Oxide Ion Conduction in Ca-Doped Yb3Ga5O12 Garnet.

Developing oxide ion conductors with new structural families is important for many energy conversion and storage techniques. Herein, a series of Ca-doped Yb3Ga5O12 garnet-type materials are prepared through a traditional solid-state reaction method, with their oxide ion conduction properties being reported for the first time. The results revealed that Ca substitution for Yb would significantly improve the conductivity of Yb3Ga5O12 from 3.57 × 10-7 S/cm at 900 °C under air to 1.66 × 10-4 S/cm, with an oxide ion transporting number of ∼0.52. The oxygen vacancy defect formation energy (∼0.127 eV) and the local structure around an oxygen vacancy were studied by atomic-level static lattice simulations based on the interatomic potential method. The oxide ion conducting mechanism was studied by the bond-valence-based method, which revealed three-dimensional pathways for oxide ion migration in both the parent and Ca-doped structures. The simulated activation energy of oxide ion migration decreased slightly from ∼0.358 eV in the parent structure to 0.346 eV in the doped one. These discoveries in the Ca-doped Yb3Ga5O12 will stimulate extensive exploitation and fundamental research on garnet-type materials.

USP25 inhibits DNA damage by stabilizing BARD1 protein in a house dust mite-induced asthmatic model in vitro and in vivo.

House dust mites (HDM) can cause DNA double-strand breaks in the lungs of asthmatic patients. However, the molecular mechanisms driving DNA damage and repair in HDM-induced asthma are yet to be elucidated. Thus, in this study, HDM treatment was applied to BEAS-2B cells and mice to mimic the pathological process of asthma in vitro and in vivo, respectively. γ-H2AX foci and expression were measured by immunofluorescence staining and western blot, respectively. The levels of interleukin (IL)-4, IL-6, IL-13, and tumour necrosis factor α (TNFα) were measured using enzyme-linked immunoassay. The expression of USP25 and BARD1 was measured by reverse transcription quantitative PCR and western blot. Co-immunoprecipitation and ubiquitination assays were employed to detect the relationship between USP25 and BARD1. As per the results, it was found that the deubiquitylating enzyme USP25 repressed HDM-induced DNA damage and the production of proinflammatory cytokines, including TNF-α, IL-4, IL-8, and IL-13, in BEAS-2B cells; in contrast, the depletion of USP25 led to the opposite effects. USP25-mediated inhibition of DNA damage and inflammation was facilitated by the stabilizing protein BARD1, which is a tumor suppressor that principally functions by promoting DNA repair and replication in BEAS-2B cells. Furthermore, USP25 was found to robustly augment BARD1 protein abundance and prevent HDM-induced DNA damage and inflammation in vivo. Taken together, these results suggest a novel mechanism contributing to DNA damage and repair in HDM-induced asthma and that selectively modulating this pathway could lead to a novel therapeutic approach for controlling and managing asthma due to HDM exposure.

Therapeutic drug monitoring of caffeine and its primary metabolites in plasma using LC-ESI-MS/MS for apnea of prematurity treatment: Evaluation of ultrapure water as a surrogate matrix.

The growing evidence has endorsed the view that therapeutic drug monitoring of caffeine for apnea of prematurity is helpful for dose tailoring when the therapeutic response is lacking or toxicity is suspected. However, plasma without caffeine is difficult to obtain. Therefore, a method was developed and validated to measure caffeine and its three primary metabolites (paraxanthine, theobromine and theophylline) using LC-ESI-MS/MS in human plasma and several surrogate matrices. The chromatographic separation of analytes was finally achieved on a Waters Symmetry C18 (4.6 × 75 mm, 3.5 µm) column. Several strategies were successfully applied to overcome the matrix effects: (a) appropriate dilution for sample cleanup; (b) a starting lower proportion of organic phase; and (c) multiple individual stable-labeled isotopic internal standards. The parallelism between the authentic matrix and surrogate matrices was convincing. The recovery of the analytes in both human plasma and rat plasma was acceptable over the linear range (0.500-50.0 µg/ml for caffeine and 0.0100-1.00 µg/ml for three metabolites). The method was successfully applied in 118 samples from 74 preterm infants with apnea of prematurity. The rat plasma or ultrapure water as a surrogate matrix is worthy of recommendation for routine therapeutic drug monitoring of caffeine.

