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.

【Objective】 To investigate the distribution of ABO and RhD blood groups among voluntary blood donors in Guangzhou, in order to ensure clinical blood safety and better serve blood donors. 【Methods】 Routine ABO and RhD blood group screening tests were carried out among voluntary blood donors from January 2021 to December 2022. The composition ratio of ABO blood group was statistically analyzed. The samples with discrepancy between forward and reverse blood grouping and negative RhD blood group samples were further verified by serological test to analyze the ABO subtypes and the reasons for missed detection. 【Results】 A total of 749 123 blood samples were screened from January 2021 to December 2022, and 513 291 samples were collected after excluding repeat blood donors, with the ABO blood groups as 208 126(40.55%) of O type, 138 859(27.05%) of A type, 130 987(25.52%) of B type and 35 319(6.88%) of AB type. The screening results showed discrepancy between forward and reverse blood grouping in 506 samples, of which 58 were with weak/non-erythrocyte reaction, 16 with erythrocyte reaction, 215 with weak/non-serum reaction, and 217 with serum reaction. Further serological test indicated that 44 samples were ABO subtypes, among which 13 were subtype A, 26 subtype B, 5 subtype AB and 3 B (A) and 14 Bombay-like blood group. The blood group with the highest missed detection rate in repeat blood donors were A3/B3 subtype (68.42%). A total of 128 unexpected antibody positive samples were detected among 513 291 samples A total of 2 277 samples were screened negative for RhD blood type, of which 2 188 were confirmed to be Rh negative (2 188/513 291, 0.43%), 89 were D variants (89/513 291, 0.02%, ) and 30 were detected with unexpected antibodies (30/2 188, 1.37%). 【Conclusion】 The ABO blood group distribution of blood donors in Guangzhou is O>A>B>AB, and the proportion of RhD negative population is 0.43%, slightly highter than 0.3%-0.4% of Han population nationwide. The ABO blood group subtype is dominated by B subtype. The detection rate and missed detection rate of A3/B3 subtypes in routine blood group tests are the highest.

[摘 要] 目的：评估干扰CD36表达白血病细胞培养上清液对血小板活化的影响及其机制。方法: 利用L1210小鼠白血病细胞上清液培养血小板4、6、12、24 h，以普通培养基培养血小板作为对照，通过流式细胞术检测血小板活化标志物P-选择素（CD62P）的表达，WB法检测CD36表达，确定上清液活化血小板最佳时间。构建CD36干扰载体转染至活化的血小板中，实验分为对照组、模型组、CD36干扰空载体组（si-CD36 NC）、CD36干扰组（si-CD36）、抑制剂组（iCRT3）、抑制剂 + CD36干扰组（iCRT3 + si-CD36），CCK-8法检测血小板活力，流式细胞术检测血小板中CD62P表达，WB法检测血小板中PECAM-1、CD36、β-catenin蛋白表达。结果: L1210小鼠白血病细胞上清液活化血小板最佳时间为12 h。与对照组相比，模型组血小板活力、CD62P表达、PECAM-1、CD36、β-catenin蛋白表达均显著上升（均P < 0.01）。与模型组相比，si-CD36和iCR73组血小板活力、CD62P表达、PECAM-1、CD36、β-catenin蛋白表达均显著下降（均P < 0.01）。与iCRT3组相比，iCRT3 + si-CD36组变化更为显著。结论: CD36干扰抑制β-catenin蛋白表达，协同Wnt/β-catenin通路抑制剂，进而抑制小鼠白血病细胞上清液介导的血小板活化。

Objective To establish a quality control mechanism based on the Poisson distribution for monitoring con-tamination in nucleic acid testing(NAT)laboratories.Methods The study collected NAT single-reactivity rates and dis-criminatory test reactivity rates from the Grifols Panther NAT system from 2022 to 2023.The Poisson distribution probability method was used to calculate the daily probability of nucleic acid single reactivity.Sensitivity and specificity of the quality control model were further validated using single-reactivity rates,discriminatory reactivity rates and ROC curve analysis,fol-lowed by proposing corresponding multi-rule quality control strategies.Results Using P=0.05 as the threshold for out-of-control,the Poisson distribution probability quality control model identified 40 out-of-control points with P<0.05.After man-ual verification using discriminatory reactivity rates,20 out-of-control points were confirmed.The sensitivity of determining out-of-control was 60.0%,and the specificity was 95.6%.Due to the high number of out-of-control points,it is recommen-ded to combine discriminatory reactivity rates and employ multi-rule quality control methods for quality monitoring.Under the multi-rule quality control,there were 18 warning points and 2 out-of-control points for NAT single reactivity from 2022 to 2023.Conclusion The multi-rule NAT single-reactivity monitoring mechanism based on the Poisson distribution probability is more suitable for nucleic acid laboratories to monitor and warn of laboratory contamination,thereby enhancing the manage-ment capabilities and detection quality of nucleic acid laboratories.

Objective To analyze the development trajectory and predictors of endocrine therapy associated arthralgia in breast cancer patients.Methods From January 2022 to July 2022,breast cancer patients in the breast medicine department or outpatients of a tertiary cancer hospital in Hunan Province were selected as respondents using a convenience sampling method.A baseline survey was conducted using the General Information Questionnaire,the Symptom Assessment Scale for Patients Treated with Endocrine Therapy for Breast Cancer,and the Self-Rating Anxiety Scale within 1 week prior to patient treatment.The Symptom Assessment Scale for Patients Treated with Endocrine Therapy for Breast Cancer was used to assess patients'arthralgia levels at 3,6,and 9 months after treatment,and data were analyzed using growth mixed model,univariate analysis of variance,and multiple logistic regression.Results A total of 418 breast cancer patients completed the follow-up,with 235 cases(56.22%)developing arthralgia.3 potential categories of arthralgia develop-ment trajectories were identified:high level-slowly increasing group(11.48%),low level-slowly increasing group(44.74%),and asymptomatic group(43.78%).The results of multifactorial analysis showed that anxiety,history of bone and joint disease,sleep duration,place of residence,monthly household income,and frequency of exercise were predictors of potential categories for the development of trajectory of arthralgia levels associated with endocrine therapy in breast cancer patients(P<0.05).Conclusion Arthralgia levels associated with endocrine therapy in breast cancer patients exhibit different trajec-tories,and clinical staff should emphasize the assessment and intervention of pain levels in patients with the anxiety,a history of bone and joint disease,poor sleep,poor finances,living in urban areas,and low frequency of exercise.