1.METTL3 regulates glucose transporter expression in placenta exposed to hyperglycemia through the mTOR signaling pathway
Jie NING ; Jing HUAI ; Shuxian WANG ; Jie YAN ; Rina SU ; Muqiu ZHANG ; Mengtong LIU ; Huixia YANG
Chinese Medical Journal 2024;137(13):1563-1575
Background::Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP.Methods::We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia. Results::mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485. Conclusion::High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.
2.Effects of targeted surveillance combined with cluster management on isolation protector use rate and hand hygiene qualification rate in caregivers of patients with respiratory tract multidrug-resistant bacterial infections
Zhen WEI ; Xiaorong TIAN ; Mengsi LI ; Ning OU ; Huixia YAN
Chinese Journal of Primary Medicine and Pharmacy 2021;28(12):1848-1851
Objective:To investigate the targeted surveillance combined with cluster management on isolation protector use rate and hand hygiene qualification rate in caregivers of patients with respiratory tract multidrug-resistant bacterial infections.Methods:Second Hospital of Shanxi Medical University began to perform targeted surveillance combined with cluster management among caregivers of patients with multidrug-resistant bacterial infections in July 2019. The caregivers of 50 patients with respiratory tract multidrug-resistant bacterial infections who were admitted before targeted surveillance combined with cluster management were included in the pre-implementation group. The caregivers of 50 patients with respiratory tract multidrug-resistant bacterial infections who were admitted after targeted surveillance combined with cluster management were included in the post-implementation group. Multidrug-resistant bacterial infections in caregivers, isolation protector use rate, environmental disinfection and hand hygiene qualification rate were compared between before and after 6 months of targeted surveillance combined with cluster management. The application value of targeted surveillance combined with cluster management in the prevention of respiratory tract multidrug-resistant bacterial infections was analyzed.Results:The number of caregivers with respiratory tract multidrug-resistant bacterial infections in the post-implementation group was lower than that in the pre-implementation group (5 vs. 13, P < 0.05). The proportion of caregivers who wear a mask (94.11%), isolation clothes (80.39%) and gloves (98.03%) in the post-implementation group was significantly higher than that in the pre-implementation group (70.00%, 62.00%, 78.00%, χ2 = 10.027, 4.911, 9.683, all P < 0.05). The proportion of caregivers who were qualified in terms of hand hygiene (82.35%), object surface (76.47%), and keeping the air fresh in the post-implementation group was significantly higher than that in the pre-implementation group (64.00%, 58.00%, 64.00%, χ2 = 4.341, 3.915, 5.450, all P < 0.05). Conclusion:Targeted surveillance combined with cluster management can effectively help prevent respiratory tract multidrug-resistant bacterial infections in caregivers and increase isolation protector use rate and hand hygiene qualification rate.
3.Study on Extraction Technology Optimization and Structural Characterization and of Fritillaria pallidiflora Poly- saccharide
Abuduwaili AYITUXUN ; Rouzi PAERHATI ; Yanhua GAO ; Mutailifu PAIHEERDING ; Nuerxiati REHEBATI ; Huixia NING ; Yili ABULIMITI
China Pharmacy 2020;31(3):276-281
OBJECTIVE:To optimize the extractio n technology of Fritillaria pallidiflora polysaccharides(FPSP),and to study its structure. METHODS :Using the yield of FPSP as response value ,Box-Behnken design-response surface methodology was adopted to optimize solid-liquid ratio ,extraction temperature and extraction time of FPSP extraction technology. Structural properties of FPSP was characterized by UV spectrum ,FTIR,GC-MS,Congo red staining ,SEM,XRD and thermogravimetric analysis. RESULTS:The optimal technology parameters of FPSP were solid-liquid ratio of 1∶28(g/mL),extraction temperature of 94 ℃, extraction time of 2.5 h;the yield of FPSP was 16.25%(n=3),the error of which to theoretical yield (16.58%)was 0.33%. FPSP contained xylose ,glucose and galactose with a molar ratio of 1∶58.02∶0.73,and trace amount of mannose ;there was a weak absorption peak near the wavelength of 280 nm;belonged to α-configuration pyranopolysaccharide. FPSP was in triple-helical structure. The surface of FPSP was a network structure formed by irregular particles. FPSP had both crystalline and amorphous structures. FPSP had good thermostability. CONCLUSIONS :The optimized extraction technology of FPSP is reasonable ,and has high extraction yield. The research might provide reference for the further development and utilization of F. pallidiflora .
