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.

Hepatocellular carcinoma (HCC) develops within a profoundly immunosuppressive tumor immune microenvironment (TIME), which limits the efficacy of immunotherapy. Polarization of tumor-associated macrophages (TAMs) toward a pro-tumorigenic M2 phenotype is a major driver of immune escape. Ferroptosis, an iron-dependent regulated cell death program, intersects with hepatic iron metabolism and immune regulation and thus offers promising points of therapeutic intervention. This review systematically elucidates the mechanistic role of TAM ferroptosis in HCC immune evasion and highlights a “bidirectional regulation” intervention strategy grounded in the Traditional Chinese medicine (TCM) principle of “fortifying healthy qi and eliminating pathogens” (Fuzheng Quxie). This strategy employs “eliminating pathogens” (Quxie) approaches to exploit the metabolic vulnerability of M2-like TAMs and precisely induce their ferroptosis. Moreover, it utilizes “fortifying healthy qi” (Fuzheng) approaches to protect M1-like TAMs and CD8⁺ T cells from oxidative damage. This parallel “induction-protection” paradigm demonstrates the unique advantages of TCM in systemically remodeling TIME through multitarget synergistic actions. Accordingly, precision regulation of TAM ferroptosis based on the Fuzheng Quxie theory represents a promising integrative Chinese-Western medicine strategy for overcoming current bottlenecks in HCC immunotherapy, although its clinical translational potential warrants further validation.

Aim To investigate the effect of triptolide(TP)on corticosterone(CORT)-induced depression-like behaviors in mice and explore the antidepressant mechanism of TP based on the CREB/BDNF/TrkB sig-naling pathway.Methods Sixty 8-week-old male C57BL/6J mice were randomly divided into five groups:control group,CORT group,TP groups of low and high doses(10,30 μg·kg-1),and fluoxetine(FLU)group(10 mg·kg-1).Except for the control group,the other groups received subcutaneous injec-tions of CORT for three consecutive weeks to establish the model of depression.During the last two weeks of modeling,normal saline,TP and FLU were adminis-tered via intraperitoneal injection respectively.After the administration,depression-like behaviors in mice were assessed using forced swimming test,tail suspen-sion test,and sucrose preference test.Biochemical methods were used to measure the levels of SOD and MDA in the hippocampus and prefrontal cortex(PFC).Cell apoptosis was detected by TUNEL meth-od.Immunohistochemistry,immunofluorescence,and Western blotting were employed to detect the expres-sion of apoptosis/autophagy-related proteins,synaptic structure markers,and proteins related to the CREB/BDNF/TrkB signaling pathway.Results TP signifi-cantly ameliorated CORT-induced depression-like be-haviors in mice,mainly manifested by reduced immo-bility time in the tail suspension test and forced swim-ming test,and increased sucrose preference rate.TP alleviated CORT-induced oxidative stress by increasing SOD levels and reducing MDA production in brain tis-sue.Additionally,TP also inhibited apoptosis and ex-cessive autophagy of neurons in the hippocampus and prefrontal cortex,maintained synaptic plasticity,and significantly upregulated the expression of p-CREB,BDNF,and TrkB.Conclusions TP exhibits potential antidepressant effect in mice by upregulating the CREB/BDNF/TrkB signaling pathway,reducing oxida-tive stress,inhibiting excessive neuronal apoptosis and autophagy,and improving synaptic plasticity.

