Combination of transbronchial cryobiopsy based clinic-radiologic-pathologic strategy and metagenomic next-generation sequencing for differential diagnosis of rapidly progressive diffuse parenchymal lung diseases

BackgroundThe complicated spectrum of rapidly progressive diffused parenchymal lung diseases (RP-DPLD) creates obstacles to the precise diagnosis and treatment. We evaluated the differential diagnostic value of transbronchial cryobiopsy (TBCB) based clinic-radiologic-pathologic (CRP) strategy combined with bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) in RP-DPLD patients.MethodsRP-DPLD patients who underwent the diagnostic strategy of TBCB-based CRP combined with BALF mNGS at Shanghai East Hospital from May 2020 to Oct 2022 were retrospectively analyzed. Clinical characteristics were summarized, including demographic data, high-resolution computed tomography (HRCT) findings, histopathology of TBCB and microbiological results. Diagnostic value of the combined strategy, as well as the sensitivity, specificity, and positive detection rates of mNGS were evaluated.ResultsA total of 115 RP-DPLD patients were enrolled, with a mean age of 64.4 years old and a male proportion of 54.8%. The pulmonary imaging findings in most patients were complex and diverse, with all patients showing bilateral lung diffuse lesions in HRCT, and progressively aggravated imaging changes within one month. After combining TBCB-based CRP strategy with mNGS, all participants received a corresponding diagnosis with 100% diagnostic yield. In these patients, 58.3% (67/115) were diagnosed with noninfectious RP-DPLD and 41.7% (48/115) with infection-related RP-DPLD. There were 86.1% of cases with known etiology according to the DPLD classification. BALF mNGS and traditional pathogen detection methods were performed in all patients, the positive detection rates were 50.4% (58/115) and 32.2% (37/115), respectively. Meanwhile, the mNGS showed significantly higher sensitivity and negative predictive value than the traditional pathogen detection methods for the diagnosis of infection-related RP-DPLD (100% vs 60.4% (p<0.001), 100% vs 75.6% (p<0.001), respectively). Among noninfectious RP-DPLD patients, the true negative rate of mNGS was 85.1% (57/67). All patients had their treatment regimen modified and the 30-day mortality was 7.0%.ConclusionThe novel strategy of TBCB-based CRP combined with mNGS provided dependable and sufficient evidence for the diagnosis, meanwhile further improved the accuracy of RP-DPLD treatment, as well as the prognosis of patients. Our results highlight the significant value of combined strategy in determining whether the RP-DPLD patients were infection associated or not

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Social Support and the Incidence of Cognitive Impairment Among Older Adults in China: Findings From the Chinese Longitudinal Healthy Longevity Survey Study

Objective Social support shows a protective effect against cognitive impairment in older adults. However, the longitudinal relationship between the distinct sources of social support and the incidence of cognitive impairment remains unclear. This study aims to investigate the association between different sources of social support and the incidence of cognitive impairment among older adults in China. Method We used longitudinal data (2005-2014) from the Chinese Longitudinal Healthy Longevity Survey (CLHLS, 2005-2014, mean follow-up years 5.32 +/- 2.64). In total, 5897 participants (aged 81.7 +/- 9.7 years, range 65-112 years, 49.0% male) were enrolled. Cognitive impairment was measured by the Mini-Mental State Examination (MMSE). Social support included support from family and friends (marital status; contacts with family and friends; children's visits; siblings' visits, sick care; money received from and money given to children) and the availability of support from social community (social service and social security). We calculated subdistribution hazard ratios (SHR) of cognitive impairment by establishing Cox regression models, adjusting for residence, gender, age, education, participation in physical exercise, activities of daily living, smoking, drinking, negative psychological well-being, baseline cognitive function, occupation, leisure activities, and diseases. Results During a 9-year follow-up, 1047 participants developed cognitive impairment. Participants who were married had a 16.0% lower risk of developing cognitive impairment compared to the widowed older adults after controlling for all covariates, but the protective effect of being married was no longer significant (p = 0.067) when additional adjustment was made for all types of social support. Children's visits were significantly associated with the risk of cognitive impairment after controlling for all types of social support and covariate variables (SHR = 0.808, 95% confidence interval, 0.669-0.975, p = 0.026). Conclusion Children's visits were consistently associated with a lower incidence of cognitive impairment in Chinese older adults

Highly active electrocatalysts for oxygen reduction from carbon-supported copper-phthalocyanine synthesized by high temperature treatment

The active, carbon-supported copper phthalocyanine (CuPc/C) nano-catalyst, as a novel cathode catalyst for oxygen reduction reaction, is synthesized via a combined solvent-impregnation along with the high temperature treatment. The catalytic activities of both pyrolyzed and unpyrolyzed catalysts are screened by linear sweep voltammetry (LSV) employing a rotating disk electrode (RDE) technique to quantitatively obtain the oxygen reduction reaction (ORR) kinetic constants and the reaction mechanisms. The results show that heat-treatment can significantly improve the ORR activity of the catalyst, and the optimal heat-treated temperature is around 800 \ub0C, under which, an onset potential of 0.10 V and a half-wave potential of 120.05 V are achieved in alkaline electrolyte. Besides the ORR kinetic rate is increased, the ORR electron transfer number is also increased from 2.5 to 3.6 with increasing heat-treatment temperature from 600 to 800 \ub0C. Also, the effect of catalyst loading in the catalyst layer on the corresponding ORR activity is also studied, and finds that increasing the catalyst loading, the catalyzed ORR kinetic current density can be significantly increased. For a fully understanding of this heat-treatment temperature effect, XRD, TEM, SEM\u2013EDX, TG and XPS are used to identify the catalyst structure and composition. TG results demonstrated that the presence of Cu prevents phthalocyanine from thermal decomposition, thus contribute to higher nitrogen content which can form more Cu\u2013Nx activity sites for the ORR. XPS analysis indicates that both pyridinic-N and graphitic-N may be responsible for the enhanced ORR activity.Peer reviewed: YesNRC publication: Ye

Effects of Integrated Traditional Chinese and Western Medicine for the Treatment of Lupus Nephritis: A Meta-Analysis of Randomized Trials

After a thorough search through the database as CNKI database, VIP database, Wanfang database, PubMed, and Cochrane Library, the clinical experimental articles have been selected out on the effects of Integrated Traditional Chinese and Western Medicine on the treatment of lupus nephritis. A meta-analysis was carried out in terms of clinical efficacy criteria and safety criteria by RevMan 5.3 software. Based on the results, we cautiously conclude that Integrated Traditional Chinese and Western Medicine used for lupus nephritis could improve the clinical efficacy while at same time lower the 24-hour urine protein, serum creatinine, and adverse drug reactions

Peer-to-peer electricity trading of interconnected flexible distribution networks based on non-cooperative games

With the integration of power electronic devices represented by soft open points (SOPs), distribution networks have gradually evolved into interconnected flexible distribution networks (FDNs). Considering the deregulation of electricity market and user privacy, multiple stakeholders have participated in the operation of FDNs. Peer-to-peer (P2P) electricity trading is promising to alleviate operational problems of interconnected FDNs. As multiple regions pursue the maximum profits individually, non-cooperative game methods can be utilized to realize fair profit allocation in P2P trading. In this paper, a non-cooperative game-based P2P trading method is proposed to meet the electricity trading needs of multi-region interconnected FDNs. First, based on non-cooperative games, a two-layer P2P electricity trading framework is established to realize cost reduction and voltage profile improvement of multi-region interconnected FDNs. Then, a P2P trading adjustment mechanism is designed to improve the operational profits of SOP, in which spatial active power trading adjustment, temporal dispatching of energy storage (ES) link and reactive power support are incorporated. Finally, the effectiveness of the proposed method is verified based on a practical distribution network with four-terminal SOP in Tianjin. The results show that the proposed P2P electricity trading method can promote the economic operation performance of interconnected FDNs and improve the operational profit of SOP

Synthesis of nano-octahedral MgO via a solvothermal-solid-decomposition method for the removal of methyl orange from aqueous solutions

Nano magnesium oxide has wide applications, and MgO with (111) facets has wider potential applications than MgO with (100) facets (e.g., in catalysis and adsorption). However, nano MgO with (111) polar faces has not been studied throughly, so the preparation of nano-octahedral MgO (N-O-MgO) with eight exposed (111) facets remains a great challenge. Herein, we successfully synthesised N-O-MgO via an effective solvothermal-solid-decomposition method and studied its adsorption performance. The obtained N-O-MgO showed excellent performance (229.36 mg g(-1)) for methyl orange (MO). The adsorption follows the pseudo-second-order kinetic equation and the Langmuir isotherm model. The dimensionless parameter R-L (0.042) and Gibbs free energy Delta G (-6.538 kJ mol(-1)) revealed that the adsorption of MO on N-O-MgO was a spontaneous and feasible process. The adsorption of MO and methyl blue (MB) on N-O-MgO were studied to determine the adsorption sites. Based on these experiments and analysis, it was determined that the adsorption sites were magnesium ions and the adsorption mechanism was proposed to describe the adsorption process

Trace Metal(loid) Migration from Road Dust to Local Vegetables and Tree Tissues and the Bioaccessibility-Based Health Risk: Impacts of Vehicle Operation-Associated Emissions

