1.Effect of Coptidis Rhizoma-Fermentum Rubrum on Non-Alcoholic Fatty Liver Disease in Mice Based on Nrf2/GPX4 Ferroptosis Axis
Yang YANG ; Xiaobo ZHANG ; Yong ZHANG ; Fuming LU ; Yaqi LUO ; Xiaoyi WU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):30-36
ObjectiveTo observe the effects of Coptidis Rhizoma-Fermentum Rubrum on non-alcoholic fatty liver disease (NAFLD) in mice and explore its possible mechanisms. MethodSixty male SPF C57BL/6J mice were randomly divided into six groups: control group, model group, low-, medium-, and high-dose Coptidis Rhizoma-Fermentum Rubrum group (0.75, 1.5, 3 g·kg-1), and metformin group (0.075 g·kg-1), with 10 mice in each group. NAFLD mouse models were induced by high-fat diet feeding for 24 weeks. The low, medium, and high-dose Coptidis Rhizoma-Fermentum Rubrum groups were administered corresponding doses of Coptidis Rhizoma-Fermentum Rubrum by gavage, while the control and model groups received an equivalent amount of saline for four weeks. Serum total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), and liver function markers including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using an automatic biochemical analyzer. Hematoxylin-eosin (HE) and oil red O staining were used to detect liver lipid deposition, and Prussian blue staining was used to measure liver ferrous ion levels. Western blot was performed to detect the expression of key proteins in the nuclear factor erythroid-2-related factor 2 (Nrf2)-glutathione peroxidase 4 (GPX4) axis. ResultAfter 24 weeks of high-fat feeding, compared with the control group, the model group showed significant increases in body weight, liver weight and liver index, and serum lipid levels (P<0.01), as well as substantial hepatic lipid deposition with marked steatosis. Compared with the model group, Coptidis Rhizoma-Fermentum Rubrum intervention reduced body weight (P<0.01), liver weight and liver index (P<0.01), and serum lipid levels (P<0.05, P<0.01), improved liver function (P<0.01), and decreased hepatic lipid deposition, with the low-dose Coptidis Rhizoma-Fermentum Rubrum group showing the best effect. Western blot results showed that compared with those in the control group, the expression levels of Nrf2, heme oxygenase-1 (HO-1), kelch-like ECH-associated protein 1(Keap1), and GPX4 proteins in the model group were decreased (P<0.05, P<0.01). Compared with the model group, Coptidis Rhizoma-Fermentum Rubrum increased the expression levels of these proteins (P<0.05, P<0.01). ConclusionCoptidis Rhizoma-Fermentum Rubrum can alleviate fatty liver in mice, improve liver function, and reduce hepatic lipid deposition, possibly by regulating the Nrf2/GPX4 ferroptosis axis.
2.Long non-coding RNA AW112010 improves insulin resistance in adipocytes of aging mice through the miR-204/POU2F2 axis
Rui WANG ; Shuwen WANG ; Yifan ZHANG ; Yaqi HU ; Qi YUAN ; Yuan WEN ; Xiaoling CHEN ; Ting LU ; Ying ZHENG ; Zhiyong LIN ; Mengzhen XUE ; Yaqi WANG ; Fangqi XIA ; Leiqi ZHU ; Chengfu YUAN
Chinese Journal of Endocrinology and Metabolism 2024;40(1):44-52
Objective:To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway.Methods:In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results:RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased.Conclusion:Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.
3.Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer
Shi QIU ; Yaqi QIU ; Linghui DENG ; Ling NIE ; Liming GE ; Xiaonan ZHENG ; Di JIN ; Kun JIN ; Xianghong ZHOU ; Xingyang SU ; Boyu CAI ; Jiakun LI ; Xiang TU ; Lina GONG ; Liangren LIU ; Zhenhua LIU ; Yige BAO ; Jianzhong AI ; Tianhai LIN ; Lu YANG ; Qiang WEI
Chinese Medical Journal 2024;137(2):209-221
Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
4.Research progress in the automatic identification and tracking of surgical instruments for endovascular intervention under X-ray fluoroscopy
Journal of Interventional Radiology 2024;33(7):699-703
The automatic identification and tracking of surgical instruments for endovascular interventions is beneficial for precise,intelligent,minimally-invasive diagnosis and treatment of vascular diseases as well as for the automation of surgical robots.With the continuous development of artificial intelligence(AI),the accuracy and real-time performance of identification and tracking technology have also been constantly improved,which can better meet the clinical requirements.This article reviews the research progress in the automatic identification and tracking of surgical instruments for endovascular interventions under X-ray fluoroscopy.The content of this article mainly includes the following three aspects:(1)summarizing and describing the relevant techniques of automatic identification and tracking of interventional surgical instruments;(2)summarizing the identification and tracking algorithms of interventional surgical instruments from the perspectives of complete supervision and weak supervision;and(3)comprehensively summarizing the application scope of the technology of automatic identification and tracking of interventional surgical instruments,including surgical assistance decision-making,surgical intelligent navigation and surgical augmented reality(AR)technology training.
