ObjectiveTo explore the effects of Qingxin Jieyu granules on ventricular remodeling of mice after myocardial infarction， and their regulatory role in mitophagy. MethodsSixty male C57BL/6 mice were randomly assigned to six groups： sham-operated group， model group， Qingxin Jieyu granules low-， medium-， and high-dose groups （1.3， 2.6， 5.2 g·kg^-1）， and sacubitril valsartan sodium group （0.03 g·kg^-1）， with 10 mice per group. Except for the sham-operated group， all other groups utilized left anterior descending coronary artery ligation to build a myocardial infarction model. Ultrasound was used to measure left ventricular parameters， including end-diastolic and end-systolic diameters （LVIDd， LVIDs）， diastolic and systolic posterior wall thickness （LVPWd， LVPWs）， end-diastolic and end-systolic volumes （LV Vold， LV Vols）， left ventricular ejection fraction （LVEF）， and fractional shortening （LVFS）. Additionally， the heart mass index and heart weight/tibia length ratio of mice were calculated. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify brain natriuretic peptide （BNP）， creatine kinase isoenzyme （CK-MB）， angiotensinⅡ （AngⅡ）， and lactate dehydrogenase （LDH） levels in the serum of mice. Histological analysis using hematoxylin-eosin （HE） and Masson staining was conducted to examine morphological changes in myocardial tissue. Immunohistochemistry assessed the expression of vascular growth factors， including basic fibroblast growth factor （bFGF） and vascular endothelial growth factor （VEGF）. Transmission electron microscopy was used to scrutinize mitochondrial morphology in the myocardial tissue of mice. Western blot was performed to analyze the expression of phosphorylated adenosine monophosphate activated protein kinase （p-AMPK） and phosphorylated mammalian target of rapamycin （p-mTOR） proteins in myocardial tissue from each experimental group. ResultsCompared to the sham-operated group， the model group mice exhibited significantly elevated levels of LV Vold， LV Vols， LVIDd， LVIDs， cardiac mass index， heart weight/tibia length ratio， BNP， LDH， and p-mTOR protein expression （P<0.05）， along with decreased levels of LVPWd， LVPWs， LVEF， LVFS， and p-AMPK protein expression （P<0.05）. The model group also displayed substantial inflammatory cell infiltration， collagen deposition in myocardial cells， reduced expression of bFGF and VEGF， mitochondrial swelling， and cristae fragmentation. Compared to the model group， the sacubitril/valsartan group and mid-dose Qingxin Jieyu granules group showed significant reductions in LVIDs， LV Vold， LV Vols， BNP， CK-MB， LDH， and p-mTOR protein expression （P<0.05）， coupled with increases in LVEF， LVFS， and p-AMPK expression （P<0.05）. Improvements were observed across all treatment groups， including reduced inflammatory cell infiltration and collagen deposition， increased bFGF and VEGF expression， alleviated mitochondrial swelling， and the presence of autophagosomes and lysosomes. ConclusionThe results show that Qingxin Jieyu granules can regulate mitochondrial autophagy in myocardial tissue and inhibit ventricular remodeling to improve cardiac performance， by up-regulating the p-AMPK expression in the myocardial tissue of mice with ventricular remodeling after myocardial infarction， and down-regulating the p-mTOR expression.

ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule(QXJYG)against atherosclerosis(AS)based on network pharmacology.Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology.Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline,atorvastatin(13.15 mg/kg),or QXJYG at 0.99,1.98,and 3.96 g/kg for 8 weeks(n=6).Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta.Blood lipids and serum levels of Ang II,ET-1,TXA2,PGI2,and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA.The expressions of LOX-1,PPARγ,RXRα,p-P65,VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry.Results The rat models of AS showed obvious abdominal aorta wall thickening,increased pulse wave velocity and pulse index,decreased inner diameter of the abdominal aorta,elevated levels of TC,LDL-C,Ang II,ET-1 and TXA2,and lowered levels of HDL-C and PGI2.QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta,decreased serum levels of TC,LDL-C,Ang II,ET-1 and TXA2,and increased the levels of HDL-C and PGI2.Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism,PPAR and NF-κB pathways.Consistently,treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1,P-P65,VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats.Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level,reducing LOX-1 expression,activating PPARγ and RXRα,and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Objective:To investigate risk factors for in-stent restenosis (ISR) after percutaneous transluminal angioplasty and stenting (PTAS) in patients with severe symptomatic intracranial carotid stenosis.Methods:Consecutive patients with severe symptomatic intracranial carotid stenosis underwent PTAS in the Department of Neurology, Jining First People's Hospital from December 2021 to June 2023 were retrospectively included. Clinical and procedure related data were collected, and periprocedural complications were recorded. Imaging follow-up was used to evaluate ISR after 6 months. Multivariate logistic regression analysis was used to determine independent risk factors for ISR. Results:A total of 73 patients were enroled, including 45 males (61.6%), aged 61.49±7.78 years. The median follow-up time was 8 months (interquartile range, 7-9 months; range, 6-10 months), with 19 cases (26.0%) experiencing ISR, of which 1 (1.4%) had symptomatic ISR. Multivariate logistic regression analysis showed that the higher degree of residual stenosis immediately after procedure (odds ratio [ OR] 1.102, 95% confidence interval [ CI] 1.004-1.209; P=0.040), accompanied by moderate to severe cerebrovascular stenosis in other areas ( OR 6.638, 95% CI 1.106-39.835; P=0.038) and low preprocedural white blood cell count ( OR 0.541, 95% CI 0.308-0.952; P=0.033) were the independent risk factors for ISR. Conclusion:The higher degree of residual stenosis immediately after procedure, accompanied by moderate to severe cerebrovascular stenosis in other areas, and lower preprocedural white blood cell count are the risk factors for the occurrence of ISR after PTAS in patients with severe intracranial carotid stenosis.

Intracranial atherosclerotic stenosis (ICAS) is closely associated with cognitive impairment and dementia. This article reviews the manifestations, mechanisms, and interventions of cognitive impairment in patients with ICAS, aiming at increasing attention to ICAS, early identification and intervention, and delaying the occurrence and deterioration of cognitive impairment.

Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of ischemic stroke worldwide. A variety of factors are associated with the occurrence and development of ICAS, including gender, age, persistent inflammatory state, hypertension, hyperlipidemia and diabetes. Early identification and appropriate management of risk factors for ICAS are of great significance for actively preventing and treating ICAS and reducing the risk of ischemic stroke occurrence and recurrence.

Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule(QXJYG)against atherosclerosis(AS)based on network pharmacology.Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology.Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline,atorvastatin(13.15 mg/kg),or QXJYG at 0.99,1.98,and 3.96 g/kg for 8 weeks(n=6).Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta.Blood lipids and serum levels of Ang II,ET-1,TXA2,PGI2,and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA.The expressions of LOX-1,PPARγ,RXRα,p-P65,VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry.Results The rat models of AS showed obvious abdominal aorta wall thickening,increased pulse wave velocity and pulse index,decreased inner diameter of the abdominal aorta,elevated levels of TC,LDL-C,Ang II,ET-1 and TXA2,and lowered levels of HDL-C and PGI2.QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta,decreased serum levels of TC,LDL-C,Ang II,ET-1 and TXA2,and increased the levels of HDL-C and PGI2.Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism,PPAR and NF-κB pathways.Consistently,treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1,P-P65,VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats.Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level,reducing LOX-1 expression,activating PPARγ and RXRα,and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Intracranial atherosclerotic stenosis (ICAS) is the main cause of ischemic stroke. Endovascular therapy (EVT) is a method of treating symptomatic ICAS, and in-stent restenosis (ISR) is an important factor affecting the efficacy of EVT. This article summarizes the influencing factors of ISR in patients with ICAS receiving EVT treatment.

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.