Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Advanced atherosclerosis is the major global cause of death, as featured by the aggregation of apoptotic cells (ACs) in necrotic cores. The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis. In this study, we constructed self-assembled procyanidins (PC) NPs for loading pitavastatin (Pita). The designed HA@PC@Pita NPs with hyaluronic acid (HA) modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC. In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages. Simultaneously, HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy, a selective autophagy of lipid droplets. In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE ^-/- mice model with advanced atherosclerosis. Taken together, this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.

The diagnosis of hematological disorders is currently established from the combined results of different tests, including those assessing morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology (M) (collectively known as the MICM classification). In this workflow, most of the results are interpreted manually (i.e., by a human, without automation), which is expertise-dependent, labor-intensive, time-consuming, and with inherent interobserver variability. Also, with advances in instruments and technologies, the data is gaining higher dimensionality and throughput, making additional challenges for manual analysis. Recently, artificial intelligence (AI) has emerged as a promising tool in clinical hematology to ensure timely diagnosis, precise risk stratification, and treatment success. In this review, we summarize the current advances, limitations, and challenges of AI models and raise potential strategies for improving their performance in each sector of the MICM pipeline. Finally, we share perspectives, highlight future directions, and call for extensive interdisciplinary cooperation to perfect AI with wise human-level strategies and promote its integration into the clinical workflow.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

The release of the Measures of Ethical Review of Life Sciences and Medical Research Involving Humans has brought new requirements to the field of ethical review in health management research.Based on the background of new regulations and combining the characteristics of the health management discipline,this paper explored the needs and necessity of ethical review in health management research.In the Measures,the ethical governance of health management research was updated,the concept of exemption from the ethical review was put forward,as well as the importance of protecting the rights and interests of research participants and the protection of personal information were emphasized.This paper also explored the ethical review framework for health management research,including the formulation of operational standards for exemption from ethical review,the refinement of standardized ethical review work systems and processes,and the clarification of information data source verification.These explorations aimed to provide an ethical guarantee for health management research,promote its healthy development,and ensure that the rights and interests of research participants are fully respected and protected.Through research,it is hoped that the ethical level of health management research can be further improved,promoting the development of the discipline and social progress.

OBJECTIVE To know about the working mode and human resource status of pharmacy intravenous admixture services （PIVAS） in national medical institutions. METHODS Through questionnaire survey， the national PIVAS was invited to fill out questionnaire and statistical analysis was performed on the effective sample data related to PIVAS working mode and human resources in the questionnaire. RESULTS In this study， 761 PIVAS from 722 medical institutions of 29 provinces were involved in the questionnaire survey， with 471 valid questionnaires for working mode and 441 valid questionnaires for human resources survey. In terms of working mode， among 471 PIVAS， 292 PIVAS （62.0%） were in pharmacist-alone mode， and 176 PIVAS （37.4%） were in pharmacist-nurse cooperative mode； there was no significant difference in the types of medical orders received by PIVAS between these two working modes except for the other medical orders （P＞0.05）. In terms of human resource setting， among 441 PIVAS， the average number of total staff of single PIVAS was 24（16，33）， including 11（6，19） pharmacists， 7（2，13） nursing staff， and 3（1，5） workers； there was a statistically significant difference in the number of personnel among three groups （P＜ 0.01）. The per capita income of PIVAS respondents in 2019 was [7.9（4.8，10.7）]×104 yuan， and in 2021 it was [8.8（5.8，11.7）]× 104 yuan， with an increase of 9.0% compared to 2019. The difference between the two groups was statistically significant （P＜ 0.01）. CONCLUSIONS Medical institutions’ PIVAS in China had not fully implemented the pharmacist-alone work model， and some medical institutions had chosen a pharmacist-nurse cooperative mode. It is suggested that relevant departments formulate corresponding qualification requirements and training standards for nursing personnel as soon as possible based on sufficient research on PIVAS’s demand for nursing professionals.

