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 revise Guidelines for Diagnosis and Treatment of Commom Diseases of Pediatrics in Traditional Chinese Medicine·Recurrent Respiratory Tract Infections in Children through the Delphi method-based expert questionnaire survey.Methods Bsaed on a comprehensive literature review,the expert questionnaire was developed for the 2024 Edition of the guidelines.Using the Delphi method,the questionnaire was distributed in three rounds to gather expert opinions.Statistical analyses were conducted on expert positivity coefficients and consensus levels,evaluated by expert familiarity,the concentration of expert opinions,and their degree of coordination.Results After three rounds of consultation,consensus was achieved among experts regarding the terminology and definitions,diagnosis,syndrome differentiation,treatment,prevention and health related to recurrent respiratory tract infections in children.This led to the formulation of a draft version of the 2024 Edition of the guidelines for further consultation.Conclusion The participating experts were geographically diverse,held senior titles,and possessed extensive clinical experience,ensuring the credibility of the findings.Their high level of engagement throughout the survey process indicates strong motivation.The content of the expert questionnaire of the Guidelines for the Diagnosis and Treatment of Traditional Chinese Medicine in Children with Recurrent Respiratory Tract Infections in Children(2024 Edition)objectively reflects the core perspectives of the experts,and the results are authentic and reliable,providing a solid foundation for the development of the guidelines.

Objective To explore syndrome and treatment law of TCM in treating pediatric pneumonia convalescence;To provide references for clinical syndrome differentiation and treatment.Methods The relevant literature about TCM in treating pediatric pneumonia convalescence was retrieved from CNKI,SinoMed,VIP,Wanfang Data and PubMed from the establishment of the databases to December 31,2024.Diagnostic basis,syndrome elements and TCM prescription information were extracted.Excel 2021 was used for frequency statistics,SPSS Modeler 18.0 was used for association rule analysis,Gephi 0.10.1 was used to complete complex network analysis,and Origin 2025 was used for data visualization.Results A total of 171 articles were included.Diagnosis basis predominantly involved symptoms,signs and course of the disease.TCM syndrome element distribution predominantly involved the lung,spleen,qi deficiency,yin deficiency,phlegm,dampness,blood stasis and heat,often presenting as a mixture of deficiency and excess patterns.A total of 98 prescriptions were collected,with high-frequency herbs primarily including tonifying and deficiency-replenishing herbs,and phlegm-resolving and antitussive herbs.The herbal properties and tastes were mainly warm,neutral,slightly cold,and sweet,bitter,pungent,primarily associated with the lung and spleen meridians.Complex network analysis identified three core patterns of syndrome-herb interactions.Conclusion The diagnosis of pediatric pneumonia convalescence relies on symptoms,signs and course of the disease as key criteria.The syndrome is often characterized by a deficiency-excess complex.Treatment should integrate the dynamic interactions among syndrome elements and adjust the balance between reinforcing healthy qi and eliminating pathogens based on the proportional weight of deficiency and excess.For deficiency patterns,it is necessary to focus on tonifying qi and nourishing yin.For concurrent syndromes or pathological factors,additional methods such as resolving phlegm,clearing heat,regulating qi,drying dampness,promoting digestion,cooling blood,and activating blood circulation may be incorporated.

