1.Analysis of the impact of intraoperative RhE antigen-matched transfusion on early prognosis in liver transplant patients
Xiaochao YU ; Xinyuan GAO ; Fan HAI ; Chao YANG ; Xingyu HOU ; Yaping XING ; Hongqiang GAO ; Hongwei ZHANG ; Gang SU ; Ronghua XU
Chinese Journal of Blood Transfusion 2026;39(1):44-50
Objective: To investigate the impact of RhE antigen-matched transfusion during liver transplantation on early postoperative recovery and complications. Methods: In this retrospective cohort study, ninety-five patients undergoing liver transplantation at Kunming First People's Hospital between January 2022 and July 2025 were enrolled. Patients were divided into two groups: Group 1 (RhE-mismatched transfusion, n=57) and Group 2 (RhE-matched transfusion, n=38). The baseline data, complete blood counts, hepatic and renal function, coagulation parameters, and complication rates between the two groups were compared at postoperative days 1, 3, 5, 7, and 10. Survival analysis was performed using the Kaplan-Meier method. Results: The baseline characteristics were well-balanced and comparable between the two groups (all P>0.05). The early postoperative mortality rate in the mismatched group (31.58%, 18/57) was significantly higher than that in the matched group (10.53%, 4/38) (P=0.017). The incidence of postoperative hepatic encephalopathy was significantly higher in the mismatched group (50.88%, 29/57) than in the matched group (10.53%, 4/38) (P<0.001). The incidence of postoperative haemorrhage in the mismatched group (24.56%, 14/57) was higher than that in the matched group (5.26%, 2/38), with a statistically significant difference (P=0.014). The incidence of perioperative infection in the mismatched group (28.07%, 16/57) was higher than that in the matched group (10.53%, 4/38), with a statistically significant difference (P=0.04). Corresponding odds ratios (OR) and 95% confidence intervals indicated a lower risk of these adverse events in the matched group. On postoperative day 1, the change in activated partial thromboplastin time (-1.6, 20.5) in the mismatched group was greater than in the matched group (-0.2, 5.5). The change in international normalised ratio (-0.56, 1.22) in the mismatched group was greater than in the matched group (-0.18, 0.32), while the change in albumin (-4.0, 4.8) was smaller in the mismatched group than in the matched group (-2.5, 8.8). On postoperative day 5, the change in albumin (-0.41±7.83) in the mismatched group was smaller than in the matched group (2.68±4.53). At postoperative day 7, the change in albumin in the mismatched group (-0.61±7.38) was smaller than that in the matched group (2.51±5.85), while the change in D-dimer in the mismatched group (0.73, 7.4) was greater than that in the matched group (-1.6, 4.3). On postoperative day 10, the mismatched group exhibited significantly higher fibrinogen levels (-1.21, 1.78) than the matched group (-0.49, 0.97), and significantly longer prothrombin times (-11.3, -2.7) than the matched group (-6.2, -0.8) (all P<0.05). The matched group exhibited a mean overall survival (OS) of 32.803 months (95% CI:29.171-36.436 months), significantly exceeding the mismatched group's 28.996 months (95% CI:24.202-33.790 months). The log-rank test yielded statistically significant results (χ
=4.307, P=0.038). Conclusion: Implementing RhE blood group-matched transfusion during liver transplantation may help reduce early postoperative mortality and the incidence of major complication rates, promote faster recovery of coagulation and liver function, and thereby improve short-term patient outcomes.
2.Assessment of health exposure risks from preservatives in beverages sold near primary schools in Anshun
XU Lin, QU Guangsheng, DAI Qian, LU Shunhua, CAI Guixiang, ZHANG Jialin, WEI Gang
Chinese Journal of School Health 2026;47(1):129-133
Objective:
To quantitatively assess the health risk of preservatives from beverages around primary schools in Anshun City, and to provide scientific basis for precise food safety supervision.
Methods:
From December 2023 to July 2024, 602 beverage samples were randomly collected from within 100 meters of 19 primary schools in Anshun City. The content of benzoic acid, sorbic acid, and dehydroacetic acid was detected according to GB 5009 series standards. Combined with children s physiological parameters (body weight 30 kg, daily intake 0.15 L), the Hazard Quotient (HQ) and Hazard Index (HI) models were used to evaluate health risks.
