1.Establishment of a New Hyperglycemic Obesity Cardiac Dysfunction Mouse Model with Triacsin C
Xiaona ZHAO ; Peng WANG ; Maoqing YE ; Xinkai QU
Laboratory Animal and Comparative Medicine 2024;44(6):605-612
Objective This study aims to establish a novel hyperglycemic obesity mouse model by utilizing Triacsin C, an inhibitor of acyl-CoA synthetase long-chain family member 1 (ACSL1), combined with a high-fat diet, to simulate the changes in adipose tissue and cardiac function observed in patients with obesity-related type 2 diabetes. MethodsTwenty adult SPF-grade male C57BL/6J mice were randomly divided into two groups: the Control group (injected intraperitoneally with citric acid-sodium citrate buffer, Con group) and the TC group (injected intraperitoneally with Triacsin C, TC group). After four consecutive weeks of intraperitoneal injections, both groups were fed high-fat diets. Body weight and glucose tolerance of the mice were assessed every eight weeks. The models were considered successful if fasting blood glucose exceeded 8 mmol/L or blood glucose was above 15 mmol/L two hours after glucose injection. Cardiac function, including ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), end-diastolic interventricular septal thickness (EDIVS), left ventricular ejection fraction (LVEF), and left ventricular short-axis fractional shortening (FS), was measured by echocardiography. HE staining was used to detect the changes in epididymal white adipose tissue (WAT) and brown adipose tissue (BAT). Immunofluorescence technology was used to analyze changes in CD31 and UCP1 in BAT. ACSL1 expression in myocardial tissue was tested by Western blotting. ResultsThe fasting blood glucose levels were (8.14±1.43) mmol/L in the Con group and (8.18±0.85) mmol/L in the TC group (P>0.05) , and the 2-hour postprandial blood glucose levels were (19.8±4.01) mmol/L in the Con group and (22.60±3.97) mmol/L in the TC group (P<0.05). This indicated that both groups of diabetic mouse models were successfully established. Compared to the Con group, the TC group showed poor glucose tolerance; significant decreases in LVEDD, LVEF and FS (P<0.05); significant increases in WAT and BAT areas (P<0.05); significant decreases in CD31 and UCP1 expression (P<0.05); and a significant decrease in the expression of ACSL1 in myocardial tissues (P<0.05). ConclusionCompared with the high-fat diet-induced type 2 diabetes model, the new hyperglycemic obesity and cardiac dysfunction mouse model, created by the combination of Triacsin C and a high-fat diet, is feasible and allows for easier observation of brown adipose tissue whitening, insulin resistance and cardiac dysfunction.
2.Efficacy of colonoscopy combined with X-ray stent implantation in the treatment of colorectal cancer intestinal obstruction and risk factors of postoperative delayed bleeding
Wenmei CHEN ; Xinkai ZHAO ; Minxia QIU ; Cancan KONG ; Jisun KUANG ; Yonghua HUANG ; Wei MAO
Chinese Journal of Postgraduates of Medicine 2022;45(5):428-435
Objective:To explore the effect of colonoscopy combined with X-ray stent implantation in the treatment of colorectal cancer intestinal obstruction, and analyze the risk factors of postoperative delayed bleeding.Methods:From November 2016 to December 2020, 382 patients with colorectal cancer intestinal obstruction in Hainan Provincial People′s Hospital were selected. Among them, 254 patients were treated by colonoscopy combined with X-ray stent implantation (stent implantation group), and 128 patients were treated by emergency radical resection (control group). The operation time, intraoperative bleeding, number of lymph node dissections, tumor diameter, incision length, exhaust time, hospital stay, fluid feeding time, fistulation, perioperative death and delayed bleeding were compared between 2 groups. Based on the random number generated by the computer, 254 patients who underwent colonoscopy combined with X-ray stent implantation were divided into training set (190 cases) and test set (64 cases) according to the ratio of 