ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

AIM:To investigate the protective effects of Dendrobium officinale polysaccharide(DOP)on high glucose-induced apoptosis in retinal capillary pericytes and its potential mechanism involving mitochondrial function.METHODS:Retinal capillary pericytes were allocated into five groups: normal control(NC), high glucose(HG), and three DOP treatment groups(low, DOP-L; medium, DOP-M; high, DOP-H). Pericyte ultrastructure was analyzed using transmission electron microscopy(TEM). Apoptotic rate was quantified via Annexin V-FITC staining. Mitochondrial transmembrane potential was assessed using the JC-1 probe. Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot were employed to measure expression levels of cytochrome C(Cyt C), B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), Caspase-9, and Caspase-3, respectively.RESULTS:Compared to the NC group, pericytes exposed to HG exhibited significant mitochondrial damage, elevated apoptotic rate, increased mRNA and protein expression of Cyt C, Bax, Caspase-9, and Caspase-3(all P<0.01), alongside a marked reduction in mitochondrial transmembrane potential and expression of Bcl-2 mRNA and protein(all P<0.01). In contrast, DOP treatment groups(DOP-M,DOP-H)dose-dependently ameliorated mitochondrial damage, reduced apoptotic rate, downregulated Cyt C, Bax, Caspase-9, and Caspase-3 expression, enhanced mitochondrial transmembrane potential, and upregulated Bcl-2 expression relative to the HG group(all P<0.05).CONCLUSION:DOP attenuates high glucose-induced apoptosis and mitochondrial injury in retinal capillary pericytes. The underlying mechanism may involve the restoration of mitochondrial transmembrane potential.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective:To observe the effects of moxibustion at Shenshu(BL23)and Zusanli(ST36)on Toll-like receptor 4(TLR4)-myeloid differentiation factor 88(Myd88)signaling pathway-mediated inflammatory factors in the synovial tissue of ankle joints of rats with rheumatoid arthritis(RA),and to explore the molecular and biological mechanisms underlying the anti-inflammatory and analgesic effects.Methods:A total of 24 male Sprague-Dawley(SD)rats were randomly divided into a normal group,a model group,and a moxibustion group,with 8 rats in each group.The RA model was established with exposure to wind,cold,and damp environmental factors,along with Freund's complete adjuvant.After three days of modeling,mild moxibustion was applied to bilateral Shenshu(BL23)and Zusanli(ST36)in the moxibustion group using moxa sticks of 0.9 cm in diameter for 30 min each time,once a day for 14 d.Structural changes in the synovial tissue and cells were then observed using hematoxylin-eosin staining and transmission electron microscopy,while immunohistochemistry analysis was used to detect tumor necrosis factor(TNF)-α,interleukin(IL)-17,IL-1β,and IL-6 levels.Moreover,the protein expression levels of Myd88,TLR4,and transient potential receptor vanilloid type 1(TRPV1)in the synovial tissue were detected using Western blotting,while their mRNA expression levels were detected using reverse transcription-polymerase chain reaction.Finally,the levels of IL-1β,IL-2,IL-6,IL-17A,and TNF-α in rat serum were detected using enzyme-linked immunosorbent assay.Results:Compared to the normal group,the model group exhibited notable pathological synovial tissue damage,along with significantly higher IL-1β,IL-6,and TNF-α levels(P<0.01)and a slightly higher IL-17 content(P>0.05).Furthermore,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly higher in the model group than in the normal group(P<0.01).Compared to the model group,the moxibustion group exhibited a lower degree of synovial tissue pathological damage,along with significantly lower IL-1β,IL-6,and TNF-α levels(P<0.05 or P<0.01)and a lower IL-17 content without statistical significance(P>0.05).Moreover,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels,and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly lower in the moxibustion group than in the model group(P<0.01 or P<0.05).Conclusion:Mild moxibustion at Shenshu(BL23)and Zusanli(ST36)can effectively inhibit TLR4-MyD88 signaling pathway-mediated inflammatory factor expression in the synovial tissue of ankle joints of RA rats.Furthermore,the effect of moxibustion on synovial tissue inflammation in RA rats may be attributed to TRPV1 channel activation.

