1.Effects of colchicine via Hippo signaling pathway on mouse liver cancer and its mechanism research
Yanyan XU ; Lele ZHU ; Miaomiao LI ; Yan YANG
Acta Universitatis Medicinalis Anhui 2024;59(2):185-192
Objective To investigate the effect and mechanism of colchicine on mouse liver cancer via Hippo sig-naling pathway.Methods The 6-week-old male C57BL/6J mice were randomly divided into 3 groups:diethylni-trosamine(DEN)/carbon tetrachloride(CCl4)/ethanol(C2H5OH)induced mouse liver cancer model and col-chicine(0.1 mg/kg)intervention were established in control group,model group and colchicine group.From week 1st to week 2nd,the model group and the colchicine group were intraperitoneally injected with 1.0%DEN once a week.From week 3rd to week 7th,20%CCl4 dissolved in olive oil solution(5 ml/kg)was intragastric ad-ministration twice a week.From week 8th to week 18th,20%CC14 dissolved in olive oil solution(6 ml/kg)was intragastric twice a week.The colchicine group was given continuous intragastric administration for 20 weeks.The control group was given the corresponding solvent.Liver index,alanine aminotransferase(ALT)and aspartate ami-notransferase(AST)serum biochemical indexes were detected.Western blot and immunofluorescence were used to detect the expression levels of MST1,pYAP,YAP,pTAZ and TAZ proteins in liver tissues of mice in each group.Results The liver surface of mice in the control group was smooth and soft,while the liver of mice in the model group was rough and hard with granular nodules.The above lesions were significantly improved in the colchicine group.HE staining showed that the liver lobular structure of mice in the control group was normal,while the liver lobular structure of mice in the model group was disordered,with a small amount of fat droplets,extensive tissue necrosis,inflammatory cell infiltration,and fat vacuoles.The degree of liver lesions of mice after colchicine inter-vention was significantly reduced.The results of immunofluorescence and Western blot showed that compared with the control group,the protein expression levels of pYAP and pTAZ in liver tissue of model group mice were signifi-cantly decreased,while the protein expression levels of MST1,YAP and TAZ increased.After colchicine interven-tion,the protein expression levels of MST1,pYAP and pTAZ were significantly up-regulated,while the protein ex-pression levels of YAP and TAZ were down-regulated.Conclusion The therapeutic effect of colchicine on mouse liver cancer may be related to its activated Hippo signaling pathway.
2.Application of modified percutaneous closure in the treatment of ventricular septal rupture after acute myocardial infarction
Zirui SUN ; Yu HAN ; Yuhao LIU ; Jicheng JIANG ; Yan HAN ; Lele BEN ; Jing ZHANG ; Chuanyu GAO
Chinese Journal of Cardiology 2024;52(12):1412-1416
Objective:To investigate the effect of modified percutaneous closure in the treatment of ventricular septal rupture.Methods:This study is a retrospective cohort study. Forty-four patients with ventricular septal rupture who underwent percutaneous closure at the Fuwai Central China Cardiovascular Hospital from December 2017 to October 2023 were included. According to the closure method, patients were divided into the modified group (11 cases) and the traditional group (33 cases). Surgical success was defined as successful placement of the occluder. The operation time, X-ray intake, sheath bending rate, incidence of ventricular fibrillation and pericardial tamponade, and postoperative residual shunt were compared between the two groups.Results:The age of the patients was (75.0±5.7) years, with 20 (45%) males. There were 3 cases of operation failure in the traditional group, while all patients in the modified group were successfully occluded. The procedure time in the modified group was shorter than that in the traditional group (40 (35, 45) min vs. 60 (50, 65)min, P<0.001); X-ray dose intake was lower ((442.43±73.26)mGy vs. (784.45±247.78)mGy, P<0.001). There was no occurrence of sheath bending in the modified group, while the incidence of sheath bending in the traditional surgery group was 46% (15/33), and the difference was statistically significant ( P=0.017). Intraoperative ventricular fibrillation and pericardial tamponade occurred in 7 cases (21%) and 2 cases (6%) in the traditional group respectively, while none occurred in the modified group, but the differences between the groups were not statistically significant (both P>0.05). There was no significant difference in residual shunt between the two groups (3.6 (2.5, 4.3) mm vs. 4.0 (3.5, 4.5) mm, P=0.506). Conclusion:The procedure of modified ventricular septal rupture closure is more simplified, with a lower incidence ofventricular fibrillation and pericardial tamponade.
