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IntroductionHypoxic-ischemic encephalopathy (HIE) is one of severe neonatal brain injuries, resulting from inflammation and the immune response after perinatal hypoxia and ischemia. IgG N-glycosylation plays a crucial role in various inflammatory diseases through mediating the balance between anti-inflammatory and pro-inflammatory responses. This study aimed to explore the effect of IgG N-glycosylation on the development of HIE.MethodsThis case-control study included 53 HIE patients and 57 control neonates. An ultrahigh-performance liquid chromatography (UPLC) method was used to determine the features of the plasma IgG N-glycans, by which 24 initial glycan peaks (GPs) were quantified. Multivariate logistic regression was used to examine the association between initial glycans and HIE, by which the significant parameters were used to develop a diagnostic model. Though receiver operating characteristic (ROC) curves, area under the curve (AUC) and 95% confidence interval (CI) were calculated to assess the performance of the diagnostic model.ResultsThere were significant differences in 11 initial glycans between the patient and control groups. The levels of fucosylated and galactosylated glycans were significantly lower in HIE patients than in control individuals, while sialylated glycans were higher in HIE patients (p < 0.05). A prediction model was developed using three initial IgG N-glycans and fetal distress, low birth weight, and globulin. The ROC analysis showed that this model was able to discriminate between HIE patients and healthy individuals [AUC = 0.798, 95% CI: (0.716–0.880)].DiscussionIgG N-glycosylation may play a role in the pathogenesis of HIE. Plasma IgG N-glycans are potential noninvasive biomarkers for screening individuals at high risk of HIE.

Immunoglobulin G (IgG) N-glycosylation plays a crucial role in the development of inflammatory diseases. This study aimed to evaluate the diagnostic performance of IgG for gastrointestinal (GI) cancer subtypes. A total of 749 GI cancer patients were enrolled from the Cancer Hospital, Chinese Academy of Medical Sciences, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), and pancreatic cancer (PC) patients. Hydrophilic interaction liquid chromatography using ultra-performance liquid chromatography (HILIC-UPLC) was employed to analyze the composition of the plasma IgG N-glycome. The levels of circulating inflammatory cytokines were detected by means of a Bio-Plex Pro Human Th17 Cytokine Assay. Canonical correlation analysis (CCA) was used to explore the correlation between IgG N-glycosylation patterns and inflammatory cytokines. A Lasso algorithm, accompanied by a logistic regression model, was used to develop a glycan-based model for differentiating GI cancer patients from healthy individuals. The levels of sialylation and galactosylation were significantly decreased among EC, GC, CRC, and PC patients, whereas the abundance of glycans with bisecting N-acetylglucosamine (GlcNAc) was increased in GI cancer patients in comparison with the healthy controls. Moreover, only PC patients had a decreased level of fucosylation. The levels of interleukin 1β (IL-1β), IL-31, and soluble CD40 ligand (sCD40L) were significantly higher in GI cancer patients than in the controls. In addition, the composition of IgG N-glycans was correlated with that of inflammatory cytokines (r = 0.556). The glycan-based models for diagnosing GI cancers exhibited an excellent performance, with areas under the receiver operating characteristic curves (AUCs) of 0.972 for EC, 0.871 for GC, 0.867 for CRC, and 0.907 for PC. Our findings demonstrate that IgG N-glycosylation plays an important role in modulating the pathogenesis of GI cancers. Serological IgG N-glycosylation is thus a potential candidate for noninvasively assisting in the clinical diagnosis of GI cancer subtypes.

Although the association between immunoglobulin G (IgG) N-glycosylation and metabolic traits has been previously identified, the causal association between them remains unclear. In this work, we used Mendelian randomization (MR) analysis to integrate genome-wide association studies (GWASs) and quantitative trait loci (QTLs) data in order to investigate the bidirectional causal association of IgG N-glycosylation with metabolic traits. In the forward MR analysis, 59 (including nine putatively causal glycan peaks (GPs) for body mass index (BMI) (GP1, GP6, etc.) and seven for fasting plasma glucose (FPG) (GP1, GP5, etc.)) and 15 (including five putatively causal GPs for BMI (GP2, GP11, etc.) and four for FPG (GP1, GP10, etc.)) genetically determined IgG N-glycans were identified as being associated with metabolic traits in one- and two-sample MR studies, respectively, by integrating IgG N-glycan-QTL variants with GWAS results for metabolic traits (all P