Objective:To investigate the effect and safety of etonogestrel implant and levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis.Methods:Eighty patients with adenomyosis in Northwest Women's and Children's Hospital were selected from September 2021 to September 2023. According to the random number table method, they were divided into observation group and control group, with 45 cases in each group. The patients in observation group were treated with etonogestrel implant, while the patients in control group were given LNG-IUS. The uterine conditions, visual analogue scale (VAS) score, menstrual pattern, sex hormones [estradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH)] and laboratory indicators [hemoglobin, serum ferritin (SF) and carbohydrate antigen 125] before treatment and after 12 months of treatment and incidence of adverse reactions were compared between the two groups of patients. Measurement data were expressed as xˉ±s. Repeated measures analysis of variance was used for comparison between the two groups at multiple time points. LSD-t test was used for pairwise comparison. Two independent sample t test was used for comparison between the two groups. Paired t test was used for comparison before and after treatment. Enumeration data were expressed as n (%), and χ2 test was used for comparison between groups. Results:After 12 months of treatment, the uterine volume and endometrial thickness in observation group and control group were reduced compared to before treatment [observation group: (122.72±13.52) cm 3 vs. (202.72±20.75) cm 3, (6.83±1.35) mm vs. (9.84±1.76) mm, t=21.67,9.10, respectively, both P<0.001; control group: (134.82±17.64) cm 3 vs. (203.46±20.03) cm 3, (7.52±1.52) mm vs. (9.79±1.82) mm, t=17.25,6.42, respectively, both P<0.001], and the indicators in observation group were lower than those in control group ( t=3.65, 2.28, P<0.001, P=0.025, respectively). The levels of estradiol, LH and FSH were lower than those before treatment[observation group: (1.40±0.30) nmol/L vs. (2.42±0.41) nmol/L, (10.12±1.14) U/L vs. (12.84±2.63) U/L, (5.32±0.87) U/L vs. (9.34±1.35) U/L, t=13.47,6.36,10.03, respectively, all P<0.001; control group: (1.68±0.33) nmol/L vs. (2.40±0.48) nmol/L, (11.41±1.53) U/L vs. (12.96±2.25) U/L, (7.03±1.04) U/L vs. (9.53±1.31) U/L, t=8.29,3.82,16.79, respectively, all P<0.001], and the observation group had lower levels than the control group( t=4.21,4.54,8.46, respectively, all P<0.001). Hemoglobin and SF levels were higher than those before treatment, and the levels in observation group were higher than those in control group [observation group: (116.46±3.07) mg/L vs. (109.46±3.64) mg/L, (117.33±16.46) μg/L vs. (53.82±7.52) μg/L, t=9.86,18.95, respectively, both P<0.001; control group: (114.63±3.48) mg/L vs. (110.63±3.48) mg/L, (95.34±12.63) μg/L vs. (52.58±8.21) μg/L, t=5.45,23.61, respectively, both P<0.001], and the levels in observation group were higher than those in control group( t=2.64,7.11, P=0.010, P<0.001, respectively). The level of carbohydrate antigen 125 was lower than that before treatment, [observation group:(40.31±3.10) kU/L vs.(68.31±4.75) kU/L, t=33.12, P<0.001;control group:(57.45±4.27) kU/L vs.(67.64±4.83) kU/L, t=10.60, P<0.001], and the level in observation group was lower than that in control group ( t=21.79, P<0.001). At 3, 6 and 12 months after treatment, the VAS score in both group decreased gradually, and the scores in observation group were lower than those in control group [(4.35±0.88) points vs. (4.71±0.75) points, (3.21±0.73) points vs. (3.63±0.82) points, (2.64±0.51) points vs. (3.16±0.64) points, all P<0.05]. Before treatment, there was no statistically significant difference in menstrual patterns between the two groups of patients ( P>0.05). After 12 months of treatment, the proportion of normal menstrual patterns in the implant group was higher than that in the sustained-release group [68.9% (31/45) vs. 46.7% (21/45), χ2=4.56, P=0.033], while the proportion of frequent bleeding was lower than that in the sustained-release group [6.7% (3/45) vs. 22.2% (10/45), χ2=4.41, P=0.036]. There was no statistical significant difference in the incidence of adverse reactions between the two groups during treatment [8.9% (4/45) vs. 11.1% (5/45), χ2=0.00, P=1.000]. Conclusion:Compared with LNG-IUS, etonogestrel can more effectively improve the uterine conditions, relieve the dysmenorrhea symptoms, and improve the blood related indicators, and with high safety.

