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??OBJECTIVE To improve the control rate of cancer pain and the satisfaction of community patients with cancer pain. METHODS A multidisciplinary team was built,which included community public health workers,clinical pharmacists,community physicians and tracking pharmacists. Pharmaceutical care was provided to patients with cancer pain in the community,and the effects of pharmaceutical care were evaluated. RESULTS The clinical pharmacists provided 52 times of pharmaceutical care to 17 patients,224 cases of medication problems were discovered,and 337 pieces of medication suggestions were made. After receiving pharmaceutical care,the scores of the most severe pain,the mild pain and the average pain in the past 24 h decreased from(9.12??1.34),(5.53??1.46) and (7.24??1.99) to (4.71??1.36),(1.18??0.95) and (2.41??1.18) (P< 0.01), respectively. The percentage of good medication compliance increased from 0% to 64.7% (P< 0.01). The influence of pharmaceutical care on patients included ??helping understand the drugs??, ?? taking medicine on time??, ??reducing adverse drug reaction?? ,??establishing correct concept of medication?? and ??reducing medical costs??,which got scores of (4.35??0.49),(4.53??0.51),(4.00??0.61),(4.29??0.59), and (3.76??0.66),respectively.For ??convenience of pharmaceutical care??,??pharmacist ability??, ??pharmacists?? attitude??,??symptom improvement?? and ??improvement of the quality of life??,the patients gave scores of (4.06??0.66),(4.24??0.44),(4.20??0.40),(4.41??0.71) and (4.29??0.47),respectively. CONCLUSION The problems in the drug treatment in community patients with cancer pain are numerous and complex. Pharmaceutical care can reduce the problems,improve the control rate of cancer pain, and increase the community patients' satisfaction on the management of cancer pain. The patients give positive evaluation to the pharmaceutical care.     

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??OBJECTIVE To evaluate the antibacterial effects of colistin combined with fosfomycin against Klebsiella pneumoniae carbapenemase-producing K. pneumonia in vitro. METHODS The minimal inhibitory concentration(MIC) of colistin and fosfomycin against 74 strains of KPC-Kp was determined by agar dilution method and broth microdilution method respectively.The fractional inhibitory concentration index( FICI )was calculated by checkerboard method to determine the combined effect.SixKPC-Kp strains were randomly selected to determine the time-killing curves of colistin and fosfomycin alone or in combination. RESULTS The MIC results: polymyxin sensitivity rate of 100%, fosfomycin sensitivity rate of 35.14%.The FIC results: In 74 strains,12.16% synergism, 39.19% section synergism,6.76% additive effect,41.89% irrelevant,no antagonism found.The results of time-kill assay showed that there was a significant synergistic effect between colistin and fosfomycin in fosfomycin-sensitive strains, while fosfomycin-resistant strains showed no synergistic effect. CONCLUSION In the case of fosfomycin-sensitive strains, the combination of colistin and fosfomycin has synergistic effects on KPC-Kp in vitro, and time-kill assay also shows a good synergistic effect. Resistant strains are poor in synergism.     

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??OBJECTIVE To analyze the microbial contamination and investigate the bacteriostatic efficacy of compound balloonflowers and ephedrine syrup(??). METHODS The compound balloonflowers and ephedrine syrup(??) was analyzed for the bacteriostatic efficacy, content of bacteriostatic agent and C₁₈ column was adopted with gradient elution. The mobile phase consisted of 0.02 mol??L^-1 ammonium acetate solution and methanol. The detective wavelength was set at 255 nm. The contaminating bacteria detected in the samples were identified by VITEK2 Campact, MALDI-TOF-MS and 16S rRNA sequencing, and homology analysis was conducted for the contaminating bacteria in the samples from the same enterprise. RESULTS The bacteriostatic efficacy of the products of one enterprise did not meet the requirements of Chinese Pharmacopoeia(2015 edition). There were excessive and uneven contamination of microorganisms in the samples. The dosages of bacteriostatic agents in some enterprises did not conform to the standard requirements. CONCLUSION Production enterprises should strictly control the dosages of bacteriostatic agents and the stability of the production process, and strengthen the monitoring of the sterilization effect of the whole production process to improve product quality.     

