阶段性综合考试是以国家执业医师资格考试为导向,当学生完成中医基础课程和经典课程的学习以后,在进入临床实习前和毕业前进行的考核,主要包括中医基础综合考试、中医经典等级考试、中医临床综合考试和中医毕业综合考试.阶段性综合考试有利于培养学生中西医临床思维和激发学生学习动机,同时也与高校应用型和创新型人才培养模式的要求相契合.对河北北方学院中医学类专业阶段性综合考试进行全面分析和评价可为该校阶段性考试改革提供参考.

《伤寒论》作为中医四大经典之一,在中医药人才培养中的地位举足轻重.为提高学生对本课程的学习效果,切实实现掌握基本理论,建立中医临床辨证思维和初步临床诊疗能力的课程学习目标,课程组开展了立体化递进式"伤寒论"教学模式改革,围绕以学生为中心的现代教育理念,结合对学生进行的综合、全面的学情分析,有的放矢地将多样化教学手段、多元化教学方法、多要素考核评价体系、优质化教学设计融入整个课堂教学之中,取得了良好的教学效果和学习效果.

Heweijiangni decoction (HWJND) is an effective traditional Chinese medicine prescription in clinical treatment of nonerosive reflux disease (NERD). Esophageal hypersensitivity and acid contribute to the disease. However, the exact underlying mechanism of action remains unclear. In this study, we observed the effect of HWJND on esophageal morphology in a rat model of ovalbumin (OVA)-induced visceral hypersensitivity followed by acid exposure. Esophageal morphology was assessed by measuring the extent of dilated intercellular spaces (DIS), desmosome disruption, and mitochondrial fragmentation. HWJND in low, moderate, and high doses relieved DIS and desmosome disruption in esophageal epithelium compared with model group (P<0.05 for all doses). In addition, HWJND in high dose protected mitochondria from fragmentation (P<0.05). Other findings suggest that DIS and mitochondrial fragmentation are independent events, and that omeprazole protects mitochondria. Overall, HWJND significantly resists esophageal morphology changes in OVA-induced and acid exposure rat model.

目的:观察苓桂术甘汤与茵陈蒿汤合方(茵陈苓桂术甘汤)对非酒精性脂肪性肝炎大鼠细胞自噬的影响,初步探讨合方对非酒精性脂肪性肝炎大鼠的作用机制.方法:将SPF级SD大鼠随机分为正常对照组、模型组、茵陈苓桂术甘汤组、苓桂术甘汤组、茵陈蒿汤组,采用高脂饲料法建立NASH模型;高脂饲料饲养8周并同时给药,Western Blot法测定LC3Ⅱ、LC3Ⅰ表达量,Western Blot与RT-PCR法测定肝脏p62、ATG5蛋白与基因表达水平.结果:给药后,模型组大鼠肝脏ATG5表达量、LC3Ⅱ/LC3Ⅰ比值下降,p62表达量上升(P＜0.05);与模型组比较,各给药组大鼠肝脏ATG5表达量、LC3Ⅱ/LC3Ⅰ比值有不同程度上升,p62表达量下降(P ＜0.05,P＜0.01).结论:茵陈苓桂术甘汤可能通过激活细胞自噬,从而达到改善氧化应激,防治NASH的目的.

腹泻型肠易激综合征与五脏密切相关,基于内经"魄门亦为五藏使"理论,导师李军祥教授认为魄门的启闭与五脏的生理病理密不可分.因此本文运用辨证论治的方法,分别通过从心论治、从肝论治、从脾论治、从肺论治、从肾论治五个角度出发,充分发挥中医药治疗腹泻型肠易激综合征的优势,拓宽本病的临床治疗思路,提高临床疗效.

