ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease （CHD） with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group （6 pigs） and a high-fat diet group （24 pigs）. After 2 weeks of high-fat diet feeding， the high-fat diet group was randomly subdivided into a model group， an atorvastatin group （1 mg·kg^-1）， and Danlou tablet groups （0.6 g·kg^-1 and 0.3 g·kg^-1）. All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet， underwent only coronary angiography， and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later， they underwent a coronary angiography injury procedure. After the procedure， drugs were mixed into the feed every morning for 8 consecutive weeks， with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins， and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group， the model group showed a significant increase in total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） of minipigs' serum （P<0.01）， a significant shortening in prothrombin time of （PT） （P<0.01）， a coagulation function index， and an increase in whole blood viscosity （P<0.01） and platelet aggregation rate （P<0.01）. Moreover， the platelet morphology was altered， and the contents of endothelin-1 （ET-1） and nitric oxide （NO） were significantly increased （P<0.01）. Hemodynamic parameters were obviously abnormal， including significantly decreased systolic blood pressure （SBP）， diastolic blood pressure （DBP）， mean arterial pressure （MAP）， left ventricular systolic pressure （LVSP）， and left ventricular maximal positive dp/dt （LV+dp/dt_max） （P<0.01）. Left ventricular maximal negative dp/dt （LV-dp/dt_max） was significantly increased （P<0.01）. Besides， there were myocardial cell hypertrophy， obvious edematous degeneration， massive interstitial inflammatory cell infiltration， high degree of fibrosis， and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg^-1 and 0.3 g·kg^-1 （P<0.05， P<0.01）， compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. In groups with all doses of Danlou tablet， maximum aggregation rate （MAR） and average aggregation rate （AAR） were significantly decreased （P<0.05， P<0.01）， and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg^-1， NO level in the serum was reduced （P<0.05）. In groups with all doses of Danlou tablet， DBP and MAP were significantly increased （P<0.05）. In the Danlou tablet group with 0.6 g·kg^-1， LVSP and LV+dp/dt_max were significantly increased （P<0.05， P<0.01）， and LV-dp/dt_max was significantly decreased （P<0.05）. In groups with all doses of Danlou tablet， edematous degeneration in myocardial tissue was milder， and coronary artery lesion degree was significantly alleviated. Compared with the normal control group， there were 94 differentially expressed proteins in the model group， including 81 up-regulated and 13 down-regulated proteins. Compared with the model group， the Danlou tablet group with 0.6 g·kg^-1 showed 174 differentially expressed proteins， including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation， aggregation， and adhesion effects through biological pathways such as regulation of actin cytoskeleton， platelet activation pathway， Fcγ receptor-mediated phagocytosis， as well as proteins such as growth factor receptor-bound protein 2 （GRB2）， Ras-related C3 botulinum toxin substrate 2 （RAC2）， RAC1， and heat shock protein 90 alpha family class A member 1 （HSP90AA1）. ConclusionDanlou tablet can effectively reduce platelet activation and aggregation， exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway， as well as proteins like GRB2， RAC2， RAC1， and HSP90AA1， thereby exerting a pharmacological effect in anti-platelet activation， aggregation， and adhesion.

ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

Objective:To evaluate the image quality and radiation dose in contrast-enhanced thoracic-abdominal-pelvic CT using automatic tube voltage modulation (ATVM) coupled with artificial intelligence iterative reconstruction (AIIR) versus routine tube voltage combined with Karl-3D iterative reconstruction (Karl-3D IR), and to determine the optimal noise level for AIIR in contrast-enhanced thoracic-abdominal-pelvic CT.Methods:A total of 100 patients who underwent contrast-enhanced thoracic-abdominal-pelvic CT examination in the Affiliated Hospital of Hebei University from April to October, 2023 were randomly divided into group A and group B using a random number table, with 50 patients in each group. Group A was scanned using ATVM, and images were reconstructed using AIIR with 1-5 noise levels. Group B was scanned using tube voltage 120 kVp and images were reconstructed with Karl-3D IR and noise level 5. The single-to-noise ratio (SNR), contrast-to-noise ratio (CNR), effective dose (E), and size-specific dose estimate (SSDE) were recorded or calculated for all patients or images. Subjective evaluations of all images were performed. The quality of the reconstructed images using AIIR with 1-5 noise levels were compared and the optimal noise level of AIIR for image reconstruction was determined. Image quality and radiation dose were statistically analyzed for Group A (image reconstruction with optimal AIIR noise level) and Group B.Results:The mean SNR and mean CNR of the reconstructed images using AIIR with noise levels 1, 2, and 3 in group A were higher than those using AIIR with noise levels 4 and 5. The images reconstructed using AIIR with noise levels 3 and 4 scored higher in subjective assessment than those reconstructed using AIIR with noise levels 1, 2, and 5. Therefore, noise level 3 was optimal for AIIR in reconstruction of contrast-enhanced thoracic-abdominal-pelvic CT images. The mean SNR, mean CNR, and subjective evaluation score of group A using AIIR with noise level 3 were higher than those of group B using Karl-3D IR with noise level 5 ( P<0.001). The mean SSDE and the mean E of group A were reduced by 46% and 41%, respectively, compared with those of group B. Conclusions:ATVM technology combined with the AIIR algorithm can improve image quality and reduced patient radiation dose in contrast-enhanced thoracic-abdominal-pelvic CT. Noise level 3 is optimal for AIIR in the reconstruction of arterial-phase and venous-phase contrast-enhanced thoracic-abdominal-pelvic CT images.

Objective:This study investigated the independent risk factors for lymph node metastasis（LNM）in high-risk prostate cancer（HRPCa）patients undergoing robot-assisted radical prostatectomy（RARP），and constructed a nomogram model based on clinical data to improve the accuracy and clinical practicality of preoperative prediction of LNM.Methods:A retrospective analysis was conducted on the clinical data of 218 HRPCa patients who received RARP treatment at the First Medical Center of the PLA General Hospital from January 2020 to March 2025 as the modeling group. The age of the modeling group was（66.91±6.94）years old. 75 cases（34.40%）had a history of smoking，and 48 cases（22.02%）had a history of drinking. There were a body mass index（BMI）of 25.55（23.58，27.00）kg/m 2，a total prostate-specific antigen（tPSA）of 20.59（10.42，30.61）ng/ml，a free prostate-specific antigen（fPSA）of 1.87（1.04，3.26）ng/ml，a prostate volume（PV）of（41.19±21.00）ml，a prostate-specific antigen density（PSAD）of 0.52（0.30，0.84）ng/ml 2. Among the patients，60 cases（27.52%）had a preoperative biopsy Gleason score >8，and the percentage of positive biopsy cores（PPBC）was 50%（31%，80%）. Thirty-one patients（14.22%）were staged clinically as >T 2c. The diagnostic criteria for high-risk prostate cancer（HRPCa）were defined as meeting any one of the following：PSA >20 ng/ml，Gleason score on prostate biopsy ≥8，or clinical stage ≥T 3. Among the 218 patients in the modeling cohort，67 cases（30.73%）met two of the criteria，and 7 cases（3.21%）met all three criteria. All 218 patients underwent RARP，and based on postoperative pathology，they were divided into the LNM group and the non-LNM group. The relationship between the number of diagnostic criteria met and the occurrence of LNM was analyzed. An external validation cohort included 42 HRPCa patients who underwent RARP at the Third，Fifth Medical Centers of the PLA General Hospital between January 2023 and May 2025. Their mean age was（66.79±5.92）years. Eighteen patients（42.86%）had a smoking history，and nine（21.43%）had a history of alcohol consumption. The median BMI was 26.00（23.80，27.13）kg/m 2. The median tPSA level was 17.34（8.97，27.30）ng/ml. The median fPSA was 1.51（0.83，2.52）ng/ml，and the median PV was（35.57 ± 15.25）ml. The median PSAD was 0.57（0.23，0.87）ng/ml 2，and the median PPBC was 58%（36%，71%）. Three patients（7.14%）had a clinical stage >T 2c，and 12 patients（28.57%）had a Gleason score >8 on preoperative biopsy. Univariate and multivariate binary logistic regression analyses were used to identify independent risk factors for LNM，and a nomogram model was constructed based on these factors. The predictive performance of the model was evaluated using receiver operating characteristic（ROC）curves and calibration plots，and the model was validated in the external cohort. Result:According to postoperative pathology，45 patients were classified into the LNM group，and 173 into the non-LNM group. The probability of LNM increased proportionally with the number of diagnostic criteria met for HRPCa（meeting two criteria： OR = 4.762，95% CI 2.323-9.761， P < 0.01；meeting three criteria： OR = 10.667，95% CI 2.187-52.025， P=0.003）. Binary logistic regression analysis revealed that age（ OR=0.913，95% CI 0.859-0.971， P = 0.004），tPSA（ OR=1.039，95% CI 1.018-1.061， P<0.01），PPBC（ OR = 5.656，95% CI 1.101-29.056， P = 0.038），and clinical T stage（T 2c stage： OR=2.945，95% CI 0.888-9.769， P=0.077；>T 2c stage OR = 18.351，95% CI 4.790-70.306， P < 0.01）were independent risk factors for postoperative LNM in HRPCa patients after RARP. The ROC curve of the nomogram model based on these factors showed an area under the curve（AUC）of 0.853（95% CI 0.790-0.917）. In the external validation cohort，the nomogram achieved an AUC of 0.743（95% CI 0.556-0.929）. The calibration plots demonstrated good agreement between the predicted probabilities and actual observations. Conclusions:Age，tPSA，PPBC，and clinical T stage were independent predictors of postoperative LNM in HRPCa patients undergoing RARP. The greater the number of HRPCa diagnostic criteria met，the higher the likelihood of postoperative LNM. The nomogram developed in this study could effectively predict the risk of LNM in HRPCa patients after RARP.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Non-small cell lung cancer (NSCLC) is a malignant tumor with a high global incidence rate, accounting for about 10.54% of all new cancer cases and posing a serious threat to human health. Due to significant individual variations in the efficacy of immunotherapy among NSCLC patients, it is necessary to identify accurate detection indicators to screen appropriate populations, monitor treatment efficacy, and assist in prognosis assessment. Programmed death-ligand 1 (PD-L1), as an immunosuppressive molecule expressed on the surface of tumor cells and various immune cell membranes, can serve as a "companion diagnostic" or "supplementary diagnostic" tool to guide clinical treatment decisions for metastatic NSCLC patients. Given that tumor tissue PD-L1 testing is an invasive procedure and its reliability is still under debate, the assessment of PD-L1 expression via liquid biopsies, such as circulating tumor cells, will play a significant role in predicting treatment response and prognosis in NSCLC patients.

