1.Exploring the Protective Effect of Modified Taoren Chengqi Decoction on Ventilator-induced Lung Injury in Rats Based on the Nrf2/GPX4-ferroptosis Pathway
Zhixia SUN ; Lihui WANG ; Hongliang SUO ; Hua LI ; Qian CHEN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1281-1288
Objective To explore the protective effect of modified Taoren Chengqi Decoction on ventilator-induced lung injury(VILI)in rats based on the nuclear factor-erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)-ferroptosis pathway.Methods Rats were randomly separated into the control group,the model group,the modified Taoren Chengqi Decoction group,the ML385(Nrf2 inhibitor)group,and the modified Taoren Chengqi Decoction+ML385 group,with 12 rats in each group.The rats in control group underwent tracheal intubation and kept spontaneous breathing.The rats of other groups were subjected to mechanical ventilation for 4 hours.Seven days before mechanical ventilation,medication treatment was carried out once a day for seven days.After mechanical ventilation,ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin 6(IL-6)in bronchoalveolar lavage fluid(BALF).Lung wet/dry weight ratio and lung tissue pathology of rat were detected.The reagent kit was applied to detect the content of glutathione(GSH),malonaldehyde(MDA),and Fe2+in rat lung tissue.The relative fluorescence intensity of reactive oxygen species(ROS)and 4-hydroxynonenal(4-HNE)in lung tissue was detected by immunofluorescence staining.The mRNA and protein expressions of solute carrier family 7 member 11(SLC7A11),Nrf2,GPX4 were detected.Results Compared with the control group,the lung tissue of rats in model group was severely damaged,the levels of TNF-α and IL-6 in BALF increased,lung wet/dry weight ratio,content of MDA and Fe2+,and the relative fluorescence intensity of ROS and 4-HNE increased,but the content of GSH,the mRNA and protein expressions of Nrf2,SLC7A11,and GPX4 decreased(P<0.01).Compared with the model group,the pathological damage of lung tissue in the modified Taoren Chengqi Decoction group was improved,the levels of TNF-α and IL-6 in BALF decreased,lung wet/dry weight ratio,content of MDA and Fe2+,the relative fluorescence intensity of ROS and 4-HNE decreased,the content of GSH,the mRNA and protein expressions of Nrf2,SLC7A11,and GPX4 increased(P<0.01).However,an opposite trend for corresponding indicators in the ML385 group was found(P<0.01).The pathological injury of lung tissue was alleviated,the levels of TNF-α and IL-6 in BALF decreased,lung wet/dry weight ratio,content of MDA and Fe2+,and the relative fluorescence intensity of ROS and 4-HNE decreased,GSH content,the mRNA expression of Nrf2,SLC7A11 and GPX4,as well as the protein expression of Nrf2 and GPX4 increased in modified Taoren Chengqi Decoction+ML385 group(P<0.01,P<0.05).Compared with ML385 group,the pathological injury of lung tissue was alleviated,the levels of TNF-α and IL-6 in BALF decreased,lung wet/dry weight ratio,the content of MDA and Fe2+,and the relative fluorescence intensity of ROS and 4-HNE decreased,GSH content,the mRNA and protein expression of Nrf2,SLC7A11 and GPX4 increased in modified Taoren Chengqi Decoction+ML385 group(P<0.01).Compared with the modified Taoren Chengqi Decoction group,the pathological damage in lung tissue of rats was intensified,the levels of TNF-α and IL-6 in BALF increased,lung wet/dry weight ratio,the content of MDA and Fe2+,the relative fluorescence intensity of ROS and 4-HNE increased,the content of GSH,the mRNA and protein expressions of Nrf2,SLC7A11,and GPX4 decreased(P<0.01)in modified Taoren Chengqi Decoction+ML385 group.Conclusion Modified Taoren Chengqi Decoction may improve rat VILI by activating the Nrf2/GPX4 pathway to inhibit ferroptosis.
2.Contrast-Enhanced Ultrasound in the Differential Diagnosis of Gallbladder Polypoid Lesions:A Multicenter Study
Ligang JIA ; Xiang FEI ; Xiang JING ; Mingxing LI ; Fang NIE ; Dong JIANG ; Shaoshan TANG ; Wei ZHANG ; Hong DING ; Tao SONG ; Qi ZHOU ; Bei ZHANG ; Zhixia SUN ; Xiaojuan MA ; Nianan HE ; Fang LI ; Yingqiao ZHU ; Wen CHENG ; Yukun LUO
Chinese Journal of Medical Imaging 2024;32(11):1147-1154
Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.
