Th17/Treg Cells Imbalance and GITRL Profile in Patients with Hashimoto’s Thyroiditis

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Identification and characterization of class 1 integrons among Pseudomonas aeruginosa isolates from patients in Zhenjiang, China

SummaryObjectivesThe role of integrons in the spread of antibiotic resistance has been well established. The aim of this study was to investigate the resistance profiles of Pseudomonas aeruginosa isolated from patients in Zhenjiang to 13 antibiotics, and to identify the structure and dissemination of class 1 integrons.MethodsThe Kirby–Bauer disk diffusion assay was used to determine the rate of P. aeruginosa resistance. Class 1 integrons from multidrug-resistant isolates were amplified by PCR, and their PCR products were sequenced. We also analyzed the integron structures containing the same gene cassettes by restriction fragment length polymorphism (RFLP). Isolates were genotyped by pulsed-field gel electrophoresis (PFGE).ResultsThe resistance rates were between 29.6% and 90.1%. The prevalence of class 1 integrons was 38.0%. These integrons included five gene cassettes (aadB, aac6-II, blaPSE-1, dfrA17, and aadA5). The dfrA17 and aadA5 gene cassettes were found most often.ConclusionsClass 1 integrons were found to be widespread in P. aeruginosa isolated from clinical samples in the Zhenjiang area of China. The antibiotic resistance rates in class 1 integron-positive strains of P. aeruginosa were noticeably higher than those in class 1 integron-negative strains. PFGE showed that particular clones were circulating among patients

Discrepancies of video head impulse test results in patients with idiopathic sudden sensorineural hearing loss with vertigo and vestibular neuritis

ObjectiveSudden sensorineural hearing loss with vertigo (SHLV) and vestibular neuritis (VN) remain frequent causes of acute vestibular syndrome (AVS). The aim of study was to compare the results of video head impulse test (vHIT) in patients with SHLV and VN. The characteristics of high-frequency vestibule-ocular reflex (VOR) and the differences of the pathophysiological mechanisms underlying these two AVS were explored.MethodsFifty-seven SHLV patients and 31 VN patients were enrolled. vHIT was conducted at the initial presentation. The VOR gains and occurrence of corrective saccades (CSs) of anterior, horizontal, and posterior semicircular canals (SCCs) in two groups were analyzed. Pathological vHIT results refer to impaired VOR gains and presence of CSs.ResultsIn SHLV group, pathological vHIT results was most prevalent in the posterior SCC on the affected side (30/57, 52.63%), followed by horizontal (12/57, 21.05%) and anterior SCC (3/57, 5.26%). In VN group, pathological vHIT preferentially affected horizontal SCC (24/31, 77.42%), followed by anterior (10/31, 32.26%) and posterior SCC (9/31, 29.03%) on the affected side. As for anterior and horizontal SCC on the affected side, the incidences of pathological vHIT results in VN group were significantly higher than those in SHLV group (β = 2.905, p < 0.01; β = 2.183, p < 0.001). There were no significant differences in the incidence of pathological vHIT result in posterior SCC between two groups.ConclusionComparison of vHIT results in patients with SHLV and VN revealed discrepancies in the pattern of SCCs impairments, which may be explained by different pathophysiological mechanisms underlying these two vestibular disorders presenting as AVS

Enhanced HMGB1 Expression May Contribute to Th17 Cells Activation in Rheumatoid Arthritis

Rheumatoid arthritis(RA) is a common autoimmune disease associated with Th17 cells, but what about the effect of high-mobility group box chromosomal protein 1 (HMGB1) and the relationship between Th17-associated factors and HMGB1 in RA remains unknown. In the present study, we investigated the mRNA levels of HMGB1, RORγt, and IL-17 in peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis by quantitative real-time PCR (RT-qPCR), and the concentrations of HMGB1, IL-17, and IL-23 in plasma were detected by ELISA. And then, the effect of HMGB1 on Th17 cells differentiation was analyzed in vitro. Our clinical studies showed that the mRNAs of HMGB1, RORγt, and IL-17 in patients were higher than that in health control (P < 0.05), especially in active RA patients (P < 0.05). The plasma HMGB1, IL-17, and IL-23 in RA patients were also higher than that in health control (P < 0.05); there was a positive correlation between the expression levels of HMGB1 and the amount of CRP, ERS, and RF in plasma. In vitro, the IL-17-produced CD4+T cells were increased with 100 ng/mL rHMGB1 for 12h, which indicated that the increased HMGB1 might contribute to Th17 cells activation in RA patients

