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1.
Objective: One appealing strategy to overcome and prevent resistant problem is the use of combined two or more antibacterial substances. Lawsone methyl ether(LME) is the naphthoquinone found in the leaves of Impatiens balsamina. The objective of this study is to determine the interaction of LME with some antibiotics(ampicillin, tetracycline, norfloxacin, and clotrimazole) and a natural compound, artocarpin against methicillin-resistant Staphylococcus aureus(MRSA), Candida albicans, and Trychophyton rubrum.Methods: A broth microdilution method was used to determine the minimum inhibition concentration(MIC). Synergistic effects were evaluated at their own MIC using the checkerboard method and time-kill assay.Results: LME showed moderate antibacterial activity against MRSA with MIC value of 15.6 μg/mL, and exhibited strong antifungal activities against T. rubrum and C. albicans with MIC values of 7.8 and 3.9 μg/m L,respectively. The interaction of LME with the natural compound artocarpin against MRSA produced a synergy with fractional inhibitory concentration index(FICI) value of 0.31, while the combination of LME and clotrimazole exhibited synergy against C. albicans and T. rubrum with FICI values of 0.38 and 0.24, respectively. The time-kill assays confirmed that the compounds in combination enhanced their antimicrobial activities against the resistant microorganisms with different degrees.Conclusion: LME in combination with clotrimazole exhibited synergy effect against C. albicans and T.rubrum. In combination with artocarpin, it showed synergy effect against MRSA.  相似文献   

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AIM: To investigate the active constituents of Lignum Sappan (Caesalpinia sappan L.) on growth-related signaling and cell mitosis. METHOD: The influence of the ethyl acetate (EtOAc) extract of Lignum Sappan and its constituents on growth-related signaling were evaluated by a luciferase assay in cells stably- transfected with NF-κB, STAT1, or STAT3 responsive luciferase reporter plasmid. The inhibitory effect on the cell cycle was determined by flow cytometric analysis. The anti-tumor activities were assessed in vitro and in vivo. RESULTS: The EtOAc extract of Lignum Sappan had inhibitory activities on growth-related signaling and cell mitosis. Three major active compounds were sappanchalcone, brazilin, and butein. Sappanchalcone blocked cell cycle progression in the G2/M phase, brazilin inhibited TNFα/NF-κB signaling, while butein inhibited IL-6/STAT3 signaling, as well as TNFα/NF-κB signaling. The three compounds all demonstrated cytotoxic activities against human tumor cells in vitro. In a S180 tumor cell-bearing mice model, the anti-tumor efficacy of the EtOAc extract was better than the individual compounds acting alone. CONCLUSION: These results indicate that Lignum Sappan contains multiple active compounds with different antitumor activities, which act synergistically to enhance their anti-tumor effects. The EtOAc extract of Lignum Sappan may be better than individual active constituent as a novel medicine for the treatment of cancer.  相似文献   

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Objective: The objective of the study was to identify Nrf2 activators from differently treated Morinda citrifolia L. fruit juices and their cytotoxicity. Materials and Methods: Noni fruit juices were prepared by different treatments: unripe(T1), ripe(T2), purchased(T3), and Noni juices fermented with Lactobacillus plantarum(T4). These extracts were tested for Nrf2 activation and nuclear factor kappa B(NF-κB) inhibition activities. These active extracts were further studied for their nuclear Nrf2 translocation and induction of HO-1 protein expression. Finally, the active extracts were purified using open column chromatography and RP-high pressure liquid chromatography(HPLC) techniques through bioassay-guided separation. Moreover, all Noni juice samples were tested for cytotoxicity using mammalian cell-based methylthiazoltetrazolium(MTT) assay. Results: Only purchased(T3) and ripe Noni fruit juices fermented with LP at 22℃(T4–22) showed strongest Nrf2 activation and NF-κB inhibitory activity. Further, these two extracts enhanced the nuclear accumulation of Nrf2 after 2 h and also promoted Nrf2 and HO-1 nuclear translocation. Induction of HO-1 gene expression of Hep G2/ARE cells treated with T3 confirmed that it is a potent inducer of the Nrf2 target gene HO-1. Bioassay-guided separation resulted in subfractions with high Nrf2 activity. The strongest Nrf2 active subfraction led to the identification of scopoletin as an Nrf2 activator. Moreover, none of the tested samples showed any cytotoxicity for the MTT assay. Conclusions: The presence of potential Nrf2 activators in the Noni fruit juices that were nontoxic in our MTT assay could mitigate the production of harmful reactive species in the biological systems, and thereby, could helpful in alleviating and prevention of chronic diseases.  相似文献   

