放射性心脏损伤动物模型相关实验研究进展

当利用放射线对胸部恶性肿瘤进行治疗时，位于纵隔的心脏会不可幸免受到照射，从而诱发放射性心脏损伤（radiation-induced heart disease, RIHD）。随着手术以及放化疗技术的提升，肿瘤患者生存时间得到延长，使得RIHD这一放疗远期并发症被越来越多的报道。因此，学者们对于RIHD的研究逐渐升温。目前国内外学者关于该疾病尚未形成统一的认识，临床上缺乏有效阻止其发生的方法。动物模型研究可为临床该疾病治疗及预防提供可靠证据，为此本文回顾分析近年来放射性心脏损伤动物模型实验研究情况，旨在为后续实验开展及临床应用提供参考。     

结直肠癌化疗患者营养状况及营养治疗研究进展

结直肠癌是常见的消化道肿瘤，其营养不良发生率高且严重。化疗是结直肠癌常见治疗方式之一，并与营养不良独立相关，化疗后患营养不良风险增大且营养不良进一步加重。同时，营养不良可导致患者化疗疗效差及预后不良，并增加化疗相关不良反应、影响患者生活质量及降低生存率等。营养治疗能够有效改善患者营养状况，在肿瘤综合治疗中有重要作用，且多学科团队合作是有效的营养干预模式。目前营养治疗主要包括营养咨询、口服营养补充剂、肠内营养和肠外营养等，相关指南和研究表明在营养治疗时应首选口服营养补充剂及肠内营养，仅在采用以上治疗后仍存在营养不足或无法进行肠内营养时行肠外营养。本文主要对结直肠癌患者营养状况与化疗之间关系、营养治疗的最新研究进展及相关指南进行综述，以期引起临床上对结直肠癌化疗患者营养治疗方面重视并提供参考。     

1.318 μm近红外激光视网膜损伤阈值研究

目的研究1·318μm激光对视网膜的损伤效应,确定其损伤阈值。方法用输出波长1·318μm的Nd∶YAG激光为照射光源,固定照射时间0·2s,以不同剂量的激光照射散瞳后的家兔(25只)和大鼠(28只)眼睛,照射光斑直径分别为5mm和2mm,于照后1h和24h观察视网膜损伤发生率,用加权概率单位法计算损伤发生率为50%时所对应的激光剂量,即损伤阈值ED50。并于照后24h对损伤视网膜做病理切片观察。结果1·318μm激光致家兔和大鼠视网膜损伤的阈值角膜剂量分别为13·7J/cm2和10·4J/cm2,阈值角膜能量分别为2·69J和0·33J。受损视网膜可见清晰的白色凝固斑,损伤重者累及视网膜全层。结论1·318μm激光可导致家兔和大鼠视网膜损伤,损伤阈值ED50分别为13·7J/cm2和10·4J/cm2。     

CT引导下胶原酶注射颈椎间盘溶解术的临床研究

目的:研究CT引导下胶原酶注射颈椎间盘溶解术治疗颈椎间盘突出症的价值。方法:对15例颈椎间盘突出症患者在CT引导下行胶原酶注射颈椎间盘溶解术。结果:15例均成功,随访1~16个月,优良率93.3%,未见并发症发生。结论:CT引导下行胶原酶注射颈椎间盘溶解术治疗颈椎间盘突出症安全有效,值得进一步研究。     

Dexamethasone treatment attenuates early seawater instillation-induced acute lung injury in rabbits.

