1.Bioinformatics Reveals Mechanism of Xiezhuo Jiedu Precription in Treatment of Ulcerative Colitis by Regulating Autophagy
Xin KANG ; Chaodi SUN ; Jianping LIU ; Jie REN ; Mingmin DU ; Yuan ZHAO ; Xiaomeng LANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):166-173
ObjectiveTo explore the potential mechanism of Xiezhuo Jiedu prescription in regulating autophagy in the treatment of ulcerative colitis (UC) by bioinformatics and animal experiments. MethodsThe differentially expressed genes (DEGs) in the colonic mucosal tissue of UC patients was obtained from the Gene Expression Omnibus (GEO), and those overlapped with autophagy genes were obtained as the differentially expressed autophagy-related genes (DEARGs). DEARGs were imported into Metascape and STRING, respectively, for gene ontology/Kyoto Encyclopedia of Genes and Genomics (GO/KEGG) enrichment analysis and protein-protein interaction (PPI) analysis. Finally, 15 key DEARGs were obtained. The core DEARGs were obtained by least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic curve (ROC) analysis. The CIBERSORT deconvolution algorithm was used to analyze the immunoinfiltration of UC patients and the correlations between core DEARGs and immune cells. C57BL/6J mice were assigned into a normal group and a modeling group. The mouse model of UC was established by free drinking of 2.5% dextran sulfate sodium. The modeled mice were assigned into low-, medium-, and high-dose Xiezhuo Jiedu prescription and mesalazine groups according to the random number table method and administrated with corresponding agents by gavage for 7 days. The colonic mucosal morphology was observed by hematoxylin-eosin staining. The protein and mRNA levels of cysteinyl aspartate-specific proteinase 1 (Caspase-1), cathepsin B (CTSB), C-C motif chemokine-2 (CCL2), CXC motif receptor 4 (CXCR4), and hypoxia-inducing factor-1α (HIF-1α) in the colon tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction, respectively. ResultsThe dataset GSE87466 was screened from GEO and interlaced with autophagy genes. After PPI analysis, LASSO regression, and ROC analysis, the core DEARGs (Caspase-1, CCL2, CTSB, and CXCR4) were obtained. The results of immunoinfiltration analysis showed that the counts of NK cells, M0 macrophages, M1 macrophages, and dendritic cells in the colonic mucosal tissue of UC patients had significant differences, and core DEARGs had significant correlations with these immune cells. This result, combined with the prediction results of network pharmacology, suggested that the HIF-1α signaling pathway may play a key role in the regulation of UC by Xiezhuo Jiedu prescription. The animal experiments showed that Xiezhuo Jiedu prescription significantly alleviated colonic mucosal inflammation in UC mice. Compared with the normal group, the model group showed up-regulated protein and mRNA levels of caspase-1, CCL2, CTSB, CXCR4, and HIF-1α, which were down-regulated after treatment with Xiezhuo Jiedu prescription or mesalazine. ConclusionCaspase-1, CCL2, CTSB, and CXCR4 are autophagy genes that are closely related to the onset of UC. Xiezhuo Jiedu prescription can down-regulate the expression of core autophagy genes to alleviate the inflammation in the colonic mucosa of mice.
2.Mechanism of Xiezhuo Jiedu Recipe Regulating Ferroptosis in Treatment of Ulcerative Colitis Based on Bioinformatics and Animal Experiments
Chaodi SUN ; Jianping LIU ; Mingmin DU ; Xin KANG ; Jiancong CUI ; Yuan ZHAO ; Sujie JIA ; Xiaomeng LANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):166-173
ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes (FRGs) closely related to ulcerative colitis (UC), and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis. MethodThe differentially expressed genes (DEGs) of colonic mucosa tissue of UC patients were obtained from the GEO database, and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis, minimum absolute contraction and selection operator (LASSO) regression, and receiver operating characteristic curve (ROC) curve analysis. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of E3 ubiquitin ligase (FBXW7), zinc finger protein (ZFP36), solute carrier family 7 member 11 (SLC7A11), and Toll-like receptor 4 (TLR4) in colon tissue. The protein expression levels of FBXW7, ZFP36, SLC7A11, and TLR4 in colon tissue were detected by Western blot. ResultDataset GSE87466 was screened from the GEO database, and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis, LASSO regression, and ROC analysis, core FRGs (FBXW7, ZFP36, SLC7A11, and TLR4) were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells, M1 macrophages, plasma cells, and M2 macrophages in the colonic mucosa tissue of UC mice, and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine, while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group, the protein and mRNA expressions of FBXW7, ZFP36, SLC7A11, and TLR4 in the model group were significantly increased, and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine. ConclusionFBXW7, ZFP36, SLC7A11, and TLR4 are ferroptosis genes closely related to the pathogenesis of UC, and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.
