Differences in gut microbiota and its metabolic function among different fasting plasma glucose groups in Mongolian population of China.

BACKGROUND: Many studies reported the association between gut microbiota and type 2 diabetes mellitus (T2D), but it is still unclear which bacterial genus plays a key role and how the metabolic function of gut microbiota changes in the occurrence and development of T2D. Besides, there is a high diabetic prevalence in Mongolian population, which may be partly affected by their high calorie diet. This study identified the main bacterial genus influencing T2D in Mongolian population, and analyzed the changes of metabolic function of gut microbiome. The association between dietary factors and the relative abundance of main bacterial genus and its metabolic function was also studied. METHODS: Dietary surveys and gut microbiota test were performed on 24 Mongolian volunteers that were divided into T2D (6 cases), PRET2D (6 cases) and Control group (12 cases) according to fasting plasma glucose (FPG) values. The relative abundance and metabolic function of gut microbiome from their fecal samples were measured by metagenomic analysis. Statistic method was used to evaluate the association between dietary factors and the relative abundance of the main bacterial genus or its metabolic function. RESULTS: This study found that the Clostridium genus may be one of the key bacterial genera affecting the process of T2D. First, the relative abundance of Clostridium genus was significantly different among the three groups. Second, there was a higher relative abundance of metabolic enzymes of gut bacteria in PRET2D and T2D group than that in Control group. Third, a strong correlation between Clostridium genus and many metabolic enzymes was uncovered, many of which may be produced by the Clostridium. Last, carotene intake daily was negatively correlated with the Clostridium but positively correlated with tagaturonate reductase catalyzing interconversions of pentose and glucuronate. CONCLUSIONS: The gut Clostridium genus may play an important role in the development of T2D and it could be a potential biomarker for T2D in Mongolian population. Meanwhile, the metabolic function of gut bacteria has changed during the early stage of T2D and the changes in carbohydrate, amino acid, lipid or energy metabolism of Clostridium genus may play a critical role. In addition, the carotene intake may affect reproduction and metabolic function of Clostridium genus.

Use of Human-Centered Design Methodology to Develop a Digital Toolkit to Optimize Heart Failure Guideline-Directed Medical Therapy.

BACKGROUND: Guideline-directed medical therapies (GDMTs) improve quality of life and health outcomes for patients with heart failure (HF). However, GDMT utilization is suboptimal among patients with HF. OBJECTIVE: The aims of this study were to engage key stakeholders in semistructured, virtual human-centered design sessions to identify challenges in GDMT optimization posthospitalization and inform the development of a digital toolkit aimed at optimizing HF GDMTs. METHODS: For the human-centered design sessions, we recruited (a) clinicians who care for patients with HF across 3 hospital systems, (b) patients with HF with reduced ejection fraction (ejection fraction ≤ 40%) discharged from the hospital within 30 days of enrollment, and (c) caregivers. All participants were 18 years or older, English speaking, with Internet access. RESULTS: A total of 10 clinicians (median age, 37 years [interquartile range, 35-41], 12 years [interquartile range, 10-14] of experience caring for patients with HF, 80% women, 50% White, 50% nurse practitioners) and three patients and one caregiver (median age 57 years [IQR: 53-60], 75% men, 50% Black, 75% married) were included. Five themes emerged from the clinician sessions on challenges to GDMT optimization (eg, barriers to patient buy-in). Six themes on challenges (eg, managing medications), 4 themes on motivators (eg, regaining independence), and 3 themes on facilitators (eg, social support) to HF management arose from the patient and caregiver sessions. CONCLUSIONS: The clinician, patient, and caregiver insights identified through human-centered design will inform a digital toolkit aimed at optimizing HF GDMTs, including a patient-facing smartphone application and clinician dashboard. This digital toolkit will be evaluated in a multicenter, clinical trial.

Genetic mapping and physiological analysis of chlorophyll-deficient mutant in Brassica napus L.

