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.
目的 分析肝硬化患者门脉性肺动脉高压(PoPH)的发生率、临床特征及危险因素.方法 收集2021年3月至2022年3月于中国医科大学附属第一医院住院的115例肝硬化门静脉高压患者的一般临床资料、实验室化验及检查结果,根据超声心动图结果是否合并肺动脉高压为标准分为PoPH组和非PoPH组.分析两组患者的一般临床特征及多因素logistic回归分析肝硬化发生PoPH的独立危险因素.结果 (1)肝硬化患者PoPH的发生率为8.7％(10/115).(2)PoPH组10例,平均年龄(54.5±14.3)岁,平均肺动脉压力(44.0±4.3)mmHg.非PoPH组105例,平均年龄(56.9±10.7)岁.PoPH组患者血红蛋白(Hb)、血清白蛋白(ALB)显著低于非PoPH组(P＜0.05);PoPH组平均红细胞容积(MCV)、平均红细胞血红蛋白含量(MCH)、Child-Pugh评分及终末期肝病模型(MELD)评分显著高于非PoPH组(P＜0.05).(3)多因素logistic回归分析结果显示:低Hb(OR 0.95,95％CI0.90～1.00,P=0.034)是肝硬化门脉高压患者发生肺动脉高压的独立危险因素.结论 本研究肝硬化门脉高压患者中PoPH的发生率为8.7％,Hb和ALB降低以及MCV和MCH升高与肝硬化PoPH的发展密切相关,低Hb是肝硬化门脉高压患者发生肺动脉高压的独立危险因素.
肾脏疾病因发病机制复杂,现有治疗手段尚不能满足临床需求.随着生物制剂应用的普及,其在肾脏疾病治疗中显示出良好疗效及安全性,为难治性、重症肾病患者提供了新的治疗手段和希望.目前,临床常用的生物制剂包括抗CD20单克隆抗体(利妥昔单抗)、B淋巴细胞刺激因子特异性抑制剂(贝利尤单抗)、抗补体C5单克隆抗体(依库珠单抗)和其他生物制剂(Avacopan)等.文章结合近几年的临床指南及循证医学证据,对这些生物制剂在不同免疫相关性肾脏疾病中的应用进行总结和分析.
目的 观察重复经颅磁刺激技术(rTMS)对中晚期帕金森病患者非运动症状的疗效并探讨其可能的机制.方法 选取2017年1月至2021年3月辽宁省金秋医院70例中晚期帕金森病患者,随机分为左额叶背外侧皮质区高频治疗组及左额叶背外侧皮质区假治疗组各35例,比较两组治疗前后及治疗后1、3个月自主神经功能、情绪、睡眠、疲劳等症状的改善情况.结果 rTMS组帕金森病自主神经症状量表(SCOPA-AUT)改善显著,疗效可持续至治疗后1个月.两组14项疲劳量表(HAM-D)均有显著改善且可持续3个月,rTMS组治疗后HAM-D改善显著优于对照组,但这种优势不超过1个月.两组FS-14均有显著改善,rTMS组疗效可持续至治疗后1个月.结论 左额叶背外侧皮质区高频rTMS可以显著改善中晚期帕金森病患者自主神经功能、抑郁及疲劳感,其中自主神经功能及疲劳疗效可持续1个月.
目的 构建基于免疫基因的直肠癌预后模型,并探索直肠癌免疫治疗靶点.方法 从UCSCXena下载直肠癌数据集(TCGA-READ),从GEO网站获取直肠癌数据集(GSE87211),将TCGA-READ和GSE87211分别作为训练组和验证组,基于免疫基因应用非负矩阵分解算法划分亚型并筛选差异基因.通过Cox回归分析构建风险评分模型,并使用Kaplan-Meier生存分析和受试者工作特征(ROC)曲线评价模型的有效性.分析评分与免疫的相关性,并对样本行基因集富集分析.构建列线图并绘制校准曲线评估其可信度.结果 基于27个差异基因构建了一个3基因的预后模型,低风险组总生存期长于高风险组(P＜0.05).风险评分与多种免疫细胞和免疫检查点有关,样本富集在与癌症恶性进展有关的通路.列线图校准曲线拟合良好,有较强的应用价值.结论 预后模型有良好的预测效能,并发现潜在的直肠癌免疫治疗靶点.
目的 评估真实世界伊沙佐米治疗多发性骨髓瘤(MM)的疗效和安全性.方法 回顾性分析2019年1月至2021年1月来自中国贫血东部协作组单位(无锡市人民医院等)伊沙佐米治疗72例MM患者的血液学、细胞遗传学及疗效、安全性等数据.结果 难治/复发MM(RRMM)患者接受伊沙佐米的中位治疗周期为6.0(3.0,7.0)个,总体有效率(ORR)为56.5％;新诊断MM(NDMM)患者中位治疗周期为4.5(4.0,9.5)个,总体有效率为85.8％;转换维持治疗组患者中位治疗周期为5.0(3.0,8.0)个,其中25.8％的患者缓解程度加深;不良事件(AEs)的总体发生率为26.5％.结论 在真实世界中,伊沙佐米对RRMM、NDMM或是维持转换MM患者,具有良好的疗效和安全性.
