ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss （RPL） by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus （Shoutai Wan， Juyuan Jian）-of traditional Chinese medicine （TCM） at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c （blank group） and DBA/2 （modeling group） mice separately. Pregnant mice in the modeling group were randomly grouped as follows： high/low-dose Shoutai Wan， high/low-dose Juyuan Jian， model （RPL）， and positive control （dydrogesterone）， with 10 mice in each group. Starting from the day after the detection of the vaginal plug， mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention， the following indicators were measured. ① Macroscopic evaluation： general conditions， uterine wet weight， embryo loss rate， four coagulation parameters ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， fibrinogen （FIB）， and thrombin time （TT）］， and peripheral blood estradiol （E₂） and progesterone （Pg） levels. The decidua with embryos was stained with hematoxylin-eosin （HE） and evaluated by transmission electron microscopy （TEM）. The expression of B-cell lymphoma-2 （Bcl-2）， vascular endothelial growth factor （VEGF）， angiotensin Ⅱ （AngⅡ）， matrix metalloproteinase-2 （MMP-2）， interleukin-6 （IL-6）， leukemia inhibitory factor （LIF）， CXC chemokine ligand 12 （CXCL12）， and microtubule-associated protein 1 light chain 3 homolog （LC3）Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level： The decidua with embryos from the blank， model， high-dose Shoutai Wan， and high-dose Juyuan Jian groups （6 mice per group， with 3 single-cell samples per group， totaling 24 mice） were analyzed by the BD Rhapsody™ platform， and the whole-cell atlas was drawn by uniform manifold approximation and projection （UMAP） dimensionality reduction clustering combined with the single-cell mouse cell atlas （scMCA）. The differentially expressed genes （DEGs） and cell interaction networks were analyzed via Gene Ontology （GO）， Kyoto Encyclopedia of Genes and Genomes （KEGG）， and CellChat， and the protein-protein interaction （PPI） map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells （natural killer cells， NK cells） from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group， the RPL group showed an increase in the embryo loss rate （P<0.01）， down-regulated expression of Bcl-2， LIF， MMP-2， and Vegf in the decidua with embryos （P<0.05）， up-regulated protein levels of CXCL-12， AngⅡ， and IL-6 （P<0.05）， blocked angiogenesis， apoptosis-inflammation imbalance， and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance， and Shoutai pill showed superior performance in restoring the E₂ level to the Pg level （P<0.05）. ② Single-cell transcriptome analysis indicated that compared with the blank group， the RPL group showed differences in multiple key cell populations such as decidual cells， trophoblast cells， endothelial cells， erythroblasts， NK cells， and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group， high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer （upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes） and macrophages （upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes） through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins， cell adhesion， and programmed cell death， thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells （up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes） and macrophages （up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes）， which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D， CDH5， GDF， and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 （STAT3） and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis （TWEAK） signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7， a decreased proportion of reparative dNK4， and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1， thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method （Shoutai Wan） has an advantage in regulating the phenotypes of unfolded protein， cell adhesion， and programmed cell death， and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method （Juyuan Jian） has an advantage in regulating epithelial-mesenchymal transition （EMT）， angiogenesis， and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.

Traditional Chinese medicine （TCM）， through its multi-target and systematic regulatory effects， has demonstrated unique advantages in the treatment of gastric precancerous lesions （GPL）. At present， TCM theoretical research on GPL is mainly reflected in three aspects， the integration of macroscopic syndrome differentiation， the inflammation-carcinoma transformation mechanism， as well as the systematization and scientization of theoretical inheritance from famous TCM practitioners. High-quality evidence-based research findings serve as the foundation for clinical practice guidelines on GPL， and TCM has gained international academic recognition in the field of GPL prevention and treatment. Research on TCM mechanisms has yielded a series of important outcomes in the aspects of signaling pathways， gene expression regulation， cellular epigenetics， histone modification， and intestinal microecology. It is proposed that future research on GPL should focus on four key directions， establishing multi-omics data， exploring targeted intervention strategies on key regulatory nodes， advancing the standardization process of integrated traditional Chinese and western medicine prevention and treatment technologies， and constructing stratified screening and intervention platforms. The in-depth integration of TCM microcosmic mechanism of action with its macroscopic syndrome differentiation and treatment system， coupled with interdisciplinary research， will provide valuable references for the clinical treatment and scientific research of GPL.

