Objective To observe the efficacy and changes of iron metabolism of standard dose Roxadustat in the treatment of non-dialysis renal anemia patients with different chronic kidney disease(CKD)stages.Methods The data of 36 non-dialysis CKD3-5 patients with renal anemia and substandard hemoglobin(Hb)were retrospectively analyzed from June 2021 to October 2022 in the Department of Nephrography of the Northern Theater Command Hospital.CKD stage3 and 4 were treated as group A(20 cases),and CKD stage 5 was treated as group B(16 cases).All patients were treated with Roxadustat at the standard starting dose.The changes of anemia,biochemical and iron metabolism indexes and adverse reactions were compared before and 3 months after Roxadustat treatment.Results Before treatment,Hb,red blood cell count,hematocrit and transferrin saturation in group A were higher than those in group B,with statistical significance(P＜0.05).There was no significant difference in ferritin,serum iron and hypersensitive C-reactive protein between the two groups(P＞0.05).After treatment,the Hb compliance rate of group A and group B patients was 80.0％and 62.5％,respectively,with no statistical significance(P=0.285).There were no significant differences in Hb,hematocrit,erythrocyte count,ferritin,transferrin saturation,serum iron and hypersensitive C-reactive protein between 2 groups(P＞0.05).After treatment,Hb,hematocrit and red blood cell count were increased compared with those before treatment,and the differences were statistically significant(P＜0.05).During the treatment period,2 patients had hyperkalemia and 5 patients had mild gastrointestinal symptoms,all of which were tolerable.No adverse cardiovascular events occurred in all patients.Conclusion The standard dose of Roxadustat has good clinical efficacy and high safety in the treatment of non dialysis renal anemia patients with different CKD stages.
Objective To analyze the levels and correlation of vitamin D,ACE2,ACE and inflammatory factors in patients with type 2 diabetes mellitus and explore the interaction of vitamin D with ACE2 and inflammatory factors and the mechanism of action on the occurrence and development of diabetes.Methods A total of 87 non-diabetic controls and 96 patients with type 2 diabetes mellitus were chosen,who visited Hebei People's Hospital and were hospitalized from July 2021 to November 2021,and they were divided into non-diabetic normal vitamin D group(47 cases)and insufficient vitamin D group(40 cases),and diabetic normal vitamin D group(52 cases)and insufficient vitamin D group(44 cases)according to serum 25-hydroxyvitamin D level.Detect inflammatory indicators such as ACE,ACE2,IL-6 and TNF-α in each group,and analyze the correlation and influencing factors between vitamin D and each indicator.Results Compared with the normal vitamin D group,the vitamin D insufficiency group had significantly higher HOMA-IR,Ang Ⅱ,IL-6,and TNF-α levels and significantly lower ACE2 and IL-10 levels in both non-diabetic and diabetic patients(P＜0.05).Compared with the non-diabetic vitamin D insufficiency group,with the increase in severity of vitamin D deficiency,blood glucose,ACE and inflammatory factors were significantly increased,insulin resistance was more serious,and ACE2 and IL-10 were significantly decreased(P＜0.05).Pearson correlation analysis showed that vitamin D was negatively correlated with Ang Ⅱand IL-6,and positively correlated with IL-10 in the non-diabetic group(P＜0.05).In the diabetic group,vitamin D was positively correlated with ACE2 and IL-10,and negatively correlated with ACE,Ang Ⅱ,IL-6,TNF-α,HOMA-IR and HbA1c(all P＜0.01).Multiple linear regression analysis showed that IL-10 and Ang Ⅱ were the main influencing factors of vitamin D deficiency in the non-diabetic group(P＜0.05),which explained 33.6％of the total variation of the regression equation.In the diabetes group,ACE2,IL-6,TNF-α,IL-10 and HOMA-IR were the main influencing factors of vitamin D deficiency(P＜0.05),which explained 55.8％of the total variation of the regression equation.Conclusions Vitamin D deficiency may lead to dysregulation of ACE2,ACE/Ang Ⅱ and increased levels of inflammatory factors.Vitamin D deficiency exacerbates insulin resistance by mediating the RAS system,which is involved in the potential pathogenesis of diabetes.ACE2,ACE/Ang Ⅱ and inflammatory factors can be used as susceptible markers of vitamin D deficiency in diabetes.
