1.Mechanism of Zexie Tang in regulating macrophage M1/M2 polarization balance based on PI3K/AKT pathway
Erwen LI ; Zhenghao CUI ; Gai GAO ; Zhongxue FU ; Xiaowei ZHANG ; Hui WANG ; Zhenqiang ZHANG ; Jiangyan XU ; Zhishen XIE
Chinese Journal of Immunology 2024;40(8):1684-1691,中插1
Objective:To explore the effect and possible mechanism of Zexie Tang(ZXT)regulate the balance of M1/M2 polarization in macrophage cells.Methods:Lipid metabolism disorder mouse model was induced by Western diet(WD)in vivo,RAW264.7 cell M1/M2 macrophage model was induced by LPS/IL-4 in vitro,set up blank group,model group and ZXT group.The flu-orescence intensity of M1 and M2 macrophage markers in adipose tissue and RAW264.7 cells was observed by immunofluorescence staining;protein levels of p-AKT,AKT and COX-2 were measured by Western blot;levels of macrophage marker gene mRNAs of M1 and M2 were analysed by qPCR;IL-1β and IL-10 were measured by ELISA;content of NO was detected by Griess;binding of active components of Alismatis Rhizoma and Atractylodes Macrocephala with PI3K protein was analyzed by Docking.Results:Compared with WD group,expression of CD11c was significantly decreased in ZXT group,while expression of CD206 was significantly up-regulated;ZXT reversed LPS-induced increased in CD80 expression,down-regulated mRNA levels of M1 macrophage marker gene iNOS,etc,decreased the expression of COX-2 protein,and inhibited the secretion of IL-1β(P<0.001);ZXT promoted IL-4-induced CD206 expression,up-regulation of M2 macrophage marker gene Arg-1 and other mRNAs levels and secretion of IL-10;ZXT reversed the LPS-induced increased in NO release;p-AKT/AKT protein level increased in vivo and in vitro after ZXT administration;Docking re-sults show that many active ingredients in Alismatis Rhizoma and Atractylodes Macrocephala could form hydrogen bonds stably with PI3K protein.Conclusion:ZXT regulates the M1/M2 polarization balance of macrophages,and its mechanism may be related to the regulation of PI3K/AKT pathway.
2.Study on the mechanism of Yishen tongluo formula improving abnormal lipid metabolism based on SREBPs pathway
Liang ZHAO ; Xiaowei ZHANG ; Zhishen XIE ; Shixie XIANG ; Yafei DUAN ; Gai GAO ; Pan WANG ; Huifen MA ; Yiran SUN ; Jie CHEN ; Jiangyan XU ; Zhenqiang ZHANG
China Pharmacy 2023;34(23):2835-2840
OBJECTIVE To explore the mechanism of Yishen tongluo formula (YSTLF) in improving abnormal lipid metabolism based on the sterol regulatory element binding proteins (SREBPs) pathway. METHODS Using C57BLKS/J (db/db) mice as model and C57BLKS/J (db/m) mice as normal control, the mechanism of 1, 2.5 and 5 g/kg YSTLF improving abnormal lipid metabolism of db/db mice was investigated by determining the liver coefficient, the contents of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), observing steatosis and lipid accumulation in liver tissue of mice, detecting the protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription levels of Srebp- 1c, Srebp-2 and their downstream lipid metabolism-related target genes (Fasn, Acc1, Scd5, Fads1, Hmgcr, Dhcr24, Insig-1, Fdps) in liver tissue of mice. Using low-fat cultured human liver cancer cell HepG2 as an in vitro cell model for abnormal lipid metabolism, and 25-HC (SREBPs inhibitor, 10 μmol/L) as the control, the effects of 125, 250 and 500 μg/mL YSTLF on protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription of SREBP-1c, SREBP-2 and their downstream lipid metabolism-related target genes were investigated to verify the mechanism in vitro. RESULTS 1, 2.5, 5 g/kg YSTLF significantly reduced the levels of TC, TG and LDL, the percentage of lipid droplet-positive region in liver tissue and liver coefficient, significantly down-regulated protein expressions of Pre-SREBP-1, n-SREBP-1, Pre-SREBP-2 and n-SREBP-2, and mRNA transcription of Srebp-1c, Srebp-2 and their downstream target genes in liver tissue, while significantly increased HDL level, with statistical significance (P<0.05 or P<0.01). In the cell experiment in vitro, the expressions of the above-mentioned proteins and genes in the cells treated with YSTLF at 125, 250 and 500 μg/mL for 24 hours were consistent with those in the animal experiment; there was no significant difference in the expressions of the above-mentioned proteins and genes between inhibitor control group and 250, 500 μg/mL YSTLF groups (P>0.05). CONCLUSIONS YSTLF can regulate the expression of transcription factor SREBPs, so as to inhibit the high expression of fatty acid and cholesterol synthesis-related genes, promote the degradation of TC and TG, improve the abnormality of lipid metabolism and inhibit lipid accumulation, thus playing the role of lipid-lowering.