3.Effect of Jiawei Taoren Chengqi Decoction on autophagy in rats with mechanical ventilation-induced lung injury
Zhixia SUN ; Lihui WANG ; Hongliang SUO ; Qian CHEN
Tianjin Medical Journal 2023;51(12):1349-1355
Objective To explore the impact of Jiawei Taoren Chengqi Decoction on autophagy in rats with mechanical ventilation-induced lung injury(VILI)through adenylate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Sixty SPF male rats were randomly grouped into the sham operation group,the model group,the low-dose Jiawei Taoren Chengqi Decoction group(TCM-L group,2.85 g/kg),the high-dose Jiawei Taoren Chengqi Decoction group(TCM-H group,8.55 g/kg)and the high-dose Jiawei Taoren Chengqi Decoction + AMPK inhibitor Compound C group(TCM-H+CC group,Jiawei Taoren Chengqi Decoction 8.55 g/kg+ Compound C 250μg/kg),12 in each group.Oxygenation index(OI)was measured immediately after intubation and at 1 h,2 h and 4 h after mechanical ventilation.Bronchoalveolar lavage fluid(BALF)was collected after mechanical ventilation,levels of tumor necrosis factor(TNF)-α,interleukin(IL)-1β and IL-18 in BALF were detected by enzyme-linked immunosorbent assay(ELISA).Rats were sacrificed,and lung tissue was taken to measure the wet/dry weight(W/D)ratio.HE staining was used to observe pathological changes of lung tissue in each group of rats.Lung injury scores were carried out.Morphology of alveolar epithelial cells was observed by transmission electron microscopy.RT-qPCR was applied to detect mRNA expression levels of AMPK and mTORC1 in rat lung tissue.Western blot assay was applied to detect expression levels of AMPK,p-AMPK,mTORC1,p-mTORC1 and autophagy-related proteins in rat lung tissue.Results Compared with the sham group,the pathological damage of lung tissue was serious,lung W/D,levels of TNF-α,IL-1β and IL-18 in BALF,lung injury score,mTORC1 mRNA expression level,and p-mTORC1 protein expression were increased in the model group(P<0.05).OI values at 2 h and 4 h of mechanical ventilation,AMPK mRNA expression level,p-AMPK,LC3-II/LC3-I and Beclin-1 protein expression in lung tissue were decreased(P<0.05).Compared with the model group,the pathological damage of lung tissue was alleviated in the Chinese medicine-H group,and the trend of changes in related indexes was opposite to the above(P<0.05).Autophagosomes in alveolar epithelial cells were increased.Compound C attenuated the protective effect of Jiawei Taoren Chengqi Decoction on VILI rats(P<0.05).Conclusion Jiawei Taoren Chengqi Decoction may promote autophagy and reduce VILI in rats by activating AMPK/mTOR signaling pathway.
