In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis: a phase I study

PIXY321 is a novel fusion protein of recombinant human granulocyte- macrophage colony-stimulating factor and interleukin-3 that exhibits biologic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injection twice daily at doses of 25 to 1,000 micrograms/m2/day over 14 days to 24 patients with sarcoma before chemotherapy as part of a phase I trial. The treatment was associated with significant increases in white blood cell, neutrophil, platelet, and reticulocyte counts (all P < .001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count was gradual and peaked after the cessation of the cytokine treatment and was not clearly dose related. PIXY321 treatment also increased bone marrow (BM) cellularity and the percentage of BM cells in S phase (P < .001). In addition, there was a significant increase in the number of CD34+ cells and committed and multipotential progenitors in the peripheral blood. The ex vivo expansion capacity of peripheral blood and BM progenitor cells was preserved after the in vivo treatment with PIXY321. The treatment was well tolerated, with the most common side-effect being injection site reactions. The results of this study show the biologic and clinical activity of a genetically engineered fusion molecule of two hematopoietic cytokines in humans with normal hematopoietic function.     

Human platelets exert cytotoxic effects on tumor cells

Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.     

Hairy cell leukemia and myelomatosis: chance association or clinical manifestations of the same B-cell disease spectrum

We describe three patients who had typical features of hairy cell leukemia (HCL) and multiple myeloma (MM) at the same time. In two, both diagnoses were made within a short period of time, and in the third, HCL had been present for 2 yr before the appearance of a paraprotein, bone lesions, and plasma-cell infiltrates established the diagnosis of MM. Although this association has not been previously reported, cases of HCL with osteolytic lesions or a paraprotein band have been described. The cases described may represent clinical manifestations of closely related disorders arising from divergent differentiation from a common B-cell precursor rather than a chance association.     

基于1H-MRS脑胶质瘤影像病理分区及三维可视化模型构建的方法学研究

目的：研究氢质子磁共振波谱分析（1H-MRS）在脑胶质瘤及周边脑组织的病理分区、边界分割及组织差异化的三维重建方法.方法：选取5例拟诊为脑胶质瘤的患者,术前先行T1WI、T2WI及增强扫描,增强后行1H-MRS检查、分析,并与术后病理结果进行对照,根据多种代谢产物水平对胶质瘤进行分级及胶质瘤与周边脑组织分区.选取1例胶质瘤扫描数据以Dicom3.0格式导入3D-Doctor软件,人工分割肿瘤区、坏死区、水肿区、大脑表面,分别以不同颜色标示,以复杂面重建方法对上述结构同时进行三维重建.结果：利用1H-MRS对胶质瘤的肿瘤区及周边区域进行了大体分区,并且于术前对肿瘤进行的良恶性分级与术后病理结果相符.成功重建了肿瘤区及周边脑组织在整脑中的三维可视化模型,模型可以任意方位旋转,从不同角度再现了肿瘤的三维形态及在大脑中的空间位置,以及它们之间的相互位置关系.结论：脑胶质瘤采用1H-MRS的Cho/Cr、NAA/Cr、NAA/Cho大代谢物比值结合常规MRI对胶质瘤诊断及对胶质瘤进行无创性分级、分区是可行的.胶质瘤的三维可视化模型的构建,展现了肿瘤在活体脑中的三维空间结构及毗邻关系,为脑内占位性病变的重建和观测提供了重要的方法.对立体定向外科制定手术入路、介入放射制定放疗计划及医学教学都有很大的应用价值.     

妇炎舒胶囊联合头孢噻肟钠治疗慢性盆腔炎的临床研究

目的探讨妇炎舒胶囊联合头孢噻肟钠治疗慢性盆腔炎的临床效果。方法选择2020年2月—2020年10月在河南大学淮河医院治疗的74例慢性盆腔炎患者,随机分成对照组和治疗组,每组各37例。对照组静脉滴注注射用头孢噻肟钠,每次2 g加入生理盐水100 mL,2次/d;治疗组在对照组的基础上口服妇炎舒胶囊,5粒/次,3次/d。两组患者均治疗3周。观察两组患者临床疗效,比较治疗前后两组患者临床症候积分,血清血红素氧合酶1(HO-1)、细胞间黏附分子-1(ICAM-1)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-26(IL-26)和基质金属蛋白酶-2(MMP-2)水平,Smad-3、miRNA-224-3P和Smad-7水平,子宫血流动力学指标子宫血流搏动指数(PI)、血流最大峰值流速(Vs)和血流阻力指数(RI)。结果治疗后,治疗组总有效率为97.30%,明显高于对照组的81.08%(P0.05)。治疗后,两组中医症候评分均显著降低(P0.05),且治疗组降低更明显(P0.05)。治疗后,两组血清HO-1、ICAM-1、GM-CSF、IL-26、MMP-2水平均明显下降(P0.05),且治疗组下降更明显(P0.05)。治疗后,两组血清Smad-3水平明显降低,而miRNA-224-3P和Smad-7明显升高(P0.05),且治疗组改善更明显(P0.05)。治疗后,两组PI、RI均下降,而Vs均显著增高(P0.05),且治疗组改善更明显(P0.05)。结论妇炎舒胶囊联合注射用头孢噻肟钠治疗慢性盆腔炎可有效改善患者临床症状,降低机体炎症反应,改善血流动力学,其抗炎作用与调节miRNA-224-3P、Smad信号通路有关。     

