1.ALKBH3-regulated m1A of ALDOA potentiates glycolysis and doxorubicin resistance of triple negative breast cancer cells.
Yuhua DENG ; Zhiyan CHEN ; Peixian CHEN ; Yaming XIONG ; Chuling ZHANG ; Qiuyuan WU ; Huiqi HUANG ; Shuqing YANG ; Kun ZHANG ; Tiancheng HE ; Wei LI ; Guolin YE ; Wei LUO ; Hongsheng WANG ; Dan ZHOU
Acta Pharmaceutica Sinica B 2025;15(6):3092-3106
Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m1A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m1A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.
2.Unlocking the potential of targeted protein degradation via nanoparticle-based universal strategy.
Ti-Qiang ZHOU ; Weilun SUN ; Zhen-Zhen WEI ; Yuhua WENG ; Dongxu ZHAO ; Mengjie ZHANG ; Yuanyu HUANG
Acta Pharmaceutica Sinica B 2025;15(11):6082-6086
Targeted protein degradation via nanoparticle-based universal strategy modifies nanoparticles with antibodies and ingeniously utilizes its cellular transport characteristics. This strategy achieved targeted degradation of extracellular proteins without complex design.Image 1.
3.Influencing factors of responsive caregiving among infant mothers in Weifang City
Ziyuan FU ; Fei YANG ; Mo ZHOU ; Xinxuan LI ; Ruoning WANG ; Ningxuan CUI ; Jing HUANG ; Yixin ZHANG ; Huafang JIANG ; Yuhua GUO ; Hong ZHOU
Journal of Peking University(Health Sciences) 2025;57(3):481-486
Objective:To describe the current status of responsive caregiving behavior of infant mothers,to analyze their influencing factors and pathways using the information-motivation-behavioral skills(IMB)model,and to provide a basis for further interventions related to responsive caregiving be-haviors and comprehensive promotion of early childhood development.Methods:This study was a cross-sectional survey using convenience sampling.Questionnaires were used to collect basic information about mothers and their infants,as well as data on mothers' responsive caregiving behavior,knowledge of re-sponsive caregiving,social support,and parenting self-efficacy.Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior,and structural equa-tion modeling was used to analyze the pathways of these influencing factors.The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile(P25)of the total score.Results:Among 510 mothers of aged 0-12 months infants in Weifang City,the average score for respon-sive caregiving behavior was 16.41±3.99.The proportion of inadequate responsive caregiving was 25.7%.Mothers in the insufficient responsive caregiving group had lower scores in knowledge(7.70±1.41),social support(57.92±15.16),and parenting self-efficacy(30.36±6.48)compared with those in the sufficient group,with statistically significant differences(P<0.001).Logistic regres-sion analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting[adjusted OR(aOR)=0.795,95%CI:0.566-0.838],social support(aOR=0.979,95%CI:0.961-0.996),and parenting self-efficacy(aOR=0.894,95%CI:0.857-0.932).Structural equation modeling revealed that knowledge of responsive caregiving(β=0.089,P=0.031),social support(β=0.153,P=0.001),and parenting self-efficacy(β=0.296,P<0.001)were directly related to responsive caregiving behavior.Additionally,knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.095,P=0.014),and social support indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.497,P<0.001).Conclusion:The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory.Future development of responsive care-giving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs.Additionally,it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy,thereby promoting improvements in responsive caregiving behavior.
4.Imaging findings of pediatric atypical teratoid/rhabdoid tumor in the central nervous system
Ting GUI ; Hui ZHENG ; Jinning LI ; Caiting CHU ; Ming LIU ; Yuzhen ZHANG ; Yuhua LI ; Dengbin WANG
Journal of Practical Radiology 2025;41(11):1857-1860
Objective To explore the imaging findings of atypical teratoid/rhabdoid tumor(AT/RT)in the central nervous sys-tem of children and to improve the understanding of this disease.Methods A retrospective analysis was conducted on the imaging data of 55 children with AT/RT confirmed by pathology.Results Among the 55 AT/RT children,74.5%were under 3 years old,with a male-to-female ratio of 1.5∶1.Intracranial AT/RT appeared hyperdense or slightly hyperdense on CT scans and accompa-nied by calcification or hemorrhage occasionally.32 cases showed peripheral cystic changes in MRI images.38 cases showed heteroge-neous enhancement,9 cases showed ring-like or band-like enhancement.13 cases showed cerebrospinal fluid dissemination.The mean minimum apparent diffusion coefficient(ADC)value was(0.61±0.11)× 10-3mm2/s.Spinal AT/RT manifested as solitary or mul-tiple intramedullary and/or extradural lesions on MRI,which showed unclear boundary from the spinal cord.Hemorrhage within or at the edge of the lesion was seen in 2 cases,involvement of nerve roots and adjacent muscle tissues in 3 cases,and cerebrospinal fluid dissemination of the intracranial and spinal cord at varying degrees in 5 cases.Conclusion The imaging findings of pediatric AT/RT in the central nervous system are diverse,combining imaging characteristics with age of onset facilitates the accurate diagnosis.