3.TIPS combined with catheter-directed thrombolysis and percutaneous transhepatic portal vein catheterization thrombolysis for acute non-cirrhotic non-neoplastic portal vein thrombosis
Jie JI ; Bifei WU ; Lele YAN ; Penghua LYU ; Weizhong ZHOU ; Fu'an WANG
Chinese Journal of Interventional Imaging and Therapy 2024;21(10):583-587
Objective To comparatively observe the value of TIPS combined with catheter-directed thrombolysis and percutaneous transhepatic portal vein catheterization thrombolysis for acute non-cirrhotic non-neoplastic portal vein thrombosis(PVT).Methods Twenty-five patients with acute non-cirrhotic non-neoplastic PVT were retrospectively enrolled and clustered into TIPS group(n=17,underwent TIPS combined with catheter-directed thrombolysis)and liver puncture group(n=8,underwent percutaneous transhepatic portal vein catheterization thrombolysis)according to the access of thrombolysis.The technical success rate,duration of catheter-directed thrombolysis,complications within 7 days,as well as portal vein patency 3 months after treatment,Child-Pugh grading of liver function and occurrence of hepatic encephalopathy(HE)were recorded and compared between groups.Results The technical success rates were both 100%in 2 groups.There was no significant difference of the duration of catheter-directed thrombolysis between groups(P>0.05).The thrombolytic effect in TIPS group was better than that in liver puncture group(P<0.05).No significant difference of the occurrence of bleeding within 7 days was found between groups(P>0.05).After 3 months'follow-up,the degree of portal vein patency in TIPS group was higher than that in liver puncture group(P<0.05).No significant difference of Child-Pugh grading of liver function nor occurrence of HE was found between groups(both P>0.05).Conclusion Both TIPS combined with catheter-directed thrombolysis and percutaneous transhepatic portal vein catheterization thrombolysis were effective for treating acute non-cirrhotic non-neoplastic PVT,and the thrombolytic effect of the former was better than the latter.
4.Effects of Jiaji electroacupuncture combined with treadmill training on tibial reconstruction and VEGF expression in rats with sciatic nerve dissection injury
Yan WANG ; Jincao ZHI ; Lele ZHAO
Chinese Journal of Rehabilitation Medicine 2024;39(10):1401-1408
Objective:To observe the effects of Jiaji electroacupuncture combined with treadmill running training on tibial bone density,volume and number of blood vessels and VEGF expression after sciatic nerve amputation injury in rats,and provide theoretical basis for promoting tibial reconstruction after Jiaji electroacupuncture combined with treadmill running training. Method:A total of 180 SD rats were randomly divided into normal control group,model control group,Jiaji electroacupuncture group,treadmill group,combination treatment group(Jiaji electroacupuncture+treadmill),with 36 rats in each group.After 2,4 and 8 weeks of postoperative intervention,the rats were divided into 3 subgroups,12 in each subgroup.The model was made by suture of sciatic nerve dissociation injury.The normal control group received no intervention;the model control group received no intervention post-modeling.The Jiaji electroacupuncture group,treadmill group and combined group began to receive Jiaji electroacupunc-ture,treadmill training and combined treatment respectively on the 3rd day after surgery.Bone density of tibia was analyzed by Micro-CT scan.The number and volume of the proximal tibial vessels were analyzed by angi-ography.The expression of VEGF mRNA and protein in tibia was detected by RT-PCR and Western Blot.VEGF concentration in tibial bone marrow was determined by ELISA. Result:At 2,4 and 8 weeks post-intervention,the model control group showed significantly lower tibial bone mineral density,proximal vascular volume and quantity,VEGF mRNA and protein expression in bone tissue,and VEGF concentration in bone marrow compared to the normal control group at the same time point(P<0.05).However,overtime,the tibial bone mineral density,the volume and number of proximal blood ves-sels,VEGF mRNA and protein expression in bone tissue and VEGF concentration in bone marrow of rats in the Jiaji electroacupuncture group,treadmill group and combination group were significantly higher than those in the model control group at the same time point(P<0.05),and the combination group showed the most pro-nounced effects(P<0.05). Conclusion:Jiaji electroacupuncture combined with treadmill training may improve tibial bone mineral density by up-regulating the expression of VEGF in tibia and bone marrow.
