Identification of genetic loci jointly influencing COVID-19 and coronary heart diseases.

BACKGROUND: Comorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks. METHODS: By leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs). FINDINGS: Briefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18-0.19) to 0.23 (95% CI 0.23-0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs → COVID-19 → CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks. INTERPRETATION: Five SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of 'Long COVID-19.'

Effect of statin therapy patterns on readmission and mortality in patients with intracerebral hemorrhage.

There is limited and inconsistent evidence for the association of statin therapy and statin treatment patterns with the risk of recurrent intracerebral hemorrhage (ICH) in patients with prior ICH. To assess the association of statin therapy and its intensity, type, initiation time, and discontinuation with the risk of recurrent ICH and mortality in Chinese patients with ICH. Patients with newly diagnosed ICH in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. Post-ICH statin users (post-diagnosis only) and nonusers (never), statin discontinuers (pre-diagnosis only) and continuers (pre- and post-diagnosis) were matched on a 1:1 propensity score, respectively. Adjusted Cox proportional risk models were used to estimate the risk ratios for ICH readmission and mortality under various statin patterns. A total of 2668 post-ICH statin users and 2668 nonusers without a history of statin use were enrolled. Post-ICH statin users had a lower risk of ICH readmission (HR, 0.57; 95% CI 0.48, 0.69) and all-cause death (0.56: 0.49, 0.63) than nonusers. Low/moderate-intensity treatment was associated with a 63% lower risk of recurrent ICH compared with nonusers (0.37: 0.29, 0.46), whereas high-intensity treatment did not reduce the risk (0.93: 0.74, 1.16). Both low/moderate-intensity (0.42: 0.36, 0.48) and high-intensity statins (0.57: 0.48, 0.69) were associated with a lower risk of all-cause mortality. The risk of ICH readmission was 53% (0.47: 0.30, 0.74) lower with adherence to rosuvastatin than with atorvastatin. Only starting medication within 30 days of the first diagnosis of ICH reduced the risk of ICH readmission (0.49: 0.40, 0.60). Among patients with a history of statin use, 1807 discontinuing and 1,807 continuing users of statins were included. The risk of ICH readmission (4.00: 3.32, 4.80) and the risk of all-cause death (4.01: 3.57, 4.50) were substantially increased in statin discontinuation compared with continued statin use. Statin therapy after ICH was associated with lower risks for ICH readmission and all-cause mortality compared with non-statin therapy, especially at low/moderate intensity and early initiation of statins after ICH. Adherence to rosuvastatin was associated with a lower risk of recurrence of ICH than atorvastatin. Among patients with a statin history prior to ICH, discontinuation of statins after ICH was associated with increased risk of ICH recurrence and death.

Association of Life's Essential 8 with all-cause mortality and risk of cancer: a prospective cohort study.

BACKGROUND: No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer. METHODS: A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used. RESULTS: 12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults. CONCLUSIONS: There was a significant association of LE8 with death and cancer risk, especially for the young population.

Detecting Gene-Gene Interaction among DNA Repair Genes in Chinese non-Syndromic Cleft lip with or Without Palate Trios.

OBJECTIVE: The objective of this study is to investigate the gene-gene interactions associated with NSCL/P among DNA repair genes. DESIGN: This study included 806 NSCL/P case-parent trios from China. Quality control process was conducted for genotyped single nucleotide polymorphisms (SNPs) located in six DNA repair genes (ATR, ERCC4, RFC1, TYMS, XRCC1 and XRCC3). We tested gene-gene interactions with Cordell's method using statistical package TRIO in R software. Bonferroni corrected significance level was set as P = 4.24 × 10-4. We also test the robustness of the interactions by permutation tests. SETTING: Not applicable. PATIENTS/PARTICIPANTS: A total of 806 NSCL/P case-parent trios (complete trios: 682, incomplete trios: 124) with Chinese ancestry. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Not applicable. RESULTS: A total of 118 SNPs were extracted for the interaction tests. Fourteen pairs of significant interactions were identified after Bonferroni correction, which were confirmed in permutation tests. Twelve pairs were between ATR and ERCC4 or XRCC3. The most significant interaction occurred between rs2244500 in TYMS and rs3213403 in XRCC1(P = 8.16 × 10-15). CONCLUSIONS: The current study identified gene-gene interactions among DNA repair genes in 806 Chinese NSCL/P trios, providing additional evidence for the complicated genetic structure underlying NSCL/P. ATR, ERCC4, XRCC3, TYMS and RFC1 were suggested to be possible candidate genes for NSCL/P.

