1.The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer
Xin-Die WANG ; Da-Li FENG ; Xiang CUI ; Su ZHOU ; Peng-Fei ZHANG ; Zhi-Qiang GAO ; Li-Li ZOU ; Jun WANG
Progress in Biochemistry and Biophysics 2025;52(4):804-819
Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.
2.Clinical and genetic characteristics of congenital adrenal hyperplasia: a retrospective analysis.
Cai-Jun WANG ; Ya-Wei ZHANG ; Da-Peng LIU ; Juan JIN ; Zhao-Hui LI ; Jing GUO ; Yao-Dong ZHANG ; Hai-Hua YANG ; Wen-Qing KANG
Chinese Journal of Contemporary Pediatrics 2025;27(11):1367-1372
OBJECTIVES:
To study the clinical and genetic characteristics of children with congenital adrenal hyperplasia (CAH).
METHODS:
Clinical data, laboratory findings, and genetic test results of 63 children diagnosed with CAH at Henan Children's Hospital from January 2017 to December 2024 were retrospectively reviewed.
RESULTS:
Of the 63 patients, the mean age at the first visit was (21 ± 14) days; 29 (46%) were of male sex and 34 (54%) were of female sex. The predominant clinical manifestations were poor weight gain or weight loss (92%, 58/63), poor feeding (84%, 53/63), skin hyperpigmentation (83%, 52/63), and female external genital anomalies (100%, 34/34). Laboratory abnormalities included hyponatremia (87%, 55/63), hyperkalemia (68%, 43/63), metabolic acidosis (68%, 43/63), and markedly elevated 17-hydroxyprogesterone (92%, 58/63), testosterone (89%, 56/63), and adrenocorticotropic hormone (81%, 51/63). Among 49 patients who underwent genetic testing, CYP21A2 variants were identified in 90% (44/49), with c.293-13A/C>G (33%, 30/91) and large deletions/gene conversions (29%, 26/91) being the most frequent; STAR (8%, 4/49) and HSD3B2 (2%, 1/49) variants were also detected. Following hormone replacement therapy, electrolyte disturbances were corrected in 57 cases, with significant reductions in 17-hydroxyprogesterone, adrenocorticotropic hormone, and testosterone levels (P<0.001).
CONCLUSIONS
CAH presenting in neonates or young infants is characterized by electrolyte imbalance, external genital anomalies, and abnormal hormone levels. Genetic testing enables definitive subtype classification; in CYP21A2-related CAH, c.293-13A/C>G is a hotspot variant. These findings underscore the clinical value of genetic testing for early diagnosis and genetic counseling in CAH. Citation:Chinese Journal of Contemporary Pediatrics, 2025, 27(11): 1367-1372.
Humans
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Adrenal Hyperplasia, Congenital/diagnosis*
;
Male
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Female
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Retrospective Studies
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Infant
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Infant, Newborn
3.Colon Dialysis with Yishen Decoction Improves Autophagy Disorder in Intestinal Mucosal Epithelial Cells of Chronic Renal Failure by Regulating SIRT1 Pathway.
Yan-Jun FAN ; Jing-Ai FANG ; Su-Fen LI ; Ting LIU ; Wen-Yuan LIU ; Ya-Ling HU ; Rui-Hua WANG ; Hui LI ; Da-Lin SUN ; Guang ZHANG ; Zi-Yuan ZHANG
Chinese journal of integrative medicine 2025;31(10):899-907
OBJECTIVE:
To explore the mechanism of colon dialysis with Yishen Decoction (YS) in improving the autophagy disorder of intestinal epithelial cells in chronic renal failure (CRF) in vivo and in vitro.
METHODS:
Thirty male SD rats were randomly divided into normal, CRF, and colonic dialysis with YS groups by a random number table method (n=10). The CRF model was established by orally gavage of adenine 200 mg/(kg•d) for 4 weeks. CRF rats in the YS group were treated with colonic dialysis using YS 20 g/(kg•d) for 14 consecutive days. The serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by enzyme-linked immunosorbent assay. Pathological changes of kidney and colon tissues were observed by hematoxylin and eosin staining. Autophagosome changes in colonic epithelial cells was observed with electron microscopy. In vitro experiments, human colon cancer epithelial cells (T84) were cultured and divided into normal, urea model (74U), YS colon dialysis, autophagy activator rapamycin (Ra), autophagy inhibitor 3-methyladenine (3-MA), and SIRT1 activator resveratrol (Re) groups. RT-PCR and Western blot were used to detect the mRNA and protein expressions of zonula occludens-1 (ZO-1), Claudin-1, silent information regulator sirtuin 1 (SIRT1), LC3, and Beclin-1 both in vitro and in vivo.
