1.Effects of Yangxin Tongmai Formula (养心通脉方) on Methylation Key Genes and the PERK/ATF4/CHOP Signaling Pathway in Myocardial Tissue of Coronary Heart Disease Model Rats with Blood Stasis Syndrome
Chun ZHANG ; Shumeng ZHANG ; Yan MAO ; Xing CHEN ; Huifang KUANG ; Yi YANG ; Lingli CHEN ; Jie LI
Journal of Traditional Chinese Medicine 2026;67(7):784-791
ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula (养心通脉方, YTF) in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group (n=12) and a modeling group (n=60). The modeling group was subjected to a high-fat diet, intragastric administration of vitamin D3, and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group, YTF low-, medium-, and high-dose groups, and the atorvastatin calcium group, with 8 rats in each group and 1 rat reserved. The YTF low-, medium-, and high-dose groups received YTF at 6, 12, and 18 g/(kg·d) by gavage, respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/(kg·d) by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/(kg·d) by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration, serum lipid levels including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), myocardial enzymes including cardiac troponin T (cTnT), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH), and inflammatory factors including interleukin-1β (IL-1β) and interleukin-10 (IL-10) were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group, model group, and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group, the model group showed increased levels of TC, TG, LDL-C, cTnT, CK-MB, LDH, and IL-1β, along with decreased levels of HDL-C and IL-10 (P<0.05 or P<0.01). Compared to the model group, all treatment groups exhibited decreased levels of TC, LDL-C, CK-MB, and LDH, along with increased IL-10 levels. Among these, the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups (P<0.05 or P<0.01). HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling, disordered arrangement, pyknosis, and disappearance of nuclei, thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group, model group, and YTF high-dose group, including 109 hypermethylated and 131 hypomethylated genes; eif2ak3 was identified as a key differentially methylated gene. Compared to the control group, the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 (eIf2ak3), phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and Bax, along with a decreased level of B-cell lymphoma-2 (Bcl-2) protein (P<0.05 or P<0.01). Compared to the model group, the YTF high-dose group showed decreased protein levels of eIf2ak3, p-PERK, ATF4, CHOP, and Bax, and an increased level of Bcl-2 protein (P<0.05 or P<0.01). ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway, thereby inhibiting endoplasmic reticulum stress, reducing myocardial cell apoptosis, and exerting therapeutic effects in coronary heart disease blood stasis syndrome.
2.Risk factors for decompensated liver cirrhosis and the construction of a nomogram prediction model
Yuanyuan LIANG ; Huifang QU ; Xiyue WANG ; Yan WANG ; Hezhao ZHANG ; Jun XU
Journal of Clinical Hepatology 2026;42(6):1327-1334
ObjectiveTo investigate the independent risk factors for decompensation in patients with liver cirrhosis, to construct a nomogram-based risk assessment model, and to assess its risk assessment performance and clinical value by comparing it with Model for End-Stage Liver Disease (MELD), MELD combined with serum sodium concentration (MELD-Na), and MELD 3.0 scoring system. MethodsA retrospective analysis was performed for 514 patients with liver cirrhosis who attended The First Hospital of Shanxi Medical University from January 2020 to May 2025, and related data were collected, including demographic data and laboratory markers. According to the presence or absence of decompensation, the patients were divided into compensation group with 275 patients and decompensation group with 239 patients. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The least absolute shrinkage and selection operator regression analysis was used for screening of variables, and the multivariate logistic regression analysis was used to identify independent risk factors for decompensated liver cirrhosis and construct a nomogram model. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis were used to assess the discriminatory ability, calibration, and net clinical benefit of the model. ResultsThe multivariate logistic regression analysis showed that low hemoglobin (odds ratio [OR]=0.984, 95% confidence interval [CI]: 0.969 — 0.999, P<0.05), low lymphocytes (OR=0.564, 95%CI: 0.383 — 0.830, P<0.05), high international normalized ratio (OR=3.131, 95%CI: 1.242 — 7.891, P<0.05), and low serum sodium (OR=0.922, 95%CI: 0.872 — 0.975, P<0.05) were independent risk factors for decompensation events in patients with liver cirrhosis. Construct the prediction model equation: Logit(P)=intercept value-0.016×hemoglobin-0.573×lymphocytes+1.141×INR-0.081×serum sodium. The nomogram constructed based on these factors had a good discriminatory ability, with an area under the ROC curve (AUC) of 0.787, a specificity of 77.8%, and a sensitivity of 67.4%, and it had significantly better predictive performance than MELD score (AUC=0.718), MELD-Na score (AUC=0.719), and MELD 3.0 score (AUC=0.725). The calibration curve showed good consistency between the probability of risk assessed by the model and the observed probability. The decision curve analysis showed that compared with the MELD-based scores, this model provided higher net clinical benefit across a wide range of risk thresholds. ConclusionThis study successfully constructed and validated a nomogram risk assessment model incorporating hemoglobin, international normalized ratio, lymphocytes, and serum sodium. This model has good clinical practicability and can help to achieve early identification of high-risk patients with decompensated liver cirrhosis and optimize intervention strategies in clinical practice.
