BackgroundIndividuals with schizophrenia are prone to higher rates of hospital readmission， presenting significant clinical challenges and imposing considerable social burdens within the mental health domain. In recent years， various risk prediction models have been developed to forecast readmission in patients with schizophrenia and support clinical decision-making， but their predictive performance and clinical applicability require comprehensive evaluation. ObjectiveTo systematically evaluate the risk prediction models for readmission in patients with schizophrenia， so as to provide insights for the development of high-performance and highly applicable readmission risk prediction models for patients with schizophrenia. MethodsOn July 5， 2025， a systematic literature search was conducted across multiple electronic databases， including PubMed， Embase， Cochrane Library， Web of Science， CINAHL， CNKI， China Biomedical Literature Database， Wanfang Database， and VIP Database， to identify risk prediction models for readmission in patients with schizophrenia. The search period was from the establishment of the databases to July 1， 2025. Two researchers independently performed literature screening， data extraction， risk of bias assessment， and applicability assessment. ResultsA total of 9 studies were included in this review， encompassing 18 risk prediction models for readmission in patients with schizophrenia. Among them， 4 models reported the area under the receiver operating characteristic （ROC） curve （AUC）， ranging from 0.734 to 0.820， 16 models provided AUC values of 0.642–0.879 for internal validation， and 1 model demonstrated an AUC of 0.841 for external validation. Key predictors included disease duration and the concomitant therapy of antipsychotic medications. The risk of bias was assessed as "high" in all included studies. ConclusionThe development of risk prediction models for readmission in patients with schizophrenia remains in an exploratory stage. Although the model exhibits favorable predictive performance， it is associated with a high risk of bias and insufficient performance evaluation.

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

OBJECTIVES: Multiple myeloma (MM) is a highly heterogeneous hematologic malignancy, with disease progression driven by cytogenetic abnormalities and a complex bone marrow microenvironment. This study aims to construct a prognostic model for MM based on transcriptomic data and lipid metabolism related genes (LRGs), and to identify potential drug targets for high-risk patients to support clinical decision-making. METHODS: In this study, 2 transcriptomic datasets covering 985 newly diagnosed MM patients were retrieved from the Gene Expression Omnibus (GEO) database. Univariate Cox regression and 101 machine learning algorithms were used for gene selection. An LRG-based prognostic model was constructed using Stepwise Cox (both directions) and random survival forest (RSF) algorithms. The association between the prognostic score and clinical events was evaluated, and model performance was assessed using time-dependent receiver operating characteristic (ROC) curves and the C-index. The added predictive value of combining prognostic scores with clinical variables and staging systems was also analyzed. Differentially expressed genes between high- and low-risk groups were identified using limma and clusterProfiler and subjected to pathway enrichment analysis. Drug sensitivity analysis was conducted using the Genomics of Drug Sensitivity in Cancer (GDSC) database and oncoPredict to identify potential therapeutic targets for high-risk patients. The functional role of key LRGs in the model was validated via in vitro cell experiments. RESULTS: An LRG-based prognostic model (LRG17) was successfully developed using transcriptomic data and machine learning. The model demonstrated robust predictive performance, with area under the curve (AUC) values of 0.962, 0.912, and 0.842 for 3-, 5-, and 7-year survival, respectively. Patients were stratified into high- and low-risk groups, with high-risk patients showing significantly shorter overall survival (OS) and event-free survival (EFS) (both P<0.001) and worse clinical profiles (e.g., lower albumin, higher β2-microglobulin and lactate dehydrogenase levels). Enrichment analysis revealed that high-risk patients were significantly enriched for pathways related to chromosome segregation and mitosis, whereas low-risk patients were enriched for immune response and immune cell activation pathways. Drug screening suggested that AURKA inhibitor BMS-754807 and FGFR3 inhibitor I-BET-762 may be more effective in high-risk patients. Functional assays demonstrated that silencing of key LRG PLA2G4A significantly inhibited cell viability and induced apoptosis. CONCLUSIONS LRGs serve as promising biomarkers for prognosis prediction and risk stratification in MM. The overexpression of chromosomal instability-related and high-risk genetic event-associated genes in high-risk patients may explain their poorer outcomes. Given the observed resistance to bortezomib and lenalidomide in high-risk patients, combination therapies involving BMS-754807 or I-BET-762 may represent effective alternatives.
Humans ; Multiple Myeloma/mortality* ; Prognosis ; Lipid Metabolism/genetics* ; Transcriptome ; Machine Learning ; Male ; Female ; Gene Expression Profiling ; Algorithms

