Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

Objective : To explore the relationship between single nucleotide polymorphisms ( SNPs) in D-loop region of mitochondrial DNA ( mtDNA) and mtDNA copy number and the risk of dermatomyositis ( DM) ，and its in- fluencing factors． Methods : 74 patients with DM and 92 healthy controls were included in the study． Genomic DNA was extracted from peripheral blood and the target fragment of mtDNA D-loop region was amplified by PCR technique，and the products were subsequently sequenced．Serum levels of ROS were assessed using a high-sensi- tivity reactive oxygen species detection kit．The expression levels of cytokines，interleukin ( IL) -5，IL-13，inter- feron-γ ( IFN-γ) ，IL-2，IL-6，IL-10，tumor necrosis factor-α ( TNF-α) and IL-4 were measured using Flow Fluo- rescence Immunmicrobeads Assay．Wilcoxon rank-sum test was used to assess the potential correlation between cy- tokines and SNPs associated with DM risk．The relative copy number of mtDNA was measured using quantitative re- al-time polymerase chain reaction ( qPCR) analysis． Results : Two SNPs ( 16304T / C，16519T / C) were found to be associated with the risk of developing DM，and alleles 16304C ( χ2 = 4. 937，P = 0. 026) and 16519C ( χ2 = 4. 405，P = 0. 036) in the mitochondrial D-loop region were confirmed to be associated with DM development risk． The DM risk-associated allele 16304C was significantly associated with lower IL-4 expression ( P = 0. 016) ．The mtDNA copy number was significantly higher in DM patients than in controls ( P ＜0. 001) ． Conclusion Mitochondrial D-loop SNPs can be potential biomarkers for DM risk，and SNPs may be involved in DM by influencing cytokines．DM shows high expression of mtDNA copy number，and the increase in mtDNA copy number may lead to mitochondrial dysfunction，which triggers the pathogenesis of DM．

Objective To construct a recombinant poxvirus vector vaccine, rVTTδTK-RBD, and to evaluate its safety and immunogenicity. Methods The receptor-binding domain (RBD) gene was synthesized with reference to the gene sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was inserted into the polyclonal site of the self-constructed recombinant plasmid pSTKE, to construct the recombinant poxvirus shuttle vector pSTKE-RBD. This was then transfected into BHK-21 cells pre-infected with the vaccinia virus Tiantan strain (VTT). The recombinant poxvirus rVTTδTK-RBD was successfully obtained after several rounds of fluorescence phage screening. The effect of rVTTδTK-RBD on the body mass of BALB/c mice was detected after immunizing mice by intra-nasal vaccination. The levels of specific and neutralizing antibodies produced by rVTTδTK-RBD on BALB/c mice were analyzed after immunizing mice intramuscularly. The effect of rVTTδTK-RBD on T cell subsets in BALB/c mice was detected by flow cytometry. Results Through homologous recombination, enhanced green fluorescent protein (EGFP) screening marker, and multiple rounds of fluorescent phosphorescence phage screening, a recombinant poxvirus rVTTδTK-RBD, expressing RBD with deletions in the thymidine kinase (TK) gene, was successfully obtained, which was validated by PCR. The in vivo experiments on BALB/c mice showed that rVTTδTK-RBD was highly immunogenic against SARS-CoV-2 and significantly reduced toxicity to the body compared to the parental strain VTT. Conclusion The recombinant poxvirus vaccine rVTTδTK-RBD against SARS-CoV-2 is successfully constructed and obtained, with its safety and immunogenicity confirmed through various experiments.
Animals ; Mice ; SARS-CoV-2/genetics* ; COVID-19 ; Vaccines, Synthetic/genetics* ; Genes, Reporter ; Bacteriophages ; Mice, Inbred BALB C

Objective: To understand the influencing factors underlying physical exercise behavior among children and adolescents aged 9-18 years in Ningxia, China, in 2019, and to provide suggestions for physical exercise among children and adolescents by adopting a social ecological model. Methods: Based on data related to 12 018 children and adolescents in Ningxia aged 9-18 years old which were obtained from the National Survey on Students Constitution and Health in 2019, the survey questions scored based on the four levels of the social ecological model. Results: The proportion of children and adolescents who engaged in physical exercise for less than 1 hour a day accounted for 55.97% of the total number of people in Ningxia. Regardless of whether they were able to engage in enough physical activity, individual factors played a dominant role in influencing the behavior of the children and adolescents, and an interaction was found between influencing factors at different levels( r=-0.01, 0.01, -0.08, 0.04, P <0.01). The results of the stepwise regression analysis showed that the personal factors e.g. sports makes me healthy, I don t have enough time, muscle strength exercise, I have no movement of any relationship partner, sports make me know partner, policy in the number of physical education, number of sports meeting in a school year, the average daily lesson hold number all affect children s sports activities in time( B =-0.05-0.16, P <0.01). Conclusions The lack of physical exercise among children and adolescents in Ningxia is the result of multiple factors. Comprehensive and diversified intervention should be administered from a socio ecological framework to promote the formation of physical exercise habits among children and adolescents.

