维生素D_3治疗急性骨髓纤维化取得缓解——附一例报告

本文报道一例急性骨髓纤维化(AMF),男、52岁,严重贫血(Hb19g/L)经多种升血药物、胎肝细胞悬液输注等治疗20个月无明显好转;靠输血维持生命。经肌注维生素D_3(VD_3)后两个月病情显著缓解,不需输血,Hb稳步升至93g/L出院。随访9个月生活自理,Hb114g/L,髓象及骨髓活检均明显好转,无副反应。VD_3治疗AMF是一新进展,此病人是国内取得临床成功的首例。据文献证明VD_3在体内羟化为1,25(OH)_2D_3活性物质能抑制异常巨核细胞增生,减少促进MF的PDGF,并诱导髓细胞向单核细胞、臣噬细胞和粒细胞方向成熟,释放胶原酶促进胶原裂解,因而MF改善。     

Rickets and dysmorphic findings in a child with abetalipoproteinemia

Abetalipoproteinemia (ABL) is characterized by acanthocytosis, hypocholesterolemia, and steatorrhea. Here, we describe a case of ABL associated with rickets and dysmorphic findings and the subsequent therapeutic course in an 18-month-old male referred for evaluation for failure to thrive and chronic fatty diarrhea. Examination revealed a pale child, dysmorphic face, and signs of rickets. Laboratory examination revealed low hemoglobin (3.7 gm/dl), low albumin (28 gm/L), low cholesterol and triglyceride levels. The blood smear showed acanthocytes while the small bowel histology showed the enterocytes were distended with lipid droplets. He was diagnosed with ABL and treated with fat-soluble vitamins (ADEK), and hydrolyzed protein formula containing medium chain triglycerides. Three months later, his fatty diarrhea becomes normal stool, his serum fat-soluble vitamins normalized, and his weight increased from 4.1 kg to 5.9 kg.     

皮肌炎合并巨噬细胞活化综合征5例

<正>皮肌炎(dermatomyositis,DM)是特发性炎性肌病(idiopathic inflammatory myopathy,IIM)的一种亚型,其特征是骨骼肌和皮肤炎性细胞浸润致肌痛、肌无力,典型皮肤表现包括Gottron疹/征、向阳疹、V领征、披肩征等,皮肌炎还常并发间质性肺炎(interstitial lung disease,ILD)、关节炎、心脏疾病和恶性肿瘤等。继发于自身免疫病的噬血细胞性淋巴细胞增多症(hemophagocytic lymphohistiocytosis,HLH)也称为巨噬细胞活化综合征(macrophage activation syndrome,MAS),是一种少见的危及生命的疾病,是由淋巴细胞、巨噬细胞和促炎因子过度激活引起的严重炎症反应,常见的表现包括高热、全血细胞减少、肝脾肿大和凝血功能障碍。在MAS合并的自身免疫病类型中,幼年特发性关节炎(juvenile idiopathic arthritis,JIA)、系统性红斑狼疮(systemic lupus erythematosus,SLE)及成人斯蒂尔病(adult-ons...     

维持性血液透析并发红细胞增多症1例报告并文献复习

目的：总结维持性血液透析患者出现血红蛋白异常升高的原因。方法复习贵州省毕节市七星关区人民医院血液透析中心患者马某的病例资料,并复习相关文献。结果青年男性尿毒症患者,无肝脾肿大以及长期慢性缺氧表现,进行规律血液透析治疗5年,补充促红细胞生成素(EPO)及铁剂等纠正肾性贫血,血红蛋白在3个月内由71g/L上升至149g/L,停用EPO及铁剂等,血红蛋白仍进行性升高,最高达到173g/L。结论尿毒症患者出现血红蛋白异常升高,需要警惕出现继发性红细胞增多症。     

