Adenocarcinoma of the Ampulla of Vater: T-Stage,Chromosome 17p Allelic Loss,and Extended Pancreaticoduodenectomy are Relevant Prognostic Factors

Objective To evaluate the prognostic significance of different clinico-pathological and molecular factors, and to compare survival after standard and extended pancreaticoduodenectomy (PD) in ampulla of Vater adenocarcinoma (AVAC). Summary Background Data There are discordant data on factors affecting prognosis, and hence therapeutic choices, in AVAC. Patients and Methods Clinical-pathological factors were evaluated in 59 patients, subjected to PD for AVAC; in 42 subjects information on chromosome 17p and 18q allelic losses (LOH) and microsatellite instability (MSI) was also available. The association between survival and type of PD was investigated in the 25 patients operated between 1990 and 2001 (16 standard and nine extended). Results The overall 5- and 10-year tumor-related survival rates were 46% and 33%, respectively. Sixteen patients had T-stages 1–2, 14 T-stage 3, and 29 T-stage 4 cancers. Chromosome 17p and 18q LOH were detected in 23 (55%) and 15 cases (36%), respectively, and in 12 cases (29%) coexisted. Five cases were MSI-positive (12%). At univariate analysis, poor survival was associated with cancer ulceration (P = 0.051), poor differentiation (P = 0.008), T-stage 4 (P < 0.001), nodal metastases (P = 0.004), chromosome 17p (P < 0.001) and 18q LOH (P = 0.002), and absence of MSI (P = 0.009). At multivariate analysis, only T-stage (P = 0.002) and 17p LOH (P = 0.001) were independent predictors of survival. All patients with MSI-positive cancers were long-survivors (>12 yrs), whereas only 30% of MSI-negative cancer patients survived at 5 years. Extended pancreaticoduodenectomy was associated with a 3-year disease-related survival higher than standard resection (83% vs 31%; P = 0.018). Conclusion MSI and chromosome 17p status allow to better define prognosis within ampullary cancers at the same stage. Surgery alone resulted curative in MSI-positive cancer patients, whereas it was inadequate in patients showing allelic losses, who might benefit from adjuvant therapy. In this observational study, extended PD was associated with increased survival compared to standard procedures. Presented at the 2006 Annual Meeting of the American Hepato-Pancreato-Biliary Association, Miami Beach, Florida, March 9–12, 2006     

Facilitating antidepressant-like actions of estrogens are mediated by 5-HT1A and estrogen receptors in the rat forced swimming test

Previous studies have shown that 17beta-estradiol (E2) induces antidepressant-like actions per se and potentiates those produced by fluoxetine (FLX) in the forced swimming test (FST). The aim of the present work was to explore the participation of serotonin 1A receptors (5-HT1A) and estrogen receptors (ERs) in the antidepressant-like actions of E2, FLX or their combination in the FST. Although all antidepressants reduce behavioral immobility, antidepressants that modulate serotonergic neurotransmission increase swimming behavior whereas those that modulate the catecholaminergic neurotransmission increase climbing behavior. Thus, using this animal model, it is possible to infer which neurotransmitter system is modulating the action of an antidepressant compound. Ovariectomized female Wistar rats were used in all experiments. In the first experiment, an effective dose of E2 (10 microg/rat, -48 h) was combined with several doses (0.5, 1.0 and 2 mg/kg) of RU 58668 (a pure ER antagonist) 48 h previous to the FST. The second experiment evaluated the action of (1 mg/kg, -48 h or -23, -5 and -1 h) WAY 100635 (5-HT1A receptor antagonist) on the antidepressant-like action of FLX (10 mg/kg, -23, -5 and -1 h). In the third experiment, the effect of RU 58668 (2 mg/kg, -48) or WAY 100635 (1 mg/kg, -48 h) on the antidepressant-like action of the combination of a sub-optimal dose of E2 (2.5 microg/rat, -48 h) plus a non-effective dose of FLX (2.5 mg/kg, -23,-5 and -1 h) was evaluated. The results showed that RU 58668, the antagonist to the ER, canceled the antidepressant-like action of E2 in a dose-dependent manner. The antagonist to the 5-HT1A receptor blocked the antidepressant action of FLX only when administered simultaneously with FLX, i.e. -23, -5 and -1 h before the FST. Finally, the administration of both RU 58668, and WAY100635 canceled the antidepressant-like action of the combination of E2/FLX. These results imply that both 5-HT1A receptors and ERs participate in the facilitating actions of E2 on the antidepressant-like action of FLX in the FST.     

