Objective: Inflammatory cascade reactions play a crucial role in secondary neuronal injury in acute ischemic stroke (AIS). The aim of this study was to explore the correlations between specific serological indicators, early neurological deterioration (END), disease prognosis, and syndrome factors in AIS based on this injury mechanism. Methods: The data for this study were collected from 135 patients with AIS admitted to the emergency department of Fangshan Hospital, Beijing University of Chinese Medicine, within 24 h of onset between November 2019 and May 2021. Among these, 29 patients had complete data and experienced END. Additionally, 9 non-END patients were matched from the remaining 90 patients with complete data, resulting in a total of 38 patients for statistical analysis. Statistical methods, including logistic regression and receiver operating curves, were used to analyze the correlation between serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule-1 (ICAM-1) within 24 h of END onset, disease prognosis, and syndrome factors. Grouping criteria included END occurrence, presence of syndrome elements on the first and third day post-onset, and prognosis at 90 days post-onset. Results: All 38 cases had onset time of less than 12 h, and there were no significant differences in age, gender, and onset time between the END and non-END groups. The TNF-α serum level within 24 h of onset was not associated with the occurrence of END but was negatively correlated with all-cause mortality at 90 days [0.110; P<0.05). An elevated IL-10 serum level within 24 h of onset showed a strong negative correlation with non-disabling and good functional outcomes at 90 days post-onset (0.110; P<0.05). When the ICAM-1 serum levels exceeded 233 599.500 μg/L and 125 141.500 μg/L, respectively, the susceptibility to endogenous wind and endogenous fire on the third day of onset was 15.364 times and 6.071 times higher, respectively, than that in patients with serum levels below these thresholds. Conclusion As accessible and objective biomarkers, inflammatory serum indicators are closely associated with both disease progression and traditional Chinese medicine (TCM) syndrome elements. They enhance AIS diagnosis, assessment, and treatment and contribute to a deeper understanding of the role of TCM syndrome differentiation in AIS diagnosis and treatment.

Objective: To establish a risk prediction model for diabetic peripheral neuropathy (DPN) among patients with type 2 diabetes mellitus (T2DM), so as to provide a basis for DPN prevention and control. Methods: T2DM inpatients aged 18-65 years admitted to the department of endocrinology and metabolism at Affiliated Hospital Shandong Second Medical University from April to December 2024 were selected as study subjects. Age, T2DM duration, hypertension history, 25-hydroxyvitamin D, serum C-peptide, and high density lipoprotein cholesterol (HDL-C) were collected through electronic medical records. Risk predictors of DPN among T2DM patients were screened using multivariable logistic regression model, and a nomogram was established. The receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively. Results: A total of 598 T2DM patients were enrolled, including 359 (60.03%) males and 239 (39.97%) females. The median age was 54.50 (interquartile range, 15.00) years, the median T2DM duration was 6.00 (interquartile range, 9.00) years. There were 262 cases of T2DM patients with DPN, accounting for 43.81%. Multivariable logistic regression identified hypertension history (OR=3.260, 95%CI: 2.220-4.790), alcohol use history (OR=2.150, 95%CI: 1.390-3.310), diabetes complications (OR=0.430, 95%CI: 0.270-0.680), T2DM duration (OR=1.040, 95%CI: 1.010-1.070), body mass index (OR=1.130, 95%CI: 1.070-1.200), 25-hydroxyvitamin D (OR=0.930, 95%CI: 0.910-0.960), and HDL-C (OR=0.400, 95%CI: 0.230-0.720) as risk predictors for DPN among T2DM patients. The area under the ROC curve of the established risk prediction model was 0.774 (95%CI: 0.737-0.812), with a sensitivity of 0.710 and a specificity of 0.723. The calibration curve after repeated sampling calibration approached the standard curve. Decision curve analysis showed that when the risk threshold probability was 0.2 to 0.4, the model demonstrates favorable clinical applicability. Conclusion The risk prediction model established in this study has favorable discrimination, calibration, and clinical utility, can effectively predict the risk of DPN among T2DM patients aged 18-65 years.

