Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1％vs.0.7％,P=0.030),left main disease(43.9％vs.27.0％,P=0.018),triple vessel disease(90.9％vs.75.5％,P=0.009),and RCA chronic total occlusion disease(60.6％vs.35.5％,P＜0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9％vs.16.7％,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7％vs.9.2％,P=0.031).The rates of 1-month MACE(4.5％vs.2.6％,P=0.435)and 1-year MACE(7.6％vs.7.9％,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95％CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95％CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.

Objective:To establish a graded method to avoid mean fluorescence intensity(MFI)threshold of HLA Class I antibodies corresponding antigen,and the HLAMatchmaker program has been used to select the minimum mismatch value of donor-patient epitopes.Evaluate the application value of combining both methods in selecting HLA compatible platelets(PTL)for patients with immune platelet transfusion failure(IPTR)in improving platelet the corrected count increment(CCI).Methods:A total 7 807 PLT cross-matching compatible were performed by the solid-phase red cell adherence(SPRCA)method for 51 IPTR patients.The Luminex single antigen flow cytometry was used to detect HLA Class I antibodies in patients,and detected the MFI value for different specificity antigens of HLA Class I antibodies,was graded into strong positive group(MFI＞4 000,level 1),medium positive group(1 000＜MFI 4 000,2),weak positive group(500＜MFI≤1 000,3),and one negative control group(MFI≤500).The results of 7 807 SPRCA their negative/positive reaction wells were enrolled and statistically analyzed in different grades and the four groups,the statistical differences between the four groups were compared.Multiple applications for the select HLA Class I compatible donor events were made for patients in two cases,and HLAMatchmaker program was used to calculate the number of HLA Class I epitopes mismatches between the donors and patients.The donor with the minimum number of epitopes mismatches was selected,while avoiding the corresponding antigens of HLA Class I antibodies in levels 1 and 2,the provision of HLA compatible platelets for IPTR.After the transfusions,the CCI value of the platelet transfusion efficacy evaluation index was calculated,and the clinical evaluation of the transfusion effect was obtained through statistical analysis.Results:There were statistically significant differences in the positive results of SPRCA immunoassay among the strong positive group,medium positive group,and weak positive group of 51 IPTR patients with different specific of HLA-I class antibodies and corresponding antigens(all P＜0.001).The positive results showed a range from high to low,with strong positive group＞medium positive group＞weak positive group.There were a statistical difference among between the strongly positive or moderately positive groups and the negative control group(P＜0.001).There was no statistical difference between the weakly positive group and the negative control group(P＞0.05).The strong positive group was set as the corresponding specific HLA Class I site corresponding antigen grade 1 avoidance threshold,the medium positive group as the grade 2 avoidance thresholds,and the weak positive group as the grade 3 avoidance threshold.In the case of donor platelet shortage,it is not necessary to avoid the weak positive group.Avoiding the strategy of donor antigens and HLAMatchmaker program scores≤7 corresponding to HLA Class I antibodies of levels 1 and 2,with CCI values＞4.5 × 109/L within 24 hours,can obtain effective clinical platelet transfusion conclusions.Conclusion:When selecting HLA Class I compatible donors for IPTR patients,the grading avoids HLA Class I antibodies corresponding to donor antigens,and the donor selection strategy with the minimum scores of HLAMatchmaker program is comprehensively selected.The negative result confirmed by platelet cross-matching experiments has certain practical application value for improving platelet count in IPTR patients.

Aim To elucidate the effect of corilagin (Cor) on cholesterol metabolism in macrophages and the underlying mechanism. Methods Molecular docking was applied to predict the protein target of Cor on cellular cholesterol metabolism. The RAW264.7 macrophage foam model induced by 80 mg • L

Aim To explore the protective effect of Zishen Huoxue Prescription on OGD/R-induced primary hippocampal neuron damage in rats and the possible mechanism. Methods After the isolated primary hippocampal neurons were identified by immunofluorescence, OGD/R induced neuronal damage, and the changes of autophagic flux at different re-oxygenation time were observed by confocal laser scanning microscopy. After OGD/R-induced primary hippocampal neurons were intervened with serum containing Zishen Huoxue Prescription, cell viability was detected by CCK-8, cell apoptosis was detected by flow cytometry, autophagosomes were detected by transmission electron microscopy, and autophagy-related protein expressions were detected by Western blot. Results 10% Zishen Huoxue Prescription-containing serum could significantly improve cell viability and reduce the proportion of cell apoptosis, increase the number of autophagosomes in neurons, and up-regulate the expression of autophagy-related protein PINK1, Parkin, and pATG16L1. Conclusions Zishen Huoxue Prescription can effectively resist OGD/R-induced apoptosis of primary hippocampal neurons in rats, and its effect may be related to the regulation of PINK1-Parkin pathway to promote mitophagy.

Male ; Humans ; Germ-Line Mutation ; Prostatic Neoplasms/genetics* ; BRCA2 Protein/genetics* ; Genetic Predisposition to Disease

OBJECTIVE: To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model. METHODS: The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR⁺ ILC3^-, CCR6⁺ Nkp46^- (Lti) ILC3^-, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively. RESULTS: The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR⁺ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR⁺ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function. CONCLUSION CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR⁺ ILC3s and Lti ILC3s.
Male ; Animals ; Mice ; Colitis, Ulcerative/pathology* ; Immunity, Innate ; Butyric Acid/therapeutic use* ; Sophora ; Gastrointestinal Microbiome ; Lymphocytes ; Colon ; Colitis/pathology* ; Disease Models, Animal ; Mice, Inbred C57BL

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

OBJECTIVE: To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes. METHODS: A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents. RESULTS: The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (P_interaction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis. CONCLUSION Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.
Humans ; Male ; Middle Aged ; Aged ; Female ; Metformin/adverse effects* ; Diabetes Mellitus, Type 2/drug therapy* ; Cohort Studies ; Ischemic Stroke/complications* ; Prospective Studies ; Hypoglycemic Agents/adverse effects* ; Stroke/prevention & control* ; Retrospective Studies

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Facial Paralysis/etiology* ; Diagnosis, Differential ; Jugular Foramina ; Retrospective Studies ; Cough ; Hoarseness ; Neoplasm Recurrence, Local ; Chondrosarcoma/surgery*

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens