基于古籍方剂的中风病症-药复杂网络演变分析

目的探索中医药辨治中风病发展过程中隐含的症-药关系及演变规律。方法基于古籍构建中风病症-药网络,利用网络拓扑和节点排序特征计算、子网络相似性分析、社团发现等方法分析中风病辨治规律及演变。结果基于中风病症-药网络结构与规模的变化及节点排序特征的演变分析,挖掘出不同历史时期中风病的关键症状与核心药物,印证了中医药对中风病理论认识的演变及辨证治疗的日趋成熟。子网络相似性分析表明中风病大致可分为真中风、类中风、急中风三大类;社团发现及演变分析则挖掘出在不同历史时期均有紧密联系的症状与药物组合。结论复杂网络演变分析为研究中风病症-药复杂关系及发展规律提供新方法,所得结果可为中风病源流梳理及临床辨证治疗作参考。

全国名中医治疗慢性肾炎“症-证-药”规律分析

目的基于数据挖掘技术从“症-证-药”角度探究全国名中医治疗慢性肾炎的证治用药规律,为中医药治疗慢性肾炎提供依据。方法以名老中医的姓名和“慢性肾炎”为检索词,以作者和题名为检索字段,以中国知网数据库、万方数据库、中国生物医学数据库、维普期刊上已公开发表的文献为基础,收集各位名中医大家治疗慢性肾炎的医案,建立文献数据库,运用频数统计、关联规则分析和聚类分析等数据挖掘方法分析慢性肾炎的症状、证候及用药规律。结果四诊频次统计症状以腰酸、乏力、腰痛为主;舌象多见淡舌、淡红舌、黯舌;舌苔多见腻苔、黄苔、薄白苔;脉象多见细脉、沉脉;证型以下焦湿热证、脾肾两虚证、肾阴虚证、脾气虚证、脾肾阳虚证为主,病位证素以肾、脾为主,病性证素以阳虚、气虚以及湿热为主;治法以清热利湿、益气滋阴、温补肾阳、健脾利水为主。治疗慢性肾炎涉及中药267味,用药功效以利水渗湿为最,其次为利水消肿、清热解毒、健脾等;用药频次最高的为茯苓,其次为黄芪、泽泻、白术、山药、党参、甘草、白茅根等。症状聚类以阳虚证与气虚证症状为主,药物聚类主要以补气方、补肾阴方及活血方组合为主。结论在研究纳入的143例医案症状-证型-治法-用药规律中,慢性肾炎以气虚、阳虚症状多见,但用药多以利水为主而并非补肾药,体现了从“肾主水”论治慢性肾炎的特点。

基于朴素贝叶斯算法的全国名中医诊治儿童过敏性紫癜的症-证-药规律初探

目的 挖掘名中医辨治儿童过敏性紫癜(henoch-schonlein purpura,HSP)的中医核心症状、证型分类特征及用药规律,为临床诊治提供参考。方法 检索中国知网全文数据库中全国名中医治疗儿童HSP的相关文献及河南中医药大学图书馆医案类、临证经验类书籍,建立儿童HSP的症-证-药数据库,采用频数分析、朴素贝叶斯算法挖掘儿童HSP的核心症状、证型、药物及其关联规律。结果 共纳入664则名中医经验医案,含151个症状、12种证型、323味中药。统计分析得到的常见症状除主症双下肢紫癜外,还有腹痛、食少纳呆、关节痛、咽红、大便干结、口干口渴、神疲乏力等,常见舌象包括舌红、苔黄、苔薄、苔白、苔腻、舌淡等,常见脉象包括脉数、脉细、脉滑等;常用中药有牡丹皮、生地黄、赤芍、紫草、白茅根、连翘等,以清热药、凉血止血药为主;常见证型有血热妄行证、风热伤络证、湿热痹阻证、气不摄血证、阴虚火旺证等。朴素贝叶斯算法分析得到9个证型的核心症状及中药,如血热妄行证的核心症状为紫癜大量、斑色深红或紫红、鼻衄、口干口渴、口唇色红,核心药物有水牛角、生地黄、紫花地丁、栀子、牡丹皮等。结论 运用朴素贝叶斯算法分析名中医治疗儿童HSP症-证-药规律与临床基本一致,对临床实践有一定参考价值。

