Characteristics and prognostic impact of cancer cachexia defined by the Asian Working Group for Cachexia consensus in patients with curable gastric cancer.

BACKGROUND: Cachexia is prevalent in cancer patients. The conventional diagnostic criteria for cachexia are often based on Western evidence, lacking consensus for Asian populations. This study aims to compare Asian Working Group for Cachexia (AWGC) criteria with Fearon's criteria, assessing their differences in population characteristics and prognostic impact. METHODS: The clinical data of patients who underwent radical gastrectomy between 2013 and 2019 were prospectively collected. Cachexia diagnosis involves the utilization of either AWGC criteria and the previous international consensus proposed by Fearon et al. A scoring model is established based on the optional criteria according to the AWGC criteria. Univariate and multivariate logistic and Cox regression analysis were conducted to determine the independent effect factors for postoperative complications and overall survival. RESULTS: In a total of 1330 patients, 461 met AWGC cachexia criteria and 311 met Fearon's criteria. Excluding 262 overlapping cases, those diagnosed solely with AWGC-cachexia had higher age and lower BMI, albumin, hemoglobin, and handgrip strength compared to those by Fearon's criteria alone. AWGC-cachexia independently increased the risk of postoperative complications, whereas Fearon's criteria did not. Patients with AWGC-cachexia also exhibited shorter overall survival than Fearon's criteria. The AWGC-based cachexia grading system effectively stratifies the risks of postoperative complications and mortality. CONCLUSIONS: The AWGC criteria is more effective in diagnosing cancer cachexia in the Asian population and provide better prognostic indicators.

Myelin regulatory factor ( Myrf ) is a critical early regulator of retinal pigment epithelial development.

Myelin regulatory factor (Myrf) is a critical transcription factor in early retinal and retinal pigment epithelial development, and human variants in MYRF are a cause for nanophthalmos. Single cell RNA sequencing (scRNAseq) was performed on Myrf conditional knockout mice ( Rx>Cre Myrf fl/fl ) at 3 developmental timepoints. Myrf was expressed specifically in the RPE, and expression was abrogated in Rx>Cre Myrf fl/fl eyes. scRNAseq analysis revealed a loss of RPE cells at all timepoints resulting from cell death. GO-term analysis in the RPE revealed downregulation of melanogenesis and anatomic structure morphogenesis pathways, which were supported by electron microscopy and histologic analysis. Novel structural target genes including Ermn and Upk3b , along with macular degeneration and inherited retinal disease genes were identified as downregulated, and a strong upregulation of TGFß/BMP signaling and effectors was observed. Regulon analysis placed Myrf downstream of Pax6 and Mitf and upstream of Sox10 in RPE differentiation. Together, these results suggest a strong role for Myrf in the RPE maturation by regulating melanogenesis, cell survival, and cell structure, in part acting through suppression of TGFß signaling and activation of Sox10 . SUMMARY STATEMENT: Myrf regulates RPE development, melanogenesis, and is important for cell structure and survival, in part through regulation of Ermn , Upk3b and Sox10, and BMP/TGFb signaling.

Contribution of mono- and co-culture of Pseudomonas paralactis, Acinetobacter MN21 and Stenotrophomonas maltophilia to the spoilage of chill-stored lamb.

