OBJECTIVE To provide reference for the optimization of support policies for the development of traditional Chinese medicine preparations in medical institutions in China. METHODS Based on 102 policy documents concerning the support policies for the development support of traditional Chinese medicine preparations in medical institutions issued by the central government and 5 autonomous regions， text information was mined by ROST CM6 software， and a policy modeling consistency （PMC） index model was constructed. From the perspective of the whole life cycle， a multi-dimensional evaluation was carried out on the support policies for the development of traditional Chinese medicine preparations in medical institutions， and 48 policies closely related to the development of traditional Chinese medicine preparations in medical institutions were screened for empirical research. RESULTS & CONCLUSIONS The average PMC index of the 48 policies was 5.90， which was generally at a good level. Among them， 8 policies were excellent， 29 were good， 11 were acceptable， and no policies were rated poor. The policy samples performed well in the dimensions of policy orientation and policy evaluation， while some policies need to be further improved in terms of policy nature， policy instruments and policy content. It is suggested to establish a multi-level policy support system， strengthen financial support and transformation incentives of new drugs， so as to boost the high-quality development of traditional Chinese medicine preparations in medical institutions.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Iron is an essential trace element in the human body, crucial in maintaining normal physiological functions. Recent studies have identified iron ions as a significant factor in initiating the ferroptosis process, a novel mode of programmed cell death characterized by iron overload and lipid peroxide accumulation. The iron metabolism pathway is one of the primary mechanisms regulating ferroptosis, as it maintains iron homeostasis within the cell. Numerous studies have demonstrated that abnormalities in iron metabolism can trigger the Fenton reaction, exacerbating oxidative stress, and leading to cell membrane rupture, cellular dysfunction, and damage to tissue structures. Therefore, regulation of iron metabolism represents a key strategy for ameliorating ferroptosis and offers new insights for treating diseases associated with iron metabolism imbalances. This review first summarizes the mechanisms that regulate iron metabolic pathways in ferroptosis and discusses the connections between the pathogenesis of various diseases and iron metabolism. Next, we introduce natural and synthetic small molecule compounds, hormones, proteins, and new nanomaterials that can affect iron metabolism. Finally, we provide an overview of the challenges faced by iron regulators in clinical translation and a summary and outlook on iron metabolism in ferroptosis, aiming to pave the way for future exploration and optimization of iron metabolism regulation strategies.

Objectives To explore the causal relationship between asthma-related pneumonia and heart failure(HF)by using two-sample Mendelian randomization(MR)analysis.Methods The causal relationship between asthma-related pneumonia and HF were systematically evaluated through two-sample MR analysis based on publicly available Genome-Wide Association Study data.Inverse variance weighted(IVW),MR-Egger,weighted median,weighted mode,and simple mode methods were used.Different models were used to analyze sensitivity.Testing approaches were conducted to assess the robustness of the results.Results IVW analysis results showed that there was a causal relationship between asthma-related pneumonia and HF risk(OR=1.113,95％CI:1.027-1.206,P=0.009).HF was not found to have a causal effect on asthma-related pneumonia risk based on IVW analysis(OR=1.018,95％CI:0.780-1.328,P=0.893).The variance used in all MR analyses showed no heterogeneity or horizontal pleiotropy.The leave-one-out analysis revealed that no single nucleotide polymorphism disproportionately influenced the results,further confirming the credibility of the bidirectional MR findings.Conclusion This study established a causal relationship between asthma-related pneumonia and HF risk.No clear causal relationship between HF and asthma-related pneumonia risk was found.

Objective:To analyze the association between standardized management of clinical research, initiated by investigators and guided by clinical research management policies in healthcare institutions, and changes in the research behavior of graduate students.Methods:Theses related to cardiovascular health published by graduate students in the Sichuan-Chongqing region of China between January 2019 and June 2024 were retrieved from the China National Knowledge Infrastructure database. Multilevel models were used to analyze changes in ethical compliance awareness, research methodology standardization, and academic collaboration of graduate students before and after policy implementation. Using Shapiro Wilk test and percentage representation.Results:Among the 712 theses included in this study, the proportion of studies with ethical review reports increased from 44.50% to 55.32% following the implementation of standardized management [odds ratio ( OR)=1.80, P=0.017]. Standardized management significantly improved the quality scores of cross-sectional studies and randomized controlled trials ( P<0.001), as well as significantly increased the frequencies of multi-center collaboration ( OR=2.84, P=0.001) and intra-provincial collaboration ( OR=2.80, P=0.001). Conclusions:Standardized clinical research management shows significant association with positive changes in the research behavior of graduate students. Further optimization of management measures is recommended to comprehensively enhance the clinical research capabilities of graduate students.

