Exercise-induced modulation of miR-149-5p and MMP9 in LPS-triggered diabetic myoblast ER stress: licorice glycoside E as a potential therapeutic target

Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.

A New Definition of P-Value Involving the Maximum Likelihood Estimator

We present here an alternative definition of the P-value for statistical hypothesis test of a real-valued parameter for a continuous random variable X. Our approach uses neither the notion of Type I error nor the assumption that null hypothesis is true. Instead, the new P-value involves the maximum likelihood estimator, which is usually available for a parameter such as the mean μ or standard deviation σ of a random variable X with a common distribution.

The Prognostic Value of Pathological and Molecular Margins Marked by p53 and eIF4E in Laryngeal Carcinoma

Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was studied in 253 cases and 67 cases respectively, the latter were pathological negative margin chosen from the former. Immunohistochemisty was used to detect the expression of eIF4E and p53 proteins. Results: The rate of pathological, p53 and eIF4E positive margins was 20.2%, 19.4% and 32.8% respectively. The recurrent rate of those with positive margins was higher than that of negative margins, which including pathological margin (70.6% vs 35.1%, P =0.0000), p53 margin (69.2% vs 33.3%, P =0.018) and eIF4E margin (63.6% vs 28.9%, P =0.018); The survival rate of those with negative margins was higher than those with positive margins, including pathological margin (the 5-year cumulative survival rate was 37.52% and 64.37% respectively, P =0.0023), p53 margin (the 5-year cumulative survival rate was 24.62% and 75.69% respectively, P =0.0012) and eIF4E margin (the 5-year cumulative survival rate was 43.31% and 77.52% respectively, P =0.0006). Conclusion: The prognosis of those with both pathological and molecular positive margins was worse than that of the negative margins; Both the eIF4E and p53 were useful markers to pick out the poor prognostic patients from those with pathological negative margin, and the former seemed to be more potential.

Study on the Anti-Inflammatory and Analgesic Mechanisms of Breast Lump Resolution Detergent in a Rat Model of Breast Hyperplasia

Objective: This study aimed to investigate the anti-inflammatory and analgesic mechanisms of a breast lump resolution detergent in a rat model of breast hyperplasia. Methods: A rat model of breast hyperplasia was established using injections of estradiol benzoate combined with progesterone. The effects of the breast lump resolution detergent on nipple height and diameter in the rat model were observed, along with its impact on serum levels of estradiol (E2), prolactin (PRL), and progesterone (P). Additionally, the study examined the morphological changes in breast tissue. The impact of the breast nodule detergent on blood rheology parameters was also observed. Furthermore, the anti-inflammatory effect of the breast nodule detergent was assessed using the cotton ball granuloma experiment, and the analgesic effect was observed using the writhing test. Results: The breast lump resolution detergent reduced nipple height and diameter in the rat model, decreased serum levels of E2, PRL, and P, and alleviated pathological changes in breast tissue. It also lowered hemorheological parameters including whole blood high, medium, and low shear viscosity, plasma viscosity, red blood cell hematocrit, red blood cell aggregation index, red blood cell deformability index, red blood cell electrophoresis time, and erythrocyte sedimentation rate in the acute “blood stasis” rat model. The detergent reduced the weight of cotton ball granulomas in mice and decreased the number of writhing episodes caused by acetic acid. Conclusion: The breast lump resolution detergent demonstrates favorable therapeutic effects in treating breast hyperplasia, promoting blood circulation and removing blood stasis, exerting anti-inflammatory properties, and providing analgesic effects. The downregulation of serum E2 and PRL levels and the upregulation of P levels may be critical mechanisms underlying its efficacy.

MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1-extracellular signal-regulated kinase-1/2 axis

BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1

Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.

Effect size in papers published by the Journal of Forestry Research:A missing treasure?

P values based on standard hypothesis testing are commonly reported in articles published by the Journal of Forestry Research(JFR).However,effect sizes are barely used and reported,even if they are of direct relevance to the primary questions of many of the published studies.The incorporation of effect sizes in studies published by JFR should be encouraged and promoted.Inclusion of effect sizes as a requirement in the journal guidelines will facilitate a major change in the way data are tested and interpreted,with the ultimate goal to exempt researchers from the custom of drawing conclusions merely based upon a dichotomous statistical result(P value).Such a policy can also lead to more informed decisions of whether identified effects are of practical relevance to the forestry.

