阿利西尤单抗治疗高胆固醇血症的快速卫生技术评估

目的运用快速卫生技术评估(rHTA)方法,评价阿利西尤单抗治疗高胆固醇血症的有效性、安全性和经济性。方法计算机检索PubMed、Embase、Cochrane Library、CNKI、WanFang Data以及HTA相关网站,搜集关于阿利西尤单抗治疗高胆固醇血症的HTA报告、系统评价/Meta分析和药物经济学研究,检索时限均从建库至2022年8月14日。由2名评价者独立筛选文献、提取数据结果并评价纳入文献的质量,对结果进行定性描述与分析。结果共纳入文献38篇,其中系统评价/Meta分析28篇,经济学研究7篇,HTA报告3篇。有效性研究显示,与安慰剂或其他降脂治疗相比,阿利西尤单抗能降低低密度脂蛋白胆固醇(LDL-C)、脂蛋白a、总胆固醇、三酰甘油、载脂蛋白B、非高密度脂蛋白胆固醇,升高高密度脂蛋白胆固醇、载脂蛋白A1水平,降低主要心血管不良事件、全因死亡、脑血管事件和不稳定心绞痛风险,但未降低心血管死亡、心肌梗死和冠脉血运重建风险。安全性研究显示,与安慰剂或其他降脂治疗相比,除注射部位不良反应外,阿利西尤单抗未增加其他不良反应风险。经济性研究显示,阿利西尤单抗治疗冠心病三支病变以及LDL-C≥2.59 mmol·L^(-1)的急性冠脉综合征患者的高胆固醇血症具有经济性。结论阿利西尤单抗治疗高胆固醇血症有效性和安全性较好,多支病变或LDL-C基础水平较高的冠心病患者使用阿利西尤单抗治疗高胆固醇血症更具有经济性。

Bone marrow-derived dendritic cells pulsed with tumor lysates induce anti-tumor immunity against gastric cancer ex vivo

AIM:To investigate whether bone marrow-derived denritic cells pulsed with tumor lysates induce immunity against gastric cancer ex vivo. METHODS:c-kit+hematopoietic progenitor cells were magnetically isolated with a MiniMACS separator from BALB/c mice bone marrow cells.These cells were cultured with cytokines GM-CSF,IL-4,and TNFα to induce their maturation.They were analysed by morphological observation,phenotype analysis,and mixed lymphocyte reaction(MLR).Bone marrow-derived DCs(BM-DCs)were pulsed with tumor cell lysate obtained by rapid freezing and thawing at a 1:3 DC:tumor cell ratio.Finally,cytotoxic T lymphocyte (CTL)activity and interferon gamma(IFNγ)secretion was evaluated ex vivo. RESULTS:c-kit+hematopoietic progenitor cells from mice bone marrow cells cultured with cytokines for 8 d showed the character of typical mature DCs.Morphologically,observed by light microscope,these cells were large with oval or irregularly shaped nuclei and with many small dendrites.Phenotypically,FACS analysis showed that they expressed high levels of Ia, DEC-205,CD11b,CD80 and CD86 antigen,moderate levels of CD40,and negative for F4/80.Functionally, these cells gained the capacity to stimulate allogeneic T cells in MLR assay.However,immature DCs cultured with cytokines for 5 d did not have typical DCs phenotypic markers and could not stimulate allogeneic T cells.Ex vivo primed T cells with SGC-7901 tumor cell lysate-pulsed(TP)DCs were able to induce effective CTL activity against SGC-7901 tumor cells (E:T=100:1,69.55%±6.05%specific lysis),but not B16 tumor cells,and produced higher levels of IFNγwhen stimulated with SGC-7901 tumor cells but not when stimulated with BB1166 tumor cells(1575.31±60.25 pg/mL in SGC-7901 group vs 164.11±18.52 pg/mL in B16 group,P<0.01). CONCLUSION:BM-derived DCs pulsed with tumor lysates can induce anti-tumor immunity specific to gastric cancer ex vivo.