Objective:To analyze the association between standardized management of clinical research, initiated by investigators and guided by clinical research management policies in healthcare institutions, and changes in the research behavior of graduate students.Methods:Theses related to cardiovascular health published by graduate students in the Sichuan-Chongqing region of China between January 2019 and June 2024 were retrieved from the China National Knowledge Infrastructure database. Multilevel models were used to analyze changes in ethical compliance awareness, research methodology standardization, and academic collaboration of graduate students before and after policy implementation. Using Shapiro Wilk test and percentage representation.Results:Among the 712 theses included in this study, the proportion of studies with ethical review reports increased from 44.50% to 55.32% following the implementation of standardized management [odds ratio ( OR)=1.80, P=0.017]. Standardized management significantly improved the quality scores of cross-sectional studies and randomized controlled trials ( P<0.001), as well as significantly increased the frequencies of multi-center collaboration ( OR=2.84, P=0.001) and intra-provincial collaboration ( OR=2.80, P=0.001). Conclusions:Standardized clinical research management shows significant association with positive changes in the research behavior of graduate students. Further optimization of management measures is recommended to comprehensively enhance the clinical research capabilities of graduate students.

Objectives To explore the causal relationship between asthma-related pneumonia and heart failure(HF)by using two-sample Mendelian randomization(MR)analysis.Methods The causal relationship between asthma-related pneumonia and HF were systematically evaluated through two-sample MR analysis based on publicly available Genome-Wide Association Study data.Inverse variance weighted(IVW),MR-Egger,weighted median,weighted mode,and simple mode methods were used.Different models were used to analyze sensitivity.Testing approaches were conducted to assess the robustness of the results.Results IVW analysis results showed that there was a causal relationship between asthma-related pneumonia and HF risk(OR=1.113,95％CI:1.027-1.206,P=0.009).HF was not found to have a causal effect on asthma-related pneumonia risk based on IVW analysis(OR=1.018,95％CI:0.780-1.328,P=0.893).The variance used in all MR analyses showed no heterogeneity or horizontal pleiotropy.The leave-one-out analysis revealed that no single nucleotide polymorphism disproportionately influenced the results,further confirming the credibility of the bidirectional MR findings.Conclusion This study established a causal relationship between asthma-related pneumonia and HF risk.No clear causal relationship between HF and asthma-related pneumonia risk was found.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Metabolic reprogramming plays a critical role in tumorigenesis and tumor progression.The metabolism and the proliferation of tumors are regulated by both intrinsic factors within the tumor and the availability of metabolites in the tumor microenvironment(TME).The metabolic niche within the TME is primarily orchestrated at 3 levels:1)the regulation of tumor metabolism by factors intrinsic to the tumors,2)the interaction between tumor cells and T cells,macrophages,and stromal cells,and 3)the metabolic heterogeneity of tumor cells within the tissue space.Herein,we provided a concise overview of the various metabolic regulatory modes observed in tumor cells.Additionally,we extensively analyzed the interaction between tumor cells and other cells within the TME,as well as the metabolic characteristics and functions of different types of cells.Ultimately,this review provides a theoretical basis and novel insights for the precision treatment of tumors.

Spinal cord injury(SCI)is a central nervous system disease with high morbidity,disability,and mortality.A series of pathological and physiological changes after SCI,including oxidative stress,can promote further deterioration of the microenvironment at the injury site,resulting in impaired neurological function.Nuclear factor E2-related factor 2(Nrf2)is highly correlated with oxidative stress,suggesting that targeting the regulation of Nrf2 and alleviating oxidative stress may be an effective treatment for SCI.We consider the application of Nrf2 in post-SCI oxidative stress,based on the occurrence of oxidative stress after SCI and the relationship between oxidative stress and Nrf2.We also summarize the strategies for targeting and regulating Nrf2,including genes,non-coding RNAs,and drugs,with the aim of providing new ideas for targeted therapy of SCI.