Anti Cervix Cancer Activity of Co-immobilized Tumor Necrosis Factor-α and Interferon-γ

Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared （IR） spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope （SEM）. The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope （TEM） and fluorescence active cell sorter （FACS）. The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.

酸脂清胶囊对尿酸性肾病大鼠肾功能及TNF-α的影响

目的:观察酸脂清胶囊对尿酸性肾病大鼠肾功能及TNF-α的影响,探讨其作用的机理。方法:将6周龄SD雄性大鼠分为5组,分别为正常组、模型组、生理盐水组、酸脂清治疗组、别嘌醇治疗组。后4组用腺嘌呤、乙胺丁醇造模,成功后分别给予生理盐水、酸脂清、别嘌醇灌胃给药,3周后检测各组大鼠血中尿素氮(BUN)、肌酐(Cr)、尿酸(UA),同时用酶联反应法(Elisa法)测量各组肾脏组织中肿瘤坏死因子α(TNF-α)的含量。结果:1)造模2周后,与正常组比较,模型组大鼠血中BUN、Cr、UA均明显升高(P<0.05),证实造模成功。2)治疗3周后,与生理盐水组相比,酸脂清治疗组、别嘌醇治疗组大鼠血中BUN、UA均明显下降(P<0.05),酸脂清治疗组和别嘌醇治疗组Cr均有下降,但只有酸脂清治疗组有统计学意义(P<0.05)。3)酸脂清治疗组和别嘌醇治疗组血中BUN、Cr、UA相比,差异无统计学意义(P>0.05)。4)Elisa法测定各组TNF-α的浓度,与正常组相比,生理盐水组TNF-α明显升高(P<0.05);与生理盐水组相比,酸脂清治疗组、别嘌醇治疗组TNF-α含量明显减少(P<0.05);5)肾组织病理切片显示:与模型组相比,酸脂清治疗组、别嘌醇治疗组尿酸盐结晶沉积、炎性细胞浸润均明显减少,肾小管扩张改善。结论:酸脂清胶囊能够降低尿酸性肾病大鼠血中BUN、Cr、UA的含量,减少尿酸盐结晶在肾小管中沉积及炎性细胞浸润,降低TNF-α在肾组织中的含量,从而达到治疗的作用。

Association of TNF-α-238G/A and 308 G/A Gene Polymorphisms with Pulmonary Tuberculosis among Patients with Coal Worker’s Pneumoconiosis

Objectives Tumor necrosis factor-α （TNF-α） may play an important role in host＇s immune response to mycobacterium tuberculosis （M. tuberculosis） infection. This study was to investigate the association of TNF-α gene polymorphism with pulmonary tuberculosis （TB） among patients with coal worker＇s pneumoconiosis （CWP）. Methods A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-α gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism （PCR-RFLP）. Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher＇s exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplieative model with combined OR. All data were analyzed using SAS version 8.2 software. Results No significant difference in frequency of the TNF-α-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls （2,2=5.44, P=-0.07）. But difference in frequency of the TNF-α-308 A allele was identified between them （2,2-5.14, P=0.02）. No significant difference in frequencies of the TNF-α-238 genotype and allele （P=0.23 and P=0.09, respectively） was found between cases and controls either, with combined （GG and AA） OR of 3.96 （95% confidence interval of 1.30-12.09） at the -308 locus of the TNF-α gene, as compared to combination of the TNF-α-238 GG and TNF-α-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-α-238 GG and TNF-α-308 GA genotypes was 1.98 （95% CI of 1.06-3.71） for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-a-308 GG genotype and body mass index （OR=4.92）, as well as an interaction between the TNF-α-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-α-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated. Conclusions TNF-α-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-α-238 A allele was otherwise.

TRAF2-MLK3 interaction is essential for TNF-α-induced MLK3 activation

Mixed lineage kinase 3 （MLK3） is a mitogen-activated protein kinase kinase kinase that is activated by tumor necrosis factor-α （TNF-α） and specifically activates c-Jun N-terminal kinase （JNK） on TNF-a stimulation. The mecha- nism by which TNF-α activates MLK3 is still not known. TNF receptor-associated factors （TRAFs） are adapter molecules that are recruited to cytoplasmic end of TNF receptor and mediate the downstream signaling, including activation of JNK. Here, we report that MLK3 associates with TRAF2, TRAF5 and TRAF6; however only TRAF2 can significantly induce the kinase activity of MLK3. The interaction domain of TRAF2 maps to the TRAF domain and for MLK3 to its C-terminal half （amino acids 511-847）. Endogenous TRAF2 and MLK3 associate with each other in response to TNF-α treatment in a time-dependent manner. The association between MLK3 and TRAF2 mediates MLK3 activation and competition with the TRAF2 deletion mutant that binds to MLK3 attenuates MLK3 kinase activity in a dose-dependent manner, on TNF-α treatment. Furthermore the downstream target of MLK3, JNK was activated by TNF-α in a TRAF2-dependent manner. Hence, our data show that the direct interaction between TRAF2 and MLK3 is required for TNF-α-induced activation of MLK3 and its downstream target, JNK.

