OBJECTIVES: To investigate the application value of thromboelastography (TEG) in assessing coagulation function in children with severe hemophilia A (HA) after emicizumab (EMI) therapy. METHODS: A retrospective analysis was performed on the activated partial thromboplastin time (APTT) and TEG testing results of 17 children with severe HA before and after EMI treatment at Shenzhen Children's Hospital from January 2023 to July 2024. Correlation analysis was conducted between coagulation factor VIII (FVIII) equivalent activity and reaction time (R value) measured by TEG. RESULTS: After EMI treatment, the mean bleeding rate for children with severe HA was 1.6 events per year, with 15 children (88%) without spontaneous bleeding or joint bleeding. The children with severe HA showed a significant reduction in APTT after EMI treatment (P<0.05), with a significantly shorter APTT than the normal control group (P<0.05). There was no correlation between APTT and FVIII equivalent activity after treatment (P>0.05). After EMI treatment, TEG parameters, including R value, kinetic time, alpha angle (α), maximum amplitude, clot strength, and coagulation index, shifted from a hypocoagulable state before treatment to a nearly normal state after treatment (P<0.05). The R value demonstrated a strong negative correlation with FVIII equivalent activity (r=-0.758, P<0.05). CONCLUSIONS The bleeding condition of children with severe HA can be effectively controlled after EMI treatment. Routine APTT testing cannot reflect true coagulation function, whereas TEG testing is clinically valuable in assessing the coagulation function of children with severe HA undergoing EMI treatment.
Humans ; Thrombelastography ; Hemophilia A/physiopathology* ; Male ; Child ; Antibodies, Bispecific/therapeutic use* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Blood Coagulation/drug effects* ; Child, Preschool ; Retrospective Studies ; Female ; Partial Thromboplastin Time ; Adolescent ; Infant

Objective:This study was aimed to explore the preference and heterogeneity in community health management service model selection among older patients with multiple chronic diseases,and to provide scientific evidence for optimizing the model.Methods:A multi-stage stratified and convenience sampling approach was adopted.A discrete choice experiment was conducted with 360 elderly patients with multiple chronic diseases from six regions in Jiangsu Province.The Mixed Logit Model was used to analyze service selection preferences and willingness to pay,while the Latent Class Logit Model was applied to explore heterogeneity among patient groups.Results:Patients showed a stronger preference for a service model featuring"twice-monthly visits,medication guidance+lifestyle counseling,and face-to-face consultations,"with willingness to pay values of 170.18 CNY,162.90 CNY,and 112.70 CNY,respectively.Willingness to pay decreased as out-of-pocket costs increased.Heterogeneity analysis identified three distinct preference groups,with statistically significant differences in urban-rural distribution,income levels,and health insurance types.Conclusions and suggestions:Medication and lifestyle guidance are the most valued components of community health management services among older patients with multiple chronic diseases.Patients'demographic and socioeconomic characteristics have a structural influence on their service preferences,highlighting the need to tailor service provision to different population groups.It is recommended to enhance medication guidance capacity at the primary care level,especially in rural areas;promote physical medicine integration to improve the accuracy and effectiveness of lifestyle guidance provided by primary healthcare personnel;strengthen digital infrastructure and streamline service processes to moderately increase the frequency of face-to-face consultations;and improve the integration of medical insurance and public health funding mechanisms to enhance service accessibility and equity.