[Gene-gene/gene-environment interaction of transforming growth factor-ß signaling pathway and the risk of non-syndromic oral clefts].

OBJECTIVE: To explore the association between polymorphisms of transforming growth factor-ß (TGF-ß) signaling pathway and non-syndromic cleft lip with or without cleft palate (NSCL/P) among Asian populations, while considering gene-gene interaction and gene-environment interaction. METHODS: A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium, which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P. After stringent quality control measures, 343 single nucleotide polymorphism (SNP) spanning across 10 pivotal genes in the TGF-ß signaling pathway were selected from the original genome-wide association study(GWAS) dataset for further analysis. The transmission disequilibrium test (TDT) was used to test for SNP effects. The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction. Environmental factors collected for the study included smoking during pregnancy, passive smoking during pregnancy, alcohol intake during pregnancy, and vitamin use during pregnancy. Due to the low rates of exposure to smoking during pregnancy and alcohol consumption during pregnancy (<3%), only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed. The threshold for statistical significance was rigorously set at P =1.46×10-4, applying Bonferroni correction to account for multiple testing. RESULTS: A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P (P<0.05), but none of these associations was statistically significant after Bonferroni' s multiple test correction. However, there were 6 pairs of SNPs rs4939874 (SMAD2) and rs1864615 (TGFBR2), rs2796813 (TGFB2) and rs2132298 (TGFBR2), rs4147358 (SMAD3) and rs1346907 (TGFBR2), rs4939874 (SMAD2) and rs1019855 (TGFBR2), rs4939874 (SMAD2) and rs12490466 (TGFBR2), rs2009112 (TGFB2) and rs4075748 (TGFBR2) showed statistically significant SNP-SNP interaction (P<1.46×10-4). In contrast, the analysis of gene-environment interactions did not yield any significant results after being corrected by multiple testing. CONCLUSION: The comprehensive evaluation of SNP associations and interactions within the TGF-ß signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations. However, the significant gene-gene interactions identified suggest that the genetic architecture influencing NSCL/P risk may involve interactions between genes within the TGF-ß signaling pathway. These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

[A ssociations of short-term ambient particulate matter exposure and MTNR1B gene with triglyceride-glucose index: A family-based study].

OBJECTIVE: To explore the effects of short-term particulate matter (PM) exposure and the melatonin receptor 1B (MTNR1B) gene on triglyceride-glucose (TyG) index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China (FISSIC). METHODS: Probands and their relatives from 9 rural areas in Fangshan District, Beijing, were included in the study. PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System. TyG index was calculated by fasting triglyceride and glucose concentrations. The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models, in which covariates such as age, sex, and lifestyles were adjusted for. Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index. RESULTS: A total of 4 395 participants from 2 084 families were included in the study, and the mean age of the study participants was (58.98±8.68) years, with 53. 90% females. The results of association analyses showed that for every 10 µg/m3 increase in PM2.5 concentration, TyG index increased by 0.017 (95%CI: 0.007-0.027), while for per 10 µg/m3 increment in PM10, TyG index increased by 0.010 (95%CI: 0.003-0.017). And the associations all had lagged effects. In addition, there was a positive association between the rs10830963 polymorphism and the TyG index. For per increase in risk allele G, TyG index was elevated by 0.040 (95%CI: 0.004-0.076). The TyG index was 0.079 (95%CI: 0.005-0.152) higher in carriers of the GG genotype compared with carriers of the CC genotype. The interaction of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study. CONCLUSION: Short-term exposure to PM2.5 and PM10 were associated with higher TyG index. The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Identifying Risk Factors for Aspiration in Patients Hospitalized with Community-Acquired Pneumonia.