Objective This article focuses on the investment promotion policies at the municipal and district levels(park management committee level)of biomedical industrial parks in China at different development stages.It aims to reveal the characteristics and patterns of these policies,providing a reference for the formulation of development policies for biomedical industrial parks in China.Methods A total of 166 policies issued by three biomedical industrial parks(LifeBay,Nanjing Biotech and Pharmaceutical Valley and BioBay)from January 2013 to June 2023 were coded and quantitatively analyzed using a three-dimensional analytical framework of policy tool-development stage-issuing body.Results At the municipal level,the use of policy tools by administrative development is supply-oriented and environmental-oriented.At the district level,the types of policy tools used are closely related to the stage of the park.Start-up parks have a high proportion of supply-based policy tools,growth parks have a high proportion of demand-based policy tools,and mature parks have a high proportion of environmental policy tools.Conclusion Policy insights such as the strategic use of policy tools according to the development stage of the park,the optimization of the internal structure of the tools and the enhancement of the complementarity and coordination among the tools,and the use of policy tools to promote industrial agglomeration in line with local realities are put forward.

Objective To investigate the predictive value of pulmonary artery(Pa)to aortic(Ao)diameter ratio(Pa/Ao)for long-term major adverse cardiovascular events(MACEs)in patients with acute decompensated heart failure(ADHF).Methods ADHF patients hospitalized in the Department of Cardiology of Nanjing Drum Tower Hospital from January 2018 to January 2023 were consecutively enrolled.The data of gender,age,past medical history,laboratory examination,echocardiography,chest CT and medication were collected.The diameters of Pa and Ao were measured at the bifurcation of main pulmonary artery on chest CT,and Pa/Ao was calculated.The Kaplan-Meier method was used for survival analysis,and the Log-rank test was used to compare the survival rate between the two groups.Cox proportional hazards regression model was used to analyze the association between Pa/Ao and MACEs,and subgroup analysis was performed according to different age,sex,BMI,B-type natriuretic peptide level,and left ventricular ejection fraction.Results A total of 600 ADHF patients were enrolled,with an average age of 69.6 years and 347(57.8%)males.During a median follow-up of 306(127,624)days,327(54.5%)patients experienced MACEs.The ADHF patients were divided into Pa/Ao<0.93 group and Pa/Ao≥0.93 group according to the analysis of maximum selection rank statistics.Kaplan-Meier curve showed that the incidence of MACEs in Pa/Ao≥0.93 group was significantly higher than that in Pa/Ao<0.93 group(PLog-rank<0.001).Multivariate Cox regression analysis showed that Pa/Ao was an independent predictor of MACEs in ADHF patients(HR=11.62,95%CI:4.91～27.50,P<0.001).Subgroup analysis showed that Pa/Ao had predictive value for different ADHF populations(all P<0.05).Conclusion Elevated Pa/Ao is a predictor of long-term MACEs in ADHF patients.

