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 investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

Zhishi Shaoyaosan is the 34^th prescription in the Catalogue of Ancient Classic Formulas （Second Batch） published by the National Administration of Traditional Chinese Medicine in 2023. It is widely used in clinical practice and has a definite curative effect. However， there is currently a lack of its ancient literature analysis and textual research， and there is no corresponding Chinese patent medicine preparation. By consulting and combing the relevant ancient books of traditional Chinese medicine， this paper analyzes and conducts textual research of the origin， composition， measurement， administration， and efficacy of Zhishi Shaoyaosan. The results show that Zhishi Shaoyaosan is derived from Essentials from the Golden Cabinet written by Zhang Zhongjing in the Eastern Han Dynasty. It is mainly recorded in the name of Zhishi Shaoyaosan in the literature of the past dynasties. The prescription is composed of Aurantii Fructus Immaturus and Paeoniae Radix Alba. The processing method is stir-frying Aurantii Fructus Immaturus to scorch and using raw Paeoniae Radix Alba. The dose of the prescription recorded in the ancient books is mainly an equal amount of Aurantii Fructus Immaturus and Paeoniae Radix Alba in one square-cun spoon， taken three times a day， which is converted into a modern dose of 1.5 g each time （0.75 g Aurantii Fructus Immaturus and 0.75 g Paeoniae Radix Alba each time）. The components of the prescription are ground into powder and taken with barley porridge， three times a day. The efficacy is to break stagnated Qi， harmonize blood， and relieve restlessness and pain. It is mainly used to treat postpartum abdominal pain， acute pelvic inflammatory disease， acute cholecystitis and intestinal diseases， stroke sequelae， and other diseases. This study combs and analyzes the ancient literature recording Zhishi Shaoyaosan and clarifies the key information of the prescription， which provides a basis for promoting the research and development of its patent medicine.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

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.

The escalating pressure from global population growth, climate change, and resource consumption is intensifying the burden on traditional agricultural production. Against this backdrop, soil degradation and pollution present increasingly severe challenges, creating a vicious cycle with rising food demands. Maintaining soil health and its ecosystem services has thus become a critical prerequisite for achieving sustainable agriculture in the future. This review explores the impacts of soil carbon (C) and nitrogen (N) dynamics on soil microbial communities and their interactions. Soil C and N are key determinants of microbial diversity and community structure, intrinsically linked to soil C/N cycling, crop productivity, and ecological balance. Environmental factors such as nitrogen fertilizer application, organic matter amendment application, litter decomposition, elevated CO₂ concentrations, and nitrogen deposition significantly influence soil C and N dynamics. Changes in soil C and N content regulate microbial community dynamics and the synergistic, competitive, and antagonistic interactions among microorganisms. Meanwhile, microbial communities actively respond to alterations in soil C and N availability. The resulting shifts in microbial communities and their interactions subsequently regulate soil C/N cycling and ecosystem stability, ultimately influencing ecosystem functions. By elucidating the mechanisms underlying soil carbon-nitrogen-microbial interactions, this review significantly advances our understanding of soil ecosystem responses and feedback mechanisms in the context of global change, while also providing crucial practical guidance for enhancing soil fertility and promoting sustainable agricultural development through microbial regulation.
Soil Microbiology ; Nitrogen/metabolism* ; Carbon/metabolism* ; Soil/chemistry* ; Bacteria/growth & development* ; Fungi/metabolism* ; Ecosystem ; Fertilizers ; Agriculture

Objective:This article analyzed the current situation, similarities and differences and main problems of the registration and management systems of innovative medical devices in China and the United States.Methods:This article summarized the requirements and policies for the registration management of innovative medical devices in China and the United States, as well as the development and differences of the registration of innovative medical devices in China and the United States, and the main problems in the registration management of innovative medical devices in China.Results:At present, the development level of medical device industry in China and the United States was different, facing different development problems, and there were differences in the access standards and management methods of innovative medical devices. The registration management system established for innovative medical devices in China was gradually improving, and to a certain extent, it had promoted the enthusiasm of innovative product research and development and registration applications, but there were also problems such as unclear innovation evaluation scales, insufficient early intervention of review resources, and insufficient utilization of post-marketing data.Conclusions:Drawing on the beneficial experience of breakthrough device registration management in the United States, we will improve the registration management system for innovative products and shorten the review and approval cycle by clarifying the identification criteria for innovative medical devices, promoting the placement of review resources in the R&D stage, and further strengthening the use of post-marketing data and regulatory scientific research.