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??OBJECTIVE To evaluate the effectiveness of pharmacist-participated warfarin anticoagulation management by patient education and medication consultation on patients with pulmonary embolism(PE). METHODS A total of 204 PE patients were hospitalized in respiratory wards from March 2015 to April 2017 enrolled eventually. Evaluation endpoints including the percentage of INRs within the therapeutic range(TTR), the percentage of INRs within the expanded range(TER), INR recall intervals, bleeding events, emergency department visits and hospitalizations related to anticoagulation therapy. RESULTS TTR and TER of intervention group were(70.89??26.02)% and(87.71??20.01)% respectively, which were both significantly higher than(47.79??22.31)% and(71.23??21.47)% in control group(P=0.000). INR recall intervals were(27.48??12.81) d versus(43.35??13.65) d (P=0.000). There were no significant differences between two groups in total bleeding events(41.96% vs 29.35%, P=0.062), minor bleeding events(38.39% vs 27.17%, P=0.091) and major bleeding events(3.57% vs 2.17%, P=0.864). And a significantly decreased in emergency department visits of intervention group(9.82% vs 1.09%, P=0.008), whereas no difference was observed in hospitalizations(8.04% vs 2.17%, P=0.125). CONCLUSION Clinical pharmacists participated in anticoagulation management of pulmonary embolism patients, which helped patients to monitor INRs more regularly, INR controlling better and decrease frequency of emergency department visits.     

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??OBJECTIVE To establish a quantitative analysis of multi-components by single marker(QAMS) for the determination of three atractylenolides in Atractylodes macrocephala Koidz. METHODS UPLC method was applied to determine atractylenolide ??, ?? and ?? by external standard method (ESM)first. With this established UPLC method, atractylenolide ?? was used as the internal standard (IS)to determine the correction factors (RCFs)of the two other atractylenolides, and their contents in all the samples were calculated by their RCFs at the same time. By comparing the contents determined by the ESM and QAMS methods, the feasibility and accuracy of QAMS method were verified. RESULTS Within a certain range(atractylenolide??:3.7-59.3 ??g??mL^-1, atractylenolide ??: 3.9-63.5 ??g??mL^-1, atractylenolide ??: 7.3-116.1 ??g??mL^-1), the RCFs of atractylenolide ??, ?? to atractylenolide ?? were 0.633 and 1.895, respectively, which had good repeatability in different experimental conditions. There was no significant difference between the QAMS method and ESM method(P??0.05). CONCLUSION The QAMS method is feasible and accurate for the determination of the three atractylenolides and is beneficial to the quality control of Atractylodes macrocephala Koidz..     

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??This review provided the research progresses of the strategies of the modification and application of poly (lactic-co-glycolic acid, PLGA) nanoparticles . The preparation and modification METHODS of PLGA nanoparticles and their application according to the reported foreign literature were analysed and summaried. PLGA is a biodegradable and biocompatible polymer which is one of the most widely used materials in preparation of sustained and controlled microparticles as drug vectors. This review focuses on the METHODS of modified nanoparticles and the advantages. Emulsification method, nanoprecipitation, emulsification solvent diffusion, solvent injection method and supercritical anti-solvent technique are the main five preparation METHODS of PLGA nanoparticles.The strategies of modifition include covalent cross-link, electrostatic interaction and hydrophobic interaction. The applications of modified nanoparticles to the optimal formulation, sustained release profile, improved cellular uptake, and targeting to specific organs or cells are introduced.     

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??OBJECTIVE To explore the role of clinical pharmacists in safety management of long-term administration of oral targeted drugs by establishing a team for management of adverse reactions and providing pharmaceutical care. METHODS Inpatients receiving oral gefitinib (250 mg QD) were enrolled in the study between January 2014 and December 2014. Clinical pharmacists provided education and instruction to patients on how to deal with adverse effects during gefitinib treatment. After the discharge, the clinical pharmacists supplied regular follow-up for patients. Finally, a survey of patients?? awareness of targeted drugs was conducted after the pharmaceutical care. RESULTS The pharmaceutical care could attenuate the severity of adverse reactions. It also improved patient acceptance and understanding of targeted drugs and reduced the adverse reactions. CONCLUSION Provision of regular follow-up and strengthened patient education by pharmacists can pre-manage the adverse drug reactions of long-term oral targeted drugs treatment, achieve patient self-management and improve their medication compliance and quality of life.     

