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Background: Platelet and blood coagulation abnormalities frequently occur in cancer patients. Fibrinogen is an important hemostatic factor that regulates the hemostatic pathway. Hyperfibrinogenemia is increasing recognized as an important risk factor influencing cancer development and outcome. However, few reports have investigated the prognostic potential of fibrinogen for predicting the survival of gastric cancer (GC) patients. The primary aim of this study was to evaluate the usefulness of preoperative serum fibrinogen as a biomarker for predicating tumor progression and survival of patients with GC.Patients and Methods: This retrospective study was conducted in GC patients who underwent gastrectomy from 2005 to 2007. Patient demographics, clinicopathological characteristics, preoperative plasma fibrinogen levels and median survival time (MST) were analyzed. Univariate and multivariate proportional hazard analysis of risk factors were used.Results: This study included 1196 patients (885 males and 311 females) with GC, more than half of whom had advanced GCs. Radical lymph node dissection was performed in 71.6 % of these patients. MST was 41.9 ± 32.4 months. Patient survival was significantly affected by family GC history (p <0.05), lymph node dissection mode (p <0.001), tumor size (≥5 cm; p <0.001), tumor location (p < 0.001), poor tumor differentiation (p <0.001), tumor histologic classification (p <0.001), extent of tumor invasion (p <0.001), number of metastatic lymph nodes (p <0.001), advanced stage of disease (p <0.001), extended operation duration (>150 min; p <0.001), higher operative bleeding volume (>200 ml; p <0.001), postoperative transfusion, preoperative serum fibrinogen levels, CEA levels and CA 19-9 levels (p <0.001). Multivariate analysis indicated that the independent prognostic factors significantly associated with poor survival included non-radical lymph node dissection, palliative lymph node dissection, multi-organ involvement, advanced TNM stages, poor tumor differentiation, higher preoperative serum fibrinogen levelsand higher CA19-9 levels.Conclusions: Serum fibrinogen levels are positively correlated with advanced tumor stages and poor survival in GC patients undergoing gastrectomy. Preoperative plasma fibrinogen levels are an independent risk factor for survival in these patients. Serum fibrinogen is a useful biomarker for patients with clinically advanced GC. [ABSTRACT FROM AUTHOR]

Research on hMLH1 and hMSH2 mutations tend to focus on Lynch syndrome (LS) and LS-like colorectal cancer (CRC). No studies to date have assessed the role of hMLH1 and hMSH2 genes in mass sporadic CRC (without preselection by MSI or early age of onset). We aimed to identify novel hMLH1 and hMSH2 DNA variants, to determine the mutation frequencies and sites in both sporadic and LS CRC and their relationships with clinicopathological characteristics of CRC in Northeast of China. 452 sporadic and 21 LS CRC patients were screened for germline and somatic mutations in hMLH1 and hMSH2 genes with PCR–SSCP sequencing. We identified 11 hMLH1 and seven hMSH2 DNA variants in our study cohort. Six of them were novel: four in hMLH1 gene (IVS8-16 A>T, c.644 GAT>GTT, c.1529 CAG>CGG and c.1831 ATT>TTT) and two in hMSH2 gene (−39 C>T, insertion AACAACA at c.1127 and deletion AAG at c.1129). In sporadic CRC, germline and somatic mutation frequencies of hMLH1/hMSH2 gene were 15.59% and 17.54%, respectively (p = 0.52). Germline mutations present in hMLH1 and hMSH2 genes were 5.28% and 10.78%, respectively (p<0.01). Somatic mutations in hMLH1 and hMSH2 genes were 6.73% and 11.70%, respectively (p = 0.02). In LS CRC, both germline and somatic mutation frequencies of hMLH1/hMSH2 gene were 28.57%. The most prevalent germline mutation site in hMSH2 gene was c.1168 CTT>TTT (3.90%), a polymorphism. Somatic mutation frequency of hMLH1/hMSH2 gene was significantly different in proximal, distal colon and rectal cancer (p = 0.03). Our findings elucidate the mutation spectrum and frequency of hMLH1 and hMSH2 genes in sporadic and LS CRC, and their relationships with clinicopathological characteristics of CRC. [ABSTRACT FROM AUTHOR]

Aims: We aimed to replicate the association of the rs290487 (IVS3C/T) and rs7903146 (IVS3C/T) polymorphisms of transcription factor 7-like 2 (TCF7L2) and type 2 diabetes mellitus (T2DM) in Han Chinese people in Henan province, China. Methods: In all, 1,842 patients with T2DM and 7,777 normal glucose-tolerant controls underwent genotyping for the T2DM-associated variants rs7903146 (IVS3C/T) and rs290487 (IVS3C/T). W performed a meta-analysis of the association of the risk alleles of rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) in TCF7L2 and T2DM in Han Chinese by combining previous studies with the present study. Results: We found that T2DM was associated with the CC genotype (1.364, 1.137–1.636, p  = 0.001), the recessive model (1.457, 1.156–1.838, p  = 0.001) of rs290487 (IVS3C/T) and haplotype CC (1.116, 1.034–1.204, p  = 0.004) in Han Chinese. Moreover, our meta-analyses supported the association of the T allele (IVS3C/T) of rs7903146 (1.36, 1.24–1.48; p  = 6.404×10−12) and T2DM but not the C allele of rs290487 (IVS3C/T) (0.99, 0.85–1.15, p  = 0.890) in Han Chinese. We found no interactions between behavioral risk factors (smoking, alcohol drinking, and physical activity) and rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) polymorphisms. Conclusions: The CC genotype and the recessive model of the variant rs290487 (IVS3C/T) and CC haplotype of rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) in TCF7L2 may be associated with T2DM in Han Chinese people in Henan province, China. [ABSTRACT FROM AUTHOR]