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Arachidonic acid can be transformed into a variety of metabolites that trigger an inflammatory response through cyclooxygenase, lipoxygenase, cytochrome P450 enzymes, and other metabolic pathways. Moreover, it plays a key role in the occurrence and development of inflammatory diseases. In recent years, multi-target drugs based on the arachidonic acid metabolic pathway have become an important direction of anti-inflammatory drug research. This article summarizes the opportunities and challenges of arachidonic acid metabolic pathways as well as their interference in the development of anti-inflammatory drugs, reviews the research progress of multi-target drug design, synthesis, and anti-inflammatory activity based on the arachidonic acid metabolic pathway, and discusses the difficulties and prospects of multi-target drugs based on metabolic pathways in anti-inflammatory drug development, aiming to provide some reference and inspiration for the study of multi-target anti-inflammatory drugs based on the arachidonic acid metabolic pathway.

Objective To explore the efficacy of Da Shuyu Gao(DSG,a formulation developed from the modification of Shuyu Wan and Ziwan Decoction)in treating persistent postural-perceptual dizziness(PPPD)based on the theory of phlegm-qi obstruction.Methods A prospective study was conducted on 120 cases of PPPD patients admitted to the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2022 to July 2023.The patients were randomly divided into a combination group and a control group using a random number table,with 60 patients in each group.The control group received conventional western medicine treatment(Betahistine+Mecobalamin),while the combination group was treated with the decoction of DSG orally in addition to the conventional treatment.The treatment course for the two groups lasted for 2 months.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome score,Somatic Symptom Self-Rating Scale(SSSRS),Hamilton Anxiety Scale(HAMA)score,Hamilton Depression Scale(HAMD)score,Pittsburgh Sleep Quality Index(PSQI)score,and the frequency and duration of dizziness episodes.After two months of treatment,the clinical efficacy of the two groups was compared.Results(1)After 2 months of treatment,the total effective rate of the combination group was 93.33%(56/60),and that of the control group was 78.33%(47/60).The intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the combination group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the scores of TCM symptoms of dizziness,tinnitus,vexation,irritability,dry mouth,and bitterness in the mouth in both groups were improved compared to those before treatment(P＜0.05),and the combination group showed significant improvement compared with the control group(P＜0.01).(3)After treatment,the scores of the cognitive,imaginative,biological,irritability,and inhibitory dimension of SSSRS,as well as the total scores on the SSSRS were significantly improved in both groups compared to those before treatment(P＜0.05),and the combination group showed significant improvement compared with the control group(P＜0.01).(4)After treatment,HAMA,HAMD,and PSQI scores were significantly decreased in both groups compared to those before treatment(P＜0.05),and the decrease in the combination group was superior to that in the control group(P＜0.01).(5)After treatment,the frequency and duration of dizziness episodes were significantly decreased in both groups compared to those before treatment(P＜0.05),and the decrease in the combination group was superior to that in the control group(P＜0.01).Conclusion DSG,formulated based on the theory of phlegm-qi obstruction and clinical practice,demonstrates significant efficacy in treating PPPD.It is effective in decreasing TCM syndrome scores,alleviating somatic symptoms,improving emotional disorders such as anxiety and depression,enhancing sleep quality,and reducing the frequency and duration of dizziness episodes,thereby improving patients'quality of life.The application of DSG will provide a new approach for the clinical treatment of PPPD.

Objective To explore the relationship between baseline urinary protein levels and the onset of chronic obstructive pulmonary disease (COPD). Methods A questionnaire survey, blood and urine sample collection, physical examination, and pulmonary function test were conducted among permanent residents over 40 years old in Pudong New Area, Shanghai. The subjects were divided into four groups based on the baseline urine albumin-to-creatinine ratio (ACR) quartiles (0~1.65 mg/g, 1.65~4.89 mg/g, 4.89~10.78 mg/g, and ≥10.78 mg/g). Cox regression analysis was used to explore the relationship between ACR levels and the incidence of COPD in middle-aged and elderly people. Results Among the 3 105 subjects, the median follow-up time was 3.212 years (P25~P75：3.102~3.473). 116 new cases of COPD were observed, with an incidence density of 10.423 per 1000 person-years. The incidence densities for COPD at four ACR levels were 7.922 per 1 000 person-years, 8.300 per 1 000 person-years , 11.419 per 1 000 person-years, and 13.843 per 1 000 person-years, respectively. Cox regression analysis revealed that as the ACR level increased, there was a rising trend in the incidence rate of COPD (χ²=4.396, P=0.036). After adjusting for gender, age, education level, occupational exposure to dust, history of childhood pneumonia, smoking, family history of COPD, central obesity, and hypertension, the risk of developing COPD was 2.499 times higher (95% CI: 1.460~4.276) for ACR levels ≥10.78 mg/g compared to the reference group with a baseline ACR level of 0~1.65 mg/g. Conclusion Elevated ACR levels in middle-aged and elderly population may increase the risk of COPD, and early monitoring of urine protein levels is beneficial for COPD prevention.

