ObjectiveTo compare the effectiveness of ω-3 fatty acids and middle/light fatty acids in the intervention of rats model of bleomycin-induced pulmonary fibrosis.MethodsTotally 120 rats were randomly divided into 4 groups: normal saline (NS) group,bleomycin-induced pulmonary fibrosis without treatment group ( BLM group),middle/light fatty acids group,ω-3 fatty acids group.Lung tissues were obtained on the 7th,14th,and 21st day after modeling.The left lung were measured by using immunohistochemical methods for transforming growth factor β1 (TGF-β1) and interferon garmma ( IFN-γ).The lower lobe of the right lung underwent HE staining.Serum TGF-β1,IFN-γ,and interleukin-4 (IL-4) were measured using double-antibody sandwich ELISA.ResultsThe pulmonary alveolitis and fibrosis in the ω-3 fatty acids group was significantly milder than in middle/light fatty acids group and BLM group.On the 7th,14th,and 21st day after modeling,stronger TGF-β1 protein expression was detected in the bronehiolar epithelia of middle/light fatty acids group and BLM group and poorer IFN-γexpression in both groups.However,the opposite results were found in the ω-3 fatty acids group: on the 7th,14th,and 21st day after modeling,TGF-β1 protein expression ( 13.60 ± 5.90,10.53 ± 4.21,and 7.23 ± 2.21 )was lower ( P =0.047) and IFN-γ ( 13.85 ± 7.48,15.32 ± 2.12,and 18.74 ± 2.65 ) was stronger in ω-3 fatty acids group (P =0.041).On the 7 ,14,and 21st day after modeling,the serum IL-4 levels in the middle/light fatty acids group and BLM group became significantly higher,while the IFN-γ level in both groups was significantly lower than in ω-3 fatty acids group ( P =0.008 ) ; meanwhile,in the ω-3 fatty acids group,the serum IL-4 levels [ (8.73 ± 1.20),(5.73 ±2.03),and (4.98 ± 1.89) pg/ml] were significantly lower (P =0.044) and serum IFN-γlevels [ (5.67 ± 0.13 ),( 6.58 ± 0.64 ),and ( 7.05 ± 0.52 ) pg/ml ] were significantly higher ( P =0.048 ) on the 72,14th,and 21st day after modeling.Conclusionsω-3 fatty acids can lower TGF-β1 protein expression in rat lung tissue and reduce the surum TGF-β1 and IL-4 levels.Compared with the middle/light fatty acids,it can more effectively upregulate the expression of IFN-γ in lung tissue and increase its serum level,and thus alleviate pulmonary fibrosis in rats.

ObjectiveTo investigate the mechanism of anti-inflammatory effect of diallyl sulfide (DAS) in protection against acute lung injury (ALI) in rats with paraquat poisoning.Methods Eighty male Wistar rats were randomly divided into four groups, namely: control group, model group, dexamethasone (DXM) treatment group, and DAS treatment group, with 20 rats in each group. The model of paraquat poisoning was reproduced by single does of 70 mg/kg given by gavage, while the same volume of normal saline (NS) was given in same manner in control group. 100 mg/kg of DAS, the same volume of NS, or 1 mg/kg DXM injection were given respectively in DAS treatment group, model group, or DXM treatment group intraperitoneally after exposure to paraquat, once a day for 14 days. Five rats in each group were sacrificed at 1, 3, 7, 14 days, respectively. The inferior lobe of right lung was harvested, and the degree of lung injury was observed with hematoxylin and eosin (HE) staining under optical microscope; the upper lobe of right lung was used to determine the lung wet/dry weight (W/D) ratio and for evaluation of the degree of pulmonary edema. The expression of nuclear factor -κB (NF-κB) in the middle lobe of right lung was assessed with immunohistochemistry. The expression of tumor necrosis factor -α (TNF-α) mRNA in the left lung was determined with the reverse transcription-polymerase chain reaction (RT-PCR).Results① The pulmonary structure in control group was found to be intact. However, in the model group there were progressive pathological changes in lung, including marked edema and thickening of alveolar walls, collapse of alveoli, infiltration of inflammatory cells, alveolar wall, and obvious bleeding in the local lung tissue, and formation of transparent membrane in alveolar space. Less infiltration of inflammatory cells and no obvious destruction were found in alveolar structure in the DAS and DXM treatment groups.② Lung W/D ratio: lung W/D ratio of model group was apparently higher than that in control group at every time point, and peaking on the 3rd day (6.15±0.54 vs. 4.15±2.10,P< 0.05), and the ratio of lung W/D of DAS and DXM treatment groups was obviously lower than that in model group at every time point, especially on the 3rd day (3.99±1.26, 4.30±0.70 vs. 6.15±0.54, bothP< 0.05), but there was no significant difference between DAS and DXM treatment groups in this regard.③ The immunocytochemistry analysis revealed minimal NF-κBp65 expression in the cell nuclei of the control group, while extensive NF-κBp65 expression was found in model group. Minimal NF-κBp65 positive expression in the cytoplasm and even less positive expression in the nucleus was found in the DAS and DXM treatment groups, and integralA value was significantly lower in the DAS and DXM treatment groups than that of the model group, especially on the 3rd day [(17.98±0.06)×107, (18.53±0.04)×107 vs. (28.85±0.61)×107, bothP< 0.01], but there was no significant difference between DAS and DXM treatment groups.④ It was shown by RT-PCR that the expression of TNF-α mRNA in lung tissue of the model group was significantly higher than that in the control group on the 3rd day (gray value: 3.63±0.62 vs. 0.51±0.13, P< 0.05). The expression of TNF-α mRNA in lung tissue was significantly decreased in DAS and DXM treatment groups compared with model group (gray value: 2.49±0.57, 2.02±0.26 vs. 3.63±0.62, bothP< 0.05), but there was no significant difference between DAS and DXM treated groups.ConclusionTreatment with an intraperitoneally injection of DAS is capable of attenuate the extent of PQ-induced ALI in rats by alleviating pulmonary edema, inhibiting the expression of NF-κB and TNF-α in lung tissue, and ameliorating pathological changes in lung tissue.

