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BackgroundThe Systemic Immune-Inflammatory Index (SII) and Systemic Inflammatory Response Index (SIRI) are novel composite inflammatory markers. Previous studies suggest that obesity in individuals correlates with persistently low levels of chronic inflammation. This study aims to explore the association between SII and SIRI and Body Mass Index (BMI) among children and adolescents.MethodsA cross-sectional survey was conducted using the National Health and Nutrition Examination Survey (NHANES) dataset from 2 consecutive cycles from 2017-2020. Multivariate linear regression models were employed to examine the linear relationships between BMI and SII and SIRI. Non-linear associations were explored using smooth curve fitting and threshold effect analysis.ResultsA total of 2980 children and adolescents aged 6-19 years were included in this population-based study. In the population description of body mass index categories, we found progressively higher levels of SII and SIRI, notably peaking among obese children (SII mean ± SD: 528.83 ± 285.46; SIRI mean ± SD: 1.12 ± 0.79). Weighted multivariate linear regression confirmed a significant positive association between BMI and both inflammatory indices (P < 0.0001). Subgroup analyses revealed consistent correlations across gender divisions and highlighted a non-linear relationship between BMI and SII.ConclusionsSII and SIRI are positively associated with BMI in children and adolescents, indicating their potential as markers for assessing systemic inflammation in pediatric obesity. Further large-scale prospective studies are required to substantiate these findings.

Abstract BackgroundCardiovascular diseases (CVDs) and neoplasms are leading causes of mortality worldwide. ObjectiveThis study aims to provide a comprehensive analysis of the mortality burden and disability-adjusted life years (DALYs) attributable to CVDs and neoplasms in Western Europe, investigate associated risk factors, and identify regional disparities. Additionally, the study evaluates the effectiveness of the Action Plan for the Prevention and Control of Non-Communicable Diseases (NCDs) in promoting healthier lives in the region. MethodsThe study collected data on mortality and DALYs due to CVDs and cancers from 24 Western European countries using the Global Burden of Disease Study 2021. The analysis explored age, sex, and country-specific patterns, as well as risk factors contributing to these deaths. Additionally, the study examined time trends by calculating the annual percent change in mortality rates from 1990 to 2021 by region and cause. ResultsIn 2021, CVDs and neoplasms accounted for 27.8% and 27.1% of total deaths in Western Europe, with age-standardized death rates of 106.8 and 125.8 per 100,000, respectively. The top two CVDs in this region were ischemic heart disease and stroke, with age-standardized death rates of 47.27 (95% uncertainty interval [UI] 50.42-41.45) and 27.06 (95% UI 29.17-23.00), respectively. Similarly, the top two neoplasms were lung cancer and colorectal cancer, with age-standardized death rates of 26.4 (95% UI 27.69-24.47) and 15.1 (95% UI 16.25-13.53), respectively. Between 1990 and 2021, CVD mortality rates decreased by 61.9%, while cancer rates decreased by 28.27%. Finland had the highest CVD burden (39.5%), and Monaco had the highest rate of cancer-related deaths (34.8%). Gender differences were observed, with males experiencing a higher burden of both CVDs and cancer. Older individuals were also more at risk. Smoking had a stronger impact on CVD mortality and DALYs in males, while a higher Human Development Index was associated with increased cancer deaths and DALYs in females. ConclusionsThe study findings highlight the substantial burden of NCDs, particularly CVDs and cancer, in Western Europe. This underscores the critical need for targeted interventions and effective implementation of the Action Plan for the Prevention and Control of NCDs to achieve the goal of ensuring healthy lives for all.

Background: Many studies have shown that total sleep deprivation (TSD) impairs the attention network, which includes three subcomponents as follows: alerting, orienting, and executive control. However, the specific attention network(s) damaged by TSD remains unclear. Methods: Twenty two participants were enrolled to complete the attention network test (ANT) before and after 36 h of TSD with simultaneous electroencephalography recordings. Results: The repeated-measures analysis of variance of the response time (RT) suggested that the interaction effect between sleep conditions (before versus after TSD) and target congruence (incongruent versus congruent target) was significant; that is, the RT of the incongruent target was longer than that of the congruent target, whereas this difference disappeared after TSD. Furthermore, the interaction effect of sustained potential (SP) amplitude between the sleep conditions and target congruence was significant; that is, the incongruent target invoked a less positive sustained potential amplitude after than before TSD; whereas that invoked by the congruent target was not. Conclusion: TSD selectively impairs attention networks. TSD affects the executive control network the most, which is followed by the alerting network rather than the orienting network. This provides a new perspective for understanding how shortened sleep affects attention. Clinical Trial Registration: No: ChiCTR2400088448. Registered 19 August 2024, https://www.chictr.org.cn.