RESULTS:
Colonic dialysis with YS decreased SCr and BUN levels in CRF rats (P<0.05), and alleviated the pathological changes of renal and colon tissues. Expressions of SIRT1, ZO-1, Claudin-1, Beclin-1, and LC3II/I were increased in the YS group compared with the CRF group in vivo (P<0.05). In in vitro study, compared with normal group, the expressions of SIRT1, ZO-1, and Claudin-1 were decreased, and expressions of Beclin-1, and LC3II/I were increased in the 74U group (P<0.05). Compared with the 74U group, expressions of SIRT1, ZO-1, and Claudin-1 were increased, whereas Beclin-1, and LC3II/I were decreased in the YS group (P<0.05). The treatment of 3-MA and rapamycin regulated autophagy and the expression of SIRT1. SIRT1 activator intervention up-regulated autophagy as well as the expressions of ZO-1 and Claudin-1 compared with the 74U group (P<0.05).
CONCLUSION
Colonic dialysis with YS could improve autophagy disorder and repair CRF intestinal mucosal barrier injury by regulating SIRT1 expression in intestinal epithelial cells.
Animals
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Sirtuin 1/metabolism*
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Drugs, Chinese Herbal/therapeutic use*
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Autophagy/drug effects*
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Male
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Intestinal Mucosa/drug effects*
;
Rats, Sprague-Dawley
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Epithelial Cells/metabolism*
;
Colon/drug effects*
;
Humans
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Kidney Failure, Chronic/drug therapy*
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Signal Transduction/drug effects*
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Renal Dialysis
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Rats
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Kidney/drug effects*
4.Retraction Note: Fluoxetine is Neuroprotective in Early Brain Injury via its Anti-inflammatory and Anti-apoptotic Effects in a Rat Experimental Subarachnoid Hemorrhage Model.
Hui-Min HU ; Bin LI ; Xiao-Dong WANG ; Yun-Shan GUO ; Hua HUI ; Hai-Ping ZHANG ; Biao WANG ; Da-Geng HUANG ; Ding-Jun HAO
Neuroscience Bulletin 2025;41(11):2106-2106
5.Clinicopathological Features and HOX Transcript Antisense RNA In Situ Hybridization Detection of Myxopapillary Ependymoma.
Yu-Han ZHANG ; Zheng WANG ; LU JUN-LIANG ; Da-Chun ZHAO ; Zhen HUO
Acta Academiae Medicinae Sinicae 2025;47(1):35-41
Objective To summarize the clinicopathological features,immunohistochemical characteristics,HOX transcript antisense RNA(HOTAIR)in situ hybridization status,treatment,and prognosis of myxopapillary ependymoma(MPE). Methods A total of 17 patients diagnosed with MPE based on pathological evidence in the Department of Pathology of Peking Union Medical College Hospital from November 2006 to July 2023 were selected,and the clinicopathological data of these patients were collected.Immunohistochemical staining for trimethylation at lysine 27 of histone H3 (H3K27me3),glial fibrillary acidic protein(GFAP),and epithelial membrane antigen(EMA)and alcian blue-periodic acid Schiff(AB-PAS)staining were performed in all the patients.Sixteen patients with spinal ependymomas were selected as the control group.Tissue microarrays were prepared from 17 MPE patients and the control group.HOTAIR ISH was performed and semi-quantitatively scored,and the scores of the two groups were compared by the Wilcoxon rank-sum test. Results The 17 MPE patients aged 14-64 years,with the mean age of(37.48±16.10)years and the male-to-female ratio of 0.7∶1.Their clinical manifestations mainly included lumbosacral and lower limb pains.Microscopically,tumor cells were arranged in a papillary pattern around fibrovascular axis,with abundant myxoid materials,and tumor cells were arranged in a loose meshwork in some patients.The immunohistochemical staining results showed that 17(100%),10(58.82%),and 8(47.06%)patients expressed GFAP,EMA,and D2-40,respectively,and 2(11.76%)patients lacked expression of H3K27me3.AB-PAS staining showed blue myxoid materials in all the 17(100%)patients.HOTAIR was expressed in both MPE and control groups,with higher semi-quantitative score in the MPE group than in the control group(P=0.004).Twelve patients were followed up,with a median follow-up period of 65.50 months,during which three patients showed recurrence.Conclusions MPE exhibits typical pathological features,and the combination with immunohistochemical staining for GFAP and EMA as well as AB-PAS staining facilitates diagnosis of this disease.A small number of patients loss the expression of H3K27me3.HOTAIR is highly expressed in MPE but lacks specificity,which limits its auxiliary diagnostic value.The overall prognosis of MPE is favorable,with a few patients experiencing recurrence.