Background: Aspiration pneumonia (AP) is difficult to diagnose and has poor outcomes. This case-control study aimed to explore the risk factors and delineate the antibiotic usage for AP. Methods: Inpatients diagnosed with community-acquired pneumonia (CAP) from 2013 to 2017, enrolled in the urban employee basic medical insurance program in Beijing, were included and classified into the AP (N = 2,885) and non-AP (N = 53,825) groups. Risk factors were identified by logistic regression. Results: Older age (compared to 18-64 years, OR for 65-79 years: 4.3, 95% CI: 3.8-4.9; OR for >80 years: 6.3, 95% CI: 5.6-7.2), male (OR: 1.4, 95% CI: 1.3-1.5), cerebrovascular disease (OR: 3.1, 95% CI: 2.8-3.5), dementia (OR: 2.0, 95% CI: 1.8-2.1), vomiting (OR: 1.4, 95% CI: 1.2-1.7), Parkinson's disease (OR: 2.1, 95% CI: 1.8-2.4), and epilepsy (OR: 3.2, 95% CI: 2.8-3.7) were associated with an increased risk of AP. 92.8% of the AP patients received antibiotic therapy. Among them, patients treated with broad-spectrum antibiotics, antibiotics for injection, and combined antibiotics accounted for 93.3%, 97.9%, and 81.7%, respectively. Conclusions: Older age, male, and several comorbidities were independent risk factors for AP, and combined antibiotics treatments are common, which merits attention in accurate detection of AP in a high-risk population.

The Fujian eye cross sectional study: objectives, design, and general characteristics.

PURPOSE: To describe the objective and design of the Fujian Eye Study and to introduce the general characteristics and vision condition of this study. METHODS: The Fujian Eye Study (FJES) is a population-based cross-sectional survey on the public eye health status of residents over 50 years old in the entire Fujian Province of Southern China, which contains both urban and rural areas and coastal and inland regions. 10,044 participants were enrolled using a two-stage cluster sampling design and underwent a questionnaire and a series of standard examinations both physical and ocular. The main subgroups of data collection included age, sex, region, refractive error, education background, income, eating habits, smartphone usage in the dark, complaints of eye discomfort, history of chronic diseases, consumption of tobacco, alcohol, or tea. RESULTS: 8211 (81.8%) participants were finally included and were divided into urban populations (4678 subjects) and rural populations (3533 subjects) and coastal residents (6434 subjects) and inland residents (1777 subjects); 4836 participants were female. The mean age was 64.39 (SD 8.87) years (median 64 years; range 50-98 years). 227 (3.33%) had vision impairment (VI), 195 (2.87%) had low vision and 14 (0.21%) were blind. The mean presenting near visual acuity (PNVA) was 0.28 (0.17), the mean presenting distance visual acuity (PDVA) was 0.61 (0.30), and the mean best corrected visual acuity (BCVA) was 0.82 (0.28). CONCLUSIONS: The FJES collected detailed questionnaire information and overall ocular and physical examinations, which provide the opportunity to identify risk factors and images of VI and eye diseases and to evaluate their associations with chronic diseases and basic personal information.

The influence of temperature on the toxicity of insecticides to Nilaparvata lugens (Stål).

The toxicity of insecticides is associated with a variety of factors including temperature, and global warming is bound to lead to the outbreak of pests; therefore, it is important to study the influence of temperature on insecticide toxicity and pest control. In this study, the influence of temperature on the toxicity of insecticides to Nilaparvata lugens (BPH) was determined. The results showed that the sensitivity of BPH to cycloxaprid (LC50 = 42.5-0.388 mg/L), nitenpyram (LC50 = 3.49-0.187 mg/L), triflumezopyrim (LC50 = 0.354-0.0533 mg/L) and chlorpyrifos (LC50 = 36.3-7.41 mg/L) increased significantly when the temperature changed from 18 °C to 36 °C. BPH sensitivity to etofenprox (LC50 = 9.04-54.2 mg/L) was also affected by temperature. Additionally, the feeding amount and the activities of three detoxification enzymes [cytochrome P450 (P450), glutathione S-transferase (GST) and carboxylesterase (CarE)] of BPH at different temperatures were also measured. The feeding amounts were positively correlated with temperature increases while the activities of P450 and GST were significantly inhibited. The correlation analysis showed that changes in P450 activity (but not GST activity) were closely related to the sensitivity of BPH to cycloxaprid, nitenpyram, chlorpyrifos, and etofenprox according to the variation in temperatures. This study provides a theoretical basis for the rational use of chemical pesticides under the global warming trend and provides a reference for the integrated management of BPH in the field.