目的:探究清肠温中方对葡聚糖硫酸钠(dextran sulphate sodium,DSS)诱导慢性溃疡性结肠炎模型小鼠氧化应激作用的影响方法:90只雄性BALB/c小鼠随机分为6组,除空白组外,其余均自由饮用3％DSS方法复制慢性UC模型.用蒸馏水、清肠温中方高、中、低剂量和美沙拉秦缓释颗粒灌胃干预14d,记录体质量,ELISA法检测血清和结肠SOD、GSH-px、MDA和结肠MPO,HE染色观察结肠病理,免疫组化染色检测结肠黏膜occludin蛋白表达.结果:模型组小鼠体质量、血清和结肠中SOD、GSH-px含量、结肠黏膜occludin表达水平均明显低于空白组(P＜0.05或P＜0.01),而MDA和结肠MPO含量、病理评分均高于空白组(P＜0.01).清肠温中方中剂量组和美沙拉秦组小鼠体质量、血清和结肠SOD、GSH-px含量、结肠黏膜occludin表达水平均高于模型组(P＜0.05),而MDA和结肠MPO含量、病理评分均低于模型组(P＜0.05).结论:对于DSS诱导的慢性UC模型小鼠,清肠温中方可以促进机体抗氧化、抑制氧化作用,减轻氧化应激反应从而起到治疗作用.

Objective:To observe the effects of HWJNF on receptors of 5-hydroxytryptamine in rats with non-erosive gastroesophageal reflux disease.Methods:The SD rats were randomly divided into control group,model group,omeprazole group and the high,medium and low HWJNF groups.Except for the control group,the rats of all the other groups received basalovalbumin-sensitization combined with intra-esophageal mucosal acid exposure to establish NERD models.Then,the treatment was given for 2 weeks.The comparative observation was carried out on the expression of 5-HT3R and 5-HT4R with the methods of Western Blot and RT-PCR.Results:The omeprazole group and the high,medium and low HWJNF groups showed lower expressive levels of 5-HT3R in the esophageal than the model group (P＜0.05).However,the levels of 5-HT4R didn't show statistical differences among the omeprazole group and the high,medium and low HWJNF groups and model groups (P＞0.05);The middle and low HW.JNF groups showed lower expressive levels of 5-HT3RmRNA in the esophageal than the model group (P＜0.01 or P＜0.05).However,there was no difference among the omeprazole group and the high,medium and low HWJNF groups and model groups in 5-HT4RmRNA (P＞0.05).Conclusion:HWJNF may regulate esophagus-visceral sensitivity to treat NERD according reducing 5-HT3R expression in the esophageal.

目的 研究清肠温中方对2,4,6-三硝基苯磺酸(2,4,6-trinitro-Benzenesulfonic acid,TNBS)诱导的溃疡性结肠炎(ulcerative colitis,UC)大鼠氧化应激的影响.方法 70只雄性SD大鼠随机分为7组,每组10只,除空白组外,其余大鼠均用5％TNBS/无水乙醇保留灌肠3天复制UC模型,造模后分别用蒸馏水、清肠温中方高、中、低剂量、美沙拉秦缓释颗粒和乌梅丸颗粒剂灌胃干预10天,测量称取大鼠结肠长度、湿重,酶联免疫吸附法检测血清和结肠组织中SOD、GSH-px、MDA含量.结果 与空白组比较:模型组大鼠结肠湿重明显增加(P<0.01),长度明显缩短(P<0.01);血清及结肠组织SOD、GSH-px明显降低(P<0.01),MDA明显升高(P<0.01).与模型组比较:清肠温中方中剂量、美沙拉秦和乌梅丸组结肠湿重减轻(P<0.05);美沙拉秦结肠长度明显增加(P<0.01),乌梅丸组长度增加(P<0.05);血清及结肠组织指标综合比较,清肠温中方中剂量和美沙拉秦组SOD、GSH-px活性增加(P<0.05),MDA含量减少(P<0.05).结论 清肠温中方可以使TNBS诱导的UC大鼠抗氧化作用增强、氧化作用降低,改善氧化/抗氧化失衡,起到治疗UC大鼠的效果.

Objective To investigate the effect of Tongxie Anchang decoction on the expression of TRPV1 and the content of serum SP and CGRP in rats with diarrhea predominant irritable bowel syndrome. Methods The model of IBS-D was made by intracolonic instillation of acetic acid, balloon rectal dilatation and tail clamping stimulation. After the modeling, 60 SD rats were randomly divided into blank group, model group, intervention group (low-dosage, middle-dosage, high-dosage) and control group. Rats were observed before and after treatment of Abdominal withdrawal reflex (AWR) score and Bristol score; Western Blot was used to detect the expression of TRPV1 in colon, and the expressions of TRPV1mRNA in colon were detected by Real-Time and PCR; The expression of serum substance P(SP) and calcitonin gene related peptide (CGRP) were tested by Elisa. Results Compared with control group, the rats in the model group of visceral sensitivity threshold decreased (P<0.05, P<0.01), fecal Bristol score was significantly increased (P<0.01); After treatment, The visceral sensitivity threshold of rats in low, medium and high dose groups and Dicetel group was increased (P<0.05, P<0.01), fecal Bristol grading score was decrease (P<0.01), colon TRPV1 protein expression decreased (P<0.05, P<0.01), TRPV1mRNA expression decreased (P<0.01),serum levels of SP and CGRP were decreased(P<0.05,P<0.01).Conclusion Tongxie Anchang decoction can reduce visceral hypersensitivity of IBS-D rats, the mechanism may be achieved by downregulating colon TRPV1 protein expression, decreasing colon TRPV1 mRNA expression, decreasing the Serum SP and CGRP levels, and upregulating visceral sensitivity.

目的 观察温中健脾、清热燥湿法对TNBS/无水乙醇诱导的寒热错杂证溃疡性结肠炎(UC)大鼠及Occludin蛋白的作用影响并探讨其作用机制.方法 70只雄性SD大鼠随机分为7组,除空白组外,其余均用5％ TNBS/无水乙醇保留灌肠3d复制寒热错杂证UC大鼠模型,造模后分别用蒸馏水,清肠温中浸膏高、中、低剂量,美沙拉秦缓释颗粒和乌梅丸颗粒剂灌胃干预10d,记录大鼠疾病活动指数、结肠黏膜损伤指数(CM-DI),观察结肠组织病理改变,免疫组化染色观察Occludin蛋白表达.结果 与空白组比较:模型组大鼠体质量明显减轻(P＜ 0.01);便潜血、便质、CMDI、结肠组织病理评分明显升高(P＜0.01);结肠Occludin蛋白表达明显减少(P＜0.01).与模型组比较:中药中剂量、乌梅丸和美沙拉秦组体质量均增加((P＜ 0.05或P＜0.01);中药中剂量和美沙拉秦组便潜血和便质评分下降(P＜0.05),病理组织评分明显降低(P＜0.01),Occludin蛋白表达明显增加(P＜0.01);美沙拉秦组CMDI评分降低(P＜0.05),中药组评分下降但差异尚无统计学意义(P＞0.05).结论 温中健脾、清热燥湿法可以减轻TNBS/无水乙醇诱导的寒热错杂证UC大鼠疾病程度,改善体质量、便潜血和便质,减轻结肠黏膜损伤,修复结肠黏膜组织病变并增加Occludin蛋白表达,提高肠上皮细胞间紧密连接完整性,从而起到治疗UC的效果.

With the rapid pace of life in modern society and the changing diet structure,irritable bowel syndrome in the clinical incidence was increasing year by year.Irritable bowel syndrome (IBS) is a common digestive system disease,because of its lack of biochemical indicators of abnormal changes,it is called functional gastrointestinal diseases.And diarrhea-predominant IBS is easy to relapse,difficult to cure,and it has a long course,so it is called chronic refractory disease.The etiology and pathogenesis of this disease is more complex,is not yet clear.In recent years,traditional Chinese medicine in the treatment of IBS,especially diarrhea-predominant IBS achieved good clinical results,the text will overview the pathogenesis of IBS-D and the research progress of the intervention with Chinese medicine.