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Objective Traditional Chinese medicines(TCMs) as natural therapeutic agents have been widely used and received great attention over the world.However,the information on them to cause herb-drug interactions mediated by cytochrome P450(CYP) enzymes is limited.The present study aims to evaluate the inhibitory effects of 11 commonly used TCMs,including Nelumbinis Folium,Ginseng Radix et Rhizoma,Ziziphi Spinosae Semen,Chrysanthemi Flos,Lonicera Japonica Flos,Lycii Fructus,Cassiae Semen,Poria,Crataegi Fructus,Schisandrae Chinensis Fructus,and Polygonati Rhizoma,on the five human major CYP isoenzymes 2C19,2D6,3A4,2E1,and 2C9.Methods An in vitro cocktail method was used.Results The aqueous extracts of all tested TCMs were found no significant inhibitory effect,with IC_(50) values higher than 100 μg/mL while,the ethanolic extracts of some herbs showed more potent inhibition.These herbs include Nelumbinis Folium with IC_(50) values of 1 2.05 and 61.43 μg/mL on CYP2D6 and CYP2E1,Schisandrae Chinensis Fructus with IC_(50) values of 64.42 and 47.24 μg/mL on CYP2C1 9and CYP3A4,and Chrysanthemi Flos with IC_(50) values of 45.25 μg/mL on CYP2C9,respectively.Conclusion Co-administration of these TCMs and their products with conventional medicines should be paid much attention to,and their potential inhibitory effects on CYP enzyme activities need to be further investigated.  相似文献   

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OBJECTIVE: To study the effects of extracts from Honghua (Flos Carthaml~ on lipopolysaccharide in- duced nitric oxide (NO) production in RAW 264.7 cells and the influence of the extracts on yeast a-glucosidase activity. The total flavonoid content of the extracts was also determined. METHODS: Cytotoxicity of the extracts to RAW 264.7 cells was evaluated by the ATPliteTM method. Inhibitory effects of the extracts on NO production were evaluated by Griess assay. Curcumin was used as a positive control. Screening of extracts for po- tential a-glucosidase inhibitors was done by a fiuo- rometric assay. The assay was based on the hydroly- sis of 4-methylumbelliferyl-a-D-glucopyranoside toform the fluorescent product, 4-methylumbellifer- one. Acarbose was used as a positive control. The total t3avonoid content was tested using kaempfer- ol as the standard. RESULTS: There were significant inhibitory effects on NO production when the extracts were 25-100 μg/ mL (P〈0.05) and curcumin was 2-4 μg/mL (P〈 0.001). The extracts showed an inhibitory effect on a-glucosidase activity at the concentrations of 15.6-125 μg/mL with a half maximal (50%)inhibito- ry concentration (ICs0) of (32.8± 5.7) μg/mL, com- pared with the ICs0 of acarbose at (1.8±0.4) μg/mL. There was a significant difference between the two IC50 values (P〈0.001). The total content of flavo- noids per gram of dried herb was 1.14 mg. CONCLUSION: Honghua (Flos Carthami) showed in- hibitory effects on NO production in activated RAW 264.7 macrophage cells and an inhibitory effect on yeast a-glucosidase. There might be a relationship between these pharmacological effects and its fla- vonoid content.  相似文献   