5.Recent Advances of Animal Models of Renal Interstitial Fibrosis
Can LAI ; Lele LI ; Tala HU ; Yan MENG
Laboratory Animal and Comparative Medicine 2023;43(2):163-172
Renal interstitial fibrosis is a common pathway in the progression of many renal diseases. Whether it is chronic kidney disease or acute kidney injury that cannot be fully recovered, the progression process mostly enters end-stage renal failure after renal interstitial fibrosis. The animal model of renal interstitial fibrosis is an important research tool for exploring the pathogenesis of renal interstitial fibrosis and new diagnostic and treatment methods. Different animal models have their own characteristics. Researchers can establish different models based on their own experience and experimental purposes, and carry out scientific research on this basis to provide more new methods for the prevention and treatment of kidney diseases. The authors focused on several common animal models of renal interstitial fibrosis to provide the reference for related researchers, including surgical models induced by unilateral ureteral obstruction, ischemia-reperfusion injury, 5/6 nephrectomy, and microembolization; chemical models induced by cyclosporine A, adriamycin, aristolochic acid, mercuric chloride(HgCl2), gentamicin, cisplatin, and adenine; transgenic hybridization and kidney injury molecule 1 (KIM-1) induced transgenic modification model; composite model induced by bilateral ischemia-reperfusion injury (BIRI) combined with gentamicin, unilateral nephrectomy combined with angiotensin II (Ang II), and unilateral ischemia-reperfusion injury (UIRI) combined with pLVX-shTNC plasmid.
6.Role of Netrin-1 and Slit2 in regulating the imbalance of Rho GTPases after Jiaji electroacupuncture combined with nerve mobilization for sciatic nerve injury in rabbits
Li ZHANG ; Shanhong WU ; Lele ZHAO ; Yan WANG
Chinese Journal of Rehabilitation Theory and Practice 2022;28(8):914-926
ObjectiveTo observe the effect of Jiaji electroacupuncture combined with neurodynamic mobilization on nerve conduction velocity and the expression of Netrin-1, Slit2 and Rho GTPases after sciatic nerve injury in rabbits. MethodsA total of 216 New Zealand rabbits were randomly divided into nomal control group (NC), vector virus group (VV), Jiaji electroacupuncture combined with neurodynamic mobilization group (EN), Netrin-1 group (N1), Slit2 group (S2) and N1+S2 group. Each group was divided into three subgroups according to the postoperative treatment time points (one, two and four weeks), with twelve rabbits in each subgroup. The rabbit model of Sunderland Ⅲ degree injury of the left sciatic nerve was established by clamping method. There was no intervention in NC, and virus was injected during the preparation of the model. Jiaji electroacupuncture and neurodynamic mobilization were administrated three days after operation in EN group. Nerve conduction velocity of sciatic nerve was measured with electromyography. The sciatic nerve and L4-6 spinal cords were obtained, the expression of Netrin-1 and Slit2 mRNA were detected real-time quantitative polymerase chain reaction and immunofluorescence double staining, and the expression of Rac1, Cdc42 and RhoA protein were observed via Western blotting. ResultsOne, two and four weeks after modeling, the nerve conduction velocity was more in EN group and N1+S2 group than in N1 group and S2 group (P < 0.05); the Netrin-1 and Slit2 mRNA expression were higher in the EN group and N1+S2 group than in the VV group and NC group (P < 0.05); the protein expression of Rac1 and Cdc42 were higher, and the protein expression of RhoA was lower in EN group and N1+S2 group than in N1 group, S2 group and VV group (P < 0.05). ConclusionJiaji electroacupuncture combined with nerve mobilization may promote the axonal regeneration by regulating the expression of Netrin-1 and Slit2, adjusting the imbalance of Rho GTPases enzyme system, and then promoting cytoskeleton reorganization and peripheral nerve regeneration after injury.
7.Screening tools, predictors and predictive models for post-stroke delirium
Lele FAN ; Liang MA ; Yan XU ; Jie YU ; Xiao MIAO
International Journal of Cerebrovascular Diseases 2022;30(8):616-620
Delirium is a common complication after stroke. Post-stroke delirium is associated with the poor outcome and increased mortality. This article reviews the screening tools, predictive factors and predictive models of post-stroke delirium.
