Hepatocellular carcinoma （HCC） is a common primary malignant tumor. In recent years， the role of ubiquitin-specific proteases （USPs） in HCC has attracted widespread attention. USPs are a class of key deubiquitinating enzymes that affect a variety of biological processes by regulating the ubiquitination status of proteins. Studies have shown that USPs participate in the regulation of cell proliferation， apoptosis， migration， and invasion by deubiquitinating various tumor-related proteins. In addition， the abnormal expression of USPs is closely associated with the prognosis of HCC patients and may thus be used as potential biomarkers and therapeutic targets. This article reviews the research advances in USPs in HCC and explores their key roles in the development， progression， and metastasis of HCC. A deep understanding of the mechanism of action of USPs in HCC not only helps to reveal the pathogenesis of HCC， but also provides a scientific basis for developing new diagnostic tools and treatment strategies. Future research should further explore the regulatory effect of USPs in HCC， in order to provide more effective means for the clinical treatment of HCC.

Liver cancer has high prevalence and mortality rates around the world， and its development and progression are closely associated with the interaction between the tumor microenvironment and tumor-associated macrophages （TAMs）. TAMs play a significant role in immune suppression， immune escape， cell proliferation， invasion， metastasis， and drug resistance in liver cancer. Traditional Chinese medicine （TCM）， with its unique therapeutic concepts and methods， has shown great potential in regulating TAMs and improving the prognosis of liver cancer. This article reviews the role and molecular mechanisms of TCM in regulating TAMs for the treatment of liver cancer， discusses the key role of TAMs in the progression of liver cancer， and analyzes the impact of Chinese medicinal components on the recruitment， polarization， and activity of TAMs and the expression of related factors based on TCM theory. Studies have shown that TCM can regulate the polarization state of TAMs， promote the formation of M1-type antitumor macrophages， and inhibit the activity of M2-type tumor macrophages， thereby playing a role in inhibiting the proliferation of liver cancer cells， promoting apoptosis， inhibiting angiogenesis， and enhancing immune response. In addition， this article also summarizes the molecular targets and mechanisms of action of TCM monomers， compound prescriptions， and novel preparations in the treatment of liver cancer， such as inhibiting the secretion of cytokines by TAMs， regulating signaling pathways， and affecting metabolic pathways， in order to provide a scientific basis for the application of TCM in liver cancer treatment and offer new ideas for immunotherapy for liver cancer.

Objective:To investigate the CT image characteristics of anterior ethmoidal artery（AEA） through CT scan and its significance in nasal endoscopic surgery. Methods:A retrospective study of 82 patients（164 sides） with chronic sinusitis was conducted. All patients underwent CT scan and the images were reconstructed. The AEA classification was used and calculate the rate of AEA suspension. The AEA was classified, and the suspension rate of the AEA was calculated. The height of the lateral lamella of the cribriform plate （LLCP） was measured, and Keros classification was performed. The relationship between Keros classification and AEA suspension was analyzed. The supraorbital ethmoidal cell （SOEC） was identified, and its relationship with AEA suspension was analyzed. Results:Type Ⅰ AEA accounted for 42.07%（69/164）. Type Ⅱ AEA accounted for 22.56%（37/164）. Type Ⅲ AEA accounted for 35.37%（58/164）. The suspension rate was 35.37%. The average height of the LLCP was （3.7±1.8） mm. In the Keros classification, type Ⅰaccounted for 53.05%（87/164）, Type Ⅱaccounted for 37.80%（62/164）. Type Ⅲ accounted for 9.15%（15/164）. The results of the Spearman analysis showed that there was a moderate positive correlation between the Keros classification and the suspension of the AEA（r=0.526, P<0.01）. Among 164 sides, SOEC was present in 15 sides. The suspension rate of AEA in the group with SOEC was significantly higher than that in the group without SOEC（P<0.01）. Conclusion:Sinus CT and multiplanar reconstruction can clarify the image characteristics of AEA and its relationship with surrounding structures. When the level of Keros classification is higher or SOEC is present, the suspension rate of AEA increases significantly. It is of great significance to clarify the characteristics of AEA before surgery in order to avoid injury during surgery.
Humans ; Retrospective Studies ; Endoscopy ; Ethmoid Sinus/diagnostic imaging* ; Tomography, X-Ray Computed ; Arteries/diagnostic imaging* ; Sinusitis/diagnostic imaging* ; Male ; Female ; Middle Aged ; Adult ; Aged

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Objective: To observe the effects of Danggui Shaoyao powder (DSP) on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor (PPARγ)-liver X receptor (LXRα)-adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) pathway regulation. Methods: Eight C57BL/6J male mice were selected as the control group, and 24 ApoE−/− male mice were randomly divided into the atherosclerosis model (AS) group, atorvastatin calcium (AC) group, and DSP group (n = 8 each group). To establish an AS model, ApoE−/− mice were fed a high-fat diet for 16 weeks. Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining. Triglyceride (TG), cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were determined in the livers using a single-reagent GPO-PAP method. Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver. Results: After 16 weeks of a high-fat diet, ApoE−/− mice showed more Oil Red O staining in the aorta and liver compared to the CONT group. Compared to the AS group, the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees. Furthermore, DSP significantly reduced the hepatic lipid area in ApoE−/− mice (P < .001) and decreased the levels of TG, TC, and LDL-C in liver (P < .001, P = .027, P < .001, respectively). DSP also significantly increased the levels of PPARγ, LXRα, ABCA1, and ABCG1 mRNA expression, as well as the PPARγ, LXRα, ABCA1, and ABCG1 protein expression in liver. Conclusion DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.

