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Abnormal aggregation of amyloid-β protein (Aβ) in brain plays a vital role in the occurrence of Alzheimer's disease (AD). Hence, inhibiting Aβ aggregation is one major tactic for therapy of AD. Previous studies have found that tolcapone can inhibit Aβ42 aggregation and reduce the cytotoxicity induced by Aβ42 aggregates, but clinical studies have found that tolcapone has strong liver toxicity. To reduce the liver toxicity of tolcapone, its side chain structure was modified to obtain its derivative phenethyl (E)-2-cyano-3-(3,4 dihydroxy-5-nitrobenzene)-acrylate (PCDNA). Thioflavin T (ThT) and atomic force microscopy (AFM) assays were used to explore the inhibitory effect of PCDNA on Aβ42 fibrillogenesis. The cytotoxicity assays were used to explore the inhibitory effect of PCDNA against the cytotoxicity induced by Aβ42 aggregates. In addition, the depolymerization effect of PCDNA on mature Aβ42 fibrils was also explored. Finally, molecular docking was used to explore the interaction between PCDNA and Aβ42 pentamer. These results lay the foundation for the study of the structural analogues of tolcapone as Aβ inhibitors.
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OBJECTIVE@#To evaluate the involvement of different CD4 T cell subtypes in the anti-asthmatic effects of acupuncture in asthmatic mice.@*METHODS@#BALB/c mice were challenged by ovalbumin (OVA) for the establishment of experimental asthma model. Mice were divided into 4 groups by a random number table including the normal control, asthma model, acupuncture and sham acupuncture groups (14 per group). Acupoints Dazhui (GV 14), bilateral Fengmen (BL 12) and Feishu (BL 13) were selected for manual acupuncture treatment every other day for 4 weeks and Huantiao (GB 30) was selected for sham acupuncture. Airway hyperresponsiveness was examined by Buxco Pulmonary System. Pulmonary histopathology analysis was performed for inflammatory cell infiltration and mucus hypersecretion by haematoxylin eosin staining and periodic acid-Schiffstaining. Inflammatory mediators assays of serum were investigated by enzyme-linked immunosorbent assay and Bio-Plex. CD4 T cell subpopulations including the expression levels of important factors in T lymphocyte polarization in lung tissue were examined by flow cytometric and Western blot analyses. Related pathways were detected by Western blot assay.@*RESULTS@#Compared with the OVA-induced asthma model group, acupuncture could attenuate airway hyperresponsiveness, inhibit inflammatory cell infiltration and mucus hypersecretion (P<0.05 or P<0.01). Furthermore, acupuncture increased the expressions of T-bet and Foxp3, the cell numbers of CD4 interferon gamma (IFN-γ) and CD4 Foxp3 in lung tissue and the level of Treg type cytokine interleukin (IL)-10 in serum (P<0.05 or P<0.01). Meanwhile, acupuncture reduced the RAR-related orphan receptor gamma t (RORγt) level, the cell numbers of CD4 IL-17A as well as the levels of IL-5, IL-13 and IL-17A in serum (P<0.05 or P<0.01). In addition, both acupuncture and sham acupuncture could inhibit the phosphorylation of p38 and p44/42 (P<0.01).@*CONCLUSION@#Acupuncture could alleviate allergic airway inflammation by strengthening the activities of Th1 and Treg, thus regulating the balance of CD4 T cell subtypes in experimental asthmatic mice.
