Distinct microbiome of tongue coating and gut in type 2 diabetes with yellow tongue coating.

The gut microbiome plays a critical role in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the inconvenience of obtaining fecal samples hinders the clinical application of gut microbiome analysis. In this study, we hypothesized that tongue coating color is associated with the severity of T2DM. Therefore, we aimed to compare tongue coating, gut microbiomes, and various clinical parameters between patients with T2DM with yellow (YC) and non-yellow tongue coatings (NYC). Tongue coating and gut microbiomes of 27 patients with T2DM (13 with YC and 14 with NYC) were analyzed using 16S rDNA gene sequencing technology. Additionally, we measured glycated hemoglobin (HbA1c), random blood glucose (RBG), fasting blood glucose (FBG), postprandial blood glucose (PBG), insulin (INS), glucagon (GC), body mass index (BMI), and homeostasis model assessment of ß-cell function (HOMA-ß) levels for each patient. The correlation between tongue coating and the gut microbiomes was also analyzed. Our findings provide evidence that the levels of Lactobacillus spp. are significantly higher in both the tongue coating and the gut microbiomes of patients with YC. Additionally, we observed that elevated INS and GC levels, along with decreased BMI and HOMA-ß levels, were indicative of a more severe condition in patients with T2DM with YC. Moreover, our results suggest that the composition of the tongue coating may reflect the presence of Lactobacillus spp. in the gut. These results provide insights regarding the potential relationship between tongue coating color, the gut microbiome, and T2DM.

Association between type 1 diabetes and systemic lupus erythematosus: a Mendelian randomization study.

OBJECTIVES: Observational studies have shown that there is a bidirectional relationship between type 1 diabetes (T1D) and systemic lupus erythematosus (SLE); the causality of this association remains elusive and may be affected by confusion and reverse causality. There is also a lack of large-scale randomized controlled trials to verify. Therefore, this Mendelian randomization (MR) study aimed to investigate the causal association between T1D and SLE. METHODS: We aggregated data using publicly available genome-wide association studies (GWAS), all from European populations. Select independent (R2 < 0.001) and closely related to exposure (P < 5 × 10-8) as instrumental variables (IVs). The inverse-variance weighted (IVW) method was used as the primary method. We also used MR-Egger, the weighted median method, MR-Robust, MR-Lasso, and other methods leveraged as supplements. RESULTS: T1D had a positive causal association with SLE (IVW, odds ratio [OR] = 1.358, 95% confidence interval [CI], 1.205 - 1.530; P < 0.001). The causal association was verified in an independent validation set (IVW, OR = 1.137, 95% CI, 1.033 - 1.251; P = 0.001). SLE had a positive causal association with T1D (IVW, OR = 1.108, 95% CI, 1.074 - 1.144; P < 0.001). The causal association was verified in an independent validation set (IVW, OR = 1.085, 95% CI, 1.046 - 1.127; P < 0.001). These results have also been verified by sensitivity analysis. CONCLUSION: The MR analysis results indicated a causal association between T1D and SLE. Therefore, further research is needed to clarify the potential biological mechanism between T1D and SLE. Key Points • Observational studies have shown that there is a bidirectional relationship between T1D and SLE. • We evaluated causal effects between T1D and SLE by Mendelian randomization analyses. • The MR analysis results indicated a causal association between T1D and SLE.

Autoimmune diseases and orthognathic surgery: A case series of 12 patients.

Autoimmune diseases result from the immune system attacking native cells and tissues due to the recognition of "self" antigens as foreign antigens. This group of disorders is associated with an increased risk of complications after surgical interventions, as the immune system may cause tissue destruction. The study aimed to investigate the risk of surgical complications in patients with autoimmune diseases, who are at a higher risk of complications due to their condition. Among 886 patients who underwent orthognathic surgery, twelve types of autoimmune diseases with 22 patients were identified. For this case-series study, 12 patients were selected with a follow-up period of at least two years. The surgical procedures were executed by a single surgical team, which involved single or multi-piece Le Fort I osteotomy, Hunsuck/Epker modification of bilateral sagittal split osteotomy (BSSO), and/or genioplasty. The recorded outcome variables were postoperative adverse events, including respiratory or blood-related complications, wound infection, neurosensory disturbances, temporomandibular joint (TMJ) complications, and relapse. Only two patients recovered after surgery without any postoperative complications, whereas others had delayed recovery from neurosensory disturbance (5/12), infection (5/12), TMJ complications (2/12), and other complications. The findings of this study suggest that patients with autoimmune diseases undergoing orthognathic surgery are at higher risk of complications, highlighting the importance of careful consideration of patient selection and risk stratification before surgical intervention. The study also emphasizes the importance of close postoperative follow-up to detect and manage complications promptly.

