Hepatic sinusoidal capillarization is the first event in the process of fibrogenesis， and inhibiting hepatic sinusoidal capillarization can effectively improve the pathological process of liver fibrosis. Various studies have shown that traditional Chinese medicine can significantly inhibit hepatic sinusoidal capillarization. This article systematically reviews the effective constituents， monomers， and compound prescriptions of traditional Chinese medicine， summarizes their mechanism of action in inhibiting hepatic sinusoidal capillarization， and analyzes the theoretical core of traditional Chinese medicine in inhibiting hepatic sinusoidal capillarization from the perspective of traditional Chinese medicine， in order to provide ideas and literature support for the treatment of liver fibrosis.

Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

OBJECTIVE To investigate the improving effect of Yiqi yangyin huoxue formula on renal injury in immunoglobulin A nephropathy （IgAN） rats， and explore its potential molecular mechanism based on nuclear-enriched abundant transcript 1 （NEAT1）/receptor of activated C kinase 1 （RACK1）/NOD-like receptor family pyrin domain containing 3 （NLRP3） pathway.METHODS SD rats were divided into blank group and model-establishing group. Rats in the model-establishing group were induced to establish IgAN model by combined treatment of bovine serum albumin， carbon tetrachloride and lipopolysaccharide. Rats with successful model establishment were randomly divided into model group， prednisone acetate group （6.25 mg/kg）， low-dose and high-dose Yiqi yangyin huoxue formula groups （11， 22 g/kg）. Each group was intragastrically administered corresponding drugs or normal saline once a day for 6 consecutive weeks. After the last administration， urinary red blood cell count， 24-hour urinary total protein （24 h-UTP）， serum creatinine （Cr）， blood urea nitrogen （BUN）， albumin （ALB）， alanine amino-transferase （ALT） and interleukin-1β （IL-1β） levels were detected. Pathomorphological changes of renal tissues and immunoglobulin A （IgA） deposition in glomerular mesangial region were observed. The mRNA expression of NEAT1， as well as mRNA and protein expression levels of RACK1 and NLRP3 in renal tissues were determined.RESULTS Compared with the blank group， the model group presented glomerular mesangial matrix hyperplasia accompanied by inflammatory cell infiltration， and extensive renal tubular dilation with focal atrophy. The levels of 24 h-UTP， urinary red blood cell count， serum IL-1β， Cr， BUN， ALT， mean fluorescence intensity of IgA deposition in glomerular mesangial area， mRNA expression level of NEAT1， mRNA and protein expression levels of RACK1 and NLRP3 in renal tissues were significantly increased （ P ＜0.05）， while serum ALB level was significantly decreased （ P ＜0.05）. Compared with the model group， the glomerular structure was basically restored and renal tubular injury was obviously alleviated in low-dose and high-dose Yiqi yangyin huoxue formula groups； all the above quantitative indicators were significantly reversed （ P ＜0.05）.CONCLUSIONS Yiqi yangyin huoxue formula can mitigate the inflammatory response and ameliorate renal injury in IgAN rats， and its mechanism may be related to the inhibition of NEAT1/RACK1/NLRP3 pathway activity.

AIM:The study aims to investigate the effects of Huayu-Qutan formula(HYQT)-medicated serum on oleic acid-induced lipid damage and endoplasmic reticulum stress(ERS)in HepG2 cells,and to explore the mecha-nism underlying the prevention and treatment of lipid metabolism disorders by HYQT.METHODS:The HepG2 cells were treated with various concentrations of oleic acid,and CCK8 assay,oil red O staining and ELISA were used to identify the optimal treatment concentration and time of oleic acid and HYQT-medicated serum.Moreover,the cells were divided into control,model,thapsigargin(Tg),and Tg+HYQT groups.Cellular lipid deposition was measured using oil red O staining,while triglyceride(TG)and free fatty acid(FFA)levels were assessed by ELISA.Transmission electron micros-copy was used to examine endoplasmic reticulum structures,and RT-qPCR and Wes fully automated protein quantification analysis system were used to measure the mRNA and protein expression of glucose-regulated protein 78(GRP78),sterol regulatory element binding protein 1c(SREBP1c),acetyl coenzyme A carboxylase(ACC1),fatty acid synthase(FAS)and stearoyl coenzyme A desaturase 1(SCD1)in different groups.RESULTS:Significant lipid deposition was induced in HepG2 cells after treatment with 1 000 μmol/L oleic acid,while treatment with serum containing 10%HYQT for 48 h was found to be optimal.Compared with control group,the cells in model group showed significant deposition of oil red O-stained lipid droplets in the cytoplasm,associated with endoplasmic reticulum expansion,ERS,and nuclear condensa-tion.The TG and FFA levels,and the mRNA and protein expression levels of GRP78,SREBP1c,ACC1,FAS and SCD1 were increased significantly(P<0.01).Compared with model group,the cells treated with HYQT-mediated serum showed marked decrease in the number of lipid droplets in the cytoplasm,with restored endoplasmic reticulum morphology.The TG and FFA levels were significantly reduced(P<0.01),and the mRNA and protein levels of factors related to ERS and de novo fatty acid synthesis were markedly decreased(P<0.01).Treatment with Tg,an ERS agonist,led to greater accu-mulation of cytoplasmic lipid droplets and increased endoplasmic reticulum expansion.Marked variations in the morpholo-gy and size of the endoplasmic reticulum were observed,with fusion and clustering of vacuoles.The TG and FFA levels,and the expression of ERS-and fatty acid synthesis-related factors were increased(P<0.01).Compared with Tg group,the cells treated with Tg+HYQT showed reduced number of cytoplasmic lipid droplets,attenuated endoplasmic reticulum dilation,and decreased number and volume of vacuoles,while the TG and FFA levels and the expression of ERS-and fatty acid synthesis-associated factors were significantly decreased(P<0.01).CONCLUSION:Serum containing HYQT alle-viates oleic acid-induced lipid damage in HepG2 cells by inhibiting ERS-induced de novo synthesis of fatty acids.