To investigate the phenotype and genomic characterization of a mucoid-type Salmonella Saintpaul ST50 isolate from a urinary tract infection patient,promoting clinical diagnosis and treatment for urinary tract infections caused by Salmo-nella spp.Culture-based quantitative counts of midstream urine sample from the patient were conducted,and further biochemi-cal identification,mass spectrometry detection,serum agglutination test and antimicrobial susceptibility test(AST)were con-ducted on Salmonella isolate(2024JD5).Whole-genome sequencing(WGS)was performed on isolate 2024JD5 to predict sero-type,multilocus sequence type(MLST),resistance genes,and virulence genes.Two smooth-type of Salmonella Saintpaul ST50 were selected as comparative genomic reference strains from the Chinese local Salmonella genome database.The literature reviews of global Salmonella serotype of urinary tract infection were summarized.Specific serum agglutination confir-mation of isolate 2024JD5 failed due to characterization of the mucus type.The strain 2024JD5 was predicted as Salmonella Saintpaul(4,5,12:e,h:1,2)ST50 using WGS,and was resistant to ciprofloxacin,nalidixic acid,chloramphenicol and tetracy-cline with carrying aminoglycoside resistance genes aac(6')-Ⅰaa and aph(3)-Ⅱa,chloramphenicol resistance gene floR,tetra-cycline resistance gene tet,quinolone resistance gene qnrS1,and S83Y substitution in the gyrA gene was found in the quinolo-ne resistance determination region(QRDR).In addition,the strain 2024JD4 carried six types of non-plasmid-based mobile ge-netic elements and 144 virulence genes,including 71 secretion transporter genes and 58 fimbriae adhesion genes,respectively.Four types of fimbriae regulatory genes(csgB,csgC,fimW,fimY)were absent in comparison with smooth-type Salmonella Saintpaul.The literature reviews showed Salmonella Saintpaul was currently a rare Salmonella serotype in cases of urinary tract infections worldwide.Salmonella Saintpaul ST50 with mucoid-type is the pathogen of urinary tract infection with multi-drug resistant phenotypic and genotypic characteristics,and the high mucoid expression may be related to the compensatory mechanism of fimbriae regulatory genes absence in urinary tract colonization and adaptation.WGS combined with the Chinese local Salmonella genome database can effectively solve the diagnosis and biosafety assessments of rare Salmonella phenotypes.

Objective·To study the regulatory effect of saikosaponin A(SSA)on the differentiation,apoptosis,and immunosuppressive function of myeloid-derived suppressor cells(MDSCs)in mice,and to explore their molecular mechanism.Methods·Recombinant mouse granulocyte-macrophage colony-stimulating factor(GM-CSF)was used to induce the differentiation of mouse bone marrow cells(BMCs)into MDSCs,or magnetic beads were used to sort MDSCs from tumor-bearing mice.After treating MDSCs with different concentrations(0,2.5,5.0 mg/L),flow cytometry(FCM)was used to detect the differentiation and apoptosis of MDSCs,as well as the expression levels of liver X receptor α(LXRα),arginase-1(Arg-1),and reactive oxygen species(ROS).At the same time,the effects of MDSCs on the proliferation function of T cells,and the effects on the nuclear factor κB(NF-κB),and signal transducer and activator of transcription 1(STAT1)signaling pathways were also detected.The mRNA levels of LXRα and Arg-1 were detected by quantitative real-time PCR(qPCR).Mice were given SSA by gavage(ig)or intraperitoneal injection(ip),and the mice were sacrificed after administration;and body mass,spleen weight,and spleen index were calculated.FCM was used to detect the proportion of immune cells in the spleen of mice.Results·SSA could up-regulate the expression level of LXRα in MDSCs,reduce the differentiation of M-MDSCs,induce apoptosis of MDSCs,reduce the expression levels of Arg-1 and ROS in MDSCs,and reduce the inhibitory effect of MDSCs on T cell proliferation.SSA inhibited the phosphorylation levels of NF-κB and STAT1 in MDSCs.The mice treated with SSA by gavage or intraperitoneal injection showed no significant changes in body weight and spleen index.Both modes of administration can reduce the proportion of MDSCs and their subset M-MDSCs in mice,but had different degrees of regulatory effects on other immune cells.Conclusion·SSA could regulate the differentiation and apoptosis of MDSCs,and inhibit their immunosuppressive function,which may be associated with the up-regulation of LXRα expression,and down-regulation of the NF-κB and STAT1 signaling pathways in MDSCs.