Purpose: To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis. Methods: A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR) and 95% confidence intervals (95% CI) were calculated. Results: The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8–24.1%). They were 18.7% (95% CI: 14.7–23.6%) and 16.4% (95% CI: 11.9–22.0%) in sporadic and Lynch syndrome (LS) CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215–2.215; P = 0.001), tumor location (pooled OR = 3.804, 95% CI: 2.715–5.329; P<0.001), tumor differentiation (pooled OR = 2.131, 95% CI: 1.464–3.102; P<0.001), MSI (OR: 27.096, 95% CI: 13.717–53.526; P<0.001). Significant associations were also observed between MLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427–34.631; P<0.001) and 9.419 (95% CI: 2.613–33.953; P = 0.001), respectively). Conclusion: The frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are common health problems worldwide. Tumor necrosis factor (TNF) is a type of cytokine that induces inflammation and inhibits tumorigenesis. Several studies have assessed the relationship between the polymorphism of TNF-α-308 G>A and the susceptibility to IBD and CRC; however, the results have been controversial. In addition, the hypothesis whether the increased risk of CRC in IBD patients could be partly ascribed to the polymorphism of TNF-α-308 G>A was unclear. Therefore, we conducted this meta-analysis to confirm these associations. Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated on the basis of data from 14, 18, and 7 studies from a total of 27 studies for the associations between the polymorphism of TNF-α-308 G>A and ulcerative colitis, Crohn's disease (CD) and CRC. In Europeans, the AA genotype increased the risk of ulcerative colitis (UC) (OR, 2.041; 95% CI, 1.261-3.301) and CD (OR, 1.730; 95% CI, 1.168-2.564) significantly, without obvious heterogeneity and publication bias. Meanwhile, the GA genotype increased the risk of UC in Asians (OR, 2.360; 95% CI, 1.269-4.390) significantly. However, no significant association was observed for CRC in any ethnic population. The results of this meta-analysis suggested that the polymorphism of TNF-α-308 G>A participates in modifying the susceptibility to UC and CD in Europeans and Asians. The increased risk of CRC in IBD patients should be clarified as the combined effects of polymorphisms in TNF-α and other cytokines, and the interaction with environmental factors, in future studies. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Type 2 diabetes increases the risk of cirrhosis and liver cancer. Noninvasive and early assessment of liver fibrosis is essential. We aimed to develop a score to aid in the initial assessment of liver fibrosis in the diabetic population.A fibrosis investigating navigator in diabetes (FIND) score was developed and validated in the NHANES dataset (2017–2020). Fibrosis was defined as a liver stiffness measurement (LSM) ≥8.0 kPa. The diagnostic accuracies of FIB‐4, NFS, LiverRisk, steatosis‐associated fibrosis estimator (SAFE) and metabolic dysfunction–associated fibrosis (MAF‐5) were compared. FIND was also externally validated in various liver diseases via biopsy as a reference in an Asian centre between 2016 and 2020. Finally, we examined the prognostic implications of the FIND index utilizing data from the UK Biobank cohort (2006–2010).The FIND score model yielded an AUROC of 0.781 for the prediction of an LSM ≥8 kPa in the validation set, which was consistently greater than that of other available models (all p < 0.05). In the whole NHANES dataset, the 85% sensitivity cut‐off of 0.16 corresponded to a NPV of 91.9%, whereas the 85% specificity cut‐off of 0.31 corresponded to a PPV of 50.6%. FIND displayed overall accuracies similar to those of the other models in staging fibrosis stages, with biopsy used as a reference. In the UK Biobank cohort, FIND >0.31 was associated with an increased risk of all‐cause and liver‐related mortality in the diabetic population in adjusted models (HR, 1.75; 95% CI, 1.62–1.89; HR, 23.59; 95% CI, 13.67–40.69).In diabetes patients, the novel FIND score performs well in identifying subjects at risk of liver fibrosis and predicting all‐cause and liver‐related mortality. [ABSTRACT FROM AUTHOR]

Background: While the TyG index has been studied in relation to stroke risk, there is a lack of research integrating fat distribution indicators like Body Roundness Index (BRI) and Fat Mass Index (FMI). Additionally, comparative studies across multiple regions are scarce. This study investigates the association between obesity-related parameters and stroke incidence, examining the mediation effects of multimorbidity, using data from rural areas in China and the United Kingdom. Methods: This cohort study included 60,685 participants (6,980 from China and 53,705 from UK). The obesity-related parameters were calculated using established formulas. The TyG index was determined as ln [TG (mg/dL) × GLU (mg/dL) / 2]. Additionally, composite indices were created by multiplying the TyG index by BMI, WC, FMI, and RBI to assess obesity-related risks. Cox regression analyses were employed on the relationship between Triglyceride Glucose index related parameters and stroke risk. Multiple mediation analysis was applied to assess the contributions of multimorbidity to obesity indicators in stroke occurrence. Results: After excluding those who developed stroke within two years of enrollment, the Chinese cohort (6,638 subjects, median follow-up 4.33 years) had 237 ischemic and 21 hemorrhagic strokes. The UK cohort (53,631 subjects, median follow-up 13.85 years) had 742 ischemic and 316 hemorrhagic strokes. Chinese residents had lower BMI but higher visceral obesity (BRI), higher prevalence of multimorbidity, and higher stroke incidence compared to UK residents. Cox analyses demonstrated significant associations between BMI/TyG indices and ischemic stroke in both Chinese and UK populations, which diminished after adjusting for multimorbidity. In the Chinese rural cohort, only TyG-BRI (HR:1.13, 95%CI:0.99–1.30) approached statistical significance after full adjustment for mediators. In contrast, in the UK cohort, significant associations persisted for most TyG Index indicators when full adjustment for mediators, including BMI (HR: 1.17, 95% CI: 1.09–1.26), TyG-BMI (HR: 1.16, 95% CI: 1.07–1.26), TyG-WC (HR: 1.13, 95% CI: 1.03–1.25), TyG-FMI (HR: 1.17, 95% CI: 1.07–1.28), and TyG-RBI (HR: 1.15, 95% CI: 1.06–1.24). TyG-BRI also showed the best predictive performance for ischemic stroke in Chinese rural residents (AUC > 0.7) and exhibited an almost linear relationship with ischemic stroke occurrence. Additionally, TyG-BRI presented a U-shaped relationship with the risk of hemorrhagic stroke incidence in the UK (poverall = 0.041, pnon-linear = 0.017). Multimorbidity mediated the relationship between TyG indices, and ischemic stroke incidence in both cohorts. The mediation percentage for multimorbidity was higher than the sum of individual chronic diseases, with a higher mediation percentage in the Chinese cohort (up to 51%) compared to the UK cohort (up to 27.2%). Conclusions: Chinese rural residents exhibit higher levels of visceral obesity compared to residents in UK, leading to greater stroke susceptibility mediated by multimorbidity. These findings underscore the importance of comprehensive management of multimorbidity for stroke prevention. The TyG-BRI may serve as a promising predictor of ischemic stroke incidence among rural community residents. [ABSTRACT FROM AUTHOR]