Association of UCP3,APN,and TNF-α Gene Polymorphisms with Type 2 Diabetes in a Population of Northern Chinese Han Patients

We observed the polymorphism distribution and coaction of uncoupling protein 3（UCP3）-55C/T,adiponectin（APN）＋45T/G and tumor necrosis factor（TNF）-α-308G/A on the onset and development of T2DM in a Northern Chinese Han population of 213[100 type 2 diabete（T2DM） patients and 113 health control subjects] by polymerase chain reaction-restriction fragment length polymorphisum（PCR-RFLP） method.Results demonstrate the polymorphism of UCP3-55C/T,APN＋45T/G,and TNF-α-308G/A related to T2DM onset and developement.And the individuals carrying UCP3-55T,APN＋45G and TNF-α-308A allele had higher T2DM risk.Those results are the first report to evaluate the association of the coaction of UCP3,APN,TNF-α genes polymorphism on T2DM risk and the susceptibility of T2DM in the Northern Chinese Han population.

Effect of electroacupuncture on egg quality and tumor necrosis factor-a of patients with polycystic ovarian syndrome

Objective To observe the effect of electroacupuncture （EA） on egg quality of polycystic ovarian syndrome （PCOS） patients, and to explore its mechanism. Methods Two hundred patients who received in vitro fertilization-embryo transfer （IVF-ET） were divided into an EA group （102 cases） and a control group （98 cases） according to random number table. All the patients in the two groups were given Diane-35 and gonadotropin-releasing hormone agonist （GnRH-α） for ovarian hyperstimulation. Besides, EA intervention was applied to Shenshu （肾俞 BL 23）, Qihai （气海 GV 6）, Zusanli （足三里ST 36）, Sanyinjiao （三阴交 SP 6）, Neiguan （内关 PC 6） and Zigong （子宫 EX-CA1）, etc. in the EA group. Then egg quality, final outcome of pregnancy and levels of tumor necrosis factor-α （TNF-α） were compared between the two groups. Results （1） EA intervention significantly improved high quality embryo rate of PCOS patients （P〈0.05）, and clinical pregnancy rate was increased by 8.36%; （2） EA intervention significantly reduced the TNF-α levels of follicular fluid （13.61±15.46 vs 34.09±93.53, P〈0.05）; （3） TNF-α levels of serum and follicular fluid in the pregnancy group were lower than those of non-pregnancy group [pregnancy group： （53.91±63.32） pg/mL, （14.93±25.37） pg/mL, nonpregnancy group： （76.82 ± 82.96） pg/mL, （25.04 ± 35.79） pg/mL], and the differences were significant （both P〈0.05）. Conclusion EA improves egg quality of PCOS patients and increases the clinical pregnancy rate of IVF-ET, the mechanism may be related to TNF-α levels.

TIME-AND DOSE-DEPENDENT UP-REGULATION OF TNF-α mRNA AFTER IRRADIATION OF HUMAN NSCLC CELL LINES IN VITRO

Objective： Even though radiotherapy plays a major role in the local treatment of non-small cell lung cancer （NSCLC）, little is known about the molecular effects of irradiation in this tumor. In the present study, we examined two NSCLC cell lines for their endogenous production of TNF-α after irradiation. To investigate the radiation-induced TNF-α production in NSCLC cell lines. Methods： Two human NSCLC cell lines （A549： squamous; NCI-H596： adenosquamous） were investigated for their TNF-α mRNA （real-time RT-PCR） after exposure to different irradiation doses （2, 5, 10, 20, 30, 40 Gy） and time intervals （1, 3, 6, 12, 24, 48 or 72 h）. The TNF-α mRNA expression was quantified by real-time RT-PCR. The clonogenic survival was evaluated after irradiation with 2, 4, 6 and 8 Gy. Results： Non-irradiated NSCLC cells exhibited no or very low TNF-α expression. For the NCI-H596 cell line, TNF-α expression was significantly elevated 1～12 h （maximum 6h： 568fold increase relative to unirradiated cells） in a time-dependent manner. The radiation-induced increase could be observed after irradiation with 2 Gy reaching maximal at 40 Gy, with 83 times higher than normal controls. The clonogenic survival of these cell lines was nearly identical. Conclusion： NCI-H596 cells produce significant quantities of TNF-α following irradiation in a time- and dose-dependent manner. The pro-inflammatory cytokine TNF-α is a key mediator for the pathogenesis of radiation pneumonitis. Radiation-induced endogenous TNF-α expression in NSCLC cells may affect the normal lung adjacent to the tumor and may be associated with an adverse clinical outcome of the patient.