Objective:To investigate the composition of immune cells and fibroblastic reticular cells (FRCs) in the lymph nodes (LNs) follicles of human immunodeficiency virus (HIV)-infected individuals with varying immune statuses, and their association with HIV replication.Methods:Neck LNs samples were collected from 4 treatment-naive, newly diagnosed HIV-infected individuals with diverse immune statuses. RNA in situ sequencing was employed, with imaging achieved via rolling circle amplification and fluorescence labeling. By integrating cell segmentation and nuclear staining, single-cell data from up to one hundred thousand cells were generated per paraffin tissue section. Using lymphoid follicles as the unit of analysis, compositional changes in immune cells and FRCs were characterized, and their correlations with viral replication were evaluated. Results:The peripheral blood CD4 + T cell counts of samples LN_1, LN_2, LN_3, and LN_4 exhibited a sequential decrease. A total of 31, 15, 16, and 18 structurally intact follicles were identified in each sample, respectively. In the follicles of LN_1, the proportion of HIV-replicating cells positively correlated with cDCs abundance ( R2=0.2, P=0.011), and HIV RNA signals were spatially colocalized with cDCs and FRCs. In the follicles of LN_2, HIV RNA molecules showed preferential enrichment within FRCs. In sample LN_3, HIV RNA enrichment was observed in both cDCs and CD4 + T cells. In sample LN_4, the proportion of cells with HIV replication was positively correlated with the proportions of the following cells: cDCs ( R2=0.38, P=0.006 4), CD4 + T cells ( R2=0.28, P=0.025), and FRCs ( R2=0.26, P=0.029), and HIV RNA molecules were detected in cDCs, CD4 + T cells, and FRCs. LN_1 and LN_2 samples showed a trend toward negative correlation between HIV-replicating cell proportion and CD8 + T cells proportion. LN_4 sample demonstrated a significant positive correlation between HIV-replicating cell proportion and CD8 + T cells proportion ( R2=0.23, P=0.046). Conclusions:RNA in situ sequencing technology reveals unique distribution patterns of immune cells and viral replication in LNs follicles of HIV-infected individuals. The follicular immune microenvironment exhibits distinct characteristics associated with peripheral blood CD4 + T cell counts, providing novel insights into the spatial dynamics of HIV persistence and immune cell interactions during infection.

Objective To revise Guidelines for Diagnosis and Treatment of Commom Diseases of Pediatrics in Traditional Chinese Medicine·Recurrent Respiratory Tract Infections in Children through the Delphi method-based expert questionnaire survey.Methods Bsaed on a comprehensive literature review,the expert questionnaire was developed for the 2024 Edition of the guidelines.Using the Delphi method,the questionnaire was distributed in three rounds to gather expert opinions.Statistical analyses were conducted on expert positivity coefficients and consensus levels,evaluated by expert familiarity,the concentration of expert opinions,and their degree of coordination.Results After three rounds of consultation,consensus was achieved among experts regarding the terminology and definitions,diagnosis,syndrome differentiation,treatment,prevention and health related to recurrent respiratory tract infections in children.This led to the formulation of a draft version of the 2024 Edition of the guidelines for further consultation.Conclusion The participating experts were geographically diverse,held senior titles,and possessed extensive clinical experience,ensuring the credibility of the findings.Their high level of engagement throughout the survey process indicates strong motivation.The content of the expert questionnaire of the Guidelines for the Diagnosis and Treatment of Traditional Chinese Medicine in Children with Recurrent Respiratory Tract Infections in Children(2024 Edition)objectively reflects the core perspectives of the experts,and the results are authentic and reliable,providing a solid foundation for the development of the guidelines.

Objective To explore syndrome and treatment law of TCM in treating pediatric pneumonia convalescence;To provide references for clinical syndrome differentiation and treatment.Methods The relevant literature about TCM in treating pediatric pneumonia convalescence was retrieved from CNKI,SinoMed,VIP,Wanfang Data and PubMed from the establishment of the databases to December 31,2024.Diagnostic basis,syndrome elements and TCM prescription information were extracted.Excel 2021 was used for frequency statistics,SPSS Modeler 18.0 was used for association rule analysis,Gephi 0.10.1 was used to complete complex network analysis,and Origin 2025 was used for data visualization.Results A total of 171 articles were included.Diagnosis basis predominantly involved symptoms,signs and course of the disease.TCM syndrome element distribution predominantly involved the lung,spleen,qi deficiency,yin deficiency,phlegm,dampness,blood stasis and heat,often presenting as a mixture of deficiency and excess patterns.A total of 98 prescriptions were collected,with high-frequency herbs primarily including tonifying and deficiency-replenishing herbs,and phlegm-resolving and antitussive herbs.The herbal properties and tastes were mainly warm,neutral,slightly cold,and sweet,bitter,pungent,primarily associated with the lung and spleen meridians.Complex network analysis identified three core patterns of syndrome-herb interactions.Conclusion The diagnosis of pediatric pneumonia convalescence relies on symptoms,signs and course of the disease as key criteria.The syndrome is often characterized by a deficiency-excess complex.Treatment should integrate the dynamic interactions among syndrome elements and adjust the balance between reinforcing healthy qi and eliminating pathogens based on the proportional weight of deficiency and excess.For deficiency patterns,it is necessary to focus on tonifying qi and nourishing yin.For concurrent syndromes or pathological factors,additional methods such as resolving phlegm,clearing heat,regulating qi,drying dampness,promoting digestion,cooling blood,and activating blood circulation may be incorporated.

