1.The mechanism of emodin inhibiting YAP1 and FOXD1 in gastric cancer AGS cells and its related study
Tian GU ; Chunhong LIU ; Fei ZHANG ; Wei QIAN ; Yanqiu ZHU ; Mingliang CHU ; Jiemin LIU
The Journal of Practical Medicine 2024;40(1):59-64,71
Objective To explore the possible mechanism of emodin in inhibiting proliferation,migration,and invasion of AGS cells and in suppressing the expressions of YAP1 and FOXD1.Methods Normal gastric cell GES-1 and gastric cancer cell AGS were cultured with different concentrations of emodin.CCK8 test,scratch test and Transwell assay were used to verify changes in the biological phenotype of AGS cells.TCGA database was applied to analyze expressions of HK2,YAP1 and FOXD1 in gastric cancer tissues and normal gastric tissues.Western blotting method was used to detect the impacts of emodin on HK2,YAP1 and FOXD1 proteins in AGS cells.Exogenous pyruvic acid was added to verify the changes in YAP1 and FOXD1.Results The IC50 of emodin was significantly higher in GES-1 cells than in AGS cells(P<0.05).CCK8 proliferation test,scratch test,and Transwell assay showed that emodin significantly inhibited the biological abilities of AGS(P<0.05 for comparisons).Analysis on the TCGA bioinformatics database found that the expression of key enzymes HK2 in the glycolysis pathway and oncogenes YAP1 and FOXD1 was significantly higher in gastric cancer tissues than in normal gastric tissues(P<0.05 for comparisons).Emodin significantly inhibited the protein expressions of key glycolytic enzymes HK2 and oncogenes YAP1 and FOXD1(P<0.05 for comparisons).With supplement of exogenous glycolytic metabolite pyruvate,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased(P<0.05 for comparisons).Conclusions Emodin has a significant pharmacological inhibitory effect on gastric cancer AGS cells,markedly suppressing their biological phenotype.Emodin not only significantly inhibits the key enzyme HK2 in glycolysis metabolism,but also the protein expressions of oncogenes YAP1 and FOXD1.With the addition of exogenous pyruvate to enhance the glycolytic metabolic pathway,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased.The above results suggest a close association of YAP1 and FOXD1 with glycolytic metabolism.Emodin may inhibit oncogenes YAP1 and FOXD1 through the glycolytic metabolism of gastric cancer AGS cells.
2.Efficacy and safety of amphotericin B combined with posaconazole in the treatment of cryptococcal meningitis complicated with AIDS
Lu ZHANG ; Yanqiu LU ; Dan LIU ; Jing HU
China Pharmacy 2024;35(16):2018-2022
OBJECTIVE To observe the efficacy and safety of amphotericin B combined with posaconazole in the treatment of patients with AIDS combined with cryptococcal meningitis (CM). METHODS The data of 44 patients with AIDS combined with CM admitted to Chongqing Public Health Medical Center and the First Affiliated Hospital of Army Military Medical University from January 2021 to June 2023 were collected retrospectively. They were divided into amphotericin B combined with flucytosine (AmB+FC) group and amphotericin B combined with posaconazole (AmB+POS) group according to treatment regimen, with 22 cases in each group. AmB+FC group was given Amphotericin B for injection+Flucytosine injection; AmB+POS group was given Amphotericin B for injection+posaconazole injection. After 12 weeks of treatment, clinical efficacies of two groups, clinical symptoms and the negative coversion rate of cerebrospinal fluid, and laboratory test results before and after treatment were observed in 2 groups, and the occurrence of adverse drug reactions was recorded in 2 groups. RESULTS After 12 weeks of treatment, the total effective rate, the incidences of fever, blurred vision, leukopenia, anemia, renal function abnormalities, hypokalemia, liver function abnormalities, rash, and peripheral neuropathy were compared between the two groups, and the differences were not statistically significant (P>0.05). The negative coversion rate of cerebrospinal fluid in AmB+POS group was significantly higher than AmB+FC group; the incidences of headache, nausea and vomiting symptoms, and the incidence of any adverse events were significantly lower than AmB+FC group (P<0.05). The cerebrospinal fluid pressure and cerebrospinal fluid protein content of the two groups were significantly lower than those before treatment, and the cerebrospinal fluid glucose content and cerebrospinal fluid chloride content were significantly higher than those before treatment (P<0.05); however, the differences were not statistically significant between 2 groups (P>0.05). CONCL USIONS Amphotericin B combined with posaconazole improves the negative coversion rate of cerebrospinal fluid and relieves clinical symptoms in patients with AIDS combined with CM with good safety.