Objective: To address systemic challenges in the blood system, such as supply-demand imbalance, inefficient allocation, and inappropriate clinical use, while bridging gaps in current theories regarding the integration of social mobilization, institutional practice, and policy coordination. It sought to construct a system dynamics model spanning from macro to micro levels to analyze the blood management system holistically. Methods: Key variables were identified by a systematic literature search in both Chinese and English databases. An improved Delphi method was then employed to conduct expert consultations across different fields, leading to the selection and determination of core variable sets for each sub-model. Furthermore, by defining their logical relationships, a system dynamics model was constructed to systematically analyze the operation mechanism of the blood management system. Results: Four core sub-models were developed: 1) A macro "Dynamic Balance" model quantifying regional supply-demand equilibrium and inventory control; 2) a mobilization "Three-Layer Funnel" model analyzing how socio-cultural factors, service channels, and policy incentives influence donation behavior; 3) an institutional "Dual-Cycle Regulation" model revealing hospital blood usage is driven by both disease burden (demand cycle) and management practices (regulation cycle); and 4) an individual "Three-Layer Filter" model standardizing clinical transfusion decisions based on necessity, risk-benefit, and context. These were integrated into a "Multi-Layer Linkage and Feedback" model, elucidating bidirectional interactions among five levels: policy environment, regional supply, blood station mobilization, hospital application, and clinical decision-making. Conclusion: This study constructed a system dynamics model for blood management. By defining key variables and their logical relationships, it systematically analyzes the system′s operational mechanism. The integrated framework connects multiple levels—regional supply, voluntary donation, hospital blood use, and clinical decision-making—revealing their intrinsic linkages. Future efforts should employ systems thinking to synergistically enhance supply-side mobilization, demand-side management, systemic regulation, and decision standardization to build a safe, efficient, and sustainable blood security system.

Objective:To explore the application effect of interventional teaching in undergraduate nursing internship in operating rooms.Methods:A total of 98 undergraduate nursing students who worked as interns in the operating room during the two school years from June 2022 to February 2024 were selected as research subjects. Students who entered the program from June 2022 to February 2023 were enrolled into control group (50 students), and those who entered from June 2023 to February 2024 were enrolled into experimental group (48 students). The students conducted their internships in batches (with 4 to 5 students per subgroup) following a departmental rotation mechanism. The control group received routine teaching, while the experimental group received interventional teaching. At the end of the internship, the two groups were compared for their performance, including basic and specialized knowledge, skills, theory, and operation; patient reception, tripartite verification, and intraoperative cooperation for planned video-assisted thoracoscopic bullectomy; and their degrees of satisfaction with the teaching. The t-test was performed using SPSS 26.0. Results:The experimental group achieved significantly higher theoretical scores than the control group [(91.69±4.51) vs. (74.52±6.06)]. Meanwhile, the experimental group was significantly superior to the control group in operational performance, including surgical hand disinfection [(96.08±1.93) vs. (92.14±3.07)] and wearing and removing sterile surgical gowns and sterile gloves [(97.00±1.75) vs. (94.10±3.48)). In terms of specialized knowledge and skills, specifically, patient reception and third-party verification in simulated surgical nursing, the experimental group achieved higher scores than the control group [(98.77±0.69) vs. (94.04±2.56); (98.54±0.65) vs. (94.64±2.65)]. In terms of intraoperative cooperation, the experimental group showed a slight advantage over the control group. The experimental group had higher degrees of satisfaction with teaching than the control group, including course design, implementation methods, course arrangement, teaching attitude, teaching methods, degree of participation, gains, and assistance.Conclusions:After adopting interventional teaching, the teaching effect for nursing internship in operating rooms is better. It improves the various assessment scores of nursing students, enhances their comprehensive abilities and degrees of satisfaction with teaching, and reinforces the teaching abilities in operating rooms.

