A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Objective:To investigate the gene expression profile of children with non-Hodgkin lymphoma (NHL) and to analyze the clinical significance of circulating tumor DNA (ctDNA) in children with NHL based on next-generation sequencing technology.Methods:A retrospective case series study was conducted. The clinical data of 46 children with NHL who underwent genetic analysis of 122 lymphoma related genes whole exome in pathological tissues and (or) peripheral blood before treatment by using NGS technology in the First Affiliated Hospital of Zhengzhou University from July 2019 to August 2023 were collected. Among the 46 children, 19 cases had the simple extraction of peripheral blood to isolate ctDNA and 19 cases had the simple acquisition of pathological tissue specimens genome DNA (gDNA) for genetic testing, and 8 cases had peripheral blood ctDNA and tissue samples at the same time for detection. The gene expression profile of the whole group and different pathologic types of children were summarized. Kaplan Meier method was used to analyze the overall survival of children with mutations and those without mutations, and the corresponding relationship between peripheral blood ctDNA detected by NGS and gene mutations detected by biopsy gDNA was analyzed.Results:Among the 46 children with NHL, 38 cases (82.6%) were male and 8 cases (17.4%) were female; the median age [ M ( Q1, Q3)] was 9 (6, 11) years. There were 5 cases of ALK-positive anaplastic large cell lymphoma, 16 cases of Burkitt lymphoma (BL), 9 cases of B-cell lymphoblastic lymphoma (B-LBL), 10 cases of T-cell lymphoblastic lymphoma (T-LBL), 4 cases of high-grade B-cell lymphoma-not otherwise specified (HGBL-NOS), 1 case of small intestine NK/T-cell lymphoma, and the remaining 1 case was classified as aggressive B-cell lymphoma which was not further classified due to insufficient tissue specimens. A total of 9 fusion genes were detected in 18 cases (39.1%). The median number of mutated genes was 1 (0, 4) (range from 0 to 6). Among 46 cases, 26 cases (56.5%) had at least 1 gene mutation, and 18 cases (39.1%) had ≥ 3 gene mutations. Among 36 mutant genes, the top 5 mutation rates were MYC (17.4%, 8/46), DDX3X (17.4%, 8/46), NRAS (13.0%, 6/46), NOTCH1 (10.8%,5/46), PHF6 (10.8%, 5/46), TP53 (8.7%, 4/46), ID3 (8.7%, 4/46), ARID1A (8.7%, 4/46), PTEN (6.5%,3/46), FOXO1 (6.5%,3/46), KMT2D (6.5%, 3/46). Among 8 pediatric cases with DDX3X gene mutation, 5 cases were BL and 8 cases were all male; among 5 BL pediatric cases with DDX3X gene mutation, 4 cases were accompanied with MYC gene mutation. There were great differences in gene expression profile among different pathological types of NHL in children. Ras/protein phosphatase/MARK signaling pathway related gene mutations occurred in 20 cases (43.5%), mainly in children with B-LBL. Mutations associated with transcription factor regulation and epigenetic modification occurred in 28.3% (13 cases) and 23.9% (11 cases), respectively. The mutation rates of PI3K-AKt and JAK-STAT signaling pathway were 15.2% (7 cases) and 13.0% (6 cases), respectively, in which PHF6, ID3 and ARID1A with high mutation rate mainly occurred in BL children. The median follow-up was 21.25 (13.55, 29.20) months, and the median overall survival time was 21.10 (11.72, 29.20) months. At the end of last follow-up time, 40 cases (87.0%) survived and 6 cases (13.0%) died. Among 16 cases with BL, the median overall survival time was 12.5 months (95% CI: 0.8-24.2 months) in the DDX3X mutation group (5 cases), 23.2 months (95% CI:19.0-27.4 months) in the DDX3X non-mutation group (11 cases), and the difference in the overall survival was not statistically significant between the 2 groups ( P = 0.214). A total of 16 mutated genes were identified in 8 cases of children who obtained peripheral blood ctDNA and tissue samples gDNA at the same time, 5 mutated genes found in ctDNA were detected in the corresponding tissues gDNA, while 16 mutated genes were found in tissue gDNA detection. ctDNA and gDNA test results were identical in 2 of the 8 pediatric cases. Relevant mutations were detected in the tissue samples gDNA in 5 cases, but ctDNA test was negative. Conclusions:Genetic mutation analysis based on NGS technology revealed genetic heterogeneity among different NHL subtypes and involved multiple signaling pathways, indicating that different pathological types of NHL have different molecular pathogenesis. ctDNA analysis based on NGS technology can assist tissue biopsy to dynamically monitor gene changes within tumors.

