Hypoxia inducible factors(HIFs)are core molecules that enable the body to adapt to hypoxia environments.By sensing changes in intracellular oxygen pressure,HIFs regulate gene expression related to hypoxia adaptation,thereby enhancing the body's hypoxia tolerance at cellular,tissue and organ levels.On the other hand,HIFs promote the generation of red blood cells,angiogenesis,and regulate the body's energy metabolism,thereby improving its hypoxia tolerance.The enhancement of hypoxia tolerance is of great significance for the prevention and treatment of hypoxia-related diseases,upgrading of athletes'performance,enhancement of workers'efficiency at high-altitudes,and the improvement of individu-als'quality of life.This article reviews the relationships between HIFs and hypoxia tolerance as well as related mechanisms in order to provide strategies for enhancing hypoxia tolerance in the body.

Objective To identify mechanisms regulating disease progression in rat models of pulmonary arterial hy-pertension(PAH).Methods Rat PAH models were established using subcutaneous monocrotaline(MCT)injec-tion and the SU5416/hypoxia(SU/Hx)method.Transcriptomic sequencing of lung tissues was performed to identify gene expression and pathway alterations in PAH rats,followed by a comparative analysis with transcriptomic data of patients with idiopathic pulmonary arterial hypertension(IPAH)in NCBI database.Results Inflammatory-related genes such as CXCL9,CCL24,and SECTM1 were upregulated in both PAH rat models and IPAH patient lungs,while genes such as DGKG and DOCK9 were downregulated(P＜0.05).Pathways related to endothelial cell proliferation regulation and extracellular matrix(ECM)remodeling were significantly upregulated(P＜0.05).Conclusions The imbalance in endothelial cell proliferation and abnormal ECM remodeling may collectively contribute to PAH pathogenesis.Further exploration of these signaling pathways may provide deep in-sights for early diagnosis and targeted therapy of PAH.

Chronic thromboembolic pulmonary hypertension(CTEPH)is a form of pulmonary hypertension caused by unresolved thrombi and chronic embolization in the pulmonary arteries.In recent years,multi-omics technologies have provided multidimensional insights into CTEPH.Single-cell transcriptomics has identified key pathogenic cell subsets and related mechanisms;Genomics has revealed susceptibility genes associated with coagulation;Proteomics has uncovered differentially expressed proteins closely linked to vascular remodeling;And metabolomics has characterized metabolic reprogramming features and potential sub-typing biomarkers.This review summarizes re-cent advances in these omics fields and discusses their value and prospects in mechanistic exploration,biomarker discovery,and personalized therapeutic strategies.

Objective:To explore the correlation of different HBV DNA loads with peripheral blood lymphocyte subsets and interleukin-6 (IL-6) in patients with chronic hepatitis B.Methods:A cross-sectional study was conducted. A total of 519 patients with chronic hepatitis B admitted to the Fifth Medical Center of the General Hospital of the People′s Liberation Army from April 2019 to June 2024 were included. The patients were divided into high, medium, and low viral load groups and a negative group based on HBV DNA load. Another 100 healthy individuals who underwent physical examinations during the same period were recruited as the control group. The quantities of peripheral blood lymphocyte subsets and IL-6 levels were compared among the groups. Meanwhile, alanine aminotransferase (ALT) levels were recorded and compared among the groups. The correlation of HBV DNA levels with lymphocyte subsets and IL-6 was analyzed using Pearson correlation analysis.Results:HBV DNA loads were negatively correlated with the counts of CD3 +, CD4 +, CD8 +, CD19 +, and CD56 + lymphocyte subsets (correlation coefficients r were -0.483, -0.508, -0.524, -0.573, and -0.561, respectively; all P<0.001) and positively correlated with IL-6 levels ( r=0.862, P<0.05). Compared with the control group, the counts of each lymphocyte subset were higher in the high, medium, and low viral load groups ( P<0.05). In the HBV DNA-negative chronic hepatitis B group, the counts of CD8 + and CD19 + lymphocyte subsets were significantly higher [712.32(526.00,898.64) and 495.62(345.74,645.50) cells/μl] than those in the control group [612.10(479.89,744.31) and 470.32 (396.00,544.64) cells/μl] ( P<0.05). Conclusion:The degree of HBV replication activity in patients with chronic hepatitis B is associated with the immune status of the body, and negatively correlated with the quantities of lymphocyte subsets and positively correlated with IL-6 levels.

Angiopoietin-like proteins(ANGPTLs)are a family of proteins that are structurally similar to angio-poietin.So far,eight ANGPTLs have been discovered,namely ANGPTL1 to ANGPTL8.They are not only angiogenic fac-tors,but also play a pivotal role in various pathophysiological processes such as glucose and lipid metabolism,redox regu-lation,chronic inflammation and cancer,and having a close connection with the occurrence and development of metabolic diseases.This review focuses on the mechanism of action of ANGPTLs in metabolic associated fatty liver disease,in order to make a contribution to the prevention and treatment of MAFLD and concurrent diseases.