Objective To investigate the effect of pecto-intercostal fascial block(PIFB)-PECS Ⅱ block-general anesthesia on hemodynamics and stress response in patients undergoing modified radical mastectomy for breast cancer.Methods A total of 95 patients with breast cancer who underwent modified radical mastectomy in the hospital from November 2021 to November 2023 were enrolled in this study.They were divided into the control group(n=46)and the observation group(n=49)according to the anesthesia mode.The control group received PECS Ⅱ block-general anesthesia and the observation group received PIFB-PECS Ⅱ block-general anesthesia.The dosage of remifentanil,the dosage of cisatracurium,recovery time,tracheal extubation time,postoperative analgesia pump compression times,VAS scores,hemodynamics(HR,MAP),oxidative stress response(SOD,CAT,MDA),and hyperthermia were compared between the two groups Susceptibility to MMSE score and adverse reactions.Results The dosage of remifentanil,dosage of cisatracurium,effective pressing times of analgesia pump within 48 h,wake-up time,tracheal extubation time and time to postoperative first pressing in the observation group were lower and shorter than those in the control group(P＜0.05).The observation group had lower VAS scores than the control group after surgery(P＜0.05).The HR of after anesthesia induction(T1),at tracheal intubation(T2),at the beginning of surgery(T3)and at the end of surgery(T4)in the observation group was(78.45±6.12)times/min,(100.28±11.54)times/min,(103.90±14.82)times/min and(93.66±9.17)times/min,respectively,which were lower than the control group[(84.66±7.04)times/min,(112.33±13.28)times/min,(122.44±17.06)times/min and(106.26±11.03)times/min,respectively].MAP of T1,T2,T3 and T4 in the observation group were(67.73±4.09)mmHg,(75.22±9.51)mmHg,(90.76±10.77)mmHg and(82.50±8.63)mmHg,respectively,the control groups were(70.10±5.66)mmHg,(82.62±10.17)mmHg,(96.43±12.59)mmHg and(90.82±11.04)mmHg,respectively.There was a statistically significant difference between the two groups(P＜0.05).The levels of SOD,CAT and MDA in both groups at 24 hours and 72 hours after the operation were all higher than those before the operation(P＜0.05).The SOD levels in the observation group were(83.22±15.44)nU/ml and(77.41±10.39)nU/ml at 24 h and 72 h after operation.It was lower than that of the control group,which was(90.40±18.23)nU/ml and(82.80±13.18)nU/ml.The CAT scores of observation group were(16.20±5.03)kU/L and(14.12±3.27)kU/L at 24 h and 72 h after operation,which were lower than those of control group[(20.75±6.57)kU/L and(17.06±4.35)kU/L].The MDA levels in the observation group were(5.12±1.33)mmol/L and(3.23±0.76)mmol/L at 24 h and 72 h after surgery,which were lower than those in the control group[(6.03±2.24)mmol/L and(4.88±1.05)mmol/L],and the differences were statistically significant(all P＜0.05).The MMSE scores of the observation group were(28.01±1.35)and(28.46±1.39),which were higher than those of the control group[(26.44±1.08)and(27.36±1.23)](P＜0.05).Conclusion Applying PIFB-PECS Ⅱ block-general anesthesia in modified radical mastectomy for breast cancer can maintain hemodynamic stability,reduce oxidative stress and alleviate the damage to cognitive function,with high safety.

