In vivo treatment with recombinant IL-12 protects C57BL/6J mice against secondary alveolar echinococcosis

Using an experimental model of hepatic Echinococcus multilocularis infection in C57BL/6J mice, intraperitoneal administration of 0.8 μg of recombinant IL-12 to mice with an established infection was shown to reduce the parasite burden as soon as two weeks after the end of treatment. At that time, in vitro Echinococcus multilocularis -induced spleen T cell proliferative responses as well as IFN-γ and IL-5 production were higher in IL-12 treated mice than in untreated mice. Administration of 0.8 μg of IL-12 at the time of infection was shown to be without effect on the parasite establishment. However, this treatment greatly inhibited the subsequent metacestode development. Indeed, ten weeks after infection, it induced a complete healing in 37.5% of mice. At that time, the development of metastases was inhibited in 68.75% of IL-12-treated mice. This reduction of parasite burden was mainly associated with a strong proliferation of spleen cells to E. multilocularis antigen and with a high IFN-γ production. Altogether, our results show that IL-12 is of crucial importance in inhibiting the larval growth after the metacestode establishment in the liver and suggest that this cytokine could be of potential value in the treatment of human alveolar echinococcosis .     

RP-HPLC法测定β-司他夫定的有关物质

目的:建立了β-司他夫定原料有关物质的RP-HPLC测定方法和水解破坏制备系统适用性试验溶液方法。方法:采用Agilent 1100型高效液相色谱仪,使用SUPELCOSIL LC-18-DB(4.6 mm×250 mm,5μm)色谱柱,以0.01 mol·L-1醋酸铵溶液-乙腈(96.5∶3.5)和0.01 mol·L-1醋酸铵溶液-乙腈(75∶25)为流动相,梯度洗脱,检测波长254 nm,柱温25℃。结果:β-司他夫定和4种已知杂质及其他未知杂质均能达到有效分离;经水解破坏产生的α-司他夫定与β-司他夫定的分离度均达2.8;β-司他夫定、胸腺嘧啶、β-胸苷与5-O’-苯甲酰-司他夫定线性范围分别为0.51~26μg·m L-1(r=1.000)、0.13~27μg·m L-1(r=1.000)、0.50~25μg·m L-1(r=1.000)、1.7~6.3μg·m L-1(r=1.000),已知杂质胸腺嘧啶、β-胸苷与5-O’-苯甲酰-司他夫定的平均加样回收率(n=9)分别为102.8%(RSD=1.5%)、100.6%(RSD=0.9%)、101.9%(RSD=2.1%);β-司他夫定与3种已知杂质的最小检出量均在2.5 ng以下;经水解破坏制备的系统适用性溶液的重复性良好;供试品溶液在4℃下的30 h内基本稳定。结论:本方法灵敏、准确、可靠,专属性强,可用于β-司他夫定原料的有关物质测定。     

幽门螺杆菌感染对胃黏膜病理变化的影响

背景：幽门螺杆菌(H．pylori)感染已被公认为慢性胃炎和消化性溃疡的重要危险因素，根除H．pylori能加速消化性溃疡的愈合，但其对胃黏膜病理变化的影响尚有待进一步探索。目的：了解根除H．pylori对慢性胃炎胃黏膜病理变化和癌前状态的影响。方法：采用多中心随机对照临床试验和回顾性队列研究，样本选自胃癌高发区：上海郊区的金山区和奉贤区。共纳入360例经内镜检查证实有H．pylori感染的慢性胃炎伴或不伴十二指肠溃疡患者，随机分为两组。治疗组用三联疗法(质子泵抑制剂或Hz受体阻滞剂加两种抗生素)治疗，对照组单纯慢性胃炎患者予西沙必利、十二指肠溃疡患者予西米替丁治疗。在第1年和第4年末随访胃镜，根据H．pylori是否根除将患者分为两组：H．pylori阳性组和H．pylori阴性组。所有胃黏膜活检标本由两位病理科医师统一复读。结果：至第4年末，有120例患者完成全部随访，其中H．pylori持续根除组54例，阳转组5例；H．pylori持续未根除组45例，阴转组16例。持续根除组第1年随访时，活动性炎症比例减少(P＜O．05)；第4年随访时，慢性炎症和肠化程度以及活动性炎症比例减少(P＜O．05)。持续未根除组第1年随访时，慢性炎症程度增加(P＜O．05)；第4年随访时，慢性炎症和肠化程度以及活动性炎症比例增加(P＜O．05)，萎缩程度较第1年随访时增加(P＜O．05)。结论：根除H．pylori可以减轻慢性胃炎的炎症程度，防止肠化的发生和发展。     

Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.     