Associations between antipsychotics and the risk of incident cardiovascular diseases in individuals with schizophrenia: a nested case-control study.

BACKGROUND: The association between antipsychotics and cardiovascular diseases (CVDs) remains significant yet unestablished, especially in Chinese populations. OBJECTIVE: To investigate the risk of CVDs associated with antipsychotics among Chinese individuals with schizophrenia. METHODS: We conducted a nested case-control study on individuals diagnosed with schizophrenia in Shandong, China. The case group included individuals diagnosed with incident CVDs between 2012 and 2020. Each case was randomly matched with up to three controls. We used weighted logistic regression models to assess the risk of CVDs associated with antipsychotics and restricted cubic spline analysis to explore the dose-response relationship. FINDINGS: In total, 2493 cases and 7478 matched controls were included in the analysis. Compared with non-users, any antipsychotics use was associated with higher risk of any CVDs (weighted OR=1.54, 95% CI 1.32 to 1.79), with the risk mainly driven by ischaemic heart diseases (weighted OR=2.26, 95% CI 1.71 to 2.99). Treatments with haloperidol, aripiprazole, quetiapine, olanzapine, risperidone, sulpiride and chlorpromazine were associated with increased risk of CVDs. A non-linear dose-response relationship between dosage of antipsychotics and risk of CVDs was observed, with a sharp increase in risk in the beginning and then flattening out with higher doses. CONCLUSIONS: Use of antipsychotics was associated with increased risk of incident CVDs among individuals with schizophrenia, and the risk varied substantially among different antipsychotics and specific CVDs. CLINICAL IMPLICATIONS: Clinicians should consider the cardiovascular risk of antipsychotics and choose the appropriate type and dose of drugs in the treatment of schizophrenia.

Postoperative complications in asthmatic patients following orthognathic surgery: A two-year follow-up study.

BACKGROUND: Lack of evidence exists related to the incidence of postoperative complications in asthmatic patients following orthognathic surgery. The present study aimed to assess the incidence and risk factors of postoperative complications in asthmatic patients following orthognathic surgery. MATERIAL AND METHODS: A retrospective cohort study was conducted which consisted of two groups of patients i.e., asthmatic and systemically healthy patients, who underwent conventional orthognathic surgical procedures (Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty). The recorded postoperative complications in both groups of patients included infection, relapse, altered facial sensation, temporomandibular joint disorder, respiratory complications, and hemorrhage-related events. The association between baseline variables and complications for identifying the possible risk factors was assessed using bivariate analysis and a logistic regression model. RESULTS: A total of 886 patients underwent orthognathic surgery over a period of 6-years. Following the eligibility criteria, 16 patients were recruited in the asthmatic group and 278 patients were systemically healthy. The most common complications in the asthmatic patients were altered sensation (37.5%) followed by TMJ disorder (25.0%) and relapse (18.8%). These patients were associated with an increased risk of relapse (P = 0.048) compared to healthy patients. Following adjustment of baseline variables, increased risk of relapse was still associated with asthma (odds ratio [OR]. = 4.704, P = 0.027). CONCLUSION: Asthmatic patients suffer from a significantly higher risk of relapse and need to be closely monitored following orthognathic surgery to ensure a stable outcome. Asthma does not seem to have a significant impact on other postoperative complications.

Building a knowledge base for colorectal cancer patient care using formal concept analysis.

