Objective: To develop a dual-branch deep learning framework for accurate multi-label classification of fundus diseases, addressing the key limitations of insufficient complementary feature extraction and inadequate cross-modal feature fusion in existing automated diagnostic methods. Methods: The fundus multi-label classification dataset with 12 disease categories (FMLC-12) dataset was constructed by integrating complementary samples from Ocular Disease Intelligent Recognition (ODIR) and Retinal Fundus Multi-Disease Image Dataset (RFMiD), yielding 6 936 fundus images across 12 retinal pathology categories, and the framework was validated on both FMLC-12 and ODIR. Inspired by the holistic multi-regional assessment principle of the Five Wheels theory in traditional Chinese medicine (TCM) ophthalmology, the dual-branch multi-label network (DBMNet) was developed as a novel framework integrating complementary visual feature extraction with pathological correlation modeling. The architecture employed a TransNeXt backbone within a dual-branch design: one branch processed red-green-blue (RGB) images to capture color-dependent features, such as vascular patterns and lesion morphology, while the other processed grayscale-converted images to enhance subtle textural details and contrast variations. A feature interaction module (FIM) effectively integrated the multi-scale features from both branches. Comprehensive ablation studies were conducted to evaluate the contributions of the dual-branch architecture and the FIM. The performance of DBMNet was compared against four state-of-the-art methods, including EfficientNet Ensemble, transfer learning-based convolutional neural network (CNN), BFENet, and EyeDeep-Net, using mean average precision (mAP), F1-score, and Cohen's kappa coefficient. Results: The dual-branch architecture improved mAP by 15.44 percentage points over the single-branch TransNeXt baseline, increasing from 34.41% to 44.24%, and the addition of FIM further boosted mAP to 49.85%. On FMLC-12, DBMNet achieved an mAP of 49.85%, a Cohen’s kappa coefficient of 62.14%, and an F1-score of 70.21%. Compared with BFENet (mAP: 45.42%, kappa: 46.64%, F1-score: 71.34%), DBMNet outperformed it by 4.43 percentage points in mAP and 15.50 percentage points in kappa, while BFENet achieved a marginally higher F1-score. On ODIR, DBMNet achieved an F1-score of 85.50%, comparable to state-of-the-art methods. Conclusion DBMNet effectively integrates RGB and grayscale visual modalities through a dual-branch architecture, significantly improving multi-label fundus disease classification. The framework not only addresses the issue of insufficient feature fusion in existing methods but also demonstrates outstanding performance in balancing detection across both common and rare diseases, providing a promising and clinically applicable pathway for standardized, intelligent fundus disease classification.

ObjectiveTaking Aurantii Fructus Immaturus juice（AFI）-processed Atractylodis Macrocephalae Rhizoma（AMR） as an example， this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products， investigate the key differential components， evaluate their anti-inflammatory activities， and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry（GC-MS） and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology（NIST）17 database， comparison with retention index（RI） and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine （TCM） spectral library， in conjunction with PubChem and MassBank， characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） value >1. Components with high log₂fold change（FC） among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide（NO） production in a lipopolysaccharide（LPS）-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay（ELISA） was used to detect the effects of the differential components on tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6， and monocyte chemotactic protein（MCP）-1 levels， and immunofluorescence（IF） was employed to assess their effects on nuclear transcription factor（NF）-κB p65 translocation， thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR， among which， sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components， 36 compounds were identified， and the main differential components were flavonoids， sesquiterpenoids， and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products， representing compounds directly introduced during processing. Five compounds， including atractylenolide Ⅲ， tangeritin， nobiletin， hesperidin and narirutin， were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L^-1 tangerine and narirutin could significantly inhibit LPS-induced NO production（P<0.01） in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7（P<0.05）， while narirutin significantly inhibited the levels of TNF-α， IL-1β， MCP-1 and IL-6（P<0.01）. IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR， and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.

