IL-15在兔膝创伤性关节炎模型中的表达研究

目的观察兔膝创伤性关节炎早期白介素15(IL-15)炎性因子的表达及其变化,以进一步探讨创伤性关节炎的发生机制。方法将48只健康新西兰大白兔随机分为实验组和对照组,每组24只。实验组行左后膝关节前后交叉韧带切断和内侧半月板切除术;对照组行单侧膝关节切开术作为假手术对照。2组分别在术后6、12、24h,1、2、3、4周7个时间点抽取关节液,采用酶联免疫吸附法(ELISA)测定关节液中IL-15含量表达。组织学观察其关节软骨和滑膜的变化。结果48只大白兔中进入结果分析29只。2组术后6h兔膝关节液中IL-15含量较其他时间点明显增高(P<0.05);术后1周IL-15表达较术后24h明显降低(P<0.05);术后1、2、3、4周4个时间点的IL-15表达成升高趋势;实验组术后各时间点IL-15含量均高于对照组(均P<0.05)。实验组术后4周,关节软骨失去原有的光泽,呈灰黄色,有裂纹,HE染色见表层略不平整,有小裂隙,纤维组织增生,玻璃样变性,局灶性软骨基质异染性减弱,软骨细胞减少,软骨基质纤维化。结论创伤后兔膝创伤性关节炎早期IL-15高表达,关节软骨及滑膜退变,创伤性关节炎早期与IL-15关系密切。     

Effects of benzodiazepine receptor ligands on the performance of an operant delayed matching to position task in rats: opposite effects of FG 7142 and lorazepam

The effects of a series of benzodiazepine (BZ) receptor ligands, ranging from a full agonist through to partial inverse agonists, were examined on short term working memory in the rat. The behavioural paradigm used was a discrete trial, operant delayed matching to position task, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. The benzodiazepine receptor (BZR) full agonist lorazepam (0.25, 0.375 and 0.5 mg/kg) dose and delay dependently impaired matching accuracy. Lorazepam also increased the latency to respond and decreased the number of nose pokes made into the food tray during the delays. In contrast, the BZR partial agonist ZK 95 962 (1, 3, 10 mg/kg) did not affect matching accuracy, but did increase the speed of responding. The BZR antagonist ZK 93 426 (1.25, 5, 25 mg/kg) had no effects in this paradigm. The BZR weak partial inverse agonists Ro 15-4513 (0.1, 1 and 10 mg/kg) and ZK 90 886 (1, 3 and 10 mg/kg) did not affect accuracy of performance. However, both of these drugs increased the latency to respond and decreased nose poke responses. These motoric effects were particularly strong following 10 mg/kg Ro 15-4513. This shows that the effects of drugs on the accuracy of responding and on the speed of responding can be dissociated. The BZR partial inverse agonist FG 7142 had effects on matching accuracy that were dependent upon dose. The lowest dose of FG 7142 (1 mg/kg) significantly improved accuracy, whereas the highest dose (10 mg/kg) impaired accuracy. This impairment induced by FG 7142 (10 mg/kg) was accompanied by an increase in the latency to respond and a decrease in the number of nose pokes. Taken together, these results show that the accuracy of delayed matching performance can be modulated in opposite ways by the BZR full agonist lorazepam and a low dose of the BZR partial inverse agonist, FG 7142.     

Benzodiazepine receptor ligands and the consumption of a highly palatable diet in non-deprived male rats

Non-deprived rats were familiarised with a highly palatable diet until baseline consumption in a 60-min daily access period had stabilised. The benzodiazepine receptor agonist midazolam (1.25–10.0 mg/kg, IP) produced a large, dose-related increase in food consumption during the first 30 min of access. It also produced significant, short-term hyperphagia in animals which had been partially pre-satiated on the diet before drug administration, an effect which was reversible by the benzodiazepine receptor antagonist Ro15-1788. Administered alone, Ro15-1788 (1.25–10.0 mg/kg, IP) had no intrinsic activity in the food consumption test. In contrast, CGS 8216 (2.5–40.0 mg/kg, IP) produced a marked dose-related suppression of food intake. This anorectic effect was shared by two benzodiazepine receptor inverse agonists, FG 7142 and DMCM, which also produced dose-dependent reductions in consumption. The effects on feeding produced by FG 7142 (20 mg/kg, IP) and DMCM (1.25 mg/kg, IP) were reversed by either Ro15-1788 (2.5 and 5.0 mg/kg) or midazolam (5.0 and 10.0 mg/kg). A matched anorectic effect produced by CGS 8216 (40 mg/kg) was not, however, reversed by either Ro15-1788 or midazolam. This suggests that at a high dose CGS 8216 may act by a mechanism different from that of the two inverse agonists. The feeding test described in the report proved sensitive to both hyperphagic and anorectic effects of drugs active at benzodiazepine receptors, pointing to a possible bi-directional control of palatable food consumption.     

KIF15 expression characteristics: Relevance toneo-adjuvant chemotherapy efficacy in breast cancer

Objective The relationship between the expression of kinesin family member 15 (KIF15) and clinicopathological features in breast cancer (BC) remains controversial. In this study, we aimed to explore the influence of KIF15 expression on the efficacy of neoadjuvant chemotherapy (NAC) and evaluate its clinical value in predicting prognosis for BC patients. Methods Immunohistochemistry was used to detect KIF15 expression in 93 BC patients undergoing NAC to analyze the relationship between KIF15 expression and clinical efficacy and analytical parameters. Results Of the 93 BC patients enrolled, 24.73％ who underwent NAC had higher KIF15 expression levels, showing positive correlations with ER, HER-2, Ki67, and lymph node metastasis (P < 0.05). The clinical benefit of NAC was 70.97％, and the major histological response (MHR) rate was 61.29％. The effective therapeutic rate in patients with high KIF15 expression was 95.65％, while the MHR rate was 65.22％. Various molecular BC subtypes with varied clinical and pathological responses exhibited correlation to a large extent. Of all the BC patients studied, 84％ of the triple-negative breast cancer (TNBC) patients were evaluated as clinically effective, and 52％ of the TNBC patients were evaluated as pathologically effective, and these values were significantly higher than those of the other molecular types (P < 0.05). The expression of KIF15 in 25 TNBC patients showed positive correlations with lymph node metastasis. Conclusion Overexpression of KIF15 was shown to increase BC sensitivity to chemotherapy and demonstrated better outcomes.     