There is very little evidence on the value of giving corticoids in cases of seawater drowning induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Therefore, this study aimed to investigate whether dexamethasone treatment can attenuate seawater instillation-induced acute lung injury in rabbits. Seawater (4 ml/kg body weight) was instilled into the lower trachea of ventilated, anesthetized rabbits. Then these rabbits were assigned randomly 20 min later to receive intravenous injection of 1mg/kg body weight of dexamethasone (dissolving in 2 ml of normal saline) or 2 ml of normal saline. All animals demonstrated immediate drops in arterial oxygen tension (PaO2) and the total thoracic compliance, which were significantly improved after 2 h of dexamethasone treatment. Histopathological study also indicated that dexamethasone treatment markedly attenuated lung histopathological changes, alveolar hemorrhage and inflammatory cells infiltration with evidence of decreasing of myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-alpha) concentration in lung tissue. In addition, dexamethasone treatment reduced extravascular lung water and lung epithelial-endothelial barrier permeability, up-regulated the expression of surfactant protein-A (SP-A) and alpha-epithelial Na+ channel, and increased Na+/K+-adenosine triphosphatase (Na+/K+-ATPase) activity and Na+/K+-ATPase-alpha1 protein abundance. Thus, these data indicate that dexamethasone treatment might be of benefit in patients with seawater aspiration-induced ALI.     

Effect of Induction Therapy Protocols on Transplant Outcomes in Crossmatch Positive Renal Allograft Recipients Desensitized with IVIG

Here we retrospectively examine the efficacy of two antibody induction regimens using Zenapax or Thymoglobulin in patients with positive complement-dependent cytotoxicity crossmatches (CDC-CMXs) desensitized with IVIG (intravenous immunoglobulin). Between January 1999 and March 2005, 97 patients with (+) CDC-CMXs received kidney transplants (43 deceased donors/54 living donors). All patients received at least 2 g/kg IVIG (maximum four doses) until an acceptable CMX was obtained. Patients were divided into two groups: 1. IVIG + Zenapax (n = 58), 2. IVIG + Thymoglobulin (n = 39). A total of 94% of patients in Group 1 and 84% in G2 have at least 2 years of follow up. Patient and graft survival was 96%/84% in Group 1 and 100%/90% in Group 2, p = NS. The number and severity of AR episodes were similar (36% Group 1 vs. 31% Group 2, p = NS) as was the incidence of C4d (+) antibody-mediated rejection (AMR) (Banff Grade II/III) (22% Group 1 vs. 21% Group 2). Mean serum creatinines (SCrs) at 24 months were similar (Group 1: 1.4 +/- 0.7 vs. G2: 1.5 +/- 0.7 mg/dL). Induction therapy with Zenapax or Thymoglobulin results in excellent patient, graft survival and graft function at 2 years. There was no increased risk of viral infections or malignancies with either agent. Neither agent was effective in reducing the incidence of AMR.     

急性出血坏死性胰腺炎肝损伤中TLR2/4mRNA的表达及氯喹的干预效应

目的： 研究急性出血坏死性胰腺炎（AHNP）肝损伤中Toll-样受体(TLR)2/4mRNA表达的变化及氯喹的干预效应。 方法：采用逆行胰胆管牛磺胆酸钠（TAC）注射造成大鼠AHNP肝损伤动物模型。动物分为假手术组（S组）、胰腺炎组和氯喹（CQ）治疗组。后2组于术后3，6，12 h分批剖杀，S组于术后6 h剖杀。观察血清淀粉酶、ALT和AST及肝组织NO和TNF-α的变化，RT-PCR方法检测各组不同时点肝组织TLR2和TLR4mRNA的表达。 结果：相对于S组，胰腺炎组大鼠3 h肝组织TLR2和TLR4mRNA表达开始增高，术后6～12 h肝组织TLR2和TLR4mRNA表达迅速达到峰值（P<0.05），肝损伤加重，血清淀粉酶升高，肝组织TNF-α浓度升高，NO浓度逐渐降低（P<0.05）；相对胰腺炎组，CQ治疗组TLR2/4mRNA表达降低（P<0.05），肝损伤程度减轻，血清淀粉酶降低，肝组织TNF-α浓度降低，NO浓度显著升高（P<0.05）。 结论：AHNP大鼠肝组织内TLR2和TLR4的基因表达上调；其表达增高可能在AHNP肝损伤的发生、发展中起重要作用。氯喹对大鼠AHNP过程中肝损伤可能有保护作用。     

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK(-/-) mice.

Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response.