血液病及实体瘤T-淋巴细胞亚群的表达

为了研究各种血液病、良性和恶性肿瘤T-淋巴细胞亚群变化关系,及其对诊断、治疗及预后的价值,采用流式细胞术、Cellquest软件及Modfie软件,对1 112例各种血液病、良性和恶性肿瘤的患者进行测定和比较,求出相关性.结果发现,慢性白血病CD3,CD4,CD8和CD4/CD8各项指标极度减低;急性白血病、MDS各项检测指标均较正常人及其它血液病患者明显下降,相互之间有显著差异(P＜0.01);溶血性贫血患者的各项检测指标较正常人及其它各组患者明显增高,尤其CD3,CD4及CD4/CD8比值增高更明显(P＜0.05);特发性血小板减少性紫癜患者CD3,CD4及CD4/CD8比值较正常人明显减低,但与再生障碍性贫血和其它疾病接近,而CD8明显高于正常人及其它血液病、肿瘤患者相互之间有显著差异(P＜0.01);缺铁性贫血、慢性病性贫血、良性肿瘤和其它血液病患者CD3,CD4和CD8虽然均较正常人及溶血性贫血患者有不同程度的减低,但较急性和慢性白血病、恶性肿瘤、粒细胞减少症、MDS患者有不同程度增高,相互之间无显著性差异.值得注意的是,上述各种检测指标异常与治疗前后,以及疾病进展、缓解、预后呈正相关.结论血液病和恶性肿瘤T-细胞亚群各项检测指标对血液病和良、恶性肿瘤诊断及鉴别诊断,以及正确指导治疗及评价预后有重要实用价值,特别对恶性血液病、恶性肿瘤转归有更重要的意义,是目前测定体内免疫活性的最适指标.     

应用本顿视觉保持测验评估非医学指征剖宫产儿童的认知功能特征

目的:探讨非医学指征剖宫产儿童在本顿视觉保持测验中的视知觉、视觉记忆、视觉结构能力等认知特征,分析剖宫产对儿童神经心理的影响,为控制人为剖宫产率提供理论支持。方法:于2003-09/10整群选取广州市几所小学三、四年级儿童作为调查对象。共发放自编的“分娩情况和一般家庭情况”调查问卷727份,回收663份,根据回收问卷中分娩方式情况,筛查出非医学指征性剖宫产儿童63例,作为剖宫产组,选择与剖宫产组儿童年龄、性别、学校、班级及家庭一般情况无显著性差异的正常阴道分娩儿童156人作为对照组。应用国内修订版本顿视觉保持测验对两组儿童的视觉记忆保持能力、视觉结构能力和延迟记忆能力进行测试,该测验的测具包括无意义的图卡片C、D、E式各10张,分为4种测验方法,A法、B法为每一图卡片呈现10s或5s后让被试默画,C法为让被试临摹图卡片,D法为每一图卡片呈现10s后间隔15s再让被试默画,本测试采用C式B法,D式C法和E式D法,采用个别施测方式,分别记录两组儿童测验的正确分(每一图卡根据全或无的原则记1或0分,总分范围0～10之间)及错误次数(错误类型分为遗漏、变形、持续、旋转、位置错误和大小错误6个范畴),基本资料进行两组间的成组t检验。结果:所有调查对象全部进入结果分析,无脱落。本顿视觉保持测验结果显示剖宫产儿童在E式D法测验中的得分低于对照组(P<0.05);在D式C法中“位置”错误类型的出现次数多于对照组(P<0.05),在E式D法中“位置”和“变形”错误类型的出现次数较对照组明显偏高(P<0.05)。结论:剖宫产儿童的视觉空间结构能力及视觉延时回忆能力存在缺陷,视空间工作记忆、视觉结构与视觉统和功能不足。     

Association of sleep duration with chronic kidney disease and proteinuria in adults: a systematic review and dose–response meta-analysis

International Urology and Nephrology - Previous studies have found that sleep duration may be associated with chronic kidney disease (CKD) and proteinuria in adults. However, the correlation...     

小腿假肢对线对静态站立时下肢受力的影响

目的:研究小腿截肢患者站立状态下假肢对线对下肢受力特性的影响.方法:以假肢侧承重线和重力线作为评价指标,改变假肢矢状面和额状面的对线,采用激光测力平台测量患者静态站立时残侧承重线和重力线的位置,研究下肢受力状况的变化.结果:假肢侧承重线受踝关节对线的影响大于腿管对线调节的影响,并且力线随腿管与接受腔的前倾而前移,而额状面对线的影响很小;矢状面内重力线主要受踝关节对线调节的影响,并且与变化角近似正比例相关.结论:矢状面假肢对线调整对残侧下肢受力状况的影响较大,而额状面的对线调整影响较小.     