Correlation between intracoronary thrombus components and coronary blood flow after percutaneous coronary intervention for acute myocardial infarction at different onset time

BACKGROUND Acute myocardial infarction(AMI)is a leading cause of mortality.Early reperfusion to restore blood flow is crucial to successful treatment.In the current reperfusion regimen,an increasing number of patients have benefited from direct percutaneous coronary intervention(PCI).In order to understand whether there is a correlation between the components of coronary thrombosis and the absence of reflow or slow blood flow after coronary stent implantation in direct PCI,we collected data on direct PCI cases in our hospital between January 2016 and November 2018.AIM To investigate the correlation between intracoronary thrombus components and coronary blood flow after stent implantation in direct PCI in AMI.METHODS We enrolled 154 patients(85 male and 69 female,aged 36–81 years)with direct PCI who underwent thrombus catheter aspiration within<3,3–6 or 6–12 h of onset of AMI between January 2016 and November 2018.The thrombus was removed for pathological examination under a microscope.The patients of the three groups according to the onset time of AMI were further divided into those with a white or red thrombus.The thrombolysis in myocardial infarction(TIMI)blood flow after stent implantation was recorded based on digital subtraction angiography during PCI.The number of patients with no-reflow and slow blood flow in each group was counted.Statistical analysis was performed based on data such as onset time,TIMI blood flow.RESULTS There were significant differences in thrombus components between the patients with acute ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction(P<0.01).In the group with PCI<3 h after onset of AMI,there was no significant difference in the incidence of no-reflow and slow-flow between the white and red thrombus groups.In the groups with PCI 3-6 and 6-12 h after onset of AMI,there was a significant difference in the incidence of no-reflow and slow-flow between the white and red thrombus groups(P<0.01).There was a significant correlation between the onset time of AMI and the occurrences of no-reflow and slow blood flow during PCI(P<0.01).CONCLUSION In direct PCI,the onset time of AMI and color of coronary thrombus are often used to predict whether there will be no reflow or slow blood flow after stent implantation.

Efficacy of Different Treatment Regimens for Antiphospholipid Syndrome-related Recurrent Spontaneous Abortion

Background： Antiphospholipid syndrome （APS）-related immune factors are considered as an important cause of recurrent spontaneous abortion （RSA）. Anticoagulant and anti-inflammatory treatments are believed to effectively improve adverse pregnancy outcomes by affecting the abnormal autoimmune response of the maternal-fetal interface. The aim of this study was to observe the clinical characteristics and treatment outcomes of anticoagulant regimens and anti-inflammatory plus anticoagulation regimens for APS-related RSA. Methods： APS-related RSA cases from September 2011 to September 2016 at Peking University Third Hospital were retrospectively analyzed. The patients were assigned to study group （anti-inflammation plus anticoagulation） and control group （simple anticoagulation）, The incidence of repeat abortion, the incidence of placental dysfunction, the gestational weeks of pregnancy, and the mean weight of the fetus were observed. Results： The pregnancy and neonatal outcome indicators of the repeat pregnancy loss rate （ 11. 11% vs. 22.70%）, placental dysfunction-related diseases （6.35% vs. 15.60%）, the mean birth weight of infants born after 24 weeks gestation （3152.4 ± 844.67 g vs. 2765.76 ± 816.40 g）, full-ternl delivery weight （3456.28 ±419.79 g vs. 3076.18±518.79 g）, the proportions of low birth weight infants （ 12.70% vs. 21.98%）, and small for gestational age （6.35% vs. 14.18%） differed significantly between the study and control groups （all P 〈 0.05）. The incidence of preterm delivery, term delivery, and stillbirth was not significantly different between the two groups, and there was no significant difference between the study and control groups in gestational age at birth （37.6 ± 3.3 weeks vs. 36.9 ± 3.2 weeks： P 〉 0.05）. Conclusion： The anti-inflammatory and anticoagulation regimen is more effective than the simple anticoagulation regimen in the treatlnent of APS recurrent abortion.