BackgroundGiven the etiological complexity of cognitive impairment, no effective cure currently exists for precise treatment of dementia. Although scholars have noted tourism’s potential role in managing cognitive impairment and mild dementia, more robust empirical investigation is needed in this area. This study aimed to examine the associations between tourism and cognitive impairment and dementia in older Chinese adults.MethodFrom a nationwide community-based cohort, 6,717 individuals aged ≥60 were recruited from 2011 to 2014, of whom 669 (9.96%) had had at least one tourism experience in the 2 years prior to enrollment. All the participants were then prospectively followed up until 2018. The association between tourism and cognitive impairment was examined by the Cox proportional hazards regression model. The adjusted hazard ratio (aHR) and its 95% confidence interval (CI) were calculated to evaluate the effect of tourism experience on cognitive impairment and dementia.ResultsA total of 1,416 individuals were newly diagnosed with cognitive impairment and 139 individuals with dementia onset during follow-up. The incidence of cognitive impairment was significantly lower among participants with tourism experiences (316.94 per 10,000 person-years) than those without such experiences (552.38 per 10,000 person-years). Cox regression showed that tourism decreased the risk of cognitive impairment (aHR = 0.69, 95% CI: 0.41–0.62) when adjusted for behavioral covariates and characteristics. Compared with participants without tourism experiences, those with 1, 2, and ≥3 tourism experiences had a lower risk of cognitive impairment with the aHRs of 0.72 (95% CI: 0.52–0.99), 0.65 (0.42–1.01), and 0.68 (0.44–0.98), respectively. Tourism experiences also reduced participants’ risk of dementia (aHR = 0.41, 95% CI: 0.19–0.89).ConclusionOur findings demonstrated associations between tourism and reduced risks of cognitive impairment and dementia in older Chinese adults. Thus, tourism could serve as a novel approach to dementia prevention.

BackgroundLupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients.MethodsThis case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography (HILIC-UPLC). A multivariate logistic regression model was used to explore the associations between IgG N-glycans and LN. A diagnostic model was developed using the significant glycans as well as demographic factors. The performance of IgG N-glycans in the diagnosis of LN was evaluated by receiver operating characteristic (ROC) curve analysis, and the area under the curve (AUC) and its 95% confidence interval (CI) were calculated.ResultsThere were significant differences in 9 initial glycans (GP2, GP4, GP6, GP8, GP10, GP14, GP16, GP18 and GP23) between women with SLE with and without LN (P < 0.05). The levels of sialylated, galactosylated and fucosylated glycans were significantly lower in the LN patients than in the control group, while bisected N-acetylglucosamine (GlcNAc) glycans were increased in LN patients (P < 0.05). GP8, GP10, GP18, and anemia were included in our diagnostic model, which performed well in differentiating female SLE patients with LN from those without LN (AUC = 0.792, 95% CI: 0.727 to 0.858).ConclusionOur findings indicate that decreased sialylation, galactosylation, and core fucosylation and increased bisecting GlcNAc might play a role in the development of LN by upregulating the proinflammatory response of IgG. IgG N-glycans can serve as potential biomarkers to differentiate individuals with LN among SLE patients.

Three-dimensional printing models (3DPs) have been widely used in medical anatomy training. However, the 3DPs evaluation results differ depending on such factors as the training objects, experimental design, organ parts, and test content. Thus, this systematic evaluation was carried out to better understand the role of 3DPs in different populations and different experimental designs. Controlled (CON) studies of 3DPs were retrieved from PubMed and Web of Science databases, where the participants were medical students or residents. The teaching content is the anatomical knowledge of human organs. One evaluation indicator is the mastery of anatomical knowledge after training, and the other is the satisfaction of participants with 3DPs. On the whole, the performance of the 3DPs group was higher than that of the CON group; however, there was no statistical difference in the resident subgroup, and there was no statistical difference for 3DPs vs. 3D visual imaging (3DI). In terms of satisfaction rate, the summary data showed that the difference between the 3DPs group (83.6%) vs. the CON group (69.6%) (binary variable) was not statistically significant, with p > 0.05. 3DPs has a positive effect on anatomy teaching, although there are no statistical differences in the performance tests of individual subgroups; participants generally had good evaluations and satisfaction with 3DPs. 3DPs still faces challenges in production cost, raw material source, authenticity, durability, etc. The future of 3D-printing-model-assisted anatomy teaching is worthy of expectation.

BackgroundPeromyscopsylla hesperomys and Orchopeas sexdentatus are regarded to be representative plague vectors in the United States. The incidence of plague is rising globally, possibly due to climate change and environmental damage. Environmental factors such as temperature and precipitation have a significant impact on the temporal and spatial distribution of plague vectors.MethodsMaximum entropy models (MaxEnt) were utilized to predict the distributions of these two fleas and their trends into the future. The main environmental factors influencing the distribution of these two fleas were analyzed. A risk assessment system was constructed to calculate the invasion risk values of the species.ResultsTemperature has a significant effect on the distribution of the potentially suitable areas for P. hesperomys and O. sexdentatus. They have the potential to survive in suitable areas of China in the future. The risk assessment system indicated that the risk level for the invasion of these two species into China was moderate.ConclusionIn order to achieve early detection, early interception, and early management, China should perfect its monitoring infrastructure and develop scientific prevention and control strategies to prevent the invasion of foreign flea vectors.

