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Purpose: There is an increasing interest in modern orthopaedic practice to empower patients to participate in shared decision-making. Decision aids are thought to be helpful in this process. Before creating decision aids for patients with osteoarthritis in the knee or hip, the goal was to identify the needs of patients and physicians when deciding about the treatment. Specifically, this study tested the null hypothesis that there is no significant difference in decisional conflict between patients with knee or hip osteoarthritis and orthopaedic surgeons.Methods: Thirty-three orthopaedic surgeons and 172 patients with either knee or hip osteoarthritis were surveyed. Patients entered their demographic information and completed the Knee Injury and Osteoarthritis Outcome Score/Hip Disability and Osteoarthritis Outcome Score, the Assessment of Needs survey based on the Ottawa Decision Support Framework, the Decisional Conflict Scale, the Pain Self-Efficacy Questionnaire, the Patient-Doctor Relationship Questionnaire-9, the Pain Anxiety Symptoms Scale and the Patient Health Questionnaire. Physicians entered their demographic and professional information and completed the Assessment of Needs survey based on the Ottawa Decision Support Framework and the Decisional Conflict Scale.Results: The results showed that there was a significant difference (P < 0.01) between patients [mean (SD), 33 (19)] and physicians [mean (SD), 24 (14)], regarding decisional conflict about the treatment of knee and hip osteoarthritis. It also showed that patients' decisional conflict was associated with the patient-doctor relationship, and there was a need for information and clearness of one's values for risks and benefits.Conclusion: Patients had a higher magnitude of decisional conflict than physicians and that the level of decisional conflict was positively influenced by the patient-doctor relationship. Patients had high needs regarding information and clearness of one's values for risks and benefits.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Nitrous oxide (NO) reduction of online precalciner-type kiln systems by coal reburning was investigated experimentally using a one-dimensional furnace system. NO reduction can reach as high as ∼70-80% in the tested reburning zone stoichiometry range (SR2) of ∼0.6-1.0. The NO reduction efficiency of bituminous coal is lower than that of anthracite (0.5 < SR2 <0.65). A higher temperature can lead to a higher NO reduction efficiency since 0.6 < SR2 < 0.7. There is an exponential correlation between the NO reduction efficiency and residence time, which may be influenced by several parameters, such as reburning zone stoichiometry and reburning coal characteristics. © 2015 American Institute of Chemical Engineers Environ Prog, 35: 439-446, 2016 [ABSTRACT FROM AUTHOR]

New geochronological and geochemical data were presented for the Early Carboniferous basaltic to andesitic volcanic rocks and Late Carboniferous granitic intrusions in the Aqishan–Yamansu Belt of Eastern Tianshan, NW China. Zircon U–Pb dating indicates that the andesite and granite were emplaced at 330 Ma and 321 Ma, respectively. The andesitic rocks of the Yamansu Formation (FM) display subalkaline to calc-alkaline characteristics with moderate SiO2, relatively high Mg# values, and low Cr, Co and Ni, indicating an origin from mantle-derived melts. Their relatively low εNd(t) values (–0.02 ~ +0.61) and old TDM ages (TDM = 1.39–1.40 Ga) suggest a mantle source with addition of old crustal materials. Their high Rb/Y and Ba/La, low Nb/Y and Th/Yb ratios elucidate that the magma sources were probably metasomatized by slab-derived fluids. Besides, the high Th and low Ce/Th and Ba/Th ratios of the andesites suggest a contribution from subducted sediment–derived melts. Integrated with the depletion in high field strength elements and enrichment in light rare earth elements (LREEs), we suggest that the Yamansu andesites were formed by partial melting of relatively enriched mantle wedge metasomatized by both subducted sediment-derived melts and fluids. The basalts of the Tugutublak Formation (TF) have high MgO, Mg# (56–58) and εNd(t) (+5.9 ~ +6.3) values with enriched in LREEs and depleted in Nb–Ta–Ti anomalies, implying an arc setting. Their high Ba/Th, Ba/La and low Th/Ta, Th/Yb ratios suggest that the slab-derived fluids were involved. The basaltic andesites of the TF have higher SiO2, lower Mg# (48–50), Cr, Ni and εNd(t) (+1.21) values than the basalts of this formation, indicating that they were evolved from the basaltic magma. Therefore, the Carboniferous volcanic rocks in this study indicate that the Aqishan–Yamansu Belt was in a subduction background. The granites intruding into the TF show typical characteristics of I-type granite. Their highly positive εHf(t) values (+14 ~ +17) suggest a significant contribution from juvenile basaltic lower crust. Moreover, changes in the Dy/Yb and Ho/Yb ratios of Late Paleozoic felsic igneous rocks in the Aqishan–Yamansu Belt imply that the crust underwent four periods of thickening and thinning, which were likely triggered by the variation of subduction angles. [ABSTRACT FROM AUTHOR]