Humans
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Ependymoma/metabolism*
;
Male
;
Adult
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Female
;
Adolescent
;
Middle Aged
;
In Situ Hybridization
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Young Adult
;
RNA, Antisense/genetics*
;
Immunohistochemistry
;
Prognosis
6.Dosimetric effect of calculation grid size on stereotactic body radiation therapy of lung cancer in helical tomotherapy planning system
Xia-Yu HANG ; Wan-Rong JIANG ; Yi-Kun LI ; Jun HU ; Yan ZHANG ; Ruo-Qi CAO ; Nan XU ; Lei WANG ; Jin-Da ZHOU ; Xiang-Dong SUN
Chinese Medical Equipment Journal 2024;45(2):52-57
Objective To investigate the dosimetric effects of different calculation grid size(CGS)in helical tomotherapy(HT)planning system on stereotactic body radiation therapy(SBRT)for non-small cell lung cancer(NSCLC).Methods Nine NSCLC patients receiving radiation therapy for the first time at some hospital from March 2019 to December 2022 were selected as the subjects.SBRT planning was carried out through the HT system with three different CGS plans(Fine,Normal,and Coarse)and the same pitch,modulation factor(MF)and optimization conditions,and the target area indexes of the three CGS plans were compared including conformity index(CI),homogeneity index(HI),dosimetric parameters of the organ at risk(OAR),point dose verification pass rate,treatment time,number of monitor units and Sinograms.SPSS 22.0 was used for statistical analysis.Results For target area HI,there weres significant differences between CGS Fine plan and Coarse plan and between CGS Normal plan and Coarse plan(P<0.05),while no statistical differences were found between CGS Fine plan and Normal plan(P>0.05).For target area CI,there were significant differences between CGS Fine plan and Coarse plan(P<0.05),while no statistical differences were found between CGS Fine plan and Normal plan and between CGS Normal plan and Coarse plan(P>0.05).For OAR dosimetric parameters,CGS Fine plan and Coarse plan had significant differences in heart Dmax and Dmean,esophageal Dmax and Dmean,V5,V20,V30 and Dmean of the whole lung and affected lung,V5 and Dmax of the affected lung and heart V10 and V30(P<0.05),CGS Normal plan and Coarse plan had obvious differences in esophageal Dmax(P<0.05),and the remained dosimetric parameters were not statistically significant(P>0.05).Fine,Normal and Coarse plans had the point dose verifica-tion pass rates being 0.96%,1.50%and 1.77%,respectively.In terms of treatment time and number of monitor units,there were significant differences between Fine plan and Coarse plan(P<0.05)while no statistical differences were found between Fine and Normal plans and between Normal and Coarse plans(P>0.05).Sinograms analyses showed Fine plan had evenly distributed segment color gradient,Coarse plan had areas of very dark and very light color gradients and Normal plan was somewhere in between.Conclusion Low CGS has to be used as much as possible to obtain accurate dose distribution during SBRT planning for NSCLC patients,which contributes to the execution of the radiation therapy plan and the prevention of ad-verse effects.[Chinese Medical Equipment Journal,2024,45(2):52-57]
7.Dosimetric comparison of anal sphincter and its substructures with different radiotherapy techniques for rectal cancer
Geng LI ; Fei DENG ; Yong-Jun LI ; Da-Li FENG ; Xin LI ; Zhuo KONG ; Ji-Ping WANG ; Min ZOU
Chinese Medical Equipment Journal 2024;45(8):63-67
Objective To compare the dosimetric effects of volume modulated arc therapy(VMAT)and intensity modulated radiation therapy(I M RT)on the anal sphincter(AS)and its sub-structures in neoadjuvant radiotherapy for rectal cancer to facilitate the selection of radiotherapy techniques.Methods Fifty rectal cancer patients receiving neoadjuvant radiotherapy were selected,and 2 types of radiotherapy plans,including coplanar double full-arc VMAT and coplanar seven-field homo-geneous IMRT,were designed based on the CT images of the patients,respectively.Under the premise of ensuring that the irradiated doses to the target area and the major organs at risk reached the standard and met the clinical requirements,AS and its substructures were added as the organs at risk for dosimetric evaluation.The absolute dose parameters and relative dose parameters of AS and its substructures were counted by dose-volume histograms.Statistical analysis was performed using IBM SPSS 22.0 software.Results The VMAT plan had the relative dose parameters V20,V30,and V40 of AS and its substructures lower those of the IMRT plan,the differences were statistically significant(P<0.05),while the differences in V5 and V 10 were not statistically significant(P>0.05).The VMAT plan had the absolute dose parameterDmeanlower while the D2%slightly higher than those of the IMRT plan,the differences were statistically significant(P<0.05).The difference in D98%between the two plans was not statistically significant(P>0.05).Conclusion During rectal cancer radiotherapy VMAT generally behaves better than IMRT in protecting AS and its sub-structures and decreasing injuries of AS and its sub-structures dosimetrically.[Chinese Medical Equipment Journal,2024,45(8):63-67]
