In recent years, the prevalence of obstructive coronary artery disease has continued to rise. Despite the widespread application of strategies such as intensive pharmacotherapy, coronary artery bypass grafting, or percutaneous coronary intervention, a subset of patients still experience recurrent angina symptoms, which severely impacts their quality of life. For such cases of refractory angina (RA), researchers domestically and internationally have explored therapeutic approaches such as spinal cord stimulation, transmyocardial laser revascularization, and sympathectomy. However, existing studies are largely limited to small-scale clinical trials, and their clinical translation still faces challenges due to insufficient validation of safety and efficacy. Injectable hydrogels, as functional materials with hydrophilic three-dimensional network structures, demonstrate unique advantages in the treatment of RA. They can not only provide mechanical support but also serve as controlled-release carriers for drugs and proteins, and synergize with gene therapy and stem cell therapy to promotemyocardial tissue repair. This article systematically reviews the application prospects of injectable hydrogels in the treatment of RA, aiming to provide insights for future therapeutic strategies.

ObjectiveTo investigate the prevalence of cardiovascular diseases and their influencing factors in community-based schizophrenia patients in Shanghai, and to provide a scientific basis for the early identification and prevention of cardiovascular disease in this population. MethodsBased on the Shanghai community cohort with severe mental disorders in 2022, a total of 3 954 community-based schizophrenia patients were identified and included in this study through a stratified cluster sampling method. Basic information and relevant clinical data (including metabolic index data) were collected through questionnaire survey, physical examination and laboratory testing. Univariate analyses were performed using the chi-square tests, and multivariate logistic regression analyses were employed to identify influencing factors of comorbid cardiovascular diseases. ResultsA total of 3 954 community-based schizophrenia patients were included, of which a total of 1 237 (31.28%) patients had comorbid cardiovascular diseases. Multivariate logistic regression analyses showed that age 60 years old or above (OR=5.524, 95%CI: 3.716‒8.214), smoking behavior (OR=1.328, 95%CI: 1.042‒1.692), overweight (OR=1.900, 95%CI: 1.046‒3.451) or obesity (OR=2.678, 95%CI: 1.439‒4.985), elevated blood pressure (OR=1.546, 95%CI: 1.294‒1.846), abnormal fasting blood glucose (OR=1.552, 95%CI: 1.322‒1.823) and high-density lipoprotein cholesterol abnormalities (OR=1.283, 95%CI: 1.025‒1.606) were positively associated with the risk of comorbid cardiovascular diseases in patients with schizophrenia, while educational attainment of college/bachelor’s degree or above (OR=0.640, 95%CI: 0.450‒0.910) and being unmarried (OR=0.552, 95%CI: 0.457‒0.667) were negatively associated with the risk of cardiovascular diseases comorbidity. ConclusionAdvanced age, unhealthy behaviors and lifestyles, as well as abnormalities in blood pressure, blood glucose, and blood lipids, could all increase the risk of comorbid cardiovascular diseases in community schizophrenia patients. It is suggested to strengthen the monitoring and management of these risk factors in this population in the future, so as to achieve early detection, early diagnosis and early intervention of cardiovascular diseases.

Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

Objective:To investigate the outcomes of endoscopic balloon dilation laryngoplasty （EBDL） in managing acquired subglottic stenosis in children. Methods:A retrospective analysis of clinical data from patients who underwent endoscopic balloon dilation for secondary subglottic stenosis between January 2017 and January 2024 at Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital of Fudan University, Shanghai. The study included 10 children （6 males, 4 females） aged between 13 days and 3 years at the time of their first procedure, with an average age of 7 months. Subglottic stenosis was graded according to the Myer-Cotton classification, with two cases classified as grade Ⅱ and eight cases as grade Ⅲ. All patients had a history of tracheal intubation, including seven for rescue purposes and three for operations. Eight cases were complicated by other conditions: two with atrial septal defect, patent ductus arteriosus, and patent foramen ovale; two with patent foramen ovale only; one with atrial septal defect and extreme deafness in the left ear; one with a brain tumor and hydrocephalus; one with a traumatic diaphragmatic hernia and hepatic rupture; and one case complicated by type Ⅰ laryngeal cleft. Prior to surgery, all children required respiratory support-seven needed high-flow oxygen while three required CPAP. Results:All ten cases underwent endoscopic balloon dilation under spontaneous respiration and general anesthesia, totaling fourteen dilations （an average of 1.4 dilations per person） without any complications. Post-surgery air permeability tests showed that eight cases had grade Ⅰ stenosis while two had grade Ⅱ stenosis. The follow-up period ranged from six months to six years （average duration: 46 months）. Following treatment, all patients no longer required respiratory support or experienced significant mobility limitations. Conclusion:Endoscopic balloon dilation under general anesthesia is deemed safe and effective in treating secondary subglottic stenosis. Early diagnosis coupled with prompt intervention can help avoid tracheotomy procedures altogether. Standard tracheoscopy combined with breathability testing represents a crucial approach to assess normal airway diameter and effectively reduce or prevent secondary subglottic stenosis following re-intubation.
Humans ; Laryngostenosis/surgery* ; Male ; Female ; Retrospective Studies ; Laryngoplasty/methods* ; Child, Preschool ; Infant ; Dilatation/methods* ; Laryngoscopy/methods* ; Treatment Outcome ; Endoscopy

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.

