Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.

Objective:To explore the effect of ezetimibe combined with atorvastatin on the efficacy,blood lipids,ca-rotid ultrasound indicators in patients with coronary heart disease(CHD)and its safety.Methods:This randomized controlled study enrolled 98 CHD patients admitted to 945th Hospital of the PLA Joint Logistic Support Force be-tween June 2021 and June 2023.Patients were divided into intervention group and control group with 49 cases in each group.Patients in the control group was treated with atorvastatin-bascd routine medication comparing to those in intervention group receiving additional ezetimibe,both groups were treated for 90 d.Clinical efficacy,blood lipids,carotid ultrasound indicators,endothelial function indicators,and incidence of adverse reactions were compared between two groups.Results:Compared with patients in the control group,those in the intervention group had significant higher total effective rate(91.83％vs.73.47％,P=0.016).Compared with patients in the control group after treatment,those in intervention group had significant lower levels of low density lipoprotein cho-lesterol(LDL-C)[(2.74±0.61)mmol/L vs.(3.42±0.66)mmol/L],total cholesterol(TC)[(3.80±0.89)mmol/L vs.(4.69±1.02)mmol/L],triglyceride(TG)[(1.79±0.53)mmol/L vs.(2.35±0.62)mmol/L],re-sistance index(RI)[(52.02±6.32)％vs.(57.95±6.02)％],carotid intima-media thickness(IMT)[(0.91±0.17)mm vs.(1.08±0.24)mm],von Willebrand factor(vWF)[(19.03±3.76)mg/L vs.(23.41±4.42)mg/L],angiotensin Ⅱ(Ang Ⅱ)[(45.83±5.87)ng/L vs.(52.87±6.01)ng/L](P＜0.001 all);and significant high-er high density lipoprotein cholesterol(HDL-C)[(1.63±0.32)mmol/L vs.(1.35±0.27)mmol/L],peak systol-ic velocity(PSV)[(47.93±5.26)cm/s vs.(41.32±4.98)cm/s],end-diastolic velocity(EDV)[(36.14±5.10)cm/s vs.(30.73±4.48)cm/s],pulse index(PI)[(85.98±9.03)％vs.(78.42±8.82)％],vascular endothelial growth factor receptor 1(VEGFR1)[(289.14±32.98)ng/L vs.(258.34±29.32)ng/L](P＜0.001 all).There was no significant difference in the incidence of adverse reactions between the two groups(P=0.538).Conclusion:Ezetimibe combined with atorvastatin possesses significant therapeutic effect on CHD patients,which could signifi-cantly reduce blood lipids,improve the carotid blood flow velocity and vascular endothelial function with good safety.

Objective:To explore the correlation between ASXL1 gene mutation characteristics and clinical manifestations and prognosis in patients with myelodysplastic syndrome(MDS).Methods:The clinical date of 264 patients with MDS in Xuzhou Central Hospital,Southeast University from August 2010 to April 2024 was retrospectively analyzed.The patients were divided into ASXL1wt group and ASXL1mut group according to the presence of ASXL1 gene mutation,and the correlation between gene mutation characteristics and clinical manifestations and prognosis was analyzed.Results:Compared with ASXL1wt group,the ASXL1mut group had a higher age of onset(P＜0.05),a higher proportion of males(P＜0.05),while the incidence of del(5q)was lower(P＜0.01).The mutation frequency of ASXL1 in MDS patients was 21.97％,and most of them were frameshift mutations.The p.Gly646fs was the most common amino acid variant,with a mutation frequency of 20.69％.The median overall survival(OS)and leukemia-free survival of patients with this sequence variant was 18.1 and 23.8 months,respectively,while in those without this sequence variant was 30 months and not reached,and the differences were statistically significant(P＜0.05).The results of multivariate analysis showed that the mutation of NRAS,WT1,KIT gene and the p.Gly646fs sequence mutation of ASXL1 gene were independent prognostic factors for OS in ASXL1mut patients.The median OS of ASXL1wt and ASXL1mut patients was 27.9(21.3-40.4)and 23.7(18.6-NA)months,respectively(P＞0.05).Among 58 ASXL1mut patients,5 cases(8.6％)transformed to acute leukemia,including 3 cases with RUNX1 mutation and 3 cases with TET2 mutation.Among 206 ASXL1wt patients,28 cases(13.6％)transformed to acute leukemia.The difference in leukemia transformation rate between the two groups was not statistically significant(P＞0.05).The efficacy of different treatment regimens was similar in the ASXL1mut group,while in the ASXL1wt group,patients receiving allogeneic hematopoietic stem cell transplantation had a significantly better prognosis than those receiving other treatment regimens(P＜0.001).The overall response rate to demethylation therapy was 68.7％and 67.6％in ASXL1mut and ASXL1wt group,respectively,and the difference between the two groups was not significant(P＞0.05).Conclusion:The overall survival of MDS patients with ASXL1mut is poor.The patients with p.Gly646fs sequence mutation have a higher proportion of bone marrow blasts and a worse prognosis.There are no statistical differences in efficacy of different treatment strategies in ASXL1mut group.ASXL1 mutation shows no significant effect on the response of MDS to hypomethylating agent therapy.

