Optimazation Dosage Study of the Combination of Chlorogenic and Geniposide on Non-alcoholic Fatty Liver Disease

目的：本研究通过运用数学模型均匀设计法，观察中药有效成分绿原酸、栀子苷配伍使用对高脂饮食诱导非酒精性脂肪性肝病（NAFLD）大鼠模型所产生的药理效应。并从多角度指标分析绿原酸、栀子苷对NAFLD脂质代谢紊乱、肝脏炎症损伤病理状态的影响，筛选出绿原酸-栀子苷组合抗NAFLD的最优剂量配比，探索中药复方治疗NAFLD的药效基础。 方法：1、均匀设计筛选实验：55只雄性Wistar大鼠，随机分为正常组、造模组。正常组普通饲料喂养，造模组采用改良高脂饲料饮食8周诱导NAFLD大鼠模型。造模组自第5周开始随机分为模型组和6组药物组。药物组以绿原酸、栀子苷作为考察因子，选用U6（64）均匀表进行组方设计...Abstract Objective: To observe the effects of the combination of chlorogenic acid and geniposide, which are effective components of Chinese medicine, on experimental rat model of Non-alcoholic fatty liver disease （NAFLD）induced by high fat diet, we applied uniform design method to establish the the mathematical model. What's more, we chose muti-angle indexs to analyse the effects of chlorogenic a...学位：医学硕士院系专业：医学院_中医内科学学号：2452012115323

Clinical Research of Kangshi Kangxian Recipe Treating on Hepatic Fibrosis of Chronic Hepatitis B

目的观察康氏抗纤方治疗慢性乙型肝炎肝纤维化的临床疗效,探讨其对肝组织N-花生四烯酸氨基乙醇(; arachidonoylethanolamine,AEA) 、2-花生四烯酸甘油( 2-arachidonoylglycerol,2-AG); 、大麻素受体1( cannabinoid receptor 1,CBR1) mRNA、大麻素受体2( cannabinoid receptor; 1,CBR2); mRNA含量变化的影响。方法将110例慢性乙型肝炎肝纤维化患者按随机数字表法分为治疗组和对照组,每组55例。治疗组予中药康氏抗纤方联合恩替卡韦分; 散片治疗,对照组用恩替卡韦分散片单药治疗,两组均治疗48周。判定两组临床疗效,检测血清ALT水平,HBV; DNA、HBsAg、HBsAb定量,肝组织病理、肝硬度变化,肝组织AEA、 2-AG含量和CBR1、CBR2; mRNA表达水平。结果与对照组比较,治疗组的临床总有效率、HBsAg阴转率、肝组织纤维化分期疗效有效率均高于对照组(chi~2 =; 4.453,4.152,6.364,均P < 0.05); 。与本组治疗前比较,治疗后两组患者肝纤维化瞬时弹性测定值、AEA、2-AG含量及CBR1、CBR2 mRNA表达均降低(均P <; 0.05),且治疗组降低更明显(均P < 0.05); 。肝组织病理显示:治疗后治疗组肝小叶结构基本完整,肝细胞轻度水样变性,汇管区纤维组织无增生,局部少量淋巴细胞浸润,炎症及纤维化较对照组明显改善。; 结论康氏抗纤方具有提高慢性乙型肝炎肝纤维化患者的临床总有效率、HBsAg阴转率、肝组织纤维化分期疗效有效率,其作用机制可能与调节内源性大麻素系统; 有关。Objective To observe the clinical effect of Kangshi Kangxian Decoction (; KSKXD) in treating on patients of hepatic fibrosis of chronic hepatitis; B ( CHB),and to explore the mechanisms of KSKXD by regulating the; contents of arachidonoylethanolamine ( AEA),2-arachidonoylglycerol (; 2-AG),cannabinoid receptor 1 ( CBR1 mRNA) and cannabinoid receptor 2 (; CBR2 mRNA) in the liver tissue. Methods Totally 110 patients with; hepatic fibrosis of CHB were assigned to the treatment group and the; control group according to random digit table,55 cases in each group.; The treatment group was treated with Chinese herb KSKXD combined with; Entecavir,and the control group was treated with Entecavir. Both of the; two groups were treated for 48 weeks. The clinical efficacy of the two; groups was determined. The serum ALT levels,HBV DNA, HBsAg and HBsAb; quantification,liver pathological changes,liver stiffness; changes,contents of AEA and 2-AG,mRNA expression of CBR1 and CBR2 in the; liver tissue were detected. Results The total effective rate,HBsAg; negative conversion rate,hepatic fibrosis staging and curative effect; rate of the treatment group were higher than those of the control group; (chi~2 = 4.453,4.152,6.364,allP <0.05). After treatment,the; instantaneous elasticity of liver fibrosis,the contents of AEA and; 2-AG,the mRNA expressions of CBR1 and CBR2 in the liver tissue in the; two groups were decreased compared to those of the same group before; treatment (P < 0.05),and the treatment group had better effect than that; of the control group (P < 0.05). The pathological changes in the; treatment group after treatment indicated the liver lobules; integrity,mild hydropic degeneration of liver cells,periportal fibrous; tissue hyperplasia,local small lymphocytic infiltration,which fibrosis; and inflammation were better than those of the control group.; Conclusions KSKXD was effective in the treatment of hepatic fibrosis of; CHB, which improved total effective rate,HBsAg seroconversion rate and; liver fibrosis stage efficiency. And its mechanism maybe related to the; regulation of the endocannabinoid system.国家自然科学基金资助项目; 福建省科技计划引导性项目; 厦门市科技惠民项目; 福建中医药大学临床专项校管课题基

