Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Objective:To investigate the clinicopathological features, pathological classification, and molecular characteristics of pulmonary hamartomas.Methods:A retrospective analysis was conducted on 316 cases of pulmonary hamartomas diagnosed at Nanjing Chest Hospital, Nanjing, China from January 2015 to June 2024. Next generation sequencing (NGS) was performed on 15 cases of this study. The clinical data, histopathological features, immunophenotypes, and molecular alterations were analyzed. Relevant literature was reviewed.Results:Among the 316 patients, there were 154 males and 162 females, with an average age of 56±10 years. Among the 316 cases, 310 were intrapulmonary hamartomas and 6 were intraluminal bronchial hamartomas. Microscopically, there were complex proliferative mesenchymal components and epithelial components, presenting various combinations and hamartomatous morphologies. These hamartomas were morphologically classified into mesenchymal-type hamartomas (cartilaginous, fibrous, smooth muscle, adipose tissue, and mixed types) and epithelial-mesenchymal mixed-type hamartomas (respiratory epithelial-mesenchymal mixed and mucosal gland-mesenchymal mixed types). The cartilaginous hamartomas accounted for 72.8% (230/316) of them, and the non-cartilaginous hamartoma accounted for 27.2% (86/316). Secondary changes such as calcification, ossification, collagenization, mucin degeneration, and cystic changes were commonly present. The immunophenotype was CK7 +/TTF1 + for respiratory epithelial cells, or TTF1 -/CK7 +/p40 + for interstitial cells. Interstitial cells might express desmin, SMA, S-100, caldesmon, etc, while CD34 +/CD10 +/ER + spindle-shaped interstitial cells were also commonly noted. Genetic variations were detected in 11 of the 15 cases that were subject to NGS, including HMGA2-related fusion genes, EP300 mutations, FLT1 mutations, JAK1 mutations, SETD2 and TAP2 mutations, and high-copy amplification of CDK4/PHF1/TSPAN31. The patients were followed up for 6 to 110 months without any known recurrence or metastasis. Conclusions:Pulmonary hamartomas mainly occur in the peripheral lung parenchyma, with the cartilaginous type being the most common. Their clinical pathological and molecular features of pulmonary hamartomas are characterized and the histological types are roughly ascertained in this study, with emphasis of the key points of diagnosis and differential diagnosis. Classification of pulmonary hamartomas is valuable for guiding future research. Pulmonary hamartomas overall have a good prognosis. However, those with cystic changes or intraluminal hamartomas in the bronchus may cause serious airway lesions and therefore require special attention.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Objective:To investigate the clinicopathological features, pathological classification, and molecular characteristics of pulmonary hamartomas.Methods:A retrospective analysis was conducted on 316 cases of pulmonary hamartomas diagnosed at Nanjing Chest Hospital, Nanjing, China from January 2015 to June 2024. Next generation sequencing (NGS) was performed on 15 cases of this study. The clinical data, histopathological features, immunophenotypes, and molecular alterations were analyzed. Relevant literature was reviewed.Results:Among the 316 patients, there were 154 males and 162 females, with an average age of 56±10 years. Among the 316 cases, 310 were intrapulmonary hamartomas and 6 were intraluminal bronchial hamartomas. Microscopically, there were complex proliferative mesenchymal components and epithelial components, presenting various combinations and hamartomatous morphologies. These hamartomas were morphologically classified into mesenchymal-type hamartomas (cartilaginous, fibrous, smooth muscle, adipose tissue, and mixed types) and epithelial-mesenchymal mixed-type hamartomas (respiratory epithelial-mesenchymal mixed and mucosal gland-mesenchymal mixed types). The cartilaginous hamartomas accounted for 72.8% (230/316) of them, and the non-cartilaginous hamartoma accounted for 27.2% (86/316). Secondary changes such as calcification, ossification, collagenization, mucin degeneration, and cystic changes were commonly present. The immunophenotype was CK7 +/TTF1 + for respiratory epithelial cells, or TTF1 -/CK7 +/p40 + for interstitial cells. Interstitial cells might express desmin, SMA, S-100, caldesmon, etc, while CD34 +/CD10 +/ER + spindle-shaped interstitial cells were also commonly noted. Genetic variations were detected in 11 of the 15 cases that were subject to NGS, including HMGA2-related fusion genes, EP300 mutations, FLT1 mutations, JAK1 mutations, SETD2 and TAP2 mutations, and high-copy amplification of CDK4/PHF1/TSPAN31. The patients were followed up for 6 to 110 months without any known recurrence or metastasis. Conclusions:Pulmonary hamartomas mainly occur in the peripheral lung parenchyma, with the cartilaginous type being the most common. Their clinical pathological and molecular features of pulmonary hamartomas are characterized and the histological types are roughly ascertained in this study, with emphasis of the key points of diagnosis and differential diagnosis. Classification of pulmonary hamartomas is valuable for guiding future research. Pulmonary hamartomas overall have a good prognosis. However, those with cystic changes or intraluminal hamartomas in the bronchus may cause serious airway lesions and therefore require special attention.