3.Clinical diagnostic value of MRI combined with serum CYR61 and CXCL1 for acute stroke
Juan TIAN ; Huifang WANG ; Weijing ZHANG
Chinese Journal of Radiological Health 2026;35(3):394-400
Objective To evaluate the clinical utility of combining magnetic resonance imaging (MRI) findings with serum levels of cysteine-rich protein 61 (CYR61) and C-X-C motif chemokine ligand 1 (CXCL1) for early identification of acute stroke. Methods The study was conducted 205 patients with suspected acute stroke admitted to the neurology department of our hospital between April 2021 and April 2024. Based on brain CT imaging and clinical diagnosis, 119 patients were acute stroke group and 86 to non-acute stroke group. All patients underwent MRI examination. Serum levels of CYR61 and CXCL1 were measured. Receiver operating characteristic (ROC) curves were generated to assess diagnostic value, and Kappa tests were used to performed to evaluate the consistency. Results Serum level of CYR61 and CXCL1were significantly higher in the acute stroke group than in the non-acute stroke group (P<0.05). The area under the ROC curve (AUC) for serum CYR61 in diagnosing acute stroke was 0.867 (95%CI: 0.819-0.915), with diagnostic threshold of 6.02 μg/L; for CXCL1, the AUC was 0.818 (95%CI: 0.762-0.875), with a threshold of 1.28 ng/mL. The Kappa values for agreement between MRI, serum CYR61, and CXCL1 clinical diagnosis results were 0.766, 0.586, and 0.528, respectively, the Kappa value for the consistency between the combination of the three with clinical diagnosis results was 0.920 (P<0.05). The sensitivity, negative predictive value, and accuracy of the combination of MRI, serum CYR61, and CXCL1 were obviously higher than that of the individual diagnosis, and the specificity and positive predictive value were obviously higher than that of the individual diagnosis of serum CYR61 and CXCL1 (P<0.05). Conclusion The clinical diagnostic accuracy of MRI combined with serum CYR61 and CXCL1 in the diagnosis of acute stroke is high, the combined diagnosis is obviously better than the individual diagnosis of each indicator.
4.Effects of the Bushen Zhuyun Formula(补肾助孕方)on JAK2/STAT3 Signaling Pathway and Macrophage Polarization in Uterine Tissues of Mice with Embryo Implantation Failure
Yunan LIU ; Huifang ZHOU ; Chen WANG ; Mengwen ZHANG ; Ping CHEN
Journal of Traditional Chinese Medicine 2026;67(16):1767-1774
ObjectiveTo explore the effect of Bushen Zhuyun Formula(补肾助孕方, BZF) on macrophage pola-rization in mouse uterine tissue with embryo implantation failure based on the janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) signaling pathway. MethodsFifty female and 25 male C57BL/6 mice were randomly divided into five groups including blank group, model group, low- and high-dose BZF groups, and dydrogesterone group, with 10 female and 5 male mice in each group. Except for the blank group, female mice in the estrous phase were subjected to superovulation induction. At 18:00 on the same day, female mice were co-housed with male mice at a ratio of 2∶1. The presence of sperm in vaginal exfoliated cells was examined on the following day, which was designated as gestational day 1 (GD1). On GD4, an oil-based mifepristone solution was subcutaneously injected into the neck region of female mice to establish an embryo implantation dysfunction model. Beginning on GD1, mice in the low- and high-dose BZF groups were given 11.18 and 22.36 g/kg of the BZF solution by gavage, respectively. The dydrogesterone group was given 2.6 mg/kg of dydrogesterone solution by gavage. The blank group and the model group were given 10 g/kg of normal saline by gavage once daily. Interventions were administered once a day until GD4. On GD5, uterine tissues were collected, and HE staining was performed to evaluate endometrial morphology, endometrial thickness, and glandular number in female mice. The proportions of M1 and M2 macrophages in uterine tissues were detected by flow cytometry, and the levels of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) in uterine tissue were measured by ELISA. The protein expression levels of Janus kinase 2 (JAK2), phosphorylated JAK2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3) in uterine tissue were detected by western blotting, and the mRNA expressions of JAK2, STAT3, IL-10, and TGF-β1 in uterine tissue was detected by real-time quantitative PCR. ResultsCompared to the blank group, the