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ABSTRACT Background Hepatocellular carcinoma (HCC) is a prevalent malignancy with a high mortality rate worldwide. Suppressor of cytokine signaling (SOCS) family members play important roles in the proliferation, metabolism, and immunity of HCC cells by regulating cytokines and growth factors. However, it remains uncertain whether the level of SOCS family members can affect the prognosis of HCC patients. Aims This study aimed to comprehensively assess the role and mechanisms of SOCS family members in the development of HCC and to guide clinical selection. Methods We investigated the expression levels of SOCS family genes in HCC patients and their associations with various clinicopathological characteristics. We also utilized a public database to analyze the changes in the expression, potential functions, transcription factors, and immune invasion of SOCS family members. Additionally, we examined the prognostic value of the SOC family for HCC and its correlation with the SOC family and ferroptosis‐related genes. Results This study revealed that the expression of SOCS2‐7, and CISH was downregulated in HCC. The SOCS4, SOCS5, and SOCS7 genes were associated with the clinicopathological features of HCC patients. SOCS family genes are mainly related to the PIK3R3, GHR, and TNS4 pathways. Additionally, this study revealed that STAT3, PPAR‐gamma 2, and IRF‐2 are important transcription factors that regulate SOCS family members. The expression levels of SOCS family members are closely related to immune infiltration in liver cancer. The study also indicated that SOCS2 and SOCS4 are risk‐related genes for predicting the prognosis of patients with liver cancer. Finally, this study suggested that the SOCS2 gene may be involved in the development and progression of HCC. Conclusion Our study enhances the current understanding of SOCS gene function in liver cancer and can help clinicians select appropriate drugs and predict the prognosis of HCC patients.

BackgroundCurrently, the prognosis of advanced intrahepatic cholangiocarcinoma (ICC) is poor, and the current treatment methods are not effective.ObjectiveThe aim of this study was to evaluate the anticancer efficacy of chemotherapy combined with PD-1 inhibitors and tyrosine kinase inhibitors (TKIs) in patients with ICC.MethodsWe retrospectively screened patients with advanced intrahepatic cholangiocarcinoma (ICC) who received chemotherapy combined with lenvatinib and PD-1. We evaluated overall survival (OS), progression-free survival (PFS), the objective response rate (ORR), the disease control rate (DCR), the tumor shrinkage rate, and safety.ResultsWe enrolled 95 patients with ICC and divided them into three groups with a median follow-up duration of 15.1 months. The chemotherapy group (chemo-regimen group), chemotherapy combined with immune checkpoint inhibitors (dual-regimen group), and chemotherapy combined with lenvatinib (triple-regimen group) had median OS times of 13.1 months, 20.8 months, and 39.6 months, respectively. Notably, the triple-regimen group had a significantly longer OS than did the chemo-regimen and dual-regimen groups. The chemo-regimen group, dual-regimen group, and triple-regimen group reported median PFS durations of 4.8 months, 11.9 months, and 23.4 months, respectively. Both combination groups exhibited significantly longer PFS than the chemotherapy-only group (P

Abstract Background The objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC—apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA). Methods Our study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation. Results The test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P

The past few years have witnessed an increasing incidence of nodular goiter (NG), with a well-documented higher prevalence in females than males. This gender disparity has led research to focus primarily on female subjects, potentially overlooking common pathogenic mechanisms in both sexes. In this study, we investigated the shared pathogenesis of NG in males and females. Utilizing a rat model and RNA sequencing, we identified differentially expressed genes associated with the disease. We further validated these findings in normal human thyroid cells and human papillary thyroid cancer cells. A randomized experiment was conducted with equal numbers of male and female rats divided into control and NG model groups. The NG model was established using propylthiouracil and various assessments such as thyroid ultrasonography, thyroid index, thyroid function, and thyroid histology were performed. Transcriptome analysis revealed numerous upregulated and downregulated genes in both male and female model groups. Key genes like KDR, FLT1, PDGFB, and CAV1, and pathways including PI3K-Akt, MAPK, Ras, fluid shear stress and atherosclerosis, calcium signaling, and Rap1 signaling pathways were linked with the disease. Western blot and immunofluorescence analysis confirmed these findings, which were further supported by cell-based experiments. In conclusion, our findings suggest that abnormal expression of specific genes and pathways leading to irregular cell growth, blood vessel formation, and inflammation may be common factors in the pathogenesis of NG in both males and females.