Opposite Genetic Effects of CMIP Polymorphisms on the Risk of Type 2 Diabetes and Obesity: A Family-Based Study in China.

C-Maf Inducing Protein (CMIP) gene polymorphisms were reported to be associated with type 2 diabetes mellitus (T2DM). Whether the association between CMIP and T2DM is mediated via obesity-related phenotypes is still unclear. We analyzed the association of CMIP rs2925979 with T2DM and a comprehensive set of obesity-related phenotypes in 1576 families ascertained from a Chinese population. These families included a total of 3444 siblings (1582 with T2DM, 963 with prediabetes, and 899 with a normal glucose level). Using multi-level mixed effects regression models, we found that each copy of CMIP rs2925979_T allele was associated with a 29% higher risk of T2DM in females (p = 9.30 × 10-4), while it was not significantly associated with T2DM in males (p = 0.705). Meanwhile, rs2925979_T allele was associated with lower levels of body mass index (BMI), waist circumference (WC), hip circumference (HC), percentage of body fat (PBF), PBF of arms, PBF of legs, and PBF of trunk in nondiabetes females (all p < 0.05). The opposite associations of rs2925979_T allele with T2DM and obesity-related phenotypes suggest that CMIP may exert independent pleiotropic effects on T2DM and obesity-related phenotypes in females.

Associations between homocysteine metabolism related SNPs and carotid intima-media thickness: a Chinese sib pair study.

Carotid intima-media thickness (CIMT) is a good surrogate for atherosclerosis. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. We aim to investigate the relationships between homocysteine (Hcy) related biochemical indexes and CIMT, the associations between Hcy related SNPs and CIMT, as well as the potential gene-gene interactions. The present study recruited full siblings (186 eligible families with 424 individuals) with no history of cardiovascular events from a rural area of Beijing. We examined CIMT, intima-media thickness for common carotid artery (CCA-IMT) and carotid bifurcation, tested plasma levels for Hcy, vitamin B6 (VB6), vitamin B12 (VB12) and folic acid (FA), and genotyped 9 SNPs on MTHFR, MTR, MTRR, BHMT, SHMT1, CBS genes. Associations between SNPs and biochemical indexes and CIMT indexes were analyzed using family-based association test analysis. We used multi-level mixed-effects regression model to verify SNP-CIMT associations and to explore the potential gene-gene interactions. VB6, VB12 and FA were negatively correlated with CIMT indexes (p < 0.05). rs2851391 T allele was associated with decreased plasma VB12 levels (p = 0.036). In FABT, CBS rs2851391 was significantly associated with CCA-IMT (p = 0.021) and CIMT (p = 0.019). In multi-level mixed-effects regression model, CBS rs2851391 was positively significantly associated with CCA-IMT (Coef = 0.032, se = 0.009, raw p < 0.001) after Bonferoni correction (corrected α = 0.0056). Gene-gene interactions were found between CBS rs2851391 and BHMT rs10037045 for CCA-IMT (p = 0.011), as well as between CBS rs2851391 and MTR rs1805087 for CCA-IMT (p = 0.007) and CIMT (p = 0.022). Significant associations are found between Hcy metabolism related genetic polymorphisms, biochemical indexes and CIMT indexes. There are complex interactions between genetic polymorphisms for CCA-IMT and CIMT.

Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013.

