Search

Background: Transplant recipients are at high risk of coronavirus disease 2019, and a timely supply of antivirals should be prioritized for those patients. Complicated drug‒drug interactions limit the use of Paxlovid (nirmatrelvir/ritonavir) coadministered with tacrolimus. Here, we report a patient with a kidney transplant who received Paxlovid and reduced-dose tacrolimus at the same time and suffered a severe tacrolimus toxicity., Case Presentation: We present a 56-year-old man of Han ethnicity with a kidney transplant who suffered from coronavirus disease 2019 twice. For the first infection, the immunosuppressants were substituted by dexamethasone when the patient used Paxlovid, and everything went well. For the second time, tacrolimus at a reduced dose concomitant with Paxlovid caused severe diarrhea, inducing combined diabetic ketoacidosis and a hyperglycemic hyperosmolar state., Conclusion: This case challenges the dose-adjustment strategy of managing drug‒drug interactions. We suggest that tacrolimus should be stopped when Paxlovid is applied and that corticosteroids could be a good substitution., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To observe the efficacy and safety of Kangbingdu granules (KBD) in the treatment of influenza. Methods: A multicenter, randomized, double-blind, double-dummy, and positive-drug parallel control trial was conducted in 27 Grade ⅢA hospitals in China and the subjects were randomly assigned to the KBD test group or the oseltamivir phosphate capsule control group at a ratio of 1∶1. 200 subjects were planned to be enrolled in each group. The experimental group was given KBD (18g each time, 3 times a day) and oseltamivir phosphate simulator orally, while the control group was given oseltamivir phosphate capsule (75 mg each time, twice a day) and KBD simulator orally for 5 days. The primary efficacy indicators included the remission time of major clinical symptoms and the time of complete defervescence. The secondary efficacy indicators included dosage of acetaminophen, the change of traditional Chinese medicine (TCM) syndrome score and the remission time of other important clinical symptoms. The efficacy of KBD in the test group and Oseltamivir phosphate control group were compared. Adverse events or adverse reactions were observed at the same time to evaluate the safety of KBD Granules. Results: A total of 393 subjects from 27 Grade ⅢA hospitals in China were enrolled. The experimental group included 195 subjects and 191 subjects (97.95%) completed the trial, While the control group included 198 subjects and 195 subjects (98.48%) completed the trial. There was no significant difference in the shedding rate and rejection rate between the two groups ( P >0.05). In the Full Analysis Set (FAS), the mean age of the experimental group was (34.9±14.4) years old, with 83 males (42.78%). The mean age of the control group was (33.3±13.5) years old, with 78 males (39.59%). There were no statistically significant differences between the two groups in demographic data, physical examination, viral pathogen detection, total score of TCM syndromes and scores of each symptom at baseline ( P >0.05). In the FAS, the remission time M ( Q 1 , Q 3 ) of major clinical symptoms was 3.0 (3.0, 4.0) days in the experimental group and 3.0 (3.0, 4.0) days in the control group, and the difference was not statistically significant ( P >0.05). The time M ( Q 1 , Q 3 ) of complete defervescence was 34.0 (20.3, 49.0) hours in the experimental group and 36.5 (19.6, 48.8) hours in the control group, and the difference was not statistically significant ( P >0.05). KBD granules had the same effect as Oseltamivir phosphate capsule ( P >0.05) in terms of acetaminophen dosage, TCM syndrome effect and disappearance rate of most important clinical symptoms. Meanwhile, the disappearance rate of dizziness and chest distress on day 3 in the KBD granules group was better than that of oseltamivir phosphate capsule ( P< 0.05). Conclusion: KBD granules have the same efficacy as Oseltamivir Phosphate capsule in the treatment of influenza and the drug safety is good.

