目的 观察地西他滨联合HA方案(高三尖杉脂碱+阿糖胞苷)对老年急性髓系白血病(acute myeloid leukemia,AML)患者诱导化疗的效果及安全性.方法 回顾性分析2018年1月至2020年2月解放军总医院第七医学中心接受地西他滨联合HA方案诱导化疗的10例老年AML患者,观察其总缓解率及总生存率.结果 所有患者均应用地西他滨联合HA方案诱导化疗1~2个周期,3例达完全缓解,4例达部分缓解,1例病情稳定,2例病情进展,总缓解率达70.0%.1例患者放弃治疗后死亡,1例患者在化疗后骨髓抑制期合并严重感染而死亡,2例患者复发后死亡,总生存率达60.0%.9例发生Ⅲ~Ⅳ级骨髓抑制,7例发生严重感染,2例发生败血症,5例发生肺部感染,2例为侵袭性真菌感染,1例患者出现消化道出血,经积极补充血小板、凝血因子后好转,无Ⅲ~Ⅳ级恶心、呕吐及肝功能损害.结论 对老年AML患者应用地西他滨联合HA方案诱导化疗,效果显著,耐受性良好.
目的 观察附子煎剂灌胃对阳气亏虚型脓毒性休克患者心功能的改善作用.方法 选择阳气亏虚型脓毒性休克患者72例,随机分为干预组和对照组,各36例.两组均按2016国际脓毒症和感染性休克管理指南实施治疗,干预组在此基础上给予9g附子煎剂灌胃,每6小时1次,共8次;对照组给予等量开水灌胃.观察两组患者入院时(0 h)、治疗后12 h、24 h、48 h的临床指标,包括平均动脉压(MAP)、血乳酸(Lac)、N末端B型脑钠肽前体(NT-ProBNP),以及超声监测指标:下腔静脉内径呼吸变异率(IVC-V)、每搏输出量(SV)、左室射血分数(LVEF)、左心室舒张早期最大血流/心房收缩期二尖瓣最大血流(E/A)、右心室面积变化分数(RVFAC),比较两组患者血管活性药物使用时间、ICU住院时间、28 d病死率以及不良反应.结果 治疗后12 h,干预组患者的MAP高于对照组,差异有统计学意义(t=2.13,P<0.05),治疗后12 h、24 h、48 h,干预组血Lac、NT-ProBNP均低于对照组,差异均有统计学意义(t分别=2.50、2.80、3.84、4.96、11.05、25.58,P均<0.05).治疗24 h后,干预组IVC-V大于对照组,差异有统计学意义(t=2.26,P<0.05).治疗后24 h、48 h,干预组LVEF大于对照组,差异均有统计学意义(t分别=2.79、2.23,P均<0.05),治疗后12 h、24 h、48 h,干预组SV、E/A、RVFAC均大于对照组,差异均有统计学意义(t分别=2.01、3.29、3.64、7.86、2.77、4.87、2.86、2.13、2.49,P均<0.05).干预组的血管活性药物使用时间、ICU住院时间均低于对照组,差异均有统计学意义(t分别=4.21、2.08,P均<0.05);但两组28 d病死率比较,差异均无统计学意义(χ2=1.15,P>0.05).两组患者的不良反应发生率,包括肝肾功能、凝血功能、心律失常、TnI异常、肢端坏死、误吸等,差异均无统计学意义(χ2分别=0.07、0.22、0.56、0.00、1.01、0.16,P均>0.05).结论 附子煎剂灌胃可改善阳气亏虚型脓毒性休克患者的血流动力学参数和组织氧代谢,增强其心功能,改善临床预后,且不增加不良反应的发生.
Dear Editor, Haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT),a curative therapy for severe aplastic anemia (SAA) patients,has been used clinically for decades.Two models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with SAA.The first is referred to as the "Beijing protocol" (Xu et al.,2017),and comprises a conditioning regimen using busulfex (BU),cyclophosphamide (CY),and anti-thymocyte globulin (ATG) followed by granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (BM) and/or peripheral blood (PB) hematopoietic stem cells (HSCs).The second is a recently developed,post-transplant cyclophosphamide (PTCY)-based protocol (Clay et al.,2014).To date,there have been no studies to determine the better one for haploHSCT in patients with acquired SAA.