To better constrain Ca isotopic fractionation during volcanic magma differentiation, we report Ca isotope data for a series of volcanic glasses from the eastern Manus Basin that represent a continuum of compositions comprising basaltic andesite, andesite, dacite, and rhyolite. Our results show that these volcanic glasses exhibit ~0.25‰ variation in Ca isotopic compositions, with δ44/40Ca ranging from 0.81 ± 0.04 to 1.05 ± 0.04‰. The similar trace element patterns and Sr-Nd isotopic compositions exclude source heterogeneity as the cause of the varied Ca isotopic compositions. Due to their low K/Ca ratios and young age, the Ca isotopic variations cannot be attributed to 40K decay. Instead, the observed Ca isotopic variations are primarily controlled by their lithology. Specifically, δ44/40Ca of basaltic andesite (0.81 ± 0.04) and andesite (0.82 ± 0.01) are similar to the averages of reported mid-ocean ridge basalts (MORBs; 0.84 ± 0.10; 2SD, N = 26) and back-arc basin basalts (BABBs; 0.80 ± 0.08; 2SD, N = 21) in literature, but do not correlate with SiO 2 or MgO contents, indicating the Ca isotopic fractionation is insignificant during intermediate-mafic magma evolution. As magma differentiation continues, δ44/40Ca of dacite and rhyolite evolves from 0.85 ± 0.01 to 1.05 ± 0.04‰. Moreover, δ44/40Ca of felsic glasses are negatively correlated with Eu/Eu*, which suggests that the increasing δ44/40Ca of felsic glasses is most likely related to plagioclase (Pl) fractional crystallization. Therefore, we conclude that Ca isotopes can behave differently at different stages of volcanic magma differentiation. Modeling of fractional crystallization using rhyolite-MELTS shows that the relative Ca fractions in crystallized minerals (e.g., Pl vs. Cpx) and the Ca isotopic fractionation factor between the residual melt and crystallized Pl (α melt-Pl , which is likely related to the An number of Pl, magma temperature and kinetic effects during crystallization), provide a plausible explanation for the behavior of Ca isotopes during volcanic magma differentiation. [ABSTRACT FROM AUTHOR]

Calcium isotopes can potentially be used to trace many geological processes. Characterizing the Ca isotopic compositions of marine sediments is a precondition for using Ca isotopes to trace the recycling of marine sediments into the mantle and mantle-derived rocks. The best way to achieve this goal is to investigate different types of marine sediments that are adjacent to subduction zones and would undergo subduction in the future. Here, we present high-precision Ca isotopic data for marine sediments from the Deep Sea Drilling Project (DSDP) Sites 543 and 144 along the Lesser Antilles forearc region, to constrain the Ca isotope signatures of marine sediments with various components and assess their possible effects on δ44/40Ca of the local mantle and arc lavas via subduction. Our results show that the δ44/40Ca values of these marine sediments vary from 0.10 to 1.21‰ and depend on lithology. Carbonate-rich sediments from Site 144 exhibit δ44/40Ca values in the range of 0.10–0.58‰ with a weighted average value of 0.36‰, which is ∼0.6‰ lower than that of the mantle. In comparison, δ44/40Ca of clay-rich sediments from Site 543 range from 0.79 to 1.21‰ with a mantle-like mean value of 0.96‰. The data obtained here suggest that carbonate- and clay-rich marine sediments differ significantly both in Ca isotopic compositions and CaO contents. Recycling of these sediments will result in different effects on the isotopic compositions of the local mantle and probably affect the local arc lavas. Specifically, carbonate-rich sediments from Site 144 with high CaO contents and light Ca isotopic compositions can alter the local mantle to lower δ44/40Ca signatures, which is expected in the southern Lesser Antilles arc lavas. [ABSTRACT FROM AUTHOR]