Update on recommendations for the diagnosis and treatment of SARS-CoV-2 infection in children.

Since the outbreak of novel coronavirus infection pneumonia in Wuhan City, China, in late 2019, such cases have been gradually reported in other parts of China and abroad. Children have become susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their immature immune function. As the outbreak has progressed, more cases of novel coronavirus infection/pneumonia in children have been reported. Compared with adults, the impact of SARS-CoV-2 infection in children is less severe, with a lower incidence and susceptibility in children, which results in fewer children being tested, thereby underestimating the actual number of infections. Therefore, strengthening the diagnosis of the disease is particularly important for children, and early and clear diagnosis can determine treatment strategies and reduce the harm caused by the disease to children. According to the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (trial version 7) issued by National Health Committee and the latest diagnosis and treatment strategies for novel coronavirus infection pneumonia in children, this review summarizes current strategies on diagnosis and treatment of SARS-CoV-2 infection in children.

Microbial contributions to bronchial asthma occurrence in children: A metagenomic study.

Bronchial asthma, a common chronic respiratory disease in children, is traditionally regarded as a noninfectious disease. Current hypotheses, however, argue that asthma can be caused by microbial infection. We, therefore, hypothesize that a variety of microbes are more commonly found in the sputum of children with asthma, and these microbes may contribute to the occurrence and development of asthma. The present study proposes to use metagenomic approach to explore microbial diversity and to identify the microbial community characteristics of sputum from children with asthma. We found that microbial communities in the sputum of children differed significantly between asthmatics and controls. Kruskal-Wallis testing showed that 16 phyla, 104 genera, and 159 species were significantly downregulated, whereas two phyla including Platyhelminthes phylum and Chordata phylum, two genera including Spirometra genus and Homo sapiens, and the Spirometra erinaceieuropaei species were significantly upregulated in asthma patients compared with controls (P < 0.05). Among them, H. sapiens and S. erinaceieuropaei exhibited 2.3- and 2.0-fold overabundance in asthmatics vs controls, respectively. Meanwhile, metastats assay demonstrated that 31 phyla, 400 genera, and 813 species were significantly downregulated, whereas two phyla, 10 genera, and 16 species were significantly upregulated in asthma patients compared with controls (P < 0.05). Among them, Tetrahymena thermophila and Candidatus Zinderia insecticola exhibited 4.7-fold overabundance in asthmatics vs controls. Our study establishes a link between microbial infection and the mechanisms leading to asthma development, which will be useful for developing novel diagnostic biomarkers and aiding in the prevention and control of asthma.

Urine metabolic profiles in paediatric asthma.

BACKGROUND AND OBJECTIVE: Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology. METHODS: Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes. RESULTS: We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold-change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma. CONCLUSION: Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.

Der p 1 and Der p 2 specific immunoglobulin E measurement for diagnosis of Dermatophagoides pteronyssinus allergy: A systematic review and meta-analysis.

BACKGROUND: A clinical history of allergic symptoms and a skin-prick test with house-dust mite crude extracts are standard diagnostic procedures for Dermatophagoides pteronyssinus allergy. Specific immunoglobulin E (IgE) responses to Der p 1 and Der p 2 allergens have been used for the diagnosis of D. pteronyssinus allergy; however, evaluation of the diagnostic performance of Der p 1 and Der p 2 specific IgE (sIgE) produced inconsistent findings. We sought to evaluate the diagnostic accuracy of Der p 1 sIgE and Der p 2 sIgE measurement in the diagnosis of D. pteronyssinus allergy by performing a systematic review and meta-analysis of previously published studies. METHODS: Several medical literature electronic data bases were searched for related literature published through August 1, 2016. A bivariate model was used to pool estimates of sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating curves as the main diagnostic measures. RESULTS: Eight studies, which involved 1095 patients, were included in our analysis. The pooled estimates of sensitivity, specificity, and diagnostic odds ratio for Der p 1 were 0.84, 0.97, and 166.57, respectively. The combined results for Der p 2 were a sensitivity of 0.87, specificity of 1.00, and a diagnostic odds ratio of 17342.35. The areas under the summary receiver operating curves for Der p 1 sIgE and Der p 2 sIgE were 0.94 and 0.98, respectively. CONCLUSION: Our results supported the use of Der p 1 and Der p 2 sIgE in the diagnosis of D. pteronyssinus allergy. Both displayed good diagnostic performance and would be useful in a clinical setting in the accurate diagnosis of dust mite allergy.

