Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice

Effective tuberculosis (TB) vaccine should target tubercle bacilli with various metabolic states and confer long-term protective immunity. In this study, we constructed a novel multi-stage TB subunit vaccine based on fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-HspX (LT69 for short) which combined early expressed antigens and latency-associated antigen. The fusion protein was mixed with an adjuvant being composed of N, N’-dimethyl-N, N’-dioctadecylammonium bromide (DDA) and polyriboinosinic polyribocytidylic acid (PolyI:C) to construct subunit vaccine, whose immunogenicity and protective ability were evaluated in C57BL/6 mice. The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge. Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination. In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.National Major Science and Technology Projects (China) (2012ZX10003-008-006)National Natural Science Foundation (China) (31470895)National Natural Science Foundation (China) (81072499)China. Ministry of Education (Doctoral Fund 20120211110038

Latest Study on the Relationship between Pathological Process of Inflammatory Injury and the Syndrome of Spleen Deficiency and Fluid Retention in Alzheimer’s Disease

Inflammation exists throughout the incidence and progression of Alzheimer’s disease (AD). Traditional Chinese medicine (TCM) differentiates the pathogenesis of AD as kidney essence deficiency and qi and blood deficiency as well as blood stasis in syndromes, whose action mechanisms are all associated with the intervention in its inflammatory process. Our preliminary studies both in clinic and in vitro have demonstrated that the syndrome of spleen deficiency and fluid retention has also been an important pathogenesis for the incidence and development of AD. Hence, the paper aims to further illustrate the correlation between inflammatory process in AD and the syndrome of spleen deficiency and fluid retention, laying solid foundation for the application of invigorating the spleen and eliminating the dampness in clinic, and enriching the theoretical connotation for AD prevention and treatment in TCM

Fusion Cytokines IL-7-Linker-IL-15 Promote Mycobacterium Tuberculosis Subunit Vaccine to Induce Central Memory like T Cell-Mediated Immunity

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is among the most serious infectious diseases worldwide. Adjuvanted protein subunit vaccines have been demonstrated as a kind of promising novel vaccine. This study proposed to investigate whether cytokines interliukine-7 (IL-7) and interliukine-15 (IL-15) help TB subunit vaccines induce long-term cell-mediated immune responses, which are required for vaccination against TB. In this study, mice were immunized with the M. tuberculosis protein subunit vaccines combined with adnovirus-mediated cytokines IL-7, IL-15, IL-7-IL-15, and IL-7-Linker-IL-15 at 0, 2, and 4 weeks, respectively. Twenty weeks after the last immunization, the long-term immune responses, especially the central memory-like T cells (TCM like cell)-mediated immune responses, were determined with the methods of cultured IFN-γ-ELISPOT, expanded secondary immune responses, cell proliferation, and protective efficacy against Mycobacterium bovis Bacilli Calmette-Guerin (BCG) challenge, etc. The results showed that the group of vaccine + rAd-IL-7-Linker-IL-15 induced a stronger long-term antigen-specific TCM like cells-mediated immune responses and had higher protective efficacy against BCG challenge than the vaccine + rAd-vector control group, the vaccine + rAd-IL-7 and the vaccine + rAd-IL-15 groups. This study indicated that rAd-IL-7-Linker-IL-15 improved the TB subunit vaccine’s efficacy by augmenting TCM like cells and provided long-term protective efficacy against Mycobacteria

Accuracy of CHIRPS Satellite-Rainfall Products over Mainland China

Precipitation is the main component of global water cycle. At present, satellite quantitative precipitation estimates (QPEs) are widely applied in the scientific community. However, the evaluations of satellite QPEs have some limitations in terms of the deficiency in observation, evaluation methodology, the selection of time windows for evaluation and short periods for evaluation. The objective of this work is to make some improvements by evaluating the spatio-temporal pattern of the long-terms Climate Hazard Group InfraRed Precipitation Satellite’s (CHIRPS’s) QPEs over mainland China. In this study, we compared the daily precipitation estimates from CHIRPS with 2480 rain gauges across China and gridded observation using several statistical metrics in the long-term period of 1981–2014. The results show that there is significant difference between point evaluation and grid evaluation for CHIRPS. CHIRPS has better performance for a large amount of precipitation than it does for arid and semi-arid land. The change in good performance zones has strong relationship with monsoon’s movement. Therefore, CHIRPS performs better in river basins of southern China and exhibits poor performance in river basins in northwestern and northern China. Moreover, CHIRPS exhibits better in warm season than in Winter, owing to its limited ability to detect snowfall. Nevertheless, CHIRPS is moderately sensitive to the precipitation from typhoon weather systems. The limitations for CHIRPS result from the Tropical Rainfall Measuring Mission (TRMM) 3B42 estimates’ accuracy and valid spatial coverage

Comparing Regional Distribution Equity among Doctors in China before and after the 2009 Medical Reform Policy: A Data Analysis from 2002 to 2017