胃泌素对胃癌细胞SGC7901 Reg Ⅰ基因转录因子的效应

目的 探讨胃泌素对胃癌细胞SGC7901 Reg Ⅰ(Reg Ⅰ)基因转录因子的效应.方法 应用巢式PCR技术从胃癌细胞SGC7901基因组DNA扩增Reg Ⅰ基因启动子1414bp片段,将该片段插入pMD19-T载体,序列分析鉴定.应用随机引物法以地高辛分别标记1414bp及其HindⅢ酶切800bp和614bp片段,经灵敏度检测后,作为探针.应用Genomatix MatInspector在线分析软件分析Reg Ⅰ基因启动子1414bp片段的转录因子结合位点.分别以10-7 mol/L和10-8mol/L胃泌素G-17处理胃癌细胞SGC7901 48h,提取核蛋白.应用DNA-蛋白质印迹法(Southern blotting),分别以地高辛标记的1414bp、800bp和614bp片段为探针检测胃泌素对胃癌细胞SGC7901 Reg Ⅰ基因转录因子的效应.结果 1414bp探针可检测到20条蛋白主带.胃泌素孵育后,带型没有变化,但是一些条带的灰度值改变,带9、12、13、14、15和16的灰度值明显降低(P＜0.05);不同浓度胃泌素处理组之间上述6个条带的灰度值差异不明显(P＞0.05).614bp探针可检测到灰度值变化的6条主带中的带9、12和13,胃泌素处理后,此3条主带的灰度值明显降低(P＜0.05).800bp探针可检测到灰度值变化的6条主带中的带9、12和14,胃泌素处理后,仅带14的灰度值明显降低(P＜0.05).614bp和800bp探针均未检出带15和带16.结论 胃癌细胞SGC7901Reg Ⅰ基因表达由多个转录因子协同调控.降低几个转录因子的结合活性可能是胃泌素上调胃癌细胞SGC7901Reg Ⅰ基因表达的途径之一.     

乙型肝炎病毒对肝内TGF-β1/Smads信号通路的作用

 目的：探讨乙型肝炎病毒（HBV）对肝内TGF-β1蛋白表达及Smads信号通路的作用,为制定慢性乙肝肝纤维化临床治疗策略提供理论依据。方法：(1)运用免疫组化PV-6000法检测对照组和慢性乙肝组肝组织中TGF-β1、HBsAg和HBcAg的表达,并采用荧光定量PCR法测定慢性乙肝患者血清HBV DNA含量。(2)应用体外细胞培养技术培养HBV刺激的人肝星状细胞系LX-2细胞,Western blotting方法测定其细胞内TGF-β1、Smad3和Smad7的蛋白表达。结果：(1)慢性乙肝组肝组织内TGF-β1的表达高于对照组（P＜0.01）;肝内TGF-β1表达水平与血清HBV DNA含量呈正相关（P＜0.01）,且HBcAg阳性肝组织水平较高（P＜0.01）。(2)体外细胞学实验中,HBV刺激组LX-2细胞内TGF-β1和Smad3蛋白含量高于对照组和HBV+抗-TGF-β1组（P＜0.01）;Smad7蛋白表达差异无统计学意义（P>0.05）。结论：(1)TGF-β1在慢性乙肝患者肝组织中的表达与血清HBV DNA含量及肝内HBcAg的表达有关。(2)在TGF-β1/Smads信号通路中,HBV致纤维化作用机制以Smad3的正性调控为主,Smad7的作用不明显。     

