重症急性呼吸综合征患者血浆细胞因子水平的动态改变

目的　探讨重症急性呼吸综合征 (SARS)患者肺部严重炎症反应的发生机制。方法　选择 2 4例本院确诊的SARS患者 ,于发病第 1、第 2、第 3～ 4周及康复出院后 1个月 (发病 8～ 9周 )收集抗凝静脉血 ,以定量ELISA法检测其血浆白细胞介素 (IL) 1β、IL 2、IL 4、IL 8、IL 10、IL 12 p70、干扰素γ(IFNγ)及肿瘤坏死因子α(TNFα)水平在病程中的改变。并选择 12例正常人作为对照。结果　数据以中位数 (四分位数间距 )表示 ,与正常对照组 [IL 8:6 2 8ng/L( 3 4 3ng/L) ;TNFα :3 77ng/L( 3 4 0ng/L) ]相比 ,所有SARS病人在发病第 1周血浆IL 8浓度明显升高 [31 2 3ng/L( 78 5 1ng/L) ],P <0 0 1,75 % ( 18/2 4 )的病人在发病 3～ 4周达到最高峰 14 9 6 5ng/L( 2 4 5 97ng/L) ,P <0 0 1,至出院后 1个月 (发病 8～ 9周 )平均血浆IL 8浓度降至 8 2 3ng/L( 8 0 7ng/L)。血浆TNFα浓度也有异常升高 ,在发病第 2周为 2 3 12ng/L( 2 6 7 33ng/L) ,P <0 0 1,发病 3～ 4周达到高峰136 35ng/L( 4 76 83ng/L) ,P <0 0 5 ,出院后 1个月下降至 94 88ng/L( 2 77 18ng/L) ,仍高于正常水平 (P <0 0 1)。其他 6种细胞因子与对照组比较 ,差异无显著性。结论　SARS病人体内发生着复杂的细胞因子网络性连锁反应 ,由此产     

Multiple lines of evidence on the genetic relatedness of the parthenogenetic and bisexual Haemaphysalis longicornis (Acari: Ixodidae)

As an obligate hematophagous ectoparasite, the hard tick Haemaphysalis longicornis exhibits two reproductive strategies, bisexual reproduction, and obligate parthenogenesis, which have attracted a widespread attention. However, the speciation of parthenogenetic population remained ambiguous due to its similarity in morphology but the remarkable differences in cytogenetics as compared with those of the bisexual ones. In the present study, we explored several new lines of genetic evidence to resolve this controversial issue. The number of the chromosomes in two lineages was checked by classical methods and their total DNA levels were determined utilizing flowcytometry. In addition, the sequences of 12S rDNA, 16S rDNA, cytochrome c oxidase I and II (COI, COII) and internal transcribed spacer-2 (ITS-2) genes were used to assess their phylogenetic relationship. We observed that the chromosome ploidy of bisexual and parthenogenetic H. longicornis collected by our laboratory was diploid and triploid, respectively. Flowcytometry analysis indicated a ratio close to 2:3 in the DNA contents of bisexual to parthenogenetic H. longicornis. Although the chromosome ploidy is different, their gene sequences are extremely similar. Analogous to the intra-species genetic difference of other invertebrates, sequence differences of all loci examined are below 2%. Phylogenetic trees constructed from 12S rDNA, 16S rDNA, COI, and ITS-2 genes revealed that they were all in the same monophyletic clade instead of splitting independently into evolutional branches. Moreover, according to 4× Rule, the K/θ ratio of two reproductive populations calculated based on COI was much smaller than four, strongly supporting that they belong to the same species. Therefore, we conclude that the evolutionary process just disturbs the chromosome ploidy and the sexual determination of parthenogenetic population and that it would be better to consider parthenogenetic H. longicornis as a metapopulation rather than a cryptic species.     

ATP生物荧光检测法提高ICU轮科医生手卫生依从性的效果

目的了解ATP生物荧光检测法在短时间内提高内科重症监护室（ICU）轮科医生手卫生依从性和合格率的效果。方法首先对内科ICU轮科医生手卫生的现状进行基线摸底调查,根据结果制定监测频率和方法。然后采用ATP生物荧光检测法随机对医生的手卫生进行现场检测和结果反馈。对干预后的医生手卫生情况进行调查。结果基线摸底调查阶段共采样120人次,医生手卫生总体合格率为73.33%,手卫生依从率只有14.17%。采用ATP现场检测和反馈的干预方法后,医生手卫生合格率提高至82.24%（χ2=13.68,P=0.008）;干预中洗手依从率最高,达到69.44%。结论ATP生物荧光检测法现场监测医生手卫生情况并及时反馈,可以提高医生手卫生的依从性和合格率。     

电离辐射与放射工作者染色体畸变率研究的meta分析

目的用meta分析方法进一步总结电离辐射与放射工作者外周血淋巴细胞染色体畸变的关系。方法搜索有关文献,以检查细胞数、染色体畸变细胞数和畸变率为基本数据,根据对研究数据的异质性检验,用率差（RD）作为效应值,然后使用固定效应模型或随机效应模型进行meta分析。结果电离辐射对放射工作者外周血淋巴细胞染色体RD合并值为0.006,RD合并值的95%CI为（0.002,0.009）,放射组的染色体畸变率高于对照组。结论电离辐射与放射工作者的外周血淋巴细胞染色体畸变率有显著的相关性。     