Objective: To explore the longitudinal association between organophosphate esters (OPEs) exposure and blood pressure in children, so as to provide a reference for identifying the effects of OPEs exposure on child health. Methods: A total of 404 children from the Beijing Child Growth and Health Cohort (PROC) were enrolled using a case cohort study design, baseline physical examination, urine collection, questionnaires survey were administered in 2018 and follow up surveys in 2019-2020 and 2023. Participants were divided into case group ( n =140) and control group ( n =264) according to the observation of new onset of high blood pressure during the follow up period. High performance liquid chromatography tandem mass spectrometry was used to detect diethyl phosphate (DEP)，bis (2-chloroethyl) phosphate (BCEP)，bis (1-chloro-2-propyl) phosphate, (BCIPP), diphenyl phosphate(DPHP), dibutyl phosphate (DnBP), bis (1,3-dichloro-2-propyl) phosphate(BDCIPP), bis(2-butoxyethyl) phosphate(BBOEP), bis (2-butoxyethyl) 2-hydroxyethyl phosphate (BBOEHEP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP). Generalized linear mixed models and Quantile g computation models were developed to analyze the longitudinal associations between OPEs individual/mixed exposure and blood pressure in children. Results: The detection range of 9 OPEs metabolites,including DEP, BCEP, BCIPP, DPHP, DnBP, BDCIPP, BBOEP, BBOEHEP and 4-OH-TPHP at three time points (baseline, first follow up and second follow up) were 27.7%-92.1%, 24.0%-99.3% and 39.2%-90.9% respectively. Without adjustment for covariates such as gender, age, body mass index, Tanner stage, parental education, and monthly household income, and family history of hypertension, the increase of BDCIPP concentration and mixed exposure of OPEs may reduce children s systolic blood pressure( β= -0.85，-2.40，95%CI=-1.69--0.01，-3.30--1.50，P <0.05). After adjusting for the covariates, the longitudinal association of individual OPEs or mixed exposure with pediatric BP was not statistically significant ( P >0.05). Conclusion Children are commonly exposed to OPEs, and although no significant longitudinal associations are observed between exposure to OPEs and blood pressure among school aged children in Beijing, it is recommended that child exposure should be minimized whenever possible.

Objective: To explore sex difference in the cardiovascular health (CVH) status of 6-8 year old children in Beijing, so as to inform the early intervention of CVH related lifestyles. Methods: Based on the Beijing Children s Growth and Health Cohort (PROC), baseline physical examination, sequential questionnaire survey, and laboratory tests were conducted among 1 914 grade 1 students. Children s CVH and its subscales (health behaviors and health factors) scores were calculated according to the Life s Essential 8 (LE 8) index and categorized into high, moderate, and low CVH. CVH scores were reported as medians and interquartile ranges; sex differences were compared using the Chi square test and Wilcoxon test. Results: Among the 1 914 participants, the percentages of high, moderate, and low CVH were 35.7%, 63.5%, and 0.8%, respectively, and the percentages of high, moderate, and low health behavior scores were 25.9%, 67.5%, and 6.6%, respectively, with no statistically significant differences between sex ( χ 2=2.30, 0.07, P >0.05). The rates of high, moderate, and low health factor scores for boys and girls were 61.1%, 36.0%, 2.9% and 71.1%, 28.4%, 0.5%, respectively, with a statistically significant sex difference ( χ 2=31.88, P < 0.01). The overall CVH score was 76.0(70.0, 83.0), 76.0(69.0, 82.0) for boys, and 77.0(71.0, 83.0) for girls. Among the health behavior metrics, sleep scores were the best and physical activity scores were the worst[100.0(90.0,100.0), 40.0(20.0, 80.0 )]; among the health factor metrics, blood glucose scores were the best and lipid scores were the worst[100.0(100.0,100.0), 60.0(40.0,100.0)]. In respect to health factors, there were significant gender differences in body mass index, blood lipids, blood sugar, and blood pressure scores ( Z =-6.92, 3.01, -6.60, -2.30, <0.05), but there were no significant gender differences in diet, physical activity, nicotine exposure, or sleep scores with regards to health behaviors ( Z =0.99, 0.88, -0.13, 0.36, P > 0.05 ). Compared to boys, girls in the low and moderate CVH groups had high health factor scores despite low health behavior scores. Conclusion Most 6 to 8-year-old children in Beijing were found to have relatively good CVH, and optimization of children s CVH status can be achieved by promoting healthier lifestyles and monitoring health factors, especially among boys.