ObjectiveTo investigate the current status of emergency management for severe mental disorders in Shanghai, and to provide countermeasures and suggestions for the establishment of a sound emergency management system for severe mental disorders and the enhancement of emergency management capability. MethodsA questionnaire survey and qualitative interviews were used to conduct an investigation into the emergency management in 17 district-level mental illness prevention and control institutions in Shanghai, which includes the basic situation of emergency management for severe mental disorders, the construction of emergency response teams and personnel, emergency preparedness drills and training, emergency management plans and rules and regulations, and problems encountered in emergency management. ResultsIn terms of emergency management mechanism and basic situation, resources such as personnel allocation, security funds and green channel were well equipped in each district-level mental illness prevention and control institution in Shanghai. However, the equipment of some hardware facilities was still insufficient to some extent. Therefore, further improvement on the emergency management mechanism for severe mental disorders was needed. With regard to the construction of emergency team and personnel allocation, the majority were those aged between 35‒<45 years old, with a bachelor’s degree, and more than 10 years of working experience. For example, 90.27% staff in district-level mental illness prevention and control institution had a bachelor’s degree or above, which was higher than that among the staff in community-level (73.60%); staff majored in clinical medicine in district-level institution accounted for the proportion at 52.71%, higher than that among the staff in community-level (28.86%); 57.24% staff in district-level institution had an intermediate professional title, higher than that among the staff in community-level (42.28%); and 69.90% staff in district-level institution had more than 10 years of working experience, higher than that among the staff in community-level (43.62%). In the aspect of emergency drills and training, all district-level mental illness prevention and control institutions in Shanghai had a high demand for emergency training, and the weak aspects mainly focused on lack of emergency service protocols, skills of addressing technical challenges, and construction of effectiveness evaluation system. Moreover, the teaching methods were primarily centered on case analysis, simulation drills, interactive discussions, and so forth. Concerning emergency management plans and rules and regulations, all districts in Shanghai had relatively established well-developed systems for emergency response plans, emergency response leadership groups, and emergency response operational task forces for severe mental disorders. About half of the institutions had established other rules and regulations related to emergency management of severe mental disorders in addition to emergency plans. ConclusionShanghai has initially established an emergency management system for severe mental disorders, but it is still fragile in specialized training for emergency management of severe mental disorders, construction of emergency management mechanisms, and the building-up of grassroots emergency teams. Further priorities should include strengthening emergency management training, enhancing the construction of emergency management personnel teams, and gradually establishing a more comprehensive and integrated emergency management mechanism for severe mental disorders.

Objective:To understand the pathogen distribution characteristics of acute lower respiratory tract infections (ALRTI) in hospitalized children in the Department of Respiratory Medicine, Capital Center for Chlidren's Health, Capital Medical University from 2019 to 2023, and to analyze their epidemiological features.Methods:A retrospective analysis was conducted, including 5 558 children aged 0-18 years who were hospitalized and diagnosed with ALRTI in the respiratory department of Capital Center for Chlidren's Health, Capital Medical University from December 8, 2019, to December 31, 2023. Nasopharyngeal swabs, sputum, and bronchoalveolar lavage fluid specimens were collected for pathogen detection.Results:Among the 5 558 ALRTI hospitalized children, the positive detection rate of pathogens was 81.81% (4 547/5 558). In bronchoalveolar lavage fluid specimens, Mycoplasma pneumoniae had the highest detection rate (33.52%), while Streptococcus pneumoniae had the highest detection rate (24.38%) in upper respiratory tract specimens. Mycoplasma pneumoniae (54.21%, χ2=1 034.58, P<0.001) and adenovirus (5.09%, χ2=10.84, P=0.013) were most common in school-age children, human rhinovirus was more common in toddlers (26.42%, χ2=122.36, P<0.001), and respiratory syncytial virus had the highest infection rate in infants (28.61%, χ2=326.47, P<0.001). A total of 52.06% of the children had mixed infections (2 367/4 547), with the highest proportion of mixed infections in infants (62.54%). During the post- non-pharmaceutical interventions (NPIs) period, the proportions of Mycoplasma pneumoniae (69.88% vs. 58.16%), human rhinovirus (30.37% vs. 14.02%), adenovirus (51.16% vs. 6.45%), influenza A virus (36.46% vs. 16.67%), and mixed infections (33.33% vs. 19.04%) in school-age children were significantly higher than during the NPIs period. In contrast, the proportions of respiratory syncytial virus (33.19% vs. 19.42%), adenovirus (11.29% vs. 4.65%), and mixed infections (17.75% vs. 10.89%) in infants were significantly lower than during the NPIs period. Conclusion:NPIs have changed the detection rate and epidemiology of respiratory pathogens in hospitalized children. After the end of NPIs, outbreaks of some pathogens may occur, so it is necessary to strengthen rapid pathogen detection, population surveillance, and health education.

