Objectives:To investigate the factors affecting the formation of coronary collateral circulation(CCC)in patients with chronic total occlusion(CTO)lesion of coronary artery.Methods:A total of 305 consecutive patients who were hospitalized in the department of cardiology of the First Hospital of Lanzhou University from December 2022 to December 2023 and CTO lesions were confirmed by coronary angiography in at least one major coronary artery were included.The clinical data were collected,and the patients were divided into poor CCC group(Rentrop grade 0-1,n=109)and good CCC group(Rentrop grade 2-3,n=196)according to Rentrop criteria.Univariate logistic regression and multivariate logistic regression analysis were used to investigate the risk factors of poor CCC formation in CTO lesion patients.Results:There were 109 patients with poor CCC formation and 196 patients with good CCC formation in this cohort.The levels of white blood cell count,neutrophil count,platelet count,platelet to lymphocyte ratio,neutrophil to lymphocyte ratio,systemic immunoinflammatory index(SII),lipoprotein a and fibringen(Fib)were significantly higher,lymphocyte count and mean platelet volume were significantly lower in patients with poor CCC formation than in patients with good CCC formation(all P<0.05).Multivariate logistic regression analysis showed that higher SII(OR=1.004,95%CI:1.003-1.006,P<0.001),Fib(OR=1.546,95%CI:1.038-2.301,P=0.032)levels were independent predictors of poor CCC formation in CTO lesion patients.Conclusions:Higher levels of SII and Fib are independently correlated with poor CCC formation,which may be used as clinical predictor of poor CCC formation in CTO lesion patients.

Objective:To screen potential comorbid genes shared between inflammatory bowel disease(IBD)and colorectal cancer(CRC),and to explore the relationship between the key gene a disintegrin and metalloprotease 8(ADAM8)and the pathogenesis of IBD and CRC,as well as the underlying mechanisms.Methods:Transcriptomic data and corresponding clinical information for IBD and CRC were downloaded from the GEO database and TCGA database.Differential expression analysis,prognostic gene screening,and intersection analysis were performed to identify shared genes.Multiple datasets were used to analyze and validate the expression patterns of ADAM8 in IBD and CRC and its correlation with clinicopathological features.Survival analysis was conducted to evaluate the prognostic value of ADAM8 in CRC.Functional and pathway enrichment analyses were conducted to explore the potential mechanisms by which ADAM8 influences CRC progression.The correlation between ADAM8 and tumor microenvironment components was further assessed using tumor microenvironmental algorithms.The database data was validated by detecting the expression in Chinese CRC tissues using immunohistochemistry(IHC).Results:ADAM8 was identified as a potential shared comorbidity gene in IBD and CRC.ADAM8 was significantly upregulated in both IBD and CRC tissues(all P<0.01),and its high expression was associated with disease progression(P<0.01).CRC patients with high ADAM8 expression had shorter overall survival(OS)(P<0.05 or P<0.01).ADAM8 was also significantly highly expressed in Chinese CRC tissues(P<0.01).Pathway analysis revealed that ADAM8 expression was closely linked to immune cell migration,cytokine production,and immune receptor interactions.Additionally,ADAM8 expression positively correlated with immune cell infiltration,including neutrophils and macrophages(P<0.01 or P<0.001).Conclusion:ADAM8 is highly expressed in IBD and CRC tissues and is closely associated with patient prognosis,disease progression,and immune cell infiltration.It holds promise as a common therapeutic target for both diseases.