Objective:To explore the clinical significance of the dominant B-cell epitope peptide of the human cytomegalovirus (HCMV) UL95 gene, as well as the correlation between the plasma UL95 specific antibody levels and clinical indicators in systemic lupus erythematosus (SLE) patients, in order to find auxiliary diagnostic indicators for SLE.Methods:A non-randomized control study was conducted to analyze the sequencial characteristics and polymorphisms of HCMV UL95 gene, and bioinformatics analysis and chemical synthesis were used to synthesize UL95 dominant B cell epitope short peptides, which were used as coating antigens. Enzyme-linked immunosorbent assay (ELISA) assay was used to detect the specific antibody levels of plasma UL95 of 97 SLE patients and 35 healthy controls (HC). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of UL95 short peptide antibodies for SLE diagnosis. Pearson correlation test was used to analyze the correlation between UL95 specific antibody levels and clinical indicators in SLE patients.Results:The nucleotide sequence similarity of UL95 gene was 92.9%-100%, and the amino acid sequence similarity was 92.1%-100%, whose sequences were highly conserved and homologous. A comprehensive prediction of multiple parameters resulted in 6 possible dominant B cell epitopes, named (Bp1, Bp2, Bp3, Bp4, Bp5, Bp6) respectively. The ELISA results showed that the levels of plasma UL95 specific antibodies (0.35±0.12) in SLE patients were significantly higher than those of the HC group (0.28±0.10)( t=3.091, P=0.002). The area under the ROC curve for distinguishing SLE and HC was 0.703, with a sensitivity of 54.6% and a specificity of 88.6%. In addition, the UL95 specifific antibody levels ( OD value) in the middle-high activity subgroup (systemic lupus erythematosus disease activity index, SLEDAI≥4) were higher (0.36±0.10) than those in the low activity subgroup (SLEDAI<4)(0.30±0.07) ( t=?2.055, P=0.044). UL95 specific antibody levels were positively correlated with clinical indicators such as total immunoglobulin G (IgG) and total immunoglobulin M (IgM), while negatively correlated with complement component 3 (C3), complement component 4 (C4), and platelet count. Conclusions:The antibody level of UL95 is closely related to the activity of lupus disease. The Bp1 (10-21) peptide segment of UL95 has important significance for the auxiliary diagnosis of SLE and is expected to become a new reference indicator.

Objective: To explore the association of body fat mass and distribution indices including fat mass percentage (FMP), visceral fat area (VFA) and percentage of trunk fat mass (%TFM) with blood pressure in children to inform early management of blood pressure in children. Methods: Based on the Beijing Child Growth and Health Cohort in Shunyi District, lifestyle questionnaire survey, baseline and follow up physical examination were conducted among children from October to November 2018 and September 2020. Bioelectrical impedance analysis (BIA) was used to measure the body composition, and 1 098 participants with completed data were finally included. Results: Both body fat indices and blood pressure increased with age in boys and girls. For FMP, VFA, and %TFM, no significant differences presented between sex at baseline, while FMP, VFA, and %TFM were significantly higher in boys than girls at follow up ( t=2.73, 3.76, 3.41, P <0.01). Before and after adjusting for age, height and lifestyles or not, linear mixed effect models showed longitudinal associations existing between body fat indices and blood pressure in both boys and girls ( β=0.64-3.48, P <0.05). The association coefficients of body fat indices with systolic blood pressure were ranked as %TFM>FMP>VFA in both boys and girls. The association coefficients of body fat indices with diastolic blood pressure were ranked sequentially as FMP>%TFM>VFA in boys, and VFA>FMP>%TFM in girls. Conclusion Longitudinal associations are observed between body fat indices and blood pressure in children. Primordial prevention of high pressure should pay attention on body fat distribution.