Importance: Previous studies have shown increasing prevalence of diabetes in China, which now has the world's largest diabetes epidemic. Objectives: To estimate the recent prevalence and to investigate the ethnic variation of diabetes and prediabetes in the Chinese adult population. Design, Setting, and Participants: A nationally representative cross-sectional survey in 2013 in mainland China, which consisted of 170 287 participants. Exposures: Fasting plasma glucose and hemoglobin A1c levels were measured for all participants. A 2-hour oral glucose tolerance test was conducted for all participants without diagnosed diabetes. Main Outcomes and Measures: Primary outcomes were total diabetes and prediabetes defined according to the 2010 American Diabetes Association criteria. Awareness and treatment were also evaluated. Hemoglobin A1c concentration of less than 7.0% among treated diabetes patients was considered adequate glycemic control. Minority ethnic groups in China with at least 1000 participants (Tibetan, Zhuang, Manchu, Uyghur, and Muslim) were compared with Han participants. Results: Among the Chinese adult population, the estimated standardized prevalence of total diagnosed and undiagnosed diabetes was 10.9% (95% CI, 10.4%-11.5%); that of diagnosed diabetes, 4.0% (95% CI, 3.6%-4.3%); and that of prediabetes, 35.7% (95% CI, 34.1%-37.4%). Among persons with diabetes, 36.5% (95% CI, 34.3%-38.6%) were aware of their diagnosis and 32.2% (95% CI, 30.1%-34.2%) were treated; 49.2% (95% CI, 46.9%-51.5%) of patients treated had adequate glycemic control. Tibetan and Muslim Chinese had significantly lower crude prevalence of diabetes than Han participants (14.7% [95% CI, 14.6%-14.9%] for Han, 4.3% [95% CI, 3.5%-5.0%] for Tibetan, and 10.6% [95% CI, 9.3%-11.9%] for Muslim; P < .001 for Tibetan and Muslim compared with Han). In the multivariable logistic models, the adjusted odds ratios compared with Han participants were 0.42 (95% CI, 0.35-0.50) for diabetes and 0.77 (95% CI, 0.71-0.84) for prediabetes for Tibetan Chinese and 0.73 (95% CI, 0.63-0.85) for diabetes and 0.78 (95% CI, 0.71-0.86) for prediabetes in Muslim Chinese. Conclusions and Relevance: Among adults in China, the estimated overall prevalence of diabetes was 10.9%, and that for prediabetes was 35.7%. Differences from previous estimates for 2010 may be due to an alternate method of measuring hemoglobin A1c.

Pre-pregnancy BMI, gestational weight gain and postpartum weight retention: a meta-analysis of observational studies.

OBJECTIVE: To determine the association of gestational weight gain (GWG) or pre-pregnancy BMI with postpartum weight retention (PPWR). DESIGN: Meta-analysis. SETTING: PubMed, Cochrane Controlled Trials Register, EMBASE, Science Citation Index Expanded, Current Contents Connects and Biosis Previews were used to search articles. SUBJECTS: Publications that described the influence of pre-pregnancy BMI or GWG on PPWR. RESULTS: Seventeen studies that satisfied the eligibility criteria were included in the analyses. Women with inadequate and excessive GWG had significantly lower mean PPWR of -2·14 kg (95 % CI -2·43, -1·85 kg) and higher PPWR of 3·21 kg (95 % CI 2·79, 3·62 kg), respectively, than women with adequate GWG. When postpartum time spans were stratified into 1-3 months, 3-6 months, 6-12 months, 12-36 months and ≥15 years, the association between inadequate GWG and PPWR faded over time and became insignificant (-1·42 kg; 95 % CI -3·08, 0·24 kg) after ≥15 years. However, PPWR in women with excess GWG exhibited a U-shaped trend; that is, a decline during the early postpartum time span (year 1) and then an increase in the following period. Meta-analysis of qualitative studies showed a significant relationship between excessive GWG and higher PPWR risk (OR=2·08; 95 % CI 1·60, 2·70). Moreover, meta-analysis of pre-pregnancy BMI on PPWR indicated that mean PPWR decreased with increasing BMI group. CONCLUSIONS: These findings suggest that GWG, rather than pre-pregnancy BMI, determines the shorter- or longer-term PPWR.

Gene-Diet Interaction between SIRT6 and Soybean Intake for Different Levels of Pulse Wave Velocity.