Objectives Over the coming decades, China is expected to face the largest worldwide increase in dementia incidence. Mobile health (mHealth) may improve the accessibility of dementia prevention strategies, targeting lifestyle-related risk factors. Our aim is to explore the needs and views of Chinese older adults regarding healthy lifestyles to prevent cardiovascular disease (CVD) and dementia through mHealth, supporting the Prevention of Dementia using Mobile Phone Applications (PRODEMOS) study.Design Qualitative semi-structured interview study, using thematic analysis.Setting Primary and secondary care in Beijing and Tai’an, China.Participants Older adults aged 55 and over without dementia with an increased dementia risk, possessing a smartphone. Participants were recruited through seven hospitals participating in the PRODEMOS study, purposively sampled on age, sex, living area and history of CVD and diabetes.Results We performed 26 interviews with participants aged 55–86 years. Three main themes were identified: valuing a healthy lifestyle, sociocultural expectations and need for guidance. First, following a healthy lifestyle was generally deemed important. In addition to generic healthy behaviours, participants regarded certain specific Chinese lifestyle practices as important to prevent disease. Second, the sociocultural context played a crucial role, as an important motive to avoid disease was to limit the care burden put on family members. However, time-consuming family obligations and other social values could also impede healthy behaviours such as regular physical activity. Finally, there seemed to be a need for reliable and personalised lifestyle advice and for guidance from a health professional.Conclusions The Chinese older adults included in this study highly value a healthy lifestyle. They express a need for personalised lifestyle support in order to adopt healthy behaviours. Potentially, the PRODEMOS mHealth intervention can meet these needs through blended lifestyle support to improve risk factors for dementia and CVD.Trial registration number ISRCTN15986016; Pre-results.

Termination of eukaryotic RNA polymerase III (Pol III)-mediated transcription occurs when the polymerase reaches a stretch of four or more deoxythymidine nucleotides (poly-dT) on the non-template strand. Here, the authors present the 3.6 Å cryo-EM structure of a human Pol III pre-termination complex (PTC) that was assembled on a 7 dT-containing DNA template and discuss the mechanism of poly-dT-dependent transcription termination of Pol III.

BackgroundStroke patients have to face a high risk of recurrence, especially for those with comorbid T2DM, which usually lead to much more serious neurologic damage and an increased likelihood of death. This study aimed to explore determinants of stroke relapse among patients with comorbid T2DM.Materials and methodsWe conducted this case-control study nested a prospective cohort of ischemic stroke (IS) with comorbid T2DM. During 36-month follow-up, the second stroke occurred in 84 diabetic IS patients who were allocated into the case group, while 613 patients without recurrence were the controls. We collected the demographic data, behaviors and habits, therapies, and family history at baseline, and measured the variables during follow-up. LASSO and Logistic regression analyses were carried out to develop a prediction model of stroke recurrence. The receiver operator characteristic (ROC) curve was employed to evaluate the performance of the prediction model.ResultsCompared to participants without recurrence, the higher levels of pulse rate (78.29 ± 12.79 vs. 74.88 ± 10.93) and hypertension (72.6 vs. 61.2%) were recorded at baseline. Moreover, a lower level of physical activity (77.4 vs. 90.4%), as well as a higher proportion of hypoglycemic therapy (36.9 vs. 23.3%) was also observed during 36-month follow-up. Multivariate logistic regression revealed that higher pulse rate at admission (OR = 1.027, 95 %CI = 1.005–1.049), lacking physical activity (OR = 2.838, 95% CI = 1.418–5.620) and not receiving hypoglycemic therapy (OR = 1.697, 95% CI = 1.013–2.843) during follow-up increased the risk of stroke recurrence. We developed a prediction model using baseline pulse rate, hypoglycemic therapy, and physical activity, which produced an area under ROC curve (AUC) of 0.689.ConclusionPhysical activity and hypoglycemic therapy play a protective role for IS patients with comorbid diabetes. In addition to targeted therapeutics, the improvement of daily-life habit contributes to slowing the progress of the IS.

Primary progressive aphasia (PPA), typically resulting from a neurodegenerative disease, is characterized by a progressive loss of specific language functions while other cognitive domains are relatively unaffected. The logopenic variant, characterized by impairments of word retrieval and sentence repetition along with preserved semantic, syntactic, and motor speech abilities, is the most recently described and remains less understood than other variants due to a comparatively small number of case studies and a lack of investigations with a thorough specification. In this article, we report a 2-year follow-up case study of a 74-year-old Chinese female patient with a logopenic variant of primary progressive aphasia, including its neurolinguistic study, magnetic resonance imaging (MRI), and 11C-Pittsburgh compound B-Positron emission tomography imaging analyses, as well as gene sequencing. This case confirms that, in addition to word-finding and sentence repetition difficulties, the logopenic variant may also present with mild auditory comprehension and naming deficits attributed to impaired access to lexical representations. The observation of clinical treatment suggests the efficacy of memantine hydrochloride tablet and rivastigmine transdermal patch in slowing down the cognitive deterioration of this patient. The description and exploration of this case may shed new insights into a better understanding of the Chinese logopenic variant of primary progressive aphasia.