血清及尿液特定蛋白检测在糖尿病肾病早期诊断中的意义

目的探讨尿微量白蛋白(MA)、尿α1-微球蛋白(α1-MG)、尿β2-微球蛋白(β2-MG)及血清β2-微球蛋白(β2-MG)在糖尿病肾病早期诊断中的意义。方法收集67例2型糖尿病患者和82名正常健康人的血清及尿液,分别利用化学发光法检测血清β2-MG、放射免疫法测定尿β2-MG及散射速率比浊法测定尿MA和尿α1-MG水平。结果与正常对照组相比,糖尿病组4组特定蛋白水平明显升高,结果有显著性差异(P均<0.05);此4组蛋白在正常对照组测得的结果无一例阳性,但在糖尿病组的阳性率分别为32.8%、47.8%、35.8%、34.3%;实验还发现随着病程的延长,糖尿病组4组蛋白的阳性率也相应升高(P<0.05)。结论测定尿液中MA、α1-MG、β2-MG及血清β2-MG水平对糖尿病肾病的早期诊断具有一定意义,能够帮助患者及早发现病情,减少疾病迁延。     

糖尿病合并高血压病人血小板参数的变化及临床意义

目的研究血小板参数在糖尿病(DM)及 DM合并高血压(HBP)病人中的变化及临床意义。方法收集 2018年 10月至 2019年 8月在武汉大学人民医院确诊为 2型糖尿病(T2DM)的病人 113例,将其作为 DM组; T2DM合并 HBP病人 157例,作为 DM合并 HBP组,并按照血压水平将其分为 HBPⅠ、Ⅱ、Ⅲ级三个亚组;检测并分析两组的空腹血糖(FPG)、糖化血红蛋白(HbA1c)、血小板计数(PLT)、血小板压积(PCT)、平均血小板容积(MPV)、血小板分布宽度(PDW)及大血小板比率(P?LCR)以及通过受试者工作特征(ROC)曲线比较 PLT、MPV、PDW、P?LCR、HbA1c对 DM合并 HBP的诊断价值;并探究 DM合并不同,严重程度 HBP病人以上指标的变化趋势。结果 DM合并 HBP组的 HbA1c［8.90(7.33,10.90)%比 8.70(6.68,10.48)%］、 PLT［222.00(191.50,268.00)109/L比 206.00(179.50,236.50)109/L］、 MPV［11.10(10.45,11.60)fl比 10.20(9.85,10.60)fl］、 PDW［(13.50±2.27)fl比(11.43±1.04)fl］、 P?LCR［(33.92±7.46)%比(25.94±4.49)%］的水平明显高于 DM组,且差异有统计学意义(P＜0.05)。随着 HBP严重程度的升高, FPG、MPV、PDW、P?LCR的水平升高,呈明显的上升趋势。 P?LCR的 ROC曲线下面积(AUC)为 0.812,大于 PLT(AUC为 0.618),MPV(AUC为 0.805)、 PDW(AUC为 0.799)和 HbA1c(AUC为 0.578)对 DM合并 HBP的诊断价值最大。结论血小板参数与 DM合并 HBP的发生关系密切,对于诊断评估 DM合并 HBP有一定的价值。,     

Brief Report: Transplantation of Allogeneic Canine Bone Marrow Stored at -80 C. in Dimethyl Sulfoxide

Prompt initial bone marrow engraftment was observed in 10 lethally irradiated dogs receiving infusions of 9.8 to 30.0 x 10⁹ allogeneic marrow cellsstored at -80 C. in dimethyl sulfoxide. The 3 recipients of bone marrow fromunrelated donors, mismatched by canine histocompatibility testing, subsequently rejected their grafts and died within 16 days with marrow hypoplasia.The 3 dogs with matched unrelated donors and the 4 with matched littermate donors all showed sustained marrow engraftment. Evidence of marrowrepopulation by allogeneic cells was obtained by cytogenetic studies in oneand by change to donor red cell type in 3 instances.

Submitted on December 16, 1968 Accepted on January 28, 1969     

Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.