3.Xiezhuo Jiedu formula alleviates ulcerative colitis and regulates macrophage polarization in rats
Xin KANG ; Jianping LIU ; Jie REN ; Mingmin DU ; Yuan ZHAO ; Boqian HU ; Xiaomeng LANG
Immunological Journal 2024;40(1):65-71
This study was performed to explore the therapeutic effect of Xiezhuo Jiedu Formula on ulcerative colitis rats and its effects on β-catenin/FOSL2/ARID5A signaling pathway and macrophage polarization.Rats of ulcerative colitis was induced and divide into control group,model group,positive group(intervention with sulfasalazine),and low,medium and high-dose groups(intervention with Xiezhuo Jiedu Fang).After 14 days of intervention,the disease activity index(DAI)and colon mucosa damage index(CDMI)were calculated and used to evaluate the state of rats.HE staining was used to observe lesion tissue;ELISA was used to detect of serum levels of TNF-α and IL-6;flow cytometry was used to detect peripheral blood M1 and M2 macrophage content;RT-PCR was used to detect the mRNA expression of iNOS,CD206,and β-Catenin/FOSL2/ARID5A;immunohistochemistry was used to detect β-Catenin/FOSL2/ARID5A signaling pathway protein expression in colon tissue.Data showed that DAI score,CMDI score,and serum TNF-α and IL-6 in the low,medium,and high dose groups were significantly lower than the model group(P<0.05).HE staining showed that the colon tissue damage and inflammatory infiltration in the low,medium,and high dose groups were slighter than those in the model group(P<0.05).The rate of M1 type macrophages and iNOS mRNA in the low,medium,and high dose groups were significantly lower than those in the model group,while the rate of M2 type macrophages and CD206 mRNA were significantly higher than those in the model group(P<0.05).The mRNA and protein expressions of β-catenin and FOSL2 in colon tissue of low,medium,and high dose groups were significantly higher than those of the model group,while the mRNA level and protein expression of ARID5A were significantly lower than that of the model group(P<0.05).Taken together,Xiezhuo Jiedu formula can effectively alleviate the clinical symptoms,reduce inflammatory response,downregulate β-catenin/FOSL2/ARID5A expression,regulate macrophage polarization and promote disease recovery of ulcerative colitis in rats.
4.Practice on human genetic resources management using PDCA circle in new drug clinical research
Mingmin SUN ; Tianping LI ; Yi CHAI ; Jun ZHAO
Chinese Journal of Medical Science Research Management 2020;33(3):232-235
Objective:The paper aims to ensure the rational and legal utilization of genetic resources and maintain the national biosafety through the management of human genetic resources in clinical research carried out by medical institutions.Methods:Literature review and survey methods were adopted. Deming Circle, with focus on the four stages from planning, implementation, inspection, and countermeasures, was used to continuously improve the quality of human genetic resources management in the hospital.Results:The concept of hospital human genetic resources management was recognized and the management quality was significantly improved.Conclusions:The PDCA cycle management method is of positive significance to the management of human genetic resources in the clinical research of new drugs in medical institutions, and it is an effective way to improve the management level under current system.