Background. The activation of complement is involved in monocyte recruitment in tuberculous pleural effusion (TPE), while the role of the cleavage product of complement C3 in this process needs further research. Methods. The expression of complement components in pleural biopsy specimens of TPE patients was measured. The concentration of cleavage products of complement was tested in TPE by ELISA. Moreover, the colocalizations of C3b and CR1, C3d and CR3, and CXCL12 and CXCR4 in monocytes and pleural mesothelial cells (PMCs) isolated from TPE were determined by an immunofluorescent assay. Monocyte chemotaxis assay was analyzed via transwell chambers. Results. Three pathways of the complement system were activated in tuberculous pleurisy. In patients with TPE, C3 lysis was more active than peripheral blood in pleural cavity. Tuberculous protein Mpt64 and anaphylatoxin C3a could significantly promote CXCL12 production in human PMCs isolated from TPE. C3b-CR1, C3d-CR3, and CXCL12-CXCR4 were colocalized in PMCs and monocytes from TPE. The recruitment of monocytes into TPE mediated by PMCs could be inhibited by anti-CR1, anti-CR3, and anti-CXCL12 monoclonal antibodies (mAbs). Conclusions. Complement activates strongly in TPE, and PMCs induced monocytes to the pleural cavity through C3a, C3b, and C3d.

Abstract Background Prostate, bladder and kidney cancers are common age-related genitourinary cancers. China's population is aging at an increasing rate, so predicting the morbidity and mortality of prostate, bladder, and kidney cancer in China is of great significance to provide epidemiological evidence for forward planning and implementation of national health policies. Methods Numbers of incidences and deaths by cancer (prostate, bladder and kidney), sex (male and female) and age groups from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) Study. We applied Bayesian age-period-cohort models to predict incidences and deaths to 2030. We also calculated Age-standardized incidence rate (ASIR) and mortality rate (ASMR), their trends were quantified by estimated average percentage change (EAPC) and 95% confidence interval (CI). Results Predictions suggest that by 2030, there will be 315,310 prostate cancer cases, 192,390 bladder cancer cases and 126,980 kidney cancer cases. The ASIRs will increase to 25.54/100,000 for prostate cancer (EAPC: 2.88, 95% CI, 2.84, 2.93), 7.54/100,000 for bladder cancer (EAPC: 2.58, 95% CI, 2.54, 2.61) and 5.63/100,000 for kidney cancer (EAPC: 4.78, 95% CI, 4.54, 5.02). Number of deaths in 2030 will be 81,540, 61,220, and 41,940, respectively. Different ASMR changes are observed, the ASMR for prostate cancer will drop to 7.69/100,000 (EAPC: -0.29, 95% CI, -0.31, -0.27), the ASMR for bladder cancer will stabilize at 2.49/100,000 (EAPC: 0.00, 95% CI, -0.02, 0.03), the ASMR of kidney cancer will increase to 1.84/100,000 (EAPC: 3.45, 95% CI, 3.22, 3.67). From 1990 to 2030, higher numbers of cases and rates are reported among males and in the 60 plus age group, both ASIR and ASMR of bladder and kidney cancers presents progressively widening differences between both males and females and between the

Abstract Background Clinical research has frequently not been taught in a practical way, often resulting in a very didactic approach rendering it not very accessible for medical undergraduates. Simulation can provide an immersive, interactive, and reflective experience and may be applied to the clinical research curriculum. Methods A 7-step model, modified from Kern’s six-step approach and Khamis’s stepwise model, was used to develop the curriculum. A questionnaire survey on undergraduates’ attitude towards, knowledge and practice of clinical research and simulation education was conducted to generate a targeted needs assessment. The simulation framework was integrated into the development of educational strategies. Experts were consulted to assess the curriculum prior to implementation. Results Talent construction in China needs an innovative capability-enhanced clinical research curriculum. Sixty-six clinical undergraduates in our school completed the survey. 89.39% (59/66) of them hadn’t participated in clinical research, while 93.94% (62/66) would like to conduct clinical trials if possible. 75.76% of respondents didn’t have knowledge of or practical abilities in clinical trials. The mean score for practical ability (2.02 ± 0.92) was lower than that of knowledge (2.20 ± 0.93) (P

Abstract Background Monocytes are involved in tumor growth and metastasis, but the distribution of monocyte phenotypes and their role in the development of malignant pleural effusion (MPE) remains unknown. Methods A total of 94 MPE patients (76 diagnosed with adenocarcinoma lung cancer and 18 with squamous cell lung cancer) and 102 volunteers for health examination in Xiangya Hospital from December 2016 to December 2019 were included in the study. Results The distribution of monocyte subtypes identified by the expression of CD14 and CD16 were analyzed by flow cytometry. The proportion of CD14++CD16+ intermediate monocytes were significantly increased in pleural effusion of MPE patients. The complement system components were assayed by immunohistochemistry and ELISA, and higher expression of the classical and alternative pathways were detected in malignant pleural tissue. Transwell assay further revealed that C5a enhanced the infiltration of intermediate monocytes into the pleural cavity by promoting CCL2 production in pleural mesothelial cells (PMCs). In addition, C5a promoted the secretion of IL‐1β by intermediate monocytes. Furthermore, C5a activated in intermediate monocytes and IL‐1β released after C5a stimulation by monocytes promoted the proliferation, migration, adhesion, and epithelial‐to‐mesenchymal transition (EMT) of tumor cells, and attenuated tumor cell apoptosis. Conclusions C5a, activated by the classical and alternative pathways of the complement system, not only mediated the infiltration of intermediate monocytes by enhancing CCL2 production in PMCs but also induced IL‐1β release from the recruited monocytes in MPE. The consequence of C5a activation and the subsequent IL‐1β overexpression in intermediate monocytes contributed to MPE progression.