3.Effect of culture supernatant of human umbilical cord mesenchymal stem cells on survival,apoptosis and endometrium receptivity of human endometrial stromal cells after treated with mifepristone
Mengxue WU ; Shiling CHEN ; Yan LIU ; Xuguang MI ; Xiuying LIN ; Jianhua FU ; Yanqiu FANG
Journal of Jilin University(Medicine Edition) 2024;50(1):79-87
Objective:To discuss the effect of human umbilical cord mesenchymal stem cells culture supernatant(hUCMSCs-Sup)on the proliferation,apoptosis,and endometrium receptivity of the human endometrial stromal cells(hEndoSCs)treated with mifepristone(Ms),and to clarify the possible mechanism.Methods:The hEndoSCs were cultured in vitro and divided into control group and 40,60,80,and 100 μmol·L-1 Ms groups.The survival rates of the cells in various groups were detected by MTT assay.The hEndoSCs were divided into control group,40 μmol·L-1 Ms group,and 60 μmol·L-1 Ms group.The apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of apoptosis-related protein B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)proteins in the cells in various groups were detected by Western blotting method,and the ratio of Bcl-2/Bax was calculated.After treated with hUCMSCs-Sup,the hEndoSCs were divided into control group,Ms group,Ms+hUCMSCs-Sup group,and Ms+hUCMSCs-Sup+3-methyladenine(3-MA)group.The survival rates of the cells in various groups were detected by MTT assay;the apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of microtubule-associated protein 1 light chain 3B-Ⅱ(LC3B-Ⅱ)and microtubule-associated protein 1 light chain 3B-I(LC3B-Ⅰ)proteins in the cells in various groups were detected by Western blotting method,and the ratio of LC3B-Ⅱ/LC3B-Ⅰwas calculated;the expression levels of endometrium receptivity marker molecules mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:Compared with control group,the survival rates of the cells in 40,60,80,and 100 μmol·L-1 Ms groups were significantly decreased(P<0.05)in a time-dependent and dose-dependent manner.Compared with control group,the apoptotic rates of the cells in 40 and 60 μmol·L-1 Ms groups were significantly increased(P<0.05),and the ratios of Bcl-2/Bax were significantly decreased(P<0.05).After treated with hUCMSCs-Sup,compared with control group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms group were significantly decreased(P<0.05),the apoptotic rate was significantly increased(P<0.05),and the expression levels of homeobox A10(HOXA10),leukemia inhibitory factor(LIF),and integrin subunit beta 3(ITGB3)mRNA in the cells were significantly decreased(P<0.05);compared with Ms group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰin the cells in Ms+hUCMSCs-Sup group were significantly increased(P<0.05),the apoptotic rate was significantly decreased(P<0.05),and the expression levels of HOXA10,LIF,and ITGB3 mRNA in the cells were significantly increased(P<0.05);compared with Ms+hUCMSCs-Sup group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms+hUCMSCs-Sup+3-MA group were significantly decreased(P<0.05).Conclusion:hUCMSCs-Sup can increase the survival rate and decrease the apoptotic rate of the hEndoSCs after treated with Ms,and increase the endometrium receptivity,and its mechanism may be associated with the activation of autophagy of the hEndoSCs by hUCMSCs-Sup.
