二甲双胍联合吡格列酮治疗非酒精性脂肪性肝病合并2型糖尿病患者疗效研究*

目的 探讨应用二甲双胍联合吡格列酮治疗非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)患者的效果。方法 2018年10月～2020年10月我院收治的NAFLD合并T2DM患者86例,采用随机数字表法分为对照组43例和观察组43例,分别给予二甲双胍或二甲双胍联合吡格列酮治疗24 w。常规检测谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、空腹血糖(FPG)、糖化血红蛋白(HbA1c);采用电化学发光法检测血清空腹胰岛素(FINS),并计算稳态模型胰岛素抵抗指数(HOMA-IR)。结果 在治疗24 w末,观察组血清AST水平为(37.9±4.2)U/L,显著低于对照组【(50.7±3.8)U/L,P<0.05】,GGT水平为(64.1±6.2)U/L,显著低于对照组【(73.1±7.0)U/L,P<0.05】;FPG水平为(6.0±1.2)mmol/L,显著低于对照组【(6.8±1.5)mmol/L,P<0.05】,HbA1c水平为(7.2±1.1)%,显著低于对照组【(7.7±1.3)%,P<0.05】,HOMA-IR水平为(2.4±0.5),显著低于对照组【(2.9±0.5),P<0.05】;血清TG水平为(2.2±0.5)mmol/L,显著低于对照组【(2.6±0.4)mmol/L,P<0.05】,LDL-C水平为(3.1±0.6)mmol/L,显著低于对照组【(3.5±0.8)mmol/L,P<0.05】,而血清HDL-C水平为(1.5±0.3)mmol/L,显著高于对照组【(1.2±0.2)mmol/L,P<0.05】。结论 应用二甲双胍联合吡格列酮治疗NAFLD合并T2DM患者能有效降低血糖水平,纠正脂质代谢紊乱和胰岛素抵抗,在改善患者肝功能方面显示出有意义的苗头,值得进一步深入探讨。     

甘舒霖30R联合吡格列酮治疗2型糖尿病疗效观察

对比观察34例接受甘舒霖30R联合吡格列酮治疗,31例接受甘舒霖30R治疗的T2DM患者的PG、2hPG、HbA1c、空腹C肽、HDL-C、TG改善程度和各种不良反应。结果甘舒霖30R联合吡格列酮组与甘舒霖30R组相比,PG、2hPG、HbA1c、空腹C肽、TG值明显降低（P〈0.05）。结论甘舒霖30R联合吡格列酮治疗能更好的控制血糖,改善和恢复胰岛B细胞功能,有一定改善血脂异常作用。     

吡格列酮联合利拉鲁肽对老年2型糖尿病合并非酒精性脂肪肝患者血浆脂联素、转化生长因子-β1水平的影响

目的探讨吡格列酮联合利拉鲁肽对老年2型糖尿病合并非酒精性脂肪肝患者血浆脂联素、转化生长因子(TGF)-β1水平的影响。方法选择老年2型糖尿病合并非酒精性脂肪肝患者62例,按照随机表法分为对照组与治疗组,各31例。对照组给予利拉鲁肽治疗,观察组在对照组基础上结合吡格列酮治疗。两组疗程均为12 w。比较两组疗效,治疗前后糖代谢变化、肝功能、脂联素和TGF-β1水平变化。结果治疗组治疗总有效率显著高于对照组(χ^2=5.415,P<0.05)。治疗组治疗后空腹血糖(FPG,6.73±0.43)mmol/L、糖化血红蛋白(HbA1c,7.08%±0.32%)和2 h餐后血糖(2 h PG,9.21±0.76)mmol/L显著低于对照组〔(7.21±0.28)mmol/L、(7.71±0.41)%和(10.63±0.89)mmol/L,t=5.208、6.744、6.756,P<0.05〕。治疗组治疗后谷丙转氨酶(ALT,37.76±3.37)U/L、γ谷氨酰转肽酶(GGT,43.19±3.26)U/L和谷草转氨酶(AST,28.93±2.24)U/L显著低于对照组〔(42.18±2.78)U/L、(48.42±3.78)U/L和(32.26±2.37)U/L,t=5.633、5.834、5.686,P<0.05〕。治疗组治疗后血清脂联素(6.32±0.61)mg/L显著高于对照组〔(5.49±0.46)mg/L〕,而TGF-β1〔(7.43±0.76)μg/L〕显著低于对照组〔(9.89±1.02)μg/L,t=6.049、10.768,均P<0.05〕。结论吡格列酮联合利拉鲁肽对老年2型糖尿病合并非酒精性脂肪肝患者疗效明显,可改善患者糖代谢和肝功能,且可提高脂联素水平及降低TGF-β1水平。     