Objective:To evaluate the image quality and radiation dose in contrast-enhanced thoracic-abdominal-pelvic CT using automatic tube voltage modulation (ATVM) coupled with artificial intelligence iterative reconstruction (AIIR) versus routine tube voltage combined with Karl-3D iterative reconstruction (Karl-3D IR), and to determine the optimal noise level for AIIR in contrast-enhanced thoracic-abdominal-pelvic CT.Methods:A total of 100 patients who underwent contrast-enhanced thoracic-abdominal-pelvic CT examination in the Affiliated Hospital of Hebei University from April to October, 2023 were randomly divided into group A and group B using a random number table, with 50 patients in each group. Group A was scanned using ATVM, and images were reconstructed using AIIR with 1-5 noise levels. Group B was scanned using tube voltage 120 kVp and images were reconstructed with Karl-3D IR and noise level 5. The single-to-noise ratio (SNR), contrast-to-noise ratio (CNR), effective dose (E), and size-specific dose estimate (SSDE) were recorded or calculated for all patients or images. Subjective evaluations of all images were performed. The quality of the reconstructed images using AIIR with 1-5 noise levels were compared and the optimal noise level of AIIR for image reconstruction was determined. Image quality and radiation dose were statistically analyzed for Group A (image reconstruction with optimal AIIR noise level) and Group B.Results:The mean SNR and mean CNR of the reconstructed images using AIIR with noise levels 1, 2, and 3 in group A were higher than those using AIIR with noise levels 4 and 5. The images reconstructed using AIIR with noise levels 3 and 4 scored higher in subjective assessment than those reconstructed using AIIR with noise levels 1, 2, and 5. Therefore, noise level 3 was optimal for AIIR in reconstruction of contrast-enhanced thoracic-abdominal-pelvic CT images. The mean SNR, mean CNR, and subjective evaluation score of group A using AIIR with noise level 3 were higher than those of group B using Karl-3D IR with noise level 5 ( P<0.001). The mean SSDE and the mean E of group A were reduced by 46% and 41%, respectively, compared with those of group B. Conclusions:ATVM technology combined with the AIIR algorithm can improve image quality and reduced patient radiation dose in contrast-enhanced thoracic-abdominal-pelvic CT. Noise level 3 is optimal for AIIR in the reconstruction of arterial-phase and venous-phase contrast-enhanced thoracic-abdominal-pelvic CT images.

Objective This article focuses on the investment promotion policies at the municipal and district levels(park management committee level)of biomedical industrial parks in China at different development stages.It aims to reveal the characteristics and patterns of these policies,providing a reference for the formulation of development policies for biomedical industrial parks in China.Methods A total of 166 policies issued by three biomedical industrial parks(LifeBay,Nanjing Biotech and Pharmaceutical Valley and BioBay)from January 2013 to June 2023 were coded and quantitatively analyzed using a three-dimensional analytical framework of policy tool-development stage-issuing body.Results At the municipal level,the use of policy tools by administrative development is supply-oriented and environmental-oriented.At the district level,the types of policy tools used are closely related to the stage of the park.Start-up parks have a high proportion of supply-based policy tools,growth parks have a high proportion of demand-based policy tools,and mature parks have a high proportion of environmental policy tools.Conclusion Policy insights such as the strategic use of policy tools according to the development stage of the park,the optimization of the internal structure of the tools and the enhancement of the complementarity and coordination among the tools,and the use of policy tools to promote industrial agglomeration in line with local realities are put forward.