[Metabonomics of Syndrome Markers in Infantile Bronchial Asthma Episode].

Objective To analyze urinary metabolites of bronchial asthma children patients with phlegm-heat obstructing Fei syndrome (PHOFS) and non-PHOFS using gas chromatography-mass spec- trometry/mass spectrometer ( GC-MS/MS) , thus performing research on syndrome markers. Methods Totally 44 bronchial asthma children patients with PHOFS and non-PHOFS in onset of asthma were recrui- ted. Another 29 healthy children were also recruited. Their urine samples were analyzed by GC-MS/MS. The profiles were analyzed using orthogonal partial least squares-discriminant analysis (OPLS-DA) , vari- able importance in the projection (VIP) , and non-parametric test to determine intergroup differential metabolites. Abnormal metabolic pathways were determined by Metaboanalyst. Results Compared with the health control group, contents of fourteen substances like inositol, uric acid, stearic acid, and so on de- creased, and mino-malonic acid content increased in asthma episode children (P <0. 05). The process was mainly involved in 5 metabolic pathways such as lysine degradation and biosynthesis, pyruvate me- tabolism, and so on. Compared with the non-PHOFS group in bronchial asthma episode, contents of nine substances like oxalic acid, L-threonine, pyrimidine, and so on decreased in the PHOFS group (P < 0. 05). The process was mainly involved in 5 metabolic pathways such as pentose phosphate pathway, inositol phosphate metabolism, and so on. Conclusions Urinary metabolites are different in infantile bronchial asthma episode and healthy children. Metabolic biomarkers and pathways exist in different syn- dromes in bronchial asthma episode.

The Functional IgE-Blocking Factor Induced by Allergen-Specific Immunotherapy Correlates with IgG4 Antibodies and a Decrease of Symptoms in House Dust Mite-Allergic Children.

BACKGROUND: At present, there are no validated biomarkers reflecting or predicting the clinical efficacy of allergen-specific immunotherapy (AIT) . We aimed to investigate the correlations between clinical and immunological responses of patients undergoing house dust mite (HDM) AIT. METHODS: Sixty-nine children diagnosed with HDM allergic rhinitis and/or asthma received standardized Dermatophagoides pteronyssinus (Dp) subcutaneous AIT for 12 months. Twenty HDM-allergic children served as an open control group. Clinical symptom and medication scores were recorded and Dp-specific IgE, IgG4 and IgE-blocking factor were measured before AIT and after 4 and 12 months of AIT. RESULTS: Symptom scores decreased after 4 months and continued to decrease during 12 months of AIT. No differences in medication scores were observed between AIT and the control group during the study period. Levels of Dp IgG4 increased after 4 months and correlated to symptom scores at 12 months (r = -0.296, p = 0.013) of AIT. The Dp IgE-blocking factor increased after 4 months of AIT, and correlated with symptom scores at 4 months (r = -0.307, p = 0.010) and 12 months (r = -0.288, p = 0.016) of AIT. A strong correlation between Dp IgE-blocking factor and Dp IgG4 during AIT (4 months: r = 0.680; 12 months: r = 0.636, both p < 0.0001) was observed. Patients with IgE-blocking factor ≥0.2 after 4 months of AIT showed lower symptom scores at 12 months of AIT (p = 0.0093). CONCLUSIONS: Subcutaneous HDM AIT results in a decrease of allergic symptoms among HDM-allergic children. IgE-blocking activity increased after 4 months of AIT and correlated with clinical symptoms. A high IgE-blocking factor at an early stage of AIT is associated with fewer symptoms at a later stage of AIT.