Effects of electropuncture of acupoints on the foot Yangming stomach meridian on metabolic profiling of gastric mucosa in gastric ulcer rats

目的:采用核磁共振氢谱技术(1H; NMR)研究电针胃经穴对应激性胃溃疡大鼠胃黏膜组织代谢物谱的表达。方法:40只SD大鼠随机分为正常组、模型组、胃经组和胆经组。利用束缚-冷应激法; 制备应激性胃溃疡模型大鼠,光镜下观察大鼠胃黏膜组织病理形态学的变化,采用1H NMR技术获取胃黏膜组织1H; NMR谱,并利用模式识别方法分析各组间的代谢物谱的差异。结果:与正常组比较,模型组大鼠胃黏膜损伤和胃黏膜组织代谢轮廓差异明显,胃黏膜组织乙酸、肌; 醇、磷酸胆碱、谷氨酸、甘氨酸、乙醇胺、赖氨酸、3-羟基丁酸、缬氨酸、异亮氨酸、牛磺酸、亮氨酸和甘露醇含量上升(P<0.05),乳酸、甲硫氨酸和天; 冬氨酸含量下降(P<0.05);与模型组比较,胃经组和胆经组大鼠胃黏膜得到明显修复,胃经组大鼠胃黏膜组织代谢轮廓更接近正常大鼠,胃黏膜组织甲硫氨; 酸、天冬氨酸含量上升(P<0.05),乙酸、肌醇、磷酸胆碱、谷氨酸、甘氨酸、赖氨酸、异亮氨酸、牛磺酸、乳酸、亮氨酸和甘露醇含量下降(P<0.05; );胆经组大鼠胃黏膜组织3-羟基丁酸、甲硫氨酸含量上升(P<0.05),肌醇、磷酸胆碱、谷氨酸、乙醇胺、异亮氨酸、乳酸、亮氨酸和甘露醇含量下降(; P<0.05)。结论:电针胃经穴可调节胃溃疡大鼠胃黏膜组织特异代谢物的表达,促进胃黏膜损伤的修复。Objective: To research the effects of electropuncture of acupoints on; the foot Yangming stomach meridian on metabolic profiling of gastric; mucosa in rats of gastric ulcer induced by stressusing the 1H nuclear; magnetic resonance (1H NMR). Methods: Forty SD rats were randomly; divided into the control group, the model group, the stomach meridian; group and the gallbladder meridian group. The rat model of gastric ulcer; was induced by the restrained plus cold stress. The pathological changes; in the rat gastric mucosa tissue were observed by light microscope. The; 1H NMR spectroscopy was determined with the 1H NMR technique. And,; meanwhile the differences in the metabolic profiling were identified; with the pattern recognition method. Results: Compared to normal group,; the gastric mucosa damage and gastric mucosa metabolic profiling are; obvious, the concentration of acetic acid, choline, inositol phosphate,; glutamic acid, glycine, ethanolamine, lysine, 3-hydroxy butyric acid,; valine, isoleucine, taurine, leucine and mannitol increase and the; concentration of lactic acid, methionine and aspartic acid decrease in; model group rats (P<0.05). Compared to model group, the gastric mucosa; damage have been recovered in stomach meridian group and gallbladder; meridian group, the metabolic profiling of gastric mocusa tissue in; stomach meridian group are similar to the normal group. The; concentration of methionine, aspartic acid increase and acetic acid,; choline, inositol phosphate, glutamic acid, glycine, lysine, lactic; acid, leucine, isoleucine, taurine, and mannitol decrease in stomach; meridan group (P<0.05). The concentration of 3-hydroxy butyric acid,; methionine increase and choline, inositol phosphate, lactic acid,; leucine, isoleucine, glutamic acid, ethanol amine and mannitol decrease; in gallbladder meridian group (P<0.05). Conclusion: The electropuncture; of acupoints on the foot Yangming stomach meridian could regulate the; metabolic profiling of gastric mucosa, resulting in improving the; gastric mucosa repair of gastric ulcer rats.国家自然科学基金项目; 国家重点基础研究发展计划(973计划)项目; 广东省自然科学基金项目; 深圳市科技计划项