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??OBJECTIVE To assess the cost-effectiveness of clinical pharmaceutical care in the H. pylori(HP) eradication in outpatients with peptic ulcer.METHODS Ninty-six Outpatients with HP positive peptic ulcer from July 2015 to June 2016 were prospectively collected, and randomly divide into control group and intervention group. Patients in the control group were given the traditional outpatient service. The intervention group patients were given with pharmaceutical education and follow-up by clinical pharmacist. The score of compliance with medication, HP eradication rate and the improvement of gastrointestinal symptom were selected as outcome indicator. Time cost of intervention and fee of clinical pharmacist training were estimated and recorded as the cost of clinical pharmacy intervention. RESULTS ??Improvement of the score of compliance with medication of intervention group patients was significantly higher than the control group (1.71 vs. 0.44, P<0.01). Forty-four patients of the intervention group, while 36 patients in the control group reported less gastrointestinal symptoms (91.67% vs. 75.00%, P=0.028). The HP eradication rate of the intervention group was significantly higher than the control group (91.67% vs. 72.92%, P=0.016). ??For the hospital, the cost of pharmacy service of control group was 292.31 yuan, and 821.61 yuan of the intervention group. ??The cost-effectiveness ratio of the score of compliance with medication of control group was 664.34, while the intervention group was 480.47, which was superior to the control group. It was cost-effective. However, the cost-effectiveness ratio of HP eradication rate and the improvement of gastrointestinal symptom of the intervention group were both higher than the control group. CONCLUSION Clinical pharmaceutical care increase the cost of the hosipital. However, clinical pharmaceutical care can result in cost-effective improvement of the medication compliance.     

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目的以壳聚糖为酶触型结肠靶向给药系统的材料,研制可用于结肠靶向的多单元口服给药系统(迷你片),以期为结肠部位疾病治疗的药物输送提供重要参考。方法以结肠癌的治疗药物-吲哚美辛为模型药物,首先制备固体分散体,再采用直接压片法和包衣技术制备尤特奇-壳聚糖双层包衣结肠靶向迷你片,考察靶向迷你片在不同释放介质中的释药行为,采用小动物活体荧光成像技术考察制剂在体内的转运和吸收情况,并以比格犬为动物模型进行药动学研究和生物利用度评价。结果制备的壳聚糖多单元结肠靶向迷你片可以完整形态通过大鼠胃和小肠,并靶向在结肠部位缓慢释放,比格犬体内药动学数据表明,自制结肠靶向迷你片的释药时间显著延长,血药浓度平稳。结论本实验制备尤特奇-壳聚糖双层包衣多单元迷你片给药系统具有较好的结肠靶向性和缓释效果,可为治疗结肠疾病的制剂开发提供重要参考。     

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??OBJECTIVE To establish an analytical method for simultaneous determination of scutellarin ethyl ester and its related substances by RP-HPLC and identify the main related substances by UPLC-MS.METHODS The assay was performed on a Kromasil C₁₈ column(4.6 mm??250 mm,5 ??m),and gradient elution was used with methanol-water containting 0.2% formic acid. The flow rate was 1.0 mLmin^-1and the detection wave length was set at 335 nm.The structure of the main related substance was identified by high resolution MS.RESULTS Under the separation condition,the related substances were completely separated from the principal components.The calibration curve of scutellarin ethyl ester showed good linearity in the concentration range of 5.005-1 001 mgL^-1(r²=0.999 9). The average recovery was 99.6%. The main related substance was identified as scutellarin by LC-MS. The contents of total impurities and scutellarin were 1.14% and 0.89%, respectively.CONCLUSION The method is simple, efficient and accurate, and can be used for the quality control of scutellarin ethyl ester.     