8.Analysis of dissatisfaction and related factors following total hip arthroplasty in patients with Crowe type Ⅲ-Ⅳ de-velopmental dysplasia of the hip
Peng ZHAO ; Yu-Jun LI ; Yong DOU ; Da-Cheng WANG
China Journal of Orthopaedics and Traumatology 2024;37(4):363-367
Objective To investigate the satisfaction of patients with Crowe Ⅲ-Ⅳ developmental dysplasia of the hip(DDH)after total hip arthroplasty and the related factors.Methods A retrospective study included 169 patients with Crowe type Ⅲ-Ⅳ DDH who underwent total hip arthroplasty between March 2013 and March 2018.Patients were surveyed through WeChat,covering overall satisfaction with the operation,satisfaction with ten daily functions,and the top five questions per-ceived to have a great impact on daily life.Preoperative and postoperative hip function was evaluated by Harris score.Results One hundred and forty-five questionnaires were received,with a follow-up period ranging from 1 to 5 years with an average of(3.23±1.22)years.Among these patients,118 patients were satisfied with the surgical outcomes,while 27 patients were dissat-isfied,with the overall satisfaction rate of 81.38%(118/145).The top five problems affecting patient life were postoperative hip pain,limb length discrepancy,walking,stair climbing,and squatting.There were no statistical differences in age,sex,body mass index,preoperative Harris scores(P>0.05).However,the dissatisfied group had lower postoperative Harris scores.Post-operative hip pain and limb length discrepancy were identified as direct factors contributing to postoperative surgical dissatis-faction.Conclusion Total hip arthroplasty for patients with Crowe type Ⅲ-Ⅳ DDH is challenging.Postoperative hip pain(mild or severe)and limb length discrepancy(>2 cm)are independent risk factors for postoperative dissatisfaction.
9.Ultrasonic anatomical study and clinical application of stellate ganglion block via C7 transverse process
Ai-Li HU ; Jun-Li WANG ; Xiao-Ai CHU ; Jie-Qing CHEN ; Zong-Yu ZHA ; Da-Sheng LU ; Qin-Zhong XIA
Journal of Regional Anatomy and Operative Surgery 2024;33(7):571-575
Objective To investigate the high-frequency ultrasonic anatomical features of the adjacent C7 transverse process and its clinical value in stellate ganglion block(SGB).Methods High-frequency ultrasound was applied to obtain ultrasonographic anatomical sonogram features in the plane of bilateral C7 transverse processes in 52 cases(104 sides in total)of healthy adults and then stored for the operator to learn and correctly label each tissue structure.Fifty patients who underwent ultrasound-guided SGB were selected and divided into the BC7 group(25 cases before study)and AC7 group(25 cases after study).The operation time,SGB success rate,number of adjusted needle tips,dosage of anaesthetic and adverse reaction of patients in both group were recorded.Results The main muscles observed in the C7 plane were the longissimus and anterior scalene muscles,the ultrasonographic anatomical relationships of the vagus nerve located in the carotid sheath,the pleura located posterior to the subclavian artery,and the recurrent laryngeal nerve located in the vicinity of the branches of the inferior thyroid artery are described,and the stellate ganglion was illustrated as a flattened hypoechogenic structure visible on the deep surface of the prevertebral fascia in the region of the external cervical longissimus muscle,vertebral artery and vein,and the medial aspect of the anterior oblique muscle,and emanated the sonographic features of several hypoechoic nerve bundles.Ultrasound guided SGB was completed uneventfully in patients of both groups,and all patients developed Horner syndrome,with the SGB success rate of 100%.The operation time[(5.36±1.11)minutes]of patients in the BC7 group was longer than that in the AC7 group[(3.08±0.86)minutes],the number of adjusted needle tips[(4.20±1.00)times]of patients in the BC7 group was more than that in the AC7 group[(2.24±0.87)times],and the dosage of anaesthetic[(1.82±0.28)mL]of patients in the BC7 group was more than that in the AC7 group[(1.64±0.22)mL],all the differences were statistically significant(P<0.05).There was no significant difference in the incidence of adverse reaction between the two groups(P>0.05).Conclusion After ultrasonic learning of adjacent structures through C7 transverse process,SGB is safe and easy to perform.