Exploring the contribution of common microorganisms to spoilage is of great significance in inhibiting spoilage in lamb. This work investigated the extent of protein degradation and profile changes of free amino acids (FAAs), free fatty acids (FFAs) and volatile organic compounds (VOCs) in lamb caused by single- and co-culture of the common aerobic spoilage bacteria, P. paralactis, Ac. MN21 and S. maltophilia. Meanwhile, some key VOCs produced by the three bacteria during lamb spoilage were also screened by orthogonal partial least square discriminant analysis and difference value in VOCs content between inoculated groups and sterile group. Lamb inoculated with P. paralactis had the higher total viable counts, pH, total volatile base nitrogen and TCA-soluble peptides than those with the other two bacteria. Some FAAs and FFAs could be uniquely degraded by P. paralactis but not Ac. MN21 and S. maltophilia, such as Arg, Glu, C15:0, C18:0 and C18:1n9t. Co-culture of the three bacteria significantly promoted the overall spoilage, including bacterial growth, proteolysis and lipolysis. Key VOCs produced by P. paralactis were 2, 3-octanedione, those by Ac. MN21 were 1-octanol, octanal, hexanoic acid, 1-pentanol and hexanoic acid methyl ester, and that by S. maltophilia were hexanoic acid. The production of extensive key-VOCs was significantly and negatively correlated with C20:0, C23:0 and C18:ln9t degradation. This study can provide a basis for inhibiting common spoilage bacteria and promoting high-quality processing of fresh lamb.

Assessing clinical pathological characteristics and gene expression patterns associated with hepatoid adenocarcinoma of the stomach.

OBJECTIVE: The objective of this study is to assess the clinical pathological attributes of Hepatoid Adenocarcinoma of the Stomach (HAS) and to delineate the differential diagnostic considerations about it. METHOD: The investigation involved analyzing 31 HAS cases using histomorphological assessment, immunohistochemical profiling, and relevant gene detection methodologies. RESULTS: Among the 31 HAS cases, 9 (29.0%) were of trabecular hepatoid adenocarcinoma of the stomach, 7 (22.6%) were of glandular hepatoid adenocarcinoma of the stomach, 4 (12.9%) were of nesting hepatoid adenocarcinoma of the stomach, 3 (9.7%) were of clear cell hepatoid adenocarcinoma of the stomach, and 8 (25.8%) were of diverse hepatoid adenocarcinoma of the stomach. Of these 31 cases, 24 were male, accounting for 77.4% of the cases. Serum alpha-fetoprotein (AFP) levels were notably elevated, with radioimmunoassay results reaching 1240 ng/ml; 28 out of 31 cases had AFP levels below 25 µg/l, accounting for 90.3%. Related genes: HER2 protein indicated positive expression on the cell membrane in 35.5% (11/31) of the cases; HER2 gene amplification detected by the FISH technique was 12.9% (4/31). Tumoral stromal lymphocytes exhibited a PD-1 positive expression rate of 58.1% (18/31). In gastric cancer tissues, the PD-L1 positive rate was 45.1% (14/31). CONCLUSION: HAS represents a distinctive subtype of gastric cancer with a propensity for mimicking other forms of tumors, underscoring the significance of discerning its unique histopathological attributes for accurate differential diagnosis and tailored therapeutic interventions.

Improved object detection method for unmanned driving based on Transformers.

The object detection method serves as the core technology within the unmanned driving perception module, extensively employed for detecting vehicles, pedestrians, traffic signs, and various objects. However, existing object detection methods still encounter three challenges in intricate unmanned driving scenarios: unsatisfactory performance in multi-scale object detection, inadequate accuracy in detecting small objects, and occurrences of false positives and missed detections in densely occluded environments. Therefore, this study proposes an improved object detection method for unmanned driving, leveraging Transformer architecture to address these challenges. First, a multi-scale Transformer feature extraction method integrated with channel attention is used to enhance the network's capability in extracting features across different scales. Second, a training method incorporating Query Denoising with Gaussian decay was employed to enhance the network's proficiency in learning representations of small objects. Third, a hybrid matching method combining Optimal Transport and Hungarian algorithms was used to facilitate the matching process between predicted and actual values, thereby enriching the network with more informative positive sample features. Experimental evaluations conducted on datasets including KITTI demonstrate that the proposed method achieves 3% higher mean Average Precision (mAP) than that of the existing methodologies.

Associations between organophosphate esters and bone mineral density in adults in the United States: 2011-2018 NHANES.