球体形成实验联合药物筛选建立耐顺铂胰腺癌干细胞株

目的 探索建立顺铂耐药人胰腺癌干细胞株,并进行初步鉴定.方法 通过球体形成实验联合顺铂药物筛选建立耐顺铂胰腺癌干细胞株;MTT法计算耐药指数;免疫荧光半定量检测OCT-4、SOX-2表达水平,检测干细胞标记物;免疫荧光半定量检测MUC-1表达水平,检测细胞分化能力;通过流式细胞仪测量侧群细胞和表面特异抗原标记（CD44＋/CD24＋）检测肿瘤干细胞含量.结果 耐顺铂干细胞株的耐药指数是亲代株PANC-1的71.5倍;干细胞标记物的免疫荧光检测发现,耐药株中OCT-4、SOX-2、MUC-1均有不同程度的表达;耐药干细胞株及亲代株SP细胞比例分别为（25.1±1.1）％和（7.8士0.9）％,差异有统计学意义（t=6.89,P＜ 0.01）;耐药株及亲代株中CD44＋/CD24＋表型的细胞亚群分别占（20.8±1.3）％和（2.4±0.8）％,差异有统计学意义（t=16.13,P＜ 0.01）.结论 球体形成实验联合顺铂药物筛选能建立耐顺铂胰腺癌细胞株,该细胞株能高效富集胰腺癌肿瘤干细胞.     

660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600–1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migration and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2, an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 106 bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2 for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypoxic-ischemic brain damage.     

Two new 12-membered macrolides from the endophytic fungal strain Cladosprium colocasiae A801 of Callistemon viminalis

Two new polyketide metabolites, the 12-membered macrolides 4-hydroxy-12-methyloxacyclododecane-2,5,6-trione (1) and 12-methyloxacyclododecane-2,5,6-trione (2), were isolated from the endophytic fungal strain Cladosprium colocasiae A801 of the plant Callistemon viminalis, together with five known derivatives. Their structures were fully characterized by means of detailed spectroscopic analysis for new structures, and in comparison with published data for known compounds. The antibacterial, cytotoxic, and α-glucosidase inhibitory activities of the new compounds 1 and 2 were evaluated.     

Toxicity evaluation and nasal mucosal tissue deposition of dexamethasone-infused mucoadhesive in situ nasal gelling systems

To demonstrate safety of a developed intranasal dexamethasone-infused in situ gelling formulation, quantification of a validated clinical biomarker indicative of cytotoxic potential using a human sinonasal explant model was first confirmed. Systematic cytotoxicity studies using the lactate dehydrogenase (LDH) detection assay revealed no elevation from baseline, in LDH levels, with tissue integrity of explanted human nasal mucosa also maintained; this was further corroborated using tissue histopathological examination. Next, with safety confirmed ex vivo, freshly excised human nasal tissue was utilised to quantify dexamethasone release from the lead sol–gel systems; this being achieved through development and validation of a HPLC-UV analytical method, which reliably quantified controlled therapeutic release and deposition into mucosal tissue. Collectively, these findings indicate promise in the safety of each excipient within the concentrations employed in the functional sol–gel system, complemented by successful and reliable drug release and deposition into human nasal mucosal tissue. These findings pave the way for application of the dexamethasone-based sol–gel system to the extended delivery of corticosteroids to nasal mucosa in the management of localised inflammatory conditions of an acute and chronic nature, such as chronic rhinosinusitis, which can be expected to benefit from controlled and extended drug delivery characteristics imparted by appropriately engineered in situ gelling systems.     

Chronic Trypanosoma congolense infections in mice cause a sustained disruption of the B‐cell homeostasis in the bone marrow and spleen

Trypanosoma congolense is one of the main species responsible for Animal African Trypanosomosis (AAT). As preventive vaccination strategies for AAT have been unsuccessful so far, investigating the mechanisms underlying vaccine failure has to be prioritized. In T. brucei and T. vivax infections, recent studies revealed a rapid onset of destruction of the host B‐cell compartment, resulting in the loss of memory recall capacity. To assess such effect in experimental T. congolense trypanosomosis, we performed infections with both the cloned Tc13 parasite, which is considered as a standard model system for T. congolense rodent infections and the noncloned TRT55 field isolate. These infections differ in their virulence level in the C57BL/6 mouse model for trypanosomosis. We show that early on, an irreversible depletion of all developmental B cells stages occur. Subsequently, in the spleen, a detrimental decrease in immature B cells is followed by a significant and permanent depletion of Marginal zone B cells and Follicular B cells. The severity of these events later on in infection correlated with the virulence level of the parasite stock. In line with this, it was observed that later‐stage infection‐induced IgGs were largely nonspecific, in particular in the more virulent TRT55 infection model.     

3,4-亚甲二氧苯基甲酰吗啉与AMPA受体的结合作用研究

目的 研究3,4-亚甲二氧苯基甲酰吗啉（化合物1）与AMPA受体的结合作用。方法 采用放射性配体受体结合试验测定化合物1与AMPA受体结合的IC₅₀值;采用分子对接技术研究化合物1与AMPA受体的结合能力和结合模式。结果 化合物1与AMPA受体结合的IC₅₀值为1.74×10^-9 mol·L^-1,具有较强的结合能力;化合物1与AMPA受体的结合能为-5.46 kcal·mol^-1,同样表明结合能力较强。结合的驱动力主要是氢键、疏水作用和静电作用。化合物1结构中O原子可与AMPA受体的Ser108、Ser242氨基酸残基形成氢键,这可能是该化合物与AMPA受体结合的重要位点。结论 化合物1可与AMPA结合,且结合能力较强。