Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS' survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (^HAP-1NP_DC+LND) was further tailored in the optimal synergistic ratio for targeted and synergistic metabolic modulation of FLS to alleviate RA symptoms. Upon targeted uptake by FLS in inflamed joints, ^HAP-1NP_DC+LND released DC and LND within the intracellular reductive microenvironment, where DC hinders glucose uptake and LND suppresses glycolytic enzymes to eliminate FLS synergistically. Additionally, the secretion of lactic acid and pro-inflammatory factors from FLS were reduced, thereby disrupting the crosstalk between FLS and pro-inflammatory macrophages. Finally, ^HAP-1NP_DC+LND demonstrated promising efficacy in a mouse model of collagen-induced arthritis (CIA). Overall, this research provides valuable insights into novel therapeutic strategies for the safe and effective of treatment RA through targeted and synergistic metabolic modulation of FLS.

Objective:This study aims to initially establish a scoring system for comprehensively reflecting the severity of intracranial atherosclerotic lesions and to explore the correlation between this score and atherosclerotic risk factors as well as stroke events.Methods:This study retrospectively analyzed patients who underwent head and neck computer tomography angiography(CTA)examinations and had head MRI examinations within one month before or after the CTA examination from January 2021 to August 2024 in Beijing Hospital.An intracranial atherosclerosis disease score(ICADS)system was constructed based on the degree and number of vascular stenosis.The relationship between ICADS and atherosclerotic risk factors was explored by grouping patients according to the quartile of ICADS.Patients were divided into acute stroke group and non-acute stroke group to compare differences in ICADS and cerebrovascular disease risk factors between the two groups, and to investigate the correlation between stroke events and ICADS.Results:There were statistically significant differences in the proportions of patients with hypertension and diabetes among different ICADS groups.Multiple linear regression analysis showed that hypertension( B=1.17, 95% CI: 0.20-2.14, P<0.05)and diabetes( B=2.75, 95% CI: 1.85-3.64, P<0.001)were risk factors for higher ICADS.The ICADS was higher in the acute stroke group than in the non-acute stroke group(9 vs.6, P<0.001), and a higher ICADS was identified as a risk factor for stroke( OR=1.10, 95% CI: 1.07-1.14, P<0.001). Conclusions:ICADS can comprehensively reflect the severity of intracranial atherosclerotic lesions and is correlated with stroke events, making it useful for clinical screening of high-risk patients for stroke.

Objective:To investigate the relationship between the changes in extracellular vesicles (EVs) size distribution before and after cardiopulmonary bypass (CPB) cardiac surgery and postoperative coagulation function.Methods:A total of 103 patients undergoing cardiac surgery with CPB were enrolled. Venous blood samples were collected at preoperation, postoperative 12 h and 3 days. Additionally, 50 age- and gender-matched healthy volunteers served as a control group. EVs were isolated using gradient centrifugation, and their size distribution was assessed by dynamic light scattering (DLS). The relationship between EV size characteristics, including peak diameter, peak height, and interquartile range( IQR), and postoperative coagulation function was analyzed. Results:Compared to patients with normal postoperative coagulation function, those with postoperative coagulation dysfunction had lower size at peak and IQR, and significantly higher peak intensity. Logistic regression analysis indicated that elevated peak intensity and lower size at peak and IQR were risk factors for coagulation dysfunction. The area under the curve ( AUC) for diagnosing coagulation dysfunction with 12 h postoperative EVs peak intensity was 0.76, with a positive predictive value of 85% at the optimal cutoff of 8.2; the AUC for IQR was 0.84, with a sensitivity of 83%, specificity of 82%, and negative predictive value of 86% at the optimal cutoff of 125.05 nm. Conclusion:The size distribution of circulating EVs show a correlation with coagulation function after cardiac surgery with CPB and may serve as a novel biomarker to predict postoperative coagulation dysfunction.