Aims Materials and Methods Results Conclusions This study aimed to identify the distinct change trajectories of the Chinese visceral adiposity index (CVAI) over time and to investigate their associations with risk of type 2 diabetes mellitus (T2DM).This study included 52 394 participants from the prospective project, the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China‐PAR). The CVAI was calculated using measures of age, body mass index, waist circumference, triglycerides and high‐density lipoprotein cholesterol. Latent mixture modelling was conducted to fit distinct trajectory patterns. The logistic regression model was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of T2DM with various CVAI trajectory patterns.Four distinct CVAI trajectory patterns were identified: low‐increasing, moderate‐increasing, moderate high‐increasing and high‐increasing. Compared with low‐increasing CVAI, participants with moderate‐increasing (OR 1.73, 95% CI 1.49–2.00), moderate high‐increasing (3.48, 3.01–4.03) and high‐increasing CVAI (5.50, 4.67–6.47) had a significantly increased risk of T2DM. Similar trajectory patterns were identified in both men and women. The ORs (95% CI) for moderate‐increasing, moderate high‐increasing and high‐increasing groups were 3.28 (2.56–4.19), 7.85 (6.09–10.13) and 13.21 (9.98–17.49) in women respectively, and 1.20 (0.99–1.45), 2.18 (1.82–2.62) and 3.60 (2.93–4.43) in men respectively, when compared to the low‐increasing CVAI group. Further, significant effect modifications for age, smoking and physical activity (all Pinteraction <0.05) were observed in the relationship between CVAI trajectory patterns and T2DM.Initially high and persistently elevated CVAI is significantly associated with an increased risk of T2DM, with a particular focus on women, younger people, nonsmokers and physically inactive individuals. Continuous monitoring of CVAI levels will benefit effective identification, early intervention and management of individuals at high risk of T2DM. [ABSTRACT FROM AUTHOR]

Several epidemiological studies have investigated the association between sugar intake, the levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the risk of hypertension, but findings have been inconsistent. We carried out a systematic review and meta-analysis of observational studies to examine the associations between sugar intake, hypertension risk, and BP levels. Articles published up to February 2, 2021 were sourced through PubMed, EMBASE and Web of Science. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a fixed- or random-effects model. Restricted cubic splines were used to evaluate dose-response associations. Overall, 35 studies were included in the present meta-analysis (23 for hypertension and 12 for BP). Sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) were positively associated with hypertension risk: 1.26 (95% CI, 1.15–1.37) and 1.10 (1.07–1.13) per 250-g/day increment, respectively. For SBP, only SSBs were significant with a pooled β value of 0.24 mmHg (95% CI, 0.12–0.36) per 250 g increase. Fructose, sucrose, and added sugar, however, were shown to be associated with elevated DBP with 0.83 mmHg (0.07–1.59), 1.10 mmHg (0.12–2.08), and 5.15 mmHg (0.09–10.21), respectively. Current evidence supports the harmful effects of sugar intake for hypertension and BP level, especially SSBs, ASBs, and total sugar intake. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to investigate the association between air pollution and DNA methylation in adults from published observational studies. PubMed, Web of Science and Embase databases were systematically searched for available studies on the association between air pollution and DNA methylation published up to March 9, 2021. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS). Meta-analysis was used to summarize the combined estimates for the association between air pollutants and global DNA methylation levels. Heterogeneity was assessed with the Cochran Q test and quantified with the I 2 statistic. In total, 38 articles were included in this study: 16 using global methylation, 18 using candidate genes, and 11 using EWAS, with 7 studies using more than one approach. Meta-analysis revealed an imprecise but inverse association between exposure to PM 2.5 and global DNA methylation (for each 10-μg/m3 PM 2.5 , combined estimate: 0.39; 95% confidence interval: 0.97 - 0.19). The candidate-gene results were consistent for the ERCC3 and SOX2 genes, suggesting hypermethylation in ERCC3 associated with benzene and that in SOX2 associated with PM 2.5 exposure. EWAS identified 201 CpG sites and 148 differentially methylated regions that showed differential methylation associated with air pollution. Among the 307 genes investigated in 11 EWAS, a locus in nucleoredoxin gene was found to be positively associated with PM 2.5 in two studies. Current meta-analysis indicates that PM 2.5 is imprecisely and inversely associated with DNA methylation. The candidate-gene results consistently suggest hypermethylation in ERCC3 associated with benzene exposure and that in SOX2 associated with PM 2.5 exposure. The Kyoto Encyclopedia of Genes and Genomes (KEGG) network analyses revealed that these genes were associated with African trypanosomiasis, Malaria, Antifolate resistance, Graft-versus-host disease, and so on. More evidence is needed to clarify the association between air pollution and DNA methylation. [Display omitted] • Imprecise but inverse association between PM 2.5 and global DNA methylation is found. • Consistent results show hypermethylation in ERCC3 gene is associated with benzene. • Consistent results show hypermethylation in SOX2 gene is associated with PM 2.5. • Consistent results show hypermethylation in NXN gene is associated with PM 2.5. • Most of the identified genes are associated with African trypanosomiasis, Malaria. [ABSTRACT FROM AUTHOR]

The relationship between pregnancy loss and the risk of cardiovascular diseases (CVDs) remains a matter of debate. Our intention in conducting this meta -analysis was to analyze the relationship between miscarriage and stillbirth and risk of CVDs. PubMed, Embase, and Web of Science were systematically searched up to May 30, 2023 for all relevant studies. The random-effects model was applied to estimate the pooled relative risks (RRs) and 95% confidence intervals (95% CIs). We evaluated RR estimates for the risk of CVDs with each additional miscarriage and stillbirth through generalized least squares regression. Twenty-three articles were incorporated into the meta -analysis. For women with a history of miscarriage, the pooled RRs for the risk of total CVDs, coronary heart disease (CHD), stroke, and total CVD deaths were 1.16 (95 % CI 1.10–1.22), 1.26 (1.12–1.41), 1.13 (1.03–1.24), and 1.20 (1.01–1.42), respectively. For women with a history of stillbirth, the pooled RRs for the risk of total CVDs, CHD, stroke, and total CVD deaths were 1.60 (1.34–1.89), 1.30 (1.12–1.50), 1.37 (1.06–1.78), and 1.95 (1.05–3.63), respectively. With each additional miscarriage, the risk increased for total CVDs (1.08, 1.04–1.13), CHD (1.08, 1.04–1.13), and stroke (1.05, 1.00–1.10). With each additional stillbirth, the risk increased for total CVDs (1.11, 1.03–1.21) and CHD (1.13, 1.07–1.19). This meta -analysis indicates that both miscarriages and stillbirths are related to a higher risk of total CVDs, CHD, stroke, and total CVD deaths. The risk of total CVDs and CHD increased with the number of miscarriages or stillbirths. [ABSTRACT FROM AUTHOR]

Aims: To identify the trajectories of body mass index (BMI) and waist circumference (WC), and assess the associations of BMI trajectory, WC trajectory, or the two combined, with type 2 diabetes mellitus (T2DM) risk in Chinese adults. Materials and Methods: This study was based on a prospective project—the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China‐PAR). A total of 54 434 participants (39.21% men) who were measured on at least two occasions were included. Three slowly increasing trajectory patterns were identified for BMI, and four for WC, by latent mixed modelling. A nine‐category variable was derived by combining the WC trajectory (low, moderate, moderate‐high/high) and the BMI trajectory (low, moderate, high). Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Results: The risk of developing T2DM increased with elevated BMI or WC trajectory levels (all ptrend <0.001). The risks were 2.85 (2.59–3.14) for high BMI trajectory and 4.34 (3.78–4.99) for high WC trajectory versus low trajectory groups, respectively. The association was more pronounced among younger individuals (pinteraction <0.001). In the joint analysis, compared to participants with low WC and BMI trajectory, those with moderate‐high/high WC combined with high BMI trajectory had the highest risk of T2DM (OR 3.96, 95% CI 3.48–4.50); even those who maintained moderate‐high/high WC but low BMI trajectory showed a higher T2DM risk (OR 3.00, 95% CI 2.31–3.91). Conclusions: This study suggests that simultaneous dynamic and continuous monitoring of BMI and WC may contribute more than single measurements to predicting T2DM risk and determining preventive strategies. [ABSTRACT FROM AUTHOR]