叶天士通络法治疗痹症特色用药规律研究

基于中医久病入络理论,通络法治疗痹症具有独特优势,故借助古今医案云平台、SPSS Modeler和中医药整合药理学研究平台v2.0对通络法治疗痹症的“病-证-症-方-药-靶”多维网络全方位进行深入研究。总结《临证指南医案》治疗痹症的“病-证-症-方-药”规律以及内在联系,梳理《临证指南医案》治疗痹症的常用通络法以及用药规律,解释不同通络法治疗痹症的物质基础和生物学机制,从病的层面为中医药治疗痹症处方选药提供临床依据,从证的层面为通络法治疗痹症的潜在药物发现及实验研究提供参考。

基于时间序列相似性分析探讨中风方剂中的症—药演变规律

【目的】基于中医古籍智能检索平台,采用时间序列相似性分析方法探索治疗中风方剂的症-药演变规律,为中风的临床诊疗提供参考。【方法】筛选治疗中风的方剂,对中风相关症状与治疗中风方剂的药物进行提取与标准化,依据方剂所属古籍的成书或刊刻时间,形成时间序列数据,依据形态相似距离评估不同历史时期的症-症、药-药、症-药间相似性,从而探寻治疗中风方剂中症-药的演变规律。【结果】共收集公元341-1949年间的2065首治疗中风的方剂,涉及中医古籍258本。症-症相关性分析得到3类有关中风的症状群;全时期的症-药时间序列中共记录中药643味,频次居前100位的中药可聚为4类中药群。症-药相关性分析结果显示症状群Ⅰ(真中风症状群)与中药群Ⅰ相关性最显著,症状群Ⅱ(类中风症状群)与中药群Ⅱ相关性最显著,症状群Ⅲ(急中风症状群)与中药群Ⅰ相关性最显著。【结论】通过中风症-药时间序列相似性分析发现,中风相关症状逐渐形成真中风、类中风与急中风3组症状群,与其密切相关的中药可分为4类,各症状群与各中药群关系迥异,其中药配伍日益丰富,治法组合也逐渐完善。挖掘所得结果可为中医药治疗中风的理论发展和临床应用提供一定的参考。

基于关联规则分析明清古籍中疫病文献的药-症关系

目的分析明清两代15本医籍、医案、医话中660例疫病诊疗的方药特色及药症关系。方法基于关联规则挖掘。结果在单味药及药对与症状之间均发现了一些有意义的关联关系。显示疫病总属热邪为患,易伤及营血、易耗伤气阴。治疗以清热为大法,主用清热药。急证清心醒神,善用开窍药。后期补虚扶正,重用补益药。清热药物中,清气分热药最多,清热凉血药次之,解表药常常随症加减,说明"入营犹可透热转气"的理论在疫病的治疗中具有一定的应用价值。结论数据挖掘的结果与中医疫病的治法及用药基本相符,能初步揭示明清医家对疫病诊疗的学术思想及治疫经验。

高血压病肝阳上亢证“病-证-症-方-药”证治规律的探讨

高血压病中肝阳上亢证是高血压各期及不同病程中构成比最高最常见的证型,并有日渐快速增长的趋势,在现有相关理论的基础上,建立"病-证-症-方-药"证治理论体系,对多方面、多靶点防治疾病,最大限度地降低心脑血管病的死亡和病残的总风险,保护靶器官的结构和功能,提高生活质量,更好地服务于临床,并进一步强化中医的诊疗优势,将中医药推向现代化、国际化,将发挥至关重要的作用。

