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.

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.

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.

Objectives:To investigate the prognostic difference of different revascularization strategies in AMI patients with multi-vessel disease and diabetes.Methods:AMI patients with multi-vessel disease and diabetes admitted to the Department of Cardiology of the First Hospital of Lanzhou University from January 2022 to June 2024 were retrospectively included.Patients were divided into non complete revascularization(NCR)group(n=166),staged complete revascularization(SCR)group(n=152)and immediate complete revascularization(ICR)group(n=120).Baseline clinical characteristics,coronary angiography data and postoperative medication were compared among the groups.Primary endpoint was the major adverse cardiovascular and cerebrovascular events(MACCE)during follow-up.MACCE includes all-cause mortality,cardiogenic mortality,non-fatal myocardial infarction,unplanned revascularization and stroke.The log-rank test was used to analyze the significance of the differences in the cumulative incidence of MACCE among the three groups.Cox regression was used to explore the influencing factors of poor prognosis in patients.Results:There were statistically significant differences among NCR group,SCR group and ICR group in terms of the history of previous percutaneous coronary intervention,the use of intraoperative coronary intravascular ultrasound(IVUS)and the dosage of contrast agent(all P<0.05).During a median follow-up of 21(11,25)months,MACCE events occurred in 59 cases(35.5%)in the NCR group,26 cases(17.1%)in the SCR group,and 30 cases(25.0%)in the ICR group.The Kaplan-Meier curve showed that the differences in the cumulative incidence of MACCE among the three groups were statistically significant(log-rank P<0.001).Using the Bonferroni correction(adjusted α′=0.05/3≈0.0167),pairwise comparisons revealed statistically significant differences between the NCR and SCR groups(log-rank P<0.001)and between the NCR and ICR groups(log-rank P=0.011).However,no statistically significant difference was observed between the SCR and ICR groups(log-rank P=0.228).Cox multivariate regression analysis demonstrated that history of hypertension was an independent risk factor for MACCE in AMI patients with multivessel coronary artery disease and diabetes(HR=1.71,95%CI:1.10-2.64,P<0.05).The difference in the incidence of MACCE between the SCR group and the NCR group was statistically significant(HR=0.45,95%CI:0.28-0.73,P=0.001).Conclusions:Staged complete revascularization serves as the preferred revascularization strategy for AMI patients with multivessel coronary disease and diabetes mellitus.Additionally,for patients with concomitant hypertension,blood pressure management should be intensified to reduce the risk of MACCE.

Objectives:To investigate the prognostic difference of different revascularization strategies in AMI patients with multi-vessel disease and diabetes.Methods:AMI patients with multi-vessel disease and diabetes admitted to the Department of Cardiology of the First Hospital of Lanzhou University from January 2022 to June 2024 were retrospectively included.Patients were divided into non complete revascularization(NCR)group(n=166),staged complete revascularization(SCR)group(n=152)and immediate complete revascularization(ICR)group(n=120).Baseline clinical characteristics,coronary angiography data and postoperative medication were compared among the groups.Primary endpoint was the major adverse cardiovascular and cerebrovascular events(MACCE)during follow-up.MACCE includes all-cause mortality,cardiogenic mortality,non-fatal myocardial infarction,unplanned revascularization and stroke.The log-rank test was used to analyze the significance of the differences in the cumulative incidence of MACCE among the three groups.Cox regression was used to explore the influencing factors of poor prognosis in patients.Results:There were statistically significant differences among NCR group,SCR group and ICR group in terms of the history of previous percutaneous coronary intervention,the use of intraoperative coronary intravascular ultrasound(IVUS)and the dosage of contrast agent(all P<0.05).During a median follow-up of 21(11,25)months,MACCE events occurred in 59 cases(35.5%)in the NCR group,26 cases(17.1%)in the SCR group,and 30 cases(25.0%)in the ICR group.The Kaplan-Meier curve showed that the differences in the cumulative incidence of MACCE among the three groups were statistically significant(log-rank P<0.001).Using the Bonferroni correction(adjusted α′=0.05/3≈0.0167),pairwise comparisons revealed statistically significant differences between the NCR and SCR groups(log-rank P<0.001)and between the NCR and ICR groups(log-rank P=0.011).However,no statistically significant difference was observed between the SCR and ICR groups(log-rank P=0.228).Cox multivariate regression analysis demonstrated that history of hypertension was an independent risk factor for MACCE in AMI patients with multivessel coronary artery disease and diabetes(HR=1.71,95%CI:1.10-2.64,P<0.05).The difference in the incidence of MACCE between the SCR group and the NCR group was statistically significant(HR=0.45,95%CI:0.28-0.73,P=0.001).Conclusions:Staged complete revascularization serves as the preferred revascularization strategy for AMI patients with multivessel coronary disease and diabetes mellitus.Additionally,for patients with concomitant hypertension,blood pressure management should be intensified to reduce the risk of MACCE.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.

A chemical investigation on

Objective To construct a eukaryotic expression plasmid carrying human full-length Notch ligand Delta-like 3 (DLL3) gene and study the effect of DLL3 knockdown and overexpression on the proliferation of gastric cancer cells in vitro. Methods Human full-length DLL3 gene was amplified by PCR and cloned into the eukaryotic expression vector pCMV-Tag4. After verification by restriction enzymes and sequencing, the recombinant DLL3/pCMV-Tag4 vector was transiently transfected into HEK293T cells, in which the expressions of human DLL3 mRNA and protein were detected using real-time quantitative PCR and Western blotting, respectively. The expression of DLL3 in normal gastric epithelial cells and gastric cancer cell lines was detected by qRT-PCR and Western blotting. DLL3/pCMV-Tag4 was transfected into 3 gastric cancer cell lines, and their proliferation was assessed with MTT assay. Human gastric cancer cells MGC803 and MKN45 were also transfected with a specific human DLL3-siRNA to assess the effect of DLL3 down-expression on the cell proliferation. Results The recombinant eukaryotic expression vector DLL3/pCMV-Tag4 was successfully constructed and human full-length DLL3 was expressed in HEK293T cells. MTT assay showed that DLL3 over-expression obviously promoted the proliferation and down-regulation of DLL3 inhibited the proliferation of the gastric cancer cells. Conclusion DLL3 overexpression can promote the proliferation of gastric cancer cells in vitro, and down-regulation of DLL3 inhibits the proliferation of gastrc cancer cells,which provides a novel strategy for targeted thrapy of gastric cancer.

OBJECTIVE:To provide references and suggestions for expiration date management of dismounted drugs in China.METHODS:The main contents about compliance policy for expiration date of repackaged drugs in America were summarized.The current situation and problems of expiration date management of dismounted drugs in China were analyzed to provide suggestions for standardizing expiration date management of dismounted drugs in China.RESULTS & CONCLUSIONS:The compliance policy for expiration date of repackaged drugs in America contain determination principle of expiration date of repackaged drugs,repackaged container standard,etc.In contrast,the expiration date management of dismounted drugs in China is lack of specific standards and requirements;major issues are as follows as the concept of expiration date of dismounted drugs is ambiguous and container management is not standardized.It is suggested that relevant departments can refer to compliance policy for expiration date of repackaged drugs in America,define the method of determining the expiration date of the dismounted drugs,and standardize the standards and management of packaging containers so as to standardize expiration date management of dismounted drugs in China practically.