Echinocandin B (ECB) is a key precursor of the antifungal drug anidulafungin. It is a secondary metabolite of Aspergillus nidulans, and its titer in fermentation is significantly affected by the ECB synthesis pathway and cell morphology. In this study, the key genes related to the transcription activation, hydroxylation, and cell morphology during ECB biosynthesis were investigated to increase the fermentation titer of ECB and to change the cell morphology of Aspergillus nidulans to reduce the viscosity of the fermentation broth. The results indicated that after overexpression of ecdB and ecdK, the ECB titer increased by 25.8% and 23.7%, respectively, compared with that of the wild-type strain, reaching (2 030.5±99.2) mg/L and (1 996.4±151.4) mg/L. However, the deletion of fksA associated with cell wall synthesis resulted in damage to the cell wall, affecting strain growth and product synthesis. The engineered strain overexpressing ecdB was fermented in a 50-L bioreactor, in which the ECB titer reached 2 234.5 mg/L. The findings laid a research foundation for the subsequent metabolic engineering of this strain.
Fermentation ; Aspergillus nidulans/genetics* ; Echinocandins/genetics* ; Bioreactors/microbiology* ; Fungal Proteins/biosynthesis* ; Metabolic Engineering

Inhibitory cells derived from bone marrow are a kind of inhibitory cells derived from bone marrow.These cells are not only related to tumor growth,but also participate in the inflammatory immune process.Therefore,we established a rat model of chronic osteomyelitis,and used gemcitabine to inhibit the cell growth ratio of MDSCs.We detected the ratio of MDSCs in bone marrow and spleen of rats by flow cytometry and immunofluorescence,detected the changes of inflammatory factors in peripheral blood by ELISA,and analyzed the inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-11)in peripheral blood of normal rats,osteomyelitis rats and rats after gemcitabine inhibition.The results showed that the proportion of MDSCs cells in bone marrow and spleen of osteomyelitis model rats was increased,but it was significantly decreased in gemcitabine group(P<0.05).Levels of inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-17,IFN-γ,TGF-β)were positively correlated with the change of MDSCs cell proportion(P<0.05).From the results,it can be inferred that the change of the proportion of MDSCs cells in rat osteomyelitis is positively related to the inflammatory factors,and gemcitabine can reduce inflammatory factors by inhibiting MDSCs.

Marine fungi are important members of the marine microbiome, which have been paid growing attention by scientists in recent years. The secondary metabolites of marine fungi have been reported to contain rich and diverse compounds with novel structures (Chen et al., 2019). Aspergillus terreus, the higher level marine fungus of the Aspergillus genus (family of Trichocomaceae, order of Eurotiales, class of Eurotiomycetes, phylum of Ascomycota), is widely distributed in both sea and land. In our previous study, the coral-derived A. terreus strain C23-3 exhibited potential in producing other biologically active (with antioxidant, acetylcholinesterase inhibition, and anti-inflammatory activity) compounds like arylbutyrolactones, territrems, and isoflavones, and high sensitivity to the chemical regulation of secondary metabolism (Yang et al., 2019, 2020; Nie et al., 2020; Ma et al., 2021). Moreover, we have isolated two different benzaldehydes, including a benzaldehyde with a novel structure, from A. terreus C23-3 which was derived from Pectinia paeonia of Xuwen, Zhanjiang City, Guangdong Province, China.
Acetylcholinesterase/metabolism* ; Animals ; Anthozoa/microbiology* ; Anti-Inflammatory Agents/pharmacology* ; Aspergillus/chemistry* ; Benzaldehydes/pharmacology* ; Mice ; RAW 264.7 Cells ; Signal Transduction

There is uniformed definition of rare diseases in children, which can be viewed as rare diseases that develop in childhood, or the childhood of patients with rare diseases. Rare diseases are rarely seen in clinical setting, various in types and difficult to diagnose and treat. In the past few years, with the rapid development of medical technology and the establishment and wide application of rare disease management systems, great progress has been made in the diagnosis and treatment of rare diseases. Although the management of rare diseases is being gradually expanded and enhanced, there are still challenges, or opportunities for further improvement. China is a vast country with imbalanced distribution of medical resources. In many places, people have limited knowledge about the pathogenesis of many rare diseases. Capacities vary in the detection, diagnosis, and treatment of rare disease in different places. As a result, most rare diseases are either misdiagnosed or not diagnosed at all. Therefore, it is of great significance to establish a hierarchical system for the management of rare diseases, i.e., appropriate triage, risk stratification, early diagnosis and scientific treatment, and integrate regional resources into rare disease management. Studies have confirmed the existance of heterogeneity of rare diseases, with more than half of them occurring at birth or in childhood and that they are associated with a high mortality rate and a high incidence of functional disabilities in survivors. Therefore, rare diseases in child-ren deserve more attention. Standardized, protocol-based, law-based management of rare diseases in children is in urgent need. The article aims to discuss the status quo of the management of rare diseases in children, to summarize the clinical progress of rare diseases in children and to explore its prospects in the future, in the hope to provide some reference for the management of rare diseases in children.