Objective:Based on multivariate analysis of the influencing factors of fecal pollution after radical re-section in children with congenital megacolon,a risk prediction model was constructed and evaluated.Methods:A total of 200 children with Hirschsprung's disease who underwent radical surgery at Nanyang Central Hospital of Henan Province from June 2020 to June 2023 were selected,and all children were followed up for 1 year.According to the occurrence of postoperative fecal incontinence,the children were divided into the non-occurrence group and the oc-currence group.Univariate Logistic regression analysis was performed on all possible influencing factors,and the back-ward stepwise regression method was used to screen out the relevant factors affecting postoperative fecal inconti-nence in children with Hirschsprung's disease after radical surgery.A risk prediction model was constructed based on these relevant factors,and its efficacy was verified using calibration curves,the Hosmer-Lemeshow test,and ROC curves.Results:Postoperative fecal incontinence occurred in 19.50%(39/200)of the children.A statistically signifi-cant difference was observed between the non-occurrence group and the occurrence group in terms of the following data(P＜0.05):age,preoperative nutritional support,need for auxiliary defecation before surgery,length of the dis-eased intestinal segment,educational level of caregivers,preoperative hypoproteinemia,resection range,postoperative diet compliance of the children,postoperative defecation training of the children,postoperative enterocolitis,and post-operative anal dilatation therapy.Multivariate Logistic regression analysis showed that preoperative nutritional support,need for auxiliary defecation before surgery,length of the diseased intestinal segment,educational level of caregivers,postoperative diet compliance of the children,postoperative defecation training of the children,postoperative entero-colitis,and postoperative anal dilatation therapy were all independent influencing factors for postoperative fecal inconti-nence in children with Hirschsprung's Disease after radical surgery(P＜0.05).Among these factors,the educational level of caregivers was the strongest predictor of postoperative fecal incontinence in children with Hirschsprung's dis-ease after radical surgery.Results of the calibration curve showed that the concordance index of the risk prediction model for postoperative fecal incontinence in children with Hirschsprung's Disease after radical surgery was 0.837.The Hosmer-Lemeshow test results indicated no statistically significant difference between the predicted values and the actual values of risk prediction(P＜0.05),suggesting that the model had a good fit and high prediction accuracy.Re-sults of the ROC curve showed that the area under the curve(AUC)of the risk prediction model for predicting postop-erative fecal incontinence in children with Hirschsprung's Disease after radical surgery was 0.887(95%CI:0.762～1.000,P＜0.05),with a sensitivity of 0.914,a specificity of 0.763,and a Youden index of 0.677.These findings indicate that the risk prediction model has moderate discriminative ability and good predictive performance.Conclusion:Preop-erative nutritional support,need for auxiliary defecation before surgery,length of the diseased intestinal segment,edu-cational level of caregivers,postoperative diet compliance of children,postoperative defecation training of children,postoperative enterocolitis,and postoperative anal dilatation therapy are all independent influencing factors for postop-erative fecal incontinence in children with Hirschsprung's disease after radical surgery.The risk prediction model for postoperative fecal incontinence in children with Hirschsprung's disease after radical surgery,established based on multivariate analysis,is helpful for early identification of high-risk groups and timely implementation of individualized in-tervention measures.

Objective:To analyze the expression of serum thymidine kinase 1 (TK1), interleukin-22 (IL-22) and IL-6 in patients with breast cancer and their relationship with postoperative recurrence.Methods:100 patients with breast cancer from Jan. 2021 to Jan. 2023 were included as the observation group, and 30 healthy women who underwent physical examination in the First People’s Hospital of Jiande during the same period were included as the control group. Serum TK1, IL-22 and IL-6 levels were compared and local recurrence was followed up after surgery. Patients were separated into the recurrence subgroup and non-recurrence subgroup according to postoperative recurrence. The levels of serum TK1, IL-22, IL-6 and clinicopathological features were compared, and the influencing factors of postoperative recurrence of breast cancer were analyzed by multivariate Logistic regression. Receiver operating characteristic curve (ROC) was drawn to evaluate the predictive efficacy of serum TK1, IL-22 and IL-6 in postoperative breast cancer recurrence.Results:Serum TK1, IL-22 and IL-6 levels in the observation group were significantly higher ( t=15.91, 21.99, 9.17, P<0.05); Among the 100 patients with breast cancer, 22 recurred and 78 did not recurred. The proportion of lymph node metastasis, the proportion of postoperative chemotherapy, the proportion of postoperative radiotherapy, serum TK1, serum IL-22 and serum IL-6 levels in the recurrence subgroup were significantly higher than those in the non-recurrence subgroup ( χ2/ t=8.09, 4.74, 4.76, 4.24, 4.43, 5.31, P<0.05); Stepwise Logistic regression showed that lymph node metastasis, high TK1, high IL-22 and high IL-6 were risk factors for postoperative recurrence of breast cancer patients, and standard postoperative chemotherapy and postoperative radiotherapy were protective factors (Wald χ2value =13.424, 4.689, 4.631, 7.334, 8.925, 5.855, P<0.05); The area under the curve (AUC) of TK1, IL-22, IL-6 and combined detection for predicting postoperative recurrence of breast cancer patients were 0.779, 0.739, 0.816 and 0.893, respectively ( AUC=0.779, 0.739, 0.816, 0.893, P<0.05) . Conclusions:Serum TK1, IL-22 and IL-6 levels increase in patients with breast cancer. High TK1, IL-22 and IL-6 levels are risk factors for postoperative recurrence of breast cancer, and combined detection has a good predictive effect on postoperative recurrence of breast cancer.