BACKGROUND: Leaf color mutants have reduced photosynthetic efficiency, which has severely negative impacts on crop growth and economic product yield. There are different chlorophyll mutants in Arabidopsis and crops that can be used for genetic control and molecular mechanism studies of chlorophyll biosynthesis, chloroplast development and photoefficiency. Chlorophyll mutants in Brassica napus are mostly used for mapping and location research but are rarely used for physiological research. The chlorophyll-deficient mutant in this experiment were both genetically mapped and physiologically analyzed. RESULTS: In this study, yellow leaf mutant of Brassica napus L. mutated by ethyl methyl sulfone (EMS) had significantly lower chlorophyll a, b and carotenoid contents than the wild type, and the net photosynthetic efficiency, stomatal conductance and transpiration rate were all significantly reduced. The mutant had sparse chloroplast distribution and weak autofluorescence. The granule stacks were reduced, and the shape was extremely irregular, with more broken stromal lamella. Transcriptome data analysis enriched the differentially expressed genes mainly in phenylpropane and sugar metabolism. The mutant was mapped to a 2.72 Mb region on A01 by using BSA-Seq, and the region was validated by SSR markers. CONCLUSIONS: The mutant chlorophyll content and photosynthetic efficiency were significantly reduced compared with those of the wild type. Abnormal chloroplasts and thylakoids less connected to the stroma lamella appeared in the mutant. This work on the mutant will facilitate the process of cloning the BnaA01.cd gene and provide more genetic and physiological information concerning chloroplast development in Brassica napus.

Effects of water-soluble components of atmospheric particulates from rare earth mining areas in China on lung cancer cell cycle.

BACKGROUND: This study aims to investigate the effects of water soluble particulate matter (WSPM) on the viability and protein expression profile of human lung adenocarcinoma cell A549 in the Bayou Obo rare earth mining area, and explore the influence of WSPM on the A549 cell cycle. RESULTS: It was found that WSPM can inhibit the viability of A549 cells and induce cell arrest in the G2/M phase. Compared with controls, exposure to WSPM10 and WSPM2.5 induced 134 and 116 proteins to be differentially expressed in A549 cells, respectively. In addition, 33 and 31 differentially expressed proteins were further confirmed, and was consistent with the proteomic analysis. The most prominent enrichment in ribosome-associated proteins were presented. When RPL6, RPL13, or RPL18A gene expression was inhibited, A549 cells were arrested in the G1 phase, affecting the expression of Cyclin D1, p21, RB1, Cyclin A2, Cyclin B1, CDC25A, CDK2, CHEK2 and E2F1. Furthermore, the La3+, Ce3+, Nd3+ and F- in WSPM also inhibited the viability of A549 cells. After 24 h of exposure to 2 mM of NaF, A549 cells were also arrested in the G2/M phase, while the other three compounds did not have this effect. These four compounds affected the cell cycle regulatory factors in A549 cells, mainly focusing on effecting the expression of CDK2, CDK4, RB1, ATM, TP53 and MDM2 genes. These results are consistent with the those from WSPM exposure. CONCLUSIONS: These results revealed that WSPM from rare earth mines decreased the viability of A549 cells, and induced cell cycle G2/M phase arrest, and even apoptosis, which may be independent of the NF-κB/MYD88 pathway, and be perceived by the TLR4 receptor. The dysfunction of the cell cycle is correlated to the down-expression of ribosomal proteins (RPs). However, it is not the direct reason for the A549 cell arrest in the G2/M phase. La3+, Ce3+, and F- are probably the main toxic substances in WSPM, and may be regulate the A549 cell cycle by affecting the expression of genes, such as MDM2, RB1, ATM, TP53, E2F1, CDK2 and CDK4. These results indicate the importance for further research into the relationship between APM and lung cancer.

Barriers to prescribing glucose-lowering therapies with cardiometabolic benefits.

BACKGROUND: The adoption of 2 classes of new diabetes medications, glucagon-like peptide 1 receptor agonists (GLP1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i), has been slow in the United States despite their cardiovascular benefits in addition to their glucose-lowering effect. The objective of this study was to identify providers' perspectives about prescribing GLP1RA and SGLT2i. METHODS: In this survey study, a questionnaire was administered between May 17, 2018, and June 11, 2018, in a large academic health care system. Ninety providers who practice in endocrinology, primary care, or cardiology responded the questionnaire, with a 36.3% response rate. The questionnaire explored knowledge, comfort level, beliefs, perceived barriers, and hypothetical clinical decisions about prescribing GLP1RA and SGLT2i. RESULTS: Findings suggested a division of views from endocrinology and primary care providers versus cardiology providers. More than 88% of endocrinology providers and about 50% of primary care providers prescribed GLP1RA or SGLT2i at least 6 times a year, whereas less than 7% of cardiology providers prescribed either medication. All endocrinology providers, approximately 78% of primary care providers, and only 21% of cardiology providers were very comfortable or comfortable in all 4 knowledge aspects about GLP1RA and SGLT2i. Major barriers to prescribing GLP1RA and SGLT2i for endocrinology and primary care providers were cost and nonapproved prior authorizations, yet the top 3 reported barriers for cardiology providers were lack of knowledge about these medications, concerns of introducing confusion into diabetes care, and discomfort of prescribing diabetes medications. CONCLUSIONS: Barriers to prescribing GLP1RA or SGLT2i are unique for endocrinology, primary care, and cardiology providers. Given the cardiovascular benefits of these medications, this study suggests specific areas and potential opportunities for clinicians to improve care for patients with diabetes and cardiovascular disease.