Clinical and Histopathological Analysis on Features of 15 Cases with Urticarial Vasculitis

目的探讨荨麻疹性血管炎(UV)的临床和组织病理特征。方法分析15例UV患者的皮疹特点、实验室检查结果及组织病理学改变情况。结果男7例,女8例,男∶女=1∶1.14。平均年龄37.4岁,平均病程14.2月。皮疹以水肿性红斑(73.3%)和风团(60.0%)多见,全身不对称分布,伴瘙痒或疼痛。实验室检查异常以ESR加快(55.6%)和CRP升高(40.0%)多见,高免疫球蛋白血症和低补体血症者仅26.7%。组织病理显示所有患者均有程度不等的真皮浅层小静脉炎。结论UV是一种真皮浅层小静脉炎,但可累及皮下组织小动脉。Objective To analyze the clinical and histopathological features of urticarial vasculitis(UV).Methods Fifteen patients with urticarial vasculitis were examined of skin lesions,laboratory abnormalities and histopathological features.Results Among fifteen patients,seven were men and eight were women with a ratio of 1 to 1.14,the average age was 37.4 years,average duration was 14.2 months.The most common skin lesions were edematous erythema(73.3%)and wheals(60.0%),which were asymmetrically distributed on the whole body.The most common laboratory abnormalities were elevated ESR(55.6%)and CRP(40.0%).Hyperimmunoglobulinemia and hypocomplementemia were detected in only 26.7% of the patients.Histopathological examination revealed dermal veinulitis in all patients.Conclusion UV is a dermal veinulitis,in which subcutaneous arteries may be affected