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease with different responses to targeted therapies due to various factors, and the treatment effect differs significantly between individuals. Personalize medical treatment (PMT) is a method that takes individual patient characteristics into consideration, making it the most effective way to deal with this issue. Patient similarity and clustering analysis is an important aspect of PMT. This paper describes how to build a knowledge base using formal concept analysis (FCA), which clusters patients based on their similarity and preserves the relations between clusters in hierarchical structural form. METHODS: Prognostic factors (attributes) of 2442 CRC patients, including patient age, cancer cell differentiation, lymphatic invasion and metastasis stages were used to build a formal context in FCA. A concept was defined as a set of patients with their shared attributes. The formal context was formed based on the similarity scores between each concept identified from the dataset, which can be used as a knowledge base. RESULTS: A hierarchical knowledge base was constructed along with the clinical records of the diagnosed CRC patients. For each new patient, a similarity score to each existing concept in the knowledge base can be retrieved with different similarity calculations. The ranked similarity scores that are associated with the concepts can offer references for treatment plans. CONCLUSIONS: Patients that share the same concept indicates the potential similar effect from same clinical procedures or treatments. In conjunction with a clinician's ability to undergo flexible analyses and apply appropriate judgement, the knowledge base allows faster and more effective decisions to be made for patient treatment and care.

Postoperative complications following orthognathic surgery in patients with rheumatic diseases: A 2-year follow-up study.

OBJECTIVE: The purpose of this study was to describe the complications following orthognathic surgery in patients with rheumatic diseases and to evaluate rheumatic disease as a possible risk factor. METHODS: A retrospective cohort study was conducted during a 6-year period. The sample consisted of rheumatic and healthy patients who underwent orthognathic surgery. The outcome variables included infection, relapse, respiratory complications, hemorrhage, neurosensory disturbances, temporomandibular joint complications, and removal of osteosynthesis material. Bivariate analysis and logistic regression were applied to identify rheumatic disease as an independent risk factor for complications after orthognathic surgery. RESULTS: Twenty patients were identified as having rheumatic diseases (male: 2; female: 18; mean age: 37.8 ± 13.6 years), and 278 patients were systemically healthy (male: 105; female: 173; mean age: 25.8 ± 11.8 years). The most frequent complications in rheumatic and healthy patients were delayed recovery from neurosensory disturbance (55% and 33%), removal of osteosynthesis material (45% and 26%), and infection (35% and 7%). Following adjustment for possible confounders, rheumatic disease showed a significant association with infection (OR = 4.191, p = 0.016). CONCLUSION: Patients with rheumatic diseases are at a higher risk of postoperative infection following orthognathic surgery compared to healthy patients.

Causal relationship between type 1 diabetes and hypothyroidism: A Mendelian randomization study.

OBJECTIVES: Although an association between type 1 diabetes (T1D) and hypothyroidism has been found in multiple observational studies, whether T1D plays a causal role in the development of hypothyroidism remains uncertain. Therefore, this Mendelian randomization (MR) study aimed to investigate the causal association between T1D and hypothyroidism. METHODS: Independent single-nucleotide polymorphisms associated with T1D with genome-wide significance were selected as instrumental variables from a large genome-wide association study (GWAS) of T1D. Hypothyroidism GWAS summary statistics were obtained from the Thyroidomics Consortium. The inverse-variance weighted (IVW) method was used as the primary analysis for estimating the effect of the exposure on the outcome. We also used MR-Egger, the weighted median method, MR-Robust, and other methods to confirm the results. RESULTS: T1D had a positive causal association with hypothyroidism [IVW, odds ratio (OR) = 1.083, 95% confidence interval (CI), 1.046-1.122; p < .001]. MR-Egger regression indicated that directional pleiotropy did not bias the result (intercept = 0.006; p = .295). The causal association was verified in an independent validation set (IVW, OR = 1.099, 95% CI, 1.018-1.186; p = .017). The results were robust according to various MR methods, and the results of the reverse MR analysis did not support reverse causation (p > .05). CONCLUSIONS: The MR analysis results indicated a causal association between T1D and hypothyroidism. Therefore, it is recommended that patients with T1D undergo thyroid function tests regularly to minimize the risk of undiagnosed hypothyroidism among young patients with T1D.

Identification of novel proteins associated with movement-related adverse antipsychotic effects by integrating GWAS data and human brain proteomes.

