Increased Risk of Acute Myocardial Infarction in Systemic Sclerosis: A Nationwide Population-based Study

Purpose

Systemic sclerosis is a life-threatening autoimmune disease characterized by vasculopathy, which results in myocardial involvement in an extremely high percentage of patients. Nevertheless, there have been no large-scale epidemiological studies about the risk of acute myocardial infarction in patients with systemic sclerosis. The aims of this study were to evaluate the hazard ratio (HR) and risk factors of acute myocardial infarction in patients with systemic sclerosis, as well as to compare the risks of acute myocardial infarction among systemic sclerosis patients taking different immunosuppressors.

Methods

The study cohort included 1344 patients with systemic sclerosis and 13,440 (1:10) age-, sex-, and comorbidity-matched controls during the period between 1997 and 2006, from the National Health Insurance Research Database. We compared the risk of acute myocardial infarction between patients with systemic sclerosis and controls and calculated the adjusted HRs for acute myocardial infarction in systemic sclerosis patients taking immunosuppressors and not taking immunosuppressors.

Results

The incidence rates of acute myocardial infarction were 535 and 313 cases per 100,000 person-years for systemic sclerosis cohort and reference cohort, respectively (P <.001, unadjusted). After adjusting for age, sex, and underlying medical diseases on Cox proportional hazards model, systemic sclerosis was found to be an independent risk factor for acute myocardial infarction (HR 2.45). Other risk factors included hypertension (HR 2.08) and diabetes (HR 2.14). The multivariate adjusted HR for acute myocardial infarction did not decrease among the systemic sclerosis patients taking systemic steroids, penicillamine, cyclophosphamide, azathioprine, methotrexate, or cyclosporine.

Conclusion

Systemic sclerosis is independently associated with an increased risk of acute myocardial infarction. Immunosuppressors do not lower the risk of acute myocardial infarction in our study.     

以循证医学方法为百草枯中毒制定治疗方案

目的 根据循证医学理论和原则,为急性百草枯(PQ)中毒患者制定循证治疗方案并实施相应的循证治疗,以期在目前现有证据的支持下,达到最佳化治疗的目的.方法 选择1例PQ中毒患者,根据患者的临床情况,提出血液净化治疗和免疫抑制剂治疗的临床问题.检索Cochrane临床试验数据库(2010年第1期)、MEDLINE (1950年至2010年1月)和中国生物医学文献数据库(CBM,1978年至2010年),纳入PQ中毒治疗的系统评价、Meta分析和临床随机对照试验(RCT),根据所获证据为该例患者制定循证治疗的方案.治疗结束并随访1年.结果 根据检索结果分析,共纳入7篇PQ中毒相关文献.证据显示,血液净化可延长患者的存活时间,但不能降低病死率;糖皮质激素与环磷酰胺联合冲击疗法可提高患者的生存率.结合该例患者的病情和意愿,给予相应循证治疗,治疗结束后好转出院,随访1年无并发症出现.结论 以目前循证医学最佳证据、结合患者情况制定治疗方案,能提高PQ中毒患者的近期疗效,但远期预后尚需更长时间的随访观察.     

影响肾移植术后患者服药依从性的因素调查及护理干预研究

目的调查影响肾移植术后服用免疫抑制剂患者服药依从性的因素,制定针对性的护理干预措施并评定其效果。方法采取向患者和护士分别进行问卷调查的方法找出影响服药依从性的因素,提出针对性的护理干预方法。收集2017年全年肾移植患者100例,分成干预组和对照组。干预组共分为接受单一措施组及接受所有措施组4组。使用修订Morisky服药依从性调查问卷评价干预效果,结果分为依从性好与不好两种。使用卡方检验分析组间差异。结果主要影响服药依从性的因素为:①缺乏按嘱服药的重要性的知识。②服药管理问题。③对患者的出院后的管理不足。经过干预,干预组的合格率为84%,高于对照组的60%(P<0.05)。综合干预组的合格率91.3%,明显高于对照组(P<0.05)。其他各组的两两比较未显示出有统计意义的差异。结论本研究发现了影响肾移植术后服用免疫抑制剂患者服药依从性的几项重要因素。针对性的干预措施能改善服药依从性,综合性的干预措施相对单一干预措施有更为为明确的效果。     

肾移植术后巨细胞病毒性肺炎临床分析

目的探讨肾移植术后巨细胞病毒(CMV)性肺炎临床特点、治疗和转归.方法采用免疫细胞化学法检测外周血白细胞CMV抗原诊断活动性CMV感染,CMV肺炎患者给予静滴更昔洛韦和(或)膦甲酸钠治疗,严重者停用或减少免疫抑制剂.结果 56例(3.1%)肾移植受者术后发生CMV肺炎,均有发热、干咳、X线胸片示间质性肺炎,31例(55.3%)出现低氧血症,27例需呼吸机辅助呼吸;17例严重CMV肺炎患者需停用免疫抑制剂;56例患者存活率为69.6%.结论肾移植术后CMV肺炎以间质性肺炎、低氧血症为突出表现,病死率高,更昔洛韦和膦甲酸钠是治疗CMV肺炎的有效药物.     