5.Effects of health education on brucellosis, iodine deficiency disorders and leprosy in Tongguan County of Weinan City, Shaanxi Province
Aizhu ZHAO ; Mingmin WEI ; Min ZHOU
Chinese Journal of Endemiology 2019;38(7):570-573
Objective To explore the methods and effects of health education on brucellosis, iodine deficiency disorders and leprosy, and consolidate the achievements of endemic diseases and leprosy control. Methods Three groups of local residents, students and medical staff were selected for health education intervention in Tongguan County of Weinan City, Shaanxi Province in 2017. Among the three groups, the choice of different propaganda modes (brucellosis case warning film, iodine deficiency disorders public service advertisement, leprosy knowledge preaching, etc.) and propaganda materials (promotional foldout, brochure, leaflet, shopping bag, etc.) were compared. At the same time, questionnaire survey was used to compare the awareness rate of health knowledge before and after intervention. Results A total of 375 people were surveyed. On the propaganda modes , 296 people chose to watch the brucellosis case warning film, accounting for 78.93% (296/375); 184 people chose to watch the iodine deficiency disorders public service advertisement, accounting for 49.07% (184/375); 286 people chose leprosy knowledge preaching, accounting for 76.27% (286/375); and 117 people chose to read information , accounting for 31.20% (117/375). On the propaganda materials, 185 people chose promotional foldout, accounting for 49.33% (185/375); 232 people chose brochure, accounting for 61.87% (232/375); 76 people chose leaflet, accounting for 20.27% (76/375); 277 people chose shopping bag, accounting for 73.87% (277/375); and 286 people chose exercise book, accounting for 76.27% (286/375). Before intervention, the total awareness of health knowledge of brucellosis, iodine deficiency disorders and leprosy was 62.18% (4197/6750), 61.49% (1153/1875) and 30.02% (788/2625), respectively; after intervention, the total awareness of health knowledge of brucellosis, iodine deficiency disorders and leprosy was 91.13%(6151/6750), 89.49%(1678/1875) and 89.22%(2342/2625), respectively . The differences were statistically significant before and after intervention (χ2= 1580.30, 397.28, 1910.65, P < 0.01). Conclusions Warning film, knowledge preaching and the issuance of shopping bag and exercise book methods are more popular and more easily accepted by all types of people. Short term health education has a certain effect. In order to acquire and form good health knowledge behaviors really, it is necessary to carry out long-term, extensive and sustained, and diversified work of healthy education.
6. Evaluation of causes and clinical effects of revision surgery after artificial hip replacement
Bin HE ; Miaofeng ZHANG ; Yue SHEN ; Xiang ZHAO ; Zhimin YING ; Mingmin SHI ; Wei WANG ; Shigui YAN
Chinese Journal of Orthopaedics 2019;39(15):909-917
Objective:
To investigate the clinical effects of primary revision after artificial hip replacement and causes of revision surgery.
Methods:
A total of 344 patients who underwent revision surgery after total hip arthroplasty (THA) and artificial femoral head replacement from January 2010 to December 2016 were retrospectively analyzed. There were 141 males and 203 fe-males, with a mean age 65.64±10.81 years (28-87 years). A total of 351 hip revisions were performed in 344 patients with 7 pa-tients in bilateral revisions. All patients were followed up for 60.38±22.75 months (24-105 months). All patients with periprosthet-ic infection underwent two-stage revision after prosthesis placement, and all others underwent one-stage revision. The clinical out-comes of revision surgery were assessed with the Harris hip score and the survival rate of the revision prosthesis. According to the duration from artificial hip replacement to revision surgery, all patients were divided into early revision (less than 5 years) and late revision (more than 5 years) groups. They were also divided into two groups according to the age of the patient in revision sur-gery: >55-year-old and ≤55-year-old groups. The causes of revision, hip reoperation and re-revision were recorded.