Purpose – As the world grapples with the pervasive effects of the coronavirus pandemic, a notable disconnect has emerged in the public's understanding of scientific and medical research. Particularly, the travel industry has become unquestionably vulnerable amid the COVID-19 outbreak; this pandemic has interrupted the industry's operations with devastating economic consequences. This paper aims to highlight the importance of deconstructing barriers between medical science and public awareness related to COVID-19, taking tourism as a case in point. It also discusses the role of interdisciplinary research in facilitating the tourism and hospitality industry's recovery and alleviating tourists' uncertainties in the wake of COVID-19. Design/methodology/approach – This paper offers a synthesis of news coverage from several media outlets, framed within the literature on knowledge transformation across disciplines. This framing focuses on the medical sciences (e.g. public health) and social sciences (e.g. tourism management) to identify gaps between medical scientific knowledge and public awareness in the context of COVID-19. The authors' experience in public health and tourism management further demonstrates a missing link between academic research and the information made available in public health and everyday settings. A potential research agenda is proposed accordingly. Findings – This paper summarizes how salient issues related to knowledge transfer can become intensified during a global pandemic, such as medical research not being communicated in plain language, which leads some citizens to feel apathetic about findings. Reporting on the prevalence and anticipated consequences of disease outbreaks can hence be difficult, especially early in the development of diseases such as COVID-19. Research limitations/implications – By assuming a cross-disciplinary perspective on medical/health and social science research, this paper encourages academic and practical collaboration to bring medical research to the masses. This paper also outlines several research directions to promote public health, safety and sustainability through tourism. Practical implications – This paper highlights that it is essential for medical knowledge to be disseminated in a manner that promotes public understanding. The tourism and hospitality industry can benefit from an essential understanding of medical findings, particularly during this pandemic. Without a firm grasp on COVID-19's origins and treatment, the tourism and hospitality industry will likely struggle to recover from this catastrophe. Social implications – Taking COVID-19 as a case in point, this study advocates leveraging the strengths of disparate domains to bring medical findings to a wider audience and showcase cutting-edge developments for the greater good. This study also emphasizes the importance of engaging the general public in reputable scientific research findings to increase public awareness in a professional and accurate manner. Originality/value – This paper presents a unique and critical discussion of the gap between medical science knowledge and public awareness, as well as its implications for tourism and hospitality recovery after COVID-19, with a focus on applying medical scientific knowledge to post-pandemic industry recovery. 研究目的 – 當全球正與冠狀病毒流行病所帶來的廣泛影響抗衡之際，公眾對科學和醫學研究的理解卻出現了一個令人關注的脫節現象。在2019冠狀病毒病爆發期間，旅遊業無疑格外受到影響。這流行病中斷了旅遊業的運作，給業界帶來毀滅性的經濟影響。本文旨在以旅遊業為一個適時的例子、強調我們必須剖析與2019冠狀病毒病相關的醫學與公共意識之間的障礙。本文亦討論跨學科研究對促進2019冠狀病毒病疫情後旅遊及酒店業的復甦、及減低旅客的不確定性所扮演的角色。 研究設計/方法/理念 – 本文提供一個來自數個媒體管道的新聞報導的綜合論述，而這論述是在與跨學科知識轉化相關的文獻領域內陳述而成的。論述的重點放在醫學科學(例如公共衛生) 和社會科學(例如觀光管理) 上，目的是確定在2019冠狀病毒病的背景下、醫學知識與公共意識之間的差距。作者們在公共衛生及觀光管理方面的經歷進一步顯示學術研究、與公共衛生和日常環境上的公開資訊之間缺乏銜接，本文就此提出一個研究議程。 研究結果 – 本文總結與知識轉化相關的顯著問題如何會在全球流行病爆發期間變得更嚴重。譬如、醫學研究的資訊會因沒有以通俗語言來傳遞而令有些國民對其研究結果漠不關心。因此，關於疾病的傳播和爆發所預期的影響的信息是難於廣傳的，特別是在像2019冠狀病毒病等疾病形成的初期。 原創性 – 本文就醫學知識與公共意識之間的差距作出了一個獨特、有批判性的討論，亦論述這差距對2019冠狀病毒病疫情過後旅遊及酒店業復甦的意義。討論的焦點放在如何應用醫學知識在疫情後幫助產業復甦上。 研究的局限/含意 – 作者們採用涵蓋醫學/衛生和社會科學研究的跨學科角度，鼓勵學者與從事實務人員相互合作、以便把醫學研究帶給廣泛的民眾。本文亦概述多個研究方向，透過旅遊業來推動公共衛生、公眾安全及可持續性。 實際意義 – 本文強調醫學知識必須透過能提高公共意識的方式來傳遞。旅遊及酒店業會因我們對醫學研究結果擁有必要的認識而受惠，尤其是在這流行病蔓延的期間。若我們對2019冠狀病毒病的病源和療法沒有確切的了解，則旅遊及酒店業將難從這災難中恢復過來。 對社會的意義 – 本研究利用2019冠狀病毒病這個適時的例子，來提倡借助各個不同領域的優點，為了謀求公眾的利益、把醫學的研究結果帶給更多民眾、及傳達醫療最新發展的信息。本研究亦強調以專業、精準的方法，引起公眾對可信賴的科學研究結果產生興趣，從而提高公共意識至為重要。