Objective To develop a method for monitoring unconstrained sleep respiration suitable for daily use at home, so as to realize high precision screening of sleep apnea syndrome (SAS) or other respiratory diseases without affecting normal sleep. Methods A new unconstrained measurement method using sheet-type flexible pressure sensor was proposed. This method could obtain the information of respiratory motions of the chest and abdomen by measuring the pressure fluctuations of the chest and abdomen acting on the mattress. Experiments were conducted on ten healthy subjects to confirm effectiveness of the proposed method by comparing the result of the unconstrained measurement and those of respiratory inductance plethysmography (RIP) using band sensors, respectively. Results Sheet-type flexible pressure sensor could measure the pressure fluctuations of the chest and abdomen acting on the mattress during respiration and obtain respiratory waveform and respiratory rate. The respiratory rate measured with the sheet-type flexible pressure sensor agreed with those obtained by RIP. The gender and the lying position greatly affected whether the phases of the pressure fluctuations of the chest and abdomen measured with the flexible sensor differed from those obtained by RIP. The chest respiratory finite element model was established to analyze the phase difference of respiratory movement. Conclusions Sheet-type flexible pressure sensor is effective to monitor unconstrained sleep respiration, indicating the potential to identify the SAS types. But further researches of motion decoupling are required to identify the phase difference between the chest motion and the abdomen motion, which are coupled with each other.

Objective:To investigate the correlation between single nucleotide polymorphism of corticosteroids receptor gene(NR3C1)and children with asthma and to analyze the efficacy of inhaled corticosteroid(ICS)treatment.Methods:The study included a control group(100 healthy children)who participated in the physical examination and an asthma group(101 children with bronchial asthma)who were hospitalized in the General Hospital of the Northern Theater Command from October 2018 to October 2020.Genomic DNA was extracted from peripheral blood samples of all enrolled subjects and then the polymorphism of the glucocorticoid receptor gene locus of NR3C1 was analyzed using SNaPshot SNP gene detection technology.The comparisons of allele frequency in rs41423247、rs7701443 between two groups were performed and the treatment effects of ICS in the asthma group were evaluated at the 12th week of treatment.Results:The frequencies of GG, GC, and CC genotypes of rs41423247 locus of NR3C1 were 75.2%, 21.8%, and 3.0% in the asthma group and 72.0%, 24.0%, and 4.0% in the control group, respectively, and there were no statistically significant differences between the two groups( χ2=0.333, P>0.05). The frequencies of GG, GA, and AA genotypes of rs7701443 locus of NR3C1 were 45.5%, 39.6%, and 14.9% in the asthma group and 56.0%, 31.0%, and 13.0% in the control group, respectively, and there were no statistically significant differences between the two groups( χ2=2.259, P>0.05). After ICS treatment, the C-ACT/ACT scores were not significantly improved in children with CC genotypes at rs41423247 locus( P>0.05), while children with GG and GC genotypes were obviously improved( P<0.05). The scores of C-ACT/ACT showed obvious differences among three genotypes of rs41423247 locus after treatment with ICS( P<0.05). The C-ACT/ACT scores of all were significantly improved in children with GG, GA, or AA genotypes at rs7701443 locus after treatment with ICS( P<0.05), while there was no significant difference among those three genotypes( P>0.05). Significantly improved pulmonary function following ICS treatment in children with asthma was observed in GG and GC genotypes of rs41423247 locus of NR3C1( P<0.05), while only MMEF was improved in CC genotype( P<0.05). Meanwhile, those pulmonary function indexes were improved in all genotypes of rs7701443 after treatment with ICS( P<0.05). Conclusion:Both rs41423247 and rs7701443 locus at NR3C1 gene have polymorphisms.But there were no significant differences in the polymorphism of rs41423247 and rs7701443 locus of NR3C1 between the asthma group and the control group.Different genotype frequencies of rs41423247 and rs7701443 at NR3C1 locus in children with asthma have different effects on ICS treatment.