Establishment and Application of Respiratory Syncytial Virus Animal Model

人呼吸道合胞病毒（HumanRespiratorySyncytiaVirus，hRSV）是全球范围内引起下呼吸道感染主要病原体之一。其感染人群年龄分布广，新生儿与老年人是主要高危人群。据报道，几乎所有小于2周岁婴幼儿都有RSV感染经历，婴幼儿发病住院率高达2.5-4%。RSV引起大于65周岁的老年人感染率为3-4%，病死率约为2%。早产儿、先天性心脏病、先天性支气管及肺发育不良、免疫缺陷的婴幼儿RSV病死率率高达5%，造成严重的医疗负担。 RSV无安全、有效疫苗上市，唯一获准上市的预防性RSV药物为中和性单抗palivizumab(Synagis&reg;)，特异性识别RSV融合蛋白。Syn...Respiratory syncytial virus (RSV) is one of major pathogens for lower respiratory tract infection. It has a large infected age distribution, including almost all the population from the newborn to the elderly. It is reported that almost all children under two-year old have been infected by RSV. Hospitalization of infants due to RSV infections is 2.5-4% each year. Data from a variety of studies sug...学位：医学硕士院系专业：公共卫生学院_流行病与卫生统计学学号：3272013115055

Combination CXCL9 Antibodies with FTY720 Prolongs the Survival of Cardiac Retransplantation Allografts in a Rat Model

实验目的 趋化因子的基因表达上调和随之发生的T淋巴细胞在移植物中的募集发生在 同种异体器官移植急性排斥反应和器官移植血管病变的早期。在本研究中我们尝 试使用联合趋化因子CXCL9抗体和FTY720的免疫抑制方案，抑制记忆性T细胞 的增殖，调节T细胞细胞因子的分泌，加速淋巴归巢，减少再次心脏移植物中的 淋巴细胞浸润，从而延长大鼠再次心脏移植物的存活时间。 实验方法 BN大鼠作为实验受体，LEW大鼠作为实验供体。颈部套管法异位心脏移植术 后4周进行再次腹部异位心脏移植术。根据不同的免疫抑制方案将大鼠分为四组。 对照组：再次心脏移植术后使用生理盐水处理。单用趋化因子CXCL9抗体组...Objective: Up-regulation of Chemokine genes and consequent recruitment of T lymphocytes in the graft are the early events in acute allograft rejection in organ transplantation and organ transplant vasculopathy. In this study, we try to use the combined chemokines CXCL9 antibodies and FTY720 immunosuppression, inhibit the proliferation of memory T c...学位：医学硕士院系专业：医学院_外科学学号：2452012115318

Studies on Pathogens and Pathology of Several Common Diseases in Cultured Mud Crab,Scylla paramamosain

本文对养殖拟穴青蟹3种常见疾病的病原和病理变化进行了研究，依照发病症状和养殖户的习惯，将3种常见疾病分别称为“红芒病”、“白芒病”和“斑点病”。采用细菌16SrRNA基因检测技术，并结合分离菌株的菌落、菌体的形态学观察，对患病青蟹体内分离到的4株异常菌进行了分类鉴定，并通过人工感染实验确定分离菌株的致病性，进一步分析青蟹3种常见疾病的病因。同时，从病原的分离纯化、人工感染和组织病理观察等方面初步性地研究了一例青蟹亲体疾病，以期为青蟹的疾病诊断与防治提供理论指导。本实验的主要结果和结论如下： 1青蟹“红芒病”和“白芒病”的病因探讨及组织病理学观察 传统的细菌分离培养实验结果表明，患“白芒病”...A survey was conducted in three cases of common diseases and the unkown-death disease of mud crabs,Scylla paramamosain,which were cultured in farms located along the coast of Fujian Province.The pathogens and pathology of diseased crab were studied using the classical methods of isolating the microorganisms and virus from their hosts.Furthermore,the 16S rRNA gene technique,artificial infection tes...学位：理学硕士院系专业：海洋与环境学院海洋学系_海洋生物学学号：2242006115230

Intervention effect of salidroside on liver fat synthesis and oxidation of non-alcoholic fatty liver in rats induced by high-fat diet