Objective: To evaluate the performance of platelet efficacy score (PEscore) in predicting platelet transfusion efficacy in hematological patients. Methods: A total of 485 patients with hematological diseases, including 298 males (62.09±15.45 years) and 187 females (59.17±16.52 years) who received platelet transfusion from January 1, 2021 to December 31, 2024 were enrolled in this study. Clinical data of the patients such as diagnosis, gender, age, number of platelet transfusion, and platelet antibody data were analyzed to investigate the incidence and influencing factors of platelet transfusion refractoriness in hematological patients at our hospital. ROC curve was used to evaluate the performance of PEscore model in predicting platelet transfusion efficacy. The predictive performance of PEscore model was validated by calculating its sensitivity, specificity, and accuracy in 115 clinical cases. Results: The incidence of platelet transfusion refractoriness in 485 cases was 29.90% (145/485). Significant differences (P<0.05) were observed between the effective and ineffective platelet transfusion groups regarding the following factors: diagnosis: lymphoma [55.32% (26/47) vs 44.68% (21/47)], the number of previous platelet transfusions [≥25: 60.78% (31/51) vs 39.22% (20/51)], platelet antibody screening result [positive: 33.76% (53/157) vs 66.24% (104/157)], and platelet transfusion volume (×10 /L) [>6: 62.71% (74/118) vs 37.29% (44/118)]. The area under the ROC curve of PEscore was 0.876. The cut-off points and corresponding sensitivity and specificity were 19.90.59% and 69.44%, respectively. The results of clinical application showed that the sensitivity, specificity and accuracy of the PEscore model for predicting platelet transfusion were 87.50%, 93.41% and 92.17%, respectively. Conclusion: The incidence of platelet transfusion refractoriness in hematological patients is relatively high. PEscore prediction model has a good performance in predicting the effect of platelet transfusion, which can provide a reliable basis for predicting the effect of platelet transfusion in hematological patients before blood transfusion.

The placenta is a regulator of maternal-fetal circulation，regulating nutrient and waste exchange，endocrine function，and immune response. The placental vascular structure is the basis of the placental exchange function and the key to maternal-fetal circulation. Placental vascular changes may affect fetal growth and cardiovascular development，and even the origin of postnatal health and disease. The placenta is crucial in fetal growth and development and future health，but our understanding of placental vascular structure is still insufficient. This article reviews the imaging methods and progress of placental imaging，focusing on the placental microvascular imaging technology，which aims to provide a method reference for prenatal evaluation and monitoring of placental vascular structure by realizing the visualization of placental vascular structure. Based on this new technology，it is expected to provide new ideas for the study of the hemodynamic mechanisms of fetal growth and cardiovascular development in the future.

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.

Objective To explore the mechanism of Glaucocalyxin A(GLA)in inhibiting ovalbumin(OVA)-induced airway remodeling in asthmatic mice through the topoisomerase Ⅱ α(TOP2A)/cyclin-dependent kinase 1(CDK1)signaling pathway.Methods Forty Balb/c mice were randomly divided into 5 groups:the control group,the model group,the low-dose GLA group,the high-dose GLA group and the Dexamethasone group,with 8 mice in each group.The effect of GLA on airway remodeling was examined by immunohistochemical staining,ELISA and other methods,and bioinformatics methods were used to predict new targets of GLA.The action targets of TOP2A were screened using the STRING database,and the interaction relationship between the two was verified by co-immunoprecipitation.In vitro,GLA and siRNA were used to interfere with interleukin-4(IL-4)-stimulated human airway epithelial cells BEAS-2B.The expressions of TOP2A,epidermal growth factor receptor(EGFR),Integrin β1,focal adhesion kinase(FAK),β-catenin,CDK1 and DRP1 were detected by Western Blot.Results GLA intervention could significantly reduce OVA-induced asthma airway remodeling,airway smooth muscle thickening,collagen deposition around the airway,the number of eosinophils in alveolar lavage fluid,the expression of pro-inflammatory cytokines such as IL-4,and the level of serum IgE.The new target of GLA screened out was TOP2A,which was highly expressed in the lung tissue of the asthma airway remodeling model.GLA intervention could down-regulate its expression.In vitro,intervention with GLA and si-TOP2A could significantly down-regulate the expressions of IL-4-induced TOP2A,EGFR,Integrin β1,FAK and β-catenin.Further studies have found that TOP2A had an interaction relationship with CDK1.si-TOP2A could downregulate the expression of CDK1,and knockdown of CDK1 could significantly down-regulate the expression of phosphorylated DRP1.Conclusion GLA may alleviate asthma airway remodeling by targeting the TOP2A/CDK1 signaling pathway,providing experimental evidence for the clinical diagnosis and treatment of asthma airway remodeling in asthma.

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.