On the Strong Law of Large Numbers for Non-Independent B-Valued Random Variables

This paper investigates some conditions which imply the strong laws of large numbers for Banach space valued random variable sequences. Some generalizations of the Marcinkiewicz-Zygmund theorem and the Hoffmann-J?rgensen and Pisier theorem are obtained. Key words strong law of large numbers - Banach space valued random variable sequence - p-smoothable Banach space CLC number O 211.4 - O 211.6 Foundation item: Supported by the National Natural Science Foundation of China (10071058)Biography: Gan Shi-xin (1939-), male, Professor, research direction: martingale theory, probability limiting theory and Banach space geometry theory.

清肾颗粒对大鼠NRK-52E细胞转分化模型miR-23b和PINK1/Parkin通路的影响

目的 探讨TGF-β1诱导大鼠NRK-52E细胞转分化模型中miR-23b对PINK1/Parkin通路的靶向调节机制,并阐明清肾颗粒含药血清对NRK-52E细胞转分化的干预机理。方法 采用超高效液相色谱(UPLC)指纹图谱法对清肾颗粒进行全指纹图谱分析。构建TGF-β1诱导大鼠NRK-52E细胞转分化模型,转染siRNA后分为模拟物空载对照组、miR-23b-5p模拟物组、抑制剂空载对照组、miR-23b-5p抑制剂组,观察miR-23b-5p对PINK1表达量的影响。再将NRK-52E细胞分组为正常组、TGF-β1组、清肾颗粒组、miR-23b-mimic-NC组、miR-23b-mimic组、miR-23b-mimic+清肾颗粒组,Western blot法检测NRK-52E细胞中Pink1、Parkin、LC3Ⅱ、Beclin-1、P62、α-SMA蛋白表达,RT-qPCR法检测NRK-52E细胞中miR-23b-5p、Pink1、Parkin、Beclin-1、α-SMA mRNA的表达,双荧光素酶报告基因实验检测miR-23b-5p与PINK1的靶向关系。结果 UPLC指纹图谱法鉴定出清肾颗粒中11个活性成分。miR-23b-5p过表达后,PINK1 mRNA表达量也显著增加(P<0.05);而miR-23b-5p表达沉默后,PINK1 mRNA表达量也显著减少(P<0.05)。双荧光素酶报告显示,Rno-miR-23b-5p能显著下调Rno-PINK1-WT荧光素酶活性(P<0.05),但未能下调突变Rno-PINK1-mut荧光素酶活性(P>0.05)。清肾颗粒含药血清干预实验发现,TGF-β1组的miR-23b-5p、Pink1、Parkin、Beclin-1、LC3Ⅱ表达及LC3Ⅱ/Ⅰ比值均明显低于正常组,P62和α-SMA表达明显高于正常组(P<0.05)。清肾颗粒组和miR-23b-mimic组的miR-23b-5p、Pink1、Parkin、Beclin-1、LC3Ⅱ表达及LC3Ⅱ/Ⅰ比值均明显高于TGF-β1组,P62和α-SMA表达明显低于TGF-β1组(P<0.05)。miR-23b-mimic+清肾颗粒组的表现更优于miR-23b-mimic组(P<0.05)。结论 清肾颗粒能够上调NRK-52E细胞内miR-23b-5p表达,并通过增强PINK1/Parkin通路介导的线粒体自噬活性,抑制NRK-52E细胞转分化进程。

Linc01419调控miR-34a-5p/E2F3轴促进膀胱癌细胞增殖与侵袭

目的:探讨长链非编码RNA Linc01419对膀胱癌细胞增殖和侵袭的影响及作用机制。方法:通过UALCAN软件(https://ualcan.path.uab.edu/)分析TCGA数据库中Linc01419在膀胱癌组织与正常膀胱组织中的表达差异;采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RT-qPCR)检测Linc01419在不同膀胱癌细胞系、22例经病理证实为膀胱癌的手术患者的肿瘤组织及癌旁正常膀胱组织中的表达水平;应用细胞增殖/毒性检测(cell counting kit-8,CCK-8)实验和Transwell小室侵袭实验检测敲低Linc01419表达对膀胱癌细胞增殖与侵袭的影响;采用双荧光素酶报告基因检测法分析Linc01419与miR-34a-5p及miR-34a-5p与E2F3之间的靶向调控关系。结果:UALCAN数据库分析显示相较正常膀胱组织,Linc01419在膀胱癌组织中显著高表达(P<0.001);RT-qPCR分析结果显示相较癌旁正常膀胱组织,Linc01419在22例膀胱癌组织中表达明显上调(P<0.001),与UALCAN数据库分析结果一致;Linc01419在4株膀胱癌细胞中的表达明显高于正常膀胱上皮细胞(P<0.01);敲低Linc01419表达,可显著抑制膀胱癌细胞的增殖、侵袭及N-cadherin、PCNA蛋白的表达,而显著促进E-cadherin的蛋白表达(P<0.05);miR-34a-5p过表达对膀胱癌细胞具有类似的抑制作用;双荧光素酶报告基因实验、RIP及Pull-down实验证实Linc01419可靶向结合miR-34a-5p,而后者进一步介导了对E2F3的靶向调控;抑制miR-34a-5p表达,可显著削弱Linc01419沉默对膀胱癌细胞生物学行为及E-cadherin、N-cadherin、PCNA、E2F3表达的影响。结论:Linc01419在膀胱癌中异常高表达,其通过调控miR-34a-5p/E2F3轴促进膀胱癌细胞增殖和侵袭,很可能是膀胱癌发生、发展过程中的一个重要环节。