Background: The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and triglyceride-glucose (TyG) index are novel indexes for insulin resistance (IR). We aimed to evaluate associations of TG/HDL-C and TyG with arterial stiffness risk. Methods: We enrolled 1979 participants from the Rural Chinese Cohort Study, examining arterial stiffness by brachial-ankle pulse wave velocity (baPWV). Logistic and linear regression models were employed to calculate effect estimates. For meta-analysis, we searched relevant articles from PubMed, Embase and Web of Science up to August 26, 2023. The fixed-effects or random-effects models were used to calculate the pooled estimates. We evaluated dose-response associations using restricted cubic splines. Results: For cross-sectional studies, the adjusted ORs (95%CIs) for arterial stiffness were 1.12 (1.01–1.23) and 1.78 (1.38–2.30) for per 1 unit increment in TG/HDL-C and TyG. In the meta-analysis, the pooled ORs (95% CIs) were 1.26 (1.14–1.39) and 1.57 (1.36–1.82) for per 1 unit increment of TG/HDL-C and TyG. Additionally, both TG/HDL-C and TyG were positively related to PWV, with β of 0.09 (95% CI 0.04–0.14) and 0.57 (95% CI 0.35–0.78) m/s. We also found linear associations of TG/HDL-C and TyG with arterial stiffness risk. Conclusions: High TG/HDL-C and TyG were related to increased arterial stiffness risk, indicating TG/HDL-C and TyG may be convincing predictors of arterial stiffness. [ABSTRACT FROM AUTHOR]

Purpose: This meta‐analysis evaluated the relationship between overweight/obesity and depressive disorders in children and adolescents. Methods: We examined the databases of PubMed, Embase and Web of Science for pertinent observational studies released up until 20 February 2022. The pooled relative risks (RRs) and 95% confidence intervals (CIs) of obesity and overweight with depressive disorder were calculated by means of random‐effects models. The Newcastle‐Ottawa Quality Assessment Scale and Agency for Healthcare Research and Quality scale were adopted to evaluate the study quality. Results: Finally, for this meta‐analysis, we evaluated 22 observational publications covering 175 135 participants (5 cohort study articles, 1 case–control study article and 16 cross‐sectional study articles). A significant positive association was found between obesity and the risk of depression (RR 1.32, 95% CI 1.09–1.60, I2 = 79.90%, Pheterogeneity < 0.001) and in the association between obesity and depressive symptoms (RR 1.16, 95% CI: 1.00–1.35, I2 = 25.0%, Pheterogeneity = 0.247). On sensitivity analysis, the pooled RRs remained robust. Subgroup analysis indicated that obese children and teenagers in western countries were more prone to depression. Conclusion: Evidence from this meta‐analysis, based on observational studies, supported the idea that obese children and adolescents are more likely to experience depression and depressive symptoms. [ABSTRACT FROM AUTHOR]

Aims: To investigate the association of methylation risk score (MRS) and its interactions with environmental factors with type 2 diabetes mellitus (T2DM) risk. Methods: We conducted a nested case–control study with 241 onset cases and 241 matched controls. Conditional logistic regression models were employed to identify risk CpG sites. Simple and weighted MRSs were constructed based on the methylation levels of ATP‐binding cassette G1 gene, fat mass and obesity associated gene, potassium voltage‐gated channel member 1 gene, and thioredoxin‐interacting protein gene previously associated with T2DM to estimate the association of MRS with T2DM risk. Stratified analyses were used to investigate interactions between MRS and environmental factors. Results: A total of 10 CpG loci were identified from the aforementioned genes to calculate MRS. After controlling for potential confounding factors, taking tertile 1 as reference, the odds ratios (ORs) and 95% confidence intervals (CIs) for T2DM of tertile 3 was 2.39 (1.36–4.20) for simple MRS and 2.59 (1.45–4.63) for weighted MRS. With per SD score increment in MRS, the OR (95% CI) was 1.66 (1.29–2.14) and 1.60 (1.24–2.08) for simple and weighted MRSs, respectively. J‐curved associations were observed between both simple and weighted MRSs and T2DM risks. Additionally, multiplication interactions for smoking and hypertension with simple MRS on the risk of T2DM were found, similarly for smoking and obesity with weighted MRS on the risk of T2DM (all Pinteraction <.05). Conclusion: Elevated simple and weighted MRSs were associated with increased risk of T2DM. Environmental risk factors may influence the association between MRS and T2DM. [ABSTRACT FROM AUTHOR]

Background: This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic stroke, and heart failure). Methods: Genetic associations with mtDNA copy number were obtained from a genome-wide association study (GWAS) summary statistics from the UK biobank (n = 395,718) and cardio-metabolic disease were from largest available GWAS summary statistics. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. We repeated this in the opposite direction using instruments for cardio-metabolic disease. Results: Genetically predicted mtDNA copy number was not associated with risk of obesity (P = 0.148), hypertension (P = 0.515), dyslipidemia (P = 0.684), T2DM (P = 0.631), CAD (P = 0.199), stroke (P = 0.314), ischemic stroke (P = 0.633), and heart failure (P = 0.708). Regarding the reverse directions, we only found that genetically predicted dyslipidemia was associated with decreased levels of mtDNA copy number in the IVW analysis (β= − 0.060, 95% CI − 0.044 to − 0.076; P = 2.416e−14) and there was suggestive of evidence for a potential causal association between CAD and mtDNA copy number (β= − 0.021, 95% CI − 0.003 to − 0.039; P = 0.025). Sensitivity and replication analyses showed the stable findings. Conclusions: Findings of this Mendelian randomization study did not support a causal effect of mtDNA copy number in the development of cardiometabolic disease, but found dyslipidemia and CAD can lead to reduced mtDNA copy number. These findings have implications for mtDNA copy number as a biomarker of dyslipidemia and CAD in clinical practice. [ABSTRACT FROM AUTHOR]