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??OBJECTIVE To study the protective effects of sparstolonin B(8,5'-dihydroxy-4-phenyl-5,2'-oxidoisocoumarin,SsnB) on mouse with intracerebral haemorrhage(ICH). METHODS The effect of SsnB on neuronal cell death induced by Hb using a microglia-neuron transwell system was investigated. Autologous nonanticoagulated blood was collected from the tail artery of the mouse and then injected into the striatum using a syringe pump. Neurological deficit of the mouse with ICH was assessed 1, 3, 5 and 7 d after SsnB administration using modified neurological severity score system,and brain water content of the mouse cerebral tissues after ICH was measured at the same day. The concentrations of pro-inflammatory cytokines in perihematoma tissues, including interleukin-6, interleukin-1?? and tumor necrosis factor-??, were measured by ELISA assay. RESULTS The RESULTS show that SsnB significantly reduced the neurological deficit scores and the brain water content, and inhibited the levels of IL-6, IL-1?? and TNF-?? at first day and third day after ICH. CONCLUSION SsnB can improve the brain injury in mouse induced by ICH. The mechanism may involve increased the neuronal survival rate and decreased expression of pro-inflammatory cytokines of mouse after ICH.     

Ginkgolide B reduces neuronal cell apoptosis in the hemorrhagic rat brain: possible involvement of Toll-like receptor 4/nuclear factor-kappa B pathway

Ethnopharmacological relevance

Ginkgolide B (GB) is one of the ginkgolides that have been isolated from leaves and root bark of the Chinese tree Ginkgo biloba L. (Ginkgoaceae), and is a specific and potent antagonist of platelet activating factor. There is a large body of data showing that GB possesses a markedly neuroprotective property against ischemia-induced impairment in vivo and in vitro. Recently it has been found that GB can inhibit the inflammation in the rat brain tissues with ischemia/reperfusion injury and in the astrocytes treated with lipopolysaccharide, as well as protect neurons against beta-amyloid 25-35 and ischemia-induced apoptosis. However, there have been few reports on the influence of GB on intracerebral hemorrhage (ICH). This study was to investigate the effects of intraperitoneal GB on neuronal cell apoptosis, inflammatory cytokines and Toll-like receptor4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway after ICH.

Materials and methods

Wistar rats obtained an intraperitoneal injection of 5, 10 and 20 mg/kg GB after ICH once a day till day 5. Rats were sacrificed by decapitation at hour 2, 6 and 12, as well as day 1, 2, 3 and 5 after ICH. Gene expressions of TLR-4 and NF-κB, concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) as well as number of apoptotic neuronal cells in hemorrhagic rat brain tissues were determined.

Results

The administration of 10 and 20 mg/kg GB could significantly suppress gene expressions of TLR-4 and NF-κB, lessen concentrations of TNF-α, IL-1β and IL-6 as well as reduce number of apoptotic neuronal cells in hemorrhagic rat brain tissues by Least-significant Difference test (P < 0.05), but the administration of 5 mg/kg GB not (P > 0.05). However, a clear concentration-response relationship was not found.

Conclusions

GB may inhibit TLR4/NF-κB-dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis after ICH, which may support the use of G. biloba extracts for the treatment of ICH.     

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??OBJECTIVE To investigate the inhibitory effects of phenolic glycoside compound xylocontroside D on neurotoxicity of primary cultured cortical neurons induced by A??_1-42. METHODS The primary cortical neurons and microglia cells derived from rat cerebral tissues were used and neurotoxicity were induced by A??_1-42. Then the thiazolyl blue tetrazolium bromide test(MTT) was applied for detecting cell survivability; cells were incubated with CH₃-H₂DCF-DA for evaluating cellular endogenous reactive oxygen species(ROS) level by flow cytometry;fluorescent staining of 8-hydroxy-2-deoxyguanosine(8-OH-DG) was applied for identifying the metabolites of ROS based DNA damage; fluorescent imaging was applied for illustrating the activation of microglia cells and the enzyme-linked immunosorbent assay(ELISA) was applied for analysis of pro-inflammatory cytokines, cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), interleukin-1beta(IL-1??) and tumor necrosis factor alpha(TNF-??). RESULTS Xylocontroside D showed significant inhibitory effects on A??_1-42 induced neurotoxicity, including cell death, cellular endogenous ROS levels and DNA damage caused by ROS reaction. Moreover, this compound could also prevent the activation of microglia, decrease the production or secretion of pro-inflammatory cytokines that produced by activated microglia, such as COX-1, COX-2, IL-1?? and TNF-??. CONCLUSION Our RESULTS indicated that xylocontroside D was able to inhibit the oxidative stress injury and neuroinflammation of primary cultured cortical neurons induced by A??_1-42.     

