Objective:To explore the pathogenesis,clinical features,treatment strategies,and prognosis of pediatric lymphoepithelioma-like carcinoma(LELC).Methods:A retrospective analysis was conducted on the clinical data of patients with LELC aged<18 years,treated at Sun Yat-sen University Cancer Center from March 2008 to June 2023.Results:A total of 19 children and adolescents were included in the analys-is,comprising 10 males(52.6%)and 9 females(47.4%),with a median age of 12.9(4.3-17.0)years.Fourteen patients(73.7%)lived in Guangdong province,with the remainder scattered across other regions.Primary LELC sites were the mediastinum(11 cases,57.9%),parot-id glands(4 cases,21%),neck(1 case,5.3%),lungs(1 case,5.3%),salivary glands(1 case,5.3%),and submandibular glands(1 case,5.3%).Among these,15 patients(78.9%)had at least one distant metastasis at initial diagnosis,with common metastasis sites being cervical lymph nodes.Multivariate Cox regression analysis identified tumor volume≥801 cm3 as an independent adverse prognostic factor of poor overall survival(OS)(P<0.01).The 2-year OS and progression-free survival(PFS)rates were 84.2%and 57.9%,respectively.The 2-year OS for pa-tients who underwent surgery,chemotherapy,and radiotherapy was 100%,compared with 25%for those who received only partial treat-ment(P=0.007).The 2-year PFS rate was significantly higher in patients receiving first-line combination therapy with programmed death-1(PD-1)antibodies(100%)compared with those not treated with PD-1 antibodies(38.5%)(P=0.020).For patients with tumor volume≥801 cm3,the 2-year OS was 40.0%,whereas for those with a tumor volume<801 cm3,the 2-year OS was 100%(P<0.001).The 2-year OS for pa-tients who underwent radiotherapy was 100%,while it was 0 for those who did not receive radiotherapy(P<0.001).Conclusions:Pediatric LELC exhibits a relatively favorable prognosis with multidisciplinary treatment,including surgery,chemotherapy,and radiotherapy.The com-bined use of PD-1 antibodies at the time of initial diagnosis could offer potential benefits and warrants further exploration.

Objective:To explore the pathogenesis,clinical features,treatment strategies,and prognosis of pediatric lymphoepithelioma-like carcinoma(LELC).Methods:A retrospective analysis was conducted on the clinical data of patients with LELC aged<18 years,treated at Sun Yat-sen University Cancer Center from March 2008 to June 2023.Results:A total of 19 children and adolescents were included in the analys-is,comprising 10 males(52.6%)and 9 females(47.4%),with a median age of 12.9(4.3-17.0)years.Fourteen patients(73.7%)lived in Guangdong province,with the remainder scattered across other regions.Primary LELC sites were the mediastinum(11 cases,57.9%),parot-id glands(4 cases,21%),neck(1 case,5.3%),lungs(1 case,5.3%),salivary glands(1 case,5.3%),and submandibular glands(1 case,5.3%).Among these,15 patients(78.9%)had at least one distant metastasis at initial diagnosis,with common metastasis sites being cervical lymph nodes.Multivariate Cox regression analysis identified tumor volume≥801 cm3 as an independent adverse prognostic factor of poor overall survival(OS)(P<0.01).The 2-year OS and progression-free survival(PFS)rates were 84.2%and 57.9%,respectively.The 2-year OS for pa-tients who underwent surgery,chemotherapy,and radiotherapy was 100%,compared with 25%for those who received only partial treat-ment(P=0.007).The 2-year PFS rate was significantly higher in patients receiving first-line combination therapy with programmed death-1(PD-1)antibodies(100%)compared with those not treated with PD-1 antibodies(38.5%)(P=0.020).For patients with tumor volume≥801 cm3,the 2-year OS was 40.0%,whereas for those with a tumor volume<801 cm3,the 2-year OS was 100%(P<0.001).The 2-year OS for pa-tients who underwent radiotherapy was 100%,while it was 0 for those who did not receive radiotherapy(P<0.001).Conclusions:Pediatric LELC exhibits a relatively favorable prognosis with multidisciplinary treatment,including surgery,chemotherapy,and radiotherapy.The com-bined use of PD-1 antibodies at the time of initial diagnosis could offer potential benefits and warrants further exploration.