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 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:To investigate the current situation of developmental coordination disorder in preschool children in Taiyuan, providing evidence for developing health strategies for preschool children in this city.Methods:We selected 11 126 preschool children aged 3-5 years from 24 kindergartens in Taiyuan using the cluster random sampling method during November-December 2018. Each preschool child was tested with the developmental coordination disorder questionnaire for young children.Results:The incidence of developmental coordination disorder was 3.4%, and the incidence of suspected developmental coordination disorder was 5.4%, and the incidences of which were higher in boys than in girls ( χ2 = 9.46, P < 0.01). The incidence of developmental coordination disorder decreased with aging ( r = -0.06, P < 0.01). The incidence of developmental coordination disorder was negatively correlated with parents' education level and maternal passive smoking during pregnancy ( r = -0.11, P < 0.01; r = -0.12, P < 0.01; r = -0.03, P < 0.01). Lower parents' education level and maternal passive smoking during pregnancy led to a higher incidence of developmental coordination disorder in children. Conclusion:Preschool children from Taiyuan had a lower incidence of developmental coordination disorder than those from economically developed south areas. The higher the gross domestic product in the areas where the kindergartens locate, the lower the incidence of developmental coordination disorder ( r = 0.03, P < 0.01). Environmental factors have a certain impact on developmental coordination disorders in preschool children. Parents, kindergarten teachers, and child health workers should take active intervention measures against the adverse factors in the early development environment of children.

【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.

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.

Abstract Attention deficit hyperactivity disorder (ADHD) is a common childhood psycho behavioral disorder, the exact cause of which is currently unclear. It is generally believed that its incidence is a combination of biological, environmental, and psychological factors. In China at present, the common intervention measures for this disorder are mainly drug treatments, and non medication treatment including EEG Biofeedback environmental Modifications and Self regulation, is relatively inadequate. Non medication treatment is generally targeted at the social function defects associated with this disease; its efficacy is longer lasting and it is safer. This article analyzes the principles, methods, efficacy, shortcomings, and prospects of the non medication treatment of ADHD.

Objective:To investigate the functional imaging parameters that effectively distinguish isocitrate dehydrogenase (IDH) gene mutation status in clinical practice with long echo time (TE) point-resolved spectroscopy (PRESS) MRS.Methods:Totally 25 patients with suspected diagnosis of low grade gliomas(LGGs; Grade II) were recruited prospectively and divided into IDH mutation group and IDH wild group according to pathological results in the study. All patients were scanned with long TE PRESS MRS. In addition, IDH mutational status was determined by post-operation Sanger sequencing. The t test or Mann-Whitney U test was used to analyze the differences of 2-hydroxyglutarate (2HG), Glutamate (Glu), Glutamine (Gln) and 2HG/Glu+Gln between the IDH mutation group and the IDH wild group, then ROC curve was plotted with statistically significant indexes to obtain the efficacy of predicting IDH mutation status. Results:Of the 25 patients, 19 had IDH mutant gliomas and 6 had IDH wild-type gliomas. 2HG, Glu, Gln and 2HG/Glu+Gln in IDH mutated group were 1.42 (1.09, 1.93)mmol/L, (1.74±1.31)mmol/L, (1.68±0.66)mmol/L, 0.55 (0.28, 0.77), respectively; while the corresponding values were 0.00 (0.00, 1.30)mmol/L, (3.28±1.02)mmol/L, (2.55±1.47)mmol/L, 0.00 (0.00, 0.26) in IDH gene wild type group, respectively. The differences of 2HG, Glu, and 2HG/Glu+Gln between the two groups were statistically significant ( P values were 0.030, 0.016, 0.004, respectively). The area under the ROC curve of 2HG/Glu+Gln was the largest (0.877), and the sensitivity was the highest (84.2%). Conclusion:The integration of 2HG with Glu and Gln can effectively realize the noninvasive assessment of IDH mutation status.

【Objective】 To investigate the unqualified rate of anti-HIV detection of blood screening laboratories in Beijing-Tianjin-Hebei region, and explore the differences in anti-HIV detection ability and influencing factors in each laboratory. 【Methods】 Through filling questionnaires via e-mail, the anti-HIV ELISA unqualified rate and confirmed (WB) positive results (data) from January to December 2018 from 15 blood screening laboratories in Beijing-Tianjin-Hebei region were collected. Our laboratory was responsible for data collection and confirmation, and statistics software SPSS22.0 was used for analysis. 【Results】 1) There was a statistically significant difference among the unqualified rate of anti-HIV ELISA(6.77‱~35.71‱) and confirmed positive rate(0.60‱~3.56‱) in 15 blood screening laboratories in Beijing-Tianjin-Hebei region (P<0.05); 2) There were significant differencse among the ELISA unqualified rate and the confirmed positive rate of 8 reagents for anti-HIV detection(P<0.01), and the sensitivity of the 4th generation detection reagent and the imported reagent was higher than that of the 3rd generation reagent and the domestic reagent. The anti-HIV ELISA unqualified rate of R5 was the highest (19.08‱). 3)There were significant differences in the anti-HIV ELISA unqualified rate of R1, R2, R3, R5 and R7 reagents among different blood station laboratories(P<0.05), and there were no significant differences in the anti-HIV ELISA unqualified rate of R4, R6 and R8 reagents among different blood station laboratories(P>0.05). 4)The unqualified rate of anti-HIV ELISA of laboratories using different regents showed significant differences(P<0.05), except H, J, M. The unqualified rate of imported reagent was significantly higher than that of domestic reagents of laboratories using imported and domestic reagents combinations(P<0.05), except O. 62.5% (5/8) laboratories using domestic 3^rd and 4^th generation reagent combination showed significant differences in the unqualified rates among different reagents(P<0.05); 5) The positive rate of single-reagent(62.02%~95.45%)in 15 blood screening laboratories showed significant difference(P<0.001), and A was the lowest (62.02%). 【Conclusion】 The anti-HIV detection ability among 15 blood screening laboratories in Beijing-Tianjin-Hebei region is quite different. The application of different reagents is the main factor for the difference, and other factors such as personnel, instruments and test strategies also has a great impact on the detection of anti-HIV. It is still necessary to promote the process of homogenization of blood testing quality among blood screening laboratories in Beijing-Tianjin-Hebei region.