Objective To investigate the predictive value of serum human epididymis protein 4(HE4)levels in primary Sj?gren's syndrome(pSS)patients for renal injury.Methods A retrospective analysis of 77 pSS patients admitted to the Second People's Hospital of Yichang from September 2021 to August 2023 was performed,including 43 cases of renal injury group 34 instances of non-renal injury group,and 54 healthy physical examination subjects(HCs)as control group.Fasting peripheral venous blood(4ml)was collected to detect the serum levels of HE4,Cys-C,TNF-α,CR,C3,C4,immunoglobulin,Anti-SSA,Anti-SSB and other indicators,and analyzed the value of HE4 in the early diagnosis of kidney injury in pSS patients.Results Compared with HCs,the pSS patients had increased levels of HE4(120.02±103.86 pmol/L vs 57.5±16.52 pmol/L),Cys-C(1.30±0.81mg/L vs 0.87±014 mg/L),and the differences were statistically significant(t=4.382,3.860,all P<0.05).The serum levels of HE4,CR and TNF-α in the renal damage group were higher than those in the non-renal damage group,and the differences were statistically significant(t/χ2=2.552～4.371,all P<0.05).Pearson correlation analysis showed that,the levels of serum HE4,Cys-C,CR and TNF-α were all positively correlated with renal damage in pSS(r=0.287～0.546,all P<0.05).Logistic regression analysis showed that elevated serum HE4 level might be an independent risk factor for inducing renal damage in pSS(Wald χ2=11.932,P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the best cut-offvalue of serum HE4 for the diagnosis of pSS renal damage was 70.46pmol/L,the maximum Youden index was 0.625,AUC(95%CI)=0.876(0.799～0.954).Conclusion The serum HE4 level in patients with pSS is positively correlated with renal injury and has predictive value for the occurrence of renal injury.

BACKGROUND:Stem cell transplantation has a promising therapeutic prospect in the treatment of myocardial infarction,but the efficacy of stem cell transplantation is limited by the low homing efficiency of transplanted cells to the heart and the low retention rate and survival rate in the heart.Exercise therapy is an important integral component of cardiac rehabilitation for patients with myocardial infarction.However,the role of exercise in stem cell therapy for myocardial infarction has not yet been clarified.OBJECTIVE:To investigate the effect of exercise(including acute exercise and chronic exercise)on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction.METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group or combination group with random number table method(n=20).Myocardial infarction model of rats in model group,transplantation group,or combination group was made by coronary artery ligation.24 hours after the model was made,the combination group underwent aerobic exercise for 8 weeks(chronic exercise,30 min/d,5 days per week),and within 5 minutes after the first exercise(acute exercise).SD rat bone marrow mesenchymal stem cells labeled with green fluorescent protein were injected into the tail vein of the transplantation group and the combination group.A part of animals from each group were taken 24 hours after the first exercise.The survival rate of stem cells transplanted into rat myocardium,sex-determining region of Y,protein expression of homing factors,oxidative stress,and inflammatory response parameters were measured.After 72 hours of the last exercise,the remaining rats were taken to detect cardiac structure and function,myocardial histological changes,and the number of Ki67+cells.RESULTS AND CONCLUSION:(1)After acute exercise:Compared with sham operation group,myocardial reactive oxygen species level,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression increased(P<0.05),and superoxide dismutase activity decreased(P<0.05)in model group.Compared with model group,reactive oxygen species,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression reduced(P<0.05),superoxidation dismutase activity,stromal cell-derived factor 1α,and CXC chemokine receptor 4 protein expression increased(P<0.05)in transplantation and combination groups.Compared with the transplantation group,reactive oxygen species,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression decreased(P<0.05),stem cell survival rate,sex-determining region of Y mRNA expression,superoxide dismutase activity,stromal cell-derived factor 1α,and CXC chemokine receptor 4 protein expression increased(P<0.05)in combination group.(2)After chronic exercise:Compared with sham operation group,cardiomyocyte cross-sectional area and collagen content increased(P<0.05),left ventricular ejection fraction and left ventricular short-axis shortening rate decreased(P<0.05)in model group.Compared with model group,cardiomyocyte cross-sectional area and collagen content decreased(P<0.05),Ki67+cells increased(P<0.05)in transplantation group.Compared with transplantation group,collagen content decreased(P<0.05),cardiomyocyte cross-sectional area,left ventricular ejection fraction,left ventricular short-axis shortening rate,and Ki67+cells increased(P<0.05)in the combination group.(3)Acute exercise improves the survival rate of exogenous stem cells by promoting stem cell homing and improving myocardial microenvironment,while chronic exercise can stimulate cardiomyocyte proliferation,inhibit cardiac remodeling,and enhance cardiac function after stem cell transplantation.Therefore,exercise can help to optimize the efficacy of stem cell transplantation after myocardial infarction in rats.

