Primary myelofibrosis with concurrent CALR and MPL mutations: A case report

BACKGROUNDPrimary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by recurrent mutations in the JAK2, CALR, and MPL genes. The CALR and MPL co-mutation is very rare. To our knowledge, no more than five cases have been reported. Here, we report a case of PMF in which a CALR and MPL co-mutation was detected by next-generation sequencing (NGS) technology, and a literature review was performed.CASE SUMMARYA 73-year-old woman was admitted to our hospital in 2018 due to abdominal distension. The patient had splenomegaly, lymphadenopathy, leukopenia, anemia, and immature granulocytes in peripheral blood. There were dacrocytes and atypical megakaryocytes in bone marrow, and megakaryocytic proliferation was very active, accompanied by reticulin fibrosis grade 2. By NGS analysis of the bone marrow sample, we detected mutations in CALR, MPL, and PIK3RI, while JAK2 V617F and BCR-ABL were negative. Therefore, the patient was diagnosed with PMF and received oral ruxolitinib. However, the spleen and hematologic responses were poor. We review the literature, analyze previous reports of the mutation sites in our patient and differences between our patient and other reported cases of co-mutated CALR and MPL genes, and discuss the reason why the CALR and MPL co-mutations are rare and possible mechanisms and their impact on the prognosis of patients.CONCLUSIONCALR and MPL mutations can be concurrent in MPN, but they are rare. The use of NGS may help to identify more patients with co-mutated CALR and MPL genes. This will help to further explore the mechanism and its impact on these patients to develop appropriate treatment strategies.     

Kidney stone disease and cardiovascular events: a study on bidirectional causality based on mendelian randomization

BackgroundKidney stone disease (KSD) has been reported to be associated with several cardiovascular diseases. However, the causality between the conditions remains unknown. In the study, we performed a study on bidirectional causality by two-sample Mendelian randomization (MR) to investigate the causality between KSD and cardiovascular diseases including coronary atherosclerosis, hypertension, and cardiomyopathy.MethodsIn the recent study, we performed a bidirectional two-sample MR study using available genome-wide association summary data from the online database MRBASE. We identified genetic variants associated with KSD in one European population from UK Biobank (version 2, n=462,933). Two phenotypes of samples were chosen from the population to define our genetic instrumental variables: (I) samples with the phenotype of kidney stone/ureter stone/bladder stone (ukb-b-8297), and (II) samples with the phenotype of kidney stone surgery/lithotripsy (ukb-b-13537). For cardiovascular diseases, we picked up another independent European population from FinnGen Biobank (n=93,421). We selected the exposure and outcome SNPs and then performed the two-sample MR using R package.ResultsAfter bidirectional causality by two-sample MR, we verified that genetic predisposition to KSD could increase the risk of coronary atherosclerosis (OR: 4.45×1037; SE=±7.80×10¹⁴, P for MR-Egger =0.024) and cardiomyopathy (OR: 5.35×10¹³; SE=±7.18×10⁶, P for IVW=0.045 for finn-a-I9_CARDMYO, and OR: 3.60×10²⁵; SE=±3.26×10¹², P for IVW=0.041 for finn-a-I9_CARDMYOOTH) when we used ukb-b-13537 as exposure group. Furthermore, hypertension could increase the risk of KSD (OR: 1.001; SE=±1.00, P for IVW=0.003) when we used ukb-b-8297 as exposure group, without detected pleiotropy bias (P>0.05).ConclusionsWe confirmed KSD may trigger causal pathological processes including coronary atherosclerosis and cardiomyopathy. Furthermore, hypertension may causally affect KSD.     

围手术期舒适护理在糖尿病性视网膜病变玻璃体切除术患者中的应用效果

目的 观察围手术期舒适护理在糖尿病性视网膜病变玻璃体切除术患者中的应用效果.方法 选择2018年1月至2021年1月我院收治的90例糖尿病性视网膜病变玻璃体切除术患者作为研究对象,将其随机分为对照组和试验组,各45例.对照组开展围手术期常规护理,试验组开展围手术期舒适护理.比较两组的手术时间、住院时间、血糖指标及并发症...     

创伤复苏单元功能分级及配置探讨

创伤复苏单元是严重创伤患者到达医院后进行复苏及损伤控制的重要场所.不同级别的创伤中心对于创伤复苏单元的要求不尽相同,从简单固定、液体复苏到完成影像学检查和损伤控制手术,不同配置的创伤复苏单元承载不同的功能.本文就不同功能分级的创伤复苏单元相应设备配置情况进行讨论,以帮助完成创伤中心的标准化建设.     

合成紫花茄皂甙诱导人肝癌细胞株Bel-7402凋亡的作用机制

背景与目的:紫花茄(SolanumindicumL.)是一种有抗炎和治疗跌打损伤作用的传统中草药,含有丰富的结构独特的薯蓣皂甙,即紫花茄皂甙。我们的研究结果已证实,数种合成紫花茄皂甙有强抗肿瘤效果。本研究探讨合成紫花茄皂甙Ⅰ("-D-木吡喃糖基-(1→3)-[#-L-鼠李吡喃糖基-(1→2)]-"-D-半乳吡喃糖基薯蓣苷)的抗肿瘤机制。方法:以不同浓度紫花茄皂甙处理人肝癌细胞Bel-7402后,用酸性磷酸酶(acidphosphataseassay,APA)法测定增殖抑制率和IC50。用结晶紫染色显微镜观察细胞的形态学变化。用蛋白免疫印迹法检测凋亡过程中相关蛋白的变化。结果:紫花茄皂甙对Bel-7402细胞有明显的增殖抑制作用,在皂甙Ⅰ作用72h后的IC50为4.20μg/ml。光学显微镜下可见细胞密度降低,胞质中出现膜泡等形态学变化。蛋白免疫印迹检测结果显示,紫花茄皂甙Ⅰ作用后细胞质中的细胞色素c含量明显增加,Caspase-3被激活,细胞内的poly(ADR-ribose)polymerase(PARP)蛋白被剪切。结论:紫花茄皂甙对人肝癌细胞的增殖抑制呈浓度相关性,且通过线粒体依赖性通路诱导肿瘤细胞凋亡。     