Genome-wide association studies (GWAS) have identified some variants for movement-related adverse antipsychotic effects (MAAE), while how these variants confer MAAE remains unclear. We used the probabilistic Mendelian randomization (PMR) method to identify candidate proteins for MAAE by integrating MAAE GWASs and protein quantitative trait loci (pQTL) data. An independent pQTL data from the Banner project and brain-derived eQTL data were used to perform confirmatory PMR. A total of 56 proteins were identified as candidate targets for MAAE after false discovery rates (FDR) correction, such as GRIN2B, ADRA1A, and PED4B. 12 genes were replicated in the confirmatory PMR, and 18 genes had consistent evidence at the transcript level. Furthermore, we investigated the associations between candidate proteins and the motor symptoms of Parkinson's disease (PD). There were 24, 38, and 10 candidate proteins that were significantly associated with PD, PD motor subtypes, and PD motor progression, respectively. Enrichment analysis identified 34 GO terms and 17 pathways that may be involved in MAAE, such as glutamatergic synapse, glutamate receptor complex, and GABAergic synapse. Our study identified multiple candidate genes and pathways that were associated with MAAE, providing new insights into the biological mechanism of MAAE and targets for further mechanistic and therapeutic studies.

Effects of antipsychotics on triglyceride trajectories and its implications in CVD: A longitudinal cohort study.

BACKGROUND: Although the association between short-term antipsychotics exposure and triglycerides (TG) levels has been confirmed, the effects of long-term antipsychotics exposure on TG trajectories and its implications in cardiovascular disease (CVD) remains largely unknown. METHODS: A total of 39,988 participants with at least 3 TG measurements between January 2014 and February 2021 were included in this longitudinal study, with a median follow-up was 4.48 years. A latent class growth mixed model (LCGMM) was used to identify TG trajectories. Based on the LCGMM parameters, we calculated the area under the curve (AUC) and estimated the effect of antipsychotics on AUC and TG trajectory slopes. The primary outcome was CVD events. We also investigated and compared the association between antipsychotics and CVD in subgroups stratified by TG trajectory and TG levels. FINDINGS: A total of 11,543 CVD events were documented and the incidence density was 64.64 per 1000 person-years. We identified two TG trajectories labeled as inverse-U shape (30.77%, n=12306) and low-decreasing (69.23%, n=27682). The antipsychotic exposure increased total AUC by 13% and increased the slopes of TG trajectories before age 48 years. In the inverse-U and low-decreasing group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for antipsychotics associated with CVD were 1.40 (1.21-1.62) and 1.29 (1.14-1.45), respectively, and the difference between the two trajectory groups become larger with the increase of the antipsychotic exposure. The association of antipsychotics with CVD (HR=1.72, 95%CI: 1.36-2.19) in inverse-U trajectory and high TG group was stronger than that in other subgroups. INTERPRETATION: Long-term antipsychotic exposure increased the TG burden and TG increase rate early in life. The strength of the association between antipsychotics and CVD risk in the inverse-U group was stronger than that in the low-decreasing group. FUNDING: The National Key Research and Development Program of China, Shandong Province Major Science and Technology Innovation Project, and National Natural Science Foundation of China.

Exposure to various ambient air pollutants increases the risk of venous thromboembolism: A cohort study in UK Biobank.

Epidemiological evidence for the association between air pollutants exposure and venous thromboembolism (VTE) remains controversial. In this study, a total of 389,659 participants from the UK Biobank who were free of VTE in 2010 were included, and the annual mean concentrations of air pollutants near where participants lived were collected. During a median follow-up period of 8.25 years, 4986 VTEs were determined from the hospital admission records. The Cox proportional hazard model was used to examine the association between air pollutants and VTE. We firstly investigated the associations between air pollutants concentration and VTE and found only NO2 and NO increased VTE risk (P < 0.05). We further calculated the product of air pollutant concentrations and outdoor time to measure personal daily cumulative exposure and found that the hazard rates (HRs) of VTE for a 50-µg/m3∗day increase in daily cumulative exposure to PM10, PM2.5, PM2.5-10, NO, and NO2 were 1.08 (1.05-1.12), 1.16 (1.09-1.24), 1.23 (1.11-1.37), 1.04 (1.01-1.06), and 1.05 (1.03-1.08), respectively. To measure joint exposure to various air pollutants and its effect on VTE, we created a weighted air pollutants exposure score (APES) and found a dose-response relationship between APES and VTE risk (P < 0.001 for trend). Compared with participants in the lowest quintile of APES, the HRs of VTE were 1.19 (1.08-1.30) for those within the highest quintile groups. Furthermore, we also found the effect of air pollutants on VTE was statistically significant only in individuals with low-middle VTE genetic risk score (GRS) (P < 0.05), but not in the high VTE GRS groups (P > 0.05). Our findings suggest that exposure to various air pollutants including PM2.5, PM2.5-10, PM10, NO, and NO2, either individually or jointly, were associated with an increased risk of VTE in a dose-response pattern. Our study highlights the importance of a comprehensive assessment of various air pollutants in VTE prevention.