Soybean is a common food for the Chinese people. We aimed to investigate the risk for brachial ankle pulse wave velocity (baPWV) with inflammatory-related SNPs and soybean. baPWV was measured, and 16 inflammatory-related SNPs located on ADIPOQ, CDH13, SIRT3, SIRT6, CXCL12, CXCR4, NOS1, PON1 and CDKN2B were genotyped in 1749 Chinese participants recruited from various communities. ADIPOQ rs12495941 (GT/TT vs. GG: crude OR = 1.27, p = 0.044) and SIRT6 rs107251 (CT/TT vs. CC: crude OR = 0.74, p = 0.009) were associated with abnormal baPWV (baPWV ≥ 1700 cm/s). After adjustment for conventional environmental risk factors, rs12495941 was associated with abnormal baPWV (GT/TT vs. GG: adjusted OR = 1.43, p = 0.011), but the association between rs107251 and abnormal baPWV was not significant (CT/TT vs. CC: adjusted OR = 0.83, p = 0.173). The interaction between rs107251 and soybean intake for different levels of baPWV was statistically significant (p = 0.017). Compared with a high level of soybean intake, a low level of soybean intake can significantly decrease the risk of abnormal baPWV in individuals of rs107251 CT/TT genotypes (≤ 100 vs. > 100 g/week: adjusted OR = 0.542, p = 0.003). In this study, associations between ADIPOQ rs12495941, SIRT6 rs107251 and baPWV, as well as an interaction between SIRT6 rs107251 and soybean intake for different levels of baPWV were found.

[Data of the quantitative orofacial somatosensory functions of healthy subjects and its influence factors analysis].

OBJECTIVE: To establish the preliminary somatosensory data stratified by gender, age group, and sites in the trigeminal region through standardized quantitative sensory testing on healthy individuals, and to evaluate the effects of gender, age, and sites on somatosensory functions. METHODS: The standardised QST battery developed by the German Research Network on Neuropathic Pain consists totally of 13 different parameters. A total of 70 healthy individuals participated. The subjects were stratified into two groups according to age: younger group (16 female, 16 male, age 24-40 years old) and elder group (20 female, 18 male, age 41-69 years old). The test was performed bilaterally over the infraorbital, mental, and hand regions. RESULTS: The preliminary orofacial somatosensory data stratified by gender, age group, and sites were presented. Female were more sensitive than male for most of the parameters (P<0.05). Age had a significant effect on most of the parameters (P<0.05), the younger group was more sensitive compared with the elder group (P<0.01) for heat pain threshold (HPT): younger group (38.07±2.94) °C, elder group (39.85±3.52) °C; warmth detection threshold (WDT): younger group (1.40±0.74) °C, elder group (1.89±1.14) °C; mechanical detection threshold (MDT): younger group (0.73±1.66) mN, elder group (1.41±2.82) mN; pressure pain threshold (PPT): younger group (171.71±92.51) kPa, elder group (196.36±73.73) kPa; cold pain threshold (CPT): younger group (25.90±5.38) °C, elder group (21.64±6.78) °C; cold detection threshold (CDT): younger group (-0.97±0.55) °C, elder group (-1.36±0.90) °C, and wind-up ratio (WUR): younger group (3.33± 2.20), elder group (2.67±1.68). The inverse results were demonstrated for mechanical pain threshold (MPT): younger group (111.50±88.93) mN, elder group (104.49±94.94) mN; mechanical pain sensitivity (MPS): younger group (6.96±5.61), elder group (8.93±6.53), and vibration detection threshold (VDT): younger group (7.44±0.52) scale, elder group (7.55±0.48) scale (P<0.05). Somatosensory function was site dependent (P<0.001), the two trigeminal sites (infraorbital and mental) were more sensitive than the hand for CDT, HPT, WDT, thermal sensory limen (TSL), MDT, MPT, MPS, and PPT (P<0.001), but the inverse result was observed for VDT (P<0.001). CONCLUSION: The preliminary orofacial somatosensory data of Han Ethnicity stratified by gender, age group, and sites were established. The study evaluated the effects of gender, age and sites on orofacial somatosensory functions by employment standardized quantitative sensory testing.

Cohort profile: the Fangshan Cohort Study of cardiovascular epidemiology in Beijing, China.