5.Research on analysis model of big data of comprehensive performance of visual medical equipment
Yi QIN ; Yuhua GU ; Yaju ZHANG ; Lei WANG ; Xinmei GU
China Medical Equipment 2025;22(4):135-142
Objective:To build a big data analysis model of comprehensive performance of medical equipment,so as to improve the management efficiency and fine management level for medical equipment of hospital.Methods:The big data analysis model of comprehensive performances of medical equipment was developed through building a data integration platform,and integrating multi-business system data of hospital,and including quantified social benefit data and relative data of the process of procurement and maintenance,which established index system of performance analysis with multi-dimensions and multi-layers.It realized the presentation of evaluation results of performance of medical equipment in the form of visual data reports.Results:The big data analysis model for the comprehensive performance of medical equipment has set a system with more than 10 indicators,which included social-benefit indicators,evaluation indicators of comprehensive performance,income indicators,and the indicator of recovery period of investment,and visual report with 35 pages.Each layer of the performance of equipment was analyzed from 35 angles,which realized a comprehensive,multi-dimensional and refined evaluation for the performance of medical equipment of hospital.Its'agile,easy-to-use,efficient response and automation features can significantly improve work efficiency of business.The model realized automatic data collection through interfaces and other means,and reduced manual input errors,which data accuracy rate was>99%.The results of testing the performance data of equipment for three consecutive years by using this model indicated that the consuming time of single calculation of business system of hospital was shortened from>20 min to 5-8 s.Conclusion:The big data analysis model of comprehensive performance of medical equipment can help hospital to identify,prevent and control risks in advance,and improve the efficiency of internal control,and enhance management efficiency and fine management level for hospital,and provide support for management decision for medical equipment of hospital.
6.Investigation on the current status of information systems in CSSD of hospitals in China
Ying ZHANG ; Yuhua GAO ; Sainan QIAO ; Jian SHEN ; Baohua LI
China Medical Equipment 2025;22(5):142-146
Objective:To investigate the status of development and application of information system of central sterile supply department(CSSD)in hospitals of China,so as to provide references for the promotion of CSSD information system in hospital.Methods:Hierarchical sampling method was adopted to combine with CSSD Professional Committee of Chinese Nursing Association to design questionnaire for Questionnaire Star Network Survey about basic information,CSSD information system,whether the CSSD information system connected with equipment,tracing links and tracing levels,identification method of apparatuses,automation of equipment in 3,074 hospitals of 22 provinces,4 municipalities directly under the central government,and 5 autonomous regions.Results:In 3,074 hospitals,1,811 hospitals(accounting for 58.91%)adopted the CSSD information system.The utilization rate of tertiary hospitals was 81.90%for the information system,which was higher than that(34.51%)in secondary hospitals,and the difference was statistically significant(x2=636.65,P<0.05).The proportion of hospitals that included the recycling,cleaning,disinfection,inspection and packaging,sterilization,storage,and distribution links of CSSD internal management into information management was all>88%,while the utilization link only accounted for 15.18%.The proportion that surgical apparatuses and the apparatuses of clinical diagnosis and treatment were included in management was higher in 1811 hospitals that used CSSD information system,which were respectively 88.02%and 84.70%,while the proportion of surgical soft endoscope was lower,which only was 49.20%.A total of 84.37%of hospitals conducted informatization management for using extracorporeal apparatuses and implants.The connection rates of the main CSSD equipment,which included the washing and disinfection machine,the pressure steam sterilizer and the low-temperature sterilizer,were connected with information system were respectively 56.60%,63.06%and 43.95%.The full compatibility between the information system and all monitoring methods did not be realized in these hospitals.Barcode was the main identification form(69.91%)of the CSSD information system,and personnel management was the most common management module(53.62%)of the information system.The utilization rate(2.93%-5.14%)of automated equipment was low,and 35.45%of the CSSD information systems had the function of automatic emergency handling.Conclusion:The CSSD informatization management of China has achieved remarkable results,but there are still problems such as insufficient connection of equipment,inclusion of monitoring data,and insufficient automation and intelligence.It is necessary to increase the promotion efforts to promote the high-quality development of hospitals.
