Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

BACKGROUND: The optimal apolipoprotein or lipid measures for identifying statin-treated patients with coronary artery disease (CAD) at residual cardiovascular risk remain controversial. This study aimed to compare the predictive powers of apolipoprotein B (apoB), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apoB/apolipoprotein A-1 (apoA-1) and non-HDL-C/HDL-C for myocardial infarction (MI) in CAD patients treated with statins in the setting of secondary prevention. METHODS: The study included 9191 statin-treated CAD patients with a five-year median follow-up. All measures were analyzed as continuous variables and concordance/discordance groups by medians. The hazard ratio (HR) with 95% CI was estimated by Cox proportional hazards regression. Patients were classified by the clinical presentation of CAD for further analysis. RESULTS: The high-apoB-low-LDL-C and the high-non-HDL-C-low-LDL-C categories yielded HR of 1.40 (95% CI: 1.04-1.88) and 1.51 (95% CI: 1.07-2.13) for MI, respectively, whereas discordant high LDL-C with low apoB or non-HDL-C was not associated with the risk of MI. No association of MI with discordant apoB versus non-HDL-C, apoB/apoA-1 versus apoB, non-HDL-C/HDL-C versus non-HDL-C, or apoB/apoA-1 versus non-HDL-C/HDL-C was observed. Similar patterns were found in patients with acute coronary syndrome. In contrast, no association was observed between any concordance/discordance category and the risk of MI in patients with chronic coronary syndrome. CONCLUSIONS ApoB and non-HDL-C better predict MI in statin-treated CAD patients than LDL-C, especially in patients with acute coronary syndrome. ApoB/apoA-1 and non-HDL-C/HDL-C show no superiority to apoB and non-HDL-C for predicting MI.

Objective To explore the potential targets and synergistic mechanisms of Kushen Decoction for the treatment of cryptosporidiosis using network pharmacology and molecular docking methods. Methods The main active ingredients of Kushen Decoction were captured from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TC-MSP) and the Universal Protein Resource (UniProt) database, and the potential targets were predicted. In addition, the active ingredients of Kushen Decoction that were not included in the TCMSP database were retrieved in CNKI, WanFang Data, CBM, PubMed and Web of Science databases, and the target genes of all supplemented active ingredients were predicted using the online TargetNet database. Network construction and analysis were performed using the Cytoscape software, and cryptosporidiosis-related targets were retrieved in the Comparative Toxicogenomics Database and GeneCards database. The protein-protein interaction (PPI) network was created using the STRING database, and the DAVID database was used for GO enrichment and KEGG pathway analyses. The tissue distribution of key targets was investigated using the BioGPS database, and the AutoDockTools software was employed to verify the molecular docking results. Results A total of 38 active ingredients of Kushen Decoction were screened, and the core ingredients included quercetin, (+)-14α-hydroxymatrine and apigenin. A total of 831 targets of Kushen Decoction and 512 cryptosporidiosis-related targets were predicted, and PPI network analysis revealed 69 key targets, including AKT1, TNF and IL-6. There were 303 biological processes, 46 molecular functions and 29 cellular components involved in the treatment of cryptosporidiosis with Kushen Decoction, and 13 KEGG pathways played a therapeutic role in the synergistic mechanisms of multiple targets, such as Toll-like receptor (TLR), nuclear factor kappa B(NF)-κB, nucleotide binding oligomerization domain like receptor (NLR) signal pathways. The core targets were mainly distributed in the hematologic and immune systems. Molecular docking analysis showed that the binding energy between active ingredients and key targets were all less than 0 kJ/mol, indicating the strong binding of ligands to receptors. Conclusions The active ingredients of Kushen Decoction, such as quercetin, (+)-14α-hydroxymatrine and apigenin, may act on targets like AKT1, TNF, IL-6 to modulate TLR, NLR and NF-κB signaling pathways to play a synergistic role in the treatment of cryptosporidiosis in the hematologic and immune system.

