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.

Neovascular age-related macular degeneration(ARMD)is a condition where various causes induce the formation of choroidal neovascularization(CNV)in the macula, leading to macular hemorrhage, accumulation of fluid, and development of fibrosis, resulting in a large, dark spot in the center of the visual field, causing severe central vision loss in over 90% of patients. Endothelial progenitor cells(EPCs)are a heterogeneous group of cells that play a crucial role in neovascularization. Under pathological stimulation, EPCs are mobilized into the systemic circulation, migrate toward the avascular zone, and promote the restoration of blood vessels and endothelialization in the damaged area. Toll-like receptors(TLRs)are pattern recognition receptors and type Ⅰ transmembrane proteins that are mainly expressed in monocytes, dendritic cells, and other immune cells, recognizing the surface of pathogens and transmitting signals to cells, participating in the innate immune response and adaptive immune response. Studies have shown that most TLRs are involved in the development of neovascularization, and EPCs can express TLRs. Therefore, exploring the role of EPCs/TLRs in the pathogenesis of ARMD can help us understand the disease and may provide new insights for targeted therapy in the future.

Objective:To compare the prevalence and progression of subclinical atherosclerosis (SA) in populations with different cardiovascular disease (CVD) risks in China, and clarify the relationship between CVD risk stratification and SA.Methods:All participants were from Beijing Community-Based Cohort of Atherosclerosis. A total of 1 462 participants underwent carotid ultrasound and coronary computed tomography scan during 2008-2009 and 2013-2014. After excluding 191 participants with history of CVD and incomplete baseline data, 1 271 participants were included in final analysis. The 10-year CVD risk for participants were calculated based on the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) equation, and risk stratification was performed. The prevalence and progression of SA was determined by carotid intima-media thickness (cIMT), carotid plaque score and coronary artery calcification (CAC) score.Results:In the participants included in this study, 536 (42.2%), 418 (32.9%) and 317 (24.9%) were classified to have low, intermediate and high 10-year risk, respectively. With the rising level of 10-year risk, the proportion of patients with SA and SA progression increased. In low, intermediate and high CVD risk groups, the proportions of participants with CAC were 16.4%, 36.4% and 52.0% (trend P<0.001); and 15.4%, 36.4% and 53.6% had progression of CAC during follow-up, respectively (trend P<0.001); compared with low-risk group, RRs for CAC progression of intermediate and high-risk groups were 2.316 (95% CI: 1.714-3.129) and 3.322 (95% CI: 2.472-4.463), respectively (trend P<0.001). The trend of relationship between CVD risk stratification and cIMT and carotid plaque progression were consistent with CAC. Conclusions:This current study shows CVD risk stratification is closely related to the prevalence and progression of atherosclerosis in Chinese population. However, many people with low CVD risk have atherosclerotic change in their carotid and coronary artery.

Angiogenesis is a key step involving physiological and pathological processes, and pro/antiangiogenic factors are involved in angiogenesis throughout. Melatonin is a product synthesized by the pineal gland of the human brain and acts in various systems of the body. This article briefly describes the wide range of biological roles and physiological functions of melatonin, and summarizes that melatonin regulates pro-/anti-angiogenic factors(e.g., vascular endothelial growth factor/matrix metalloproteinase)under different conditions and is involved in angiogenesis in fundus diseases(e.g., age-related macular degeneration, diabetic retinopathy, and central serous choroioretinopathy); in addition, it also summarizes that melatonin regulates various cytokines, inflammatory factors and signaling pathways to produce anti-inflammatory, antioxidant and immune responses in fundus diseases, and thus obtaining the application and potential treatment of melatonin in fundus vascular diseases, with a view to providing new ideas and therapeutic targets for the treatment of fundus diseases.

Aging is a necessary process for organisms.The antioxidant capacity in the body decreases, which induces the activation of inflammasomes, autophagy dysregulation, protein misfolding in the lens, resulting in lens opacification. With the increase of age, the secretion of melatonin and glutathione(GSH)gradually decreased, and the pro-oxidant/pro-inflammatory factors increased, which created ideal conditions for the formation of age-related cataract(ARC). A series of changes such as oxidative stress, inflammation and autophagy dysregulation accompany the occurrence of aging, which is also the basis of various diseases. Melatonin has antioxidant, anti-inflammatory, regulation of autophagy and circadian rhythm effects, and has shown benefits in age-related macular degeneration(ARMD), diabetic retinopathy(DR), and glaucoma. Although phacoemulsification and lens implantation have developed maturely, they consume a lot of medical resources. This article reviews the research of melatonin in ARC, which may prevent/delay the formation of ARC, thereby reducing the economic burden of patients and reducing the loss of medical resources.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Objectives:This study aims to investigate the association between cumulative fasting blood glucose(FBG)and presence of coronary artery calcification(CAC). Methods:A total of 1 113 participants were recruited from the Beijing Community-based Cohort of Atherosclerosis.Anthropometric measurements and laboratory examinations including FBG were performed in 1998,2008-2009 and 2013-2014 respectively,and coronary CT scan was performed in 2013-2014.Participants were classified into 4 groups according to the level of cumulative FBG(10-year weighted cumulative value of at least 2 FBGs):<50.0 mmol/L group(n=495),50.0-55.9 mmol/L group(n=345),56.0-69.9 mmol/L group(n=176),and≥70.0 mmol/L group(n=97).CAC score>0 was defined as presence of CAC.Multivariable logistic regression model was applied to analyze the impact of cumulative FBG exposure on the risk of CAC,and subgroup analyses were conducted according to factors such as sex and age. Results:The mean age of enrolled participants was(59.7±6.4)years,523(47.0%)were male and 478(42.9%)had CAC.The proportion of subjects with CAC increased with the increment of cumulative FBG.Compared with the<50.0 mmol/L group,the multivariable-adjusted OR(95%CI)for CAC in the 50.0-55.9 mmol/L group,56.0-69.9 mmol/L group,and≥70.0 mmol/L group were 1.43(1.04-1.98),1.92(1.24-2.99)and 2.79(1.35-5.77),respectively(Ptrend<0.05).The risk for CAC increased by 34%per 10 mmol/L increase in cumulative FBG,with OR(95%CI)of 1.34(1.12-1.59).There was no statistically significant difference in the risk of CAC presence for each 10 mmol/L increase in cumulative FBG level between the subgroups(all P≥0.05). Conclusions:Elevated cumulative FBG is a risk factor for the prevalence of CAC,indicating the importance of maintaining healthy FBG in preventing the occurrence of CAC.

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 confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.