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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.

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.

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.

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

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.

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.

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.

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 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.

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]