1.Analysis of status and associated factors of wasting among primary and secondary school students in Guangxi, 2021-2025
Chinese Journal of School Health 2026;47(9):1246-1251
Objective:
To analyze the status of wasting among primary and secondary school students in Guangxi from 2021 to 2025, to explore the factors associated with wasting, so as to provide scientific evidence for improving student s nutrition.
Methods:
Based on the National Surveillance and Intervention Program on Common Diseases and Health Risk Factors among Students, a stratified cluster random sampling was adopted from 2021 to 2025 to recruit 71 077, 236 511, 243 466, 249 619 and 246 259 primary and secondary school students in Guangxi for physical examination and questionnaire survey. The χ 2 test was used for intergroup comparisons. Chi-square trend test was used to conduct trend analysis. Multilevel Logistic regression model was employed to identify factors associated with wasting.
Results:
The overall wasting detection rate was 11.65% during 2021-2025. Over the five year period, the rate exhibited a S shaped fluctuation pattern characterized by "decline-rise-decline" and the difference across years was statistically significant ( χ 2=230.53, P <0.05). Multilevel Logistic regression analysis showed that male students ( OR = 1.63 ), primary school students ( OR =1.53) and junior high school students ( OR =1.12), boarding students ( OR =1.08), and students with adequate sleep duration ( OR =1.12) were positively correlated with the risk of wasting (all P <0.05). Students who consumed sugar sweetened beverages ≥1 time/day ( OR =0.93), ate fresh fruit ≥1 time/day ( OR =0.95), had moderate to vigorous physical activity for more than 60 minutes per day ( OR =0.88), and had moderate to vigorous physical activity for more than 60 minutes per day on more than half of weekend days ( OR =0.88) were negatively correlated with the risk of wasting (all P <0.05).
Conclusions
Wasting status among primary and secondary school students in Guangxi improved between 2021 and 2025, though fluctuations persisted. Greater attention should be paid to the nutritional status of male students and boarding students. While cultivating balanced dietary habits and appropriate exercise behaviors, the complex relationship between sleep and malnutrition should also be given due consideration.
2.Extracorporeal blood purification therapy for acute poisoning in Jiangsu Province, China: a cross-sectional, multicenter real-world study
Li QIAO ; Jinsong ZHANG ; Jianrong CHEN ; Lijun LIU ; Ping GENG ; Hong SUN ; Yeping DU ; Zhiguang TIAN ; Jianjun MA ; Rushan YANG ; Jiancheng DONG ; Zheng QIN ; Shanshan WU ; Yumin PAN ; Yigang WU
Chinese Journal of Emergency Medicine 2025;34(3):369-375
Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.
3.Treatment Based on Syndrome Differentiation in Internal Injury Fever Based on ZHANG Jingyue's Theory of"Ministerial Fire Has Tangible Position"
Yuxiao QIN ; Xiang LI ; Jianjun GU
Journal of Zhejiang Chinese Medical University 2025;49(1):59-64
[Objective]Based on ZHANG Jingyue's theory of"ministerial fire has a place and is visible",to explore the syndrome differentiation thinking and treatment plan about injury fever syndrome differentiation,in order to provide new ideas for the clinical treatment of internal injury fever such as deficiency fever,spermatorrhea,blood syndrome,diabetes syndrome and so on.[Methods]By studying the relevant works of ZHANG Jingyue's Jingyue Encyclopedia and Classified Classic,combined with the works of other doctors such as LIU Wansu,ZHU Danxi,LI Dongyuan,etc.,it discussed the application of ministerial fire thought in the syndrome differentiation and treatment of internal injury fever.Combined with medical records,three ideas of syndrome differentiation and treatment of internal injury fever were summarized:spleen-Qi deficiency,Yin essence deficiency and original Yang deficiency,corresponding to three treatment methods of regulating middle-Jiao,benefiting essence and blood,and warming body origin.Combined with clinical practice,it summarized the diagnostic and treatment thought of internal injury fever,and discussed the role of ZHANG Jingyue's ministerial fire theory in the treatment of specific febrile diseases such as deficiency fever,spermatorrhea,blood syndrome and diabetes syndrome.[Results]ZHANG Jingyue believed that ministerial fire"has a place",which was born in Mingmen and all over the viscera.All endogenous fevers in the human body were related to it.And ZHANG proposed that the incidence of internal injury fever was mainly deficiency,and ministerial fire was"tangible",which could be differentiated and treated according to the fact that ministerial fire must be damaged by"blood Qi,viscera and other evidence".Its pathogenesis mainly included three aspects:spleen-Qi deficiency,Yin essence deficiency and original Yang deficiency.The diagnosis and treatment should pay attention to regulating the middle palace and heat,benefiting essence and blood to make fire,warming kidney and life to absorb fire.According to the syndrome differentiation situation,in terms of medication,it should pay attention to the use of sweet and warm,sweet and cold drugs also warming and tonifying Yang prescriptions flexibly.[Conclusion]ZHANG Jingyue had a very profound understanding of the theory of ministerial fire.On the basis of absorbing the essence of predecessor's thoughts,he often had his own new insights.His theory of ministerial fire had important value in discussing the pathogenesis and treatment of internal injury fever,which was worthy of reference for the later generations.