Objective:To explore the effect of Duanteng Yimu decoction （DTYM） on the activation of the human umbilical vein endothelial cell （HUVEC） model and the effect on related activated proteins and vascular endothelial growth factor （VEGF） signaling pathway. Method:After DTYM （200， 400 g·mL^-1） treatment of HUVEC induced by VEGF and tumor necrosis factor-α （TNF-α）， cell proliferation， migration， and tubulogenesis were detected by cell counting kit-8 （CCK-8） assay， 5-ethynyl-2'-deoxyuridine （EdU） assay， transwell migration assay， phalloidin staining， and matrix gel card method. The mRNA expression of adhesion factors， including E-selectin， intercellular adhesion molecule-1 （ICAM-1）， and vascular cell adhesion molecule-1 （VCAM-1） was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of von Willebrand factor （VWF）， platelet-endothelial cell adhesion molecule-31 （CD31）， angiogenic factor cysteine-rich-61 （CYR61）， angiopoietin-1 （ANG-1）， VEGF， and VEGF receptor-2 （VEGFR2） was detected by Western blot. Immunofluorescence was used to determine CD31 expression. Result:Compared with the normal group， the model group showed potentiated proliferation， migration， and tubulogenesis of HUVEC （P<0.05， P<0.01）， elevated mRNA expression of E-selectin， ICAM-1， and VCAM-1 （P<0.01）， up-regulated protein expression of VWF， CD31， ANG-1， CYR61， VEGF-α， and phospho （p）-VEGFR2 （P<0.05， P<0.01）， and increased CD31 immunofluorescence intensity （P<0.01）. Compared with the model group， the DTYM groups displayed blunted proliferation， migration， and tubulogenesis of HUVEC （P<0.05， P<0.01）， decreased mRNA expression of E-selectin， ICAM-1， and VCAM-1 （P<0.05， P<0.01）， down-regulated protein expression of VWF， CD31， ANG-1， CYR61， VEGF-α， and p-VEGFR2 （P<0.05， P<0.01）， and weakened CD31 immunofluorescence intensity （P<0.01）. Conclusion:DTYM inhibits HUVEC proliferation， migration， adhesion， and tubulogenesis， which is associated with the regulation of CD31， VWF， CYR61， and ANG-1 expression in HUVEC and the VEGF signaling pathway.

Objective:To investigate the mechanism of Duanteng Yimu decoction （DTYM） in the inhibition of pannus formation in collagen-induced arthritis （CIA） mice. Method:Twenty-four SPF-grade DBA/1 male mice were randomly divided into the following four groups： a blank group （NC group）， a model group （CIA group）， a methotrexate group （MTX group）， and a DTYM group， with six mice in each group. The mice， except for those in the NC group， were modeled. From the second immunization， the medium， MTX （1 mg·kg^-1）， and DTYM （15.4 g·kg^-1） were administered at an equal volume by gavage for 35 days. Mice were observed for general condition and the arthritis index. The knee and ankle joints were scanned by microcomputed tomography （micro CT）. Hematoxylin-eosin （HE） and safranin O/fast green staining were performed to observe pathological changes. Immunohistochemistry was performed to detect the expression of platelet/endothelial cell adhesion molecule-1 （CD31）， vascular endothelial growth factor-α （VEGF-α）， vascular endothelial growth factor receptor 2 （VEGFR2）， and phosphorylated（p）-VEGFR2. Result:Compared with the NC group， the CIA group showed red and swollen ankle joints， increased arthritis index scores （P<0.05， P<0.01）， manifest injury in the knee and ankle joints， reduced cartilage thickness， elevated Micro CT bone destruction scores of knee and ankle joints （P<0.01）， and up-regulated absorbance values of synovial CD31， VEGF-α， VEGFR2， and p-VEGFR2 （P<0.01）. Compared with the CIA group， the DTYM group showed relieved ankle joint redness and swelling， reduced arthritis index scores of mice three weeks after administration （P<0.05， P<0.01）， intact joint surfaces of the knee and ankle joints， thickened cartilage， declining Micro CT bone destruction scores in both the knee and ankle joints （P<0.05， P<0.01）， and lowered absorbance values of CD31， VEGF-α， VEGFR2， and p-VEGFR2 in the synovium （P<0.01）. Conclusion:DTYM can inhibit the pannus formation in CIA mice presumedly by regulating the VEGF pathway.