Angiopoietin-like proteins(ANGPTLs)are a family of proteins that are structurally similar to angio-poietin.So far,eight ANGPTLs have been discovered,namely ANGPTL1 to ANGPTL8.They are not only angiogenic fac-tors,but also play a pivotal role in various pathophysiological processes such as glucose and lipid metabolism,redox regu-lation,chronic inflammation and cancer,and having a close connection with the occurrence and development of metabolic diseases.This review focuses on the mechanism of action of ANGPTLs in metabolic associated fatty liver disease,in order to make a contribution to the prevention and treatment of MAFLD and concurrent diseases.

Objective:To explore the correlation of different HBV DNA loads with peripheral blood lymphocyte subsets and interleukin-6 (IL-6) in patients with chronic hepatitis B.Methods:A cross-sectional study was conducted. A total of 519 patients with chronic hepatitis B admitted to the Fifth Medical Center of the General Hospital of the People′s Liberation Army from April 2019 to June 2024 were included. The patients were divided into high, medium, and low viral load groups and a negative group based on HBV DNA load. Another 100 healthy individuals who underwent physical examinations during the same period were recruited as the control group. The quantities of peripheral blood lymphocyte subsets and IL-6 levels were compared among the groups. Meanwhile, alanine aminotransferase (ALT) levels were recorded and compared among the groups. The correlation of HBV DNA levels with lymphocyte subsets and IL-6 was analyzed using Pearson correlation analysis.Results:HBV DNA loads were negatively correlated with the counts of CD3 +, CD4 +, CD8 +, CD19 +, and CD56 + lymphocyte subsets (correlation coefficients r were -0.483, -0.508, -0.524, -0.573, and -0.561, respectively; all P<0.001) and positively correlated with IL-6 levels ( r=0.862, P<0.05). Compared with the control group, the counts of each lymphocyte subset were higher in the high, medium, and low viral load groups ( P<0.05). In the HBV DNA-negative chronic hepatitis B group, the counts of CD8 + and CD19 + lymphocyte subsets were significantly higher [712.32(526.00,898.64) and 495.62(345.74,645.50) cells/μl] than those in the control group [612.10(479.89,744.31) and 470.32 (396.00,544.64) cells/μl] ( P<0.05). Conclusion:The degree of HBV replication activity in patients with chronic hepatitis B is associated with the immune status of the body, and negatively correlated with the quantities of lymphocyte subsets and positively correlated with IL-6 levels.

Pulmonary arterial hypertension(PAH)is a complex pulmonary vascular disease characterized by pro-gressive elevation of mean pulmonary artery pressure resulted from the pathological feature of pulmonary vascular re-modeling.Without medical intervention,PAH can eventually lead to right heart failure and death of patients.Up to the present,there are few treatment options for PAH are still mainly function through pulmonary vasodilation.Although these treatments can alleviate symptoms,the prognosis remains poor.In recent years,breakthroughs have been made in understanding the pathogenesis of PAH,thus support the development of new treatment strategies tar-geting at dysregulation of signaling pathways in PAH.This review focuses on five critical pathways and the relevant drugs those entered phase Ⅱ clinical trials and discusses their therapeutic potential,so to provide a basis for future research on targeting therapies for PAH patients.

Nonalcoholic fatty liver disease(NAFLD)has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma.However,the pathogenesis of NAFLD remains unclear,and there is still a lack of specific treatment measures.Sterol regulatory element-binding proteins(SREBP)are an important nuclear transcription factor,which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol,fatty acids,and triglycerides,and therefore,SREBP are a target for the treatment of metabolic diseases.This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD.It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage.Therefore,excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD.In conclusion,SREBP is a promising therapeutic target for NAFLD;the molecular mechanism of SREBP in lipid metabolism is regulated by many factors,and these factors are being deeply explored and analyzed,which has an important clinical significance for the treatment of NAFLD.

Objective To explore the application and prospects of artificial intelligence (AI) in metabolic associated fatty liver disease (MAFLD) based on bibliometrics. Methods Relevant literature on the application of AI technology in MAFLD was retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was conducted using CiteSpace, VOSviewer, R package "bibliometrix", and online bibliometric analysis was platformed to identify hotspots and trends in this field. Results A total of 303 eligible articles were obtained. Since 2017, the number of papers in this field had experienced explosive growth. The United States was leading the research on the application of AI in MAFLD and was the most frequent participant in international cooperation. San Diego of University of California was the institution with the highest number of publications. Rohit Loomba was the author with the highest number of publications, having published 14 articles. The co-cited keyword clustering labels revealed 10 major clusters: digital image analysis, machine learning, computer-aided diagnosis, fibrosis stage, automated quantitative analysis, metaproteomics, non-invasive diagnosis, ultrasonography, electronic health records, and knowledge representation. Current research on the application of AI in MAFLD mainly focused on the diagnosis, differential diagnosis, and staging of MAFLD. Image recognition and analysis, intelligent assisted diagnosis, AI algorithms, and monitoring disease progression will be important research directions for AI in MAFLD. Conclusion Research on the application of AI in MAFLD is experiencing exponential growth. Given enormous potential and clinical application prospects of this field, the application of AI in MAFLD-related areas will remain a research hotspot in the future.