Background: It's still controversial whether Helicobacter pylori (H. pylori) eradication can reverse atrophic gastritis (AG) and intestinal metaplasia (IM). Therefore, we performed a meta‐analysis to estimate the effect of H. pylori eradication on AG and IM. Methods: We searched the PubMed, Web of Science and EMBASE datasets through April 2023 for epidemiological studies, which provided mean glandular atrophy (GA) or IM score before and after H. pylori eradication, or provided ORs, RRs or HRs and 95% CIs for the association of AG or IM with H. pylori eradication. Weighted mean difference (WMD) and pooled ORs and 95%CIs were used to estimate the effect of H. pylori eradication on AG and IM. Results: Twenty articles with a total of 5242 participants were included in this meta‐analysis. H. pylori eradication significantly decreased GA score in the antrum (WMD −0.36; 95% CI: −0.52, −0.19, p < 0.01), GA score in the corpus (WMD −0.35; 95% CI: −0.52, −0.19, p < 0.01), IM score in the antrum (WMD −0.16; 95% CI: −0.26, −0.07, p < 0.01) and IM score in the corpus (WMD −0.20; 95% CI: −0.37, −0.04, p = 0.01). H. pylori eradication significantly improved AG (pooled OR 2.96; 95% CI: 1.70, 5.14, p < 0.01) and IM (pooled OR 2.41; 95% CI: 1.24, 4.70, p < 0.01). The association remained significant in the subgroup analyses by study design, sites of lesions, regions and follow‐up time. Although Publication bias was observed for AG, the association remained significant after trim‐and‐fill adjustment. Conclusions: H. pylori eradication could significantly improve AG and IM at early stage. [ABSTRACT FROM AUTHOR]

Purpose: Cuproptosis, a novel programmed cell death, plays an important role in glioma growth, angiogenesis, and immune response. Nonetheless, the role of cuproptosis-related genes (CRGs) in the prognosis and tumor microenvironment (TME) of gliomas remains unknown. Methods: By non-negative matrix factorization consensus clustering, 1286 glioma patients were classified based on the mRNA expression levels of 27 CRGs and investigated the association of immune infiltration and clinical characteristics with cuproptosis subtypes. A CRG-score system was constructed using LASSO and multivariate Cox regression methods and validated in independent cohorts to predict the prognosis of glioma patients. Results: Glioma patients were divided into two cuproptosis subtypes. Cluster C2 was enriched in immune-related pathways, had higher macrophage M2, neutrophils, and CD8 + T cells, and poorer prognosis compared with cluster C1 which was enriched in metabolism-related pathways. We further constructed and validated the ten-gene CRG risk scores. Glioma patients in the high CRG-score group had higher tumor mutation burden, higher TME scores, and poorer prognoses compared with the low CRG-score group. Additionally, the AUC value of the CRG-score was 0.778 in predicting the prognosis of gliomas. WHO grading, IDH mutation, 1p/19q codeletion, and MGMT methylation were significant differences between high and low CRG-score groups. Conclusion: This study demonstrated that CRG-score was related to immune cell infiltration and could accurately predict gliomas' prognosis. Our findings may provide a novel understanding of the potential role of cuproptosis molecular pattern and TME in the immune response and prognosis of glioma patients. [ABSTRACT FROM AUTHOR]

Purpose: The potential role of epithelium-specific genes through the adenoma-carcinoma sequence in the development of colorectal cancer (CRC) remains unknown. Therefore, we integrated single-cell RNA sequencing and bulk RNA sequencing data to select diagnosis and prognosis biomarkers for CRC. Methods: The CRC scRNA-seq dataset was used to describe the cellular landscape of normal intestinal mucosa, adenoma and CRC and to further select epithelium-specific clusters. Differentially expressed genes (DEGs) of epithelium-specific clusters were identified between intestinal lesion and normal mucosa in the scRNA-seq data throughout the adenoma-carcinoma sequence. Diagnostic biomarkers and prognostic biomarker (the risk score) for CRC were selected in the bulk RNA-seq dataset based on DEGs shared by the adenoma epithelium-specific cluster and the CRC epithelium-specific cluster (shared-DEGs). Results: Among the 1063 shared-DEGs, we selected 38 gene expression biomarkers and 3 methylation biomarkers that had promising diagnostic power in plasma. Multivariate Cox regression identified 174 shared-DEGs as prognostic genes for CRC. We combined 1000 times LASSO-Cox regression and two-way stepwise regression to select 10 prognostic shared-DEGs to construct the risk score in the CRC meta-dataset. In the external validation dataset, the 1- and 5-year AUCs of the risk score were higher than those of stage, the pyroptosis-related genes (PRG) score and the cuproptosis-related genes (CRG) score. In addition, the risk score was closely associated with the immune infiltration of CRC. Conclusion: The combined analysis of the scRNA-seq dataset and the bulk RNA-seq dataset in this study provides reliable biomarkers for the diagnosis and prognosis of CRC. [ABSTRACT FROM AUTHOR]

While noise pollution from transportation has become an important public health problem, the relationships between different sources of traffic noise and cardiovascular diseases (CVDs) remain inconclusive. A comprehensive meta-analysis was therefore conducted to quantitatively assess the effects of long-term exposure to road traffic, railway, and aircraft noise on CVDs and relevant subtypes. We systematically retrieved PubMed, Embase, and Web of Science for articles published before April 4, 2022. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated by the fixed- or random-effects models. In total, 23 articles were included in our meta-analysis. The risk of CVDs increased by 2% (RR 1.020, 95% CI 1.006–1.035) and 1.6% (RR 1.016, 95% CI 1.000–1.032) for every 10 dB increment of road traffic and aircraft noise. For CVD subtypes, the risk increased by 3.4% (1.034, 1.026–1.043) for stroke and 5% (1.050, 1.006–1.096) for heart failure with each 10 dB increment of road traffic noise; the risk of atrial fibrillation increased by 1.1% (1.011, 1.002–1.021) with each 10 dB increment of railway noise; and the risk increased by 1% (1.010, 1.003–1.017) for myocardial infarction, 2.7% (1.027, 1.004–1.050) for atrial fibrillation, and 2.3% (1.023, 1.016–1.030) for heart failure with each 10 dB increment in aircraft noise. Further, effects from road traffic, railway, and aircraft noise all followed positive linear trends with CVDs. Long-term exposure to traffic noise is positively related to the incidence risk of cardiovascular events, especially road traffic noise which significantly increases the risk of CVDs, stroke, and heart failure. [ABSTRACT FROM AUTHOR]

