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

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.

Objective:To investigate the changes in the expression levels of long non-coding ribonucleic acids (lncRNAs) in human lymphocytes induced by low-dose ionizing radiation (LDIR) and the potential of lncRNAs as radiation biomarkers.Methods:Human immortalized lymphocytes (AHH-1) were irradiated with 0, 0.05, and 0.1 Gy of γ-rays at 24 h to extract RNAs for whole transcriptome sequencing. The sequencing was performed based on the 0, 0.05, and 0.1 Gy groups. The differentially expressed lncRNAs induced by LDIR were identified. The molecular functions, biological processes, and signaling pathway enrichment of differentially expressed genes were analyzed through the Gene Ontology (GO) analysis. Candidate lncRNAs were preliminarily validated using the qRT-PCR method. AHH-1 cells were irradiated with 0, 0.02, 0.05, 0.075, 0.1, and 0.2 Gy to extract the total RNAs at 4, 24, 48, 72, 96, and 120 h. The dose-response relationship of candidate lncRNAs was detected and analyzed. Peripheral blood sampled from eight healthy persons was irradiated with 0, 0.02, 0.05, 0.075, 0.1, and 0.2 Gy in vitro, followed by culturing for 24 h and 48 h to further verify the changes in the expression levels of radiation-responsive lncRNAs at the cellular level. Results:A total of 44 lncRNAs that were significantly up- or down-regulated after 0.05 and 0.1 Gy irradiation were initially identified through transcriptome sequencing. Among them, lncRNAs with over two-fold differential expression included SNHG1, SNHG15, NEAT1, and PRC1-AS1. At the cellular level, compared to 0 Gy, the relative expression level of PRC1-AS1 after 4 h to 48 h of γ-ray irradiation, was significantly elevated at 0.05, 0.075, and 0.1 Gy( t= -3.11 to 1.23, P < 0.05). In contrast, the relative expression level of NEAT1 was significantly up-regulated in a dose range of 0.02 to 0.1 Gy ( t=-2.47 to 2.10, P < 0.05). At the level of human peripheral blood, the relative expression levels of PRC1-AS1 and NEAT1 were significantly increased at 24 h after 0 to 0.2 Gy irradiation ( t=-3.79 to -1.96, P < 0.05). Conclusion:The PRC1-AS1 and NEAT1 with significant changes in expression levels serve as potential LDIR biomarkers.

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.

Objective:To investigate the changes in the expression levels of long non-coding ribonucleic acids (lncRNAs) in human lymphocytes induced by low-dose ionizing radiation (LDIR) and the potential of lncRNAs as radiation biomarkers.Methods:Human immortalized lymphocytes (AHH-1) were irradiated with 0, 0.05, and 0.1 Gy of γ-rays at 24 h to extract RNAs for whole transcriptome sequencing. The sequencing was performed based on the 0, 0.05, and 0.1 Gy groups. The differentially expressed lncRNAs induced by LDIR were identified. The molecular functions, biological processes, and signaling pathway enrichment of differentially expressed genes were analyzed through the Gene Ontology (GO) analysis. Candidate lncRNAs were preliminarily validated using the qRT-PCR method. AHH-1 cells were irradiated with 0, 0.02, 0.05, 0.075, 0.1, and 0.2 Gy to extract the total RNAs at 4, 24, 48, 72, 96, and 120 h. The dose-response relationship of candidate lncRNAs was detected and analyzed. Peripheral blood sampled from eight healthy persons was irradiated with 0, 0.02, 0.05, 0.075, 0.1, and 0.2 Gy in vitro, followed by culturing for 24 h and 48 h to further verify the changes in the expression levels of radiation-responsive lncRNAs at the cellular level. Results:A total of 44 lncRNAs that were significantly up- or down-regulated after 0.05 and 0.1 Gy irradiation were initially identified through transcriptome sequencing. Among them, lncRNAs with over two-fold differential expression included SNHG1, SNHG15, NEAT1, and PRC1-AS1. At the cellular level, compared to 0 Gy, the relative expression level of PRC1-AS1 after 4 h to 48 h of γ-ray irradiation, was significantly elevated at 0.05, 0.075, and 0.1 Gy( t= -3.11 to 1.23, P < 0.05). In contrast, the relative expression level of NEAT1 was significantly up-regulated in a dose range of 0.02 to 0.1 Gy ( t=-2.47 to 2.10, P < 0.05). At the level of human peripheral blood, the relative expression levels of PRC1-AS1 and NEAT1 were significantly increased at 24 h after 0 to 0.2 Gy irradiation ( t=-3.79 to -1.96, P < 0.05). Conclusion:The PRC1-AS1 and NEAT1 with significant changes in expression levels serve as potential LDIR biomarkers.