腹膜损伤生物学标志物的研究进展

终末期肾脏病已成为全球广泛关注的健康问题,腹膜透析是公认的、有效的肾脏替代治疗方法之一,腹膜结构和功能的完整性对于腹膜透析治疗至关重要。如何早期识别腹膜损伤并加以干预,已受到广泛关注。多种细胞因子、生长因子、微小RNA、代谢产物和蛋白酶在腹膜损伤过程中发挥重要作用,有望用于评价腹膜病理改变、预测腹膜功能,为临床治疗提供...     

根除Hp对高原地区Hp相关性慢性胃炎病理变迁和溃疡转归的影响

目的:观察根除幽门螺杆菌(Hp)感染对高原地区Hp相关性慢性胃炎病理变迁和溃疡转归的短期影响。方法:对Hp阳性的37例慢性胃炎和30例溃疡患者均给予以洛赛克为中心加两种抗生素的三联一周疗法,停药一月后复查Hp并观察胃镜和病理组织学变化,与根除Hp治疗前进行对比分析,同时统计Hp根除组和未根除组溃疡的愈合率。结果:37例慢性胃炎中32例Hp被根除,30例溃疡中14例Hp被根除(2例未复查),平均Hp根除率70.77%;Hp根除前慢性胃炎组中有19例胃炎活动,治疗后16例Hp被根除,根除者胃炎活动完全消退,消退率100%,而3例Hp未根除者仅1例胃炎活动完全消退,消退率33.33%(P<0.05);28例溃疡在Hp根除治疗前均有胃炎活动的病理组织学改变,14例Hp根除者中,13例胃炎活动完全消退,消退率92.86%,14例Hp未根除者中,只有6例胃炎活动完全消退,消退率42.86%(P<0.05);所有的慢性胃炎和溃疡患者胃窦粘膜均有不同程度的萎缩、肠化和异型增生,两组Hp根除前后其上述病理组织学变化均无明显改善(P>0.05);Hp根除组溃疡全部愈合,愈合率达100%,未根除组只有8例愈合,愈合率为57.14%,两组比较Hp根除组溃疡愈合率显著高于未根除组(P<0.05)。结论:根除Hp感染可使绝大部分胃炎的活动性消退,并可明显提高溃疡的愈合率,而Hp根除后短时间内无慢性胃炎(萎缩、肠化、异型增生)逆转的病理组织学表现,需长期随访观察。     

高原地区Hp相关性胃癌前病变患者血清6种细胞因子水平的变化

目的:观察青海高原地区幽门螺杆菌(Hp)相关性胃癌前病变患者血清Th1/Th2细胞因子(IL-1β、IL-2、IL-4、IL-6、IL-8、TNF)水平变化,以探讨其在发病中的可能免疫致病机制。方法:应用放免法(RIA)测定25例慢性萎缩性胃炎(CAG)、17例肠化生(IM)、15例异型增生(Dys)患者血清IL-1β、IL-2、IL-4、IL-6、IL-8、TNF的含量。比较Hp感染与非感染胃癌前病变患者之间;Hp感染CAG炎症活动与非活动患者之间;Hp感染CAG、IM、Dys患者之间血清6种细胞因子含量的差别。结果:Hp感染与非感染胃癌前病变患者之间6种细胞因子含量均无显著性差别(P>0.05);Hp感染CAG炎症活动者血清IL-4含量显著低于非活动者(P<0.05);IM和Dys者均非常显著低于CAG(P<0.01),IL-2在Dys组显著高于CAG(P<0.05)。结论:本地区Hp相关性胃癌前病变中存在血清Th1/Th2失衡,表现为随着胃癌前病变的逐级加重,T淋巴细胞高表达IL-2伴随IL-4低表达现象。     

针灸治疗中年女性慢性疲劳综合征42例

慢性疲劳综合征(chronic fatigue syndrome,CFS)是亚健康状态最主要的一种表现形式,目前CFS的发病机制尚不清楚,亦无特效的针对性治疗方法及药物,美国疾病控制中心(CDC)预测,慢性疲劳将成为21世纪人类健康的主要问题之一[1].笔者根据中年女性易好发此病的特点,从中医的整体观念出发,自2004年6月～2005年12月间采用针灸疗法调治心脾进行治疗,结果在改善临床症状方面取得满意疗效,现报道如下.     

血管性痴呆患者血脂及甲状腺激素变化的临床观察

目的 探讨血管性痴呆（VaD）与血清胆固醇、甘油三酯、甲状腺激素的关系。方法 对35例VaD和16例健康对照组血清胆固醇、甘油三酯、甲状腺激素进行测定,并进行组间对比研究。结果 VaD组血清胆固醇、甘油三酯明显高于对照组（P〈0．05）,并且VaD组甘油三酯水平与对照组相比差异更明显（P〈0．01）,VaD组血清总T4（TT4）水平明显高于健康对照组（P〈0．01）,而总T3（TT3）及TSH两组之间无显著性差异。结论 甲状腺激素代谢异常可能与VaD发病有关;血清胆固醇和甘油三醌增高与VaD有明显的关系,降低胆固醇及血脂可能对VaD预防和治疗有益。