As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

Inherited thrombocytopenia is a group of heterogeneous inherited diseases mainly characterized by platelet count defects. It is a monogenic disease caused by mutations in various genes. Animal models are crucial for studying the pathogenesis and treatment strategies of inherited thrombocytopenia. Previous reviews on animal models of inherited thrombocytopenia have mostly focused on a single species, such as mice or zebrafish. This article systematically summarizes the construction, phenotypes, and characteristics of multiple animal models (mice, zebrafish, and primate animal) of inherited thrombocytopenia-causing genes, thereby providing a systematic reference for a comprehensive understanding of the research progress of its animal models.

ObjectiveBased on the established characteristic profiles， quantitative analysis of multiple components， and chemometric analysis of Taraxacum mongolicum， the quality of different T. mongolicum germplasms was evaluated at the chemical level， thereby providing a reference for the screening of high-quality germplasms and the rational utilization of wild resources. MethodsAn ultra-performance liquid chromatography （UPLC） was employed to establish characteristic profiles. Principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA） were then adopted to screen and comprehensively rank marker compounds. ResultsThe UPLC fingerprint of T. mongolicum germplasm identified 13 chromatographic peaks corresponding to gallic acid， coumaric acid， neochlorogenic acid， monocaffeoyltartaric acid， chlorogenic acid， cryptochlorogenic acid， caffeic acid， p-coumaric acid， cichoric acid， luteoloside， isochlorogenic acid B， isochlorogenic acid A， and isochlorogenic acid C. Combined with chemometric analysis such as PCA and PLS-DA， eight core markers （cichoric acid， luteoloside， cryptochlorogenic acid， isochlorogenic acid B， chlorogenic acid， caffeic acid， isochlorogenic acid C， and isochlorogenic acid A） were screened for distinguishing wild and cultivated germplasms. Additionally， eight core markers （cichoric acid， caffeic acid， luteoloside， chlorogenic acid， cryptochlorogenic acid， isochlorogenic acid A， monocaffeoyltartaric acid， and neochlorogenic acid） were selected for the evaluation and screening of different T. mongolicum germplasms. ConclusionThis study establishes a UPLC analysis method capable of simultaneously determining 13 characteristic components in T. mongolicum， such as cichoric acid and chlorogenic acid， as well as their precursor compound contents in the biosynthetic pathway. Based on the above methods， three T. mongolicum germplasms （PGY-004， PGY-009， and PGY-010） with promising medicinal potential are selected for subsequent research on variety breeding. The present study provides a reference for quality control of Taraxacum mongolicum， germplasm screening， and the rational development and utilization of wild resources.

OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2，5-diene-1，4-cyclohexanedione （DMDD）， an active component from Averrhoa carambola root， on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 （NCOA4/FTH1/ATG8） axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-， medium-， and high-dose （12.5， 25， 50 mg/kg） groups， while an additional non-modeled control group was established， with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration， the levels of fasting blood glucose （FBG）， serum lactate dehydrogenase （LDH）， and creatine kinase isoenzyme MB （CK-MB） were measured. Myocardial pathological changes， degree of fibrosis， and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4， FTH1， ATG8， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in cardiac tissue were measured. RESULTS Compared with model group， each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels， the myocardial cell death index and NCOA4 protein positive index，the protein expression levels of NCOA4， FTH1， and ATG8 in cardiac tissue were significantly decreased （ P ＜0.001）， while the protein expression levels of SLC7A11 and GPX4 were significantly increased （ P ＜0.001）. CONCLUSIONS DMDD can reduce blood glucose levels， alleviate myocardial histopathological injury， and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.

