Objective To investigate the impact of red blood cell suspension infusion across various perioperative periods on patients with valvular heart disease. Methods The patients with valvular heart disease admitted to Tianjin Chest Hospital from 2018 to 2020 were selected. Based on the timing of perioperative red cell suspension infusion, patients were categorized into three groups: a group 1 receiving intraoperative red cell suspension infusion, a group 2 receiving red cell suspension infusion within 24 hours after entering the ICU, and a group 3 receiving red cell suspension infusion at both time points. The laboratory results, perioperative blood component infusion volume, and other relevant parameters were retrospectively analyzed. After propensity score matching, the differences in different variables among the three groups were compared. Results After propensity score matching, 102 patients were enrolled, including 52 males and 50 females, with an average age of (61.74±10.58) years. There were 34 patients in each group. The preoperative hemoglobin (Hb) value of the group 2 was significantly higher than that of the group 1 and the group 3, and the amount of red cell suspension and autoblood transfusion was the lowest (P<0.05). Group 1 had the highest postoperative Hb, as well as the highest Hb and hematocrit (HCT) levels within 24 hours post-surgery (P<0.05). The group 1 had the lowest plasma, platelet and cryoprecipitate infusion volumes, and the shortest cardiopulmonary bypass time, aortic occlusion time, postoperative ICU stay and hospital stay, and the least blood loss and total drainage volume (P<0.05). The difference between postoperative and preoperative Hb (△Hb1) was highest in group 1 (P<0.05). Conclusion For patients with valvular heart disease, intraoperative-only infusion of red blood cell suspension is associated with a better prognosis at discharge and during follow-up.

BACKGROUND/OBJECTIVES: Deoxyshikonin (DSK) has been reported to inhibit tumor growth in various types of cancers, but its roles and action mechanisms in breast cancer (BC) are unclear. This study examined the anti-cancer function and mechanism of DSK in BC.MATERIALS/METHODS: MDA-MB-231 and BT549, human BC cells, were used. The cell viability and apoptosis levels were examined using Cell Counting Kit-8 experiments and flow cytometry, respectively. The expression of apoptosis-related factors (Ki-67, Bax, and Bcl-2), CD206, CD168, and proteins involved in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)uclear factor (NF)-κB pathway was evaluated by Western blot analysis. The cell invasion ability was determined using the Transwell experiment. The levels of interleukin (IL)-10 and transforming growth factor (TGF)-β were detected using an enzyme-linked immunosorbent assay. The in vivo functions of DSK were assessed using a xenograft mouse model. RESULTS: DSK inhibited cell proliferation, enhanced cell apoptosis, and reduced the cell invasion of MDA-MB-231 and BT549 cells. DSK also reduced the levels of CD206 and CD168 proteins, as well as IL-10 and TGF-β in phorbol 12-myristate 13-acetate-induced THP-1 cells.DSK downregulated the expression of the phosphorylated (p)-PI3K, p-AKT, and p-NF-κB proteins in cells. These effects were reversed by 740 Y-P (PI3K/AKT activator). In addition, DSK significantly reduced the tumor volume and weight in a xenograft mouse model. DSK increased the level of cell apoptosis and decreased the expression of Ki-67 and CD206 in subcutaneous tumor tissue. DSK also inactivated the PI3K/AKT/NF-κB pathway proteins. CONCLUSION DSK inhibits the proliferation, invasion, and tumor immune microenvironment of BC cells by inactivating the PI3K/AKT/NF-κB pathway, indicating that DSK may be a potential therapeutic option for BC treatment.

Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Objective To explore the differences in coronary-based and lesion-based fat attenuation index(FAI)in patients with coronary artery disease(CAD)across different risk stratifications,and to compare the diagnostic efficiency of coronary-based and lesion-based FAI in stable CAD patients with myocardial ischemia.Methods The patients with CAD,who underwent preoperative coronary CT angiography(CCTA)and invasive coronary angiography(ICA)with coronary fractional flow reserve(FFR)measurement between Apr 2019 and Oct 2022 in Zhongshan Hospital,Fudan University,were retrospectively collected.There were 57 cases of acute coronary syndrome(ACS)patients and 206 cases of stable CAD patients included following inclusion criteria.The coronary-based and lesion-based FAI were measured,and the differences in these indices were recorded and analyzed among ACS patients,ischemic and non-ischemic groups of stable CAD patients(FFR=0.8 as the threshold).ROC curves were utilized to assess the diagnostic efficiency of coronary-based and lesion-based FAI for myocardial ischemia in stable CAD patients.Results The coronary-based FAI and lesion-based FAI in ACS patients were significantly higher than those in stable CAD patients[coronary-based FAI:(-72.40±6.83)HU vs.(-76.82±9.01)HU,P<0.001;lesion-based FAI:(-65.65±4.79)HU vs.(-77.48±8.64)HU,P<0.001].Among stable CAD patients,the lesion-based FAI in the ischemic group was significantly higher than that in the non-ischemic group[(-69.28±5.65)HU vs.(-80.10±7.75)HU,P<0.001].The diagnostic efficiency of lesion-based FAI for predicting myocardial ischemia in stable CAD patients was superior to coronary-based FAI(AUC:0.892 vs.0.525,Z=9.803,P<0.001).Conclusion Coronary-based and lesion-based FAI tended to be higher in ACS patients than in stable CAD patients,suggesting a potential for stratifying CAD patients with different risks.Lesion-based FAI showed some promise in evaluating myocardial ischemia among stable CAD patients.

Objective To explore the clinicopathological characteristics and prognosis of multiple-molecular classifier endometrioid adenocarcinomas with DNA polymerase epsilon catalytic subunit(POLE)mutations.Methods In this study,we involved 261 patients with endometrioid adenocarcinoma admitted to the Shengjing Hospital of China Medical University.We detected the expression of the POLE gene and that of p53 protein and mismatch repair(MMR)proteins using gene sequencing and immunohistochemistry,respectively.We analyzed the correlation between different molecular classifications and clinicopathological characteristics using x2 or Fisher test,and Kaplan-Meier survival curves to analyze patients' prognosis.Results We identified nine multiple-molecular classifier cases of endome-trioid adenocarcinoma with POLE mutations,including six POLE mutated+p53 abnormal(POLE mut+p53abn)and three POLE mutated+MMR-deficient(POLE mut+dMMR)cases.Patients with POLE mut+p53abn exhibited significant differences from those with p53abn in terms of the pathological characteristics of tumor-infiltrating lymphocytes and the presence of tumors with peritumoral lymphocyte infiltra-tion(P＜0.05),while no statistically significant difference was present compared to patients with POLE mut(P＞0.05).Kaplan-Meier sur-vival curve analysis revealed that the progression-free survival rates of patients with POLE mut+p53abn and POLE mut+dMMR(100.0％)were higher than those of patients with p53abn(50.0％)and dMMR(8.8％,P＜0.05).Conclusion The clinicopathological characteris-tics of patients with POLE mut+p53abn are similar to those with POLE mut.Both patients with POLE mut+p53abn and POLE mut+dMMR display a good prognosis.

Objective:To construct a multimodal induction educational system suitable for standardized pediatric residency training bases, and to evaluate its effectiveness, thereby obtaining suggestions for further improvement.Methods:Twelve residents newly enrolled in the 2023 standardized residency training program who commenced their first-year training were included as study subjects. The induction educational system comprised multiple modules: department introduction, training plan and assessment requirements, departmental workflow, routine diagnosis and treatment of major diseases, specialized skills/procedures, and lifestyle guidance. Training materials and methods were tailored to the characteristics of each training module. Checklists were used for supervision and review, and a competency checklist was designed to evaluate residents' mastery of the training at two weeks of induction, which would guarantee the effectiveness of the training. A questionnaire survey, powered by wjx.cn, was used to obtain the experience and suggestions from the residents and ward instructors on induction education, and content ranking analysis was performed on the survey results.Results:The survey revealed that, before starting a new rotation, residents' top three educational needs were departmental workflow, routine diagnosis and treatment of common diseases, and specialized skills/procedures. Residents preferred face-to-face lectures and demonstrations by attending physicians or senior residents; instructors suggested improving relevant materials (such as resident physician manuals and video materials) and face-to-face lectures. The residents considered the current induction educational system to be greatly beneficial in basic theories, treatment principles, basic skills, and auxiliary examination processes.Conclusions:Through the above research, a multimodal induction educational system suitable for the standardized pediatric residency training base in the Peking University First Hospital has been preliminarily established, and suggestions for further improvement have been obtained, which is conducive to further improving the system and residents' post competency.