Genome-wide exploration and characterization of miR172/euAP2 genes in Brassica napus L. for likely role in flower organ development.

BACKGROUND: APETALA2-like genes encode plant-specific transcription factors, some of which possess one microRNA172 (miR172) binding site. The miR172 and its target euAP2 genes are involved in the process of phase transformation and flower organ development in many plants. However, the roles of miR172 and its target AP2 genes remain largely unknown in Brassica napus (B. napus). RESULTS: In this study, 19 euAP2 and four miR172 genes were identified in the B. napus genome. A sequence analysis suggested that 17 euAP2 genes were targeted by Bna-miR172 in the 3' coding region. EuAP2s were classified into five major groups in B.napus. This classification was consistent with the exon-intron structure and motif organization. An analysis of the nonsynonymous and synonymous substitution rates revealed that the euAP2 genes had gone through purifying selection. Whole genome duplication (WGD) or segmental duplication events played a major role in the expansion of the euAP2 gene family. A cis-regulatory element (CRE) analysis suggested that the euAP2s were involved in the response to light, hormones, stress, and developmental processes including circadian control, endosperm and meristem expression. Expression analysis of the miR172-targeted euAP2s in nine different tissues showed diverse spatiotemporal expression patterns. Most euAP2 genes were highly expressed in the floral organs, suggesting their specific functions in flower development. BnaAP2-1, BnaAP2-5 and BnaTOE1-2 had higher expression levels in late-flowering material than early-flowering material based on RNA-seq and qRT-PCR, indicating that they may act as floral suppressors. CONCLUSIONS: Overall, analyses of the evolution, structure, tissue specificity and expression of the euAP2 genes were peformed in B.napus. Based on the RNA-seq and experimental data, euAP2 may be involved in flower development. Three euAP2 genes (BnaAP2-1, BnaAP2-5 and BnaTOE1-2) might be regarded as floral suppressors. The results of this study provide insights for further functional characterization of the miR172 /euAP2 module in B.napus.

LDL acts as an opsonin enhancing the phagocytosis of group A Streptococcus by monocyte and whole human blood.

Low-density lipoprotein (LDL) binds to group A Streptococcus (GAS) through Sc11 protein, and scavenger receptor CD36 of monocyte mediates the endocytosis of native or modified LDL. Therefore, we hypothesized that LDL might be an opsonin enhancing the phagocytosis of LDL-bound GAS by monocyte. The results showed that LDL could significantly promote U937 cell to phagocytose M28 (ATCC BAA1064) and M41 (ATCC 12373, AM41)-type GAS, and the phagocytosis rates were significantly increased, compared with LDL-free group. LDL, however, did not enhance the phagocytosis of M41 (CMCC 32198, CM41) or M6 (ATCC BAA946)-type GAS since these two strains did not bind to LDL. CD36 was the major scavenger receptor mediating the uptake of LDL-bound GAS by monocyte U937 cells since anti-CD36 antibody abolished the phagocytosis of LDL-opsonized GAS but anti-CD4 antibody did not. Most of AM41-type GAS cells were killed in human blood, whereas only a few CM41-type cells were phagocytosed. Moreover, recombinant Scl1 (rScl1) derived from M41-type GAS could significantly decrease the opsonophagocytosis of AM41 but not CM41-type GAS because the rScl1 competitively blocked the binding of AM41-type GAS to LDL. Therefore, our findings suggest that LDL may be an opsonin to enhance CD36-dependent opsonic phagocytosis of GAS by monocyte.

High-density lipoprotein acts as an opsonin to enhance phagocytosis of group A streptococcus by U937 cells.