Relationships between the varied ciliated respiratory epithelium abnormalities and severity of Mycoplasma pneumoniae pneumonia.

BACKGROUND: The pathogenesis of Mycoplasma pneumoniae infection involves cytoadherence of M. pneumoniae to the ciliated respiratory epithelium (CRE), followed by CRE injury caused by the M. pneumoniae. However, whether CRE abnormalities are related to the severity of M. pneumoniae pneumonia (MP) remains to be determined. METHODS: Thirty-eight patients with MP and 8 controls who underwent fiber-optic bronchoscopy with bronchial biopsy were included in this study. Patients with MP were divided into 2 groups: a mild disease group (12 patients) and a severe disease group (26 patients). The clinical features, laboratory findings, chest radiographic findings, and CRE abnormalities were characterized. RESULTS: Patients with severe pneumonia had a higher epithelial integrity score than those with mild pneumonia (5.1 ± 0.76 vs 3.8 ± 0.75; p < 0.01). Patients with severe CRE abnormalities had a longer duration of fever (p < 0.01), higher C-reactive protein (p < 0.01), and lower proportion of blood lymphocytes (p < 0.05) compared to those with mild abnormalities. Patients with a positive bacteria culture had a higher epithelial integrity score compared to those with a negative culture (6.0 ± 0.44 vs 4.8 ± 0.71; p < 0.01). CONCLUSIONS: CRE abnormalities are closely related to the severity of MP. These findings extend our current knowledge of MP.

Clinical study of electro-acupuncture treatment with different intensities for functional constipation patients.

Functional constipation (FC) is a common functional bowel disorder disease that affects life quality of a large number of people. This study aimed to explore the impact of different intensities of electro-acupuncture (EA) treatment for FC patients. Totally, 111 patients with FC meeting the Rome III criteria were randomly assigned to different intensities of EA groups (low and high intensity of EA groups) and medicine-controlled (MC) group. In EA groups, patients were treated with EA at quchi (LI11) and shangjuxu (ST37) bilaterally for 4 weeks, 5 times/week in the first 2 weeks, and 3 times/week in the last 2 weeks. In MC group, 5 mg mosapride citrate was administered orally 3 times/day for 4 weeks. Spontaneous bowel movement frequency each day was recorded using a constipation diary. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to assess the patients' psychological state. Cortisol (CORT), substance P (SP), and vasoactive intestinal polypeptide (VIP) were evaluated at baseline and at the end of 4 weeks after treatment. As compared with the baseline, there was statistically significant increase in stool frequency every week (P<0.01), but there was no statistically significant difference among the three groups. As compared with the baseline, after 4 weeks of EA therapy, the scores of SDS and serum levels of CORT were decreased significantly in low intensity of EA group (P<0.01), and the serum levels of SP and VIP were increased significantly (P<0.05); the scores of SAS and SDS and serum levels of CORT were decreased significantly in high intensity of EA group (P<0.05), and the serum levels of SP and VIP were increased significantly (P<0.05); the serum levels of CORT and VIP were increased significantly in MC group (P<0.05). As compared with MC group, after 4 weeks of treatment, the serum levels of SP were signifcicantly increased in low intensity of EA group (P<0.01). Low and high intensities of EA could increase the stool frequency, improve the FC patient's anxiety and depression, reduce the serum levels of CORT, and increase the serum levels of SP and VIP effectively. It is concluded that both low and high intensities of EA are effective for FC patients, but there is no significant difference between the low and high intensities of EA.

Mining and evaluation of adverse event signals for capmatinib based on the FAERS database.