BackgroundPrecise breast cancer–related mortality forecasts are required for public health program and healthcare service planning. A number of stochastic model–based approaches for predicting mortality have been developed. The trends shown by mortality data from various diseases and countries are critical to the effectiveness of these models. This study illustrates the unconventional statistical method for estimating and predicting the mortality risk between the early-onset and screen-age/late-onset breast cancer population in China and Pakistan using the Lee–Carter model.MethodsLongitudinal death data for female breast cancer from 1990 to 2019 obtained from the Global Burden of Disease study database were used to compare statistical approach between early-onset (age group, 25–49 years) and screen-age/late-onset (age group, 50–84 years) population. We evaluated the model performance both within (training period, 1990–2010) and outside (test period, 2011–2019) data forecast accuracy using the different error measures and graphical analysis. Finally, using the Lee–Carter model, we predicted the general index for the time period (2011 to 2030) and derived corresponding life expectancy at birth for the female breast cancer population using life tables.ResultsStudy findings revealed that the Lee–Carter approach to predict breast cancer mortality rate outperformed in the screen-age/late-onset compared with that in the early-onset population in terms of goodness of fit and within and outside forecast accuracy check. Moreover, the trend in forecast error was decreasing gradually in the screen-age/late-onset compared with that in the early-onset breast cancer population in China and Pakistan. Furthermore, we observed that this approach had provided almost comparable results between the early-onset and screen-age/late-onset population in forecast accuracy for more varying mortality behavior over time like in Pakistan. Both the early-onset and screen-age/late-onset populations in Pakistan were expected to have an increase in breast cancer mortality by 2030. whereas, for China, it was expected to decrease in the early-onset population.ConclusionThe Lee–Carter model can be used to estimate breast cancer mortality and so to project future life expectancy at birth, especially in the screen-age/late-onset population. As a result, it is suggested that this approach may be useful and convenient for predicting cancer-related mortality even when epidemiological and demographic disease data sets are limited. According to model predictions for breast cancer mortality, improved health facilities for disease diagnosis, control, and prevention are required to reduce the disease’s future burden, particularly in less developed countries.

Background and aimsComplement activation is essential for tuberculosis pleural effusion. However, little is known about the value of complement regulatory protein (CD46, CD55, and CD59) in the differential diagnosis of tuberculosis.Materials and methodsNinety-nine patients with exudative pleural effusion admitted to Xiangya Hospital of Central South University from June 1, 2021to November 14, 2022 were enrolled. The expression levels of soluble CD46 (sCD46), soluble CD55 (sCD55), and soluble CD59 (sCD59) in pleural effusion were quantified by enzyme-linked immunosorbent assay, and the receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic and co-diagnostic values.ResultsThe ADA level is higher in TPE patients than non-TPE patients. It is well-found that TPE patients had lower levels of sCD46, sCD55, and sCD59 compared with non-TPE patients. Moreover, the expression of sCD46, sCD55, and sCD59 in pleural effusion was negatively correlated with ADA. In addition, the diagnostic efficacy of sCD46, sCD55 and sCD59 was comparable to that of ADA, with 0.896, 0.857, 0.858 and 0.893, respectively. Furthermore, combine detection of sCD46, sCD55, sCD59 and ADA could improve the diagnostic accuracy.ConclusionsComplement regulatory factors (CD46, CD55, and CD59) were validated by this project to be promising candidate biomarkers for the diagnosis of TPE with high accuracy. The combination of the CD46, CD55, and CD59 and ADA assay exist a better diagnostic value in TPE.