Abstract The prevalence of pathological germline mutations in colorectal cancer has been widely studied, as germline mutations in the DNA mismatch repair genes hMLH1 and hMSH2 confer a high risk of colorectal cancer. However, because the sample size and population of previous studies are very different from each other, the conclusions still remain controversial. In this paper, Databases such as PubMed were applied to search for related papers. The data were imported into Comprehensive Meta-Analysis V2, which was used to estimate the weighted prevalence of hMLH1 and hMSH2 pathological mutations and compare the differences of prevalence among different family histories, ethnicities and related factors. This study collected and utilized data from 102 papers. In the Amsterdam-criteria positive group, the prevalence of pathological germline mutations of the hMLH1 and hMSH2 genes was 28.55% (95%CI 26.04%–31.19%) and 19.41% (95%CI 15.88%–23.51%), respectively, and the prevalence of germline mutations in hMLH1/hMSH2 was 15.44%/10.02%, 20.43%/13.26% and 15.43%/11.70% in Asian, American multiethnic and European/Australian populations, respectively. Substitution mutations accounted for the largest proportion of germline mutations (hMLH1: 52.34%, hMSH2: 43.25%). The total prevalence of mutations of hMLH1 and hMSH2 in Amsterdam-criteria positive, Amsterdam-criteria negative and sporadic colorectal cancers was around 45%, 25% and 15%, respectively, and there were no obvious differences in the prevalence of germline mutations among different ethnicities. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas (STS) are rare malignant tumors of mesenchymal origin, which are easy to metastasize and relapse and are a great threat to human health. In our previous study, the abnormal expression of neurofibromin 1 (NF1) is observed in tumor tissue of STS, and the NF1 gene is regulated by miRNAs. The study aimed to assess the association between NF1-related miRNA gene polymorphisms and the risk of STS. In this case–control study, the information and peripheral blood were collected from 169 patients with STS and 170 healthy controls. Six single-nucleotide polymorphisms of the NF1-related miRNAs were investigated and genotyped using a Sequenom MassARRAY® matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. The association between the polymorphisms and the risk of STS was estimated using unconditional logistic regression analysis. There was a significant statistical difference on genotype distribution of miR-199a2 rs12139213 between the case group and the control group (p = 0.026). Comparing with individuals with wild-type AA, individuals with the AT/TT genotype had a 1.753-fold (odds ratio [OR] = 1.753, 95% confidence interval [CI] = 1.090–2.819, p = 0.021) increased risk of STS and 1.907-fold (OR = 1.907, 95% CI = 1.173–3.102, p = 0.009) increased risk of STS adjusted for age and smoking status. Individuals with the AG/GG genotype for miR24–3p rs4743988 displayed a significantly reduced risk of STS compared with individuals with homozygous mutations AA (OR = 0.605, 95% CI = 0.376–0.973, p = 0.038). Individuals carrying the AT/TT genotype for miR-199a2 rs12139213 or the AA genotype for miR24–3p rs4743988 may be susceptible to STS, which could be potential biomarkers for the diagnosis of STS. [ABSTRACT FROM AUTHOR]

To estimate the associations of stroke risk with plasma metabolites, metabolic risk score (MRS), the combinations of MRS with hypertension or lifestyle, and lifestyle-related metabolic signature. To assess the improvement of the stroke risk prediction model through the incorporation of MRS.A total of 77,315 participants from the UK Biobank were included in this study. Xgboost and LASSO-Cox regression were used to select metabolites and construct MRS. Elastic net regression was utilized to construct the lifestyle-related metabolic signature. Multivariate Cox regression was used to estimate the associations between metabolites, MRS, the combinations of MRS with hypertension or lifestyle, lifestyle-related metabolic signature, and stroke risk.We identified 48, 63, 39, and 4 metabolites associated with the risk of stroke, ischemic stroke (IS), subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH), respectively. High MRS significantly increased the risk of stroke (HR = 2.65 (95% confidence interval (CI): 2.09−3.35)), IS (HR = 2.45 (95% CI: 1.89−3.17)), ICH (HR = 2.74 (95% CI: 1.55−4.85)), and SAH (HR = 4.64 (95% CI: 2.25−9.56)). In the combination analyses, compared with normal systolic blood pressure (SBP) and low MRS, normal/high SBP, and high MRS significantly increased stroke risk (HR = 5.80 (95% CI: 2.75–12.27)/6.37 (95% CI: 3.22−12.62)). A favorable/unfavorable lifestyle and high MRS also significantly increased stroke risk (HR = 2.38 (95% CI: 1.73–3.28)/3.86 (95% CI: 2.63−5.67)) compared with a favorable lifestyle and low MRS. Incorporating MRS into the 15-year stroke and IS risk prediction model increased the areas under the curves (AUCs) from 0.746 to 0.766 and from 0.771 to 0.811, respectively. The metabolic signature was correlated with adherence to a healthy lifestyle (r = 0.414; P = 2.22e−16) and inversely associated with stroke risk (HR = 0.80 (95% CI: 0.73–0.86)).Various metabolites and MRS were significantly associated with the risk of stroke, IS, ICH, and SAH. Individuals with a high MRS may face an elevated stroke risk among populations with high SBP or unhealthy lifestyle, even those with normal SBP or healthy lifestyle. MRS provided modest improvement to the stroke risk prediction model. The lifestyle-related metabolic signature could reduce 20% stroke risk. [ABSTRACT FROM AUTHOR]

Background: Recent studies have reported conflicting associations between egg consumption and the risk of all-cause or cardiovascular disease (CVD) mortality, including ischemic heart disease (IHD) mortality and stroke mortality. With accumulating evidence, up-to-date evidence about the association should be synthesized.Objectives: We aimed to assess the association of the risk of all-cause and CVD mortality with egg consumption.Methods: We searched the PubMed, Embase, and Web of Science databases through 3 November, 2021 for observational studies conducted in participants ≥18 y of age and which provided ORs, RRs, or HRs and 95% CIs for ≥3 egg consumption categories or for increased intake of egg addressing the associations of interest. A random-effects model was used to pool the reported risk estimates. Restricted cubic splines were used to examine the dose-response association.Results: Twenty-four articles with 48 reports (25 for all-cause mortality, 11 for CVD mortality, 6 for IHD mortality, and 6 for stroke mortality) involving 11,890,695 participants were included. Intake of each 1-egg/d increment was associated with increased risk of all-cause mortality (RR: 1.06; 95% CI: 1.02, 1.10; P = 0.008), but the association was restricted to women, Americans, and studies with adjustments for hyperlipidemia. Egg consumption was linearly associated with CVD mortality only in participants >60 y of age, Americans, studies with follow-up duration ≥15 y, and studies with adjustments for hyperlipidemia (P ≤ 0.018). No significant association was found between egg consumption and IHD or stroke mortality (P ≥ 0.080).Conclusions: Egg consumption was linearly associated with a modestly increased risk of all-cause mortality and, in older participants, Americans, and studies with longer follow-up or adjustments for hyperlipidemia, CVD mortality. These findings suggest that it may be prudent to avoid high egg consumption. [ABSTRACT FROM AUTHOR]