Objective:To investigate the mediating effect of inflammatory factors in the association between low density lipoprotein-cholesterol(LDL-C) and thyroid associated ophthalmopathy(TAO).Methods:This study was a prospective study, which icluded a total of 86 patients with Graves′ disease who attended the Department of Endocrinology of the First Affiliated Hospital of Zhengzhou University from January 2021 to June 2022. Among them, there were 56 patients with Graves′ disease accompanied by TAO, including 30 cases in the inactive group and 26 in the active group. Additionally, there were 30 cases having Graves′ disease alone. The relationship between LDL-C, inflammatory factors, and the onset and activity of TAO were analyzed using binary logistic regression. Mediation analysis was used to explore the mediating effect of inflammatory factors in the association between LDL-C and TAO onset and activity.Results:Interleukin(IL) -6 was a potential mediator that linking the association between LDL-C and TAO onset: LDL-C had a direct effect on TAO(Total effect value=0.274, 95% CI 0.161-0.386), while IL-6(mediated effect=0.067, 95% CI 0.011-0.123) and IL-17(mediated effect=0.042, 95% CI 0.007-0.077) partially mediated the effect of LDL-C on TAO, accounting for 24.45% and 15.33% of the total effect, respectively. IL-6 was a potential mediator of the association between LDL-C and TAO activity: LDL-C had a direct effect on TAO activity(Total effect value=0.320, 95% CI 0.204-0.435), and IL-6(mediated effect=0.103, 95% CI 0.021-0.185) partially mediated the effect of LDL-C on TAO activity, with a mediation effect of 32.19%. Conclusion:IL-6 plays a partiall mediating role in the association of LDL-C with TAO onset and activity.

Astaxanthine (AST) has important biological activities including antioxidant and anti-inflammatory effects that could alleviate neurological and heart diseases, but its role in the prevention of cisplatin-induced hearing loss (CIHL) is not yet well understood. In our study, a steady interaction between AST and the E3 ligase adapter Kelch-like ECH-associated protein 1, a predominant repressor of nuclear factor erythroid 2-related factor 2 (NRF2), was performed and tested via computer molecular docking and dynamics. AST protected against cisplatin-induced ototoxicity via NRF2 mediated pathway using quantitative PCR and Western blotting. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential revealed that AST reduced ROS overexpression and mitochondrial dysfunction. Moreover, AST exerted anti-apoptosis effects in mouse cochlear explants using immunofluorescence staining and HEI-OC1 cell lines using quantitative PCR and Western blotting. Finally, AST combined with poloxamer was injected into the middle ear through the tympanum, and the protection against CIHL was evaluated using the acoustic brain stem test and immunofluorescent staining in adult mice. Our results suggest that AST reduced ROS overexpression, mitochondrial dysfunction, and apoptosis via NRF2-mediated pathway in cisplatin-exposed HEI-OC1 cell lines and mouse cochlear explants, finally promoting cell survival. Our study demonstrates that AST is a candidate therapeutic agent for CIHL.

Objective: To explore the correlation between obesity and first ejaculation in boys aged 11-18 years old in Ningxia in 2019, and to provide the theoretical reference for puberty development among obese boys. Methods: Using the method of stratified random cluster sampling, 5 240 boys aged 11- 18 were selected from Yinchuan, Zhongwei, Wuzhong and Guyuan in Ningxia Hui Autonomous Region. Height, weight, and first ejaculation were obtained.Body mass index (BMI) was calculated to determine nutritional status, and the χ 2 test was used to compare the differences between groups of nutritional status; the probability unit regression method was used to calculater the soth percentile age at ejaculation, and the U test was applied to compare the differences in age at ejaculation between groups. Results: The rates of overweight and obesity among boys aged 11 to 18 years in Ningxia Hui Autonomous Region in 2019 were 15.5% and 8.8%. The detection rate of overweight and obesity among urban boys was 17.8% and 10.5% and the detection rate of overweight and obesity among rural boys was 12.9% and 6.9%,respectively. The 50 th percentile age at half ejaculation among urban boys aged 11 to 18 years was 14.94 years; the 50 th percentile age at ejaculation among rural boys was 15.33 years( P <0.01). The 50 th percentile age at ejaculation was 15.61, 15.10, 15.05 and 15.05 years for boys in the wasted, normal weight, overweight and obese groups, respectively. Conclusion Nutritional status was not associated with age at first ejaculation in the present study,but warrants farther investigation.