Celiac disease presenting as severe osteopenia

The authors describe a unique presentation of celiac disease as multiple non-traumatic fractures in a young male without gastrointestinal complaints. A 29-year-old man presented with back pain and was found to have a non-traumatic compression fracture of the lumbar and thoracic spine on plain X-ray. Dual-energy x-ray absorptiometry (DXA) confirmed osteoporosis at the L3/L4 vertebral bodies. Parathyroid hormone (PTH), calcium, and vitamin D levels were normal. He had no gastrointestinal complaints, but serologic studies were positive to include an elevated gliadin IgA Ab, gliadin IgG Ab, and an elevated tissue transglutaminase IgA Ab. He was treated with a gluten-free diet, calcium, and vitamin D supplementation as well as teriparatide. Follow up bone density showed improvement and has no further fractures to date. Primary care physicians, gastroenterologists, and endocrinologists must have a high index of clinical suspicion for celiac disease in any patient who presents with low bone density regardless of the serum 25-OH vitamin D levels or presence of gastrointestinal complaints.     

Hypercobalaminemia Induced by an Energy Drink after Total Gastrectomy: A Case Report

We encountered a case of hypercobalaminemia induced by oral intake of an energy drink after total gastrectomy. The patient was referred to our hospital due to findings suspicious for gastric cancer on screening. A 20 mm type 0-IIc lesion was detected in the gastric subcardia on esophagogastroduodenoscopy. Total gastrectomy followed by Roux-en-Y reconstruction was performed. He was discharged without complications. His basal serum vitamin B₁₂ level was initially maintained with monthly intramuscular injections of vitamin B₁₂. After 9 months, his serum vitamin B₁₂ level suddenly increased up to 36-fold higher than the normal range and persisted there for one year without vitamin B₁₂ injections. The patient ultimately reported consuming half a bottle of an energy drink each day during this time period. This case demonstrates the risk of unexpected hypervitaminemia resulting from self-administration of nutritional supplements.     

程序性死亡蛋白-1抑制剂治疗晚期肺癌出现垂体免疫不良反应3例

程序性死亡蛋白-1(programmed cell death protein 1,PD-1)及其配体-1(PD-1 ligand 1,PD-L1)的抑制剂广泛用于肺癌治疗,但引起的免疫相关不良反应(immune related adverse events,irAEs)值得关注。垂体irAEs包括垂体炎和垂体功能减退,常见于细胞毒T淋巴细胞相关抗原-4抑制剂治疗后,而较少见于PD-1/PD-L1抑制剂治疗后。孤立性促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)缺乏是垂体irAEs的一种特殊亚型,不伴垂体其他功能紊乱和垂体肿大。本研究报告3例晚期肺癌患者,PD-1抑制剂治疗后出现孤立性ACTH缺乏及其他irAEs。病例1是68岁男性患者,先确诊PD-L1高表达的肺腺癌,采用帕博利珠单抗(pembrolizumab)单药治疗,期间出现免疫性肝炎,经高剂量甲基泼尼松龙[0.5~1.0 mg/(kg·d)]治疗后缓解;间隔11个月又确诊原发性胃癌,故在帕博利珠单抗基础上增加阿帕替尼(apatinib)治疗;帕博利珠单抗治疗共17次后,患者的肺癌和胃癌均未进展,但出现严重恶心和无力,此时甲基泼尼松龙已停药10个月,血液生化检查提示重度低钠血症(121 mmol/L,参考值137~147 mmol/L,下同),8:00 a.m.皮质醇(<1 μg/dL,参考值5~25 μg/dL,下同)和ACTH(2.2 ng/L,参考值7.2~63.3 ng/L,下同)降低,但甲状腺功能、性激素和泌乳素均正常。病例2是66岁男性肺腺癌患者,参加新型PD-1抑制剂HX008联合化疗的Ⅱ期临床研究(登记号:CTR20202387)。治疗5个月(共7次用药)后,患者的肺癌达到部分缓解,但恶心和呕吐却突然加重,伴轻度呼吸困难和双下肢无力,其血液生化检查提示轻度低钠血症(135 mmol/L),8:00 a.m.皮质醇(4.3 μg/dL)和ACTH(1.5 ng/L)降低,但甲状腺功能正常;同时肺CT显示中度免疫性肺炎。病例3是63岁男性肺鳞状细胞癌患者,一线使用信迪利单抗(sintilimab)联合化疗,肺癌最佳疗效为部分缓解,仅出现轻度免疫性皮疹;治疗5周期后,肺癌进展,此后6个月未使用免疫治疗;再次免疫治疗前,常规评估发现8:00 a.m.血皮质醇降低(1.5 μg/dL),ACTH正常(8.0 ng/L),但无肾上腺皮质功能减退症状,使用替雷利珠单抗(tislelizumab)联合化疗2周期后出现肺部感染伴持续低热、中度无力和重度低钠血症(116 mmol/L),此时, 8:00 a.m.血皮质醇为3.1 μg/dL,ACTH为7.2 ng/L,甲状腺功能、性激素和泌乳素均正常。这3例患者均无头痛和视力障碍,脑磁共振成像均未见垂体肿大或垂体柄增粗,且无动态变化。患者均接受了泼尼松(2.5~5 mg/d)激素替代治疗,相关症状缓解后均恢复PD-1抑制剂治疗。病例2较特殊,其因同时伴有中度免疫性肺炎而采用高剂量泼尼松[1 mg/(kg·d)]治疗,并逐渐减量至生理替代剂量,8:00 a.m.血皮质醇和ACTH恢复并维持正常,但其他两例患者的垂体功能减退均未恢复。本组病例提示,PD-1抑制剂诱发的垂体irAEs可表现为孤立性ACTH缺乏,其发病时间跨度大,临床表现不特异,恢复模式也不同。因此,对PD-1抑制剂治疗的患者,尤其是疗效好的患者,要定期监测垂体相关内分泌激素水平,警惕垂体irAEs。     