Purpose To investigate the clinicopathological characteristics and prognostic correlation of the WHO(2021)new grading system of invasive pulmonary adenocarcinoma in stageⅠ pulmonary adenocarcinoma.Methods The clinical data of 447 patients with stage Ⅰ pulmonary adenocarcinoma were collect-ed,and all cases were evaluated according to the new grading system for invasive pulmonary adenocarcinoma.The immunohis-tochemical EnVision two-step method and elastic fiber staining were used to analyze the clinicopathological features with review of the relevant literature.Results In 447 patients with stage Ⅰlung adenocarcinoma,Napsin A and TTF-1 expression were posi-tive,p40 expression was negative,and Ki-67 proliferation index was higher than 5％in 177 patients(39.6％).There were 39 cases(8.7％)of positive pleural invasion in the visceral layer revealed by elastic fiber staining.The pleural invasion in stage Ⅰpulmonary adenocarcinoma patients was significantly higher than that in grades 2 and 3,the difference was statistically significant(P＜0.05).Patients with different grades of stage Ⅰ pulmonary adenocarcinoma were associated with gender,smoking history,surgical mode,chemotherapy,targeted medication,clinical stage,pathological classification,degree of differentiation,tumor size,vascular invasion,visceral pleural invasion,spread through air space(STAS)and Ki-67 index(P＜0.05).Survival analy-sis showed that there were statistically significant differences in disease free survival(DFS)and overall survival(OS)among different grades(grade 1＞grade 2＞grade 3)(P＜0.05).Cox regression analysis showed that WHO(2021)new grading of invasive pulmonary adenocarcinoma,visceral pleural invasion and Ki-67 proliferation index were independent risk factors for prognosis of patients with stage Ⅰ pulmonary adenocarcinoma.Conclusion The WHO(2021)new grading system of invasive pulmonary adenocarcinoma has good prognostic significance for stage Ⅰ pulmonary adenocarcinoma,and appropriate intervention for high-risk patients.It can effectively assist its postoperative treatment and has application value.

Objective: This study aims to investigate the willingness and influencing factors of COVID-19 vaccination among Chinese middle school students, and to provide a reference for promoting the implementation of COVID-19 vaccination among middle school students. Methods: An online survey was conducted among middle school students in Beijing, Anqing of Anhui Province, Xi an of Shaanxi Province and Shenzhen of Guangdong Province, and 9 153 participants were enrolled in the present study. Single factor analysis and multinomial Logistic regression was used to determine the related factors of COVID-19 vaccination willingness. Results: The prevalence of vaccine acceptance, vaccine hesitancy and vaccine refusal among middle school students were 60.05%, 31.59% and 8.36%, respectively. The results of Chi square analysis showed there were significant difference of COVID-19 vaccination willingness among sex, school residence, grade, region, vaccination willingness of surrounding classmates, vaccination willingness of others, fear of SARS-CoV-2 and risk of SARS-CoV-2 infection( χ 2=8.43-1 059.43, P <0.05). Multinomial Logistic regression analysis presented that, compared to "vaccine acceptance" group, those girls, non resident in school, living in Beijing or Anqing, disagree or uncertain with influenced by peers, disagree or uncertain with influenced by others, uncertain with fear of SARS-CoV-2, disagree or uncertain with having risk of SARS-CoV-2 infection were more likely to show vaccine hesitancy( OR =1.22,1.21,1.49,1.69,1.75,2.54,1.41,2.32,3.32,1.99,2.38, P <0.05). And those non boarding in school, living in Beijing or Xi an, disagree or uncertainty influenced by peers, disagree or uncertainty influenced by others, disagree with fear of SARS- CoV- 2, disagree or uncertainty in having risk of SARS-CoV-2 infection were more likely to show vaccine refusal ( OR =1.27, 2.29 ,1.46,3.88,2.37,2.31,1.47,2.14,4.24,1.47, P <0.05). Conclusion The willingness of COVID-19 vaccination among middle school students in four cities is low, and targeted interventions should be advocated to form herd immunity.