OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Objective:To investigate the feasibility of ultra-low dose (ULD) CT pulmonary angiography (CTPA) combined with deep learning reconstruction (DLR) in the diagnosis of pulmonary embolism (PE).Methods:This cross-sectional study prospectively enrolled 100 patients with suspected PE who underwent CTPA examination in Zhongshan Hospital Fudan University, and Shanghai Geriatric Medical Center from April to July 2024, and were randomly divided into the routine dose (RD) group and ULD group according to block randomization. Effective dose (ED) were calculated. The noise index of RD group and ULD group was set to 10 and 20, respectively. Other scanning parameters and contrast agent injection protocol were the same. The CT images of RD group were reconstructed using hybrid iterative reconstruction (HIR), while ULD images were reconstructed with HIR and DLR (ULD-HIR subgroup and ULD-DLR subgroup). The image quality of the three groups of images was subjectively evaluated (overall image noise, pulmonary artery display) and objectively evaluated [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) of the images] respectively. Finally, the diagnostic results of PE by the expert committee composed of three chief physicians were taken as the gold standard, and one physician with lower qualifications independently evaluated the diagnostic rate of PE in the three groups of images. Objective image quality parameters across the three groups were compared using ANOVA, with LSD post hoc test was used for multiple comparisons. Subjective scores among the three groups were analyzed using the Kruskal-Wallis H test, with Bonferroni corrected pairwise post hoc test was applied for multiple pairwise comparisons. Results:The ED in the RD group and ULD group were (2.7±0.5) mSv and (0.7±0.2) mSv, respectively, and the differences were statistically significant ( t=26.42, P<0.001). The overall differences in CT values of pulmonary arteries at all levels in the images of the RD group, the ULD-HIR subgroup, and the ULD-DLR subgroup were not statistically significant ( P>0.05).The RD group, ULD-HIR subgroup and ULD-DLR subgroup overall differences in SNR and CNR at all levels pulmonary arteries were statistically significant ( P<0.001), in which except for the differences in CNR and SNR values of the left pulmonary arterial trunk in the RD group and the ULD-HIR subgroup, and SNR values of basal segment pulmonary artery of the lower lobe of the left lung, which were not statistically significant ( P>0.05), the differences of the rest of the indexes in the pairwise comparisons between the groups were statistically significant ( P<0.05). The overall differences in the subjective scores of image pulmonary vascular display and image noise in the RD group, ULD-HIR subgroup and ULD-DLR subgroup were statistically significant ( P<0.001), except that the differences in the subjective scores of image pulmonary vascular display in the ULD-DLR subgroup were not statistically significant when compared with that of the RD group ( P>0.05) and that of the rest of the metrics in the between-groups two-by-two comparisons were all statistically significant ( P<0.05). The difference in diagnostic rates of PE in the pulmonary artery trunk, lobe and segmental levels in the images of the RD group, ULD-HIR subgroup and ULD-DLR subgroup was not statistically significant ( P>0.05). Conclusions:DLR can significantly reduce the radiation dose of CTPA examination. Even at ultra-low radiation dose, its image quality is still better than HIR reconstruction at conventional doses and preserve diagnostic accuracy of PE at the lobe level and segment level.

Objective To investigate the effects and mechanisms of high-fat diet(HFD)-induced obesity on male ze-brafish reproductive function.Methods Adult male zebrafish were divided into normal diet(ND)group and HFD group.Growth and metabolic conditions were evaluated by measuring body weight,body length,BMI,organ index,and glucose/lipid lev-els.Reproductive capacity was assessed via sperm concentration,motility,fertilization rate,and testosterone levels.Testicular tissues from both of groups were subjected to transeriptomic sequencing(RNA-seq).And qRT-PCR was used to validate the expression of genes.Results Compared to male zebrafish in ND group,the ones in HFD group exhibited hepatic steatosis and glucose/lipid meta-bolic disorders(P＜0.05).Testicular structural disorganization,along with reduced testosterone levels,decreased gonadosomatic in-dex,and impaired sperm concentration and motility occurred in HFD group(P＜0.05).GO analysis revealed that differentially ex-pressed genes were enriched in spermatogenesis and ciliary system,while KEGG analysis highlighted metabolic related pathways(pu-rine metabolism,thyroid hormone synthesis,mTOR signaling)and cell adhesion molecules.Twenty key differentially expressed genes were validated by qRT-PCR,which confirmed the reliability of RNA-Seq results.Conclusion Impairment of reproductive function induced by HFD in zebrafish may be associated with three regulatory mechanisms including ciliary system,metabolic dysregulation,and aberrant cell adhesion molecule signaling.This study provides mechanistic insights and identifies potential therapeutic targets for clinical management of diet-associated infertility.

