The association between abdominal obesity (as measured by waist circumference (WC) and waist-to-hip ratio (WHR)) and colorectal cancer (CRC) has not been fully quantified, and the magnitude of CRC risk associated with abdominal obesity is still unclear. A meta-analysis of prospective studies was performed to elucidate the CRC risk associated with abdominal obesity. Pubmed and Embase were searched for studies assessing the association between abdominal obesity and CRC risk. Relative risks (RRs) with 95% confidence intervals (95% CIs) were pooled using random-effects model of meta-analysis. Nineteen prospective cohort studies from eighteen publications were included in this meta-analysis. A total of 12,837 CRC cases were identified among 1,343,560 participants. Greater WC and WHR were significantly associated with increased risk of total colorectal cancer (WC: RR 1.42, 95% CI 1.30, 1.55; WHR: RR 1.39, 95% CI 1.25, 1.53), colon cancer (WC: RR 1.53, 95% CI 1.36, 1.72; WHR: 1.39, 95% CI 1.18, 1.63), and rectal cancer (WC: RR 1.20, 95% CI 1.03, 1.39; WHR: RR 1.22, 95% CI 1.05, 1.42). Subgroup analyses further identified the robustness of the association above. No obvious risk of publication bias was observed. In summary, abdominal obesity may play an important role in the development of CRC.

This study aimed to elucidate the effects of cholecystectomy on the risk of colorectal cancer (CRC) by conducting a meta-analysis of 10 cohort studies. The eligible cohort studies were selected by searching the PubMed and EMBASE databases from their origination to June 30, 2016, as well as by consulting the reference lists of the selected articles. Two authors individually collected the data from the 10 papers. When the data showed marked heterogeneity, we used a random-effects model to estimate the overall pooled risk; otherwise, a fixed effects model was employed. The final analysis included ten cohort studies. According to the Newcastle-Ottawa Scale (NOS), nine papers were considered high quality. After the data of these 9 studies were combined, an increased risk of CRC was found among the individuals who had undergone cholecystectomy (risk ratio (RR) 1.22; 95% confidence interval (CI) 1.08–1.38). In addition, we also found a promising increased risk for colon cancer (CC) (RR 1.30, 95% CI 1.07–1.58), but no relationship between cholecystectomy and rectum cancer (RC) (RR 1.09; 95% CI 0.89–1.34) was observed. Additionally, in the sub-group analysis of the tumor location in the colon, a positive risk for ascending colon cancer (ACC) was found (RR 1.18, 95% CI 1.11–1.26). After combining the ACC, transverse colon cancer (TCC), sigmoid colon cancer (SCC) and descending colon cancer (DCC) patients, we found a positive relationship with cholecystectomy (RR 1.18, 95% CI 1.11–1.26). Furthermore, after combining the ACC and DCC patients, we also found a positive relationship with cholecystectomy (RR 1.28; 95% CI 1.11–1.26) in the sub-group analysis. In an additional sub-group analysis of patients from Western countries, there was a positive relationship between cholecystectomy and the risk of CRC (RR 1.20; 95% CI 1.05–1.36). Furthermore, a positive relationship between female gender and CRC was also found (RR 1.17; 95% CI 1.03–1.34). However, there was no relationship between gender and CC or RC. Furthermore, no publication bias was observed, and the sensitivity analysis indicated stable results. This meta-analysis of 10 cohort studies revealed that cholecystectomy is associated with an increased risk for CRC, CC and ACC, particularly in Western countries. No relationship between cholecystectomy and RC was observed. There was no relationship between gender and either CC or RC, but a positive relationship between female gender and CRC was observed.

Immunocytes dynamically reprogram their gene expression profiles during differentiation and immunoresponse. However, the underlying mechanism remains elusive. Here, we develop a single-cell Hi-C method and systematically delineate the 3D genome and dynamic epigenetic atlas of macrophages during these processes. We propose “degree of disorder” to measure genome organizational patterns inside topologically-associated domains, which is correlated with the chromatin epigenetic states, gene expression, and chromatin structure variability in individual cells. Furthermore, we identify that NF-κB initiates systematic chromatin conformation reorganization upon Mycobacterium tuberculosis infection. The integrated Hi-C, eQTL, and GWAS analysis depicts the atlas of the long-range target genes of mycobacterial disease susceptible loci. Among these, the SNP rs1873613 is located in the anchor of a dynamic chromatin loop with LRRK2, whose inhibitor AdoCbl could be an anti-tuberculosis drug candidate. Our study provides comprehensive resources for the 3D genome structure of immunocytes and sheds insights into the order of genome organization and the coordinated gene transcription during immunoresponse.

