ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.

Objective To explore the influencing factors of coronary artery lesion severity in patients with acute coronary syndrome (ACS). Methods Clinical data of ACS patients admitted to Zhongshan Hospital, Fudan University from December 2017 to December 2019 were consecutively collected. The modified Gensini score was used to assess the severity of coronary artery lesions. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with coronary artery lesion severity. Results A total of 1 689 ACS patients were included, with an average age of (64.04±11.45) years; 1 353 (80.11%) were male, and the mean modified Gensini score was (8.12±4.03). Multivariate linear regression analysis revealed that sex (β＝0.97, P＝0.001), age (β＝0.03, P＝0.021), estimated glomerular filtration rate (eGFR; β＝－0.03, P＜0.001), low-density lipoprotein cholesterol (LDL-C; β＝0.58, P＜0.001), apolipoprotein A1 (Apo A1; β＝－1.28, P＝0.012), lipoprotein(a) [Lp(a); β＝0.001, P＝0.033], and glycated hemoglobin A_1C (HbA_1C; β＝0.45, P＜0.001) were independent influencing factors of the modified Gensini score. Conclusions Metabolic indicators, including Apo A1, LDL-C, HbA_1C, and Lp(a), may serve as risk factors for coronary artery lesion severity in ACS patients, with Apo A1 demonstrating the strongest impact.

Objective To compare the oncologic safety, surgical efficacy, and aesthetic outcomes between conventional breast-conserving surgery and axillary single-port incision insufflation endoscopic breast-conserving surgery with mini-latissimus dorsi surgery in early breast cancer patients. Methods A retrospective analysis of clinical data from 62 female patients with early breast cancer was performed. Patients were divided into two groups on the basis of surgical method: the conventional group (37 cases) and the endoscopic group (25 cases).The clinical baseline data, surgical results, and postoperative effects of the two groups were compared. Results According to the clinical baseline data, the endoscopic group had a greater maximum tumor diameter and a greater tumor-to-breast volume ratio due to expanded indications for breast-conserving surgery (P<0.001), whereas the other data revealed no statistically significant difference between the two groups (P>0.05). Compared with those in the conventional group, the total incision length in the endoscopic group was shorter [3.40(3.15, 3.60) cm vs. 7.30 (6.50, 7.60) cm, P<0.001], the postoperative drainage volume was lower (206.20±35.11 ml vs. 223.95±26.17 ml, P=0.026), but the operative time was longer (254.92±22.67 min vs. 146.78±13.01 min, P<0.001). The incision margin positive rate was 0% (0/25) in the endoscopic group, which was significantly lower than the 10.8% (4/37) in the conventional group (P=0.141). The endoscopic group had a lower incidence of complications (4% vs. 27%, P=0.047) and superior JBCS aesthetic scores at the 6-month follow-up (76% vs. 43.2%, P=0.006). Conclusion Axillary single-port incision insufflation endoscopic breast-conserving surgery with mini-latissimus dorsi surgery is not inferior to conventional procedures in terms of oncologic safety (margin-negative rate) and offers advantages in terms of scar concealment, fewer complications, and better aesthetic outcomes, especially suitable for early breast cancer patients with small-to-medium breast volumes, tumors located in the outer quadrants and mastectomy ratios of >20%.