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The incidence of non-functional pancreatic neuroendocrine neoplasms(NF-pNENs)constantly increases due to the development of imaging techniques and the popularity of routine medical examination.WHO classification system,ENETS and AJCC grading systems,widely used in clinical practice,are independent prognostic factors.According to the G grading system,NF-pNENs are classified into benign,low-grade malignant and high-grade malignant tumors.Operative indications and treatments are absolutely different for each subgroup.Lymph node metastasis closely correlates with the position and size of tumor,lymphovascular invasion and Ki-67 index.Pre-operative determination of the presence of lymph node metastasis provides significant instructions for the choice of surgery since it indicates early tumor relapse and metastasis.The advance of ultrasoundguide biopsy provides more sensitive indictors for preoperative pathological grade and lymph node metastasis.Both domestic and foreign guidelines consider the tumor size as the critical factors for surgery.For those NF-pNENs2 cm,even with local vascular and organs invasion,a routine pancreatic surgery is recommended(distal pancreatectomy or pancreatic duodenectomy according to the tumor position).Lymph node sampling or regional lymphadenectomy should be routinely performed during surgeries.For those with liver metastasis,surgical resection,locoregional ablative therapy or liver transplantation is suggested according to the situation of metastatic sites.
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Zha-xun is widely used in Tibetan medicine and is also an international traditional medicine. This article would summarize the use status and research progress of Zha-xun by various ethnic groups all over the world, and the results show that it has various synonyms but most of them imply its most characteristic feature-outflow from the rock; Zha-xun resources are distributed in various places of the world, and its bearing spots are closely related to the geological structure; there are sharp arguments on the origins of Zha-xun, mainly including the minerals origin, biological fossils origin, biological origin, etc. Zha-xun has multiple functions and is mainly used to treat stomach disease, liver disease and rheumatoid arthritis in China, and premature ejaculation, impotence, vaginitis embolism in foreign countries. "Iron" Zha-xun is used into medicines both at home and abroad. According to ancient materia medica texts, it was mainly classified into five types, including gold Zha-xun, silver Zha-xun, copper Zha-xun, iron Zha-xun and lead Zha-xun mainly based on the predominance of color rather than the minerals contained. It is commonly believed by the domestic and foreign scholars that humic acid is the main medicinal part of Zha-xun, and their studies have found that it has a variety of pharmacological activities such as anti-ulcer, anti-inflammatory, liver protection, analgesia, immune regulation, increasing sexual desire and fertility, antioxidation, antibacterial, antidiabetic, antiepileptic, antipsychotic, etc. This paper provides a scientific basis for the rational utilization of Zha-xun resources.
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OBJECTIVE To investigate the effect and mechanism of AngongNiuhuang Pill(AGNH) on neurological function and intestinal mucosal barrier in intracerebral hemorrhage (ICH). METHODS Male CD-1 mice were randomly divided into sham, ICH, AGNH 0.1 g·kg-1, AGNH 0.2 g·kg-1, and AGNH 0.4 g·kg-1groups. The ICH mice models were prepared by intrastriatal injection with collage-nase using a stereotaxic frame.Garcia test was used to evaluate the neurological function of mice.The brain water content was measured with dry/wet weight method.The permeability of intestinal mucosa was detected by FITC-D method. H&E staining was used to observe the pathological changes of intestine. The content of endotoxin in blood and the expressions of ZO-1,occludin in intestinewere also investigated.RESULTS After AGNH administration,the neurological score of mice was increased,and the brain water content was decreased(P<0.01).AGNH attenuated the ICH-induced increase of perme-ability of intestinal mucosa(P<0.01).Treatment with AGNHnot only alleviated the pathological changes of the intestine but alsoreduced the endotoxin content in blood (P<0.01).The expressions of ZO-1, occludinin AGNH groups were significantly increased compared with that of ICH group (P<0.05). CONCLUSION AGNH improves the neurological dysfunction in ICH mice and the mechanism of action is implicated in protecting the intestinal mucosa.
