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Abstract Background Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology of Alzheimer’s disease (AD). The natural psychedelic N, N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti-AD potential through protecting neuronal ER-mitochondrial interplay. Methods 3×TG-AD transgenic mice were administered with chronic DMT (2 mg/kg) for 3 weeks and then performed water maze test. The Aβ accumulation in the mice brain were determined. The Sig-1r level upon DMT treatment was tested. The effect of DMT on the ER-mitochondrial contacts site and multiple mitochondria-associated membrane (MAM)-associated proteins were examined. The effect of DMT on calcium transport between ER and mitochondria and the mitochondrial function were also evaluated. Results chronic DMT (2 mg/kg) markedly alleviated cognitive impairment of 3×TG-AD mice. In parallel, it largely diminished Aβ accumulation in the hippocampus and prefrontal cortex. DMT restored the decreased Sig-1r levels of 3×TG-AD transgenic mice. The hallucinogen reinstated the expression of multiple MAM-associated proteins in the brain of 3×TG-AD mice. DMT also prevented physical contact and calcium dynamic between the two organelles in in vitro and in vivo pathological circumstances. DMT modulated oxidative phosphorylation (OXPHOS) and ATP synthase in the in vitro model of AD. Conclusion The anti-AD effects of DMT are associated with its protection of neuronal ER-mitochondria crosstalk via the activation of Sig-1r. DMT has the potential to serve as a novel preventive and therapeutic agent against AD.

The clinical significance of measuring vessel wall thickness is widely acknowledged. Recent advancements have enabled high-resolution 3D scans of arteries and precise segmentation of their lumens and outer walls; however, most existing methods for assessing vessel wall thickness are 2D. Despite being valuable, reproducibility and accuracy of 2D techniques depend on the extracted 2D slices. Additionally, these methods fail to fully account for variations in wall thickness in all dimensions. Furthermore, most existing approaches are difficult to be extended into 3D and their measurements lack spatial localization and are primarily confined to lumen boundaries. We advocate for a shift in perspective towards recognizing vessel wall thickness measurement as inherently a 3D challenge and propose adapting the Laplacian method as an outstanding alternative. The Laplacian method is implemented using convolutions, ensuring its efficient and rapid execution on deep learning platforms. Experiments using digital phantoms and vessel wall imaging data are conducted to showcase the accuracy, reproducibility, and localization capabilities of the proposed approach. The proposed method produce consistent outcomes that remain independent of centerlines and 2D slices. Notably, this approach is applicable in both 2D and 3D scenarios. It allows for voxel-wise quantification of wall thickness, enabling precise identification of wall volumes exhibiting abnormal wall thickness. Our research highlights the urgency of transitioning to 3D methodologies for vessel wall thickness measurement. Such a transition not only acknowledges the intricate spatial variations of vessel walls, but also opens doors to more accurate, localized, and insightful diagnostic insights.

ABSTRACTCorporate inter-regional investment is an important channel for building the domestic economic cycle. This paper explores the impact of firms’ adaptation to regional culture on inter-regional investment based on the sample of newly-established inter-province subsidiaries of A-share listed firms in China from 2006 to 2017. We find that (1) Firms’ low cultural adaptation to home region promote corporate inter-regional investment. (2) Firms are more likely to invest in regions with cultural environments that are more compatible with their own culture value (3) Firms have better investment performance when investing in more culturally adapted regions through better cooperating with new stakeholders and reducing management cost. (4) The impact of cultural adaptation on inter-regional investments is also affected by the state ownership and corresponding regional formal institutions. Our findings have implications for firms to make location choice during inter-regional investment and can help governments attract capital flows.

Objectives: To determine whether glucocorticoids can improve clinical outcomes of severe fever with thrombocytopenia syndrome (SFTS) patients, and how to identify patients who may benefit from the treatment. Methods: A retrospective study was performed to include patients with confirmed SFTS from designated hospitals. The effect of glucocorticoids in reducing case fatality rate (CFR) and improving clinical recovery was evaluated by multivariate logistic regression models. Results: A total of 2478 eligible patients were analyzed, of whom 331 received glucocorticoids. An integrated parameter (L-index) based on Log10(lactate dehydrogenase*blood urea nitrogen/lymphocyte count) was constructed to discriminate disease severity. In patients with L-index >3.823 indicating severe SFTS, significantly reduced CFR was observed in patients receiving low-moderate glucocorticoid doses with ≤60 mg daily methylprednisolone or equivalent (odds ratio [OR] 0.46, 95% confidence interval [CI], 0.23-0.88), but not in patients receiving high doses. In patients with L-index ≤3.823 indicating mild SFTS, glucocorticoid treatment was significantly associated with increased CFR (OR 3.34, 95% CI, 1.35-9.51), and mainly attributable to high-dose glucocorticoids (OR 2.83, 95% CI, 1.72-4.96). Disaggregated data analysis revealed a significant effect only in patients ≤65 years old, male, and early admission within 7 days after onset, but not in their counterparts. Conclusion: Glucocorticoids are not recommended for mild patients defined by L-index