Value of fasting plasma glucose to screen gestational diabetes mellitus before the 24th gestational week in women with different pre-pregnancy body mass index

Background:Gestational diabetes mellitus(GDM)is usually diagnosed between 24th and 28th gestational week using the 75-g oral glucose tolerance test(OGTT).It is difficult to predict GDM before 24th gestational week because fast plasma glucose(FPG)decreases as the gestational age increases.It is controversial that if FPG≥5.1 mmol/L before 24th gestational week should be intervened or not.The aim of this study was to evaluate the value of FPG to screen GDM before 24th gestational week in women with different pre-pregnancy body mass index(BMI).Methods:This was a multi-region retrospective cohort study in China.Women who had a singleton live birth between June 20,2013 and November 30,2014,resided in Beijing,Guangzhou and Chengdu,and received prenatal care in 21 selected hospitals,were included in this study.Pre-pregnancy BMI,FPG before the 24th gestational week,and one-step GDM screening with 75 g-OGTT at the 24th to 28th gestational weeks were extracted from medical charts and analyzed.The pregnant women were classified into four groups based on pre-pregnancy BMI:Group A(underweight,BMI<18.5 kg/m^2),Group B(normal,BMI 18.5-23.9 kg/m^2),Group C(overweight,BMI 24.0-27.9 kg/m^2)and Group D(obesity,BMI≥28.0 kg/m^2).The trend of FPG before 24th week of gestation was described,and the sensitivity and specificity of using FPG before the 24th gestational week to diagnose GDM among different pre-pregnancy BMI groups were reported.Differences in the means between groups were evaluated using independent sample t-test and analysis of variance.Pearson Chi-square test was used for categorical variables.Results:The prevalence of GDM was 20.0%(6806/34,087)in the study population.FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week.FPG was higher in women with higher pre-pregnancy BMI.FPG before the 24th gestational week and pre-pregnancy BMI could be used to predict GDM.The incidence of GDM in women with FPG≥5.10 mmol/L in the 19th to 24th gestational weeks and pre-pregnancy overweight or obesity was significantly higher than that in women with FPG≥5.10 mmol/L and pre-pregnancy BMI<24.0 kg/m^2(78.5%[62/79]vs.52.9%[64/121],χ^2=13.425,P<0.001).Conclusions:FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week.Pre-pregnancy overweight or obesity was associated with an increased FPG value before the 24th gestational week.FPG≥5.10 mmol/L between 19 and 24 gestational weeks should be treated as GDM in women with pre-pregnancy overweight and obesity.

Analysis of the Characteristics of Pregnancy and Delivery before and after Implementation of the Two-child Policy

Background： After the two-child policy is frilly implemented, new challenges regarding pregnancy management and the treatment of pregnancy complications will arise. The aim of this study was to analyze the characteristics of pregnancy and delivery before and after the implementation of the two-child policy to make suggestions on the quality assurance of the new era of obstetrics. Methods： In total, 5895 cases of pregnant women who delivered from April 2016 to March 2017 in Peking University Third Hospital served as the study group and 5103 cases of pregnant women who delivered from January to December 2015 served as the control group. The characteristics of pregnancy and delivery were retrospectively analyzed. Results： In the study group, the percentage of pregnant women who were older （over 40 years） （3.6% vs. 2.2%）, were multipara （30.3% vs. 17.0%）, received irregular prenatal care （ 1.5% vs. 0.9%）, were transferred for treatment from a subordinate hospital （4.4% vs. 2.8%）, and were not residents of Beijing （3.8% vs. 2.2%）, were significantly increased compared with the control group （P 〈 0.05）. In the study group, the rate of a hypertensive disorder complicating pregnancy （6.4% vs. 5.0%）, gestational diabetes mellitus （25.3% vs. 23.1%）, dangerous placenta previa （3.0% vs. 2.3%）, placental implantation （2.4% vs. 1.8%）, and severe postpartum hemorrhage （2.8% vs. 1.9%） was significantly increased compared with the control group （P 〈 0.05）. In the study group, the cesarean section rate during primipara was significantly reduced compared with the control group （42.0% vs. 44.2%）. However, the rate during inultipara was significantly increased compared with the control group （P 〈 0.05）. Indications for cesarean section in the study group as well as the percentages of scared uterus and placenta previa were significantly increased compared with the control group （P 〈 0.05）. Conclusions： According to the current situation, better methods are needed to strengthen pregnancy and delivery management, reduce the rate of cesarean section, and ensure a positive outcome for mothers and babies.