3∶1. In the training set, the patients were divided into postoperative delayed bleeding and non postoperative delayed bleeding, and the clinical indicators were compared; the multivariate Logistic regression model was performed to analyze the independent risk factors of postoperative delayed bleeding, and the prediction model of postoperative delayed bleeding was established and verified according to the independent risk factors.Results:All patients in the stent implantation group were successfully implanted with stents, and the obstructive symptoms were relieved 24 to 48 h after operation. The operation time, intraoperative bleeding, incision length, fistulation rate, exhaust time, hospital stay and fluid feeding time in stent implantation group were significantly lower than those in control group: (88.89 ± 5.97) min vs. (116.58 ± 20.17) min, (33.18 ± 16.52) ml vs. (92.35 ± 25.64) ml, (4.50 ± 0.96) cm vs. (14.26 ± 2.88) cm, 10.24% (26/254) vs. 98.44% (126/128), (1.18 ± 0.58) d vs. (1.53 ± 0.77) d, (7.69 ± 5.12) d vs. (12.88 ± 6.54) d and (1.46 ± 0.68) d vs. (2.12 ± 1.18) d, the number of lymph node dissections was significantly higher than that in control group: (19.88 ± 4.47) lymph nodes vs. (17.47 ± 3.11) lymph nodes, and there were statistical differences ( P<0.01); there were no statistical differences in tumor diameter and perioperative fatality rate between 2 groups ( P>0.05). Among 190 patients in the training set, 18 patients had postoperative delayed bleeding, with an incidence of 9.47%; 172 cases did not have postoperative delayed bleeding. The age, course of obstruction, complete obstruction rate, intestinal almost occlusion rate under enteroscopy, intraoperative bleeding rate and preoperative intestinal surgery history rate in patients with postoperative delayed bleeding were significantly higher than patients without postoperative delayed bleeding: (69.52 ± 10.54) years old vs. (58.65 ± 15.87) years old, (14.56 ± 10.12) d vs. (8.13 ± 7.68) d, 11/18 vs. 20.35% (35/172), 11/18 vs. 16.28% (28/172), 7/18 vs. 11.63% (20/172) and 12/18 vs. 37.79% (65/172), and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistics regression analysis result showed that old age, long duration of obstruction, complete obstruction, almost intestinal obstruction under enteroscopy and intraoperative bleeding were independent risk factors for postoperative delayed bleeding in patients with colorectal cancer intestinal obstruction undergoing colonoscopy combined with X-ray stent implantation ( OR = 3.925, 4.802, 1.727, 2.710 and 2.581; 95% CI 1.352 to 8.330, 1.064 to 8.869, 1.063 to 2.804, 1.118 to 4.400 and 1.689 to 3.479; P<0.05 or<0.01), while the history of preoperative intestinal surgery was not related to postoperative delayed bleeding ( P>0.05). The consistency indexes of nomogram training set and test set were 0.742 and 0.726 (95% CI 0.684 to 0.845 and 0.640 to 0.812). The receiver operating characteristic (ROC) curve analysis results of 2 models showed that the area under the curve (AUC) of the training set nomogram model and Tree Augmented Na?ve Bayes (TAN) model was 0.758 and 0.752 respectively, and the AUC of the test set nomogram model and TAN model was 0.702 and 0.706 respectively. The prediction accuracy of training set nomogram model and TAN model was 84.74%(161/190) and 85.26%(162/190) respectively, the prediction accuracy of test set nomogram model and TAN model was 82.81%(53/64) and 84.38%(54/64) respectively. Conclusions:Colonoscopy combined with X-ray stent implantation is safe and feasible in patients with colorectal cancer intestinal obstruction. But for the old age, long duration of obstruction, complete obstruction, almost intestinal obstruction under colonoscopy and intraoperative bleeding, careful operation should be carried out to reduce the occurrence of postoperative delayed bleeding.
3.Effect and mechanism of targeted delivery of VEGF and CD47 dual-modifiedexosomes in treatment of acute kidney injury induced by heat stroke in rats in the desert dry hot environment.