Context: Evidence suggests that microRNA (miRNA) regulate gene expression and bone tissue homoeostasis of osteoporosis. MiR-152 has found to be abnormally expressed in osteoporosis, but its role in osteoblast differentiation has not been elucidated. Objective: To understand the potential mechanism of miR-152 in osteoblast differentiation via regulation of RICTOR. Materials and methods: The expression of miR-152 and RICTOR were tested in ovariectomized rat models of osteoporosis. Primary osteoblasts and MC3T -E1 cells were assigned into four groups, namely Control, miR-152 inhibitor, miR-control and miR-152 inhibitor + siRICTOR groups. qRT PCR and Western blot were performed to detect the expressions of miR-152 and RICTOR, respectively. MTT assay was used to evaluate cell viability, and ALP activity determination and mineralization analyses were also conducted. Results: In ovariectomy-induced osteoporotic rats, miR-152 (3.06 ± 0.35) in femoral tissues increased significantly, while RICTOR (0.31 ± 0.04) decreased. Compared with Control group, miR-152 inhibitor group presented appreciable reduction of miR-152 in primary osteoblasts and MC3T3-E1 cells, as well as remarkable increases in RICTOR, p-Akt(s473)/Akt ratio, and osteogenesis-related genes, with enhanced cell viability, ALP activity and mineralization. In comparison with cells in the miR-152 inhibitor group, those in the miR-152 inhibitor + siRICTOR group had no observable difference in miR-152, but were dramatically up-regulated in RICTOR, as well as the corresponding opposite tendencies of other factors. Conclusion: Inhibiting miR-152 promoted osteoblasts differentiation and alleviated osteoporosis by up-regulating RICTOR. Therefore, miR-152 may be an essential mediator of osteoblast differentiation and a new therapeutic strategy for osteoporosis.

Objective: To study the clinical efficacy of interactive group sandplay versus individual sandplay in the treatment of preschool children with autism spectrum disorder (ASD)., Methods: A total of 80 ASD children, aged 4-6 years, were enrolled and randomly divided into experimental and control groups, with 40 children in each group. The children in the experimental group joined group sandplay with normal children at a ratio of 1: 3, and those in the control group were treated with individual sandplay. The Aberrant Behavior Checklist (ABC) and Autism Treatment Evaluation Checklist (ATEC) were used to evaluate the treatment outcome after three months of intervention., Results: There were 33 children in the experimental group and 28 in the control group. After three months of intervention, the experimental group had significant reductions in the scores of irritability, social withdrawal, and stereotypic behavior and the total score of the ABC scale (P<0.05), and the control group had significant reductions in the scores of behavior and inappropriate speech and the total score of the ABC scale (P<0.05). Compared with the control group, the experimental group had significantly greater improvements in the score of social withdrawal and the total score of the ABC scale after three months of intervention (P<0.05). After three months of intervention, the experimental group had significant reductions in the scores of sociability, sensory and cognitive awareness, and physical/health behavior and the total score of the ATEC scale (P<0.05), and the control group had significant reductions in the scores of speech, sociability, and physical/health behavior and the total score of the ATEC scale (P<0.05). Compared with the control group, the experimental group had significantly greater improvements in the scores of speech, sociability, and sensory and cognitive awareness and the total score of the ATEC scale after intervention (P<0.01). Compared with the control group, the experimental group also had significantly greater improvements in eye contact and sand stereotyped arrangement (P<0.05)., Conclusions: Both interactive group sandplay and individual sandplay are effective in the treatment of ASD in preschool children. Interactive group sandplay is better than individual sandplay in the treatment of ASD, with significant improvements in sociability, emotion and stereotypic behavior.