葡萄膜炎继发闭角型青光眼治疗的临床观察

目的：虹膜激光切除术治疗葡萄膜炎继发闭角型青光眼的临床效果。方法回顾性分析23例32眼葡萄膜炎继发闭角型青光眼给予虹膜激光切除术后临床资料,通过视力、眼压观察治疗情况。结果术前眼压25-40 mmHg（1 mmHg=0.133 kPa）,术后终末眼压为12-21 mmHg,随访期间31眼（96.88%）眼压在正常范围内;术后视力≥0.5者14眼（43.74%）,较术前视力≥0.5者3眼（9.38%）明显提高。结论虹膜激光切除术治疗葡萄膜炎继发性闭角型青光眼是一种安全有效的方法。     

雷公藤多苷联合来氟米特治疗类风湿关节炎的系统评价

目的：系统评价雷公藤多苷联合来氟米特治疗类风湿关节炎的疗效和安全性。方法：计算机检索Cochrane library、Web of Science、Pubmed、国家知识基础设施数据库（CNKI）、中国生物医学文献数据库（CBM)、中国学术期刊数据库（CSPD）和中文科技期刊数据库（CCD）,检索时限为建库起至2020年8月14日,收集雷公藤多苷联合来氟米特治疗类风湿关节炎的临床试验资料,采用Cochrane5.1.0系统评价手册进行质量评估,采用RevMan5.3软件进行数据分析。结果：共纳入随机对照试验13项,含类风湿关节炎患者1 004例,其中观察组503例,对照组501例。Meta分析结果显示,晨僵时间（SMD=-1.55,95%CI为-1.87～-1.23）、（SMD=-2.29,95%CI为-3.46～-1.12）、关节疼痛数（SMD=-0.94,95%CI为-1.40～-0.49）、关节肿胀数（SMD=-0.78,95%CI为-1.52～-0.04）、红细胞沉降率（SMD=-1.75,95%CI为-2.38～-1.13）、C反应蛋白（SMD=-2.23,95%CI为-2.96～-1.51）、类风湿因子（SMD=-2.97,95%CI为-4.22～-1.72）、免疫球蛋白G（SMD=-0.58,95%CI为-1.10～-0.06）、白细胞介素-1（SMD=-0.84,95%CI为-1.20～-0.49）、白细胞介素-6（SMD=-4.08,95%CI为-4.86～-3.30）、肿瘤坏死因子-α（SMD=-3.24,95%CI为-3.92～-2.56）、（SMD=-0.94,95%CI为-1.30～-0.57）和可溶性细胞间黏附分子-1（SMD=-0.53,95%CI为-0.96～-0.10）,观察组均显著低于对照组;临床总有效率观察组明显优于对照组（OR=4.12,95%CI为2.74～6.18）;休息痛、免疫球蛋白A、免疫球蛋白M、白细胞介素-10和不良反应发生率观察组与对照组差异无统计学意义。结论：雷公藤多苷联合来氟米特治疗类风湿关节炎可提高患者的临床总有效率,改善类风湿关节炎患者相关的各项体征及症状,并且具有良好的安全性,值得临床推广应用;但由于受收录文献质量的限制和临床异质性的影响,研究结果尚需临床实践验证。     

Physiological functions and clinical implications of fibrinogen-like 2: A review

Fibrinogen-like 2 (FGL2) encompasses a transmembrane (mFGL2) and a soluble (sFGL2) form with differential tertiary structure and biological activities. Typically, mFGL2 functions as prothrombinase that is capable of initiating coagulation in tissue without activation of the blood clotting cascade, whereas sFGL2 largely acts as an immunosuppressor that can repress proliferation of alloreactive T lymphocytes and maturation of bone marrow dendritic cells. Protein sequences of FGL2 exhibit evolutionary conservation across wide variety of species, especially at the carboxyl terminus that contains fibrinogen related domain (FRED). The FRED of FGL2 confers specificity and complexity in the action of FGL2, including receptor recognition, calcium affiliation, and substrate binding. Constitutive expression of FGL2 during embryogenesis and in mature tissues suggests FGL2 might be physiologically important. However, excessive induction of FGL2 under certain medical conditions (e.g., pathogen invasion) could trigger complement activation, inflammatory response, cellular apoptosis, and immune dysfunctions. On the other hand, complete absence of FGL2 is also detrimental as lack of FGL2 can cause autoimmune glomerulonephritis and acute cellular rejection of xenografts. All these roles involve mFGL2, sFGL2, or their combination. Although it is not clear how mFGL2 is cleaved off its host cells and secreted into the blood, circulating sFGL2 has been found correlated with disease severity and viral loading among patients with human hepatitis B virus or hepatitis C virus infection. Further studies are warranted to understand how FGL2 expression is regulated under physiological and pathological conditions. Even more interesting is to determine whether mFGL2 can fulfill an immunoregulatory role through its FRED at carboxyl end of the molecule and, and vice versa, whether sFGL2 is procoagulant upon binding to a target cell. Knowledge in this area should shed light on development of sFGL2 as an alternative immunosuppressive agent for organ transplantation or as a biomarker for predicting disease progression, monitoring therapeutic effects, and targeting FGL2 for repression in ameliorating fulminant viral hepatitis.     

