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This phase 3 trial compared ceftolozane/tazobactam plus metronidazole vs meropenem for the treatment of complicated intra-abdominal infections. Ceftolozane/tazobactam plus metronidazole was noninferior to meropenem. High rates of presumed microbiological eradication of Enterobacteriaceae and Pseudomonas aeruginosa were found with both regimens.
Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin (CDN), the major active ingredient of the traditional Chinese medicinal herb
Alpinia katsumadai
, has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-
κ
B-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner. Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1
β
production induced by LPS
in vivo
, which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.
Background The unprecedented outbreak of 2019-nCoV pneumonia infection in Wuhan City caused global concern, the outflowing population from Wuhan was believed to be a main reason for the rapid and large-scale spread of the disease, so the government implemented a city closure measure to prevent its transmission considering the large amount of travelling before the Chinese New Year.Methods Based on the daily reported new cases and the population movement data between January 1 and 31, we examined the effects of population outflow from Wuhan on the geographical expansion of the infection in other provinces and cities of China, as well as the impacts of the city closure in Wuhan in different scenarios of closing dates.
ResultsWe observed a significantly positive association between population movement and the number of the 2019-nCoV cases. The spatial distribution of cases per unit outflow population indicated that some areas with large outflow population might have been underestimated for the infection, such as Henan and Hunan provinces. Further analysis revealed that if the city closure policy was implemented two days earlier, 1420 (95% CI: 1059, 1833) cases could have been prevented, and if Downloaded from httpsA c c e p t e d M a n u s c r i p t 4 two days later, 1462 (95% CI: 1090, 1886) more cases would be possible.
ConclusionsOur findings suggest that population movement might be one important trigger for the transmission of 2019-nCoV infection in China, and the policy of city closure is effective to control the epidemic.
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