Background: An association has been observed between primary biliary cholangitis (PBC) and systemic rheumatic diseases (SRDs) in observational studies, however the exact causal link remains unclear. We aimed to evaluate the causal effects of PBC on SRDs through Mendelian randomization (MR) analysis. Methods: The genome-wide association study (GWAS) summary data were obtained from MRC IEU OpenGWAS and FinnGen databases. Independent genetic variants for PBC were selected as instrumental variables. Inverse variance weighted was used as the main approach to evaluate the causal effects of PBC on Sjögren syndrome (SS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), mixed connective tissue disease (MCTD) and polymyositis (PM). Horizontal pleiotropy and heterogeneity were measured by MR‒Egger intercept test and Cochran’s Q value, respectively. Results: PBC had causal effects on SS (OR = 1.177, P = 8.02e-09), RA (OR = 1.071, P = 9.80e-04), SLE (OR = 1.447, P = 1.04e-09), SSc (OR = 1.399, P = 2.52e-04), MCTD (OR = 1.306, P = 4.92e-14), and PM (OR = 1.416, P = 1.16e-04). Based on the MR‒Egger intercept tests, horizontal pleiotropy was absent (all P values > 0.05). The robustness of our results was further enhanced by the leave-one-out method. Conclusions: Our research has provided new insights into PBC and SRDs, indicating casual effects on various SRDs.

Background: Upper respiratory tract infection (URTI), one of the most common respiratory diseases, has a high annual incidence. Trollius chinensis capsule has been used to treat URTI in China. However, the underlying-mechanisms remain unclear. Methods: Network pharmacology was used to explore the potential mechanism of action of Trollius chinensis capsule in URTI treatment. The active compounds in Trollius chinensis were obtained from the TCMSP, SymMap, and ETCM databases. The TCMSP, PubChem, and SwissTargetPrediction databases were used to predict potential targets of Trollius chinensis. URTI-associated targets were gathered from GeneCards and DisGeNET databases. The key targets and signaling pathways associated with URTI were selected by network topology, GO, and KEGG pathway enrichment analysis. Molecular docking was used to verify the binding activity between active compounds and key targets. Results: Quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are major active compounds in Trollius chinensis capsule. Eighty one candidate therapeutic targets were confirmed to be involved in protection of Trollius chinensis capsule against URTI. Among them, 7 key targets (TP53, IL6, AKT1, CASP3, CXCL8, MMP9, and EGFR) were verified to have good binding affinities to the main active compounds. Furthermore, enrichment analyses suggested that inflammatory response, virus infection and oxidative stress related biological processes and pathways were possibly the potential mechanism. Conclusion: Overall, the present study clarified that quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are proved to be the main effective compounds of Trollius chinensis capsule treating URTI, possibly by acting on the targets of IL6, AKT1, CASP3, CXCL8, MMP9 and EGFR to play anti-infectious, anti-viral, and anti-oxidative effects. This study provides a new understanding of the active compounds and mechanisms of Trollius chinensis capsule in URTI treatment from the perspective of network pharmacology.

脾破裂是结肠镜检查严重并发症, 但发生率很低, 属于结肠镜检查罕见并发症, 易导致误诊, 漏诊, 并未引起临床医生足够重视. 本例患者结肠镜检查后出现腹痛、休克表现, 经腹部电子计算机断层扫描检查、剖腹探查确定为脾破裂, 后经外科手术患者转危为安. 结肠镜检查后出现腹痛、休克等表现时, 应引起临床医生高度警觉, 早期识别、早期诊断、早期干预是改善患者预后的关键. 结肠镜检查是诊断结直肠疾病最常见的方法, 出血和穿孔的结肠镜检查常见并发症. 结肠镜检查并发脾破裂, 虽然罕见, 但可能出现严重后果, 应引起临床高度重视. 对于结肠镜检查后出现腹痛、休克等症状时, 临床医生应考虑脾破裂可能, 以免造成误诊.

Overlap between primary sclerosing cholangitis (PSC) and systemic lupus erythematosus (SLE) has been documented in previous studies, but the precise causal relationships between them remain elusive. This study aims to clarify the potential causal links between PSC and SLE using Mendelian randomization (MR) and transcriptomic analyses. Genome-wide association study (GWAS) summary data for PSC and SLE were obtained from the IEU OpenGWAS database. The inverse variance weighted (IVW) method was the primary approach for assessing the causal links between PSC and SLE. Potential horizontal pleiotropy and heterogeneity were evaluated to ensure the reliability of the MR results. Additionally, transcriptomic analysis was performed using data from the Gene Expression Omnibus (GEO) database to uncover potential mechanisms insights involving overlapping genes and develop a diagnostic model for PSC and SLE. Genetically predicted PSC had a significant causal effect on SLE, with an OR of 1.190 (95% CI: 1.098–1.290, P ˂.001). Conversely, SLE had causal effect on PSC with an OR of 1.130 (95% CI: 1.046–1.221, P = .002). Multivariate MR analysis by adjustment of body mass index and smoking also revealed the bidirectional causal relationships between PSC and SLE. There were no signs of horizontal pleiotropy or heterogeneity, and the robustness of these results was confirmed via leave-one-out sensitivity analysis. Through integrated transcriptomic analysis and machine learning algorithms, 5 hub genes were identified. Furthermore, the diagnostic accuracy of the 5-gene signature was confirmed via Nomogram, calibration curve, and decision curve analysis, highlighting the diagnostic potential of these hub genes for both PSC and SLE. In conclusion, our MR study successfully confirms the bidirectional causal relationships between PSC and SLE, shedding light on the intertwined nature of these 2 conditions. Moreover, we identified 5 hub genes that potentially mediate the overlap between PSC and SLE, providing valuable insights for early diagnosis and future mechanistic exploration.