[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.

Objective:To analyze the treatment-free remission (TFR) outcomes after discontinuation of tyrosine kinase inhibitor (TKI) in children with chronic myeloid leukemia (CML).Methods:In this retrospective cohort study, clinical data of 14 chronic phase CML children aged <18 years who had achieved stable deep molecular response (DMR) for ≥ 2 years after standardized treatment with TKI and had a strong desire to discontinue TKI at Henan Cancer Hospital from September 30, 2016 to January 30, 2022 were collected retrospectively. According to the different TFR outcomes after discontinuation of TKI, patients were divided into loss of major molecular response (MMR) group and without loss of MMR group, differences in clinical characteristics between the two groups of children were analyzed using Mann-Whitney U test and Fisher exact test. Results:Out of 14 children with TKI discontinuation, 7 were male and 7 were female. The age at diagnosis was 14.0 (4.8, 17.0) years, and the age at TKI discontinuation was 22.0 (12.5, 27.0) years. Among them, 8 children were treated with imatinib prior to TKI discontinuation and 6 children were treated with second-line substitution of the second-generation TKI nilotinib or dasatinib prior to TKI discontinuation. The follow-up time was 37.0 (27.8, 47.5) months, and 7 cases lost MMR at the time of discontinuation of 3.0 (2.0, 11.0) months. Eight children gained TFR at 6 months, 7 children gained TFR at 12 and 24 months. Amongst the 6 children who received second-generation TKI prior to TKI discontinuation, 2 children lost MMR at 3 and 11 months and 4 children gained TFR, among the 8 children who discontinued imatinib, 5 children lost MMR at the time 3.0 (2.0, 9.0) months and 3 children gained TFR. The age at diagnosis and TKI discontinuation, the time from TKI treatment to the acquisition of DMR, the duration of TKI treatment before TKI discontinuation, the duration of DMR before TKI discontinuation, and the number of children treated with second-generation TKI were not statistically different between the 7 children in the group that did not lose the MMR and the 7 children in the group that lost the MMR (all P>0.05) . All the 7 children with confirmed loss of MMR immediately restarted TKI therapy, and all regained DMR after 2.0 (2.0, 11.0) months of therapy. None of the children had disease progression. After TKI discontinued, only 1 child had mild bone pain, which could be relieved by oral antipyretic analgesic drugs. Conclusions:Children with CML who have achieved a durable stable DMR for≥2 years on TKI therapy can discontinue the TKI and obtain TFR. Both the longer duration of TKI therapy, the longer duration of DMR and the use of second-generation TKI therapy before TKI discontinuation, may allow more children with CML who are expecting TKI discontinuation to have access to TFR.

The aim of this study was to investigate the mechanism of quercetin in inhibiting the fer-roptosis induced by zearalenone(ZEN)via mediating the nuclear factor erythroid-2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)signaling pathway.IPEC-J2 cells were cultured in vitro and treated with ZEN(25 mg/L)and different concentrations of quercetin(10,20,40 μmol/L).Bi-ochemical methods were used to detect the levels of lactate dehydrogenase(LDH)in the cell cul-ture medium supernatant,total antioxidant capacity(T-AOC),superoxide dismutase(SOD),glu-tathione(GSH),and malondialdehyde(MDA).Fluorescence probes were used to detect the levels of Fe2+,reactive oxygen species(ROS),and lipid peroxidation.Western blot was performed to de-tect the expression levels of Nrf2,long chain acyl CoA synthetase 4(ACSL4),and GPX4.The IPEC-J2 cells were divided into the control group,ZEN group,quercetin group,and ML385(Nrf2 inhibitor)+quercetin group for further analysis.Except for the control group,the other groups were treated with ZEN in the prescence of quercetin and ML385.The changes of Nrf2/GPX4 path-way-related proteins and ferroptosis-related indexes(LDH,Fe2+,MDA,and GSH)were detected.Compared with the control group,IPEC-J2 cells in the ZEN group exhibited a decrease in cell via-bility,T-AOC,and GSH,SOD levels,Nrf2,and GPX4 protein expressions(P＜0.05),while LDH release rate,Fe2+and ROS,lipid peroxidation,MDA levels,and ACSL4 protein expression de-creased in the ZEN group(P＜0.05).Compared with ZEN group,the cell viability,the levels of T-AOC,SOD and GSH,the protein expression of Nrf2 and GPX4 in quercetin groups were increased(P＜0.05),while the LDH release rate,the levels of Fe2+,ROS,lipid peroxidation,and MDA as well as the protein expression of ACSL4 were decreased(P＜0.05).Compared with the quercetin group,the protein expression of Nrf2 and GPX4 and the level of GSH in ML385+quercetin group reduced(P＜0.05),the LDH release rate and the levels of Fe2+and MDA increased(P＜0.05).In summary,quercetin could inhibit ZEN-induced ferroptosis of IPEC-J2 cells,and its mechanism may be related to the induction of Nrf2/GPX4 signaling pathway.