With the rapid development of technologies such as wireless communications and the Internet of Things (IoT), the proliferation of IoT devices will intensify the competition for spectrum resources. The introduction of cognitive radio technology in IoT can minimize the shortage of spectrum resources. However, the open environment of cognitive IoT may involve free-riding problems. Due to the selfishness of the participants, there are usually a large number of free-riders in the system who opportunistically gain more rewards by stealing the spectrum sensing results from other participants and accessing the spectrum without spectrum sensing. However, this behavior seriously affects the fault tolerance of the system and the motivation of the participants, resulting in degrading the system’s performance. Based on the energy-harvesting cognitive IoT model, this paper considers the free-riding problem of Secondary Users (SUs). Since free-riders can harvest more energy in spectrum sensing time slots, the application of energy harvesting technology will exacerbate the free-riding behavior of selfish SUs in Cooperative Spectrum Sensing (CSS). In order to prevent the low detection performance of the system due to the free-riding behavior of too many SUs, a penalty mechanism is established to stimulate SUs to sense the spectrum normally during the sensing process. In the system model with multiple primary users (PUs) and multiple SUs, each SU considers whether to free-ride and which PU’s spectrum to sense and access in order to maximize its own interests. To address this issue, a two-layer game-based cooperative spectrum sensing and access method is proposed to improve spectrum utilization. Simulation results show that compared with traditional methods, the average throughput of the proposed TL-CSAG algorithm increased by 26.3% and the proposed method makes the SUs allocation more fair.

Abstract Immunoglobulin G (IgG) functionality can drastically change from anti- to proinflammatory by alterations in the IgG N-glycan patterns. Our previous studies have demonstrated that IgG N-glycans associated with the risk factors of dementia, such as aging, dyslipidemia, type 2 diabetes mellitus, hypertension, and ischemic stroke. Therefore, the aim is to investigate whether the effects of IgG N-glycan profiles on dementia exists in a Chinese Han population. A case–control study, including 81 patients with dementia, 81 age- and gender-matched controls with normal cognitive functioning (NC) and 108 non-matched controls with mild cognitive impairment (MCI) was performed. Plasma IgG N-glycans were separated by ultra-performance liquid chromatography. Fourteen glycan peaks reflecting decreased of sialylation and core fucosylation, and increased bisecting N-acetylglucosamine (GlcNAc) N-glycan structures were of statistically significant differences between dementia and NC groups after controlling for confounders (p

Erectile dysfunction (ED), a complication of diabetes mellitus (DM), affects 50–75% of men with diabetes. Fibroblast growth factor 21 (FGF21) is a liver-derived metabolic regulator which plays a role in insulin-independent glucose uptake in adipocytes. We designed a clinical study and an animal experiment to investigate the relationship between FGF21 and DM-induced ED. The clinical study enrolled 93 participants aged > 18 years (61 patients with type 2 DM and 32 healthy controls) from Taian City Central Hospital (TCCH) in Shandong Province, China, amongst whom the association between serum FGF21 and diabetic ED was analyzed. To further validate this association, we developed animal model of diabetic ED using Sprague-Dawley (SD) rats. Serum FGF21 concentration and FGF21 mRNA expression in penile samples of the rats were determined with Western blotting and quantitative real-time PCR. Among the 93 participants, the level of serum FGF21 was negatively correlated with the IIEF-5 score (r = -0.74, P < 0.001). The analysis on the performance of FGF21 for ED diagnosis showed that the area under the receiver operating characteristic (ROC) curve was 0.875 (95% confidence interval [CI]: 0.803 to 0.946). In the animal experiment, the levels of serum FGF21, 2-Δ Δ Ct values of FGF21 mRNA expression, and relative levels of FGF21 in penile samples were higher in the ED group compared to the DM and control groups. Our findings demonstrated an association between the FGF21 level and diabetic ED, indicating the potential of this cytokine in predicting diabetic ED.