OBJECTIVETo investigate the effect of the total flavonoids of orange peel (TFO) against adjuvant arthritis (AA) and the underlying mechanism.

METHODAA model was induced in male Wistar (correction of SD) rats by immunization with Freund's complete adjuvant Pad thickness was assayed by caliper. Pathological impairment of ankle joint was analysised by hematoxylin and eosin (H&E) staining. Levels of tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1beta and prostaglandin (PG) E2 in serum was detected by radioimmunoassay method. Cyclooxygenase (COX)-2 expression in synovium tissues was measured by Western blot assay.

RESULTThe 75 mg x kg(-1) and 150 mg x kg(-1) TFO treatment obviously decreased the pad thickness and improve the pathological impairment of ankle joint of AA rats. In addition, abnormal elevation of TNF-alpha, IL-1beta and PGE2 in serum and COX-2 expression in synovium tissues of AA rats were markedly repressed by TFO treatment.

CONCLUSIONTFO can inhibit the development of AA in rats, and the mechanism were likely due to depressing inflammatory mediators production.

Animals ; Arthritis, Experimental ; chemically induced ; drug therapy ; immunology ; Citrus sinensis ; chemistry ; Disease Models, Animal ; Flavonoids ; administration & dosage ; Freund's Adjuvant ; adverse effects ; Humans ; Interleukin-1 ; immunology ; Male ; Plant Extracts ; administration & dosage ; Random Allocation ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; immunology

D5 receptor is a subtype of dopamine D1-like receptor, and it plays a functional role in many neurological disorders. Some natural compounds from Chinese herbs, which were shown to have the property as that of receptor agonist, might provide a rich source in search of new candidates for therapeutic use. For exploring this possibility, we developed a cell-based high throughput (HTS) D5 receptor assay to screen the herb-based natural compound library established in our centre. The D5 receptor plasmid (hD5R/pcDNA3.1) and reporter gene plasmid (4 x CRE/TK/Luci/pGL3) were co-transfected into HEK293 cell line. After G418 being selected, the monoclonal cell lines bearing hD5R and the reporter gene were established and used for agonist screening. To optimize the assay condition, the effects of some factors such as cell number per well, incubation time, and the doses of SKF38393 (a potent selective partial D1-like agonist) were examined by using forskolin, a positive compound for cAMP response element. The best condition for this HTS assay included: the cell number at 5 x 10(4)/mL, the dose of forskolin at 5-20 micromol/L, the dose of SKF38393 at 100 nmol/L-100 micromol/L, and the agonist incubation time at 6 -8 h. Thereafter, water extracts from more than 200 Chinese herbs in our library were screened and three of these water extracts showed positive activity, with higher or similar activity as SKF38393. In conclusion, we have established a cell-based HTS assay for D5 receptor agonist screening, and by use of this HTS assay, 3 Chinese herbs maybe contain components exhibiting D5 receptor agonist property. This work provides an alternative vision of how to use herb medicines and a way to develop potential drugs for treatment of neurological disorders.
Cell Line ; Dopamine Agonists ; isolation & purification ; Drug Evaluation, Preclinical ; methods ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; High-Throughput Screening Assays ; methods ; Humans ; Plants, Medicinal ; chemistry ; Receptors, Dopamine D5 ; agonists

Objective To observe the clinical efficacy and safety of GINA regimen and GINA regimen combined with oral Huaiqihuang granule in the treatment of children with bronchial asthma.Methods A ran-domized,single blind,multicenter,parallel controlled clinical trial wascarried out.A total of 1 128 patients with bronchial asthma in children were randomized into two groups.The observation group were treated with GINA regimen combined with oral Huaiqihuang granule.The GINA regimen treatment group was treated by GINA reg-imen.Clinical assessment and C-ACT scores was observed in first month,third month,sixth month after treat-ment.Clinical assessment included the times of upper respiratory tract infection occurrence,bronchitis and pneu-monia,asthmatic attacks,application of emergency medicine,hospitalizations due to asthmatic.Drug adverse effect in the two groups was compared.Results The times of upper respiratory tract infection,bronchitis and pneumonia,asthmatic was significantly decreased(P <0.05 ),and C-ACTscores were significantly higher(P <0.05)in the first month,the third month,and the sixth month after treatment.There were 16 cases of drug relat-ed adverse reactions.Seven cases were in observation group(n ﹦7)(1.15%)and 9 cases in the GINA regimen treatment group(n ﹦9)(1.73%).There was no significant difference of adverse effect between the two groups (P >0.05).Conclusion The treatment of bronchial asthma in children with GINA regimen combined with oral Huaiqihuang granule can significantly reduce the incidence of respiratory infections and the number of asthmatic attacks dramatically and safely improve clinical curative effect,asthma control.

Objective To provide data reference for improving the selection criteria of the dosage forms and specifications of the electrolytes and antipyretic analgesics in the Essential Medicines List, and to improve the applicability of these medicines to children and the availability of essential medicines. Methods The market and prices of electrolytes and antipyretic analgesics were retrieved by the system. The data were processed by Excel software, and the different dosage forms were compared and analyzed. Results 8 medication classes were included for adjusting water, electrolytes and acid-base balance, and another 16 classes were analgesic, antipyretic, anti-inflammatory, anti-rheumatic and anti-gout drugs. Those medications were characterized with many registered approval numbers, manufacturers and some considerations for pediatric uses. The proper prices were given for different dosage forms and specifications. There is a room for improvement regarding the specifications of potassium, glucose injections, and acetaminophen preparations. Conclusion The selection of pharmaceutical dosage forms and specifications in the Essential Medicines List should be comprehensively evaluated from the registered approval numbers of base medicines, the manufacturers and related prices in pharmaceutical procurement platforms from various provinces, and the clinical needs for special populations. It is recommended that 10 ml: 1 g potassium chloride injection, 50 ml glucose injection，acetaminophen suppositories and drops were included in the Essential Medicines List.

OBJECTIVE：To compare the similarities and differences of antiepileptic drugs between 2019 edition of WHO Model List of Essential Medicines for Children （called“WHO-EMLc”for short ）and 2018 edition of the National Essential Medicines List （called“NEML”for short ），and to provide reference for the improvement of national essential medicines list and formulation of essential medicines list for children. METHODS ：By means of descriptive analysis ，the differences in the varieties ， dosage forms ，specifications and marker symbols of antiepileptic drugs were compared between WHO-EMLc and NEML. The marketing status of antiepileptic drugs included in WHO-EMLc and NEML were analyzed statistically. RESULTS & CONCLUSIONS：There were 9 kinds of antiepileptic drugs included in WHO-EMLc ，all of which were under the category of anticonvulsant/antiepileptic drugs. There were 6 kinds of antiepileptic drugs in NEML of China ，and the other three kinds of drugs included in WHO-EMLc were included in the category of psychotherapy drugs in NEML. Eight kinds of antiepileptic 126 drugs were shared by NEML and WHO-EMLc ， namely 109614043@qq.com carbamazepine， valproic acid ， phenytoin sodium ， pheno- barbital，lamotrigine，diazepam，lorazepam and midazolam. The special antiepileptic drug in NEML was ocazepine ，and edu.cn the special antiepileptic drug in WHO-EMLC was ethylsu c- cinate. Oral dosage forms involved in WHO-EMLc included oral solution ，ordinary tablet，enteric-coated tablet ，dispersed tablet ， etc.，while oral dosage forms involved in NEML included ordinary tablet ，dispersed tablet and oral solution. In terms of dosage form of a single drug ，the drug specifications in WHO-EMLc were more comprehensive than those in NEML. In WHO-EMLc ， lorazepam was labeled with “□”，indicating that it was more effective and safe in similar drugs . Lamotrigine ，midazolam injection and phenytoin （25 mg∶5 mL and 30 mg∶5 mL）were labeled with “*”，indicating that there were special precautions for the drug or dosage form and specification. In NEML ，diazepam was marked with “*”，and diazepam injection was marked with “△”， indicating that diazepam appeared repeatedly under different classifications ；diazepam injection should be used under the guidance of doctors with corresponding prescription qualifications or under the guidance of specialists ，and the use monitoring and efficacy evaluation should be strengthened. In addition ，most of the antiepileptic drugs included in WHO-EMLc had been marketed in China，but the dosage forms on the market were relatively simple ，which could not meet the drug demand of children. Our country could learn from WHO-EMLc selection method to further improve the national essential medicine list ，formulate essential medicine list for children which was suitable for Chinese national conditionsas soon as possible on the basis of disease spectrum and drug clinical comprehensive evaluation. At the same time ，the government should also encourage the development and production of children’s medicines to ensure that children fairly access to drugs.