8岁以下儿童末梢血血红蛋白参考范围分析

目的建立≤8岁儿童末梢血血红蛋白的参考范围。方法选择2010年5月—2011年10月在我院健康体检的≤8岁儿童1 514例,按年龄分组:3～12个月组429例,1～3岁组462例,4～8岁组623例。均经体检证明生长、发育正常,无慢性病史,无血红蛋白疾病史和贫血史,无血吸虫、钩虫、疟疾等寄生虫感染的贫血,无蚕豆病。检查前未接受过铁剂和输血治疗。结果 1 514个血红蛋白测定值,偏度系数为0.401,峰度系数为-0.117,呈近似正态分布。3～12个月组、1～3岁组、4～8岁组男童、女童及男女合计血红蛋白水平比较差异均有统计学意义(P<0.05)。3～12个月儿童血红蛋白参考范围为96～125 g/L,1～3岁儿童血红蛋白参考范围为100～129 g/L,4～8岁男童血红蛋白参考范围为101～137 g/L,4～8岁女童血红蛋白参考范围为103～131 g/L。结论不同年龄段应采用不同的血红蛋白参考范围,不同实验室应建立适合自己的血红蛋白的参考范围。     

动脉粥样硬化与骨质疏松的相关性研究

目的 分析骨钙丢失与血管壁钙沉积之间的关系，并初步观察辛伐他汀对钙动态沉积的影响。方法 28只清洁级雄性SD大鼠，分为正常对照组、VitD、组和辛伐他汀组。9周后处死大鼠，观察分析其动脉病理学改变和血管组织、骨组织钙含量的变化。结果与对照组大鼠比较，大剂量的VitD、在增加血管钙负荷的同时引发骨钙明显下降，统计学证实两者具有相关性（b=-0．015，P〈0．01）；辛伐他汀使大剂量VitD，所造成的骨钙丢失减少，血管钙沉积减轻（P〈0．01）。结论 VitD，造成的骨钙丢失并异常动员转移至血管可能是血管钙化与骨质疏松相关因素之一；辛伐他汀促骨形成，使骨钙在骨组织沉积增加的同时减轻血管钙化程度。     