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OBJECTIVE Xingnaojing injection(XNJ)is an extracts of Angong Niuhuang Pill that is a well-known traditional Chinese medicine used for the treatment of septicemia and stroke.This study aims to investigate the effect of XNJ on intestinal mucosal barrier in septicemia and intracerebral hem-orrhage(ICH)mice models.METHODS The septicemia mice models were induced by intravenous in-jection with lipopolysaccharide(20 mg·kg-1).And the ICH mice models were made by intrastriatal injec-tion of bacterial collagenase. The septicemia animals were treated intravenously with XNJ at dose of 2.5,5,10,or 15 mL·kg-1.The ICH animals were treated intravenously with XNJ at dose of 10 mL·kg-1. Thereafter, the permeability of intestinal mucosa was assayed by FITC-D method. RESULTS Com-pared with the control group(44.72±4.30),the permeability of intestinal mucosa in the mice in septice-mia group (233.68±28.18) was significantly increased (P<0.01). Treatment with XNJ at dose of 5, 10, and 15 mL·kg-1reduced the permeability of intestinal mucosa (150.45 ± 17.52,139.21 ± 17.05,132.55 ± 18.88,respectively, P<0.01)except 2.5mL·kg-1(240.71±21.42,P>0.01);Compared with sham group (57.88±7.31),the permeability of intestinal mucosa in the mice of ICH(282.25±23.78)was significantly in-creased(P<0.01). Treatment with XNJ (10 mL·kg-1)in the mice of ICH group ameliorated the change of permeability in intestinal mucosa (148.83±15.86, P<0.01). CONCLUSION XNJ exhibits the protec-tive effect on the intestinal mucosal barrier in septicemia and ICH, which will prevent the endotoxin to penetrate the intestinal mucosa and then to enter the circulation in infections and stress.
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AIM To investigate the dose-proportion relation of Tibetan medicine Siwei Jianghuang Prescription (SJP) for protective effects on diabetic nephropathy (DN),and the underlying mechanism.METHODS Diabetes mellitus rats induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) were randomly divided into model group,metformin support group,and eight SJP groups with dose-proportion variation (with reference to the uniform design method) for corresponding drug administration once a day,for four weeks.Measurement of fasting blood glucose (FBG) by a blood glucose meter,the concentrations of blood urea nitrogen (BUN),uric acid (UA),serum creatinine (SCr) and total protein (TP) by chemical methods,serum transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) by ELISA kits were conducted,the pathological morphology observation and glomerular basement membrane thickness detection by electron microscope were accomplished as well.Principal components analysis (PCA) and multivariate progressive regression analysis (MSRA) were employed to analyze the relationship between the dose-proportion to pharmacodynamics.RESULTS The resultant indexes revealed variant pharmacological improvement in each treatment group.MSRA results showed that the levels of BUN,renal index,FBG,glomerular basement membrane thickness,VEGF,Scr,and UA had correlative relations with a multiple linear or a multiple non-linear in all groups,which regression equation had a statistical significance (P ＜ 0.05);TGF-β1 level and total protein index with the dose-proportion had no linear or non-linear relation,which the regression equation statistical showed non-significance (P ＞ 0.05).In the global optimization comparison around the range of uniform design,the optimal dosage of the rats model was Curcumae Longae Rhizoma ∶ Berberidis dictyophyllae Cortex ∶ Phyllanthi Fructus ∶ Tribuli Fructus =1 ∶ 2 ∶ 1 ∶ 2.CONCLUSION Siwei Jianghuang Prescription shows better therapeutic effects on DN,which may be related to reducing the levels of BUN,renal index,FBG,glomerular basement membrane thickness,VEGF,Scr and UA.
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This study was aimed to discuss and analyze the medication rules for prescriptions containing Pterocephali Herba in Chinese Medical Encyclopedia - Tibetan Medicine, Tibetan Medicine Prescription Modern Research and Clinical Application, and Interpretation of Common Tibetan Medicines based on the collection of Pterocephali Herba and by using the "Traditional Chinese Medicine Inheritance Support system(V2.0.1)",with the use of association rules, apriori algorithm and other data mining methods. The frequency of single drug, the frequency of drug combination, the association rule and the combination of core drugs were analyzed. Through collection of the prescriptions, a total of 215 prescriptions were included, involving a total of 376 herbs. Through the "frequency statistics", the prescriptions containing Pterocephali Herba were commonly used to treat cold fever, distemper virus and arthritis. The highest frequently (frequency≥15) used drugs were Corydalis Herba, Lagotidis Herba, and Gentianae Macrophyllae Radix, et al. The most frequently used drug combinations were "Pterocephali Herba, Corydalis Herba","Pterocephali Herba, Lagotidis Herba", and "Pterocephali Herba, Gentianae Macrophyllae Radix" et al. The prescriptions containing Pterocephali Herba were used to primarily treat disease for Tourette syndrome caused by the dampness heat toxin, fever, arthritis etc, such as pestilent toxicity, pneumonia and influenza, rheumatoid arthritis etc. The drugs in the prescriptions mostly had the effects of heat-clearing and detoxifying, anti-inflammatory, dispelling wind and dampness, often in compatible use with heat-clearing drugs. The drug use was concentrated and reflected the clear thought of prescription statutes.