Objective:This study aims to initially establish a scoring system for comprehensively reflecting the severity of intracranial atherosclerotic lesions and to explore the correlation between this score and atherosclerotic risk factors as well as stroke events.Methods:This study retrospectively analyzed patients who underwent head and neck computer tomography angiography(CTA)examinations and had head MRI examinations within one month before or after the CTA examination from January 2021 to August 2024 in Beijing Hospital.An intracranial atherosclerosis disease score(ICADS)system was constructed based on the degree and number of vascular stenosis.The relationship between ICADS and atherosclerotic risk factors was explored by grouping patients according to the quartile of ICADS.Patients were divided into acute stroke group and non-acute stroke group to compare differences in ICADS and cerebrovascular disease risk factors between the two groups, and to investigate the correlation between stroke events and ICADS.Results:There were statistically significant differences in the proportions of patients with hypertension and diabetes among different ICADS groups.Multiple linear regression analysis showed that hypertension( B=1.17, 95% CI: 0.20-2.14, P<0.05)and diabetes( B=2.75, 95% CI: 1.85-3.64, P<0.001)were risk factors for higher ICADS.The ICADS was higher in the acute stroke group than in the non-acute stroke group(9 vs.6, P<0.001), and a higher ICADS was identified as a risk factor for stroke( OR=1.10, 95% CI: 1.07-1.14, P<0.001). Conclusions:ICADS can comprehensively reflect the severity of intracranial atherosclerotic lesions and is correlated with stroke events, making it useful for clinical screening of high-risk patients for stroke.

A 75-year-old female patient with postoperative colon cancer received fruquintinib (5 mg once daily, 3 weeks on and 1 week off per 4-week cycle). The patient had normal blood pressure in the past, and approximately one week after medication, she developed hypertension with systolic blood pressure 180-190 mmHg and unknown diastolic pressure. The patient′s blood pressure was with adequate control after self-administration of nifedipine sustained-release tablets twice (20 mg/dose). After 3 weeks of fruquintinib treatment, bilateral lower limb edema occurred in the patient, leading to a 1-week drug discontinuation. Upon resuming the medication for 1 day, the patient suddenly developed dyspnea and loss of consciousness. Chest CT revealed signs of heart failure. Laboratory tests showed high-sensitivity cardiac troponin I (hs-cTnI) 0.27 μg/L, creatine kinase (CK)-MB 7.13 μg/L, myoglobin 132.88 μg/L, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 4 039.8 ng/L. Fruquintinib was discontinued, and the patient received myocardial nutritional support, diuretics, anticoagulants, hepatoprotective agents, and potassium supplementation, etc. On day 2, the patient regained consciousness with hs-cTnI 0.28 μg/L, CK-MB 4.63 μg/L, myoglobin 34.25 μg/L, and NT-proBNP 10 181.3 ng/L. Antiplatelet therapy, diuretics, lipid-lowering agents, and antihypertensive treatment were initiated. On day 3, color doppler echocardiography confirmed myocardial infarction complicated by heart failure. Fruquintinib-induced acute non-ST-segment elevation myocardial infarction with acute heart failure was considered. On day 6 of fruquintinib discontinuation, NT-proBNP decreased to 295.8 ng/L, and all laboratory test parameters normalized on day 9. One month later, repeated tests showed no abnormalities in the myocardial enzyme.

