1.Clinical and genetic analysis of children with Silver-Russell syndrome.
Liming ZHANG ; Guimei PAN ; Dongxia FU ; Xue WU ; Yongxing CHEN
Chinese Journal of Medical Genetics 2026;43(4):259-264
OBJECTIVE:
To summarize the clinical and genetic characteristics of children with Silver-Russell syndrome (SRS) and improve the recognition of this disease.
METHODS:
A retrospective analysis was conducted on the clinical manifestations and genetic testing results of 29 children with SRS diagnosed at the Children's Hospital Affiliated to Zhengzhou University between March 2016 and June 2025.
RESULTS:
The 29 children had included 18 boys and 11 girls, with the age ranging from 2 months to 16 years. Their primary clinical manifestations included postnatal growth retardation (100%), small for gestational age (SGA) (100%), characteristic facial features (90%), limb asymmetry (83%), feeding difficulties (76%), ulnar deviation of the fifth finger (69%), body mass index (BMI) of < -2 SD (62%), and abnormal bone age (55%), including 15 cases with delayed bone age for an average of 1.5 years and 1 case with advanced bone age for 2.5 years. Additional manifestations included abnormal sexual development in 11 cases (38%), dental malocclusion in 11 cases (38%), allergic diseases in 10 cases (34%), cardiac diseases in 9 cases (31%), skeletal abnormalities in 7 cases (24%), renal hypoplasia in 5 cases (17%), and abnormal cranial MRI findings in 5 cases (17%). Twenty children were treated with recombinant human growth hormone (rhGH) at a dose of 0.1 ~ 0.15 U/(kg.d). Among them, 7 cases achieved annual height increase of ≥ 10 cm, 11 cases achieved annual height increase of ≥ 5 ~ 9 cm, and 2 cases achieved annual height increase < 5 cm. Twenty three children exhibited hypomethylation of imprinted genes in the chromosome region of 11p15, 4 presented maternal uniparental disomy of chromosome 7 [UPD(7)mat], and 2 had harbored nonsense variants of the HMGA2 gene.
CONCLUSION
SRS patients may present with diverse clinical manifestations including postnatal growth retardation, SGA, characteristic facial features, limb asymmetry, feeding difficulties, and ulnar deviation of the fifth finger. Most patients may exhibit abnormal methylation in the 11p15 region. rhGH therapy can improve the height of these patients.
Humans
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Silver-Russell Syndrome/diagnosis*
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Male
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Female
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Child
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Child, Preschool
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Infant
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Adolescent
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Retrospective Studies
2.The first record of Anopheles messeae (Diptera: Culicidae) parasitized by water mites in China
Xue-ru CHEN ; Wen-zhen YAO ; Yu-hao LI ; Gui-chang LI ; Tao MENG ; Qun-ling FENG ; Xin-hui LIU ; Li-hong QIAO ; Xiang-ting WU ; Xue-feng ZHANG ; Cheng-lin LI ; Xue-cheng DONG ; Da-wei WANG ; Xiao-yan SI ; Yu-hong GUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):53-57
Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.
3.Response to Comments on “Pretreatment 68Ga-PSMA-11 PET/CT to Predict the Response to Treatment With Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma”
Shao-Hao CHEN ; Xiao-Hui WU ; Qian-Ren-Shun QIU ; Shao-Ming CHEN ; Jie ZANG ; Jun-Ming ZHU ; Cheng-Long ZENG ; Wei-Bing MIAO ; Xue-Yi XUE ; Ning XU
Korean Journal of Radiology 2026;27(2):188-190
4.Comparison of Automatic Evaluation Methods for Pattern Hallucinations of Large Language Models in Traditional Chinese Medicine Syndrome Differentiation
Qinwei WU ; Yuzhu GAO ; Xingyue GOU ; Junyu YAO ; Chuangan ZHOU ; Zhengchun XUE ; Zhirong XU ; Xinlin CHEN ; Dong CAO
Journal of Traditional Chinese Medicine 2026;67(17):1845-1852