3.Inhibition of ginsenoside Rb 1 on the epithelial-mesenchymal transition of renal tubular epithelial cells by regulating TGF-β1/Smad3 signaling pathway
Zhiwen LIU ; Jiangyan XU ; Zhenqiang ZHANG ; Xiaowei ZHANG ; Gai GAO ; Mengmeng WANG ; Hui WANG ; Zhenzhen LI ; Zhishen XIE
China Pharmacy 2022;33(5):535-541
OBJECTIVE To study the effects of ginsenoside Rb 1(G-Rb1)on epithelial-mesenchymal transition (EMT)of renal tubular epithelial cells and its potential mechanism. METHODS The growth factor β1(TGF-β1)10 ng/mL was used to induce EMT of human renal tubular epithelial cells HK- 2. The morphological changes of HK- 2 cells were observed after treated with 10, 20,30 μmol/L G-Rb1 for 48 h. The transcriptional activities of biovector SBE in human embryonic kidney cell HEK 293 were determined after 24 h treatment with 1.0,2.5,5.0,10,20,30 μmol/L G-Rb1. Effects of above concentration of G-Rb 1 on the viability of HK- 2 cells were determined after 24 h of treatment. mRNA expressions of α-smooth muscle actin (α-SMA),collagen Ⅰ (COL-Ⅰ)and fibronectin (FN)in HK- 2 cells were detected after treated with 10,20,30 μmol/L G-Rb1 for 24 h. The expressions of α-SMA,Smad3,p-Smad3,COL-Ⅰ,FN and E-cadherin were detected after treated with 10,20,30 μmol/L G-Rb1 for 24 h. RESULTS G-Rb1 of 10-30 μmol/L significantly inhibited TGF-β1-induced EMT in HK- 2 cells and the increase of transcriptional activities of biovector SBE induced by TGF-β1(P<0.05),but had no effects on relative activities of HK- 2 cells(P>0.05). The protein and mRNA expressions of α-SMA,COL-Ⅰ and FN , the protein expressions of Smad 3 and p-Smad 3 were significantly up-regulated induced by TGF-β1(P<0.05),while the protein expression of E-cadherin was significantly down- regulated(P<0.05);G-Rb1 could effectively reverse aboveprotein or mRNA expressions. CONCLUSIONS G-Rb1 can protect renal tubular epithelial cells from EMT induced byxiezhishen TGF-β1 to a certain extent ,which may be related to inhibiting the activation of TGF-β1/Smad3 signaling pathway.