4.Effect of flavopiridol on the proliferation, invasiveness and apoptosis of human prostatic cancer cell line LNCaP
Ning LI ; Gang LIANG ; Hong XIAO ; Huixia ZHENG ; Jianfang LIANG
Cancer Research and Clinic 2016;28(6):366-368,372
Objective To investigate the effect of flavopiridol on the proliferation,invasiveness and apoptosis of human prostate cancer cell line LNCaP,and to explore the possibility of its application in clinical treatment.Methods MTT assay was used to detect cell proliferation,cell invasion in vitro was detected by Transwell assay,and flow cytometer was used to observe apoptosis.Results Flavopiridol inhibited the growth of LNCaP cells in a concentration-dependent and time-dependent way (P < 0.05),and reduced the ability of invasion capacity.After treated by 10 nmol/L flavopiridol for 24 h,the apoptosis rate was increased significantly to (7.5±0.9) % compared with the control group [(5.3±0.5) %] (P < 0.05).Conclusion Flavopiridol can inhibit proliferation of LNCaP cells and induce apoptosis,which may be applicable for the treatment of prostate cancer.
5.Relationship between microsatellite instability and hepatocyte growth factor expression and their prognostic significance in colorectal cancer
Guang YANG ; Huixia ZHENG ; Lina WU ; Huili WAN ; Ning LI ; Gaochao YANG ; Jianfang LIANG
Chinese Journal of Oncology 2016;38(4):283-288
Objective To investigate the expression of hepatocyte growth factor ( HGF ) and its relationship with microsatellite instability ( MSI) and their influence on survival in patients with colorectal cancer. Methods Immunohistochemistry ( IHC) was used to detect the expression of HGF and MSI in 98 specimens of colorectal cancer. Tumors lacking protein expression of any of the four mismatch repair genes (MLH1, PMS2, MSH2 or MSH6) were labelled as MSI, and the rest were considered as microsatellite stable ( MSS) . The associations between expression and clinicopathological factors were assessed using Chi?square tests. Kaplan?Meier curves, log?rank test, and Cox regression were used to analyze the association between biomarker expressions and overall survival. Results The incidence rate of MSI in 98 colorectal specimens was 32. 7%, and was statistically significantly correlated with the location of tumor and differentiation degree ( P<0.05) . The HGF?expression rate was 71.4%. The patients with an MSI tumor had a significantly higher HGF expression, compared with the patients with an MSS tumor (P=0.048). The 5?year survival rate of MSI group and MSS group were 39.8% and 58.7%, respectively (P=0.009). The 5?year survival rate of HGF?positive group and HGF?negative group were 46.2% and 67.9% ( P=0.035) . The multivariate analysis showed that lymphocytic infiltration, TMN stage, MSI and HGF are independent prognostic factors in colorectal cancer ( P<0. 05 for all ) . Conclusions HGF is highly expressed in colorectal cancer patients with microsatellite instability. Both microsatellite instability and HGF are independent factors affecting the prognosis in patient with colorectal cancer.
6.Relationship between microsatellite instability and hepatocyte growth factor expression and their prognostic significance in colorectal cancer
Guang YANG ; Huixia ZHENG ; Lina WU ; Huili WAN ; Ning LI ; Gaochao YANG ; Jianfang LIANG
Chinese Journal of Oncology 2016;38(4):283-288
Objective To investigate the expression of hepatocyte growth factor ( HGF ) and its relationship with microsatellite instability ( MSI) and their influence on survival in patients with colorectal cancer. Methods Immunohistochemistry ( IHC) was used to detect the expression of HGF and MSI in 98 specimens of colorectal cancer. Tumors lacking protein expression of any of the four mismatch repair genes (MLH1, PMS2, MSH2 or MSH6) were labelled as MSI, and the rest were considered as microsatellite stable ( MSS) . The associations between expression and clinicopathological factors were assessed using Chi?square tests. Kaplan?Meier curves, log?rank test, and Cox regression were used to analyze the association between biomarker expressions and overall survival. Results The incidence rate of MSI in 98 colorectal specimens was 32. 7%, and was statistically significantly correlated with the location of tumor and differentiation degree ( P<0.05) . The HGF?expression rate was 71.4%. The patients with an MSI tumor had a significantly higher HGF expression, compared with the patients with an MSS tumor (P=0.048). The 5?year survival rate of MSI group and MSS group were 39.8% and 58.7%, respectively (P=0.009). The 5?year survival rate of HGF?positive group and HGF?negative group were 46.2% and 67.9% ( P=0.035) . The multivariate analysis showed that lymphocytic infiltration, TMN stage, MSI and HGF are independent prognostic factors in colorectal cancer ( P<0. 05 for all ) . Conclusions HGF is highly expressed in colorectal cancer patients with microsatellite instability. Both microsatellite instability and HGF are independent factors affecting the prognosis in patient with colorectal cancer.