Objective: To investigate the impact of coronary lesion calcification on the long-term outcome of patients with coronary heart disease after percutaneous coronary intervention. Methods: In this prospective observational study, a total of 10 119 consecutive patients with coronary heart disease undergoing percutaneous coronary intervention from January 1 to December 31, 2 103 in our hospital were enrolled. The patients were divided into non/mild calcification group (8 268 cases) and moderate/severe calcification group (1 851 cases) according to the angiographic results. The primary endpoint was one-year major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, and target vessel revascularization. Results: The patients were (58.3±10.3) years old, and there were 2 355 females (23.3%). Compared with non/mild calcification group, patients in the moderate/severe calcification group were older ((60.0±10.6) years vs. (57.9±10.2) years, P<0.01), and had higher proportion of female (25.4% (470/1 851) vs. 22.8% (1 885/8 268), P=0.02), debates (33.9% (628/1 851) vs. 29.0% (2 399/8 268), P<0.01), hypertension (68.0% (1 259/1 851) vs. 63.7% (5 264/8 268), P<0.01), coronary artery bypass grafting (4.6% (85/1 851) vs. 3.2% (268/8 268), P<0.01), stroke (12.6% (233/1 851) vs. 10.4% (861/8 268), P=0.01), and renal dysfunction (6.2% (115/1 851) vs. 3.7% (303/8 268), P<0.01). Compared with non/mild calcification group, patients in themoderate/severe calcification group experienced longer procedure time (37 (24, 61) min vs. 27 (17,40) min, P<0.01) and stent length was longer (32 (23,48) mm vs. 27 (18,38) mm, P<0.01), and percent of rotational atherectomy was higher (2.56%(57/2 229) vs. 0.03% (3/11 930), P<0.01). One-year follow-up results showed that MACE (7.5% (139/1 846) vs. 4.9% (402/8 243), P<0.01), all-cause death (1.0% (19/1 846) vs. 0.6% (49/8 243), P=0.04), myocardial infarction (2.2% (41/1 846) vs. 1.4% (114/8 243), P=0.01), and target vessel revascularization (5.0% (92/1 846) vs. 3.2% (266/8 243), P<0.01) were all significantly higher in moderate/severe calcification group than in non/mild group. Multivariate Cox regression analysis showed that moderate/severe calcification was an independent predictor of MACE at one-year after the procedure (HR=1.41, 95%CI 1.16-1.72, P<0.01). Conclusion Moderate/severe calcification in coronary lesion is an independent predictor of long-term poor prognosis in coronary heart disease patients undergoing percutaneous coronary intervention.

Objective: Patients with acute coronary syndrome due to multivessel disease (MVD) were at the highest risk of adverse cardiovascular events. Neutrophil to lymphocyte ratio (NLR) was proposed as a marker of cardiovascular risk. Present study evaluated the independent predictive value of NLR for acute myocardial infarction (AMI) patients with MVD. Methods: AMI patients with MVD (n=1 433) underwent percutaneous coronary intervention (PCI) between January 2013 and December 2013 were followed up for 2 years. Patients were divided into 2 sub-groups based on an optimal cut off value of NLR to predict 2-year all-cause mortality. The primary endpoint was all-cause death. The secondary endpoint was long-term major adverse cardiovascular and cerebrovascular events (MACCE). Results: By receiver operating characteristics curve analysis, the optimal cut-off value of admission NLR to predict 2-year all-cause mortality was 3.39 (area under the curve 0.765, sensitivity 71%, specificity 73%). The high NLR group(n=396) had higher prevalence of prior myocardial infarction, prior PCI and intra-aortic balloon pump use (IABP)(P<0.01). Compared to the low NLR group (n=1 037), patients in the high NLR group were older, had higher level of neutrophil count and high-sensitivity C-reactive protein (hs-CRP) (P<0.001), but lower level of lymphocyte count, estimated glomerular filtration rate (eGFR) and ejection fraction (P<0.001). During the follow-up period, rate of long-term all-cause death was significantly higher in the high NLR group than in the low NLR group (5.1% (20/396) vs. 0.8% (8/1 037), P<0.001). Cardiac death (4.0% (16/396) vs. 0.7% (7/1 037), P<0.001) and MACCE (21.7% (86/396) vs. 12.6% (131/1 037), P<0.001) were also significantly higher in the high NLR group than in the low NLR group. Multivariate Cox analysis showed that NLR ≥ 3.39 was determined as an independent predictor of 2-year all-cause mortality (HR=3.23, 95%CI 1.38-7.54, P=0.007) and MACCE (HR=1.58, 95%CI 1.19-2.10, P=0.002) in this patient cohort after adjusting for other risk factors. Correlation analysis showed that the NLR was positively correlated with hs-CRP levels (r=0.241, P<0.001). Conclusion Our study demonstrates that admission NLR ≥ 3.39 is an independent predictor of long term all cause death and MACCE in AMI patients with MVD post PCI.