ObjectiveTo compare the performance of different automatic evaluation methods for detecting pattern hallucinations generated by large language models (LLMs) in traditional Chinese medicine (TCM) syndrome differentiation and to identify a strategy with higher overall discriminative performance against expert manual judgment. MethodsA standardized TCM syndrome-differentiation dataset containing 598 cases was constructed from case reports published in Chinese core journals indexed by Peking University Core Journals or Chinese Science Citation Database. Each of the 598 cases was submitted to five Chinese LLMs, with each model generating one syndrome-pattern output per case, yielding 2990 outputs in total. The 598 outputs generated by Qwen3-Next-80B-A3B-Thinking were independently annotated for syndrome-pattern hallucinations by two licensed TCM physicians with intermediate or higher professional titles. Disagreements were adjudicated by a third licensed TCM physician with a senior associate professional title and more than 10 years of clinical experience. The resulting consensus annotations served as the reference labels for training and validating the automated evaluation method. Based on these reference labels, three categories of automated evaluation methods were developed and compared following a progressive strategy from text-level semantic similarity, to syndrome-element structural consistency, and finally multi-feature fusion. Method A employed sentence-embedding models based on semantic similarity between pattern texts. Method B adopted a rule-based threshold method using weighted Jaccard coefficients of disease-location and disease-nature syndrome elements. Method C utilized a machine-learning classifier integrating syndrome-element matching scores, missing and redundant syndrome-element counts, and multiple semantic-similarity features. Five-fold cross-validation was used to evaluate the discriminative performance of each method against manual judgment. The optimal method was then applied to uniformly assess the pattern hallucination rates of five LLMs. ResultsIn method A, text2vec-large-chinese showed best overall performance, with an area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (PR-AUC), F1-score, sensitivity, and specificity of 0.849, 0.884, 0.794, 0.801, and 0.691, respectively. In method B, the corresponding metrics of the rule-based syndrome-element Jaccard threshold method were 0.848, 0.851, 0.817, 0.845, and 0.684, respectively; those of the LLM-based syndrome-element Jaccard method were 0.872, 0.906, 0.795, 0.764, and 0.780, respectively. In method C, the multilayer perceptron (MLP) classifier showed the best overall performance, with AUROC, PR-AUC, F1-score, sensitivity, and specificity of 0.933, 0.951, 0.871, 0.857, and 0.846, respectively. Under the unified evaluation framework combining DeepSeek-R1 syndrome-element extraction and MLP classifier, the estimated pattern hallucination rates of the five LLMs ranged from 56.0% to 77.4%. ConclusionAmong the three automatic evaluation methods, Method C integrating syndrome-element discrepancy features and text semantic features using an MLP classifier showed the highest overall discriminative performance against manual judgment, and is more suitable for evaluating syndrome hallucinations in LLM-based TCM syndrome differentiation tasks.
5.Key influencing factors and improvement strategies of prognosis in lung transplant recipients
Mengting ZHANG ; Xiaoshan LI ; Ting QIAN ; Lin MAN ; Min XIONG ; Shiqiang XUE ; Yetian QIAO ; Lin ZHU ; Jingyu CHEN ; Bo WU
Organ Transplantation 2026;17(5):875-882
In recent years, remarkable advances have been made in lung transplantation regarding donor evaluation, perioperative support, and immune regulation, laying a foundation for improving the long-term survival of recipients. The rational application of extended criteria donor lungs and the popularization of ex vivo lung perfusion technology have enhanced the utilization efficiency and safety of marginal donor lungs. Refined assessment of risk factors such as donors’ smoking history and infectious status has reduced the incidence of primary graft dysfunction and postoperative infection. In terms of recipient management, individualized assessment systems have been gradually optimized. The standardized application of intraoperative extracorporeal membrane oxygenation and the development of minimally invasive surgical techniques have effectively alleviated perioperative injuries. The optimization of postoperative immunosuppressive regimens and advances in rejection monitoring technologies have further improved the long-term survival of grafts. Nevertheless, chronic graft dysfunction and recurrent or refractory infections remain the major bottlenecks restricting long-term prognosis. Future research should focus on expanding donor sources, improving the repair quality of marginal donor lungs, promoting precise immunosuppression and anti-infection strategies, and comprehensively enhancing the long-term survival rate and quality of life of lung transplant recipients.