Objective:To study the correlation between coronary artery stenosis of coronary computed tomography angiography(CCTA)and computed tomography fractional flow reserve(CT-FFR)in single cardiac cycle.Methods:A total of 100 patients with highly suspected coronary artery stenosis who visited our hospital from Jan 2023 to Jan 2025 were selected as the study subjects.All patients underwent CCTA examination in single cardiac cycle,and the examination results were input into professional software to assess the degree of CCTA coronary artery stenosis,and CT-FFR values of them were measured and calculated.Results:According to the results of CCTA assessment,there were 15 cases with mild stenosis,61 cases with moderate stenosis,and 24 cases with severe stenosis in 100 patients with suspected coronary artery stenosis.The results of Pearson correlation analysis indicated that there was a negative correlation between CCTA coronary artery stenosis and CT-FFR in single cardiac cycle(r=-0.690,P<0.001).The area under curve(AUC)value of the receiver operating characteristic(ROC)curve of CT-FFR was 0.940(95%CI was 0.892-0.989)in assessing coronary artery stenosis,and the sensitivity,specificity,cutoff value and Youden index of that were respectively 0.776,0.933,0.815 and 0.709.Conclusion:There is a close correlation between the degree of CCTA coronary artery stenosis and CT-FFR in single cardiac cycle,which means the smaller CT-FFR value indicates higher degree of CCTA coronary artery stenosis.

Objective:To systematically explore the expression characteristics,molecular functions,and clinical prognostic associations of the SNX22 in thyroid carcinoma(THCA)through bioinformatics analysis and clinical data vali-dation,providing a novel perspective for precision medicine in thyroid cancer.Methods:Gene expression and clinical data of THCA were obtained from the TCGA and GEO databases(GSE3678,GSE65144,GSE82208).R software was used for data preprocessing,differentially expressed gene(DEG)screening,and survival analysis.The expression pat-terns,prognostic value,and immune regulatory roles of SNX22 were evaluated using PPI networks,TIMER/SCNA im-mune correlation analysis,and ESTIMATE scores.Results:Thirteen intersecting DEGs were identified from GEO data-sets,with SNX22 showing significantly higher expression in THCA tumor tissues than in normal tissues(P<0.05).Kaplan-Meier analysis revealed that high SNX22 expression was significantly associated with overall survival(OS)in THCA pa-tients(P=0.001,HR=1.70),with an ROC curve AUC of 0.745.Subgroup analysis indicated significantly elevated SNX22 expression in patients aged≤45 years and with N1 staging(P<0.05).Immune correlation analysis showed that SNX22 expression positively correlated with infiltration of multiple immune cells(P<0.05),while copy number deletions were as-sociated with reduced immune cell infiltration(P<0.05).Conclusion:SNX22 is highly expressed in thyroid cancer and is significantly associated with poor prognosis and immune microenvironment remodeling,thus having the potential to serve as a prognostic marker and immunotherapy target.

Objective To construct a home cardiac rehabilitation program based on mobile healthcare for patients undergoing transcatheter aortic valve replacement(TAVR)and validate its application effectiveness.Methods Based on the best evidence summary,using the Behavior Change Wheel as a framework,15 experts from relevant fields were invited for the Delphi expert consultation to construct a home-based cardiac rehabilitation program and devel-op an intervention system.Using convenience sampling method,72 patients from a tertiary hospital in Zhejiang Province from January to March 2024 were selected as research subjects,and the intervention was implemented from June to August 2024.They were randomly divided into an experimental group and a control group using a random number table method,with 36 cases in each group.The experimental group received a home rehabilitation program based on mobile healthcare on the basis of routine care,while the control group received routine care.The differences in outcome indicators were compared between 2 groups of patients after 12 weeks of intervention.Re-sults The expert authority coefficients for the 2 rounds of Delphi expert inquiry were 0.95,and Kendall's W were 0.591 and 0.414,respectively(P＜0.001).The final draft of the intervention plan includes 6 primary indicators,14 secondary indicators,and 25 tertiary indicators.A total of 70 patients completed the intervention,with 35 in the ex-perimental group and 35 in the control group.Before intervention,there was no statistically significant difference in home cardiac rehabilitation exercise compliance,frailty,and activities of daily living ability between the 2 groups(P＞0.05).After 12 weeks of intervention,the scores of the home-based cardiac rehabilitation exercise adherence scale in the experimental group improved compared to the control group(Z=-7.203,P＜0.001).Conclusion The home reha-bilitation program for TAVR patients based on mobile healthcare is scientific and feasible,and can effectively im-prove patients' exercise compliance with home cardiac rehabilitation.In the future,the rehabilitation program and the system can be continuously optimized in the clinical application to improve patient prognosis.