As the southernmost continental fragment in the Central Asian Orogenic Belt (CAOB), the Chinese Central Tianshan Block (CTB) is essential for understanding the evolution of the CAOB. However, its tectonic affinity with the Tarim Craton and links with supercontinent cycles are not clear. Here, we present whole-rock geochemistry, zircon ages and Hf-in-zircon isotopic data for augen- and mylonitic granitic gneisses in the eastern Chinese Central Tianshan Block (ECTB). Zircon U-Pb dating reveals that the augen- and mylonitic gneisses formed at ca. 918 Ma and 896 Ma, respectively. The gneisses have REE and HFSEs patterns comparable to the upper continental crust. Their Cr and Ni contents are similar to those of the typical S-type granites in the Lachlan belt. These rocks exhibit evolved zircon ε Hf (t) values (−9.0 to +1.6), which are consistent with those values of coeval crustal-derived rocks within the CTB. Together with the occurrence of muscovite and the existences of Paleo- to Mesoproterozoic inherited zircons (2.21–1.25 Ga), the geochemical data indicate that protoliths of these gneisses are S-type granites. These results, compiled with published geochronological data, suggest that an Archean basement was most likely absent in the CTB. The basement rocks of the CTB were dominantly produced by crustal growth in the early Mesoproterozoic and then reworked at Neoproterozoic. We suggest that the Mesoproterozoic crustal growth and the early Neoproterozoic crustal reworking were likely related to the breakup of the Nuna (ca. 1.40 Ga) and the assembly of the Rodinia (1.00–0.88 Ga), respectively. Because the CTB displays different crustal evolution from the Tarim Craton, we conclude that these two blocks have no close tectonic affinity in the Precambrian. [ABSTRACT FROM AUTHOR]

We present a new method to investigate the local optical dielectric permittivity using layered capacitors. The method has been applied to study the optical dielectric constants of Si/SiO structures without defects, with dangling bonds, and with dangling bonds passivated by H. For each of the three structures, models composed of 5, 7, and 12 Si layers were studied, and the effect of the Si layer thickness was assessed. The different local optical dielectric constants in the adjacent Si interface region were obtained for the nine models, and the effect of the Si layer thickness, the bond lengths, and the oxidation states of Si at the interface were analyzed. The results showed that the local optical dielectric constant of the structure with dangling bonds in the region adjacent to the Si interface was larger than that of the structure with no defects; and the effect of the interface defect Si on the dielectric constant is stronger than that of the Si layer thickness, and effect scope of Si reached approximate 7 Å in silicon region. [ABSTRACT FROM AUTHOR]

