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OBJECTIVES: In this study, transcriptome sequencing were performed to elucidate the molecular mechanism by which metformin inhibits head and neck squamous cell carcinoma (HNSCC) cells progression and sensitizes HNSCC cells to chemotherapy. We aimed to propose a novel chemotherapeutic approach with high efficacy and few side effects and provide a new strategy for HNSCC treatment. DESIGN: The effects of metformin on the biological behaviors of HNSCC cells were validated by CCK8 cell proliferation assays, would healing assays and flow cytometric apoptosis assays. The appropriate metformin concentrations for the experimental pretreatment of HNSCC cells were selected based on experimental results, and the treated cells were subjected to transcriptome sequencing. After bioinformatics analysis and intersection with a post-chemotherapy resistance dataset from the GEO database numbered GSE102787, the genes were identified and used to predict potential metformin targets after functional enrichment analysis. RESULTS: Metformin significantly inhibited the proliferation and migration and induced the apoptosis of Cal27 and FaDu cells. A total of 284 genes that are potentially targeted by metformin during HNSCC cell sensitization were identified by bioinformatics, and ten hub genes with high connectivity were selected. In particular, Fen1 overexpression was associated with poor prognosis in HNSCC patients. CONCLUSIONS: Our study demonstrates that Fen1 is overexpressed in HNSCC tissues compared with normal tissues and that Fen1 overexpression is a poor prognostic factor in HNSCC patients. Metformin enhances the ability of cisplatin to inhibit HNSCC progression. Further studies are needed to explore the therapeutic value of Fen1 in HNSCC.
Subject(s)
Head and Neck Neoplasms , Metformin , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/genetics , Cisplatin/pharmacology , Metformin/pharmacology , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/genetics , Biomarkers, Tumor/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , PrognosisABSTRACT
With reference to the experience of School of Stomatology, Inner Mongolia Medical University, in participating in oral skill competitions, this article analyzes and summarizes the teaching issues reflected in skill competitions and refines the teaching strategies of consolidating theoretical foundation and cultivating clinical thinking as the basis, implementing the sterile concept and maintaining standard body position and posture as the key, and standardizing operating standards and strengthening hand skills as the important points. Participating in skill competitions can help to improve the emphasis on practical skill teaching of stomatology among students and establish innovative teaching models. Meanwhile, humanistic quality education is taken seriously to improve the comprehensive qualities of students through multiple channels.
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Objective To investigate the effects of transplantation with different amount of bone marrow mesenchymal stem cells(BMSCs)on osteoporosis in ovariectomized rats.Methods The rat model of osteoporosis was prepared by ovariectom(OVX)and verified after 3 months.A total of 60 female Sprague-Dawley rats were randomly divided into 6 groups(n=10 each).The rats with shamed operation served as a sham-injured control group(sham control group).The 5 ovariectom (OVX) groups with osteoporosis were study groups as follows:(1)the negative therapy group(simple OVX group);(2)the positive therapy group(OVX+ estrogen,E2 group) by intramuscular injection;others were treated with transplantation of BMSCs by tail vein injection in low dose(LS group),middle dose (MS group)and high dose(HS group).At 8,12 and 16 weeks after intervention,body mineral density (BMD)were detected by dual-energy x-ray absorptiometry scans.After 16 weeks of intervention,rat shinbone was obtained and stained by hematoxylin-eosin(HE) staining.Results Compared with the sham control group,simple OVX group showed a reduced total body BMD and the decreased proportion of trabecular bone to bone marrow cavity area (P ＜0.05).The total body BMD and the proportion of trabecular bone to bone marrow cavity area were higher in each BMSCs transplantation groups than in simple OVX group at 8,12,16 weeks after intervention(P ＜0.05),which showed a increased trend in the total body BMD and the proportion with the increased dose of transplantation BMSCs(P＜0.05).Rats in the HS group had highest BMD and best proportion of trabecular bone to bone marrow cavity area among three doses of transplantation BMSCs.Conclusions BMSCs transplantation can significantly improve osteoporosis of ovariectomized rats with an increased total body BMD and higher proportion of trabecular bone to bone marrow cavity area,and better and longer outcomes can be achieved.