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Objective: To determine the hot/cold of South American A?aí(Euterpe oleracea Mart.). Materials and Methods: 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay was performed to compare the influence of A?aí and phellodendron bark(Cortex Phellodendri Chinensis) on the growth and proliferation of HepG2 and Hep3 B cell strains. The morphological changes of the two cell strains treated with A?aí and C. Phellodendri were observed using an inverted phase contrast microscope. Trypan blue dye exclusion assay was used to compare and analyze the toxicity effects of A?aí. The content of nicotinamide adenine dinucleotide(NADH) and the ratio of NADH/NAD+ of the treated cells were detected using a spectrophotometer to determine the influence of A?aí to the energy metabolism of the two cell strains. Results: Within the range of measured concentrations, both A?aí and C. Phellodendri displayed separately the stronger inhibitory effects on cell growth, proliferation, and energy metabolism of the two cell strains. By MTT assay, A?aí showed significant(P 0.05) or highly significant(P 0.01) inhibitory effects on cell proliferation within the concentration range of 0.25–40 μg/mL, which was similar to the effects of C. Phellodendri. From the results of microscopic examination, the morphological of lower cell density, attenuated granularity, and more outstretched cells in irregular polygonal shape could be observed in the cells treated with A?aí, which was also similar to that of C. Phellodendri. In trypan blue staining assay, all concentrations of A?aí showed negligible toxicity effects, exactly as that of C. Phellodendri. A?aí showed a highly significant effect of decreasing the content of intracellular NADH as well as the ratio of NADH/NAD+(P 0.05 and P 0.01, respectively). Conclusion: The effect of A?aí on HepG2 and Hep3 B strains just as C. Phellodendri can reduce energy metabolism and inhibit the growth and proliferation. All performance characteristics of two cell strains treated with A?aí belong to that characteristic of cold property drug. From the study results, we can deduce that the drug property of A?aí is cold.  相似文献   

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Objective To compare the chemical constituents in the essential oils from the leaves, flowers, and seeds of Elsholtzia ciliata and their antimicrobial activities. Methods The chemical constituents in essential oils were extracted by the hydro-distillation method and analyzed by GC-MS. The chemical constituents in essential oils were identified on the basis of comparison on their retention indices and MS spectrum with published data. Moreover, the antimicrobial activities of the chemical constituents in the oils against the growth of six bacteria strains and one pathogenic yeast strain were evaluated by using minimum inhibitory concentration and minimum bactericidal concentration methods. Results A total of 58 compounds were identified, while compounds 31, 35, and 36 were identified in the essential oils from the leaves, flowers, and seeds, respectively. Fifteen compounds were identified as shared constituents in the leaves, flowers, and seeds. The chemical constituents in the essential oils showed the inhibitory activities against the six bacteria strains and the yeast strain. Conclusion The major constituents are different in the essential oils of the leaves, flowers, and seeds. The major chemical constituents in the essential oils are monoterpenoids and sesquiterpenoids. And the chemical constituents in the essential oils obtained from the leaves show higher inhibitory activities especially against Bacillus subtillis CMCC63501 and Escherichia coli ATCC25922.  相似文献   

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OBJECTIVE: To investigate the effect of Young Yum pill(YYP) on inflammatory mediators in cultured RAW 264.7 cells and elucidate the nuclear factorkappa B(NF-κB)-related mechanism behind the action.METHODS: YYP was extracted with 95% ethanol Lipopolysaccharide(LPS)-stimulated RAW 264.7 macrophages were used to evaluate the effect of YYP on inflammatory mediators.Production of nitric oxide(NO) and prostaglandin E2(PGE2) were measured by Griess test and enzyme-linked immunosorbent assay, respectively.The levels of genes and proteins involved in the generation of inflammatory mediators were examined using real-time polymerase chain reaction and Western blotting, respectively.RESULTS: YYP dose-dependently suppressed LPSinduced production of NO, PGE2 and tumor necrosis factor-α(TNF-α), and elevation of mRNA and protein levels of inducible NO synthase and cyclooxygenase-2 in RAW 264.7 macrophages.These observations were associated with decreased NF-κB p65 phosphorylation and nuclear localization, enhanced Akt(protein kinase B) phosphorylation, as well as reduced inhibitor of κB(IκB) α degradation and IκB kinase α/β phosphorylation.CONCLUSION: The present study demonstrated an inhibitory effect of YYP on the NF-κB-regulated inflammatory mediators NO, PGE2 and TNF-α in LPSstimulated RAW 264.7 macrophages, providing a pharmacological basis for the use of YYP in treating inflammatory disorders.  相似文献   

