ABSTRACT
Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical trial was conducted to assess the safety and pharmacokinetics (PK) of intravenous delafloxacin in the Chinese population. A population pharmacokinetic (PopPK) model based on the clinical trial was conducted by NONMEM software. Monte Carlo simulation was performed to evaluate the antibacterial effects of delafloxacin at different doses in different Chinese populations. The PK characteristics of delafloxacin were best described by a three-compartment model with mixed linear and nonlinear clearance. Body weight was included as a covariate in the model. We simulated the AUC0-24h in a steady state at five doses in patient groups of various weights. The results indicated that for patients weighing 70 kg and treated with methicillin-resistant Staphylococcus aureus (MRSA) infections, a minimum dose of 300 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, suggesting an ideal bactericidal effect. For patients weighing less than 60 kg, a dose of 200 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, also suggesting an ideal bactericidal effect. Additionally, this trial demonstrated the high safety of delafloxacin in single-dose and multiple-dose groups of Chinese. Delafloxacin (300 mg, q12h, iv) was recommended for achieving optimal efficacy in Chinese bacterial skin infections patients. To ensure optimal efficacy, an individualized dose of 200 mg (q12h, iv) could be advised for patients weighing less than 60 kg, and 300 mg (q12h, iv) for those weighing more than 60 kg.
Subject(s)
Anti-Bacterial Agents , Fluoroquinolones , Healthy Volunteers , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Monte Carlo Method , Humans , Fluoroquinolones/pharmacokinetics , Fluoroquinolones/pharmacology , Fluoroquinolones/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Adult , Male , Methicillin-Resistant Staphylococcus aureus/drug effects , Female , Middle Aged , Administration, Intravenous , Young Adult , Area Under Curve , Body Weight/drug effectsABSTRACT
AIMS: Bruton's tyrosine kinase inhibitors (BTKIs), including first-generation ibrutinib, second-generation acalabrutinib and zanubrutinib, may be involved in the mechanisms of action related to adverse events (AEs) of the cardiovascular system. We aimed to characterize the cardiovascular AEs of BTKIs reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System, and to compare the cardiovascular risks of BTKIs. METHODS: Across all indications of three FDA-approved BTKIs, primary suspect drugs were extracted over two periods: from January 2013 to December 2022 (after the approval of the first BTKI), and from January 2020 to December 2022 (all three BTKIs on the market). Disproportionality was measured by reporting odds ratios (RORs) and information components. Additional analyses were performed without incorporating patients with underlying cardiovascular disease (CVD). RESULTS: A total of 10 353 cases included the uses of ibrutinib, acalabrutinib and zanubrutinib. Ibrutinib was significantly associated with 47 cardiovascular AEs. Acalabrutinib was associated with new signals, including cardiac failure (ROR = 1.82 [1.13-2.93]), pulmonary oedema (ROR = 2.15 [1.19-3.88]), ventricular extrasystoles (ROR = 5.18 [2.15-12.44]), heart rate irregular (ROR = 3.05 [1.53-6.11]), angina pectoris (ROR = 3.18 [1.71-5.91]) and cardiotoxicity (ROR = 25.22 [17.14-37.10]). In addition, cardiovascular events had an earlier onset in acalabrutinib users. Zanubrutinib was only associated with atrial fibrillation. Acalabrutinib and zanubrutinib had lower ROR values than ibrutinib. The AE signals were generally consistent between the population receiving and not receiving CVD medications. CONCLUSIONS: Potential cardiovascular risks identified in this study were not clearly noted on the label of marketed acalabrutinib. Caution should be paid to the cardiovascular risks of BTKIs having been or being developed.
Subject(s)
Adenine , Adverse Drug Reaction Reporting Systems , Agammaglobulinaemia Tyrosine Kinase , Benzamides , Cardiovascular Diseases , Piperidines , Protein Kinase Inhibitors , Pyrazoles , Pyrimidines , United States Food and Drug Administration , Humans , United States/epidemiology , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Piperidines/adverse effects , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Protein Kinase Inhibitors/adverse effects , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/epidemiology , Pyrazoles/adverse effects , Adenine/analogs & derivatives , Adenine/adverse effects , Pyrimidines/adverse effects , Benzamides/adverse effects , Male , Pyrazines/adverse effects , Female , Aged , Middle Aged , Databases, Factual/statistics & numerical data , AdultABSTRACT
BACKGROUND: The use of cortical strut allograft has not been determined for Vancouver type B1 or C fracture. This study aimed to evaluate the short-term efficacy of locking compression plating with or without cortical strut allograft in managing these types of fractures. METHODS: We retrospectively assessed 32 patients (17 males, 15 females; 23-88 years, mean: 67.2 years) with Vancouver type B1 or C fractures. Seventeen patients (Group A; B1 fractures in 15 hips, C fractures in 2 hips) were treated with open reduction and internal fixation with locking compression plates (group A). The other 15 patients (Group B; B1 in 14 hips, C in 1 hip) were fixed by locking compression plating combined with cortical strut allografting (group B). The fracture healing rate, healing time, complications and function were compared between these two groups. RESULTS: The mean follow-up time was 32.4 months (12 to 66), and the overall fracture union rate of the 32 patients was 96.9%. Group B had a higher fracture union rate than Group A, but the difference was not statistically significant. Group A had one case of nonunion of type B1 fracture and one case of malunion; the mean time to fracture healing was 5.3 months (3 to 9). In group B, all patients reached bony union without malunion, with a mean time of fracture healing of 5.1 months (3 to 8). CONCLUSION: Treatment of Vancouver type B1 or C fractures by locking compression plating, with or without cortical strut allografting, resulted in similar union rates in these patients. This suggest that, the use of cortical strut allografting should be decided cautiously.
