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.

Recent years have witnessed significant advancements in myopia control research through the application of diffuse optical technology(DOT)spectacle lenses. Myopia has emerged as a global public health challenge, affecting nearly half of the world's population, with childhood and adolescent myopia rates continuing to rise. DOT lenses represent an innovative myopia control intervention based on retinal contrast signal theory. These lenses incorporate micro-light scattering dots distributed across the lens surface to reduce retinal imaging contrast and modulate the influence of visual input on axial elongation, thereby slowing myopia progression. The core mechanism operates through refractive index differences between the lens substrate(1.53)and scattering dots(1.50), which generate optical scattering effects. This design maintains clear vision through a central 5 mm optical zone while effectively reducing contrast signal intensity in the peripheral retina. Large-scale randomized controlled trials, including the CYPRESS study, have demonstrated significant myopia control efficacy in children aged 6-10 years: 12-month follow-up data revealed a 74% reduction in myopia progression and a 50% reduction in axial elongation, with sustained safety and visual quality maintained over 4-year long-term follow-up. However, several aspects of DOT technology remain contentious and require further clinical validation, including its applicability across different age groups, optimal scattering dot density configurations, combined application effects with other myopia control methods, and long-term visual adaptation during extended use. This review systematically examines the theoretical foundations, design characteristics, clinical application progress, and future development directions of DOT technology, providing scientific evidence for clinical myopia prevention and control strategy formulation.

AIM: To study the early outcomes of anterior segment parameters after implantation of an implantable collamer lens with a central hole(ICL V4c)in patients with high myopia.METHODS:A total of 82 cases(160 eyes)with high myopia, including 42 males(82 eyes)and 40 females(78 eyes), aged 26.0±4.6(21 to 37)years, who underwent ICL V4c implantation at our institution from February 2019 to September 2022 and were followed up for 1 a, were included. The general characteristics of the anterior segment of the eye were measured preoperatively: spherical equivalent, mean horizontal corneal curvature, white-to-white(WTW), and axial length(AL); intraocular pressure(IOP), endothelial cell density(ECD), central anterior chamber depth(CACD), anterior chamber volume(ACV)and anterior chamber angle(ACA)were measured preoperatively and at 1 d, 1 wk, 1, 3 and 6 mo postoperatively. Furthermore, the distance from the centre of the posterior surface of the ICL V4c optical zone to the anterior surface of the lens(vault)was measured at 1 d, 1 wk, 1, 6 mo, and 1 a after surgery.RESULTS: The mean preoperative spherical equivalent of the patients was -7.56±2.55 D, mean horizontal corneal curvature was 42.89±1.47 D, WTW was 11.64±0.37 mm, and AL was 26.64±0.93 mm. The baseline IOP was 15.97±2.13 mmHg, and the differences in IOP at each time point after ICL V4c implantation compared to preoperative were not statistically significant(F=0.875, P=0.504); ECD was 2 989.30±140.78 cells/mm2 at baseline, and ECD at 6 mo after ICL V4c implantation was not statistically significant compared with preoperative ECD(t=1.475, P=0.142); CACD was 3.19±0.21 mm at baseline, and ACV was 210.30±27.7 mm3, and CACD and ACV were significantly lower than preoperative at all postoperative time points(F=111.10, 288.38, all P<0.001). The baseline ACA was 35.44°±11.27°, and the ACA at each time point after ICL V4c implantation was significantly lower than preoperatively(F=21.23, P<0.001). The vault was 665.32±184.03 μm at 1 d postoperatively, and continued to be significantly reduced at 1 wk, 1, 6 mo, and 1 a postoperatively compared with 1 d(F=52.10, P<0.001). However, it remained stable at 6 mo and 1 a postoperatively, and the difference was not statistically significant compared with vault at 1 mo postoperatively(P>0.05).CONCLUSION: ICL V4c has certain safety and efficiency in 1 a postoperative follow-up, and the parameters of the anterior segment of the eye stabilized in the early period.

Cervical Bronchogenic cysts (BC) is a rare congenital abnormality caused by abnormal budding of the embryonic foregut diverticulum. Mediastinal and intrapulmonary types are the most common sites of occurrence, and thyroid BC is rare. This article aims to report a case of resection of thyroid BC with video-assistance technology to improve the understanding of the imaging, pathology and clinical aspects of this disease.

Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

Objective:To investigate the impact of QiliQiangXin Capsules on ventricular remodeling and cardiac contraction and relaxation function in aging rats with heart failure following myocardial infarction.Methods:From August 2022 to August 2023, a total of 30 old rats were randomly assigned to three groups: sham-operated group, model group, and treatment group, with 10 rats in each group selected through a digital lottery method.The model and treatment groups were created by ligating the anterior descending branch of the left coronary artery.The rats in the treatment group received daily administration of Astragalosa hebecarpa Drabanemerosa Strong Heart Capsule(1.0 g/kg)via gavage after 4 weeks.After the 4-week drug administration period, echocardiography was performed to measure various parameters including left ventricular end-diastolic internal diameter(LVIDd), left ventricular end-systolic internal diameter(LVIDs), left ventricular ejection fraction(LVEF), left ventricular anterior wall myocardial thickness(LVAWd), mitral valve early diastolic peak flow velocity(E peak), and early diastolic velocity of mitral annulus(e peak)detected by tissue Doppler(TDI). The E/e value was calculated based on these measurements.Additionally, serum levels of B-type brain natriuretic peptide(BNP), matrix metalloproteinase 2(MMP-2), matrix metalloproteinase 9(MMP-9), and tumor necrosis factor(TNF-α)were measured using enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE)staining was employed to observe the morphological changes in myocardial tissue.Results:Compared to rats in the model group, rats in the treatment group exhibited lower left ventricular internal dimension at end-diastole(LVIDd)(9.1±0.6 mm vs.11.4±0.8 mm, P<0.01), lower left ventricular internal dimension at end-systole(LVIDs)(5.9±0.8 mm vs.8.7±0.9 mm, P<0.01), lower E/e ratio(13.4±2.0 vs.16.3±2.8, P<0.05), higher left ventricular ejection fraction(LVEF)(68.8±7.1% vs.52.0±8.4%, P<0.01), and elevated left ventricular anterior wall thickness at end-diastole(LVAWd)(1.5±0.2 mm vs.1.2±0.3 mm, P<0.05). In addition, compared to rats in the model group, the treatment group showed a decrease in brain natriuretic peptide(BNP)(0.26±0.04 μg/L vs.0.34±0.05 μg/L, P<0.01), decreased matrix metalloproteinase-2(MMP-2)(3697.0±857.7 μg/L vs.4719.5±703.5 μg/L, P<0.01), decreased matrix metalloproteinase-9(MMP-9)(87.3±13.8 μg/L vs.116.5±9.6 μg/L, P<0.01), decreased tumor necrosis factor-alpha(TNF-α)(165.3±36.9 μg/L vs.269.8±35.0 μg/L, P<0.01), and lower TNF-α levels(165.3±36.9 μg/L vs.269.8±35.0 μg/L, P<0.01). Histological examination using hematoxylin and eosin(HE)staining revealed that the treatment group had less severe cardiac myocyte arrangement disorder and inflammatory reaction compared to the model group. Conclusions:Qiliqiangxin Capsules were found to effectively delay ventricular remodeling and improve myocardial contraction and relaxation function in aging rats with heart failure after acute myocardial infarction.

Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.