We have previously demonstrated that high-density lipoprotein (HDL) can specifically bind to streptococcal collagen-like protein 1 (Scl1) of M41-type group A Streptococcus (GAS). However, the pathological or physiological significance of Scl1-HDL interaction is unknown. Here, the hypothesis that HDL acts as an opsonin to enhance phagocytosis of HDL-bound GAS by monocytes given that some scavenger receptors can mediate the endocytosis of HDL was tested by using FITC-labeled bacteria, human U937 monocytes and HDL for phagocytic assays. HDL (10 µg/mL) was found to significantly enhance internalization of M41-type (ATCC 12373) GAS by U937 cells after 60 min incubation, compared with an HDL-free group. The internalized GAS were dead after 60 min incubation with U937 cells regardless of presence and absence of HDL. Although very-low-density lipoprotein (VLDL) could specifically bind to ATCC 12373 strain, it did not promote phagocytosis of GAS. Additionally, LDL, HDL and VLDL did not enhance phagocytosis of CMCC 32198 strain because this strain did not bind to these lipoproteins. A physiological concentration of HDL (1000 µg/mL) had a similar effect. Anti-CD36 antibody completely abolished opsonic phagocytosis whereas anti-CD4 antibody did not, indicating that CD36 is the major scavenger receptor mediating the uptake of HDL-opsonized GAS by U937 cells. Furthermore, because rScl1 competitively blocked the interaction of ATCC 12373 strain with HDL recombinant Scl1 (rScl1) derived from M41-type GAS, it significantly decreased opsonophagocytosis of ATCC 12373 strain but not of CMCC 32198 strain. Therefore, our findings suggest that HDL may be an opsonin that enhances CD36-dependent opsonophagocytosis of GAS by U937 cells.

Correlations of SDF-1ɑ and XRCC1 gene polymorphisms with the risk of renal cancer development and bioinformatics studies of SDF-1α and XRCC1 and the prognosis of renal cancer.

To study the relationships between stromal cell-derived factor-1 (SDF-1ɑ) and renal cell carcinoma (RCC) susceptibility and the presence of single nucleotide polymorphisms in the human X-ray cross-complementary repair gene (XRCC1). Compare SDF-1 based on RCC related data in the TCGA database α, The expression difference of XRCC1 between RCC tissue and normal tissue; Collect 166 newly diagnosed RCC cases and 166 healthy individuals who underwent physical examinations during the same period, and detect genotype using iMLDR method. The results The rs1801157 locus (C:T) of the SDF-1α gene was not significantly associated with the pathohistological type, the rs1799782 locus (G:A) of the XRCC1 gene was associated with the pathohistological type of RCC, and there were interactions between rs1799782 and smoking, alcohol consumption, pesticide exposure, hair dye, and urine holding. The rs1799782 locus of the XRCC1 gene may be a key factor in the pathogenesis and pathological development of RCC. High SDF-1ɑ expression is a protective factor for the overall survival of patients with RCC, and SDF-1ɑ and XRCC1 may be important for the treatment of RCC.

Rationale and Design of the mTECH-Rehab Randomized Controlled Trial: Impact of a Mobile Technology Enabled Corrie Cardiac Rehabilitation Program on Functional Status and Cardiovascular Health.

BACKGROUND: Cardiac rehabilitation (CR) is an evidence-based, guideline-recommended intervention for patients recovering from a cardiac event, surgery or procedure that improves morbidity, mortality, and functional status. CR is traditionally provided in-center, which limits access and engagement, most notably among underrepresented racial and ethnic groups due to barriers including cost, scheduling, and transportation access. This study is designed to evaluate the Corrie Hybrid CR, a technology-based, multicomponent health equity-focused intervention as an alternative to traditional in-center CR among patients recovering from a cardiac event, surgery, or procedure compared with usual care alone. METHODS: The mTECH-Rehab (Impact of a Mobile Technology Enabled Corrie CR Program) trial will randomize 200 patients who either have diagnosis of myocardial infarction or who undergo coronary artery bypass grafting surgery, percutaneous coronary intervention, heart valve repair, or replacement presenting to 4 hospitals in a large academic health system in Maryland, United States, to the Corrie Hybrid CR program combined with usual care CR (intervention group) or usual care CR alone (control group) in a parallel arm, randomized controlled trial. The Corrie Hybrid CR program leverages 5 components: (1) a patient-facing mobile application that encourages behavior change, patient empowerment, and engagement with guideline-directed therapy; (2) Food and Drug Administration-approved smart devices that collect health metrics; (3) 2 upfront in-center CR sessions to facilitate personalization, self-efficacy, and evaluation for the safety of home exercise, followed by a combination of in-center and home-based sessions per participant preference; (4) a clinician dashboard to track health data; and (5) weekly virtual coaching sessions delivered over 12 weeks for education, encouragement, and risk factor modification. The primary outcome is the mean difference between the intervention versus control groups in distance walked on the 6-minute walk test (ie, functional capacity) at 12 weeks post randomization. Key secondary and exploratory outcomes include improvement in a composite cardiovascular health metric, CR engagement, quality of life, health factors (including low-density lipoprotein-cholesterol, hemoglobin A1c, weight, diet, smoking cessation, blood pressure), and psychosocial factors. Approval for the study was granted by the local institutional review board. Results of the trial will be published once data collection and analysis have been completed. CONCLUSIONS: The Corrie Hybrid CR program has the potential to improve functional status, cardiovascular health, and CR engagement and advance equity in access to cardiac rehabilitation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05238103.