Background: Noninvasive diagnostic markers that are capable of distinguishing patients with colorectal cancer (CRC) from healthy individuals or patients with other cancer types are lacking. We report the discovery and validation of a panel of methylation-based markers that specifically detect CRC. Methods: This was a large-scale discovery study based on publicly available datasets coupled with a validation study where multiple types of specimens from six cohorts with CRC, other cancer types, and healthy individuals were used to identify and validate the tissue-specific methylation patterns of CRC and assess their diagnostic performance. Results: In the discovery and validation cohort (N = 9307), ten hypermethylated CpG sites located in three genes, C20orf194, LIFR, and ZNF304, were identified as CRC-specific markers. Different analyses have suggested that these CpG sites are CRC-specific hypermethylated and play a role in transcriptional silencing of corresponding genes. A random forest model based on ten markers achieved high accuracy rates between 85.7 and 94.3% and AUCs between 0.941 and 0.970 in predicting CRC in three independent datasets and a low misclassification rate in ten other cancer types. In the in-house validation cohort (N = 354), these markers achieved consistent discriminative capabilities. In the cfDNA pilot cohort (N = 14), hypermethylation of these markers was observed in cfDNA samples from CRC patients. In the cfDNA validation cohort (N = 155), the two-gene panel yielded a sensitivity of 69.5%, specificity of 91.7%, and AUC of 0.806. Conclusions: Hypermethylation of the ten CpG sites is a CRC-specific alteration in tissue and has the potential use as a noninvasive cfDNA marker to diagnose CRC. [ABSTRACT FROM AUTHOR]

Aims: The evidence for association between cardiovascular health (CVH) metrics and type 2 diabetes mellitus (T2DM) in Chinese population is limited. We explored the association between the number of ideal CVH metrics and risk of incident T2DM in a rural Chinese population. Materials and methods: A total of 12,150 rural Chinese participants (median age 51 years) were enrolled. A Cox proportional-hazards model was used to assess the association between the number of ideal CVH metrics and risk of incident T2DM by using hazard ratios (HRs) and 95% confidence intervals (CIs). We another conducted multiplicative and additive interaction effect between the number of ideal CVH metrics and sex or age on incident T2DM, and subgroup analyses of the association were also conducted by sex and age. Results: During a median of 6.01 years of follow-up, 840 incident cases of T2DM occurred. The number of ideal CVH metrics was negatively associated with risk of incident T2DM (per unit increase: HR = 0.76, 95% CI 0.70–0.82). We also observed both multiplicative and additive interaction effect between lower number of ideal CVH metrics and sex on incident T2DM, and multiplicative interaction effect between lower number of ideal CVH metrics and age on incident T2DM was observed. The association remained statistically significant for both men and women, or participants with age < 65 years. Conclusions: Increasing number of ideal CVH metrics was associated with reduced risk of incident T2DM, which presented age- and sex-related differential associations. [ABSTRACT FROM AUTHOR]

Our study aimed to identify the trajectory patterns of lipid accumulation product (LAP) and investigate their association with the incident risk of type 2 diabetes mellitus (T2DM) in China. This study included 37,316 eligible participants, with data collected between1998 and 2021. The LAP trajectory patterns were identified through latent mixture modeling. Logistic regression models were used to examine the association between different LAP trajectory patterns and the incident risk of T2DM. Over an average period of 12.7 years, 3195 participants developed T2DM. Four LAP trajectory patterns were identified: low stable, moderate slow-increasing, high decreasing, and moderate fast-increasing. After adjusting for demographic and clinical confounders, the odds ratios (ORs) and 95 % confidence intervals (CIs) for T2DM were 1.67 (1.50, 1.86) for the moderate slow-increasing group, 1.63 (1.38, 1.94) for the high decreasing group, and 2.43 (2.07, 2.85) for the moderate fast-increasing group compared with the low stable group. Similar trajectory patterns were found in sex-specific populations as in the general population, while the elevated LAP trajectory pattern was more strongly associated with an increase in the incident risk of T2DM in females. Individuals with moderate fast-increasing LAP trajectory patterns had a 2.4 times higher risk of developing T2DM compared to those with low stable LAP patterns. More attention should be paid to preventing T2DM in people with high levels of LAP, especially females, the elderly, drinkers, and people with a history of diabetes. • Individuals with rapidly rising lipid accumulation product had a 2.4-fold higher diabetes risk. • Elevated lipid accumulation product trajectory was more strongly linked to higher diabetes risk in females. • To prevent diabetes, focus should be on managing sudden or sharp rises in lipid accumulation product. [ABSTRACT FROM AUTHOR]

186 TAMs mark genes were identified from the scRNA-seq data and the DEGs in TCGA − GTEx dataset. Based on TGGA database, 6 optimal prognostic genes were selected to construct a TAMRG-score for glioma, and the accuracy of the model was verified in CGGA database. [Display omitted] • The tumor heterogeneity of gliomas was demonstrated by scRNA-seq data. • A novel TAMRG-score to determine the prognostic of glioma. • Integrating scRNA sequencing and bulk RNA sequencing data. This study aimed to construct and validate a prognostic model based on tumor associated macrophage-related genes (TAMRGs) by integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data. The scRNA-seq data of three inhouse glioma tissues were used to identify the tumor-associated macrophages (TAMs) marker genes, the DEGs from the The Cancer Genome Atlas (TCGA) − Genotype-Tissue Expression (GTEx) dataset were used to further select TAMs marker genes. Subsequently, a TAMRG-score was constructed by Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis in the TCGA dataset and validated in the Chinese Glioma Genome Atlas (CGGA) dataset. We identified 186 TAMs marker genes, and a total of 6 optimal prognostic genes including CKS2 , LITAF , CTSB , TWISTNB , PPIF and G0S2 were selected to construct a TAMRG-score. The high TAMRG-score was significantly associated with worse prognosis (log-rank test, P <0.001). Moreover, the TAMRG-score outperformed the other three models with AUC of 0.808. Immune cell infiltration, TME scores, immune checkpoints, TMB and drug susceptibility were significantly different between TAMRG-score groups. In addition, a nomogram were constructed by combing the TAMRG-score and clinical information (Age, Grade, IDH mutation and 1p19q codeletion) to predict the survival of glioma patients with AUC of 0.909 for 1-year survival. The high TAMRG-score group was associated with a poor prognosis. A nomogram by incorporating TMARG-score could precisely predict glioma survival, and provide evidence for personalized treatment of glioma. [ABSTRACT FROM AUTHOR]