Objective:To analyze the echocardiographic and genetic characteristics of fetuses with common arterial trunk（CAT）.Methods:A retrospective analysis was conducted on 77 480 fetal echocardiograms examined at the Maternal-Fetal Medicine center in Fetal Heart Disease of Beijing Anzhen Hospital from November 2010 to November 2024.Among them，106 fetuses were initially diagnosed with CAT，and 95 cases were ultimately confirmed（0.1%，95/77 480）. The echocardiographic and genetic features of CAT fetuses were analyzed. According to the modified Van Praagh classification，CAT was divided into types A1-A4［with ventricular septal defect（VSD）］and B1-B4（without VSD）based on the origin of the pulmonary artery branches and the presence or absence of a VSD. Additionally，CAT was categorized into isolated and complex types based on the presence of associated intracardiac or extracardiac anomalies.Results:① Among the 95 confirmed CAT fetuses，type A accounted for 90.5%（86/95），and type B accounted for 9.5%（9/95）. All 9 type B CAT fetuses exhibited no overriding of the arterial trunk ， with 8 cases showing left ventricular hypoplasia accompanied by mitral atresia or absence.② Of the 95 CAT fetuses，14 were isolated（14.7%，14/95） ， and 81 were complex（85.3%，81/95）.The main associated intracardiac anomalies included：single ventricle（22 cases），complete atrioventricular septal defect（12 cases），anomalous pulmonary venous drainage（10 cases），right aortic arch with mirror-image branching（16 cases），and persistent left superior vena cava（14 cases）. ③ Genetic testing was performed in 31 fetuses，with 18 showing positive results，primarily 22q11.21 deletion syndrome（29.0%，9/31）. Conclusions:Apart from VSD，the most common intracardiac anomaly associated with CAT fetuses is single ventricle. Type B CAT without trunk overriding is often associated with left ventricular hypoplasia and mitral atresia or absence. The most frequent genetic abnormality in CAT fetuses is 22q11.21 deletion syndrome. Prenatal echocardiography should clarify the CAT subtype and associated anomalies，and genetic testing is strongly recommended for perinatal counseling and prognostic evaluation.

Corneal neovascularization(CNV)is a pathological condition characterized by the invasion of new blood vessels into the normally avascular corneal area from the corneal periphery,leading to severe vision loss and potentially blindness.Currently,surgical,physical,and pharmacological therapies are the main clinical approaches for treating CNV.Surgical treatment aims to remove abnormal vascular tissue or perform corneal trans-plantation to inhibit angiogenesis;however,it carries a risk of postoperative rejection.Physical therapy involves the direct application of non-invasive modalities,such as laser treatment,to the neovascularized area to suppress vascular growth.Nevertheless,this approach may cause damage to surrounding healthy tissues.Pharmacotherapy has recently become a research hotspot in CNV treatment due to its convenient administration.Clinically,the drugs used for CNV treatment mainly include anti-inflammatory agents,anti-VEGF drugs,and immunosuppressants,which inhibit CNV progression by targeting angiogenesis-related signaling pathways.However,these drugs often lead to drug resistance and toxic side effects.Therefore,there is an urgent need to develop more effective and safer therapeutic agents for CNV.This article reviews the current clinical treatment status of CNV and highlights recent advances in the use of small molecule extracts from traditional Chinese medicine for CNV therapy,aiming to provide potential candidate drugs and a scientific theoretical basis for clinical management of CNV.

BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Ischemic stroke (IS), a leading cause of morbidity and mortality worldwide, primarily results from blood clot formation in cerebral vessels, leading to vessel occlusion, reduced cerebral blood flow, and subsequent tissue ischemia. While thrombolytic therapies and mechanical thrombectomy remain cornerstone treatments for restoring blood flow, their clinical efficacy is significantly limited by the narrow therapeutic window, which underscores the critical need for novel, safe, and effective therapeutic strategies. In this review, we present an intensive analysis of four pathophysiological stages of IS progression and their intervention targets, and evaluate both established and emerging therapeutic strategies with the molecular mechanisms underpinning these methods, aiming to enhance the understanding of IS intervention. Additionally, we discuss current challenges in IS therapy, emphasizing the importance of timely, stage-specific approaches to optimize therapeutic outcomes. Finally, we highlight some promising research directions and innovations to advance IS field.