model group exhibited smaller and straighter endometrial glands, denser stroma, and fewer blood vessels, with reduced endometrial thickness and decreased glandular numbers. The proportion of M1 macrophages in uterine tissue increased, while the proportion of M2 macrophages and the levels of IL-10 and TGF-β1 decreased. The protein expression levels of JAK2, p-JAK2, STAT3, and p-STAT3, as well as the p-JAK2/JAK2 and p-STAT3/STAT3 ratios, were reduced. The mRNA expressions of JAK2, STAT3, IL-10, and TGF-β1 also decreased (P<0.05). Compared to the model group, the above indicators were improved in the low- and high-dose BZF groups, while some indicators were improved in the dydrogesterone group (P<0.05). Compared to the dydrogesterone group and the low-dose BZF group, the high-dose BZF group showed superior effects in improving endometrial morphology, endometrial thickness, glandular number, the proportion of M1 macrophages in uterine tissues, TGF-β1 levels, JAK2, p-JAK2, and p-STAT3 protein expression levels, the p-STAT3/STAT3 and p-JAK2/JAK2 ratios, as well as JAK2, IL-10, and TGF-β1 mRNA expressions (P<0.05). ConclusionBZF can improve the morphology of the endometrium during implantation in mice with embryo implantation failure, which may be related to specific regulation of the JAK2/STAT3 signaling pathway, modulation of macrophage polarization, and promotion of anti-inflammatory cytokine expression.
5.Analysis of the changing trends and epidemiological characteristics of hospitalized elderly patients with drug-resistant pulmonary tuberculosis in a designated hospital in Beijing
Bo LI ; Xiyu SHANG ; Yumeng DONG ; Yuqing CAO ; Huifang ZHANG ; Jiuhong LI ; Yan MA
Chinese Journal of Geriatrics 2025;44(7):883-890
Objective:To analyze the epidemiological characteristics and changing trends of elderly patients with drug-resistant pulmonary tuberculosis(DR-PTB)at Beijing Chest Hospital, Capital Medical University, in order to provide references for clinical prevention and treatment.Methods:Data were retrospectively collected from all DR-PTB cases hospitalized in the electronic medical record system of Beijing Chest Hospital from 2019 to 2023.The epidemiological characteristics including classification, gender, age, occupation and their changing trends among elderly DR-PTB patients were analyzed.Results:Among 1 981 hospitalized DR-PTB patients, 400(20.19%)were elderly[aged 60-92 years, mean(68.67±7.01)years], showing an overall increasing trend from 2019 to 2023.Mono-resistant PTB was the most common(198 cases, 49.50%), followed by multidrug-resistant PTB(170 cases, 42.50%), extensively drug-resistant PTB(21 cases, 5.25%), and polyresistant PTB(11 cases, 2.75%).Among the elderly DR-PTB patients, 287 cases(71.75%)were male, 200 cases(50.00%)were initial treatment cases, 377 cases(94.25%)were Han nationality, 165 cases(41.25%)were Beijing residents, 185 cases(46.25%)were employees of enterprises and institutions, 109 cases(27.25%)were farmers, 68 cases(17.00%)were unemployed individuals, 202 cases(50.50%)were pathogen-positive cases(smear and culture positive), and 228 cases(57.00%), 331 cases(82.75%), 196 cases(49.00%)were patients with comorbidities, complications, and extrapulmonary tuberculosis, respectively.There were no significant differences between elderly and non-elderly groups in ethnicity, treatment classification, or comorbidities(all P>0.05).However, significantly differences were found in gender ( χ2=12.718, P<0.001), occupation ( χ2=97.500, P<0.001), patient origin ( χ2=119.771, P<0.001), pathogen detection results ( χ2=10.101, P=0.001), and drug resistance patterns ( χ2=15.990, P=0.001).The proportion of elderly DR-PTB patients showed an overall increasing trend, with rises in females(25.64%-28.70%), unemployed individuals(7.69%-20.37%), other occupations(5.13%-19.40%), Han ethnicity(91.03%-99.07%), initial treatment(33.33%-57.41%), smear-negative but culture-positive cases(46.15%-53.70%), polyresistant PTB(1.28%-9.26%), and extensively drug-resistant PTB(1.28%-3.70%). Conclusions:Among elderly DR-PTB patients, the proportions of female, unemployed individuals and other occupations, initial treatment cases, smear-negative but culture-positive cases, polyresistant PTB, and extensively drug-resistant PTB are increasing annually.Future efforts should focus on targeted prevention and treatment for key populations to further reduce the rate of elderly DR-PTB.
