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.

Objective:To explore the epidemiological characteristics, clinical manifestations, laboratory findings, and imaging features of children with HRV-associated pneumonia, and to analyze the clinical features and risk factors associated with severe HRV pneumonia, providing references for clinical management.Methods:A single-center, retrospective, observational study was conducted, including 1 001 cases of HRV-positive children with pneumonia admitted to the Respiratory Department of the Affiliated Children′s Hospital of Capital Institute of Pediatrics from January 2019 to December 2023. Among them, 584 cases (58.3%) were male and 417 cases (41.7%) were female, with an age range of 0.1 to 14.9 years, a median age of 3.42 years, and a mean age of (3.92±2.75) years. According to clinical guidelines, the cases were divided into a mild pneumonia group (855 cases, 510 males, 345 females) and a severe pneumonia group (146 cases, 73 males, 73 females). Basic information, clinical, laboratory, and imaging data were collected from the electronic medical record system. Comparisons between different age groups, diagnoses, and pneumonia severity groups were performed using the χ2 test. Multivariate logistic regression analysis was used to identify risk factors for the severity of HRV pneumonia. Results:Among the 1 001 cases of HRV-associated bronchopneumonia, 146 cases (14.6%) were severe pneumonia. The age of severe HRV pneumonia patients was significantly higher than that of the mild pneumonia group (5.2 years vs. 3.7 years, t=-6.050, P<0.01). Severe HRV pneumonia had a higher incidence in autumn and winter (60.9%). Severe HRV pneumonia was associated with higher levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), neutrophils, and creatinine (correlation coefficients 0.198, 0.334, 0.104, 0.142, P<0.01), and lower levels of albumin (correlation coefficient 0.308, P<0.01). Multivariate logistic regression analysis showed that co-infection with Streptococcus pneumoniae or Mycoplasma was an independent risk factor for severe HRV pneumonia [ OR=1.611, 95% confidence interval ( CI):1.066-2.435, P<0.05; OR=3.355, 95% CI:2.062-5.458, P<0.01]. Conclusion:The infection rate of HRV is higher in preschool and school-age children. Severe HRV pneumonia is associated with increased levels of LDH, CRP, neutrophils, and creatinine, as well as decreased levels of albumin. Co-infection with Streptococcus pneumoniae or Mycoplasma may be an independent risk factor for severe HRV pneumonia. High-risk children require enhanced monitoring and early intervention to improve prognosis.

OBJECTIVE To investigate the distribution and drug resistance of the pathogens isolated from sterile body fluids in a hospital so as to provide reference for clinical treatment of the infections.METHODS The sterile body fluids specimens that were cultured positive for pathogens were retrospectively collected from a three-A hos-pital of Jiangxi Province between 2016 and 2023.The distribution and drug resistance of the isolated pathogens were observed.RESULTS Totally 16,658 strains of pathogens were isolated from the sterile body fluid speci-mens in 2016-2023,among which gram-negative bacteria accounted for 51.74％.The species of bacteria that ranked the top 5 places were as follows:Escherichia coli,Klebsiella pneumoniae,Staphylococcus epidermidis,Staphylococcus hominis,and Staphylococcus aureus.The isolation rates of methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus were 28.32％and 74.94％,respectively;the strains maintained high sensitivity to linezolid and vancomycin,with the drug resistance rates no more than 2.50％.The drug resistance rates of Enterococcus faecium and Enterococcus faecalis to linezolid and vancomycin were always less than 4.20％.Among the species of Enterobacter,the drug resistance rates of the E.coli strains to meropenem declined from 17.65％to 5.94％;conversely,the drug resistance rate of the K.pneumoniae strains to carbapenems reached high up to 54.36％,showing an upward trend on the whole.Among the non-fermenting gram-negative bacteria,the drug resistance rate of the A.baumannii strains to carbapenems remained high(about 80.00％);while the drug resistance rates of the P.aeruginosa strains to meropenem dropped from 60.71％down to 24.32％.CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the ster-ile body fluids in the hospital between 2016 and 2023.Although some major species of drug-resistant pathogens are effectively under control,the pathogens isolated from the sterile body fluid specimens maintain varying degree of drug resistance to various types of antibiotics.

Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

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 explore the epidemiological characteristics, clinical manifestations, laboratory findings, and imaging features of children with HRV-associated pneumonia, and to analyze the clinical features and risk factors associated with severe HRV pneumonia, providing references for clinical management.Methods:A single-center, retrospective, observational study was conducted, including 1 001 cases of HRV-positive children with pneumonia admitted to the Respiratory Department of the Affiliated Children′s Hospital of Capital Institute of Pediatrics from January 2019 to December 2023. Among them, 584 cases (58.3%) were male and 417 cases (41.7%) were female, with an age range of 0.1 to 14.9 years, a median age of 3.42 years, and a mean age of (3.92±2.75) years. According to clinical guidelines, the cases were divided into a mild pneumonia group (855 cases, 510 males, 345 females) and a severe pneumonia group (146 cases, 73 males, 73 females). Basic information, clinical, laboratory, and imaging data were collected from the electronic medical record system. Comparisons between different age groups, diagnoses, and pneumonia severity groups were performed using the χ2 test. Multivariate logistic regression analysis was used to identify risk factors for the severity of HRV pneumonia. Results:Among the 1 001 cases of HRV-associated bronchopneumonia, 146 cases (14.6%) were severe pneumonia. The age of severe HRV pneumonia patients was significantly higher than that of the mild pneumonia group (5.2 years vs. 3.7 years, t=-6.050, P<0.01). Severe HRV pneumonia had a higher incidence in autumn and winter (60.9%). Severe HRV pneumonia was associated with higher levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), neutrophils, and creatinine (correlation coefficients 0.198, 0.334, 0.104, 0.142, P<0.01), and lower levels of albumin (correlation coefficient 0.308, P<0.01). Multivariate logistic regression analysis showed that co-infection with Streptococcus pneumoniae or Mycoplasma was an independent risk factor for severe HRV pneumonia [ OR=1.611, 95% confidence interval ( CI):1.066-2.435, P<0.05; OR=3.355, 95% CI:2.062-5.458, P<0.01]. Conclusion:The infection rate of HRV is higher in preschool and school-age children. Severe HRV pneumonia is associated with increased levels of LDH, CRP, neutrophils, and creatinine, as well as decreased levels of albumin. Co-infection with Streptococcus pneumoniae or Mycoplasma may be an independent risk factor for severe HRV pneumonia. High-risk children require enhanced monitoring and early intervention to improve prognosis.

