OBJECTIVE To investigate the epidemiological characteristics of respiratory human adenovirus(H AdV)infections in hospitalized children in Ningbo,and to provide data for formulating infection prevention and control strategies for HAdV.METHODS A total of 65 022 children hospitalized with respiratory infections at the Women and Children's Hospital of Ningbo University from Jul.2019 to Dec.2024 were selected as the study sub-jects.Multiple reverse transcription-polymerase chain reaction(RT-PCR)and capillary electrophoresis were used to detect 11 non-bacterial pathogens.Basic and clinical information of the children was collected for analysis.RESULTS A total of 65 022 specimens were tested,with 4 292 cases tested positive for HAdV positivity,yielding a positive rate of 6.60％.The lowest positive rate was observed in 2023(3.22％),while the highest was in 2024(13.97％).Compared to the years 2019-2023,the overall HAdV positive rate was high in 2024,peaking at 26.80％in Jun.,indicating an outbreak.The total HAdV positive rate was higher in boys(6.82％)than in girls(6.32％)(P=0.006).The highest HAdV positive rate was observed in the 2 to＜6 age group(9.00％),while the lowest was in the 0 to＜1 age group(2.33％).Among the HAdV-positive specimens,2 658 cases(61.93％)were single infections,and 1 634 cases(38.07％)were co-infections.The non-bacterial respiratory pathogens with the highest co-infection rates were human rhinovirus(34.09％),Mycoplasma pneumoniae(20.44％)and human parainfluenza virus(5.75％).CONCLUSIONS A n outbreak of HAdV infections is observed among hospitalized children in Ningbo in 2024.Higher positive rates are found in boys aged 2 to＜6 years,with a certain proportion of co-infections.

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Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

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 investigate the epidemiological characteristics of respiratory human adenovirus(H AdV)infections in hospitalized children in Ningbo,and to provide data for formulating infection prevention and control strategies for HAdV.METHODS A total of 65 022 children hospitalized with respiratory infections at the Women and Children's Hospital of Ningbo University from Jul.2019 to Dec.2024 were selected as the study sub-jects.Multiple reverse transcription-polymerase chain reaction(RT-PCR)and capillary electrophoresis were used to detect 11 non-bacterial pathogens.Basic and clinical information of the children was collected for analysis.RESULTS A total of 65 022 specimens were tested,with 4 292 cases tested positive for HAdV positivity,yielding a positive rate of 6.60％.The lowest positive rate was observed in 2023(3.22％),while the highest was in 2024(13.97％).Compared to the years 2019-2023,the overall HAdV positive rate was high in 2024,peaking at 26.80％in Jun.,indicating an outbreak.The total HAdV positive rate was higher in boys(6.82％)than in girls(6.32％)(P=0.006).The highest HAdV positive rate was observed in the 2 to＜6 age group(9.00％),while the lowest was in the 0 to＜1 age group(2.33％).Among the HAdV-positive specimens,2 658 cases(61.93％)were single infections,and 1 634 cases(38.07％)were co-infections.The non-bacterial respiratory pathogens with the highest co-infection rates were human rhinovirus(34.09％),Mycoplasma pneumoniae(20.44％)and human parainfluenza virus(5.75％).CONCLUSIONS A n outbreak of HAdV infections is observed among hospitalized children in Ningbo in 2024.Higher positive rates are found in boys aged 2 to＜6 years,with a certain proportion of co-infections.

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.

Metabolism-related diseases are chronic diseases caused by genetic and environmental factors.The symptoms include insulin resistance,abnormal blood glucose and lipid levels,and elevated blood pressure.This type of illness has become a major threat to human health,and there is an urgent need to find effective treatments.Advanced glycation end products (AGE) are a group of complex and heterogeneous compounds that result from reduced interactions between the carbonyl groups of sugar and the free amino groups of proteins,lipids,and nucleic acids.Increasing evidence shows that AGE and its receptor (RAGE) are involved in the occurrence and development of such metabolism-related diseases as hypertension,diabetes,and atherosclerosis.AGE can have adverse effects on tissues through non-receptor and receptor-mediated mechanisms.In the receptor-mediated mechanism,AGE interacts with RAGE to increase the production of oxygen free radicals and activate NF-κB so that more pro-inflammatory cells are expressed and released,leading to cell damage.This article reviews the research progress in interventions with AGE and RAGE in the treatment of hypertension,diabetes,and atherosclerosis from a metabolic perspective in the hope of exploring the potential of AGE and RAGE as therapeutic targets for metabolism-related diseases.

