Investigating the shared genetic architecture between hypothyroidism and rheumatoid arthritis

BackgroundThere is still controversy regarding the relationship between hypothyroidism and rheumatoid arthritis (RA), and there has been a dearth of studies on this association. The purpose of our study was to explore the shared genetic architecture between hypothyroidism and RA.MethodsUsing public genome-wide association studies summary statistics of hypothyroidism and RA, we explored shared genetics between hypothyroidism and RA using linkage disequilibrium score regression, ρ-HESS, Pleiotropic analysis under a composite null hypothesis (PLACO), colocalization analysis, Multi-Trait Analysis of GWAS (MTAG), and transcriptome-wide association study (TWAS), and investigated causal associations using Mendelian randomization (MR).ResultsWe found a positive genetic association between hypothyroidism and RA, particularly in local genomic regions. Mendelian randomization analysis suggested a potential causal association of hypothyroidism with RA. Incorporating gene expression data, we observed that the genetic associations between hypothyroidism and RA were enriched in various tissues, including the spleen, lung, small intestine, adipose visceral, and blood. A comprehensive approach integrating PLACO, Bayesian colocalization analysis, MTAG, and TWAS, we successfully identified TYK2, IL2RA, and IRF5 as shared risk genes for both hypothyroidism and RA.ConclusionsOur investigation unveiled a shared genetic architecture between these two diseases, providing novel insights into the underlying biological mechanisms and establishing a foundation for more effective interventions

Role of HMGB1 in apoptosis-mediated sepsis lethality

Severe sepsis, a lethal syndrome after infection or injury, is the third leading cause of mortality in the United States. The pathogenesis of severe sepsis is characterized by organ damage and accumulation of apoptotic lymphocytes in the spleen, thymus, and other organs. To examine the potential causal relationships of apoptosis to organ damage, we administered Z-VAD-FMK, a broad-spectrum caspase inhibitor, to mice with sepsis. We found that Z-VAD-FMK–treated septic mice had decreased levels of high mobility group box 1 (HMGB1), a critical cytokine mediator of organ damage in severe sepsis, and suppressed apoptosis in the spleen and thymus. In vitro, apoptotic cells activate macrophages to release HMGB1. Monoclonal antibodies against HMGB1 conferred protection against organ damage but did not prevent the accumulation of apoptotic cells in the spleen. Thus, our data indicate that HMGB1 production is downstream of apoptosis on the final common pathway to organ damage in severe sepsis

Additional file 1 of X chromosome rearrangement associated with premature ovarian insufficiency as diagnosed by molecular cytogenetic methods: a case report and review of the literature

Supplementary Material

Deep Blind Fault Activity—A Fault Model of Strong <i>M_w</i> 5.5 Earthquake Seismogenic Structures in North China

North China is one of the high-risk areas for destructive and strong earthquakes in mainland China and has experienced numerous strong historical earthquakes. An earthquake of magnitude MW 5.5 struck Pingyuan County, Dezhou city, in Shandong Province, China, on 6 August 2023. This earthquake was the strongest in the eastern North China Craton since the 1976 Tangshan earthquake. Since the earthquake did not produce surface ruptures, the seismogenic structure for fault responsible for the Pingyuan MW 5.5 earthquake is still unclear. To reveal the subsurface geological structure near the earthquake epicenter, this study used high-resolution two-dimensional (2D) seismic reflection profiles and constructed a three-dimensional (3D) geometric model of the Tuqiao Fault by interpreting the faults in the seismic reflection profiles. This study further combined focal mechanism solutions, aftershock clusters, and other seismological data to discuss the seismogenic fault of the Pingyuan MW 5.5 earthquake. The results show that the Tuqiao Fault is not the seismogenic fault of the MW 5.5 earthquake. The actual seismogenic structure may be related to the NE-oriented high-angle strike-slip blind fault developed in the basement. We further propose three possible fault models for the strong seismogenic structure in North China to discuss the potential seismotectonics in this region

High seismic velocity structures control moderate to strong induced earthquake behaviors by shale gas development