[Display omitted] • Mesoproterozoic granitoids in the CTB formed in association with subduction. • A ~1.3–1.6 Ga subduction system existed encircling Nuna. • A dominant exterior subduction along the periphery of Nuna with subordinate intermittent plume activities drives the breakup of supercontinent. The dynamic mechanism responsible for the breakup of Nuna supercontinent (1.6–1.3 Ga) is a key for understanding the early to middle Mesoproterozoic environment, life and mineralization on Earth. Although much research has been done to unravel the dispersion of young supercontinents (e.g., Pangea), efforts by sorting out critical geological records to disclose the driving force for Nuna breakup are still rare. Here we focus on this issue by integrating new whole-rock geochemical data, zircon U–Pb ages, Hf-in-zircon and Nd isotopes for Mesoproterozoic granitoids in the Chinese Central Tianshan (CTB) at the Central Asian Orogenic Belt (CAOB). Moreover, global geological data in the early to middle Mesoproterozoic are compiled to place further constraints. The studied granitoids are I-type granites emplaced at ca. 1480–1450 Ma. They were formed in an active continental margin of CTB that once belonged to the Fennoscandia in the margin of Nuna. These results, together with the available geological records in CTB, CAOB and Fennoscandia, indicate a subduction system existed along the periphery of these domains in the early to middle Mesoproterozoic. This subduction system was temporally and spatially linked to the 1.6–1.3 Ga accretionary belts in the peripheral blocks of Nuna supercontinent, suggesting an encircling subduction system surrounding Nuna supercontinent. The encircling subduction system was accompanied by intermittent Mesoproterozoic plume magmatism, some of which were geochemically overprinted with subduction-related signatures, suggesting a dominant continuous circum-supercontinent subduction operating on the breakup of Nuna supercontinent. Moreover, these episodic plume-related magmatism are temporally and geodynamically linked to the exterior subduction surrounding the Nuna supercontinent. Our study therefore demonstrates that the development of an exterior subduction system gave rise to the breakup of Nuna supercontinent, which was accompanied by subordinate plume activities. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to uncover the anti-inflammatory propertity of andrographolide (AGP) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the underlying mechanisms related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway., Methods: An in vivo experiment was conducted on murine model of AECOPD through endotracheal atomization of elastase and lipopolysaccharide (LPS). Intraperitoneal AGP was administered four times. NLRP3 inflammasome pathway molecules were examined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. By using enzyme-linked immunosorbent assay (ELISA), we tested interleukin (IL)-1β levels in bronchoalveolar lavage fluid. An in vitro study was conducted to determine how AGP impacts the NLRP3 inflammasome in THP-1 derived macrophages. The levels of molecules involved in the pathway were measured. Furthermore, molecular docking analyses were carried out to investigate the interactions between AGP and pathway targets., Results: In the in vivo study, NLRP3 inflammasome activation was observed in mice experiencing AECOPD. The administration of high-dose AGP demonstrated a mitigating effect on inflammatory cells infiltration in the lungs. Moreover, AGP administration effectively suppressed the expression of NLRP3, apoptosis associated speck-like protein that contains a CARD (PYCARD), cysteinyl aspartate-specific protease-1 (Caspase-1), IL-1β, and IL-18 at both the genetic and protein levels. In the in vitro experiment, IL-1β levels were significantly elevated in THP-1 derived macrophages with activated inflammasome compared to the control group. Furthermore, the downregulation of NLRP3, CASP1, and IL1B genes was observed upon the inhibition of NLRP3 expression through small interfering RNA (siRNA). AGP demonstrated inhibitory effects on the gene expression and protein levels of NLRP3, Caspase-1, and IL-1β. Additionally, molecular docking analysis confirmed that AGP exhibited a favorable binding affinity with all five targets of the pathway., Conclusion: AGP effectively inhibited NLRP3 inflammasome activation and mitigated the inflammatory reaction of AECOPD both in animal models and in vitro experiments, highlighting the potential of AGP as a treatment for AECOPD with anti-inflammatory properties., Competing Interests: The authors declare that they have no competing interests., (© 2024 Yu et al.)

Background: Dyspnea, a common symptom of chronic respiratory diseases (CRDs), is closely linked to higher levels of functional impairment and death, leading to significant societal and financial challenges. Despite numerous clinical trials and systematic reviews suggested the potential benefits of acupuncture for chronic obstructive pulmonary disease (COPD) and lung cancer, there is currently insufficient evidence to conclusively prove its effectiveness in alleviating dyspnea in patients with CRDs., Methods: To compile and evaluate the existing data on the effectiveness and safety of acupuncture for managing dyspnea in CRDs. Randomized controlled trials investigating acupuncture for the treatment of dyspnea in patients with CRDs, such as COPD, lung cancer, asthma, bronchiectasis, interstitial lung disease, chronic pulmonary heart disease and bronchitis, were searched and retrieved from five electronic databases in English or Chinese., Results: A total of 23 studies meeting the inclusion criteria were found in databases, covering various CRDs such as COPD, lung cancer, and asthma. A meta-analysis that compared acupuncture to a control group (which included no acupuncture and sham acupuncture) found significant advantages for acupuncture in reducing dyspnea severity ( P  = 0.0003), increasing 6MWD ( P  < 0.00001), improving quality of life measured by St. George's Respiratory Questionnaire ( P  = 0.03) and karnofsky performance status score ( P  < 0.00001). No significance was found in breathing physiology represented by FEV 1 ( P  = 0.34) and FVC ( P  = 0.15). There was a comparable incidence of negative outcomes in both groups ( P  = 0.07). Results were consistent when compared to sham acupuncture. In addition, subgroup analyses were also consistent when different diseases or types of acupuncture were analyzed., Conclusions: Acupuncture may be an effective and safe non-pharmacological complementary intervention to relief dyspnea for patients with CRDs. Nevertheless, research with high quality and large sample sizes is needed for further investigation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Rationale: Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome., Objectives: To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes., Methods: We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data., Results: Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota., Conclusions: Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment., (© 2024. The Author(s).)