This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone Marrow Transplantation Registry Group (CBMTRG). For each PTCy, G-CSF/ATG subjects (1:4) were selected using the nested case-pair method. In total, 220 patients including 176 in G-CSF/ATG group and 44 in PTCy group were analyzed. The incidences of 30-day neutrophil engraftment (88.6% vs. 96.6%, P =0.001), 90-day platelet engraftment (84.1% vs. 94.2%, P =0.04), the median time to neutrophil engraftment (17 days vs. 12 days, P =0.000) and platelet engraftment (22 days vs. 17 days, P =0.001) were significantly inferior in PTCy group. The incidences of grades 2–4 and 3–4 acute graft-versus-host disease (GVHD), chronic GVHD and severe chronic GVHD were comparable. Among G-CSF/ATG and PTCy groups, the 3-year progression-free survival, overall survival, cumulative incidences of nonrelapse mortality and relapse was 74.3% vs. 61% ( P =0.045), 78.3% vs. 65.2% ( P =0.039), 12% vs. 27.3% ( P =0.008), and 14.9% vs. 11.7% ( P =0.61), respectively. G-CSF/ATG can achieve better engraftment, PFS and OS, and lower incidence of NRM compared to PTCy in myeloablative haplo-HSCT for hematologic malignancies.
B-cell acute lymphoblastic leukemia (B-ALL) with MLL-rearrangements (MLL-r) is rare in pediatric patients (aged > 1 year), and optimal treatment strategies remain unclear. This study aimed to retrospectively evaluate the clinical characteristics, outcomes, and effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) of 37 non-infant children with t(v;11q23)/MLL-r B-ALL. Their 4-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 69.8 %, 58.2 %, and 39.1 %, respectively, and differed significantly between patients receiving allo-HSCT (18/19 cases received haploidentical [haplo]-HSCT) at the first complete remission (HSCT at CR1, n - 19; 87.4 %, 89.5 % and 5.3 %) and those continuing consolidation therapy (Non-HSCT at CR1, n = 18; 52.2 %, 25.9 %, and 74.1 %, respectively), and the p values were 0.022,< 0.001 and < 0.001, respectively. Of the 13 patients experiencing relapse during consolidation chemotherapy, the five continuing with chemotherapy only died within 44 months, and the eight patients opting for allo-HSCT after CR2 had a 4-year OS of 57.1 %. Multivariate analysis revealed HSCT at CR1 as the only independent protective factor for OS, EFS, and CIR. The present results indicate that allo-HSCT (especially haplo-HSCT) at CR1 may decrease the relapse rate and improve the prognosis of non-infant children with t(v;11q23)/ MLL-r B-ALL.
目的:探讨EPOCH-L方案治疗复发难治性T细胞淋巴瘤的疗效及安全性.方法:回顾性分析解放军某医院2012年1月至2017年1月收治的12例复发难治性T细胞淋巴瘤患者的临床资料,均采用EPOCH-L方案化疗(依托泊苷50 mg/m2第1~4天、吡柔比星10 mg/m2第1~4天、长春地辛1 mg/d第1~4天、环磷酰胺750 mg/m2第5天、泼尼龙60 mg/m2第1~5天、培门冬酶2500iu/m2第6天)3~6个周期,并随机选取同期进行异基因造血干细胞移植治疗的12例复发难治性T细胞淋巴瘤患者为对照组,比较两组的临床疗效及不良反应的发生情况.结果:随访至2018年1月,EPOCH-L方案组患者取得完全缓解4例(33.3%),部分缓解4例(33.3%),总有效率为66.7%,中位生存期为23.7(7~65)个月,随访期间总生存率为25%;对照组患者中位生存期为9.2(3~60)个月,无病生存率为41.7%,总体生存时间分布差异无统计学意义(P=0.683).实验组没有患者死于化疗合并症(0.0%),对照组4例死于移植合并症(33.3%),差异有统计学意义(P=0.028).结论:EPOCH-L方案治疗复发难治性T细胞淋巴瘤的临床效果与异基因造血干细胞移植治疗相当,且安全性较高.