Metabolism-related diseases are chronic diseases caused by genetic and environmental factors.The symptoms include insulin resistance,abnormal blood glucose and lipid levels,and elevated blood pressure.This type of illness has become a major threat to human health,and there is an urgent need to find effective treatments.Advanced glycation end products (AGE) are a group of complex and heterogeneous compounds that result from reduced interactions between the carbonyl groups of sugar and the free amino groups of proteins,lipids,and nucleic acids.Increasing evidence shows that AGE and its receptor (RAGE) are involved in the occurrence and development of such metabolism-related diseases as hypertension,diabetes,and atherosclerosis.AGE can have adverse effects on tissues through non-receptor and receptor-mediated mechanisms.In the receptor-mediated mechanism,AGE interacts with RAGE to increase the production of oxygen free radicals and activate NF-κB so that more pro-inflammatory cells are expressed and released,leading to cell damage.This article reviews the research progress in interventions with AGE and RAGE in the treatment of hypertension,diabetes,and atherosclerosis from a metabolic perspective in the hope of exploring the potential of AGE and RAGE as therapeutic targets for metabolism-related diseases.

Objective To investigate the clinical distribution,antimicrobial resistance,carbapenemase resistance genes,virulence genes,capsular serotypes and ST subtypes of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains in intensive care unit of a tertiary hospital in Hunan Province for better management of CRKP infections.Methods CRKP strains were isolated from 8 intensive care units of the First People's Hospital of Chenzhou City from January 2020 to December 2021.The isolates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and tested by VITEK Compact 2 for antimicrobial susceptibility.Carbapenemase phenotype was detected by modified carbapenem inactivation method(mCIM).The capsular serotypes were determined by wzi sequencing.Carbapenem resistance genes and virulence genes were identified by PCR and Sanger sequencing.The strains were also analyzed by multilocus sequence typing(MLST)in terms of ST subtypes.Results The 75 CRKP strains were mainly isolated from geriatric ICU(28.0％)and neurosurgery ICU(20.0％).Overall,6.7％(5/75)and 16.0％(12/75)of the CRKP strains were resistant to tigecycline and ceftazidime-avibactam,respectively.The CRKP strains(＞96.0％resistant)were highly resistant to carbapenems,cephalosporins,β-lactam/β-lactamase inhibitor combinations,and levofloxacin.PCR and sequencing analysis found blaKPC-2 gene in 61 strains(81.3％),blaNDM-1 gene in 11 strains(14.7％),blaNDM-5 gene in 1 strain(1.3％),and blaOXA-48 gene in 2 strains(2.7％).MLST revealed that ST11(54.7％,41/75),ST1883(13.3％,10/75),and ST307(6.7％,5/75)were the top three ST subtypes.All ST11 and ST1883 CRKP strains harbored blaKPC-2.KL64(38.7％,29/75)and KL47(25.3％,19/75)were the most prevalent capsular serotypes among the 75 CRKP strains.The most common virulence genes among these CRKP strains were rmpA2(48.0％,36/75),iroN(38.7％,23/75)and iucA(37.3％,15/75).Conclusions The CRKP strains isolated from the intensive care units were mainly ST11-KL64 and ST11-KL47 types.Most of the strains harbor blaKPC-2 and virulence gene,and associated with high level antimicrobial resistance.It is urgent to strengthen the monitoring of molecular epidemiological characteristics of CRKP in order to inform individualized and precision treatment of CRKP infections.