基于关联规则的新安“王氏内科”代表医家论治咳嗽的药-症规律

目的:利用关联规则Apriori算法探讨新安"王氏内科"代表医家治疗咳嗽的药-症规律。方法:收集新安"王氏内科"代表医家治疗咳嗽效验医案共234案,利用Excel 2016建立药物、症状数据库,进行频数与关联规则分析。结果:药物频数分析得出治疗咳嗽前四位药物分别是苦杏仁、款冬花、紫菀、茯苓,重在化痰止咳,健脾利水;根据四诊信息频数统计结果可归纳为痰相关、热相关、风相关、郁相关;药物关联规则提取出"王氏内科"医家治疗咳嗽常用药对为苦杏仁→射干、款冬花→百部等;药物与四诊关联规则结果显示脉濡弦与五味子、葶苈子、佛耳草→紫菀等关联度较高;咳声重浊与鹅管石、远志→鹅管石、半夏→化橘红关联度较高;痰鸣与佛耳草、葶苈子、干姜→佛耳草等关联度较高;咳声重浊与舌白苔腻与半夏→化橘红关联度较高。药物与四诊关联规则结果显示脉濡弦与五味子、葶苈子、佛耳草+紫菀三者关联度较高;咳声重浊与鹅管石、远志+鹅管石、半夏+化橘红三者关联度较高;痰鸣与佛耳草、葶苈子、干姜+佛耳草三者关联度较高;咳声重浊与舌白苔腻与半夏+化橘红二者关联度较高。结论:"王氏内科"代表医家临证治疗咳嗽特点鲜明,将辨证与辨症相结合,以化痰为要,重视肺气的宣降,重视培护脾胃,培土生金。

基于TabNet的周仲瑛教授辨治甲状腺功能亢进病机预测模型及用药规律研究

目的以周仲瑛教授治疗甲状腺功能亢进(甲亢)的临床病案为研究对象,探索运用基于神经网络的TabNet模型发现甲亢的诊疗规律,为传承名老中医学术思想、辅助临床诊疗提供方法参考。方法基于周仲瑛教授及其团队的临床甲亢诊疗医案,构建标准化、结构化训练数据,研究基于注意力机制和稀疏特征选择机制的算法,通过输入标准化临床表现,标准化舌象、脉象构建病机预测模型,分析核心症状、病机和药物以及三者之间的联系。结果通过训练好的预测模型对肝郁、肝火、痰饮、肾虚、阴虚、瘀血6个病机进行预测,与决策树、随机森林等经典算法构建的多标签分类模型相比,本模型分类和预测指标均较好。通过决策树算法进行挖掘,总结6个核心病机对应中药社团:醋柴胡、夏枯草、牡蛎、炙鳖甲、玄参、天冬、麦冬等。结论在临床医案数据上运用TabNet算法,构建基于临床表现、舌象和脉象的病机预测模型,可有效地预测核心病机,进而发现“症-机-药”之间的联系,为名老中医学术思想的传承和临床辅助诊疗决策提供方法学参考。

基于数据挖掘探讨中医药治疗肝癌用药规律

目的:基于回顾性数据挖掘肝癌临床症状及中药处方,研究肝癌的核心药物配伍规律及方药的用药特点。方法:收集2017年4月至2019年5月期间于湖北省中医院就诊的肝癌患者的病历,提取入院阳性症状和住院期间患者服用的中药处方,采用频数统计、复杂网络分析、关联规则、聚类分析等方法,挖掘肝癌核心症状及常用药对,统计分析药物四气五味、归经。结果:复杂网络分析提示乏力、纳差、睡眠差、肝区不适、腹胀、口干、小便黄症状为强链接关系。发现肝癌用药药性以寒、温为主,药味以甘平为主,苦药次之,药物归经集中为脾经、肺经,其次是肝胃经。处方复杂网络和关联规则分析得出白术、茯苓、黄芪、丹参、茵陈、半枝莲、半夏等药物之间存在强链接关系,肝癌常用药对分别是:炒麦芽-炒谷芽;茯苓-白花蛇舌草,黄芪;茯苓-百花蛇舌草,白术;白术-太子参,茯苓;茯苓-神曲,丹参。选取高频药物进行聚类分析,得出4个药物聚类,具有扶正健脾、化痰、祛瘀、疏肝、软坚、解毒抑癌等对症治疗的遣方用药特点。结论:肝癌主要以乏力、纳差、睡眠差、肝区不适、腹胀、口干、小便黄等虚实夹杂类症状为主,用药以“解毒”“化痰”“祛瘀”“扶正补虚”,辅以疏肝为基本治疗原则。

Effects of fructose-1,6-diphosphate on concentration of calcium and activities of sarcoplosnic Ca^(2+)-ATPase in cardiomyocytes of Adriamycin-treated rats