Abstract Background Insomnia is a highly prevalent symptom occurred during and post-chemotherapy. Acupuncture may have beneficial effects in the management of chemotherapy-associated insomnia. This study was conducted to determine the efficacy and safety of acupuncture in improving chemotherapy-associated insomnia in breast cancer patients. Methods This assessor-participant blinded, randomized, sham-controlled trial was conducted from November 2019 to January 2022 (follow-up completed July 2022). Participants were referred by oncologists from two Hong Kong hospitals. Assessments and interventions were conducted at the outpatient clinic of School of Chinese Medicine, the University of Hong Kong. The 138 breast cancer patients with chemotherapy-associated insomnia were randomly assigned to receive either 15 sessions of active acupuncture regimen by combining needling into body acupoints and acupressure on auricular acupoints or sham acupuncture control (69 each) for 18 weeks, followed by 24 weeks of follow-up. The primary outcome was measured using Insomnia Severity Index (ISI). Secondary outcomes included the Pittsburgh Sleep Quality Index, Actiwatch and sleep diary for sleep parameters, depression and anxiety, fatigue and pain, and quality of life. Results There were 87.7% (121/138) participants who completed the primary endpoint (week-6). The active acupuncture regimen was not superior to the sham control in reducing ISI score from baseline to 6 weeks (mean difference: − 0.4, 95% CI − 1.8–1.1; P = 0.609), but produced short-term treatment and long-term follow-up better outcomes in improving sleep onset latency, total sleep time, sleep efficiency, anxiety, depression, and quality of life. Participants of the active acupuncture group had a pronouncedly higher cessation rate of sleeping medications than the sham control (56.5% vs. 14.3%, P = 0.011). All treatment-related adverse events were mild. No participants discontinued treatments due to adverse events. Conclusion The active acupuncture regimen could be considered as an effective option for the management of chemotherapy-associated insomnia. It also could serve as a tapering approach to reduce and even replace the use of sleeping medications in breast cancer patients. Trial registration Clinicaltrials.gov : NCT04144309. Registered 30 October 2019.

IntroductionCarotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are associated with increased carotid atherosclerosis, though the exact association between APOE and carotid plaque is uncertain. The study aimed to evaluate the association between APOE and carotid plaque.MethodsA systematic review was performed to retrieve all studies which examined the association between carotid plaque and APOE. This study was conducted in accordance with the PRISMA guidelines. Independent readers extracted the relevant data from each study including the type of imaging assessment, plaque definition, frequency of APOE E4 carrier status and type of genotyping. Meta-analyses with an assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model.ResultsAfter screening 838 studies, 17 studies were included for systematic review. A meta-analysis of 5 published studies showed a significant association between ε4 homozygosity and carotid plaque [odds ratio (OR), 1.53; 95% CI, 1.16, 2.02; p = .003]. Additionally, there was a significant association between patients possessing at least one ε4 allele, heterozygotes or homozygotes, and carotid plaque (OR, 1.25; 95% CI, 1.03, 1.52; p = .03). Lastly, there was no association between ε4 heterozygosity and carotid plaque (OR, 1.08; 95% CI, 0.93, 1.26; p = .30).ConclusionAPOE ε4 allele is significantly associated with extracranial carotid atherosclerotic plaque, especially for homozygous individuals.

Using the exogenous shock of the COVID-19 pandemic, we examine whether vertical integration creates value for firms when facing increasing uncertainty. Using cross-sectional data during the outbreak of the COVID-19 pandemic, we find that there is a significant and positive correlation between vertical integration and cumulative abnormal return in the event window of the COVID-19. Furthermore, when external transaction costs are higher or internal organization costs are lower during the COVID-19 pandemic, the above results are more pronounced. Our results indicate that vertical integration could avoid uncertainty, reduce transaction costs, hence improving corporate value, providing empirical evidence for theories about the uncertainty and vertical integration in transaction-cost economics.

Objectives: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with a high case fatality rate. Key gaps remained as to the assessment of the clinical picture in fatal cases. Methods: A retrospective study was performed on 496 patients with fatal SFTS. The dynamic pattern of clinical manifestations and laboratory indicators were delineated. Results: The mean age of the fatal cases was 69.0 years (standard deviation: 9.3), and 52.8% were male. The median clinical course from disease onset to death was 11 (interquartile range: 10-13) days. A total of 11 laboratory indicators (neutrophil %, platelet, aspartate aminotransferase, aspartate aminotransferase/alanine transaminase, lactate dehydrogenase, creatine kinase, cystatin C, D-dimer, activated partial thromboplastin time, thrombin time, glucose) persistently deviated from normality across hospitalization. The critical time points when the rapid worsening of the indicators was at 6-9 days after disease onset. Alanine transaminase, AST, lactate dehydrogenase, total bile acid, gamma-glutamyl transpeptidase, and glucose were all elevated to a more pronounced level in fatal cases of those aged ≤70 years. Conclusion: The fatal outcome was developed in rather a short course after the disease onset of SFTS. High vigilance should be put on the key time points when the severe worsening and severe complications occur.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in human patients. The effect of virus variations on virulence and related clinical significance is unclear. We prospectively recruited SFTSV-infected patients in a hotspot region of SFTS endemic in China from 2011 to 2020, sequenced whole genome of SFTSV, and assessed the association of virus genomic variants with clinical data, viremia, and inflammatory response. We identified seven viral clades (I-VII) based on phylogenetic characterization of 805 SFTSV genome sequences. A significantly increased case fatality rate (32.9%) was revealed in one unique clade (IV) that possesses a specific co-mutation pattern, compared to other three common clades (I, 16.7%; II, 13.8%; and III, 11.8%). The phenotype-genotype association (hazard ratios ranged 1.327-2.916) was confirmed by multivariate regression adjusting age, sex, and hospitalization delay. We revealed a pronounced inflammation response featured by more production of CXCL9, IL-10, IL-6, IP-10, M-CSF, and IL-1β, in clade IV, which was also related to severe complications. We observed enhanced cytokine expression from clade IV inoculated PBMCs and infected mice. Moreover, the neutralization activity of convalescent serum from patients infected with one specified clade was remarkably reduced to other viral clades. Together, our findings revealed a significant association between one specific viral clade and SFTS fatality, highlighting the need for molecular surveillance for highly lethal strains in endemic regions and unravelled the importance of evaluating cross-clade effect in development of vaccines and therapeutics.

ABSTRACT: Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease with high mortality, was first reported in 2009 in China and subsequently endemic to South Korea, Japan, Vietnam, and Myanmar. This disease is transmitted predominantly by tick bites and potentially human-to-human. Personal protective equipments (PPEs) have been recommended to prevent SFTS human-to-human transmission, whereas the specific use of PPEs and the effect on viral transmission have rarely been reported. This report identified a family cluster of six patients with SFTS virus (SFTSV) infection. All five secondary patients had been wearing gloves and masks when exposed to the blood of the index patient, but none of them wore goggles or face shields for eye protection. Ocular route was suggested as a highly possible mode for SFTSV transmission through epidemiological, serological, and phylogenetic analysis. Eye protection should be stressed for clinicians when exposed to blood or bloody secretions.