BACKGROUND: Organophosphate esters (OPEs) are used extensively as flame retardants and plasticizers. Laboratory studies have shown that OPEs exhibit osteotoxicity by inhibiting osteoblast differentiation; however, little is known about how OPEs exposure is associated with bone health in humans. OBJECTIVES: We conducted a cross-sectional study to investigate the association between OPEs exposure and bone mineral density (BMD) in adults in the United States using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES). METHODS: Multivariate linear regression models were used to assess the association between concentrations of individual OPE metabolites and BMDs. We also used the Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models to estimate joint associations between OPE mixture exposure and BMDs. All the analyses were stratified according to gender. RESULTS: A total of 3546 participants (median age, 40 years [IQR, 30-50 years]; 50.11% male) were included in this study. Five urinary OPE metabolites with a detection rate of > 50% were analyzed. After adjusting for the potential confounders, OPE metabolite concentrations were associated with decreased total-body BMD and lumbar spine BMD in males, although some associations only reached significance for bis(1-chloro-2-propyl) phosphate (BCPP), dibutyl phosphate (DBUP), and bis(2-chloroethyl) phosphate (BCEP) (ß = -0.013, 95% CI: -0.026, -0.001 for BCPP and total-body BMD; ß = -0.022, 95% CI: -0.043, -0.0001 for DBUP and lumbar spine BMD; ß=-0.018, 95% CI: -0.034, -0.002 for BCEP and lumbar spine BMD). OPE mixture exposure was also inversely associated with BMD in males, as demonstrated in the BMKR and qgcomp models. CONCLUSIONS: This study provides preliminary evidence that urinary OPE metabolite concentrations are inversely associated with BMD. The results also suggested that males were more vulnerable than females. However, further studies are required to confirm these findings.

Regulating NCOA4-Mediated Ferritinophagy for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury.

Ischemic stroke presents a global health challenge, necessitating an in-depth comprehension of its pathophysiology and therapeutic strategies. While reperfusion therapy salvages brain tissue, it also triggers detrimental cerebral ischemia-reperfusion injury (CIRI). In our investigation, we observed the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in an oxygen-glucose deprivation/reoxygenation (OGD/R) model using HT22 cells (P < 0.05). This activation contributed to oxidative stress (P < 0.05), enhanced autophagy (P < 0.05) and cell death (P < 0.05) during CIRI. Silencing NCOA4 effectively mitigated OGD/R-induced damage (P < 0.05). These findings suggested that targeting NCOA4-mediated ferritinophagy held promise for preventing and treating CIRI. Subsequently, we substantiated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway effectively regulated the NCOA4-mediated ferritinophagy, by applying the cGAS inhibitor RU.521 and performing NCOA4 overexpression (P < 0.05). Suppressing the cGAS-STING pathway efficiently curtailed ferritinophagy (P < 0.05), oxidative stress (P < 0.05), and cell damage (P < 0.05) of CIRI, while NCOA4 overexpression could alleviate this effect (P < 0.05). Finally, we elucidated the specific molecular mechanism underlying the protective effect of the iron chelator deferoxamine (DFO) on CIRI. Our findings revealed that DFO alleviated hypoxia-reoxygenation injury in HT22 cells through inhibiting NCOA4-mediated ferritinophagy and reducing ferrous ion levels (P < 0.05). However, the protective effects of DFO were counteracted by cGAS overexpression (P < 0.05). In summary, our results indicated that the activation of the cGAS-STING pathway intensified cerebral damage during CIRI by inducing NCOA4-mediated ferritinophagy. Administering the iron chelator DFO effectively attenuated NCOA4-induced ferritinophagy, thereby alleviating CIRI. Nevertheless, the role of the cGAS-STING pathway in CIRI regulation likely involves intricate mechanisms, necessitating further validation in subsequent investigations.

Quantifying the dose-response relationship between exercise and health-related quality of life in patients undergoing haemodialysis: A meta-analysis.