Objective:To investigate the relationship between rs2075748 and rs542269 single nucleotide polymorphisms of cholinergic muscarinic receptor 1 (CHRM1)gene and susceptibility of childhood asthma, as well as the differences of pulmonary function and serum acetylcholine(Ach)levels among different genotypes.Methods:A total of 156 asthmatic children who were treated in the outpatient or hospitalized in the General Hospital of the Northern Theater Command from September 2018 to September 2020 were selected as the case group, while 134 non-asthmatic children who had a healthy physical examination were selected as the control group.The SNaPshot SNP typing technique was used to analyze the genotype of the CHRM1 gene rs2075748 and rs542269 of the study subjects.Serum Ach level was detected by double antibody sandwich method, and the pulmonary function of the case group was detected.Results:After analyzing the CHRM1 gene polymorphism, it was found that the CC, CT, and TT genotype frequencies at rs2075748 were 65.4%, 28.8%, 5.8% in the case group, and 62.8%, 32.4%, 4.8% in the control group.The C and T allele frequencies were 79.8% and 20.2% in the case group, 74.3% and 25.7% in the control group.There were no significant difference in the genotype and allele frequency distribution between the two group ( χ2=2.688, 2.530, both P>0.05), and there were no significant difference in the recessive and dominant modes between the two groups ( χ2=0.338, 2.686, both P>0.05). The TT and CT genotype frequencies at rs542269 locus were 72.4% and 27.6% in the case group, 62.7% and 37.3% in the control group.The T and C allele frequency were 86.2% and 13.8% in the case group, 81.3% and 18.7% in the control group.The genotype and allele frequency distribution were not obvious different between the two group ( χ2=3.145, 2.544, both P>0.05). The risk of asthma with variant CT and TT at rs2075748 locus of CHRM1 gene were not statistically different from that of wild-type CC (both P>0.05), and the risk of asthma with variant CT at rs542269 locus was no different from that of wild-type TT ( P>0.05). The difference in FEF50% Pred and FEF75% Pred of different genotypes at rs2075748 were statistically significant( F=3.118, 4.808, both P<0.05), wild-type CC was lower than variant CT(both P<0.05). There were no statistically significant difference in pulmonary function among different genotypes at rs542269 (both P>0.05). There was significant difference in serum Ach level between different genotypes of rs2075748 ( F=4.716, P<0.05), variant CT was lower than wild-type CC ( P<0.05), variant TT was lower than wild-type CC ( P<0.05), while no significant difference was find between variant CT and TT ( P>0.05). There was no significant difference in serum Ach level between different genotypes of rs542269 ( P>0.05). Conclusion:The rs2075748 locus of CHRM1 gene is not susceptible to asthma, but it may be related to the small airway function of asthmatic children, besides there are differences in serum Ach levels with different genotypes, and the variant serum Ach level is lower.The rs542269 locus is not a susceptibility site for asthma, and there are no difference in pulmonary function and serum Ach levels in asthmatic children with different genotypes.

BACKGROUND: Staphylococcus aureus has become the most important pathogen of osteomyelitis In the world. An excellent and standard homogenous animal model plays an Important role regarding the Infectious mechanism of osteomyelitis, the acquisition of new preventive and therapeutic measures, and the application of new technologies in clinical practice. OBJECTIVE: To review the research progress and problems in the construction of animal models of Staphylococcus aureus-associated osteomyelitis at home and abroad. METHODS: A computer-based search of CNKI, PubMed, MEDLINE, Embase, and Cochrane was performed for relevant articles concerning the experimental osteomyelitis model, including review, basic research and clinical research, published from January 2010 to June 2019. The keywords were "Staphylococcus aureus; bone Infection; osteomyelitis; Implant-associated osteomyelitis; bone defect osteomyelitis; fracture osteomyelitis; biofilm; experimental osteomyelitis model" in Chinese and English, respectively. After Initial screening of titles and abstracts and exclusion of irrelevant articles, 45 eligible articles were Included In final analysis. RESULTS AND CONCLUSION: Construction of an osteomyelitis animal model is related to many factors. Although researchers from various countries have continuously Improved and gradually quantified the Infection process In recent years, a unified standard has not yet been developed. To date, there is no single microbiology or Imaging method to determine bone Infection. In animal models of acute osteomyelitis, the use of microbiological tests such as nuc RTQ-PCR and bioluminescence tomography can dynamically monitor and quantify the bone Infection process at an early stage. In the animal model of chronic osteomyelitis, we can dynamically observe the process of osteolysis and bone remodeling based on the micro-CT and MRI images. Advanced Imaging technologies such as18F-FDG PET/CT can be used to confirm or exclude chronic osteomyelitis with high diagnostic accuracy. The use of animal models of osteomyelitis contributes to standardizing the number and activity of infected bacteria during early diagnosis and quantified treatment, which Is the direction for further research.