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

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective:To investigate the inhibitory effect and molecular mechanism of microRNA-30d (miR-30d) in the process of proliferation, migration and invasion of malignant mesothelioma cell line MSTO-211H.Methods:In April 2017, the human MSTO-211H cells was used to establish miR-30d overexpressed MSTO-211H cell model by transfection of miR-30d mimics. The qRT-PCR was performed to detect the expression level of miR-30d in the cells transfected miR-30d mimics. The effects of miR-30d on the proliferation, apoptosis, migration and invasion of MSTO-211H cells were analyzed by CCK-8 experiment, flow cytometry, cell scratch experiment and Transwell method.Results:After transfection of miR-30d, the expression level of miR-30d in the MSTO-211H+miR-30d cells group was significantly higher than MSTO-211H+miR NC cells group ( P<0.01) . The cell activity of MSTO-211H+miR-30d group (105.13%±2.35%) was significantly lower than MSTO-211H+miR NC cells group (115.40%±1.35%) , and the level of apoptosis (3.97%±0.36%) was significantly higher than MSTO-211H+miR NC cells group (1.47%±0.10%) ( P<0.01) . The relative migration areas at 12 and 24 h of MSTO-211H+miR-30d cells group (9.35±3.16 μm 2 and 58.19±1.82 μm 2) were significantly lower than MSTO-211H+miR NC cells group (54.42 ±5.26 μm 2 and 88.32 ±1.96 μm 2) ( P<0.01) . Compared with the MSTO-211H+miR NC cells group, the numbers of cell migration and cell invasion were reduced in the MSTO-211H+miR-30d cells group ( P<0.01) . Conclusion:miR-30d can regulate the progression of malignant pleural mesothelioma by inhibiting the proliferation, apoptosis, migration and invasion of MSTO-211H cells.

Objective:To investigate the inhibitory effect and molecular mechanism of microRNA-30d (miR-30d) in the process of proliferation, migration and invasion of malignant mesothelioma cell line MSTO-211H.Methods:In April 2017, the human MSTO-211H cells was used to establish miR-30d overexpressed MSTO-211H cell model by transfection of miR-30d mimics. The qRT-PCR was performed to detect the expression level of miR-30d in the cells transfected miR-30d mimics. The effects of miR-30d on the proliferation, apoptosis, migration and invasion of MSTO-211H cells were analyzed by CCK-8 experiment, flow cytometry, cell scratch experiment and Transwell method.Results:After transfection of miR-30d, the expression level of miR-30d in the MSTO-211H+miR-30d cells group was significantly higher than MSTO-211H+miR NC cells group ( P<0.01) . The cell activity of MSTO-211H+miR-30d group (105.13%±2.35%) was significantly lower than MSTO-211H+miR NC cells group (115.40%±1.35%) , and the level of apoptosis (3.97%±0.36%) was significantly higher than MSTO-211H+miR NC cells group (1.47%±0.10%) ( P<0.01) . The relative migration areas at 12 and 24 h of MSTO-211H+miR-30d cells group (9.35±3.16 μm 2 and 58.19±1.82 μm 2) were significantly lower than MSTO-211H+miR NC cells group (54.42 ±5.26 μm 2 and 88.32 ±1.96 μm 2) ( P<0.01) . Compared with the MSTO-211H+miR NC cells group, the numbers of cell migration and cell invasion were reduced in the MSTO-211H+miR-30d cells group ( P<0.01) . Conclusion:miR-30d can regulate the progression of malignant pleural mesothelioma by inhibiting the proliferation, apoptosis, migration and invasion of MSTO-211H cells.

