Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

Acute carbon monoxide poisoning (ACMP) is one of the most common gas poisonings in the emergency department, with tens of thousands of people seeking medical attention for carbon monoxide (CO) poisoning each year. The severity of poisoning is dependent upon environmental and human factors, with hypoxia and oxidative stress being important mechanisms of cardiac toxicity induced by CO. Myocardial involvement is common in moderate to severe ACMP, including myocardial injury, myocardial infarction, arrhythmia, and sudden death, which are associated with a high risk of death. Ferroptosis is a cell death mechanism caused by iron-dependent lipid peroxidation (LPO), although ferroptosis has been shown to play a critical role in various cardiovascular diseases, the potential mechanism by which it contributes to ACMP-induced myocardial injury is unclear. This review discusses the established link between ferroptosis and cardiovascular disease and summarizes the potential role of ferroptosis in ACMP-induced myocardial injury and the detrimental effects of ACMP on the heart. Elucidating these mechanisms could guide the development of novel therapeutic strategies that target ferroptosis to mitigate ACMP-induced myocardial injury. This review aims to provide a theoretical foundation for future research on the potential use of ferroptosis as a therapeutic target for ACMP-induced myocardial injury.
Humans ; Carbon Monoxide Poisoning/complications* ; Ferroptosis ; Lipid Peroxidation ; Myocardium/pathology* ; Oxidative Stress

Objective:To explore the changes of oxidative stress(OS),DNA damage and the occurrence of cellular premature aging of human immortalized keratinocytes(HaCaT)after that was radiated by X-ray with different doses.Methods:HaCaT cells were radiated by X-ray,and they were divided into 0 Gy group,5 Gy group and 10 Gy group according to the irradiation dose.The levels of intracellular reactive oxygen species(ROS)were detected by 2,7-Dichlorofluorescein diacetate(DCFH-DA)fluorescent probe,and the intracellular content of malondialdehyde(MDA)of lipid peroxidation products and the activity of superoxide dismutase(SOD)were measured by colorimetry.Immunofluorescence staining was used to detect the phosphorylated histone 2A variant(γ-H2AX)in HaCaT cells that were radiated by X-ray with different doses.Cell count kit-8(CCK-8)was used to detect the effect of X-ray with different doses on the proliferation of HaCaT cells after X-ray with different doses radiated them.β-Galactosidase staining was used to detect the proportion of premature aging cells.The changes of p21 and p53 protein expressions after X-ray irradiation were detected by Western blot.Results:After HaCaT cells were radiated by X-ray for 24h,the fluorescence intensity of 2',7'-Dichlorofluorescein(DCF)in 5 Gy and 10 Gy groups were significantly higher than that in the 0 Gy group,and the MDA contents of them were significantly higher than that in the control group,and the SOD activities of them were significantly lower than that in the control group(F=38.35,92.22,5.22,P<0.05),respectively.The change of γ-H2AX focus showed a dose-dependent significant increase at 1 h after irradiation,and the difference between them and control group was statistically significant(F=129.3,P<0.05).At 6h,24h and 48h after X-ray radiated HaCaT cells,the cell proliferation abilities of 5 Gy group and 10 Gy group were significantly decreased than that of 0 Gy group(F=116.41,62.20,34.29,P<0.01),and the β-Galactosidase activity of the two groups were significantly increased than that of 0 Gy group,and the difference was significant(F=1629.22,P<0.01).At 72h after X-ray with different doses radiated HaCaT cells,the expression levels of p21 and p53 proteins of 5 Gy group and 10 Gy group increased,and the differences of them among three groups were significant(F=104.4,66.69,P<0.01),respectively.Conclusion:Ionizing radiation can induce the occurrences of oxidative stress and DNA damage in HaCaT cells,and cause the occurrence of cellular premature aging.

Based on an overreview of Chinese radiological health standards, the Chinese radiological health standards currently in effect for biodosimetry were analyzed with respect to their current status, application and existing problems. Furthermore the improvement measures and development trends were put forward.