4.How do female mosquitoes determine the most suitable males for mating?
Yitong LI ; Dong LI ; Xiaofei LIU ; Ying WANG ; Tingting LIU ; Yanqiu XU ; Shengqun DENG
Chinese Journal of Schistosomiasis Control 2024;36(3):321-328
More than 80% of the world’s populations are at risk of vector-borne diseases, with mosquito-borne diseases as a significant global public health problem. Mosquito populations control is critical to interrupting the transmission of mosquito-borne diseases. This review summarizes the physical attributes, smell, vision, touch, and hearing of mosquitoes to unravel the preferences of female mosquitoes, and describes the mechanisms underlying the best male mating by female mosquitoes, so as to provide new insights into management of mosquito-borne diseases.
5.Research progress in evaluation of type 2 diabetic peripheral neuropathy animal model
Ziyue ZHU ; Lu WANG ; Junpeng YAO ; Huilin LIU ; Yanqiu LI ; Ying LI ; Wei ZHANG
Chinese Journal of Comparative Medicine 2024;34(1):139-145,157
Diabetic peripheral neuropathy is a common diabetic complication.Presently,our understanding of its pathogenesis is incomplete,and there are no effective treatment options.In-depth research requires the use of animal experiments.The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments into type 2 diabetic peripheral neuropathy.However,but there has been a lack of systematic interrogation and analysis of the evaluation method used with type 2 diabetic peripheral neuropathy models.Therefore,the author reviewed the recent data,summarized and analyzed the evaluation method used for animal models of type 2 diabetic peripheral neuropathy of small and large nerve fibers,and proposed future directions for development,providing a reference for related research.
6.Mechanism of Qingre Huayu Jianpi Prescription Inhibiting Development of Colitis-associated Colorectal Cancer in Mice
Yanqiu ZHENG ; Yihui YOU ; Junyu KE ; Jinbin SONG ; Yongqiang WU ; Changhui LIU ; Yanwu LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):83-90
ObjectiveTo explore the effect of Qingre Huayu Jianpi prescription (QHJ) on colitis-associated colorectal cancer (CAC) in mice, and its related mechanism. MethodC57BL/6 mice were randomly divided into four groups including the normal, model, QHJ low-dose (QHJ-L, 10 g·kg-1), and QHJ high-dose (QHJ-H, 40 g·kg-1) groups. Azoxymethane (AOM) and dextran sodium sulfate (DSS) were combined to chemically build a CAC mouse model for 14 weeks. Each drug group was given intragastrically from the 5th week to the 14th week, once per day. An equal volume of water was fed to the normal and model groups. The mouse survival rate, colon length, weight, and pathological alterations were assessed. The protein expressions of Wnt-3a protein signaling (Wnt3a), β-catenin, Non-phosphor-β-catenin (Non-p-β-catenin), and cholesterol-binding glycoproteins 133 (CD133) were detected by Western blot. The localization and expression of the cluster of differentiation (CD) 80 and CD11 antigen-like family member B (CD11b) were detected by immunohistochemistry (IHC). The colon organoids derived from CAC mice were isolated and cultured to detect the expression of Wnt signaling pathway-related proteins. ResultThe survival rate of the CAC mice was improved by QHJ treatment and the number of colon tumors was inhibited significantly. Compared with those in the normal group, the expression levels of Wnt3a, β-catenin, Non-p-β-catenin, and CD133 in colon tissues in the model group were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the levels of Wnt3a and β-catenin in the QHJ-L group were significantly decreased (P<0.01), and the protein levels of Wnt3a, β-catenin, Non-p-β-catenin, and CD133 in the QHJ-H group were significantly decreased (P<0.05, P<0.01). Meanwhile, the expression level of CD11b in the model group was significantly increased compared with that in the normal group while the CD80 level was significantly decreased (P<0.05, P<0.01). Compared with those in the model group, CD11b in QHJ-L and QHJ-H groups was significantly decreased, and CD80 was significantly increased(P<0.05, P<0.01). The expressions of Non-p-β-catenin and CD133 in colonic organoids of CAC model mice were significantly increased, while QHJ treatment could inhibit the expressions of Non-p-β-catenin and CD133 in colonic organoids (P<0.01). ConclusionQHJ could inhibit the inflammation-cancer development in CAC mice, the mechanism of which might be related to regulating the microenvironment and inhibiting the over-activation of Wnt signaling.