US Trends in Cholesterol Screening, Lipid Levels, and Lipid-Lowering Medication Use in US Adults, 1999 to 2018.

Background Understanding current trends in cholesterol screening, lipid levels, and lipid management therapies may inform health policy and practice. Methods and Results In 50 928 US adult National Health and Nutrition Examination Survey (NHANES) participants, trends were assessed in cholesterol screening, mean levels of total cholesterol, triglycerides, low-density-lipoprotein cholesterol, and lipid-lowering medication use from 1999 through 2018. Point estimates were also calculated using the 2017 to March 2020 prepandemic data set. The age- and sex-adjusted proportion of having cholesterol screened within 5 years increased from 63.2% (95% CI, 60.0-66.3) in 1999 to 2000 to 72.5% (95% CI, 69.5-75.3) in 2017 to 2018 (P<0.001 for linear trend). Mean total cholesterol decreased from 203.3 mg/dL (95% CI, 201.0-205.7) in 1999 to 2000 to 188.4 mg/dL in 2017 to 2018 (95% CI, 185.4-191.5) (P<0.001 for nonlinear trend). The mean triglyceride level decreased from 121.3 mg/dL (95% CI, 116.4-126.4) in 1999 to 2000 to 91.4 mg/dL (95% CI, 88.4-94.6) in 2017 to 2018 (P<0.001 for nonlinear trend). Low-density lipoprotein cholesterol decreased from 127.9 mg/dL (95% CI, 125.3-130.5) in 1999 to 2000 to 111.7 mg/dL (95% CI, 109.0-114.4) in 2017 to 2018 (P<0.001 for nonlinear trend). Among statin-eligible US adults, the proportion of statin use increased from 14.9% (95% CI, 12.2-17.9) in 1999 to 2000 to 27.8% (95% CI, 23.0-33.2) in 2017 to 2018 (P<0.001 for nonlinear trend). Statin use increased in adults with diabetes aged 40 to 75 years from 21.4% in 1999 to 2000 to 51.9% in 2017 to 2018 (P<0.001 for overall linear trend). Statin use plateaued in all other groups. The proportions of using ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors were 3.7% (95% CI, 1.3-9.8) and 0.03% (95% CI, 0.01-0.15) in 2017 to March 2020, respectively. Conclusions From 1999 through 2018, cholesterol screening increased while mean total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels decreased, with a modest increase in statin use and low uptake of nonstatin therapy in the US population.

Cardiovascular health trajectories and subsequent cardiovascular disease and mortality: The multi-ethnic study of atherosclerosis (MESA).

Objective: Longitudinal trajectories of cardiovascular health (CVH) may reflect vascular risk burden due to prolonged cumulative exposure to non-ideal CVH levels. Identifying individuals who have a higher risk CVH trajectory may facilitate treatment, screening, and prevention. We aimed to characterize 10-year trajectories of CVH and examine the associations between CVH trajectories and subsequent cardiovascular disease (CVD) and mortality. Methods: We analyzed 3674 MESA participants who completed four exams and remained CVD-free from 2000 to 2011. A 12-point CVH score was calculated based on physical activity, smoking status, body mass index, cholesterol, blood pressure, and glucose. Ideal CVH was defined as a score ≥ 9. Group-based trajectory modeling was used to identify trajectories of ideal CVH. Cox models were used to examine the association of CVH trajectories with incident CVD and death from 2011 to 2018, adjusting for age, sex, race/ethnicity, income, education, and marital status. Results: Three trajectories were identified based on the probability of achieving ideal CVH: high (n = 1251), medium (n = 760), and persistently low (n = 1663). Almost half (45.3%) of the participants had a persistently low trajectory. During a median of 7.7 years follow-up, 392 incident CVD events and 459 deaths occurred. Compared with the high CVH group, participants in the persistently low CVH trajectory group had elevated risks for CVD (adjusted hazard ratios 1.49, 95% confidence interval 1.15-1.93) and mortality (1.34, 1.06-1.70), and participants in the medium group had moderate risks for CVD (1.17, 0.86-1.59) and mortality (1.15, 0.87-1.53) (p-value for trend 0.002 for CVD, 0.014 for mortality). Conclusion: Persistently nonideal CVH is a common trajectory. Targeted prevention programs might benefit individuals with persistently nonideal CVH given their elevated risk of subsequent CVD and mortality.