Objective:To investigate the serotype distribution and drug resistance of Streptococcus pneumoniae ( S. pneumoniae) isolated in Urumqi Children′s Hospital and to evaluate the significances of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing infection and controlling drug resistance. Methods:The S. pneumoniae isolates stored in clinical laboratory of Urumqi Children′s Hospital from January to December in 2018 were re-cultured.The serotypes were detected by capsule swelling experiment to assess the coverage rate of PCV13.The minimum inhibitory concentration (MIC) of Penicillin, Amoxicillin, Cefotaxime and Ceftriaxone were detected by E-test method, and the susceptibility of the isolates to Meropenem and other 9 antibiotics was detected by VITEC 2 Compact system. Results:A total of 225 S. pneumoniae strains were identified.The common serotypes were 19F (32.9%), 23F (12.0%), 19A (10.7%), 6B (10.2%) and 6A (8.0%). PCV13 coverage rate was 80.4%.There was no significant difference in serotype distribution and PCV13 coverage between children < 2 years old and ≥ 2 years old, as well as between Han and minority people.The 57.8% and 31.7% strains showed intermediate susceptibility and resistance against oral Penicillin, respectively.Based on the breakpoints for meningitis, 89.4% strains were resistant against pare-nteral Penicillin, and 47.5% and 64.6% strains were non-susceptible (mainly intermediately susceptible) to Ceftria-xone and Cefotaxime, respectively.The resistance rates of strains against Erythromycin, Sulfamethoxazole-trimethoprim and Tetracycline were as high as 98.1%, 67.6% and 89.6%, respectively.More than 90% tested isolates were susceptible to Amoxicillin, Meropenem, Levofloxacin or Moxifloxacin.PCV13 strains were more resistant to Penicillin than non-PCV13 strains. Conclusions:The serotypes 19F, 23F, 19A, 6B and 6A are common among the S. pneumoniae isolated in Urumqi.The coverage rate of PCV13 is about 80%.There was no significant difference in serotype distribution between Han and minority nationality children. S. pneumoniae were frequently resistant against Erythromycin.The high resistance to Penicillin and other beta-lactams should be taken into account when treatment is decided for suspected pneumococcal meningitis.Universal administration of PCV13 would be effective strategy to prevent pneumococcal infection in children and to control the drug resistance of S. pneumoniae.

Objective:To determine whether these Streptococcus pneumoniae isolates identified by routine cli-nical methods that cannot be serotyped by the quellung reaction contain other species of viridans group streptococci and to determine the antibiotic susceptibility to provide reference for clinical medicine. Methods:A total of 105 isolates identified as Streptococcus pneumoniae by routine methods with negative quellung reaction results were enrolled in this study.Multilocus sequence analysis (MLSA) and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS) were used to identify species of these isolates.Broth microdilution method was used to detect susceptibilities of 14 antibiotics. Results:Twenty-four of the 105 isolates were identified as Streptococcus pseudopneumoniae by MLSA, and the remaining 81 were Streptococcus pneumoniae.Six isolates of Streptococcus pseudopneumoniae were misidentified as Streptococcus pneumoniae, and 3 isolates as Streptococcus mitis/ oralis by MALDI-TOF-MS; and 6 isolates of Streptococcus pneumoniae were misidentified as Streptococcus pseudopneumoniae.All isolates were susceptible to Vancomycin, Levofloxacin and Moxifloxacin.The non-susceptibility rates between Streptococcus Pneumoniae and Streptococcus pseudopneumoniae against Ceftriaxone(28.4% vs.58.4%), Chloramphenicol(39.5% vs.4.2%), Erythromycin(77.8% vs.95.8%) and Azithromycin(75.3% vs.95.8%) were obviously different. Conclusions:Routine clinical methods may misidentify some Streptococcus pseudopneumoniae as Streptococcus pneumoniae, and so does the MALDI-TOF-MS.In addition, Streptococcus pneumoniae isolates with negative results of the quellung reaction showed differences in antimicrobial resistance.And misidentification may affect the evaluation of pathogenic bacteria and antibiotic resistance.

L_9(3~4) orthogonal experiment design was used to optimize the preparation of the patches,and investigate its affecting factors and skin irritation. Eugenol was taken as the index component to study the release behavior in vitro and percutaneous penetration of Cangai oil transfersomes patches by HPLC.The results showed that the optimal prescription for preparing Cangai oil transfersomes patches were Eudragit E100 0.6 g, succinic acid 0.08 g,triethyl citrate 0.25 g,glycerol 0.2 g.Patches prepared by the preferred preparation had a flat appearance without obvious bubbles.The initial adhesion was 18.33±2.52, the stickiness was(30.01±2.45) min,and the peel strength was(5.62±0.95) kN·m~(-1).The results of affecting factors experiment showed the order of factors affecting its adhesion was humidity>temperature>lighting,and the skin irritation test results showed no significant skin irritation after 24 h of single administration. The results of drug release behavior in vitro showed that the release and the percutaneous penetration of both Cangai oil patches and Cangai oil transfersomes patches conformed to the Higuchi equation.The release amount of eugenol were 80.66% and 82.25% at 72 h, with no significant difference. The cumulative permeation area of eugenol per unit area reached(0.195 6±0.065 9),(0.131 0±0.045 5) mg·cm~(-2) at 72 h, with significant differences(P<0.05).The experiment results proved that the preparation process of Cangai oil transfersomes patches was stable,and the prepared patches had a good adhesion. At the same time,the preparation of transfersomes patches could alleviate and control the release of the drug to a certain extent, and provide a certain experimental basis for clinical pediatric drug safety.
Administration, Cutaneous ; Drug Carriers ; Drug Liberation ; Humans ; Plant Oils/pharmacology* ; Polymethacrylic Acids ; Skin/drug effects* ; Skin Absorption ; Transdermal Patch