7.Application of intelligent information technology in the field of medical equipment management
Lingguang MENG ; Yuan WANG ; Dong LIU ; Yanqiu MENG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(3):520-524
With the rapid development of information technology,what has been widely used in the field of medical and health care includes the home detection of aging population in communities,intelligent health management,special patient positioning care management,information sharing,and interconnection management,which has also brought new opportunities for the innovative management of medical equipment in recent years.We have taken"sense,knowledge and action"as the core,and effectively improved the level of lean management of medical equipment through data acquisition,data modeling and analysis,and remote service or decision response.This paper aims to summarize the application and research progress of intelligent information technology in the lean management of medical equipment in order to provide new ideas for the refined management of medical equipment.
8.Characteristics of Early Cardiac Involvement in 45 Patients With Fabry Disease Monitored by Ultrasonic Cardiogram
Jie LI ; Min YE ; Rui FAN ; Jingwei ZHANG ; Yanqiu LIU ; Yili CHEN ; Yugang DONG ; Fengjuan YAO
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(4):613-621
[Objective]To evaluate the changes in cardiac structure and ventricular function in patients with Ander-son-Fabry Disease(AFD)by two-dimensional speckle tracking echocardiography(2D-STE)and to explore the character-istics of their early cardiac involvement.[Methods]All 45 patients diagnosed with AFD in this observational study under-went routine ultrasonic cardiogram(UCG)examination and 2D-STE.The patients were divided into 2 groups based on UCG measurements:with left ventricular hypertrophy(interventricular septum or posterior left ventricular wall thickness≥12 mm)and without left ventricular hypertrophy.TomTec software was used to analyze the echocardiographic images,then the baseline data,UCG routine parameters and myocardial strain of the two groups were compared.[Results]The study in-cluded 27 males(60.0%)and 18 females(40.0%),with an average age of(32.33±16.11),17 cases(37.78%)with left ventricular hypertrophy and 28 cases(62.22%)without left ventricular hypertrophy.All patients had normal left ventricu-lar ejection fraction(LVEF)(>50%).Compared with those without left ventricular hypertrophy,patients with left ventric-ular hypertrophy had significantly more target organ involvement,significantly higher E/A and average E/E' ratios(P<0.05).No statistical difference was found in global and segmental longitudinal strain(LS),circumferential strain(CS)and radial strain(RS)of the endocardium and myocardium between the two groups(all P>0.05).There were lower abso-lute values of global and segmental LS and CS in the myocardium than in the endocardium(all P<0.05),and higher abso-lute values of LS and RS in the mid segment than in the basal and apical segments(all P<0.05).[Conclusions]There is no significant association between early systolic dysfunction and left ventricular wall thickness.2D-STE strain can be used to detect AFD in the early stage.Ventricular wall myocardium exhibits more serious involvement than endocardium and mid segment was less involved than the apical and basal segments.
9.Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease: Prospective cohort study and genetic analyses
Wenqiang ZHANG ; Li ZHANG ; Chenghan XIAO ; Xueyao WU ; Huijie CUI ; Chao YANG ; Peijing YAN ; Mingshuang TANG ; Yutong WANG ; Lin CHEN ; Yunjie LIU ; Yanqiu ZOU ; Ling ZHANG ; Chunxia YANG ; Yuqin YAO ; Jiayuan LI ; Zhenmi LIU ; Xia JIANG ; Ben ZHANG
Chinese Medical Journal 2024;137(5):577-587
Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.