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.

OBJECTIVES: To evaluate the strategies and outcomes of assisted reproductive technology (ART) for fertility preservation and promotion in women with malignant tumors, and to analyze ART outcomes across different tumor types. METHODS: We conducted a retrospective analysis of female patients who underwent ART for fertility preservation or treatment at the Reproductive Center of the Women's Hospital, Zhejiang University School of Medicine, between January 1, 2018, and December 31, 2023. A total of 163 ART-aided pregnancy patients with malignant tumors were included in the case group, among which 6 patients underwent embryo cryopreservation for fertility preservation before radiotherapy or chemotherapy. Additionally, 11 unmarried women underwent oocyte cryopreservation due to borderline ovarian tumors, ovarian cancer, breast cancer, or hematological malignancies. The control group was selected from women without a history of malignant tumors who received ART treatment during the same period, using propensity score matching at a ratio of 1∶2, resulting in 326 cases. Data were collected through the reproductive medical record system and telephone follow-up (as of October 31, 2024). Baseline characteristics, controlled ovarian hyperstimulation parameters, laboratory indicators, and pregnancy outcomes were compared between case and control groups and among patients with different tumor types, and the tumor recurrence of the patients was followed up. RESULTS: Patients in the case group had significantly lower ovarian reserve (AMH, AFC) and a higher proportion of diminished ovarian reserve compared to the control group (all P<0.01). Regarding the ovulation induction protocol, the proportion of patients using the minimal stimulation protocol in the case group was significantly higher than that in the control group (29.45% vs. 12.88%, P<0.01), and the total dosage of gonadotropins used was lower (P<0.01). In terms of assisted reproductive outcomes, there were no statistically significant differences between the two groups in the number of retrieved oocytes, number of high-quality embryos, fertilization rate, cumulative pregnancy rate, cumulative live birth rate, or miscarriage rate (all P>0.05). However, the number of oocyte retrieval cycles and embryo transfer cycles required to achieve a live birth outcome in the case group were significantly higher than those in the control group (both P<0.05). Subgroup analysis showed that there were no significant differences in cumulative pregnancy rate and live birth rate among patients with different tumor types (thyroid cancer, reproductive system tumors, breast cancer, lung cancer). Nevertheless, lung cancer patients had the lowest ovarian reserve and required the most oocyte retrieval cycles due to their older age; breast cancer patients had a relatively lower fertilization rate partially because some of them were complicated with male factors. A follow-up of 154 tumor patients (with a follow-up rate of 88.5%) revealed that 6 patients (4.20%) had tumor recurrence, and 1 breast cancer patient died due to tumor recurrence. None of the 11 unmarried patients who had undergone oocyte cryopreservation had used the cryopreserved oocytes for assisted pregnancy yet, and 1 patient who had undergone fertility preservation died due to tumor recurrence. CONCLUSIONS Women of reproductive age with malignant tumors are at risk of diminished fertility. ART can effectively preserve and promote fertility, enabling favorable pregnancy and live birth outcomes. It is recommended to initiate a multidisciplinary assessment promptly prior to radiotherapy/chemotherapy and formulate an individualized ART regimen for fertility preservation or promotion, so as to achieve reproductive goals or safeguard future fertility potential.

AIM: To evaluate the diagnostic value of serum Th1-type cytokine levels and extraocular muscle-related parameters in thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective study was conducted on 45 patients diagnosed with TAO in our hospital from January 2023 to December 2024, and 20 normal volunteers during the same period as controls. Venous blood samples of the patients were collected to detect the concentrations of Th1-type cytokines [interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), and interleukin-12(IL-12)] in the serum. Additionally, the end diastolic velocity(Ved), velocity maximum(Vmax), resistance index(RI)of the central retinal artery, as well as the thickness and left-right diameter of the medial rectus muscle were measured. Logistic regression model was used to analyze the risk factors of TAO, and receiver operating characteristic curve(ROC)was adopted to evaluate the diagnostic efficacy of each index for the occurrence of TAO.RESULTS: The general information of the two groups was comparable. Compared with the normal control group, the serum concentrations of IFN-γ and TNF-α in TAO patients were significantly increased, Ved and Vmax were lower than those in the control group, and RI and the thickness of the medial rectus muscle were higher than those in the control group(all P<0.05). Logistic regression analysis showed that serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle were all risk factors for TAO. ROC curve analysis indicated that the AUCs of serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle for the diagnostic efficacy of TAO were 0.756, 0.769, 0.732, and 0.642, respectively. The combined detection of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle had an AUC of 0.840 and a Youden index of 0.59, which was superior to the detection of a single indicator.CONCLUSION: The levels of serum Th1-type cytokines and extraocular muscle-related ultrasound indicators have certain value in the diagnosis of TAO. The combination of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle has better diagnosis efficiency in TAO, which can provide a certain reference for the early diagnosis of TAO.