The effect of spinal cord injury on the expression of TGF-β and TNF-α in rat articular cartilage

Objective： To observe the expression of TGF-β and TNF-α in the spinal cord injured rat model and discuss the significance of the articular cartilage metabolism. Methods： 36 SD female rats were randomly divided into 2 groups： Rats models of spinal cord injury were implemented by Allen method. T10 laminectomy was performed in the control group. Both groups of rats were killed respectively in 1w, 3w and 6w. Hematoxylin-eosin stain was given to each slice in the model group and control group. Immunohistochemical stain was applied by using ABC method in the expression of TGF-β and TNF-α. Those expressed level were performed in image analysis and statistics process. Results： TGF-β and TNF-α were mainly distributed on the surface layer of the articular cartilage, with a weak expression in control group. The expression of TNF-α in the model group was more significant than that in the control group in the lw, and still remained an evident difference with that in control group until the 6w（P 〈 0.05）. TGF-β expression of the model group had no remarkable difference with the control group in the lw （P 〉 0.05） and prominently became stronger at 6w（P 〈 0.05）. Conclusion： The expression of TNF-α occurred early in the development of spinal cord injury, and the expression of TGF-β became stronger with the revival of spinal neural function. Both expressions were strengthened in articular cartilage in the 3rd week.

β-七叶皂苷钠对重型脑损伤患者血清肿瘤坏死因子-α的影响

目的研究β-七叶皂苷钠对重型脑损伤患者血清肿瘤坏死因子-α(TNF-α)的影响及其临床意义。方法 60例重型脑损伤患者分为治疗组和对照组各30例,对照组给予神经外科常规治疗,治疗组在常规治疗基础上给予β-七叶皂苷钠。分别于治疗前,治疗后第1、2、3、5、7天测定血清TNF-α,于治疗3个月后进行格拉斯哥结局量表(GOS)评分。结果治疗3 d后,治疗组血清TNF-α较对照组下降(P<0.05);治疗3个月后,治疗组GOS评分优于对照组(P<0.05)。结论β-七叶皂苷钠是治疗重型脑损伤的有效手段之一,血清TNF-α的动态变化能够预测治疗结局。

二甲双胍对2型糖尿病患者血浆ET-1和血清hs-CRP、TNF2水平的影响

目的探讨了二甲双胍对DM2T2DM患者血浆ET-1和血清HS-CRP、TNF2水平的影响。方法应用放射免疫分析法和免疫比浊法对33例T2DM患者进行了血浆ET-1和血清HS-CRP、TNF2水平检测,并与35名正常健康人做比较。结果 T2DM患者在治疗前血浆ET-1和血清HS-CRP.TNF2水平均非常显著地高于正常人组(P<0.01)经二甲双胍治疗了3个月后,血浆ET-1和血清HS-CRP、TNF2水平与正常人比较无显著性差异(P>0.05)且ET-1水平与HS-CRP、TNF2水平成正相关(R=0.618 4、0.594 8 P<0.01)。结论二甲双胍具有改善血管内皮功能的作用。

阻塞性睡眠呼吸暂停低通气综合征与肿瘤坏死因子-α

肿瘤坏死因子-α与阻塞性睡眠呼吸暂停低通气综合征(OSAHS)密切相关。本文将初步探讨OSAHS中肿瘤坏死因子-α的产生机制,以及肿瘤坏死因子-α在OSAHS并发的心、脑血管等疾病中的作用机理进行综述。对从分子水平认识OSAHS的致病机理和今后研究综合防治具有一定意义。

Tumor necrosis factor receptor superfamily member 9 is upregulated in the endothelium and tumor cells in melanoma brain metastasis