A novel 1,2-benzenediamine derivative FC-99 suppresses TLR3 expression and ameliorates disease symptoms in a mouse model of sepsis

Background and Purpose

Sepsis is a clinical condition characterized by overwhelming systemic inflammation with high mortality rate and high prevalence, but effective treatment is still lacking. Toll-like receptor 3 (TLR3) is an endogenous sensor, thought to regulate the amplification of immune response during sepsis. Modulators of TLR3 have an advantage in the treatment of sepsis. Here, we aimed to explore the mechanism of a monosubstituted 1,2-benzenediamine derivative FC-99 {N¹-[(4-methoxy)methyl]-4-methyl-1,2-benzenediamine}on modulating TLR3 expression and its therapeutic potential on mouse model of sepsis.

Experimental Approach

Cells were pretreated with FC-99 followed by poly(I:C) or IFN-α stimulation; TLR3 and other indicators were assayed. Female C57BL/6 mice were subjected to sham or caecal ligation puncture (CLP) surgery after i.p. injection of vehicle or FC-99; serum and tissues were collected for further experiments.

Key Results

FC-99 suppressed inflammatory response induced by poly(I:C) with no effect on cell viability or uptake of poly(I:C). FC-99 also inhibited TLR3 expression induced by not only poly(I:C) but also by exogenous IFN-α. This inhibition of FC-99 was related to the poly(I:C)-evoked IRF3/IFN-α/JAK/STAT1 signalling pathway. In CLP-induced model of sepsis, FC-99 administration decreased mice mortality and serum levels of inflammatory factors, attenuated multiple organ dysfunction and enhanced bacterial clearance. Accordingly, systemic and local expression of TLR3 was reduced by FC-99 in vivo.

Conclusion and Implications

FC-99 reversed TLR3 expression and ameliorate CLP-induced sepsis in mice. Thus, FC-99 will be a potential therapeutic candidate for sepsis.Table of Links

粉防己碱、清胰汤对重症急性胰腺炎猪血胃泌素、胃动素的影响

目的　应用去氧胆酸钠诱发香猪重症急性胰腺炎 (severe acute pancreatitis,SAP)模型 ,观察粉防己碱、清胰汤对 SAP香猪血胃肠激素水平的影响。　方法　用 32只贵州香猪 ,雌雄不拘 ,随机分为 4组 :生理盐水 (NS)对照组 ;粉防己碱 (tetrandrine,Tet)组 ;中药清胰汤 (chinese medicine qing yitang,CMQ)组 ;Tet+ CMQ联合组。各组受试动物术前禁食 12 h,禁水 6 h,无菌手术行门静脉、腔静脉插管 ,经胰管逆行加压推注 5 %去氧胆酸钠 (0 .5 ml/ kg体重 )复制 SAP模型 ,制模后 1h静脉滴注 NS或相应药物、胃管推注 NS或相应药物。分别于制模前 ,制模后 1h、6 h、12 h、2 4 h、4 8h、72 h、96 h同时采门静脉血和中心静脉血 ,分离血浆或血清 ,用放免法检测血浆胃动素和血清胃泌素水平 ;记录观察时间内 (96 h)各组动物的死亡率 ;取第 96小时动物的胰腺、十二指肠 ,作常规病理检查。　结果　与 NS组相比 ,粉防己碱、清胰汤均可降低 SAP香猪 96 h内的死亡率 ;可显著降低各时间点门静脉、中心静脉(除制模前、制模后 1h外 )血清胃泌素的浓度 (P<0 .0 1) ,可增加血浆胃动素的浓度 (P<0 .0 1) ;作用效果二者相当 (P>0 .0 5 ) ,而联合组的作用更为显著 (P<0 .0 1或 P<0 .0 5 )。用药组的胰腺、十二指肠病理变化也较 NS组明     

Ultrasmall bimodal nanomolecules enhanced tumor angiogenesis contrast with endothelial cell targeting and molecular pharmacokinetics

Nonintrusive and precise imaging for tumor angiogenesis is critical in accurate assessment of cancer diagnosis and prognosis. However, reticulo-endothelial system (RES) capture and inadequate accumulation remain major bottlenecks for current nanoparticle to retain at tumor angiogenesis site. Herein, we report the ultrasmall contrast agent (cNGR-Au:Gd@GSH NMs) could accumulate at tumor vasculature site and enhance the tumor angiogenesis-contrast. It is demonstrated that by loading Au and Gd atom into the naturally-occurring glutathione (GSH) shell with cNGR peptide modification, cNGR-Au:Gd@GSH NMs exhibit the high X-ray photon absorption, longer rotational correlation time and efficient tumor vascular endothelia cell targeting. In vivo studies further indicate the cNGR-Au:Gd@GSH NMs prominently enhance tumor angiogenesis-contrast both on the computed tomography (CT) and magnetic resonance imaging (MRI) modalities by escaping the RES capture and target delivering. Our data imply that the cNGR-Au:Gd@GSH NMs may serve as the high-efficiency contrast agent to assess tumor angiogenesis in a nonintrusive technique.     