Objective: This meta-analysis aims to explore the dose-response relationship of aerobic exercise or aerobic combined resistance exercise on cardiopulmonary function in maintenance hemodialysis（MHD）, with the goal of aiding in the formulation of precise exercise prescriptions. Methods: A literature search up to August 18, 2023, was conducted in databases including Web of Science, among others, focusing on the effects of exercise interventions on cardiopulmonary function in hemodialysis patients.Two researchers independently conducted literature screening, data extraction, and an assessment of study methodology quality. A dose-response meta-analysis was carried out using a one-stage cubic spline mixed-effects model, followed by stratified analyses based on intervention period, intervention method, and exercise environment. Results: A nonlinear dose-response relationship was observed between exercise and 6-minute walk test (6WMT) as well as peak oxygen uptake (VO2Peak) in hemodialysis patients. The optimal exercise dose for the 6WMT across the full exposure range was 922 METs-min/week, with VO2Peak increasing with the dose. The effects were influenced by the type of exercise, intervention period, and exercise environment. An exercise dose of 500 METs-min/week and 619 METs-min/week was found sufficient to achieve the minimal clinically important differences (MCID) for 6WMT and VO2Peak, respectively. Conclusion: There is a significant association between the dose of exercise and its effects. With appropriate adjustment of variables, even low-dose exercise can lead to clinically significant improvements in cardiopulmonary function.

Histopathological staging of atrophic lesions of gastric mucosa.

Objective: To study the histopathological staging of atrophic lesions of the gastric mucosa. Methods: Histology and immunohistochemistry were used to closely examine 2144 specimens of atrophic gastric mucosa that were taken from endoscopic biopsies. Results: When the gastric mucosa epithelium is affected by infection, chemical stimulation, immune factors, genetic factors, and other factors, it may cause an atrophy of gastric mucosa epithelium and a decrease in the number of glands, intestinal metaplasia, hyperplasia of smooth muscle fibers, and atrophy of stem cells in the proliferative zone. In this study, we characterized the above lesions as atrophic lesions of the gastric mucosa. Based on the morphological and histological characteristics of the lesion, as well as the law of cell proliferation and transformation during its occurrence and development, we propose five stages. We also noted the onset age, gender correlation, and histopathological characteristics of each stage of gastric mucosal atrophies. Conclusion: Understanding the pathological staging of gastric mucosal atrophy is essential for treating patients correctly and keeping track of changes in malignant cells. It is also very important in preventing the initiation of gastric cancer or from getting worse.

Causal learning by infants and young children: From computational theories to language practices.

Causal reasoning-the ability to reason about causal relations between events-is fundamental to understanding how the world works. This paper reviews two prominent theories on early causal learning and offers possibilities for theory bridging. Both theories grow out of computational modeling and have significant areas of overlap while differing in several respects. Explanation-Based Learning (EBL) focuses on young infants' learning about causal concepts of physical objects and events, whereas Bayesian models have been used to describe causal reasoning beyond infancy across various concept domains. Connecting the two models offers a more integrated approach to clarifying the developmental processes in causal reasoning from early infancy through later childhood. We further suggest that everyday language practices offer a promising space for theory bridging. We provide a review of selective work on caregiver-child conversations, in particular, on the use of scaffolding language including causal talk and pedagogical questions. Linking the research on language practices to the two cognitive theories, we point out directions for further research to integrate EBL and Bayesian models and clarify how causal learning unfolds in real life. This article is categorized under: Psychology > Learning Cognitive Biology > Cognitive Development.

Effects of aerobic exercise on children's executive function and academic performance: A systematic review and meta-analysis.