Objective:To explore the effectiveness of applying the learning group teaching method based on primary care guidelines for diagnosis and treatment of common diseases in the standardized training of general practice residents (referred to as "general practice resident training").Methods:This study was a randomized controlled trial. A total of 48 trainees enrolled in the general practice residency program at the Affiliated Huai′an No.1 People′s Hospital of Nanjing Medical University from September 2023 to August 2024 were included. They were divided into the observation group and the control group using a random number table method, with 24 trainees in each group. At baseline, general information such as age, sex, and education level of the trainees was collected, and their relevant theoretical knowledge was assessed. The control group trainees were intervened using the traditional teaching method, while the observation group trainees were intervened using the learning group teaching method based on the diagnosis and treatment guidelines for common diseases at primary care level. The teaching activities lasted for 1 year, with sessions held once a month, for a total of 12 sessions. At the end of the intervention, all trainees were assessed on theoretical knowledge, case analysis, and clinical skills. In addition, questionnaires were used separately to survey the trainees′ satisfaction in both groups, as well as the teaching satisfaction of instructors in the observation group.Results:The observation group included 18 females (75%), with a median age of 25 (24, 26) years, while the control group had 16 females (67%), with a median age of 25 (24, 26) years. There was no statistically significant difference in the age, proportion of female trainees, proportion of rural order oriented free medical students, proportion of undergraduate students, proportion of first-year trainees, and theoretical knowledge test scores before the implementation of intervention measures between the two groups of trainees (all P>0.05). At the end of the intervention, the theoretical knowledge, case analysis, and clinical skill test scores of the observation group were higher than those of the control group (all P<0.05). All 48 trainees participated in the survey. The observation group trainees were found to be more satisfied than the control group with the teaching methods, knowledge mastery, clinical diagnosis and treatment thinking, stimulation of learning interest, self-learning ability, teaching interest, interpersonal communication ability, teamwork ability, and community problem-solving ability (all P<0.05). Of the four teachers in the observation group who participated in the satisfaction survey, all expressed satisfaction with the teaching method and its content. They all believed that the teaching method helped them to broaden their teaching ideas and improve their teaching abilities and skills. Conclusions:The learning group teaching method, which is based on the diagnosis and treatment guidelines for common diseases at primary care level, can effectively enhance the theoretical knowledge, case analysis ability, and clinical skills of the trainees. This teaching method is highly effective, with both trainees and teachers expressing great satisfaction.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Gastrointestinal(GI)cancers are prevalent globally,with leading incidence and mortality rates among malignant tumors.Despite notable advancements in surgical resection,radiotherapy,and chemotherapy,the overall survival rates remain low.Hence,it is imperative to explore alternative approaches that enhance patient outcomes.Cluster of differentiation 47(CD47),serving as an early diagnostic marker,is predominantly overexpressed in GI cancers and associated with poor prognosis.Targeting the CD47-signal regulatory protein alpha(SIRPα)signaling pathway may provide a novel strategy for GI cancers treatment This study summarizes current knowledge of the structure and function of CD47 and SIRPα,their roles in signaling pathways,the prognostic significance of CD47,therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer,and highlights key issues for future investigations.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Gastrointestinal (GI) cancers are prevalent globally, with leading incidence and mortality rates among malignant tumors. Despite notable advancements in surgical resection, radiotherapy, and chemotherapy, the overall survival rates remain low. Hence, it is imperative to explore alternative approaches that enhance patient outcomes. Cluster of differentiation 47 (CD47), serving as an early diagnostic marker, is predominantly overexpressed in GI cancers and associated with poor prognosis. Targeting the CD47-signal regulatory protein alpha (SIRPα) signaling pathway may provide a novel strategy for GI cancers treatment. This study summarizes current knowledge of the structure and function of CD47 and SIRPα, their roles in signaling pathways, the prognostic significance of CD47, therapeutic strategies targeting the CD47-SIRPα signaling pathway in GI cancer, and highlights key issues for future investigations.

Objective To investigate the value of flexible subtraction CE-Boost technique combined with low dosage contrast agents for CT pulmonary angiography(CTPA).Methods A total of 68 patients who would undergo CTPA examination due to suspected pulmonary embolism(PE)were prospectively enrolled and randomly divided into study group(n=34)and control group(n=34)using block randomization method.After injecting 25 ml contrast agents at a flow rate of 2.5 ml/s in study group or 50 ml contrast agents at a flow rate of 3.5 ml/s in control group,CTPA scanning were performed with identical parameters.For images in study group,hybrid iterative reconstruction was performed,followed by flexible subtraction CE-Boost post-processing to obtain CE-Boost CTPA.For images in control group,conventional CTPA was obtained with hybrid iterative reconstruction.Subjective and objective evaluations of image quality were compared between groups.Taken the final clinical diagnosis as standard,the accuracy rate of diagnosing PE were compared between groups.Results There were 7 cases of pulmonary artery main trunk PE and 15 cases of pulmonary lobe-level PE in study group,while in control group there were 8 cases and 17 cases.No statistical difference of subjective scores of CTPA was found between groups(P＞0.05).CT values of the main pulmonary artery,bilateral pulmonary artery trunks and lower lobes of both lungs,signal-to-noise ratio or contrast-to-noise ratio in CTPA were not significantly different between groups(all P＞0.05),while no significant difference of the accuracy rate of CTPA for diagnosing PE of pulmonary artery main trunk(100％[7/7]vs.100％[8/8])nor pulmonary lobe-level PE(86.67％[13/15]vs.88.24％[15/17])was detected between groups(all P＞0.05).Conclusion Flexible subtraction CE-Boost technique combined with low dosage contrast agents for CTPA could reduce contrast agent dosage without affecting image quality.