6.Cancer Incidence and Mortality in Henan Province in 2020 and Trends from 2010 to 2020
Kexin YI ; Ranran QIE ; Yin LIU ; Huifang XU ; Hong WANG ; Jinyu ZHANG ; Shaokai ZHANG
China Cancer 2025;34(11):829-837
[Purpose]To analyze the cancer incidence and mortality in 2020 and trends from 2010 to 2020 in Henan Province.[Methods]Data from cancer registries in Henan Province from 2010 to 2020 were collected and evaluated.Incidence and mortality rates were calculated by urban/rural areas,sex and age,and the incidence and mortality of cancers in the whole province in 2020 were estimated based on population data released by Henan Provincial Bureau of Statistics.Age-standardized rates were calculated according to the age-standardized rate of Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW).Joinpoint 5.4.0 soft-ware was used to construct a regression model to analyze the changing trends of malignant tumors from 2010 to 2020,and the average annual percentage change(AAPC)and 95%confidence in-terval were calculated.[Results]In 2020,the estimated number of new cancer cases in Henan Province was 299 148,with a crude incidence rate of 259.38/105,ASIRC of 201.09/105(204.56/105 for males and 200.45/105 for females)and ASIRW of 196.46/105(203.43/105 for males and 192.22/105 for females).The ASIRC was higher in urban areas(208.10/105)than that in rural areas(197.74/105).The top five cancer types in male were lung,stomach,liver,esophagus,and colorectal cancers,while the top five in female were breast,lung,thyroid,cervical,and esophageal cancers.The estimated number of cancer deaths was 172 070,with a crude mortality rate of 149.20/105 and ASMRC of 106.52/105(137.22/105 for males and 78.04/105 for females)and ASMRW of 106.24/105(137.05/105 for males and 77.91/105 for females).The ASMRC was higher in rural areas(109.92/105)than that in urban areas(99.49/105).The top five causes of cancer death in male were lung,stomach,liver,esophagus,and colorectal cancers,and those in female were lung,esophagus,stomach,liver,and breast cancers.From 2010 to 2020,the trends of ASIRC remained stable(AAPC=0.14%,P=0.572),while the ASMRC showed a significant decreasing trend(AAPC=-1.46%,P=0.011).[Conclusion]Lung cancer,breast cancer and digestive system cancers are the main malignant tumors threatening the health of residents in Henan Province.The incidence and mor-tality of common malignant tumors show significant gender and urban-rural differences.It is neces-sary to further optimize the prevention and control of malignant tumors,formulate targeted inter-vention strategies based on population characteristics,and improve the health awareness of the whole population.