The Relationship between VEGF and AGT Gene Single Nucleotide Polymorphisms and Susceptibility to Renal and Bladder Cancers.

BACKGROUND: We aimed to examine the relationships between the angiotensinogen (AGT) and vascular endothelial growth factor (VEGF) gene single nucleotide polymorphisms and susceptibility to bladder and kidney cancers. METHODS: A 1:1 paired case-control study was conducted, which included 143 newly diagnosed kidney cancer cases, 182 newly diagnosed bladder cancer cases, and healthy subjects in the same period collected from two hospitals. Medical records and a questionnaire were used to obtain relevant information. Genotypes were determined by improved multiple ligase detection reaction (iMLDR) and VEGF serum expression levels were detected by enzyme-linked immunosorbent assays (ELISAs). RESULTS: The VEGF gene/genotype frequencies of rs833061 and rs1570360 were statistically different among various pathological grades of kidney cancer, while the AGT rs699 gene/genotype frequencies were statistically different among various pathological types of bladder cancer. In kidney cancer, rs699 was associated with smoking, drinking, and hair coloring, while in bladder cancer, rs699, rs1570360, rs3025039, and rs833061 were associated with smoking, drinking, hair coloring, exercise, and urine holding. CONCLUSIONS: This work will help identify biomarkers that can predict the early metastasis and recurrence of kidney or bladder cancer, as well as help improve patient survival rates by predicting their susceptibility. SIGNIFICANCE: This work will provide reference for the prevention and treatment of kidney and bladder cancers.

Pan-cancer analysis reveals IGFL2 as a potential target for cancer prognosis and immunotherapy.

Insulin-like growth factor like family member 2 (IGFL2) is a gene in the IGFL family, located on chromosome 19, whose role in cancer is unclear, and the aim of this study was to investigate the relevance of IGFL2 expression, prognosis, immunity, and mutation in pan-cancer. Obtaining information from The Cancer Genome Atlas and The Genotype-Tissue Expression Project (GTEx) databases for expression analysis and combining with The Gene Expression Profile Interaction Analysis database for prognostic aspects. Analysis of immune cell infiltration by TIMER and CIBERSORT algorithms. Calculation of correlation of immune-related genes with IGFL2 expression and tumor mutational burden and microsatellite instability. Mutations and DNA methylation were analyzed using the cBioPortal database and the UALCAN database, and functional enrichment was performed using Gene set enrichment analysis (GSEA). IGFL2 expression is significantly elevated in tumor tissue and high expression has a worse prognosis in most cancers. In immune correlation analysis, it was associated with most immune cells and immune-related genes. In most cancers, IGFL2 methylation is lower and the group with mutations in IGFL2 has a worse prognosis than the normal group. The GSEA analysis showed that IGFL2 was significantly enriched in signaling and metabolism. IGFL2 may be involved in the development of many types of cancer, influencing the course of cancer with different biological functions. It may also be a biomarker for tumor immunotherapy.

The meningococcal adhesin NhhA provokes proinflammatory responses in macrophages via toll-like receptor 4-dependent and -independent pathways.

Activation of macrophages by Toll-like receptors (TLRs) and functionally related proteins is essential for host defense and innate immunity. TLRs recognize a wide variety of pathogen-associated molecules. Here, we demonstrate that the meningococcal outer membrane protein NhhA has immunostimulatory functions and triggers release of proinflammatory cytokines from macrophages. NhhA-induced cytokine release was found to proceed via two distinct pathways in RAW 264.7 macrophages. Interleukin-6 (IL-6) secretion was dependent on activation of TLR4 and required the TLR signaling adaptor protein MyD88. In contrast, release of tumor necrosis factor (TNF) was TLR4 and MyD88 independent. Both pathways involved NF-κB-dependent gene regulation. Using a PCR-based screen, we could identify additional targets of NhhA-dependent gene activation such as the cytokines and growth factors IL-1α, IL-1ß, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). In human monocyte-derived macrophages, G-CSF, GM-CSF, and IL-6 were found to be major targets of NhhA-dependent gene regulation. NhhA induced transcription of IL-6 and G-CSF mRNA via TLR4-dependent pathways, whereas GM-CSF transcription was induced via TLR4-independent pathways. These data provide new insights into the role of NhhA in host-pathogen interaction.