Objective: To investigate the effects of exercise on executive function in children, providing an evidence-based foundation to inform future research in school physical education and health education. Methods: We searched ten databases: Cochrane Library, Scopus, OVID, Web of Science, PubMed, EBSCOhost, SPORTDiscus, PsycINFO, CNKI, WANFANG DATA, VIP, and SinoMed, and eight articles were included. Applying the revised Cochrane Risk of Bias Tool for Randomized Trials (RoB2), funnel plots and Egger regression analysis were integrated with R meta-analysis to screen for publication bias. The quality of the evidence was appraised using the Grading system. Results: The included literature contained 2655 participants, with 1308 in the experimental group and 1347 in the control group. The results indicated that the aerobic exercise group considerably improved inhibitory control in children compared to the control group [SMD = 0.29, 95% CI (0.05, 0.54), P = 0.018]; working memory [SMD = 0.25, 95% CI (0.07, 0.42), P = 0.005]; and cognitive flexibility [SMD = 0.36, 95% CI (0.17, 0.54), P < 0.001]. However, the findings indicated that only aerobic exercise interventions extending beyond 50 weeks positively influenced academic performance in children [SMD = 1.19, 95% CI (0.34, 2.04), P = 0.006]. The results of an Egger regression analysis revealed that the p-values for inhibitory control, working memory, cognitive flexibility, and academic performance were more significant than 0.1. The Grade system said that the quality of evidence was all low regarding the level of evidence. Conclusion: Aerobic exercise enhanced executive function but only aerobic exercise interventions extending beyond 50 weeks demonstrated a significant effect on the academic performance of children. Due to the low quality of evidence presented in this study, additional high-quality randomized controlled trials are needed to confirm these findings.

Algorithm of automatic identification of diabetic retinopathy foci based on ultra-widefield scanning laser ophthalmoscopy.

AIM: To propose an algorithm for automatic detection of diabetic retinopathy (DR) lesions based on ultra-widefield scanning laser ophthalmoscopy (SLO). METHODS: The algorithm utilized the FasterRCNN (Faster Regions with CNN features)+ResNet50 (Residua Network 50)+FPN (Feature Pyramid Networks) method for detecting hemorrhagic spots, cotton wool spots, exudates, and microaneurysms in DR ultra-widefield SLO. Subimage segmentation combined with a deeper residual network FasterRCNN+ResNet50 was employed for feature extraction to enhance intelligent learning rate. Feature fusion was carried out by the feature pyramid network FPN, which significantly improved lesion detection rates in SLO fundus images. RESULTS: By analyzing 1076 ultra-widefield SLO images provided by our hospital, with a resolution of 2600×2048 dpi, the accuracy rates for hemorrhagic spots, cotton wool spots, exudates, and microaneurysms were found to be 87.23%, 83.57%, 86.75%, and 54.94%, respectively. CONCLUSION: The proposed algorithm demonstrates intelligent detection of DR lesions in ultra-widefield SLO, providing significant advantages over traditional fundus color imaging intelligent diagnosis algorithms.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Flow Channel with Wrinkles and Calcium Sites in a Ca-MOF for Direct One-Step Ethylene Purification from C2 Gases and MTO Products Separation.

The strategy of flow channel with wrinkles and calcium sites for single-step C2H4 purification from C2 gases and methanol-to-olefins (MTO) products separation was realized in FJI-Y9. The adsorption amounts showed a total reversal order of C3H6 > C2H6 > C2H2 > C2H4 at 298 K. Modeling indicated that the wrinkles and Ca2+ facilitated the full contact of C3H6 and C2H6. Breakthrough experiments illustrated that FJI-Y9 could yield pure C2H4 in a single step with a productivity of 0.78 mmol g-1. In a lone adsorption/desorption cycle for MTO product separation, the productivities of C3H6 and C2H4 were 1.96 and 1.29 mol g-1, standing as the highest recorded values.

Unusual presentation of PD-1 inhibitors in people living with HIV with advanced gastric cancer: Case report.