Objective:To evaluate whether there is a difference between the lesion volumes detected by 18F-FDG PET/CT imaging and 11C-choline PET/CT imaging based on different threshold delineation methods in patients with nasopharyngeal carcinoma, and to recommend a more clinically appropriate threshold method with reference to lesion volume detected by enhanced MRI. Methods:A retrospective study was conducted on 37 patients(27 males, 10 females, age (51.2±11.9) years) with nasopharyngeal carcinoma diagnosed in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between October 2015 and May 2017. All patients underwent nasopharyngeal enhanced MRI, 18F-FDG PET/CT and 11C-choline PET/CT scans. Advantage Workstation 4.6 software was used to fuse images of the 3 imaging examinations. The lesion contour was sketched manually based on enhanced MRI sequences to obtain VMRI, and the lesion was sketched in PET images to obtain the corresponding metabolic tumor volume (MTV) by absolute threshold method, relative threshold method and background threshold method respectively. The correlation between ROIs sketched by different threshold methods and ROI in MRI was evaluated by using the Dice similarity coefficient (DSC). Friedman test or repeated measures analysis of variance (corrected by Greenhouse-Geisser) was employed to analyze the differences of MTV or DSC obtained by using 3 threshold methods. Wilcoxon signed-rank test or paired t-test was used to compare the data of different imaging methods. Results:In 18F-FDG PET/CT results, MTVs obtained by using the absolute threshold method, relative threshold method, and background threshold method were 13.21(5.47, 23.16), 10.13(5.67, 16.81), and 13.68(5.77, 25.52)mm 3, respectively, with significant differences ( χ2=17.89, P<0.001). The corresponding DSC differences for the 3 methods were also significant (0.43±0.19, 0.38±0.17 and 0.44±0.17; F=16.35, P<0.001). In 11C-choline PET/CT results, MTV differences based on the 3 threshold methods were significantly different (14.96(6.80, 32.27), 16.28(12.23, 32.47) and 18.97(14.38, 37.02)mm 3;χ2=10.45, P=0.005), and the DSC differences were also significant (0.52±0.21, 0.58±0.13 and 0.62±0.13; F=16.37, P<0.001). The differences in MTV and DSC between FDG and choline groups were also significant ( Z=-3.87, t=-5.57, both P<0.001). The differences between MTVs of 18F-FDG imaging/ 11C-choline imaging and VMRI (24.35(14.48, 36.89)mm 3) were all significantly different ( Z values: from -5.03 to -2.59, all P<0.05). Conclusions:Compared with 18F-FDG PET/CT, the preoperative 11C-choline PET/CT imaging in patients with nasopharyngeal carcinoma is closer to enhanced MRI (gold standard) in the lesion delineation. Compared with ROIs of the other 2 threshold delineation methods, the ROI obtained by the background threshold method is closer to that in enhanced MRI.

Objective:To evaluate the clinical value of 11C-methyl- L-methionine (MET) PET/MR in the differential diagnosis between neoplastic and non-neoplastic brain lesions. Methods:From July 2017 to May 2022, a total of 34 patients (19 males, 15 females, age 8-81 years) who received 11C-MET PET/MR imaging for suspected brain tumors in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively enrolled. Postoperative pathological or clinical follow-up results were used as the gold standard. Diagnostic performance of 11C-MET PET/MR and contrast-enhanced MRI was evaluated by ROC curve analysis and Delong test, as well as the diagnostic performance of PET metabolic parameters (SUV and target to background ratio (TBR)), MRI multi-sequence parameters (cerebral blood flow (CBF), relative CBF (rCBF), apparent diffusion coefficient (ADC), relative ADC (rADC), choline/creatine (Cho/Cr) and choline/ N-acetylaspartate (Cho/NAA)) and their combination. Results:A total of 35 lesions of 34 patients were enrolled, including 12 (34.3%) non-neoplastic lesions and 23(65.7%) neoplastic lesions. The diagnostic sensitivity, specificity, and accuracy for 11C-MET PET/MR were 91.3%(21/23), 12/12, and 94.3%(33/35), in contrast to 16/18, 2/10, and 64.3%(18/28) for contrast-enhanced MRI. Maximum TBR (TBR max) showed the highest discriminative value (AUC=0.877, 95% CI: 0.692-1.000). The combination of TBR max, minimum ADC (ADC min), rCBF, and Cho/NAA could achieve a higher diagnostic performance (AUC=0.918, 95% CI: 0.816-1.000), although the difference was not statistically significant ( Z=-0.42, P=0.676). Conclusion:Multiple quantitative parameters of 11C-MET PET/MR are beneficial to distinguish neoplastic from non-neoplastic brain lesions, and their combination may improve the diagnostic confidence.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.