原发性干燥综合征(primary Sj?gren's syndrome,pSS)以口眼干燥为主要临床表现,抗SSA/SSB抗体是本病的标志性抗体,多个pSS国际分类标准将抗SSA抗体/抗SSB抗体阳性作为诊断条件之一.然而,当患者抗SSA/SSB抗体阴性,口眼干燥的症状轻微,并同时以突出的肾脏损害为首要表现时,诊断较为困难.现报道1例以肾损害为首要表现的抗SSA/SSB抗体阴性的pSS病例,以期进一步提高临床医生对该病的认识,避免漏诊或误诊.
目的 探究低氧诱导因子脯氨酸羟化酶抑制剂——罗沙司他对治疗维持性血液透析患者贫血疗效的差异及相关因素.方法 回顾性分析2019年11月至2020年6月于河北省人民医院规律透析且初次应用罗沙司他的36例患者的临床资料,检测基线及服用罗沙司他2、4、6、8周时血红蛋白(Hb)水平,按用药后各检测点Hb较基线的涨幅情况分为A组(Hb涨幅≥10g/L)和B组(Hb涨幅＜10g/L或降低);对比两组间基线数据的差异,并探究相关性.结果 服用罗沙司他2周、4周时A组铁蛋白及年龄显著高于B组,差异有统计学意义(P＜0.05);服用罗沙司他6周、8周时A组年龄显著高于B组,差异有统计学意义(P＜0.05);服用罗沙司他2周(rs=0.359,P=0.031)、4周(rs=0.493,P=0.003)、6周(rs=0.496,P=0.003)、8周(rs=0.417,P=0.018)时的血红蛋白与年龄呈正相关;各检测时间点Hb与基线铁蛋白间无相关性(P＞0.05).结论 年龄及基线铁蛋白水平可能影响维持性血液透析患者初次应用罗沙司他的疗效.
难治性幽门螺杆菌(Helicobacter pylori,Hp)感染是目前临床医生面临的重要难题.新近发表的国内外共识对难治性Hp感染均给予了重点关注.为了更好的帮助临床医生认识和应对难治性Hp感染,文章将重点阐述我国Hp感染耐药和治疗现状,并进一步分析难治性Hp感染的原因,介绍难治性Hp感染的处理原则.
慢性乙型肝炎(chronic hepatitis B,CHB)和慢性丙型肝炎(chronic hepatitis C,CHC)是威胁我国人民健康的重要公共卫生问题,是肝硬化和肝细胞癌(hepatocellular carcinoma,HCC)发生的主要危险因素.抗病毒治疗能够显著延缓疾病进展,降低CHB、CHC相关肝硬化失代偿和肝细胞癌风险,改善远期预后.在抗病毒治疗过程中,利用传统或新型的指标及其模型,可有效地监测抗病毒治疗疗效和疾病进展,可作为指导病毒性肝炎精准诊疗的重要工具.基于生物学标志物指导的诊疗策略有望进一步提升我国病毒性肝炎患者的治疗疗效,降低相关病死率,助力实现世界卫生组织提出的"2030年病毒性肝炎相关病死率下降65％"的宏伟目标.
胃黄色瘤(gastric xanthoma,GX)又称为胃黄斑瘤、胃黄弹性瘤、网状内皮细胞瘤或胃脂质岛,于1910年由Endo首次报道并命名,胃镜检出率0.8％～4.0％,尸体解剖检查发生率1.9％～58％[1-2].GX多发生于老年人,好发年龄为40岁以上,男女发生率相当,男女比例约1.11 ∶1.GX无特异性临床表现,患者主诉症状大多与伴随胃部疾病相关,诊断主要依靠内镜下表现、组织病理学活检以及阿利新蓝-过碘酸雪夫(AB-PAS)组化染色,需要注意的是内镜下和印戒细胞癌鉴别.胃镜检查多于胃窦、小弯侧近圆形白色或黄白色的隆起性斑块,界限清楚,多为单发,也可多发,直径在0.2～1 cm之间.其病理组织学特征主要表现为胃黏膜固有层呈巢状或块状聚集的充满脂质的巨噬细胞,即泡沫细胞,伴有不同程度的慢性炎症改变;免疫组化AB-PAS染色多呈阴性,CD68阳性.
血管钙化(VC)常见于慢性肾脏病(CKD)患者,其严重程度及发生率随CKD进展而升高.诸多危险因素参与其发生发展,主要包括高龄、高血压、糖尿病、血脂异常等传统危险因素以及高磷血症、高钙血症、甲状旁腺功能亢进或低下等"非传统"危险因素.对于显著高磷血症需要个体化高剂量磷结合剂治疗者、等待肾移植者、CKDG5D期患者和医师评估后认为需要检查的患者进行VC评估是必要的.电子束CT(EBCT)、多层螺旋CT(MSCT)灵敏度及特异度较高,是VC诊断的金标准.目前尚缺乏明确的治疗措施防治VC.VC的管理一般从控制或纠正VC发生、发展的危险因素入手.文章围绕中晚期CKD患者VC危险因素及发病机制、诊断、评估及管理作一论述,旨在加深临床医师对该类疾病的认知,促进中晚期CKD患者VC早诊断、早治疗、早获益.
