OBJECTIVE To optimize the formulation for sustained-release particles of matrine(MAT) and paeonol(PAE) and to primarily evaluate their quality. METHODS The sustained-release particles were fabricated by the extrusion-spheronization method. Single factor analysis was conducted on the main sustained-release materials and their dosage, auxiliary sustained-release materials, and the total amount and proportion of mixed sustained-release materials, using the cumulative release rates of MAT and PAE in vitro as evaluation indicators. By combining central composition design-response surface methodology, the formulation of sustained-release materials was optimized, and the effects of the total amount and mass ratio of ethyl cellulose(EC) and chitosan(CS) on the cumulative release rate and release synchronization of MAT and PAE were investigated. The formulation characteristics, in vitro release, and preliminary stability tests of MAT-PAE-SRPs were evaluated, and the release process kinetic equation was fitted. RESULTS The optimized formulation contained 23.5% EC and 17.1% CS as sustained-release materials. The yield, repose angle, bulk density and friability of final particles were 97.23%, 38.1°, 0.74 g·mL−1 and 0.74%, respectively. The particles showed sustained release pattern in various media and released faster in acidic media with its release percentage >90% at 12 h. The release profile of MAT was fitted best with first order equation, and that of paeonol with Higuchi equation. The formation of SRPs improved the stability of both drugs. CONCLUSION The sustained-release effect of MAT-PAE-SRPs prepared by sustained-release materials EC and CS is significant, and the cumulative release rate and release synchronization of MAT and PAE are good, which can provide reference for the research of dual loaded sustained-release formulations.

The changes of blood-brain barrier (BBB) permeability after ischemic stroke (IS) have important effects on brain edema, brain immune inflammation, hemorrhage transformation and angiogenesis and recanalization in convalescence. Recent studies have shown that the high permeability of BBB is gradually caused by significant up-regulation of endothelial transcytosis (transcellular pathway) several hours after IS and the disintegration of tight junctions (paracellular pathway) several days after IS; the up-regulation of transcytosis is earlier than tight junction destruction and independent of tight junction destruction. Therefore, maintaining a low endothelial transcytosis rate and maintaining a complete tight junction play key roles in the physiological function and brain homeostasis of BBB. The transcellular transport occurrence and regulation have become new topics in targeted therapy of BBB after IS. This review briefly summarizes the biological classification and cellular structure of endothelial transcytosis in BBB, reviews the molecular mechanisms that have been found in recent years to regulate this pathway, and summarizes the post-stroke therapeutic drugs and methods that target this pathway, besides, the relevant treatment strategies and research entry points are prospected.

Objective To determine clinical features and rupture risk of anterior communicating artery (AComA) aneurysms in different age groups. Methods The clinical data of 519 consecutive patients with AComA aneurysms in the First Affiliated Hospital of Wenzhou Medical University between December 2007 and February 2015 were reviewed and divided into younger group (<65 years) and older group (≥65 years). The clinical characteristics and aneurysm morphologies were compared between the two groups. Results There were 390 aneurysms in younger group, and 129 in older groups. For the younger group, hypertension,the size of the aneurysms, maximum height, perpendicular height, size ratio (SR), aspect ratio (AR), aneurysm angle, A1 segment configuration, morphology showed significantly differences in ruptured aneurysms group compared with those in unruptured aneurysms (P<0.05). The multivariate analysis showed that significant difference between the two groups was aneurysm size ( OR＝1.461,95% CI 1.027-2.079, P＝0.035). For the older group, there were statistically significant differences in hypertension,size of the aneurysms, maximum height, perpendicular height, SR, aneurysm angle, vessel size and the distribution of aneurysm projection between the ruptured aneurysms group and unruptured aneurysms group (P<0.05). The multivariate analysis showed that SR ( OR＝11.516,95% CI 1.782-74.445,P＝0.01) was the only significant predictor of aneurysm rupture. Between the younger and older groups,the distributions of sex, hypertension, smoke, vessel size and SR were statistically significant (P < 0.05). Conclusions For younger people, the males who smoked are more likely to have AcomA aneurysms and the size of the aneurysms is independent risk of aneurysm rupture. For older people, the females with hypertension also more often have AcomA aneurysms and the SR is independently associated with aneurysm rupture.

Chinese medicinal materials occupy an important position in China's health industry. However, its overall quality needs to be improved and it is in urgent need of regulation. Exploring the formation of effective organizational mechanisms and industry models has become an urgent need of the industry. In this context, the alliance of coconstruction and sharing Chinese herbal medicine base came into being. The alliance is based on the pursuit of the quality of Chinese herbal medicines and continues to promote the construction of Chinese herbal medicines. The Alliance provides a platform for economic and scientific cooperation in the industry. Its purpose is to guide the promotion of the standardization of local varieties and the construction of modern Chinese medicine agricultural enterprises based on the development needs of Chinese herbal medicine resources and the common interests of all members. As an important content, we will strive to expand the new pattern of coordinated development of traditional Chinese medicine agriculture and industry, explore the establishment of a new organizational system for modern Chinese medicine agricultural production with controllable quality, output and price under the link of production and demand. For the sustainable, stable and healthy development of the Chinese medicine industry, it will serve 1.3 billion people and serve humanity, provide high-quality sustainable Chinese herbal medicine resources. Since its establishment six years ago, the alliance has carried out work on key aspects such as standardized production of Chinese herbal medicines, plant protection, decoction processing, supply and demand docking, medicinal materials standards, poverty alleviation, breeding, and provided technical support to enterprises. During this period, the alliance also proposed the concept of"three-no and one- all"requires the members to take the lead in achieving the standards of"sulfur- free processing, no aflatoxin pollution, pollution-free, traceable throughout the whole", setting a benchmark for the industry.

Objective To investigate the incidence and predictors of cerebral infarction in patients with ruptured ACoA aneurysms, and to provide diagnostic and therapeutic information.Methods A total of 319 patients with ruptured ACoA aneurysms in our hospital from January 2009 to February 2015 were reviewed in this study. The author collected data regarding clinical characteristics, and measured the aneurysm morphologies on CTA images. Age, flow angle, vessel angle were analyzed by independent-samples t tests in patients with or without cerebral infarction. Mann-Whitney U tests were used for aneurysm size, aneurysm height, perpendicular height, neck size, size ratio, aspect ratio, aneurysm angle , World Federation of Neurosurgical Societies (WFNS) grade at admission and Fisher grade. Chi-square tests and Fisher's exact tests were used for sex, histories of hypertension, smoking and stroke, treatment modalities, anterior cerebral A1 segment configuration and angiographic vasospasm on CTA images. The multivariate logistic regression analyses were used to determine the independent risk factors of cerebral infarction using the stepwise regression method. Results Of the 319 patients, there were 253 without and 66 patients with cerebral infarction. Differences of age(53±11 vs 57±12,respectively;t=-2.415, P=0.016), Fisher grade [Ⅰ 23(9.1%), Ⅱ 27(10.7%), Ⅲ 74(29.2%), Ⅳ 129(51.0%) vs Ⅰ 1(1.5%), Ⅱ 7 (10.6% ), Ⅲ 13(19.7% ), Ⅳ 45(68.2% ), respectively;Z=-2.541, P=0.035] and treatment modalities [endovascular coil embolization 155(61.3% ), neurosurgical clipping 98(38.7% ) vs endovascular coil embolization 23(34.8%), neurosurgical clipping 43(65.2%), respectively;χ2=14.810, P<0.001] reached statistical significance. Multivariate analysis showed that Fisher grade Ⅳ(OR=10.36,95%CI 1.34-80.29, P=0.025) and neurosurgical clipping (OR=3.28, 95% CI 1.84-5.86,P<0.001)still had statistical significance. Conclusions Cerebral infarction in patients with ruptured ACoA aneurysms may be associated with Fisher grade and treatment modalities. Although there is difference between the two groups in age, it is not a predictor of the occurrence of cerebral infarction.

Objective To investigate the morphological factors related to the rupture of very small (≤3mm) anterior communicating artery (AComA) aneurysms, which provides basis for decision-making of whether or not taking intervention in very small un-ruptured AComA aneurysms. Methods (1) One hundred patients with primary AComA aneurysms, admitted to our hospital from January 2008 to June 2013, were enrolled; 84 AComA aneurysms were ruptured while 16 were un-ruptured; the morphological parameters of aneurysms were obtained by three-dimensional reconstruction with CT angiography (CTA) of the patients, and the clinical data and aneurysm morphological parameters were compared between the ruptured aneurysm group and the un-ruptured aneurysm group; multivariate Logistic regression was used to analyze the risk factors of small aneurysm rupture in the AComA, and receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of size ratio (SR) of maximum tumor depth to proximal carrier artery diameter in rupture of small aneurysms in the AComA. (2) Ninety-nine patients with primary AComA aneurysms, admitted to our hospital from June 2013 to January 2016, were enrolled; the parameters from the above analyses were applied to these patients to verify their predictive effectiveness. Results (1) Perpendicular height, AR value (Height/Neck), SR value and vessel angle were significantly different between ruptured aneurysm group and un-ruptured aneurysm group (P<0.05); multivariate Logistic analysis indicated that SR value was the independent risk factor of rupture of very small AComA aneurysms (OR=4.201, 95％CI: 1.175-15.019, P=0.012), and the lager the SR value, the higher the risk of rupture; ROC curve analysis revealed that the area under the curve was 0.699 with the optimal cut-off value being 0.9, and its diagnostic sensitivity, specificity and accuracy was 0.786, 0.625 and 0.760, respectively. (2) The SR value was then applied to the 99 patients, showing a stable predictive potential with sensitivity, specificity and accuracy of 0.676, 0.714 and 0.687, respectively. Conclusion SR value (≥0.9) is identified as independent morphological risk factor for rupture of very small AComA aneurysms; SR value is closely related to the state of aneurysms, which help make a better individualized and effective decision on the treatment of very small AComA aneurysms in clinic.

Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome of Salvia miltiorrhiza Bunge (also known as the Chinese herb Danshen), and is widely used to treat atherosclerosis. The pregnane X receptor (PXR) is a nuclear receptor that is a key regulator of xenobiotic and endobiotic detoxification. Tan IIA is an efficacious PXR agonist that has a potential protective effect on endothelial injuries induced by xenobiotics and endobiotics via PXR activation. Previously numerous studies have demonstrated the possible effects of Tan IIA on human umbilical vein endothelial cells, but the further mechanism for its exerts the protective effect is not well established. To study the protective effects of Tan IIA against hydrogen peroxide (H₂O₂) in human umbilical vein endothelial cells (HUVECs), we pretreated cells with or without different concentrations of Tan IIA for 24 h, then exposed the cells to 400 μM H₂O₂ for another 3 h. Therefore, our data strongly suggests that Tan IIA may lead to increased regeneration of glutathione (GSH) from the glutathione disulfide (GSSG) produced during the GSH peroxidase-catalyzed decomposition of H₂O₂ in HUVECs, and the PXR plays a significant role in this process. Tan IIA may also exert protective effects against H₂O₂-induced apoptosis through the mitochondrial apoptosis pathway associated with the participation of PXR. Tan IIA protected HUVECs from inflammatory mediators triggered by H₂O₂ via PXR activation. In conclusion, Tan IIA protected HUVECs against H₂O₂-induced cell injury through PXR-dependent mechanisms.
Apoptosis ; Asian Continental Ancestry Group ; Atherosclerosis ; Endothelial Cells* ; Glutathione ; Glutathione Disulfide ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogen Peroxide ; Inflammation ; Oxidative Stress ; Regeneration ; Rhizome ; Salvia miltiorrhiza ; Triacetoneamine-N-Oxyl ; Xenobiotics

Objective To investigate the immunological characteristics and clinical significance of reactive plasmacytosis in patients with severe fever with throbocytopenia syndrome (SFTS).Methods Bunyavirus-infected patients who were diagnosed with SFTS were collected from March 2015 to October 2015 in Taizhou Hospital.Morphology analysis of bone marrow and peripheral blood (PB) smear, as well as flow cytometry analysis of plasma cell immune phenotype from peripheral blood were conducted.Serum immunoglobulin levels and helper T hymphocytes (Th)1/Th2 cytokine expressions were detected.Mann-Whitney U test was used.Results PB plasma cells from all of the SFTS patients increased in varying degrees, and the phenotype of the plasma cells was CD19+CD38++CD45+CD138+, which indicated normal mature plasma cells.The ratio of PB plasma cells was >0.030 in 10/16 patients, and >0.300 in 2/16 patients.The ratios of PB plasma cells in the patients with severe and critical groups were significantly higher than that in the mild group (0.052 vs 0.016, P<0.05).Monocytoid histiocytes and hemophagocytes were observed in the BM morphology of 9 patients.Three of them were diagnosed as hemophagocytic lymphohistiocytosis (HLH).The ratio of plasma cells was more than 0.030 in the bone marrow of 8 patients.The serum levels of interlewkin (IL)-6, IL-10 and interferon (IFN)-γ in acute phase were significantly elevated with the median level of 49.75 ng/L, 26.98 ng/L (reference value 2.6 to 4.9 ng/L) and 17.57 ng/L, respectively.While the levels of IL-2, IL-4 and twmor necrosis fautor(TNF)-α were not significantly changed.The serum IL-6 and IL-10 levels in the patients with severe and critical groups were both significantly higher than those in the mild group (IL-6: 132.36 vs 22.81 ng/L;IL-10: 75.28 vs 6.33 ng/L, both P<0.05), but the difference of IFN-γ level was not significant (P>0.05).The serum IgG, IgA and IgM levels did not increase in acute stage, with the median of 11.6 g/L, 2.56 g/L and 1.60 g/L (reference value 0.46 to 3.04 g/L), respectively.Conclusion The patients with SFTS show excessive humoral and cellular immunity, and the severity of disease is positively correlated with the ratio of peripheral plasma cells and the levels of cytokines IL-6 and IL-10.