MMP25和E-cadherin在类风湿关节炎中的诊断价值

目的探讨基质金属蛋白酶25(Matrix metalloproteinase 25,MMP25)和E-钙黏蛋白(E-cadherin)对类风湿关节炎的诊断意义。方法选取2020年1月至2023年10月我院67例类风湿关节炎患者为实验组,同期50例健康体检人群为对照组;采用酶联免疫吸附试验(ELISA)检测二组血清中MMP25和E-cadherin蛋白水平。收集实验组患者ESR、CRP、CCP、RF、DAS28-ESR、DAS28-CRP指标,以及是否为初诊、是否合并并发症(贫血、间质性肺炎等)、病程、临床活动度等级,并与MMP25和E-cadherin水平进行相关性分析。结果实验组血清MMP25和E-cadherin水平均高于对照组,差异均有统计学意义(P<0.001)。与ESR、CRP、CCP和RF等指标进行散点图和简单线性回归性分析,结果显示:不同临床活动度患者表达MMP25水平差异有统计学意义(P<0.001),MMP25与病程(β=0.479,P<0.001),MMP25与CRP(β=0.271,P<0.05),MMP25与DAS28-ESR(β=0.660,P<0.001)和MMP25与DAS28-CRP(β=0.624,P<0.001)均有相关性。不同临床活动度患者表达E-cadherin水平差异有统计学意义(P<0.001),E-cadherin与ESR(β=0.425,P<0.001),E-cadherin与CRP(β=0.328,P<0.05),E-cadherin与DAS28-ESR(β=0.746,P<0.001),E-cadherin与DAS28-CRP(β=0.671,P<0.001)均有相关性。多重线性回归分析结果显示,MMP25表达水平与临床活动度正相关(β=1.032,P<0.001),E-cadherin表达水平与临床活动度正相关(β=0.407,P<0.05)、与病程长短正相关(β=0.497,P<0.001)。结论MMP25和E-cadherin表达水平可以作为类风湿关节炎评估临床活动度的标志物,此外,E-cadherin表达水平也可以衡量患者病程长短。

p16/Ki-67双染检测、HPVE6/E7mRNA检测在宫颈病变诊断中的价值研究

目的:探讨p16/Ki-67双染检测、HPVE6/E7mRNA检测在宫颈病变诊断中的价值。方法:选择2021年4月至2023年2月我院收治的605例高危型HPV阳性患者为研究对象,所有患者入院后均进行阴道镜检查与病理活检,取患者细胞学样本分别进行p16/Ki-67双染检测、HPVE6/E7mRNA检测。比较两种方法单独检查与联合检测对宫颈病变阳性检出率的差异;比较三种检查方法对宫颈病变诊断效能的差异。结果:联合检测检出CIN1~3阳性率均高于p16/Ki-67双标记、HPVE6/E7mRNA检测(P<0.05);三种检测方式的浸润癌阳性检出率比较无明显差异(P>0.05)。Kappa检验分析结果显示,p16/Ki-67双标记与HPVE6/E7mRNA检查结果与病理诊断结果具有较好的一致性(Kappa值=0.719,P<0.05);联合检测结果与病理诊断结果具有高度的一致性(Kappa值=0.894,P<0.05)。联合检测对宫颈病变的诊断灵敏度、特异性与准确率高于p16/Ki-67双标记与HPVE6/E7mRNA检查(P<0.05)。结论:p16Ki-67双染与HPVE6/E7mRNA联合检测可准确检出宫颈病变程度,对宫颈病变疾病类型的鉴别可提供充足可靠的数据支持,联合检查的诊断效能较好,对患者后续相关治疗开展有积极指导意义。