Background and purpose Atherosclerosis is a very complex process influenced by various systemic and local factors. Therefore, in patients with bilateral carotid plaques (BCPs), there may be differences in carotid plaque vulnerability between the sides. We aimed to investigate the differences in BCP characteristics in patients with BCPs using magnetic resonance vessel wall imaging (MR-VWI).Methods Participants with BCPs were selected for subanalysis from a multicentre study of Chinese Atherosclerosis Risk Evaluation II. We measured carotid plaque burden, identified each plaque component and measured their volume or area bilaterally on MR-VWI. Paired comparisons of the burden and components of BCPs were performed.Results In all, 540 patients with BCPs were eligible for analysis. Compared with the right carotid artery (CA), larger mean lumen area (p

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high fatality rate. How the glucose level might affect the clinical outcome remains obscure. Methods: A multicenter study was performed in 2 hospitals from 2011 to 2021. Patients with SFTS and acute hyperglycemia (admission fasting plasma glucose [FPG] ≥7 mmol/L), postadmission hyperglycemia (admission FPG

Abstract Developing novel risk markers for vascular contributions to cognitive impairment and dementia is important. This study aimed to extract total length, branch number and average tortuosity of intracranial distal arteries (A2, M2, P2 and more distal) from non-contrast enhanced magnetic resonance angiography (NCE-MRA) images, and explore their associations with global cognition. In 29 subjects (aged 40–90 years) with carotid atherosclerotic disease, the 3 intracranial vascular features on two NCE-MRA techniques (i.e. time of flight, TOF and simultaneous non-contrast angiography and intraplaque hemorrhage, SNAP) were extracted using a custom-developed software named iCafe. Arterial spin labeling (ASL) and phase contrast (PC) cerebral blood flow (CBF) were measured as references. Linear regression was performed to study their associations with global cognition, measured with the Montreal Cognitive Assessment (MoCA). Intracranial artery length and number of branches on NCE-MRA, ASL CBF and PC CBF were found to be positively associated with MoCA scores (P

Abstract Background Severe fever with thrombocytopenia (SFTS) caused by SFTS virus (SFTSV) was a tick-borne hemorrhagic fever that posed significant threat to human health in Eastern Asia. The study was designed to measure the seroprevalence of SFTSV antibody in healthy population residing in a high endemic region. Methods A cohort study was performed on healthy residents in Shangcheng County in Xinyang City from April to December in 2018, where the highest SFTS incidence in China was reported. Anti-SFTSV IgG was measured by indirect enzyme-linked immunosorbent assay and neutralizing antibody (NAb) was detected by using PRNT50. The logistic regression models were performed to analyze the variables that were associated with seropositive rates. Results Totally 886 individuals were recruited. The baseline seroprevalence that was tested before the epidemic season was 11.9% (70/587) for IgG and 6.8% (40/587) for NAb, which was increased to 13.4% (47/350) and 7.7% (27/350) during the epidemic season, and further to 15.8% (80/508) and 9.8% (50/508) post epidemic. The IgG antibody-based seropositivity was significantly related to the patients aged ≥ 70 years old [adjusted odds ratio (OR) = 2.440, 95% confidence interval (CI): 1.334–4.461 compared to the group of

Abstract Background Acute perimyocarditis is a rare extra-intestinal manifestation in Crohn’s disease which required multimodality imaging to confirm the diagnosis. Here we present a case of acute perimyocarditis as the first presentation of Crohn’s disease. To date, this is the first case presentation reporting the use of 18F-FDG PET/CT Scan for diagnosing such condition. Case presentation A 25-year-old male presented to our hospital with severe persistent pleuritic sharp left-sided chest pain. This was his second hospital admission in the past 4 months for chest pain and diarrhea. At the first hospitalization, he was diagnosed with viral perimyocarditis and irritable bowel syndrome. Laboratory findings, electrocardiogram, and cardiac magnetic resonance imaging results confirm the diagnostic of perimyocarditis. Virology, bacteriology, parasitology, and autoimmune evaluations were unremarkable. Colonoscopy, colorectal biopsy, and 18FGD PET findings confirmed manifestation of perimyocarditis, Crohn’s disease, and negative for sarcoidosis. Conclusions Looking at the overall clinical picture and investigation results of colonoscopy, colorectal biopsy findings, as well as multi-modality imaging with echocardiography, 18FDG PET—scan and CMRI, the patient was diagnosed to have perimyocarditis attending Chron’s disease flare up as a rare extra-intestinal manifestation.

As stock index adjustments comprise a basic system of capital market, their potential influence on analysts’ earnings forecasts is worthy of research. Based on a research sample of 23 adjustments to the CSI 300 Index from June 2007 to June 2018 and the backup stocks announced during the same period, this study examines the impact of additions to stock index on analysts’ forecast optimism using a staggered difference-in-differences model. The research results show that after stocks are added to the stock index, analysts’ earnings forecast optimism about these stocks increases significantly. Cross-sectional analysis indicates that this increase is more significant when the market is bullish, institutional ownership is low, the ratio of listed brokerage firms is low, star analyst coverage is low, firms show seasoned equity offering activity, the ratio of analysts from the top five brokerage firms ranked by commission income is high, and the analysts’ brokerage firms are shareholders. However, analyst-level tests find that analysts’ ability helps to reduce the impact of additions to stock index on earnings forecast optimism. Furthermore, additions to stock index significantly increase analyst coverage and forecast divergence. Economic consequences tests find additions to stock index significantly increases stock price synchronization, which is partly mediated by analysts’ earnings forecast optimism. This study enriches the literature on the impact of basic capital market systems and analyst behavior. The findings suggest that investors should rationally evaluate analysts’ earnings forecasts for stocks added to the stock index and obtain further information from various channels to improve asset allocation efficiency.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS), an emerging tickborne infectious disease caused by a novel banyangvirus (SFTS virus, SFTSV), was endemic in several Asian countries with a high mortality up to 30%. Until recently, SFTSV-associated re-infection have not been reported and investigated. Case presentation A 42-year-old female patient was identified as a case of SFTS with re-infection, with two episodes of SFTSV infection on June 2018 and May 2020. The diagnosis of SFTS was confirmed by detection of SFTSV RNA in the blood samples using real-time reverse-transcription polymerase chain reaction and antibodies specific for SFTSV using enzyme linked immunosorbent assay. The changes of viremia and antibody response differed between the two episodes. Phylogenetic analysis showed the two viral genome sequences were in the same clade, but showing 0.6% dissimilarity of the nearly whole nucleotide sequence. Analysis of clinical data revealed that the second episode showed milder illness than that of the first episode. Conclusions Epidemiological and clinical findings, viral whole genomic sequences, and serological evidence, provided evidence for the re-infection of SFTSV rather than prolonged viral shedding or relapse of the original infection. The patients with re-infection of SFTSV may be at high odds of clinically inapparent or mildly symptomatic. More attention should be directed towards the long-term follow up of the recovered patients in the future, to explicitly acquire the decay profile of their immunity response. Graphic abstract