4.Clinical experience summary of gastroinstinal injury caused by magnets ingestion in children
Jindu ZHAO ; Qun GAO ; Zhenqiang ZHANG ; Zhubin PAN ; Chen CHEN
International Journal of Surgery 2022;49(1):34-39,F3
Objective:To explore the clinical characteristic, pathogenesis, diagnosis and treatment strategies of gastroinstinal injury caused by magnets ingestion in children.Methods:A retrospective analysis of 46 patients with gastrointestinal tract magnets ingestion in Anhui Provincial Children′s Hospital from October 2017 to September 2021 was performed. Patients were divided into different groups according to gastroinstinal perforation. Some basic information was collected, including gender, age, duration of swallow foreign bodies, quantity of foreign bodies, symptoms, white blood cell, neutrophil, C-reactive protein, therapeutic method, gastroinstinal injury and follow up. Logistic regression. Univariate analysis and multivariate Logistic regression were used to analysis the risk factors of gastroinstinal perforation. Continuous parametric data were summarized using median and interquartile range, differences were evaluated using Wilcoxon Mann-Whitney test.Noncontinuous data were analyzed using chi-square test or corrected chi-square test.Results:Among the 46 patients, there were 33 males and 13 females. The median age was 3 years, with a range of 8 months to 11years. 34 cases had a history of ingesting magnets. The common number of ingested magnets was 2-10 (25 cases). Vomiting (18 cases) and abdominal pain (13 cases)were the commonest complaint. 6 cases tend to pass through the gastrointestinal tract uneventfully, and the remaining cases were successfully extracted by endoscopy (5 cases) and surgery(35 cases). Gastroinstinal perforation was found in 28 cases, and the majority of perforation was located in the ileum (18 cases). Univariate analysis showed that symptom, white blood cell, neutrophil, and CRP were associated with gastroinstinal perforation ( P<0.05). Multivariate Logistic regression analysis showed that symptom( OR=4.715, 95% CI: 1.074-20.696, P=0.040) and CRP( OR=11.605, 95% CI: 1.132-118.981, P=0.039) were independent factors for gastroinstinal perforation. There was no significant correlation between the number of magnets and gastroinstinal perforation ( r=0.276, P>0.05). Conclusions:The ingestion of magnetic foreign bodies in children often requires urgent management.When magnets are located within the prepyloric part of the GI tract, retrieval by endoscopy is recommended.The surgical intervention is required as soon as possible due to the failure of endoscopic treatment.
5.Risk factors for prognosis of primary intussusception treated by enema reduction in children based on propensity score matching analysis
Jindu ZHAO ; Qun GAO ; Xianying LU ; Zhenqiang ZHANG ; Zhubin PAN ; Chen CHEN ; Yixin HU
International Journal of Surgery 2022;49(5):314-319,C2
Objective:To evaluate the risk factors for prognosis of primary intussusception treated by enema reduction in children.Methods:A retrospective analysis of 519 patients with primary intussusception in Anhui Provincial Children′s Hospital from January 2017 to December 2020 was performed. Among the 519 patients, there were 346 males and 173 females. The median age was 15 months, with a range of 3 to 69 months, some basic information was collected. Patients were divided into bad prognosis group ( n=71) and good prognosis group ( n=448) according to prognosis.Propensity score matching (PSM) was conducted to reduce confounding bias between the groups. Conditional logistic regression were used to analysis the risk factors of primary intussusception treated by enema reduction. Results:There were 71 cases of poor prognosis among 519 primary intussusception patients, incidence was 13.7%.Before PSM, there was significant difference in 6 covariates, including gender, age, duration of symptoms, bloody stool, diarrhoea and fever between two group ( P<0.05). There was no significant difference in abdominal pain and vomit between two group ( P>0.05). With propensity score matching, 69 pairs of patients were sucessfully matched. After PSM, distribution of the above covariates reached equilibrium between two groups ( P>0.05). There were statistically significant differences in enema reduction, mass location, seroperitoneum, lactic acid and overweight/obese between the two groups ( P<0.05). Conditional logistic regression analysis confirmed that enema reduction( OR=3.478, 95% CI: 1.150-10.517, P=0.027), mass location ( OR=6.596, 95% CI: 1.669-26.056, P=0.007), lactic acid( OR=1.012, 95% CI: 1.003-1.021, P=0.010), overweight/obese ( OR=6.085, 95% CI: 1.650-22.436, P=0.007) were independent factors for predicting prognosis of primary intussusception treated by enema reduction. Conclusions:AER, mass located left hemicolon, elevated lactic acid and overweight/obese were independent risk factors for poor prognosis of primary intussusception treated by enema reduction.
6.Clinicopathological features of liposarcoma of the extremities: analysis of 14 cases
Xue LI ; Ying WU ; Shaoxiang LI ; Zhenqiang LI ; Yu BIAN ; Chunyan GUAN ; Zifen GAO ; Gehong DONG
Cancer Research and Clinic 2020;32(6):405-409
Objective:To investigate the clinicopathological characteristics, diagnosis and differential diagnosis of liposarcoma of the extremities.Methods:Fourteen patients with atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL), dedifferentiated liposarcoma (DDL) and myxoid liposarcoma (ML) in Beijing Tiantan Hospital of Capital Medical University from March 2002 to December 2019 were collected. Fluorescence in situ hybridization (FISH) and immunohistochemical staining were used to detect the MDM2 gene amplification and expressions of S-100, CDK4 and MDM2 proteins in tumor tissues. The characteristics of different types of liposarcoma were comprehensively analyzed combined with clinical data and histopathological characteristics.Results:The age of 14 patients was (55.6±16.7) years old, with 10 males and 4 females. There were 2 cases of ALT/WDL, 6 cases of DDL, and 6 cases of ML. Immunohistochemistry showed that S-100 was positive in all patients and the patterns were scattered, partial and extensive. CDK4 and MDM2 were positive in both ALT/WDL and DDL, and weakly expressed in ML (4 cases). Vimentin was positive in all patients. MDM2 gene amplification was detected in 2 cases of ALT/WDL and 6 cases of DDL.Conclusion:Liposarcoma has a high incidence and obvious morphological diversity, accurate diagnosis is critical to the prognosis and treatment of the tumor.