Objective: To observe the effects of fructose-1,6-diphosphate (FDP) on serum levels of cardiac troponin 1 (cTnl) and creatine kinase-MB (CK-MB), as well as the concentration of calcium in cardiomyocytes (Myo[Ca2+]) and activity of sarcoplosnic Ca2+-ATPase (SRCa2+-ATPase) in Adriamycin (ADR)-treated rats. Methods: Rats were intraperitoneally injected with ADR (2.5 mg/kg every other day for 6 times) and then with different dosages of FDP (every other day for twenty-one times). Bi-antibodies sandwich Enzyme linked immune absorption assay (ELISA) was performed to detect serum level of cTnl. CK-MB was detected by monoclonal antibody, Myo[Ca2+] was detected by fluorescent spectrophotometry and the activity of SRCa2+-ATPase was detected by inorganic phosphate method. Results: FDP (300, 600, 1200 mg/kg) significantly reduced the serum levels of cTnl and CK-MB, while at the same time decreased calcium concentration and increased SRCa2+-ATPase activity in cardiomyocytes of ADR-treated rats (P<0.01). Conclusions: FDP might alleviate the cardiotoxic effects induced by ADR through decreasing calcium level as well as increasing SRCa2+-ATPase activity in cardiomyocytes.

Interaction or relationship between Helicobacter pylori and non-steroidal anti-inflammatory drugs in upper gastrointestinal diseases

According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs （NSAID） independently and significantly increase the risk of gastroduodenal ulcer and ulcer bleeding. Their coincidence is frequent, demonstration of a possible relationship and consequent attitude is of important implications. But unfortunately, no consensus has been approved in the past years and their interactions are still controversial. H pylori and NSAID are known to share a number of pathogenic mechanisms, but there is no evidence for the significant synergic action between these two risk factors. Their relationship is independent, additive, synergistic or antagonistic without considering the influence of other factors because studies on this subject are different in almost all aspects of their methodology, including the definition of a NSAID user as well as the types, doses, duration and their indications for NSAID use, as well as their end-points, definition of dyspepsia and regimes used for eradication of H pylori. These might contribute to the conflicting results and opinions. H pylori infection in humans does not act synergistically with NSAID on ulcer healing, and there is no need to eradicate it. This notion is supported by the finding that the eradication of H pylori does not affect NSAID induced gastropathy treated with omeprazole and that H pylori infection induces a strong cyclooxygenase-2 （COX-2） expression resulting in excessive biosynthesis of gastroprotective prostaglandin which in turn counteracts NSAID-induced gastropathy and heals the existing ulcer. Other investigators claimed that H pylori infection acts synergistically with NSAID on ulcer development, and H pylori should be eradicated, particularly at the start of long-term NSAID therapy. Eradication of H pylori prior to NSAID treatment does not appear to accelerate ulcer healing or to prevent recurrent ulcers in NSAID users. However, some recommendations can be drawn from the results of clinical trails.

Non-steroidal anti-inflammatory drug-induced small bowel injuries identified by double-balloon endoscopy

AIM： To clarify clinical features of the NSAID-induced sma bowel lesions using a new method of endoscopy. METHODS： This is a retrospective study and we analyzed seven patients with small bowel lesions while taking NSAIDs among 61 patients who had undergone doubleballoon endoscopy because of gastro-intestinal bleeding or anemia between September 2000 and March 2004, at .lichi Medical School Hospital in Japan. Neither conventional EGD nor colonoscopy revealed any lesions of potential bleeding sources including ulcerations. Double-balloon endoscopy was carried out from oral approach in three patients, from anal approach in three patients, and from both approaches in one patient. RESULTS： Ulcers or erosions were observed in the ileum in six patients and in the jejunum in one patient, respectively. The ulcers were multiple in all the patients with different features from tiny punched out ulcers to deep ulcerations with oozing hemorrhage or scar. All the patients recovered uneventfully and had full resolution of symptoms after suspension of the drug. CONCLUSION： NSAIDs can induce injuries in the small bowel even in patients without any lesions in both the stomach and colon.

