SUMMARY Background Avian influenza A(H7N9) virus has caused human infections in China since 2013, and a large epidemic in 2016–17 has prompted concerns of whether the epidemiology has changed to suggest an increasing pandemic threat. Our study aimed to describe the epidemiological characteristics, clinical severity, and time-to-event distributions of A(H7N9) case-patients in the 2016–17 epidemic wave compared with previous waves. Methods We obtained information about all laboratory-confirmed human cases of A(H7N9) virus infection reported in mainland China as of 23 February 2017. We described the epidemiological characteristics across epidemic waves, and estimated the risk for death, mechanical ventilation, and admission to the intensive care unit for patients who required hospitalization for medical reasons. We estimated the incubation periods, and time delays from illness onset to hospital admission, illness onset to initiation of antiviral treatment, and hospital admission to death or discharge. Findings The 2016–17 A(H7N9) epidemic wave began earlier, spread to more counties in affected provinces and had more confirmed cases than previous epidemic waves. There was an increase in the proportion of cases in middle-aged adults and in semi-urban and rural residents. The clinical severity of hospitalized cases in 2016–17 was comparable to the previous epidemic waves. Interpretation Age distribution and case sources changed gradually across epidemic waves, while clinical severity has not changed substantially. Continued vigilance and sustained intensive control efforts are needed to minimize the risk of human infection with A(H7N9) virus. Funding The National Science Fund for Distinguished Young Scholars (grant no. 81525023).
Background Shufeng Jiedu capsules (SFJDC), a patented herbal drug composed of eight medicinal plants, is used for the treatment of different viral respiratory tract infectious diseases. Based on its antiviral, anti-inflammatory and immunoregulatory activity in acute lung injury, SFJDC might be a promising candidate for the treatment of COVID-19. Purpose To evaluate the antiviral and anti-inflammatory properties and to discover the mechanism of action of SFJDC as a potential drug for the treatment of COVID-19. Furthermore, the study should determine the clinical effectiveness of SFJDC for the treatment of COVID-19. Design We analyzed the antiviral and anti-inflammatory effects of SFJDC in a HCoV-229E mouse model on lung index, virus load in the lung, the release of cytokines, and on T- and B-lymphocytes. The mechanism of action was further investigated by network analysis. Additionally, we investigated data from a clinical pragmatic real-world study for patients with confirmed COVID-19, to evaluate the clinical effect of SFJDC and to determine the best time to start the treatment. Results SFJDC significantly reduced the virus load in the lung of HCoV-229E mice (from 1109.29±696.75 to 0±0 copies/ml), decreased inflammatory factors IL-6, IL-10, TNF-α, and IFN-γ in the lung, and increased the amount of CD4 + and CD8 + cells in the blood compared to the model group. Network analysis revealed that SFJDC reduces the activity of NFκB via several signaling pathways. Quercetin, wogonin, and polydatin bind directly to the main protease (M pro ) of SARS-CoV-2. Clinical data showed that SFJDC, added to standard antiviral therapy (AVD), significantly reduced the clinical recovery time of COVID-19 and fatigue (from 3.55±4.09 to 1.19±2.28 days) as well as cough (from 5.67±5.64 to 3.47±3.75) days compared to AVD alone. SFJDC therapy was significantly more effective when used within the first 8 days after the onset of symptoms. Conclusion SFJDC might be a promising drug for the treatment of COVID-19, but large-scale randomized, double-blinded, placebo-controlled clinical trials are needed to complement the real-world evidence. It might be beneficial to start SFJDC treatment as early as possible in suspected cases of COVID-19.
The fifth epidemic wave of avian influenza A(H7N9) virus in China during 2016–2017 demonstrated a geographic range expansion and caused more human cases than any previous wave. The factors that may explain the recent range expansion and surge in incidence remain unknown. We investigated the effect of anthropogenic, poultry, and wetland variables on all epidemic waves. Poultry predictor variables became much more important in the last 2 epidemic waves than they were previously, supporting the assumption of much wider H7N9 transmission in the chicken reservoir. We show that the future range expansion of H7N9 to northern China may increase the risk of H7N9 epidemic peaks coinciding in time and space with those of seasonal influenza, leading to a higher risk of reassortments than before, although the risk is still low so far.
BackgroundHuman brucellosis has become a major public health problem in China. However, the available clinical data on brucellosis cases are limited.MethodsWe retrospectively reviewed medical charts of 2041 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. These patients were admitted to the Sixth People’s Hospital of the Xinjiang Uygur Autonomous region between 1st January and 31st December 2014. Data on these patients were collected from hospital medical records.ResultsMany patients presented with fatigue (67%), fever (64%), arthralgia (63%) and sweating (54%). High erythrocyte sedimentation rate (ESR) (69%), high C-reactive protein (CRP) (39%), high alanine aminotransferase (ALT) (33%) and high aspartate aminotransferase (AST) (20%) were the most common laboratory findings, especially in acute patients. There was evidence of focal involvement in 90% of patients. A total of 61.5% of brucellosis patients recovered. Multivariate logistic regression analyses suggested that the risk factors key to unfavorable prognosis were: age≥45 years (OR = 1.75, 95% CI 1.36–2.24), back pain (OR = 1.50, 95% CI 1.16–1.94) and joint tenderness (OR = 1.73, 95% CI 1.13–2.65). The increasing duration of the illness increased the risk of poor prognosis.ConclusionPatients with brucellosis showed different characteristics in different clinical stages. In China, the chronicity rate of human brucellosis is high. The risk of poor prognosis is increased in patients aged 45 years or older, patients who have had brucellosis for a substantial period of time, and patients with back pain or joint tenderness. The clinical management of brucellosis should be improved to include sensitive diagnostic methods for subacute and chronic brucellosis.
The aim of the present study was to investigate the pharmacological mechanism of matrine in treatment of COVID-19 combined with liver injury. Potential targets related to matrine, COVID-19 and liver injury were identified from several databases. We constructed PPI network and screened the core targets according to the degree value. Then, GO and KEGG enrichment were carried out. Molecular docking technology was used to verify the affinity between matrine and the crystal structure of core target protein. Finally, real-time RT-PCR was used to detect the effects of matrine on hub gene expression in liver tissue of liver injury mice and lung tissue of lung injury mice to further confirm the results of network pharmacological analysis. The results show that six core targets including AKT1, TP53, TNF, IL6, BCL2L1 and ATM were identified. The potential therapeutic mechanism of matrine on COVID-19 combined with liver injury is closely related to regulate antiviral process, improve immune system and regulate the level of inflammatory factors. Molecular docking showed that matrine could spontaneously bind to the receptor protein and had strong binding force. Real-time RT-PCR demonstrated that matrine could significantly reduce the expression of AKT1, TP53, TNF, IL6 and ATM in mice with liver injury or lung injury (P < 0.05), and increase the expression of BCL2L1 to a certain extent (P > 0.05). Our results indicate that matrine can achieve simultaneous intervention of COVID-19 combined with liver injury by multi-dimensional pharmacological mechanism.
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