ObjectiveTo investigate the mechanism of Guizhi Fulingwan （GFW） against hepatic fibrosis， focusing on elucidating the regulatory effect of GFW on the mitochondrial DNA （mtDNA）/NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific proteinase-1 （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsForty-two male Sprague-Dawley （SD） rats were randomly allocated into six groups （n=7）： control， model， low/medium/high-dose （0.14， 0.28， 0.56 g·kg^-1·d^-1） GFW （GFW-L， GFW-M， GFW-H）， and Dahuang Zhechong pills （DZW， 1.8 g·kg^-1·d^-1）. The rat model of hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. General conditions of the rats were observed. Serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured. Liver histopathology and collagen deposition were observed through hematoxylin and eosin （HE） staining and Masson's trichrome staining. Transmission electron microscopy （TEM） was employed to observe structural alterations and damage of cellular ultrastructures including mitochondria. Mitochondrial membrane potential （MMP， ΔΨ_m） was detected by flow cytometry. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of mtDNA and NLRP3 in the liver tissue were quantified by Real-time polymerase chain reaction （Real-time PCR）. The protein levels of key molecules in the NLRP3/Caspase-1/GSDMD signaling pathway in the liver tissue were determined by Western blot. ResultsCompared with the control group， the model group exhibited a decrease in body weight （P<0.01）， an increase in liver index （P<0.01）， elevations in serum ALT and AST levels （P<0.01）， and typical fibrotic features such as disorganized hepatocytes， inflammatory infiltration， and increased collagen deposition in the liver tissue. TEM revealed significant karyotheca degeneration， mitochondrial swelling， endoplasmic reticulum expansion， and organelle efflux in the model group. In addition， the model group showed decreased ΔΨ_m （P<0.01）， up-regulated mRNA levels of mtDNA and NLRP3 （P<0.01） and protein levels of NLRP3， Caspase-1， and GSDMD （P<0.01） in the liver tissue， and increased serum levels of IL-1β and IL-18 （P<0.01）. Compared with that in the model group， the body weight increased in GFW-L， GFW-M， and DZW groups （P<0.05） and markedly increased in the GFW-H group （P<0.01）. The liver index decreased in the GFW groups and DZW group （P<0.01）. The serum ALT level declined in the GFW-L group （P<0.05）， and the serum ALT and AST levels decreased in the GFW-M， GFW-H， and DZW groups （P<0.01）. Histopathological damage and fibrosis were alleviated to varying degrees， and TEM revealed mitigated ultrastructural injuries including mitophagy， mitochondrial swelling， and endoplasmic reticulum expansion in the drug intervention groups. The ΔΨ_m increased in GFW groups without statistical significance. The mRNA level of mtDNA in the liver tissue was down-regulated in the GFW-M （P<0.05）， GFW-H （P<0.01）， and DZW （P<0.01） groups. The mRNA level of NLRP3 was down-regulated in GFW-M， GFW-H， and DZW groups （P<0.01）. Western blot analysis showed significantly down-regulated protein level of NLRP3 in all the GFW groups and the DZW group （P<0.01）. The protein level of GSDMD-N was down-regulated in GFW-H and DZW groups （P<0.01）. The protein level of cleaved Caspase-1 was down-regulated in GFW-M （P<0.05）， GFW-H （P<0.01）， and DZW （P<0.01） groups. In addition， the serum levels of IL-1β and IL-18 declined in GFW-H and DZW groups （P<0.01）. ConclusionGFW can suppress pyroptosis to ameliorate CCl₄-induced hepatic fibrosis， potentially through mitigating mitochondrial damage， inhibiting inflammasome assembly and activation， and blocking pro-inflammatory cytokine release.

Non-alcoholic fatty liver disease （NAFLD） is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease， and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase （AMPK）， as a regulatory hub for maintaining cellular energy homeostasis， can coordinate key cellular processes such as adipogenesis， glucose metabolism， and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis， enhancing mitochondrial β-oxidation， regulating inflammation and oxidative stress， and promoting autophagy. Accordingly， AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine （TCM）， with low toxicity， high accessibility， and multi-component， multi-target synergistic effects， has demonstrated unique value in NAFLD treatment， particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM， and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 （SIRT1） and peroxisome proliferator-activated receptor α （PPARα）. They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets， exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years， elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment， basic research， and drug development.