7.Expression of enhancer of zeste homolog2 in colorectal adenocarcinoma and its significance
Qing LI ; Jianfang LIANG ; Huixia ZHENG ; Ning LI ; Gang LIANG ; Hong XIAO
Cancer Research and Clinic 2015;27(1):15-18
Objective To investigate the expression of the enhancer of zeste homolog 2 (EZH2) gene and its significance in colorectal adenocarcinoma.Methods Immunohistochemistry and Western blot was used to assess the expression of EZH2 in human colorectal adenocarcinoma tissues,colorectal adenoma tissues and non-cancerous adjacent colorectal tissues.The relationships between EZH2 and each clinical pathology parameter were analyzed.Results The results of immunohistochemical trail showed that the expression rates of EZH2 in colorectal adenocarcinoma,colorectal adenoma and non-cancerous adjacent colorectal tissues were 80.56 % (87/108),62.5 % (25/40) and 5.00 % (2/40),respectively (P < 0.05).Western blot revealed that the expression level of EZH2 in colorectal adenocarcinoma tissues,colorectal adenoma tissues and non-cancerous adjacent colorectal tissues level 0.549±0.145,0.283±0.023 and 0.107±0.022,respectively.The level in colorectal adenocarcinoma tissues (0.549±0.145) and colorectal adenoma (0.283±0.023) was significantly higher than that in non-cancerous adjacent colorectal tissues (0.107±0.022).Compared with colorectal adenoma tissues,level in colorectal adenocarcinoma tissues was significantly higher.There were significant differences among the three groups (F =20.113,P < 0.05).The ratio of high expression level of EZH2 in colorectal adenocarcinoma tissues was closed related with tumorgenesis,differentiation,TNM staging and lymphatic metastsis (all P < 0.05).However,no correlation was revealed between EZH2 expression and the age,gender (both P > 0.05).Conclusion The expression of EZH2 may be associated with the tumorgenesis invasion,metastasis and progression of colorectal adenocarcinoma.
8.Expression of protein interacting with Cα kinase 1 in colorectal adenocarcinoma and its significance
Hongbian GAO ; Ning LI ; Huixia ZHENG ; Jianfang LIANG ; Gang LIANG ; Huili WAN ; Hong XIAO
Cancer Research and Clinic 2014;26(6):373-376,380
Objective To investigate the expression of protein interacting with Cα kinase 1 (PICK1) and its significance in colorectal adenocarcinoma.Methods The expression of PICK1 were detected by immunohistochemistry and Western blot methods in tissues of colorectal adenocarcinoma,colorectal adenoma,colorectal polyp and adjacent tissues.The correlation between PICK1 and clinical pathological data was explored.Results Immunohistochemical assay showed that the positive ratio of PICK1 protein was 72.5 % (74/102),and overexpressed in 31 cases (30.4 %,31/102) with colorectal adenocarcinoma.The ratio of high expression level of PICK1 in colorectal adenoma tissues (22.2 %,8/36) was significantly higher than that in the adjacent tissues (0,0/40) (P < 0.05).The ratio of high expression level of PICK1 in colorectal polyp tissues (5.6 %,2/36) was no statistically difference compared with that of the adjacent tissues (P > 0.05).Western blot analysis revealed that the expression of PICK1 in colorectal adenocarcinoma (1.10±0.04) was significantly higher than that in the adjacent tissues (0.75±0.07) (P < 0.05).The result showed significant correlation with the tumor location,the degree of differentiation,depth of invasion,TNM stages and lymph metastasis (all P < 0.05).However,there is no correlation was revealed between PICK1 expression and the patients age,gender (both P > 0.05).Conclusion The expression of PICK1 may be associated with the tumorgenesis,progression,invasion and metastasis of colorectal adenocarcinoma,which contributes to the prognosis of patients.