Traffic activities release large amounts of trace metal(loid)s in urban environments. However, the impact of vehicle operation-associated emissions on trace metal(loid) enrichment in road dust and the potential migration of these trace metal(loid)s to the surrounding environment remain unclear. We evaluated the contamination, sequential fraction, and bioaccessibility of trace metal(loid)s in urban environments by assessing their presence in road dust, garden vegetables, and tree tissues, including bark and aerial roots, at a traffic-training venue impacted by vehicle operation emissions and, finally, calculated the bioaccessibility-based health risk. The results indicated a significant accumulation of trace metal(loid)s in road dust, with the highest lead (Pb), cadmium (Cd), and antimony (Sb) concentrations in the garage entrance area due to higher vehicle volumes, frequent vehicle starts and stops, and lower speeds. Aerial roots exposed to hill start conditions exhibited the highest Pb, Zn, and Sb levels, potentially caused by high road dust resuspension, confirming that this tree tissue is an appropriate bioindicator. Sequential extraction revealed high percentages of carbonate-, Fe/Mn oxide-, and organic/sulphide-associated fractions of Pb, copper (Cu), and zinc (Zn) in road dust, while most Cd, Cr, Ni, and Sb occurred as residual fractions. According to the potential mobilizable fractions in sequential extraction, the in vitro gastrointestinal method could be more suitable than the physiologically based extraction test to evaluate the bioaccessibility-related risk of traffic-impacted road dust. The bioaccessibility-based health risk assessment of the road dust or soil confirmed no concern about noncarcinogenic risk, while the major risk originated from Pb although leaded gasoline was prohibited before the venue establishment. Furthermore, the cancer risks (CRs) analysis showed the probable occurrence of carcinogenic health effects from Cd and Ni to adults and from Cd, Cr, and Ni to children. Furthermore, the Cd and Pb concentrations in the edible leaves of cabbage and radish growing in gardens were higher than the recommended maximum value. This study focused on the health risks of road dust directly impacted by vehicle emissions and provides accurate predictions of trace metal(loid) contamination sources in the urban environment

Brain structural and functional alterations in MOG antibody disease

BACKGROUND: The impact of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) on brain structure and function is unknown. OBJECTIVES: The aim of this study was to study the multimodal brain MRI alterations in MOGAD and to investigate their clinical significance. METHODS: A total of 17 MOGAD, 20 aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4 + NMOSD), and 28 healthy controls (HC) were prospectively recruited. Voxel-wise gray matter (GM) volume, fractional anisotropy (FA), mean diffusivity (MD), and degree centrality (DC) were compared between groups. Clinical associations and differential diagnosis were determined using partial correlation and stepwise logistic regression. RESULTS: In comparison with HC, MOGAD had GM atrophy in frontal and temporal lobe, insula, thalamus, and hippocampus, and WM fiber disruption in optic radiation and anterior/posterior corona radiata; DC decreased in cerebellum and increased in temporal lobe. Compared to AQP4 + NMOSD, MOGAD presented lower GM volume in postcentral gyrus and decreased DC in cerebellum. Hippocampus/parahippocampus atrophy associated with Expanded Disability Status Scale (R = -0.55, p = 0.04) and California Verbal Learning Test (R = 0.62, p = 0.031). The differentiation of MOGAD from AQP4 + NMOSD achieved an accuracy of 95% using FA in splenium of corpus callosum and DC in occipital gyrus. CONCLUSION: Distinct structural and functional alterations were identified in MOGAD. Hippocampus/parahippocampus atrophy associated with clinical disability and cognitive impairment

Mesenchymal stem cell-derived exosomal microRNA-367–3p alleviates experimental autoimmune encephalomyelitis via inhibition of microglial ferroptosis by targeting EZH2

Multiple sclerosis (MS) is an autoimmune, inflammatory demyelinating disorder of the central nervous system. Accumulating evidence has underscored the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exos) containing bioactive compounds in MS. Herein, the current study sought to characterize the mechanism of BMSC-Exos harboring miR-367–3p both in BV2 microglia by Erastin-induced ferroptosis and in experimental autoimmune encephalomyelitis (EAE), a typical animal model of MS. Exosomes were firstly isolated from BMSCs and identified for further use. BV2 microglia were co-cultured with miR-367–3p-containing BMSC-Exos, followed by an assessment of cell ferroptosis. Mechanistic exploration was furthered by the interaction of miR-367–3p and its downstream regulators. Lastly, BMSC-Exos harboring miR-367–3p were injected into EAE mice for in vivo validation. BMSC-Exos carrying miR-367–3p restrained microglial ferroptosis in vitro. Mechanistically, miR-367–3p could bind to Enhancer of zeste homolog 2 (EZH2) and restrain EZH2 expression, leading to the over-expression of solute carrier family 7 member 11 (SLC7A11). Meanwhile, over-expression of SLC7A11 resulted in Glutathione Peroxidase 4 (GPX4) activation and ferroptosis suppression. Ectopic expression of EZH2 in vitro negated the protective effects of BMSC-Exos. Furthermore, BMSC-Exos containing miR-367–3p relieved the severity of EAE by suppressing ferroptosis and restraining EZH2 expression in vivo. Collectively, our findings suggest that BMSC-Exos carrying miR-367–3p brings about a significant decline in microglia ferroptosis by repressing EZH2 and alleviating the severity of EAE in vivo, suggesting a possible role of miR-367–3p overexpression in the treatment strategy of EAE. Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request