Premature mortality from four chronic diseases in Wuhai, China and impact on life expectancy, 2015 to 2020.

To analyze the change trend of life expectancy, the change trend of premature death due to 4 major chronic diseases, and its impact on the life expectancy of Wuhai residents from 2015 to 2020, and to provide evidence for the prevention and control of chronic diseases in this area. The data on population death comes from the Wuhai City Residents' Causes of Death Network Reporting System and the total population is calculated using statistics from Wuhai City's permanent population management, from 2015 to 2020. Premature mortality from the 4 main chronic illnesses was calculated using the abridged life table approach. The impact of premature death from chronic diseases on life expectancy was analyzed using the Arriaga method. The increasing trend of life expectancy of Wuhai citizens was not statistically significant from 2015 to 2020 (t = 2.570, P = .062). Each year, men had a lower life expectancy than women (P < .05). From 2015 to 2020, the downward trend of premature deaths caused by the 4 major non-communicable diseases in Wuhai City was statistically significant (EAPC = -7.74%, P = .041). Premature death from cancer and chronic respiratory disorders decreased, both of which were statistically significant (EAPC < 0, P < .05). The decline in premature mortality from cancer, cardiovascular and cerebrovascular disorders, and chronic respiratory system diseases has contributed to increased life expectancy. Diabetes's rise in premature mortality made a possible "negative contribution" to life expectancy (-0.036 years, -1.79%). From 2015 to 2020, the decreasing trend of the overall premature mortality caused by the 4 major non-communicable diseases in Wuhai was statistically significant, and the life expectancy of females was higher than that of males. We should concentrate on the prevention and control of major chronic illnesses in males, as well as the influence of changes in diabetes-related early mortality on life expectancy.

Short-term association of PM 2.5 /PM 10 on lung cancer mortality in Wuhai city, China (2015-2019): a time series analysis.

OBJECTIVE: The objective of this study was to evaluate the relationship between short-term fine particulate matter (PM 2.5 )/inhalable particulate matter (PM 10 ) exposure and lung cancer mortality. METHOD: From 2015 to 2019, data concerning air pollution, meteorology, and deaths were obtained in Wuhai, China. The association between PM 2.5 /PM 10 and lung cancer mortality was investigated using time series analysis. RESULT: According to the single-pollutant model, a 10 µg/m 3 increase in PM 2.5 /PM 10 was associated with an excess risk of 7.95% (95% CI, 2.22-13.95%), and 2.44% (95% CI, 0.32-4.62%), respectively ( P < 0.05). PM 2.5 /PM 10 had a stronger impact on men and the elderly (>65 years old). Particulate matter had a larger influence on lung cancer mortality during the warm season than the cold season. Furthermore, except for PM 2.5 and PM 10 , the two-pollution model indicated that the other models were statistically significant. The study's single and dual pollutant models were both relatively robust. CONCLUSION: Short-term exposure to PM 2.5 /PM 10 was correlated with a higher risk of lung cancer death in Wuhai, particularly among men and the elderly (>65 years old). Exposure to PM 2.5 /PM 10 really does have a bigger effect on the population during the warm season. Moreover, it is essential that health administration departments should strengthen their regulatory mechanisms for particulate emissions and take the responsibility for safeguarding the vulnerable populations.

Comparative mortality according to peripheral artery disease and coronary heart disease/stroke in the United States.