BACKGROUND: Urbanizing rural areas in China face a rapidly growing cardiovascular disease burden. Epidemiologic studies and effective preventive strategies are urgently needed. METHODS: The Fangshan Cohort Study is a prospective study that began in 2008 and targets local residents aged 40 years or older living in 3 towns in the Fangshan district of Beijing. The baseline examination included a questionnaire on medical history, health knowledge, and behaviors related to cardiovascular disease, as well as physical and blood biochemical examinations. The questionnaire survey will be readministered every 2 years. A system for surveillance of mortality and morbidity of cardiovascular disease is under development. RESULTS: A total of 20 115 adults (6710 men and 13 405 women) were investigated at baseline (participation rate = 84.5%). The data indicate that overweight/obesity is a serious public health issue in Fangshan: average body mass index was 25.4 kg/m(2) among men and 26.5 kg/m(2) among women, and the prevalences of overweight and obesity were 43.6% and 10.3% among men and 47.0% and 17.7% among women. CONCLUSIONS: The Fangshan Cohort Study will provide data on cardiovascular risk factors and disease profile, which will assist in developing appropriate prevention and control strategies for cardiovascular disease in rural Chinese communities.

Genome-wide interaction-based association analysis identified multiple new susceptibility Loci for common diseases.

Genome-wide interaction-based association (GWIBA) analysis has the potential to identify novel susceptibility loci. These interaction effects could be missed with the prevailing approaches in genome-wide association studies (GWAS). However, no convincing loci have been discovered exclusively from GWIBA methods, and the intensive computation involved is a major barrier for application. Here, we developed a fast, multi-thread/parallel program named "pair-wise interaction-based association mapping" (PIAM) for exhaustive two-locus searches. With this program, we performed a complete GWIBA analysis on seven diseases with stringent control for false positives, and we validated the results for three of these diseases. We identified one pair-wise interaction between a previously identified locus, C1orf106, and one new locus, TEC, that was specific for Crohn's disease, with a Bonferroni corrected P < 0.05 (P = 0.039). This interaction was replicated with a pair of proxy linked loci (P = 0.013) on an independent dataset. Five other interactions had corrected P < 0.5. We identified the allelic effect of a locus close to SLC7A13 for coronary artery disease. This was replicated with a linked locus on an independent dataset (P = 1.09 × 10⁻7). Through a local validation analysis that evaluated association signals, rather than locus-based associations, we found that several other regions showed association/interaction signals with nominal P < 0.05. In conclusion, this study demonstrated that the GWIBA approach was successful for identifying novel loci, and the results provide new insights into the genetic architecture of common diseases. In addition, our PIAM program was capable of handling very large GWAS datasets that are likely to be produced in the future.

Nanoformulations for the diagnosis and treatment of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive phase of metabolic dysfunction-associated steatotic liver disease (MASLD) that develops into irreversible liver cirrhosis and hepatocellular carcinoma, ultimately necessitating liver transplantation as the sole life-saving option. However, given the drawbacks of liver transplantation, including invasiveness, chronic immunosuppression, and a lack of donor livers, prompt diagnosis and effective treatment are indispensable. Due to the limitations of liver biopsy and conventional imaging modalities in diagnosing MASH, as well as the potential hazards associated with liver-protecting medicines, numerous nanoformulations have been created for MASH theranostics. Particularly, there has been significant study interest in artificial nanoparticles, natural biomaterials, and bionic nanoparticles that exhibit exceptional biocompatibility and bioavailability. In this review, we summarized extracellular vesicles (EVs)-based omics analysis and Fe3O4-based functional magnetic nanoparticles as magnetic resonance imaging (MRI) contrast agents for MASH diagnosis. Additionally, artificial nanoparticles such as organic and inorganic nanoparticles, as well as natural biomaterials such as cells and cell-derived EVs and bionic nanoparticles including cell membrane-coated nanoparticles, have also been reported for MASH treatment owing to their specific targeting and superior therapeutic effect. This review has the potential to stimulate advancements in nanoformulation fabrication techniques. By exploring their compatibility with cell biology, it could lead to the creation of innovative material systems for efficient theragnostic uses for MASH. STATEMENT OF SIGNIFICANCE: People with metabolic dysfunction-associated steatohepatitis (MASH) will progress to fibrosis, cirrhosis, or even liver cancer. It is imperative to establish effective theragnostic techniques to stop MASH from progressing into a lethal condition. In our review, we summarize the advancement of artificial, natural, and bionic nanoparticles applied in MASH theragnosis. Furthermore, the issues that need to be resolved for these cutting-edge techniques are summarized to realize a more significant clinical impact. We forecast the key fields that will advance further as nanotechnology and MASH research progress. Generally, our discovery has significant implications for the advancement of nanoformulation fabrication techniques, and their potential to be compatible with cell biology could lead to the creation of innovative materials systems for effective MASH theragnostic.