Objective To conduct a retrospective analysis of the correlation among bedaquiline(BDQ)plasma concentrations,relevant clinical factors,and disease prognosis.Methods In this retrospective study,22 patients diagnosed with rifampicin-resistant tuberculosis(RR-TB),multidrug-resistant tuberculosis(MDR-TB),or pre-extensively drug-resistant tuberculosis(pre-XDR-TB)were enrolled.These patients were admitted to the tuberculosis ward of our hospital between February 2022 and October 2024.All patients were administered a treatment regimen containing BDQ.The cohort comprised 6 RR-TB patients(27.27%),12 MDR-TB patients(54.55%),and 4 pre-XDR-TB patients(18.18%).Peripheral blood samples were collected 2 hours after the oral administration of Bedaquiline.The plasma concentration of Bedaquiline was measured using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Spearman correlation analysis was performed using R studio software with the ggplot2 and corrplot packages.The factors included the blood concentration of bedaquiline,electrocardiogram QTcF(QT interval corrected by the Fridericia method),liver and kidney function parameters,weight,age,body mass index,sex,blood uric acid level,serum creatinine level,and other relevant indicators.Results In 22 patients treated with BDQ,the plasma concentration reached a peak after 1.5 weeks of administration,and gradually stabilized after 2 weeks.The plasma concentration was approximately 1-3 μg/mL.After 24 weeks of withdrawal of bedaquiline,patients were continued to monitor their bedaquiline concentration and found that BDQ blood concentration in peripheral blood was approximate 1 μg/mL up to 36 weeks.The serum concentration of BDQ was not correlated with age,body weight,BMI,ALT,AST,GGT,TDiL,urea,uric acid and QT interval,but correlated with sputum negative transformation and serum creatinine.The correlation analysis between serum concentration of BDQ and acid-fast staining of sputum smear showed,the difference was significant(r=0.35,P<0.05).In addition,the correlation analysis between serum BDQ concentration and serum creatinine showed,the difference was significant(r=0.34,P<0.05).The results of multiple linear regression analysis showed that BDQ blood concentration was positively correlated with Scr level,and Scr was an independent factor affecting BDQ blood concentration.20 cases(90.9%,20/22)were cured,1 case died of Covid-19 virus infection,1 case was recurrence.Conclusions Regimens containing bedaquiline seem to exhibit relatively high safety profiles and good tolerability among patients with rifampicin-resistant,multidrug-resistant,or pre-extensively drug-resistant tuberculosis,typically yielding favorable treatment outcomes.The BDQ shows a positive correlation with serum creatinine(SCr).Consequently,close surveillance of BDQ levels and renal function remains of utmost importance throughout the treatment course.