Under the background of Chinese market segmentation, whether government-led administrative division adjustments can promote regional economic integration is a practical issue. Taking interregional firms’ stock price comovement as a micro measurement of regional integration, this paper investigates the regional integration effect of administrative division adjustments, i.e., city–county mergers. We find that stock price comovement between county-level and municipal district-level firms in the merged counties and municipal districts significantly improve after city–county mergers, particularly in regions with a higher degree of market segmentation and lower degree of marketization. We further find that the increase in stock price comovement caused by city–county mergers emerges from the increase in comovement of real activities between firms in the merged counties and municipal districts. Taken together, our results suggest that government-led administrative division adjustments effectively promote regional integration.

Abstract Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus with high fatality and an expanding endemic. Currently, effective anti-SFTSV intervention remains unavailable. Favipiravir (T-705) was recently reported to show in vitro and in animal model antiviral efficacy against SFTSV. Here, we conducted a single-blind, randomized controlled trial to assess the efficacy and safety of T-705 in treating SFTS (Chinese Clinical Trial Registry website, number ChiCTR1900023350). From May to August 2018, laboratory-confirmed SFTS patients were recruited from a designated hospital and randomly assigned to receive oral T-705 in combination with supportive care or supportive care only. Fatal outcome occurred in 9.5% (7/74) of T-705 treated patients and 18.3% (13/71) of controls (odds ratio, 0.466, 95% CI, 0.174–1.247). Cox regression showed a significant reduction in case fatality rate (CFR) with an adjusted hazard ratio of 0.366 (95% CI, 0.142–0.944). Among the low-viral load subgroup (RT-PCR cycle threshold ≥26), T-705 treatment significantly reduced CFR from 11.5 to 1.6% (P = 0.029), while no between-arm difference was observed in the high-viral load subgroup (RT-PCR cycle threshold

Abstract Background It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events. Methods In a subgroup (N = 465) of Systolic Blood Pressure Intervention Trial. (SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR

We investigate how product market competition affects corporate voluntary disclosure decisions, specifically regarding supply-chain information. Our results, based on a sample of manufacturing companies listed in China from 2010 to 2016, show that companies in more competitive industries disclose less customer/supplier information. The main results stand through several robustness tests. Further analyses show that the negative relationship between product market competitiveness and supply-chain information disclosure is stronger when the disclosure contains more incremental information and when competitors are more capable of gaining competitive advantage using the disclosed information. Our study contributes to the understanding of both the relationship between product market competition and voluntary disclosure decisions and the regulation of information disclosure to build a transparent capital market.

Using a unique dataset of audit days in China from 2006 to 2011, this paper examines the relationship between audit effort and audit quality from the perspective of audit process and audit output. The results show that audit effort significantly increases the probability of audit adjustments, which inhibits positive earnings management and improves the quality of audited financial statements. We also find that audit effort does not have a significant effect on the issuance of modified audit opinions overall, but that a modified audit opinion is more likely to be issued in the absence of an audit adjustment. Furthermore, we find that the impact of audit effort on audit quality is attenuated when clients are more complex and when audit firms are larger. Collectively, our evidence suggests that audit effort plays an important role in improving audit quality by influencing audit process and audit output. Our study extends the literature on the impact of audit effort on audit quality in emerging markets, and the conclusions have important implications for the improvement of China’s audit market efficiency. Keywords: Audit effort, Audit adjustment, Audit opinion, Audit quality

Quantitative analysis of blood vessel wall structures is important to study atherosclerotic diseases and assess cardiovascular event risks. To achieve this, accurate identification of vessel luminal and outer wall contours is needed. Computer-assisted tools exist, but manual preprocessing steps, such as region of interest identification and/or boundary initialization, are still needed. In addition, prior knowledge of the ring shape of vessel walls has not been fully explored in designing segmentation methods. In this work, a fully automated artery localization and vessel wall segmentation system is proposed. A tracklet refinement algorithm was adapted to robustly identify the artery of interest from a neural network-based artery centerline identification architecture. Image patches were extracted from the centerlines and converted in a polar coordinate system for vessel wall segmentation. The segmentation method used 3D polar information and overcame problems such as contour discontinuity, complex vessel geometry, and interference from neighboring vessels. Verified by a large (>32000 images) carotid artery dataset collected from multiple sites, the proposed system was shown to better automatically segment the vessel wall than traditional vessel wall segmentation methods or standard convolutional neural network approaches. In addition, a segmentation uncertainty score was estimated to effectively identify slices likely to have errors and prompt manual confirmation of the segmentation. This robust vessel wall segmentation system has applications in different vascular beds and will facilitate vessel wall feature extraction and cardiovascular risk assessment.