10.Effect of Wnt/β-catenin signaling pathway inhibitor MS AB on fibrogenic responses of human endometrial stromal cells
Feina WANG ; Xuguang MI ; Xiuying LIN ; Jianhua FU ; Lei LIU ; Xinyue YU ; Huanhuan ZANG ; Linjun LIU ; Shiling CHEN ; Yanqiu FANG
Journal of Jilin University(Medicine Edition) 2024;50(5):1266-1274
Objective:To discuss the effect of Wnt/β-catenin signaling pathway inhibitor methyl 3-{[(4-methyl-phenyl)sulfonyl]amino } benzoate(MS AB)on the fibrogenic response of the human endometrial stromal cells(HESCs),and to provide the foundation for the application of MSAB in the target therapy of intrauteriue adhesion(JUA).Methods:The normal HESCs were cultured in vitro and divided into two groups:control group and transforming growth factor β1(TGF-β1)group;the HESCs from the adhesion part of the IUA patients were cultured in vitro,regarded as IUA group.Western blotting method was used to detect the expression levels of fibrotic marker protein type Ⅰ collagen α1(COL1A1)in the cells in various groups at different time points(0,12,24,48,and 60 h)after treated with TGF-β1.MTT assay was used to detect the proliferation activities of the cells in various groups.Western blotting method was used to detect the expression levels of the fibrotic marker protein COL1A1,stromal marker proteins such as N-cadherin and α-smooth muscle actin(α-SMA),and Wnt/β-catenin signaling pathway-related protein β-catenin in the cells in control and IUA groups.Based on the MSAB concentrations,the normal HESCs were divided into 0(control),0.25,0.50,0.75,and 1.00 μmol·L-1 MSAB groups,and MTT assay was used to detect the survival rates of the cells in various groups.After treated with MSAB,the normal HESCs were divided into control group(normal HESCs),TGF-β1 group(10 μg·L-1 TGF-β1 induced normal HESCs for 24 h then the drug was withdrawn,replaced with complete culture medium,and the cells continued to be cultured for 24 h),and MSAB group(10 μg·L-1 TGF-β1 induced normal HESCs for 24 h then the drug was withdrawn,replaced with a complete medium containing 0.75 μmol·L-1 MSAB and the cells continued to be cultured for 24 h).Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of epithelial-mesenchymal transition(EMT)-related transcription factors Snail,Slug,Smuc,ZEB1,and ZEB2,and COL1A1 mRNA in the cells in various groups.Western blotting method was used to detect the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in various groups.Results:Compared with control group(after treated with TGF-β1 for 0 h),the expression levels of COL1A1 proteins in the HESCs after treated with TGF-β1 for 12,24,48,and 60 h in TGF-β1 group were increased(P<0.05 or P<0.01).Compared with control group,there was no significant difference in the proliferation activity of the HESCs in IUA and TGF-β1 groups(P>0.05).Compared with control group,the expression levels of COL1A1,β-catenin,N-cadherin,and α-SMA proteins in the cells in IUA group were increased(P<0.05 or P<0.01).Compared with control group,the survival rates of the cells in 0.75 and 1.00 μmol·L-1 MSAB groups were decreased(P<0.05 or P<0.01).Compared with control group,the expression levels of Snail,Slug,and COL1A1 mRNA in the cells in TGF-β1 group were increased(P<0.05 or P<0.01);compared with TGF-β1 group,the expression levels of Snail,Slug,and COL1A1 mRNA in the cells in MSAB group were decreased(P<0.05 or P<0.01).Compared with control group,after treated with TGF-β1 for 24 h,the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in TGF-β1 group were increased(P<0.01);compared with TGF-β1 group,the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in MSAB group were decreased(P<0.05 or P<0.01).Conclusion:MSAB can inhibit the fibrogenic responses of the HESCs in vitro,and the results provide the theoretical basis for the application of MSAB in the target therapy of IUA.

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