4.61) cm/s, EDV was (15.67±3.42) cm/s, VM was (12.43±3.15) cm/s. PS, EDV and VM in benign group were (15.63±4.24) cm/s, (8.95±3.04) cm/s and (17.08±4.21) cm/s respectively, and those in malignant group were higher than those in benign group ( P<0.05). RI in the malignant group was 0.35±0.06, RI in the benign group was 0.58±0.13, and RI in the malignant group was lower than that in the benign group ( P<0.05). Multivariate regression analysis showed that lesion diameter, solid echo, inner wall with papilla, PS, EDV, VM, Cyfra21-1, Fer and RI were all independent risk factors for ovarian malignant lesions, and lesion diameter, solid echo, inner wall with papilla, PS, EDV, VM, Cyfra21-1 and Fer were positively correlated with ovarian malignant lesions. RI was negatively correlated with ovarian malignant lesions ( P<0.05). ROC curve results showed that the diagnostic efficiency of the combined model was higher than that of the single use of Doppler ultrasound, Cyfra21-1 and Fer. Conclusion:The combined diagnosis model of color Doppler ultrasound, Cyfra21-1 and Fer is helpful to improve the diagnostic efficiency of ovarian malignant lesions.

Background Sleep disturbances in children and adolescents have become a global public health concern,with pronounced issues in the Western China.Despite this,research on the prevalence of insomnia and its influencing factors among children and adolescents in Chongqing is still lacking.Objective To understand the prevalence of insomnia and analyze its influencing factors among children and adolescents in Chongqing,so as to provide references for clinical interventions and preventive strategies of insomnia.Methods A stratified random sampling method was used to select 9 969 children and adolescents in Chongqing from November to December 2021.Insomnia Severity Index(ISI)and a self-designed questionnaire on awareness of core mental health knowledge were administered.Binary Logistic regression analysis was used to identify the influencing factors of insomnia in this population.Results A total of 3 578 children and adolescents(35.89％)were found to have insomnia symptoms.There were statistically significant differences in the detection of insomnia symptoms among gender,ethnicity,education level,domicile,only-child status,parental education level,introversion/extroversion,parental relationship,average monthly per capita income,family history of mental illness,medical insurance coverage,living situation and understanding of mental health knowledge(P<0.05 or 0.01).Binary Logistic regression analysis identified several risk factors for insomnia,including female gender(OR=1.301,95％CI:1.192～1.419),ethnic minority status(OR=1.163,95％CI:1.015～1.333),junior high school for education level(OR=1.985,95％CI:1.774～2.220),senior high school for education level(OR=3.085,95％CI:2.749～3.462),non-only-child status(OR=1.127,95％CI:1.013～1.253),degree of harmony between parents is not high or not harmonious[(OR=1.846,95％CI:1.669～2.041 for relatively harmonious;OR=2.524,95％CI:2.214～2.877 for generally harmonious;OR=2.452,95％CI:1.999～3.007 for not very harmonious;OR=2.926,95％CI:2.307～3.710 for very discordant)]and incomplete medical insurance coverage(OR=1.218,95％CI:1.093～1.358).Protective factors included an extroverted personality(OR=0.838,95％CI:0.766～0.917),absence of family history of mental illness(OR=0.719,95％CI:0.549～0.941),junior high school for mother's education level(OR=0.822,95％CI:0.734～0.920),senior high school or secondary specialized school for mother's education level(OR=0.862,95％CI:0.752～0.988),college and above for mother's education level(OR=0.748,95％CI:0.633～0.884)and knowledge of mental health(OR=0.854,95％CI:0.778～0.937).Conclusion The problem of insomnia among children and adolescents in Chongqing is quite serious.Risk factors for insomnia include female gender,ethnic minority status,higher education levels,being a non-only child,poor family relationships and incomplete medical insurance.Conversely,an extroverted personality,absence of family history of mental illness,higher maternal education and knowledge of mental health serve as protective factors against insomnia.