Objective:To translate Evidence-based Practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale into Chinese, and evaluate its reliability and validity.Methods:The Chinese version of the EBP-KAPF scale was determined through translation, adaptation, recall, review and pre-investigation. From July to August 2022, 250 clinicians from 28 provinces (autonomous regions and municipalities directly under the Central Government) were selected by using the convenience sampling method. A self-made questionnaire was used to investigate the EBP-KAPF scale in Chinese to investigate the EBM ability of clinicians, including the basic information of the respondents, the learning and use of Evidence-based medicine courses and related software. The item analysis, validity and reliability evaluation of the Chinese version of the EBP-KAPF scale were performed.Results:The Chinese version of the EBP-KAPF scale included 26 items in four dimensions: knowledge mastery, attitude, personal application and future use. A total of 265 questionnaires were sent out (including self-made questionnaires and the Chinese version of the EBP-KAPF scale), and 250 effective questionnaires were obtained, with a total effective rate of 94.3%. The total score of the Chinese version of the EBP-KAPF scale was (102.85±17.48) points, and the scores of knowledge mastery, attitude, personal application and future use sub-scales were (27.22±4.47), (13.56±7.70), (20.07±6.78), and (42.00±9.00) points, respectively. Except for item 16, all items were correlated with the total score of the scale, and the correlation coefficient ranged from 0.456 to 0.828. After item 16 was deleted, the determination values of the remaining 25 items ranged from 4.287 to 18.262 ( P<0.001). After item was removed one by one, the Cronbach′s α coefficient of the scale ranged from 0.870 to 0.888. After item 16 was removed, the Chinese version of the 25-item EBP-KAPF scale had good content validity, structural validity and discriminant validity. The content validity index (I-CVI) at the item level ranged from 0.875 to 1.000, and the content validity index at the overall agreement scale level was 0.615. The average S-CVI values were 0.952, and the probability of correction ( K*) values were 0.87 to 1.00. The results of confirmatory factor analysis showed that the structure fit was good [comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)=0.957, root mean square error of approximation (RMSEA)=0.060, χ2/ df=1.889]. Discriminant validity analysis showed that there were statistically significant differences in the EBP-KAPF scores among clinicians of different ages, evidence-based medicine course learning and related software use ( P<0.05). After item 16 was removed, the Cronbach′s α coefficient of the Chinese version of the EBP-KAPF scale was 0.893, and the Guttman half coefficients of each dimension were 0.915, 0.901, 0.812 and 0.906, respectively. The correlation coefficients were 0.902-0.982, 0.507-0.953, 0.517-0.744 and 0.632-0.986, respectively. Conclusion:The Chinese version of the EBP-KAPF scale is simple, easy to understand, unambiguous, and has good validity and reliability.

Objective:To translate Evidence-based Practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale into Chinese, and evaluate its reliability and validity.Methods:The Chinese version of the EBP-KAPF scale was determined through translation, adaptation, recall, review and pre-investigation. From July to August 2022, 250 clinicians from 28 provinces (autonomous regions and municipalities directly under the Central Government) were selected by using the convenience sampling method. A self-made questionnaire was used to investigate the EBP-KAPF scale in Chinese to investigate the EBM ability of clinicians, including the basic information of the respondents, the learning and use of Evidence-based medicine courses and related software. The item analysis, validity and reliability evaluation of the Chinese version of the EBP-KAPF scale were performed.Results:The Chinese version of the EBP-KAPF scale included 26 items in four dimensions: knowledge mastery, attitude, personal application and future use. A total of 265 questionnaires were sent out (including self-made questionnaires and the Chinese version of the EBP-KAPF scale), and 250 effective questionnaires were obtained, with a total effective rate of 94.3%. The total score of the Chinese version of the EBP-KAPF scale was (102.85±17.48) points, and the scores of knowledge mastery, attitude, personal application and future use sub-scales were (27.22±4.47), (13.56±7.70), (20.07±6.78), and (42.00±9.00) points, respectively. Except for item 16, all items were correlated with the total score of the scale, and the correlation coefficient ranged from 0.456 to 0.828. After item 16 was deleted, the determination values of the remaining 25 items ranged from 4.287 to 18.262 ( P<0.001). After item was removed one by one, the Cronbach′s α coefficient of the scale ranged from 0.870 to 0.888. After item 16 was removed, the Chinese version of the 25-item EBP-KAPF scale had good content validity, structural validity and discriminant validity. The content validity index (I-CVI) at the item level ranged from 0.875 to 1.000, and the content validity index at the overall agreement scale level was 0.615. The average S-CVI values were 0.952, and the probability of correction ( K*) values were 0.87 to 1.00. The results of confirmatory factor analysis showed that the structure fit was good [comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)=0.957, root mean square error of approximation (RMSEA)=0.060, χ2/ df=1.889]. Discriminant validity analysis showed that there were statistically significant differences in the EBP-KAPF scores among clinicians of different ages, evidence-based medicine course learning and related software use ( P<0.05). After item 16 was removed, the Cronbach′s α coefficient of the Chinese version of the EBP-KAPF scale was 0.893, and the Guttman half coefficients of each dimension were 0.915, 0.901, 0.812 and 0.906, respectively. The correlation coefficients were 0.902-0.982, 0.507-0.953, 0.517-0.744 and 0.632-0.986, respectively. Conclusion:The Chinese version of the EBP-KAPF scale is simple, easy to understand, unambiguous, and has good validity and reliability.