Aim:The cytokine receptor tumor necrosis factor receptor superfamily member 9(TNFRSF9)is mainly considered to be a co-stimulatory activation marker in hematopoietic cells.Several preclinical models have shown a dramatic beneficial effect of treatment approaches targeting TNFRSF9 with agonistic antibodies.However,preliminary clinical phase I/II studies were stopped after the occurrence of several severe deleterious side effects.In a previous study,it was demonstrated that TNFRSF9 was strongly expressed by reactive astrocytes in primary central nervous system(CNS)tumors,but was largely absent from tumor or inflammatory cells.The aim of the present study was to address the cellular source of TNFRSF9 expression in the setting of human melanoma brain metastasis,a highly immunogenic tumor with a prominent tropism to the CNS.Methods:Melanoma brain metastasis was analyzed in a cohort of 78 patients by immunohistochemistry for TNFRSF9 and its expression was correlated with clinicopathological parameters including sex,age,survival,tumor size,number of tumor spots,and BRAF V600E expression status.Results:Tumor necrosis factor receptor superfamily member 9 was frequently expressed independently on both melanoma and endothelial cells.In addition,TNFRSF9 was also present on smooth muscle cells of larger vessels and on a subset of lymphomonocytic tumor infiltrates.No association between TNFRSF9 expression and patient survival or other clinicopathological parameters was seen.Of note,several cases showed a gradual increase in TNFRSF9 expression on tumor cells with increasing distance from blood vessels,an observation that might be linked to hypoxia-driven TNFRSF9 expression in tumor cells.Conclusion:The findings indicate that the cellular source of TNFRSF9 in melanoma brain metastasis largely exceeds the lymphomonocytic pool,and therefore further careful(re-)assessment of potential TNFRSF9 functions in cell types other than hematopoietic cells is needed.Furthermore,the hypothesis of hypoxia-driven TNFRSF9 expression in brain metastasis melanoma cells requires further functional testing.

慢性阻塞性肺疾病急性加重期血清瘦素与肺功能关系的临床研究

目的：探讨血清瘦素（ leptin ）与慢性阻塞性肺疾病（ chronic obstructive pulmonary disease， COPD）急性加重期患者肺功能的关系。方法选择COPD急性加重期患者35例、COPD稳定期患者38例及健康志愿者30例，抽取空腹血。用放免法测定血清瘦素、用酶联免疫吸附法（ELISA）测定肿瘤坏死因子-α（TNF-α）及用全自动生化仪检测C-反应蛋白（CRP）；检测肺功能，记录1 s用力呼气量（ FEVl ）、最大通气量（ MVV）、肺一氧化碳弥散量（ DLCO ）等指标、分析COPD急性加重期患者血清瘦素水平与TNF-α、CRP、肺功能等的相关性。结果①COPD急性加重期患者血清瘦素、TNF-α、CRP均明显高于COPD稳定期组和对照组，而FEVl、MVV、DLCO则明显低于后者；②COPD急性加重期患者血清瘦素与TNF-α、CRP呈正相关，与FEVl、MVV、DLCO呈负相关。结论血清瘦素可判断COPD急性加重期预后，可以评估肺功能损害风险。

孕妇牙周健康状况与早产发生的相关性

目的：探讨孕妇牙周健康状况与早产发生的关系并分析相关高危因素。方法对162例早产孕妇（早产组）和150正常足月产妇（对照组）的牙周健康状况及生活习惯、社会因素进行统计，并对早产和牙周炎的关系进行分析；分别使用ELISA、免疫比浊法和放射免疫法对牙龈卟啉单胞菌的细胞表面抗原IgG（ Pg IgG）水平、血浆C反应蛋白（CRP）和白细胞介素－6（IL－6）及肿瘤坏死因子－α（TNF－α）进行测定。结果二元logistic模型发现早产与牙周炎之间有显著相关性（OR＝2．39，95％CI 1．26～4．52）。早产组和对照组在距离上次口腔科就诊时间（P＜0．05）、刷牙频率（P＜0．05）、吸烟习惯（P＜0．05）、每年是否常规进行口腔检查（P＜0．001）和孕检次数（ P＜0．001）方面差异有统计学意义。早产合并牙周炎孕妇血清中TNF－α、IL－6、CRP水平和Pg IgG滴度的光密度值均显著高于不合并牙周炎的对照组（ P＜0．05）；不合并牙周炎的孕妇中早产组IL－6显著高于对照组（ P＜0．05）。结论早产与牙周炎之间具有相关性，不良的口腔卫生习惯为牙周炎孕妇发生早产的高危因素。合并牙周炎的孕妇血浆炎性因子和Pg IgG的检测对早产的发生具有一定预测作用。