肝储备功能测定中三种静脉注药方法的比较

目的 比较肝储备功能测定中三种不同的静脉注药方法,合理选取最佳方法,达到简化流程,节约成本,提高检测准确性的目的。方法 选取肝脏术后停留中心静脉导管并需进行肝储备功能测定的患者 100 例,每名患者都按照三种不同的静脉注药方法进行检测,比较三种测定方法得到的K 和R15 值有无统计学差异。方法一,在肘静脉留置针推注药液后立即予生理盐水冲管;方法二,药液量增加留置针管道的容量 0.4 mL,经肘静脉留置针推注后无须冲管;方法三,经中心静脉导管推注药液,不冲管。结果 三种方法得到的K 值和R15 值均无统计学差异;方法三血药浓度峰值出现时间更早,但并不影响最终检测结果。结论 肝储备功能测定的三种静脉注药方法均可顺利完成给药过程,结果数据接近,但采用中心静脉导管给药效果更好。     

Perianal Paget’s disease: case report and review of the literature

A peri-anal skin lesion, often eczema-like and with symptoms of pruritus, that does not resolve after classical local therapy should be biopsied. We present a case of peri-anal extramammary Paget’s disease (EMDP) and associated anal adenocarcinoma. Reviewing the literature, more than 30% of patients with EMDP present a second primary tumour in their past, present or future history. In Europe, the risk of developing a new primary tumour in patients with this condition is increased compared with the standard population. In cases of peri-anal Paget’s disease (PPD), specific histochemical markers allow us to differentiate between a primary and a secondary form, the secondary one is strongly associated with colorectal and anal tumours. We provide information about the most commonly suggested therapy for PPD with or without associated malignancy and about the recommended follow-up.     

TRAF2 regulates peripheral CD8+ T‐cell and NKT‐cell homeostasis by modulating sensitivity to IL‐15

In this study, a critical and novel role for TNF receptor (TNFR) associated factor 2 (TRAF2) is elucidated for peripheral CD8⁺ T‐cell and NKT‐cell homeostasis. Mice deficient in TRAF2 only in their T cells (TRAF2TKO) show ∼40% reduction in effector memory and ∼50% reduction in naïve CD8⁺ T‐cell subsets. IL‐15‐dependent populations were reduced further, as TRAF2TKO mice displayed a marked ∼70% reduction in central memory CD8⁺CD44^hiCD122⁺ T cells and ∼80% decrease in NKT cells. TRAF2TKO CD8⁺CD44^hi T cells exhibited impaired dose‐dependent proliferation to exogenous IL‐15. In contrast, TRAF2TKO CD8⁺ T cells proliferated normally to anti‐CD3 and TRAF2TKO CD8⁺CD44^hi T cells exhibited normal proliferation to exogenous IL‐2. TRAF2TKO CD8⁺ T cells expressed normal levels of IL‐15‐associated receptors and possessed functional IL‐15‐mediated STAT5 phosphorylation, however TRAF2 deletion caused increased AKT activation. Loss of CD8⁺CD44^hiCD122⁺ and NKT cells was mechanistically linked to an inability to respond to IL‐15. The reduced CD8⁺CD44^hiCD122⁺ T‐cell and NKT‐cell populations in TRAF2TKO mice were rescued in the presence of high dose IL‐15 by IL‐15/IL‐15Rα complex administration. These studies demonstrate a critical role for TRAF2 in the maintenance of peripheral CD8⁺ CD44^hiCD122⁺ T‐cell and NKT‐cell homeostasis by modulating sensitivity to T‐cell intrinsic growth factors such as IL‐15.     

HBME‐1 and CD15 immunocytochemistry in the follicular variant of thyroid papillary carcinoma

Papillary carcinoma is the most common thyroid malignancy. As the cytological diagnosis of papillary carcinoma is not difficult in patients with the usual type of lesion, fine‐needle aspiration (FNA) cytology is an effective method for preoperative evaluation. However, this modality is often ineffective in identifying the follicular variant of papillary thyroid carcinoma (FVPTC) due to its similarity to other follicular lesions and the incompleteness of typical nuclear features. Therefore, we investigated the expression of immunocytochemical markers of papillary carcinoma in cytological specimens of FVPTC and evaluated their utilities. The immunoreactivity of HBME‐1 and CD15 was investigated using 50 imprint smear cytological specimens obtained from thyroid lesions, including 13 FVPTC. The sensitivity and specificity of HBME‐1 for FVPTC were 92% and 89%, respectively, while those of CD15 were 23% and 100%, respectively. In conclusion, HBME‐1 is a sensitive marker of papillary carcinoma, including both usual type and FVPTC, in cytological specimens. Therefore, using HBME‐1 immunocytochemistry in FNA cytology will lead to reduction of the incidence of false‐negative diagnoses of FVPTC. Although CD15 is apparently inferior in terms of sensitivity for FVPTC, its excellent specificity will support the definitive diagnosis of thyroid malignancies, including FVPTC, after screening with HBME‐1.