ObjectivePulmonary valve (PV) stenosis affects cardiac pulmonary function and exercise performance. A cardiopulmonary exercise test (CPET) combined with a transthoracic echocardiogram (TTE) can measure exercise performance, disease progression, and treatment effects. We assessed the exercise capacity in children with PV stenosis by conducting CPET and TTE.MethodsFrom 2005 to 2021, 84 patients with PV stenosis aged 6–18 years were enrolled; 43 were treated with balloon pulmonary valvuloplasty (BPV) (Group A), and 41 received follow-up care (Group B), and their CPET and pulmonary function test results were compared with 84 healthy, matched individuals (Control). We also conducted TTE to compare the peak pulmonary artery pulse wave velocity and pulmonary valve (PV) area before and after catheterization and follow-up care.ResultsThere were no significant differences among the CPET parameters of the patient groups and controls in anaerobic metabolic equivalent (MET) (group A: 6.44 ± 0.58; group B: 6.28 ± 0.47, control: 6.92 ± 0.39, p = 0.110), peak MET (group A: 9.32 ± 0.74; group B: 9.13 ± 0.63; control: 9.80 ± 0.52, p = 0.263), and heart rate recovery (group A: 28.04 ± 4.70; group B: 26.44 ± 3.43, control:26.10 ± 2.42, p = 0.718). No significant differences were found in the pulmonary functions between the three groups. The pulmonary artery pulse wave velocity significantly decreased after catheterization (3.97 ± 1.50 vs. 1.95 ± 0.94, p < 0.0001), but not after follow-up care (1.67 ± 0.77 vs. 1.75 ± 0.66, p = 0.129). The pulmonary vale area significantly improved in group A (0.89 ± 0.71 vs. 1.16 ± 0.58, p < 0.0001), whereas only insignificant progression of PV stenosis was observed in group B (1.60 ± 0.64 vs. 1.57 ± 0.65, p = 0.110).ConclusionsPatients treated with BPV had a similar exercise capacity with that of patients under follow-up care and the healthy controls. Larger or multi-center studies should be conducted to confirm the physical fitness of pediatric patients with PV stenosis after management.

Background: We sought to determine if the morphological and compositional features of chronic internal carotid artery occlusion (CICAO), as assessed by MR vessel wall imaging (MR-VWI), initially predict successful endovascular recanalization. Methods: Consecutive patients with CICAO scheduled for endovascular recanalization were recruited. MR-VWI was performed within 1 week prior to surgery for evaluating the following features: proximal stump morphology, extent of occlusion, occlusion with collapse, arterial tortuosity, the presence of hyperintense signals (HIS) and calcification in the occluded C1 segment. Multivariate logistic regression was used to identify features associated with technical success and construct a prediction model. Results: Eighty-three patients were recruited, of which fifty-seven (68.7%) were recanalized successfully. The morphological and compositional characteristics of CICAO were associated with successful recanalization, including occlusions limited to C1 and extensive HIS, as well as the absence of extensive calcification, absence of high tortuosity, and absence of artery collapse. The MR CICAO score that comprised the five predictors showed a high predictive ability (area under the curve: 0.888, p < 0.001). Conclusion: the MR-VWI characteristics of CICAO predicted the technical success of endovascular recanalization and may be leveraged for identifying patients with a high probability of successful recanalization.

This case illustrates an unusual presentation of diffuse large B cell lymphoma (DLBCL) with florid central nervous system disease and an isolated right coronary artery lesion. Differentials included primary central nervous system lymphoma with IgG4-related disease of the right coronary artery, versus Stage IV DLBCL of the right coronary artery with CNS involvement. This case posed a diagnostic conundrum and challenged the choice of optimal treatment.

Background: Iron ions affect the expression of outer membrane protein A (OmpA), a major pathogenic protein in Acinetobacter baumannii.Objective: To analyze the effect of iron ions on the expression of the OmpA protein of A. baumannii and explore its association with the virulence of OmpA.Methods: Site-directed mutagenesis was used to construct ompA gene deletion strains and gene repair strains. The OmpA protein expression of A. baumannii under culture with different contents of iron ions was detected. The virulence of A. baumannii with different OmpA protein expression levels were evaluated in macrophages and mice.Results: OmpA protein levels of the three strains were enhanced under iron-rich conditions. They were reduced in the presence of the iron-chelating agent 2,2′-bipyridine. A. baumannii wild type and + ompA had a remarkable toxic effect on RAW246.7 macrophages (P < 0.05). In contrast, the ΔompA had a significantly reduced toxic effect on RAW246.7 macrophages (P < 0.05). The levels of the inflammatory factors IL-1β, IL-6, IL-8, and TNFα in the mice spleen were significantly increased in the + ompA strain treatment group compared with the ΔompA strain group (all P < 0.05). In addition, the levels were higher in the presence of iron ions than in the presence of the chelating agent.Conclusion: Iron-rich conditions increase the OmpA protein expression of A. baumannii. Strains with high OmpA protein expression were more invasive, which may be a key determinant of A. baumannii infection and pathogenicity. Iron control strategies might be used for the management of A. baumannii.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease with high mortality. However, detailed analysis is lacking to explore the complex effect of sex with age or comorbidities.Methods: A retrospective cohort study was performed among 2,938 SFTS patients entered during 2011–2020 in Xinyang, China. The case fatality rate (CFR) was estimated for their association with sex, age, and comorbidities by an interactive way. The difference of immune response between sex was explored in an age dependent way.Results: An overall CFR of 15.3% (450/2,938) was obtained, which appeared to be higher in males than in females [17.7% vs. 13.6%, adjusted odds ratio (aOR) = 1.24; 95% CI, 1.00–1.53; P = 0.048] and increased dramatically with age (P < 0.001). The associations between sex and SFTS fatal outcome were age-dependent and varied according to the status of comorbidities. The mortality-related risk conferred by older age was more pronounced in males, with aOR (95% CI) to be 5.76 (3.75–8.84) vs. 5.30 (3.54–7.95) in female. Sex-stratified analysis disclosed significant associations between death and comorbidities among female patients (aOR = 1.87, 95% CI: 1.40–2.49; P < 0.001), while none among males. Among females, the significant associations between presence of comorbidity and fatal outcome differed among age groups, with aOR (95% CI) decreased from 2.28 (1.16–4.46) in ≤60 years, to 2.06 (1.34–3.18) in 60–70 years and further to 1.55 (0.97–2.47) in >70 years. Altogether 194 SFTS patients were randomly selected for the test of B cells, natural killer (NK) cells, CD4 cells percentages, and anti-SFTSV IgM antibody level, the results revealed that males >60 years had significantly decreased percentages of B cells, CD4 cells, lower anti-SFTSV IgM antibody titer, and increased level of NK cells than male aged ≤60 years, while none of these age specific differences was observed in the females. This finding underlies the more pronounced age specific difference in CFR among male than female.Conclusions: Males had a significantly higher mortality of SFTS than did females, and more likely to be affected by aging for SFTS mortality. This difference can be explained by the effect from comorbidities and the host immunity. It is essential to take a sex- and age-based approach to SFTS treatment and management.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality, however with no effective therapy available. Methods: The effect of favipiravir (FPV) in treating SFTS was evaluated by an integrated analysis on data collected from a single-arm study (n=428), a surveillance study (n=2350) and published data from a randomized controlled trial study (n=145). A 1:1 propensity score matching was performed to include 780 patients: 390 received FPV and 390 received supportive therapy only. Case fatality rates (CFRs), clinical progress, and adverse effects were compared. Findings: FPV treatment had significantly reduced CFR from 20.0% to 9.0% (odds ratio 0.38, 95% confidence interval 0.23-0.65), however showing heterogeneity when patients were grouped by age, onset-to-admission interval, initial viral load and therapy duration. The effect of FPV was significant only among patients aged ≤70 years, with onset-to-admission interval ≤5 days, therapy duration ≥5 days or baseline viral load ≤1 × 106 copies/mL. Age-stratified analysis revealed no benefit in the aging group >70 years, regardless of their sex, onset-to-admission interval, therapy duration or baseline viral load. However, for both ≤60 and 60-70 years groups, therapy duration and baseline viral load differentially affected FPV therapy efficiency. Hyperuricemia and thrombocytopenia, as the major adverse response of FPV usage, were observed in >70 years patients. Interpretation: FPV was safe in treating SFTS patients but showed no benefit for those aged >70 years. Instant FPV therapy could highly benefit SFTS patients aged 60-70 years. Funding: China Natural Science Foundation (No. 81825019, 82073617 and 81722041) and China Mega-project for Infectious Diseases (2018ZX10713002 and 2015ZX09102022).