miR-150-5p靶向ZEB1调控EMT对子宫内膜癌细胞恶性生物学行为的影响

目的探讨微小RNA-150-5p(miR-150-5p)是否可靶向锌指E盒结合蛋白1(ZEB1)调控子宫内膜癌(EC)细胞上皮间质转化(EMT)进而影响癌细胞的恶性生物学行为。方法RT-qPCR技术检测正常子宫内膜和EC组织中、子宫内膜上皮细胞系hEEC及EC细胞系Ishikawa和HEC-1-A中miR-150-5p相对表达量。过表达miR-150-5p,MTT法、菌落形成实验、伤口愈合实验和Transwell实验分别评估Ishikawa细胞活力、克隆形成、迁移及侵袭能力;双荧光素酶报告基因实验验证miR-150-5p与ZEB1的靶向关系;RT-qPCR检测miR-150-5p及ZEB1 mRNA相对表达量;Western blot技术检测ZEB1、E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)及基质金属蛋白酶9(MMP-9)蛋白表达量。结果与正常子宫内膜组织比较,EC组织中miR-150-5p相对表达量降低(P<0.05);与hEEC细胞比较,HEC-1-A细胞和Ishikawa细胞中miR-150-5p相对表达量降低(P<0.05),Ishikawa细胞中最低(P<0.05)。与空白组比较,miR-150-5p mimics组细胞490 nm处吸光度值、细胞菌落数、迁移数和侵袭数、ZEB1 mRNA和蛋白相对表达量及N-cadherin、Vimentin和MMP-9蛋白相对表达量显著降低,miR-150-5p相对表达量、E-cadherin蛋白相对表达量显著升高(P<0.05)。经生物信息学分析,ZEB1被预测为miR-150-5p的潜在靶基因。结论miR-150-5p可靶向ZEB1抑制癌细胞的恶性生物学行为,其作用机制可能与调控EC细胞EMT进展有关。

The Hjek-Rnyi Inequlity For Banach Space Valued Random Variable Sequences and Its Application

In this paper we prove the following Hajek Renyi inequality:Let 0<p≤1 ,then for any Banach space B , any L p integrable B valued random variable sequence {D n,n≥1} ,any real number sequence {b n,n≥1} with 0<b n↑∞ ,any integer n≥1 ,there exits a constant C=C p>0 (only depending on p ) such thatP( sup j≥nji=1D ib j≥ε)≤Cε -p (∞j=n+1E‖D j‖ pb p j+nj=1E‖D j‖ pb p n) In the other direction,we prove some strong laws of large numbers and the integrability of the maximal functions for B valued random variable sequences by using this inequality and the Hajeck Renyi inequality we have obtained recently.Some known results are extended and improved.

Two-Parameter Vector-Valued Martingales and Geometrical Properties of Banach Spaces

We obtained a number of inequalities and laws of large numbers for two parameter vector valued martingales.In the other direction we characterized p smoothness and q convexity of Banach spaces by using these inequalities and laws of large numbers for two parameter vector valued martingales.

Davis's Inequalities for Two-Parameter Banach Space Valued Strong Martingales and Geometrical Properties of Banach Spaces

In this paper we investigated theL 1 norm inequalities of theP square and the maximal functions of two-parameterB-valued strong martingales, which can be applied to characterizep-smoothness andq-convexity of Banach spaces.

Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males

AIM:To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu Province, in Chinese males. METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2E1 *c1/*c2, ALDH2 *1/*2 and ADH1B *1/*1 genotypes). A total of 80 esophageal cancer cases and 480 controls were recruited. RESULTS: Compared with controls, cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with > 30 drink-years (28.8% vs 13.5%). Heavier alcohol consumption and alcohol drinking with > 30 drink- years increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96-3.21). CYP2E1 (*c1/*c1), ALDH2 (*1/*2) and ADH1B (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance (P = 0.014; P = 0.094; P = 0.0001 respectively). There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2 *1/*2 as well as ADH1B encoded by ADH1B *1/*1 and CYP2E1 encoded by CYP2E1 *c1/*c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 (*1/*1 genotype) as well as ADH1B (*1/*2 + *2/*2) and CYP2E1 (*c1/*c2 + *c2/*c2) genotypes, with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31) respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 (*1/*2) combined the ADH1B (*1/*1) genotype or ALDH2 (*1/*2) combined the CYP2E1 (*c1/*c1) genotype leads to synergistic interactions, higher than drinkers with ALDH2 (*1/*1) + ADH1B (*1/*2 + *2/*2), ALDH2 (*1/*1) + CYP2E1 (*c1/*c2 + *c2/*c2) respectively , ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no synergistic interaction. CONCLUSION: In our study, we found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for ESCC, and that there was a synergistic interaction among polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in Chinese males living in Gansu Province, China.