Objective: To study the clinical effect of integrated sandplay therapy in preschool children with Asperger syndrome (AS)., Methods: A total of 44 preschool children with AS were randomly divided into an experimental group and a control group, with 22 children in each group. The children in the control group were given routine training, and those in the experimental group were given integrated sandplay therapy in addition to the routine training. The treatment response was assess by the Social Responsiveness Scale (SRS), emotional recognition tools and changes in sandplay theme characteristics after 6 months of treatment., Results: Before intervention, there were no significant differences between the two groups in the total score of SRS, the score of each factor of SRS, and correct rates of facial expression recognition of the upright position, inverted position, upper face and lower face (P>0.05). After 6 months of intervention, both groups had significant reductions in the total score of SRS and the score of each factor of SRS (P<0.01); the control group had significant increases in the correct rates of facial expression recognition of all positions except the upright position (P<0.05), while the experimental group had significant increases in the correct rates of facial expression recognition of all positions (P<0.05). Compared with the control group after intervention, the experimental group had significantly lower total score of SRS and scores of all factors of SRS except social perception (P<0.01) and significantly higher correct rates of facial expression recognition of all positions (P<0.01). The experimental group had a significant change in the number of sandplay theme characteristics after intervention (P<0.01)., Conclusions: Integrated sandplay therapy can improve social responsiveness and emotion recognition ability in preschool children with AS.

Some studies have indicated that the Wnt/β-catenin signaling pathway is activated following spinal cord injury, and expression levels of specific proteins, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β, are significantly altered. We hypothesized that methylprednisolone treatment contributes to functional recovery after spinal cord injury by inhibiting apoptosis and activating the Wnt/β-catenin signaling pathway. In the current study, 30 mg/kg methylprednisolone was injected into rats with spinal cord injury immediately post-injury and at 1 and 2 days post-injury. Basso, Beattie, and Bresnahan scores showed that methylprednisolone treatment significantly promoted locomotor functional recovery between 2 and 6 weeks post-injury. The number of surviving motor neurons increased, whereas the lesion size significantly decreased following methylprednisolone treatment at 7 days post-injury. Additionally, caspase-3, caspase-9, and Bax protein expression levels and the number of apoptotic cells were reduced at 3 and 7 days post-injury, while Bcl-2 levels at 7 days post-injury were higher in methylprednisolone-treated rats compared with saline-treated rats. At 3 and 7 days post-injury, methylprednisolone up-regulated expression and activation of the Wnt/β-catenin signaling pathway, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β phosphorylation. These results indicate that methylprednisolone-induced neuroprotection may correlate with activation of the Wnt/β-catenin signaling pathway., Competing Interests: Conflicts of Interest: None declared.

During thermal decomposition of azobisisobutyronitrile (AIBN), the endothermic process of phase transition disturbed exothermic decomposition, which brought deformation in its thermal graphs. Therefore, exact kinetic parameters of the decomposition could not be obtained by the existing kinetics analytic models, and the accurate enthalpy data of the decomposition and phase transition were not available. Two methods, i.e., a solvent method and a mathematical method, were introduced in this paper to resolve the coupling phenomenon. In the former method, AIBN was dissolved into aniline to eliminate the endothermic process and obtain curves of the liquid-state decomposition. In the latter method, MATLAB software was employed to get the "pure" exothermic decomposition curve without the influence of phase transition by fitting coupling curves within the section after the transition point and extrapolating to the initial stage of decomposition. Moreover, the kinetic parameters of the "pure" exothermic decomposition of AIBN obtained by the mathematical fitting agreed with the results from the solvent method, verifying the accuracy of the decoupling. The research is of great significance for comprehending the exact characteristics of thermal behaviors and safety parameters of AIBN. It also provides a great help to determine the safe operating temperature and alarm temperature for processes in industry., (Copyright © 2014. Published by Elsevier B.V.)

Neutrophils provide the first line of defense against invading pathogens and have been reported to play a key role in bovine mammary immune. To examine the differential expression of proteins in neutrophils between clinical mastitis and healthy dairy cows, a 2-dimensional electrophoresis gel map with high repeatability was constructed for bovine neutrophils. From this map, seven differentially expressed proteins were identified by MALDI-TOF MS which are believed to be involved in pathways such as cell metabolism, oxidative stress, and inflammatory reaction. The differentially expressed proteins identified in this study may provide the basis for bovine mastitis resistance breeding research.