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. Conclusion This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Objective:This study aimed to investigate the effect of tumor lysis syndrome (TLS) on the prognosis of children and adolescents with intermediate- or high-risk high-grade mature B-cell nonHodgkin lymphoma (HG B-NHL) .Methods:This study collected the clinical data and prognosis of 283 patients aged <18 years with newly diagnosed intermediate- or high-risk HG B-NHL treated at the Sun Yat-sen University Cancer Center from January 2010 to December 2022. The clinical characteristics, laboratory indicators during TLS, and prognosis of the patients were analyzed. The optimal cutoff values of laboratory indicators during TLS were identified using R studio according to event-free survival (EFS) .Results:Of the 283 patients enrolled, the median age was 7 (range: 1-18) years and the male-to-female ratio was 3.6∶1, 76 (26.9%) developed TLS, and 207 (73.1%) did not. Patients with TLS demonstrated higher proportions of the pathological subtype Burkitt lymphoma, high-risk stratification, age <12 years, and LDH of ≥1 000 IU/L compared with patients without TLS (all P<0.05). The 5-year EFS and overall survival (OS) rates of the entire group were (84.5±2.2) % and (88.2±2.0) %, respectively. The 5-year OS rate of patients with TLS was significantly lower than that of those without TLS [ (80.8±4.6) % vs (91.0±2.0) %, P=0.01]. Among patients with TLS, those with serum uric acid of ≤612.7 μmol/L ( n=36) exhibited lower 5-year EFS [ (67.8±8.1) % vs (87.5±5.2) %, P=0.04] and OS rates [ (69.9±8.1) % vs (90.0±4.7) %, P=0.04] compared with those with uric acid of >612.7 μmol/L ( n=40). Similarly, patients with serum phosphate of ≤1.89 mmol/L ( n=58) demonstrated lower 5-year EFS [ (71.6±6.0) % vs 100%, P=0.02] and OS rates [ (74.8±5.8) % vs 100%, P=0.03] compared with those with phosphate of >1.89 mmol/L ( n=18) . Conclusions:TLS is associated with poor prognosis in patients with HG B-NHL. Patients with lower serum uric acid and phosphate levels during TLS demonstrated worse prognoses, indicating their potential value in predicting prognosis and guiding stratified treatment.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.

Objective:This study aimed to investigate the effect of tumor lysis syndrome (TLS) on the prognosis of children and adolescents with intermediate- or high-risk high-grade mature B-cell nonHodgkin lymphoma (HG B-NHL) .Methods:This study collected the clinical data and prognosis of 283 patients aged <18 years with newly diagnosed intermediate- or high-risk HG B-NHL treated at the Sun Yat-sen University Cancer Center from January 2010 to December 2022. The clinical characteristics, laboratory indicators during TLS, and prognosis of the patients were analyzed. The optimal cutoff values of laboratory indicators during TLS were identified using R studio according to event-free survival (EFS) .Results:Of the 283 patients enrolled, the median age was 7 (range: 1-18) years and the male-to-female ratio was 3.6∶1, 76 (26.9%) developed TLS, and 207 (73.1%) did not. Patients with TLS demonstrated higher proportions of the pathological subtype Burkitt lymphoma, high-risk stratification, age <12 years, and LDH of ≥1 000 IU/L compared with patients without TLS (all P<0.05). The 5-year EFS and overall survival (OS) rates of the entire group were (84.5±2.2) % and (88.2±2.0) %, respectively. The 5-year OS rate of patients with TLS was significantly lower than that of those without TLS [ (80.8±4.6) % vs (91.0±2.0) %, P=0.01]. Among patients with TLS, those with serum uric acid of ≤612.7 μmol/L ( n=36) exhibited lower 5-year EFS [ (67.8±8.1) % vs (87.5±5.2) %, P=0.04] and OS rates [ (69.9±8.1) % vs (90.0±4.7) %, P=0.04] compared with those with uric acid of >612.7 μmol/L ( n=40). Similarly, patients with serum phosphate of ≤1.89 mmol/L ( n=58) demonstrated lower 5-year EFS [ (71.6±6.0) % vs 100%, P=0.02] and OS rates [ (74.8±5.8) % vs 100%, P=0.03] compared with those with phosphate of >1.89 mmol/L ( n=18) . Conclusions:TLS is associated with poor prognosis in patients with HG B-NHL. Patients with lower serum uric acid and phosphate levels during TLS demonstrated worse prognoses, indicating their potential value in predicting prognosis and guiding stratified treatment.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