脓毒血症患者外周血Th17细胞与细胞因子表达的变化

目的：监测脓毒症患者外周血Th17细胞和细胞因子IL-17、IL-6的表达水平．探讨脓毒血症患者免疫功能变化的可能机制。方法：取2010年4月至11月住我院ICU病房的脓毒症患者62例。采用流式细胞术检测外周血Th17％（Th17／CD4＋T）。应用ELISA（酶联免疫吸附方法）检测血浆IL-17和IL-6的表达水平。同时选取来自我院查体中心的健康查体者30例作为对照组。结果：脓毒症患者外周血Th17％明显高于健康对照组[（6．94±1.95）比（1.91±0,32）％,P〈0．01];血浆IL-17,IL-6的表然亦最著高于对照组[（56．52±16．06）pg／ml比（19．59±1．98）pg／ml;（220,68±86．41）pg／ml比（24.39±0,87）Pg／ml]。患者血浆IL-17与IL-6表达水平里正相关（r=0．886．p〈0.01）。Th17的表达与IL-17、IL-6的表达亦呈正相关,（r1=20．846,r2=0．891．均P〈0．01）.结论：脓毒血症患者外周血中Th17％增加．血浆IL-17及IL-6表达水平亦升高．提示Th17可能参与脓毒症的发病机制。     

支气管哮喘患儿Th1/Th2细胞免疫平衡变化研究

目的探讨支气管哮喘患儿Th1/Th2细胞免疫平衡变化及其机制。方法选择急性发作期支气管哮喘患儿30名作为发作组,选择30名缓解期支气管哮喘患儿作为缓解组,选择30名健康小儿作为对照组,采用流式细胞仪检测各组静脉血Th1、Th2表达情况,采用酶联免疫吸附法检测三组患儿血清IL-4、IL-10、IFN-γ水平,比较各组患者Th1/Th2及血清IL-4、IL-10、IFN-γ表达变化水平。结果发作组静脉血Th1/Th2低于对照组及缓解组,血清IL-4、IL-10水平高于对照组及缓解组,IFN-γ水平低于对照组及缓解组。缓解组静脉血Th1/Th2低于对照组,血清IL-4、IL-10水平高于对照组,血清IFN-γ水平低于对照组。结论支气管哮喘患儿存在Th1/Th2免疫失衡,其可能是小儿支气管哮喘的发病机制之一。     

吗替麦考酚酯抑制小鼠TH17细胞的分化和增殖

目的 通过观察吗替麦考酚酯(MMF)对小鼠辅助性T淋巴细胞17(TH 17细胞)分化和增殖的影响,探讨MMF的免疫抑制作用及其机制.方法 采用随机数字表法将小鼠分为MMF组与对照组,每组8只.MMF组小鼠每天给予MMF 40 mg·kg-1·d-1灌胃,对照组小鼠每天给予等体积生理盐水灌胃.3周后取小鼠外周血和脾脏,采用流式细胞术检测小鼠外周血和脾细胞中TH17细胞和CD4+CD25+调节性T淋巴细胞(Treg细胞)的比例,并计算出TH 17细胞与Treg细胞的比值;采用酶联免疫吸附试验法分别检测两组小鼠血清中白细胞介素(IL)-17和IL-23的浓度.结果 MMF组外周血和脾细胞中TH17细胞比例分别为(1.95±0.08)％和(2.42±0.06)％,对照组分别为(3.19±0.07)％和(4.21±0.25)％,两组比较,差异均有统计学意义(P＜0.05).MMF组外周血和脾细胞中TH 17细胞与Treg细胞的比值均显著低于对照组(P＜0.05).MMF组小鼠血清IL-17水平明显低于对照组(P＜0.05),而血清IL-23水平高于对照组(P＜0.05).结论 MMF能够明显抑制小鼠体内TH17细胞的分化与增殖,降低TH 17细胞与Treg细胞的比值,减少IL-17的分泌,有利于诱导免疫耐受.     