Abstract Moderate to strong earthquakes have been induced worldwide by shale gas development, however, it is still unclear what factors control their behaviors. Here we use local seismic networks to reliably determine the source attributes of dozens of M > 3 earthquakes and obtain a high-resolution shear-wave velocity model using ambient noise tomography. These earthquakes are found to occur close to the target shale formations in depth and along high seismic velocity boundaries. The magnitudes and co-seismic slip distributions of the 2018 Xingwen $${M}_{{{{{{\rm{L}}}}}}}5.7$$ M L 5.7 and 2019 Gongxian $${M}_{{{{{{\rm{L}}}}}}}5.3$$ M L 5.3 earthquakes are further determined jointly by seismic waveforms and InSAR data, and the co-seismic slips of these two earthquakes correlate with high seismic velocity zones along the fault planes. Thus, the distribution of high velocity zones near the target shale formations, together with the stress state modulated by hydraulic fracturing controls induced earthquake behaviors and is critical for understanding the seismic potentials of hydraulic fracturing

Table_1_Investigating the shared genetic architecture between hypothyroidism and rheumatoid arthritis.docx

BackgroundThere is still controversy regarding the relationship between hypothyroidism and rheumatoid arthritis (RA), and there has been a dearth of studies on this association. The purpose of our study was to explore the shared genetic architecture between hypothyroidism and RA.MethodsUsing public genome-wide association studies summary statistics of hypothyroidism and RA, we explored shared genetics between hypothyroidism and RA using linkage disequilibrium score regression, ρ-HESS, Pleiotropic analysis under a composite null hypothesis (PLACO), colocalization analysis, Multi-Trait Analysis of GWAS (MTAG), and transcriptome-wide association study (TWAS), and investigated causal associations using Mendelian randomization (MR).ResultsWe found a positive genetic association between hypothyroidism and RA, particularly in local genomic regions. Mendelian randomization analysis suggested a potential causal association of hypothyroidism with RA. Incorporating gene expression data, we observed that the genetic associations between hypothyroidism and RA were enriched in various tissues, including the spleen, lung, small intestine, adipose visceral, and blood. A comprehensive approach integrating PLACO, Bayesian colocalization analysis, MTAG, and TWAS, we successfully identified TYK2, IL2RA, and IRF5 as shared risk genes for both hypothyroidism and RA.ConclusionsOur investigation unveiled a shared genetic architecture between these two diseases, providing novel insights into the underlying biological mechanisms and establishing a foundation for more effective interventions.</p

CA153 in Breast Secretions as a Potential Molecular Marker for Diagnosing Breast Cancer: A Meta Analysis

<div><p>Purpose</p><p>Many studies have reported that carbohydrate antigen 153 (CA153) in breast secretions (BS) can discriminate breast cancer (BC) patients from healthy individuals, indicating CA153 in BS as a potential index for BC. This meta-analysis aimed to evaluate the actual diagnostic value of CA153 in BS.</p><p>Methods</p><p>Related papers were obtained from Pubmed, Embase, Scopus, Ovid, Sciverse, the Cochrane library, Chinese Biomedical literature Database (CBM), Technology of Chongqing (VIP), Wan Fang Data, and Chinese National Knowledge Infrastructure (CNKI). Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of CA153 in BS for BC diagnosis were analyzed with the random effect model. SROC and the area under the curve (AUC) were applied to assess overall diagnostic efficiency.</p><p>Results</p><p>This meta-analysis included five studies with a total of 329 BC patients and 381 healthy subjects. For CA153 in BS, the summary sensitivity, specificity, and DOR to diagnose BC were 0.63 (95% confidence interval (CI): 0.57∼0.68), 0.82 (95% CI: 0.78∼0.86), and 9.18 (95% CI: 4.22∼19.95), respectively. Furthermore, the AUC of BS CA153 in the diagnosis of BC was 0.8614.</p><p>Conclusions</p><p>CA153 in BS is a valuable molecular marker in diagnosing BC and should be applied in standard clinical practices of BC screening upon confirmation of our findings in a larger prospective study.</p></div

The overall diagnostic performance of CA153 in BS, shown by SROC.

<p>Each circle represents a study. The SROC curve is symmetric and the AUC is 0.8614, suggesting a moderate diagnostic accuracy for BC.</p

A literature screening flow diagram and quality assessment schematic diagram for the included articles.

<p><b>(A)</b> A flow diagram of screening eligible studies. <b>(B)</b> Presentation of data quality evaluated with the QUADAS-2 tool, showing “risk of bias” and “concerns of applicability” of each eligible study (with risk of bias in the “flow and timing” domain).</p