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: Asthma, one of the most widespread chronic respiratory diseases, has placed a considerable economic and social stress on China. This study examines the burden of asthma in China from 1990 to 2021 and forecasts future trends, providing guidance for establishing focused preventive and regulatory strategies. METHODS: Utilizing data from the Global Burden of Disease Database 2021, the analysis of trends in asthma burden was conducted for China from 1990 to 2021. Key indicators such as incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were analysed. The investigation applied the estimated annual percentage change (EAPC), average annual percentage change (AAPC), and age-period-cohort model (APCM) to evaluate these trends. Furthermore, predictions for incidence and mortality in 2035 were generated using the Bayesian APCM and the Nordpred model. RESULTS: In 2021, there were 25,015,668 prevalent asthma cases in China, alongside 3,934,875 new cases and 26,233 deaths. The age-standardized incidence rate and age-standardized death rate for 2021 were 364.17 (95% uncertainty interval [95% UI]: 283.22-494.1) per 100,000 population and 1.47 (95% UI: 1.15-1.79) per 100,000 population, respectively. The age-standardized rates (ASRs) for incidence were detected to be elevated in the 0-4 years age group, and the prevalence was significantly higher in the 5-9 years age group compared to other cohorts. ASR for incidence and prevalence of asthma in China were lower than that in the global average. Between 1990 and 2021, the ASR of incidence, prevalence, mortality, and DALYs demonstrated a downward trajectory, with EAPC values of -1.17, -1.57, -4.69, and -2.98, respectively. People aged 0-9 years and over 60 years experienced a disproportionately higher disease burden. Projections indicate that the ASRs for incidence will continue to rise, whereas the death will continue to decline by 2035. CONCLUSIONS Between 1990 and 2021, a general reduction in the asthma burden in China was observed. However, the burden remains particularly high among people aged 0-9 years and over 60 years, underscoring the need for targeted interventions and policies to address the ongoing challenges of asthma.
Humans ; Asthma/mortality* ; China/epidemiology* ; Global Burden of Disease ; Incidence ; Disability-Adjusted Life Years ; Male ; Adult ; Middle Aged ; Child ; Adolescent ; Female ; Prevalence ; Child, Preschool ; Infant ; Aged ; Young Adult ; Infant, Newborn ; Bayes Theorem

AIM: To investigate the risk factors associated with the recurrence of macular edema secondary to branch retinal vein occlusion(BRVO-ME)after anti-vascular endothelial growth factor(anti-VEGF)therapy.METHODS:A total of 32 patients(32 eyes)with BRVO-ME who were treated at the ophthalmology department of the Affiliated Hospital of Shandong Second Medical University from February 2021 to June 2022 were selected. They were treated with a 3+pro re nata (PRN)anti-VEGF regimen and followed up for 6 mo. Following 3 consecutive anti-VEGF injections, patients were categorized into a non-recurrence group and a recurrence group based on central macular thickness(CMT)measured by optical coherence tomography(OCT)at 6 mo post-treatment. Aqueous humor levels of various cytokines levels were quantified using suspension assay method. Demographic characteristics, CMT, and cytokine levels were compared between the two groups, and their correlations with the recurrence of BRVO-ME after anti-VEGF treatment were analyzed.RESULTS:At 6 months post-treatment, ME resolved in 19 eyes(no recurrence group), while 13 eyes showed persistent or recurrent ME(recurrence group). Compared to baseline, the CMT significantly improved in both groups at 1 d, 1, and 6 mo post-treatment(all P<0.05). However, the recurrence group exhibited significantly higher baseline, 1 d and 6 mo post-treatment CMT values than the non-recurrence group(all P<0.05). The aqueous humor levels of VEGF and monocyte chemoattractant protein-1(MCP-1)at baseline were significantly higher in the recurrence group than the non-recurrence group(all P<0.05). Spearman correlation analysis revealed positive associations between baseline CMT and interlukin IL-1β, IL-5, IL-12, MCP-1 and IP-10 levels(all P<0.05). Multivariable Logistic regression analysis identified baseline CMT and MCP-1 levels as independent risk factors for BRVO-ME recurrence(OR>1, P<0.05).CONCLUSION: Elevated baseline CMT and aqueous humor MCP-1 levels were identified as independent risk factors for BRVO-ME recurrence after anti-VEGF therapy. Patients exhibiting higher baseline CMT and MCP-1 levels demonstrated significantly increased susceptibility to recurrence.

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.