ObjectiveTo determine whether Jinshui Huanxian component formula Ⅱ （ECC-JHF Ⅱ） and matrix hardness interfere with the process of epithelial-mesenchymal transition （EMT） during pulmonary fibrosis by regulating integrin β₁ （ITG β₁）， and to elucidate the underlying mechanism. MethodsA pulmonary fibrosis mouse model was established by a single intratracheal instillation of bleomycin （BLM）. To observe the disease progression at various time points， the mice were sacrificed before modeling and on days 7， 14， 21， 28 and 42 after modeling for assessment of relevant indicators. To evaluate the therapeutic effect of drug intervention， the mice were given ECC-JHF Ⅱ and pirfenidone （PFD） by gavage starting on day 29 after modeling for 14 days of treatment， after which the mice were sacrificed. Pulmonary function， pathological changes， collagen deposition， lung tissue hardness and EMT markers were detected. Polyethylene glycol （PEG） composite hydrogels with different hardness were prepared in vitro using biomaterials such as eight-arm polyethylene glycol thiol （PEG-SH） and eight-arm polyethylene glycol maleimide （PEG-MAL）. Human type Ⅱ alveolar epithelial cells cultured in hard matrix culture dishes were treated with low， medium， and high doses of ECC-JHF Ⅱ （15.31， 30.63， 61.25 mg·L^-1） to observe the intervention effect of ECC-JHF Ⅱ on EMT induced by transforming growth factor beta 1 （TGF-β₁）. Human type Ⅱ alveolar epithelial cells cultured on soft （3.8 kPa） and hard （culture dishes， ~ GPa） matrices were treated with ECC-JHF Ⅱ， respectively. The mRNA and fluorescence expression levels of the epithelial marker E-cadherin （CDH1）， the mesenchymal marker N-cadherin （CDH2） and vimentin （VIM）， as well as ITG β₁， were detected by real-time quantitative polymerase chain reaction （Real-time PCR） and immunofluorescence. Western blot was used to detect the protein expression of CDH1， CDH2 and ITG β₁， and the biomechanical mechanism of ECC-JHF Ⅱ on EMT and pulmonary fibrosis was further verified by knocking down and specific activation of ITG β₁. ResultsECC-JHF Ⅱ treatment improved BLM-induced pulmonary fibrosis in mice， as evidenced by significantly increased minute ventilation （MV） and 50% expiratory flow at tidal volume （EF₅₀） （P<0.05）， and significantly increased tidal volume （TV） after treatment （P<0.01） compared with the model group. Immunohistopathological analysis revealed attenuated inflammation and alveolar injury， reduced deposition of type Ⅰ collagen （Col-Ⅰ）， and significantly decreased lung tissue stiffness （P<0.01）， thereby alleviating disease progression. The real-time PCR results showed that， compared with the model group， the ECC-JHF Ⅱ group showed increased CDH1 expression and decreased CDH2 and VIM expression in mouse lung tissues （P<0.05， P<0.01）， indicating that ECC-JHF Ⅱ inhibited the EMT process to ameliorate pulmonary fibrosis. In vitro experimental results showed that both ECC-JHF Ⅱ and matrix softening reversed the EMT phenotype switch. Specifically， compared with the hard matrix group， the cells cultured on the soft matrix exhibited significantly upregulated expression of the epithelial marker CDH1 （P<0.01） and significantly downregulated expression of the mesenchymal markers CDH2 and VIM （P<0.05）. Furthermore， ECC-JHF Ⅱ inhibited the expression of ITG β₁ both in vitro and in vivo. Knockdown and specific activation of ITG β₁ further confirmed that ITG β₁ is involved in the regulatory process by which ECC-JHF Ⅱ inhibits EMT and ameliorates pulmonary fibrosis. ConclusionECC-JHF Ⅱ and matrix softening can block the EMT process and ameliorate pulmonary fibrosis， and the underlying mechanism may be associated with the inhibition of ITG β₁-mediated mechanotransduction. This study reveals a novel mechanism of ECC-JHF Ⅱ intervention in pulmonary fibrosis from a biomechanical perspective.