8.Construction and validation of predictive model for post-stroke delirium in patients with acute ischemic stroke
Lele FAN ; Liang MA ; Yan XU ; Jie YU ; Xiao MIAO
International Journal of Cerebrovascular Diseases 2022;30(9):664-670
Objective:To construct a predictive model of post-stroke delirium (PSD) in patients with acute ischemic stroke (AIS), and to verify its predictive value.Methods:Patients with AIS admitted to the Department of Neurology, Lianyungang Hospital Affiliated to Xuzhou Medical University from February to May 2022 were enrolled prospectively. They were divided into modeling group and validation group according to the order of enrollment. Depending on whether the patients had delirium or not, the patients in the modeling group were divided into delirium group and non-delirium group. The independent risk factors for PSD were determined by multivariable logistic regression analysis, and the prediction model of PSD was constructed accordingly. The predictive value of the model was verified by the receiver operating characteristic curve. Results:Three hundred and fifty patients with AIS were included in the modeling group, of which 71 (20.28%) had PSD. The validation group included 150 patients with AIS, and 36 of them (24.00%) had PSD. Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.036, 95% confidence interval [ CI] 1.000-1.074; P=0.050], National Institutes of Health Stroke Scale (NIHSS) score ( OR 1.607, 95% CI 1.438-1.797; P<0.001), neutrophil/lymphocyte ratio (NLR) ( OR 1.135, 95% CI 1.016-1.267; P=0.025), and atrial fibrillation ( OR 5.528, 95% CI 1.315-23.245; P=0.020) were the independent risk factors for PSD. The predictive model was Z=0.036×age+0.475×NIHSS score+0.127×NLR+1.710×assignment of atrial fibrillation - 10.160. The area under the curve of the model was 0.935, and the sensitivity and specificity were 97.2% and 82.5% respectively. Conclusion:This model can effectively predict the PSD risk of patients with AIS, with higher sensitivity and specificity, and can provide a basis for PSD screening of patients with AIS.
9.Investigate developmental coordination disorder of kindergarten children in Zhejiang Province
Wencong RUAN ; Jing LI ; Yinjia ZHANG ; Shuhong ZHENG ; Dong WANG ; Hong YU ; Jinping CHEN ; Yinyan BAO ; Li SHAO ; Lele FU ; Yan ZOU ; Jing HUA ; Haifeng LI
Chinese Journal of Preventive Medicine 2022;56(6):838-842
In order to investigate developmental coordination disorder (DCD) of kindergarten children in Zhejiang province, 200 ordinary kindergartens were randomly selected by stratified random sampling in 11 prefecture-level cities of Zhejiang Province, and 38 900 children from 1 000 classes in each grade were then randomly selected into the study from June 2019 to December 2019. The Little DCD Questionnaire and a self-designed questionnaire were used to screen the DCD of those children. There were 36 807 valid questionnaires, and 6.50% (2 391/36 807) of them were positive results. The results showed that boy, age ≤5 years, overweight or obesity, left handedness, comorbidity with motor or developmental disorders and premature infants were risk factors of DCD in children. As for parents and families, maternal gestational age<20 years, maternal overweight or obesity before pregnancy, low-middle level education of parents, direct family and low income of family were also associated with DCD in children. Therefore, it is necessary to conduct early prevention and intervention strategies targeting on identified risk factors among relevant population.
10.Investigate developmental coordination disorder of kindergarten children in Zhejiang Province
Wencong RUAN ; Jing LI ; Yinjia ZHANG ; Shuhong ZHENG ; Dong WANG ; Hong YU ; Jinping CHEN ; Yinyan BAO ; Li SHAO ; Lele FU ; Yan ZOU ; Jing HUA ; Haifeng LI
Chinese Journal of Preventive Medicine 2022;56(6):838-842
In order to investigate developmental coordination disorder (DCD) of kindergarten children in Zhejiang province, 200 ordinary kindergartens were randomly selected by stratified random sampling in 11 prefecture-level cities of Zhejiang Province, and 38 900 children from 1 000 classes in each grade were then randomly selected into the study from June 2019 to December 2019. The Little DCD Questionnaire and a self-designed questionnaire were used to screen the DCD of those children. There were 36 807 valid questionnaires, and 6.50% (2 391/36 807) of them were positive results. The results showed that boy, age ≤5 years, overweight or obesity, left handedness, comorbidity with motor or developmental disorders and premature infants were risk factors of DCD in children. As for parents and families, maternal gestational age<20 years, maternal overweight or obesity before pregnancy, low-middle level education of parents, direct family and low income of family were also associated with DCD in children. Therefore, it is necessary to conduct early prevention and intervention strategies targeting on identified risk factors among relevant population.

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