Objective:To investigate the mediating effect of psychological stress between sleep disorder and fatigue in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) .Methods:Convenience sampling was used to select 305 ACS patients with PCI from August to September 2024 in China-Japan Union Hospital of Jilin University. General Information Questionnaire, Multidimensional Fatigue Inventory-20 (MFI-20), Symptom Checklist 90 (SCL-90), and Pittsburgh Sleep Quality Index (PSQI) were used to survey the patients at discharge, and one month after discharge.Results:The MFI-20, SCL-90, and PSQI scores at discharge of 305 patients with PCI for ACS were (59.27±18.33), (141.09±49.08), and (10.72±4.95), respectively. The MFI-20, SCL-90, and PSQI scores at one month after discharge were (55.58±19.28), (134.08±44.29), and (9.17±5.20), respectively. Mediating effect analysis showed that at discharge, the direct effect of sleep disorder on fatigue was 0.403, the mediating effect was 0.216, and the total effect was 0.619, with the mediating effect accounting for 34.89% of the total effect. One month after discharge, the direct effect of sleep disorder on fatigue was 0.385, the mediating effect was 0.355, and the total effect was 0.740, with the mediating effect accounting for 47.97% of the total effect.Conclusions:Psychological stress plays a mediating role between sleep disorder and fatigue at different time points in ACS patients undergoing PCI. Clinical attention should be paid to sleep disorders and psychological stress of ACS patients undergoing PCI, so as to improve their fatigue.

Objective:To understand the status of bone health literacy in middle-aged and older female breast cancer patients undergoing chemotherapy and analyze its influencing factors using structural equation modeling.Methods:A convenience sampling method was used to select 250 middle-aged and older breast cancer patients undergoing chemotherapy in two tertiary hospitals in Xi'an from May to October 2024. Patients were surveyed using a general information questionnaire, the Bone Health Literacy Scale for Middle-Aged and Older Women, the Perceived Social Support Scale, and the General Self-Efficacy Scale. Pearson correlation analysis was used to examine the correlations among bone health literacy, perceived social support, and self-efficacy.Results:A total of 250 questionnaires were distributed, and 239 valid questionnaires were recovered, yielding an effective response rate of 95.6% (239/250). The mean score of the Bone Health Literacy Scale among the 239 patients was (39.71±8.16). Bone health literacy was positively correlated with perceived social support and self-efficacy ( P<0.01). Perceived social support directly affected bone health literacy and could also indirectly influence it through general self-efficacy, with an indirect effect value of 0.367, accounting for 45.2% of the total effect (0.367/0.812) . Conclusions:Healthcare professionals should implement effective interventions to enhance patients' perceived social support and strengthen their self-efficacy, thereby improving bone health literacy.

Aim To study the role and mechanism of ML210 in glioma.Methods The cell viability was detected by CCK8 assay.The percentage of dead cells was detected by SYTOXstaining.The role of ferroptosis-signaling pathway in gliomas was detected bygenomics.Cell proliferation was observed by EdU staining and clone formation assay.Cell migration ability was detec-ted by scratch healing assay.The apoptosis was detec-ted by flow cytometry.Cell mitochondrial function was assesses by JC-1 staining.The mechanism of action of ML210 was detected by molecular docking coupled with immunoblotting assay(Western blot).The levels of ROS,MDA were observed by ELISA.Results Compared with the control group,ML210 treatment dose-dependently decreased glioma cell viability,in-hibited cell proliferation,migration,and increased cell apoptosis and mitochondrial dysfunction,which were reversed by ferroptosis antagonists.Gene microarray screening showed that 688 genes of the ferroptosissig-naling pathway were aberrant and 10 signaling path-ways were altered in gliomas.Molecular docking re-sults showed that ML210 binding to GPX4 significantly inhibited the protein expression level of GPX4 and pro-moted the elevation of ROS and MDA levels.Conclu-sions ML210 produces anti-glioma cells via GPX4-mediated ferroptosis pathway.