BackgroundBrazil, Russia, India, China, South Africa, and 30 other Asian nations make up the BRICS-Plus, a group of developing countries that account for about half of the world’s population and contribute significantly to the global illness burden. This study aimed to analyzed the epidemiological burden of female breast cancer (BC) across the BRICS-Plus from 1990 to 2019 and studied the associations with age, period, birth cohort and countries’ sociodemographic index (SDI).MethodsThe BC mortality and incidence estimates came from the 2019 Global Burden of Disease Study. We estimated cohort and period effects in BC outcomes between 1990 and 2019 using age-period-cohort (APC) modeling. The maximum likelihood (ML) of the APC-model Poisson with log (Y) based on the natural-spline function was used to estimate the rate ratio (RR). We used annualized rate of change (AROC) to quantify change over the previous 30 years in BC across BRICS-Plus and compare it to the global.ResultsIn 2019, there were about 1.98 million female BC cases (age-standardized rate of 45.86 [95% UI: 41.91, 49.76]) and 0.69 million deaths (age-standardized rate of 15.88 [95% UI: 14.66, 17.07]) around the globe. Among them, 45.4% of incident cases and 51.3% of deaths were attributed to the BRICS-Plus. China (41.1% cases and 26.5% deaths) and India (16.1% cases and 23.1% deaths) had the largest proportion of incident cases and deaths among the BRICS-Plus nations in 2019. Pakistan came in third with 5.6% cases and 8.8% deaths. Over the past three decades, from 1990 to 2019, the BRICS-Plus region’s greatest AROC was seen in Lesotho (2.61%; 95%UI: 1.99-2.99). The birth cohort impacts on BC vary significantly among the BRICS-Plus nations. Overall, the risk of case-fatality rate tended to decline in all BRICS-Plus nations, notably in South Asian Association for Regional Cooperation (SAARC) and China-ASEAN Free Trade Area (China-ASEAN FTA) countries, and the drop in risk in the most recent cohort was lowest in China and the Maldives. Additionally, there was a substantial negative link between SDI and case fatality rate (r1990= -0.91, p

Abstract Organoids are derived from stem cells or organ-specific progenitors. They display structures and functions consistent with organs in vivo. Multiple types of organoids, including lung organoids, can be generated. Organoids are applied widely in development, disease modelling, regenerative medicine, and other multiple aspects. Various human pulmonary diseases caused by several factors can be induced and lead to different degrees of lung epithelial injury. Epithelial repair involves the participation of multiple cells and signalling pathways. Lung organoids provide an excellent platform to model injury to and repair of lungs. Here, we review the recent methods of cultivating lung organoids, applications of lung organoids in epithelial repair after injury, and understanding the mechanisms of epithelial repair investigated using lung organoids. By using lung organoids, we can discover the regulatory mechanisms related to the repair of lung epithelia. This strategy could provide new insights for more effective management of lung diseases and the development of new drugs.

Abstract Background The novel coronavirus disease (COVID-19) was first reported in Wuhan, China. The mass population mobility in China during the Spring Festival has been considered a driver to the transmission of COVID-19, but it still needs more empirical discussion. Methods Based on the panel data from Hubei, China between January 6th and February 6th, 2020, a random effects model was used to estimate the impact of population mobility on the transmission of COVID-19. Stata version 12.0 was used, and p

ABSTRACT Lyme disease (LD) is a heavy public health burden. The most common manifestations of LD include erythema migrans (EM), Lyme neuroborreliosis (LNB), and Lyme arthritis (LA). The efficacy and safety of antibiotics for treating LD is still controversial. Thus, we performed a network meta-analysis (NMA) to obtain more data and tried to solve this problem. We searched studies in the databases of Embase and PubMed from the date of their establishments until 22 April 2021. Odds ratios (ORs) were used to assess dichotomous outcomes. A total of 31 randomized controlled trials (RCTs) involving 2,748 patients and 11 antibiotics were included. Oral amoxicillin (1.5 g/day), oral azithromycin (0.5 g/day), injectable ceftriaxone, and injectable cefotaxime were effective for treating LD (range of ORs, 1.02 to 1,610.43). Cefuroxime and penicillin were safe for treating LD (range of ORs, 0.027 to 0.98). Amoxicillin was effective for treating EM (range of ORs, 1.18 to 25.66). Based on the results, we thought oral amoxicillin (1.5 g/day), oral azithromycin (0.5 g/day), injectable ceftriaxone, and injectable cefotaxime were effective for treating LD. Cefuroxime and penicillin were safe for treating LD. Amoxicillin was effective for treating EM. We did not observe evidence proving the advantage of doxycycline in efficacy and safety for treating LD, LA, LNB, and EM of children or adults. We did not have sufficient data to prove the significant difference of efficacy for treating LA and LNB in adults and LD in children, the significant difference of safety of oral drugs for treating LD, and the significant difference of safety of drugs for treating EM. IMPORTANCE Some previous studies investigated the efficacy and safety of antibiotics for treating Lyme disease (LD). However, due to technical limitations, several questions regarding the routes of drug administration and the dosages of drug are still unclear, which might be causing problems for clinicians. Hence, we performed network meta-analysis (NMA) to quantitatively analyze the clinical data published during the last 40 years. Here, we demonstrate the evidence regarding the efficacy and safety of antibiotics commonly used for treating LD in adults and children. We found that amoxicillin, azithromycin, ceftriaxone, and cefotaxime were effective for treating LD, but we did not observe significant efficacy and safety of doxycycline for treating LD.