水蛭素对大鼠实验性脑出血急性期保护作用的研究

目的:通过观察凝血酶特异性抑制剂-水蛭素对脑出血后血肿周围组织胶质纤维酸性蛋白(GFAP)表达及脑组织含水量变化的影响,探讨水蛭素在脑出血后继发性损伤中的保护作用。方法:采用自体未抗凝动脉血注入法,制作实验性脑出血动物模型。将大鼠随机分为正常对照组,脑出血组,水蛭素组。光镜下定性观察脑出血后血肿周围组织的病理变化;采用干湿比重法定量测定脑组织含水量;免疫组化染色观察脑出血后GFAP的变化。结果:光镜示从脑出血后6 h开始血肿周围组织水肿进行性加重,3 d达高峰。脑出血后脑组织含水量逐渐增加,从1 d开始增加显著(P<0.05),3 d达高峰,7 d较3 d组虽有所下降,但与正常对照组相比差异显著。脑出血后1 dGFAP表达明显增强,随后持续增加,7 d达高峰。水蛭素组较相同时间点脑出血组血肿周围组织病理损伤减轻;脑组织含水量降低(P<0.05);GFAP表达有所下降(P<0.05)。直线回归分析表明,脑出血后1周内GFAP的变化与脑组织含水量变化呈正相关关系。结论:脑出血后1周内血肿局部应用凝血酶特异性抑制剂-水蛭素具有保护作用,并为脑出血的治疗提供一种新的给药途径。     

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??OBJECTIVE To explore the protection mechanism of orthogonal compatibility of puerarin(A),ligustrazine(B), astragaloside IV(C) and catalpolon(D),the main active ingredients from yangyin tongnao granules, on SD rats damaged by ischemic reperfusion injury, and select the optimal combination. METHODS SD rats were randomly divided into sham operation group, model group, orthogonal compatibility group and positive control group. The rat middle cerebral artery occlusion (MCAO) model was established. The compatibility of components was arranged by L₉(34) orthogonal design. The symptoms of neurological deficit in rats and the pathological changes in hippocampus were observed; TTC staining was used to detect the cerebral infarction volume. IHC was used to evaluate the expression of NLRP3 protein ischemic brain tissue. RT-PCR was used to detect the expressions of ASC, caspase-1, IL-1, mRNA, IL-18 and MMP-9 in the hippocampal of brain tissue. The RESULTS of orthogonal test were analyzed by range analysis. RESULTS The orthogonal combination groups could effectively improve neurological deficits in cerebral ischemia reperfusion injury, reduce infarction volume, inhibit the expression of NLRP3 inflammasome, decrease the expression of ASC, caspase-1, IL-1, IL-18 and MMP-9. The analysis of test results showed that the combination with ligustrazine 100 mg??kg^-1,puerarin 20 mg??kg^-1, astragaloside ?? 80 mg??kg^-1 and catalpol 20 mg??kg^-1 was the superior one. CONCLUSION The main active ingredients combination of yangyin tongnao granules played a protective mechanism on focal cerebral ischemia reperfusion injury rats. Its mechanism might be related to inhibition of NLRP3 inflammasome,down-regulation of ASC, caspase-1, IL-1, IL-18 and MMP-9.     