6.Clinical efficacy of escitalopram combined with transcutaneous cervical vagus nerve stimulation therapy for patients with major depressive disorder and its effect on plasma IL-6 and IL-10 levels
Jin LI ; Jinbo SUN ; Di WU ; Wenjun WU ; Runzhu SUN ; Shanshan XUE ; Yapeng CUI ; Huaning WANG ; Yihuan CHEN
Sichuan Mental Health 2025;38(1):7-13
BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression, which may contribute to the anti-inflammatory properties of vagus nerve stimulation (VNS), whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation (tcVNS) in treating major depressive disorder (MDD) and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression, anxiety and sleep quality as well as the plasma levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) in MDD patients, in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21, 2019 to April 17, 2024, 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group (n=23) and control group (n=22) using random number table method. All patients were treated with escitalopram. On this basis, study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation, and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment, Hamilton Depression Scale-17 item (HAMD-17) was used to assess depressive symptoms, and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score, anxiety/somatization subfactor score and insomnia subfactor score in both groups (Wald χ2=315.226, 495.481, 82.420, P<0.01). After 4 weeks of treatment, HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group, with statistically significant differences (Wald χ2=4.967, 32.543, P<0.05 or 0.01), while no statistically significant difference was found in the insomnia subfactor score between two groups (Wald χ2=0.819, P=0.366). Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups (Wald χ2=21.792, 5.242, P<0.05 or 0.01). Compared with baseline data, a reduction in plasma IL-6 levels was detected in both groups (Wald χ2=22.015, 6.803, P<0.01), and an increase in plasma IL-10 levels was reported in study group (Wald χ2=5.118, P=0.024) after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms, anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally, it helps reduce plasma IL-6 levels and increase IL-10 levels. [Funded by Shaanxi Provincial Key Research and Development Program-General Project (number, 2023-YBSF-185), www.clinicaltrials.gov number, NCT04037111]
7.Changing antimicrobial resistance profiles of Burkholderia cepacia in hospitals across China:results from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Chunyue GE ; Yunjian HU ; Xiaoman AI ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Hui LI ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(5):557-562
Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1%(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5%,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3%(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1%)were isolated from sputum and respiratory secretions,followed by urine(10.7%)and blood samples(8.1%).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1%.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4%in the patients<18 years old to 20.6%in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.
8.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
9.Mechanism of Shaoyaotang in Modulating MDSCs-related Immunosuppressive Microenvironment in Prevention and Treatment of Colitis-associated Carcinogenesis
Xue CHEN ; Chenglei WANG ; Bingwei YANG ; Haoyu ZHAI ; Ying WU ; Weidong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):10-19
ObjectiveTo explore the mechanism of Shaoyaotang in the prevention and treatment of colitis-associated carcinogenesis (CAC) based on myeloid-derived suppressor cells (MDSCs)-related immunosuppressive microenvironment. MethodsA total of 140 six-week-old SPF FVB male mice were randomly divided into seven groups: Blank group, Shaoyaotang without model group (7.12 g·kg-1), model group, sulfasalazine group (0.52 g·kg-1), Shaoyaotang low-dose group (3.56 g·kg-1), Shaoyaotang medium-dose group (7.12 g·kg-1) and Shaoyaotang high-dose group (14.24 g·kg-1), with 20 mice in each group. The blank control group and the Shaoyaotang without model group received a single intraperitoneal injection of physiological saline (10 mg·kg-1), while the other five groups were given a single intraperitoneal injection of azoxymethane (AOM) (10 mg·kg-1). After 1 week, the mice were given drinking water containing 2% dextran sulfate sodium (DSS) for 1 week, followed by normal drinking water for 2 weeks. This cycle was repeated three times over a total period of 14 weeks to establish the CAC mouse model. Each group was administered gavage once daily for 2 weeks starting on the 14th day of the experiment, followed by three times a week until the end of the experiment. The body weight of the mice was recorded weekly. Mice were sacrificed on the 28th and 98th days of the experiment. After dissection, the colon length, colon weight, spleen weight, tumor size, and tumor number were measured. Hematoxylin and eosin (HE) staining was used to assess the pathological morphology of colon tumor tissue. Flow cytometry was used to detect MDSCs, regulatory T cells (Tregs), CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in the spleen. Immunohistochemistry was used to detect the expression levels of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated nuclear factor-κB (p-NF-κB), and hypoxia-inducible factor 1α (HIF-1α) in the colon tissue. ResultsOn day 14, compared with the blank group, the body weight of the model group was significantly reduced (P<0.01), reaching its lowest point on day 28 (23.39 ± 0.95 ) g. On days 28 and 98, compared with the blank group, the colon length in the model group was significantly shortened (P<0.01), the colon index significantly increased (P<0.01), the spleen index significantly increased (P<0.01), and the tumor load significantly increased (P<0.01). HE staining showed that in the model group, tumor cells, a large number of inflammatory cell infiltrates, goblet cell disappearance, and crypt loss were observed. In each dose group of Shaoyaotang, the damage to the colonic mucosa, inflammatory cell infiltration, and crypt structure destruction were alleviated. Compared with the model group, the body weight of mice in each dose group of Shaoyaotang increased. On day 98, the colon length was significantly increased (P<0.01), the colon index significantly decreased (P<0.01), the spleen index significantly decreased (P<0.01), and the tumor burden significantly decreased (P<0.01) in each Shaoyaotang dose group. On days 28 and 98, MDSCs and Tregs in the spleen of the medium- and high-dose Shaoyaotang groups were significantly reduced (P<0.01), while CD4+ T cells and the CD4+/CD8+ T cell ratio were significantly increased (P<0.01). The proportion of CD8+ T cells in the spleen and the expression levels of PD-1 and PD-L1 in the colon tissues of mice in each Shaoyaotang dose group were significantly increased to varying degrees (P<0.05, P<0.01). On days 28 and 98, the expression of p-AMPK-positive cells in the colon tissue of the medium- and high-dose Shaoyaotang groups was significantly increased (P<0.01), while the expression of p-NF-κB and HIF-1α was significantly reduced (P<0.01). ConclusionShaoyaotang can regulate MDSC recruitment and modulate the immune function of T lymphocyte subsets to inhibit the occurrence and development of AOM/DSS-induced CAC in mice. The mechanism may be related to the activation of the AMPK/NF-κB/HIF-1α pathway.
