无创吸入式麻醉精准肺野照射装置在小鼠肺损伤研究中的应用

目的 探索小鼠放射性肺损伤模型中大批量、快速、低成本实现全肺野精准照射的有效方法,普及这一重要放射生物学模型在多领域的应用。方法 采用8~10周龄C57BL6雌性小鼠,使用micro-CT三维重建图像进行肺部解剖学参数测量并确定放射野范围（n=12）。结合标准化胸腔暴露及固定、无创通气麻醉等手段建立"一体化"麻醉、固定、定位装置,借助常规医用直线加速器完成批量小鼠精准肺野照射。结果 小鼠CT图像三维重建后在冠状位与矢狀位图像上确定肺结构的解剖位置与尺寸平均值。并进一步根据小鼠呼吸频率及幅度确定受呼吸频率影响的肺野上界、中线和下界,并将测量值标记于专门设计的肺野照射装置用来指导实际操作。本装置大致可分为小鼠固定架和麻醉通气系统两部分构成。固定架用以安置每排10只小鼠用弹力栓妥善固定暴露胸腔。照射中通过麻醉面罩全程给予异氟烷混合气体,确保实验过程中小鼠处于深度麻醉以及均匀呼吸动度。结论 本研究设计的集麻醉、固定、定位为一体的"弹匣式"小鼠肺野照射装置,可显著增加胸部放射实验的准确性、简易性、安全性、稳定性和高效性。大幅减低实验成本和对高端辐照设备的依赖,具有一定的实际应用及推广价值。     

Relationship Among Radiological Measurements of Anterior Mediastinal Fat and Outcomes of Lung Transplantation in Fibrotic Patients

ObjectiveLung transplantation (LT) for pulmonary fibrosis is related to higher mortality than other transplant indications. We aim to assess whether the amount of anterior mediastinal fat (AMF) was associated to early and long-term outcomes in fibrotic patients undergoing LT.MethodsRetrospective analysis of 92 consecutive single lung transplants (SLT) for pulmonary fibrosis over a 10-year period. AMF dimensions were measured on preoperative CT-scan: anteroposterior axis (AP), transverse axis (T), and height (H). AMF volumes (V) were calculated by the formula: AP × T × H × 3.14/6.According to the radiological AMF dimensions, patients were distributed into two groups: low-AMF (V < 20 cm³) and high-AMF (V > 20 cm³), and early and long-term outcomes were compared by univariable and multivariable analyses.ResultsThere were 92 SLT: 73M/19F, 53 ± 11 [14–68] years old. 30-Day mortality (low-AMF vs. high-AMF): 5 (5.4%) vs. 15 (16.3%), p = 0.014. Patients developing primary graft dysfunction within 72 h post-transplant, and those dying within 30 days post-transplant presented higher AMF volumes: 21.1 ± 19.8 vs. 43.3 ± 24.7 cm³ (p = 0.03) and 24.4 ± 24.2 vs. 56.9 ± 63.6 cm³ (p < 0.01) respectively. Overall survival (low-AMF vs. high-AMF) (1, 3, and 5 years): 85%, 81%, 78% vs. 55%, 40%, 33% (p < 0.001).Factors predicting 30-day mortality were: BMI (HR = 0.77, p = 0.011), AMF volume (HR = 1.04, p = 0.018), CPB (HR = 1.42, p = 0.002), ischaemic time (HR = 1.01, p = 0.009).Factors predicting survival were: AMF volume (HR = 1.02, p < 0.001), CPB (HR = 3.17, p = 0.003), ischaemic time (HR = 1.01, p = 0.001).ConclusionPreoperative radiological assessment of mediastinal fat dimensions and volumes may be a useful tool to identify fibrotic patients at higher risk of mortality after single lung transplantation.     

Oxidized casein impairs antioxidant defense system and induces hepatic and renal injury in mice

ScopeOxidized protein products (OPPs) can be easily found in meat and milk during processing and storage. Evidence supports that accumulation of endogenous OPPs plays a negative role in physiological metabolism. However, the impacts of dietary OPPs and the mechanisms have not been elucidated yet. The present study evaluated whether oral oxidized casein would destruct the antioxidant defense system and cause potential oxidized injury in mice liver and kidney.Methods and resultsWe performed oxidized casein (modified respectively by H₂O₂–Cu and HClO) feeding experiments using KM mice (20–22 g). A 10-weeks feeding of oxidized casein as basal protein caused oxidative stress by increasing protein carbonylation (PC), advanced oxidation protein products (AOPPs), dityrosine (Dityr), lipid peroxidation and ROS levels in mice liver, kidney and blood (P < 0.05). In mice liver and kidney, the mRNA expression of Nrf2, γ-GCS, HO-1, GPX-3, and GPX-4 up-regulated, the protein level of Nrf2 in nucleus increased. However, activities of anti-oxidant enzymes (CAT, SOD, and GPX) decreased (P < 0.05). Moreover, histopathological examination displayed the formation of fibrous septa in mice liver and kidney after oxidized casein feeding.ConclusionOxidized casein impairs antioxidant defense system and induces hepatic and renal fibrosis.     

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

BACKGROUNDIn a previous paper, we reported a high prevalence of donor-specific antibody (DSA) in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.AIMTo clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients.METHODSWe performed a retrospective analysis of 123 pediatric liver transplantation (LT) recipients who participated in yearly follow-ups including Luminex testing for DSA at our center. The cohort was split into two groups according to the DSA status (DSA-positive n = 54, DSA-negative n = 69). Groups were compared with regard to liver function, biopsy findings, graft survival, need for re-LT and immunosuppressive medication.RESULTSDSA-positive pediatric patients showed a higher prevalence of chronic rejection (P = 0.01), fibrosis (P < 0.001) and re-transplantation (P = 0.018) than DSA-negative patients. Class II DSAs particularly influenced graft survival. Alleles DQ2, DQ7, DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis. Mean fluorescence intensity levels and DSA number did not impact graft survival. Previous episodes of chronic rejection might lead to DSA development.CONCLUSIONDSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT. Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibody-mediated rejection improved early identification of patients at risk of graft loss.     