Humans are born under the nourishment of heaven and earth qi.The physiological and pathological functions of the human body are influenced by the alternation of cold and heat in the four seasons.Allergic diseases often occur or worsen during seasonal transitions,corresponding to the theory of the spleen dominating the end of the four seasons in traditional Chinese medicine.Splenic dysfunction disrupts the body's internal clock during seasonal transitions,making it unable to adapt to external climate changes,causing the onset or exacerbation of specific allergic symptoms.The theory of"the spleen serves as the guard"originated from Huangdi Neijing,which is a succinct summary of the role of the spleen in defending the body against external pathogens.The theory emphasizes that the spleen transports drinks and foods internally to supplement healthy qi,and regulates defensive qi externally to protect the whole body.This theory is closely linked to the seasonal changes in immune function,thereby influencing the seasonal onset of allergic diseases.This paper explores the roles of the spleen in time-based self-regulation and immune defense against seasonal allergic diseases according to the theory of"spleen serves as the grard."The dysfunction of this protective mechanism,which leads to disharmony in nutritive qi and defensive qi,internal production of phlegm-dampness,and zang-fu organs malnutrition,are the key factors causing recurrent and persistent allergic diseases during seasonal transitions.This study provides insights for elucidating the mechanisms behind seasonal allergic disease outbreaks and their prevention.

Humans are born under the nourishment of heaven and earth qi.The physiological and pathological functions of the human body are influenced by the alternation of cold and heat in the four seasons.Allergic diseases often occur or worsen during seasonal transitions,corresponding to the theory of the spleen dominating the end of the four seasons in traditional Chinese medicine.Splenic dysfunction disrupts the body's internal clock during seasonal transitions,making it unable to adapt to external climate changes,causing the onset or exacerbation of specific allergic symptoms.The theory of"the spleen serves as the guard"originated from Huangdi Neijing,which is a succinct summary of the role of the spleen in defending the body against external pathogens.The theory emphasizes that the spleen transports drinks and foods internally to supplement healthy qi,and regulates defensive qi externally to protect the whole body.This theory is closely linked to the seasonal changes in immune function,thereby influencing the seasonal onset of allergic diseases.This paper explores the roles of the spleen in time-based self-regulation and immune defense against seasonal allergic diseases according to the theory of"spleen serves as the grard."The dysfunction of this protective mechanism,which leads to disharmony in nutritive qi and defensive qi,internal production of phlegm-dampness,and zang-fu organs malnutrition,are the key factors causing recurrent and persistent allergic diseases during seasonal transitions.This study provides insights for elucidating the mechanisms behind seasonal allergic disease outbreaks and their prevention.

Humans are born under the nourishment of heaven and earth qi.The physiological and pathological functions of the human body are influenced by the alternation of cold and heat in the four seasons.Allergic diseases often occur or worsen during seasonal transitions,corresponding to the theory of the spleen dominating the end of the four seasons in traditional Chinese medicine.Splenic dysfunction disrupts the body's internal clock during seasonal transitions,making it unable to adapt to external climate changes,causing the onset or exacerbation of specific allergic symptoms.The theory of"the spleen serves as the guard"originated from Huangdi Neijing,which is a succinct summary of the role of the spleen in defending the body against external pathogens.The theory emphasizes that the spleen transports drinks and foods internally to supplement healthy qi,and regulates defensive qi externally to protect the whole body.This theory is closely linked to the seasonal changes in immune function,thereby influencing the seasonal onset of allergic diseases.This paper explores the roles of the spleen in time-based self-regulation and immune defense against seasonal allergic diseases according to the theory of"spleen serves as the grard."The dysfunction of this protective mechanism,which leads to disharmony in nutritive qi and defensive qi,internal production of phlegm-dampness,and zang-fu organs malnutrition,are the key factors causing recurrent and persistent allergic diseases during seasonal transitions.This study provides insights for elucidating the mechanisms behind seasonal allergic disease outbreaks and their prevention.

Humans are born under the nourishment of heaven and earth qi.The physiological and pathological functions of the human body are influenced by the alternation of cold and heat in the four seasons.Allergic diseases often occur or worsen during seasonal transitions,corresponding to the theory of the spleen dominating the end of the four seasons in traditional Chinese medicine.Splenic dysfunction disrupts the body's internal clock during seasonal transitions,making it unable to adapt to external climate changes,causing the onset or exacerbation of specific allergic symptoms.The theory of"the spleen serves as the guard"originated from Huangdi Neijing,which is a succinct summary of the role of the spleen in defending the body against external pathogens.The theory emphasizes that the spleen transports drinks and foods internally to supplement healthy qi,and regulates defensive qi externally to protect the whole body.This theory is closely linked to the seasonal changes in immune function,thereby influencing the seasonal onset of allergic diseases.This paper explores the roles of the spleen in time-based self-regulation and immune defense against seasonal allergic diseases according to the theory of"spleen serves as the grard."The dysfunction of this protective mechanism,which leads to disharmony in nutritive qi and defensive qi,internal production of phlegm-dampness,and zang-fu organs malnutrition,are the key factors causing recurrent and persistent allergic diseases during seasonal transitions.This study provides insights for elucidating the mechanisms behind seasonal allergic disease outbreaks and their prevention.