Objective:To investigate the value of a multi-parameter MRI nomogram model in evaluating the recurrence risk of hormone receptor (HR)-positive breast cancer.Methods:This study was a retrospective cross-sectional study. A retrospective analysis was conducted on the clinicopathological data (age, menopausal status, axillary lymph node metastasis, etc.) and imaging data of 220 patients with HR-positive breast cancer who underwent breast MRI examination and were pathologically confirmed at the Second Affiliated Hospital of Nantong University from January 2018 to December 2023. All patients underwent preoperative MRI examinations. Their MRI features were analyzed, and the maximum diameter of the lesion and the apparent diffusion coefficient (ADC) value were measured. Finally, the clinical treatment score (CTS5 score) after 5 years was calculated, and all patients were divided into a low recurrence risk (CTS5 score 3.13 points) and a medium to high recurrence risk (CTS5 score≥3.13 points) group. The patients were followed up through the electronic medical record system or by phone until December 31, 2024 to determine recurrence status. The patients were divided into the recurrence group and the non-recurrence group. The differences in clinicopathological data, MRI features and CTS5 scores between the recurrence group and the non-recurrence group were compared using independent sample t-tests, Mann-Whitney U tests or χ2 tests. Indicators with P0.05 in the univariate analysis were included in the multivariate logistic regression to screen the independent risk factors for predicting the recurrence of HR receptor-positive breast cancer, and a nomogram was constructed to establish the nomogram model. The receiver operating characteristic curves and the area under the curve (AUC) were used to evaluate the efficacy of the nomogram model in predicting the postoperative recurrence risk of patients with HR-positive breast cancer. The variance inflation factor (VIF) was used to evaluate the multicollinearity among independent variables. Calibration curves and decision curve analysis (DCA) were used to assess the fit and net clinical benefit of the nomogram model. Results:Among 220 patients with HR-positive breast cancer, 196 cases were in the non-recurrence group and 24 cases were in the recurrence group. There were statistically significant differences in the maximum diameter of the lesion, axillary lymph node metastasis, ADC value, CTS5 grouping, and CTS5 score between the recurrence group and the non-recurrence group ( P0.05). Multivariate logistic regression analysis showed that the maximum diameter of the lesion ( OR=1.110, 95% CI 1.169-1.503, P0.001), ADC value ( OR=0.993, 95% CI 0.993?0.989, P0.001), and axillary lymph node metastasis ( OR=8.842; 95% CI 2.120?36.884, P=0.003) were independent factors influencing postoperative recurrence in patients with HR-positive breast cancer, and a nomogram model was constructed based on this. VIF analysis showed that no significant multicollinearity was detected among the variables (VIF5). The AUC value of the nomogram model for predicting postoperative recurrence in patients with HR-positive breast cancer was 0.868 (95% CI 0.794-0.942), the sensitivity was 0.875, and the specificity was 0.781. The calibration curve showed that the prediction curve of this model for predicting postoperative recurrence in HR-positive breast cancer patients was basically consistent with the ideal curve trend. DCA showed that this model had a relatively high clinical benefit within the threshold probability range of 0.01% to 90.00%. Conclusion:The nomogram constructed based on multi-parameter MRI features can predict the postoperative recurrence risk of HR-positive breast cancer patients, with good consistency and predictive ability.

Objective To summarize the role of clinical pharmacists in pharmaceutical care in the treatment of patients with pneumocystis jirovecii pneumonia secondary to immune-mediated colitis.Methods The association of immune-mediated colitis induced by serplulimab was evaluated by clinical pharmacist,anti-infective regimen for pneumocystis jirovecii pneumonia was put forward,addressed concerns regarding the impact of trimethoprim/sulfamethoxazole on the efficacy of fecal microbiota transplantation,pharmaceutical care for whole therapeutic process of the patient was monitored.Results Through pharmaceutical care and collaborating with physicians,the patient's pneumocystis jirovecii pneumonia was significantly improved,and the clinical and endoscopic remission of immune-mediated colitis after two fecal microbiota transplantation were achieved.Conclusion To ensure the safety and effectiveness of immune-mediated colitis and pneumocystis jirovecii pneumonia for patients,clinical pharmacists should play the role of participation and pharmaceutical care.

Objective To explore the correlation between the proximal angle of carotid atherosclerotic plaques and neovascularization scores,and their clinical application value in predicting recurrent cerebral infarction.Methods A total of 88 patients who underwent carotid plaque ultrasound examination in our hospital were selected.According to CT/MRI results,patients were divided into the non-cerebral infarction group(45 cases)and the cerebral infarction group(43 cases).Conventional ultrasound examination was performed followed by contrast-enhanced ultrasound.Plaque length,thickness and proximal angle were measured,and the neovascularization score of the proximal end was evaluated using contrast-enhanced ultrasound,and the results were compared and analyzed.Results In the cerebral infarction group,plaque thickness,proximal angle,and neovascularization score were significantly higher than those in the non-cerebral infarction group(P＜0.05),while there was no significant difference in plaque length.The proportion of plaques with a proximal neovascularization score of 2 or 3 was higher in the cerebral infarction group than those of the non-cerebral infarction group(79.1%vs.24.4%,P＜0.01).A positive correlation was found between the proximal angle and neovascularization score in all patients(rs=0.374,P＜0.01).There was no significant difference between the area under the ROC curve for neovascularization score in predicting recurrent cerebral infarction and the proximal angle(P＞0.05).The optimal cutoff value of the proximal angle was 18.8,and the sensitivity and the specificity for predicting recurrent cerebral infarction were 93.0%and 62.2%.In the cerebral infarction group,seven patients(16.3%)had recurrent infarction within one year,and these patients had higher proximal neovascularization scores,with angles greater than 18.8°.Conclusion There is a strong correlation between proximal angle of carotid plaques and neovascularization score,which has a positive predictive role in the recurrence of cerebral infarction,providing a reliable auxiliary diagnostic basis for clinical practice.