Although chimeric antigen receptor T cells (CAR-T) targeted at CD19 or CD22 have achieved high complete remission (CR) in refractory/relapsed B-cell acute lymphoblastic leukaemia (B-ALL), it is uncertain if allogeneic haematopoietic stem cell transplantation (allo-HSCT) should be performed after CAR-T therapy to accomplish a sustainable remission. Fifty-two cases with relapsed/refractory B-ALL who underwent allo-HSCT after CR by CD19 or CD22 CAR-T were enrolled. The median time from CAR-T infusion to allo-HSCT was 50 (34-98) days. Myeloablative reduced-intensity conditioning (RIC) with total body irradiation/fludarabine-based or busulfan/fludarabine-based regimens was used. Incidences of grade II-IV acute graft-versus-host disease (aGVHD) and severe aGVHD were 23·1% and 5·8% respectively. Of 48 evaluable cases, 16 developed chronic GVHD (cGVHD) and in three of them the pattern was extensive. With a median follow-up of 334 (41-479) days, one-year overall survival and event-free survival (EFS) were 87·7% and 73·0%. One-year relapse rate and transplant-related mortality (TRM) were 24·7% and 2·2% respectively. With quick bridge to allo-HSCT after CAR-T therapy, high EFS for refractory/relapsed B-ALL has been achieved in this relatively large cohort. Our myeloablative RIC regimens have resulted in low incidences of aGVHD, cGVHD, viral reactivation and very low TRM even majority of transplants from haploidentical donors. Long-term follow-up is warranted.
背景:研究表明,异基因造血干细胞移植后应用血小板生成素在造血调控、造血重建等方面有一定作用,为临床推广应用提供理论基础.目的:分析血小板生成素在异基因造血干细胞移植治疗重型再生障碍性贫血中促进血小板植入的临床疗效和安全性.方法:2012年1月至2017年1月共入选50例接受异基因造血干细胞移植治疗的重型再生障碍性贫血患者,分为治疗组和对照组各25例,其中男28例,女22例,平均年龄27.8(16-48)岁,治疗组在移植后7 d起应用血小板生成素300 U/kg,连续14 d,比较两组患者血小板植入后在≥20×109 L-1、50×109 L-1和100×109 L-1的时间节点及血小板中位输注次数.该治疗方案得到解放军陆军总医院伦理委员会批准和患者知情同意.结果与结论:两组患者均获造血重建,治疗组和对照组血小板≥20×109 L-1、50×109 L-1和100×109 L-1的中位时间分别为16.2,19.3,30.2 d和18.8,25.8,38.5 d,治疗组血小板植入时间比对照组分别提前2.6,6.5, 8.3 d,辐照血小板中位输注次数分别为6.8次和9.5次,两组数据结果显示差异有显著性意义(P < 0.05).随访至2017年7月,两组患者无病生存率分别为80%,72%.结果表明,血小板生成素能够促进异基因造血干细胞移植后血小板植入及恢复,且患者耐受性好,值得临床进一步推广应用.