目的 探讨气囊辅助式小肠镜(以下简称"小肠镜")在小肠疾病诊疗中的有效性及安全性.方法 回顾性分析2005年11月至2019年10月在南昌大学第一附属医院接受小肠镜诊疗患者的临床、内镜及病理资料.结果 最常见的小肠镜阳性诊断为非特异性肠炎(14.4％)、克罗恩病(9.9％)和小肠肿瘤(8.6％).非特异性肠炎、克罗恩病、梅克尔憩室的检出率男性高于女性,血管畸形的检出率女性高于男性;克罗恩病、梅克尔憩室检出率青年患者较高,小肠肿瘤、血管畸形检出率老年患者较高;接受小肠镜检查的患者最常见临床表现是腹痛(42.0％)和不明原因消化道出血(OGIB)(32.9％),OGIB患者的小肠疾病检出率显著高于腹痛患者(67.6％比36.7％,P＜0.001).小肠镜诊疗操作并发症发生率为0.6％.结论 气囊辅助式小肠镜是一种有效且安全的小肠疾病诊疗方法.
无痛性甲状腺炎(painlessthyroiditis,PT),又称静息型甲状腺炎(silent thyroiditis)、亚急性淋巴细胞性甲状腺炎(subacute lymphocytic thyroiditis)、淋巴细胞性甲状腺炎伴自发缓解性甲亢、亢进性甲状腺炎(hyperthyroiditis)或非典型甲状腺炎(nonclassical thyroiditis).其发病病因和机制尚未明确,可能与自身免疫、病毒感染、妊娠、碘过量及环境和遗传等因素有关[1].糖尿病酮症酸中毒(diabetic ketoacidosis,DKA)是由于胰岛素不足和升糖激素不适当升高引起的糖、脂肪、蛋白质和水盐与酸碱代谢严重紊乱综合征,是糖尿病的严重急性并发症.以往的文献研究结果显示,DKA与甲状腺激素水平有紧密关联,DKA患者的甲状腺功能出现明显异常,主要表现为甲状腺激素FT3和FT4明显降低,低T3综合征的发生率明显升高,但继发PT、一过性甲亢的病例国内外尚未见报道.研究者在2020年12月至2021年6月共观察到2例DKA继发PT的病例,予以报道如下,旨在提高临床医生对这一疾病现象的认识,避免误诊及过度医疗.
高血压是以体循环动脉压增高为主要表现的临床综合征,分为原发性高血压及继发性高血压.原发性高血压病因尚不明确,受环境和遗传因素影响,原发性高血压患者约占高血压患者的90％[1].大量营养流行病学研究膳食营养素与高血压的关联,如单不饱和脂肪酸、多不饱和脂肪酸、矿物质和膳食多酚均具有抗高血压的潜在作用[2-6].饮食摄入对肠道菌群的改变具有重要作用,而肠道菌群又通过多种途径导致高血压的发展[7-12].本文综述了膳食营养因素对原发性高血压的影响,为预防和减少原发性高血压提出依据.
目的 探讨干扰素(IFN)-α对骨髓增殖性肿瘤(MPN)患者炎症因子及免疫细胞的影响.方法 收集天津医科大学第二医院2021年6月至2022年11月25例JAK2V617F突变MPN患者骨髓与外周血样本,检测IFN-α治疗前后34个细胞因子差异与外周血淋巴细胞表型的变化,分析IFN-α治疗对患者炎症因子及免疫细胞的影响.结果 IFN-α治疗后MPN患者血浆白细胞介素(IL)-1、IL-12、CCL3、CXCL10、CXCL12、肿瘤坏死因子(TNF)-α、TNF-β水平升高,IL-4、IL-10、Notch-1、转化生长因子(TGF)-β1、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)、成纤维细胞生长因子-1(FGF1)水平降低.IFN-α治疗后JAK2V617F突变负荷(V617F％)降低的水平与血浆VEGF降低有相关性.IFN-α治疗后,MPN患者外周血中总体淋巴细胞比例增高.其中,CD8+HLA-DR+T细胞和效应T细胞(T-eff)亚群增高;CD56bright自然杀伤(NK)细胞比例显著扩增,CD56dim NK细胞比例降低;树突状细胞(DC)中浆细胞样DC(pDC)比例增加.结论 IFN-α治疗后,促炎细胞因子IL-1、TNF-α等升高.抗炎细胞因子IL-4、IL-10等下降.IFN-α治疗后V617F％与VEFG降低的正相关性可能是IFN-α治疗减少纤维化进展的机制.IFN-α治疗后,T-eff细胞、NK细胞和DC细胞比例的变化与各细胞因子改变的相关性需要进一步探讨.