中西医结合治疗脓毒症的临床疗效观察

目的：探讨益气活血解毒中药汤剂治疗脓毒症的临床疗效。方法将62例脓毒症患者采用信封随机法分为对照组（31例）、治疗组（31例）。对照组给予脓毒症西医常规治疗，治疗组在脓毒症西医常规治疗基础上加用益气活血解毒法中药汤剂中西医结合治疗。分析比较两组炎性因子、病情危重程度评分、住ICU时间及28 d病死率。结果治疗组治疗后IL-6、TNF -α水平较对照组明显下降（P＜0．05），住ICU时间较对照组明显缩短（P＜0．05），APACHEⅡ评分明显低于对照组（P＜0．05），28 d病死率低于对照组（26．7％vs 37．9％，P＝0．048）。结论益气活血解毒法可明显降低炎性因子IL-6及TNF-α水平，缩短住ICU时间，提高28 d生存率。

复方柴芩退热颗粒对发热大鼠模型退热作用的研究

目的:研究复方柴芩退热颗粒对2,4二硝基苯酚及细菌内毒素所致大鼠发热模型的退热作用,进一步明确该颗粒的退热效果,初步探讨其退热机制。方法:将SPF级SD大鼠随机分为正常对照组、模型组、酚麻美敏片组[给药剂量0.148 g/(kg·d)]、小柴胡冲剂组[给药剂量2.160 g/(kg·d)]、复方柴芩退热颗粒高、中、低剂量组[给药剂量分别为6.480、3.240、1.620 g/(kg·d)]。各给药组按相应剂量灌胃给药,正常对照组、模型组同法给予等体积的蒸馏水,每天1次,连续给药5天,第4天各组动物均开始禁食不禁水24 h,末次给药前开始造模。造模实验一:除正常对照组外,余各组大鼠均皮下注射2,4-二硝基苯酚17 mg/kg,正常对照组皮下注射同体积生理盐水;造模实验二:除正常对照组外,余各组大鼠均腹腔注射细菌内毒素80μg/kg。测大鼠各时间点的体温和血清中白细胞介素-1β(IL-1β)、前列腺素E2(PGE2)、肿瘤坏死因子-α(TNF-α)的含量。结果:实验一:与正常对照组比较,模型组大鼠造模后1 h、2 h、3 h体温上升值均显著升高,大鼠血清IL-1β、PGE2含量均显著升高(P<0.01)。与模型组比较,酚麻美敏片组、小柴胡冲剂组、复方柴芩退热颗粒高、中、低剂量组大鼠血清IL-1β、PGE2含量均明显降低(P<0.05,P<0.01);酚麻美敏片组大鼠在造模后1 h、2 h、3 h体温上升值均显著降低(P<0.05,P<0.01);小柴胡冲剂组大鼠在造模后2 h、3 h体温上升值均显著降低(P<0.05,P<0.01);复方柴芩退热颗粒高、低剂量组在造模后1 h、2 h、3 h体温上升值均明显降低(P<0.05,P<0.01);复方柴芩退热颗粒中剂量组在造模后2 h、3 h体温上升值均明显降低(P<0.05)。实验二:与正常对照组比较,模型组大鼠造模后2 h、4 h、6 h、8 h体温上升值均显著升高,大鼠血清PGE2、TNF-α含量均显著升高(P<0.01)。与模型组比较,酚麻美敏片组、小柴胡冲剂组、复方柴芩退热颗粒高、中、低剂量组大鼠血清PGE2、TNF-α含量均明显降低(P<0.05,P<0.01);酚麻美敏片组大鼠在造模后2 h、4 h、6 h体温上升值均显著降低(P<0.05,P<0.01);小柴胡冲剂组、复方柴芩退热颗粒高、中、低剂量组在造模后2 h、4 h体温上升值均明显降低(P<0.05,P<0.01)。结论:复方柴芩退热颗粒对2,4二硝基苯酚及细菌内毒素所致大鼠发热均有降温作用,能有效降低大鼠血清PGE2、IL-1β和血清TNF-α含量,对大鼠实验性高热模型有较好的解热作用。