With economic development, the health of river ecosystems is becoming severely threatened because of the increasing effects of human activities on river ecosystems. Here, 101 sites along regional river systems in Beijing rivers were investigated from autumn 2020 to summer 2021. A total of 34 metrics, including aquatic organisms, hydrology, water quality, and habitat, were calculated to be the candidate indicators. Principal component and correlation analyses were used to select the core metrics from the candidate indicators, and the weight of each core metric was estimated using the entropy method. The integrated index of stream ecological health was constructed to assess the health condition of the Beijing rivers. The results of the PCA and correlation analyses revealed that eleven metrics were selected as the core metrics to construct the integrated index of stream ecological health, including water temperature, flow velocity, BOD 5 , NH 4 + -N, Cu, the density of phytoplankton and zooplankton, the Shannon-Wiener diversity index of macroinvertebrates and fish, the BMWP index, and the qualitative habitat evaluation index. According to the health assessment results, 4.95% of the sampling sites were healthy, 23.76% were subhealthy, and 71.29% were in a fair or below healthy state. The river health status showed strong spatial heterogeneity, and the river health statuses in the northern and western regions were relatively good, whereas the river health status in the central and southeastern regions were relatively poor. The results of four aspects stream ecosystem assessment showed that the overall water quality of the rivers was "subhealthy" and the aquatic organisms and habitat were "general poor," but the hydrology was "poor." The evaluation results of five water systems demonstrated that the Chaobai River had the best health status, followed by that of the Yongding River, Daqing River, and Jiyun River, and the Beiyun River had the worst health status. Maintaining river ecological baseflow, ensuring river system connectivity, and improving and restoring the river habitat environment are the key aspects of river ecological restoration and protection in Beijing in the future.

Background: Assessment of head-cervical spine motion (HCSM) is a vital index of functional evaluation for cervical surgery, but there is a lack of HCSM datasets in the healthy population and no suitable tools to measure HCSM in clinical practice. The objectives of this study were to obtain the normal values of HCSM in a healthy population, test the reliability and validity of an APP "G-Plus," and analyze related influencing factors of HCSM., Methods: We measured HCSM in 6 directions of 500 healthy people with a CROM apparatus and "G-Plus." The intraclass correlation coefficient (ICC) was used to test the reliability of "G-Plus." The validity of "G-Plus" measurements as compared with the CROM apparatus was tested by Bland-Altman statistics. We used multiple linear regression analysis to test the correlation among age, gender, body mass index (BMI), neck configuration (ratio of cervical circumference to cervical length), and HCSM., Results: Excellent interrater and intrarater reliability were demonstrated for CROM (ICC:0.929-0.993) and "G-Plus" (ICC: 0.898-0.991). Bland-Altman plots demonstrated an acceptable agreement between CROM and "G-Plus." Age was negatively correlated with HCSM. HCSM in females was superior to males except for flexion. Neck configuration affected HCSM in the direction of extension, right lateral flexion, and left and right rotation. BMI was correlated with flexion and extension., Conclusions: "G-Plus" is a reliable and convenient tool for HCSM measurement in clinical practice. The presentation of datasets of HCSM in healthy population provides a basic reference for cervical function assessment. Age, gender, BMI, and neck configuration are significantly correlated to HCSM., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In recent years, acupuncture has gained great progress in the treatment of chronic respiratory diseases (CRD), and the clinical effect is remarkable, but its underlying mechanisms are relatively complex, with the anti-inflammatory effect being the primary aspect. Based on the literature both at home and abroad, we found that the anti-inflammatory mechanism of acupuncture mainly involves chemokines, kinase-related pathways, helper T cells, epigenetic modification, autophagy, vagal-mediated cholinergic anti-inflammatory pathway, etc. The researches on some anti-inflammatory mechanisms are still in the initial stage, the relationship among various pathways, and the key factors affecting the effect of acupuncture, such as acupoint selection, stimulation intensity and needling depth, etc. warrant further exploration in the future.