2型糖尿病合并非酒精性脂肪肝患者经吡格列酮治疗后核苷酸结合寡聚化结构域样受体蛋白3的变化

目的 探讨吡格列酮治疗2型糖尿病（T2DM）合并非酒精性脂肪肝（NAFLD）患者血清核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)水平的改变。方法 收集上海健康医学院附属周浦医院内分泌科2021年1月到2022年10月就诊的T2DM合并NAFLD患者80例，随机分为对照组及吡格列酮治疗组，随访4周。分析两组研究对象基线及随访时血糖、血脂、肌酐、谷丙转氨酶等生化指标；运用ELISA双抗体夹心法检测外周血NLRP3水平。结果 最终吡格列酮组35例、对照组36例完成全部试验。吡格列酮组基线血清NLRP3为（5.4±1.1）μg/L，随访时为（4.8±0.8）μg/L，有明显下降；而对照组基线血清NLRP3为（5.2±1.0）μg/L，随访时为（5.2±0.8）μg/L，无明显改变，并且随访时吡格列酮组血清NLRP3水平低于对照组。除随访时吡格列酮组TC水平高于对照组外，两组间血糖、血脂、肝肾功能均无明显差异。结论 T2DM合并NAFLD患者使用吡格列酮治疗后在改善糖脂代谢的同时，也可以降低血清NLRP3水平。     

吡格列酮对糖尿病大鼠胰岛β细胞的保护作用及机制探讨

目的观察吡格列酮对糖尿病大鼠胰岛β细胞的保护作用,并探讨其机制。方法将雄性Wistar大鼠30只随机分为三组各10只。模型组、吡格列酮组采用腹腔注射链脲佐菌素建立糖尿病大鼠模型,对照组腹腔注射等量枸橼酸缓冲液;造模成功后吡格列酮组予吡格列酮10 mg/（kg·d）灌胃,另两组予等量生理盐水灌胃。16周后断尾取血测空腹血糖（FPG）,心包取血测糖化血红蛋白（HbA1c）和空腹胰岛素水平（FINS）,并计算胰岛素抵抗指数（HOMA-IR）,另取胰腺组织行HE染色,电镜下观察病理变化。结果吡格列酮组FPG、HbA1c、FINS、HOMA-IR水平明显低于模型组,病理改变轻于模型组。结论吡格列酮对糖尿病大鼠胰岛β细胞有保护作用,其机制可能为降低血糖、HbA1c和FINS,改善糖毒性和胰岛素抵抗。     

吡格列酮和二甲双胍联合诺和灵30R治疗2型糖尿病疗效分析

目的探索吡格列酮和二甲双胍联合诺和灵30R治疗2型糖尿病疗效。方法选取2015年4月—2017年4月期间该院收治的100例2型糖尿病患者,将其抽签化分组,两组各有50例,对照组和观察组分别采用二甲双胍+诺和灵30R治疗和吡格列酮+二甲双胍+诺和灵30R治疗。结果观察组患者的CHOL(6.05±0.39)mmol/L、LDL-C(10.05±2.46)mmol/L、hs-CRP(2.51±0.98)mg/mL、BMI(26.05±1.44)kg/m~2、2 hPG(8.14±1.36)mmol/L、FBG(6.42±0.69)mmol/L、HbA1c(6.05±1.05)%、低血糖发生率(2.00%)、血糖达标时间(7.05±2.96)d、胰岛素用量(38.48±3.52)U均优于对照组(P0.05)。结论吡格列酮+二甲双胍+诺和灵30R治疗2型糖尿病患者效果显著。     