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AIM: To investigate the effects of feeding phenylalanine (Phe) and tyrosine (Tyr) on the accumulation of total phenolic compounds and four phenylethanoid glycosides (PeGs) to a cell suspension culture of the parasitic plant Cistanche deserticola.METHOD: A cell suspension culture of C. deserticola was established and precursors of different concentrations were fed. In each group, the cell was sampled at the 24^th day after inoculation. The content of total phenolic compounds and four PeGs compounds were determined using the Folin-Ciocalteu method and an HPLC method, respectively.RESULTS: In the Phe fed cells, the maximum PeGs yield was achieved when Phe was fed at 1.5 mmol·L^-1 and the yield reached 1.13 times the control cell concentration. In the Tyr fed cells, the maximum yield of PeGs was 1.60 times of control when 0.75 mmol·L^-1 Tyr was fed to the cells. Furthermore, it was found that the salidroside yield was 4.01 times of control group when 5 mmol·L^-1 Tyr was fed.CONCLUSION: Tyr is a better precursor for PeGs accumulation compared with Phe, and the rate limiting enzymes might be involved in the Tyr branch.  相似文献   

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OBJECTIVE; To observe capillary blood flow at acu- points during acupuncture treatment of primary dysmenorrhea and gain new insights into its anal- gesic mechanism. METHODS: Patients with primary dysmenorrhea were enrolled and randomly assigned to a treat- ment or control group. Subjects' symptoms were differentiated into various Traditional Chinese Medi- cine (TCM) syndromes and treated for 10 sessions with puncturing acupuncture or self-pressing right-hand Hegu (LI 4), adding other acupoints based on syndrome. Laser speckle was used tocompare the change in the vasomotor amplitude and perfusion of the capillaries in Hegu (LI 4) be- fore and during the treatment. Each subject was re- quired to finish the period pain symptoms observa- tion form, verbal rating scales, numerical rating scale, pain rating index, face rating scale, Zung self-rating depression scale, Zung self-rating anxi- ety scale, and numerical rating scale before and af- ter treatments. RESULTS: After 10 sessions, the symptom scores, pain index (PI), and visual analog scale (VAS) de- creased significantly in treatment group. The vol- ume of blood flow in Hegu (LI 4) declined slightly. No significant evidence supported that needling caused capillary contraction, but the capillary vaso- motor amplitude at Hegu (LI 4) increased remark- ably. CONCLUSION: Acupuncture can increase the capil- lary blood flow, thus promoting the flow of Qi and blood in terms of TCM theory, which facilitates pain relief.  相似文献   

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OBJECTIVE: To investigate the combinatorial ef- fects of conception and governor vessel electroacu- puncture (EA) and human umbilical cord blood-de- rived mesenchymal stem cells (HUCB-MSCs) on pathomorphologic lesion and cellular apoptosis in rats with cerebral ischemia/reperfusion. METHODS: With the HUCB-MSCs isolated, cultured and identified and the models of cerebral isch- emia-reperfusion established, the HUCB-MSCs of passage three were intracranially transplanted andthe EA at conception and governor vessels was ap- plied. The pathomorphologic lesion by hematoxy- lin-eosin staining and the cellular apoptosis by ter- minal deoxynucleotidyl transferase-mediated nick-end labeling method around the ischemic fo- cus were observed. RESULTS: The cultured adherent HUCB-MSCs ex- hibited a spindle shape and expressed MSC-specif- ic markers, with the cell purity and proliferation rate significantly increasing after the primary pas- sage. HE staining showed that there were no patho- logical changes observed in the sham surgery group. However, in the PBS transplantation group, degeneration and necrosis of a great number of nerve cells were seen. In both the HUCB-MSCs transplantation group and the HUCB-MSCs trans- plantation + EA group, reparative changes of the pathomorphism of the tissue were found. Both combination treatment and simple MSCs treat- ment were able to improve the pathomorphorlogic lesion following cerebral ischemia and reduce the abnormal TUNEL-positive numbers, with former better than latter. CONCLUSION: HUCB-MSCs improve pathological lesions and inhibit the cellular apoptosis around the cerebral ischemic area. EA at conception and governor vessels also improve pathological lesion and inhibit the cellular apoptosis in rats treated with HUCB-MSCs transplantation, which effects were superior to that of simple HUCB-MSCs trans- plantation.  相似文献   