Corr-Track: Category-Level 6D Pose Tracking with Soft-Correspondence Matrix Estimation.

Category-level pose tracking methods can continuously track the pose of objects without requiring any prior knowledge of the specific shape of the tracked instance. This makes them advantageous in augmented reality and virtual reality applications. The key challenge is how to train neural networks to accurately predict the poses of objects they have never seen before and exhibit strong generalization performance. We propose a novel category-level 6D pose tracking method Corr-Track, which is capable of accurately tracking objects belonging to the same category from depth video streams. Our approach utilizes direct soft correspondence constraints to train a neural network, which estimates bidirectional soft correspondences between sparsely sampled point clouds of objects in two frames. We first introduce a soft correspondence matrix for pose tracking tasks and establish effective constraints through direct spatial point-to-point correspondence representations in the sparse point cloud correspondence matrix. We propose the "point cloud expansion" strategy to address the "point cloud shrinkage" problem resulting from soft correspondences. This strategy ensures that the corresponding point cloud accurately reproduces the shape of the target point cloud, leading to precise pose tracking results. We evaluated our approach on the NOCS-REAL275 and Wild6D dataset and observed superior performance compared to previous methods. Additionally, we conducted cross-category experiments that further demonstrated its generalization capability.

The combined effects of arteriosclerosis and diabetes on cardiovascular disease risk.

The morbidity and mortality of cardiovascular disease (CVD) rank first among common diseases. Arteriosclerosis and diabetes are risk factors for CVDs, which influence each other. However, their combined effects on CVDs are still unclear. In this study, people who participated in brachial-ankle pulse wave velocity (baPWV) testing and the annual physical examination of the Kailuan Group Finance Co., Ltd., from January 1, 2010, to December 31, 2020, were selected, and their anthropometric, biochemical and epidemiological data were collected. The participants were divided into four groups according to diabetes and arteriosclerosis diagnosis and follow-up. Cox proportional hazards regression and subdistribution hazard models were used to analyse the combined effects of arteriosclerosis and diabetes on CVDs. Multiple sensitivity analyses were also performed. A total of 59,268 Asian populations were selected, including 14,425 females (28.11%) with an average age of 48.10 (± 12.72) years. During follow-up, 1830 subjects developed CVDs (mean follow-up period, 4.72 years). The cumulative incidence rates of the healthy control, diabetes, arteriosclerosis, and comorbidity groups were 5.04% (807/38781), 15.17% (253/3860), 17.04% (465/5987), and 25.59% (305/2684), respectively. The results of multivariate Cox regression analysis showed that compared with the healthy control group, the risk of CVD in the diabetes, arteriosclerosis, and comorbidity groups was significantly increased. Their HR values were 1.88 (95% CI 1.62-2.18), 1.40 (95% CI 1.23-1.60), and 2.10 (95% CI 1.80-2.45), respectively. The results of the sensitivity analysis were robust. For each one standard increase in fasting blood glucose or baPWV, the HR values for CVDs were 1.16 (95% CI 1.12-1.20) and 1.22 (95% CI 1.16-1.28), respectively. The results indicated that both arteriosclerosis and diabetes lead to an increased risk of CVDs. The risk of CVDs, coronary atherosclerotic heart disease, heart failure, stroke, coronary artery bypass grafting and ischemic stroke in patients with arteriosclerosis and diabetes was significantly higher than that in patients with arteriosclerosis or diabetes alone. Therefore, the primary prevention of CVDs in patients with arteriosclerosis complicated with diabetes needs more attention.