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Background Glial cells perform specialized function in many aspects of the development,homeostasis,and function of neurons.Retinal ganglion cells (RGCs)and glia interactions are critically important in glaucomatous neurodegeneration.However,the precise mechanisms of glial activation and ganglion cells damage are still remained unclear. Objective This study was to assess the early responses of glial cells in the retina,optic nerve and optic chiasm in rat models of acute high intraocular pressure (IOP),and to examine the expression of nestin,a neuronal progenitor marker,in the reactive glias. Methods Acute high IOP of 110 mmHg was induced in the right eyes of 6 clean adult female Wistar rats by infusing normal saline solution into the anterior chamber for 60 minutes.Three normal matched Wistar rats were used as controls.The rats were sacrificed by overanaesthesia and sections of retina,optic nerve and optic chiasm were collected on 3 days and 7 days after the injection.Rat retina was examined by Nissl staining to illustrate the gross structure changes.Loss of axons of RGCs in the optic nerve was assessed by immunostaining of β Ⅲ-tubulin.Double labeling of glia] fibrillary acidic protein (GFAP) and nestin was performed in sections of retina,optic nerve and optic chiasm to evaluate the glial responses.The use of the animals complied with Statement of Animal Ethic Committee of Peking University Third Hospital. Results In control rats,GFAP-positive glial cells were observed in the retina,optic nerve and optic chiasm,where only weak positive response for nestin was noticed.Three days after acute IOP elevation,thickness of inner plexus form layer was significantlydecreased in comparison with the control rats.A loss of 46％ RGCs was found in the rats with ocular hypertension.Obvious increase of GFAP expression was displayed in the retina,and processes of GFAP-positive glia cells extended into outer retina accompanied with significant up regulation of nestin.Axons in the optic nerve demonstrated a tendency of degeneration.Nestin expression increased significantly in the GFAP-positive glias in the optic nerve.Cross-sectional area of optic chiasm corresponding to the injured retina decreased relative to its countcrpart.Astrocyte like GFAP and nestin-colabeled glials were observed in this part of optic chiasm.The pathological changes of the retina,optic nerve and optic chiasm in hypertensive eyes aggravated on 7 days. Conclusions Acute ocular hypertension induce early onset of RGCs loss and axon degeneration.Neuronal injury is accompanied with glial reaction.Reactive glial cells express neuronal progenitor markers.The structural changes of the optic nerve and optic chiasm occur simultaneously with the high IOP.
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OBJECTIVE To investigate the point prevalence of nosocomial infection(NI) and discover the problems in the management of NI in a hospital.METHODS A team of surveyors were trained to inquire history of illness,do physical examination for inpatients and collect some necessary data from medical records on a single day.Questionnaires about NI cases were filled out and analyzed.RESULTS From 1500 patients,1493(99.53%) patients were investigated,the point prevalence and case prevalence of NI were 5.69% and 6.03%;the highest prevalence appeared in internal medicine at 8.54%;lower respiratory tract infections accounted for 38.89%;the detection rate of multi-drug resistant(MDR) bacteria was 49.23%;antimicrobial utilization rate was 48.69%.CONCLUSIONS The prevalence survey is a rapid and efficient method,which could offer evidence of target surveillance of NI.