AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1～4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.

AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1～4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

[摘 要] 目的：探讨四氧化三铁（Fe3O4）纳米粒子（PION）作为药物载体增强二氢卟吩e6（chlorin e6，Ce6）在胶质瘤中的增效作用。方法：采用高温降解法和相转移法制备PEG-Fe3O4@Ce6复合纳米粒子（PION@E6），用水合粒径分析、透射电镜、胶体稳定性分析、紫外可见光吸收光谱等方法对PION@E6进行鉴定。CCK-8法检测胶质瘤U251细胞的增殖活性，流式细胞术检测细胞的凋亡水平，DCFH-DA探针法检测细胞中活性氧（reactive oxygen species，ROS）的水平。构建BALB/c-nu裸鼠胶质瘤U251细胞移植瘤模型，动物活体荧光成像术及磁共振成像（MRI）观察PION@E6及Ce6在移植瘤中的潴留时间，比较PION@E6声动力治疗组及Ce6声动力治疗组的第28天生存情况及肿瘤体积。结果：PION@E6的核心粒径为10 nm、水合粒径为（37.86±12.90）nm，具有良好的水溶性和稳定性；吸收光谱及XRD图谱显示Ce6已经负载到Fe3O4纳米粒子上。与Ce6声动力组比较，PION@E6声动力组U251细胞的增殖活性显著下降（P<0.05），细胞凋亡率显著升高（均P<0.05），细胞中ROS水平显著升高（P<0.05）。荷瘤裸鼠胶质瘤U251细胞移植瘤治疗实验结果显示，与Ce6声动力治疗组比较，PION@E6声动力治疗组裸鼠移植瘤组织中潴留时间显著延长（P<0.05），存活的裸鼠数显著增多，移植瘤体积显著缩小（P<0.01）。结论：Fe3O4纳米粒子对Ce6介导的胶质瘤U251细胞声动力治疗具有明显的增效作用。

[摘 要] 目的：探讨超微氧化铁纳米粒子（ultrasmall iron oxide nanoparticle，USIONP）对人肝细胞癌HepG2细胞迁移和侵袭的影响及其可能的机制。方法：采用粒径分析仪和透射电镜分别分析USIONP的水合粒径和核心粒径，Zeta电位和胶体稳定性实验分析USIONP的分散性及其稳定性以鉴定USIONP的成功制备；用不同质量浓度USIONP（0、50、100、200 μg/ml）或200 μg/ml USIONP+5 mmol/L 3-MA（自噬抑制剂）联合处理HepG2细胞，CCK-8法检测HepG2细胞的增殖活力，Transwell法检测细胞的迁移和侵袭能力，WB实验检测自噬标志物Beclin1、LC3、p62的表达，2’,7’-二氯二氢荧光素二醋酸（DCFH-DA）法测定细胞内活性氧（ROS）水平，铁离子比色法检测细胞内铁离子水平。结果：USIONP的平均水合粒径为（37.86±12.90） nm、核心粒径约10 nm，Zeta电位为–23.8 mV，有良好的水溶分散性，证实了USIONP的成功制备。随USIONP质量浓度升高和处理时间延长，HepG2细胞的增殖活力明显降低（均P<0.05）；与对照组相比，200 μg/ml USIONP处理HepG2细胞24 h后，迁移、侵袭细胞数量均显著减少（均P<0.05），而3-MA能够部分抵消上述影响（均P<0.05）。与对照组相比，100、200 μg/ml USIONP处理组的HepG2细胞中Beclin1和LC3Ⅱ蛋白相对表达水平均显著升高（均P<0.05），而p62蛋白表达水平下降（均P<0.05）；200 μg/ml USIONP可显著提高细胞内ROS水平与铁离子水平，而加入3-MA可阻断其作用（均P<0.05）。结论：USIONP能促进HepG2细胞发生自噬，而自噬通路激活后降解USIONP释放铁离子和导致细胞ROS水平升高，从而抑制HepG2细胞的迁移和侵袭。