Background An artificial intelligence vessel segmentation tool, Fully Automated and Robust Analysis Technique for Popliteal Artery Evaluation (FRAPPE), was used to analyze a large databank of popliteal arteries imaged through the OAI (Osteoarthritis Initiative) to study the impact of atherosclerosis risk factors on vessel dimensions and characterize remodeling patterns. Methods and Results Magnetic resonance images from 4668 subjects contributing 9189 popliteal arteries were analyzed using FRAPPE. Age ranged from 45 to 79 years (median, 61), and 58% were women. Mean lumen diameter, mean outer wall diameter, and mean wall thickness (MWT) were measured per artery. Their median values were 5.8 mm (interquartile range, 5.2–6.5 mm), 7.3 mm (interquartile range, 6.7–8.1 mm), and 0.78 mm (interquartile range, 0.73–0.84 mm) respectively. MWT was associated with multiple cardiovascular risk factors, with age (4.2% increase in MWT per 10‐year increase in age; 95% CI, 3.9%–4.5%) and sex (8.6% higher MWT in men than women; 95% CI, 7.7%–9.3%) being predominant. On average, lumen and outer wall diameters increased with increasing MWT until the thickness was 0.92 mm for men and 0.84 mm for women. After this point, lumen diameter decreased steadily, more rapidly in men than women (−7.9% versus −6.1% per 25% increase in MWT; P

Abstract Background To determine the usefulness of the size of carotid artery intraplaque hemorrhage (IPH) in discriminating the risk of acute ischemic stroke using cardiovascular magnetic resonance (CMR) vessel wall imaging. Methods Symptomatic patients with carotid atherosclerotic plaque who participated in a cross-sectional, multicenter study of CARE-II (NCT02017756) were included. All patients underwent carotid and brain CMR imaging. Carotid plaque burden and the size of plaque compositions including calcification, lipid-rich necrotic core (LRNC), and IPH were measured. Presence of acute cerebral infarct (ACI) in ipsilateral hemisphere of carotid plaque was determined. The relationship between carotid plaque features and presence of ipsilateral ACI was then analyzed. Results Of 687 recruited patients (62.7 ± 10.1 years; 69.4% males) with carotid plaque, 28.5% had ACI in ipsilateral hemispheres. Logistic regression revealed that carotid plaque burden was significantly associated with the presence of ACI before and after adjusted for clinical confounding factors. The volume of LRNC, %LRNC volume, volume of IPH, and %IPH volume were significantly associated with ACI before (volume of LRNC: OR = 1.297, p = 0.005; %LRNC volume: OR = 1.119, p = 0.018; volume of IPH: OR = 2.514, p = 0.003; %IPH volume: OR = 2.202, p = 0.003) and after (volume of LRNC: OR = 1.312, p = 0.006; %LRNC volume: OR = 1.90, p = 0.034; volume of IPH: OR = 2.907, p = 0.007; % IPH volume: OR = 2.374, p = 0.004) adjusted for clinical confounding factors. The association between volume of IPH and ACI remained statistically significant after further adjusted for plaque volume (OR = 2.813, p = 0.016) or both plaque volume and volume of LRNC (OR = 4.044, p = 0.024). Conclusions In symptomatic patients with carotid atherosclerotic plaques, the size of IPH is independently associated with ipsilateral ACI, suggesting the size of IPH might be a useful indicator for the risk of ACI. Trial registration Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique Identifier: NCT02017756.