BackgroundAtherosclerosis is considered a crucial component in the pathogenesis of decreased cognitive function, as occurs in vascular cognitive impairment (VCI). Inflammation and the immune response play a significant role in the development of many chronic diseases. Immunoglobulin G (IgG) N-glycosylation has been implicated in the development of a variety of diseases by affecting the anti-inflammatory and proinflammatory responses of IgG. This study aimed to investigate the association between IgG N-glycosylation and VCI in a sample of patients with atherosclerosis through a case-control study.MethodWe recruited a total of 330 patients with atherosclerosis to participate in this case-control study, including 165 VCI patients and 165 sex- and age-matched participants with normal cognitive function. The plasma IgG N-glycans of participants were separated by ultrahigh-performance liquid chromatography. An enzyme-linked immunosorbent assay (ELISA) kit was used to determine the corresponding serum inflammatory factors. Atherosclerosis was diagnosed by carotid ultrasound, and the diagnosis of VCI was based on the “Guidelines for the Diagnosis and Treatment of Vascular Cognitive Impairment in China (2019)”. A multivariate logistic regression model was used to explore the association between IgG N-glycans and VCI. We also analyzed the relationship between IgG N-glycans and the inflammatory state of VCI through canonical correlation analysis (CCA).ResultsThrough the multivariate logistic regression analysis, 8 glycans and 13 derived traits reflecting decreased sialylation and galactosylation and increased bisecting GlcNAc significantly differed between the case and control groups after adjusting for confounding factors (P < 0.05, q < 0.05). Similarly, the differences in TNF-α, IL-6, and IL-10 were statistically significant between the case and control groups after adjusting for the effects of confounding factors (P < 0.05, q < 0.05). The CCA results showed that VCI-related initial N-glycans were significantly correlated with VCI-related inflammatory factors (r = 0.272, P = 0.004). The combined AUC value (AUCcombined = 0.885) of 7 initial glycans and inflammatory factors was higher than their respective values (AUCinitial glycans = 0.818, AUCinflammatory factors = 0.773).ConclusionThe findings indicate that decreased sialylation and galactosylation and increased bisecting GlcNAc reflected by IgG N-glycans might affect the occurrence of VCI in patients with atherosclerosis though promoting the proinflammatory function of IgG. IgG N-glycans may serve as potential biomarkers to distinguish VCI in individuals with atherosclerosis.

Evidence from observational studies for the effect of tea consumption on obesity is inconclusive. This study aimed to verify the causal association between tea consumption and obesity through a two-sample Mendelian randomization (MR) analysis in general population-based datasets. The genetic instruments, single nucleotide polymorphisms (SNPs) associated with tea consumption habits, were obtained from genome-wide association studies (GWAS): UK Biobank, Nurses’ Health Study, Health Professionals Follow-up Study, and Women’s Genome Health Study. The effect of the genetic instruments on obesity was analyzed using the UK Biobank dataset (among ∼500,000 participants). The causal relationship between tea consumption and obesity was analyzed by five methods of MR analyses: inverse variance weighted (IVW) method, MR-Egger regression method, weighted median estimator (WME), weighted mode, and simple mode. Ninety-one SNPs were identified as genetic instruments in our study. A mild causation was found by IVW (odds ratio [OR] = 0.998, 95% confidence interval [CI] = 0.996 to 1.000, p = 0.049]), which is commonly used in two-sample MR analysis, indicating that tea consumption has a statistically significant but medically weak effect on obesity control. However, the other four approaches did not show significance. Since there was no heterogeneity and pleiotropy in this study, the IVW approach has the priority of recommendation. Further studies are needed to clarify the effects of tea consumption on obesity-related health problems in detail.

Misunderstanding temporal coincidence of adverse events during mass vaccination and invalid assessment of possible safety concerns have negative effects on immunization programs, leading to low immunization coverage. We conducted this systematic review and meta-analysis to identify the incidence rates of GBS that are temporally associated with viral vaccine administration but might not be attributable to the vaccines. By literature search in Embase and PubMed, we included 48 publications and 2,110,441,600 participants. The pooled incidence rate of GBS was 3.09 per million persons (95% confidence interval [CI]: 2.67 to 3.51) within six weeks of vaccination, equally 2.47 per 100,000 person-year (95%CI: 2.14 to 2.81). Subgroup analyses illustrated that the pooled rates were 2.77 per million persons (95%CI: 2.47 to 3.07) for individuals who received the influenza vaccine and 2.44 per million persons (95%CI: 0.97 to 3.91) for human papillomavirus (HPV) vaccines, respectively. Our findings evidence the GBS-associated safety of virus vaccines. We present a reference for the evaluation of post-vaccination GBS rates in mass immunization campaigns, including the SARS-CoV-2 vaccine.