吡格列酮和阿卡波糖对老年2型糖尿病合并高血压患者的疗效比较

目的：观察吡格列酮和阿卡波糖两种经典降糖药物对2型糖尿病合并高血压患者的疗效比较。方法选择2011年5月至2013年5月在第四军医大学西京医院住院的糖尿病伴高血压患者150例,其中男82例,女68例,年龄61-89岁。将入选者随机分为两组（每组75例）,分别接受吡格列酮和阿卡波糖治疗。观察治疗前和治疗后12周的收缩压（SBP）、舒张压（DBP）、糖化血红蛋白（HbA1c）、血清肿瘤坏死因子α（TNF-α）、脂联素（APN）、胰岛素抵抗指数稳态模型（HOMA-IR）、尿白蛋白排泄率（AER）、左心室肥厚（LVH）、血清中内皮祖细胞（EPC）相关因子CD34及血管内皮生长因子受体2（VEGFR-2）、一氧化氮（NO）、一氧化氮合酶（NOS）的变化。结果吡格列酮组患者在治疗12周后 SBP/DBP均降至140/90mmHg以下,与阿卡波糖组比较差异有统计学意义（P＜0.05）。治疗12周后,吡格列酮组APN含量较阿卡波糖组升高（P＜0.05）,HbA1c水平较阿卡波糖组降低（P＜0.05）,TNF-α和HOMA-IR较阿卡波糖组降低（P＜0.05）。吡格列酮组血尿素氮（BUN）、血肌酐（SCr）较阿卡波糖组降低（P＜0.05）,AER和LVH也较阿卡波糖组降低（P＜0.05）,CD34及VEGFR-2水平较阿卡波糖组明显升高（P＜0.01）、NO和NOS的含量较阿卡波糖组明显升高（P＜0.01）。结论与阿卡波糖治疗相比较,采用吡格列酮治疗2型糖尿病合并高血压患者,可降低HbA1c水平,升高血清APN浓度,减少对肾功能的损害;降低LVH,保护心脏的效应显著;同时降低血清CD34及VEGFR-2水平,使EPC耗损减少;提高血清NO和NOS的含量,具有保护血管、延缓血管硬化进程的功能。     

胰岛素联合维格列汀治疗2型糖尿病合并中度肾损伤患者的有效性和安全性

选取2012年12月至2013年11月于天津医科大学代谢病医院和天津滨海新区解放路社区卫生服务中心门诊或住院治疗的胰岛素治疗且血糖控制不佳的中度肾损伤的2型糖尿病（T2DM）患者143例,在现有胰岛素不变的基础上加用维格列汀50 mg每日1次口服治疗12周.比较治疗前后糖化血红蛋白（HbA1c）、空腹血糖（FPG）、预估肾小球滤过率（eGFR）、血红蛋白（Hb）和胰岛素用量变化情况,评估用药后的不良事件以及患者和医师的满意度.132例患者完成12周维格列汀药物治疗.与治疗前相比,治疗后HbA1c降低0.7％,FPG降低了1.8 mmol/L,胰岛素用量减少了8.0U,治疗前后差异具有统计学意义[分别为：（8.4±0.8）％比（7.7±1.2）％,=7.515;（10.6±2.6）比（8.8±1.4） mmol/L,t =9.476;（51 ±16）比（43±15） U/d,t=4.421;均P＜0.05];Hb和eGFR治疗前后无差异（均P ＞0.05）.治疗中无胰腺炎、死亡等严重不良事件的发生.医师对于中度肾损伤患者应用维格列汀治疗的满意度达94.7％,患者自身的满意度为94.0％.胰岛素联合维格列汀50 mg每日1次可改善中度肾损伤患者的血糖水平,同时具有良好的耐受性和安全性.     

吡格列酮干预对糖尿病肾病患者尿单核细胞趋化蛋白-1的影响

目的 探讨吡格列酮对糖尿病肾病(DN)患者尿单核细胞趋化蛋白-1(MCP-1)的影响.方法 80例患者随机分为吡格列酮组和对照组(完成71例).吡格列酮组加服吡格列酮15 mg/d连续6个月.服药前、服药后3个月、6个月分别留取空腹血测定血糖、糖化血红蛋白(HbA1c);留取晨尿液测定MCP-1、微量白蛋白/肌酐(Alb/Cr).结果 吡格列酮组血糖、HbA1c较治疗前有所下降,但无统计学意义(P＞0.05),尿MCP -1、Alb/Cr显著降低(均P＜ 0.05).结论 吡格列酮除具备降糖作用外对肾脏还有保护作用.     

诺和锐、二甲双胍及吡格列酮联用治疗超重及肥胖T2DM的效果观察

目的探讨诺和锐、二甲双胍和吡格列酮联合治疗超重及肥胖2型糖尿病（T2DM）患者的临床疗效。方法将60例超重及肥胖T2DM患者随机分为A、B、C三组各20例,A组予诺和灵30R皮下注射;B组予诺和锐三餐前及中效胰岛素每晚睡前皮下注射;C组在B组基础上口服二甲双胍和吡格列酮,治疗目标均为空腹血糖（FBG）4—7mmol／L、餐后2h血糖7—10mmol／L、糖化血红蛋白（HbA1c）〈6．5％,各组疗程均为12周。治疗前后分别采用放免法测定FBG、餐后2h血糖及HbA1c;记录胰岛素用量及低血糖发生率。结果治疗后三组FBG均较治疗前显著降低,但组间比较无显著差异;B、C组餐后2h血糖、HbA1c均显著低于A组,且C组HbA1c显著低于B组（P均〈0．05）;胰岛素用量c组〈A组〈B组,B、C组低血糖反应发生率显著低于A组（P均〈0．05）。结论诺和锐、吡格列酮及二甲双胍联合治疗超重及肥胖T2DM患者,可降低餐后血糖、改善血糖控制、减少胰岛素用量及低血糖事件。     