Objective:To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou(CHERRY)study.Methods:A decision-analytic Markov model was used to simulate and compare different antihy-pertensive initiation strategies,including:Strategy 1,initiation of antihypertensive therapy for Chinese adults with systolic blood pressure(SBP)≥140 mmHg(2020 Chinese guideline on the primary preven-tion of cardiovascular diseases);Strategy 2,initiation of antihypertensive therapy for Chinese adults with SBP≥130 mmHg;Strategy 3,initiation of antihypertensive therapy for Chinese adults with SBP ≥140 mmHg,or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases(2017 American College of Cardiology/American Heart Association guideline for the prevention,detection,evaluation,and management of high blood pressure in adults);Strategy 4,initiation of antihypertensive therapy for Chinese adults with SBP≥ 160 mmHg,or with SBP between 140 and 160 mmHg and at high risk of car-diovascular diseases(2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults:Diagnosis and management).The high 10-year cardiovascular risk was de-fined as the predicted risk over 10％based on the 2019 World Health Organization cardiovascular disease risk charts.Different strategies were simulated by the Markov model for ten years(cycles),with parame-ters mainly from the CHERRY study or published literature.After ten cycles of simulation,the numbers of quality-adjusted life years(QALY),cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy,and the numbers needed to treat(NNT)for each cardiovas-cular event or all-cause death could be prevented were calculated to assess the intervention efficiency.One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilis-tic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.Results:A to-tal of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included.Com-pared with strategy 1,the number of cardiovascular events that could be prevented in strategy 2 increased by 666(95％UI:334-975),while the NNT per cardiovascular event prevented increased by 10(95％UI:7-20).In contrast to strategy 1,the number of cardiovascular events that could be prevented in strategy 3 increased by 388(95％UI:194-569),and the NNT per cardiovascular event prevented decreased by 6(95％UI:4-12),suggesting that strategy 3 had better health benefits and intervention efficiency.Compared to strategy 1,although the number of cardiovascular events that could be prevented decreased by 193(95％UI:98-281)in strategy 4,the NNT per cardiovascular event prevented decreased by 18(95％UI:13-37)with better efficiency.The results were consistent in the sensitivity analyses.Conclusion:When initiating antihypertensive therapy in an economically developed area of China,the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold.The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.

Objective:To explore classification models for radiosensitive lipid metabolites in human peripheral blood by combining lipidomics with multiple machine learning (ML) algorithms.Methods:Totally 97 peripheral blood samples were collected from 25 leukemia cases admitted to a general hospital in Beijing from March to September 2023 who were ready to undergo bone marrow transplantation, including 0 Gy blood samples before irradiation in the control group ( n=24), and 73 blood samples after irradiation at doses of 4, 8 and 12 Gy in the radiation group ( n=73), and the targeted lipidomic based on the ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) platform method to analyze the differences of different lipids between control and radiation groups. Then, lipids responsive to radiation doses of 0-12 Gy were identified using linear regression. Finally, classification models were constructed using five ML algorithms based on the training set, followed by the validation and evaluation of these models using the validation set. Results:Compared with the control group, the differences in the concentration changes of 62 lipids in 9 classes of lipid metabolites sensitive to radiation group were statistically significant ( t=-4.91 to 4.74, P<0.05), including sphingomyelins(SMs), cholesteryl esters(CEs), ceramides(Cers), phosphatidylinositols(PIs), hexosylceramides(HexCers), lysophosphatidylcholines (LysoPCs), phosphatidylcholines (PCOs), phosphatidylethanolamines (PEs), and lysophosphatidylethanolamines (LysoPEs). Twenty lipids responsive to radiation doses of 0-12 Gy were identified, namely 11 SMs, 7 CEs, 1 Cer, and 1 PI. The five models based on ML algorithms of decision tree (DT), support vector machine (SVM), light gradient boosting machine (Light GBM), random forest (RF), and K-nearest neighbors (KNN) all exhibited high goodness of fit (F1=0.69-1.00) and high sensitivity. The evaluation and validation metrics revealed that the RF-based model yielded the optimal radiation classification discrimination (sensitivity: 1.00; accuracy: 0.72; F1 score: 0.80). Conclusions:Lipid metabolites responsive to radiation and lipids responsive to radiation dose in human samples were identified using targeted lipidomics. The RF-based model can provide new ideas for exploring models of human radiosensitive lipid metabolites.