Genome-wide association studies (GWAS) have identified over 60 genetic loci associated with immunoglobulin G (IgG) N-glycosylation; however, the causal genes and their abundance in relevant tissues are uncertain. Leveraging data from GWAS summary statistics for 8,090 Europeans, and large-scale expression quantitative trait loci (eQTL) data from the genotype-tissue expression of 53 types of tissues (GTEx v7), we derived a linkage disequilibrium score for the specific expression of genes (LDSC-SEG) and conducted a transcriptome-wide association study (TWAS). We identified 55 gene associations whose predicted levels of expression were significantly associated with IgG N-glycosylation in 14 tissues. Three working scenarios, i.e., tissue-specific, pleiotropic, and coassociated, were observed for candidate genetic predisposition affecting IgG N-glycosylation traits. Furthermore, pathway enrichment showed several IgG N-glycosylation-related pathways, such as asparagine N-linked glycosylation, N-glycan biosynthesis and transport to the Golgi and subsequent modification. Through phenome-wide association studies (PheWAS), most genetic variants underlying TWAS hits were found to be correlated with health measures (height, waist-hip ratio, systolic blood pressure) and diseases, such as systemic lupus erythematosus, inflammatory bowel disease, and Parkinson’s disease, which are related to IgG N-glycosylation. Our study provides an atlas of genetic regulatory loci and their target genes within functionally relevant tissues, for further studies on the mechanisms of IgG N-glycosylation and its related diseases.

Coronavirus disease 2019 (COVID-19) remains a major health challenge globally. Previous studies have suggested that changes in the glycosylation of IgG are closely associated with the severity of COVID-19. This study aimed to compare the profiles of IgG N-glycome between COVID-19 patients and healthy controls. A case-control study was conducted, in which 104 COVID-19 patients and 104 age- and sex-matched healthy individuals were recruited. Serum IgG N-glycome composition was analyzed by hydrophilic interaction liquid chromatography with the ultra-high-performance liquid chromatography (HILIC-UPLC) approach. COVID-19 patients have a decreased level of IgG fucosylation, which upregulates antibody-dependent cell cytotoxicity (ADCC) in acute immune responses. In severe cases, a low level of IgG sialylation contributes to the ADCC-regulated enhancement of inflammatory cytokines. The decreases in sialylation and galactosylation play a role in COVID-19 pathogenesis via the activation of the lectin-initiated alternative complement pathway. IgG N-glycosylation underlines the complex clinical phenotypes of SARS-CoV-2 infection.

BackgroundIn epidemiological studies, it has been proven that the occurrence of type 2 diabetes mellitus (T2DM) is related to an increased risk of infectious diseases. However, it is still unclear whether the relationship is casual.MethodsWe employed a two-sample Mendelian randomization (MR) to clarify the causal effect of T2DM on high-frequency infectious diseases: sepsis, skin and soft tissue infections (SSTIs), urinary tract infections (UTIs), pneumonia, and genito-urinary infection (GUI) in pregnancy. And then, we analyzed the genome-wide association study (GWAS) meta-analysis of European-descent individuals and conducted T2DM-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) that were associated with genome-wide significance (p < 5 × 10–8). MR estimates were obtained using the inverse variance-weighted (IVW), the MR-Egger regression, the simple mode (SM), weighted median, and weighted mode.ResultsThe UK Biobank (UKB) cohort (n > 500,000) provided data for GWASs on infectious diseases. MR analysis showed little evidence of a causal relationship of T2DM with five mentioned infections’ (sepsis, SSTI, UTI, pneumonia, and GUI in pregnancy) susceptibility [odds ratio (OR) = 0.99999, p = 0.916; OR = 0.99986, p = 0.233; OR = 0.99973, p = 0.224; OR = 0.99997, p = 0.686; OR, 1.00002, p = 0.766]. Sensitivity analysis showed similar results, indicating the robustness of causality. There were no heterogeneity and pleiotropic bias.ConclusionT2DM would not be causally associated with high-frequency infectious diseases (including sepsis, SSTI, UTI, pneumonia, and GUI in pregnancy).

Introduction Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%–40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk.Methods and analysis The prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness–implementation hybrid design, taking place in the UK and China. People are eligible if they are 55–75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention.Ethics and dissemination The PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London—Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People’s Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal.Trial registration number ISRCTN15986016.

BACKGROUND Metabolically healthy obesity (MHO) and metabolically healthy overweight (MH-OW) have been suggested to be important and emerging phenotypes with an increased risk of cardiovascular disease (CVD). However, whether MHO and MH-OW are associated with all-cause mortality remains inconsistent.METHODS The association of MHO and MH-OW and all-cause mortality was determined in a Chinese community-based prospective cohort study (the Kailuan study), including 93,272 adults at baseline. Data were analyzed from 2006 to 2017. Participants were categorized into 6 mutually exclusive groups, according to BMI and metabolic syndrome (MetS) status. The primary outcome was all-cause death, and accidental deaths were excluded.RESULTS During a median follow-up of 11.04 years (interquartile range, 10.74–11.22 years), 8977 deaths occurred. Compared with healthy participants with normal BMI (MH-NW), MH-OW participants had the lowest risk of all-cause mortality (multivariate-adjusted HR [aHR], 0.926; 95% CI, 0.861–0.997), whereas there was no increased or decreased risk for MHO (aHR, 1.009; 95% CI, 0.886–1.148). Stratified analyses and sensitivity analyses further validated that there was a nonsignificant association between MHO and all-cause mortality.CONCLUSIONS Overweight and obesity do not predict increased risk of all-cause mortality in metabolic healthy Chinese individuals.FUNDING National Natural Science Foundation of China (NSFC; 81673247, 81872682 and 81773527), the NSFC Joint Project, and the Australian National Health and Medical Research Council (NHMRC; NSFC 81561128020-NHMRC APP1112767).