Acute lung injury （ALI） is a critical respiratory emergency caused by various non-cardiogenic factors， including severe pulmonary and extrapulmonary infections， lung contusion， and sepsis. Its pathological features are centered on alveolar-capillary barrier dysfunction， uncontrolled inflammatory responses， and impaired alveolar fluid clearance， manifesting as refractory hypoxemia and respiratory distress， with a poor clinical prognosis. Modern studies have revealed that mitochondrial dysfunction and glucose metabolic reprogramming in macrophages， characterized by hyperactivated glycolysis， drive pro-inflammatory polarization and represent a key mechanism leading to excessive inflammatory responses and disease progression in ALI. Therefore， targeting macrophage glycolysis may be a potential therapeutic strategy for ALI. The Plain Questions： Special Discussion on Channels and Vessels in Huangdi's Internal Classic states that "The spleen disseminates essence upward to the lungs". When the spleen fails in transport and transformation， the distribution of refined nutrients becomes disordered， resulting in the endogenous generation of turbid pathogens that obstruct the pulmonary collaterals， causing failure of lung dispersion and descent and leading to dyspneic reversal. This forms the dynamic pathological pattern of ''deficiency in the root with excess in the manifestation''， thereby proposing the core pathogenesis of ALI as ''spleen deficiency with transport dysfunction and turbid pathogens obstructing the lungs''. This process is intrinsically associated with the inflammatory cascade triggered by disordered macrophage glucose metabolism. Taking the theory of ''spleen failing to disperse essence'' as the entry point， the present study systematically elucidates the progressive pathological mechanism of "energy metabolism disorder-cytokine storm'' in ALI from the perspectives of the ''spleen deficiency-turbid obstruction'' pathogenesis and macrophage glycolysis-pro-inflammatory polarization. In addition， we summarize Chinese medicine compound formulas and monomeric components that ''restore spleen transport and eliminate turbid pathogens''， and explore their potential mechanisms in the treatment of ALI by regulating macrophage metabolic phenotypes to improve the state of ''spleen failing to disperse essence''. This provides a molecular basis for elucidating the ''spleen-lung'' energy metabolism dialogue， deepens understanding of the multi-target regulatory mechanisms of herbal prescriptions， and promotes the deep integration of classical theory with modern medicine.