Objective:To investigate the composition of immune cells and fibroblastic reticular cells (FRCs) in the lymph nodes (LNs) follicles of human immunodeficiency virus (HIV)-infected individuals with varying immune statuses, and their association with HIV replication.Methods:Neck LNs samples were collected from 4 treatment-naive, newly diagnosed HIV-infected individuals with diverse immune statuses. RNA in situ sequencing was employed, with imaging achieved via rolling circle amplification and fluorescence labeling. By integrating cell segmentation and nuclear staining, single-cell data from up to one hundred thousand cells were generated per paraffin tissue section. Using lymphoid follicles as the unit of analysis, compositional changes in immune cells and FRCs were characterized, and their correlations with viral replication were evaluated. Results:The peripheral blood CD4 + T cell counts of samples LN_1, LN_2, LN_3, and LN_4 exhibited a sequential decrease. A total of 31, 15, 16, and 18 structurally intact follicles were identified in each sample, respectively. In the follicles of LN_1, the proportion of HIV-replicating cells positively correlated with cDCs abundance ( R2=0.2, P=0.011), and HIV RNA signals were spatially colocalized with cDCs and FRCs. In the follicles of LN_2, HIV RNA molecules showed preferential enrichment within FRCs. In sample LN_3, HIV RNA enrichment was observed in both cDCs and CD4 + T cells. In sample LN_4, the proportion of cells with HIV replication was positively correlated with the proportions of the following cells: cDCs ( R2=0.38, P=0.006 4), CD4 + T cells ( R2=0.28, P=0.025), and FRCs ( R2=0.26, P=0.029), and HIV RNA molecules were detected in cDCs, CD4 + T cells, and FRCs. LN_1 and LN_2 samples showed a trend toward negative correlation between HIV-replicating cell proportion and CD8 + T cells proportion. LN_4 sample demonstrated a significant positive correlation between HIV-replicating cell proportion and CD8 + T cells proportion ( R2=0.23, P=0.046). Conclusions:RNA in situ sequencing technology reveals unique distribution patterns of immune cells and viral replication in LNs follicles of HIV-infected individuals. The follicular immune microenvironment exhibits distinct characteristics associated with peripheral blood CD4 + T cell counts, providing novel insights into the spatial dynamics of HIV persistence and immune cell interactions during infection.

Objective:To investigate the risk factors of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients in plain-sand areas and loess hilly areas of Gansu province.Methods:A total of 1 599 T2DM patients who participated in chronic disease and risk factors monitoring and basic public health service management were selected by multi-stage stratified random sampling method in the sandy plain areas and loess hilly areas of Gansu province. Questionnaire survey, physical measurement and laboratory tests were performed. Multivariate binary logistic model was used to analyze the influencing factors.Results:The prevalence of DKD was 22.1% (174/787) among T2DM patients in the sandy plain areas and 19.1%(155/812) in the loess hilly area, respectively. Hypertension ( OR=3.022), hyperuricemia ( OR=2.114) and HbA1c≥7%( OR=2.231) were the risk factors for DKD in the plain-sand areas, and the risk of DKD increased with age. In the loess hilly areas, female sex ( OR=0.379) was the protective factor for DKD; while duration of disease≥10 years ( OR=2.476), hyperuricemia ( OR=1.907), HbA1c≥7% ( OR=1.927) were the risk factors for DKD; and the risk of DKD increased with the increase of age, and decreased with the increase of per capita monthly income. Conclusions:The prevalence of DKD and its influencing factors are different between sandy plain areas and loess hilly areas in Gansu province. The prevention and treatment of hypertension should be given more attention in sandy plain areas. In addition, the screening of DKD should be conducted among T2DM patients, particularly for those with old age, hyperuricemia and HbA1c≥7% in both areas of the province.

