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

Purpose The purpose of this study was to in-vestigate programmed death ligand-1(PD-L1)expression in gastric adenocarcinoma(GAC)patients and the consistency of immunohistochemical(IHC)detection of four different clones of PD-L1 antibodies,so as to provide reference for the gradual standardization of PD-L1 IHC detection in gastric adenocarcino-ma and subsequent clinical studies.Methods This study col-lected surgically resected and pathologically confirmed specimens from 286 gastric adenocarcinoma patients,and specimens were stained with four antibodies:PD-L1 22C3,SP263,E1L3N and SP142.The consistency of the antibodies was statistically ana-lyzed under different critical values using two scoring criteria:comprehensive positive score(CPS)and tumor proportion score(TPS).Results Regardless of the TPS and CPS cut-off val-ues,the positive rate of 22C3 was the highest among the four an-tibodies.Consistency analysis showed that E1L3N had good con-sistency with SP142(κ=0.612)and SP263(κ=0.660)only when the cut-off value of CPS positive was 1.In addition,the consistency between the other antibodies was only moderate or poor.Conclusion The four PD-L1 antibodies exhibited incon-sistent concordance across various TPS and CPS positive thresh-olds,so it is not recommended to exchange reagents during clini-cal testing of GAC and the test results shall be documented in accordance with the specification.

To implement the strategy of healthy China and promote the construction of "new medicine science", it is urgent to focus on new needs and challenges to advance the reform of medical education curricula in China. Using literature research methods, we summarize the process of modern medical education curriculum reforms in the United States, and discuss the main features of the third-round reforms—introducing the concept of value-based medicine, offering health systems science courses, and promoting the curriculum system reform from the perspectives of learning time, curriculum integration, and learning methods. Based on these features, we put forward the enlightenment for the reform of medical education curricula in China.

Objective:To explore the application of observation teaching discussion (OTD) in vascular surgery nursing intern teaching under the guidance of process-oriented guided inquiry learning (POGIL) theory.Methods:Forty nursing students who were doing their internship in The First Affiliated Hospital of Xi'an Jiaotong University from July 2022 to July 2023 were randomly divided into two groups using a random number table: control group (20 students, OTD teaching) and observation group (20 students, POGIL theory-guided teaching) . The two groups were compared for competence assessment scores before entering the department and 3 days prior to departure from the department, autonomous learning ability scale scores, Competency Inventory for Registered Nurses (CIRN) scores, and Chinese Problem Solving Inventory (CPSI) scores. T-tests and chi-square tests were conducted using SPSS 22.0. Results:Three days prior to departure from the department, the theoretical performance and practical performance were significantly better in the observation group [(91.67±5.22) and (89.69±4.36) points, respectively] than in the control group [(84.53±4.75) and (82.41±4.18) points, respectively] ( P<0.05). The observation group also performed significantly better than the control group in autonomous learning ability scale score [(139.52±13.52) vs. (128.86±10.76)], CIRN score [(207.73±6.23) vs. (195.67±5.98)], and CPSI score [(103.60±4.72) vs. (92.18±5.03)] (all P<0.05). Conclusions:The application of OTD in vascular surgery nursing intern teaching under the guidance of POGIL theory can improve the autonomous learning ability, core ability, and problem-solving ability of nursing interns.

Based on the domestic and foreign research on the application of self-disclosure in gynecological cancer patients, the relevant concepts, main modes of self-disclosure, measuring tools, research status and influencing factors of self-disclosure in gynecological cancer patients are reviewed. In order to provide a reference for the research on self-disclosure of gynecological cancer population, and promote the development of self-disclosure.

Objective:To investigate the level of functional fitness of elderly hypertensive patients in the community and to analyze its influencing factors.Methods:A cross-sectional survey was used from November 2021 to September 2022, questionnaire survey and Senior Functional Fitness Test (SFT) were conducted on 189 elderly hypertensive patients in the community by convenience sampling method, multiple linear regression was used to analyze the influencing factors of SFT in elderly hypertensive patients in the community.Results:Totally 189 cases of community-aged hypertensive patients completed the investigation, 88 cases were male and 101 were female. The total SFT score of community-aged hypertensive patients was (58.61 ± 16.07). Single factor analysis showed that there were significant differences in SFT scores among patients with different gender, age and education ( t=-2.57, F=6.24, 7.54, all P<0.05). Multifactorial analysis revealed that age ( t=-5.55), gender ( t=2.63), and literacy ( t=5.69) were influential factors in the total SFT scores of community-dwelling elderly hypertensive patients (all P<0.05). Conclusions:Age, gender, and literacy level are the main factors affecting the total SFT scores of elderly hypertensive patients in the community, and community caregivers should pay close attention to the above elderly hypertensive population.