Objective: To conduct a comprehensive data analysis based on the FDA's Adverse Event Reporting System (FAERS) to mine possible adverse event (AE) signals of Capmatinib, providing valuable references for its clinical application. Methods: Capmatinib was the primary suspected drug in the search of FAERS database from the second quarter of 2020 to the fourth quarter of 2023. Data processing, screening, and classification were performed using methods such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Results: A total of 1,991 AE reports directly related to Capmatinib were screened, identifying 269 Preferred Terms (PTs) involving 26 System Organ Classes (SOCs). Besides the AEs recorded in the drug label (such as edema, nausea, fatigue, and dyspnea), the study unearthed other high-risk AEs not listed in the label, including Renal and urinary disorders, Vocal cord paralysis, and Ear and labyrinth disorders. Among these, renal and urinary disorders, and ear and labyrinth disorders had a higher frequency and intensity of signals, suggesting that their mechanisms of occurrence could be a future research direction. Conclusion: This study uncovered new potential AEs of Capmatinib based on the FAERS database, providing reference for its safe clinical use. Special attention should be given to the occurrence of ear and labyrinth disorders and renal and urinary disorders, primarily presenting as pseudo-acute kidney injury, during treatment.

Unveiling the multifaceted realm of human papillomavirus: a comprehensive exploration of biology, interactions, and advances in cancer management.

Human Papillomavirus (HPV), an extensive family of DNA viruses, manifests as a persistent global health challenge. Persistent HPV infection is now firmly established as a significant aetiological factor for a spectrum of malignancies. In this review, we examine the latest insights into HPV biology and its intricate relationship with the host. We delve into the complex dynamics of co-infections involving HPV alongside other viruses, such as HIV, EBV, and HSV, as well as the burgeoning role of the microbiome in cancer development. We also explore recent advancements in understanding the specific contributions of HPV in the development of various cancers, encompassing cancers of the anogenital region, head and neck, as well as breast, lung, and prostate. Moreover, we focus on the current preventive strategies, including vaccination and screening methods, and therapeutic interventions that range from traditional approaches like surgery and chemotherapy to emerging modalities such as targeted therapies and immunotherapies. Additionally, we provide a forward-looking view on the future directions of HPV research, highlighting potential areas of exploration to further our understanding and management of HPV and its associated cancers. Collectively, this review is positioned to deepen readers' understanding of HPV biology and its complex interplay with cancer biology. It presents innovative strategies for the prevention, management, and therapeutic intervention of HPV-associated malignancies.

Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine.

Background: The house dust mite (HDM) is widely recognized as the most prevalent allergen in allergic diseases. Allergen-specific immunotherapy (AIT) has been successfully implemented in clinical treatment for HDM. Hypoallergenic B-cell epitope-based vaccine designed by artificial intelligence (AI) represents a significant progression of recombinant hypoallergenic allergen derivatives. Method: The three-dimensional protein structure of Der f 36 was constructed using Alphafold2. AI-based tools were employed to predict B-cell epitopes, which were subsequently verified through IgE-reaction testing. Hypoallergenic Der f 36 was then synthesized, expressed, and purified. The reduced allergenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoblotting, and basophil activation test. T-cell response to hypoallergenic Der f 36 and Der f 36 was evaluated based on cytokine expression in the peripheral blood mononuclear cells (PBMCs) of patients. The immunogenicity was evaluated and compared through rabbit immunization with hypoallergenic Der f 36 and Der f 36, respectively. The inhibitory effect of the blocking IgG antibody on the specific IgE-binding activity and basophil activation of Der f 36 allergen was also examined. Results: The final selected non-allergic B-cell epitopes were 25-48, 57-67, 107-112, 142-151, and 176-184. Hypoallergenic Der f 36 showed significant reduction in IgE-binding activity. The competitive inhibition of IgE-binding to Der f 36 was investigated using the hypoallergenic Der f 36, and only 20% inhibition could be achieved, which is greatly reduced when compared with inhibition by Der f 36 (98%). The hypoallergenic Der f 36 exhibited a low basophil-stimulating ratio similar to that of the negative control, and it could induce an increasing level of IFN-γ but not Th2 cytokines IL-5 and IL-13 in PBMCs. The vaccine-specific rabbit blocking IgG antibodies could inhibit the patients' IgE binding and basophil stimulation activity of Derf 36. Conclusion: This study represents the first application of an AI strategy to facilitate the development of a B-cell epitope-based hypoallergenic Der f 36 vaccine, which may become a promising immunotherapy for HDM-allergic patients due to its reduced allergenicity and its high immunogenicity in inducing blocking of IgG.