Hemocyanins present in the hemolymph of invertebrates are multifunctional proteins that are responsible for oxygen transport and play crucial roles in the immune system. They have also been identified as a source of antimicrobial peptides during infection in mollusks. Hemocyanin has also been identified in the cephalopod ancestor Nautilus, but antimicrobial peptides derived from the hemocyanin of Nautilus pompilius have not been reported. Here, the bactericidal activity of six predicted peptides from N. pompilius hemocyanin and seven mutant peptides was analyzed. Among those peptides, a mutant peptide with 15 amino acids (1RVFAGFLRHGIKRSR15), NpHM4, showed relatively high antibacterial activity. NpHM4 was determined to have typical antimicrobial peptide characteristics, including a positive charge (+5.25) and a high hydrophobic residue ratio (40%), and it was predicted to form an alpha-helical structure. In addition, NpHM4 exhibited significant antibacterial activity against Gram-negative bacteria (MBC = 30 μM for Vibrio alginolyticus), with no cytotoxicity to mammalian cells even at a high concentration of 180 µM. Upon contact with V. alginolyticus cells, we confirmed that the bactericidal activity of NpHM4 was coupled with membrane permeabilization, which was further confirmed via ultrastructural images using a scanning electron microscope. Therefore, our study provides a rationalization for the development and optimization of antimicrobial peptide from the cephalopod ancestor Nautilus, paving the way for future novel AMP development with broad applications.

Comprehensive quantification of intracranial artery features may help to assess and understand regional variations of blood supply during early brain development and aging. We analyzed vasculature features of 27 healthy infants during natural sleep, 13 infants at 7-months (7.3 ± 1.0 month), and 14 infants at 12-months (11.7 ± 0.4 month), and 13 older healthy, awake adults (62.8 ± 8.7 years) to investigate age-related vascular differences as a preliminary study of vascular changes associated with brain development. 3D time-of-flight (TOF) magnetic resonance angiography (MRA) acquisitions were processed in iCafe, a technique to quantify arterial features (http://icafe.clatfd.cn), to characterize intracranial vasculature. Overall, adult subjects were found to have increased ACA length, tortuosity, and vasculature density compared to both 7-month-old and 12-month-old infants, as well as MCA length compared to 7-month-old infants. No brain laterality differences were observed for any vascular measures in either infant or adult age groups. Reduced skull and brain sharpness, indicative of increased head motion and brain/vascular pulsation, respectively, were observed in infants but not correlated with length, tortuosity, or vasculature density measures. Quantitative analysis of TOF MRA using iCafe may provide an objective approach for systematic study of infant brain vascular development and for clinical assessment of adult and pediatric brain vascular diseases.

Objectives To develop a model of in-hospital mortality using medical record front page (MRFP) data and assess its validity in case-mix standardisation by comparison with a model developed using the complete medical record data.Design A nationally representative retrospective study.Setting Representative hospitals in China, covering 161 hospitals in modelling cohort and 156 hospitals in validation cohort.Participants Representative patients admitted for acute myocardial infarction. 8370 patients in modelling cohort and 9704 patients in validation cohort.Primary outcome measures In-hospital mortality, which was defined explicitly as death that occurred during hospitalisation, and the hospital-level risk standardised mortality rate (RSMR).Results A total of 14 variables were included in the model predicting in-hospital mortality based on MRFP data, with the area under receiver operating characteristic curve of 0.78 among modelling cohort and 0.79 among validation cohort. The median of absolute difference between the hospital RSMR predicted by hierarchical generalised linear models established based on MRFP data and complete medical record data, which was built as ‘reference model’, was 0.08% (10th and 90th percentiles: −1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar.Conclusions The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is a serious infectious disease with a fatality of up to 30%. To identify the severity of SFTS precisely and quickly is important in clinical practice.MethodsFrom June to July 2020, 71 patients admitted to the Infectious Department of Joint Logistics Support Force No. 990 Hospital were enrolled in this study. The most frequently observed symptoms and laboratory parameters on admission were collected by investigating patients' electronic records. Decision trees were built to identify the severity of SFTS. Accuracy and Youden's index were calculated to evaluate the identification capacity of the models.ResultsClinical characteristics, including body temperature (p = 0.011), the size of the lymphadenectasis (p = 0.021), and cough (p = 0.017), and neurologic symptoms, including lassitude (pConclusionDecision trees can be applied to predict the severity of SFTS.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It's suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS.

Background and purpose To investigate differences in the characteristics of carotid atherosclerotic plaques of symptomatic subjects in northern and southern China using MRI.Methods Sixty-three subjects in northern China (mean age: 59.1±8.6 years, 45 men) and 56 subjects in southern China (mean age: 60.4±8.6 years, 38 men) were included. All subjects underwent carotid artery multicontrast vessel wall MRI. Plaque morphology, calcification, lipid-rich necrotic core, intraplaque haemorrhage, luminal surface disruption and high-risk plaque were measured and identified. All plaque characteristics were compared between subjects in northern and southern China using Mann-Whitney U test or χ2 test.Results Compared with subjects in southern China, those in northern China had significantly greater areas for lumen (57.7±14.9 mm2 vs 50.4±18.3 mm2, p=0.009), wall (38.4±13.1 mm2 vs 31.9±11.7 mm2, p0.05).Conclusion Subjects in northern China have significantly larger vessel size and may have a higher prevalence of vulnerable plaques than those in southern China. Our findings provide additional perspective to optimise the management of cerebrovascular disease in individuals in different regions in China.Trial registration number NCT02017756