Purpose To explore the role and mechanism by which the forkhead box C1(FOXC1)promoter up-stream transcript(FOXCUT)regulates proliferation and invasion of non-small cell lung carcinoma(NSCLC)cells.Methods Bioinformatic analysis and RT-qPCR were used to quantify FOXCUT expression in NSCLC tissues.After FOXCUT knockdown in NSCLC cell lines,cell proliferation was examined using CCK-8 and EdU assays,and invasion was evaluated by Transwell assay.The expression of E-cadherin,vimentin,N-cadherin,and FOXC1 was detected by Western blot.FOXCUT-silenced H460 cells were constructed using lentiviruses and subcutaneously injected into nude mice to observe tumor growth.To rescue FOXC1 expression,an FOXC1 expression plasmid was transfected into FOX-CUT-knockdown cells.LncBook 2.0,ENCORI,and TargetScan databases were queried to predict miRNAs that inter-act with FOXCUT and FOXC1.Results FOXCUT expression was significantly higher in NSCLC tissues than in normal lung tissues(normal:0.24±0.22 vs NSCLC:0.68±0.76,t=5.94,P＜0.001),and patients with high FOXCUT expression had a poorer prognosis(P＜0.01).FOXCUT interference markedly repressed NSCLC cells' proliferation and invasion(P＜0.01).FOXCUT knockdown significantly upregulated E-cadherin and downregulated vimentin and N-cadherin(P＜0.01).In vivo,FOXCUT-silenced cells formed significantly smaller tumors in nude mice(P＜0.01).FOXCUT knockdown markedly reduced FOXC1 expression(P＜0.01).Overexpression of FOXC1 in FOX-CUT-depleted cells rescued cell proliferation(P＜0.01).Bioinformatic analysis identified 8 miRNAs potentially co-regulated by FOXCUT and FOXC1.Conclusion Knockdown of FOXCUT restrains NSCLC cell proliferation and inva-sion,possibly through suppression of FOXC1 expression.

Objective:This study retrospectively analyzed the clinical characteristics of patients newly diagnosed with acute myeloid leukemia (AML) who were admitted to the hematology intensive care unit (HCU) with critical illness. It also examined factors associated with critical illness and early mortality in these patients.Methods:Clinical data were collected from 91 newly diagnosed AML patients admitted to the HCU of the Department of Hematology, First Affiliated Hospital of Soochow University, from October 2020 to 2024. Reasons for HCU admission, major therapeutic interventions, and risk factors for critical illness and early mortality were analyzed.Results:The median time from diagnosis to HCU admission was 3 days ( IQR: 3–9 days), and the median HCU stay was 10 days ( IQR: 3–23 days). Of the 91 patients, 71 were admitted to the HCU before induction chemotherapy, while 20 were transferred to the HCU after its initiation. The leading causes of HCU admission were pulmonary infection (78.0% ), respiratory failure (44.0% ), hepatic insufficiency (28.6% ), renal insufficiency (27.5% ), disseminated intravascular coagulation (DIC; 25.3% ), and sepsis (23.1% ). Median Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) and SOFA scores at HCU admission were 14 ( IQR: 11–18) and the median Sepsis Related Organ Failure Assessment (SOFA) score was 7 ( IQR: 4, 10). Major HCU interventions included vasoactive drugs, noninvasive and invasive mechanical ventilation, continuous renal replacement therapy, therapeutic leukocyte clearance, and cardiopulmonary resuscitation. Among patients receiving induction chemotherapy, the composite complete remission rate was 65.4%, and the overall remission rate was 88.5%. Thirty-five (38.5% ) patients died within 28 days of HCU admission. Independent risk factors for 28-day mortality were DIC ( OR=9.350, 95% CI 1.999–43.745, P=0.005), sepsis ( OR=6.817, 95% CI 1.571–29.582, P=0.010), and cardiac insufficiency ( OR=12.281, 95% CI 2.385–63.254, P=0.003) . Conclusion:The main reason for HCU admission in newly diagnosed critically ill AML patients was pulmonary infection. Nearly 40% of patients experisenced early death, and DIC, sepsis, and heart failure were factors influencing early mortatlity.

Objective To investigate the factors influencing international normalized ratio (INR)>3.0 in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Methods A retrospective analysis was performed on the clinical data of patients who underwent mechanical heart valve replacement surgery and received warfarin anticoagulation therapy at West China Hospital of Sichuan University from January 1, 2011 to June 30, 2022. Based on the discharge INR values, patients were divided into two groups: an INR≤3.0 group and an INR>3.0 group. The factors associated with INR>3.0 at the time of discharge were analyzed. Results A total of 8901 patients were enrolled, including 3409 males and 5492 females, with a median age of 49.3 (43.5, 55.6) years. The gender, body mass index (BMI), New York Heart Association (NYHA) cardiac function grading, INR, glutamic oxaloacetic transaminase, and preoperative prothrombin time (PT) were statistically different between the two groups (P<0.05). Multivariate logistic regression analysis revealed that lower BMI, preoperative PT>15 s, and mitral valve replacement were independent risk factors for INR>3.0 at discharge (P<0.05). Conclusion BMI, preoperative PT, and surgical site are factors influencing INR>3.0 at discharge in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Special attention should be given to patients with lower BMI, longer preoperative PT, and mitral valve replacement to avoid excessive anticoagulation therapy.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Readiness for Hospital Discharge(RHD)refers to a multidimensional assessment of a patient's ability to transition safely from hospital to home,encompassing physiological stability,psychological preparedness,and social support adequacy.For patients requiring Home Nutrition Support(HNS),discharge readiness is particularly critical due to their heightened need for post-discharge specialized care,which significantly influences long-term recovery and quality of life.This paper reviews the concept,influencing factors,and unmet needs of RHD in patients with HNS and proposes targeted strategies to enhance discharge preparedness.By addressing gaps in current practices,we aim to optimize RHD in this vulnerable population and provide clinicians with evidence-based guidance for developing effective discharge plans.