Background The association between occupational physical activity (OPA) and cardiometabolic risk factors remains controversial, potentially due to differences in the associations between OPA and various cardiometabolic indicators, as well as the lack of a clearly defined optimal OPA range for multiple-indicator synergistic benefits. Objective To investigate the relationship between OPA and cardiometabolic risk factors in individuals at high risk of cardiovascular disease (CVD) in Hubei Province, and to explore an optimal OPA range for multi-indicator improvements. Methods Data were derived from the Hubei Province dataset of the China Health Evaluation And Risk Reduction Through Nationwide Teamwork from 2015 to 2023, including 19028 high-risk CVD individuals. OPA (metabolic equivalent·h·d⁻¹, MET·h·d⁻¹) was assessed using the China Kadoorie Biobank physical activity questionnaire, anthropometric measurements (height, weight, waist circumference) and cardiometabolic indicators (blood pressure, fasting blood glucose, lipid profiles) were measured. Multivariate logistic regression was used to analyze the association between logOPA quartiles (Q1-Q4) and abnormal cardiometabolic indicators, while restricted cubic spline (RCS) models were employed to explore their dose-response relationships. Subgroup and interaction analyses were also conducted by gender. Results The median OPA of all participants was 12.86 MET·h·d⁻¹ (male: 14.40 MET·h·d⁻¹, female: 11.14 MET·h·d⁻¹). After adjusting for confounders, compared with the Q1 group, logOPA in the Q4 group was associated with 20% (OR=0.80, 95%CI: 0.72, 0.89), 14% (OR=0.86, 95%CI: 0.78, 0.96), and 13% (OR=0.87, 95%CI: 0.79, 0.95) reduction in the risk of abdominal obesity, low high-density lipoprotein cholesterol (HDL-C), and metabolic syndrome (MS), respectively, and 33% (OR=1.33, 95%CI: 1.18, 1.49), 33% (OR=1.33, 95%CI: 1.18, 1.50), and 38% (OR=1.38, 95%CI: 1.21, 1.57) increase in the risk of high total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), and high non-HDL-C, respectively. Similar trends were observed in males and females, with significant positive associations of logOPA with high TC and high non-HDL-C in males (P_interaction<0.05). The risk of low HDL-C decreased rapidly when logOPA was more than 2.213 (OPA>9.14 MET·h·d⁻¹), showing an inverted L-shaped trend. The risk of high TC, high LDL-C, and high non-HDL-C increased beyond logOPA thresholds of 3.244, 2.476, and 3.377 (OPA >25.64, 11.89, and 29.28 MET·h·d⁻¹), respectively, showing a J-shaped trend. However, logOPA exhibited a U-shaped nonlinear dose-response relationship with blood pressure and fasting blood glucose abnormalities (P_non-linear<0.05) , with minimal risks at logOPA 2.969 and 2.372 (OPA of 19.47 and 10.72 MET·h·d⁻¹). Conclusion OPA exhibits heterogeneous dose-response patterns across cardiometabolic indicators. Integrating the inverted L-, J-, and U-shaped association patterns, we suggest an optimal OPA range of 9.14−25.64 MET·h·d⁻¹ for multiple cardiometabolic indicators in total individuals at high-risk of CVD, with ranges of 9.61−31.34 MET·h·d⁻¹ for males and 8.97−22.87 MET·h·d⁻¹ for females. These findings provide critical evidence for developing OPA interventions strategies targeting high-risk population for CVD.

Objective To monitor the dynamic changes in liver stiffness and their correlation with clinical indicators among chronic hepatitis B virus (HBV) infected individuals in Wuwei City, Gansu Province, and to provide important evidence for the early detection and effective intervention of liver fibrosis (LF) progression. Methods Based on the Wuwei Hepatitis B Specialty Cohort, this study conducted annual serological and FibroScan ultrasonographic examinations for 3 882 chronic HBV-infected individuals. Over an average of 4 years of follow-up, the liver fibrosis outcome was monitored, and influencing factors were analyzed by constructing a logistic regression model. Results Among the 2 053 chronic HBV-infected individuals who completed at least one follow-up, baseline LF grades F0 to F4 were distributed as follows: 1 581 cases (77.0%), 164 cases (8.0%), 99 cases (4.8%), 110 cases (5.4%), and 99 cases (4.8%), respectively. Significant differences were observed among the five groups in terms of age, gender, smoking, antiviral treatment, liver function indicators, control attenuation index (CAP), and liver stiffness measurement (LSM) (P<0.05). After an average of 4 years of follow-up, 1 686 cases (17.9/100 person-years) showed no significant change in LF grade, 260 cases (2.8/100 person-years) demonstrated a decrease in LF grade, and 107 cases (1.1/100 person-years) exhibited an increase in LF grade. Stratified by baseline treatment status, among patients with chronic HBV infection who did not undergo treatment, baseline alanine aminotransferase (ALT) (OR=5.50, 95%CI：1.79-16.83, P=0.003) and LSM (OR=3.35, 95%CI：1.23-9.13, P=0.018) were identified as risk factors for LF progression. In contrast, among patients who underwent antiviral treatment, baseline aspartate aminotransferase (AST) (OR=2.23, 95%CI：1.41-3.53, P<0.001) and total bilirubin (TBIL) (OR=1.79, 95%CI：1.14-2.81, P=0.012) levels were identified as risk factors for LF progression. Conclusion LSM and liver function indicators, such as ALT, AST, and TBIL, are important influencing factors for LF progression. The monitoring of LSM and liver function indicators will be of great significance for the prevention and early diagnosis of liver cirrhosis.