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.

Objective To evaluate the cost–utility of lecanemab and donanemab in the treatment of early Alzheimer’s disease （AD） in China. Methods A Markov model was developed from a societal perspective to compare standard of care （SOC）, lecanemab plus SOC, and donanemab plus SOC in terms of costs, quality-adjusted life years （QALY）, and incremental cost–utility ratios （ICUR）. Deterministic and probabilistic sensitivity analyses were conducted to assess parameter uncertainty. Results Both intervention strategies increased QALY compared with SOC but were associated with substantially higher costs, and neither was cost-effective under the current willingness-to-pay threshold. Conclusion Lecanemab and donanemab may be more appropriately considered within a multi-tiered healthcare reimbursement framework in China rather than relying solely on basic medical insurance.

Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
Spermatogenesis/physiology* ; Animals ; Male ; Mice ; Epigenesis, Genetic ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Histones/metabolism* ; RNA Interference ; Testis/metabolism* ; Methylation ; Mice, Knockout ; Histone Demethylases

An 11-year-old boy presented with erythematous plaques over the bilateral mandibular and mental regions for 2 years, accompanied by cough and dyspnea for more than 2 months. Chest computed tomography angiography revealed marked stenosis of the right pulmonary artery, irregular aortic caliber, and aortic wall thickening. Histopathological examination of the skin lesion, including immunohistochemistry and special stains, confirmed a chronic suppurative inflammation. Whole-exome sequencing was negative. A final diagnosis of granuloma faciale and Takayasu arteritis was established. Combination therapy with systemic tocilizumab, prednisone, and methotrexate, along with topical 0.1% tacrolimus ointment, resulted in a favorable clinical response. This report summarizes the clinical features of a pediatric case of granuloma faciale and Takayasu arteritis and reviews the etiology, diagnostic approach, and current treatment strategies for the disorders, aiming to enhance clinicians' understanding of these conditions.
Humans ; Male ; Child ; Takayasu Arteritis/diagnosis* ; Facial Dermatoses/diagnosis*

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.

Objective:To investigate the effects of Roxadustat and recombinant human erythropoietin (rHuEPO) on novel inflammatory immune indices in anemic patients with non-dialysis type 2 diabetes mellitus combined with chronic kidney disease (CKD).Methods:A retrospective case-control study was performed in this study. Patients with non-dialysis type 2 diabetes mellitus combined with CKD admitted to Shanghai First People's Hospital from December 2015 to December 2023 were selected. Among those patients, 252 cases were treated with rHuEPO (rHuEPO group) and 103 cases were treated with Roxadustat (Roxadustat group). Both group had a course of treatment over three months. The baseline data and novel inflammatory immunity indices, systemic immuno-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) were compared between the two groups of patients before and after 3 months of treatment.Results:The differences in gender, age, body mass index, systolic blood pressure, diastolic blood pressure, history of cardiovascular and cerebrovascular disease, history of hypertension, estimated glomerular filtration rate, and use of hypoglycemic, antihypertensive, and lipid-lowering medications were not statistically significant when compared between the two groups of patients (all P>0.05). Before treatment, the differences in NLR, PLR, SII, and LMR between the two groups were not statistically significant (all P>0.05); after 3 months of treatment, NLR, PLR, SII, and LMR were lower in both groups than before treatment [rHuEPO group: (2.3±0.8)% vs. (2.8±0.8)%, (83±33)% vs. (160±49)%, (2.3±0.8)% vs. (3.1±0.7)%, (476±227)% vs. (594±243)%, with t values of 9.25, 23. 20, 26.67, and 9.62, respectively, all P<0.001; Roxadustat group: (1.7±0.6)% versus (2.9±1.0)%, (72±30)% versus (162±47)%, (2.0±0.8)% versus (3.1±0.9)%, (408±151)% versus (605±267)%, with t values of 8. 38, 14.27, 8.62, and 5.97, respectively, all P<0.001], and NLR, PLR, and SII were lower in the Roxadustat group than in the rHuEPO group ( t=5.00, P<0.001, t=2.44, P=0.015, t=2.09, P=0.040). Conclusion:In patients with anemia in non-dialysis type 2 diabetes mellitus associated with CKD,Roxadustat had similar ability of reducing the level of novel inflammatory markers compared to rHuEPO.