老年口腔溃疡患者血清肿瘤坏死因子α变化研究

目的：研究老年口腔溃疡患者血清肿瘤坏死因子（ TNF-α）变化并讨论其临床意义。方法：老年口腔溃疡患者102例，年龄69．1±11．6岁。选择体检健康人26例作正常对照，年龄66．3±6．4岁。血清TNF-α含量用双抗体夹心ELISA法测定，8例重型患者进行病理组织学检查。结果：老年口腔溃疡血清TNF-α含量（g/L）明显高于正常对照（46．1±11．7 vs 25．3±10．4，P＜0．01），重型（n＝14，53．7±19．1，P＜0．01）和中型（n＝53，43．1±10．5， P＜0．01）明显高于轻型（n＝35，34．1±9．6，P＜0．01），即重型TNF-α含量＞中型＞轻型。8例组织病理学检查包括5例是淋巴细胞、浆细胞和单核巨噬细胞浸润的炎症，3例是炎症伴有增生。结论：老年口腔溃疡血清TNF-α含量可明显增高，病变越重增加越明显，且病理改变是炎症或伴增生，疾病发生发展与TNF-α变化有关。

Surface charge tunable nanoparticles for TNF-α siRNA oral delivery for treating ulcerative colitis

Nanopartide （NP） drug delivery systems have been successfully designed and implemented to orally deliver small interfering RNAs （siRNAs） for inflammatory disorders. However, the influence of surface charge on orally administered siRNA nanocarriers has not been investigated. In this study, we prepared structurally related poly（ethylene glycol）-block-poly（lactic-co-glycolic acid） （PEG5K-b-PLGA10K） NPs with the assistance of a synthesized lipid featuring surface amine groups for subsequent charge tuning. NPs were prepared by a double emulsion method, and their surface charge could be tuned and controlled by a succinylation reaction to yield NPs with different surface charges, while maintaining their size and composition. The prepared NPs were termed as aminated NPs （ANPs）, plain NPs （PNPs）, or carboxylated NPs （CNPs） based on their surface charge. All NPs exhibited the desired structural stability and siRNA integrity after enzymatic degradation. In vivo studies showed that ANPs significantly accumulated in inflamed colons, and they were successful in decreasing TNF-α secretion and mRNA expression levels while maintaining colonic histology in a murine model of acute ulcerative colitis （UC）. This study described a methodology to modify the surface charge of siRNA-encapsulating polymeric NPs and highlighted the influence of surface charge on oral delivery of siRNA for localized inflammatory disorders.

Relationship between peritoneal macrophages and inflammatory reaction in a rat model of severe acute pancreatitis

Objective To investigate the relationship between peritoneal macrophages(PMAs)and inflammatory reaction in a rat model of severe acute pancreatitis(SAP).Methods Sprague-Dawley rats were randomly divided into control group and SAP group.To induce SAP in rats,40 g/L sodium taurocholate(0.1 mL/100 g)was injected into the pancreatic duct through retrograde exposure of pancreatic bile duct in hepatic porta.One-third of rats were sacrificed at 3,6 or 12 h after modeling.PMAs were extracted,and incubated for 24 h in a humidified 5% carbon dioxide incubator.The expressions of tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)mRNA in PMAs were measured by semi-quantitative RT-PCR.The levels of TNF-α and IL-1β in culture medium and serum were evaluated.The histological changes of pancreas were examined.Results The expressions of TNF-α mRNA and IL-1β mRNA in PMAs were significantly higher in SAP group than in control group at each time point(P<0.01).The concentrations of TNF-α and IL-1β in culture medium and serum were significantly elevated in SAP group compared with control group(P<0.01).The histological analysis of pancreas indicated that the damage was more severe in SAP group than in control group(P<0.01).Conclusion PMAs secrete cytokines into pancreatitis-associated ascitic fluid,and this study demonstrates a correlation between SAP and the activation of PMAs.

The efficacy and safety of thalidomide for treating metastatic breast cancer:a systematic review

Objective This systematic review was conducted to investigate the efficacy and safety of thalidomide in metastatic breast cancer(MBC).Methods Based on pre-defined inclusion and exclusion criteria,data were independently collected from different databases by three investigators.Overall,three studies were included.Results The included studies indicated that no patient achieved a partial or complete response from different thalidomide dose levels.Thalidomide was well-tolerated at doses of 100 mg,200 mg,and 400 mg.In all three studies,common side effects included constipation,somnolence,fatigue,peripheral neuropathy,and dry mouth.Circulating angiogenic factors were not significantly correlated with disease progression.Conclusion The available evidence indicates that single-agent thalidomide has little or no activity in patients with MBC.