Objective: To observe the safety and impact of short-term anticoagulant therapy on prognosis after selective percutaneous coronary intervention (PCI) in patients with coronary artery disease. Methods: From January 2013 to December 2013, 9 769 consecutive patients underwent selective PCI in Fuwai Hospital were retrospectively included in this study. Patients were divided into two groups, including non-post-PCI anticoagulant therapy group and low-dose and short-time post-PCI anticoagulant therapy group (enoxaparin 0.4 ml/12 h or fondaparinux 2.5 mg/day by subcutaneous injection for 2-3 days after PCI). All patients were evaluated at 30 days, 180 days and 12 months for major adverse coronary and cerebral events (MACCE) including all-cause death, myocardial infarction, revascularization and stroke as well as in-stent thrombosis and bleeding events. Data from 1 755 pairs of patients were analysis after propensity score matching. The clinical outcomes were compared between groups by using Kaplan-Meier survival analysis before and after propensity score matching. Multivariable Cox analysis was used to define the impact and determinants of post-PCI anticoagulation on clinical outcomes. Results: one thousand seven hundred and fifty-five (18.0%) patients didn′t receive post-PCI anticoagulation and 8 014 (82.0%) patients received post-PCI anticoagulation, 5 666 (58.0%) patients received enoxaparin and 2 348 (24.0%) patients received fondaparinux. Patients were younger and incidence of female patients was less, incidence of renal dysfunction and acute coronary syndrome were higher in low-dose and short-time post-PCI anticoagulant therapy group than in non-post-PCI anticoagulation group (all P<0.05). Similarly, patients with post-PCI anticoagulation were associated with more left main coronary artery lesion and branch lesion (P<0.05). Post-PCI anticoagulation patients were associated with less trans-femoral process, more drug-eluting stents implantation and less simple balloon dilatation (all P<0.05). Nine thousand seven hundred and seventeen (99.5%) patients completed 2 years follow up. Post-PCI anticoagulation patients had significantly lower 30-day all-cause death (0.05% (4 cases) vs. 0.46% (8 cases), P<0.001) and stroke (0 vs. 0.11% (2 cases), P=0.003), lower 180-day all-cause death (0.17% (14 cases) vs. 0.57% (10 cases), P=0.002), revascularization (2.07% (166 cases) vs. 3.71% (65 cases), P<0.001) and MACCE (3.49% (280 cases) vs. 5.47% (96 cases), P<0.001), lower 2-year revascularization (7.61% (610 cases) vs. 12.84% (225 cases), P<0.001) and MACCE (10.92 (875 cases) vs. 16.01% (281 cases), P<0.001). Multivariable Cox regression analysis showed that post-PCI anticoagulant therapy was an independent protective factor of 30-day (HR=0.17, 95%CI 0.05-0.62, P=0.007), 180-day all-cause death (HR=0.37, 95%CI 0.16-0.87, P=0.023) and MACCE (HR=0.74, 95%CI 0.58-0.94, P=0.013), 2-year MACCE (HR=0.71, 95%CI 0.62-0.81, P<0.001). After propensity score matching, post-PCI anticoagulation therapy remained as an independent protective factor of 30-day all-cause death (HR=0.11, 95%CI 0.01-0.92, P=0.042) and 2-year MACCE (HR=0.81, 95%CI 0.68-0.96, P=0.015). Conclusions Low-dose and short-time post-PCI anticoagulant therapy may decrease 30-day all-cause death, 180-day all-cause death and MACCE and 2-year MACCE, and meanwhile this option does not increase bleeding risk in patients underwent selective PCI.

BACKGROUND: It is currently unclear if fibrinogen is a risk factor for adverse events in patients receiving percutaneous coronary intervention (PCI) or merely serves as a marker of pre-existing comorbidities and other causal factors. We therefore investigated the association between fibrinogen levels and 2-year all-cause mortality, and compared the additional predictive value of adding fibrinogen to a basic model including traditional risk factors in patients receiving contemporary PCI. METHODS: A total of 6293 patients undergoing PCI with measured baseline fibrinogen levels were enrolled from January to December 2013 in Fuwai Hospital. Patients were divided into three groups according to tertiles of baseline fibrinogen levels: low fibrinogen, <2.98 g/L; medium fibrinogen, 2.98 to 3.58 g/L; and high fibrinogen, ≥3.58 g/L. Independent predictors of 2-year clinical outcomes were determined by multivariate Cox proportional hazards regression modeling. The increased discriminative value of fibrinogen for predicting all-cause mortality was assessed using the C-statistic and integrated discrimination improvement (IDI). RESULTS: The 2-year all-cause mortality rate was 1.2%. It was significantly higher in the high fibrinogen compared with the low and medium fibrinogen groups according to Kaplan-Meier analyses (1.7% vs. 0.9% and 1.7% vs. 1.0%, respectively; log-rank, P = 0.022). Fibrinogen was significantly associated with all-cause mortality according to multivariate Cox regression (hazard ratio 1.339, 95% confidence interval: 1.109-1.763, P = 0.005), together with traditional risk factors including age, sex, diabetes mellitus, left ventricular ejection fraction, creatinine clearance, and low-density lipoprotein cholesterol. The area under the curve for all-cause mortality in the basic model including traditional risk factors was 0.776, and this value increased to 0.787 when fibrinogen was added to the model (IDI = 0.003, Z = 0.140, P = 0.889). CONCLUSIONS Fibrinogen is associated with 2-year all-cause mortality in patients receiving PCI, but provides no additional information over a model including traditional risk factors.
Acute Coronary Syndrome ; blood ; therapy ; Aged ; Fasting ; blood ; Female ; Fibrinogen ; analysis ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Percutaneous Coronary Intervention ; Proportional Hazards Models ; Risk Factors