Objective: To explore the relationship between gene polymorphism of GABAA receptors and childhood autism by detecting rs140682, rs2081648 and rs140679 site of single nucleotide polymorphism (SNP) in GABAA receptors gene., Methods: A total of 94 children with autism and 124 normal children were enrolled in a hospital from November 2010 to May 2011. Childhood autism rating scale (CARS) and autism behavior checklist (ABC) were used to evaluate or investigate the case group. After collecting venous blood and extracting the genome DNA, the allele and genotype of SNP rs140682, rs2081648 and rs140679 site in GABAA receptors gene were detected by PCR-RFLP. The allele and genotype of case group and control group were analyzed by χ(2) test, while the score of scales was analyzed by Spearman rank correlation analysis., Results: The age of the case group was 5.12 ± 0.32, and it was 5.25 ± 0.27 in the control group (P < 0.05). In case group, the frequency of genotype CC, CT and TT of rs140682 site was 44, 41 and 9, while it was 48, 65, and 11 in control group (P > 0.05), respectively. The frequency of genotype AA, AG and GG of rs2081648 site was 8, 58 and 28 in case group, while it was 12, 49 and 63 in control group (P < 0.05), respectively. In case group, the frequency of genotype CC, CT and TT of rs140679 site was 15, 36 and 43, while it was 18, 59 and 47 in control group (P > 0.05), respectively. It was revealed by Spearman rank correlation analysis that of rs2081648 site, there was a positive correlation between genotype AG and sensation factor (S), social intercourse factor (R), and language factor (L) of autism behavior checklist (ABC) (r values were 0.149, 0.165 and 0.155, all P values < 0.05). A negative correlation between genotype GG and S, R, L and self-help factor (V) was proved (r values were -0.140, -0.173, -0.158 and -0.135, all P values < 0.05). There was a positive correlation between allele A and R and L factors (r values were 0.153 and 0.137, all P values < 0.05), while a negative correlation between allele G and R and L factors (r values were -0.153 and -0.137, all P values < 0.05). In case group, 42 children were diagnosed with mild-to-moderate autism, while 52 children were severe autism. There was no statistically significant correlation between allele or genotype of SNP rs140682 and rs140679 site and the degree of autism (P > 0.05). There was a positive correlation between allele A and genotype AG and the degree of autism (r values were 0.147 and 0.616, all P values < 0.05), while a negative correlation between allele G and genotype GG and the degree of autism (r values were -0.159 and -0.616, all P values < 0.05)., Conclusion: The SNP rs2081648 site which located in GABAA receptors gene may be related to autism. No evidence for significant association between rs140682 and rs140679 site and autism was found.

Aim: To evaluate the effects of electromagnetic irradiation of 2000 μW/cm(2); exposure on mRNA and protein expression levels of immunoreactive protein and mRNA of NMDA receptor 2A subunit in rats hippocampal, and to explore the mechanism of electromagnetic irradiation induced learning and memory impairment., Methods: Rats were randomly divided into normal control group, sham-radiated group, and 1 h/d, 2 h/d, and 3 h/d radiation groups. The rats in the radiation groups were fixed after microwave exposure of 2000 μW/cm(2);, then their learning and memory abilities were tested by Morris water maze experiment, the change of NR2A protein in hippocampal neurons of each group of rats were measured with immunohistochmistry and Western blot techniques, and the expression of NR2A mRNA in hippocampus were determined by RT-PCR., Results: Compared with the normal control group, each index of the sham-radiated group has no significant change (P>0.05), while the latency of rats of radiated group in Morris water maze test were significantly longer (P<0.05). In the radiation group, the hippocampal neurons of rats showing evident reduction in the ratio of NR2A positive cells, irregular, and arrayed in disorder. Moreover, the expession of NR2A protein and its mRNA in hippocampal neurons were significant decreased (P<0.05)., Conclusion: Electromagnetic irradiation of 2000 μW/cm(2); exposure can impair the learning and memory abilities of rats possibly through a mechanism correlated with the lower expression of NR2A protein and its mRNA in hippocampus.