5.Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver disease
Chen PANPAN ; Zhu ZIHAN ; Geng HAOYUAN ; Cui XIAOQING ; Han YUHAO ; Wang LEI ; Zhang YAQI ; Lu HENG ; Wang XIAO ; Zhang YUN ; Sun CHENGLONG
Journal of Pharmaceutical Analysis 2024;14(4):552-561
Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a"multi-omics"platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.
6.Ingredients of Panax notoginseng compound formula modulate inflam-mation and intestinal flora to attenuate endometrial fibrosis in rats with intrauterine adhesion
Mengchen TAN ; Wen'e LIU ; Lu MA ; Yuxin ZENG ; Xue'er YANG ; Yaqi ZHAO ; Ying PENG ; Qiang AO ; Hui LIU ; Minyan LI
Chinese Journal of Pathophysiology 2024;40(11):2135-2144
AIM:To investigate the effects of Panax notoginseng compound formula(PN)on endometrial fibro-sis by regulating inflammatory reaction and intestinal flora(IF)in a rat model of intrauterine adhesion(IUA).METHODS:The rat IUA model was established by following the mechanical injury method.A total of 50 rats were randomly divided in-to sham group,model group,low-dose(210 mg/kg)PN group,medium-dose(420 mg/kg)PN group and high-dose(840 mg/kg)PN group.After 8 weeks of intragastric administration,the uterus was collected to observe morphological changes with naked eye.The degree of uterine tissue damage and fibrosis was evaluated through hematoxylin-eosin(HE)and Mas-son staining.The collagen type Ⅰ(Col Ⅰ)was detected by immunohistochemistry.The interleukin-6(IL-6)and IL-10 pro-tein expression was detected by Western blot.The levels of IL-6,IL-1β,tumor necrosis factor-α(TNF-α)and vascular endothelial growth factor B(VEGFB)were detected by enzyme-linked immunosorbent assay(ELISA).The IF diversity and population structure were observed by 16S amplicon.RESULTS:Compared with the sham group,the uteruses of rats in the model group showed:reduced elasticity,accompanied by congestion and edema;decreased number of glands and blood vessels,and thinned endometrium(P<0.01);increased collagen fibers and Col Ⅰ protein expression(P<0.01);sig-nificantly increased IL-1β,IL-6,TNF-α and VEGFB levels in the uterine tissue(P<0.01);decreased IL-10 level(P<0.01);and reduced IF diversity(P<0.05).Compared with the model group,the drug intervention groups exhibited:re-covered elasticity of the uterus and relieved congestion and edema;increased number of endometrial glands and blood ves-sels(P<0.05);decreased collagen fibers and Col Ⅰ protein expression(P<0.01);reduced IL-1β,IL-6,and TNF-α lev-els to varying degrees in the uterine tissue(P<0.05);elevated IL-10 level(P<0.01);and improved IF diversity(P<0.05).CONCLUSION:The PN is able to significantly improve the endometrial tissue fibrosis in IUA rats.The under-lying mechanisms may be related to the inhibition of IL-6,IL-1β and TNF-α expression,up-regulation of IL-10,and im-provement of IF diversity.
7.Construction of nursing quality evaluation index system for radionuclide wards
Yaqi LU ; Xia SHEN ; Qianqian LI ; Qingbo YANG ; Xuehui NAN ; Lili WEI
Chinese Journal of Modern Nursing 2024;30(21):2890-2896
Objective:To construct the nursing quality evaluation index system for radionuclide wards, so as to provide scientific basis for monitoring the quality of nursing work in radionuclide wards.Methods:With Donabedian's "structure-process-outcome" three-dimensional quality evaluation model as the theoretical framework, literature review, Delphi method and analytic hierarchy process were used to determine the contents and weights of the evaluation index system of nursing quality in radionuclide wards. The enthusiasm of experts was expressed by the effective recovery rate of the questionnaire, the authority coefficient of experts was expressed by the authority coefficient, and the coordination degree of expert opinions was expressed by the coefficient of variation and the Kendall's harmony coefficient.Results:The effective recovery rates of the two rounds of expert correspondence questionnaires were 100.00% (15/15), the expert authority coefficients were 0.880 and 0.900, the coefficient of variation were 0.10-0.26 and 0-0.16 and the Kendall's harmony coefficients were 0.131 and 0.187 ( P<0.01). The final constructed nursing quality evaluation index system for radionuclide wards included three primary indicators, 12 secondary indicators and 56 tertiary indicators. Conclusions:The constructed nursing quality evaluation index system for radionuclide wards is scientific, reliable, practical and specialized, which is close to clinical nursing work and can provide a good evaluation method for nursing quality evaluation in radionuclide wards.
