1.Zhenwutang Ameliorates Diabetic Kidney Disease in Mice with Spleen-kidney Yang Deficiency via Nrf2/HO-1/GPX4 Signaling Pathway
Zhe ZHAO ; Guangshun CHEN ; Min BAI ; Yuqiu JIN ; Mengyuan TIAN ; Bing SONG ; Zhenhua LIU ; Yanying ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):29-37
ObjectiveTo investigate the effect and mechanism of Zhenwutang on renal oxidative damage in the mouse model of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency via the nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodTwenty-five 7-week-old SPF-grade male db/m mice and 95 7-week-old SPF-grade male db/db mice were adaptively fed for a week. A blank group was set with the db/m mice without treatment, and the other mice were administrated with Rhei Radix et Rhizoma decoction and hydrocortisone for the modeling of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency. The modeled mice were randomized into the model, irbesartan (25 mg·kg-1), and high-, medium-, low-dose (33.8, 16.9, 8.45 g·kg-1) Zhenwutang groups (n=15) and administrated with corresponding drugs for 8 weeks. The survival status of mice was observed, and the traditional Chinese medicine (TCM) syndrome score was recorded. The indicators related to spleen-kidney Yang deficiency, fasting blood glucose (FBG), and renal function indicators were determined. Hematoxylin-eosin staining was employed to observe the histopathological changes of the renal tissue in each group. Biochemical kits were used to determine the oxidative stress-related indicators in the renal tissue. Real-time polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels, respectively, of Nrf2, HO-1, glutamate-cysteine ligase catalytic subunit (GCLC), and GPX4 in the renal tissue of mice in each group. ResultCompared with the blank group, the modeling increased the TCM syndrome score (P<0.05), elevated the estradiol (E2) and FBG levels (P<0.05), lowered the testosterone (T), triiodothyronine (T3), and tetraiodothyronine (T4) levels (P<0.05), and weakened the renal function (P<0.05). In addition, the modeling led to glomerular hypertrophy and glomerular mesangial and basal thickening, decreased the catalase (CAT) activity, total antioxidant capacity (T-AOC), and glutathione (GSH) content (P<0.05), increased the malondialdehyde (MDA) content (P<0.05), and down-regulated the mRNA and protein levels of Nrf2, HO-1, GCLC, and GPX4 in the renal tissue (P<0.05). Compared with the model group, high and medium doses of Zhenwutang decreased the TCM syndrome score and E2 content (P<0.05), increased the T, T3, and T4 content (P<0.05), improved the renal function (P<0.05), alleviated the pathological changes in the renal tissue, increased CAT, T-AOC, and GSH (P<0.05), reduced MDA (P<0.05), and up-regulated the mRNA and protein levels of Nrf2, HO-1, GCLC, and GPX4 in the renal tissue (P<0.05). ConclusionZhenwutang can improve the general state and renal function and reduce the oxidative damage and pathological changes in the renal tissue of db/db mice with spleen-kidney Yang deficiency by regulating the Nrf2/HO-1/GPX4 signaling pathway.
2.Effect of shoulder-high head back-up position on airway obstruction and hypoxia during fiberoptic bronchoscopy under non-intubated general anesthesia
Guangshun LIU ; Yahong WANG ; Yuhang QUAN ; Kezhong YE ; Xiangwu ZHANG ; Zhiyong LYU
The Journal of Clinical Anesthesiology 2024;40(6):570-575
Objective To observe the effect of shoulder-high head back-up position on airway ob-struction and hypoxia during fiberoptic bronchoscopy under non-intubated general anesthesia.Methods A total of 170 patients undergoing painless fiberoptic bronchoscopy,97 males and 73 females,aged 18-64 years,BMI 18.5-28.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were randomly divided into two groups by ran-dom number method:observation group(group D,n=84)and control group(group C,n=83).Group D adopted the shoulder-high head back-up position,and group C adopted the supine position.All the pa-tients received intravenous general anesthesia of propfol combined with sufentanil,and were oxygenated via an ordinary endoscopic mask with an oxygen flow rate of 8-10 L/min.Fiberoptic bronchoscopy was per-formed when the modified observer assessment of alertness and sedation(MOAA/S)score was≤1 point.The number of cases in which hypoxia occurred and corrective measures were taken were recorded.The changes of HR,SBP,DBP,and SpO2 before induction of anesthesia(T1),1 minute after induction of an-esthesia(T2),endotracheal surface anesthesia(T3),at the time of examination(T4),and at the end of the examination(T5)were recorded.The degree of obstruction of the retropalatal space and retroglossal space at T2 were recorded.The level of glottic exposure and operating comfort of the endoscopist were recor-ded during the examination,and the incidence of postoperative neck discomfort,postoperative headache,postoperative dizziness,and nausea and vomiting were recorded.Results Compared with group C,the in-cidence of intraoperative moderate hypoxia,severe hypoxia,jaw support,and assisted ventilation was signifi-cantly decreased in group D(P<0.05).Compared with T1,the HR were significantly increased at T3 and T4(P<0.05),SBP and DBP were significantly decreased at T2,T4,and T5(P<0.05),SpO2 was sig-nificantly increased at T2 and decreased at T4 in the two groups(P<0.05),and SpO2 in group C was sig-nificantly decreased at T3(P<0.05).Compared with group C,SpO2 was significantly increased at T4,the incidence of non-obstruction in the retrolingual space was significantly increased,and the incidence of com-plete obstruction in the retrolingual space was significantly decreased at T2,and the incidence of good glottic exposure was significantly increased,the incidence of poor glottic exposure was significantly decreased,and the incidence of good operating comfort of the endoscopist was significantly increased in group D(P<0.05).There was no significant difference in the incidence of postoperative adverse events between the two groups.Conclusion Shoulder-high head back-up position can alleviate airway obstruction and reduce the incidence of hypoxia during fiberoptic bronchoscopy under non-intubated general anesthesia.