Salt-dependent conformational diversity of alternating poly (Glu-Leu)

Alternating poly(Glu-Leu) was synthesized by the condensation of the corresponding dipeptide p-nitrophenyl ester at high concentration. It exhibits a random coil structure in pure water at neutral pH. Addition of monovalent cations, such as NH⁺₄ to a final 0.1 M solution, induces a transition to a water soluble β-structure. The salt effect is quite selective since no transition was observed with Li⁺, Na⁺ or Cs⁺ ions. Addition of 0.5 equiv. of calcium, cobalt or manganese chlorides per glutamyl residue induces similar coil to β-sheet transitions. No polymer precipitation was observed at these very low salt concentrations. Addition of 0.5 equiv. of Cu²⁺ or 0.15 equiv. of Fe³⁺ induces a coil to α-helix transition. Molecular modeling has been used to understand tentatively the main factors controlling the different conformations observed with the various metal ions. © Munksgaard 1997.     

大鼠胰肠和胰膀胱重建式单纯胰腺移植模型的比较研究

目的　探讨大鼠单纯胰腺移植 (PTA )的不同手术方法的效果。方法　近交系SD大鼠为供、受体 ,分为正常对照组 (NDC组 ) 10只 ,糖尿病组 (DC组 ) 10只 ,胰肠重建式组 (E D组 )和胰膀胱重建式组 (B D组 )各 2 2只。血管吻合采用供胰腺腹主动脉绊 (含脾动脉 )和门静脉绊 (含脾静脉 )与受体腹主动脉及左肾静脉分别行端侧和端端吻合 (袖套式 )。并于术前和术后 1,3 ,7,14 ,3 0d监测受体体重、进食量、饮水量和空腹血糖。并分析失败原因。结果　E D组受体手术时间长于B D组 (P<0 .0 5 )。E D组除 11例 ( 5 0 % )、B D组除 12例 ( 5 4.3 % )于 1个月内死亡或胰腺失去功能外 ,其余动物均存活 1个月以上。E D组术后并发症主要为胰漏及继发性胰腺炎 ;B D组主要为尿路并发症 ,前者并发症发生率略低于后者。成功的PTA后受体第 1天血糖即下降 ,第 3天基本达到正常水平 ;饮水量、进食量、尿量均减少 ,14d后基本稳定。结论　成功的E D和B D重建式PTA均可有效地恢复糖尿病大鼠内分泌功能。防治术后并发症是移植成功的关键     

Gingival and mucosal reactions after intensive chlorhexidine gel treatment with or without oral hygiene measures

Abstract – The aim of this study was to elucidate whether soft tissue reactions during chlorhexidine (CHX) treatment might be associated with meticulous oral hygiene measures. A commercially available 1% chlorhexidine digluconate gel (Hibitane Dental Gel) was applied in a custom tray for the mandibular arch, 10 min daily, for 14 days. A split mouth approach was used to allow evaluation of the effect of oral hygiene measures with toothbrush, toothpaste, and dental floss on one side of the arch. During the treatment period, 8 out of 12 subjects developed gingival and/or mucosal reactions appearing as white patches or ulcerations. Both the gingival reactions on the buccal marginal gingiva and the mucosal reactions near the margin of the custom tray occurred only when the gel treatment was combined with meticulous oral hygiene measures. The white patches, which could easily be detached, leaving ulcerated areas, consisted entirely of stratified squamous epithelium. The findings suggest that intensive treatment with chlorhexidine gel, in individually fitted custom trays, combined with meticulous oral hygiene measures may induce toxic effects on the surface layers of the gingiva and mucosa.     

煤矿井下工人血中自由基和白介素-6的变化

选择接触煤尘5、10、15、20年的各50名工人为研究对象,另选50名不接尘者作对照。取工人静脉血测定血浆NO、SOD、MDA和IL-6水平进行比较分析。接尘组血浆NO、SOD和MDA水平同对照组比较,差异有统计学意义(P<0.05,P<0.01),接尘组血浆IL-6水平均高于对照组。提示接触煤尘可能导致自由基和IL-6产生增多,并参与了煤尘对机体的损伤作用。