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 investigate the clinical efficacy and safety of endoscopic ultrasonography-guided(EUS-guided)enterocolon anastomosis in treating patients with malignant bowel obstruction(MBO).Methods The clinical data of 12 patients with MBO,who underwent EUS-guided enterocolon anastomosis at the Nanjing Drum Tower Hospital of China from April 2023 to December 2023,were collected.The perioperative clinical efficacy and safety were retrospectively analyzed.Results Successful EUS-guided enterocolon anastomosis was accomplished in all the 12 patients,with a technical success rate of 100％(12/12).The clinical success rate was 83.3％(11/12),one patient developed obstruction of the stent.The clinical symptoms were relieved in 2-68 hours after treatment,and the time to resume defecation and exhaust was(18.02±15.75)hours.Within one week after the operation,4 patients took liquid diet and 8 patients took semi-fluid diet.Each dimension score of the Quality of Life Core-30 scale of The European Organization for Research and Treatment of Cancer(EORTC QLQ-C30)was remarkably improved,the patient's overall health score was increased from preoperative median 5 points to postoperative 8 points(P＜0.001).During the operation,stent displacement occurred in 2 patients,and the operation was successfully completed after promptly taking remedial measures.After operation,11 patients developed fever(37.5-39.4 ℃),and all the patients were discharged smoothly after symptomatic treatment.No complication such as bleeding,perforation,or stent displacement occurred.Conclusion EUS-guided enterocolon anastomosis is clinically safe and effective,it can effectively relieve the clinical symptoms and improve the quality of life of patients with MBO.

Objective To investigate the value of secreted frizzled-related protein 1(SFRP1),GATA binding protein 3(GATA3)combined with human papillomavirus deoxyribonucleic acid(HPV-DNA)in predicting the risk of postoperative recurrence of high-grade cervical intraepithelial neoplasia(CIN)with positive thin-prep cytologic test(TCT).Methods A total of 200 patients with high-grade CIN and positive TCT results from July 2021 to July 2023 were selected as study subjects.All patients underwent cervical conization,and were divided into recurrence group and non-recurrence group according to the recurrence status one year after surgery.The clinical data,HPV-DNA viral load,and the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cer-vical tissues were compared between the two groups.The HPV-DNA viral load,SFRP1 mRNA,and GATA3 mRNA expression levels in patients with different CIN grades were compared,and their cor-relations with CIN grade and the risk of postoperative recurrence were analyzed.The predictive val-ues of SFRP1,GATA3,and HPV-DNA for the risk of postoperative recurrence were analyzed.Results Among 200 patients,2 were lost during the follow-up period.The recurrence group(n=30)had higher proportions of CIN grade Ⅲ,glandular involvement,positive surgical margins,high-risk human papillomavirus(HPV),higher HPV-DNA viral load,and a higher proportion of HPV positivity at 6 months after surgery compared with the non-recurrence group(n=168),and the differences were statistically significant(P＜0.05).The relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues of the recurrence group were lower than those of the non-recur-rence group,and the differences were statistically significant(P＜0.001).The HPV-DNA level in pa-tients with CIN grade Ⅲ was higher than that in those with CIN grade Ⅱ,and the relative expres-sion levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were lower than those in patients with CIN grade Ⅱ,and the differences were all statistically significant(P＜0.001).Spearman cor-relation analysis showed that HPV-DNA was positively correlated with CIN grade(P＜0.001),while the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were neg-atively correlated with CIN grade(P＜0.001).Logistic regression analysis showed that HPV-DNA,the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were independ-ent influencing factors for the risk of postoperative recurrence(P＜0.001).The receiver operating characteristic(ROC)curve results showed that the areas under the curve(AUCs)for predicting the risk of postoperative recurrence by HPV-DNA,the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were 0.787,0.781,and 0.764,respectively,with sensitivities of 80.00％,76.67％,and 76.67％,and specificities of 74.40％,73.81％,and 67.26％,respec-tively.The AUC for the combined prediction of the risk of postoperative recurrence by the three indica-tors was 0.924,with a sensitivity of 80.00％and a specificity of 93.45％,which was superior to the pre-dictive values of each indicator alone(Z=3.159,3.306,4.018,P＜0.001).Conclusion HPV-DNA,SFRP1,and GATA3 in cervical tissues have certain predictive values for the risk of postoperative re-currence in patients with high-grade CIN and positive TCT results,and combined detection can im-prove the predictive efficacy.

Objective:To explore the predictive value of cervical length(CL)measured at 16-24 weeks of ges-tation for spontaneous preterm birth in twin pregnancies.Methods:A retrospective study was conducted on 1001 twin pregnancy cases,including 569 cases in the spontaneous preterm birth group and 432 cases in the term birth group.Univariate and multivariate Logistic regression analyses were used to identify factors associated with spon-taneous preterm birth.The predictive value of CL for spontaneous preterm birth was analyzed by the receiver op-erating characteristic(ROC)curve.Results:At 16-24 weeks of pregnancy,the CL in the spontaneous preterm birth group(3.460±0.866 cm)was significantly shorter than that in the term birth group(3.711±0.589 cm),and the difference was statistically significant(P=0.005).There were statistically significant differences in the cervical fun-neling and its morphology between the term birth group and the spontaneous preterm birth group(P<0.05).Multivariate Logistic regression analysis showed that monochorionicity(aOR 0.161,95％ CI 0.074-0.351) and CL at 16-24 weeks of pregnancy(aOR 0.655,95％ CI 0.496-0.864) were influencing factors for spontaneous preterm birth(P <0.05).ROC curve analysis indicated that a CL cutoff of 3.045 cm at 16-24 weeks of pregnancy predicted spontaneous preterm birth before 34 weeks,with a sensitivity of 90.2％ ,specificity of 64.9％ ,and an area under the curve of 0.650.Conclusions:Measurement of CL at 16-24 weeks of pregnancy is a potential predictor of spontaneous preterm birth in twin pregnancies.In addition,when establishing a prediction model for spontaneous preterm birth,future research should also consider cervical funnel morphology.

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.