Image1_Sex-specific comparison of clinical characteristics and prognosis in Crohn’s disease: A retrospective cohort study of 611 patients in China.JPEG

Background: Real-world data on the impact of sex on the disease progression and prognosis of Crohn’s disease (CD) from large-scale Chinese cohorts are lacking.Aims: This study aimed to evaluate sex disparities in the clinical characteristics of, disease progression behaviours of and surgery-related risk factors for CD.Methods: A retrospective cohort study comprising 611 patients consecutively diagnosed with CD at Peking Union Medical College Hospital from January 2000 to December 2020 was conducted. Multivariate Cox regression and survival analyses was performed to assess the risk factors for disease progression and CD-related surgery in sex subgroups.Results: Male sex was an independent protective factor against multisystemic extraintestinal manifestations [EIMs] (HR: 0.52, p = 0.03) and a risk factor for intestinal perforation (HR: 1.85, p = 0.01). Male patients had longer EIM-free survival (p = 0.024) and shorter intestinal perforation-free survival (PFS) than females (p = 0.012). Of the 397 patients with the A2 classification, male patients had a higher risk of CD-related surgery (HR: 1.80, p = 0.028) and shorter surgery-free survival (SFS) than female patients (p = 0.04).Conclusion: Sex disparities in disease progression and outcomes of CD were revealed in a single Chinese centre. Male sex was independently associated with worse disease progression and prognosis including multisystemic EIMs and perforation, which suggests the need for individualized management according to risk classification.</p

Demographic characteristics of new cases with IBD in North of China.

<p>Demographic characteristics of new cases with IBD in North of China.</p

Age-standardized incidence rate (per 100,000) of IBD overall, CD, and UC in North of China.

<p>Age-standardized incidence rate (per 100,000) of IBD overall, CD, and UC in North of China.</p

Crude incidence rate (per 100,000) of IBD overall, CD, and UC in North of China.

<p>Crude incidence rate (per 100,000) of IBD overall, CD, and UC in North of China.</p

Integrative Genomic Analysis Identifies That <i>SERPINA6</i>-rs1998056 Regulated by FOXA/ERα Is Associated with Female Hepatocellular Carcinoma

<div><p>The human forkhead box A1 (FOXA1) and A2 (FOXA2) transcription factors have been found to control estrogen and androgen signaling through co-regulating target genes with sex hormone receptors. Here we used an integrative strategy to examine the hypothesis that genetic variants at FOXA1/2 binding elements may be associated with sexual dimorphism of hepatocellular carcinoma (HCC) risk. Firstly we extracted chromatin immunoprecipitation-sequencing (ChIP-seq) data of FOXA1, FOXA2 and estrogen receptor 1(ERα) from ENCODE database to obtain dual target regions of FOXA/ERα, and further intersected these regions with genes’ promoters. Then we used MATCH program to predict FOXA binding elements, in which genetic variants were retrieved by dbSNP database (NCBI, build 134). A total of 15 candidate variants were identified in this stage. Secondly we performed a case-control study with 1,081 HCC patients and 2,008 matched controls and found a significant association of <i>SERPINA6</i>-rs1998056 with female HCC risk under common genetic models (e.g. GG versus CC: OR = 2.03, 95% CI = 1.26–3.27, <i>P</i> = 0.004). Moreover, results from our real-time quantitative polymerase chain reaction (qPCR) using 72 normal liver tissues adjacent to the tumors showed that <i>SERPINA6</i> expression was significantly different among different genotypes of this variant (GG versus CC: <i>P</i> = 0.032; Group test: <i>P</i> = 0.060). In summary, our study suggested that <i>SERPINA6</i>-rs1998056 regulated by FOXA/ERα might be associated with female HCC risk.</p></div

<i>SERPINA6</i> mRNA levels in liver tissues from different genotype carriers of rs1998056.

<p>Vertical scatter plots indicated relative gene expression of <i>SERPINA6</i> for 22 CC, 38 CG and 12 GG carriers. Horizontal line indicated median mRNA level of each genotype group.</p

Distributions of characteristics among HCC patients and controls in our study.

<p>Abbreviations: SD, standard deviation.</p><p>Distributions of characteristics among HCC patients and controls in our study.</p