关节腔注射富血小板血浆对膝骨关节炎患者关节液及血浆中 IL-17 的影响

目的探讨关节腔注射富血小板血浆（platelet-rich plasma，PRP）治疗后，膝骨关节炎（osteoar-thritis，OA）患者血浆和关节滑液中 IL-17 水平变化。方法以 2015 年 1 月—2016 年 1 月接受关节腔 PRP 注射治疗（每周 1 次，连续 3 周）的 30 例膝关节 OA 患者作为研究对象（试验组），以 30 例自愿者正常膝关节作为对照（对照组）。两组研究对象性别、年龄、体质量指数比较，差异均无统计学意义（P>0.05）。试验组治疗前后采用膝关节学会评分系统（KSS）及疼痛视觉模拟评分（VAS）分别评价膝关节功能及疼痛程度。试验组患者注射 PRP 之前及第 3 次注射后 1、3、6 及 12 个月抽取肘前静脉血以及患侧关节滑液，采用 ELISA 法测量 IL-17 含量；对照组抽取肘前静脉血进行相应检测并比较。 结果PRP 注射治疗过程中，试验组患者均未出现膝关节红肿、发热等局部感染及其他不适症状。患者均获随访，随访时间 12～15 个月，平均 13.5 个月。PRP 注射治疗后各时间点 VAS 评分均较术前显著降低，KSS 评分较术前显著增加，比较差异有统计学意义（P<0.05）；治疗后各时间点间比较，差异均无统计学意义（P>0.05）。与对照组比较，试验组 PRP 治疗前后血浆 IL-17 含量均显著增高（P<0.05）。试验组治疗后各时间点血浆及关节滑液 IL-17 含量均较治疗前显著降低（P<0.05），治疗后各时间点间比较差异均无统计学意义（P>0.05）。 结论关节腔注射 PRP 治疗可显著改善膝关节 OA 患者疼痛症状及关节功能，并在一定程度上降低患者体内 IL-17 水平，但未恢复至正常水平。     

不育患者血清精子蛋白17抗体的检测及临床意义

目的:检测抗精子抗体(AsAb)阳性不育患者血清中抗精子蛋白17(Sp17)的抗体,探讨该抗体在免疫性不育血清学诊断和免疫避孕方面的潜在应用价值。方法:用重组人Sp17作为抗原,ELISA法检测62例AsAb阳性血清中Sp17抗体阳性率及滴度,分析AsAb中抗Sp17的含量。结果:AsAb阳性血清中Sp17抗体阳性率为56.5%,男女之间差异无显著性。Sp17抗体占AsAb的(10.09±7.45)%,结果具有统计学意义(P<0.05)。结论:Sp17是重要的精子抗原组分,血清中Sp17抗体的检测可作为不育患者辅助诊断指标,同时也提示Sp17可能是一种免疫避孕候选抗原疫苗。     

尿IL-17水平检测对评估IgA肾病病情和治疗疗效的价值

也页目的：探讨尿白细胞介素-17（IL-17）检测对评估IgA肾病（IgAN）病情严重程度和治疗疗效中的价值。方法：应用酶联免疫吸附法（ ELISA）检测79例原发性IgAN患者治疗前后的尿IL-17水平,分析患者治疗前尿IL-17水平与临床指标、牛津病理分型[系膜细胞增生（ M）、内皮细胞增生（ E）、节段硬化或黏连（ S）和肾小管萎缩/间质纤维化（ T）]的相关性;比较不同治疗方案下患者治疗前后尿IL-17水平的变化以及与疾病转归的关系。结果：IgAN患者治疗前尿IL-17的水平较正常对照显著升高并且与尿中性粒细胞明胶酶相关脂质运载蛋白（ NGAL）的水平和24 h尿蛋白呈正相关、与eGFR呈负相关。根据牛津病理分型,E1组患者的尿IL-17水平显著高于E0组,T1组和T2组患者的尿IL-17水平分别显著高于T0组,M0组与M1组、S0组与S1组、T1组与T2组的尿IL-17水平差异均无统计学意义。治疗6个月后,在单用血管紧张素转换酶抑制剂（ ACEI）治疗的患者中治疗显效组的尿IL-17水平较治疗前显著下降,而治疗无效组的尿IL-17水平较治疗前无显著下降;ACEI联合糖皮质激素治疗的患者中治疗有效组和无效组在治疗后的尿IL-17水平较治疗前均显著下降。结论：尿IL-17水平在评估IgAN患者的病情和疗效预判方面具有潜在的临床实用价值。     

辅助生殖患者宫腔粘连术后应用人工周期促内膜修复的疗效及对生育结局的影响

目的评价17-β雌二醇用于辅助生殖患者宫腔粘连术后促子宫内膜修复的效果及对生育结局的影响。方法 429例拟行体外受精-胚胎移植(IVF-ET)患者,因宫腔粘连经宫腔镜下行宫腔粘连分离术和放置宫内节育器术,215例术后应用17-β雌二醇+地屈孕酮行周期治疗(雌二醇2mg bid)2周期(实验组),214例不行周期治疗(对照组)。所有病例定期随诊,治疗结束后再行宫腔镜检查探查宫腔情况并取出宫内节育器,再行胚胎移植,随访治疗疗效及妊娠结局。结果实验组的宫腔镜治疗治愈率明显较对照组高,X2=-3.16,p=0.002,实验组术后胚胎移植临床妊娠率也明显较对照组高X2=-2.75,p=0.006。结论宫腔粘连术后采用17-β雌二醇周期治疗,不但有利于宫腔形态的恢复及内膜的修复,而且可以提高内膜的容受性,明显改善妊娠结局。