10.Establishment and transfer management of veno-arterial extracorporeal membrane oxygenation in patients with difficult downtime during cardiopulmonary bypass surgery
Ke FANG ; Huanhuan DA ; Ruixiang SUN ; Jun WANG ; Jiaoting WANG ; Haijiao JIANG ; Tao WANG ; Qiancheng XU
Chinese Critical Care Medicine 2024;36(4):415-421
Objective:To investigate the establishment method, coordination points and safe transport management strategy of vena-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with downtime difficulties during cardiopulmonary bypass (CPB).Methods:A observation study was conducted. The patients admitted to the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from January 2020 to October 2022 were enrolled. These patients could not be separated from CPB and received VA-ECMO-assisted CPB surgery. The clinical data of the patients were recorded, including the basic information of the patients, the data of VA-ECMO establishment and transport process, the clinical indicators before and after VA-ECMO installation, the operation data of VA-ECMO and clinical outcomes. The experience was summarized from the aspects of extracorporeal membrane oxygenation (ECMO) establishment, transport process, team cooperation, and adverse events during transport. The clinical indicators before and after ECMO operation were compared. According to whether ECMO was successfully weaned, the patients were divided into a successful weaning group and a failure weaning group, and the clinical data between the two groups were compared.Results:Eighteen patients who underwent VA-ECMO-assisted CPB were enrolled, including 10 males and 8 females. The average age was (56.7±12.3) years old. Preoperative left ventricular ejection fraction (LVEF) was 0.46±0.10, and the main reasons for switching to VA-ECMO assistance included right ventricular systolic weakness in 6 cases, total cardiac systolic weakness in 5 cases, left ventricular systolic weakness in 4 cases, high pulmonary arterial pressure in 2 cases, and intractable ventricular fibrillation in 1 case. Among the 18 patients transferred from CPB to VA-ECMO, 10 cases were successfully weaned and 8 cases failed. In ICU, 8 cases survived, 5 cases died, and 5 cases gave up treatment and discharged. The average time for successful CPB to VA-ECMO establishment was (24.6±7.4) minutes, initial blood flow was (3.3±0.4) L/min, and transit time was (8.4±1.5) minutes. ECMO-assisted duration averaged (82.0±69.3) hours. Adverse events occurred in 9 patients during ECMO establishment and transfer. Post-ECMO onboarding for 4 hours, significant improvements were noted in blood lactic acid (Lac), pH value, mean arterial pressure (MAP), central venous oxygen saturation (ScvO 2) as compared with pre-ECMO onboarding [Lac (mmol/L): 10.5±7.0 vs. 15.2±6.8, pH value: 7.38±0.92 vs. 7.26±0.87, MAP (mmHg, 1 mmHg≈0.133 kPa): 74.9±13.7 vs. 58.4±17.0, ScvO 2: 0.678±0.065 vs. 0.611±0.061, all P < 0.01], and vasoactive-inotropic score (VIS) was also decreased (39.8±29.8 vs. 68.9±64.4, P < 0.01). Compared with successful weaning group, the patients in the failed weaning group exhibited higher pre-machine Lac (mmol/L: 18.8±7.8 vs. 12.3±4.3, P < 0.05), longer CPB time [minutes: 238.0 (208.8, 351.2) vs. 200.0 (185.8, 217.0), P < 0.05], and shorter ECMO-assisted time [hours: 19.5 (11.0, 58.8) vs. 94.5 (65.8, 179.8), P < 0.01]. However, there was no statistically significant difference in pre-machine pH value, ScvO 2, MAP, VIS score, and initial blood flow and establishment time of ECMO between the two groups. Conclusions:VA-ECMO is an effective circulatory aid for CPB surgery that cannot be weaned after CPB. The establishment and transfer of CPB "bridge" to ECMO aid depends on multi-disciplinary treatment (MDT) cooperation. The success rate of ECMO weaning is related to the Lac and CPB duration. If it is not possible to detach from the CPB successfully, VA-ECMO should be initiated as early as possible.

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