1.Construction of Nomogram Prediction Model for Malnutrition in Patients with Lung Cancer undergoing Chemotherapy
Zhiying SONG ; Huifang WANG ; Jia CHEN
Journal of Medical Research 2025;54(4):111-115,156
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.
2.Identify the factors associated with treatment-free remission outcomes after imatinib discontinuation in children and adolescent patients with chronic myeloid leukemia
Huifang ZHAO ; Qian JIANG ; Weiming LI ; Yu ZHU ; Bingcheng LIU ; Qingshu ZENG ; Shuxia GUO ; Lixin LIANG ; Chunlei ZHANG ; Yingling ZU ; Yongping SONG ; Yanli ZHANG
Chinese Journal of Hematology 2025;46(9):800-805
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.
3.Identify the factors associated with treatment-free remission outcomes after imatinib discontinuation in children and adolescent patients with chronic myeloid leukemia
Huifang ZHAO ; Qian JIANG ; Weiming LI ; Yu ZHU ; Bingcheng LIU ; Qingshu ZENG ; Shuxia GUO ; Lixin LIANG ; Chunlei ZHANG ; Yingling ZU ; Yongping SONG ; Yanli ZHANG
Chinese Journal of Hematology 2025;46(9):800-805
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.
4.Quercetin inhibits zearalenone-induced ferroptosis of porcine small intestinal epi-thelial cells via regulating Nrf2/GPX4 signaling pathway
Haiyan CHEN ; Huifang LU ; Zhigao CAO ; Panfeng SUN ; Shouxuan LIU ; Chao SONG
Chinese Journal of Veterinary Science 2025;45(3):527-534,593
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.
5.Erratum: Author correction to "PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism" Acta Pharm Sin B 13 (2023) 157-173.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2025;15(4):2297-2299
[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].
6.Clinical analysis of treatment free remission outcomes after discontinuation of tyrosine kinase inhibitors in childhood chronic myeloid leukemia
Huifang ZHAO ; Lixin LIANG ; Yingling ZU ; Chunlei ZHANG ; Juan WANG ; Xianwei WANG ; Yongping SONG ; Xudong WEI ; Yanli ZHANG
Chinese Journal of Pediatrics 2025;63(3):272-277
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.
7.Construction of Nomogram Prediction Model for Malnutrition in Patients with Lung Cancer undergoing Chemotherapy
Zhiying SONG ; Huifang WANG ; Jia CHEN
Journal of Medical Research 2025;54(4):111-115,156
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.
8.Quercetin inhibits zearalenone-induced ferroptosis of porcine small intestinal epi-thelial cells via regulating Nrf2/GPX4 signaling pathway
Haiyan CHEN ; Huifang LU ; Zhigao CAO ; Panfeng SUN ; Shouxuan LIU ; Chao SONG
Chinese Journal of Veterinary Science 2025;45(3):527-534,593
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.
9.Clinical analysis of treatment free remission outcomes after discontinuation of tyrosine kinase inhibitors in childhood chronic myeloid leukemia
Huifang ZHAO ; Lixin LIANG ; Yingling ZU ; Chunlei ZHANG ; Juan WANG ; Xianwei WANG ; Yongping SONG ; Xudong WEI ; Yanli ZHANG
Chinese Journal of Pediatrics 2025;63(3):272-277
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.
10.A Bayesian network for estimating hypertension risk due to occupational aluminum exposure
Le ZHAO ; Jinzhu YIN ; Jiaping HUAN ; Xiao HAN ; Dan ZHAO ; Jing SONG ; Linping WANG ; Huifang ZHANG ; Baolong PAN ; Qiao NIU ; Xiaoting LU
Chronic Diseases and Translational Medicine 2024;10(2):130-139
Background::The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN).Methods::In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN.Results::The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90-14.25), 6.92 (2.51-19.08), and 7.33 (2.69-20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09-4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 μg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%.Conclusions::The prevalence of hypertension increased significantly with the increase of plasma aluminum level.

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