PM2.5-derived exosomal long noncoding RNA PAET participates in childhood asthma by enhancing DNA damage via m6A-dependent OXPHOS regulation.

Fine particulate matter (PM2.5) is known to enhance DNA damage levels and is involved in respiratory diseases. Exosomes can carry noncoding RNAs, especially long noncoding RNAs (lncRNAs), as regulators of DNA damage, which participate in diseases. However, their role in PM2.5-induced childhood asthma remains unclear. We performed RNA-seq to profile aberrantly expressed exosomal lncRNAs derived from PM2.5-treated human bronchial epithelial (HBE) cell models. The role of exosomal lncRNAs in childhood asthma was determined in a case-control study. The intercellular communication mechanisms of exosomal lncRNA on DNA damage were determined in vitro. Exosomes secreted by PM2.5-treated HBE cells (PM2.5-Exos) could increase the DNA damage levels of recipient HBE cells and promote the expression levels of airway remodeling-related markers in sensitive human bronchial smooth muscle cells (HBSMCs). LncRNA PM2.5-associated exosomal transcript (PAET) was highly expressed in PM2.5-Exos and was associated with PM2.5 exposure in childhood asthma. Mechanistically, exosomal lncRNA PAET promoted methyltransferase-like 3 (METTL3) accumulation by increasing its stability, which stimulated N6-methyladenosine (m6A) modification of cytochrome c oxidase subunit 4I1 (COX4I1), and COX4I1 levels were decreased in a mechanism dependent on the m6A "reader" YTH domain family 3 (YTHDF3). COX4I1 deficiency subsequently disrupted oxidative phosphorylation (OXPHOS), resulting in attenuated adenosine triphosphate (ATP) production and accumulation of reactive oxygen species (ROS), which increased DNA damage levels. This comprehensive study extends the understanding of PM2.5-induced childhood asthma via DNA damage and identifies exosomal lncRNA PAET as a potential target for childhood asthma.

Risk factor analysis and prediction model construction for severe adenovirus pneumonia in children.

BACKGROUND: Severe adenovirus pneumonia in children has a high mortality rate, but research on risk prediction models is lacking. Such models are essential as they allow individualized predictions and assess whether children will likely progress to severe disease. METHODS: A retrospective analysis was performed on children with adenovirus pneumonia who were hospitalized at the Children's Hospital of Nanjing Medical University from January 2017 to March 2024. The patients were grouped according to clinical factors, and the groups were compared using Ridge regression and multiple logistic regression to identify risk factors associated with severe adenovirus pneumonia. A prediction model was constructed, and its value in clinical application was evaluated. RESULTS: 699 patients were included in the study, with 284 in the severe group and 415 in the general group. Through the screening of 44 variables, the final risk factors for severe adenovirus pneumonia in children as the levels of neutrophils (OR = 1.086, 95% CI: 1.054‒1.119, P < 0.001), D-dimer (OR = 1.005, 95% CI: 1.003‒1.007, P < 0.001), fibrinogen degradation products (OR = 1.341, 95% CI: 1.034‒1.738, P = 0.027), B cells (OR = 1.076, 95%CI: 1.046‒1.107, P < 0.001), and lactate dehydrogenase (OR = 1.008, 95% CI: 1.005‒1.011, P < 0.001). The value of the area under the receiver operating characteristic curve was 0.974, the 95% CI was 0.963-0.985, and the P-value of the Hosmer-Lemeshow test was 0.547 (P > 0.05), indicating that the model had strong predictive power. CONCLUSION: In this study, the clinical variables of children with adenovirus pneumonia were retrospectively analyzed to identify risk factors for severe disease. A prediction model for severe disease was constructed and evaluated, showing good application value.