Objective:To evaluate the effect of blunt separation method on peripherally inserted central venous catheters.Methods:The randomized controlled trials regard to the effect of blunt separation method on peripheral central venous catheters were retrieved from CNKI, Wan fang Data Knowledge Service Platform, CQVIP, CBM, Cochrane, PubMed, EMBASE and Web of science from January 2010 to March 2021, two researchers performed quality assessments and extracted data according to Cochrane evaluation manual standards. RevMan 5. 4 software was used for statistical analysis.Results:A total of 11 randomized controlled trials were analyzed, including 1379 participants. The meta-analysis results showed that there was no statistical difference in the successful rate of one-time sheath delivery ( OR=1.62, 95% CI 0.92-2.86, P>0.05). However, patients in blunt separation group showed lower blood loss ( OR=0.24, 95% CI 0.11-0.50, P<0.05), lower the incidence of seepage at puncture site ( OR=0.18, 95% CI 0.09-0.37, P<0.05) than those in traditional skin expansion group at 24h after catheterization, and less the time of maintenance within 7 days after catheterization ( MD=-0.95, 95% CI-1.78--0.11, respectively, P<0.05). Conclusions:Blunt separation method can significantly reduce the incidence of complications and the time of catheter maintenance. Due to the limited quality of included studies, more high quality studies are needed to verify the conclusions.

Objective:Comparison of four methods in intraoperative abduction angles (AA) measurements of human cast immobilization in developmental dysplasia of the hip (DDH) by visual inspection and electronic software according to different body surface markers.Methods:Data were retrospectively collected from January 2019 to November 2021 in a total of 27 patients (54 hips) who underwent closed or simple open reduction. There were 6 males and 21 females with an average age of 13.2 months. Five doctors used visual inspection and mobile phone software to measure the AA of the hip joint immediately during the operation, and compared with the postoperative MRI measurement results (AA-MRI). The four methods of intraoperative measurement were: Junior visualization (AA-JV), the intersection angle between the line connecting the center of the popliteal fossa and the contact center of the plaster frame and the line connecting the two ischial tuberosities; the same methods as method one by Senior visualization (AA-SV); the intersection angle between the line connecting the center of the popliteal fossa and the center of the anus and the line connecting the ischial tubercle (anus-popliteal, AA-AP); the intersection of the vertical line between the center of the popliteal fossa and the groin and the horizontal line of the center of the anus and the vertical line connecting the two ischial tuberosities intersect (anus-groin crease-popliteal, AA-AGCP). The t-test, correlation coefficient, linear regression and Bland-Altman test were used to evaluate the measurements. Results:Comparing the four intraoperative and postoperative AA-MRI measurement methods, AA-JV (42.69°±4.13°) < AA-SV (44.80°±4.08°) < AA-AGCP (46.25°±5.15°) < AA-MRI (47.68°±4.21°) < AA-AP (51.77°±5.30°), and the difference between AA-JV and AA-SV, AA-AP and AA-AGCP was statistically significant ( t=2.53, P=0.013; t=5.47, P=0.001), there was no significant difference between AA-AGCP and AA-MRI ( t=1.57, P=0.118). The inter-group agreement of the five methods ICC test ranged from 0.807 to 0.892, and the intra-group average agreement of AA-MRI was 0.948. All ICC results were greater than 0.75 with good agreement. Linear regression results showed that the four intraoperative measurement methods had a good or moderate linear relationship with AA-MRI, AA-AGCP ( R 2=0.499)>AA-AP ( R 2=0.318)>AA-SV ( R 2=0.253)>AA-JV ( R 2=0.217), AA-AGCP was the best measurement method. The results of Bland-Altman scatterplot of AA-AGCP and AA-MRI were in good agreement, the mean and standard deviation of bias were -0.796±3.247, and the limit of agreement was 95% LoA (-7.16, -5.57). Conclusion:The AA method of visualization before Spica casting was smaller than truth. The method AA-AGCP objectively by landmarks was the advocated means measuring abduction angle during operation with highly consistency, agreement and easily performed.