Humans ; Bipolar Disorder ; Schizophrenia ; Depression ; Electroencephalography

Objective To investigate the efficacy of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) and the treatment measures for poor response in previously untreated chronic hepatitis B (CHB) patients with high viral load. Methods A total of 165 CHB patients who received antiviral therapy and met the inclusion criteria in Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, from June 2016 to July 2021 were enrolled. The patients enrolled had a baseline HBV DNA level of > 6lg copies/ml and were previously untreated CHB patients who had used ETV or TDF for 48 weeks, and quantitative real-time PCR was used to measure HBV DNA. Virologic response rate was calculated after 48 weeks of treatment; a logistic regression analysis was used to investigate the influencing factors for the response of HBV DNA < 500 copies/mL and HBV DNA < 100 copies /mL at 48 weeks; a stratified analysis was performed to compare the virologic response rate of HBV DNA < 500 copies /ml and HBV DNA < 100 copies/ml after 48 weeks between the patients with different ages, sexes, baseline HBV DNA levels, baseline alanine aminotransferase (ALT) levels, types of first-line medication, and HBeAg statuses. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups, and the binary logistic regression model was used for multivariate analysis. Results After 48 weeks of treatment, 85.5% (141/165) of the patients achieved an HBV DNA load of < 500 copies/mL, and 66.1% (109/165) of the patients achieved an HBV DNA load of < 100 copies /mL, with no significant difference in treatment outcome between the ETV group and the TDF group. The multivariate logistic regression analysis showed that sex( OR =2.793, 95% CI : 1.197-6.517), baseline HBV DNA( OR =0.369, 95% CI : 0.142-0.959), baseline ALT( OR =4.556, 95% CI : 1.770-11.732), and baseline HBeAg( OR =0.120, 95% CI : 0.033-0.429) were influencing factors for complete virologic response(all P < 0.05). For the patients with normal ALT (≤40 U/L) at baseline, 75.6% (34/45) achieved an HBV DNA load of < 500 copies/mL after 48 weeks of treatment, and 53.3% (24/45) achieved an HBV DNA load of < 100 copies/mL, with no significant difference in treatment outcome between the ETV group and the TDF group. For the patients with abnormal ALT (> 40 U/L) at baseline, 89.2% (107/120) achieved an HBV DNA load of < 500 copies/mL after 48 weeks of treatment, and the proportion of such patients in the TDF group was significantly higher than that in the ETV group (96.1% vs 84.1%, χ 2 =4.386, P =0.036); 70.8% (85/120) achieved an HBV DNA load of < 100 copies/mL, the proportion of such patients was no significant difference between the TDF group and the ETV group (78.4% vs 65.2%). The response of HBV DNA < 100 copies/ml of the normal baseline ALT group and the abnormal baseline ALT group, there were no significant differences between the patients aged≤30 years and aged > 30 years (77.8% vs 47.2%, 85.2% vs 66.7%). For the patients who did not achieve complete virologic response (HBV DNA ≥100 copies/mL) after 48 weeks of treatment, 87.9% (29/33) achieved complete virologic response after the original treatment regimen was prolonged for 48 weeks, and 100% (9/9) of the patients achieved complete virologic response after switching to or adding the first-line nucleos(t)ide analogues (NUCs) without cross-resistance sites with the original regimen for another 48 weeks. Conclusion The patients aged > 30 years should receive antiviral therapy as early as possible, regardless of viral load and ALT level, especially those with a family history of liver cirrhosis or hepatocellular carcinoma; the patients aged ≤30 years who have a normal ALT level and a high viral load should consider initiating antiviral therapy after providing informed consent. For the patients with poor response after 48 weeks of treatment, first-line NUCs without cross-resistance sites with the original regimen should be switched to or added in time.