目的 探讨改良急诊床边肺部超声检查(bedside lung ultrasound in emergency,BLUE)方案在ICU患者肺实变(包括肺不张)评估中的应用价值.方法 对2015年6月至2016年12月入住ICU的66例呼吸衰竭患者,进行改良BLUE方案检查,依次探查上蓝点、下蓝点、膈肌线、后侧壁肺泡胸膜综合征点、后蓝点区域,辨认并对比双侧的超声征象.以肺部超声组织样征、碎片征、支气管充气征诊断肺实变.并在完成改良BLUE方案检查后3h内行X线胸片和胸部CT检查,以胸部CT检查结果为金标准,评价改良BLUE方案诊断肺实变的效能.结果 66例患者132侧胸部CT检查诊断肺实变95侧(72.0%),其中改良BLUE方案检查诊断90侧(68.2%),X线胸片诊断35侧(26.5%);改良BLUE方案诊断肺实变的灵敏度为0.95,特异度为1.00,准确率为96.2%.配对资料McNemar检验提示,B超与CT诊断的一致性较好(Kappa=0.765).结论 肺部改良BLUE方案对肺实变的诊断有较高灵敏度、特异度及准确率,值得在临床进一步推广应用.
OBJECTIVE To study the long-term efficacy and safety of CD19 chimeric antigen receptor T cells (CAR-T) in the treatment of relapsed patients with B-cell acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS A total of 7 patients with B-cell ALL relapsed after allo-HSCT were treated with CD19 CAR-T cells from September 2015 to March 2018. Among them, 6 had hematological recurrence and 1 had positive of MRD. They all were treated with a single infusion of CAR-T cells. FC chemotherapy regimen was administered before transfusion. The median number of CAR-T cells transfused was 6.0 (range 4.0-8.6) )×106/kg. Long-term efficacy and toxicity were evaluated. RESULTS Bone marrow examination performed at d 30 after CAR-T infusion showed that all 7 patients achieved complete remission and MRD negative, grade I CRS for 1 case and grade II CRS for 6 cases, two of them had mild neurotoxicity, which was controlled by treatment. Two patients presented grade VI intestinal GVHD after CAR-T infusion. The median follow-up time was 18 months (range 12-42). Follow-up showed that two patients relapsed at 9 months and 14 months after treatment, out of 2 patients one died of progressive disease and the other reachived the hematological remission, but MRD was positive after CD22 CAR-T cell therapy. At present, five patients are disease-free survival, moreover showed complete donor chimerism. One year after CAR-T cell therapy, the results of immune reconstitution showed that CD4 level was more than 300×106/L in 5 patients who disease-free survived. Among them, 3 patients had poor recovery of immunoglobulin and received gamma globulin replacement therapy. CONCLUSION All patients are followed up for at least one year. The preliminary efficacy and safety are satisfactory. CAR-T cell infusion is an effective method for the treatment of B-ALL recurrence after allo-HSCT.
[This corrects the article DOI: 10.18632/oncotarget.22612.].
Objective To ana1yze the therapeutic effect of p1asma exchange(PE)in the treatment of hyperbi1irubi-nemia after a11o-HSCT.Method From October 2009 to October 2016,nine patients(16 events a1together)received PE due to hyperbi1irubinemia after a11o-HSCT.The 1iver function,bi1irubin and prothrombin time activity were com-pared before and after the treatment.Adverse effects were observed in the same time.Result A11 9 patients were trea-ted with p1asma exchange tota11y 16 times;After the treatment,serum tota1 bi1irubin(TB)and direct bi1irubin(DB) decreased.The decreased 1eve1s in b1ood ce11s,a1bumin and prothrombin time activity were not statistica11y signifi-cant.Conclusion P1asma exchange therapy may reduce the serum bi1irubin 1eve1 in a certain extent.But the effect of p1asma exchange on prognosis remains to be further studied.