7.Application of magnetic resonance enterography and ectopic gastric mucosa imaging in children with lower gastrointestinal hemorrhage
Qun GAO ; Zhubin PAN ; Jindu ZHAO ; Jun HU ; He HUANG ; Xianying LU ; Zhenqiang ZHANG
Chinese Journal of Applied Clinical Pediatrics 2017;32(7):501-505
Objective To evaluate the diagnostic value of magnetic resonance enterography(MRE)and ectopic gastric mucosa imaging(EGMI)in children with lower gastrointestinal hemorrhage.Methods The clinical data including gender,age,amount of bleeding and preoperative minimum hemoglobin(Hb)levels of 54 children with lower gastrointestinal hemorrhage were collected,who received surgical exploration in Department of Pediatric Surgery,Anhui Provincial Children's Hospital between February 2014 and April 2016.Children were divided into lesion group and non-lesion group according to the findings of surgical exploration.Lesion group were defined as children with Meckel's diverticulum(MD)or duplication of the small intestine by surgery and postoperative pathological findings.A total of 36 cases,25 cases of boys,11 cases of girls,aged(2.86±1.59)years old.Non-lesion group were defined as children,who underwent operation with negative result or with lesions but not MD or duplication of the small intestine.A total of 18 cases,14 cases of boys,4 cases of girls,aged(3.87±1.62)years old.MRE and EGMI were performed when the children stopped bleeding,before the inspection,should fasting for 4-6 h.SPSS 13.0 software was used for statistical processing.The evaluation of EGMI,MRE and the both in diagnosing MD or duplication of the small intestine were conducted by receiver operating characteristic curve(ROC).According to the principles of biggest gain best diagnostic value by Youden index,and the degree of sensitivity and specificity was calculated at this time,P<0.05 for the difference was statistically significant.Results There was no significant differences statistically in gender between 2 groups(x2=0.415,P>0.05).There were statistically significant differences in age,amount of bleeding and preoperative minimum hemoglobin levels(t=2.179,2.027,2.222,all P<0.05).There were statistically significant differences in classification comparison by EGMI and MRE between 2 groups(x2=15.226,29.121,all P<0.01).The optimal cut-off value of EGMI and MRE in the diagnosis of enteric malformation was more than level 3,and the suspected positive and being positive value was assigned as positive results.According to the cut-off value above,EGMI,MRE and EGMI plus MRE in series and in parallel in the diagnosis of enteric malformation,the areas under curves(AUC)were 0.809,0.917,0.750 and 0.847,respectively.The sensitivity was 61.1%,75.0%,55.6%and 80.6%,respectively.The specificity was 90.4%,94.4%,94.4%and 88.9%,respectively.The Youden's indexes were 0.515,0.694,0.500 and 0.695,respectively.The optimal cut-off value of age and preoperative minimum hemoglobin levels in the diagnosis of enteric malformation were 2.92 years and 80 g/L,respectively.The AUC was 0.761 and 0.672.The Youden's indexes were 0.515 and 0.333.There was no significant differences statistically in AUC compared with age,MRE and EGMI(all P<0.05).Conclusions The high diagnostic value in children with lower gastrointestinal hemorrhage is found by using MRE and EGMI.Then,MRE as a separate diagnosis method is also worthy of clinical application.