Results:
In the 351 hip revisions, a total of 238 (67.8%) had aseptic loosening, 41 (11.7%) periprosthetic fractures, 30 (8.5%) periprosthetic infection, 23 (6.6%) recurrent dislocation and 19 (5.4%) the eccentric liner wear. The infection rate was significantly higher in the early revision group (21.1%) than that in the late revision group (4.2%) (χ2=24.443,
7.In Vitro Dissolution Feature of Chuangxiong Powder
Yang LIU ; Beiran LV ; Baosheng ZHAO ; Guopeng WANG ; Xiaoyan HAN ; Lei ZHANG ; Honghuan DONG ; Meiling ZHU ; Li WEI ; Mingmin TANG
Chinese Journal of Information on Traditional Chinese Medicine 2014;(2):88-91
Objective To compare the dissolution of Chuangxiong powder in different medium and discuss the dissolution characteristics in vitro of Changxiong powder. Methods The paddle method was adopted, the UV spectrophotometric method was developed to determine the in vitro dissolution quantity of Changxiong powder in five medium (water, 0.1 mol/L hydrochloric acid, acetate buffer of pH 4.5, phosphate buffer of pH 6.8, phosphate buffer of pH 7.4) with ferulic acid as index, and evaluated by drawing the dissolution curve and using the similar factor method and Weibull model. Results The dissolution quantity of Changxiong oral powder in five medium was different. The dissolution quantity in water, 0.1 mol/L hydrochloric acid, acetate buffer of pH 4.5 and phosphate buffer of pH 6.8 was similar and fit Weibull model, but it mutated in phosphate buffer of pH 7.4 and reached the maximum amount at 30 min. Conclusion The dissolution quantity of Changxiong powder is gradually increasing and the time is shorted in the medium from acidic to neutral then to alkaline. Dissolution curve is similar in the acidic and neutral medium. Changxiong powder dissolves out fast and completely in the alkaline medium.
8.Evaluation of the diagnostic criteria of gestational metabolic syndrome and analysis of the risk factors
Jianmin NIU ; Qiong LEI ; Lijuan Lü ; Jiying WEN ; Xiaohong LIN ; Dongmei DUAN ; Xi CHEN ; Yuheng ZHOU ; Caiyuan MAI ; Guocheng LIU ; Mingmin HOU ; Lina ZHAO ; Jing YI
Chinese Journal of Obstetrics and Gynecology 2013;(2):92-97
Objectives To investigate gestational multiple metabolic abnormalities aggregation and diagnostic criteria for gestational metabolic syndrome(GMS),and to analyze the risk factors of GMS.Methods A cohort study recruiting 309 pregnant women with preeclampsia,627 pregnant women with gestational diabetes mellitus(GDM)and 1245 normal pregnant women was performed from January 2008 to December 2011 in Guangdong Women and Children's Hospital.Information regarding age,gestational weeks,basic blood pressure,admission blood pressure,height and body mass index(BMI)before pregnancy was recorded.Biochemical indicators including fasting plasma glucose(FPG),fasting insulin (FINS),total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),free fatty acids(FFA)were tested.GMS was diagnosed with three or all of the following conditions:(1)overweight and/or obesity before pregnancy(BMI ≥ 25 kg/m2);(2)hypertension with blood pressure ≥ 140/90 mm Hg(1 mm Hg =0.133 kPa);(3)hyperglycemia:diagnosed as GDM;(4)dyslipidemia with TG≥3.23 mmol/L The incidence of GMS of the three groups were calculated and the risk factors were analyzed.Results(1)The age,gestational weeks,basic blood pressure,admission blood pressure,BMI before pregnancy of women with preeclampsia and women with GDM were significantly different compared to normal women,respectively(P < 0.01).(2)Biochemical indicators of women with preeclampsia were as following:FPG(4.6 ± 1.0)mmol/L,FINS(10.1 ± 5.6)mU/L,TC(6.3 ±1.6)mmol/L,TG(3.9 ± 1.8)mmol/L,HDL-C(1.4 ±0.4)mmol/L,LDL-C(3.0 ± 1.0)mmol/L,FFA (0.8 ±0.4)mmol/L.And those in women with GDM were:FPG(4.7 ± 0.9)mmoL/L,FINS(10.2 ± 5.8)mU/L,TC(5.7 ± 1.3)mmol/L,TG(3.2 ± 1.1)mmol/L,HDL-C(1.4 ± 0.4)mmol/L,LDL-C (2.7 ± 0.9)mmol/L,FFA(0.6 ± 0.3)mmol/L In normal pregnant women they were:FPG(4.3 ±0.5)mmol/L,FINS(9.0±4.4)mU/L,TC(5.7 ±1.1)mmol/L,TG(2.8 ±1.1)mmol/L,HDL-C (1.5 ± 0.4)mmol/L,LDL-C(2.9 ± 0.8)mmol/L,FFA(0.6 ± 0.2)mmol/L Statistic differences were found in preeclampsia and GDM women compared to normal women respectively(P < 0.01).(3)The prevalence of GMS in preeclampsia group and in GDM group was 26.2%(81/309)and 13.6%(85/627),statistically different from that of the control group(0)(P <0.01).(4)Compared to normal women,women with preeclampsia had higher risk of developing GMS(OR =1.62,95 % CI 1.31-2.00,P < 0.01).The risk factors were BMI(OR =1.29,95% CI 1.13-1.47)and TG(OR =2.49,95% CI 1.87-3.31).Also,women with GDM had higher risk of developing GMS than normal women(OR =1.27,95% CI 1.09-1.49,P < 0.01),and the risk factors were BMI(OR =1.13,95 % CI 1.04-1.23)and TG(OR =1.16,95 % CI 1.02-1.33).TG was the independent risk factor in both preeclampsia women and GDM women(P < 0.01,P < 0.05).HDL-C seemed to have less importance in identifying GMS(P > 0.05).Conclusions According to the GMS diagnostic criteria used in this study,some preeclampsia patients and some GDM women had aggregation of multiple metabolic abnormalities including pre-pregnancy overweight/obesity,hyperglycemia,high blood pressure and dyslipidemia.TG was the independent risk factor for GMS.HDL-C seemed to have less importance in identifying GMS.