泼尼松联合阿法骨化醇治疗原发性肾病综合征的临床观察

目的观察泼尼松联合阿法骨化醇治疗原发性肾病综合征的临床疗效。方法选择2008年1月—2009年10月住院及门诊治疗的原发性肾病综合征患者56例,随机分为2组:C组28例常规泼尼松治疗,T组28例常规泼尼松联合阿法骨化醇(0.5μg/d)治疗,比较2组治疗前后临床症状的改善,血清钙、磷、甲状旁腺激素(PTH)、25-(OH)_2D_3以及1,25-(OH)_2D_3水平以及尿蛋白定量变化。结果治疗3、6及12个月后,T组缓解率均明显高于C组(P<0.05)。治疗6个月,C组患者24 h尿蛋白下降(P<0.05),血钙、血磷、血25-(OH)_2D_3及1,25-(OH)_2D_3、PTH水平稍有改善,但差异无统计学意义(P>0.05);T组血钙、25-(OH)_2D_3及1,25-(OH)_2D_3水平上升(P<0.05),24 h尿蛋白、PTH水平下降(P<0.05),且与C组治疗后相比,差异具有统计学意义(P<0.05),而血磷水平无明显变化(P>0.05)。结论泼尼松联合阿法骨化醇治疗原发性肾病综合征疗效明显。     

血红蛋白水平对中晚期食管癌放射治疗预后的影响

目的　研究血红蛋白(Hb)水平对中晚期食管癌放射治疗预后的影响。方法　回顾性分析接受放射治疗的中晚期食管癌84例，其中Hb＜110g/L者17例，Hb≥110g/L者67例，采用Kaplan-Meier法计算局部控制率和生存率。结果　外周血Hb＜110g/L病例的生存率和局部控制率均差于Hb≥110g/L的病例，而且差异有显著性(P＜0.05)。结论　放疗期间Hb水平对中晚期食管癌放射治疗预后有显著影响。Hb水平越低，局部控制率和生存率越差。     

Invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome--a case report

We report a case of invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome, and briefly discuss the association of bladder cancer and cyclophosphamide. A 6-year-old boy, who was diagnosed as having nephrotic syndrome, was treated with oral administration of prednisolone and cyclophosphamide for 4 years, receiving a total dose of 49.5 g cyclophosphamide. At age 27, a gross hematuria with bloody clots appeared and he presented with postrenal renal failure. He underwent a radical cystourethrectomy and ileal conduit for stage a pT3a pN0 M0 transitional cell carcinoma of the bladder. He was not given any adjuvant treatments because of his renal insufficiency, and he died from the disease 14 months after radical surgery.     

Effects of Nutrient Fortified Complementary Food Supplements on Anemia of Infants and Young Children in Poor Rural of Gansu

Objective To assess the effectiveness of complementary food supplements with protein and multi-micronutrients on hemoglobin and anemia in infants and young children. Methods In 5 poor counties of Gansu, 984 children aged 6-12 months were enrolled and divided into two groups. In addition to the usual home-made complementary food, all the children were fed one sachet of either Formula Ⅰ or Formula Ⅱ supplements each day. Protein and micronutrients were provided in Formula Ⅰ, while the same energy intake was secured in Formula Ⅱ as in Formula Ⅰ. A massive dose of vitamin A was supplemented to all the children every 6 months. Hemoglobin test was done at the same time. Results Prevalence of anemia was about 35% in both Formula Ⅰ and Formula Ⅱ group at baseline, and there were no differences in hemoglobin concentration between the two groups, During the 6-month and 12-month supplementation, hemoglobin of children in Formula Ⅰ group was higher than that in Formula Ⅱ group （P〈0.05）, and hemoglobin increase in Formula Ⅰ group was significantly higher than that in Formula Ⅱ group （P〈0.001）. After 6- and 12-mouth supplementation, the prevalence of anemia in Formula Ⅰ group dropped to 19.1% and 8.2% respectively, and it was 28.0% and 12.4% in Formula 2 group. The prevalence of anemia in Formula Ⅰ group was significantly lower than that in Formula Ⅱ group （P〈0.05）. After adjusting age and hemoglobin level at baseline, the hemoglobin increase at age of 24 months in formula 1 group was higher （10.7 g/L vs 7.9 g/L, P〈0.0001）. Conclusion Micronutrient fortified complementary food supplements, with large-dose vitamin A, is effective for children aged 6-12 months in terms of iron deficiency prevention.     