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

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 explore the correlation between ASXL1 gene mutation characteristics and clinical manifestations and prognosis in patients with myelodysplastic syndrome(MDS).Methods:The clinical date of 264 patients with MDS in Xuzhou Central Hospital,Southeast University from August 2010 to April 2024 was retrospectively analyzed.The patients were divided into ASXL1wt group and ASXL1mut group according to the presence of ASXL1 gene mutation,and the correlation between gene mutation characteristics and clinical manifestations and prognosis was analyzed.Results:Compared with ASXL1wt group,the ASXL1mut group had a higher age of onset(P＜0.05),a higher proportion of males(P＜0.05),while the incidence of del(5q)was lower(P＜0.01).The mutation frequency of ASXL1 in MDS patients was 21.97％,and most of them were frameshift mutations.The p.Gly646fs was the most common amino acid variant,with a mutation frequency of 20.69％.The median overall survival(OS)and leukemia-free survival of patients with this sequence variant was 18.1 and 23.8 months,respectively,while in those without this sequence variant was 30 months and not reached,and the differences were statistically significant(P＜0.05).The results of multivariate analysis showed that the mutation of NRAS,WT1,KIT gene and the p.Gly646fs sequence mutation of ASXL1 gene were independent prognostic factors for OS in ASXL1mut patients.The median OS of ASXL1wt and ASXL1mut patients was 27.9(21.3-40.4)and 23.7(18.6-NA)months,respectively(P＞0.05).Among 58 ASXL1mut patients,5 cases(8.6％)transformed to acute leukemia,including 3 cases with RUNX1 mutation and 3 cases with TET2 mutation.Among 206 ASXL1wt patients,28 cases(13.6％)transformed to acute leukemia.The difference in leukemia transformation rate between the two groups was not statistically significant(P＞0.05).The efficacy of different treatment regimens was similar in the ASXL1mut group,while in the ASXL1wt group,patients receiving allogeneic hematopoietic stem cell transplantation had a significantly better prognosis than those receiving other treatment regimens(P＜0.001).The overall response rate to demethylation therapy was 68.7％and 67.6％in ASXL1mut and ASXL1wt group,respectively,and the difference between the two groups was not significant(P＞0.05).Conclusion:The overall survival of MDS patients with ASXL1mut is poor.The patients with p.Gly646fs sequence mutation have a higher proportion of bone marrow blasts and a worse prognosis.There are no statistical differences in efficacy of different treatment strategies in ASXL1mut group.ASXL1 mutation shows no significant effect on the response of MDS to hypomethylating agent therapy.

Objective:To explore and analyze the correlation between the expression of mismatch repair(MMR)protein and programmed death ligand 1(PD-L1)in colorectal cancer(CRC)tissue and clinical pathological characteristics.Methods:The study period were from July 2021 to December 2024,200 cases of colorectal cancer patients treated in our hospital were selected as the research subjects.Collected all patient lesion tissue samples(lesion group)and adjacent tissue samples(located ≥5 cm from the tumor edge,adjacent group),and used the immunohistochemistry(IHC)method to detect the expression of Mismatch repair(MMR)(MLH1,MSH2,MSH6,and PMS2)protein and PD-L1 protein.Investigated the clinical and pathological characteristics of patients and conducted correlation analysis.Results:The positive rates of dMMR and pMMR protein expression in the lesion group were 39.00％and 70.00％,respectively,while those in the adjacent cancer group were 11.00％and 89.00％,respectively.There were significant difference compared between the lesion group and the adjacent cancer group(P＜0.05).The positive rate of PD-L1 protein expression in the lesion group were 25.00％,while that in the adjacent cancer group were 80.00％.The expression of PD-L1 protein in the lesion group were significantly lower than that in the adjacent cancer group(P＜0.05).There were significant differences in the positive rates of MMR and PD-L1 protein expression among patients with different histological differentiation,clinical stages,and lymph node metastasis(P＜0.05),while there were no significant differences in the positive rates of MMR and PD-L1 protein expression among patients of different genders,ages,and disease sites(P＞0.05).Spearman analysis showed there were correlation between the expression of MMR and PD-L1 proteins in colorectal cancer tissues and clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis(P＜0.05).Conclusion:Low expression of MMR and PD-L1 proteins are commonly observed in colorectal cancer tissues.The expression of MMR and PD-L1 proteins in colorectal cancer tissues are correlated with clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis.