Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

[Co-accumulation characters of soil organic carbon and nitrogen under broadleaved Korean pine and Betula platyphylla secondary forests in Changbai Mountain, China.] / 长白山阔叶红松林和杨桦次生林土壤有机碳氮的协同积累特征.

The retrogressive succession is an important driver for dynamics of soil organic carbon (SOC) and total nitrogen (TN). We studied the quantitative distribution and synergistic accumulation characteristics of soil organic carbon and nitrogen in the primary broadleaved Korean pine (KP) forest and Betula platyphylla (BP) secondary forest in Changbai Mountain through paired plot approach. Further, we analyzed the changes of carbon pool and carbon sink effect in temperate forest soil caused by secondary succession and their carbon-nitrogen coupling mechanism. The results showed that the BP forest accumulated more organic carbon and nitrogen in the surface and subsurface soil (0-20 cm) than the KP forest, with relatively low soil C/N. Compared with KP forest, soil organic carbon storage in BP forest (0-20 cm) was higher by 14.7 t·hm-2, equivalent to a soil carbon sink gain of 29.4 g·m-2·a-1. SOC and TN concentrations were positively correlated in each soil layer of all forest types, causing a co-accumulative relationship between SOC and TN. The coefficient of determination (R2) between SOC and TN in the upper soil layers of BP forest was significantly higher than that of the KP forest, indicating that SOC accumulation under the relatively N-rich BP forest was more dependent on the accumulation of organic nitrogen. In the upper soil layers (0-10 cm) where organic matter concentrated, there was no significant difference in light fraction organic carbon and nitrogen stock between the two forest types, whereas the content, stock, and allocation percentage of heavy fraction organic carbon and nitrogen of BP forest were all significantly higher than that of the KP forest, with an average increment of 8.5 t·hm-2 in heavy fraction organic carbon stock. Those results indicated that the increase of soil organic carbon and nitrogen during secondary succession was mainly due to the increases of soil organic carbon and nitrogen pools in mineral-bound stability. The carbon-nitrogen coupling mechanisms in litter decomposition and soil organic matter formation was an important driving mechanisms underlying the changes of soil organic carbon and nitrogen pools during secondary succession.

[Study on realgar nanoparticles inhibition of adenovirus replication at the gene level].

OBJECTIVE: Modeling HAdV-3 infect Hep-2 cells in vitro. The effect of realgar nanoparticles on the expression of HAdV-3 is detected by using fluorescent quantitative PCR. METHODS: The experiment is divided into four groups: Hep-2 cells control group, HAdV-3 virus control group, realgar nanoparticle group and ribavirin group. In order to detect HAdV-3 viral load, add realgar nanoparticles and ribavirin in vitro and remain that vitro for 24 hours when HAdV-3 has infected Hep-2 cells, extract total DNA of Hep-2 cells infected by HAdV-3, and establish Real-time PCR reaction system of every experimental groups. RESULT: The Hep-2 cells group has no amplification curve, the Ct value is greater than 35, which illustrate HAdV-3 pathogen detection is negative. However, realgar nanoparticles group, ribavirin group and the HAdV-3 group have amplification curve, the Ct values are 29.30 +/- 0.08, 33.05 +/- 1.29, 26.01 +/- 0.25 respectively, which illustrate HAdV-3 pathogen detection is positive. The viral copy amount of the adenovirus group(66 699 932 +/- 23.85) is more than that of realgar nanoparticles group (912 435.44 +/- 16.57), and much greater than that of ribavirin group (459 124.84 +/- 12.82) (P < 0.05). CONCLUSION: The model of Hep-2 cell infected by HAdV-3 is reliable. The method of quantitative PCR is sensitive and specific. Realgar nanoparticles have a certain inhibition role for adenovirus nucleic acid replication.

[Study on the effect of realgar nanoparticles on reducing the respiratory syncytial virus type A (RSV-a) replication in vitro].

This study was to establish a model to explore anti- RSV effect of different administration method of Chinese medicine realgar on respiratory syncytial virus type A (RSV-A) replication in Hep-2 cells. Using high-energy ball milling with distilled water to prepare realgar nanoparticles,the concentration of nanometer realgar was tested by molybdenum blue staining method and the size of realgar nanoparticles was tested on Nano Series. Cell culture with ribavirin as a positive control was applied to observe the effect of anti-respiratory syncytial virus type A replication through prevention, treatment or direct inactivation of three different drug administration methods. Realgar nano-particles was found to be a potential inhibitor of RSV-A in a concentration-dependent manner with the median toxic concentration(TC50) of 0.649 microg/mL in Hep-2 cell culture. The median inhibition concentration (IC50) was 0.20 microg/mL when drug was added before virus infection. The IC50 was 0.13 microg/mL when drug was added after virus infection,and it was 0.16 microg/mL when the drug was mixed with virus and added. The therapeutic index (TI) was 3.18, 4.99 and 4.11, respectively. The results showed realgar nanoparticles could inhibit the replication of the RSV and inactivate the RSV in vitro.

[The influence of representative herbs of clearing and detoxifying drugs effect on inflammatory cytokines expression of mice lung homogenate infected by influenza virus FM1].

OBJECTIVE: In order to screen out a certain kind of traditional medicine which has a better role in immune regulatory, the influence of representatives of heat clearing and detoxicating herb on inflammatory cytokines protein expression of mice lung homogenate infected by FM1 have been observed. METHOD: Modeling mice infected by FM1. On the first, third, fifth and seventh day after FM1 infection, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), and gamma-interferon (IFN-gamma) expression in mice lung homogenate of normal control group, model control group, scutellari group, isatidis group, pulsatilla group, polygonum cuspidatum group and oldenlandia group have been tested by ELISA method. RESULT: The expression of TNF-alpha, IL-6, IFN-gamma and IL-10 in mice lung homogenate reaches its peak on the third day after FM1 infection, significantly higher than the control group (P < 0.05). Scutellari and isatidis are two representatives of heat clearing and detoxicating herb, which can decrease the expression of TNF-alpha, IL-6 and IL-1 and increase the expression of IL-10, IFN-gamma. The effect are more pronounced and statistically significant (P < 0.05) on the third and fifth day after infection, pulsatilla, polygonum cuspidatum and oldenlandia can also regulate the inflammatory cytokines, but the effect are not so obvious as scutellari and isatidis. CONCLUSION: Scutellari and isatidis, two representatives of heat clearing and detoxicating herb, have a good intervention on immune damage caused by influenza virus through adjusting the balance of inflammatory cytokines and anti-inflammatory cytokines.

[Study on the effect of realgar nanoparticles anti-adenovirus in vitro].

OBJECTIVE: This study was to establish a model that adenovirus type 3 (HAdV-3) infected on Hep-2 cell in order to explore anti-adenovirus3 (HAdV-3) effect of Chinese medicine realgar in vitro. METHOD: Use high-energy ball milling with distilled water to prepare realgar nanoparticles. The concentration of nanometer realgar was tested by molybdenum blue staining method and realgar nanoparticles' particle size was tested on Nano Series. The technique of cell culture with ribavirin as positiv control was to observe anti-adenovirus effect through prevention, treatment and direct inactivation of three kinds of drug delivery. RESULT: This drug was found to be a potential inhibitor of HAdV-3 in a concentration-dependent manner with the median toxic concentration (TC50) of 0.649 microg/ml in Hep-2 Cell culture. The median inhibition concentration (IC50) was 0.255 microg/ml when drug was added before infection. The IC50 was 0.142 microg/ml when drug was added after virus infection, and it was 0.117 microg/ml as the drug was added after it mixed with virus. The therapeutic index (TI) was 2.55, 4.57 and 5.55 respectively. CONCLUSION: The direct inactivation effect of realgar nanoparticles is the most evident in three drug deliveries manner with the same concentration in vitro.