Objective: To compare the clinical characteristics and long-term prognosis between male and female patients with premature coronary artery disease (PCAD) post coronary intervention, and analyse the risk factors of major adverse cardio-cerebrovascular events (MACCE) and bleeding events. Methods: This was a prospective single-center observational study. From January 2013 to December 2013, 4 744 patients diagnosed as PCAD and treated with percutaneous coronary intervention (PCI) in Fuwai Hospital were enrolled. The general clinical data, laboratory results and interventional treatment data of all patients were collected, and patients were followed up for 2 years after PCI and the incidence of events including MACCE and bleeding was analyzed. The baseline data and clinical events of PCAD patients of different genders were compared. Survival curves were estimated by Kaplan-Meier method. Univariate and multivariate Cox regression were used to analyze whether gender was an influencing factor of different clinical events of PCAD patients within 2 years after PCI, and other relevant influencing factors of MACCE and bleeding events. Results: Among the 4 744 PCAD patients included, there were 3 390 (71.5%) male aged (47.0±5.4) years old and 1 354 (28.5%) female aged (57.0±5.8) years old. Compared with female patients, male patients had higher body mass index, higher proportion of hyperlipidemia, smoking, myocardial infarction, previous PCI, preoperative estimated glomerular filtration rate, ST-segment elevation myocardial infarction, radial artery approach, intravenous ultrasound use and chronic occlusive lesions (all P<0.05). Age, left ventricular ejection fraction, prevalence of hypertension, diabetes mellitus, past stroke history, non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and the use of calcium channel blockers were lower in male patients than in female patients (all P<0.05). The 2-year follow-up results showed that the incidence of BARC type 1 hemorrhage was significantly higher in female patients than in male patients (6.9%(92/1 343) vs. 3.7%(126/3 378), P<0.001); however, the incidence of MACCE, all-cause death, cardiac death, recurrent myocardial infarction, revascularization (target vessel revascularization and target lesion revascularization), stent thrombosis, stroke and BARC type 2-5 hemorrhage were similar between the two groups (all P>0.05). Multivariate Cox regression analysis showed that gender was an independent risk factor for BARC type 1 bleeding in PCAD patients (HR=2.180, 95%CI 1.392-3.416, P<0.001), but it was not an independent risk factor for MACCE and BARC type 2-5 bleeding(all P>0.05). Hyperlipidemia, preoperative SYNTAX score, multivessel lesions and NSTE-ACS were the independent risk factors for MACCE in PCAD patients with PCI (the HRs(95%CI) were 1.289(1.052-1.580), 1.030(1.019-1.042), 1.758(1.365-2.264), 1.264(1.040-1.537), respectively); gender (HR=1.579, 95%CI 1.085-2.297, P=0.017), hyperlipidemia (HR=1.305, 95%CI 1.005-1.695, P=0.046), anticoagulant drugs including low molecular weight heparin (HR=1.321, 95%CI 1.002-1.741, P=0.048) or sulfonate(HR=1.659, 95%CI 1.198-2.298, P=0.002) were the independent risk factors for bleeding events. Conclusions There are differences in clinical and coronary artery lesion characteristics between different genders in patients with PCAD. The incidence of minor bleeding is significantly higher in female PCAD patients than in male PCAD patients. Hyperlipidemia, preoperative SYNTAX score, multivessel lesions and NSTE-ACS are the independent risk factors for MACCE, and gender, hyperlipidemia, anticoagulant drugs including low molecular weight heparin or sulfonate are the independent risk factors for bleeding events in patients with PCAD.