Background: Studies have reported that RNA-binding proteins (RBPs) are dysregulated in multiple cancers and are correlated with the progression and prognosis of disease. However, the functions of RBPs in non-small cell lung cancer (NSCLC) remain unclear. The present study aimed to explore the function of RBPs in NSCLC and their prognostic and therapeutic value. Methods: The mRNA expression profiles, DNA methylation data, gene mutation data, copy number variation data, and corresponding clinical information on NSCLC were downloaded from The Cancer Genome Atlas, Gene Expression Omnibus, and the University of California Santa Cruz Xena databases. The differentially expressed RBPs were identified between tumor and control tissues, and the expression and prognostic value of these RBPs were systemically investigated by bioinformatics analysis. A quantitative polymerase chain reaction (qPCR) was performed to validate the dysregulated genes in the prognostic signature. Results: A prognostic RBP-related signature was successfully constructed based on eight RBPs represented as a risk score using least absolute shrinkage and selection operator (LASSO) regression analysis. The high-risk group had a worse overall survival (OS) probability than the low-risk group ( p < 0.001) with 1-, 3-, and 5-year area under the receiver operator characteristic curve values of 0.671, 0.638, and 0.637, respectively. The risk score was associated with the stage of disease ( p < 0.05) and was an independent prognostic factor for NSCLC when adjusted for age and UICC stage ( p < 0.001, hazard ratio (HR): 1.888). The constructed nomogram showed a good predictive value. The P53 , focal adhesion, and NOD-like receptor signaling pathways were the primary pathways in the high-risk group (adjusted p value <0.05). The high-risk group was correlated with increased immune infiltration ( p < 0.05), upregulated relative expression levels of programmed cell death 1 ( PD1 ) ( p = 0.015), cytotoxic T-lymphocyte-associated protein 4 ( CTLA4 ) ( p = 0.042), higher gene mutation frequency, higher tumor mutational burden ( p = 0.034), and better chemotherapy response ( p < 0.001). The signature was successfully validated using the GSE26939, GSE31210, GSE30219, and GSE157009 datasets. Dysregulation of these genes in patients with NSCLC was confirmed using the qPCR in an independent cohort ( p < 0.05). Conclusion: An RBP-related signature was successfully constructed to predict prognosis in NSCLC, functioning as a reference for individualized therapy, including immunotherapy and chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miao, Chen, Du, Xiao and Fu.)