GLCCI1 plays a significant role in modulating glucocorticoid (GC) sensitivity in asthma. This project determines the underlying mechanism that GLCCI1 deficiency attenuates GC sensitivity in dexamethasone (Dex)-treated Ovalbumin (OVA)-induced asthma mice and epithelial cells through upregulating binding of IRF1:GRIP1 and IRF3:GRIP1. Dexamethasone treatment led to less reduced inflammation, airway hyperresponsiveness, and activation of the components responsible for GC activity, as determined by decreased GR and glucocorticoid receptor interacting protein 1 (GRIP1) expression but augmented IRF1 and IRF3 expression in GLCCI1−/− asthmatic mice compared with wild type asthmatic mice. Moreover, the recruitment of GRIP1 to GR was downregulated, while the individual recruitment of GRIP1 to IRF1 and IRF3 was upregulated in GLCCI1−/− Dex-treated asthmatic mice compared to wild type Dex-treated asthmatic mice. We also found that GLCCI1 knockdown reduced GR and GRIP1 expression but increased IRF1 and IRF3 expression in Beas2B and A549 cells. Additionally, GLCCI1 silencing increased the interactions between GRIP1 with IRF1 and GRIP1 with IRF3, but decreased the recruitment of GRIP1 to GR. These studies support a critical but previously unrecognized effect of GLCCI1 expression on epithelial cells in asthma GC responses by which GLCCI1 deficiency reduces the GR and GRIP1 interaction but competitively enhances the recruitment of GRIP1 to IRF1 and IRF3.

The complement system is activated in tuberculous pleural effusion (TPE), with increased levels of the anaphylatoxins stimulating pleural mesothelial cells (PMCs) to secrete chemokines, which recruit nonclassical monocytes to the pleural cavity. The differentiation and recruitment of naive CD4+ T cells are induced by pleural cytokines and PMC-produced chemokines in TPE. However, it is unclear whether anaphylatoxins orchestrate CD4+ T cell response via interactions between PMCs and monocytes in TPE. In this study, CD16+ and CD16- monocytes isolated from TPE patients were cocultured with PMCs pretreated with anaphylatoxins. After removing the PMCs, the conditioned monocytes were cocultured with CD4+ T cells. The levels of the cytokines were measured in PMCs and monocyte subsets treated separately with anaphylatoxins. The costimulatory molecules were assessed in conditioned monocyte subsets. Furthermore, CD4+ T cell response was evaluated in different coculture systems. The results indicated that anaphylatoxins induced PMCs and CD16+ monocytes to secrete abundant cytokines capable of only inducing Th17 expansion, but Th1 was feeble. In addition, costimulatory molecules were more highly expressed in CD16+ than in CD16- monocytes isolated from TPE. The interactions between monocytes and PMCs enhanced the ability of PMCs and monocytes to produce cytokines and that of monocytes to express HLA-DR, CD40, CD80 and CD86, which synergistically induced Th17 expansion. In the above process, anaphylatoxins enhanced the interactions between monocytes and PMCs by increasing the level of the cytokines IL-1β, IL-6, IL-23 and upregulating the phenotype of CD40 and CD80 in CD16+ monocytes. Collectively, these data indicate that anaphylatoxins play a central role in orchestrating Th17 response mainly via interactions between CD16+ monocytes and PMCs in TPE.

BackgroundLyme neuroborreliosis (LNB) is one of the most dangerous manifestations of Lyme disease, but the pathogenesis and inflammatory mechanisms are not fully understood.MethodsCultured explants from the frontal cortex of rhesus monkey brain (n=3) were treated with live Borrelia burgdorferi (Bb) or phosphate-buffered saline (PBS) for 6, 12, and 24 h. Total protein was collected for sequencing and bioinformatics analysis. In addition, changes in protein expression in the explants over time following Bb treatment were screened.ResultsWe identified 1237 differentially expressed proteins (DEPs; fold change ≥1.5 or ≤0.67, P-value ≤0.05). One of these, growth-associated protein 43 (GAP-43), was highly expressed at all time points in the explants. The results of the protein-protein interaction network analysis of DEPs suggested that GAP-43 plays a role in the neuroinflammation associated with LNB. In HMC3 cells incubated with live Bb or PBS for 6, 12, and 24 h, real-time PCR and western blot analyses confirmed the increase of GAP-43 mRNA and protein, respectively.ConclusionsElevated GAP-43 expression is a potential marker for LNB that may be useful for diagnosis or treatment.

Rotavirus immunization strategies have become part of a comprehensive global public health program to control rotavirus-associated gastroenteritis, particularly in infants and children in developing countries. Several studies have reported the efficacy of different rotavirus vaccine dosing schedules, but with mixed findings. Therefore a systematic review of the published literature on rotavirus vaccination dosing schedules using the live attenuated RV1 rotavirus vaccine in infants and children, including randomized controlled clinical trials (RCTs), published between January 1998 to January 2018 was conducted, with meta-analysis of the published data. The literature search was performed using six databases. The initial review identified 495 publications, of which three satisfied the selection eligibility criteria. The three studies that assessed RV1 rotavirus vaccine immunogenicity compared a two-dose vaccination schedule with a three-dose vaccination schedule. The use of a three-dose vaccination schedule did not show a statistically significant seroconversion rate when compared with a two-dose vaccination schedule (OR = 0.87; 95% CI,: 0.65–-1.17;, p- = 0.298). Analysis of included studies with one-month follow-up time showed that the three-dose vaccination schedule did not result in have significantly increased geometric mean concentrations (GMCs) compared with the two-dose vaccination schedule (p = 0.311).Rotavirus immunogenicity did not increase significantly with the three-dose schedule at 6, 10 and 14 weeks with the two-dose schedule at 10 and 14 weeks. These findings indicate that further controlled studies should be undertaken to support the optimum immunization schedules for rotavirus in terms of clinical effectiveness and cost-effectiveness, particularly for infants and children in developing countries.