Background: Nightshift work introduces light at night and causes circadian rhythm among night workers, who are considered to be at increased risk of cancer. However, in the last 2 years, nine population-based studies reported insignificant associations between night-shift work and cancer risks. We aimed to conduct an updated systematic review and meta-analysis to ascertain the effect of night-shift work on the incidence of cancers.Methods: Our protocol was registered in PROSPERO and complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Embase, PubMed, and Web of Science databases were used to comprehensively search studies published up to May 31, 2019. The random-effect model (Der Simonian-Laird method) was carried out to combine the risk estimates of night-shift work for cancers. The dose-response meta-analysis was performed to verify whether the association was in a dose-dependent manner.Results: Our literature searching retrieved 1,660 publications. Included in the meta-analyses were 57 eligible studies with 8,477,849 participants (mean age 55 years; 2,560,886 men, 4,220,154 women, and 1,696,809 not mentioned). The pooled results showed that night-shift work was not associated with the risk of breast cancer (OR = 1.009, 95% CI = 0.984–1.033), prostate cancer (OR = 1.027, 95% CI = 0.982–1.071), ovarian cancer (OR = 1.027, 95% CI = 0.942–1.113), pancreatic cancer (OR = 1.007, 95% CI = 0.910–1.104), colorectal cancer (OR = 1.016, 95% CI = 0.964–1.068), non-Hodgkin's lymph (OR = 1.046, 95% CI = 0.994–1.098), and stomach cancer (OR = 1.064, 95% CI = 0.971–1.157), while night-shift work was associated with a reduction of lung cancer (OR = 0.949, 95% CI = 0.903–0.996), and skin cancer (OR = 0.916, 95% CI = 0.879–0.953). The dose-response meta-analysis found that cancer risk was not significantly elevated with the increased light exposure of night- shift work.Conclusion: This systematic review of 57 observational studies did not find an overall association between ever-exposure to night-shift work and the risk of breast, prostate ovarian, pancreatic, colorectal, non-Hodgkin's lymph, and stomach cancers.

Background: Esophageal cancer (EC) causes more than 400 thousand deaths per year, and half of them occur in China. There are discrepancies regarding the survival of EC patients between population-based surveillance studies and hospital-based studies.Objectives: We aimed to synthesize the survival data from hospital-based EC studies in the Chinese population from 2000 to 2018 and to compare the survival rates between EC patients with different clinical classifications.Methods: The protocol of this systematic review was registered in PROSPERO (CRD-42019121559). We searched Embase, PubMed, CNKI, and Wanfang databases for studies published between January 1, 2000 and December 31, 2018. We calculated the pooled survival rates and 95% confidence intervals (CIs) by Stata software (V14.0).Results: Our literature search identified 933 studies, of which 331 studies with 79,777 EC patients met the inclusion criteria and were included in meta-analyses. The pooled survival rates were 74.1% (95% CI: 72.6–75.7%) for 1-year survival, 49.0% (95% CI: 44.2–53.8%) for 2-years survival, 46.0% (95% CI: 42.6–49.5%) for 3-years survival, and 40.1% (95% CI: 33.7–46.4%) for 5-years survival. An increased tendency toward EC survival was verified from 2000 to 2018. In addition, discrepancies were observed between EC patients with different clinical classifications (e.g., stages, histologic types, and cancer sites).Conclusions: Our findings showed a higher survival rate in hospital-based studies than population-based surveillance studies. Although this hospital-based study is subject to potential representability and publication bias, it offers insight into the prognosis of patients with EC in China.

Background: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. Methods: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent. We analyzed the largest ever genome-wide association studies of stroke in Europe from the MEGASTROKE collaboration with 40,585 stroke cases and 406,111 controls. The weighted median (WM), the penalized weighted median (PWM), the inverse variance weighted (IVW), the penalized inverse variance weighted (PIVW), the robust inverse variance weighted (RIVW), and the Mendelian randomization-Egger (MR-Egger) methods were conducted for the MR analysis to estimate a causal effect and detect the directional pleiotropy. Results: No significant association between genetically determined TL with overall IS, LAS, or CES were found (all p > 0.05). SVS was associated with TL by the RIVW method (odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.54⁻0.97, p = 0.028), after excluding rs9420907, rs10936599, and rs2736100. Conclusions: By a series of causal inference approaches using SNPs as IVs, no strong evidence to support the causal effect of shorter TL on IS and its subtypes were found.