Angiogenesis is important in pathophysiological processes, including the pathogenesis of acute monocytic leukemia (AML). MicroRNA‑21 (miR‑21) is overexpressed and exhibits oncogenic activity in cancer. However, the biological mechanism underlying the effect of miR‑21 in AML remains to be fully elucidated. In the present study, the expression levels of miR‑21 and vascular endothelial growth factor (VEGF) were determined in 26 patients with AML and 28 healthy individuals. The secretion of VEGF was also measured following the transfection of THP‑1 cells with miR‑21 mimic or inhibitor. The supernatants of the THP‑1 cells, which were transfected with miR‑21 mimic, inhibitor or small interfering RNA (si)VEGF, respectively, were used to incubate human umbilical vein endothelial cells (HUVECs), following which tube formation of the HUVECs was measured. miR‑21 targets were predicted using a biological target prediction website and confirmed using a luciferase assay. The effects of interleukin (IL)‑12 were investigated by examining the tube formation of HUVECs and the secretion of VEGF following recombinant human (rh) IL‑12 pretreatment. The results revealed that miR‑21 and VEGF expression was significantly increased in the peripheral blood monocytes of the patients, compared with the healthy controls. There was negative correlation between the expression of IL‑12 and miR‑21 in the serum of patients with AML. Furthermore, supernatant VEGF levels from the miR‑21 mimic‑transfected THP‑1 cells were increased, whereas a decreasing trend was observed in the miR‑21 inhibitor group. The angiogenic ability of the HUVECs pretreated with supernatant from the THP‑1 cells transfected with miR‑21 mimic was higher, and was lower in THP‑1 cells co‑transfected with miR‑21 mimic and siVEGF, compared with the miR‑21 mimic only group. A luciferase assay demonstrated that IL‑12 was the direct target of miR‑21, and the level of IL‑12 in the supernatant of THP‑1 cells transfected with miR‑21 mimic was increased. IL‑12 pretreatment increased VEGF expression and angiogenic ability in HUVECs. The inactivation of miR‑21 or activation of its target gene may be a potential therapeutic strategy in human AML.
目的 探讨危重患者早期肠内营养幽门后喂养方式对肠内营养耐受性及临床预后的影响.方法 本次研究为前瞻性随机对照试验.选择接受机械通气且实施肠内营养的危重症患者70例,根据随机数字表法分成幽门前喂养组35例和幽门后喂养组35例.幽门前喂养组留置鼻胃管,幽门后喂养组留置鼻肠管.两组患者均使用瑞代营养液经营养泵持续泵入,每日18 h,连续观察7 d,7 d内肠内营养达到目标热卡量.观察7 d内患者的肠内营养耐受性、呼吸机相关性肺炎(VAP)、ICU住院时间、机械通气时间及病死率.结果 幽门后喂养组胃残余量过多、返流的发生率低于幽门前喂养组,差异均有统计学意义(χ2分别=4.20、4.63,P均<0.05);但幽门后喂养组腹泻发生率高于幽门前喂养组(χ2=5.08,P<0.05);两组患者在误吸及肠内营养不耐受的发生率、VAP发生率、院病死率、机械通气时间及ICU住院时间比较,差异均无统计学意义(χ2分别=1.94、0.24、1.06、0.13,t分别=0.75、0.44,P均>0.05).结论ICU危重患者早期肠内营养使用幽门后喂养途径增加腹泻的发生,但减少胃残余量过多及返流风险.
Objective To investigate the effects of same calorie intake of different enteral nutrition (EN) on blood glucose in patients with mechanical ventilation.Methods A total of 60 critically ill patients who were admitted to the Department of Intensive Care Unit (ICU) of Taizhou Combined Traditional Chinese and Western Medicine Hospital and received mechanical ventilation from January 2015 to January 2017 were selected. According to the random number table method, the patients were divided into a control group and a study group, 30cases in each group. The patients in the control group were given EN suspension (nutrison fibre), patients in the study group received EN emulsion (fresubin diabetes), on the first day, 1/3 standard calorie was supplied, if the patient had no any discomfort, on the second day 1/2 standard heat was given, from the third day to the tenth day they took the full amount and achieved complete EN (TEN).The fasting blood glucose (FBG), 2 hours postprandial blood glucose (2 h PBG) and glycated hemoglobin (HbA1) level before and after the EN for 10 days were observed, the gastrointestinal tolerance, dosage of insulin, inflammation related indexes, the incidence of ventilator associated pneumonia (VAP) and fatality were analyzed in the two groups.Results Compared with those before EN support, the FBG and 2 h PBG were decreased after the support for 10 days in both groups, the dosage of insulin used was decreased, and the degrees of decrease were more marked in the study group than those in the control group [FBG (mmol/L): 8.03±1.69 vs. 8.87±1.75, 2 h PBG (mmol/L): 8.25±1.98 vs. 10.43±2.34, dosage of insulin (U/d): 38.02±3.24 vs. 40.87±3.48, allP < 0.05], but there was no statistical significant difference in HbA1 level between the two groups [(7.36±1.53)% vs. (7.37±1.29)%,P > 0.05]. The incidence of gastrointestinal intolerance was lower in study group than that in control group [6.67% (2/30) vs. 10.0% (3/30)], but there was no statistical significant difference between the two groups (P > 0.05). Compared with those before EN support, the levels of γ-interferon (IFN-γ) were significantly increased (P < 0.05), while the tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-8) levels were significantly decreased after 10 days of EN support, but no statistical significant differences were found (allP > 0.05) between the two groups. During the treatment in the two groups, the incidence of VAP and mortality were relatively low, and there were no statistical significant differences were seen between the two groups (bothP > 0.05).Conclusions The blood glucose control of fresubin diabetes in patients with mechanical ventilation is superior to that of nutrison fibre, fresubin diabetes can reduce the dosage of insulin, decrease the levels of inflammatory factors and conducive to the prognosis of the patients.
BACKGROUND: Autoreactive T cells are a group of specialized cells that exert a peripheral immunosuppressive effectthrough certain mechanisms ensuring self-tolerance within the adaptive immune system. The discovery of the latestsurface markers for natural CD4+CD25+ regulatory T cells has re-emphasized the concept of peripheral regulation orsuppression of T cells. Several groups have begun to investigate the role of regulatory T cells in animal models ofallogeneic hematopoietic stem cell transplantation.OBJECTIVE: To review the recent results regarding protection from graft-versus-host disease by adoptively transferredCD4+ CD25+ regulatory T cells in mice and to discuss the latest findings from clinical studies on hematopoietic stem celltransplantation.METHODS: We retrieved CNKI, PubMed and Medline databases for articles concerning CD4+CD25+ regulatory T cellsand graft-versus-host disease published from 2000 to 2015. According to inclusion and exclusion criteria, 46 paperswere included in result analysis.RESULTS AND CONCLUSION: CD4+CD25+ regulatory T cells expressing the transcriptional repressor FOXP3 mediateimmunoregulatory functions and are critical for the prevention of autoimmune diseases. As peripheral tolerance inductionis a prerequisite for successful allogeneic hematopoietic stem cell transplantation, the role of CD4+CD25+ regulatory Tcells in transplantation models and clinical trials is now under investigation in many laboratories. CD4+CD25+ regulatoryT cells play an important role in the development of graft-versus-host disease after allogeneic hematopoietic stem celltransplantation. CD4+CD25+ regulatory T cells not only effectively prevent and treat graft-versus-host disease but alsoretain graft-versus-leukemia effect.
Nowadays, the regular recommended dose of decitabine for the treatment of myelodysplastic syndrome (MDS) is 20 mg/m2/day for 5 consecutive days with a relatively high incidence of treatment-related morbidities and costs. In this study, a retrospective and multicenter analysis was performed to explore the very-low-dose decitabine schedule for the treatment of patients with IPSS intermediate- or high-risk MDS. A total of 31 newly diagnosed MDS cases from 14 hospitals in Beijing received decitabine monotherapy (decitabine 6 mg/m2/day intravenously for 7 consecutive days, repeated every 4 weeks). With a medium follow-up of 4 months, 10 patients achieved complete remission (32.3%), 8 (25.8%) partial remission, and 3 (9.7%) hematological improvement. The overall response rate (ORR) was 67.7%. Rates of 21.7% for severe infections and 11.6% for severe bleedings were observed among all courses. The median cost of each course was USD 5,300, 3,000, 2,900, and 2,000, respectively. Multivariate analysis identified bone marrow blast cells ≥10% and a Charlson comorbidity index ≥1 as 2 independent factors for efficacy. In conclusion, very-low-dose decitabine showed relatively good efficacy, good tolerance, and low medical cost in the treatment of intermediate- or high-risk MDS. Elderly patients with more than 1 complication or patients with a higher proportion of blast cells may be the most suitable candidates for this regimen.