Background: With the increased number of patients discharged after having COVID-19, more and more studies have reported cases whose retesting was positive (RP) during the convalescent period, which brings a new public health challenge to the world. Methods: We searched PubMed, Web of Science, The Cochrane Library, CNKI, WanFang and VIP from December 1, 2019 to December 31, 2020. The included studies were assessed using JBI critical appraisal tools and Newcastle-Ottawa Scale. The RP rate of discharge patients was analyzed by a meta-analysis. We adhered to PRISMA reporting guideline. Findings: We have included 117 studies with 2669 RP participants after discharge. The methodological quality of 66 case reports were low to high, 42 case series and 3 cohort study were moderate to high, 3 case-control studies were moderate and 3 cross-sectional studies were low to moderate. The clinical manifestations of most RP patients were mild or asymptomatic, and CT imaging and laboratory examinations were usually normal. The existing risk factors suggest that more attention should be paid to sever patients, elderly patients, and patients with co-morbidities. The summary RP rate was 12·2% (95% CI 10·6–13·7) with high heterogeneity (I2 = 85%). Interpretation: To date, the causes and risk factors of RP result in discharged patients are not fully understood. High-quality etiological and clinical studies are needed to investigate these issues to further help us to make strategies to control and prevent its occurrence.

Stroke is the first leading cause of death in China, and low fruit intake is suggested to be one of the most important risk factors for stroke mortality. However, the trends of stroke mortality attributable to low fruit intake remain unclear in China. Therefore, this study aimed to investigate the long-term trends of stroke mortality attributable to low fruit intake by sex in China during 1990–2017. Data were obtained from the Global Burden of Disease 2017 study; the annual percentage change (APC) and average annual percentage change (AAPC) were estimated by joinpoint regression analysis, and the net age, period, and cohort effects were estimated using the age–period–cohort model with an intrinsic estimator algorithm (APC-IE). The crude mortality rates (CMRs) increased for males and decreased for females from 1990 to 2017. The age-standardized mortality rates (ASMRs) for both males and females showed consecutive significant declines from 1990 to 2017. By APC analysis, substantially increasing age effects were presented from 25 to 79 years for both sexes. The independent period and cohort effects progressively decreased during the entire period for both sexes, with a faster decrease for females than for males. Males and elder groups were the high-risk population for stroke mortality caused by low fruit intake. Although the mortality risk showed a decreasing trend, the fruit intake was still low for the Chinese population. Therefore, effective strategies and global awareness are essential to improve the current situation of low fruit intake, thereby preventing and reducing the stroke mortality risk caused by low fruit intake in China.

Ixodes ticks are the main vectors for a number of zoonotic diseases, including Lyme disease. Ticks secrete saliva directly into a mammalian host while feeding on the host's blood. This action serves to modulate host immunity and coagulation, thus allowing ticks to attach and feed upon their host. One of the most extensively studied components of tick saliva is Salp15. Research has shown that this protein binds specifically to CD4 molecules on the surface of T lymphocytes, interferes with TCR-mediated signaling transduction, inhibits CD4+ T cell activation and proliferation, and impedes the secretion of interleukin 2 (IL-2). Salp15 also binds specifically to dendritic cell dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) to up-regulate the expression of CD73 in regulatory T cells. Collectively, these findings render this salivary protein a potential candidate for a range of therapeutic applications. Here, we discuss our current understanding of Salp15 and the mechanisms that might be used to treat disease.

Abstract Background Ischaemic heart disease (IHD) is a major barrier to sustainable human development, but its health burden and geographic distribution among provinces of China remain unclear. This study aimed to estimate IHD burden in provinces of China, and attributable to risk factors from 1990 to 2015. Methods Data were collected from the Global Burden of Disease 2015 Study, which evaluated IHD burden and attributable risk factors using deaths and disability-adjusted life years (DALYs). Statistical models including cause of death ensemble modelling, Bayesian meta-regression analysis, and comparative risk assessment approaches were applied to reduce bias and produce comprehensive results of IHD deaths, DALYs and attributable risks. The 95% uncertainty intervals (UIs) were calculated and reported for mortality and DALYs. Results The age-standardised death rate per 100,000 people increased by 13.3% from 101.3 (95%UI: 95.3–107.5) to 114.8 (95%UI: 109.8–120.1) from 1990 to 2015 in China, whereas the age-standardised DALY rate declined 3.9% to 1760.2 per 100,000 people (95%UI: 1671.6–1864.3). In 2015, the age-standardised death rate per 100,000 people was the highest in Heilongjiang (187.4, 95%UI: 161.6–217.5) and the lowest in Shanghai (44.2, 95%UI: 37.0–53.1), and the age-standardised DALY rate per 100,000 people was the highest in Xinjiang (3040.8, 95%UI: 2488.8–3735.4) and the lowest in Shanghai (524.4, 95%UI: 434.7–638.4). Geographically, the age-standardised death and DALY rates for southern provinces were lower than northern provinces, especially in southeastern coastal provinces. 95.3% of the IHD burden in China was attributable to environmental, behavioural and metabolic risk factors. The five leading IHD risks in 2015 were high systolic blood pressure, high total cholesterol, diet high in sodium, diet low in whole grains, and smoking. Conclusions Population growth and ageing has led to a steady increase in the IHD burden. Regional disparities in IHD burden were observed in provinces of China. The distribution characteristics of IHD burden provide guidance for decision makers to formulate targeted preventive policies and interventions.