4.Advances in neoadjuvant therapy for locally advanced resectable esophageal cancer
Xiaozheng KANG ; Ruixiang ZHANG ; Zhen WANG ; Xiankai CHEN ; Yong LI ; Jianjun QIN ; Yin LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):153-159
Neoadjuvant therapy has become the standard treatment for locally advanced resectable esophageal cancer, significantly improving long-term survival compared to surgery alone. Neoadjuvant therapy has evolved to include various strategies, such as concurrent chemoradiotherapy, chemotherapy, immunotherapy, or targeted combination therapy. This enriches clinical treatment options and provides a more personalized and scientific treatment approach for patients. This article aims to comprehensively summarize current academic research hot topics, review the rationale and evaluation measures of neoadjuvant therapy, discuss challenges in restaging methods after neoadjuvant therapy, and identify the advantages and disadvantages of various neoadjuvant therapeutic strategies.
5.Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T-cell differentiation.
Qiao LIU ; Wei DONG ; Rong LIU ; Luming XU ; Ling RAN ; Ziying XIE ; Shun LEI ; Xingxing SU ; Zhengliang YUE ; Dan XIONG ; Lisha WANG ; Shuqiong WEN ; Yan ZHANG ; Jianjun HU ; Chenxi QIN ; Yongchang CHEN ; Bo ZHU ; Xiangyu CHEN ; Xia WU ; Lifan XU ; Qizhao HUANG ; Yingjiao CAO ; Lilin YE ; Zhonghui TANG
Protein & Cell 2025;16(7):575-601
Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism*
;
Cell Differentiation
;
Chromatin/immunology*
;
Animals
;
Mice
;
Immunologic Memory
;
Epigenesis, Genetic
;
SOXC Transcription Factors/immunology*
;
NF-E2-Related Factor 2/immunology*
;
Mice, Inbred C57BL
;
Gene Regulatory Networks
;
Enhancer Elements, Genetic
6.The influence of two-way referral model on treatment and prognosis of patients with chronic heart failure
Yijun SUN ; Xinyu ZHANG ; Yue HU ; Zongwei LIN ; Jie XIAO ; Peng LI ; Xin ZHAO ; Huafang ZHANG ; Bo QIN ; Dequan JIA ; Tao ZHANG ; Jian MA ; Hongping CHEN ; Chunju ZHANG ; Xinwei GENG ; Kaiyan ZHANG ; Man ZHENG ; Fenglei ZHANG ; Yan LANG ; Hegong HOU ; Peng LIU ; Haifeng JIA ; Jianjun LU ; Kai ZHAO ; Hui ZHAO ; Jiechang XU ; Mi ZHANG ; Xiuxin LI ; Dongxia ZHANG ; Lin ZHONG ; Hui ZHAO ; Fangfang LIU ; Yan LIU ; Dongxia MIAO ; Chengwei WANG ; Hui ZHANG ; Chen WANG ; Fen WANG ; Xuejuan ZHANG ; Huixia LYU ; Xiaoping JI
Chinese Journal of Cardiology 2025;53(11):1244-1253
Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.