Objective:To study the effect of Qingchang Wenzhong Decoction on balance of Th1/Th2 in chronic ulcerative colitis (UC) model mice induced by dextran sulphate sodium.Methods:90 male BALB/c mice were divided into 6 groups randomly.Except the blank group,they drank 3％ DSS solution freely for 7days,and distilled water were supplied for another 7 days.One period contained 14days and 3 periods were used for copying the chronic UC model.Afterwards,they were gavaged with corresponding medications for 14days.The disease activity index (DAI),TNF-α,IL-1β,IL-4,IL-5 and IL-6 of serum were observed by enzyme linked immunoassay and NF-κB p50 proteins were found by immunohistochemistry.Results:Compared with the blank group,score of DAI,IL-6,IL-1β and TNF-α in serum were increased apparently (P＜ 0.01),while IL-4 and IL-5 were diminished(P＜0.01),and NF-κB in colonic mucosa was increased significantly in model group(P＜0.01).Compared with the model mice,score of DAI,IL-6,IL-1β and TNF-α in serum were decreased (P＜0.05),while IL-4 and IL-5 were increased (P＜ 0.05),and the expression of NF-κB was diminished in Qingchang Wenzhong Decoction groups (P＜0.05),especially in the mild dose group and mesalazine group.Conclusion:Qingchang Wenzhong Decoction can decrease Th1,increase Th2,and reduce NF-κB in colonic mucosa to repair the balance between them,so as to treat UC.

BACKGROUND:Ulcerative colitis (UC) is a kind of complex immune disease, the pathogenesis of which remains elusive. Destruction of the intestinal barrier, extreme inflammation, oxidative stress, and apoptosis might play key roles in the development of UC. In previous studies, we observed that Qingchang Wenzhong granule (QCWZG) had the exact effect on the remission of UC in the clinic; however, the underlying mechanism has not been identified. This study aimed to reveal the effects of QCWZG on the intestinal physical barrier and the interactive network of inflammation, oxidative stress, and apoptosis in rats with dextran sulfate sodium (DSS)-induced colitis.METHODS:Sixty rats were randomly divided into six groups: blank group, model group, high/mild/low-dose QCWZG groups, and mesalazine group. The rats in the experimental group drank 4% DSS for 7 days and 1% DSS for the subsequent 7 days. Different medications or distilled water was supplied by intragastric administration for 7 days. The levels of colitis and indices related to inflammation, oxidative stress, and apoptosis were assessed.RESULTS:Compared with the model group, the QCWZG group (P < 0.05) demonstrated attenuated disease activity index, colonic mucosa disease index, histological lesions, and colonic weights; lower levels of inflammatory substances, such as interleukin (IL)-1α, IL-6, tumor necrosis factor-α, and myeloperoxidase; lower levels of malondialdehyde; and increased levels of superoxide dismutase and glutathione peroxidase. The QCWZG group also demonstrated elevated expression of Bcl-2 and occluding but downregulated db expression of Bax and caspase 3 in the colon.CONCLUSION:QCWZG could relieve rats with DSS-induced colitis from UC symptoms by improving the intestinal physical barrier, which resists the interactive network of inflammation, oxidative stress, apoptosis, and their overactivated interactions.

Objective: To study the effects of intestine-clearing middle energizer-warming prescription on inflammatory factors of TNBS-induced ulcerative colitis(UC)rat model.Methods: Seventy male SD rats were ran-domized into seven groups,besides the blank group,other rats accepted retention enema of 5％TNBS/absolute ethyl alcohol to duplicate UC models,after modeling,the rats were intervened with distilled water,high,moderate and low doses of intestine-clearing middle energizer-warming prescription,mesalazine sustained release granules and the granules of W uMei pills for ten days respectively,disease activity index(DAI)and general state of the rats were recorded,the contents of IL-13,IFN-γ,IL-6 and TNF-α in the serum were detected by enzyme linked immunosor-bent assay(ELISA),and the expressions of NF-κB p50 protein in the intestinal mucosa were observed by immuno-histochemical staining.Results: After drug intervention,compared with the blank group,DAI of the rats in the model group increased obviously(P＜0.01),the contents of IFN-γ,IL-6 and TNF-α in the serum evaluated notably(P＜0.01),the contents of IL-13 lowered remarkably(P＜0.01); the expressions of NF-κB p50 protein in the intestinal mucosa up regulated(P＜0.01).Compared with different indexes of the model group,these in moderate dose group of intes-tine-clearing middle energizer-warming prescription and mesalazine group improved(P＜0.05).Conclusion: Intes-tine-clearing middle energizer-warming prescription could treat UC rats by reducing the inflammatory factors of UC rats and increasing the expressions of inflammatory factors.