Anterior cruciate ligament (ACL) injury is a common sports-related knee injury. Its early clinical symptoms include knee swelling, pain with restricted movement, and may progress to knee instability and even secondary osteoarthritis in later stages, significantly affecting the patients′ athletic performance and quality of life. Arthroscopic ACL reconstruction is currently regarded as the gold standard treatment for ACL injuries. However, due to the factors including surgical techniques and rehabilitation protocols, the probability of patients returning to their pre-injury sports level postoperatively remains suboptimal. Therefore, developing individualized preoperative and postoperative rehabilitation protocds are particularly crucial. Traditionally, rehabilitation was implemented postoperatively, overlooking the significance of preoperative rehabilitation. Preoperative rehabilitation primarily involves comprehensive management and functional training, which can enhance patient satisfaction, reduce postoperative complications, and shorten the return-to-sport duration. Standardized preoperative rehabilitation is essential for enabling patients to return to sports promptly after surgery, however, there remain controversies regarding the optimal timing, training intensity, and duration of preoperative rehabilitation. To this end, the authors reviewed the application of preoperative rehabilitation in ACL reconstruction, aiming to provide references for establishing standardized preoperative rehabilitation protocols in clinical practice.

Objective:To investigate the effect of the stress-induced protein sestrin 3(SESN3)on tumor proliferation and the sensitivity to endocrine therapy in hormone receptor-positive(HR+)breast cancer(BC)and its mechanism.Methods:The cancer genome atlas(TCGA)database was used to analyze the expression level of SESN3 in breast cancer tissue and paracancerous tissue.The clinical samples of breast cancer tissue and paracancerous tissue were collected,and immunohistochemistry(IHC)microarray was used to vali-date the expression of SESN3.Western blot was used to measure the protein expression level of SESN3 in BC cell lines with different pathological subtypes.HR+BC cell lines were used to establish the models of SESN3 overexpression and knockdown,and cell counting kit-8(CCK-8)assay and colony formation assay were used to assess the proliferative capacity of cells;Western blot was used to ana-lyze cell cycle alterations;a subcutaneous xenograft mouse model was used to validate the effect of SESN3 on proliferation in vivo.The bioinformatics analysis and Western blot were used to investigate the downstream mechanisms of SESN3 in regulating proliferation.Results:The analysis of TCGA database and clinical samples showed that the expression of the SESN3 gene in BC tissue was signifi-cantly lower than that in paracancerous tissue,and the patients with high SESN3 expression had a longer progression-free survival time.Compared with the other subtypes of BC cell lines,the HR+BC cells lines MCF-7 and T-47D had a relatively high expression level of SESN3.MCF-7 and T-47D cell lines were used to establish the cell models of knockdown(MCF-7KD and T-47DKD)and overexpres-sion(MCF-7OE and T-47DOE),and compared with the control group,MCF-7KD and T-47DKD cells showed increases in proliferative capacity and the proportion of cells arrested in the G2 and M phases.In vivo tumorigenesis experiments showed a significant increase in tumor growth in mice in the MCF-7KD group.The bioinfor-matics analyses showed a significant negative correlation between the mammalian Target of Rapamycin(mTOR)signaling pathway and SESN3 expression,and Western blot validation showed a significant increase in the expression of mTOR in MCF-7KD and T-47DKD cells,as well as reductions in the protein expression levels of autophagy-related genes.Subsequently,we further confirmed that the knockdown of MCF-7 and T-47D cells led to a decreased sensitivity to endocrine therapy.In addition,MCF-7、T-47D、MCF-7KD、and T-47DKD cell lines were treated with the mTOR inhibitor everolimus(EVE),and there was a significant reduction in proliferative capac-ity in the MCF-7KD group and the T-47DKD group;since the mTOR pathway reduced the sensitivity to endocrine therapy by reducing cell apopto-sis,there was a significant increase in the sensitivity to endocrine therapy with tamoxifen(TAM).Conclusion:The inte-grated database analysis,clinical sample validation,and in vivo/in vitro experimental models show that SESN3 inhibits the proliferation of HR+BC cells via the mTOR pathway and enhances the sensitivity to endocrine therapy.