OBJECTIVE To know about the pharmacy intravenous admixture charge and operation balance of pharmacy intravenous admixture services （PIVAS） in national medical institutions. METHODS Using questionnaire survey method， the national PIVAS leaders were invited to fill in the questionnaire， investigation and statistical analysis of the drug dispensing charge standard and the income and expenditure situations of PIVAS nationwide were conducted. RESULTS A total of 761 PIVAS completed the questionnaire， among which 466 PIVAS （61.2%） had already started implementing pharmacy intravenous admixture charge， mainly in tertiary hospitals. The charge standards for chemotherapy drugs and parenteral nutrition solutions were relatively high， while the standards for packaged drugs were the lowest， with differences in charge standards among provinces（P＜0.05）. Among the 25 provinces that reported annual drug preparation fee revenue， Hubei had the highest revenue in both 2019 and 2021. In 2019， the number of PIVAS with a balance of payments was more than that of PIVAS with an imbalance of payments， but the number of PIVAS with an imbalance of payments in 2021 exceeded the number of PIVAS with a balance of payments （P＜0.05）； among them， eight provinces were unbalanced in 2019 and 2021， such as Tianjin， Chongqing， Guizhou， etc. CONCLUSIONS PIVAS charge standards of the surveyed medical institutions in all provinces are not unified. It is suggested to improve the charge standard further， formulate the charge adjustment cycle， and promote a sustainable development of PIVAS.

The complement system is a protein response system with a precise regulatory mechanism, which has the functions of mediating inflammation, regulating immune response, dissolving cells and clearing immune complexes. Diabetic retinopathy(DR)is a common and severe ocular complication of diabetes and one of the common irreversible blinding eye diseases in ophthalmology, and its pathogenesis is complex, including hypoxia, oxidative stress, inflammation and abnormal polyol metabolism pathway. In recent years, there has been more and more evidence that dysregulation and inflammation of immune system are important factors in the pathogenesis of DR, and a variety of complement proteins play an important role in key processes such as inflammation regulation and angiogenesis. Therefore, the central purpose of this review is to discuss the role of the complement system and related regulatory proteins in DR, with the aim of elucidating the close relationship between the complement proteins and the occurrence and development of DR, and providing important references and new ideas for the prevention and treatment of DR. At the same time, the clinical research of complement system-targeted drugs is further elaborated.

BACKGROUND:Studies have found that glucagon-like peptide-1 and its analogues have a significant neuroprotective effect,and some drugs have been applied to the clinical stage Ⅲ study of Alzheimer's disease.However,the mechanism of its neuroprotective effect is still unclear,which needs to be further explored and clarified. OBJECTIVE:To screen out the genes related to the pathogenesis of Alzheimer's disease and the related targets of semaglutide for the treatment of Alzheimer's disease based on bioinformatics and network pharmacology analyses,to identify the potential target genes by comprehensive analysis of the two and to verify them at the cellular level. METHODS:Using DisGeNET database,differentially expressed genes between Alzheimer's disease patients and healthy population were screened out.The chemical structure formula and two-dimensional structure diagram of semaglutide were obtained using PubChem online database.GO/KEGG enrichment analysis was performed using DAVID online database.A protein-protein interaction network was constructed by using the STRING database.The HPA database was used to determine the distribution characteristics of the target proteins in various human tissues.Finally,western blot was used to detect relevant protein expression in HT22 cells after semaglutide intervention. RESULTS AND CONCLUSION:With the dataset in DisGeNET database,3 374 differentially expressed genes between Alzheimer's disease patients and healthy people were obtained,and meanwhile,101 target genes of semaglutide potential drugs were obtained.There were 23 intersection genes between them.Ten key genes were identified based on the protein-protein interaction network,which were silent information regulator 1(SIRT1),CASP9,CCND1,CASP1,KEAP1,DLG4,CASP4,GRB2,GRIA1,and EDNRA.The results of GO gene functional annotation analysis of key genes showed that the positive regulatory activity of cysteine endopeptidase,the positive regulation of proteolysis,and the positive regulation of cysteine endopeptidase involved the cytoplasmic part of the apoptotic activity process;AMPA glutamate receptor complex,inflammatory complex,CARD domain binding,cysteine endopeptidase activity,and cysteine endopeptidase activity were involved in the apoptotic process.The results of KEGG signaling pathway analysis indicated that colorectal cancer,non-small cell carcinoma,and endometrial carcinoma were related to immune infiltration,inflammation and autophagic apoptosis.In addition,according to the association ranking of key genes and their distribution in different tissues of HPA online database,SIRT1 was identified as the most significant differential gene.The expression level of SIRT1 protein was significantly down-regulated in HT22 cells after β-amyloid protein 1-42 treatment,but it could be significantly increased after being treated with semaglutide.To conclude,SIRT1 may be a target gene for semaglutide in the treatment of Alzheimer's disease.