妊娠时间与肺结核复发的相关性研究及诊治对策

目的 分析肺结核史患者妊娠时间和肺结核复发间相关性.方法 选取我院收治的有肺结核史的妊娠妇女576例作为研究对象,对其妊娠前肺结核治疗、治愈后妊娠时间、妊娠后复发肺结核等进行分析,总结有肺结核史育龄女性的妊娠时间和肺结核复发之间的关系.结果 肺结核治愈后不同时间段妊娠者的结核复发率比较,差异具有显著性（P＜0.05）,停药后间隔时间越久妊娠,肺结核复发的几率越小.结论 加强孕期痰菌检查,及早发现复发肺结核,提高母婴安全.     

我国骨关节结核诊治的回顾与展望

骨关节结核是危害人们健康的严重感染性疾病,近95％由他处结核病继发而来.罹患骨关节结核疾病后几乎均将致残,严重影响人们的健康、工作和生活.建国以来在党和国家的关心和支持下,骨关节结核的诊治水平取得了长足进步.时至今日,由于多种原因,学科发展和被重视程度受到一定的制约,同整个医疗行业的发展不相适应.回顾过去,展望未来,我们需要重新审视骨关节结核的诊治方法,努力推进骨关节结核诊疗技术的科学发展.     

Effect of phosphorylation of MAPK and Stat3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44~(MAPK), p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44~(MAPK), p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44~(MAPK) and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between P42/44~(MAPK) and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Raf/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44~(MAPK), c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.     

Overweight and Obesity and Progression of ADPKD

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Replication and Inhibitors of Enteroviruses and Parechoviruses

The Enterovirus (EV) and Parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, EV-A71, EV-D68, and human parechoviruses (HPeV). They cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. At the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all EVs and HPeVs due to the great number of serotypes. Therefore, a lot of effort is being invested in the development of antiviral drugs. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. As such, a good understanding of the complex process of virus replication is pivotal in the design of antiviral strategies goes hand in hand with a good understanding of the complex process of virus replication. In this review, we will give an overview of the current state of knowledge of EV and HPeV replication and how this can be inhibited by small-molecule inhibitors.     

Effects of sex and time of day on metabolism and excretion of corticosterone in urine and feces of mice

Non-invasive techniques to monitor stress hormones in small animals like mice offer several advantages and are highly demanded in laboratory as well as in field research. Since knowledge about the species-specific metabolism and excretion of glucocorticoids is essential to develop such a technique, we conducted radiometabolism studies in mice (Mus musculus f. domesticus, strain C57BL/6J). Each mouse was injected intraperitoneally with 740 kBq of 3H-labelled corticosterone and all voided urine and fecal samples were collected for five days. In a first experiment 16 animals (eight of each sex) received the injection at 9 a.m., while eight mice (four of each sex) were injected at 9 p.m. in a second experiment. In both experiments radioactive metabolites were recovered predominantly in the feces, although males excreted significantly higher proportions via the feces (about 73%) than females (about 53%). Peak radioactivity in the urine was detected within about 2h after injection, while in the feces peak concentrations were observed later (depending on the time of injection: about 10h postinjection in experiment 1 and about 4h postinjection in experiment 2, thus proving an effect of the time of day). The number and relative abundance of fecal [3H]corticosterone metabolites was determined by high performance liquid chromatography (HPLC). The HPLC separations revealed that corticosterone was extensively metabolized mainly to more polar substances. Regarding the types of metabolites formed, significant differences were found between males and females, but not between the experiments. Additionally, the immunoreactivity of these metabolites was assessed by screening the HPLC fractions with four enzyme immunoassays (EIA). However, only a newly established EIA for 5alpha-pregnane-3beta,11beta,21-triol-20-one (measuring corticosterone metabolites with a 5alpha-3beta,11beta-diol structure) detected several peaks of radioactive metabolites with high intensity in both sexes, while the other EIAs showed only minor immunoreactivity. Thus, our study for the first time provides substantial information about metabolism and excretion of corticosterone in urine and feces of mice and is the first demonstrating a significant impact of the animals' sex and the time of day. Based on these data it should be possible to monitor adrenocortical activity non-invasively in this species by measuring fecal corticosterone metabolites with the newly developed EIA. Since mice are extensively used in research world-wide, this could open new perspectives in various fields from ecology to behavioral endocrinology.     