Abstract Background There have been conflicting data regarding the risk of sudden cardiac death (SCD) in Asian population with reduced left ventricular ejection fraction (LVEF). We aim to study mortality outcome and its risk predictors in patients with reduced LVEF who declined an implantable cardioverter defibrillator (ICD) implantation and assess whether current ICD guidelines for primary prevention are applicable to the population in Singapore. Methods This prospective observational study involved 240 consecutive patients who fulfilled the ACC/AHA/HRS criteria for ICD implantation for primary prevention of SCD but declined ICD implantation. Baseline characteristics and mortality outcomes through May 2017 were collected via case‐note review after a mean follow‐up of 44.8 ± 16.6 months. Results Majority of our patients were Chinese (71.3%), followed by Malays (16.2%) and Indians (10.8%). Mean age (±SD) was 61 ± 10 years, and 84% were male. Majority were in New York Heart Association (NYHA) functional classes I (46.7%) and II (46.3%). Over a mean follow‐up of 44.8 ± 16.6 months, all‐cause mortality rate was 34.6%. Diabetes mellitus (HR = 1.57; 95% CI, 1.01‐2.44; P = 0.047) and chronic kidney disease (CKD; HR = 1.95; 95% CI, 1.17‐3.23; P = 0.010) were independent predictors of mortality. Patients in NYHA classes II (HR = 2.15; 95% CI, 1.32‐3.50; P = 0.002) and III (HR = 2.82; 95% CI, 1.34‐5.96; P = 0.007) showed higher risk of death. Conclusion The mortality rate was comparable with major primary prevention trials. ICD guideline recommendations for primary prevention may thus be applicable to our local population. Patients with diabetes, CKD, and poorer NYHA status exhibited higher mortality rates.

Abstract Background Lower extremity peripheral artery disease has become a significant health burden worldwide. Since the treatment strategies can be different if atherosclerotic disease involves different femoral artery segments, it is important to assess plaque distribution among different segments of femoral arteries. We sought to investigate the longitudinal distribution of subclinical femoral artery atherosclerosis in asymptomatic elderly adults using cardiovascular magnetic resonance (CMR) vessel wall imaging. Methods Asymptomatic elderly subjects underwent three-dimensional (3D) CMR vessel wall imaging for femoral arteries. The 3D motion sensitized-driven equilibrium prepared rapid gradient-echo (3D-MERGE) sequence was acquired from the common femoral artery to the popliteal artery. The femoral artery was divided into 4 segments: common femoral artery (CFA), proximal superficial femoral artery (pSFA), adductor canal (AC) segment of femoral artery, and popliteal artery (PA). The morphological characteristics including lumen area, wall area, maximum and minimum wall thickness, normalized wall index (NWI = wall area / [lumen area + wall area] × 100%), and eccentricity index ([maximum wall thickness - minimum wall thickness] / maximum wall thickness), luminal stenosis, and presence of atherosclerotic plaque were evaluated and compared between bilateral sides and among different femoral artery segments in each side of femoral artery. The associations between ankle-brachial index (ABI) and cardiovascular risk factors and femoral artery plaque characteristics were also determined. Results Of 107 recruited subjects (71.9 ± 5.6 years; 48 males), 70 (65.4%) were found to have femoral artery plaques. The atherosclerotic plaques were most frequently found in PA (41.1%) and CFA (40.2%) segments, followed by pSFA (31.8%) and AC (23.4%) segments (p = 0.002). Similarly, PA and CFA segments showed significantly greater maximum wall thickness and eccentricity index compared with pSFA and AC segments (all p

Abstract Background Image registration is an important research topic in the field of image processing. Applying image registration to vascular image allows multiple images to be strengthened and fused, which has practical value in disease detection, clinical assisted therapy, etc. However, it is hard to register vascular structures with high noise and large difference in an efficient and effective method. Results Different from common image registration methods based on area or features, which were sensitive to distortion and uncertainty in vascular structure, we proposed a novel registration method based on network structure and circuit simulation. Vessel images were transformed to graph networks and segmented to branches to reduce the calculation complexity. Weighted graph networks were then converted to circuits, in which node voltages of the circuit reflecting the vessel structures were used for node registration. The experiments in the two-dimensional and three-dimensional simulation and clinical image sets showed the success of our proposed method in registration. Conclusions The proposed vascular image registration method based on network structure and circuit simulation is stable, fault tolerant and efficient, which is a useful complement to the current mainstream image registration methods.

HDL efflux capacity and HDL particle size are associated with atherosclerotic CVD (ASCVD) events in middle-aged individuals; however, it is unclear whether these associations are present in older adults. We sampled 402 Chicago Healthy Aging Study participants who underwent a dedicated carotid MRI assessment for lipid-rich necrotic core (LRNC) plaque. We measured HDL particle size, HDL particle number, and LDL particle number with NMR spectroscopy, as well as HDL efflux capacity. We quantified the associations between HDL particle size and HDL efflux using adjusted linear regression models. We quantified associations between the presence of LRNC and HDL and LDL particle number, HDL particle size, and HDL efflux capacity using adjusted logistic regression models. HDL efflux capacity was directly associated with large (β = 0.037, P < 0.001) and medium (β = 0.0065, P = 0.002) HDL particle concentration and inversely associated with small (β = −0.0049, P = 0.018) HDL particle concentration in multivariable adjusted models. HDL efflux capacity and HDL particle number were inversely associated with prevalent LRNC plaque in unadjusted models (odds ratio: 0.5; 95% confidence interval: 0.26, 0.96), but not after multivariable adjustment. HDL particle size was not associated with prevalent LRNC. HDL particle size was significantly associated with HDL efflux capacity, suggesting that differences in HDL efflux capacity may be due to structural differences in HDL particles. Future research is needed to determine whether HDL efflux is a marker of ASCVD risk in older populations.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus SFTSV. Currently our knowledge of the host-related factors that influence the pathogenesis of disease is inadequate to allow prediction of fatal outcome. Here we conducted a prospective study of the largest database on the SFTS patients, to identify the presence of comorbidities in SFTS, and estimate their effect on the fatal outcome. Among 2096 patients eligible for inclusion, we identified nine kinds of comorbidities, from which hyperlipidemia (12.2%; 95% CI: 10.8%-13.6%), hypertension (11.0%; 95% CI: 9.6%-12.3%), chronic viral hepatitis (CVH) (9.3%; 95% CI: 8.1%-10.5%), and diabetes mellitus (DM) (6.8%; 95% CI: 5.7%-7.9%) were prevalent. Higher risk of death was found in patients with DM (adjusted OR = 2.304; 95% CI: 1.520-3.492; P