This paper seeks to determine the effect of combination anti-PD-1 and antiretroviral therapy (ART) on people living with HIV (PLWH) with advanced gastric cancer. In our case, a PLWH with recurrent locally advanced gastric cancer was treated with anti-PD-1 inhibitor and ART. A significant reduction in tumor lesions (as demonstrated by contrast-enhanced CT imaging) and a better quality of life were achieved following treatment. There have been limited studies on the treatment of PLWH with advanced gastric cancer. Chemotherapy is most often used, however, with unsatisfactory outcomes. to date, there have been no published reports on the use of PD-1 inhibitors in PLWH with advanced gastric cancer. Our report provides a valuable reference for future management of such patients.

Gender associations between phthalate exposure and biomarkers of oxidative stress: A prospective cohort study.

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.

Distribution, seasonal variation and ecological risk assessment of phthalates in the Yitong River, a typical urban watercourse located in Northeast China.

Phthalates (PAEs) are a typical class of endocrine disruptors (EEDs). As one of the most commonly used plasticizers, they have received widespread attention due to their wide application in various countries and high detection rates in various environmental media. To be able to clarify the contamination status of PAEs pollutants in a typical northern cold-temperate urban river, 30 water samples from Yitong River in Changchun City, northern China were collected, during the 2023 dry season (March), normal season (May) and wet season (July). Using these samples, a total of 16 target PAEs are investigated. The resulting total PAEs concentrations are: dry season 408 to 1494 ng/L, wet season 491 to 1299 ng/L, and normal season 341 to 780 ng/L. The average concentration of the 16 PAEs over the three seasons is 773 ng/L. Di-2-ethylhexyl phthalate (DEHP) and Dibutyl phthalate (DBP) have the highest concentrations, ranging from 12 to 403 ng/L and 28-680 ng/L respectively. The ecological risks within the Yitong River Basin are evaluated based on the degree of PAEs contamination. DBP and DEHP pose higher risk assessment levels for algae, crustaceans and fish than the other target PAEs. The accurate determination of PAEs provided baseline data on PAEs for the management of the Yitong River, which is of great significance for the prediction of ecological risk assessment and the development of corresponding control measures, supported further research on PAEs in the cold-temperate zone aquatic environments, and shed light on the seasonal variations of PAEs in the Northeast region in the future. Moreover, considering the bioaccumulation and persistence of PAEs, it is necessary to continue to pay attention to the pollution status of cold-temperate zones rivers and the changes in ecological risks in the future.

Tofacitinib Treatment for Pretibial Myxedema.

This case report describes tofacitinib treatment for 2 patients with pretibial myxedema.

Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study.

Background: Gender differences existed in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Observational studies have revealed associations between sex hormones and IBD, such as estrogen and testosterone. However, the exact relationship between these sex hormones and IBD is unclear. Method: Based on the genome-wide association studies data of eight sex hormones, two sex hormone receptors, sex hormone-binding globulin (SHBG), total IBD and its two subtypes, we performed a two-sample Mendelian randomization (MR) study to analyze their mutual relationship. For estradiol (E2), progesterone (PROG), bioavailable testosterone (BAT), total testosterone (TT) and SHBG, sex-stratified MR analyses were also performed. Inverse variance weighted method, MR-Egger regression and Weighted median method were used for causal analyses. Sensitivity analyses were conducted to test the stability of causal relationships. Besides, a reverse MR analysis was performed to estimate the reverse causation. Results: E2 (P=0.028) and TT (P=0.034) had protective effects on CD. Sex-stratified analyses revealed protective roles of E2 in males on total IBD (P=0.038) and CD (P=0.020). TT in females had protective effects on total IBD (P=0.025) and CD (P=0.029), and BAT in females decreased the risk of developing CD (P=0.047) and UC (P=0.036). Moreover, SHBG in males was also associated with a decreased risk of CD (P=0.021). The reversed MR analysis showed that CD was negatively correlated with estrogen receptor (P=0.046). UC was negatively correlated with PROG in females (P=0.015) and positively correlated with SHBG levels in males (P=0.046). Conclusion: Findings of this study revealed the mutual causal associations between sex hormones and the risk of developing IBD.