7.Clinical significance of trisomy 7 signaled by non-invasive prenatal testing and a literature review
Xinxin TANG ; Ting YIN ; Min CHEN ; Zhiwei WANG ; Yue ZHANG ; Fang ZHANG ; Yunqiu DU ; Yuhua SUN ; Leilei WANG
Chinese Journal of Medical Genetics 2025;42(1):12-17
Objective:To explore the clinical significance of trisomy 7 signaled by non-invasive prenatal testing (NIPT).Methods:Pregnant women with high risk for trisomy 7 by NIPT from January 2017 to December 2023 were selected as the study subjects, and the results of prenatal diagnosis and follow-up were analyzed. Literature related to pregnant women with a high risk for trisomy 7 by NIPT from January 2016 to July 2024 was retrieved from China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure and PubMed database. Relevant information such as the incidence of trisomy 7 by NIPT, positive predictive value (PPV), and pregnancy outcomes were collected. This study has been approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No. JS2022010).Results:A total of 51 women with a high risk for trisomy 7 by NIPT were identified. Thirty-two of them had chosen chromosomal microarray analysis (CMA) of amniotic fluid cells, and 1 case of mosaic trisomy 7 was detected, which had yielded a PPV of 3.13%. Four women had opted termination of pregnancy, 1 had miscarriage, 4 had pre-term and/or low weight birth, whilst the remaining 42(82.4%) had full-term delivery. In total 19 literature were retrieved, which had involved 278 cases of trisomy 7 signaled by NIPT, among which 5 fetuses with mosaic trisomy 7 (3.14%) were confirmed. Among the 211 women with follow-up outcomes, 2 (0.95%) had intrauterine growth restriction, 3 (1.42%) had abnormal fetal structure detected by ultrasound, 2 (0.95%) had miscarriage, 9 (4.27%) underwent pregnancy termination, 28 (13.27%) had preterm and/or low weight birth, whilst 167 (79.14%) had normal delivery. In 18 cases, chromosomal analysis of placental tissue was carried out, and 17 were confirmed to have mosaicism trisomy 7.Conclusion:The PPV for trisomy 7 signaled by NIPT is extremely low. Although most of such women had a full term delivery, adverse pregnancy outcomes may still occur in a minority of cases. Clinicians should provide adequate genetic counseling for such women and recommend appropriate prenatal diagnosis strategies and optimal perinatal management plans.
8.Construction of evaluation index system of infectious disease prevention and control ability in colleges and universities
Chinese Journal of School Health 2025;46(3):438-442
Objective:
To construct a scientific and perfect evaluation index system of infectious disease prevention and control ability in colleges and universities, so as to provide reference tools for colleges and universities to effectively respond to infectious disease.
Methods:
The initial framework of the evaluation index system of infectious disease prevention and control ability in colleges and universities was constructed by using literature analysis method. Experts familiar with infectious disease prevention and control or school health work were selected to conduct two rounds( n =16,18) of Delphi expert consultation for determining the evaluation index system. Analytical hierarchy process was used to calculate the index weights and combined weights. About 198 prevention and control personnel were conveniently selected from 3 universities in Inner Mongolia Autonomous Region to comprehensively evaluate the evaluation indicators by using fuzzy comprehensive evaluation method.
Results:
After two rounds of Delphi consultation questionnaire, the effective recovery rates were 80.0% and 90.0%, the expert authority levels were 0.89 and 0.86, the expert harmony coefficients for Kendall W were 0.166 and 0.310, and the variation coefficient of each index was <0.25. Finally, the evaluation index system of infectious disease prevention and control ability of colleges and universities included 4 first level indicators, 14 second level indicators and 75 third level indicators. The weights of prevention and monitoring and early warning, organizational system guarantee, emergency management, rehabilitation and summary were 0.176, 0.476, 0.268 and 0.080, respectively. The top 3 weights of the secondary indexes were 0.623 for infectious disease surveillance and early warning, 0.595 for loss assessment and 0.370 for emergency response. The score of fuzzy comprehensive evaluation of the index system of infectious disease prevention and control ability in colleges and universities was 79.148, suggesting a high level.
Conclusion
The established evaluation index system of infectious disease prevention and control ability in colleges and universities is scientific and reasonable, which is conducive to provide tool reference for the evaluation of infectious disease prevention and control ability in colleges and universities.
9.Systemic lupus erythematosus related thrombotic microangiopathy: A retrospective study based on Chinese SLE Treatment and Research Group (CSTAR) registry.
Yupei ZHANG ; Nan JIANG ; Zhen CHEN ; Xinwang DUAN ; Xiaofei SHI ; Hongbin LI ; Zhenyu JIANG ; Yuhua WANG ; Yanhong WANG ; Jiuliang ZHAO ; Qian WANG ; Xinping TIAN ; Mengtao LI ; Xiaofeng ZENG
Chinese Medical Journal 2025;138(5):613-615
10.Novel CD19 Fast-CAR-T cells vs. CD19 conventional CAR-T cells for the treatment of relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia.
Xu TAN ; Jishi WANG ; Shangjun CHEN ; Li LIU ; Yuhua LI ; Sanfang TU ; Hai YI ; Jian ZHOU ; Sanbin WANG ; Ligen LIU ; Jian GE ; Yongxian HU ; Xiaoqi WANG ; Lu WANG ; Guo CHEN ; Han YAO ; Cheng ZHANG ; Xi ZHANG
Chinese Medical Journal 2025;138(19):2491-2497
BACKGROUND:
Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL.
METHODS:
A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups.
RESULTS:
Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups.
CONCLUSION
Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.


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