心电图、心电向量图与冠状动脉造影结果对比分析

目的:通过分析心电图(Electrocardiogram,ECG)和心电向量图(Vectorcardiogram,VCG)的改变与冠脉造影（CAG）结果进行对比,探讨ECG、VCG在冠状动脉病变中的诊断价值。方法: 选择2008年1月~2009年12月临床拟诊断为冠心病患者108例,行常规ECG、VCG检查,并于1周内进行CAG,对检查结果依据各自的诊断标准进行判定,以CAG为标准诊断法,利用四格表法,计算相关评价真实性的指标并进行比较。结果: ①VCG检测的灵敏度、特异度、准确度显著高于ECG(P<0.05,P<0．01)。②ECG、VCG阳性率与冠脉病变支数组间比较:在单支病变、双支病变中,VCG阳性率明显高于ECG(P<0.05),左主干或三支病变无统计学意义;组内比较:ECG组左主干或三支病变组较单支病变、双支病变阳性率高(P<0.05,P<0.01);VCG组左主干或三支病变组较单支病变阳性率高(P<0.05);与双支病变阳性率比较无统计学意义;③ECG、VCG阳性率与冠脉病变程度组间比较:冠脉病变狭窄50%～69%的VCG阳性率明显高于ECG (P<0.05),其他两组阳性率比较无统计学意义;组内比较:ECG组冠脉病变狭窄≥90%较50%～69%、70%～89%的阳性率高(P<0.05,P<0.01); VCG组狭窄≥90%较50%～69%阳性率高（P<0.01),其他无统计学意义。结论: VCG对冠心病检测价值显著高于ECG。     

Detection and characterization of the product of hydroethidine and intracellular superoxide by HPLC and limitations of fluorescence

Here we report the structural characterization of the product formed from the reaction between hydroethidine (HE) and superoxide (O(2)(.-)). By using mass spectral and NMR techniques, the chemical structure of this product was determined as 2-hydroxyethidium (2-OH-E(+)). By using an authentic standard, we developed an HPLC approach to detect and quantitate the reaction product of HE and O(2)(.-) formed in bovine aortic endothelial cells after treatment with menadione or antimycin A to induce intracellular reactive oxygen species. Concomitantly, we used a spin trap, 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO), to detect and identify the structure of reactive oxygen species formed. BMPO trapped the O(2)(.-) that formed extracellularly and was detected as the BMPO-OH adduct during use of the EPR technique. BMPO, being cell-permeable, inhibited the intracellular formation of 2-OH-E(+). However, the intracellular BMPO spin adduct was not detected. The definitive characterization of the reaction product of O(2)(.-) with HE described here forms the basis of an unambiguous assay for intracellular detection and quantitation of O(2)(.-). Analysis of the fluorescence characteristics of ethidium (E(+)) and 2-OH-E(+) strongly suggests that the currently available fluorescence methodology is not suitable for quantitating intracellular O(2)(.-). We conclude that the HPLC/fluorescence assay using HE as a probe is more suitable [corrected] for detecting intracellular O(2)(.-).     

大鼠骨髓间充质干细胞的分离培养和外源基因的导入

目的探讨绿色荧光蛋白基因转染骨髓间质干细胞的可行性。方法采用F icoll-PaqueTMP lus淋巴细胞分离液,根据细胞密度梯度原理,分离大鼠骨髓间充质干细胞(rM SC s)并进行体外原代培养和传代扩增,倒置相差显微镜观察细胞生长情况,免疫细胞化学法对其初步鉴定。流式细胞仪分析转染效率。结果原代和传代培养的细胞呈现梭形外观,具有较强的生长增殖能力;细胞均一表达CD44、CD54、CD106、CD29抗原。电穿孔法转染rM SC s转染率为32.8%±3%。结论采用比重为1.077 g/L的F icoll-PaqueTMP lus能分离获得大鼠骨髓间充质干细胞,经原代培养和传代培养能够迅速扩增。电穿孔法具有较高的介导外源基因表达于rM SC s的效率。     

Effect of phosphorylation of MAPK and Stat3 and expression of c-fas and c-jun proteins on hepatocarcinogenesis and their clinical significance

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.