Bisphosphonate use and gastrointestinal tract cancer risk:Meta-analysis of observational studies

AIM:To perform a meta-analysis of observational studies to further elucidate the relationship between oral bisphosphonate use and gastrointestinal cancer risk.METHODS:Systematic literature search was conducted in MEDLINE,EMBASE,and the Cochrane Library to identify studies through January 2011.Search terms were "bisphosphonates" or trade names of the drugs,and "observational studies" or "cohort studies" or "case-control studies".Two evaluators reviewed and selected articles on the basis of predetermined selection criteria as followed:(1) observational studies(casecontrol or cohort studies) on bisphosphonate use;(2) with at least 2 years of follow-up;and(3) reported data on the incidence of cancer diagnosis.The DerSimonian and Laird random effects model were used to calculate the pooled relative risk(RR) with 95% confidence interval(CI).Two-by-two contingency table was used to calculate the outcomes not suitable for meta-analysis.Subgroup meta-analyses were conducted for the type of cancer(esophageal,gastric and colorectal cancers).Sensitivity analyses were performed to examine the effect sizes when only studies with long-term follow-up(mean 5 years;subgroup 3 years) were included.RESULTS:Of 740 screened articles,3 cohort studies and 3 case-control studies were included in the analyses.At first,4 cohort studies and 3 case-control studies were selected for the analyses but one cohort study was excluded because the cancer outcomes were not categorized by type of gastrointestinal cancer.More than 124 686 subjects participated in the 3 cohort studies.The mean follow-up time in all of the cohort studies combined was approximately 3.88 years.The 3 casecontrol studies reported 3070 esophageal cancer cases and 15 417 controls,2018 gastric cancer cases and 10 007 controls,and 11 574 colorectal cancer cases and 53 955 controls.The percentage of study participants who used bisphosphonate was 2.8% among the cases and 2.9% among the controls.The meta-analysis of all the studies found no significant association between bisphosphonate use and gastrointestinal cancer.Also no statistically significant association was found in a meta-analysis of long-term follow-up studies.There was no negative association between bisphosphonate use and the incidence of esophageal cancer in the overall analysis(RR 0.96,95% CI:0.65-1.42,I 2 = 52.8%,P = 0.076) and no statistically significant association with long-term follow-up(RR 1.74,95% CI:0.97-3.10,I 2 = 58.8%,P = 0.119).No negative association was found in the studies reporting the risk of gastric cancer(RR 0.89,95% CI:0.71-1.13,I 2 = 0.0%,P = 0.472).In case of colorectal cancer,there was no association between colorectal cancer and bisphosphonate use(RR 0.62,95% CI:0.30-1.29,I 2 = 88.0%,P = 0.004) and also in the analysis with long-term follow-up(RR 0.61,95% CI:0.28-1.35,I 2 = 84.6%,P = 0.011).CONCLUSION:Oral bisphosphonate use had no significant effect on gastrointestinal cancer risk.However,this finding should be validated in randomized controlled trials with long-term follow-up.

Education-based approach to addressing non-evidence-based practice in preventing NSAID-associated gastrointestinal complications

AIM:To evaluate an evidence-based educational program for improving strategies for prevention of non-steroidal anti-inflammatory drug(NSAID)-associated gastrointestinal(GI)complications. METHODS:Four hundred and fifty-six specialists replied to a questionnaire that covered issues related to NSAID-induced adverse effects.They also collected data from their last five consecutive patients before and after they had attended an evidence-based seminar on GI prevention strategies. RESULTS:Four hundred and forty-one of 456 specialists(96.7%)participated in the survey,and 382(83.7%)in the education-based study that recorded data from 3728 patients.The specialists overestimated the risk of GI complications with NSAIDs,underestimated the GI safety profile of coxibs,but were aware of the risk factors and of the current prevention strategies.Proton pump inhibitors were co-prescribed with NSAIDs in>80% of patients with and without risk factors.The educational program had little impact on prescribing habits.CONCLUSION:Specialists are informed of advances in NSAID-associated adverse effects and have high rates of GI-prevention therapy.Our educational program did not alter these rates.

Inhibition of N-methyl-N-nitrosourea-induced gastric tumorigenesis by Liuwei Dihuang Pill in db/db mice

AIM To investigate the inhibitory effect of Liuwei Dihuang Pill(LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea(MNU) in diabetic mice.METHODS Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP. MNU was administrated for 20 wk to induce gastric carcinogenesis. LDP was administrated for 10 wk for improvement of insulin resistance. Body weight and food intake were measured every week. Blood samples were collected for assays of fasting blood glucose, insulin, insulin-like growth factor(IGF)-1, adiponectin and leptin. Stomach tissues were collected for histopathological analysis, immunohistochemical staining of Ki67, quantitative reverse transcriptionpolymerase chain reaction and western blotting. RESULTS The incidence of MNU-induced gastric dysplasia was significantly elevated in diabetic(db/db) mice relative to the control(db/m) mice. The incidence of gastricdysplasia was significantly reduced by LDP with suppression of cell proliferation, as demonstrated by a decrease in Ki67 staining. Hyperglycemia, hyperinsulinemia and serum IGF-1 were inhibited by LDP. Expression of IGF-1 and insulin receptor m RNAs was decreased, phosphorylation of IGF-1 receptor and AKT protein was reduced in the stomach tissues by LDP. In addition, adiponectin was increased and leptin was decreased in the serum by LDP. CONCLUSION LDP decreased risk of gastric dysplasia in type 2 diabetic mice by down-regulation of IGF and insulin activity and correction of adipokines disorders.