3.Artificial Intelligence in the Prediction of Gastrointestinal Stromal Tumors on Endoscopic Ultrasonography Images: Development, Validation and Comparison with Endosonographers
Yi LU ; Jiachuan WU ; Minhui HU ; Qinghua ZHONG ; Limian ER ; Huihui SHI ; Weihui CHENG ; Ke CHEN ; Yuan LIU ; Bingfeng QIU ; Qiancheng XU ; Guangshun LAI ; Yufeng WANG ; Yuxuan LUO ; Jinbao MU ; Wenjie ZHANG ; Min ZHI ; Jiachen SUN
Gut and Liver 2023;17(6):874-883
Background/Aims:
The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation.
Methods:
We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals.
Results:
A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers.
Conclusions
We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.
4.Traditional Chinese Medicine Against Liver Fibrosis Based on Autophagy: A Review
Mengyuan TIAN ; Ming ZHANG ; Zhe ZHAO ; Yuqiu JIN ; Guangshun CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(21):255-263
Hepatic fibrosis (HF) is a widespread disease caused by various forms of chronic liver injury, significantly impacting human health. HF often has an insidious onset with inconspicuous symptoms, but in its advanced stages, it can progress to cirrhosis or even hepatocellular carcinoma. The pathogenic mechanisms of HF are highly complex, primarily characterized by excessive extracellular matrix (ECM) deposition. Autophagy is a lysosome-mediated degradation system employed by cells to recycle cellular contents, eliminate aggregated proteins, damaged organelles, and invading pathogens (such as viruses and bacteria) to maintain normal cellular function and dynamic balance. Autophagy can regulate various signaling pathways and factors, including mammalian target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK), and transforming growth factor-β (TGF-β), to reduce the activation of hepatic stellate cells (HSCs) and hepatocyte necrosis and apoptosis, thereby mitigating ECM deposition and slowing the progression of HF. Numerous studies also suggest that traditional Chinese medicine (TCM) can effectively treat HF, and its mechanism of action may be related to autophagy. This article provides a review by summarizing recent literature in China and abroad on the mechanisms of autophagy, related signaling factors and pathways, as well as the role of TCM in regulating autophagy for the prevention and treatment of HF, aiming to offer insights and references for the development of TCM in the prevention and clinical rational medication in the treatment of HF.
5.To Explore the Mechanism of Ferulic Acid Against Liver Fibrosis Based on Network Pharmacology and Cell Experiment
Mohan SUN ; Qiuju ZHANG ; Zhe ZHAO ; Yuqiu JIN ; Mengyuan TIAN ; Guangshun CHEN
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(12):3908-3919
Objective To study the mechanism of ferulic acid(FA)on hepatic fibrosis(HF)based on network pharmacology,and establish an in vitro model of rat hepatic stellate Cell-T6(HSC-T6)according to the results.Methods The potential targets of FA were screened through PubChem,swisstargetprediction and pharmmapper,and overlapped with the FA targets screened in disgenet,genecards and OMIM.Then,protein protein interaction(PPI)was analyzed by using string platform.Gene ontology(go)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out for key targets by using R64 4.0.3,and the"component target disease"network diagram was constructed by Cytoscape 3.7.2 software.Based on this,the proliferation of HSC-T6 was detected by cell counting kit-8(CCK-8)method,and the grouping was determined:blank group and low-dose group(100 μg·mL-1 FA),medium dose group(200 μg·mL-1 FA),high dose group(400 μg·mL-1 FA)and positive control group(200 μg·mL-1 colchicine),the migration ability of HSC-T6 was detected by scratch test,and the content of HSC-T6 was detected by enzyme linked immunosorbent assay(ELISA)α-Alpha smooth muscle actin,α-Flow cytometry was used to detect the changes of HSC-T6 cycle,quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the relative expression of JAK2 and STAT3 mRNA,and Western Blot was used to detect the molecular expression of JAK2 and STAT3 protein.Results 254 intersection targets of FA and HF were obtained.The core targets were signal transducer and activvator of Transcription(STAT3),albumin(ALB),protein kinase B(AKT1),tumor suppressor protein p53(TP53),epidermal growth factor receptor(EGFR)and caspase-3(CASP3).KEGG analysis showed that the action pathway of FA on HF mainly involved phosphatidylinositol 3 kinase protein kinase B(PI3K-Akt),vascular endothelial growth factor(VEGF),Janus kinase/signal transducer and activator of transcription(JAK/STAT)Tumor necrosis factor(TNF)and other pathways.The experimental results showed that in CCK-8 experiment,scratch experiment and ELISA experiment,compared with the blank group,the cell proliferation rate,migration ability and the expression of α-SMA protein decreased significantly(P<0.05).Compared with the blank group,the cycle arrest rate of low,medium and high dose groups and positive control group increased significantly(P<0.05).Compared with the blank group,the molecular weight and mRNA expression of JAK2 and STAT3 protein in low,medium and high dose groups and positive control group decreased gradually(P<0.05).Conclusion FA has the characteristics of multi-channel and multi-target.FA may inhibit the apoptosis of hepatic stellate cell(HSC)by down regulating JAK2 and STAT3 targets.