BACKGROUND Schizophrenia is a multigene disease with a complex etiology and different clinical manifestations. It is of great significance to understand the etiology and pathogenesis of schizophrenia patients from different clinical dimensions and to interpret the potential molecular changes of schizophrenia patients from different clinical dimensions. MATERIAL AND METHODS RNA-Seq was performed on peripheral blood leukocytes of 50 patients with schizophrenia and 50 healthy controls. Phenotypic information of patients with schizophrenia was collected during blood sampling. Differentially expressed genes (DEGs) were screened by the edgeR package of R software. To better analyze the correlation between DEG expression values, explore the potential association between differential genes and clinical dimensions of schizophrenia, and identify hub genes, we constructed a DEG co-expression network using weighted gene co-expression network analysis (WGCNA). RESULTS We provide the transcription profiles of peripheral blood leukocytes in patients with schizophrenia and found a gene module (including 89 genes) closely related to the clinical dimension of abnormal psychomotor behavior in schizophrenia. CONCLUSIONS The findings enhance our understanding of the biological processes of schizophrenia, enabling us to identify specific clinical dimensions of genes for diagnosis and prognostic markers and possibly for targeted therapy.

Background: Sarcopenia is a progressive generalized skeletal muscle disorder that causes the accelerated loss of muscle mass and function. Osteoporosis is a systemic condition of the skeleton that results in low bone mass and quality. Several studies have suggested that osteoporosis and sarcopenia are interrelated; however, a few studies indicate the lack of a significant association between sarcopenia and osteoporosis. We aimed to evaluate the association between sarcopenia and osteoporosis via a systematic review and pooled analysis. Methods: From the inception of the PubMed and Embase databases until September 2022, we conducted a systematic search for studies evaluating the relationship between sarcopenia and osteoporosis. Study appraisal and synthesis methods: We included observational studies that provided 95% confidence intervals (CIs) and risk estimates. Two reviewers independently extracted data and assessed the quality of the research. The random-effects model was applied to the pool analysis, and the odds ratios (ORs) and 95% CIs were finally calculated. Results: The primary statistic was the mutual risk between sarcopenia and osteoporosis. According to the inclusion criteria, 56 studies (796,914 participants) were finally included. Sarcopenia was significantly correlative to the risk of osteoporosis (OR, 3.06; 95% CI, 2.30–4.08), and each standard deviation increase in relative appendicular skeletal muscle mass was significantly related to a decreased risk of osteoporosis (OR, 0.65; 95% CI, 0.56–0.75). Osteoporosis observably referred to a higher risk of sarcopenia (OR, 2.63; 95% CI, 1.98–3.49). Conclusion: Our research indicated that sarcopenia and osteoporosis are highly positively correlated. Osteoporosis is closely associated with the risk of sarcopenia. Our finding highlights the importance of sarcopenia screening for those at risk of osteoporosis, and vice versa. However, heterogeneity was noted among the studies, and this might have influenced the accuracy of the results. Therefore, the results of our study should be interpreted with caution.

Secreted frizzled-related protein-1 (SFRP1) is a negative regulatory molecule of the WNT signaling pathway and serves as a therapeutic target for bone formation in osteoporosis. In this study, we first established an ovariectomized (OVX) rat model to simulate postmenopausal osteoporosis and found significant changes in miR-542-3p and sFRP1 expression by RNA sequencing and qRT-PCR. In addition, there was a significant negative correlation between miR-542-3p and sFRP1 mRNA levels in postmenopausal women with osteoporosis. We found that miR-542-3p inhibited the expression of sFRP1 mRNA by luciferase reporter assay. When the miR-542-3p binding site in sFRP1 3'UTR was deleted, it did not affect its expression. Western blot results showed that miR-542-3p inhibited the expression of SFRP1 protein. The expression of SFRP1 was significantly increased in osteoblast-induced mesenchymal stem cells (MSC), whereas the expression of miR-542-3p was significantly decreased. And miR-542-3p transfected MSCs showed a significant increase in osteoblast-specific marker expression, indicating that miR-542-3p is necessary for MSC differentiation. Inhibition of miR-542-3p reduced bone formation, confirmed miR-542-3p play a role in bone formation in vivo. In general, these data suggest that miR-542-3p plays an important role in bone formation via inhibiting SFRP1 expression and inducing osteoblast differentiation. This article is protected by copyright. All rights reserved