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OBJECTIVE: To investigate the curative effects of Xuebijing (XBJ) injection, a Chinese patent medi- cine, on severe pulmonary contusion (PC). METHODS: Sixty-three patients with PC were ran- domized to conventional therapy plus XBJ injec- tion (n=33) or conventional therapy alone (n=30). Between groups differences in corticosteroid treat- ment, immune regulation therapy, hemofiltration, infusion volume, transfusion volume and antibiotic period were measured, as were intensive care unit(ICU)-free time, ventilation time, 28-day mortality rate and incidence of ventilation-associated pneu- monia (VAP). Serum concentrations of procalcito- nin (PCT), tumor necrosis factor-a (TNF-a), interleu- kin (IL)-6, and 11_-10, white blood cell (WBC) counts and percentages of human leukocyte antigen DR/ CD14+ (HLA-DR/CD14+) peripheral blood mononu- clear cells were compared. Markers of ventilation were determined by blood gas analysis and ventila- tor parameters. RESULTS: WBC counts and serum concentrations of PCT, TNF-a, 11.-6 and IL-10 were reduced signifi- cantly more quickly, and CD14+ percentage was in- creased significantly earlier, in the XBJ group than in the control group (P〈0.05 each). The level of ven- tilation and oxygenation index were ameliorated earlier in the XBJ than in the control group (P〈 0.05). XBJ treatment significantly reduced ICU-free time, ventilation time and incidence of VAP (P〈0.05 each), but had no effect on 28-day mortality rate (P〉0.05). CONCLUSION: XBJ treatment can shorten ICU-free and ventilation times and reduce the incidence of VAP, improving outcomes in patients with severe PC. XBJ may act by regulating inflammation and im- munity, alleviating systemic inflammatory response syndrome induced by trauma.  相似文献   

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OBJECTIVE: To research the curative effect of Chi- nese herbs for clearing away heat, promoting diure- sis, nourishing the kidney, and consolidating es- sence in children with Henoch-Schonlein purpura nephritis(HSPN) with internal accumulation of damp-toxin using randomized controlled observa- tions on large samples. To seek the mechanism of the therapy and its scope of indications. METHODS: Overall, 186 children with HSPN were randomly divided into two groups: treatment group(n=126) treated with Chinese herbs for clear- ing heat and promoting diuresis and a control group(n=60) treated with Western Medicine. The treatment was carried out for three courses of 4 weeks each. We recorded changes in patient urine routines, 24 h urinary protein, blood-coagulating series, immunoglobulin and T-cell subgroups, and improvements in main symptoms. We evaluated the alleviation of clinical symptoms and the im- provement of proteinuria, hematuria, and other lab-oratory test results. Finally, we analyzed the patient population suitable for this therapy according to the relationship between the grouping of patient body weight and curative effect. RESULTS: Damp-heat syndrome improved in the treatment group, with a significant difference in to- tal effective rate after a 4-week treatment(χ2= 13.5220, P=0.0002) and in curative rate after a 12-week treatment(χ2=6.3410, P=0.0118), com- pared to those in the control group.The curative ef- fect in the treatment group was greater than that in the control group but there was no statistical dif- ference between the two groups. The curative ef- fect after a 4-week treatment of patients in the treatment group weighing 30 kg or less based on Traditional Chinese Medicine(TCM) signs and uri- nary protein was significantly greater than that in the control group. However, there was no statistical difference in the curative effect on urinary red cells and various indexes after a 12-week treatment be- tween the two groups. CONCLUSION: Therapy for clearing away heat, pro- moting diuresis, nourishing the kidney, and consoli- dating essence using TCM is effective in children with HSPN from internal accumulation of damp-toxin. The therapy is especially suitable for patients weighing 30 kg or less. The curative effect may be related to the improvement of immune function and blood-coagulation.  相似文献   