Objective To construct an animal model of dilated cardiomyopathy(DCM)with heart failure toxin syndrome that conforms to the characteristics of traditional Chinese medicine(TCM)syndrome and identify potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.Methods Fifteen male SD rats were divided into a blank control,doxorubicin,or DCM with heart failure toxin syndrome group using a random number table method,with five rats per group.The doxorubicin group received intraperitoneal injection of doxorubicin at a dose of 1.25 mg/kg,administered on the first and fourth days of each week,along with a standard diet.The DCM with heart failure toxin syndrome group,in addition to the doxorubicin treatment,was given 42％white liquor(10 mL/kg)via gavage every other day,along with a 45％high-fat feed and 10％fructose water.The blank control group received intraperitoneal injection of an equivalent volume of phosphate-buffered saline at the same time points as the doxorubicin group,along with a standard diet.The model was established for 10 weeks.At the fourth and tenth weeks of modeling,echocardiography was performed to measure left ventricular ejection fraction(LVEF),fractional shortening(FS),systolic left ventricular posterior wall thickness(LVPWs),diastolic left ventricular posterior wall thickness,systolic left ventricular internal diameter(LVIDs),and diastolic left ventricular internal diameter(LVIDd);macroscopic changes in fur color of the rats were assessed using the red-green-blue colorimetric method.After modeling,the open field test was conducted to evaluate the exercise tolerance of the rats,and the grip strength test was performed to assess changes in forelimb grip strength.Hematoxylin-eosin,Masson,and wheat germ agglutinin staining were used to evaluate pathological changes in cardiac tissue.Bulk RNA sequencing analysis was performed to identify differentially expressed genes(DEGs)in the hearts of rats between the blank control and the DCM with heart failure toxin syndrome groups.Using DCM,the Blue value of rat fur color,and forelimb grip strength as phenotypic traits,weighted gene co-expression network analysis(WGCNA)was performed to screen for characteristic module gene sets(MEs)associated with DCM with heart failure toxin syndrome.Overlapping analysis was performed on DEGs,immune-related gene sets,and MEs,and the intersecting genes were identified as potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.The sensitivity and specificity of these targets were evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared with the blank control group,at the tenth week of modeling,the LVEF,FS,and LVPWs of rats in the doxorubicin group and the DCM with heart failure toxin syndrome group decreased,whereas LVIDs and LVIDd increased,and the movement distance of the open field test and forelimb grip strength were reduced(P＜0.05).At the 10th week of modeling,the Blue value of fur color in the DCM with heart failure toxin syndrome group was significantly lower than that of the blank control and doxorubicin groups(P＜0.05).Compared with the blank control group,rats in the doxorubicin and DCM with heart failure toxin syndrome groups exhibited significant cardiac dilation and increased immune cell infiltration in cardiac tissue,accompanied by collagen deposition and cardiomyocyte hypertrophy.Bulk RNA sequencing identified 2,003 DEGs,including 1,082 downregulated genes and 921 upregulated genes.WGCNA results revealed that the MEturquoise module had the strongest positive correlation with DCM and the strongest negative correlation with the Blue value and forelimb grip strength.The overlapping analysis identified four intersecting genes:bone morphogenetic protein 6(Bmp6),serine-threonine-protein kinase 1(Pak1),proto-oncogene JunD(JunD),and S100 calcium-binding protein A3(S100A3).ROC curve analysis demonstrated that these four genes exhibited high sensitivity and specificity for DCM with heart failure toxin syndrome.Conclusion The rat model constructed by intraperitoneal injection of doxorubicin combined with a high-fat feed,fructose water,and white liquor gavage closely aligns with the characteristics of the DCM with heart failure toxin syndrome.Bmp6,JunD,Pak1,and S100A3 are potential biomarkers or therapeutic targets for DCM heart failure toxin syndrome.