Objective Logistic regression model was used to analyze the risk factors of liver cancer in patients with hepatitis B virus-related cirrhosis. Methods A retrospective analysis was performed on 504 patients with hepatitis B cirrhosis who were treated in a hospital from April 2021 to April 2024. The occurrence of liver cancer was counted. The risk factors of liver cancer in patients with HBV-related cirrhosis were analyzed by logistic regression analysis. Results Among the 504 patients with hepatitis B cirrhosis, 101 patients developed liver cancer and 403 patients did not develop liver cancer, which were included in the liver cancer group (n=101) and the non-liver cancer group (n=403).. Among hepatitis B cirrhosis, the incidence rate of liver cancer was 20.04%. Compared with the non-liver cancer group, the proportion of patients with long-term drinking history, family history of liver cancer, history of diabetes mellitus, antiviral therapy, and HBV-DNA load>104 were higher in the liver cancer group (P<0.05). logistic regression analysis found that long-term drinking history (OR=3.077, 95%CI: 1.130-8.378, P=0.028), history of diabetes mellitus (OR=3.747, 95%CI: 1.765-7.954, P=0.001), no antiviral therapy (OR=3.466, 95%CI: 1.337-8.985, P=0.011) and HBV-DNA load>104 (OR=3.149, 95%CI: 1.353-7.328, P=0.008) could independently affect the occurrence of liver cancer in patients with hepatitis B cirrhosis. Conclusion According to logistic regression analysis, long-term drinking history, history of diabetes mellitus, no antiviral therapy, and HBV-DNA load>104 are risk factors for liver cancer in patients with HBV-related cirrhosis.

According to the theory of cancer toxin pathogenesis， tumors are complex syndromes centered on cancer toxin， characterized by multiple time points and locations， interwoven pathogenic toxins， and a combination of deficiency and excess. Postoperative recurrence of colorectal cancer is a dynamic spatiotemporal process. In this paper， the core pathogenesis of postoperative recurrence of colorectal cancer， namely "deficiency of spleen qi， with damp-heat stasis toxin"， has been discussed based on spatiotemporal evolution of cancer toxin. It is suggested that spleen qi depletion leading to the proliferation of cancer toxin represents the temporal characteristic of postoperative recurrence， while the stasis of damp-heat facilitating the aggregation and spread of cancer toxin refelct its spatial pattern. This paper has constructed a holistic spatiotemporal prevention and treatment strategy according to different stages before and after recurrence. Before recurrence， the focus is on prevention， and it is suggested to rectify the healthy qi and fortify spleen， clear heat and resolve dampness， unblock collaterals and remove toxin. After recurrence， the focus should be on treatment， and the strategy is combating cancer and removing toxin， breaking the blood to eliminate disease， regulating and tonifying the zang-fu （脏腑） organs.

Objective: To investigate the role of ferroptosis in transfusion-related acute lung injury (TRALI) and evaluate the efficacy of the specific inhibitor Ferrostatin-1 (Fer-1), thereby to provide a basis for the prevention and treatment of TRALI. Methods: This study utilized a ”2-hit” model to induce TRALI in mice. The mouse model of TRALI was validated through survival curve analysis, lung tissue wet/dry weight ratio (W/D), myeloperoxidase (MPO) activity, and total protein concentration in lung tissue. Samples from the TRALI model group, LPS group, and control group (n=6) were collected. The occurrence of ferroptosis in TRALI was confirmed by measuring key ferroptosis indicators, including iron concentration in lung tissue, malondialdehyde (MDA) level, lipid peroxidation products (LPO) level, and expression levels of related proteins (GPX4, ACSL4). Additionally, a Fer-1 intervention group was added to evaluate its preventive and therapeutic effects. The survival rates and clinical symptoms of the four groups (n=6) were dynamically monitored, and the degrees of lung injury were assessed. Ferroptosis-related indicators were also measured to elucidate the protective mechanism of Fer-1. Results: A mouse model of TRALI was successfully established. Compared to the control and LPS groups, the TRALI group showed significantly higher levels of ferrous iron [(18.32±1.11) nmol/well, MDA [(14.68±0.96) μmol/L], and LPO [(1.60±0.02) μmol/L] in lung tissue (all P<0.01), along with a downregulation of GPX4 and an upregulation of ACSL4. Fer-1 pretreatment significantly reversed these abnormalities: the W/D ratio decreased to 4.01±0.43, and MPO activity significantly decreased [Fer-1 group: (21 606±4 235) pg/mL vs TRALI group: (30 724±2 616) pg/mL], the total protein concentration in lung tissue of the Fer-1 group decreased by approximately 40.8% compared to the TRALI group (all P<0.01). These changes indicate that the lung injury in mice was alleviated after treatment. Following Fer-1 intervention, ferrous iron concentration [(7.46±1.83) nmol/well] was restored to a level close to that of the control group [(5.48±0.70) nmol/well]. Lipid peroxidation tests further revealed that Fer-1 intervention reduced MDA and LPO levels by 35.8% and 29.4%, respectively (P<0.001). Additionally, the expression levels of GPX4 and ACSL4 proteins returned to near-normal levels in the treated mice (both P>0.05). Conclusion: The progression of TRALI is closely related to the activation of ferroptosis, characterized by iron overload, lipid peroxidation accumulation, and the imbalance of GPX4/ACSL4. Ferrostatin-1 significantly alleviates pulmonary edema and inflammatory damage by inhibiting the ferroptosis pathway, suggesting that targeting ferroptosis may provide a new therapeutic strategy for TRALI.