Inhibition of hypoxia-induced proliferation of pulmonary arterial smooth muscle cells by a mTOR siRNA-loaded cyclodextrin nanovector

The proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a key pathophysiological component of vascular remodeling in pulmonary arterial hypertension (PAH), an intractable disease, for which pharmacotherapy is limited and only slight improvement in survival outcomes have achieved over the past few decades. RNA interference provides a highly promising strategy to the treatment of this chronic lung disease, while efficient delivery of small interfering RNA (siRNA) remains a key challenge for the development of clinically acceptable siRNA therapeutics. With the aim to construct useful nanomedicines, the mammalian target of rapamycin (mTOR) siRNA was loaded into hybrid nanoparticles based on low molecular weight (Mw) polyethylenimine (PEI) and a pH-responsive cyclodextrin material (Ac-aCD) or poly(lactic-co-glycolic acid) (PLGA). This hybrid nanoplatform gave rise to desirable siRNA loading, and the payload release could be modulated by the hydrolysis characteristics of carrier materials. Fluorescence observation and flow cytometry quantification suggested that both Ac-aCD and PLGA nanovectors (NVs) may enter PASMCs under either normoxia or hypoxia conditions as well as in the presence of serum, with uptake and transfection efficiency significantly higher than those of cationic vectors such as PEI with Mw of 25 kDa (PEI25k) and Lipofectamine 2000 (Lipo 2k). Hybrid Ac-aCD or PLGA NV containing siRNA remarkably inhibited proliferation and activated apoptosis of hypoxic PASMCs, largely resulting from effective suppression of mTOR signaling as evidenced by significantly lowered expression of mTOR mRNA and phosphorylated protein. Moreover, these hybrid nanomedicines were more effective than commonly used cationic vectors like PEI25k and Lipo 2k, with respect to cell growth inhibition, apoptosis activation, and expression attenuation of mTOR mRNA and protein. Therefore, mTOR siRNA nanomedicines based on hybrid Ac-aCD or PLGA NV may be promising therapeutics for diseases related to hypoxic abnormal growth of PASMCs.     

Simultaneous detection of acetaminophen and 4-aminophenol with an electrochemical sensor based on silver–palladium bimetal nanoparticles and reduced graphene oxide

In this paper, Ag–Pd bimetallic nanoparticles uniformly distributed on reduced graphene oxide (rGO) were synthesized by redox reaction between Pd²⁺, Ag⁺and GO, and were characterized by X-ray diffractometry, field emission scanning electron microscopy, electrochemical impedance spectroscopy and thermal gravimetric analyses. A novel electrochemical sensor was constructed based on these nanocomposites using glassy carbon as a substrate. Under optimal conditions, the linear ranges were 0.50–300.00 μM for PA and 1.00–300.00 μM for 4-AP, with the detection limits of 0.23 μM for PA and 0.013 μM for 4-AP, respectively. This sensor was successfully applied to the determination of PA in pharmaceutical formulations and gave satisfactory results with a lower detection limit, wider linear range and good reproducibility.

Simultaneous detection of acetaminophen and 4-aminophenol with a highly sensitive electrochemical sensor based on silver–palladium bimetal nanoparticles and reduced graphene oxide.     

海南省新生儿G6PD缺乏症筛查十年回顾分析

目的寻找海南省人群葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症发病情况和基因突变特点。方法对海南省2007至2016年出生的914520名新生儿的干血斑使用荧光斑点法进行G6PD活性筛查。初筛可疑标本召回使用G6PD/6-磷酸葡萄糖脱氢酶(6GPD)比值法进行确诊,对2016年确诊为G6PD缺乏的患儿的3012份干血斑使用多色探针荧光PCR熔解曲线法进行基因分型。结果海南省10年间在914520例新生儿中初筛阳性36314例,确诊了26370例G6PD缺乏,发病率为2.88%(26370/914520)。以民族划分,汉族人群G6PD发病率2.80%(21688/774555)。黎族人群发病率3.45%(4292/124419),黎族和汉族发病率比较,差异具有统计学意义(χ^2=161.261,P=0.000)。苗族人群发病率3.31%(212/6401),苗族和汉族发病率相比较差异具有统计学意义(χ^2=6.104,P=0.013)。其他民族人群发病率为1.95%(178/9145),与汉族发病率相比较差异具有统计学意义(χ^2=24.283,P=0.000)。在3012例G6PD确诊病例中共检出13种基因突变,其中c.1376 G>T、c.1388 G>A、c.95 A>G和c.1024 C>T突变合并约占91.74%。其中经基因测序发现16种基因型以外的2种突变,即c.86C>T和c.1311C>T。结论海南省新生儿人群G6PD发病率高,G6PD发病有民族和地域差异。海南省人群基因突变主要以c.1376G>T、c.1388G>A、c.95 A>G和c.1024 C>T为主。