Background: Currently, there is no tuberculosis (TB) vaccine recommended for use in latent TB infections and healthy adults. M72/AS01E is a new peptide vaccine currently under development, which may improve protection against TB disease. This vaccine has been investigated in several phase I/II clinical trials. We conducted a meta-analysis to clarify the immunogenicity and safety of the M72/AS01E peptide vaccine.Methods: We searched the PubMed, Embase, and Cochrane Library databases for published studies (until December 2018) investigating this candidate vaccine. A meta-analysis was performed using the standard methods and procedures established by the Cochrane Collaboration.Results: Seven eligible studies—involving 4,590 participants—were selected. The analysis revealed a vaccine efficacy was 57.0%, significantly higher abundance of polyfunctional M72-specific CD4+ T cells [standardized mean difference (SMD) = 2.58] in the vaccine group vs. the control group, the highest seropositivity rate [relative risk (RR) = 74.87] at 1 month after the second dose of vaccination (Day 60), and sustained elevated anti-M72 IgG geometric mean concentration at study end (Day 210) (SWD = 4.94). Compared with the control, participants who received vaccination were at increased risk of local injection site redness [relative risk (RR) = 5.99], local swelling (RR = 7.57), malaise (RR = 3.01), and fatigue (RR = 3.17). However, they were not at increased risk of headache (RR = 1.57), myalgia (RR = 0.97), and pain (RR = 3.02).Conclusion: The M72/AS01E vaccine against TB is safe and effective. Although the vaccine is associated with a mild adverse reaction, it is promising for the prevention of TB in healthy adults.

Lyme disease, reffered to as Lyme borreliosis, is a tick-borne zoonotic disease caused by Borrelia burgdorferi spirochetes. Lyme arthritis, the most common, serious and harmful manifestation during the late stages of Lyme disease, is closely associated with the Borrelia burgdorferi basic membrane protein A (BmpA). Chemokines are also reported to have an important role in Lyme arthritis. Toll-like receptors (TLRs) recognize and bind to pathogen-associated molecules which are structurally conserved among microbes, to activate transcriptional events, including cytokine production, inflammation, and tissue damage. We speculated that BmpA could induce a storm of proinflammatory chemokines via TLRs and downstream moleculars, and that TLR1, TLR2, TLR5, TLR6 and the adaptor protein, MyD88, may be involved in this process. We explored this hypothesis using the human monocytic leukemia cell line, THP-1, and recombinant BmpA (rBmpA). Cell surface TLR1 and TLR2 were neutralized using specific antibodies before stimulation with rBmpA and analysis of chemokine secretion using a chemokine chip. Further, the expressions level of the four TLRs and MyD88 were analyzed following stimulation with rBmpA. Stimulation with rBmpA resulted in elevated levels of seven cytokines. Further, TLR1 and TLR2 antibody treated cells exhibited an overall reduction in rBmpA-induced chemokine expression. TLR1, TLR2, and MyD88 expression levels (both mRNA and protein) increased after stimulation with rBmpA. Our data confirm that TLR1, TLR2, and MyD88 are involved in BmpA-induced proinflammatory chemokines, which may be closely involved in Lyme arthritis pathogenesis.

Lyme neuroborreliosis (LNB) is the most dangerous manifestation of Lyme disease caused by the spirochete Borrelia burgdorferi which can reach the central nervous system most commonly presenting with lymphocytic meningitis; however, the molecular basis for neuroborreliosis is still poorly understood. We incubated explants from the frontal cortex of three rhesus brains with medium alone or medium with added live Borrelia burgdorferi for 6, 12, and 24 h and isolated RNA from each group was used for RNA sequencing with further bioinformatic analysis. Transcriptomic differences between the ex vivo model of live Borrelia burgdorferi with rhesus frontal cortex tissue explants and the controls during the progression of the infection were identified. A total of 2249, 1064, and 420 genes were significantly altered, of which 80.7, 52.9, and 19.8% were upregulated and 19.3, 47.1, 80.2% were downregulated at 6, 12, and 24 h, respectively. Gene ontology and KEGG pathway analyses revealed various pathways related to immune and inflammatory responses during the spirochete infection were enriched which is suggested to have a causal role in the pathogenesis of neurological Lyme disease. Moreover, we propose that the overexpressed FOLR2 which was demonstrated by the real-time PCR and western blotting could play a key role in neuroinflammation of the neuroborreliosis based on PPI analysis for the first time. To our knowledge, this is the first study to provide comprehensive information regarding the transcriptomic signatures that occur in the frontal cortex of the brain upon exposure to Borrelia burgdorferi, and suggest that FOLR2 is a promising target that is associated with neuroinflammation and may represent a new diagnostic or therapeutic marker in LNB.