Background: Gallstone disease (GSD) is a common and costly biliary disorder. Multiple studies have investigated the associations between blood lipid metabolism and GSD risk; however, the results are inconsistent. This research aimed to comprehensively evaluate the relationships among serum total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and GSD risk. Methods: Firstly, a multi-center cross-sectional study was carried out. Subjects who participated in the health examination in three hospitals between January 2015 and May 2020 were recruited. Multivariable logistic regression was used to investigate blood lipid metabolism associated with GSD risk. Then, a meta-analysis was performed to verify the associations further. Medline and Embase databases were systematically searched before June 10, 2021. The DerSimonian and Laird random-effect model was utilized when the heterogeneity was high; otherwise, fixed-effect model was adopted. Results: There were 548,934 eligible participants included in the multi-center study, and 45,392 of them were diagnosed with GSD. The results demonstrated that total cholesterol and HDL cholesterol were negatively associated with GSD risk in both high vs. low model and per mmol/L increase model, while triglyceride was positively associated with GSD risk in the per unit increase model. In the meta-analysis, 104 studies with approximately 3 million participants were finally included. The results verified that HDL cholesterol [odds ratio (OR) = 0.636, P = 5.97 × 10− 16 in high vs low model; OR = 0.974, P = 6.07 × 10− 05 in per unit model] and triglyceride (OR = 1.192, P = 3.47 × 10− 05 in high vs. low model; OR = 1.011, P = 5.12 × 10− 05 in per unit model) were related to GSD risk in the two models. Conclusions: The findings indicated that low HDL cholesterol levels and high triglyceride levels were risk factors for GSD. This study provides a basis for identifying the population at high risk for GSD and implementing tertiary prevention strategies for GSD, thus contributing to GSD prevention as well as disease burden relief. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of laser alone therapy and laser combination therapy (mainly combined with other kinds of laser or steroids) for keloid. PubMed, Embase and Web of Science were searched for relevant articles from inception to June 2020. Comprehensive Meta-Analysis software 2.0 (CMA) was used to perform the meta-analysis. A total of 29 articles were included in this meta-analysis. During the mean follow-up of 14 (1–84) months, the overall improvement rates of baseline Vancouver scar scale (VSS) score and itch were 0.454 (95%CI 0.351–0.561, I2 = 0) and 0.786 (95%CI 0.613–0.895, I2 = 0) in the laser combination therapy group. The improvement rates of scar height and flexibility in the laser combination therapy group were 0.629 (95%CI 0.519–0.727, I2 = 52.089) and 0.784 (95%CI 0.251–0.975, I2 = 89.420). The average improvement rate of the scar score in laser combination therapy was 0.338 (0.201–0.510); however, there were insufficient data for laser alone therapy comparison. The laser combination therapy had a greater pain improvement rate, 0.580 (0.389–0.750) versus 0.420 (0.224–0.645), compared to laser alone therapy, and a greater degree of good or excellent (> 50%) improvement in the overall scar, 0.636 (95%CI 0.347–0.852) versus 0.149 (95%CI 0.032–0.482), with laser alone therapy. Moreover, a lower regrowth rate of 0.187 (0.129–0.263) versus 0.249 (0.060–0.631), a lower post-treatment pigmentation rate of 0.125 (0.091–0.169) versus 0.135 (0.058–0.282), and a lower infection rate of 0.047 (0.009–0.209) versus 0.076 (0.012–0.351) were observed in the laser combination therapy compared with those rates in the laser alone therapy. The overall effect of laser combination therapy was better than that of laser alone therapy, and the incidence of adverse reactions was lower in laser combination therapy than in laser alone therapy. [ABSTRACT FROM AUTHOR]

Background: The discordance of the low-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with alterative lipid parameters may explain the inconsistent association of CIMT with the LDL-C/HDL-C ratio. Therefore, this study aimed to explore the associations between LDL-C/HDL-C ratio discordance with alternative lipid parameters and elevated carotid intima-media thickness (CIMT) risk in a large cohort in Beijing, China. Methods: In total, 13,612 adults who didn't have elevated CIMT at baseline and who participated in at least one follow-up of annual examination between 2009 and 2016 were included in this cohort study. A multivariable Cox regression model was utilized to evaluate the associations of discordance of the LDL-C/HDL-C ratio with TC, TGs, LDL-C and HDL-C with elevated CIMT risk. Results: During 37,999 person-years of follow-up, 2004 individuals (1274 men and 730 women) developed elevated CIMT. Among individuals with normal TC and TGs, 16.6 and 15.2% individuals had a discordantly high LDL-C/HDL-C ratio, respectively, and the risk of elevated CIMT increased by 1.54 (95% CI 1.33, 1.77) and 1.53 (95% CI 1.33, 1.76), respectively, comparing to individuals with a concordantly low LDL-C/HDL-C ratio. A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with LDL-C and HDL-C (P < 0.001). A low LDL-C/HDL-C ratio with discordantly normal HDL-C and high LDL-C (13.2% of individuals) had a 32% (HR = 1.32, 95% CI 1.11, 1.57) higher risk of elevated CIMT than concordantly low LDL-C and normal HDL-C. Sensitivity analysis by excluding CIMT developed in the first 2 years follow-up further confirmed the above results. Conclusions: A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with TC, TGs, LDL-C and HDL-C Even a low LDL-C/HDL-C ratio with discordantly high LDL-C and normal HDL-C could also significantly increase CIMT risk. Individuals should maintain both the LDL-C/HDL-C ratio and LDL-C at normal levels to prevent elevated CIMT. [ABSTRACT FROM AUTHOR]

While a number of genes have been implicated in melanoma susceptibility, the role of protein-coding variation in melanoma development and progression remains underexplored. To better characterize the role of germline coding variation in melanoma, we conducted a whole-exome case-control and somatic-germline interaction study involving 322 skin cutaneous melanoma cases from The Cancer Genome Atlas and 3607 controls of European ancestry. We controlled for cross-platform technological stratification using XPAT and conducted gene-based association tests using VAAST 2. Four established melanoma susceptibility genes achieved nominal statistical significance, MC1R (p = .0014), MITF (p = .0165) BRCA2 (p = .0206), and MTAP (p = .0393). We also observed a suggestive association for FANCA (p = .002), a gene previously implicated in melanoma survival. The association signal for BRCA2 was driven primarily by likely gene disrupting (LGD) variants, with an Odds Ratio (OR) of 5.62 (95% Confidence Interval (CI) 1.03–30.1). In contrast, the association signals for MC1R and MITF were driven primarily by predicted pathogenic missense variants, with estimated ORs of 1.4 to 3.0 for MC1R and 4.1 for MITF . MTAP exhibited an excess of both LGD and predicted damaging missense variants among cases, with ORs of 5.62 and 3.72, respectively, although neither category was significant. For individuals with known or predicted damaging variants, age of disease onset was significantly lower for two of the four genes, MC1R (p = .005) and MTAP (p = .035). In an analysis of germline carrier status and overlapping copy number alterations, we observed no evidence to support a two-hit model of carcinogenesis in any of the four genes. Although MC1R carriers were represented proportionally among the four molecular tumor subtypes, these individuals accounted for 69% of ultraviolet (UV) radiation mutational signatures among triple-wild type tumors (p = .040), highlighting the increased sensitivity to UV exposure among individuals with loss-of-function variants in MC1R . [ABSTRACT FROM AUTHOR]