OBJECTIVE To study the improvement effect and mechanism of Shengmai powder on heart failure （HF） mice with qi-yin deficiency. METHODS The mice were randomly divided into blank group （water）， model group （water）， Shengmai powder low-， medium-， and high-dose groups [2.61， 5.22 and 10.44 g/kg （based on crude drug dosage）] and positive control group （metoprolol， 30 mg/kg）， with 10 mice in each group. Except for the blank group， all other groups were subcutaneously injected with D-galactose， and a qi-yin deficiency HF mice model was established by continuous food restriction and weight-bearing swimming. At the same time of modeling， the corresponding medicine/water was gavaged once a day for five weeks. The general state of mice was recorded and the traditional Chinese medicine （TCM） syndrome score was evaluated. Behavioral experiments were conducted to investigate the total distance of open field action， the percentage of immobility time， and the swimming exhaustion time of mice. The contents of aspartate transaminase （AST）， creatine kinase （CK） and lactate dehydrogenase （LDH） in the serum of mice were detected； cardiac function indexes [heart rate， left ventricular ejection fraction （LVEF）， left ventricular end systolic diameter （LVESD）， left ventricular end diastolic diameter （LVEDD）， left ventricular mass index and whole heart mass index] were all detected； the histopathological morphology of mice myocardium was observed； the level of cardiomyocyte apoptosis in mice was detected； mRNA expression levels of B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Cleaved-caspase-3 in myocardial tissue of mice were detected； the phosphorylation levels of sarcoplasmic reticulum calcium regulatory related proteins [ryanodine receptor 2 （RyR2） and phospholamban （PLB）] in myocardial tissue of mice were detected. RESULTS Compared with the blank group， the body weight， total distance of open field action， swimming exhaustion time， LVEF， LVEDD， Bcl-2 mRNA expression level in myocardial tissue and PLB protein phosphorylation level in the model group were significantly reduced/shortened （P＜0.05）； TCM syndrome score， the percentage of immobility time， heart rate， LVESD， left ventricular mass index， whole heart mass index， cardiomyocyte apoptosis rate， the contents of CK， LDH and AST in serum， mRNA expression levels of Cleaved-caspase-3 and Bax and the phosphorylation level of RyR2 protein in myocardial tissue were significantly increased （P＜0.05）； there were inflammatory cell infiltration， disordered cell arrangement and obvious myocardial interstitial fibrosis in myocardial tissue. After the intervention of Shengmai powder， most of the above quantitative indexes in mice were significantly reversed （P＜0.05）， the inflammatory cell infiltration in myocardial tissue was reduced， and the degree of fibrosis was significantly reduced. CONCLUSIONS Shengmai powder can improve cardiac function， reduce the level of cardiomyocyte apoptosis and myocardial fibrosis in HF mice with qi-yin deficiency. Its mechanism may be related to the regulation of the expression of sarcoplasmic reticulum calcium regulation related proteins.