Results:
The total detection rate of preservatives from beverages around primary schools was 63.0%, and the total over limit rate was 9.0%. The detection rate of preservatives in flavored beverages was the highest (72.6%), and the highest over limit rate of preservatives in special purpose beverages was the highest (17.2%). The single preservative HQ (benzoic acid up to 0.47 ) and mixed HI (up to 0.55) of all samples were below 1(safety threshold). However, the HQ value of benzoic acid in flavored beverages (0.47) was 2.9 times that of sorbic acid (0.16), contributing significantly to health risk. Sensitivity analysis showed that if the daily consumption increased to 0.3 L, the HI value of flavored beverages would rise to 1.11, exceeding the safety threshold. Enterprise scale analysis showed that the exceedance rate of special purpose beverages in large enterprises reached 30.0%, while micro enterprises, accounting for a dominant market share (52.2%), constituted the main source of children s daily exposure to their products.
Conclusions
The overall health risk of perservatives in beverages sold near primary schools in Anshun City is controllable, but there is a noticeable risk of gradient. The risk of children’s exposure to preservatives through beverage consumption should not be ignored.
3.Effects of Shujin Jiannao Formula (舒筋健脑方) on Neural Repair and PI3K-Akt-mTOR Pathway of Brain Tissue in Cerebral Palsy Model Rats
Ruiqin YU ; Yanjun MO ; Houjun ZHANG ; Gang LIU ; Zhuoluo ZHOU ; Zechen RUAN ; Lin XU ; Xiaohong MU
Journal of Traditional Chinese Medicine 2025;66(10):1038-1045
ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula (舒筋健脑方) for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group, model group, and Shujin Jiannao Formula group, with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling, rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/(kg·d) by gavage, while the normal group and model group were given normal saline 10 ml/(kg·d) by gavage once a day. After one week of intervention, the rats' body weight was measured, and Zea-Longa scores, the righting reflex test, and the hindlimb suspension test were conducted for assessment; hematoxylin-eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissue, and the number of Nissl-positive neurons was counted; enzyme-linked immunosorbent assay (ELISA) was employed to measure levels of inflammatory cytokines in the brain tissue, specifically interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α); immunofluorescence was used to detect the expression levels of neurofilament protein 200 (NF200) and myelin basic protein (MBP) in brain tissue; Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt/PKB/Rac), and mammalian target of rapamycin (mTOR) in brain tissue. ResultsCompared with the normal group, rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test (P<0.01); pathological findings revealed loose structure in the cerebral cortex, hippocampal atrophy, and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated, and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced, and immunofluorescence intensity of NF200 and MBP, as well as protein expression levels of PI3K and mTOR, significantly decreased (P<0.05 or P<0.01). Compared with the model group, rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores (P<0.05); pathological damage in brain tissue alleviated, levels of IL-1β and TNF-α reduced, the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased, and the immunofluorescence intensity of NF200 and MBP, as well as the protein levels of PI3K and mTOR, significantly elevated (P<0.05 or P<0.01). There were no statistically significant differences among the groups in body weight, body-turning time, or AKT protein levels in brain tissue (P>0.05). ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy, exert neurorestorative effects, and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.
4.Mechanism of vanillic acid against cardiac fibrosis induced by isoproterenol in mice based on Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways.
Hai-Bo HE ; Mian WU ; Jie XU ; Qian-Qian XU ; Fang-Zhu WAN ; Hua-Qiao ZHONG ; Ji-Hong ZHANG ; Gang ZHOU ; Hui-Lin QIN ; Hao-Ran LI ; Hai-Ming TANG
China Journal of Chinese Materia Medica 2025;50(8):2193-2208
This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals
;
Isoproterenol/adverse effects*
;
Male
;
Mice
;
Signal Transduction/drug effects*
;
Vanillic Acid/administration & dosage*
;
Dynamins/genetics*
;
Mice, Inbred C57BL
;
Fibrosis/genetics*
;
Apoptosis/drug effects*
;
Mitochondria/metabolism*
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
;
Myocardium/metabolism*
;
Humans
5.Clinical features and prognosis of children with influenza-associated encephalopathy: an analysis of 23 cases.
Dan WANG ; Hu GUO ; Chun-Feng WU ; Gang ZHANG ; Min XU
Chinese Journal of Contemporary Pediatrics 2025;27(7):829-833
OBJECTIVES:
To study the clinical and imaging features of children with influenza-associated encephalopathy (IAE), and to investigate the influencing factors for prognosis.
METHODS:
A retrospective analysis was conducted on the medical data (clinical data, laboratory examinations, imaging data, and prognosis) of 23 children with IAE who were diagnosed and treated in Children's Hospital of Nanjing Medical University from May 2022 to April 2023.