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

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 analyze the discriminatory positive rate(DPR)of individual donor-nucleic acid test (ID-NAT)mode of blood screening laboratories in the Beijing-Tianjin-Hebei Region, explore the possible reasons for DPR differences among blood station laboratories and the measures to lesson the differences, in order to lay a foundation for realizing the homogenization of detection quality of blood screening laboratories in Beijing-Tianjin-Hebei Region. 【Methods】 The number of triplex-positive samples and discriminatory -positive samples of A, B, C, and D blood station laboratories, which submitted to ID-NAT system, in Beijing-Tianjin-Hebei Region from January to December 2018 were collected by a questionnaire of Quality Supervise Index of Blood Station Laboratories in Beijing-Tianjin-Hebei Region. The triplex-positive samples were divided into solo-positive samples(NAT⁺ ELISA^-) and dual-positive samples(NAT⁺ ELISA⁺ ). The changes of total DPR of A, B and C blood screening laboratories in different months was analyzed and compared respectively. The differences of total DPR of ID-NAT, DPR of NAT⁺ ELISA⁺ samples, and DPR between NAT⁺ ELISA^-samples and NAT⁺ ELISA⁺ samples of A, B, and C blood screening laboratories during January 2018 to December 2018 was analyzed and compared. The difference of DPR of NAT⁺ ELISA^-samples among A, B, C, and D blood station laboratories was also compared. 【Results】 Significant difference in total DPR was noticed in different months of A, B, and C blood station laboratories from January to December 2018(P<0.05), with the highest DPRs of A, B and C laboratory at 91.67%, 72.73%. and 80.39%, the lowest DPRs at 65.88%, 21.05%, and 7.69%, respectively. Significant statistical differences in the total DPR and the DPR of NAT⁺ ELISA⁺ samples were found among A, B, and C blood station laboratories(P<0.05). Significant statistical differences in the DPR of NAT⁺ ELISA^- samples were found among A, B, C, and D laboratories(P<0.05). The DPR of NAT⁺ ELISA⁺ samples of A and B blood station laboratories (95.97% and 85.25%) were significantly higher than those of NAT⁺ ELISA^-samples (36.36% and 30.71%)(P<0.05). However, the DPR of NAT⁺ ELISA⁺ samples of C blood station laboratory (32.63%) was significantly lower than that of NAT⁺ ELISA^-samples (44.39%)(P <0.05). 【Conclusion】 There were significant differences in the total DPR, the DPR of NAT⁺ ELISA^-samples and NAT⁺ ELISA⁺ samples that were detected by ID-NAT system in 2018 among blood station laboratories in the Beijing-Tianjin-Hebei Region, and the total discriminatory positive rate in different months was also different for the same blood station. It is necessary to explore the reasons leading to the differences and seek solutions in order to achieve the homogenization of detection quality of blood screening laboratories in Beijing-Tianjin-Hebei Region.

Aim To investigate the slope ratio method for the determination of anticoagulant activity of leeches. Methods Three batches of leeches, four groups of Japanese medical vermiculite yinpian and fifteen groups of leech preparations were chosen, with contrast medicinal leeches herbs and Philippine cattle leech contrast medicinal materials, and different concentrations of leaching solutions were prepared in parallel. APTT value was determined after anticoagulant activity was determined by slope ratio method for the joint validation of laboratory, intermediate precision and accuracy between the linear range. Results The slope ratio method was accurate and accurate in the determination of anticoagulant activity of leeches, with linearity between 64% and 156% relative titer level. Conclusion Slope ratio method can be used to determine the anticoagulant activity of leeches.