Objective: To understand the nutritional status and physical quality of children and adolescents aged 6-18 in Ningxia in 2019, so as to provide scientific basis for health promotion children and adolescents. Methods: A total of 16 076 children and adolescents aged 6-18 years old from Ningxia were selected by multi stage stratified cluster random sampling. Weight, height and physical fitness indexes (50 m running, standing long jump, sitting forward flexion) were measured and analyzed. The Chi square test was carried out to compare differences between groups, and the relationship between nutritional status and physical fitness was assessed by Logistic regression models. Results: In 2019, detection rate of stunting loss rate, overweight and obesity rate of children and adolescents aged 6-18 in Ningxia were 6.9%, 12.6% and 8.7%, respectively. The below average rates of sitting forward flexion, 50 m running and standing long jump were 10.0%, 8.6% and 26.7%, respectively, while the passing rates were 63.5%, 63.7% and 55.5%, respectively. The good rates were 14.7%, 11.7% and 12.3%, and the excellent rates were 11.8%, 16.0 % and 5.5%, respectively. The passing rates of sitting forward flexion, 50 m running and standing long jump in stunting group were lower than those in the normal weight group ( OR=0.75, 0.72, 0.77, P ＜0.05); the passing rates of 50 m run and standing long jump in the overweight group was lower than that of normal weight group ( OR=0.79, 0.52, P ＜0.05); the passing rates of sitting forward flexion, 50 m running and standing long jump in the obese group were lower than those in the normal weight group ( OR=0.73, 0.52, 0.32, P ＜0.05). Conclusion In 2019, children and adolescents in Ningxia have the doublel burden of stunting, overweight and obesity. Physical fitness is associated with nutritional status, suggesting weight control might be helpful to keep fitness among children and adolescents.

Objective:To evaluate the efficacy and safety of dupilumab in the treatment of adult prurigo nodularis.Methods:A prospective study was conducted on patients with prurigo nodularis who received the treatment with dupilumab in Peking University People′s Hospital from January 2021 to November 2021. Efficacy was assessed using the Investigator′s Global Assessment (IGA) , Numerical Rating Scale (NRS) and Dermatology Life Quality Index (DLQI) at weeks 0, 4 and 16. Wilcoxon signed-rank test and paired t test were used to analyze changes in the above parameters before and after treatment. Results:A total of 17 patients were enrolled in this study, including 12 females and 5 males, aged 48.47 ± 16.26 years. After 16-week treatment with dupilumab, the pruritus NRS score decreased from 8.00 ± 1.50 at baseline to 1.29 ± 0.85 ( t = 6.98, P < 0.001) , the sleeplessness NRS score decreased from 5.18 ± 2.98 at baseline to 0.12 ± 0.49 ( t = 12.55, P < 0.001) , and the DLQI score declined from 13.29 ± 4.03 at baseline to 0.88 ± 0.70 ( t = 16.39, P < 0.001) ; at week 16, the IGA grade of all the 17 patients decreased from 3 - 4 at baseline to 0 - 2, 16 achieved IGA grades 0 - 1, and 12 achieved IGA grade 0. During the treatment, mild conjunctivitis occurred in 2 cases, local injection reaction occurred in 1, and both conditions were improved after short-term symptomatic treatment. Conclusion:Dupilumab is markedly effective and safe in the treatment of adult prurigo nodularis.

Objective:To study the influencing factors of influenza-associated severe acute respiratory illness (SARI) in children younger than 5 years of old in Suzhou, and to provide evidence to support the improvement of prevention and control strategies for influenza in children.Methods:We conducted a prospective influenza surveillance for hospitalized SARI and outpatient influenza-like illness (ILI) at Children′s Hospital of Soochow University from April 2011 to March 2017. We compared the clinical and other characteristics of influenza-positive patients with SARI to those with ILI to find the differences and to identify influencing factors of influenza-associated SARI, using χ2 test and unconditional logistic regression. Results:We found 786 cases of influenza-associated ILI and 413 cases of influenza-associated SARI during the study period. Cough, runny nose, shortness of breath, asthma or wheezing were more common in influenza-associated SARI than in influenza-associated ILI ( P<0.01). Univariate and multivariate logistic regression showed that the influencing factors which significantly associated with increased risk of influenza-associated SARI were as follows: younger age (<6 months OR=3.6, 6-23 months a OR=2.5), respiratory infection history within 3 months (a OR=4.5), chronic lung disease history ( OR=3.4), fever above 39.0 ℃ (39.0-39.9 ℃ a OR=2.4, ≥40.0 ℃ a OR=6.0), and the presence of A/H1N1 (a OR=2.3), A/H3N2 (a OR=1.9). Conclusion:Children younger than 2 years old, with a history of chronic lung disease, a history of respiratory infection within 3 months, or with a fever peak above 39.0 ℃ should seek medical advice as soon as possible or receive annual influenza vaccination to reduce the incidence of influenza-associated serious outcomes.