BACKGROUND AND AIMS: A recent trial reported that patients with peripheral artery disease (PAD) without coronary heart disease or stroke (CHD/stroke) had worse prognosis than those with CHD/stroke without PAD. However, community-based data are lacking. The purpose of this study was to compare mortality according to the status of PAD and CHD/stroke in the general population. METHODS: In 6780 participants (aged ≥40 years) from the National Health and Nutrition Examination Surveys 1999-2004, we compared mortality risk according to PAD (ankle-brachial index ≤0.9) and CHD/stroke (self-report) at baseline using the Kaplan-Meier method and multivariable Cox models accounting for sampling weights. RESULTS: The prevalence of having both PAD and CHD/stroke was 1.6%. The prevalence of PAD without CHD/stroke and CHD/stroke without PAD was 4.1% and 8.5%, respectively (85.8% without PAD or CHD/stroke). Over a median follow-up of 12.8 years, 21.2% died. Individuals with both PAD and CHD/stroke had the worst survival (25.5% at 12 years). Those with PAD without CHD/stroke had the second worst prognosis (47.7%), followed by those with CHD/stroke without PAD (53.2%) and those without CHD/stroke or PAD (87.2%). Adjusted hazard ratio of mortality was 2.70 (95% CI, 2.07-3.53) for PAD with CHD/stroke, 1.81 (1.54-2.12) in CHD/stroke without PAD, and 1.68 (1.35-2.08) in PAD without CHD/stroke vs. no CHD/stroke or PAD. CONCLUSIONS: In the US adults, PAD contributed to increased mortality in persons with and without CHD/stroke. The prognosis of PAD without CHD/stroke was no better than that of CHD/stroke without PAD. These results suggest the importance of recognizing the presence of PAD in the community.

Analysis of Dietary Supplement Use and Influencing Factors in the Mongolian Population.

Objective: Dietary supplements (DS) may improve micronutrient deficiencies, but the unique eating habits and cultural customs of the Chinese Mongolian population affect their choice of DS. Therefore, this study adopted a cross-sectional method to explore the current status of DS use and to assess the influencing factors in the Mongolian population in Inner Mongolia, China. Methods: We used a multistage random cluster sampling method to select 1,434 Mongolian people aged ≥ 18 years in Hohhot and Xilinhot, Inner Mongolia. Data regarding general patient characteristics and DS use through questionnaire surveys were obtained, and the blood plasma was collected for biochemical index detection. The binary logistic regression and decision tree algorithm were used to predict the factors influencing DS use among the Mongolian population. Results: Among 1,434 participants that completed the baseline survey, the usage rate of DS was 18.83%, and more women than men used DS (P = 0.017). Higher use of DS was reported among individuals aged ≤ 34 years, but this difference is not statistically significant (P = 0.052). Usage rate was higher among those living in urban areas (P < 0.001), those with higher education (P < 0.001), those engaged in mental work (P < 0.001), and nonsmokers (P = 0.019). The biochemical test results showed that the proportion of people with abnormal total cholesterol levels using DS was lower (P = 0.003), but that of those with abnormal triglyceride levels using DS was higher (P = 0.001), compared with the proportion of those with normal levels in each case. The most commonly used supplement was calcium (58.15%). Education level was the main factor affecting DS intake. The results of the binary logistic regression model and decision tree model both showed that region, educational level, and abnormal triglyceride levels were significant factors influencing DS intake among Mongolians. Conclusion: Findings from this study indicate that DS intake is uncommon in the Mongolian population. In addition, sex, region, education level, and triglyceride levels may influence DS use.

Application of the very high risk criterion and evaluation of cholesterol guideline adherence in acute myocardial infarction patients at an urban academic medical center.

Objective: The 2018 AHA/ACC cholesterol guidelines recommend considering non-statin agents among very high-risk (VHR) patients with LDL-C ≥ 70 mg/dL after maximizing statin therapy. We aimed to evaluate the prevalence of VHR status in acute myocardial infarction (AMI) patients at hospital discharge and the adherence to guideline-directed cholesterol therapy (GDCT) within one-year follow-up post-AMI. Methods: We performed a retrospective analysis of patients who suffered a type 1 AMI between October 2015 and March 2019, and then were followed at our institution for 1 year after hospital discharge. We calculated the percentage of patients at VHR and among those with follow up lipid panels, we determined the proportion able to achieve GDCT. Results: The mean age of the 331 AMI patients was 61.0 (SD 11.9) years and 33.6% were women. Overall, 268 (81.0%) patients were categorized as having VHR at discharge. Among patients at VHR, a lipid panel was rechecked in 153 individuals (57.1%) within 1 year of discharge, with the median time to lipid recheck being 22.4 weeks (interquartile range: 10.9-40.7 weeks). Among those with a lipid panel re-check, 100 (65.4%) of patients achieved GDCT. Conclusions: Approximately 4 out of 5 AMI patients were considered VHR per the 2018 AHA/ACC guidelines, only about half had follow up lipid panels in the year following AMI, and about two-thirds of those with follow up lipid panels achieved GDCT.