7.Treatment Based on Syndrome Differentiation in Internal Injury Fever Based on ZHANG Jingyue's Theory of"Ministerial Fire Has Tangible Position"
Yuxiao QIN ; Xiang LI ; Jianjun GU
Journal of Zhejiang Chinese Medical University 2025;49(1):59-64
[Objective]Based on ZHANG Jingyue's theory of"ministerial fire has a place and is visible",to explore the syndrome differentiation thinking and treatment plan about injury fever syndrome differentiation,in order to provide new ideas for the clinical treatment of internal injury fever such as deficiency fever,spermatorrhea,blood syndrome,diabetes syndrome and so on.[Methods]By studying the relevant works of ZHANG Jingyue's Jingyue Encyclopedia and Classified Classic,combined with the works of other doctors such as LIU Wansu,ZHU Danxi,LI Dongyuan,etc.,it discussed the application of ministerial fire thought in the syndrome differentiation and treatment of internal injury fever.Combined with medical records,three ideas of syndrome differentiation and treatment of internal injury fever were summarized:spleen-Qi deficiency,Yin essence deficiency and original Yang deficiency,corresponding to three treatment methods of regulating middle-Jiao,benefiting essence and blood,and warming body origin.Combined with clinical practice,it summarized the diagnostic and treatment thought of internal injury fever,and discussed the role of ZHANG Jingyue's ministerial fire theory in the treatment of specific febrile diseases such as deficiency fever,spermatorrhea,blood syndrome and diabetes syndrome.[Results]ZHANG Jingyue believed that ministerial fire"has a place",which was born in Mingmen and all over the viscera.All endogenous fevers in the human body were related to it.And ZHANG proposed that the incidence of internal injury fever was mainly deficiency,and ministerial fire was"tangible",which could be differentiated and treated according to the fact that ministerial fire must be damaged by"blood Qi,viscera and other evidence".Its pathogenesis mainly included three aspects:spleen-Qi deficiency,Yin essence deficiency and original Yang deficiency.The diagnosis and treatment should pay attention to regulating the middle palace and heat,benefiting essence and blood to make fire,warming kidney and life to absorb fire.According to the syndrome differentiation situation,in terms of medication,it should pay attention to the use of sweet and warm,sweet and cold drugs also warming and tonifying Yang prescriptions flexibly.[Conclusion]ZHANG Jingyue had a very profound understanding of the theory of ministerial fire.On the basis of absorbing the essence of predecessor's thoughts,he often had his own new insights.His theory of ministerial fire had important value in discussing the pathogenesis and treatment of internal injury fever,which was worthy of reference for the later generations.
8.The influence of two-way referral model on treatment and prognosis of patients with chronic heart failure
Yijun SUN ; Xinyu ZHANG ; Yue HU ; Zongwei LIN ; Jie XIAO ; Peng LI ; Xin ZHAO ; Huafang ZHANG ; Bo QIN ; Dequan JIA ; Tao ZHANG ; Jian MA ; Hongping CHEN ; Chunju ZHANG ; Xinwei GENG ; Kaiyan ZHANG ; Man ZHENG ; Fenglei ZHANG ; Yan LANG ; Hegong HOU ; Peng LIU ; Haifeng JIA ; Jianjun LU ; Kai ZHAO ; Hui ZHAO ; Jiechang XU ; Mi ZHANG ; Xiuxin LI ; Dongxia ZHANG ; Lin ZHONG ; Hui ZHAO ; Fangfang LIU ; Yan LIU ; Dongxia MIAO ; Chengwei WANG ; Hui ZHANG ; Chen WANG ; Fen WANG ; Xuejuan ZHANG ; Huixia LYU ; Xiaoping JI
Chinese Journal of Cardiology 2025;53(11):1244-1253
Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.
9.Analysis of virus gene subtypes and drug resistance monitoring results of newly reported HIV/AIDS population in Anhui Province from 2020 to 2023
Yizu QIN ; Yuelan SHEN ; Aiwen LIU ; Jianjun WU ; Lifeng MIU ; Qin FANG ; Chenxi SHUAI ; Lin JIN
Chinese Journal of Preventive Medicine 2024;58(8):1204-1212
Objective:To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023.Methods:An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University′s HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis.Results:A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance ( χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4 +T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4 +T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion:The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4 +T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.
10.Magnesium lithospermate B enhances the potential of human-induced pluripotent stem cell-derived cardiomyocytes for myocardial repair
Chengming FAN ; Kele QIN ; Daniel Chukwuemeka IROEGBU ; Kun XIANG ; Yibo GONG ; Qing GUAN ; Wenxiang WANG ; Jun PENG ; Jianjun GUO ; Xun WU ; Jinfu YANG
Chinese Medical Journal 2024;137(15):1857-1869
Background::We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model.Methods::In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups ( n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs. Results::After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro. Conclusions::MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.


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