Background: Although China began implementing medical reforms in 2009 aimed at fair allocation of the regional distribution of doctors, little is known of their impact. This study analyzed the geographic distribution of doctors from 2002 to 2017. Methods: This study calculated the Gini coefficient and Theil index among doctors in the eastern, central, and western regions (Category 1) of China, and in urban and rural areas (Category 2). The statistical significance of fairness changes was analyzed using the Mann–Whitney U test. Results: The annual growth rates of the number of doctors for the periods from 2002 to 2009 and 2010 to 2017 were 2.38% and 4.44%. The Gini coefficients among Category 1 were lower than those in Category 2, and statistically decreased after the medical reforms (P < 0.01) but continued to increase in Category 2 (P = 0.463). In 2017, the Theil decomposition result of Category 1 was 74.33% for the between-group, and in Category 2, it was 95.22% for the within-group. Conclusions: The fairness among the regional distribution of doctors in Category 1 is now at a high level and is better than that before the reforms. While the fairness in Category 2 is worse than that before the reforms, it causes moderate inequality and is continually decreasing. Overall unfairness was found to be derived from the between-group

A first look at the effects of long inter-pregnancy interval and advanced maternal age on perinatal outcomes: A retrospective cohort study.

BackgroundAfter China's One-child Policy was replaced with the Two-child Policy in 2013, the rate of second pregnancies with a longer inter-pregnancy interval (IPI) has suddenly increased in that country; however, the effect of long IPIs (≥49 months) on perinatal outcomes remains unreported.MethodsThis was a retrospective cohort study in China from July 2015 through June 2016. We used univariate and multivariate logistic regression models to test the associations among IPI, maternal age, and perinatal outcome (preterm delivery, term low birthweight, and small-for-gestational age). We included baseline factors and variables with biological plausibility as confounders.ResultsOur analytic sample included 3309 second pregnancies. The mean IPI was 75.36 months. Compared with second pregnancies with a short IPI of 7-24 months, those with long IPIs had higher adjusted odds ratios (ORs) of preterm delivery (1.70-2.00 [95% CI 1.20-3.33]) and term low birthweight (2.16-2.68 [1.10-6.17]), but not small-for-gestational age. The mean maternal age at current delivery was 32.0 years. Compared with the reference group (25-29 years), second pregnancies for the oldest maternal age group (≥35 years) showed no statistically significant increased ORs for adverse perinatal outcomes.ConclusionLong IPI is a significant contributor to preterm delivery and term low birthweight. Health care providers need to pay close attention to preterm delivery prevention and fetal growth during prenatal care for second pregnancies where the mothers have long IPIs

A study protocol of mobile phone app-based cognitive behaviour training for the prevention of postpartum depression among high-risk mothers

Background The changes in China’s family planning policy in recent years have led to changes in the age structure of pregnant women, and the prevalence of postpartum depression (PPD) is also on the rise. Cognitive Behaviour Training (CBT) as an effective intervention is widely used for postpartum depression. However, the shortage and health disparities of mental health resources, the stigma of postpartum depression in postpartum women and the need for postpartum recovery and child care prevent postpartum women from seeking traditional face-to-face CBT. Therefore, the purpose of this proposed study is to examine the effect of mobile phone applications (App) based CBT on postpartum depression, anxiety, pressure and parenting sense of competence. Methods A double blind, randomized controlled trial will be used in this study to examine the effectiveness of App-based CBT in reducing the prevalence of postpartum depression compared with usual postpartum care in China. A total of 120 participants will be recruited in this study. The intervention consists of a weekly theme module app for continuous six weeks, each module including learning content and assignments. The control group received usual postpartum care content through the App. Outcome measures include postpartum depression, anxiety, pressure and parenting sense of competence at 0-, 3- and 6-month after the intervention. Discussion If our intervention is effective, it will provide a time-friendly and unrestricted intervention for the psychological care of perinatal women, which can effectively solve the shortage and unevenness of mental health resources. Trial registration Chinese Clinical Trial Registry, ChiCTR1900020735. Registered 15 January 2019

The human platelet transcriptome and proteome is altered and pro-thrombotic functional responses are increased during prolonged hypoxia exposure at high altitude

Exposure to hypoxia, through ascension to high altitudes (HAs), air travel, or human disease, is associated with an increased incidence of thrombosis in some settings. Mechanisms underpinning this increased thrombosis risk remain incompletely understood, and the effects of more sustained hypoxia on the human platelet molecular signature and associated functional responses have never been examined. We examined the effects of prolonged (≥2 months continuously) hypobaric hypoxia on platelets isolated from subjects residing at HA (3,700 meters) and, for comparison, matched subjects residing under normoxia conditions at sea level (50 meters). Using complementary transcriptomic, proteomic, and functional methods, we identified that the human platelet transcriptome is markedly altered under prolonged exposure to hypobaric hypoxia at HA. Among the significantly, differentially expressed genes (mRNA and protein), were those having canonical roles in platelet activation and thrombosis, including membrane glycoproteins (e.g. GP4, GP6, GP9), integrin subunits (e.g. ITGA2B), and alpha-granule chemokines (e.g. SELP, PF4V1). Platelets from subjects residing at HA were hyperactive, as demonstrated by increased engagement and adhesion to fibrinogen, fewer alpha granules by transmission electron microscopy, increased circulating PF4 and ADP, and significantly enhanced clot retraction. In conclusion, we identify that prolonged hypobaric hypoxia exposure due to HA alters the platelet transcriptome and proteome, triggering increased functional activation responses that may contribute to thrombosis. Our findings may also have relevance across a range of human diseases where chronic hypoxia, platelet activation, and thrombosis are increased