8.A single-center research of peroral endoscopic myotomy for primary achalasia in patients over 60 years old
Xin ZHAO ; Ningli CHAI ; Qingzhen WU ; Runxiang DU ; Lu YE ; Xiao LI ; Huikai LI ; Yaqi ZHAI ; Enqiang LINGHU
Chinese Journal of Digestive Endoscopy 2023;40(2):98-103
Objective:To explore the therapeutic effect of peroral endoscopic myotomy (POEM) for primary achalasia (AC) in patients aged over 60 years.Methods:Data of 146 patients aged ≥60 years (the elderly group) and 146 patients aged 18-59 years (the adult group) who received POEM from November 2010 to September 2019 at the Digestive Endoscopy Center of PLA General Hospital were retrospectively analyzed. Baseline data, surgery data, surgery-related complications and surgery-related efficacy were compared.Results:There was no significant difference in gender, Ling classification, HRM classification or previous treatment between the two groups ( P>0.05). All 292 patients successfully underwent POEM surgery. The clinical success (Eckardt score ≤3) rates in the elderly group and the adult group were 96.33% (105/109) and 96.77% (90/93), respectively with no significant difference between the two groups ( χ2=0.030, P>0.05). There was no significant difference in the length of myotomy between the two groups (7.09±2.49 cm VS 7.12±2.24 cm, t=0.472, P>0.05). Complications occurred in 26 cases (17.81%) in the elderly group and 21 cases (14.38%) in the adult group with no significant difference between the two groups ( χ2=0.634, P>0.05). There was no significant difference in the postoperative hospital stay (12.61±9.69 days VS 11.00±4.43 days, t=1.825, P>0.05) or the incidence of gastroesophageal reflux [43.33% (13/30) VS 51.52% (17/33), χ2=0.422, P>0.05] between the elderly group and the adult group. Conclusion:The efficacy of POEM for AC patients over 60 years old is equivalent to that of adult patients, and the incidence of complications is similar. POEM is safe and effective for AC patients over 60 years old.
9.Effects of Dexmedetomidine on Postoperative Delirium in Liver Tumor Resection Elderly Patients with Sleep Disorders
Xiaoxi LI ; Yaqi LI ; Changhong MIAO ; Xihua LU ; Changsheng LI
China Pharmacy 2021;32(14):1758-1763
OBJECTIVE:To investigate the effects of d exmedetomidine on postoperative delirium (POD) in liver tumor resection elderly patients with sleep disorder (SD). METHODS :Totally 80 patients undergoing liver tumor resection with preoperative Pittsburgh sleep quality index (PSQI)score ≥7 were selected from the Affiliated Cancer Hospital of Zhengzhou University from Jan. 1st,2020 to Oct. 31st,2020. They were randomly divided into group SD and group Dex according random number table ,with 40 cases in each group. At the same time ,40 patients with preoperative PSQI score <7 were selected as group C. Thirty min before anesthesia induction ,Dexmedetomidine hydrochloride injection 0.4 μg/kg was injected intravenously in group Dex. Etomidate emulsion injection ,Sufentanil citrate injection and Rocuronium bromide injection were used for anesthesia induction in 3 groups,and Ropofol medium/long chain fat emulsion injection + Remifentanil hydrochloride for injection was used to maintain anesthesia. The drug use ,operation time ,PACU stay time and postoperative hospital stay were recorded in 3 groups. The cognitive function was evaluated 2 h before operation and 1,3,5,7 days after operation. The occurrence of POD was observed. The plasma levels of IL- 6 and S 100β were measured 2 h before operation ,2 h after operation ,1,3,5 days after operation. The occurrence of ADR was recorded. RESULTS :There was no statisti cal significance in intraoperativ e drug use and operation time among 3 groups (P>0.05). The PACU stay time , the incidence of POD and the duration of POD in group SD an d lixxi18@126.com group Dex were significantly higher or longer than group C , while the Dex group was significantly lower or shorter thangroup SD (P<0.05). The postoperative hospitalization stay ofgroup SD was significantly longer than group C and group Dex (P<0.05),and there was no statistical significance between group Dex and group C (P>0.05). Before operation ,there was no statistical significance in MMSE scores or plasma levels of IL- 6 and S100β among 3 groups(P>0.05). MMSE scores of group C 1,3 days after operation ,those of group SD and group Dex 1,3,5 and 7 days after operation were significantly lower than those before operation. MMSE scores of group SD and group Dex 1,3,5 and 7 days after operation were significantly lower than group C at corresponding period ;the group Dex was significantly higher than the group SD at corresponding period (P<0.05). The plasma levels of IL- 6 and S 100 β at different time points were significantly higher than before operation ,and the group SD and group Dex were significantly higher than the group C ,and the group Dex was significantly lower than group SD at corresponding period (P<0.05). There was no statistical significance in the total incidence of ADR among 3 groups(P>0.05). CONCLUSIONS :SD can promote the occurrence of POD in liver tumor resection elderly patients. Dexmetomidine can reduce the incidence of POD in elderly patients with preoperative SD ,the mechanism of which may be associated with the inhibition of IL- 6 and S 100β expression and the alleviation of brain injury with good safety.
10.Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging.
Zhonghua WANG ; Wenqing FU ; Meiling HUO ; Bingshu HE ; Yaqi LIU ; Lu TIAN ; Wanfang LI ; Zhi ZHOU ; Baili WANG ; Jianzhen XIA ; Yanhua CHEN ; Jinfeng WEI ; Zeper ABLIZ
Acta Pharmaceutica Sinica B 2021;11(11):3665-3677
Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.

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