目的:基于肝脏脂肪合成和氧化环节,探讨红景天苷防治非酒精性脂肪肝的作用机制。方法:采用单纯高脂饮食14周诱导的大鼠非酒精性脂肪肝模型。在造模第9; 周起,随机分为模型组、红景天苷组和罗格列酮对照组,灌胃给药6周。观察肝组织病理变化;肝组织甘油三酯(TG)、游离脂肪酸(FFA)含量的变化;肝组; 织乙酰辅酶A羧化酶(ACCase)、丙二酰辅酶A (Mallonyl CoA)、脂肪酸合成酶(FAS)、肉毒碱棕榈酰转移酶-1; (CPT-1)含量的变化;肝组织ACCaseCPT-1; mRNA水平的变化。结果:模型组肝组织出现显著的肝细胞脂肪变性及空泡样变,肝组织TG、FFA、ACCase、FAS、 Malonyl; CoA含量和ACCase; mRNA水平较正常组均显著升高(P<0.01),CPT-1含量和mRNA水平较正常组显著降低(P<0.01)。红景天苷组的上述病理改变显著减轻,; 肝组织TG、FFA、ACCase、 Malonyl CoA、FAS含量和ACCase mRNA水平显著低于模型组(P<0.01) ,; CPT-1含量和; mRNA水平显著高于模型组(P<0.01)。结论:红景天苷能抑制肝脏脂肪合成,促进脂肪酸氧化,这可能是其防治非酒精性脂肪肝的重要机制。Objective: To explore the mechanism of salidroside on non-alcoholic; fatty liver disease based on liver fat synthesis and oxidation. Methods:; Non-alcoholic fatty liver disease model was induced by high-fat diet for; 14 weeks. From the ninth week, the rats were randomly divided into model; group, salidroside group and rosiglitazone group, and were given a; gavage for six weeks. The observing items including: pathological; changes of liver tissue (HE staining); changes of contents of; triglycerides (TG) and free fatty acid (FFA) in liver tissue; changes of; contents of acetyl-Coacarboxylase (ACCase), malonyl CoA, fatty acid; synthase(FAS) and carnitine palmitoyl transterase-l(CPT-l); changes of; mRNA levels of ACCase and CPT-1 in liver tissue. Results: Hepatocellular; steatosis and vacuolar degeneration were observed in the liver tissue of; the model group. The contents of TG, FFA, ACCase, Malonyl CoA, FAS and; mRNA level of ACCase in model group were significantly higher than those; of the normal group (P<0.01). The content and mRNA level of CPT-1 were; significantly lower than those of normal group (P<0.01). Hepatic; pathological changes in salidroside group were significantly reduced.; The contents of TG, FFA, ACCase, Malonyl CoA, FAS and mRNA level of; ACCase were significantly lower than those of model group (P<0.01). The; content and mRNA level of CPT-1 were significantly higher than those of; model group (P<0.01). Conclusion: Salidroside can inhibit liver fat; synthesis and promote the oxidation of fatty acid, which may be an; important mechanism of salidroside for prevention and treatment of; non-alcoholic fatty liver disease.国家自然科学基金项目; 浙江省自然科学基金项

The Role of PI3K/Akt/HIF-1α Signaling Pathway in Bleomycin-Induced Pulmonary Fibrosis in Mice