RESULTS:
Among the 23 patients, 18 (78%) had influenza A and 5 (22%) had influenza B. All patients had fever and encephalopathy, and 20 patients (87%) had seizures, while 11 patients (48%) had persistent convulsions. There were 10 patients (43%) with an increase in alanine aminotransferase, 14 (61%) with an increase in aspartate aminotransferase, and 18 (78%) with an increase in lactate dehydrogenase. Abnormal imaging findings were observed in 20 patients (87%), among whom 10 (43%) had acute necrotizing encephalopathy. All 23 patients received peramivir or oseltamivir. Of all patients, 12 (52%) achieved complete recovery, 5 (22%) had varying degrees of neurological dysfunction, and 6 (26%) died. Compared with the good prognosis group, the poor prognosis group had significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (P<0.05).
CONCLUSIONS
Fever and convulsions are the most common symptoms of children with IAE, and acute necrotizing encephalopathy is the most common clinical imaging syndrome. Increases in alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase have a certain value in predicting poor prognosis.
Humans
;
Influenza, Human/complications*
;
Male
;
Prognosis
;
Female
;
Child, Preschool
;
Retrospective Studies
;
Infant
;
Child
;
Brain Diseases/etiology*
6.Establishment and Preliminary Application of qPCR-Based Genotyping Method for Diego, MNS and Kell Blood Groups of Red Blood Cells.
Bing ZHANG ; Gang XU ; Wen-Jian HU ; Xiao-Zhen HONG ; Xian-Guo XU
Journal of Experimental Hematology 2025;33(5):1429-1434
OBJECTIVE:
To establish a genotyping method for Diego, MNS and Kell blood groups based on quantitative real-time PCR (qPCR) technology, and preliminarily apply it to the screening of rare blood groups in blood donors.
METHODS:
Blood group gene standards containing heterozygous and homozygous alleles were prepared by blood group serological and PCR-SBT methods. Specific amplification primers and hybridization probes were designed, and explore to establish the qPCR method for detecting Diego, MNS, and Kell blood group genotypes. Then the established qPCR method was used to identify blood group genotypes of 186 blood donor samples.
RESULTS:
A method based on qPCR technology was established to identify Dia/Dib, S/s and K/k blood group antigens. The genotyping results of the gene standard samples were consistent with the serological testing results and genotypes detected by PCR-SBT. qPCR testing of 186 samples identified 11 cases of DI*A/B heterozygosity and 19 cases of GYPB*S/s heterozygosity, and the rest were DI*B/B, GYPB*s/s, KEL*02/02 homozygosity. No rare blood group genotypes of DI*A/A, GYPB*S/S, KEL*01.01/01.01 were found.
CONCLUSION
The established qPCR method is suitable for genotyping on Diego, MNS and Kell blood group, and it can be used for batch screening of blood donors and the establishment of rare blood group bank.
Humans
;
Genotype
;
Genotyping Techniques/methods*
;
Real-Time Polymerase Chain Reaction/methods*
;
Blood Group Antigens/genetics*
;
Kell Blood-Group System/genetics*
;
Blood Donors
;
Blood Grouping and Crossmatching/methods*
;
Erythrocytes
;
MNSs Blood-Group System/genetics*
7.Xiangshao Granules Ameliorate Post-stroke Depression by Inhibiting Activation of Microglia and IDO1 Expression in Hippocampus and Prefrontal Cortex.
Cheng-Gang LI ; Lu-Shan XU ; Liang SUN ; Yu-Hao XU ; Xiang CAO ; Chen-Chen ZHAO ; Sheng-Nan XIA ; Qing-Xiu ZHANG ; Yun XU
Chinese journal of integrative medicine 2025;31(1):28-38
OBJECTIVE:
To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms.
METHODS:
Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively.
RESULTS:
The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 β, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01).
CONCLUSION
XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.
Animals
;
Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism*
;
Depression/etiology*
;
Drugs, Chinese Herbal/therapeutic use*
;
Hippocampus/metabolism*
;
Male
;
Mice, Inbred C57BL
;
Prefrontal Cortex/pathology*
;
Microglia/metabolism*
;
Stroke/drug therapy*
;
Disease Models, Animal
;
Mice
;
Behavior, Animal/drug effects*
8.Epidemiology of atrial fibrillation/atrial flutter and its risk factors from 1990 to 2021: a systematic analysis and Mendelian randomization study based on the China and Global Burden of Disease Study 2021.
