Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective:To explore the intervention effect of Yuxuebi tablet （YXB） on collagen-induced arthritis （CIA） in rats and its anti-inflammatory mechanism. Method:Following CIA modeling， the rats in the drug administration groups were separately treated with intragastric administration of YXB （0.1， 0.2， and 0.4 g·kg^-1） and methotrexate （MTX， 0.4 mg·kg^-1）， once a day. The incidence of CIA， mechanical pain threshold （MPT） and cold pain threshold （CPT） were evaluated once every three days. After continuous administration for 30 days， the peripheral blood of rats was collected for the determination of platelet （PLT） count and fibrinogen （FIB） content. The hematoxylin-eosin （HE） staining was conducted to analyze the pathological changes in joint tissues. The protein expression levels of interleukin （IL）-1β， IL-8， nuclear transcription factor-κB （NF-κB） p65， phosphorylated NF-κB （p-NF-κB） p65， Ras， and Raf-1 in joint tissues of CIA rats were detected by immunohistochemistry （IHC） and Western blot. The rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） were induced by tumor necrosis factor-α （TNF-α， 10 μg·L^-1） in vitro and then subjected to transwell migration/invasion assay， followed by the detection of protein expression levels of Ras， Raf-1， and p-NF-κB p65 in RA-FLS by Western blot. Result:Compared with the control group， the model group exhibited an increased incidence of CIA， significantly decreased MPT （P<0.05，P<0.01）， elevated CPT （P<0.01） and PLT and FIB in the peripheral blood， worsened histopathological score of joints， enhanced RA-FLS migration and invasion， and up-regulated inflammatory factors （P<0.01）. The comparison with the model group revealed that YXB at different doses obviously reduced the incidence of CIA， increased MPT， down-regulated CPT and PLT and FIB in the peripheral blood （P<0.05，P<0.01）， ameliorated the pathological changes like synovial hyperplasia and bone and cartilage destruction （P<0.05，P<0.01）， and inhibited RA-FLS migration and invasion. Besides， the low-， medium-， and high-dose YXB reversed the IL-1β， IL-8， Ras， Raf-1， and p-NF-κB p65 expression in joint tissues of CIA rats to different extents， as well as the protein expression of Ras， Raf-1 and p-NF-κB p65 in RA-FLS （P<0.05，P<0.01）. Conclusion:YXB reduces the incidence of CIA， ameliorates the clinical symptoms of RA and the pathological changes in joint tissues， and inhibits the formation of synovium， which may be attributed to its inhibition against Ras/Raf-1/NF-κB signaling pathway.

Objective:To investigate the predicting value of high sensitivity C-reactive protein (hs-CRP) and albumin (Alb) ratio on prognosis of patients with in-hospital cardiac arrest (IHCA).Methods:A total of 107 patients with IHCA and spontaneous circulation recovery (ROSC) after cardiopulmonary resuscitation (CPR) in the Affiliated Hospital of Xuzhou Medical University during January 1, 2017 and September 30, 2020 were selected as the subjects and divided into the survival group and death group according to the survival condition on day 14 after IHCA. The correlation between ratio of high sensitivity C-reactive protein/albumin (hs-CRP/Alb) and the prognosis of patients was analyzed.Results:No statistical significant differences were found between the survival and death groups in sex, age, medical history, ECG monitoring, recovery ventilation mode, percentage of first monitoring of heart rate and pre-resuscitation Alb (all P > 0.05). However, there were significant differences in the percentage of non-cardiogenic CA and adrenaline dose > 5 mg, time of CPR, concentrations of blood lactic acid, Alb, hs-CRP, and ratio of hs-CRP/Alb (all P < 0.05). Logistic regression analysis showed that percentage of adrenaline dose > 5 mg, concentration of blood lactic acid, time of CPR, and ratio of hs-CRP/Alb were independent risk factors for predicting death. ROC curve analysis showed that hs-CRP/Alb ratio, and concentration of hs-CRP and Alb had predictive value on the death of patients with IHCA; the areas under the curves of hs-CRP/Alb ratio, hs-CRP and Alb concentration were 0.876, 0.864 and 0.745, respectively. The predictive efficiency of hs-CRP/Alb ratio was better than that of hs-CRP concentration or Alb concentration. Conclusions:hs-CRP/Alb ratio has predictive value for the prognosis of patients with IHCA and the predictive value is superior to that of hs-CRP and Alb concentration.