Introduction: Increasing numbers of patients with non-haematological diseases are infected with invasive pulmonary aspergillosis (IPA), with a high mortality reported which is mainly due to delayed diagnosis. The diagnostic capability of mycological tests for IPA including galactomannan test, (1,3)-β-D-glucan test, lateral flow assay, lateral flow device and PCR for the non-haematological patients remains unknown. This protocol aims to conduct a systematic review and meta-analysis of the diagnostic performance of mycological tests to facilitate the early diagnosis and treatments of IPA in non-haematological diseases., Methods and Analysis: Database including PubMed, CENTRAL and EMBASE will be searched from 2002 until the publication of results. Cohort or cross-sectional studies that assessing the diagnostic capability of mycological tests for IPA in patients with non-haematological diseases will be included. The true-positive, false-positive, true-negative and false-negative of each test will be extracted and pooled in bivariate random-effects model, by which the sensitivity and specificity will be calculated with 95% CI. The second outcomes will include positive (negative) likelihood ratio, area under the receiver operating characteristic curve and diagnostic OR will also be computed in the bivariate model. When applicable, subgroup analysis will be performed with several prespecified covariates to explore potential sources of heterogeneity. Factors that may impact the diagnostic effects of mycological tests will be examined by sensitivity analysis. The risk of bias will be appraised by the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2)., Ethics and Dissemination: This protocol is not involved with ethics approval, and the results will be peer-reviewed and disseminated on a recognised journal., Prospero Registration Number: CRD42021241820., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Methods: Totally, 24 BALB/c mice were assigned to the AR group, control group, GzmB group, and blank group (each n  = 6). The blank group was normally fed without treatment, and the other three groups were treated by ovalbumin (OVA) to induce AR models, in which the GzmB group was intranasally injected with lentiviral vector suppressing GzmB expression during the second immunization, while the control group was given the GzmB-blank vector. The times of AR pathological behaviours such as sneezing and scratching the nose of mice were observed and counted. The nasal lavage fluid of each mouse was acquired, and then, the mouse was executed by cervical dislocation, followed by collection of blood and nasal mucosa tissues. Then, ELISA was adopted for quantifying immunoglobulin E (IgE), interleukin (IL)-4, IL-6, and histamine (HA), and nasal mucosa tissues were treated by HE and TUNEL staining to observing their histopathological manifestations. PCR and western blot (WB) were adopted for quantifying GzmB and miR-378a-3p. Additionally, with NP69 cells, dual luciferase reporter (DLR) assay was carried out for determining the targeting association of GzmB with miR-378a-3p. Another 24 mice were assigned to the AR group, GzmB group, miR-378a-3p group, and GzmB+ miR-378a-3p group (each n  = 6). The AR and GzmB groups were treated as above. The miR-378a-3p group was intervened by lentiviral vector suppressing miR-378a-3p, while the GzmB+ miR-378a-3p group was given GzmB and lentiviral vector suppressing miR-378a-3p meantime. A rescue assay was conducted through repeating the above tests., Results: The times of sneezing and rubbing the nose and the levels of IgE, IL-4, IL-6, and HA were similar between the control and AR groups (all P > 0.05), and these items of the two groups were all higher than those of the blank and GzmB groups (all P < 0.05). However, no notable difference was observed in IL-4 and IL-6 levels between the GzmB and blank groups (both P > 0.05), while higher levels of other detection results were found in the former group than in the latter (all P < 0.05). The staining results revealed obvious congestion, oedema, and necrosis structures in the nasal mucosa epithelium of the control and AR groups and also revealed a large number of infiltrating eosinophils and notable increase of apoptotic nasal mucosa epithelial cells. The GzmB group showed notably improved nasal mucosa tissues, and its infiltration and apoptosis of eosinophils were more notable than those of the blank group, but notably weaker than those of the AR and control groups. Additionally, the PCR and WB results revealed similar miR-378a-3p and GzmB levels in nasal mucosa between the control and AR groups (both P > 0.05), and a notable decrease of miR-378a-3p and a notable increase of GzmB in both groups (both P < 0.05). The DLR a ssay revealed notably suppressed fluorescence activity of GzmB-WT in NP69 cells after transfection of miR-378a-3p mimics ( P < 0.05) and notably down regulated GzmB protein after increase of miR-378a-3p ( P <0.05). Finally, the rescue assay revealed that downregulating miR-378a-3p aggravated the pathological changes of AR ( P < 0.05) and also completely reversed the impacts of inhibiting GzmB on the pathological behaviours of AR mice., Conclusions: MiR-378a-3p can accelerate the pathological development of AR through targeted inhibition on the release of pro-inflammatory factors such as IgE and HA activated by GzmB, so it is a promising molecular target of AR therapy and offers a novel research direction for the complete cure of AR., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xuping Wang et al.)

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a central regulator of immunity. TRAF3 is often somatically mutated in B cell malignancies, but its role in human immunity is not defined. Here, in five unrelated families, we describe an immune dysregulation syndrome of recurrent bacterial infections, autoimmunity, systemic inflammation, B cell lymphoproliferation, and hypergammaglobulinemia. Affected individuals each had monoallelic mutations in TRAF3 that reduced TRAF3 expression. Immunophenotyping showed that patients' B cells were dysregulated, exhibiting increased nuclear factor-κB 2 activation, elevated mitochondrial respiration, and heightened inflammatory responses. Patients had mild CD4 + T cell lymphopenia, with a reduced proportion of naïve T cells but increased regulatory T cells and circulating T follicular helper cells. Guided by this clinical phenotype, targeted analyses demonstrated that common genetic variants, which also reduce TRAF3 expression, are associated with an increased risk of B cell malignancies, systemic lupus erythematosus, higher immunoglobulin levels, and bacterial infections in the wider population. Reduced TRAF3 conveys disease risks by driving B cell hyperactivity via intrinsic activation of multiple intracellular proinflammatory pathways and increased mitochondrial respiration, with a likely contribution from dysregulated T cell help. Thus, we define monogenic TRAF3 haploinsufficiency syndrome and demonstrate how common TRAF3 variants affect a range of human diseases.