Acute leukemia (AL) is the most popular malignant tumor in children. Currently little has been known about the relationship between childhood AL pathogenesis and whole-genome methylation level. As the polymorphism of DNA methyltransferase (DNMT) gene can affect DNA methylation level, we investigated the whole genome methylation level in childhood AL patients. Meanwhile, the relationship between DNMT1 gene polymorphism and susceptibility of childhood AL was also been investigated. A case-control study was performed recruiting childhood AL patients and age-matched healthy children (N=168 each). PCR-ligase detective response (PCR-LDR) typing method was used to study the genotype distribution of human DNMT1 gene at rs2228611 and rs10854076 loci. Pyrophosphate sequencing was used to measure LINE-1 methylation level. Allele frequency of two loci fits HardyWeinberg equilibrium (P>0.05). Significant difference of genotype and allele frequency existed at locus rs10854076 but not locus rs2228611 between patients and healthy people. Allele C was found to be a risk factor for AL. A significant difference of LINE-1 methylation level existed between the two groups, as AL patients had lower methylation level (P<0.05). Specifically, LINE-1 methylation level at locus rs10854076 but not at rs2228611 had significant difference between patients and controls. Polymorphism of DNMT1 gene at locus rs10854076 is related with children AL susceptibility, possibly via affecting LINE-1 methylation level.
当机体营养摄取未达到代谢要求时就会导致营养不良,重症患者由于手术、烧伤及败血症等原因引起的机体蛋白和能量代谢的改变更加容易导致营养不良[1].肠内营养(EN)作为重症患者营养支持首选的方法,与肠外营养相比具有简便、成本低、感染并发症少及保护肠黏膜屏障等优势[2].然而在EN喂养过程中患者易发生不耐受现象,使得医护人员不得不减少或终止EN,且EN喂养不耐受与肺炎的发生及重症监护病房(ICU)住院时间延长相关[3].因此,充分了解EN不耐受原因并采取相应的预防和治疗措施以减少喂养不耐受现象的发生,现将EN喂养不耐受的临床表现、影响因素及其改善措施综述如下.
AIMS:To investigate the association of several single nucleotide polymorphisms (SNPs) within vascular endothelial growth factor (VEGF) and vitamin D receptor (VDR) gene polymorphisms and additional gene- gene and gene- smoking interaction with multiple myeloma (MM) risk in Chinese population. METHODS:Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association between 6 SNPs within VEGF and VDR gene, additional gene- gene and gene- smoking interaction on MM risk. RESULTS:MM risk is significantly higher in carriers with the rs699947- A allele within VEGF gene than those with CC genotype (CA+ AA versus CC), adjusted OR (95%CI) =1.72 (1.19-2.33), and higher in carriers with rs2228570- T allele within VDR gene than those with CC genotype (CT+ TT versus CC), adjusted OR (95%CI) = 1.68 (1.26-2.17). We also found a significant two-locus model (p=0.0010) involving rs699947 and rs2228570, and a significant two-locus model (p=0.0107) involving rs2228570 andsmoking. Participants with rs699947- CA+AA and rs2228570- CT+TT genotype had the highest MM risk, compared to participants with rs699947- CC and rs2228570- CC genotype, OR (95%CI) = 3.12 (1.82 -4.61). Smokers with rs2228570- CT+TT genotype had the highest MM risk, compared to never- smokers with rs2228570- CC genotype, OR (95%CI) = 3.27 (1.74-4.86). CONCLUSIONS:We found that the A allele of rs699947 within VEGF and T allele of rs2228570 within VDR gene, interaction between rs699947 and rs2228570, rs2228570 andsmoking were all associated with increased MM risk.