抗纤散在慢性乙型肝炎抗纤维化治疗中的作用研究

目的:研究抗纤散(KXS)在慢性乙型肝炎(CHB,慢乙肝)抗纤维化治疗中的作用.方法:将40例慢性乙型肝炎患者随机分为两组,治疗组及对照组各20例.对照组给予保肝、退黄、降酶药物治疗,治疗组每日给予抗纤散汤剂200ml,分两次口服,其他治疗方案同对照组.治疗两个疗程后,分别检测两组患者血清乙肝标志物及丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、总胆红素(TBil)、Ⅲ型前胶原PCⅢ、层粘连蛋白(LN)、透明质酸(HA)的含量.结果:治疗组13例HBeAg( )阴转7例,对照组11例HBeAg( )只有1例转阴,治疗组患者血清ALT、AT、TBil、PCⅢ、LN、HA含量检测提示均显著低于对照组(P＜0.05).结论:抗纤散在慢性乙型肝炎抗纤维化治疗中有确切疗效.     

疏肝补肾方对肝纤维化大鼠睾丸酮及促肾上腺皮质激素的调节

目的:观察疏肝补肾方对肝纤维化大鼠睾丸酮(Te)、促肾上肾皮质激素(ACTH)的调节作用。方法:采用二甲基亚硝胺复制大鼠慢性肝损伤模型,检测不同剂量组大鼠的血清Te、ACTH水平。结果:肝纤维化大鼠血清Te、ACTH水平明显低于正常对照组(P<0.01),经中药治疗后,两组大鼠肝组织病理改变基本恢复正常,其血清Te、ACTH亦趋于正常(P>0.05)。组间差异不明显(P>0.05)。结论:疏肝补肾方在抗肝纤维化同时具有改善激素紊乱的作用。     

中药复方金三莪治疗肝纤维化的临床研究

目的:观察中药复方金三莪在慢性乙型肝炎患者中抗肝纤维化的疗效.方法:选取147例慢性乙型肝炎患者,随机分为中药组、γ-IFN组及对照组,分别采用金三莪、γ-IFN及一般护肝治疗.观察治疗前后及随访3个月时,各组患者症状、体征、肝功能、肝纤维化指标及B超影像学变化,按非创伤性指标的肝纤维化疗效评估标准,评价中药复方金三莪抗肝纤维化疗效.结果:中药组患者治疗后总有效率为80.8%,与对照组(41.3%)比较差异有显著性意义(P＜0.01),而与γ-IFN组(81.6%)比较差异无显著性意义(P＞0.05);中药组患者治疗后肝功能指标、肝纤维化指标、B超影像学结果均较对照组有明显的改善(P＜0.01);与γ-IFN组患者比较差异无显著性意义(P＞0.05),随访3个月各项指标仍维持稳定,治疗过程中未出现不良反应.结论:中药复方金三莪能有效降低患者肝纤维化指标,改善患者肝功能,有明显的抗肝纤维化疗效,与γ-IFN组相比抗肝纤维化疗效差异无显著性意义,且无γ-IFN所易致的发热、骨髓抑制等副作用,值得在临床上广泛应用.     

胰腺星状细胞凋亡研究进展

胰腺纤维化是各类慢性胰腺炎的共同特征,胰腺星状细胞(PSC)在胰腺纤维化进程中起重要作用。诱导胰腺星状细胞发生凋亡不仅可抑制纤维化的进展,而且还能为慢性胰腺炎的治疗提供可能的理想途径。但目前胰腺星状细胞凋亡的具体机制尚未完全明了,国内尚无相关报道。     

Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases

AIM: To evaluate the prevalence of genetic and acquired prothrombotic risk factors and their association with the extent of fibrosis and fatty infiltration in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Forty-four patients with chronic hepatitis (28 men and 16 women, with mean age of 45±11 and 49±12 years, respectively) constituted the patient population of this study. The groups were divided as follows: 15 patients with fatty liver (FL); 15 with non-alcoholic steatohepatitis (NASH); 14 with chronic viral hepatitis (CH) diagnosed by histology and liver technetium scan or ultrasound; and 10 healthy individuals. Thrombophilic, coagulation factors and genetic mutations were diagnosed by standard hemostatic and molecular coagulation assays. RESULTS: Activated protein C (APC) resistance and protein S were the most prevalent thrombotic risk factors (6% and 10% in NAFLD vs 21% and 14% in CH; P<0.01 and P<0.05, respectively). One thrombotic risk factor was identified in 41% of patients (23% mild fibrosis, 18% severe fibrosis) and two thrombotic risk factors in 6% of patients with NAFLD and severe fibrosis. While no differences in APC ratio, lupus anticoagulant, fibrinogen, factor V Leiden, prothrombin, and MTHFR mutation were found. Protein S levels were significantly lower in NASH patients than in patients with FL alone (92±19 vs 106±2, P<0.01). Protein C levels were markedly higher in patients with NAFLD and mild or severe fibrosis as compared to the patients with CH, respectively (128±40 vs 96±14, P<0.001 or 129±36 CONCLUSION: Up to 46% of patients with NAFLD may have thrombotic risk factors, and the presence of thrombotic risk factors is correlated with the extent of hepatic fibrosis, suggesting a crucial role of the coagulation system in the pathogenesis of hepatic fibrosis.