Xiaobo HAN ; Xinkai DENG ; Hong LI ; Chao LIU ; Jiawei GAO ; Xiao LI ; Yahao CHAI ; Xiaoli HAN ; Hongwei HAN ; Yinjie ZHAO ; Xi YANG ; Lei ZHANG
Journal of Army Medical University 2024;46(18):2057-2068
Objective To develop an effective method for delivering VEGF and CD47 double-modified exosomes to treat renal damage induced by heat stroke so as to reduce and repair renal damage.Methods A plasmid fusion-expressing VEGF and CD47 targeting renal injury was constructed,transfected into rat bone marrow derived mesenchymal stem cells (BMMSCs),and then fusion-exosomes were isolated and extracted.Transmission electron microscopy,nanoparticle tracking analysis,and Western blotting were used to identify the obtained exosomes.Rats were intravenously injected with 200 μg of DiD-labeled unmodified exosomes,VEGF-modified exosomes and VEGF-CD47 double-modified exosomes,respectively,through the tail vein,and the effects of exosomes on the kidneys were detected and analyzed using a small animal in vivo imaging instrument.A total of 60 SD rats were randomly divided into 6 groups,with 10 rats in each group,that is,blank control group (group A),heat stroke-induced renal injury model receiving PBS in 12,24 and 36 h after modelling (group B),empty plasmid group (group C),Exos group (group D),ExosVEGF group (group E) and ExosVEGF-CD47.Kidney tissue and blood samples were collected in 72 h after 3 times of treatment.Pathological changes in kidney tissue were observed at the tissue level and the damage were scored.Changes in serum blood urea nitrogen (BUN)and serum creatinine (Scr)levels were detected to evaluate the therapeutic effect.Western blotting and qRT-PCR were used to analyze the expression of the pro-inflammatory factors TNF-α and NF-κB,the proliferation regulatory signaling molecules Ki67,FGF2,pAMPK and pERK,and the fibrosis regulatory molecule FGF23,in order to comprehensively analyze the effects on proliferation and inhibition of fibrosis.Results BMMSCs and ExosVEGF-CD47 were successfully isolated and characterized,and a rat model of acute kidney injury was effectively constructed.Higher fluorescence intensity was found in the kidney tissue of the Exos VEGF-CD47group than the Exos-Ctrl group and Exos VEGF group (P<0.05).In 72 h after treatment,the ExosVEGF-CD47 group had significantly lower serum BUN and Scr levels (P<0.0001),and notably lower Tubular casts score (P<0.0001),decreased levels of pro-inflammatory factors TNF-α and NF-κB (P<0.0001),up-regulated Ki67 and FGF2 expression (P<0.05),and down-regulated FGF23 expression (P<0.0001)when compared with the AKI+Exos group and AKI+ExosVEGF group.Conclusion VEGF and CD47 show promise in targeting acute kidney injury induced by heat stroke,effectively mitigate damage and facilitate repair,which may be due to exosome-mediated inhibition of renal tissue inflammation,promotion of proliferation,and inhibition of fibrosis.
4.New intraoral digital impression with pneumatic gingival retraction used in the restoration of crown for posterior teeth: a case report
Xinkai XU ; Meizi ZHANG ; Zhongning LIU ; Yuchun SUN ; Hu CHEN ; Weiwei LI ; Xiaoyi ZHAO ; Yongjie JIA ; Shujuan XIAO ; Chao MA ; Xiaojun CHEN ; Tengfei JIANG ; Xiaobo ZHAO ; Sukun TIAN
Chinese Journal of Stomatology 2024;59(10):1044-1048
In fixed prosthodontics, clear exposure of the preparation margin is the prerequisite for obtaining accurate digital impressions and improving the marginal fit of restorations. To resolve the issues associated with the cord retraction technique, such as pain, acute injury, and prolonged procedural time, this study proposes a new technology for intraoral digital impression taking with pneumatic gingival retraction. The new scanning head blows a high-speed airflow that instantaneously separates the free gingiva, locally exposing the subgingival preparation margin. Combined with the farthest point preservation stitching algorithm based on the distance from the normal vector and high-speed laser scanning photography, it achieves global preparation edge data and gingival reconstruction, realizing painless, non-invasive, and efficient precise acquisition of the preparation margin. Using this new technique, a patient with a full porcelain crown restoration on a posterior tooth was treated. The digital impression revealed a clear margin of the preparation, and the crown made from this data has a good marginal fit.