Objective:To screen radiosensitive lipid metabolites in rat small intestine and analyze their metabolic pathways, in order to provide scientific basis for radiation enteropathy biomarkers.Methods:The total body irradiation of 60Co γ rays was performed to rats with different doses of 0, 1, 2, 3, 5 and 8 Gy. The changes of lipids in small intestine were studied by targeted lipidomics method based on liquid chromatography coupled mass spectrometry (LC-MS). Results:Fifteen lipids in small intestine were screened as radiosensitive metabolites at 3 d after irradiation, including 4 up-regulated lipids and 11 down-regulated lipids( t=-6.395, 5.998, 5.836, -5.503, -5.449, -5.422, 4.841, 4.802, 4.621, 4.457, 4.426, 4.373, 4.110, 3.945, 3.902, P< 0.05 and FDR < 0.05). The metabolic pathways of sphingolipid, glycerophosphoplipid were significantly enriched. Four phosphatidyl serines (PS)increased while 1 phosphatidic acid(PA), 2 sphingomyelins(SM) and 4 fatty acids(FA)decreased in a good dose-response manner( R2> 0.80, P< 0.05), which were more potential radiation enteropathy biomarkers. Conclusions:Lipid metabolites in rat small intestine were significantly changed after the rat was total body irradiated with 60Co γ-rays.Eleven lipids with good dose-response relationship were more potential to be radiation enteropathy biomarkers.

Objective:To explore the feasibility of the optimized cytokinesis-block (CB) assay on radiation-induced nucleoplasmic bridge (NPB), and to provide a scientific basis for the application of NPB in biological dose estimation.Methods:Human peripheral blood in vitro was irradiated with 2 Gy 60Co γ-rays at a dose rate of 1 Gy/min (0 Gy control group). According to the culture time after irradiation, blood samples were divided into group 48, 56, 68 and 72 h. Cytochalasin-B (Cyt-B) with a concentration of 6 μg/ml was added into the samples at 28 h and harvested at 48, 56, 68 and 72 h after irradiation, respectively. On the other hand, the blood samples were treated with different concentration of Cyt-B i. e., 0.6, 1, 2, 6 and 10 μg/ml at the beginning of culture (0 h) and harvested at 68 h after irradiation. The proportion of mononucleated, binucleated and multinucleated cells, radiation-induced NPB and micronucleus (MN) frequencies were analyzed. Results:The nuclear division index (NDI) and proportion of binucleated cells at 2 Gy and 0 Gy had tendency of increasing with cell culture time. NPB frequencies (0.023 0-0.033 0/cell) and MN frequencies had no significantly difference ( P> 0.05). With the increase of Cyt-B concentration, NDI and the proportion of binucleated cells in group 2 Gy and 0 Gy also increased, but NPB frequencies (0.023 0-0.047 0/cell) had no significant difference ( P> 0.05). MN frequencies of group 10 μg/ml were significantly lower than that of group 6 μg/ml ( U=2.74, P< 0.01). Conclusions:Cell culture time and Cyt-B concentration had no significant influence on radiation-induced NPB frequencies, suggesting that NPB could be obtained by appropriately reducing cell culture time and Cyt-B could be added into blood samples at the beginning of culture. But this protocol reduced the number of cells for further analysis, and thus its feasibility for dose estimation still need to be studied.