Objective To construct an animal model of dilated cardiomyopathy(DCM)with heart failure toxin syndrome that conforms to the characteristics of traditional Chinese medicine(TCM)syndrome and identify potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.Methods Fifteen male SD rats were divided into a blank control,doxorubicin,or DCM with heart failure toxin syndrome group using a random number table method,with five rats per group.The doxorubicin group received intraperitoneal injection of doxorubicin at a dose of 1.25 mg/kg,administered on the first and fourth days of each week,along with a standard diet.The DCM with heart failure toxin syndrome group,in addition to the doxorubicin treatment,was given 42％white liquor(10 mL/kg)via gavage every other day,along with a 45％high-fat feed and 10％fructose water.The blank control group received intraperitoneal injection of an equivalent volume of phosphate-buffered saline at the same time points as the doxorubicin group,along with a standard diet.The model was established for 10 weeks.At the fourth and tenth weeks of modeling,echocardiography was performed to measure left ventricular ejection fraction(LVEF),fractional shortening(FS),systolic left ventricular posterior wall thickness(LVPWs),diastolic left ventricular posterior wall thickness,systolic left ventricular internal diameter(LVIDs),and diastolic left ventricular internal diameter(LVIDd);macroscopic changes in fur color of the rats were assessed using the red-green-blue colorimetric method.After modeling,the open field test was conducted to evaluate the exercise tolerance of the rats,and the grip strength test was performed to assess changes in forelimb grip strength.Hematoxylin-eosin,Masson,and wheat germ agglutinin staining were used to evaluate pathological changes in cardiac tissue.Bulk RNA sequencing analysis was performed to identify differentially expressed genes(DEGs)in the hearts of rats between the blank control and the DCM with heart failure toxin syndrome groups.Using DCM,the Blue value of rat fur color,and forelimb grip strength as phenotypic traits,weighted gene co-expression network analysis(WGCNA)was performed to screen for characteristic module gene sets(MEs)associated with DCM with heart failure toxin syndrome.Overlapping analysis was performed on DEGs,immune-related gene sets,and MEs,and the intersecting genes were identified as potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.The sensitivity and specificity of these targets were evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared with the blank control group,at the tenth week of modeling,the LVEF,FS,and LVPWs of rats in the doxorubicin group and the DCM with heart failure toxin syndrome group decreased,whereas LVIDs and LVIDd increased,and the movement distance of the open field test and forelimb grip strength were reduced(P＜0.05).At the 10th week of modeling,the Blue value of fur color in the DCM with heart failure toxin syndrome group was significantly lower than that of the blank control and doxorubicin groups(P＜0.05).Compared with the blank control group,rats in the doxorubicin and DCM with heart failure toxin syndrome groups exhibited significant cardiac dilation and increased immune cell infiltration in cardiac tissue,accompanied by collagen deposition and cardiomyocyte hypertrophy.Bulk RNA sequencing identified 2,003 DEGs,including 1,082 downregulated genes and 921 upregulated genes.WGCNA results revealed that the MEturquoise module had the strongest positive correlation with DCM and the strongest negative correlation with the Blue value and forelimb grip strength.The overlapping analysis identified four intersecting genes:bone morphogenetic protein 6(Bmp6),serine-threonine-protein kinase 1(Pak1),proto-oncogene JunD(JunD),and S100 calcium-binding protein A3(S100A3).ROC curve analysis demonstrated that these four genes exhibited high sensitivity and specificity for DCM with heart failure toxin syndrome.Conclusion The rat model constructed by intraperitoneal injection of doxorubicin combined with a high-fat feed,fructose water,and white liquor gavage closely aligns with the characteristics of the DCM with heart failure toxin syndrome.Bmp6,JunD,Pak1,and S100A3 are potential biomarkers or therapeutic targets for DCM heart failure toxin syndrome.