Abstract Objectives Allergic rhinitis (AR) refers to a form of respiratory inflammation that mainly affects the sinonasal mucosa. The purpose of this study was to explore the level of immune cell infiltration and the pathogenesis of AR. Methods We performed a comprehensive analysis of two gene expression profiles (GSE50223 and GSE50101, a total of 30 patients with AR and 31 healthy controls). CIBERSORT was used to evaluate the immune cell infiltration levels. Weighted gene coexpression network analysis was applied to explore potential genes or gene modules related to immune status, and enrichment analyses including gene ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene set variation analysis, were performed to analyze the potential mechanisms in AR. A protein–protein interaction network was constructed to investigate the hub genes, and consensus clustering was conducted to identify the molecular subtypes of AR. Results Compared to the healthy controls, patients with AR had high abundance levels and proportions of CD4+ memory‐activated T cells. One hundred and eight immune‐related differentially expressed genes were identified. Enrichment analysis suggested that AR was mainly related to leukocyte cell‐cell adhesion, cytokine‐cytokine receptor interaction, T‐cell activation, and T‐cell receptor signaling pathway. Ten hub genes, including TYROBP, CSF1R, TLR8, FCER1G, SPI1, ITGAM, CYBB, FCGR2A, CCR1, and HCK, which were related to immune response, might be crucial to the pathogenesis of AR. Three molecular subtypes with significantly different immune statuses were identified. Conclusion This study improves our understanding of the molecular mechanisms in AR via comprehensive strategies and provides potential diagnostic biomarkers and therapeutic targets of AR.

Two-dimensional (2D) Janus transition metal dichalcogenides MXY manifest novel physical properties owing to the breaking of out-of-plane mirror symmetry. Recently, the 2H phase of MoSH has been demonstrated to possess intrinsic superconductivity, whereas the 1T phase exhibits a charge density waves state. In this paper, we have systematically studied the stability and electron–phonon interaction characteristics of MoSLi. Our results have shown that both the 2H and 1T phases of MoSLi are stable, as indicated by the phonon spectrum and the ab initio molecular dynamics. However, the 1T phase exhibits an electron–phonon coupling constant that is twice as large as that of the 2H phase. In contrast to MoSH, the 1T phase of MoSLi exhibits intrinsic superconductivity. By employing the ab initio anisotropic Migdal-Eliashberg formalism, we have revealed the two-gap superconducting nature of 1T-MoSLi, with a transition temperature (Tc) of 14.8 K. The detailed analysis indicates that the superconductivity in 1T-MoSLi primarily originates from the interplay between the vibration of the phonon modes in the low-frequency region and the dz2 orbital. These findings provide a fresh perspective on superconductivity within Janus structures. [ABSTRACT FROM AUTHOR]

This paper explores the formation mechanisms of various architectural forms in a cultural transition region. A field investigation involving 504 ancestral shrines with Guangfu and Hakka styles in Shenzhen was performed. Then, spatial distribution analysis was conducted to reveal the regional structure of aggregation, penetration and juxtaposition of the architectural forms. Case studies were adopted to explain the integration modes of the architectural forms. The results show that, juxtaposition, as a typical mode of coexistence of architectural forms in cultural transition zones, mainly occurs in regions dominated by weak cultures. Through gathering densely in a small region, a weak culture can gain the ability to compete with a strong culture, thus forming a basis for achieving an equilibrium state. The approaches to the integration of architectural forms are diverse. The transformation of the architectural plane involves changes in social organization and cultural essence. The alteration of construction details and decoration involves a compromise regarding noncritical elements adopted by the weak culture to maintain its original characteristics. Finally, their shared human and natural environmental “genes” give the buildings in the cultural transition region an underlying commonality. This study offers a significant addition to the cultural geography and architectural morphology literature.