三种免疫抑制剂对HBV质粒感染小鼠HBV复制的影响*

目的 应用小鼠模型评价3种临床常用的免疫抑制剂对乙型肝炎病毒（HBV）复制的影响。方法 利用高压水注射法将HBV质粒pAAV/HBV1.2导入Balb/C小鼠肝内,建立小鼠HBV复制模型;将Balb/C小鼠随机分成4组,每组10只,分别给予生理盐水（Saline）、FK506、DEX和CYP处理。1w后,将供体C57BL/6小鼠皮瓣移植至上述经免疫抑制剂或生理盐水处理的Balb/C小鼠,皮肤移植后继续使用上述免疫抑制剂或生理盐水至观察期结束。采用电化学免疫发光法检测血清HBsAg、HBsAb和HBcAb水平,采用Real-time PCR法检测血清病毒载量。结果 FK506、地塞米松和环磷酰胺处理小鼠移植皮瓣的存活时间分别为（21.50±3.09） d、（21.50±3.09） d和（21.40±1.52） d,分别较生理盐水处理组（8.67±1.86） d明显延长[P=0.037、P=0.000和P=0.000];FK506处理组小鼠HBV复制及其抗体产生与对照组无显著性差异,地塞米松处理组在药物处理期间能维持病毒复制,但停药后病毒DNA和HBsAg迅速下降至检测水平以下,至观察终点仍未检出HBsAb和HBcAb阳性,环磷酰胺能明显延长小鼠HBV复制的持续时间,即使在停药后16 w血清HBV DNA和HBsAg均维持在较高水平,HBcAb和HBsAb持续阴性。结论 环磷酰胺而非FK506处理可在Balb/C小鼠模型中建立HBV持续复制模型。     

Properties of human pre- and post-implantation embryo-associated immunosuppressor factor(s)

Embryo-associated immunosuppressor factor (EASF), a factor detected by its suppressive property on the concanavalin A (ConA) stimulated lymphocyte proliferation assay, was purified from human embryo growth media of in vitro fertilized ova (pre-implantation source) and from pregnancy sera (post-implantation source) as 3 fractions, CM-1, CM-3 and CM-6, the immunosuppressive properties of which were studied. The results show that, (i) the 3 fractions of EASF from both sources suppressed ConA- and pokeweed mitogen (PWM)-induced lymphocyte proliferation, suggesting that they have suppressive effects on both T and B cells; (ii) all 3 EASFs were suppressive when added at the early phase of ConA-supplemented cultures; (iii) CM-1 of both sources were suppressive when added to PWM-supplemented cultures between 24 and 48 h; and (iv) CM-6 of both sources showed an irreversible immunosuppressive effect on PWM-induced lymphocyte proliferation, demonstrating that some similarities exist in the immunosuppressive property of EASF from the 2 sources. On the other hand, (i) CM-6 of pre- and post-implantation EASF were immunosuppressive when added to the PWM-supplemented cultures at 24–48 h and 0–16 h, respectively; and (ii) the CM-6 fraction of pregnancy sera, but not the CM-6 fraction of embryo growth media, possessed an irreversible immunosuppressive effect on ConA-supplemented cultures. This active process by which EASF affects T cell and B cell functions directly may be one of several responses by which the maternal immune response against the fetus is prevented.     

Embryo-Associated Immunosuppressor Factor is Produced at the Maternal-Fetal Interface in Human Pregnancy

PROBLEM : To study whether embryo associated immunosuppressor factor (EASF) is synthesized at the maternal-fetal interface. METHOD : Anti-EASF monoclonal antibody H5D12 was used to identify EASF. Paraffin-embedded sections were prepared from placental and fetal tissues and immunohistochemistry was done by the avidin-biotin-peroxidase technique. EASF was affinity purified using H5D12-Sepharose 4B from culture media of placental villi and analyzed for immunosuppressive activity (by Concanavalin A-induced lymphocyte proliferation assay) and molecular weight identity (by metabolic labeling studies with ³⁵S-methionine followed by immunoprecipitation and SDS-PAGE). RESULTS : Immunohistochemical studies demonstrates intense immunostaining of villous syncytiotrophoblast and cytotrophoblast cells of first trimester placental tissues. Hoffbauer cells and decidual cells stained positive. The same cells in second and third trimester placental tissues stained weakly. However, the endothelium and smooth muscle cells of fetal blood vessels, fetal ovarian stroma and primordial follicles, kidney epithelium, cerebral neurons, and glial cells all stained negative. The affinity-purified EASF from the conditioned media of placental villi (less than 12 wk gestational age) was identified as a 37-kDa molecule with immunosuppressive activity. Metabolic labeling studies revealed that placental villi from early gestational age secretes a major factor of 37-kDa and minor factors of 41-kDa and 47-kDa molecular weight. CONCLUSIONS : Monoclonal antibody H5D12 identifies a factor that is produced by the pre-implantation embryo and also synthesized by decidua and trophoblast cells.