Influence of systemic comorbidities on the complications of orthognathic surgery: A scoping review.

The potential impact of systemic comorbidities has not yet been thoroughly explored in orthognathic surgery. Therefore, the following scoping review was conducted to accumulate evidence on the possible impact of systemic comorbidities on the orthognathic surgery complications. PubMed, Embase, Cochrane, and Web of Science databases were searched up to April 2022 to identify studies about patients with systemic comorbidities who underwent orthognathic surgery. A total of 12,938 articles were screened, and seven articles met the inclusion criteria. Only one study had control group, other six articles had a non-comparative study design. The current evidence suggests a high impact of rheumatic diseases and neuromuscular disorders on the surgery- and patient-related postoperative complications following orthognathic surgery. At the same instance, the findings of the review should be interpreted with caution due to a lack of substantial evidence for extrapolating the findings to a contemporary surgical practice.

Prevalence of systemic conditions in an orthognathic surgery population: A 20-year single-center study.

OBJECTIVE: To describe the prevalence and characteristics of patients with systemic conditions in an orthognathic surgery population. STUDY DESIGN: A retrospective review was conducted of 1653 patients undergoing orthognathic surgery between 2001 and 2020. Patients were grouped per category of systemic condition and relevant information was retrieved from medical records. Clinical and perioperative characteristics were compared between patients with and without systemic conditions using χ2 tests and 95% confidence intervals. Age was compared using a cumulative logit model. RESULTS: The proportion of patients with systemic conditions undergoing orthognathic surgery was 16% (272 of 1653 patients). Patients with systemic conditions were on average 6 years older than patients without systemic conditions (P < .001). Significant differences in age compared to healthy patients were found for endocrinological (12 years; 95% confidence interval [CI], 8-16 years), gastrointestinal (10 years; 95% CI, 3-18 years), pneumological (5 years; 95% CI, 2-13 years), and cardiovascular disorders (17 years; 95% CI, 12-21 years). CONCLUSION: Nearly 1 out of 6 patients undergoing orthognathic surgery has a systemic condition. Knowledge of the prevalence and characteristics of these patients creates awareness among surgeons and a foundation for future studies on perioperative management.

H7N9 virus infection triggers lethal cytokine storm by activating gasdermin E-mediated pyroptosis of lung alveolar epithelial cells.

The H7N9 influenza virus emerged in China in 2013, causing more than 1560 human infections, 39% of which were fatal. A 'cytokine storm' in the lungs of H7N9 patients has been linked to a poor prognosis and death; however, the underlying mechanism that triggers the cytokine storm is unknown. Here, we found that efficient replication of the H7N9 virus in mouse lungs activates gasdermin E (GSDME)-mediated pyroptosis in alveolar epithelial cells, and that the released cytosolic contents then trigger a cytokine storm. Knockout of Gsdme switched the manner of death of A549 and human primary alveolar epithelial cells from pyroptosis to apoptosis upon H7N9 virus infection, and Gsdme knockout mice survived H7N9 virus lethal infection. Our findings reveal that GSDME activation is a key and unique mechanism for the pulmonary cytokine storm and lethal outcome of H7N9 virus infection and thus opens a new door for the development of antivirals against the H7N9 virus.