9.Expression and significance of Dysadherin mRNA in renal clear cell carcinoma
Hong XIAO ; Guiling FAN ; Huixia ZHENG ; Gang LIANG ; Yanglu ZHAO ; Ning LI ; Caixia CHENG ; Hongkun WANG ; Jianfang LIANG
Cancer Research and Clinic 2012;24(8):512-514
Objective To investigate the expression of Dysadherin and analyze its role in renal clear cell carcinoma (RCCC).Methods RT-PCR and immunohistochemical were used to detect the expression of Dysadherin in 60 cases of fresh RCCC and 60 adjacent normal renal tissues(male 35,female 25; age 37-78,median age 61; >7 cm 24,≤7 cm 36; Ⅰ/Ⅱ 39,Ⅲ/Ⅳ 21).Results Dysadherin mRNA expression in RCCC tissues (2.0043±0.2890) was higher than that in adjacent normal renal tissues (0.8461 ±0.2479) (t =6.8020,P < 0.05).Dysadherin expression was associated with nuclear grade.The expression of Dysadherin in nucleus grade Ⅲ and Ⅳ tumors were significantly higher than that in nucleus grade Ⅰ and Ⅱ tumors [the mRNA expression were 4.6224±0.3194,2.7780±0.2288,the positive rates of protein were 64.1% (25/39),95.2 % (20/21) (t =6.5750,x2 =5.495,P < 0.05)].There was no association between the expression of Dysadherin with sex (t =1.0530,x2 =0.023),age(t =0.0511,x2 =0.089) and tumor size (t =1.0330,x2 =0.370) (P > 0.05).Conclusion In RCCC,Dysadherin expression is positively associated with tumor aggressiveness based on grading.It seems that Dysadherin may be a valuable prognostic marker in RCCC.
10.Effects of sevoflurane pretreatment on myocardial injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass
Chengjie GAO ; Jingui YU ; Huixia WANG ; Bo LI ; Xiaoming Lü ; Lufeng XU ; Guimao CAO ; Jishun NING ; Guanhua JIANG ; Aijun NIU ; Hailong DONG
Chinese Journal of Anesthesiology 2012;32(3):278-281
Objective To investigate the effects of sevoflurane pretreatment on the myocardial injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Twenty NYHA class Ⅱ or Ⅲ patients,aged < 60 yr,undergoing cardiac valve replacement with CPB,were randomly divided into 2 groups (n =10 each):sevoflurane group (group S) and control group (group C).The patients were premeditated with intramuscular morphine and scopolamine.Anesthesia was induced with iv injection of midazolam 0.05-0.08 mg/kg,fentanyl 10-15 μg/kg and pipecuronium 0.08-0.10 mg/kg.Anesthesia was maintained with intermittent iv boluses of midazolam,fentanyl and pipecuronium and in addition sevoflurane was inhaled before aortic clamping and the end-tidal concentration was rapidly increased to 1.0% and maintained at the level for 5 min in group S.Blood samples were taken from the central vein before skin incision (T1),immediately after aortic clamping (T2 ),at 0 and 30 min after aortic unclamping (T3-4),and at 2,6,12 and 24 h after operation (T5-8) for determination of the concentration of serum cardiac troponin Ⅰ (cTnI) and activities of creatine kinase (CK) and creatine kinase isoenzyme-MB (CK-MB).Myocardial specimens were taken from right auricle before aortic clamping and at 10 min after aortic unclamping for electron microscopic examination.Results The concentration of serum cTnI and activities of CK and CK-MB were significantly increased at T4-8 in both groups ( P < 0.05).The serum cTnI concentration at T4-8 and the activities of CK and CK-MB at T8 were significantly lower in group S than in group C ( P <0.05).Different degrees of mitochondrial swelling were observed after aortic unclamping in both groups,but the changes were milder in group S than in group C.Conclusion Sevoflurane pretreatment can attenuate the myocardial injury in patients undergoing cardiac valve replacement with CPB.

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