Objective:To summarize and analyze the results of chromosome karyotype in children with neuroblastoma (NB) with bone marrow metastasis at first diagnosis, and to discuss the clinical significance.Methods:G-banding was applied to the analysis of chromosome karyotype of patients who were regularly treated in the Hematological and Oncology Center in Beijing Children′s Hospital from January 2015 to December 2017, and all the patients were followed up until December 31, 2018.Their clinical features and prognosis were analyzed.Results:(1) There were 120 cases with bone marrow metastasis, including 74 boys and 46 girls, and 98 cases (81.7%) were ≥ 18 months.Among 60 cases with normal chromosome, 56 cases (93.3%) were in International Neuroblastoma Staging System(INSS)-Ⅳ phase, and 4 cases in INSS-Ⅳs phase; there were 2 low-risk (LR) cases, 9 intermediate-risk (MR) cases, and 49 high-risk (HR) cases (81.7%); 7 cases had MYCN gene amplifications.All 60 patients with chromosome abnormalities were in INSS-Ⅳ phase; there was 1 case in MR and 59 cases (98.3%) in HR; 14 cases had MYCN gene amplifications.(2) Among 60 children (50%) with chromosome abnormalities, 4 children had number abnormalities, 14 children had structural abnormalities, and 42 children had both number and structural chromosome abnormalities.Chromosome 21, 10, 11 deletions were the most common in number abnormalities; structural abnormalities involving 11q, 1p, 3p segments had a high incidence.(3) Seventeen cases of children with normal chromosome had tumor progression or recurrence during the 4 to 44-month follow-up period, and 31 cases of children with chromosome abnormalities had tumor progression or recurrence during the 2 to 42-month follow-up period.The 3-year overall survival rate and event-free survival rate of all children were 60.0% and 48.4%, respectively; children in the normal chromosome group had a 3-year overall survival rate of 74.2% and an event-free survival rate of 65.7%; the 3-year overall survival rate and event-free survival rate of children with chromosome abnormalities were 47.5% and 24.9%, respectively.Most children suffering from tumor progression or recurrence had chromosome 10 deletion, and abnormal structure of 11q, 1p, 2p segments. Conclusion:The chromosomal abnormality rate of Nb children's tumor cells is high, but the repetition rate is low, and the individual difference is obvious.The deletion of chromosome 10, abnormal regional structure of 11q, 1p and 2p segments may be poor prognostic factors for NB.Chromosome karyotype analysis of bone marrow samples is feasible, which can provide a basis for more accurate risk stratification and treatment.

Objective:To study the effects of licochalcone A （LCA） on the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes （MH7A） as well as the related inflammatory factors， also to reveal the relevance between mitogen activated protein kinase （MAPK） signaling pathway and LCA regulation of MH7A cell proliferation and apoptosis. Method:MH7A cells were cultured and divided into blank group， LCA groups （10，20，40 μmol·L^-1）. The proliferation of MH7A cells was detected by methylthiazolyldiphenyl-tetrazolium bromide（MTT）and immunofluorescence staining. The cell cycle of MH7A cells was determined by flow cytometry after PI staining and apoptosis was detected by flow cytometry after Annexin V/PI staining. The effect of LCA on interleukin-1β（IL-1β） mRNA was detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. Western blot was used to detect the effect of LCA on the key proteins of MAPK signaling pathway， meanwhile， PD98059， a specific ERK inhibitor， was used to observe the expression levels of p-ERK and IL-1β. Result:Compared with blank group， LCA could inhibit the proliferation of MH7A cells in a dose-dependent manner， and the number of living cells decreased significantly（P<0.01）， while the number of early apoptotic cells increased significantly（P<0.01）. Compared with the tumor necrosis factor-α （TNF-α，10 μg·L^-1）group， LCA could reverse the expression of IL-1β mRNA induced by TNF-α（P<0.01）. and compared with the blank group， LCA also promoted the phosphorylation of ERK， JNK and p38 in a dose-dependent manner（P<0.01）. After ERK inhibitor PD98059 inhibited ERK phosphorylation， the inhibitory effect of LCA 10， 20 μmol·L^-1 on IL-1β disappeared. Conclusion:LCA can inhibit the proliferation and induce apoptosis of MH7A cells， which may be related to the phosphorylation of MAPK pathway related proteins， and then inhibit the expression of inflammatory factors.