Objective:To explore the molecular epidemiological characteristics of human metapneumovirus (HMPV) in children with acute respiratory infection (ARI) in Beijing from 2023 to 2024.Methods:In the longitudinal study, 9 834 children with ARI were enrolled from August 2023 to December 2024, including the influenza-like illness (ILI) group from emergency and outpatient department receiving influenza virus (Flu) and HMPV test and the ARI inpatient group for 13 common respiratory pathogen screening test including HMPV, Flu, respiratory syncytial virus, and so on. All respiratory samples positive with HMPV were genotyped by amplifying and sequencing of G gene and further phylogenetic analysis. The χ2 test and Wilcoxon rank-sum test were used to compare the positive rate and basic clinical data of the 2 groups. Results:Among 9 834 enrolled patient, there were 5 276 male and 4 558 female children, with age 5.4 (1.9, 8.2) years. In ILI group of 1 460 patients, there were 83 cases (5.7%) positive for HMPV, with the age 4.9 (3.6, 6.6) years and children under 6.0 years old 59 cases (71.1%). Among 8 374 ARI inpatients, there were 256 cases (3.1%) positive for HMPV, with age 3.5 (1.3, 6.4) years and children under 6.0 years old 188 cases (73.4%). The HMPV positive rate and the age of children positive for HMPV in ARI inpatient group were significantly lower than that in ILI group (both P<0.001). In December, 2024, the HMPV positive rates of ILI and ARI inpatient group (21.3% (17/80), 15.0% (47/314)) were significantly higher than the total positive rates of each group (both P<0.001). Among 279 subtyped specimens, there were 155 cases (55.6%) belonging to genotype A and 124 cases (44.4%) belonging to genotype B. Sub-lineage A2.2.2 containing 111nt-insertions was predominate one in 2023 with positive ratio 89.2% (91/102), and B2 was predominate in 2024 with positive ratio 64.4% (114/177). Conclusions:From 2023 to 2024, the positive rate of HMPV in the ILI group was higher than that in the ARI inpatient group, suggesting a common epidemic of HMPV infection. Children positive for HMPV in the ARI inpatient group were younger than that in the ILI group. A severe epidemic of HMPV was observed in the winter of 2024, which requires attention. Sub-lineage A2.2.2 with 111nt-duplicate insertions and B2 were the predominant epidemic strains in 2023 and 2024, respectively.