7.Retrospective clinical analysis of eculizumab treatment for hematopoietic stem cell transplantation-associated thrombotic microangiopathy: a report of 11 cases
Xueyi LUO ; Rui MA ; Huifang WANG ; Lu BAI ; Yun HE ; Yuanyuan ZHANG ; Tingting HAN ; Daoxing DENG ; Yuhong CHEN ; Wei HAN ; Xiaohui ZHANG ; Lanping XU ; Yu WANG ; Xiaojun HUANG ; Yuqian SUN
Chinese Journal of Hematology 2025;46(5):431-436
Objective:To evaluate the efficacy of eculizumab in treating hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) .Methods:This retrospective study included 11 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation and subsequently received eculizumab treatment at Peking University People′s Hospital between June 2018 and May 2024. The incidence of TA-TMA, treatment details, and clinical outcomes were analyzed.Results:Among the 11 included patients [4 males, 7 females; median age: 29 years (range: 9-56) ], underlying diseases were severe aplastic anemia (SAA) in 5 patients, acute lymphoblastic leukemia (ALL) in 3 patients, and acute myeloid leukemia (AML) in 3 patients. The median time to TA-TMA diagnosis was 48 days post-transplantation (range: 4-213 days), and all patients met the diagnostic criteria for high-risk TA-TMA. The median interval from TA-TMA diagnosis to the initiation of eculizumab treatment was 12 days (range: 1-56 days). Patients received a median of 3 doses of eculizumab (range: 1-14). Ten of the 11 patients were assessed as having no response (NR) to eculizumab at the end of treatment or at death. One patient achieved a partial response (PR) but subsequently died after TA-TMA relapsed due to infection. At the last follow-up, all patients were either lost to follow-up or had died. The median follow-up duration was 88 days (range: 33-326 days), and the median time from TA-TMA diagnosis to the last follow-up was 31 days (range: 21-113 days) .Conclusion:Eculizumab demonstrated poor efficacy in this TA-TMA cohort. This might be attributable to the critical and complex condition of the patients, delayed initiation of eculizumab treatment, and insufficient dosage.
8.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.
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.Value of combined detection of serum mitogen-activated protein kinase 1 and lysyl oxidase-like protein 2 in early diagnosis of cervical cancer
Xiaodan JIANG ; Huifang WANG ; Sisi CHEN ; Yiman TANG ; Zhuang ZHANG ; Meng LI
Journal of Clinical Medicine in Practice 2025;29(15):58-62,78
Objective To explore the value of combined detection of serum mitogen-activated protein kinase 1(MAPK1)and lysyl oxidase-like protein 2(LOXL2)in early diagnosis of cervical cancer.Methods A total of 218 patients with cervical lesions were selected as study group(103 ca-ses in cervical cancer group,115 cases in benign tumor group).Additionally,100 patients with cer-vical intraepithelial neoplasia grade Ⅱ were selected as precancerous lesion group,and 79 healthy in-dividuals undergoing physical examinations during the same period were selected as control group.Se-rum levels of MAPK1 and LOXL2 were measured in each group.Pearson correlation analysis was used to evaluate the correlations of serum MAPK1 and LOXL2 levels in patients with cervical cancer.Logistic regression analysis was performed to screen influencing factors for the occurrence of cervical cancer.Receiver operating characteristic(ROC)curves were plotted to assess the diagnostic efficacy of serum MAPK1 and LOXL2 for cervical cancer.Results Serum MAPK1 and LOXL2 levels in the study group were higher than those in the precancerous lesion group and the control group,and those in the precancerous lesion group were higher than those in the control group,with statistically signif-icant differences(P<0.05).The proportion of patients with high-risk human papillomavirus(HPV)infection and serum MAPK1 and LOXL2 levels in the cervical cancer group were higher than those in the benign tumor group,with statistically significant differences(P<0.05).Serum MAPK1 and LOXL2 levels in patients with stage Ⅲ to Ⅳ cervical cancer were higher than those in patients with stage Ⅰ to Ⅱ cervical cancer,with statistically significant differences(P<0.05).Pearson correlation analysis showed a positive correlation between serum MAPK1 and LOXL2 levels in patients with cervical cancer(r=0.468,P<0.001).Logistic regression analysis showed that high-risk HPV infection,MAPK1 and LOXL2 were all influencing factors for the occurrence of cervi-cal cancer(P<0.05).ROC curve analysis showed that the area under the curve(AUC)for com-bined diagnosis of serum MAPK1 and LOXL2 was 0.911,which was significantly greater than the AUCs for individual diagnoses(0.848 and 0.843,respectively).Conclusion Serum MAPK1 and LOXL2 levels in patients with cervical cancer are significantly upregulated,and the two indicators were positively correlated.High-risk HPV infection,serum MAPK1 and LOXL2 levels were influen-cing factors for the occurrence of cervical cancer.Combined detection of MAPK1 and LOXL2 levels is expected to assist in the diagnosis of cervical cancer.

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