9.Effects of sodium valproate on proliferation and apoptosis of Hep-2 cells and associated mechanism.
Junhui ZHANG ; Yulin ZHAO ; Mingmin DONG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2010;24(8):359-362
OBJECTIVE:
To observe the effect of sodium valproate (VPA) on proliferation and apoptosis of human laryngeal carcinoma Hep-2 cells and its associated mechanism.
METHOD:
Methabenzthiazuron (MTT) was used to observe the proliferation of human laryngeal carcinoma Hep-2 cells treated with various concentrations of VPA at different times. Flow cytometry(FCM) and RT-PCR were used to measure the apoptosis rate and the expression of Survivin mRNA in the Hep-2 cells treated with VPA at 3 mmol/L for different times.
RESULT:
VPA inhibited growth of Hep-2 cells in a dose-dependent and time-dependent manner (P < 0.01). The apoptosis rate increased after the treatment by VPA at 3 mmol/L. There were significant differences between different time groups (P < 0.01). The expression of Survivin mRNA of Hep-2 cells were decreased in a time dependent manner (3 mmol/L) (P < 0.01).
CONCLUSION
VPA have obvious growth inhibition and induction of apoptosis on human laryngeal cancer Hep-2 cells, its mechanism is related to decrease the expression of Survivin.
Apoptosis
;
drug effects
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Cell Line, Tumor
;
Cell Proliferation
;
drug effects
;
Flow Cytometry
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Humans
;
Inhibitor of Apoptosis Proteins
;
metabolism
;
Survivin
;
Valproic Acid
;
pharmacology
10.Detection of ADAR1 mRNA expression in larynx carcinoma tissues.
Wenfa YU ; Yulin ZHAO ; Kai WANG ; MingMin DONG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2008;22(2):73-75
OBJECTIVE:
To investigate the expressions of RNA-dependent adenosine deaminase 1(ADAR1) mRNA in larynx carcinoma tissues, and to discuss its value in the development of larynx carcinoma.
METHOD:
The expression of ADAR1 mRNA in 51 larynx carcinoma and peri-carcinoma tissues were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).
RESULT:
ADAR1 mRNA was expressed broadly; the relative intensities of its expression in larynx carcinoma, larynx peri-carcinoma samples and larynx non-carcinoma tissue samples were respectively 2.963 +/- 0.912, 0.791 +/- 0.197 and 0.910 +/- 0.311. There were remarkable difference between larynx carcinoma and larynx peri-carcinoma, larynx carcinoma and non-carcinoma tissues.
CONCLUSION
ADAR1 mRNA is expressed broadly in larynx carcinoma and may be play an important role in the development of larynx carcinoma.
Adenosine Deaminase
;
genetics
;
metabolism
;
Aged
;
Female
;
Humans
;
Laryngeal Neoplasms
;
genetics
;
metabolism
;
pathology
;
Male
;
Middle Aged
;
RNA, Messenger
;
genetics
;
RNA-Binding Proteins

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