Respiratory viral infections can directly lead to kidney damage such as IgA nephropathy (IgAN), partly due to mucosal immune system dysfunction. Although the activated C5a-C5aR1 axis results in increased Th1 and Th17 frequencies but reduced Treg frequencies in Respiratory syncytial virus (RSV) infection, how this axis affects Th cell disorders in RSV-induced IgAN exacerbation remains unknown. Here, we used a mouse model to dissect the activation of C5a-C5aR1 by RSV and the consequences on the regulation of Th1, Th17, and Treg immune responses in IgA nephropathy. RSV fusion protein was clearly deposited not only in the pulmonary interstitium but also in the glomerulus in RSV-IgAN mice, and RSV infection led to more severe pathological changes in the kidneys in IgAN mice. Blocking the C5a-C5aR1 axis resulted in a decrease in the albumin-to-creatinine ratio, and the attenuation of kidney damage in IgAN and RSV-IgAN mice might be partly attributed to the inhibition of Th cell and cytokine dysfunction. Th1, Th17 and Treg immune responses and their corelative cytokines were disrupted by RSV infection and rescued by C5aR1 inhibition. Moreover, we constructed a coculture system of human mesangial cells and CD4+ T cells and found that RSV infection might lead to CD4+ T cell production via human mesangial cells-enhanced CD4+ T cell proliferation, consequently increasing IL-17 levels. These pathological behaviors were augmented by C5a stimulation and decreased by C5aR1 inhibition. Thus, C5aR1 inhibition alters both kidney damage and Th1, Th17, and Treg cell dysfunction in RSV-induced IgAN exacerbation and locally regulates HMC antigen presentation function in the kidney. Taken together, our data offer profound evidence that blocking the C5a-C5aR1 axis might be a potential therapy for RSV-induced IgAN.

An amendment to this paper has been published and can be accessed via the original article.

Background: Brazil, Russia, India, China, South Africa, and 30 other Asian nations make up the BRICS-Plus, a group of developing countries that account for about half of the world’s population and contribute significantly to the global illness burden. This study aimed to analyzed the epidemiological burden of female breast cancer (BC) across the BRICS-Plus from 1990 to 2019 and studied the associations with age, period, birth cohort and countries’ sociodemographic index (SDI). Methods: The BC mortality and incidence estimates came from the 2019 Global Burden of Disease Study. We estimated cohort and period effects in BC outcomes between 1990 and 2019 using age-period-cohort (APC) modeling. The maximum likelihood (ML) of the APC-model Poisson with log (Y) based on the natural-spline function was used to estimate the rate ratio (RR). We used annualized rate of change (AROC) to quantify change over the previous 30 years in BC across BRICSPlus and compare it to the global. Results: In 2019, there were about 1.98 million female BC cases (age-standardized rate of 45.86 [95% UI: 41.91, 49.76]) and 0.69 million deaths (age-standardized rate of 15.88 [95% UI: 14.66, 17.07]) around the globe. Among them, 45.4% of incident cases and 51.3% of deaths were attributed to the BRICS-Plus. China (41.1% cases and 26.5% deaths) and India (16.1% cases and 23.1% deaths) had the largest proportion of incident cases and deaths among the BRICS-Plus nations in 2019. Pakistan came in third with 5.6% cases and 8.8% deaths. Over the past three decades, from 1990 to 2019, the BRICS-Plus region’s greatest AROC was seen in Lesotho (2.61%; 95%UI: 1.99-2.99). The birth cohort impacts on BC vary significantly among the BRICS-Plus nations. Overall, the risk of case-fatality rate tended to decline in all BRICS-Plus nations, notably in South Asian Association for Regional Cooperation (SAARC) and China-ASEAN Free Trade Area (China-ASEAN FTA) countries, and the drop in risk in the most recent cohort was lowest in China and the Maldives. Additionally, there was a substantial negative link between SDI and case fatality rate (r1990= -0.91, p<0.001; r2019= -0.89, p<0.001) in the BRICSPlus in both 1990 and 2019, with the Eurasian Economic Union (EEU) nations having the highest case fatality rate. Conclusions: The BC burden varies remarkably between different BRICS-Plus regions. Although the BRICS’ efforts to regulate BC succeeded, the overall improvements lagged behind those in high-income Asia-Pacific nations. Every BRICS-Plus country should strengthen specific public health approaches and policies directed at different priority groups, according to BRIC-Plus and other high-burden nations. [ABSTRACT FROM AUTHOR]