肾性贫血维持性血液透析患者EPO剂量调整与血红蛋白变异度的关系研究

目的 探讨维持性血液透析贫血达标患者促红细胞生成素(Erythropoietin,EPO)剂量微调对于血红蛋白变异的影响。方法 收集维持性血液透析肾性贫血纠正达标患者,每月检测1次血红蛋白,根据血红蛋白波动值给予EPO剂量微调(EPO基础值增加或减少15%EPO剂量)连续检测12个月,观察对血红蛋白变异的影响。结果 6个月内30%患者的血红蛋白维持在靶目标范围内,17%患者血红蛋白波动≤10 g/L,血液透析的充分性影响血红蛋白的变异度及达标率。结论 EPO剂量微调可以减少血红蛋白变异度,维持血红蛋白的稳定性。     

A Homozygotic Mutation in KDSR may Cause Keratinization Disorders and Thrombocytopenia: A Case Report

Pathogenic mutations in 3-keto-dihydrosphingosine reductase (KDSR) gene are associated with keratinization disorders and impaired platelet function. However, no case with both homozygotic mutation of KDSR and hepatic hemangioendothelioma has ever been reported due to its low prevalence. Here we report a seven months old Chinese boy with a homozygotic missense mutation in KDSR and both of his parents carry a same heterozygous mutation. He was born with thick plate-like scales overlying erythrodermic skin, but the skin symptoms were resolved spontaneously over the first month of his birth. He was also diagnosed with hepatic hemangioendothelioma at birth and accepted a resection surgery at 2 months old. At birth, his platelet count was severely low (10-20×10⁹/L) with recurrent skin and gingival bleeding. Meanwhile, he suffered a mild normocytic, normochromic anemia with normal iron and hematinic levels. The anemia spontaneously recovered over the first 6 months, while the platelet count keeped at a low level (4-20×10⁹/L). Treatment with corticosteroids, immunoglobulin or thrombopoietin was all suboptimal.     

原发性甲状旁腺功能亢进症术后甲状旁腺激素升高9例并文献复习

目的: 对经外科治疗后出现甲状旁腺激素(parathyroid hormone, PTH)升高伴正常血钙(normocalcemic parathormone elevation,NPE) 的原发性甲状旁腺功能亢进症(primary hyperparathyroidism,PHPT)患者的临床特征进行分析,提高该病的诊治能力,完善PHPT患者的术后管理。方法: 选取2017年8月至2019年11月中日友好医院内分泌科诊断为PHPT且术后6个月内出现NPE的9例患者作为研究对象,回顾性分析其临床资料和转归,并进行相关文献总结。结果: 临床特点:9例患者中6例为中老年女性,3例为男性。除1例为无症状性PHPT,其余8例主要临床表现为骨痛、肾结石及恶心、乏力。实验室检查:就诊时均血钙升高[(3.33±0.48) mmol/L],血磷降低[0.76 (0.74,0.78) mmol/L],24 h尿钙升高[8.1 (7.8,12.0) mmol/24 h],全片段甲状旁腺激素(intact parathyroid hormone, iPTH)明显升高[(546.1±257.7) ng/L],维生素D缺乏[25羟维生素D₃水平(21.0±5.7) nmol/L],骨源性碱性磷酸酶[7例41.3 (38.6,68.4) μg/L,2例>90 μg/L]及N端中段骨钙素(>71.4 μg/L)明显升高,2例患者存在肾功能异常。影像学检查:7例骨质疏松,3例患者肾脏超声见肾结石。所有患者甲状旁腺影像学检查均发现明确病灶, 其中2例为多发病灶,7例为单发病灶。治疗及转归:2例患者行甲状旁腺切除术治疗,其余患者予甲状旁腺微波热消融治疗;术后1个月患者均出现PTH升高[(255.0±101.4) ng/L],血钙正常,甲状旁腺超声未发现复发病灶。给予钙剂及维生素D联合治疗至术后6个月,PTH均显著下降,术后血钙水平始终正常。结论: PHPT术后发生NPE与术前PTH高水平、维生素D缺乏及肾功能受损可能相关,但并不意味着PHPT的复发或者存在残余病灶;术后充足的钙剂及维生素D的补充可能使患者获益;应规范对PHPT患者的术后随访,以预防和治疗术后NPE。     