8.Comparative study of mammogram and magnetic resonance imaging on diagnosis of breast ductal carcinoma in situ with or without microinvasion
Zhenqiang LIAN ; Yan ZHANG ; Qi WANG ; Simei XIE ; Anqin ZHANG ; Xiaorong HAN ; Hongyi GAO
Chinese Journal of General Surgery 2014;29(5):351-354
Objective To compare the sensitivity and diagnostic features of mammogram (MG) and magnetic resonance imaging (MRI) on diagnosis of breast ductal carcinoma in situ (DCIS) with or without microinvasion (DCIS-MI).Methods From Jan 2012 to Nov 2013,results of MG and MRI from 72 cases of DCIS or DCIS-MI were retrospectively analyzed.Results The sensitivity of MG was 52.8% (38/72).The sensitivity of MRI was 87.5% (63/72),among those 76.2% (48/63)lesions presented as non-mass-like enhancement.Sensitivity of MRI was significantly higher in DCIS-MI than DCIS (84.6% vs 100%,P =0.027).Logistic regression analysis showed calcifications was an independent factor influencing the sensitivity of MG (OR =23.785,P < 0.001).Conclusions The sensitivity of MRI is higher than MG for the diagnosis of DCIS and DCIS-MI.
9.Mesenchymal stem cells transplantation under the diagnostic ultrasound mediated microbubbles destruction in improving myocardial perfusion after rabbit myocardial ischemia
Yali XU ; Yunhua GAO ; Zheng LIU ; Kaibin TAN ; Zhenqiang FANG ; Yongliang LIU ; Pin QIAN ; Xi YANG
Chinese Journal of Ultrasonography 2009;18(9):792-796
Objective To explore the value of diagnostic ultrasound mediated microbubble destruction in improving the myocardial perfusion and left ventricular systolic function when cooperated with the mecsenchymal stem cells(MSCs) transplantation in rabbit myocardial ischemia. Methods One week after myocardial ischemia (MI) modeling,36 rabbits were divided into 3 groups,the control group(group Ⅰ) ,intravenous injection of MSCs group(group Ⅱ) and ultrasound + microbubble + MSCs group (group Ⅲ). Myocardial contrast enhancement (MCE) was performed and quantification analysis of anterior wall was assessed with Photoshop. Left ventrieular systolic function was assessed with M-mode echocardiography and bi-plane Simpson's method. CD34 expression in heart was detected with immunohistochemisty(IHC). Western blotting was applied to detect the level of VEGF in three groups. Results The differences of gray scale analyzed with histogram of Photoshop in anterior wall of ischemia myocardium between the group Ⅰ and group Ⅱ or group Ⅲ were significant,and P value was 0. 032 and 0. 000 , respectively. There were significant differences of FS between group Ⅲ (30. 43±4.09)% and group Ⅱ (26.29±2.93)%, P<0.01, and similar to group Ⅰ (19.28 ± 2.84)%. The difference of EF(%) between group Ⅲ and group Ⅱ was significant [(61.5±5.8 vs 53.6±4. 71), P<0. 05] ,or markedly significant between group Ⅲ and group Ⅰ [(61.5±5.8 vs 42.6± 5.0), P <0.01]. EF(%) assessed with bi-plane Simpson's method was significantly increased from (34.64 ± 4.59) in group Ⅰ to (41.78 ± 4.21) in group Ⅱ and (48.6±3.96) in group Ⅲ. The expression of CD34 assessed with immunohistochemistry was the highest in group Ⅲ. The level of VEGF with western blotting in group Ⅲ was significantly higher than other two groups. Conclusions It is an efficacious transplantation means of MSCs infusion under the ultrasound mediated microbubles destruction in improving the myocardial perfusion and cardiac systolic function.
10.Chemical and pharmacological research for Sect. Aptera (gentiana).
Zhenqiang MU ; Yang YU ; Hao GAO ; Weihua JIAO ; Xinsheng YAO
China Journal of Chinese Materia Medica 2009;34(16):2012-2017
Sect. Aptera (Gentiana L.) is the plant origin of Traditional Chinese Medicine (TCM) "Qinjiao", which is used to treat rheumatism and pains with a long history. The plants of Sect. Aptera mainly contain iridoids, triterpenes and steroids, and possess anti-inflammatory, analgesia, stomach invigorate and bacteria inhibitory effects, etc. Herein, we reviewed the advances of chemical and pharmacological investigations of Sect. Aptera for further research.
Animals
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Drug Therapy
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Drugs, Chinese Herbal
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chemistry
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pharmacology
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Gentiana
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chemistry
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Humans
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Plant Extracts
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chemistry
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pharmacology

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