OBJECTIVE To investigate the effects and potential mechanisms of Xiaoqinglong decoction on airway inflammation in asthma with syndrome of cold retention accumulation in lung based on the metastasis-associated lung adenocarcinoma transcript 1 （MALAT1）. METHODS Forty Wistar rats were randomly divided into blank group， model group， dexamethasone group （positive control， 1 mg/kg）， and Xiaoqinglong decoction group （2.72 g/kg）， with 10 rats in each group. A rat model of asthma with syndrome of cold retention accumulation in lung was established， and the corresponding drugs were administered once daily starting from the second day of modeling for 21 consecutive days. Lung histopathological changes and lung function were evaluated. The levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， interferron-γ （IFN-γ）， tumor necrosis factor α （TNF-α）， and interleukin-13 （IL-13） in serum were measured， and the mRNA expression levels of MALAT1， TNF- α， IL-13， IFN- γ， and transient receptor potential melastatin 2 （TRPM2） in lung tissue were determined. Twenty C57BL/6J wild-type mice and twenty C57BL/6J MALAT1（－/－）mice were randomly divided into wild-type model group， wild-type Xiaoqinglong decoction group， MALAT1 model group， and MALAT1（－/－） Xiaoqinglong decoction group， with 10 mice in each group. The same asthma model was E-mail：yan_peizheng@163.com established， and Xiaoqinglong decoction was administered once daily for 21 days starting from the second day of modeling. The serum levels of SOD， MDA， IFN-γ， TNF-α and IL-13 were measured， along with the mRNA and protein expression levels of TRPM2 in lung tissue. RESULTS The results of the rat experiment showed that， compared with model group， the airway resistance， functional residual capacity， the serum levels of IL- 13， TNF-α and MDA as well as inflammatory infiltration and collagen fiber deposition in lung tissue， and the expressions of IL- 13， TNF-α and TRPM2 in lung tissue were all significantly decreased in the treatment group （P＜0.05 or P＜0.01）. The peak expiratory flow， forced expiratory flow at 50% of forced vital capacity， the serum levels of SOD and IFN-γ， and the expression levels of IFN-γ and MALAT1 in lung tissue were significantly increased （P＜0.05 or P＜0.01）. The results of the mice experiment demonstrated that， compared with the wild-type model group， serum levels of IL-13， TNF-α and MDA in wild-type xiaoqinglong decoction group were significantly reduced （P＜0.05 or P＜0.01）， while serum IFN-γ levels and SOD activity were significantly increased （P＜0.01）. Compared with the wild-type Xiaoqinglong decoction group， the MALAT1（－/－） Xiaoqinglong decoction group showed significantly decreased serum IFN-γ levels and SOD activity （P＜0.01）， along with significantly increased levels of IL-13， TNF-α and MDA （P＜0.05 or P＜0.01）， as well as significantly elevated TRPM2 mRNA and protein expression in lung tissue （P＜0.05）. CONCLUSIONS Xiaoqinglong decoction may alleviate airway inflammation by regulating the expression of MALAT1， modulating oxidative stress， inhibiting TRPM2 activation， and reducing the release of pro-inflammatory cytokines.

OBJECTIVE To investigate the effects of Ephedra-Cinnamomum couplet medicinals on respiratory function and airway inflammation in rats with asthma of cold-fluid retention in lung syndrome and its mechanism. METHODS Sixty Wistar rats were randomly divided into blank group， model group， dexamethasone group [1 mg/（kg·d）]， and Ephedra-Cinnamomum low-， medium-， high-dose groups [0.234， 0.936， 1.872 g/（kg·d）]， with 10 rats in each group. The model and treatment groups were sensitized by intraperitoneal injection of antigen solution （ovalbumin 100 mg + aluminum hydroxide 100 mg） and challenged with 1% ovalbumin nebulization， along with exposure to a cold environment and ingestion of cold water， to establish the asthma model with cold-fluid retention in lung syndrome. From day 2， rats received corresponding drugs or normal saline intragastrically， once a day， for 21 consecutive days. The general behavioral changes in each group of rats were observed during the experimental process. The lung function parameters [peak expiratory flow （PEF）， airway resistance （Raw）， functional residual capacity （FRC）， expiratory flow at 50% of forced vital capacity （EF50%）] Δ 基金项目 国家自然科学基金青年科学基金项目（No.82004233）； were measured before modeling and after the last medication as well as serum contents of interleukin-6 （IL-6）， IL-13， tumor necrosis factor- α （TNF- α） and interferon-gamma （IFN- γ） after the last medication were determined； the histopathological morphological changes in the lung tissues of rats were also observed； mRNA expressions of IL-6， IL-3， TNF-α， IFN-γ， thymic stromal lymphopoietin （TSLP）， and Toll-like receptor 4 （TLR4）， as well as protein expressions of TSLP and TLR4 were determined in lung tissue. RESULTS Compared with model group， the lung tissue damage of rats was relieved significantly； Raw， FRC， the contents and mRNA expression levels of IL-6， IL-13 and TNF-α， as well as the mRNA and protein expressions of TSLP and TLR4 were significantly decreased （P＜0.05）， while the contents and mRNA expressions of PEF， EF50 % and IFN-γ were significantly increased in the dexamethasone group and Ephedra-Cinnamomum medium- and high-dose groups （P＜0.05）. Moreover， only a few rats in the two groups exhibited typical symptoms of asthma. CONCLUSIONS Ephedra-Cinnamomum couplet medicinals improve respiratory function and ameliorate airway inflammation in asthma rats with cold-fluid retention in lung syndrome， the mechanism of which may be associated with inhibiting TSLP/TLR4 signaling pathway and modulating Th1/Th2 imbalance.

Due to multiple factors such as the closed research and development (R&D) system and differences in international mainstream regulatory standards, the internationalization of Chinese patent medicines has been weakly promoted. Multi-case analysis based on grounded theory can identify the key factors that promote the internationalization of Chinese patent medicines in each link, so as to put forward suggestions for promoting the internationalization of Chinese patent medicines. By retrieving the research literature on the internationalization of Chinese patent medicines included in CNKI, and further searching the official websites of the corresponding enterprises, as well as the news reports, comments and analysis of related events on official websites such as Xinhua News Agency, People's Network and China Medical Device Network, 27 textual materials were obtained, 6 classic cases of international registration of Chinese patent medicines were summarized, and three-level coding was used to organize and analyze them level by level. 25 initial categories and 7 main categories were extracted, and 4 core categories were finally summarized: promote R&D and promotion in advantageous areas based on international needs, build a quality control system in line with the international standards, select appropriate national markets based on international demand, and carry out international collaborative R&D in the whole life cycle. Based on this, suggestions were put forward: in order to promote the internationalization process of Chinese patent medicines, priority disease types and product formulations should be determined based on demand during the drug discovery phase; full cycle international cooperation in drug R&D should be carried out; a Chinese patent medicines and simple preparations supervision system that is in line with the international standards in the link of drug quality supervision should be constructed; countries with flexible and experienced regulatory rules in the drug approval and marketing process should be chosen.

Objective:To observe any effect of bilateral high-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellum on the swallowing of stroke survivors with dysphagia.Methods:Thirty-eight patients with post-stroke dysphagia were randomly divided into a cerebellar stimulation group of 20 and a sham group of 18. In addition to drug therapy and physical rehabilitation training, the cerebellar stimulation group received 500 pulses of rTMS of the cerebellum daily at 10Hz and 120% of the resting movement threshold lasting 1s at 9s intervals. The sham stimulation group was treated with sham rTMS (with the angle between the stimulation coil and the scalp at 90°). Twenty minutes later, both groups were given 30 minutes of routine swallowing training daily by the same speech therapist. The treatment was administered 5 times a week for 3 weeks. Before the treatment and afterward, both groups′ swallowing was evaluated y videofluoroscopic swallowing study (VFSS), using a functional dysphagia scale (FDS) and using the Rosenbek penetration aspiration scale (PAS). Oral transport time, swallowing response time, pharyngeal transport time, laryngeal vestibular closure time and upper esophageal sphincter opening duration were recorded, and the changes in swallowing function and swallowing time parameters before and after the treatment were compared between the two groups.Results:Before the stimulation there were no significant differences between the two groups. Afterward, the average PAS and FDS scores of both groups had improved significantly, but with significantly greater improvement in the cerebellar stimulation group than in the sham group. Average oral transit time and swallow response time had shortened significantly, but with significantly shorter time, on average, in the cerebellar stimulation group.Conclusion:Bilateral high-frequency rTMS of the cerebellum can improve the swallowing of persons with dysphagia, and shorten their oral transit time and swallow response time.

To establish an animal model of acute-on-chronic liver failure (ACLF) that would replicate the pathological process of ACLF in humans, rats were administered porcine serum (PS) for 11 weeks. Liver fibrosis was determined by pathological and biochemical assessments. The animals then were injected with d-galactosamine (d-gal) and lipopolysaccharide (LPS). The survival times of animals with cirrhosis and ACLF were determined over 48 h. Other animals were killed at 0, 4, 8 and 12 h after administration of d-gal/LPS. Liver injury was assessed by histopathological analysis and biochemical indices, and apoptosis was detected by Western blot and TUNEL analysis. After PS administration for 11 weeks the serum levels of hyaluronic acid and N-procollagen type III peptide increased significantly, and serious fibrosis and cirrhosis was observed at weeks 10 and 11. Cirrhotic rats were injected with d-gal/LPS to induced ACLF; the rate of mortality over 48 h was 80%. ALT and AST levels increased markedly at 4 h, but decreased significantly at 8 and 12 h post-treatment. The total bilirubin, direct bilirubin, and total bile acids levels increased markedly at 8 and 12 h. Clotting times, TNF-and IL-6 levels increased significantly, except for 12 h post-treatment. Apoptosis, inflammation and necrosis were elevated as determined by hematoxylin-eosin staining and TUNEL assays. BCL-2 levels decreased significantly, While BAX levels increased significantly. Cytochromeexpression peaked at 8 h post-d-gal/LPS treatment. In conclusion, an ACLF model induced by PS and d-gal/LPS was established and the underlying mechanisms of ACLF development were explored.

Primary dysmenorrheal is one of the most common diseases in gynecology,which seriously affects the physical and men-tal health of women, therefore, the effective prevention and treatment of primary dysmenorrheal is a problem in medical field. The etiol-ogy of primary dysmenorrheal is very complicated, and in recent years, there are more and more domestic and foreign scholars studying on its pathogenesis and treatment. Modern medicine has some shortcomings in the treatment of dysmenorrheal including side effects and so on. Traditional Chinese medicine has unique advantages in the treatment of primary dysmenorrheal. Combined with the recent rele-vant reporters, the article reviewed the pathogenesis of primary dysmenorrheal from both traditional Chinese medicine and modern medi-cine aspects, and the research progress in traditional Chinese medicine treatment of primary dysmenorrheal was also reviewed to provide better guidance for the treatment of primary dysmenorrheal.

Objective: To optimize the extraction technology of Panax notoginseng and Scrophulariae radix from Rupixiao granule.Methods: With the dry extract rate and transfer rates of ginsenoside Rg1, ginsenoside Rb1 and harpagoside as the comprehensive index, the orthogonal design was adopted to investigate the effects of the amount and concentration of ethanol, extracting duration and times on the extraction technology.The contents of ginsenoside Rg1, ginsenoside Rb1 and harpagoside were determined by HPLC.Results: The optimal extraction technology was extracted twice with 8-fold amount of 60% ethanol with 2 h per time.The transfer rate of ginsenoside Rg1, ginsenoside Rb1 and harpagoside was (79.4%±1.56%), (42.62%±0.68%) and (44.89%±0.58%)(n=3), respectively.The dry extract rate was (20.99%±0.411%).Conclusion: The optimized extraction technology is stable and feasible, which can be used for extracting Panax notoginseng and Scrophulariae radix from Rupixiao granule.

Objective: To review the application of polymeric micelles as the vehicles in transdermal delivery systems.Methods: Based on the recently published papers, the researches of preparation, penetration mechanism, drug release and application of polymeric micelles in transdermal delivery systems were classified and summarized.Results: Polymeric micelles were extensively applied as drug vehicles due to the ability of solubilization and transdermal absorption enhancement.Conclusion: Polymeric micelles can be used as promising vehicles in transdermal delivery systems, which show a good application prospect.

Objective:To investigate the significance of metronomic therapy against Helicobacter pylori (HP) in the prevention of delayed emesis caused by chemotherapy of gastric cancer compared with the routine therapy. Methods:HP infection was confirmed by carbon 14 breath test in 69 patients. Combined chemotherapy was employed for the first time in the patients, who were divided into groups A and B. Metronomic therapy was administered to group A (n=33). Briefly, triplex medication against Helicobacter bacil i triplex was oral y ad-ministered:20 mg of omeprazole and 0.5 g of amoxicillin twice daily, with 200 mg of tinidazole once daily. Oral administration in group A was performed for 14 days from the start of chemotherapy. Simultaneously, 5-HT3 antagonists were applied. By contrast, group B (n=36) was treated with the oral triplex medication against Helicobacter bacilli:20 mg of omeprazole and 1 g of amoxicillin twice daily, with 400 mg of tinidazole once daily. Oral administration in group B was performed for 7 days from the beginning of chemotherapy with simultaneous application of 5-HT3 antagonists. Both groups were simultaneously treated with the 5-HT3 antagonist granisetron at 3 mg once daily during the administration of anti-HP therapy. HP infection was evaluated by immunohistochemistry before and after treatment. Results:The total effective rate for emesis in group A was 84.85%, which was significantly higher than that in group B (55.56%). Among the patients in group A, 15.15%demonstrated delayed emesis, compared with 44.44%of the patients in group B;the number of individuals was significantly lower in group A than in group B. The average number of chemotherapy cycles in group A was significantly higher than that in group B at 3.1 cycles;the difference between groups was statistically significant (P<0.05). In addition, the HP infection in group B was significantly lower than that in group A (P<0.05). Conclusion:Compared with one week of treatment with the conventional dose, two weeks of low-dose metronomic therapy against HP during chemotherapy can significantly reduce chemotherapy induced delayed emesis and can significantly reduce the degree of HP infection in patients with gastric cancer with HP infection.

Objective To study effects of Rupixiao granules on contraction of uterus of mice in vitro. Methods Mouse model with isolated uterine contraction was established. The mice pretreated with estradiol benzoate were sacrificed and then the uteri were taken out. The normal contractions were recorded by the biological function system. Effects of 10, 20, 30, 40, 50, 60 mg.mL-1 Rupixiao granules on spontaneous and oxytocin-induced (5 U.L-1) uterine contractions were recorded,inhibition of Rupixiao granules on mean constriction amplitude,constriction frequency and contraction activity of pitocin-pretreated uterus was observed and the inhibition rates were calculated. Results Compared with the baselines, the amplitude, frequency, activity of spontaneous uterine contraction were significantly down-regulated by Rupixiao solution at a range of 10-60 mg.mL-1 ,as well as it could inhibit oxytocin-induced spasmodic contraction of isolated uterus at 10-50 mg . mL-1 ( P<0. 01 ) . Conclusion The Rupixiao granules inhibits spontaneous contraction of isolated mouse uteri and oxytocin-induced spasm of uterine smooth muscle in vitro.