4.Effects of baicalin on depressive behavior and ERK/CREB protein in hippocampus of depression model mice
Zhixia JIA ; Jiali YANG ; Ganggang LI ; Zhuoqing CAO ; Zhigang XIAO ; Ye LU ; Guoqiang SUN ; Lin PEI
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(8):679-685
Objective:To explore the regulation effects of baicalin on the behavior as well as extracellular regulated protein kinase(ERK)and cAMP-response element binding protein(CREB) in chronic unpredictable mild stimulus(CUMS) model mice.Methods:Thirty ICR mice were randomly assigned to control(CON) group, model(CUMS) group, fluoxetine(FLU) group, baicalin high-dose(BA-H) group and baicalin low-dose(BA-L) group with 6 mice in each group.In addition to the CON group, the mice in the other four groups were modeled by CUMS method.The modeling was carried out for 42 days, and intragastric administration was carried out according to groups from the 21st day to the completion of modeling.After administration, the depression like behavior of mice was measured by sugar water preference test and water maze test.Western blot (WB) and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the protein level and mRNA level of ERK and CREB in mouse hippocampus respectively.SPSS 21.0 was used for statistical analysis.After normal test and variance homogeneity test, one-way ANOVA was used for multi group comparison, and Tukey test was used for pairwise comparison.Results:Results from the sugar preference experiment showed that compared with CON group, the sugar preference rate of CUMS group was decreased ((82.88±2.00)%, (64.49±1.24)%, t=19.11, P<0.05). Compared with CUMS group, sugar preference rate in FLU group ((81.90±1.19) %), BA-H group (77.86±2.51)%) and BA-L group ((67.98±2.56)%) increased ( t=24.83, 11.68, 3.00, all P<0.05). The results of water maze test showed that compared with CON group, the number of crossing platform ((6.33±0.82), (1.83±0.75), t=9.93, P<0.05) and the target quadrant residence time ((46.83±4.78)s, (24.25±6.12)s, t=7.13, P<0.05) of mice in CUMS group were decreased, but the the escape latency was prolonged ((14.88±3.00) s, (70.70±4.77) s, t=24.26, P<0.05). Compared with CUMS group, the number of crossing platform ((5.00±0.89)times, (5.17±0.75)times and (3.33±0.82) times, t=6.64, 7.67, 3.31, all P<0.05), and the residence time in the target quadrant ((36.80±2.66) s, (36.82±5.62) s, (33.28±3.56) s, t=4.61, 3.71, 3.13, all P<0.05) in FLU group, BA-H group and BA-L group increased, but the escape latencies were shortened ((23.37±4.86) s, (34.83±4.72) s, (62.15±5.30) s, t=17.02, 13.10, 2.94, all P<0.05). WB results showed that compared with CON group, the expression of ERK protein ((1.00±0.15), (0.36±0.10), t= 6.26, P<0.05) and CREB protein((1.00±0.12), (0.29±0.03), t=10.32, P<0.05) in hippocampus of mice in CUMS group decreased.Compared with CUMS group, ERK protein in hippocampus of mice in FLU, BA-H and BA-L groups increased ((0.87±0.05), (0.77±0.08), (0.67±0.03), t=8.25, 5.7, 5.39, all P<0.05), and CREB protein in FLU, BA-H and BA-L groups were also increased ((0.90±0.12), (0.84±0.14), (0.62±0.04), t=8.94, 6.59, 12.25, all P<0.05). qPCR results showed that compared with CON group, ERK mRNA ((1.00±0.03), (0.41±0.10), t=9.78, P<0.05) and CREB mRNA ((1.00±0.08), (0.61±0.12), t=4.62, P<0.05) were decreased in CUMS group.Compared with CUMS group, ERK mRNA in hippocampus of mice in FLU, BA-H and BA-L groups were increased ((0.71±0.08), (0.69±0.03), (0.59±0.04), t=4.15, 4.65, 2.84, all P<0.05), CREB mRNA in FLU group and BA-H group were increased ((0.87±0.08), (0.86±0.07), t=3.14, 3.19, all P<0.05). Conclusion:BA can improve the depression-like behavior of CUMS model mice.The mechanism of action may be related to the regulation of ERK and CREB proteins.
5.Progress of SLC13A5 as a potential pharmacological target of metabolic diseases
Qun NIU ; Qiushuang SUN ; Zhixia QIU ; Fang HUANG
Journal of China Pharmaceutical University 2020;51(5):607-613
The solute carrier (SLC) consists of more than 400 transport proteins mediating the influx and efflux of ions, nucleotides, sugars and other exogenous and endogenous substances across biological membranes. Over 80 SLC carrier proteins have been reported to be closely associated with human diseases, in which more than 30 SLC proteins have been regarded as the potential drug targets. SLC13A5 mediates transmembrane transport of substances such as citrate, which is connected with de novo lipid synthesis (DNL). Studies have found that SLC13A5 is related to metabolic diseases such as obesity, insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD). At present, there is no specific drug for clinical treatment of metabolic diseases caused by lipid metabolism disorders, especially NAFLD. Therefore, this paper summarizes the effect of SLC13A5 on metabolic regulation and its potential as a pharmacological target for metabolic diseases treatment, aiming to provide a reference for the research and development of drugs related to metabolic diseases.