6.Crystal structure of the African swine fever virus structural protein p35 reveals its role for core shell assembly.
Guobang LI ; Dan FU ; Guangshun ZHANG ; Dongming ZHAO ; Mingyu LI ; Xue GENG ; Dongdong SUN ; Yuhui WANG ; Cheng CHEN ; Peng JIAO ; Lin CAO ; Yu GUO ; Zihe RAO
Protein & Cell 2020;11(8):600-605
8.Structure-activity relationship optimization for lassa virus fusion inhibitors targeting the transmembrane domain of GP2.
Guangshun ZHANG ; Junyuan CAO ; Yan CAI ; Yang LIU ; Yanli LI ; Peilin WANG ; Jiao GUO ; Xiaoying JIA ; Mengmeng ZHANG ; Gengfu XIAO ; Yu GUO ; Wei WANG
Protein & Cell 2019;10(2):137-142
9.Development and clinical application of integrated network management platform for tumor radiotherapy information
Xingwang GAO ; Guangshun ZHANG ; Li CHEN ; Luosheng ZHANG ; Shaomin HUANG ; Xiaowu DENG
Chinese Journal of Radiation Oncology 2016;25(4):395-400
Objective To develop a network management system for tumor radiotherapy information that integrates process management and quality assurance functions, and to investigate its clinical value. Methods Based on the requirements of radiotherapy process quality assurance and control, the client-server ( C-S) pattern, along with SQL SERVER 2008 database structure, international standard DICOM 3.0, DICOM RT, and HL7 protocols, and system hardware and self-developed software in local area network, was adopted to establish the network management system for radiotherapy information, and clinical tests were performed to evaluate the operation performance of this platform.Results ( 1 ) The interactive integrated management platform and client-side functional modules with a uniform interface were developed.( 2) The safe and reliable standardized data interface was developed, which could be connected to accelerators, treatment planning systems, and hospital information systems developed by mainstream manufacturers.( 3) The modules for radiotherapy process management and quality assurance and management were designed and developed.( 4) The platform passed all the tests before operation and had been used in clinical departments for almost 3 years, which confirmed that the system was safe and stable during operation and that all functions designed were realized.Conclusions The integrated management platform meets the requirements for application and management of radiotherapy information and data, improves the overall work efficiency in radiotherapy department and the level of quality assurance and control, and holds promise for clinical application as a good tool for tumor radiotherapy departments.
10.Hepatitis C virus infection increases the incidence of intrahepatic cholangiocarcinoma: a Meta-analysis
Shujie PANG ; Zhipeng LIN ; Qingwang YE ; Haibin ZHANG ; Ning YANG ; Guangshun YANG
Chinese Journal of Hepatobiliary Surgery 2016;22(1):33-36
Objective A meta-analysis was conducted to evaluate the correlation between hepatitis C virus (HCV) infection and the incidence of intrahepatic cholangiocarcinoma (ICC).Methods EMBASE,MEDLINE,Web of Science,CNKI,Weipu and Wanfang databases were retrieved to identify eligible studies which were published between January 2000 and May 2015.Pooled odds ratios (OR) with 95% confidence interval (95% CI) were calculated using RevMAN 5.3.Results 14 case-control studies and 2 cohort studies were included in this study.As there was great heterogeneity among these 16 studies (Chi2 =53.18,df =15,I2 =72%,P <0.05),the random-effect model was employed.The combined risk estimates of all the studies showed a significant increase in ICC incidence with HCV infection (OR =3.96,95% CI 2.63-5.95,P < 0.05).The Begg funnel plot showed no evidence of publication bias.Conclusion HCV infection is related to an increased risk of ICC incidence.

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