Use of arrays to investigate the contribution of ATP-binding cassette transporters to drug resistance in cancer chemotherapy and prediction of chemosensitivity

Multidrug resistance （MDR） is a major problem in cancer chemotherapy. One of the best known mechanisms of MDR is the elevated expression of ATP-binding cassette （ABC） transporters. While some members of human ABC transporters have been shown to cause drug resistance with elevated expression, it is not yet known whether the over-expression of other members could also contribute to drug resistance in many model cancer cell lines and clinics. The recent development ofmicroarrays and quantitative PCR arrays for expression profiling analysis of ABC transporters has helped address these issues. In this article, various arrays with limited or full list of ABC transporter genes and their use in identifying ABC transporter genes in drug resistance and chemo-sensitivity prediction will be reviewed.

CLINICAL OBSERVATION ON TREATMENT OF 100 CASES OF NEURASTHENIA BY OTOPOINT PELLET-PRESSING THERAPY

This paper is aimed at observing the therapeutic effect of otopoint pellet-pressing therapy [auricular application of vaccaria seed (Wang Bu Liu Xing)] in the treatment of neurasthenia. Main otopoints used are Pizhixia (MA-AT 1), Chuiqian (MA-L), Ershenmen (MA-TF-1), Zhen (MA-AT), etc.. After application of plaster-adhered vaccaria seed at the otopoint, the patient is asked to press the otopoint 2-3 times daily, 3-5 min every time. After 2 courses (10 sessions) of treatment, of the 100 cases, 49 are cured, 37 have remarkable improvement and the rest 14 cases are relieved. Clinical practice shows that this therapy is effective for various kinds of neurasthenia.

Effect of Qi-protecting powder (Huqi San) on expression of c-jun, c-fos and c-myc in diethylnitrosamine-mediated hepatocarcinogenesis

To study the inhibitory effect of Huqi San （Qi- protecting powder） on rat prehepatocarcinoma induced by diethylinitrosamine （DEN） by analyzing the mutational activation of c-fos proto-oncogene and over-expression of c-jun and c-myc oncogenes. METHODS： A Solt-Farber two-step test model of prehepatocarcinoma was induced in rats by DEN and 2-acetylaminofluorene （AAF） to investigate the modifying effects of Huqi San on the expression of c-jun, c-fos and c-myc in DEN-mediated hepatocarcinogenesis. Huqi San was made of eight medicinal herbs containing glycoprival granules, in which each milliliter contains 0.38 g crude drugs. T-glutamy-transpeptidase-isoenzyme （T-GTase） was determined with histochemical methods. Level of 8-hydroxydeoxyguanosine （OHdG） formed in liver and c-jun, c-fos and c-myc proto-oncogenes were detected by immunohistochemical methods. RESULTS： The level of 8-OHdG, a mark of oxidative DNA damage, was significantly decreased in the liver of rats with prehepatocarcinoma induced by DEN who received 8 g/kg body weight or 4 g/kg body weight Huqi San before （1 wk） and after DEN exposure （4 wk）. Huqi San- treated rats showed a significant decrease in number of T-GT positive foci （P 〈 0.001, prevention group： 4.96-0.72 vs 29.46-2.17; large dose therapeutic group： 7.53-0.88 vs 29.46-2.17）. On the other hand, significant changes in expression of c-jun, c-fos and c-myc were found in Huqi San-treated rats. CONCLUSION： Activation of c-jun, c-fos and c-myc plays a crucial role in the pathogenesis of liver cancer.Huqi San can inhibit the over-expression of c-jun, c-fos and c-myc oncogenes and liver preneolastic lesions induced by DEN.

Hyperammonemia,brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication

AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.