6.Current status and enlightenment of teaching models in evidence-based medicine at home and abroad: a qualitative systematic review
Yingli LIU ; Yue LI ; Yufan WANG ; Shuqing YU ; Zhixia LI ; Beibei YUAN ; Shaowen TANG ; Tao WU ; Siyan ZHAN ; Feng SUN
Chinese Journal of Epidemiology 2020;41(12):2141-2148
Objective:To summarize the different teaching models and their effects in evidence-based medicine at home and abroad by qualitative method and systematic review.Methods:We searched the following databases (from inception to 13 May, 2019): PubMed, Embase, Proquest, Cochrane, Web of Science database and the Chinese databases (CNKI, Wanfang, SinoMed and VIP). To assess data strength and validity, risk of bias assessments were undertaken.Results:A total of 52 literatures were included in this study, including 21 Chinese-language literature and 31 English-language literature. PBL teaching model, mixed teaching model and workshop teaching model were the three teaching models with the largest number of studies in 20 teaching models.Conclusion:The evidence-based medicine teaching effect was closely related to the teaching models, so it is necessary to explore more suitable teaching models for the evidence-based medicine to improve the teaching effects.
7.Effect of miR-873 on cardiomyocyte apoptosis induced by hypoxia reoxygenation and its mechanism.
Yunjie ZHOU ; Huichao ZHANG ; Zhixia SUN
Journal of Central South University(Medical Sciences) 2019;44(8):857-863
To explore the role of miR-873 in cardiomyocyte injury induces by hypoxia reoxygenation (H/R) and its related mechanisms.
Methods: H/R model was established by culturing mouse cardiac H9c2 cells in vitro, and miR-873 mimic was transfected. The experiments were divided into a control group, a H/R group, a negative control group and a miR-873 mimic group. The expression of miR-873 was measured using real-time PCR. The protein expression levels of egl-9 family hypoxia inducible factor 3 (Egln3), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were evaluated by Western blotting. Cell apoptosis ELISA kit and cysteine-containing, aspartate-specific proteases-3 (caspase-3) activity kit was used to detect cell apoptosis and caspase-3 activity, respectively. The targeting effect of miR-873 on Egln3 were examined by the dual luciferase report gene assay, and the experiments were divided into a negative control group, a Egln3 3'-untranslated regions (3'-UTR) WT group (WT group) and a Egln3 3'-UTR MUT group (MUT group). In order to further detect the effects of Egln3 on miR-873 mimics, the Egln3 overexpressed cells were constructed, and the experiments were divided into a H/R group, a H/R+miR-873 mimic group, a H/R+pcDNA3-Egln3 (pcEgln3) group and a H/R+ miR-873 mimic+pcEgln3 group.
Results: Compared with the control group, the expression level of miR-873 was significantly decreased in the H/R group (P<0.05). Compared with the H/R group, H9c2 cell apoptosis, caspase-3 activity and the ratio of Bax/Bcl-2 were significantly reduced in the miR-873 mimic group (all P<0.05). Compared with the negative control group, the luciferase activity was significantly down-regulated in the WT group (P<0.05), while the luciferase activity was not significantly changed in the MUT group (P>0.05). In the over-expression experiment, compared with the H/R group, the cell apoptosis and the ratio of Bax/Bcl-2 were significantly reduced in the miR-873 mimic group (both P<0.05). Compared with miR-873 mimic group, the cell apoptosis and the ratio of Bax/Bcl-2 were significantly up-regulated in the H/R+pcEgln3 group and the H/R+miR-873 mimic+pcEgln3 group (all P<0.05).
Conclusion: MiR-873 can inhibit H/R- induced apoptosis of cardiomyocyte via targeting Egln3.