Objective:To compare the image quality, radiation dose, and total iodine content of abdominal computed tomography (CT) enhancement scanning of overweight and obese patients with different scanning protocols, and to explore the optimal keV image serial for abdominal CT.Methods:A total of 90 overweight or obese patients [24 kg/m 2 ≤ body mass index (BMI) < 28 kg/m 2 or BMI ≥ 28 kg/m 2] were divied into groups A, B and C, with 30 patients in each group. Group A used Gemstone spectral imaging (GSI) mode and contrast medium with 320 mg I/ml, group B used low tube voltage mode (100 kVp) and contrast medium with 370 mg I/ml, and group C used conventional tube voltage mode (120 kVp) and contrast medium with 370 mg I/ml. Monochromatic energy images at 50-70 keV (5 keV interval) were reconstructed for the arterial and portal vein phases of group A. Radiation dose and total iodine content were recorded and calculated for the 3 groups. The region of interest was placed on the organ, blood vessel, and erector spinae muscle at same level. The CT values and image noise values were measured, and the contrast-to-noise ratio (CNR) was calculated. All images were scored subjectively in double-blinded by two radiologists. One-way analysis of variance or Kruskal-Wallis H test were used to compare The CT values, CNRs, and subjective scores of each subgroup image in group A, group B and group C, and the radiation doses and total iodine contents in 3 groups were compared. The optimal keV value for group A was selected. Results:At 50-60 keV, the CT values and CNRs of arterial and portal vein phases in group A were higher ( P < 0.05) than or similar to those in groups B and C ( P > 0.05), and the subjective scores were lower than those of groups B and C at 50 and 55 keV ( H = 34.47, 41.27, P < 0.05), whereas there was no statistically significant difference at 60 keV ( P > 0.05). At 65 and 70 keV, only the CT value and CNR of the renal cortex in group A at the 65 keV of arterial phase were higher than those in groups B and C ( F = 102.38, 29.47, P < 0.001). The subjective scores were not significantly between groups B and C ( P > 0.05). There were no statistically significant difference between CT values, CNRs, or subjective scores in group B and group C ( P > 0.05). The effective doses in groups A and B were 24.72% and 25.78% lower than those in group C, respectively. Compared to groups B and C, the total iodine content in group A decreased by 12.50% and 13.34%, respectively. Conclusions:GSI model combined with a low-concentration contrast medium in abdominal CT for overweight and obese patients can meet the image quality requirements while reducing patient total iodine content and radiation dose. The optimal keV value of enhanced abdominal CT for double phases was 60 keV.

Objective To explore the clinical value of models based on clinical features and enhanced MRI radiomics for predicting the occurrence of post-acute pancreatitis diabetes mellitus(PPDM-A).Methods A retrospective selection of 161 acute pancreatitis(AP)patients was conducted,comprising 99 in the non-PPDM-A group and 62 in the PPDM-A group.They were randomly divided into training set and test set in a ratio of 7∶3.Region of interest(ROI)were delineated and radiomics features were extracted on the late arterial phase MRI images.Optimal radiomics features were selected by maximum relevance and minimum redundancy(mRMR)and least absolute shrinkage and selection operator(LASSO).Support vector machine(SVM)was used to develop three predictive models.The efficacy of the models in predicting PPDM-A was evaluated,the receiver operating characteristic(ROC)curve was drawn,and the DeLong test was employed to assess the difference in predictive capability among the models.Results In the training set,the area under the curve(AUC)of the clinical model,radiomics model,and combined model were 0.702,0.810 and 0.901,respectively,and in the test set were 0.678,0.797 and 0.830,respectively.The DeLong test revealed a statistically significant difference in the predictive capability of the combined model compared to the clinical model both in the training and test sets(training set:P＜0.001;test set:P=0.019).Conclusion The combined model based on clinical features and enhanced MRI radiomics features demonstrates good predictive effi-cacy and can provide valuable insights for clinical interventions aimed at preventing PPDM-A.