Background: Leadless pacemakers (LPs) have proven safe and effective, but device revisions remain necessary. Either replacing the LP or implanting a new adjacent LP is feasible. Replacement seems more appealing, but encapsulation and tissue adhesions may hamper the safety and efficacy of LP retrieval., Objective: We determined the incidence and cellular characteristics of tissue adherent to retrieved LPs and the potential implications for end-of-life strategy., Methods: All 15 consecutive successful Nanostim LP retrievals in a tertiary center were included. We assessed the histopathology of adherent tissue and obtained clinical characteristics., Results: Adherent tissue was present in 14 of 15 retrievals (93%; median implantation duration 36 months; range 0-96 months). The tissue consisted of fibrosis (n = 2), fibrosis and thrombus (n = 9), or thrombus only (n = 3). In short-term retrievals (<1 year), mostly fresh thrombi without fibrosis were seen. In later retrievals, the tissue consisted of fibrosis often with organizing or lytic thrombi. Fibrosis showed different stages of organization, notably early fibrocellular and later fibrosclerotic tissue. Inflammatory cells were seen (n = 4) without signs of infection. Tricuspid valve material was retrieved in 1 patient after 36 months, resulting in increased tricuspid regurgitation., Conclusion: Our results suggest that fibrosis and thrombus adherent to LPs are common and encapsulate the LP as seen in transvenous pacemakers. LPs may adhere to the tricuspid valve or subvalvular apparatus affecting retrieval safety. The end-of-life strategy should be optimized by incorporating risk stratification for excessive fibrotic encapsulation and adhesions., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy., Methods: This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course., Findings: Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78). Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets.., Interpretation: In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19., Funding: Amsterdam UMC Corona Research Fund., (© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

Purpose: There is an increasing interest in modern orthopaedic practice to empower patients to participate in shared decision-making. Decision aids are thought to be helpful in this process. Before creating decision aids for patients with osteoarthritis in the knee or hip, the goal was to identify the needs of patients and physicians when deciding about the treatment. Specifically, this study tested the null hypothesis that there is no significant difference in decisional conflict between patients with knee or hip osteoarthritis and orthopaedic surgeons., Methods: Thirty-three orthopaedic surgeons and 172 patients with either knee or hip osteoarthritis were surveyed. Patients entered their demographic information and completed the Knee Injury and Osteoarthritis Outcome Score/Hip Disability and Osteoarthritis Outcome Score, the Assessment of Needs survey based on the Ottawa Decision Support Framework, the Decisional Conflict Scale, the Pain Self-Efficacy Questionnaire, the Patient-Doctor Relationship Questionnaire-9, the Pain Anxiety Symptoms Scale and the Patient Health Questionnaire. Physicians entered their demographic and professional information and completed the Assessment of Needs survey based on the Ottawa Decision Support Framework and the Decisional Conflict Scale., Results: The results showed that there was a significant difference (P < 0.01) between patients [mean (SD), 33 (19)] and physicians [mean (SD), 24 (14)], regarding decisional conflict about the treatment of knee and hip osteoarthritis. It also showed that patients' decisional conflict was associated with the patient-doctor relationship, and there was a need for information and clearness of one's values for risks and benefits., Conclusion: Patients had a higher magnitude of decisional conflict than physicians and that the level of decisional conflict was positively influenced by the patient-doctor relationship. Patients had high needs regarding information and clearness of one's values for risks and benefits., Level of Evidence: II.

Objective: To understand the epidemic situation and characteristics of malaria in Yunnan Province, so as to provide the reference for malaria elimination., Methods: The data of malaria reported in the information system were collected and analyzed in Yunnan Province from 2011 to 2013., Results: From 2011 to 2013, totally 2 256 malaria cases were found in Yunnan Province, with a morbidity of 0.162 8 per million and three of them were death cases. The local cases mainly distributed along the boundary and accounted for 29.48%, while the imported cases mainly came from Myanmar and accounted for 70.52%. The number of endemic counties with local malaria cases decreased from 37 to 10 during the three years. The number of imported cases reached the peak in May and the local cases in June. The patients were mainly aged from 20 to 49 years old (accounted for 70.58%), and 85.24% of the cases were peasants and laborers. Totally 86.66% of cases were laboratory confirmed cases, and 13.14% were clinically diagnosed. The proportions of cases reported by hospitals, health service centers and CDCs were 33.02%, 37.06% and 29.92%, respectively., Conclusions: The prevalence of malaria in Yunnan Province decreased from 2011 to 2013. The work of malaria cases double-checked by province-level CDCs is effective. However, the awareness and accurately diagnostic capability of clinical doctors still should be strengthened.