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Apoptosis
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Cell Hypoxia
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Mice
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MicroRNAs
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Myocytes, Cardiac
8.Nursing care of patients undergoing endoscopic ultrasonography guided biliary drainage in the treatment of malignant obstructive jaundice
Cui CHEN ; Bo SUN ; Shuzhi WANG ; Shuping WANG ; Kunke WANG ; Bing HU ; Zhixia YE
Chinese Journal of Nursing 2018;53(3):310-313
This paper summarized nursing points for caring 12 cases undergoing endoscopic ultrasonography guided biliary drainage(EUS-BD) in the treatment of malignant obstructive jaundice.All patients received EUS-BD after unsuccessful endoscopic retrograde cholangiopancreatography,including 5 patients undergoing EUS guided hepaticogastrostomy(EUS-HGS) and 7 patients undergoing EUS guided choledochoduodenostomy(EUS-CDS).Nursing points included:preoperative assessment,psychological care,preoperative gastrointestinal preparation,intraoperative cardiopulmonary function monitoring,collaboration in operation,postoperative monitoring,observation and nursing care for complications such as bleeding,bile leakage and the others.The average hospital stay was 10~16 d.Two patients developed complications(16.67%).A patient undergoing EUS-HGS developed bile leakage,biliary peritonitis,and pneumoperitoneum after the procedure,but was successfully recovered by placement of a second fully covered self-expendable metal stent in the primary metal stent,percutaneous abdominal drainage and antibiotic treatment.A patient undergoing EUS-CDS developed gastrointestinal bleeding,and was successfully treated with radiological intervention.
9.Value of endoscopic ultrasonography-guided biliary drainage for malignant obstructive jaundice( with video)
Cui CHEN ; Zhixia YE ; Bo SUN ; Tiantian WANG ; Shuping WANG ; Shuzhi WANG ; Bing HU
Chinese Journal of Digestive Endoscopy 2018;35(8):557-561
Objective To analyze the efficacy of endoscopic ultrasonography-guided biliary drainage ( EUS-BD) for malignant obstructive jaundice and the management of adverse events. Methods Clinical data of 12 patients with malignant obstructive jaundice, who underwent EUS-BD between April 2016 and January 2017, were retrospectively analyzed. All patients received EUS-BD after unsuccessful ERCP, including EUS-guided hepaticogastrostomy ( EUS-HGS ) , EUS-guided antegrade stenting ( EUS-AS ) , and EUS-guided choledochoduodenostomy(EUS-CDS). Procedure outcomes, serum bilirubin and liver enzyme levels before the procedure and 1 week after, complications, treatment results, hospitalization time and follow-up were recorded. Results Two patients underwent EUS-HGS, 3 underwent EUS-AS, and 7 underwent EUS-CDS. Total bilirubin ( t=3. 462, P=0. 005 ) , direct bilirubin ( t=3. 351, P=0. 006 ) , alanine transaminase (t=2. 399, P=0. 037), γ-glutamate transpeptidase (t=3. 256, P=0. 031) reduced significantly after the procedure. Two patients ( 16. 67%) developed complications. A patient undergoing EUS-HGS developed bile leakage, biliary peritonitis, and pneumoperitoneum. A patient undergoing EUS-CDS developed upper gastrointestinal bleeding. Both patients were successfully treated. There were no other adverse events, such as acute pancreatitis, subcutaneous emphysema, pneumothorax and emphysema. No procedure-related death occurred. The mean hospital stay was 13. 75 ± 6. 92 days ( range 5-26 days ) . Conclusion EUS-BD is a safe substitute after unsuccessful ERCP when performed by experienced biliary endoscopists. However, intensive care is necessary after the procedure for early detection and management of complications.
10.Application of ultrasonography in diagnosis and differential diagnosis of Takayasu arteritis
Yu LIN ; Meihan LIU ; Weidong SHI ; Zhixia SUN ; Enqi CHEN ; Xin ZHANG ; Zhiyuan WANG
Journal of Jilin University(Medicine Edition) 2017;43(6):1268-1271,后插3
Objective:To investigate the clinical application value of ultrasound in the diagnosis and differential diagnosis of Takayasu arteritis (TA ). Methods: A total of 39 suspected TA patients were examined by ultrasonography,erythrocyte sedimentation rate (ESR),C reactive protein (CRP)and CT angiography (CTA), and the ultrasound examination results were compared and analyzed with the final chinical diagnosis results. Results:Of the 39 cases of suspected TA patients which had been examined by ultrasound,33 cases were diagnosed as TA,2 cases were diagnosed as atherosclerosis (AS),2 cases were diagnosed as fibromuscular dysplasia (FMD) and 2 cases were diagnosed as thromboangiitis obliterans (TAO).Compared with final chinical diagnosis results, 1 FMD patient was misdiagnosed as TA,and the rest of the diagnostic results were consistent with the final chinical diagnosis results.Conclusion:Ultrasound examination can provide objective and accurate basis for the diagnosis and differential diagnosis of TA,and it is an effective method of imaging examination.

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