OBJECTIVE To evaluate the potential of nanopore sequencing technology for rapid diagnosis of Talaro-myces marneffei(TM)infection.METHODS Nine patients with TM infection admitted to the Fourth People's Hospital of Nanning from May 13,2022 to Aug.3,2023 were retrospectively analyzed.Rapid diagnosis was con-ducted by nanopore sequencing technology,and a comprehensive analysis of their clinical characteristics and treat-ment processes was performed.RESULTS The 9 patients included in the study had infections in various sites such as the lungs,buttocks,blood and cervical lymph nodes.Comorbidities included AIDS,secondary pulmonary tuberculosis,non-tuberculous mycobacterial disease and adult-onset immune deficiency.Patients generally exhibited elevated C-reactive protein levels and erythrocyte sedimentation rates,along with increased neutrophil counts.Some patients had abnormal lymphocyte counts and CD4+/CD8+ratios.Microbiological tests showed positive cultures in 3 cases,positive smears in 2 cases and positive targeted detection in 6 cases.Nanopore sequencing detected various pathogens in the 9 patients.The treatment results indicated that 8 patients improved after medication,with 6 patients having medication regimens adjusted based on nanopore sequencing results.CONCLUSION Nanopore sequencing technology has shown potentials in the auxiliary diagnosis of TM infection,providing timely etiological diagnostic evidence for clinical practice.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To compare the diagnostic value of semi-quantitative parameters of fluorine 18-labelled prostate-specific membrane antigen( 18F-PSMA)positron emission tomography /computed tomography(PET/CT)and the Prostate-specific Membrane Antigen Reporting and Data System(PSMA-RADS)score for identifying benign and malignant oligo-PSMA-avid bone lesions(1-5 lesions)in elderly patients with prostate cancer. Methods:A retrospective analysis was conducted on 157 prostate cancer patients who underwent 18F-PSMA PET/CT examinations at Beijing Hospital from October 2022 to August 2024.According to the inclusion and exclusion criteria, a total of 63 patients were selected.All patients underwent 18F-PSMA PET/CT examination for the purpose of initial staging or detecting lesions with biochemical recurrence.PSMA-avid bone lesions were evaluated using the PSMA-RADS version 2.0 scoring system and the semi-quantitative parameters were measured on PSMA PET/CT images.According to the comprehensive diagnostic criteria, PSMA-avid bone lesions were divided into metastatic group and non-metastatic group.The differences in PSMA-RADS scores, semi-quantitative parameters, bone density abnormalities, and lesion distribution were compared between the two groups.Multivariate logistic regression analysis was performed to determine the factors related to the bone metastasis in prostate cancer.By plotting the receiver operating characteristic(ROC)curves and calculating the area under the curve(AUC), factors with better diagnostic performance were evaluated and screened, and the optimal diagnostic threshold for each factor in diagnosing bone metastasis was determined. Results:There were a total of 129 PSMA-avid bone lesions for 63 patients(aged 60-84 years, median age 69 years), including 35 lesions(27.1%)in the metastatic group and 94 lesions(72.9%)in the non-metastatic group.The differences between metastatic group and non-metastatic group in PSMA-RADS scores[5(4, 5) vs.3(3, 3)], maximum standardized uptake value(SUV max)[12.6(7.0, 18.4) vs.4.7(3.5, 5.9)], lesion SUV max/mediastinal blood pool SUV max ratio(lesion-to-blood pool ratio, LBR)[5.4(3.0, 8.3) vs.1.7(1.4, 2.2)], lesion SUV max/liver SUV max ratio(lesion-to-liver ratio, LLR)[2.6(1.6, 4.1) vs.0.8(0.7, 1.1)], PSMA receptor expressing tumor volume(PSMA-TV)[0.6(0.3, 1.0) vs.1.0(0.7, 1.5)], total lesion of PSMA(TL-PSMA)[4.4(2.4, 7.0) vs.2.4(1.7, 3.9)], proportion of changes in osteogenic bone density[77.1%(27/35) vs.2.1%(2/94)], proportion of lesions located in the ribs[14.3%(5/35) vs.46.8%(44/94)], and proportion of lesions located in the pelvis[54.3%(19/35) vs.20.2%(19/94)]were all statistically significant(all P<0.05). Multivariate logistic regression analysis indicated that none of the variables with statistically significant differences between groups above were independent risk factors for osseous metastasis in prostate cancer(all P>0.05). Among them, The PSMA-RADS score, LLR, LBR, and SUV max all had good diagnostic efficacy for osseous metastasis, with 0.995(95% CI: 0.987-1.000), 0.923(95% CI: 0.869-0.977), 0.898(95% CI: 0.828-0.967), and 0.890(95% CI: 0.820-0.961), respectively.The cut-off values for diagnosing osseous metastasis were 4 score for PSMA-RADS score, 0.934 for LLR, 1.990 for LBR, and 5.47 for SUV max, respectively.According to Delong's test, there were statistically significant differences in AUC between PSMA-RADS score and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)( Z-values were 2.677, 2.776, and 2.929, respectively, and P-values were 0.007, 0.006, and 0.003, respectively). Conclusions:The PSMA-RADS score(Version 2.0)and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)both have good diagnostic value in differentiating benign and malignant PSMA-avid bone lesions in elderly patients with prostate cancer, among which the PSMA-RADS score has the best diagnostic efficacy.