Phase Ⅱb trial of in vivo electroporation mediated dualplasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy

AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.

Coexistence and local Mittag–Leffler stability of fractional-order recurrent neural networks with discontinuous activation functions

In this paper, coexistence and local Mittag–Leffler stability of fractional-order recurrent neural networks with discontinuous activation functions are addressed. Because of the discontinuity of the activation function, Filippov solution of the neural network is defined. Based on Brouwer's fixed point theorem and definition of Mittag–Leffler stability, sufficient criteria are established to ensure the existence of (2k + 3)~n (k ≥ 1) equilibrium points, among which (k + 2)~n equilibrium points are locally Mittag–Leffler stable. Compared with the existing results, the derived results cover local Mittag–Leffler stability of both fractional-order and integral-order recurrent neural networks. Meanwhile discontinuous networks might have higher storage capacity than the continuous ones. Two numerical examples are elaborated to substantiate the effective of the theoretical results.

Can increased economic complexity and reduced carbon emissions of the logistics industry go hand in hand?Evidence from countries along the Belt and Road

At present,the main focus of research lies in examining the connection between economic complexity and carbon emissions as a whole,but there is a scarcity of quantitative investigations on the link between the above variables within specific industries.Therefore,this study introduces economic complexity as a new variable to build a panel model within the traditional Environmental Kuznets Curve framework.Based on the data of the countries along the Belt and Road from 1998 to 2018,we used the Granger causality test to examine the causal relationship between variables,and use the Fully Modified Ordinary Least Square and Dynamic Ordinary Least Square methods to estimate the coefficients of variables.The key factor linking economic complexity and carbon emissions in the logistics industry is technology innovation Economic complexity can explain and predict the changes in carbon emissions of logistics industry more reasonably,and the relationship between them in line with the environmental kuznets curve hypothesis.Only high-income countries can increase economic complexity while reducing carbon emissions of logistics industry.Based on the empirical analysis,it is suggested that upper-middle income and lower middle-income countries can formulate relevant policies and regulations,and high-income countries can improve the relevant policies and regulations to promote the reduction of carbon emissions of the logistics industry.Studying the impact of economic complexity on carbon emissions in the logistics industry can help better predict and respond to the impact of climate change on the logistics industry.