Parthenolide ameliorates intracerebral hemorrhage‐induced brain injury in rats

Neuroinflammation and oxidative stress are key contributors to intracranial hemorrhage (ICH)‐induced brain injury. Parthenolide (PN) is a sesquiterpene lactone that has been observed to have antioxidative, anti‐inflammatory, and neuroprotective potentials. However, the role of PN in ICH remains unclear. Therefore, we investigated the neuroprotective effects and underlying mechanisms of PN on an experimental model of ICH in rats. Our results showed that PN treatment improved neurological deficit and brain edema in ICH rats. The ipsilateral hemispheres of the brain were separated and homogenized. The concentrations of TNF‐α, interleukin (IL)‐6, and IL‐17 in the homogenates were detected by enzyme‐linked immunosorbent assay. We found that PN inhibited the production of proinflammatory cytokines in an ICH rat model. The ROS and glutathione (GSH) levels, as well as the activity of superoxide dismutase (SOD) in the homogenates were measured. ICH caused an increase in ROS level, and the decreases in GSH level and SOD activity were mitigated by PN treatment. Furthermore, PN significantly suppressed the expressions of active caspase‐3 and Bax in ipsilateral hemispheres of the brain at Day 3 after ICH, as well as increased the surviving neurons. Finally, the ICH‐induced activation of TLR4/NF‐κB pathway was suppressed by PN treatment. These findings suggested that PN could be beneficial in the therapeutic strategy for ICH treatment.     

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??OBJECTIVE To investigate the effects of microwave radiation on learning and memory abilities in mice,and to study pilose antler peptide??s intervention. METHODS Fifty mice were divided into five groups randomly, designated as control group, radiation group, pilose antler peptide (25, 50, and 100 mg??kg^-1) groups. Learning and memory impairment model in mice was established by microwave radiation of 2 450 MHz average surface power, 10.0 mW??cm^-2 for 90 min every day for 28 d .The radiation rats were treated with low-, mid-, and high-dose (25, 50, and 100 mg??kg^-1) pilose antler peptide by sc injection for 28 d. The learning and memory ability of mice was determined by avoiding darkness experiment and Y maze experiment.The contents of S100B, tumor necrosis factor-??(TNF-??), interleukin-10(IL-10), malondialdehyde (MDA), and nitric oxide(NO) in the brain of mice were determined respectively after the behavioral experiments. RESULTS Compared with control group, radiation group could shorten the latency of avoiding darkness experiments, increase the numbers of errors both in avoiding darkness experiment and in Y maze experiment. Radiation group could rise the contents of S100B ,TNF-??, IL-10, MDA and NO in the brain of mice (P<0.05 or P<0.01). Compared with radiation group, pilose antler peptide (50, 100 mg??kg^-1) groups could lengthen the latency of avoiding darkness experiments, significantly shorten the numbers of errors both in avoiding darkness experiment and in Y maze experiment, and reduce the contents of S100B ,TNF-??, MDA and NO, increase the content of IL-10 in the brain of mice (P<0.05 or P<0.01). CONCLUSION Pilose antler peptide could significantly perfect the learning and memory ability of mice exposed to microwave radiation. The mechanism may be related to its anti-oxidative actions by anti-inflammatory action , further lowering neurotoxic effects of NO.     

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??OBJECTIVE To investigate the protective effects of human recombinant neutrophil inhibitory factor and hirulog hybrid (TNHH) on focal cerebral ischemia in rats. METHODS Middle cerebral artery occlusion model was prepared in rats to imitate the focal cerebral ischemia. Rats were divided into five groups: ??blank,??sham,??focal cerebral ischemia,??ischemia+vehicle and ??ischemia+TNHH(6.75 mg??kg^-1). After persistent ischemia for 12 h, neurologic deficit score was assayed, and then scarified the animals to measure the brain infraction area by TTC staining, the brain pathological damage by HE staining, and the levels of inflammatory factor TNF-?? and IL-1?? in serum respectively by using ELISA and radio-immunity assay. RESULTS TNHH could significantly improve the neurological outcome, decrease the infraction area, alleviate brain edema and pathological injury and reduce the levels of TNF-?? and IL-1?? in rats suffered persistent focal cerebral ischemia for 12 h. CONCLUSION TNHH has significant anti-inflammatory and anti-edema effects, which could effectively alleviate focal cerebral ischemia injury in rats.