Exploring the Causal Roles of Circulating Remnant Lipid Profile on Cardiovascular and Cerebrovascular Diseases: Mendelian Randomization Study.

BACKGROUND: Causal evidence of circulating lipids especially the remnant cholesterol with cardiovascular and cerebrovascular disease (CVD) is lacking. This research aimed to explore the causal roles of extensive lipid traits especially the remnant lipids in CVD. METHODS: Two-sample Mendelian randomization (TSMR) analysis was performed based on large-scale meta-analysis datasets in European ancestry. The causal effect of 15 circulating lipid profiles including 6 conventional lipids and 9 remnant lipids on coronary heart disease (CHD) and ischemic stroke (IS), as well as the subtypes, was assessed. RESULTS: Apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were still important risk factors for CHD and myocardial infarction (MI) but not for IS. Apo B is the strongest which increased the CHD and MI risk by 44% and 41%, respectively. The odds ratios (ORs) of total TG on CHD and MI were 1.25 (95% confidence interval [CI], 1.13-1.38) and 1.24 (95% CI, 1.11-1.38), respectively. A one standard deviation difference increased TG in medium very-low-density lipoproteins (M.VLDL.TG), TG in small VLDL (S.VLDL.TG), TG in very small VLDL (XS.VLDL.TG), TG in intermediate-density lipoproteins (IDL.TG), TG in very large HDL (XL.HDL.TG), and TG in small HDL (S.HDL.TG) particles also robustly increased the risk of CHD and MI by 9-28% and 9-27%, respectively. TG in very/extremely large VLDL (XXL.VLDL.TG and XL.VLDL.TG) were insignificant or even negatively associated with CHD (in multivariable TSMR), and negatively associated with IS as well. CONCLUSION: The remnant lipids presented heterogeneity and two-sided effects for the risk of CHD and IS that may partially rely on the particle size. The findings suggested that the remnant lipids were required to be intervened according to specific components. This research confirms the importance of remnant lipids and provides causal evidence for potential targets for intervention.

Integration analysis of GWAS and expression quantitative trait loci to identify candidate genes and pathways for clozapine-related neutropaenia.

AIMS: Little is known about the genetic basis of clozapine-related neutropaenia. This study aims to explore candidate genes and pathways involved in clozapine-related neutropaenia. METHODS: This study conducted a two-stage integrative analysis of the summary statistics from the genome-wide association study (GWAS, n = 552) of the lowest absolute neutrophil count (ANC) during clozapine treatment and the summary data of the expressed quantitative trait locus (eQTL). First, we use the probabilistic Mendelian randomization (PMR-Egger) to identify genes whose expression is causally related to ANC, and then use Bayesian co-localization analysis to investigate whether there are shared causal variants between them [posterior probability for hypotheses 4 (PP.H4) > 0.80]. Finally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to explore the pathways that may be associated with ANC during clozapine treatment. RESULTS: PMR-Egger analysis identified 146 genes that may be causally associated with ANC after Bonferroni correction (P-value < 3.25e-6). Bayesian co-localization analysis identified six further genes whose gene expression shared common variants with ANC, including NT5E (PP.H4 = 0.96), GLDC (PP.H4 = 0.82), NUDT17 (PP.H4 = 0.88), MSH4 (PP.H4 = 0.88), PTER (PP.H4 = 0.89) and SERPINB6 (PP.H4 = 0.83). Enrichment analysis identified 52 GO terms and seven pathways associated with ANC, such as NAD metabolic process, drug catabolic process and glyoxylate and dicarboxylate metabolism. CONCLUSION: This study identified multiple candidate genes and pathways that may be involved in clozapine-related neutropaenia, providing novel clues for the mechanism of clozapine-related neutropaenia.

Triglyceride-Glucose Index Is Not Associated With Lung Cancer Risk: A Prospective Cohort Study in the UK Biobank.

