Objective To explore the effects and mechanism of Shengxian Yixin Granules in treating ventricular remodeling in rats with myocardial infarction based on the PI3K/AKT signaling pathway.Methods A total of 60 SD rats were randomly selected six rats as the control group,and the remaining 54 rats were used as the modeling group.Sham-operation and left anterior descending coronary artery ligation were performed respectively.The modeled rats were divided into model group,Shengxian Yixin Granules group,740Y-P group and Shengxian Yixin Granules+740Y-P group,and were given corresponding intervention for 28 days.Left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were measured by echocardiography,and left ventricular hypertrophy index was calculated,the myocardial morphology was observed by HE and Masson staining,and the protein expressions of p-PI3K,PI3K,p-AKT and AKT were detected by Western blot,RT-qPCR was used to detect the mRNA expressions of type Ⅰ collagen(Col1)and type Ⅲ collagen(Col3),and ELISA was used to detect the contents of serum cardiac troponin T(cTnT),creatine kinase-MB(CK-MB),Col1 and Col3.Results Compared with the control group,the LVEF and LVFS in the model group significantly decreased(P<0.01),the left ventricular hypertrophy index increased(P<0.01);myocardial cells were arranged disorderly,some cells were necrotic,ruptured and their nuclei were dissolved,with obvious neutrophil infiltration,the collagen fiber significantly increased,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),and the mRNA expression of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Compared with the model group,the LVEF and LVFS in Shengxian Yixin Granules group significantly improved(P<0.05,P<0.01),and left ventricular hypertrophy index decreased(P<0.05);myocardial necrosis,neutrophil infiltration and collagen fiber deposition were reduced,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly decreased(P<0.05),and the mRNA expressions of Col1 and Col3 significantly decreased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly decreased(P<0.05,P<0.01).LVEF and LVFS in 740Y-P group significantly decreased(P<0.01),and left ventricular hypertrophy index increased(P<0.05);a large number of myocardial cells were necrotic and ruptured,fibers were torn obviously,and many scar tissues were formed,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),the mRNA expressions of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Shengxian Yixin Granules+740Y-P could improve the damage of 740Y-P to the heart.Conclusion Shengxian Yixin Granules can improve ventricular remodeling in rats with heart failure,reduce myocardial fibrosis,and improve cardiac function through the PI3K/AKT signaling pathway.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Objective To explore the effects and mechanism of Shengxian Yixin Granules in treating ventricular remodeling in rats with myocardial infarction based on the PI3K/AKT signaling pathway.Methods A total of 60 SD rats were randomly selected six rats as the control group,and the remaining 54 rats were used as the modeling group.Sham-operation and left anterior descending coronary artery ligation were performed respectively.The modeled rats were divided into model group,Shengxian Yixin Granules group,740Y-P group and Shengxian Yixin Granules+740Y-P group,and were given corresponding intervention for 28 days.Left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were measured by echocardiography,and left ventricular hypertrophy index was calculated,the myocardial morphology was observed by HE and Masson staining,and the protein expressions of p-PI3K,PI3K,p-AKT and AKT were detected by Western blot,RT-qPCR was used to detect the mRNA expressions of type Ⅰ collagen(Col1)and type Ⅲ collagen(Col3),and ELISA was used to detect the contents of serum cardiac troponin T(cTnT),creatine kinase-MB(CK-MB),Col1 and Col3.Results Compared with the control group,the LVEF and LVFS in the model group significantly decreased(P<0.01),the left ventricular hypertrophy index increased(P<0.01);myocardial cells were arranged disorderly,some cells were necrotic,ruptured and their nuclei were dissolved,with obvious neutrophil infiltration,the collagen fiber significantly increased,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),and the mRNA expression of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Compared with the model group,the LVEF and LVFS in Shengxian Yixin Granules group significantly improved(P<0.05,P<0.01),and left ventricular hypertrophy index decreased(P<0.05);myocardial necrosis,neutrophil infiltration and collagen fiber deposition were reduced,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly decreased(P<0.05),and the mRNA expressions of Col1 and Col3 significantly decreased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly decreased(P<0.05,P<0.01).LVEF and LVFS in 740Y-P group significantly decreased(P<0.01),and left ventricular hypertrophy index increased(P<0.05);a large number of myocardial cells were necrotic and ruptured,fibers were torn obviously,and many scar tissues were formed,the protein expressions of p-PI3K and p-AKT in myocardial tissue significantly increased(P<0.05),the mRNA expressions of Col1 and Col3 significantly increased(P<0.01);the contents of serum cTnT,CK-MB,Col1 and Col3 significantly increased(P<0.05,P<0.01).Shengxian Yixin Granules+740Y-P could improve the damage of 740Y-P to the heart.Conclusion Shengxian Yixin Granules can improve ventricular remodeling in rats with heart failure,reduce myocardial fibrosis,and improve cardiac function through the PI3K/AKT signaling pathway.

Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

Objective To construct a hybrid decision-making model that integrates knowledge-driven and data-driven approaches,and to apply it to the etiological diagnosis of ventricular tachycardia(VT).Methods Clinical practice guidelines,expert consensus documents,and medical literature in the field of ar-rhythmia diseases from 2018 to 2023 were retrieved as knowledge sources.Retrospective electronic medical re-cord data of VT patients from Fuwai Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,from 2013 to 2023 were collected as the dataset.A knowledge-driven model was constructed using a knowledge-rule-based approach to establish clinical pathways.A three-class machine learning model for VT eti-ology diagnosis was developed based on real-world data,and the best-performing model was selected as the rep-resentative of the data-driven approach.The machine learning model was embedded into the decision nodes of the clinical pathway in the form of custom operators,forming the hybrid model.The precision,recall,and F1 score of the three models were evaluated.Results Three clinical practice guidelines were included as knowl-edge sources for the knowledge-driven model.A total of 1305 patient records were collected as the dataset,and five machine learning models were constructed,with the XGBoost model performing the best.The hybrid model adopted a knowledge-driven decision-making framework,embedding the XGBoost model into the decision nodes of a two-level classification.The precision,recall,and F1 scores of the three models were as follows:the knowledge-driven model achieved 80.4％,79.1％,and 79.7％;the data-driven model achieved 88.4％,88.5％,and 88.4％;and the hybrid model achieved 90.4％,90.2％,and 90.3％.Conclusions The hybrid model integrating knowledge-driven and data-driven approaches demonstrated higher accuracy,and all its deci-sion outcomes were based on evidence-based practices,aligning more closely with the actual diagnostic reason-ing of clinicians.Further rigorous validation is needed to assess the feasibility of widely applying the hybrid model in the medical field.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

AIM To study the chemical constituents from the leaves of Cyanocarya paliurus(Batalin)Iljinskaja and their α-glucosidase inhibitory activities.METHODS The 95%ethanol extract from the leaves of C.paliurus was isolated and purified by macroporous resin,silica gel,Sephadex LH-20,polyamide,C18 reversed-phase silica gel and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG.RESULTS Fifteen compounds were isolated and identified as cyclopaloside C(1),cyclopaloside A(2),juglanosides E(3),vaccinin A(4),ent-murin A(5),kaempferol 3-O-α-L-rhamnopyranoside(6),kaempferol-3-O-β-D-glucopyranoside(7),kaempferol-3-O-β-D-glucuronide methyl ester(8),kaempferol-3-O-β-D-glucuronide ethyl ester(9),kaempferol-3-O-β-D-glucuronide butyl ester(10),quercetin-3-O-α-L-rhamnopyranoside(11)quercetin-3-O-β-D-glucopyranoside(12),quercetin-3-O-β-D-galactopyranoside(13),quercetin-3-O-β-D-glucuronide butyl ester(14),dihydrokaempferol(15).The IC50 value of total extracts ihibited α-glucosidase was(1.83±0.04)μg/mL,and the IC50 values of compounds 1,4-5 were(29.48±1.86),(0.50±0.07),(0.71±0.07)μmol/L,respectively.CONCLUSION Compound 1 is a new tetrahydronaphthalene glycoside.Compounds 4-5,8-10 and 14 are isolated from the leaves of C.paliurus for the first time.Compounds 4-5 are relatively rare flavonoid lignans with potential inhibitory activities against α-glucosidase.