目的探讨PI3K/Akt/HIF-1α信号通路在博来霉素(BLM)诱导的小鼠肺纤维化中的作用机制。方法 56只C57BL/6小鼠随机分为对照组和实验组,实验组通过气管内滴注BLM(2.5 mg/kg)建立肺纤维化模型,对照组在相同条件下气管内滴注等量0.9%氯化钠溶液。在造模第21 d取小鼠肺组织标本行HE和Masson染色分析肺组织形态学变化;运用Ashcroft评分以及检测羟脯氨酸含量评估肺纤维化程度;Western blot方法检测PI3K/Akt/HIF-1α信号通路的变化以及肺泡表面活性物质(Pro-SPC)蛋白含量;实时定量PCR(RT-PCR)法检测胶原蛋白3(Collagen3)mRNA表达水平;免疫组织化学法检测肺组织内Collagen3蛋白和细胞凋亡数的变化。结果实验组与对照组相比,肺泡炎和肺纤维化程度明显加重,肺组织内充填大量炎细胞及纤维病灶。试验组Ashcroft评分和羟脯氨酸含量均较对照组显著升高(P<0.05)。同时,PI3K/Akt/HIF-1α信号通路在实验组肺内明显活化,并伴有Pro-SPC蛋白生成减少,Collagen3蛋白含量及mRNA水平增加,以及肺内细胞凋亡数明显增加。结论 PI3K/Akt/HIF-1α信号通路的异常活化促进了肺纤维化形成。Objective To investigate the role of PI3K/Akt/HIF-1α signaling pathway in bleomycininduced pulmonary fibrosis in mice.Methods Fifty-six C57 BL/6 mice were randomly divided into a control group and a bleomycin(BLM)group.The pulmonary fibrosis model was induced by single intratracheal instillation of BLM(2.5 mg/kg)in the BLM group.Similarly,0.9% saline was instilled directly into the trachea in the control group.Then all mice were sacrificed on 21 stday.The lungs were collected for morphometric analysis with HE and Masson staining.The degree of pulmonary fibrosis was evaluated with Ashcroft score and content of hydroxyproline.The activity of PI3 K/Akt/HIF-1α signaling pathway and prosurfactant protein C(Pro-SPC)were measured by Western blot.The level of collagen3 mRNA was assessed with quantitative real time PCR analysis.Collagen3 protein and numbers of apoptosis cells were observed with immuno-histochemistry.Results It was exhibited that the thickening alveolar septa,accumulation of inflammatory cells,and fibrous obliteration in the BLM group but not in the control group.There was a significant difference in Ashcroft score and hydryoproline content in the BLM group.Meanwhile,the activity of PI3 K/Akt/HIF-1α signaling pathway was up-regulated and the protein of Pro-SPC was decreased in the BLM group.It was revealed that the numbers of apoptosis cells,expressions of Collagen3 protein and mRNA were increased in the BLM group.Conclusion Aberrant activity of PI3 K/Akt/HIF-1α signaling pathway may aggravate the pulmonary fibrogenesis.福建省科技局课题(编号:J00162

Protection of y-39983 preconditioning from retinal ischemia-reperfusion injury in rats

AIM: To investigate the neuroprotective effect of rho-associated coiled coil-forming protein kinase(ROCK)inhibitor y-39983 on retinal ischemia reperfusion(IR)injury in rats. <p>METHODS: Sixty adult SD rats were randomly assigned into normal group(<i>n</i>=15), IR group(<i>n</i>=15), saline group(<i>n</i>=15), y-39983 group(<i>n</i>=15), and the rats in later three groups were induced retinal IR by intra-anterior chamber infusion of saline solution. Rats in the saline and y-39983 groups were intravitreously injected with normal saline and y-39983 respectively, 5 minutes prior to the induction of ischemia. The protein expression of intercellular cell adhesion molecules-1(ICAM-1)was determined by immunohistochemical staining. Retrograde labeling of retinal ganalion cells(RGCs)with fluorogold was performed to assess the number of RGCs. Histologic studies and electroretinogram were carried out to evaluate retinal damage. <p>RESULTS: The preadminisration of y-39983 decreased ICAM-1 expression, elevated the survival rate of RGCs and the recoverage rate of amplitude of b wave and O₂ wave significantly, and attenuated the IR-induced the thinning of inner retina. <p>CONCLUSION: y-39983 can protect the rat retina from IR injury at least partially by inhibiting ICAM-1 abnormal expression, suggesting that y-39983 may have therapeutic potential for the retinal diseases associated with IR