Objective:This study was aimed to explore the preference and heterogeneity in community health management service model selection among older patients with multiple chronic diseases,and to provide scientific evidence for optimizing the model.Methods:A multi-stage stratified and convenience sampling approach was adopted.A discrete choice experiment was conducted with 360 elderly patients with multiple chronic diseases from six regions in Jiangsu Province.The Mixed Logit Model was used to analyze service selection preferences and willingness to pay,while the Latent Class Logit Model was applied to explore heterogeneity among patient groups.Results:Patients showed a stronger preference for a service model featuring"twice-monthly visits,medication guidance+lifestyle counseling,and face-to-face consultations,"with willingness to pay values of 170.18 CNY,162.90 CNY,and 112.70 CNY,respectively.Willingness to pay decreased as out-of-pocket costs increased.Heterogeneity analysis identified three distinct preference groups,with statistically significant differences in urban-rural distribution,income levels,and health insurance types.Conclusions and suggestions:Medication and lifestyle guidance are the most valued components of community health management services among older patients with multiple chronic diseases.Patients'demographic and socioeconomic characteristics have a structural influence on their service preferences,highlighting the need to tailor service provision to different population groups.It is recommended to enhance medication guidance capacity at the primary care level,especially in rural areas;promote physical medicine integration to improve the accuracy and effectiveness of lifestyle guidance provided by primary healthcare personnel;strengthen digital infrastructure and streamline service processes to moderately increase the frequency of face-to-face consultations;and improve the integration of medical insurance and public health funding mechanisms to enhance service accessibility and equity.

Purpose To explore the role and mechanism by which the forkhead box C1(FOXC1)promoter up-stream transcript(FOXCUT)regulates proliferation and invasion of non-small cell lung carcinoma(NSCLC)cells.Methods Bioinformatic analysis and RT-qPCR were used to quantify FOXCUT expression in NSCLC tissues.After FOXCUT knockdown in NSCLC cell lines,cell proliferation was examined using CCK-8 and EdU assays,and invasion was evaluated by Transwell assay.The expression of E-cadherin,vimentin,N-cadherin,and FOXC1 was detected by Western blot.FOXCUT-silenced H460 cells were constructed using lentiviruses and subcutaneously injected into nude mice to observe tumor growth.To rescue FOXC1 expression,an FOXC1 expression plasmid was transfected into FOX-CUT-knockdown cells.LncBook 2.0,ENCORI,and TargetScan databases were queried to predict miRNAs that inter-act with FOXCUT and FOXC1.Results FOXCUT expression was significantly higher in NSCLC tissues than in normal lung tissues(normal:0.24±0.22 vs NSCLC:0.68±0.76,t=5.94,P＜0.001),and patients with high FOXCUT expression had a poorer prognosis(P＜0.01).FOXCUT interference markedly repressed NSCLC cells' proliferation and invasion(P＜0.01).FOXCUT knockdown significantly upregulated E-cadherin and downregulated vimentin and N-cadherin(P＜0.01).In vivo,FOXCUT-silenced cells formed significantly smaller tumors in nude mice(P＜0.01).FOXCUT knockdown markedly reduced FOXC1 expression(P＜0.01).Overexpression of FOXC1 in FOX-CUT-depleted cells rescued cell proliferation(P＜0.01).Bioinformatic analysis identified 8 miRNAs potentially co-regulated by FOXCUT and FOXC1.Conclusion Knockdown of FOXCUT restrains NSCLC cell proliferation and inva-sion,possibly through suppression of FOXC1 expression.