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AIM: To explore the therapeutic effects ofMorinda officinalis capsules (MOP) on osteoporosis in ovariectomized rats. METHOD: Six-month-old female Sprague-Dawley rats were induced for postmenopausal osteoporosis (PMOP) by bilateral ovariectomy and divided into seven groups as follows: sham-operated group, ovariectomized (OVX) control group, OVX treated with xianlinggubao (XLGB) (270 mg·kg^-1·d^-1) , OVX treated with alendronate sodium (ALN) (3 mg·kg^-1·d^-1), and OVX treated with Morinda officinalis capsule (MOP) of graded doses (90, 270 and 810 mg·kg^-1·d^-1) groups. Oral treatments were administered daily on the 4th week after ovariectomy and lasted for 12 weeks. The bone mineral density was evaluated by dual-energy X-ray absorptiometry. The tartrate-resistant acid phosphatase (TRAP), alkaline phosphatase (AKP), and osteocalcin (OC) levels in the serum and plasma were determined by standard colorimetric and enzyme immunoassays methods. Bone biomechanical properties and morphological parameters were analyzed by three-point bending test and histomorphometry respectively. RESULTS: Morinda officinalis capsules at all doses were able to significantly prevent the OVX-induced loss of bone mass due to diminishing serum AKP and TRAP levels while elevating OC level in the plasma. Morinda officinalis capsules also enhanced the bone strength and prevented the deterioration of trabecular microarchitecture. CONCLUSION: Morinda officinalis capsules possess potent anti-osteoporotic activity in OVX rats which could be an effective treatment for postmenopausal osteoporosis.  相似文献   

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王氏保赤丸系根据清代道光年间通州著名中医王胪卿祖传九世秘方配制,并由其嫡孙王绵之教授监制的纯中药制剂。该药由大黄、黄连、制天南星、川贝母等组成。方中大黄苦寒,攻积导滞,泻火凉血,行瘀通经;黄连苦寒,清热燥湿,泻火解毒;制天南星苦凉,化痰熄风定惊;川贝母苦寒,化痰止咳,清热散结。王氏  相似文献   

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Objective:To probe into the therapeutic efect of perfume stimulating olfaction with volatile oil of Acorus Gramineus on the Alzheimer's disease (AD) rat. Methods: Totally 50 adult SD rats, male,weighing 300±10 g, were randomly divided into 5 groups, normal group (group A), olfactory nerve severing model group (group B), AD model group (group C), AD model plus perfume stimulation group (group D), AD model olfactory nerve severing plus perfume stimulation group (group E), 10 rats in each group. After perfume stimulation, Morris maze test was conducted for valuating the learning and memory ability; Malondaldehyde (MDA) content, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the brain, and the brain weight were detected. Results: Compared with the AD model group,the average escape latency and swimming distance in 6 days were significantly shorter than those in the group A, B, D (P〈0.01), with no significant differences between the group C and the group E (P〉0.05); Compared with the group A, B and D, MDA content in the group C significantly increased (P〈0.01), and SOD and GSH-Px activities significantly decreased (P〈0.01), and brain weight/body weight decreased significantly in the group C (P〈0.01), with no significant differences between the group C and the group E (P〉0.05). Conclusion: Perfume stimultating olfaction with volatile oil of Acorus Gramineus can significantly increase the learning-memory ability, decrease MDA content and increase SOD and GSH-Px activities and weight of brain in AD rats.  相似文献   

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OBJECTIVE: To study information gained by Tradi- tional Chinese Medicine(TCM) four diagnostic methods and characteristics of syndrome develop- ment before and after treatment in patients with coronary heart disease, and to probe into assess- ment indexes of therapeutic effects with distinctive TCM features. METHODS: Information from the four diagnostic methods before and after treatment in 100 patients with coronary heart disease was collected using the TCM interrogation scale, a pulse condition in- strument, a tongue-face diagnosis instrument, anda voice diagnosis information collection system. Changes in the four diagnostic method results from before and after treatment were analyzed with frequency analysis and t-test methods. RESULTS: Before treatment, deficiency syndrome complicated with hyperactivity of pathogenic fac- tors was most common. After treatment, deficiency syndrome was most common. This change from complex syndromes to single syndromes indicates disease and syndrome alleviation. Frequencies of symptoms gained by interrogation after treatment for syndrome of deficiency of heart-Qi, syndrome of deficiency of heart-Yin, and turbid phlegm syn- drome were all less severe than those before treat- ment. Parameters of face color, color on all sub-re- gions of tongue, color of tongue fur, septic and greasy fur, and lip color after treatment all had sig- nificant changes. After treatment, part of the voice diagnosis parameters in the deficiency of heart-Yin and turbid phlegm syndromes had significant changes, but no significant changes were found in the deficiency of heart-Qi syndrome. CONCLUSION: Use of the TCM four diagnostic methods can provide an effective basis forTCM syn- drome diagnosis, observation of development of state of illness, and evaluation of clinical therapeu- tic effects.  相似文献   

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