Objective·To study the regulatory effect of saikosaponin A(SSA)on the differentiation,apoptosis,and immunosuppressive function of myeloid-derived suppressor cells(MDSCs)in mice,and to explore their molecular mechanism.Methods·Recombinant mouse granulocyte-macrophage colony-stimulating factor(GM-CSF)was used to induce the differentiation of mouse bone marrow cells(BMCs)into MDSCs,or magnetic beads were used to sort MDSCs from tumor-bearing mice.After treating MDSCs with different concentrations(0,2.5,5.0 mg/L),flow cytometry(FCM)was used to detect the differentiation and apoptosis of MDSCs,as well as the expression levels of liver X receptor α(LXRα),arginase-1(Arg-1),and reactive oxygen species(ROS).At the same time,the effects of MDSCs on the proliferation function of T cells,and the effects on the nuclear factor κB(NF-κB),and signal transducer and activator of transcription 1(STAT1)signaling pathways were also detected.The mRNA levels of LXRα and Arg-1 were detected by quantitative real-time PCR(qPCR).Mice were given SSA by gavage(ig)or intraperitoneal injection(ip),and the mice were sacrificed after administration;and body mass,spleen weight,and spleen index were calculated.FCM was used to detect the proportion of immune cells in the spleen of mice.Results·SSA could up-regulate the expression level of LXRα in MDSCs,reduce the differentiation of M-MDSCs,induce apoptosis of MDSCs,reduce the expression levels of Arg-1 and ROS in MDSCs,and reduce the inhibitory effect of MDSCs on T cell proliferation.SSA inhibited the phosphorylation levels of NF-κB and STAT1 in MDSCs.The mice treated with SSA by gavage or intraperitoneal injection showed no significant changes in body weight and spleen index.Both modes of administration can reduce the proportion of MDSCs and their subset M-MDSCs in mice,but had different degrees of regulatory effects on other immune cells.Conclusion·SSA could regulate the differentiation and apoptosis of MDSCs,and inhibit their immunosuppressive function,which may be associated with the up-regulation of LXRα expression,and down-regulation of the NF-κB and STAT1 signaling pathways in MDSCs.

Objective:Based on multivariate analysis of the influencing factors of fecal pollution after radical re-section in children with congenital megacolon,a risk prediction model was constructed and evaluated.Methods:A total of 200 children with Hirschsprung's disease who underwent radical surgery at Nanyang Central Hospital of Henan Province from June 2020 to June 2023 were selected,and all children were followed up for 1 year.According to the occurrence of postoperative fecal incontinence,the children were divided into the non-occurrence group and the oc-currence group.Univariate Logistic regression analysis was performed on all possible influencing factors,and the back-ward stepwise regression method was used to screen out the relevant factors affecting postoperative fecal inconti-nence in children with Hirschsprung's disease after radical surgery.A risk prediction model was constructed based on these relevant factors,and its efficacy was verified using calibration curves,the Hosmer-Lemeshow test,and ROC curves.Results:Postoperative fecal incontinence occurred in 19.50%(39/200)of the children.A statistically signifi-cant difference was observed between the non-occurrence group and the occurrence group in terms of the following data(P＜0.05):age,preoperative nutritional support,need for auxiliary defecation before surgery,length of the dis-eased intestinal segment,educational level of caregivers,preoperative hypoproteinemia,resection range,postoperative diet compliance of the children,postoperative defecation training of the children,postoperative enterocolitis,and post-operative anal dilatation therapy.Multivariate Logistic regression analysis showed that preoperative nutritional support,need for auxiliary defecation before surgery,length of the diseased intestinal segment,educational level of caregivers,postoperative diet compliance of the children,postoperative defecation training of the children,postoperative entero-colitis,and postoperative anal dilatation therapy were all independent influencing factors for postoperative fecal inconti-nence in children with Hirschsprung's Disease after radical surgery(P＜0.05).Among these factors,the educational level of caregivers was the strongest predictor of postoperative fecal incontinence in children with Hirschsprung's dis-ease after radical surgery.Results of the calibration curve showed that the concordance index of the risk prediction model for postoperative fecal incontinence in children with Hirschsprung's Disease after radical surgery was 0.837.The Hosmer-Lemeshow test results indicated no statistically significant difference between the predicted values and the actual values of risk prediction(P＜0.05),suggesting that the model had a good fit and high prediction accuracy.Re-sults of the ROC curve showed that the area under the curve(AUC)of the risk prediction model for predicting postop-erative fecal incontinence in children with Hirschsprung's Disease after radical surgery was 0.887(95%CI:0.762～1.000,P＜0.05),with a sensitivity of 0.914,a specificity of 0.763,and a Youden index of 0.677.These findings indicate that the risk prediction model has moderate discriminative ability and good predictive performance.Conclusion:Preop-erative nutritional support,need for auxiliary defecation before surgery,length of the diseased intestinal segment,edu-cational level of caregivers,postoperative diet compliance of children,postoperative defecation training of children,postoperative enterocolitis,and postoperative anal dilatation therapy are all independent influencing factors for postop-erative fecal incontinence in children with Hirschsprung's disease after radical surgery.The risk prediction model for postoperative fecal incontinence in children with Hirschsprung's disease after radical surgery,established based on multivariate analysis,is helpful for early identification of high-risk groups and timely implementation of individualized in-tervention measures.