A 75-year-old female patient with postoperative colon cancer received fruquintinib (5 mg once daily, 3 weeks on and 1 week off per 4-week cycle). The patient had normal blood pressure in the past, and approximately one week after medication, she developed hypertension with systolic blood pressure 180-190 mmHg and unknown diastolic pressure. The patient′s blood pressure was with adequate control after self-administration of nifedipine sustained-release tablets twice (20 mg/dose). After 3 weeks of fruquintinib treatment, bilateral lower limb edema occurred in the patient, leading to a 1-week drug discontinuation. Upon resuming the medication for 1 day, the patient suddenly developed dyspnea and loss of consciousness. Chest CT revealed signs of heart failure. Laboratory tests showed high-sensitivity cardiac troponin I (hs-cTnI) 0.27 μg/L, creatine kinase (CK)-MB 7.13 μg/L, myoglobin 132.88 μg/L, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 4 039.8 ng/L. Fruquintinib was discontinued, and the patient received myocardial nutritional support, diuretics, anticoagulants, hepatoprotective agents, and potassium supplementation, etc. On day 2, the patient regained consciousness with hs-cTnI 0.28 μg/L, CK-MB 4.63 μg/L, myoglobin 34.25 μg/L, and NT-proBNP 10 181.3 ng/L. Antiplatelet therapy, diuretics, lipid-lowering agents, and antihypertensive treatment were initiated. On day 3, color doppler echocardiography confirmed myocardial infarction complicated by heart failure. Fruquintinib-induced acute non-ST-segment elevation myocardial infarction with acute heart failure was considered. On day 6 of fruquintinib discontinuation, NT-proBNP decreased to 295.8 ng/L, and all laboratory test parameters normalized on day 9. One month later, repeated tests showed no abnormalities in the myocardial enzyme.

Objective:To investigate the relationship between the changes in extracellular vesicles (EVs) size distribution before and after cardiopulmonary bypass (CPB) cardiac surgery and postoperative coagulation function.Methods:A total of 103 patients undergoing cardiac surgery with CPB were enrolled. Venous blood samples were collected at preoperation, postoperative 12 h and 3 days. Additionally, 50 age- and gender-matched healthy volunteers served as a control group. EVs were isolated using gradient centrifugation, and their size distribution was assessed by dynamic light scattering (DLS). The relationship between EV size characteristics, including peak diameter, peak height, and interquartile range( IQR), and postoperative coagulation function was analyzed. Results:Compared to patients with normal postoperative coagulation function, those with postoperative coagulation dysfunction had lower size at peak and IQR, and significantly higher peak intensity. Logistic regression analysis indicated that elevated peak intensity and lower size at peak and IQR were risk factors for coagulation dysfunction. The area under the curve ( AUC) for diagnosing coagulation dysfunction with 12 h postoperative EVs peak intensity was 0.76, with a positive predictive value of 85% at the optimal cutoff of 8.2; the AUC for IQR was 0.84, with a sensitivity of 83%, specificity of 82%, and negative predictive value of 86% at the optimal cutoff of 125.05 nm. Conclusion:The size distribution of circulating EVs show a correlation with coagulation function after cardiac surgery with CPB and may serve as a novel biomarker to predict postoperative coagulation dysfunction.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Logistics informatization is importantfor promoting the high-quality development of public hospitals.It is a driving force for innovating hospital logistics management and an important practice of"green hospitals"and"smart hospitals".The logistics information system can effectively integrate people,machines,materials,and events of hospitals to achieve data-driven scientific management and improve service and management efficiency.By analyzing the current status of logistics manage-ment in the Sun Yat-sen University Cancer Center,this article proposes a transformation path to and management ideas for hospi-tal refined logistics management based on the information system,expecting to provide an insight into future information construc-tion and hospital logistics management development.

As public hospitals continue to expand,buildings continue to age,sporadic renovation projects are increas-ing,and expenditures are increasing.In order to ensure the safe,stable and efficient operation of the hospital,the piecemeal re-pair project has become an important basic guarantee for the hospital.There are many kinds of sporadic repair projects,and the projects are trivial and scattered.The contradictions among the needs,cost control,management ability and service quality of sporadic repair projects are becoming increasingly prominent,which has become the difficulty and pain point of logistics service management.In the practice of hospital sporadic repair project management,the traditional project management mode is broken,the whole process of fine management system is established,the level of management personnel and the whole process of the pro-ject are effectively integrated,and the management ability and service quality of sporadic maintenance projects are comprehensive-ly improved.