[目的]探讨茵陈二陈汤对非酒精性脂肪性肝炎(NASH)模型细胞内IRS-1ser307、PKBser473蛋白表达的影响;[方法]采用游离脂肪酸500 umol/L(棕榈酸:油酸摩尔比例为1∶2)刺激干预HepG2细胞,干预24 h建立细胞模型,采用茵陈二陈汤含药血清干预模型细胞,干预治疗24 h;选用罗格列酮、多烯磷脂酰胆碱含药血清作为治疗观察对照;Western Blot检测茵陈二陈汤对模型细胞内IRS-per307、PKBser473蛋白表达及IRS-1ser307/IRS-1、PKBser473/PKB的影响.与空白组相比,游离脂肪酸刺激24 h后,模型细胞内IRS-1ser307蛋白表达及IRS-1ser307/IRS-1水平明显升高,PKBser473蛋白及PKBser473/PKB水平显著下降;与模型组相比,茵陈二陈汤干预24 h后,模型细胞内IRS-1ser307蛋白表达(P＜0.01)及IRS-1ser307/IRS-1水平(P＜0.01)显著降低,PKBser473蛋白(P＜0.05)及PKBser473/PKB水平(P＜0.05)明显升高,且差异具有统计学意义.[结论]①茵陈二陈汤可通过调节IRS-1ser307、PKBser473蛋白表达,降低肝细胞IRS-1蛋白活化水平,促进PKB磷酸化,从而达到干预治疗作用;②茵陈二陈汤对IRS-1ser307、PKBser473蛋白的影响作用与罗格列酮及多烯磷脂酰胆碱效果相近.

流行病学研究调查显示非酒精性脂肪性肝炎 (NAFLD) 近年来发病率呈上升趋势[1], 目前不少西药在临床中已观察到可以改善NAFLD, 但治疗NAFLD疗效并不理想, 并且长期服用安全性等问题仍处于探索阶段[2-4].而中医对于NAFLD的治疗具有独特的理论和雄厚的临床基础, 在NAFLD的临床治疗中具有丰富的临床经验.随着西医对NAFLD的认识的深入, 中医学对NAFLD病因和治疗也不断有新的认识.目前, 中医界对NAFLD病因病机的认识已渐趋一致, 但具体的治疗则依学者经验不同, 呈现出多样化的特点.中医在改善肝功能、调节脂质代谢上具有比较明显的疗效和优势, 尤其是在"整体观念"和"辨证论治"的指导下, 在改善患者的生存质量上具有较为明显的优势.

Yinchen Linggui Zhugan Decoction (YCLGZGD) is the combination of Linggui Zhugan (LGZGD) and Yinchenhao (YCHD) decoctions, two famous traditional Chinese medicine prescriptions. In previous studies, we found that Yinchen Linggui Zhugan Decoction (YCLGZGD) could regulate lipid metabolism disorder and attenuate inflammation in pathological process of nonalcoholic fatty liver disease (NAFLD). However, the exact underlying mechanism remains unknown. The aim of this study was to explore the effect of Yinchen Linggui Zhugan Decoction on experimental NAFLD and its mechanism in rats with high-fat diet (HFD) which was established by 8-week administration of HFD. YCLGZGD, LGZGD, and YCHD were administered daily for 4 weeks, after which the rats were euthanized. The level of blood lipid, liver enzymes, H&E, and Oil Red O staining were determined to evaluate NAFLD severity. Western blotting and real-time polymerase chain reaction were, respectively, used to determine hepatic protein and gene expression of Keap1, Nrf2, NQO1, and HO-1. Oral YCLGZGD ameliorated HFD-induced NAFLD. Furthermore, YCLGZGD increased the protein and gene expression of Nrf2, NQO1, and HO-1 without changing Keap1. Overall, these results suggest that YCLGZGD ameliorates HFD-induced NAFLD in rats by upregulating the Nrf2/ARE signaling pathway.