The temporal trend of disease burden attributable to metabolic risk factors in China, 1990–2019 : An analysis of the Global Burden of Disease study

Background and aims: The disease burden attributable to metabolic risk factors is rapidly increasing in China, especially in older people. The objective of this study was to (i) estimate the pattern and trend of six metabolic risk factors and attributable causes in China from 1990 to 2019, (ii) ascertain its association with societal development, and (iii) compare the disease burden among the Group of 20 (G20) countries. Methods: The main outcome measures were disability-adjusted life-years (DALYs) and mortality (deaths) attributable to high fasting plasma glucose (HFPG), high systolic blood pressure (HSBP), high low-density lipoprotein (HLDL) cholesterol, high body-mass index (HBMI), kidney dysfunction (KDF), and low bone mineral density (LBMD). The average annual percent change (AAPC) between 1990 and 2019 was analyzed using Joinpoint regression. Results: For all six metabolic risk factors, the rate of DALYs and death increased with age, accelerating for individuals older than 60 and 70 for DALYs and death, respectively. The AAPC value in rate of DALYs and death were higher in male patients than in female patients across 20 age groups. A double-peak pattern was observed for AAPC in the rate of DALYs and death, peaking at age 20–49 and at age 70–95 plus. The age-standardized rate of DALYs increased for HBMI and LBMD, decreased for HFPG, HSBP, KDF, and remained stable for HLDL from 1990 to 2019. In terms of age-standardized rate of DALYs, there was an increasing trend of neoplasms and neurological disorders attributable to HFPG; diabetes and kidney diseases, neurological disorders, sense organ diseases, musculoskeletal disorders, neoplasms, cardiovascular diseases, digestive diseases to HBMI; unintentional injuries to LBMD; and musculoskeletal disorders to KDF. Among 19 countries of Group 20, in 2019, the age-standardized rate of DALYs and death were ranked fourth to sixth for HFPG, HSBP, and HLDL, but ranked 10th to 15th for LBMD, KDF, and HBMI, despite the number of DALYs and death ranked first to second for six metabolic risk factors. Conclusions: Population aging continuously accelerates the metabolic risk factor driven disease burden in China. Comprehensive and tight control of metabolic risk factors before 20 and 70 may help to mitigate the increasing disease burden and achieve healthy aging, respectively

Downregulation of Hlx

T-bet plays an important role in immunoregulation; it induces the differentiation of Th1 together with the homeobox transcription factor gene Hlx. Recent studies show that T-bet and Th1-associated factors are critical in regulating tumor development. However, the contributions of Hlx in the occurrence and development of cancer remain unknown. In this study, the Hlx, T-bet, Runx3, and IFN-γ were measured in PBMC from patients with gastric cancer and the correlation between Hlx and T-bet or IFN-γ was assessed. The expression levels of Hlx, T-bet, and IFN-γwere significantly decreased, and there was a positive correlation between Hlx and T-bet or IFN-γ. In addition, the Runx3 expression was also downregulated with the lower T-bet mRNA level. These results suggested that the decreased Hlx expression was closely associated with T-bet and Runx3 downregulations and may contribute to the development of gastric cancer

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

On the simultaneous Pell equations x2 - (4m2 - 1)y2 = y2 - pz2 = 1

Let m be a positive integer, and let p be an odd prime. By using certain properties of Pell and quartic diophantine equations with some elementary number theory methods, we prove that the system of equations x2 - (4m2 - 1)y2 = 1 and y2 - pz2 = 1 has positive integer solutions (x, y, z) if and only if p ≡ 7(mod 8) and m = 1/4 (f2-1), where (f, g) is a positive integer solution of the equation f2-pg2 = 2. Further, if the above condition is satisfied, then the system of equations has only the positive integer solution (x, y, z) = ( 1/2 (f4 - 2f2 - 1); f2 - 1; fg).Keywords: Simultaneous Pell equations, solvability conditio