OBJECTIVE To compare the antihypertensive efficacy of sacubitril/valsartan versus benazepril in patients with perimenopausal hypertension， as well as their impacts on ventricular remodeling and inflammatory fibrosis. METHODS A total of 206 perimenopausal hypertensive patients in our hospital from January 1， 2023 to December 30， 2024 were retrospectively included.These patients were enrolled and divided into benazepril group （105 cases） and sacubitril/valsartan group （101 cases）. Benazepril group received Benazepril hydrochloride tablet， and sacubitril/valsartan group received Sacubitril valsartan sodium tablet. All patients were treated for 6 months. The blood pressure（systolic blood pressure and diastolic blood pressure） and blood pressure control status before and after treatment， echocardiographic indicators （left ventricular ejection fraction， left ventricular mass index， relative wall thickness， and early-diastolic peak transmitral flow velocity/early-diastolic peak velocity of the mitral annulus）， inflammatory fibrosis related indicators（high-sensitivity C-reactive protein，ratio of monocytes to lymphocytes，and ratio of neutrophils to lymphocytes）， as well as the occurrence of adverse reactions（hypotension，hyperkalemia，and angioedema） were observed in both groups before and after treatment. RESULTS The blood pressure control rate was significantly higher in the sacubitril/valsartan group than in benazepril group （ P ＜0.05）. After treatment， the blood pressure， echocardiographic indicators（except for left ventricular ejection fraction） ，and inflammatory fibrosis related indicators were significantly lower than those before treatment within the same group， and the sacubitril/valsartan group were significantly lower than the benazepril group （ P ＜0.05）. There were no statistically significant differences in the incidence of hypotension， hyperkalemia， angioedema， and overall adverse drug reactions between the two groups （ P ＞0.05）. CONCLUSIONS Compared with benazepril， sacubitril/valsartan provides superior blood-pressure control， reverses ventricular remodeling， attenuates inflammatory fibrosis in perimenopausal hypertensive patients， while maintaining a similar safety profile.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

OBJECTIVE To systematically evaluate the effects of supplementation with different doses of vitamin D on maternal and infant outcomes in vitamin D-deficient pregnant women. METHODS Related literature on the effects of supplementing different doses of vitamin D on maternal and infant outcomes was searched in databases including CNKI， Wanfang Data， VIP， PubMed， Medline， the Cochrane Library， Embase from their inception to June 30， 2025. The risk of bias assessment tool from the Cochrane Handbook 5.1 was used to evaluate the quality of included literature. Meta-analysis of outcome indicators was performed by using RevMan 5.4 software. RESULTS A total of 15 studies were included， involving 4 664 patients [2 129 in the experimental group （daily dose ＞2 000 IU）， 2 058 in control group 1 （daily dose ≤1 000 IU） and 477 in control group 2 （daily dose ＞1 000-≤2 000 IU） ] . Meta-analysis results showed that the incidence of preeclampsia （PE） [OR＝0.71， 95%CI （0.53， 0.96）， P ＝0.03 ] ， gestational diabetes mellitus （GDM） [OR＝0.60， 95%CI （0.43， 0.84）， P ＝0.003 ] ， low birth weight of newborn [OR＝0.72， 95%CI （0.53， 0.97）， P ＝0.03 ] and macrosomia [OR＝0.53， 95%CI （0.29， 0.98）， P ＝0.04 ] in the experimental group were significant lower than control group 1； but there was no significant difference in the incidence of premature delivery [OR＝0.86， 95%CI （0.65， 1.13）， P ＝0.28 ] ， cesarean delivery [OR＝0.92， 95%CI （0.74， 1.15）， P ＝0.48 ] or stillbirth rate [OR＝0.77， 95%CI （0.48， 1.24）， P ＝0.29 ] . The incidence of low birth weight of ne wborn [OR＝0.64， 95%CI （0.41， 0.98）， P ＝0.04 ] in the experimental group was significant lower than control group 2； but there was no significant difference in the incidence of PE [OR＝0.61， 95%CI （0.25， 1.49）， P ＝0.28 ] ， the incidence of GDM [OR＝0.73， 95%CI （0.42， 1.24）， P ＝0.24 ] ， premature delivery rate [OR＝0.90， 95%CI （0.59， 1.39）， P ＝0.63 ] ， cesarean delivery rate [OR＝0.92， 95%CI （0.64， 1.33）， P ＝0.66 ] ， or stillbirth rate [OR＝0.68， 95%CI （0.24， 1.94）， P ＝0.48 ] . CONCLUSIONS Different doses of vitamin D supplementation in early pregnancy have a significant impact on maternal and infant pregnancy outcomes in vitamin D-deficient pregnant women； daily doses ＞2 000 IU have significant advantages in reducing the incidence of PE and GDM and improving the outcome of premature delivery.

Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

BACKGROUND:The diabetic microenvironment can cause excessive M1 polarization of macrophages,and this hyperglycemic inflammatory state can inhibit osteogenic differentiation of bone marrow mesenchymal stem cells,thus affecting the healing of diabetic bone defects.Studies have indicated that mogroside V possesses anti-inflammatory,antioxidant,and hypoglycemic properties.However,its potential to modulate M1 polarization of macrophages and osteogenic differentiation of bone marrow mesenchymal stem cells under high glucose and inflammatory condition remains unclear. OBJECTIVE:To explore the effect of mogroside V on regulating M1 macrophage polarization and its effect on osteogenic differentiation of bone marrow mesenchymal stem cells under high glucose and inflammatory condition. METHODS:Murine diabetic models were established using C57BL/6 mice.Bone marrow-derived macrophages were isolated from tibia and fibula of normal and diabetic mice,and cultured in low-glucose and high-glucose media.Then M1 polarization of bone marrow-derived macrophages was induced using lipopolysaccharide and interferon-γ.Bone marrow-derived macrophages were treated with 160,320,and 640 μmol/L mogroside V.Flow cytometry was employed to determine the proportion of F4/80+CD86+cells.qRT-PCR was utilized to assess mRNA expression levels of inducible nitric oxide synthase,interleukin 1β,and interleukin 6.ELISA was employed to evaluate tumor necrosis factor-α secretion in bone marrow-derived macrophage supernatants.Bone marrow mesenchymal stem cells were isolated from tibia and fibula of C57BL/6 suckling mice,and induced osteogenic differentiation using low-or high-glucose osteogenic induction medium.Bone marrow mesenchymal stem cells were treated with M1 macrophage-conditioned mediums with or without 320 μmol/L mogroside V in osteogenic differentiation process.qRT-PCR was employed to assess the mRNA expression of alkaline phosphatase,Runt-related factor 2,osteocalcin,and osteopontin on day 14 after osteogenic induction.Alizarin red staining and quantitative analysis were conducted to evaluate calcium deposition on day 21 after osteogenic induction. RESULTS AND CONCLUSION:(1)Flow cytometry results showed that with the treatment of 320 and 640 μmol/L mogroside V,the proportion of F4/80+CD86+bone marrow-derived macrophages was significantly lower than that in the high-glucose control group(P<0.05).(2)qRT-PCR results showed that with the treatment of 160,320,and 640 μmol/L mogroside V,the mRNA expression levels of inducible nitric oxide synthase and interleukin 6 were significantly lower than that in the high-glucose control group(P<0.05).With the treatment of 320 and 640 μmol/L mogroside V,the mRNA expression level of interleukin 1β was significantly lower than that in the high-glucose control group(P<0.05).(3)ELISA results exhibited that with the treatment of 160,320,and 640 μmol/L mogroside V,the tumor necrosis factor-α secretion level was significantly lower than that in the high-glucose control group(P<0.05).(4)With the treatment of 320 μmol/L mogroside V,calcium salt deposition was increased in bone marrow mesenchymal stem cells under high glucose and inflammatory conditions(P<0.05),and the mRNA relative expression levels of alkaline phosphatase,Runt-related factor 2,and osteopontin were increased(P<0.05).These findings indicate that mogroside V can promote osteogenic differentiation of bone marrow mesenchymal stem cells by inhibiting the M1 polarization of bone marrow-derived macrophages under high glucose and inflammatory conditions and reducing the generation of inflammatory factors.

ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.