This paper was aimed to study the effect of Qing-Chang Wen-Zhong (QCWZ) decoction on interferon gamma induced protein 10 (IP10) in colon tissues of rats with ulcerative colitis (UC).The UC model was induced using 4.5％ DSS added to distilled water for 7 days.At the same time,low-,medium-and high-dose of QCWZ decoction and mesalazine was given by gavage route daily.Then,the rats were killed and the colon tissues were taken.Expression level of interleukin-1 alpha (IL-1α),IL-1β,IL-6,tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) in colon were detected by Elisa assay.The expression and distribution of IP10 protein were detected by immunohistochemistry (IHC).The results showed that compared with the normal group,inflammatory factors (IL-1α,IL-1β,IL-6,TNF-α,INF-γ) and IP10 expression level in DSS-induced UC rats were significantly increased.After 7 days of intervention,inflammatory factors (IL-1α,IL-1β,IL-6,TNF-α,INF-γ) and IP10 decreased significantly (p＜0.01,p＜0.05).It was concluded that QCWZ decoction may down-regulate the expression of IP 10 and inflammatory factors (IL-1α,IL-1β,IL-6,TNF-α,INF-γ),and then inhibit intestinal inflammation and repair intestinal mucosal damage,so as to achieve the purpose of UC treatment.

Objective:To explore the changes of NGF/PLC-γ/TRPV1 signaling pathway in rat models with IBS-D and the intervention effect of Tongxie Anchang Decoction.Methods:The model of IBS-D was made by intracolonic instillation of acetic acid,balloon rectal dilatation and tail clamping stimulation.After modeling,60 SD rats were randomly divided into the model group,the intervention groups (low-dosage,middle-dosage,and high-dosage),Dicetel group and the blank group.Abdominal withdrawal reflex (AWR) scores of rats were observed before and after treatment,as well as Bristol grading score and water content of feces.Western Blot was used to detect the expression of NGF,PLC-γand TRPV1 in colon,and the mRNA expressions of NGF,PLC-γ,and TRPV1 in colon were detected by Real-Time and PCR.Results:The visceral sensitivity threshold of the model group was lower than that of the blank group (P＜0.05 or P＜0.01).Bristol score and water content were significantly increased (P＜ 0.01).After treatment,the visceral sensitivity threshold increased in the intervention groups (low-dosage,middle-dosage,and high-dosage) and Dicetel group (P ＜ 0.05 or P ＜ 0.01).Bristol grading score and water content decrease (P ＜ 0.01).Protein expression of colon N GF,PLC-γ and TRPV1 decreased (P ＜ 0.05 or P＜0.01);mRNA expression of PLC-γand TRPV1 decreased (P＜0.01).Conclusion:Tongxie Anchang Decoction can reduce visceral hypersensitivity of IBS-D rats.The mechanism may be achieved by downregulating the protein expression of colon NGF,PLC-γ and TRPV1,decreasing the mRNA expression of colon PLC-γand TRPV1,and upregulating visceral sensitivity.

ErChen and YinChen decoction (ECYCD) is an effective traditional Chinese medicine and has been widely used in traditional Chinese medicine to treat nonalcoholic steatohepatitis (NASH), with good curative effects. However, the specific mechanisms underlying these effects are unclear. In this study, we determined the efficacy of ECYCD in a high-fat diet-induced NASH rat model, established by 8-week administration of a high-fat diet. ECYCD was administered daily for 4 weeks, after which the rats were euthanized. The results demonstrated that ECYCD ameliorated high-fat diet-induced NASH, as evidenced by decreased liver indexes, reduced hepatic lipid deposition and liver injury, lower serum biochemistry markers (including low-density lipoprotein), and reduced HOMA-IR scores. Moreover, levels of free fatty acids, tumor necrosis factor, and malondialdehyde were decreased, whereas glutathione was increased in the liver. Serum high-density lipoprotein was also increased in the liver, and ECYCD regulated the c-Jun N-terminal kinase 1 (JNK1) signaling pathway by decreasing the levels of JNK1 protein, JNK1 mRNA, activator protein-(AP-) 1 protein, AP-1 mRNA, and phospho-insulin receptor substrate-(IRS-) 1(ser307) and increasing phopsho-PKBser473 levels. These results suggested that ECYCD could ameliorate high-fat diet-induced NASH in rats through JNK1 signaling. ECYCD may be a safe therapeutic option for the treatment of NASH.