微创经皮肾镜取石术治疗多囊肾合并肾结石

目的 评价微创经皮肾镜取石术（minimally invasive percutaneous nephrolithotomy,MPCNL）治疗多囊肾合并肾结石的疗效和安全性。方法 分析我院2007~2013年16例多囊肾合并肾结石患者接受MPCNL的临床资料。结果 16例均成功建立皮肾通道,平均手术时间40min,平均出血30mL,结石清除率93.75%。手术前后血红蛋白、血肌酐比较,差异无统计学意义（P〉0.05）,1月后血肌酐值下降至（142.69±76.28）μmol/L（P〉0.05）,无输血或血管栓塞病例。随访3~12个月,血红蛋白和血肌酐值稳定,结石无复发,肾囊肿无增大。结论 MPCNL是安全、有效治疗多囊肾合并肾结石的方法之一。     

β地中海贫血对血液透析患者使用重组人促红细胞生成素疗效的影响

目的探讨β地中海贫血对血透患者使用重组人促红细胞生成素(rHuEPO)改善贫血疗效的影响。方法选择伴β地中海贫血血透患者为地贫组,并选择性别、年龄等情况相似的血透患者为对照组,两组患者按常规剂量rHuEPO 120～150 IU/(kg.周)治疗3个月;3个月后,如地贫组患者血红蛋白未达标(≥110 g/L),则改用大剂量rHuEPO 200～250 IU/(kg.周)治疗3个月。结果 10例地贫组患者和10例对照组患者在治疗前血红蛋白水平差异无统计学意义,3个月常规剂量rHuEPO治疗期间rHuEPO剂量差异无统计学意义(P>0.05),但每月末地贫组血红蛋白水平明显比对照组低(P<0.01);3个月后,对照组患者贫血基本纠正,而地贫组患者血红蛋白水平虽比治疗前有所改善(P<0.01),但贫血未能纠正。后3个月地贫组患者使用大剂量rHuEPO治疗,血红蛋白水平从第1月末开始明显上升(P<0.01),并持续至第3月末,患者贫血得以纠正;期间除引起患者血压升高外未出现不可控制的恶性高血压、内瘘堵塞等严重并发症。结论β地中海贫血会影响血透患者使用rHuEPO改善贫血的疗效,大剂量rHuEPO能纠正伴β地中海贫血的血透患者贫血。     

Importance of checking anti-glomerular basement membrane antibody status in patients with anti-neutrophil cytoplasmic antibody-positive vasculitis

The case is reported of a 68-year-old man with perinuclear anti-neutrophil cytoplasmic antibody (pANCA)-associated glomerulonephritis who developed antibodies to glomerular basement membrane (anti-GBM) resulting in end stage renal failure. His pANCA titre on admission was 1:1024 IgG and he was anti-myeloperoxidase positive. A renal biopsy showed advanced sclerosing necrotising glomerulonephritis consistent with a pauci-immune ANCA-positive glomerulonephritis. He was treated with steroids and cyclophosphamide. His serum creatinine profile improved. He had a relapse of disease 16 months later, which was successfully treated. After a further 16 months, he presented with acute renal failure (creatinine 1060 micromol/l). His pANCA titre on admission was 1:64 IgG. This was treated as a further relapse of ANCA-positive vasculitis. He became oliguric and his haemoglobin concentration fell. Eight days after admission, he was found to be strongly positive for anti-GBM (138 U/ml). Despite receiving cyclophosphamide, steroids and plasma exchange, he remained dialysis-dependent.