Objective:To investigate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer.Methods:A retrospective case series study was conducted. The clinical data of 38 breast cancer patients with metastasis in other parts who received T-DXd treatment in Xi'an International Medical Center Hospital from August 2021 to August 2024 were analyzed. The clinical efficacy and incidence of adverse reactions in patients were recorded, comparison of clinical efficacy in stratified patients based on clinical characteristics was performed, and the progression-free survival (PFS) was analyzed using Kaplan-Meier method.Results:All 38 patients were female, with a median age [ M ( Q1, Q3)] of 55 (42, 60) years; according to the guidelines of the American Society of Clinical Oncology/College of American Pathologists, 13 cases (34.2%) were positive for human epidermal growth factor receptor 2 (HER2) and 25 cases (65.8%) were low in HER2 expression; the Eastern Cooperative Oncology Group (ECOG) physical status scores of 23 cases (60.5%) were 0-2 points and 15 cases (39.5%) were 3-4 points; the median number of T-DXd treatment lines was 4 (2,16) lines. According to the Response Evaluation Criteria in Solid Tumors 1.1, the objective response rate (ORR) of T-DXd treatment was 34.2% (13/38), and the disease control rate (DCR) was 78.9% (30/38); the ORR of patients aged ≤ 50 years old was higher than that of patients aged >50 years old [56.3% (9/16) vs. 18.2% (4/22)], patients with HER2 positive was lower than that of patients with low HER2 expression [100.0 (13/13) vs. 68.0% (17/25)], patients with previous tyrosine kinase inhibitor (TKI) treatment was higher than that of patients without TKI treatment [100.0% (12/12) vs. 69.2% (18/26)], and the DCR of patients with T-DXd treatment for ≥ 4 cycles was higher than that of patients with T-DXd treatment for 1-3 cycles [100.0% (25/25) vs. 38.5% (5/13)], and the differences were statistically significant (all P < 0.05). Among the 38 patients, 19 (50.0%) stopped medication due to disease progression, 11 (28.9%) stopped medication due to economic reasons, 1 (0.8%) stopped medication due to grade 3 nausea and vomiting, and 1 (0.8%) stopped medication due to grade 2 interstitial lung disease (ILD), while the remaining 6 (15.8%) were undergoing T-DXd treatment. The median follow-up time was 9.5 (3.9, 17.8) months, and 16 cases (42.1%) progressed and died; the median PFS time was 5.9 months (95% CI: 3.1-8.7 months). Adverse reactions were mostly grade 1-2; common hematological adverse reactions included leukopenia [18 cases (47.3%)], neutropenia [16 cases (42.1%)], thrombocytopenia [11 cases (28.9%)], and anemia [15 cases (39.5%)]. Non-hematological adverse reactions included nausea [28 cases (73.7%)], vomiting [15 cases (39.5%)], decreased appetite [20 cases (52.6%)], fatigue [22 cases (57.9%)], alopecia [22 cases (57.5%)], elevated aspartate aminotransferase [20 cases (52.6%)], and elevated alanine aminotransferase [15 cases (39.5%)] were more common. Two cases developed interstitial lung disease (ILD), classified as grade 1 and grade 2, respectively. After discontinuation of medication and treatment with methylprednisolone, they returned to normal. Conclusions:T-DXd ≥ 2 line therapy has good efficacy and safety in the treatment of HER2 positive or low expression metastatic breast cancer. Bone marrow suppression and gastrointestinal adverse reactions are the most common, and the occurrence of ILD should be noted in the treatment.

Objective To observe CT and MRI manifestations of polymorphous low-grade neuroepithelial tumor of the young(PLNTY).Methods Totally 21 cases of PLNTY confirmed by pathology were retrospectively enrolled,and CT and MRI manifestations of the lesions were observed.Results Single supratentorial tumor was found in all 21 cases,including 13 cases of isolated brain parenchymal type,6 cases of diffuse brain parenchymal type and 2 cases of extra parenchymal type PLNTY.Diffusion weighted imaging(DWI)showed no diffusion limitation in all 21 cases,and a few cases with mild peritumoral edema.Among 13 cases of isolated brain parenchymal PLNTY,7 cases presented as calcified nodules,5 cases presented as cystic lesions and 1 case as solid nodule.After administration of contrast agents,no enhancement was found in 11 cases,while mild local enhancement was observed in 2 cases.Six cases of diffuse brain parenchymal PLNTY presented as diffuse thickening of the cortex in lesion area,with abnormal signals in the subcortical white matter in 4 cases.After administration of contrast agents,no enhancement was found in 4 cases,while mild local enhancement was noticed in 2 cases.Two cases of extra parenchymal PLNTY presented as solid mass with calcification,with equal density on CT and mild local enhancement on enhanced MRI.Conclusion CT and MRI manifestations of PLNTY had certain characteristics.