Objective: To compare bioelectrical impedance analysis (BIA) and dual energy X ray absorptiometry (DXA) for measuring body mineral content (BMC) of children and adolescents, and to provide a basis for BIA to accurately measure BMC in children and adolescents. Methods: By using the convenience sampling method, among 1 469 children and adolescents aged 7-17 were recruited in Guangzhou from April to May 2019, the BMC was measured by DXA and BIA. The intraclass correlation coefficient ( ICC ) and Bland Altman analysis were used to evaluate the agreement between BIA and DXA. Bland Altman analysis was performed on log transformed data. The BMC was categorized into age and specific tertiles, and the agreement between methods was evaluated based on the kappa coefficients. Treating the BMC with DXA as the dependent variable, a prediction model was constructed for correcting the BIA measure. Results: The ICC s were 0.93 and 0.94 for boys and girls, respectively. In Bland Altman analysis, the limits of agreements for the BIA to DXA ratio were wide in boys and girls, ranging from 0.27-0.76 and 0.17-0.72, respectively. The kappa coefficients for categorized BMC levels were 0.57 and 0.45 for boys and girls, respectively, showing a fair to good degree of agreement. When sub grouped by BMI, the kappa coefficients for all BMI groups of boys and overweight girls were all >0.75 , with an excellent agreement. The prediction models for boys and girls were as follows: BMC DXA =-0.51+0.44× BMC BIA + 0.06× Age +0.02× BMI ; and BMC DXA =-0.55+0.43× BMC BIA +0.06× Age +0.02× BMI , respectively. The R 2 for models of boys and girls were 0.87 and 0.87, respectively. Conclusion The agreement between BIA and DXA was poor for measuring BMC, but acceptable when evaluating the categorized BMC levels, suggesting the BIA may be applied in assessment of the BMC levels when compared to the age and gender specific population. Additionally, the prediction model for correcting BMC by BIA fis well to the measurement by DXA.

Objective:To investigate the effect of combined treatment of hyperforin(HPF) and amlexanox(AM) on obesity and metabolic disorders.Methods:ob/ob mice were used as an obese mice model and treated with HPF alone(2.5 mg/kg intraperitoneal injection) or combined with AM(50 mg/kg, gavage administration) for 4 weeks. Their body weight and food intake were monitored, glucose tolerance test and insulin tolerance test were performed, serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels were detected. Nuclear magnetic resonance was used to detect the body composition and metabolic cage was used to detect the energy consumption. After sampling, HE staining was used to observed the pathological change of fat and liver tissues, Western blotting and enzyme-linked immunosorbent assay(ELISA) were used to detect the cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA) signaling pathway.Results:Compared to the vehicle-treated mice(54.07 g), HPF-treated mice showed attenuated body weight gain(51.33 g, P=0.042) and reduced total fat mass( P=0.011); while administration of HPF in combination with AM(HPF/AM) further reduced the body weight(47.61 g, P=0.041). HE staining analysis showed that HPF alone or HPF/AM treatment both decreased the diameters of adipocytes and infiltration of white fat( P=0.014, P=0.032) in brown adipose tissues, which resulted in a trend of browning. However, HPF/AM-treatment didn′t further diminish adipocytes or reduce lipid accumulation in brown adipose tissues compared to HPF-treated mice. In addition, the basal oxygen consumption rate(VO 2, P<0.001) and(VCO 2, P=0.002) of HPF-treated mice were mainly elevated in the light phase relative to that of control mice; while HPF/AM-treatment further promote the energy consumption both in the dark phase and light phase. Notably, cAMP-PKA signaling pathway was obviously activated under HPF/AM-treatment in inguinal white adipose tissue. Moreover, HPF/AM-treatment showed beneficial effects on glucose metabolism and fatty liver, as indicated by improved insulin resistance, reduced liver steatosis( P=0.049) and the serum ALT levels( P=0.008). Conclusion:Combined administration of HPF and AM is an effective strategy in the treatment of obesity, improvement of metabolic disorders and alleviation of catecholamine resistance.