Objective To explore the occurrence and development trajectories of symptoms at different time points in patients with acute pancreatitis (AP), and to analyze the influencing factors and preventive measures of development trajectories of AP symptom clusters. Methods A convenient sampling method was used to select AP who were admitted from January 2023 to December 2023 were selected and included in the study. The symptoms at different time points were recorded. The severities of symptom clusters in AP patients were explored, and the development trajectories of main symptom clusters were analyzed. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of development trajectories of symptom clusters in AP patients. Results The incidence rates of abdominal pain, dry mouth, abdominal distension and lack of energy were higher in AP patients during hospitalization. The incidence rates of lack of energy, anxiety, abdominal pain and sleep disturbance were higher on the 1^st month after discharge. The incidence rates of abdominal distension, abdominal pain, sleep disturbance and anxiety were higher on the 3^rd month after discharge. The incidence rates of anxiety, abdominal pain and irritability were higher on the 6^th month after discharge. The fatigue symptom cluster, psychological symptom cluster and gastrointestinal symptom cluster were extracted during hospitalization and on the 1^st month and the 3^rd month after discharge, and the psychological symptom cluster and gastrointestinal symptom cluster were extracted on the 6^th month. The severity scores of symptom clusters at each time point were statistically different (P<0.05). The development of gastrointestinal symptom cluster in AP patients was mainly low decline. The development of psychological symptom cluster was mainly high decline. Drinking history and diabetes mellitus were the influencing factors of development trajectory of gastrointestinal symptom cluster in AP patients (P<0.05). High disease severity, drinking history and biliary tract disease were the influencing factors of development trajectory of psychological symptom cluster in AP patients (P<0.05). Conclusion The symptom clusters of AP patients changes over time, with digestive, fatigue, and psychological symptoms being the main groups in the early stage, and psychological and digestive symptoms persisting in the later stage. Early identification and intervention are crucial for improving the prognosis of AP patients.

Objective To explore the occurrence and development trajectories of symptoms at different time points in patients with acute pancreatitis (AP), and to analyze the influencing factors and preventive measures of development trajectories of AP symptom clusters. Methods A convenient sampling method was used to select AP who were admitted from January 2023 to December 2023 were selected and included in the study. The symptoms at different time points were recorded. The severities of symptom clusters in AP patients were explored, and the development trajectories of main symptom clusters were analyzed. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of development trajectories of symptom clusters in AP patients. Results The incidence rates of abdominal pain, dry mouth, abdominal distension and lack of energy were higher in AP patients during hospitalization. The incidence rates of lack of energy, anxiety, abdominal pain and sleep disturbance were higher on the 1^st month after discharge. The incidence rates of abdominal distension, abdominal pain, sleep disturbance and anxiety were higher on the 3^rd month after discharge. The incidence rates of anxiety, abdominal pain and irritability were higher on the 6^th month after discharge. The fatigue symptom cluster, psychological symptom cluster and gastrointestinal symptom cluster were extracted during hospitalization and on the 1^st month and the 3^rd month after discharge, and the psychological symptom cluster and gastrointestinal symptom cluster were extracted on the 6^th month. The severity scores of symptom clusters at each time point were statistically different (P<0.05). The development of gastrointestinal symptom cluster in AP patients was mainly low decline. The development of psychological symptom cluster was mainly high decline. Drinking history and diabetes mellitus were the influencing factors of development trajectory of gastrointestinal symptom cluster in AP patients (P<0.05). High disease severity, drinking history and biliary tract disease were the influencing factors of development trajectory of psychological symptom cluster in AP patients (P<0.05). Conclusion The symptom clusters of AP patients changes over time, with digestive, fatigue, and psychological symptoms being the main groups in the early stage, and psychological and digestive symptoms persisting in the later stage. Early identification and intervention are crucial for improving the prognosis of AP patients.