The Limitations of Polygenic Hypothesis and Theorizing about Dual Multiple Factors and Three Normal Distributions

The original data of Nilsson-Ehle experiment in wheat were analyzed with existent genetic knowledge. It indicated that the core of polygenic hypothesis from this experiment was that a character similarity produced by additive effect of multiple genes was the basis of continuous variation. Its precondition was for effective genes to have equal effect, to show merodominance and binomial distribution and to inherit independently. In fact, quantitative characters were determined by many genes with different property, effect and behavior. So it was difficult to solve all problems of continuous variation by the aid of polygenic hypothesis. The researchers should seek new ways. With Mendelian group as research object and by means of Lyapunov central limit theorem it was proved that both genotypic value G and the environmental effect in a niche E were subordinated to the normal distribution and respectively. According to additivity of the normal distribution the phenotype P = G + E also obeyed the normal distribution P = G + E ~ and quantitative characters showed continuous variation, whether or not the linkage was presented, whether or not every gene effect was equal, whether or not there were dominance and what kind of dominance between alleles. Moreover it was discussed that the quantitative characters in self-fertilized organism and clone were submitted to the normal distribution and presented continuous variation too.

Evaluation in vinyl chloride monomer-exposed workers and the relationship between liver lesions and gene polymorphisms of metabolic enzymes

AIM： To analyze occupational health hazards exposure to doses lower than the Chinese occupational health standard in a selected VC polymerization plant in China, and also to elucidate the relationship between genetic polymorphisms and genetic susceptibility on liver lesions of workers exposed to vinyl chloride monomer （VCM）. METHODS： In order to explore the mechanism of VCM- related health effects, we used a case-control design to investigate the association between the genetic polymorphisms of metabolic enzymes and liver lesions in workers occupationally exposed to VCM. Genotypes of CYP2E1, GSTT1, GSTM1, ALDH2 and ADH2 were identified using PCR and PCR-RFLP. RESULTS： Even when the concentration of VCM was lower than the current Chinese occupational health standard, neurasthenia, pharyngeal irritation, liver ultrasonography abnormalities and hemoglobin disorders were significantly higher in exposure subjects compared to non-exposure subjects, and the relative risks （RRand 95% C1） were 1.74 （1.06-2.85）, 1.97 （1.56-2.48）, 10.69 （4.38-26.12）, and 2.07 （1.20-3.57）. CYP2E1 c1c2/c2c2 genotype was significantly associated with liver damages （OR 3.29, 95% CI 1.51-7.20, P〈0.01）. CONCLUSION： The incidences of neurasthenia and liver ultrasonography abnormalities significantly increase when the cumulative exposure dose increases. The genotypes of metabolic enzymes （CYP2E1 c1c2/c2c2, null GSTT1 and ADH2 1-1） play important roles in VCM metabolism. Polymorphisms of CYP 2E1, GSTT1 and ADH2 may be a major reason of genetic susceptibility in VCM-induced hepatic damage.

Expression of p53, p21^(CIP1/WAF1) and eIF4E in the adjacent tissues of oral squamous cell carcinoma:establishing the molecular boundary and a cancer progression model

The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma（OSCC） and adjacent tissues to establish a molecular surgical boundary and provide a cancer progression model. Biopsy samples from 50 OSCC patients were divided into T（cancer）, P1（0–0.5 cm）, P2（0.5–1 cm）, P3（1–1.5 cm） and P4（1.5–2 cm） groups based on the distances from the visible boundary of the primary focus. Twenty samples of normal mucosa were used as controls. We used immunohistochemical staining and flow cytometry to evaluate p53, p21CIP1/WAF1, e IF4 E and Ki-67 expression and to determine DNA status, respectively. Sub-mucosal invasion was present in the P1 and P2 groups as determined by haematoxylin and eosin staining.Mutant p53 expression decreased gradually from cancerous to normal mucosae, whereas p21CIP1/WAF1 expression displayed an opposite trend. e IF4 E expression decreased from cancerous to normal mucosae. Ki-67 expression, the heteroploidy ratio, S-phase fraction and proliferative index decreased gradually with the distance from the tumour centre. Based on these results, we suggest that the resection boundary in OSCC surgery should be beyond 2 cm from the tumour. Additionally, the adjacent tissues of the primary focus could be used as a model for assessing cancer progression.