Objective To analyze the influencing factors of malnutrition in patients with lung cancer undergoing chemotherapy,and construct a predictive nomogram model according to the results.Methods A retrospective analysis was made on 100 patients with lung cancer who received postoperative chemotherapy in our hospital from March 2022 to April 2024.After all the patients had completed five cycles of chemotherapy,the incidence of malnutrition was counted.According to the nutritional evaluation results,the patients were divid-ed into two groups:well-nourished group and malnourished group.The clinical data of patients were compared and the related influen-cing factors were screened by Logistic regression analysis.The nomogram model for risk prediction of malnutrition risk of lung cancer pa-tients undergoing chemotherapy was constructed,and the predictive value and fitting degree of the model were evaluated by drawing the re-ceiver operating characteristic(ROC)curve and calibration curve.Results There were 29 cases of malnutrition in 100subjects,and the other 71 patients had normal nutritional status.Among the general data with significant differences between the two groups,TNM is stageⅣ(OR=2.275,95％CI:1.242-4.169),Accompanied by digestive system adverse reactions(OR=2.142,95％CI:1.133-4.050),Low albumin(OR=2.601,95％CI:1.370-4.937),Low hemoglobin(OR=2.697,95％CI:1.483-4.903),Low prealbumin(OR=2.686,95％CI:1.460-4.941)is a risk factor for malnutrition in patients with lung cancer undergoing chemotherapy(P＜0.05).Based on the above related risk factors,a nomogram model was established to predict the occurrence of malnutrition in patients with lung cancer undergoing chemotherapy.ROC curve analysis showed that the AUC value and 95％CI of the model for predicting malnutrition in patients with lung cancer undergoing chemotherapy were 0.972 and 0.918-0.995.The calibration curve results show that the nomogram model has a good fitting degree.Conclusion TNM is stage Ⅳ,accompanied by digestive system adverse reactions,low KPS score before chem-otherapy and low levels of albumin,hemoglobin and prealbumin are all related risk factors for malnutrition in patients with lung cancer un-dergoing chemotherapy.The nomograph model based on this is also of high predictive value.

Objective To analyze the influencing factors of malnutrition in patients with lung cancer undergoing chemotherapy,and construct a predictive nomogram model according to the results.Methods A retrospective analysis was made on 100 patients with lung cancer who received postoperative chemotherapy in our hospital from March 2022 to April 2024.After all the patients had completed five cycles of chemotherapy,the incidence of malnutrition was counted.According to the nutritional evaluation results,the patients were divid-ed into two groups:well-nourished group and malnourished group.The clinical data of patients were compared and the related influen-cing factors were screened by Logistic regression analysis.The nomogram model for risk prediction of malnutrition risk of lung cancer pa-tients undergoing chemotherapy was constructed,and the predictive value and fitting degree of the model were evaluated by drawing the re-ceiver operating characteristic(ROC)curve and calibration curve.Results There were 29 cases of malnutrition in 100subjects,and the other 71 patients had normal nutritional status.Among the general data with significant differences between the two groups,TNM is stageⅣ(OR=2.275,95％CI:1.242-4.169),Accompanied by digestive system adverse reactions(OR=2.142,95％CI:1.133-4.050),Low albumin(OR=2.601,95％CI:1.370-4.937),Low hemoglobin(OR=2.697,95％CI:1.483-4.903),Low prealbumin(OR=2.686,95％CI:1.460-4.941)is a risk factor for malnutrition in patients with lung cancer undergoing chemotherapy(P＜0.05).Based on the above related risk factors,a nomogram model was established to predict the occurrence of malnutrition in patients with lung cancer undergoing chemotherapy.ROC curve analysis showed that the AUC value and 95％CI of the model for predicting malnutrition in patients with lung cancer undergoing chemotherapy were 0.972 and 0.918-0.995.The calibration curve results show that the nomogram model has a good fitting degree.Conclusion TNM is stage Ⅳ,accompanied by digestive system adverse reactions,low KPS score before chem-otherapy and low levels of albumin,hemoglobin and prealbumin are all related risk factors for malnutrition in patients with lung cancer un-dergoing chemotherapy.The nomograph model based on this is also of high predictive value.