Huihua MA ; Kuipo YAN ; Gang LIU ; Yazhou XU ; Lei ZHANG ; Yizhuo LI
Journal of Southern Medical University 2025;45(10):2182-2190
OBJECTIVES:
To analyze the changes in disease burden and risk factors of atrial fibrillation/atrial flutter (AF/AFL) in China and globally from 1990 to 2021 to provide epidemiological evidence for developing effective preventive measures for AF/AFL in China.
METHODS:
Based on data from the Global Burden of Disease Study 2021, we analyzed sex- and age-specific AF/AFL burden metrics across 204 countries or territories. Age-standardized incidence rate (ASIR), prevalence, mortality rate (ASMR), and disability-adjusted life-years (DALYs) rate (ASDR) were calculated. Joinpoint regression was employed to compute average annual percentage changes (AAPC) in trends. The risk factors were systematically evaluated and further validated using Mendelian randomization analysis.
RESULTS:
From 1990 to 2021, China experienced an increase in ASIR of AF/AFL (from 42.63 to 44.93 per 100 000), contrasting with the global decline. While China's ASMR decreased (from 4.93 to 4.33 per 100 000), global ASMR rose slightly (from 4.24 to 4.36 per 100 000). China's ASDR remained stable at 93.29 per 100 000, whereas global ASDR increased marginally (100.81 to 101.40 per 100 000). Significant sex disparities were observed: males showed higher ASIR and ASDR, while females exhibited greater ASMR and ASDR. China had higher incidence and prevalence but lower mortality and DALY rates compared to global averages. In 2021, the key risk factors for AF/AFL included elevated systolic blood pressure, high BMI, smoking, alcohol use, high-sodium diet, and low temperature. Gender-specific patterns emerged: smoking was predominant in males, whereas high BMI disproportionately affected females.
CONCLUSIONS
AF/AFL incidence and prevalence keep increasing in China, and its large population base and demographic aging pose significant public health challenges. Maintaining healthy lifestyle habits, including smoking cessation, alcohol moderation, and a low-sodium diet can help to lower AF/AFL incidence, and regular screenings is crucial for its early detection and treatment.
Humans
;
China/epidemiology*
;
Risk Factors
;
Atrial Flutter/epidemiology*
;
Atrial Fibrillation/epidemiology*
;
Mendelian Randomization Analysis
;
Male
;
Female
;
Global Burden of Disease
;
Incidence
;
Prevalence
;
Middle Aged
;
Disability-Adjusted Life Years
;
Aged
9.Correction to: Scorpion Venom Heat-Resistant Peptide is Neuroprotective Against Cerebral Ischemia-Reperfusion Injury in Association with the NMDA-MAPK Pathway.
Xu-Gang WANG ; Dan-Dan ZHU ; Na LI ; Yue-Lin HUANG ; Ying-Zi WANG ; Ting ZHANG ; Chen-Mei WANG ; Bin WANG ; Yan PENG ; Bi-Ying GE ; Shao LI ; Jie ZHAO
Neuroscience Bulletin 2025;41(3):549-550
10.Fto-dependent Vdac3 m6A Modification Regulates Neuronal Ferroptosis Induced by the Post-ICH Mass Effect and Transferrin.
Zhongmou XU ; Haiying LI ; Xiang LI ; Jinxin LU ; Chang CAO ; Lu PENG ; Lianxin LI ; John ZHANG ; Gang CHEN
Neuroscience Bulletin 2025;41(6):970-986
During the hyperacute phase of intracerebral hemorrhage (ICH), the mass effect and blood components mechanically lead to brain damage and neurotoxicity. Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake, culminating in ferroptosis in neurons. M6A (N6-methyladenosine) modification, the most prevalent mRNA modification, plays a critical role in various cell death pathways. The Fto (fat mass and obesity-associated protein) demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels. Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis. Applying nanopore direct RNA sequencing, we identified voltage-dependent anion channel 3 (Vdac3) as a potential target associated with ferroptosis. Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA. These findings elucidate the intricate interplay between Fto, Vdac3, m6A methylation, and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.
Ferroptosis/physiology*
;
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics*
;
Animals
;
Neurons/metabolism*
;
Transferrin/pharmacology*
;
Mice
;
Methylation
;
Mice, Inbred C57BL
;
Adenosine/metabolism*
;
RNA, Messenger/metabolism*
;
Male
;
Oxidative Stress/physiology*


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