BACKGROUND: The triglyceride-glucose (TyG) index is a practical substitute measure for insulin resistance (IR). The relationship between IR and lung cancer has been examined in previous studies; however, the findings have been controversial. In addition, previous studies had small sample sizes. Thus, we systematically examined the association between IR and lung cancer risk based on the UK Biobank with IR measured by the TyG index and further examined the interactions and joint effects for lung cancer. METHODS: A total of 324,334 individuals free from any type of cancer at recruitment from the UK Biobank prospective cohort were included. The participants were predominantly between 40 and 70 years old. After adjusting for relevant confounders, multivariable Cox regression models were constructed to examine the relationship between the TyG index and the risk of lung cancer. We also checked the interactions and joint effects using a polygenic risk score (PRS) for lung cancer. RESULTS: During a median follow-up of 9 years, 1,593 individuals were diagnosed with lung cancer. No association was found between the TyG index and lung cancer risk after multivariate Cox regression analysis adjusted for risk factors (hazard ratio: 0.91; 95% confidence interval: 0.64-1.18). No interaction or joint effects for genetic risk and the TyG index were observed. CONCLUSION: The TyG index was not associated with the risk of lung cancer. Our results provide limited evidence that IR is not correlated with the risk of lung cancer.

Identifying causality, genetic correlation, priority and pathways of large-scale complex exposures of breast and ovarian cancers.

BACKGROUND: Genetic correlations, causalities and pathways between large-scale complex exposures and ovarian and breast cancers need systematic exploration. METHODS: Mendelian randomisation (MR) and genetic correlation (GC) were used to identify causal biomarkers from 95 cancer-related exposures for risk of breast cancer [BC: oestrogen receptor-positive (ER + BC) and oestrogen receptor-negative (ER - BC) subtypes] and ovarian cancer [OC: high-grade serous (HGSOC), low-grade serous, invasive mucinous (IMOC), endometrioid (EOC) and clear cell (CCOC) subtypes]. RESULTS: Of 31 identified robust risk factors, 16 were new causal biomarkers for BC and OC. Body mass index (BMI), body fat mass (BFM), comparative body size at age 10 (CBS-10), waist circumference (WC) and education attainment were shared risk factors for overall BC and OC. Childhood obesity, BMI, CBS-10, WC, schizophrenia and age at menopause were significantly associated with ER + BC and ER - BC. Omega-6:omega-3 fatty acids, body fat-free mass and basal metabolic rate were positively associated with CCOC and EOC; BFM, linoleic acid, omega-6 fatty acids, CBS-10 and birth weight were significantly associated with IMOC; and body fat percentage, BFM and adiponectin were significantly associated with HGSOC. Both GC and MR identified 13 shared factors. Factors were stratified into five priority levels, and visual causal networks were constructed for future interventions. CONCLUSIONS: With analysis of large-scale exposures for breast and ovarian cancers, causalities, genetic correlations, shared or specific factors, risk factor priority and causal pathways and networks were identified.

Molecular characterization, receptor binding property, and replication in chickens and mice of H9N2 avian influenza viruses isolated from chickens, peafowls, and wild birds in eastern China.

H9N2 avian influenza viruses are widely prevalent in birds and pose an increasing threat to humans because of their enhanced virulence and transmissibility in mammals. Active surveillance on the prevalence and evolution of H9N2 viruses in different avian hosts will help develop eradication measures. We isolated 16 H9N2 viruses from chickens, green peafowls, and wild birds in eastern China from 2017 to 2019 and characterized their comparative genetic evolution, receptor-binding specificity, antigenic diversity, replication, and transmission in chickens and mice. The phylogenetic analysis indicated that the green peafowl viruses and swan reassortant shared the same ancestor with the poultry H9N2 viruses prevalent in eastern China, while the seven wild bird viruses belonged to wild bird lineage. The chicken, peafowl, and swan H9N2 viruses that belonged to the poultry lineage preferentially recognized α-2, 6-linked sialic acids (human-like receptor), but the wild bird lineage viruses can bind both α-2, 3 (avian-like receptor) and human-like receptor similarly. Interestingly, the H9N2 viruses of poultry lineage replicated well and transmitted efficiently, but the viruses of wild bird lineage replicated and transmitted with low efficiency. Importantly, the H9N2 viruses of poultry lineage replicated in higher titer in mammal cells and mice than the viruses of wild birds lineage. Altogether, our study indicates that co-circulation of the H9N2 viruses in poultry, wild birds, and ornamental birds increased their cross-transmission risk in different birds because of their widespread dissemination.