The aim of this study was to investigate the mechanism of quercetin in inhibiting the fer-roptosis induced by zearalenone(ZEN)via mediating the nuclear factor erythroid-2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)signaling pathway.IPEC-J2 cells were cultured in vitro and treated with ZEN(25 mg/L)and different concentrations of quercetin(10,20,40 μmol/L).Bi-ochemical methods were used to detect the levels of lactate dehydrogenase(LDH)in the cell cul-ture medium supernatant,total antioxidant capacity(T-AOC),superoxide dismutase(SOD),glu-tathione(GSH),and malondialdehyde(MDA).Fluorescence probes were used to detect the levels of Fe2+,reactive oxygen species(ROS),and lipid peroxidation.Western blot was performed to de-tect the expression levels of Nrf2,long chain acyl CoA synthetase 4(ACSL4),and GPX4.The IPEC-J2 cells were divided into the control group,ZEN group,quercetin group,and ML385(Nrf2 inhibitor)+quercetin group for further analysis.Except for the control group,the other groups were treated with ZEN in the prescence of quercetin and ML385.The changes of Nrf2/GPX4 path-way-related proteins and ferroptosis-related indexes(LDH,Fe2+,MDA,and GSH)were detected.Compared with the control group,IPEC-J2 cells in the ZEN group exhibited a decrease in cell via-bility,T-AOC,and GSH,SOD levels,Nrf2,and GPX4 protein expressions(P＜0.05),while LDH release rate,Fe2+and ROS,lipid peroxidation,MDA levels,and ACSL4 protein expression de-creased in the ZEN group(P＜0.05).Compared with ZEN group,the cell viability,the levels of T-AOC,SOD and GSH,the protein expression of Nrf2 and GPX4 in quercetin groups were increased(P＜0.05),while the LDH release rate,the levels of Fe2+,ROS,lipid peroxidation,and MDA as well as the protein expression of ACSL4 were decreased(P＜0.05).Compared with the quercetin group,the protein expression of Nrf2 and GPX4 and the level of GSH in ML385+quercetin group reduced(P＜0.05),the LDH release rate and the levels of Fe2+and MDA increased(P＜0.05).In summary,quercetin could inhibit ZEN-induced ferroptosis of IPEC-J2 cells,and its mechanism may be related to the induction of Nrf2/GPX4 signaling pathway.

Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.

Objective:To analyze the treatment-free remission (TFR) outcomes after discontinuation of tyrosine kinase inhibitor (TKI) in children with chronic myeloid leukemia (CML).Methods:In this retrospective cohort study, clinical data of 14 chronic phase CML children aged <18 years who had achieved stable deep molecular response (DMR) for ≥ 2 years after standardized treatment with TKI and had a strong desire to discontinue TKI at Henan Cancer Hospital from September 30, 2016 to January 30, 2022 were collected retrospectively. According to the different TFR outcomes after discontinuation of TKI, patients were divided into loss of major molecular response (MMR) group and without loss of MMR group, differences in clinical characteristics between the two groups of children were analyzed using Mann-Whitney U test and Fisher exact test. Results:Out of 14 children with TKI discontinuation, 7 were male and 7 were female. The age at diagnosis was 14.0 (4.8, 17.0) years, and the age at TKI discontinuation was 22.0 (12.5, 27.0) years. Among them, 8 children were treated with imatinib prior to TKI discontinuation and 6 children were treated with second-line substitution of the second-generation TKI nilotinib or dasatinib prior to TKI discontinuation. The follow-up time was 37.0 (27.8, 47.5) months, and 7 cases lost MMR at the time of discontinuation of 3.0 (2.0, 11.0) months. Eight children gained TFR at 6 months, 7 children gained TFR at 12 and 24 months. Amongst the 6 children who received second-generation TKI prior to TKI discontinuation, 2 children lost MMR at 3 and 11 months and 4 children gained TFR, among the 8 children who discontinued imatinib, 5 children lost MMR at the time 3.0 (2.0, 9.0) months and 3 children gained TFR. The age at diagnosis and TKI discontinuation, the time from TKI treatment to the acquisition of DMR, the duration of TKI treatment before TKI discontinuation, the duration of DMR before TKI discontinuation, and the number of children treated with second-generation TKI were not statistically different between the 7 children in the group that did not lose the MMR and the 7 children in the group that lost the MMR (all P>0.05) . All the 7 children with confirmed loss of MMR immediately restarted TKI therapy, and all regained DMR after 2.0 (2.0, 11.0) months of therapy. None of the children had disease progression. After TKI discontinued, only 1 child had mild bone pain, which could be relieved by oral antipyretic analgesic drugs. Conclusions:Children with CML who have achieved a durable stable DMR for≥2 years on TKI therapy can discontinue the TKI and obtain TFR. Both the longer duration of TKI therapy, the longer duration of DMR and the use of second-generation TKI therapy before TKI discontinuation, may allow more children with CML who are expecting TKI discontinuation to have access to TFR.