Subject(s)
Arthroplasty, Replacement, Hip , Femoral Fractures , Hip Prosthesis , Periprosthetic Fractures , Allografts , Bone Plates , Female , Femoral Fractures/diagnostic imaging , Femoral Fractures/surgery , Follow-Up Studies , Fracture Fixation, Internal/adverse effects , Fracture Healing , Humans , Male , Periprosthetic Fractures/diagnostic imaging , Periprosthetic Fractures/epidemiology , Periprosthetic Fractures/etiology , Retrospective Studies , Transplantation, Homologous , Treatment OutcomeABSTRACT
Continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants urges the development of new vaccines. We assessed the safety and immunogenicity of SYS6006.32, a bivalent vaccine (XBB.1.5/BQ.1), in healthy adults who had received SARS-CoV-2 primary vaccination. In a randomised, double-blinded, active-controlled trial, 200 participants were randomised to receive one dose of SYS6006.32 (N = 100) or a prototype-based, monovalent control vaccine SYS6006 (N = 100). Adverse events (AEs) were collected through the study. Immunogenicity was assessed by live-virus neutralising antibody (Nab) and pseudovirus Nab. 61 (61.0 %) and 60 (60.0 %) participants reported AE in the SYS6006.32 and SYS6006 groups, respectively. Most AEs were grade 1 or 2. Pain and fever were the most common injection-site and systemic AEs, respectively. No serious AEs were observed. SYS6006.32 heterologous boosting induced robust Nab responses against BA.5, XBB.1.5 and EG.5 with live-virus Nab geometric mean titres (GMTs) increased by 17.1-, 34.0-, and 48.0-fold, and pseudovirus Nab GMTs increased by 12.2-, 32.0-, and 35.1-fold, respectively, 14 days after vaccination. SYS6006.32 demonstrated a superior immunogenicity to SYS6006. SYS6006.32 also induced robust pseudovirus Nab responses against XBB.1.16, XBB.2.3, and BA.2.86, with GMTs 3- to 6-fold higher than those induced by SYS6006. In conclusion, SYS6006.32 showed good safety profile and superior immunogenicity to the monovalent vaccine SYS6006.
Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Humans , COVID-19 Vaccines/adverse effects , SARS-CoV-2 , mRNA Vaccines , COVID-19/prevention & control , Antibodies, Blocking , China , Immunogenicity, Vaccine , Antibodies, Viral , Antibodies, Neutralizing , Double-Blind MethodABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine enables quick upgrade of antigen sequence to combat emerging new variants. In an observer-blinded, randomized, placebo-controlled phase 2 trial, immunologically naïve 300 adults and 150 older participants were enrolled and randomized (1:1:1) to receive two doses of 20 µg or 30 µg of a SARS-CoV-2 mRNA vaccine (SYS6006) or placebo. Adverse events (AEs) were recorded through 30 days after the second dose. Live virus neutralizing antibody (Nab), S1 protein-specific binding antibody (S1-IgG) and cellular immunity were tested. Results showed that robust wild-type Nab response was elicited with geometric mean titers of 91.3 and 84.9 in the adults, and 74.0 and 115.9 in the elders, 14 days following the second dose (Day 35) in the 20-µg and 30-µg groups, respectively. All seroconverted for wild-type Nab except two participants. Nab against Omicron BA.5 was mild. Robust wild-type S1-IgG response was induced with geometric mean concentrations of 2751.0 and 3142.2 BAU/mL in adults, and 2474.1 and 2993.5 BAU/mL in elders at Day 35 in the 20-µg and 30-µg groups, respectively. S1-IgG against Omicron BA.2 was induced. Cellular immunity was elicited, particularly in enzyme-linked immunospot assay. The most frequent AEs were injection-site pain and fever. Most reported AEs were grade 1 or grade 2. The AE incidences were similar following the first dose and second dose. No vaccination-associated serious AE was reported. In conclusion, two-dose vaccination with SYS6006 demonstrated good safety, tolerability and immunogenicity in immunologically naïve healthy participants aged 18 years or more.
Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Aged , Humans , Antibodies, Neutralizing , Antibodies, Viral , China , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Healthy Volunteers , Immunogenicity, Vaccine , Immunoglobulin G , mRNA Vaccines , SARS-CoV-2ABSTRACT
The mechanism of glutenin and gliadin on the surface tackiness of recooked frozen cooked noodles (FCNs) is unclear. In this study, the effects of glutenin and gliadin addition on the surface tackiness of FCNs were investigated. The addition of glutenin and gliadin reduced the surface tackiness (3.60 and 3.50 N) of recooked FCNs stored for 0 min. The addition of glutenin increased the rigidity of the gluten network and the compactness of FCNs and made the FCNs have a moisture-distribution with multilayers. The addition of gliadin increased the tensile distance of FCNs, restricted water migration during frozen storage, and increased the membranous structure of the gluten network to wrap starch particles. Glutenin had a stronger effect on reducing the surface tackiness of FCNs than gliadin. In the future, the synergistic effects of different proportions of glutenin and gliadin on the gluten network of FCNs could be further studied.
Subject(s)
Gliadin , Glutens , Gliadin/chemistry , Glutens/chemistry , Food , CookingABSTRACT
Vaccination plays a key role in preventing morbidity and mortality caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the safety and immunogenicity of a SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine SYS6006. In the two randomized, observer-blinded, placebo-controlled phase 1 trials, 40 adult participants aged 18-59 years and 40 elderly participants aged 60 years or more were randomized to receive two doses of SYS6006 or placebo (saline). Adverse events (AEs) were collected through 30 days post the second vaccination. Immunogenicity was assessed by live-virus neutralizing antibody (Nab), spike protein (S1) binding antibody (S1-IgG), and cellular immunity. The result showed that 7/15, 9/15 and 4/10 adult participants, and 9/15, 8/15 and 4/10 elderly participants reported at least one AE in the 20-µg, 30-µg and placebo groups, respectively. Most AEs were grade 1. Injection-site pain was the most common AE. Two adults and one elder reported fever. No vaccination-related serious AE was reported. SYS6006 elicited wild-type Nab response with a peak geometric mean titer of 232.1 and 130.6 (adults), and 48.7 and 66.7 (elders), in the 20-µg and 30-µg groups, respectively. SYS6006 induced moderate-to-robust Nab response against Delta, and slight Nab response against Omicron BA.2 and BA.5. Robust IgG response against wild type and BA.2 was observed. Cellular immune response was induced. In conclusion, two-dose primary vaccination with SYS6006 demonstrated good safety and immunogenicity during a follow-up period of 51 days in immunologically naive population aged 18 years or more. (Trial registry: Chictr.org.cn ChiCTR2200059103 and ChiCTR2200059104).
Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Aged , Humans , Antibodies, Neutralizing , Antibodies, Viral , China , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Immunogenicity, Vaccine , Immunoglobulin G , mRNA Vaccines , RNA, Messenger , SARS-CoV-2 , Vaccination , Adolescent , Young Adult , Middle AgedABSTRACT
Xanthoxylin was the main compound (content 44.92% of total volatiles) in the leaves of Luodian B. balsamifera, which might be the key cause of failure in collecting essential oil (EO) of the leaves using general hydrodistillation in Clevenger apparatus. A modified hydrodistillation equipped with Clevenger apparatus was designed for isolating EO from the leaves. Six EOs of Luodian B. balsamifera harvested once a month from September to next February were collected successfully. The main components of EOs were δ-elemene, α-cubenene, caryophyllene, caryophyllene epoxide, γ-eudesmol, xanthoxylin, and α-eudesmol. The EOs of Luodian B. balsamifera collected from October to December had higher antioxidant activities (ACs). Combining the principal component analysis of chemical components with the results of ACs and the yields of six EOs, the leaves of Luodian B. balsamifera were suitable to be harvested in November and December to obtain EO with high quality.
Subject(s)
Antioxidants/isolation & purification , Asteraceae/chemistry , Oils, Volatile/chemistry , Antioxidants/pharmacology , China , Distillation/instrumentation , Distillation/methods , Oils, Volatile/pharmacology , Plant Leaves/chemistry , Plant Oils/chemistry , Plant Oils/pharmacology , Polycyclic Sesquiterpenes/isolation & purification , Seasons , Sesquiterpenes/isolation & purificationABSTRACT
The objective of this work is to research impacts of oxidized (OCS), acetylated (ACS) and cross-linked (CLCS) corn starch on gelatinization properties of rice flour and their gel structure during storage at 4 °C for 1 and 7 days. OCS led to significant increase of pasting temperature and solubility in blend flour but decrease of pasting viscosity and swelling power compared with rice flour, while ACS showed an opposite effect in pasting temperature and viscosity. CLCS remarkably raised pasting temperature and viscosity of blend flour and insignificant increase as increasing concentration, and the mixture showed relatively lower swelling power and solubility than rice flour. During cold storage, OCS and ACS substantially inhibited the reorganization of gel network structure and showed high stability in rheology and texture properties. CLCS accelerated the formation of gel network structure, and the mixture gel appeared to stronger rigid structure and denser microstructure than those of rice gel. Formation distinctions among these three gels were found in rheology properties, texture properties, water migration, FTIR spectra, and microstructure of SEM. Overall, CLCS improved the rice stability in heat-processing, and OCS and ACS reduced the change of rice gel quality during cold storage.