10.Nuclear translocation of NRF2 activates SLC7A11 and inhibits SAS-in-duced ferroptosis of AML cells
Yanfeng LIN ; Zhiyuan ZHENG ; Ying CHEN ; Wei WU ; Donghong LIN ; Yan XUE
Chinese Journal of Pathophysiology 2025;41(7):1289-1299
AIM:This study investigated the role of solute carrier family 7 member 11(SLC7A11)in sul-fasalazine(SAS)-induced ferroptosis in acute myeloid leukemia(AML)cells,focusing on the inhibitory effect of nuclear factor E2-related factor 2(NRF2)nuclear translocation-mediated activation of SLC7A11 on ferroptosis and its underlying mechanisms.METHODS:SAS-induced proliferation in AML cell lines,Kasumi-1 and THP-1,was assessed using the MTS assay.Cell death inhibitors were employed to determine the mode of cell death.Lipid reactive oxygen species(ROS)levels were measured by flow cytometry;Fe2+,malonodialdehyde(MDA),glutathione(GSH)levels,and glutathione per-oxidase 4(GPX4)activity were assessed using micromethods.Quantitative PCR(qPCR)was performed to evaluate changes in SLC7A11 mRNA during SAS-induced ferroptosis,while Western blot measured SLC7A11 and GPX4 protein levels.Moreover,Western blot assessed NRF2 nuclear translocation post-SAS treatment.The NRF2 inhibitor ML385 was used to validate these effects.SLC7A11 mRNA and protein levels were then measured following combined SAS and ML385 treatment via qPCR and Western blot.Cell viability and ferroptosis-related indices were evaluated under the same treatment conditions.Furthermore,a shRNA vector targeting SLC7A11 was constructed to assess changes in cell viability and ferroptosis markers after SLC7A11 knockdown with SAS.GPX4 protein levels were examined following SLC7A11 knockdown.RESULTS:SAS significantly inhibited the proliferation of Kasumi-1 and THP-1 cells at 200 μmol/L and 300 μmol/L,respectively(P<0.05).Only ferroptosis inhibitors(Fer-1 and DFO)significantly reversed SAS-induced cy-totoxicity(P<0.01).SAS increased lipid ROS,Fe2+,and MDA levels(P<0.01),while reducing GSH and GPX4 activity(P<0.01).The mRNA and protein expressions of SLC7A11 increased during SAS-induced ferroptosis(P<0.01),where-as GPX4 protein decreased significantly(P<0.01).SAS significantly increased the nuclear-to-cytoplasmic NRF2 ratio(P<0.01),which decreased upon co-treatment with ML385(P<0.05).Following SAS and ML385 co-treatment,both SLC7A11 mRNA and protein levels were downregulated(P<0.01).This combination treatment further reduced AML cell viability(P<0.01),an effect reversed by Fer-1 and DFO(P<0.01).Compared with SAS alone,the combination of SAS and ML385 significantly increased lipid ROS,Fe2+,and MDA while reducing GSH levels and GPX4 activity(P<0.01).SLC7A11 knockdown was successfully achieved.Compared with the NC shRNA group,SLC7A11 knockdown cells showed significantly decreased viability after SAS treatment,which was reversed by Fer-1 and DFO(P<0.01).Lipid ROS,Fe2+,and MDA content were significantly increased(P<0.01),and GSH and GPX4 were substantially decreased(P<0.05).Moreover,GPX4 protein expression was considerably reduced after SLC7A11 knockdown(P<0.01).CONCLUSION:SAS induces ferroptosis in AML cells.It promotes the nuclear translocation of NRF2 protein,which activates SLC7A11 ex-pression.Inhibition of NRF2 or downregulation of SLC7A11 sensitizes AML cells to SAS-induced ferroptosis.


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