Objective:To observe the changes of lung function and inflammatory factors in rat models of coal workers' pneumoconiosis at different time points.Methods:In June 2021, 96 healthy male SD rats with SPF grade were divided into 1, 3, and 6-month control group and dust staining group (coal dust group, coal silica dust group, quartz group) according to random number table method, with 8 rats in each group. After one week of adaptive feeding, a one-time non-exposed tracheal perfusion method (1 ml/ piece) was used. The dust dyeing group was given 50 g/L coal dust, coal silica mixed dust and quartz dust suspension, respectively, and the control group was given 0.9% normal saline solution. At 1, 3 and 6 months after perfusion, lung function was detected by animal lung function apparatus, then all lung tissues and alveolar lavage fluid were killed, and lung histopathological morphological changes were observed by HE staining, and the contents of interleukin (IL-1β), IL-18, IL-4 and IL-10 in alveolar lavage fluid were detected by ELISA. One-way analysis of variance was used to compare groups. Two factors (inter-group treatment factor (4 levels) and observation time factor (3 levels) ) were used in the analysis of the effects of inter-group treatment and treatment time on related indicators.Results:HE staining results showed that coal spot appeared in the lung tissue of coal dust group, coal spot and coal silicon nodule appeared in the lung tissue of coal dust group, and silicon nodule appeared in the lung tissue of quartz group. Compared with the control group, the forced vital capacity (FVC) and forced expiratory volume at 0.2 second (FEV 0.2) of rats in the dust staining group had interaction between the treatment and treatment time ( P<0.05). With the increase of dust dyeing time, FVC and FEV 0.2 decreased significantly at 3-6 months of dust dyeing, and the maximum gas volume per minute (MVV) decreased significantly at 1-3 months of dust dyeing ( P<0.05). The lowest lung function index was in quartz group, followed by coal-silica group and coal-dust group. There were statistically significant differences in the main effect and interaction effect of the pro-inflammatory factor IL-18 among all groups in treatment and treatment time (IL-18: F=70.79, 45.97, 5.90, P<0.001), and interaction existed. The highest content of inflammatory factors in alveolar lavage fluid of all dust groups was quartz group, followed by coal silica group and coal dust group. There were significant differences in the main effect and interaction effect of anti-inflammatory factors between groups and treatment time (IL-4: F=41.55, 33.01, 5.23, P<0.001, <0.001, <0.001; IL-10: F=7.46, 20.80, 2.91, P=0.002, <0.001, 0.024), and there was interaction. The highest content of anti-inflammatory factor was in quartz group, followed by coal silica group and coal dust group. Conclusion:Lung function decreased and levels of inflammatory fators increased in rat models of coal workers' pneumoconiosis, with the quartz group being the most severely damaged. Lung function is mainly impaired in thrid-six months, and the content of inflammatory factors begins to change in first-thrid months. MVV are the earliest and most obvious in lung function. IL-18 is suitable for monitoring changes in the pro-inflammatory response of coal workers' pneumoconiosis, and IL-10 is suitable for monitoring changes in anti-inflammatory response.