Background Large granular lymphocyte leukemia (LGLL) is a rare disease frequently complicated with pure red cell aplasia (PRCA) [1, 2]. STAT3 mutations have been describled in 30-40% of LGLL patients [3]. The aim of this work was to evaluate whether STAT3 mutations might be associated with specific clinical features and outcomes in LGLL-associated PRCA. Methods and results From January 2016 to July 2023, 81 patients with LGLL-associated PRCA were enrolled in the China Eastern Cooperation Group for Anemia (CECGA) database (ChiCTR2100043485). As an initial step in the STAT3 mutational analysis, we screened all patients with Sanger sequencing or Next-generation sequencing (NGS). The initial dose of CsA was 3-5mg/kg/day, and the serum concentration was adjusted to be 150-200ng/mL based on adverse reactions. After 12 months of maintenance, the dosage was slowly reduced. Cyclophosphamide combined with prednisone (CP) regimen was used as a salvage therapy for patients who failed to CsA. The initial dose of cyclophosphamide and prednisone were 100mg/day and 0.5-1mg/kg/day, respectively. Among the 81 cases, 26% of them were positive for STAT3 mutations. The clinical characteristics of patients with or without STAT3 mutation were summarized in Table 1. Patients with STAT3 mutations had a higher reticulocyte percentage (0.88% vs 0.28%, P=0.039) and red cell distribution width-coefficient of variation (18.8% vs 15.8%, P=0.008) than patients without STAT3 mutations. Y640F mutation were found in 9 of 21 cases. Subgroup analysis showed that patients with Y640F mutation were associated with younger age (44 vs 65 years old, P=0.007) and higer lymphocyte percentage in peripheral blood (63.7% vs 34.4%, P=0.033). Deep sequencing of rearranged T-cell receptor Vβ complementarity-determining region 3 by NGS was conducted in 61 patients. The predominant V-gene of LGLL clonotypes belonged to the TRBV06 family gene was detected in 12 (25%) patients. The expression of TRBV06 family gene was a litter lower in patients with STAT3 mutation than non-mutant groups (8% vs 31%, P=0.189). The complete response rate (CRR) [31% (5/16) vs 33% (19/58), P=0.909] and overall response rate (ORR) [56% (9/16) vs 50% (29/58), P=0.658] of cyclosporine (CsA) treatment were similar in patients with STAT3 mutations or not. In STAT3 mutant group, the CRR [54% (7/13) vs 31% (5/16), P=0.274] and ORR [85% (11/13) vs 56% (9/16), P=0.130] of CP regimen tended to be better than CsA . 6 patients (67%) relapsed among the 9 patients who responded to CsA in STAT3 mutant group. In patients without STAT3 mutation, 19 of 29 (66%) CsA-responders relapsed. There was no siginificant difference in the relapse-free survival between the two group (Figure 1). Discussion/Conclusions In summary, STAT3 mutation was frequently recognized in LGLL-associated PRCA, and the hotspot site was Y640F. Patients with STAT3 mutations responded to CsA as well as those without the mutation. CP regimen could be used as a salvage therapy for patients who failed to CsA. Reference 1. Balasubramanian SK, Sadaps M, Thota S, et al. Rational management approach to pure red cell aplasia. Haematologica. 2018, 103(2): 221-230. 2. Wu X, Cheng L, Liu X, et al. Clinical characteristics and outcomes of 100 adult patients with pure red cell aplasia. Ann Hematol. 2022, 101(7):1493-1498. 3. Barilà G, Teramo A, Calabretto G, et al. Stat3 mutations impact on overall survival in large granular lymphocyte leukemia: a single-center experience of 205 patients. Leukemia. 2020, 34: 1116-1124.
病毒性肝炎,特别是慢性乙型和丙型病毒性肝炎,如果没有得到及时有效的治疗,最终都将进展为肝硬化、肝衰竭或肝细胞癌等临床终点事件,导致患者死亡.在疗效评价方面,除了关注病毒学、血清学和肝功能等指标外,临床终点事件也是评价疗效的重要指标.这期文章重点关注病毒性肝炎的各种不良临床结局及其在疗效评价中的作用.
目的 评价CYP2C19基因多态性及经皮冠状动脉介入治疗(PCI)术后患者氯吡格雷抵抗对预后的影响,为以CYP2CJ9基因多态性进行抗血小板药物选择提供理论基础.方法 研究对象为2015年12月至2018年12月在沈阳市第四人民医院诊断为急性冠脉综合征(ACS)、行PCI治疗并检测CYP2C19基因型的536例患者,进行回顾性队列研究.观察CYP2C19基因多态性分布及其与氯吡格雷抵抗和主要不良心脑血管事件(MACCE)的关系,分析MACCE的危险因素,绘制5年生存曲线.结果 (1)慢、中间及快代谢型患者5年生存率无显著性差异;(2)氯吡格雷抵抗与非抵抗组相比,PCI术后患者5年生存率无显著性差异;(3)在三组不同代谢类型患者中分别对氯吡格雷抵抗与非抵抗组进行5年生存率比较,PCI术后远期生存率差异无统计学意义;(4)高龄(＞75岁)、性别(男性)、高体质指数(BMI≥24)、糖尿病、吸烟、支架数(≥3枚)、多支血管病变(≥2支)与氯吡格雷抵抗为MACCE的危险因素,而CYP2C19基因多态性不是MACCE的危险因素,高BMI及氯吡格雷抵抗是MACCE的独立危险因素.结论 CYP2C19基因多态性及氯吡格雷抵抗对患者远期生存无显著影响,高BMI患者行CYP2C19基因检测对指导抗血栓治疗更有意义.
