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

Child ; Humans ; Bronchoscopy/methods* ; Biopsy/methods* ; Lung/pathology*

Eosinophilia/genetics* ; Gene Rearrangement ; Humans ; Myeloproliferative Disorders/genetics* ; Neoplasms ; Oncogene Proteins, Fusion/genetics* ; Receptor, Platelet-Derived Growth Factor alpha/genetics*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Aim To develop an LC-MS/MS method for the determination of prucalopride(PCP)in human plasma.Methods Prucalopride -13CD3(dPCP)was used as the internal standard.The analytes were extracted from human plasma through liquid-liquid extraction method using ethyl acetate, followed by being dried, and then the reconstitution was injected into LC-MS/MS systems.Agilent ZORBAX SB C18(3.0×100 mm, 3.5 μm)column and isocratic elution system composing of methanol and 1 mmol·L-1 ammonium acetate(80:20, V/V)provided chromatographic separation of PCP and dPCP.AB Sciex API4000 mass spectrometer equipped with an electrospray ionization source in positive ion mode was employed for mass detection, and data acquisition was carried out in multiple reaction monitoring(MRM)mode.The mass transition ion-pair was followed as m/z 368.4/196.0 for PCP and m/z 374.4/198.0 for dPCP.Results PCP and dPCP were eluted at 3.6 min, with no interference in human blank plasma.PCP in human plasma showed good linearity over the concentration range of 0.058 96-7.547 μg·L-1 with the correlation coefficient of 0.996 3-0.999 6.The lower limit of quantitation of this method was 0.058 96 μg·L-1.The intra-batch and inter-batch accuracy ranged from 98.29% to 108.2%, with good precision(CV<5.2%).The average matrix factors of normal, haemolysed and lipaemic matrix human samples all ranged from 96.48% to 106.3% with CV less than 8.39%.The average extraction recoveries of PCP at low, medium and high concentrations were 89.88%, 95.27% and 94.52% respectively, with CV less than 7.21%.PCP was stable in human samples after 6 h at room temperature, 60 h at -20 ℃, 56 days or three freeze-thaw cycles at -80 ℃; meanwhile, the processed plasma samples remained stable after being stored for 24 hours in autosampler at 8 ℃.Furthermore, PCP in human blood samples was proved to be stable after 4 h at room temperature.Conclusions The present LC-MS/MS method for the determination of PCP in human plasma was convenient, accurate, sensitive, stable, specific and reproducible and was proved to be suitable for the clinical pharmacokinetics and bioequivalence studies of PCP preparations.

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation ( CONCLUSIONS A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.
Birth Weight ; Bone Diseases, Metabolic/etiology* ; China/epidemiology* ; Female ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Pregnancy ; Retrospective Studies ; Risk Factors

OBJECTIVE The purpose of this research was to develop a self-assembled micelle using biocompatible copoly-mers Pluronic F127 (F127) and Vitamin E d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) to enhance the oral bio-availability and anti-cancer efficiency of honokiol (HK). METHODS The optimized prescription honokiol micelle (HK-M) was prepared by an ethanol solvent evaporation method. HK-M was characterized by transmission electron microscopy(TEM) and HPLC. The dialysis bag method was used to assesse the cumulative amount of HK released from the HK-M. Caco-2 cells were applied to measure the permeability of HK-M. The bioavailability and in vivo anti-tumor effect were also evaluated. RE-SULTS At the ratio of 4:1 (F127:TPGS), the HK-M was transparent and colourless with a small size (23.28 ± 2.01)nm and a spherical shape. The apparent solubility of HK in HK-M was dramatically increased to 4.76 mg/mL, suggesting that HK-M had good stability. Furthermore, encapsulation in micelles led to a sustained release of HK. HK-M enhances HK's per-meability across Caco-2 cell monolayer. Compared with free HK, there was a 1.17-fold increase in the relative oral bioavail-ability for HK-M. Moreover, HK-M achieved a higher inhibition rate on tumor volume (35.17％) than HK group (14.86％). CONCLUSION These findings present an oral HK micelle formulation containing F127 and TPGS, with improved solubility,increased oral bioavailability, and enhanced anti-cancer activity.

UPLC-Q-TOF-MS technology was used to analyze the chemical constituents from classical prescription Huangqi Guizhi Wuwu Tang standard decoction. Acquity HSS T3 column(2.1 mm × 100 mm, 1.8 μm) was used as the chromatographic column, with 0.1% formic acid solution-0.1% formic acid acetonitrile as the mobile phase for gradient elution. The volume flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry data of Huangqi Guizhi Wuwu Tang standard decoction were collected in positive and negative ion modes. The chemical constituents from classical prescription Huangqi Guizhi Wuwu Tang standard decoction were analyzed and identified by Masslynx 4.1 software combined with SciFinder database, comparison with reference mate-rials, mass spectrometry data analysis and reference to relevant literature. A total of 110 compounds were analyzed and identified, including 33 flavonoids, 14 monoterpene glycosides, 8 triterpenoids, 8 gingerols, 17 phenylpropanoids, 12 organic acids, 7 amino acids and 11 other compounds. The results of this study provide an experimental basis for the further research on the substance basis and quality control of Huangqi Guizhi Wuwu Tang standard decoction.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Flavonoids/analysis* ; Glycosides ; Prescriptions ; Reference Standards

Background: The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran. Methods: A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed. Results: During 6-month follow-up, 87 participants occurred bleeding events. For every 1 × 10⁹/L increase in leukocyte count, the risk of bleeding increased by 11% (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99–1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75 × 10⁹/L. For leukocyte counts < 6.75 × 10⁹/L, the HR (95% CI) was 0.88 (0.69–1.13), and for leukocyte counts ≥ 6.75 × 10⁹/L, the HR (95% CI) was 1.28 (1.09–1.51). Conclusion: This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran. Clinical trial registration NCT02414035, https://clinicaltrials.gov.

OBJECTIVE: To investigate the risk factors for brain injury in preterm infants by a multicenter epidemiological investigation of brain injury in hospitalized preterm infants in Anhui, China. METHODS: Preterm infants who were hospitalized in the department of neonatology in 9 hospitals of Anhui Neonatal Collaboration Network between January 2016 and January 2017 were enrolled as subjects. The data of maternal pregnancy and clinical data of preterm infants were collected, and the logistic regression model was used to analyze the risk factors for brain injury in preterm infants. RESULTS: A total of 3 378 preterm infants were enrolled. Of the 3 378 preterm infants, 798 (23.56%) had periventricular-intraventricular hemorrhage (PVH-IVH), and 88 (2.60%) had periventricular leukomalacia (PVL). Intrauterine distress, anemia, hypoglycemia and necrotizing enterocolitis (NEC) were risk factors for PVH-IVH (OR=1.310, 1.591, 1.835, and 3.310 respectively; P<0.05), while a higher gestational age was a protective factor against PVH-IVH (OR=0.671, P<0.05). PVH-IVH, NEC and mechanical ventilation were risk factors for PVL (OR=4.017, 3.018, and 2.166 respectively; P<0.05), and female sex and use of pulmonary surfactant were protective factors against PVL (OR=0.514 and 0.418 respectively; P<0.05). CONCLUSIONS Asphyxia/anoxia, infection/inflammation, mechanical ventilation, anemia and hypoglycemia may increase the risk of brain injury in preterm infants.
Brain Injuries ; Cerebral Hemorrhage ; China ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Leukomalacia, Periventricular