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Objective To investigate the possible effect of citrate on electrolyte metabolism in healthy people with different genders and races and provide a reference for the possible clinical interventions.Methods A cross over,placebo-controlled study was conducted in 22 age-matched Chinese(11 males and 11 females)and 10 male Caucasian volunteers after informed consents were obtained.Volunteers received of saline solution,separated by a wash-out period of two to three weeks.Serial blood and urine samples were collected during the observation period and analyzed for the selective biochemical parameters.Results Comparable basal levels of serum albumin[male(43.05±1.81)g/L vs female(42.26±2.67)g/L]and serum ionized calcium[male(1.27±0.04)mmol/L vs female(1.26±0.04)mmol/L]were observed between different genders of Chinese volunteers.However,citrate intervention led to more pronounced decrease of ionized calcium level in Chinese females compared to Chinese males[-28.68%(-20.00%--35.2%)vs-23.84%(-16.53%--29.32%),t=3.19,P ＜ 0.01].There was no differences of the levels of serum inorganic phosphate[-18.81%(-3.16%--25.09%)vs-19.23%(-1.22%--32.16%),t=0.36,P＞0.05]and albumin[-0.32%(3.27%--7.60%)vs 1.88%(6.03%--9.31%),t=0.47,P＞0.05].Independent of gender,citrate intervention resulted in an increased excretion of urine calcium in Chinese volunteers[before 0.34(0.09-0.87)vs after 0.96(0.18-1.47),t=6.66,P ＜0.01].Compared to Caucasian males,Chinese males has a higher basal level of serum ionized calcium [(1.27±0.04)mmol/L vs(1.22±0.02)mmol/L,t=3.7,P ＜0.01]and larger amplitude basal rhythm in serum albumin level[-11.72%(-5.70%--14.21%)vs-1.74%(2.43%--7.68%),t=7.43,P ＜ 0.01].Application of citrate resulted in comparable changes of serum ionized calcium [-23.84%(-16.53%--29.32%)vs-21.95%(-18.31%--30.92%)],phosphate[-19.23%(4.65%--32.16%)vs-12.68%(0.68%--42.19%)],albumin[-0.32%(1.05%--7.60%)vs-1.39%(1.87%--7.26%)]and urine calcium excretion[237.70%(11.8%-935%)vs 234.37%(5.45%-504.00%)]between Chinese and Caucasian males(t=0.32,0.03,0.25 and 0.04 respectively,P＞0.05).Serum levels of magnesium were not influenced in all volunteers during two interventions.Conclusions Independent of race and gender,the invention of citrate results in comparable changes of serum magnesium,inorganic phosphate and albumin.The effect of citrate on ionized calcium levels between genders implicates a higher risk for hypocalcemic reactions in females compared to males undergoing automatic apheresis procedures.
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Objective To investigate the distribution of alpha2-HS glycoprotein (AHSG) gene polymorphisms and the relationships of AHSG gene polymorphisms with atherosclerosis as well as serum bone related biochemical mark-era. Methods Blood samples of 344 hospitalized female patients, aged 20 ～ 80 years, were sampled for serum bone alkaline phosphatase, cross-linked N-telopeptide of collagen type Ⅰ, cross-linked C-telopeptide of collagen type Ⅰ , osteoprotegrin and leptin were determined by ELISA. Serum TC,TG and calcium content were detected. Poly-morphism of AHSG gene was detected by polymerase chain reaction fragment length polymorphisms (PCR-RFLP) of restriction enzyme Sac Ⅰ. BMD (Norland XR-36) of the anteroposterior spine (AP), supine lateral spine (Lat) and femoral neck (FN) were measured. Morphological changes in the aorta and bone of type GG patient were detected by pathological microscopy. IMT were measured by color doppler ultrasound equipment(SEQUOIAS12). Results (1) The genotype frequency of CC, CG, and GG were 59.7%, 25.1% and 15.2% respectively in all elderly female patients. There were significant difference in blood lipids, Ca~(2+) and serum bone relative biochemical markers to different AHSG genotypes. (2)There were significant differences in the BMD of the AP, Lat, FN and IMT and the serum biochemical markers among the CC, CG and GG genotypes. (3)GG-female patients bone tissue pathology section verify the AHSG polymorphism genetic mutation and atherosclerosis, osteoporosis development of the relationship. Conclusion There was close relationship among AHSG polymorphism variation and the incidence of arteriosclerosis and osteoporosis in elderly female.
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Objective To investigate the distribution of alpha2-HS glycoprotein(AHSG) gene polymorphisms and the relationships of AHSG gene polymorphisms with atherosclerosis as well as serum bone related biochemical markers.Methods Blood samples of 344 hospitalized female patients,aged 20～80 years,were sampled for serum bone alkaline phosphatase,cross-linked N-telopeptide of collagen typeⅠ,cross-linked C-telopeptide of collagen type Ⅰ,osteoprotegrin and leptin were determined by ELISA.Serum TC,TG and calcium content were detected.Polymorphism of AHSG gene was detected by polymerase chain reaction fragment length polymorphisms(PCR-RFLP) of restriction enzyme Sac Ⅰ.BMD(Norland XR-36) of the anteroposterior spine(AP),supine lateral spine(Lat) and femoral neck(FN) were measured.Morphological changes in the aorta and bone of type GG patient were detected by pathological microscopy.IMT were measured by color doppler ultrasound equipment(SEQUOIA512).Results(1) The genotype frequency of CC,CG,and GG were 59.7%,25.1% and 15.2% respectively in all elderly female patients.There were significant difference in blood lipids,Ca2+ and serum bone relative biochemical markers to different AHSG genotypes.(2)There were significant differences in the BMD of the AP,Lat,FN and IMT and the serum biochemical markers among the CC,CG and GG genotypes.(3)GG-female patients bone tissue pathology section verify the AHSG polymorphism genetic mutation and atherosclerosis,osteoporosis development of the relationship.Conclusion There was close relationship among AHSG polymorphism variation and the incidence of arteriosclerosis and osteoporosis in elderly female.
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Objective To investigate the changes between type 2 diabetes mellitus(T2DM) with peripheral vessel disease and osteoporosis. Methods A total of 100 cases T2DM patients were divided into non-peripheral vessel disease (A group) and peripheral vessel disease (B group). B-mode ultrasonography to measure the intima-media thickness(IMT) of carotid artery,dual energy X-ray absorptiometry (DEXA) to measured bone mineral density(BMD) and VS-1000 arteriosclerosis diagnometer to measure brachi-ankle pulse wave velocity (baPWV) were used in 100 T2DM patients. The clinical data and BMD were compared between two groups. Results Compared with normal group,the BMD in T2DM patients significantly decreased.Compared with T2DM patients without peripheral vessel disease,the BMD decreased in T2DM patients with peripheral vessel disease. Conclusions Atherosclerosis in T2DM with peripheral vessel disease is probably related to osteoporosis, and the relationship between them is worth further investigation.
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Objective To evaluate the prevalence and risk factors of peripheral arterial obstructive disease(PAD) in type 2 diabetes mellitus(T2DM) patients. Methods A total of 401 patients with T2DM(201 men and 200 women),mean aged was(63.4?8.8)years.PAD was diagnosed by an ankle-brachial index(ABI)≤0.9 on either leg.Results Overall prevalence of PAD was 19.4%,without significant sexual difference.Univariate analyses disclosed age,hypertension,systolic blood pressure(SBP),low dense lipoprotein cholesterol(LDL-C) and T2DM duration as significant risk factors.In multiple Logistic regression,age,SBP,LDL-C and T2DM duration were independent risk factors with respective odds ratios(95% confidence intervals,CI) of 1.94(1.20-2.60),1.12(0.88-1.43),1.32(0.97-1.63) and 1.27(0.96-1.73) respectively.Conclusions Prevalence of PAD in T2DM patients is(19.4)% and the major risk factors were older age,higher SBP,higher LDL-C and T2DM duration.This implies that it is very important to prevent the incidence of PAD for better glucose,lipid and blood pressure control early.
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New field battle X-ray vehicle(model XCY2002-1/200) is used usually and control method is grasped too. By analyzing operation capability, the advantages and disadvantages are found, and then corresponding improvement is proposed to educe efficiency of medical support.