Prognostic value of geriatric nutritional risk index and prognostic nutritional index in hepatocellular carcinoma.

BACKGROUND: The geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI) are considered prognostic factors for several cancers. This study aimed to investigate the relationship between the GNRI and PNI for survival outcomes in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed 1666 patients with HCC who underwent hepatectomy. Restricted cubic spline regression was used to analyze the relationship between the GNRI and PNI for recurrence and mortality. Cox proportional hazards regression analysis was used to evaluate the risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Interaction analysis was performed to investigate the comprehensive effects of the GNRI, PNI, and subgroup parameters on the prognosis of patients with HCC. RESULTS: The risks of death and recurrence decreased rapidly and gradually stabilized as the GNRI and PNI scores increased. Patients with lower GNRI and PNI scores had significantly shorter OS and RFS rates than those with higher scores. Multivariate analysis showed that high GNRI [HR and 95%CI = 0.77 (0.70-0.85), P < 0.001] and PNI [HR and 95%CI = 0.77 (0.70-0.86), P < 0.001] scores were associated with decreased mortality risk. This trend was maintained by confounding variables in adjusted models despite partial interactions with clinical factors. The combined GNRI and PNI analysis showed that HCC patients with high GNRI and PNI had longer OS and RFS. CONCLUSIONS: The GNRI and PNI showed good survival predictions in patients with HCC. Combining the GNRI with PNI may help predict the prognosis of patients (age>18 years) with HCC after hepatectomy.

Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. METHODS: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric". RESULTS: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. CONCLUSIONS: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

The Global Health Threat of Monkeypox Virus: Understanding Its Biology, Transmission, and Potential Therapeutic Interventions.

Monkeypox virus (MPXV), a member of the Orthopoxvirus genus, shares its genus with Variola virus (VARV), the causative agent of smallpox, and Vaccinia virus (VACV), used for smallpox vaccination. While smallpox has been eradicated, MPXV and related poxviruses continue to pose a global health threat. Monkeypox (Mpox), similar in clinical presentation to smallpox but milder, is endemic in Central and West Africa. Sporadic outbreaks emphasize the potential for wider dissemination. Understanding their biology, transmission, immune evasion, and clinical features informs disease control strategies. The intersection of medical innovation and biotechnology with poxviruses underscores their importance in both disease and scientific advancement. Further research is essential to enhance prevention, management, and therapeutic interventions for these viruses.

Risk factors for the development of bronchiolitis obliterans in children after suffering from adenovirus pneumonia.

Introduction: Bronchiolitis obliterans (BO) is an irreversible chronic obstructive lung disease in small airways. The aim of this study was to identify the relevant risk factors for the development of BO in children after suffering from adenovirus (ADV) pneumonia. Methods: An observational cohort study that included 112 children suffering from ADV pneumonia in our institution from March 2019 to March 2020 was performed. We divided the children into a BO group and a non-BO group based on whether they did develop BO or not. Univariate analysis and multivariate logistic regression analysis were applied to identify risk factors for the development of BO. The prediction probability model was evaluated by receiver operating characteristic (ROC) curve analysis. Results: Twenty-eight children (25%) did develop BO after suffering from ADV pneumonia, while 84 children did not. Respiratory support (OR 6.772, 95% CI 2.060-22.260, P = 0.002), extended length of wheezing days (OR 1.112, 95% CI 1.040-1.189, P = 0.002) and higher lactic dehydrogenase (LDH) levels (OR 1.002, 95% CI 1.000-1.003, P = 0.012) were independently associated with the development of BO. The predictive value of this prediction probability model was validated by the ROC curve, with an area under the curve of 0.870 (95% CI 0.801-0.939, P < 0.001), a standard error of 0.035, a maximum Youden's index of 0.608, a sensitivity of 0.929, and a specificity of 0.679. Conclusions: After suffering an ADV pneumonia, children who have needed respiratory support, had a longer length of wheezing days or had higher LDH levels are more likely to develop BO.