Objective:To discuss the effect of Fuzheng Ruanjian Anticancer Formula on the malignant biological behaviors of the hepatocellular carcinoma HepG2 cells by requlating protein kinase B(Akt)/murine double minute 2(MDM2)/P53 signaling pathway.Methods:The HepG2 cells were treated with 0,0.05,0.10,0.20,0.40,0.80,1.60,3.20,and 6.40 g·mL-1 Fuzheng Ruanjian Anticancer Formula for 48 h.CCK-8 method was used to detect the survival rates of the HepG2 cells in various groups,and the concentrations of Fuzheng Ruanjian Anticancer Formula for the subsequent experiments were screened.The HepG2 cells were divided into control group,low dose of Fuzheng Ruanjian Anticancer Formula group(0.2 g·mL-1),medium dose of Fuzheng Ruanjian Anticancer Formula group(0.4 g·mL-1),high dose of Fuzheng Ruanjian Anticancer Formula group(0.8 g·mL-1),SC79 group(8 mg·L-1 SC79),and high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group(0.8 g·mL-1 Fuzheng Ruijian Anticancer Formula+8 mg·L-1 SC79).CCK-8 method was used to detect the proliferation activities of the HepG2 cells in various groups;clone formation assay was used to detect the clone formation rates of the HepG2 cells in various groups;flow cytometry was used to detect the apoptotic rates of the HepG2 cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion HepG2 cells in various groups;Western blotting method was used to detect the expression levels of proliferating cell nuclear antigen(PCNA),cysteine aspartate specific proteinase(Caspase-3),matrix metalloproteinase(MMP)-2,MMP-9,phosphorylated Akt(p-Akt),phosphorylated MDM2(p-MDM2),and P53 proteins in the HepG2 cells in various groups.Results:As the increasing of concentrations of Fuzheng Ruanjian Anticancer Formula(0,0.05,0.10,0.20,0.40,0.80,1.60,3.20,and 6.40 g·mL-1),the surival rates of the HepG2 cells were gradually decreased(P<0.05),and 0.2,0.4,and 0.8 g·mL-1 Fuzheng Ruanjian Anticancer Formula were selected for the subsequent experiments.The CCK-8 assay results showed that compared with control group,the proliferation activities of the HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05),in a dose-dependent manner,while the proliferation activity of the cells in SC79 group was significantly increased(P<0.05).Compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the proliferation activity of the HepG2 cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly increased(P<0.05).The clone formation assay results showed that compared with control group,the clone formation rates of the HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the clone formation rate of the cells in SC79 group was significantly increased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the clone formation rate of the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly increased(P<0.05).The flow cytometry results showed that compared with control group,the apoptotic rates of the HepG2 cells in low,medium,and high doses of Fuzheng Ruijian Anticancer Formula groups were significantly increased(P<0.05)in a dose-dependent manner,while the apoptotic rate of the cells in SC79 group was significantly decreased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the apoptotic rate of the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly decreased(P<0.05).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the numbers of migration and invasion cells in SC79 group were significantly increased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the numbers of migration and invasion HepG2 cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the expression levels of Caspase-3 and P53 proteins were significantly increased(P<0.05)in a dose-dependent manner,while the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in SC79 group were significantly increased(P<0.05),and the expression levels of Caspase-3 and P53 proteins were significantly decreased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group were significantly increased(P<0.05),while the expression levels of Caspase-3 and P53 proteins were significantly decreased(P<0.05).Conclusion:Fuzheng Ruanjian Anticancer Formula may inhibit the proliferation,migration,and invasion of the HepG2 cells and promote the apoptosis,and its mechanism may be related to suppressing the Akt/MDM2 signaling pathway and upregulating the P53 proteim expression.