OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

OBJECTIVE: Blood culture remains the gold standard for diagnosing bloodstream infections. Clinical laboratories must ensure the quality of blood culture processes from receipt to obtaining definitive results. We examined laboratory analytical indicators associated with positive blood culture results. METHODS: Blood cultures collected from Peking Union Medical College Hospital between January 1, 2020, and December 31, 2022, were retrospectively analyzed. The mode of transportation (piping logistics delivery vs. staff), source of blood cultures (outpatient/emergency department vs. inpatient department), rotation of personnel, and time of reception (8:00-19:59 vs. 20:00-07:59) were compared between blood culture-positive and -negative results. RESULTS: Between 2020 and 2022, the total positive rate of blood culture was 8.07%. The positive rate of blood cultures in the outpatient/emergency department was significantly higher than that in the inpatient department (12.46% vs. 5.83%; P < 0.0001). The time-to-detection of blood cultures was significantly affected by the delivery mode and personnel rotation. The blood culture positive rate of the total pre-analytical time within 1 h was significantly higher than that within 1-2 h or > 2 h ( P < 0.0170). CONCLUSION Laboratory analytical indicators such as patient source, transportation mode, and personnel rotation significantly impacted the positive detection rate or time of blood culture.
Blood Culture/statistics & numerical data* ; Humans ; Retrospective Studies ; Emergency Service, Hospital/statistics & numerical data*

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Objective To explore the risk factors for bile leakage after laparoscopic common bile duct exploration(LCBDE)with primary closure.Methods The clinical data of 560 patients with choledocholithiasis who underwent LCBDE with primary closure in Tianjin Hospital of Integrated Traditional Chinese and Western Medicine from September 2021 to September 2023 were retrospectively analyzed,and the patients were divided into the bile leak group and the non-bile leak group according to the occurrence of postoperative bile leakage.The risk factors affecting the occurrence of postoperative bile leakage were analyzed by multivariate analysis.Results A total of 64 cases(11.4% )experienced varying degrees of bile leakage,including 55 cases of grade A bile leakage,7 cases of grade B,and 2 cases of grade C.The thin common bile duct(OR=0.07,P<0.001),history of hypertension(OR=4.56,P<0.001),and high BMI(OR=1.17,P=0.002)were the risk factors for postoperative bile leakage in patients with choledocholithiasis.Conclusion Patients with thin common bile duct,hypertension and obesity are more likely to occur postoperative bile leakage.Patients with choledocholithiasis who have the above high-risk factors should be cautious in choosing LCBDE with primary closure.

Abstract: Objective　To understand and evaluate the current situation of health emergency personnel capacity building in Chongqing, clarify the main factors that affect and restrict this capacity building, and propose countermeasures and suggestions. This will provide a reference for further improving the capacities of health emergency response in Chongqing. Methods　Questionnaire surveys and expert interviews were used to analyze the current situation of health emergency personnel capacity building in 39 disease control and prevention centers and 10 medical institutions in Chongqing from four dimensions: general status, health status, training and drilling status, and health emergency capability. Spearman's rank correlation analysis was used to analyze the correlation between self-evaluation of health status and self-evaluation of sleep quality, and multiple linear regression was employed to analyze the main factors influencing emergency response capability. Results　Among Chongqing's health emergency personnel, 34.85% had a BMI of overweight or above, only 37.92% regularly conducted health monitoring, and 9.19% experienced health problems during emergencies. The proportions of personnel who participated in two or more training sessions per year, two or more drills per year, and one or more physical fitness evaluations per year were 52.07%, 22.76%, and 31.12%, respectively. The average score of emergency response capability of Chongqing's health emergency personnel was 76.11, with the lowest score in the policy advice capability (48.59). Personnel with a medical background (β=1.025), longer years of emergency response work (β=1.774), better self-evaluated physical condition (β=3.664), better self-evaluated mental condition (β=4.362), and participation in drillings twice or more per year (β=2.696) had higher scores in terms of health emergency response capability (P<0.05). Conclusions　There are still some weaknesses in the capacity building of Chongqing's health emergency response personnel. Future efforts should focus on optimizing the staffing structure of the health emergency response team, strengthening the physical training of emergency personnel in normal times and health monitoring and management under emergency conditions, continuously promoting the actual, contextual, and professional emergency training and drilling, and comprehensively improving the physical and mental quality, professional quality, and emergency response capacity of health emergency personnel through multiple approaches.

Trihelix transcription factors play important roles in plant light responses, growth and development, and stress responses. However, Trihelix has not yet been reported in Eucommia ulmoides. In this study, bioinformatics methods were used to comprehensively identify and analyze the expression patterns of the Trihelix gene family in E. ulmoides, aiming to provide a basis for further functional studies of EuGTs genes. A total of 9 Trihelix gene family members were identified in E. ulmoides, encoding proteins with 339 to 883 amino acids, with isoelectric points ranging from 5.13 to 9.39 and relative molecular weights between 36 992.06 and 97 871.61. Subcellular localization results showed that only EuGT-2 was localized in chloroplasts, while the others were located in the nucleus. The Trihelix gene family was categorized into six subfamilies: GT-1, GT-2, SH4, SIP1, GTγ, and GTδ. EuGTs were distributed among three subfamilies: SH4, GT-1, and GT-2, containing 1, 6, and 2 Trihelix proteins, respectively, with 2 to 17 exons. The promoters of EuGTs contained various cis-acting elements related to hormones, stress, photoperiod, and growth and development. Collinearity analysis revealed 5 collinear gene pairs between E. ulmoides and Arabidopsis thaliana, and 14 collinear gene pairs between E. ulmoides and Populus. Expression pattern analysis showed that EuGTs exhibited tissue-specific expression: EuGT-1, EuGT-2 had the highest expression levels in leaves, EuGT-4, EuGT-6, EuGT-9 had the highest transcriptional levels in marginal peel, and EuGT-5、EuGT-8 were predominantly expressed in the xylem. As leaves developed, EuGTs showed a trend of asynchronous changes. No significant differences in EuGTs expression were observed between male and female flowers, with high expression levels mainly during the induction stage of flowering. The qRT-PCR analysis indicated that most EuGTs genes were most highly expressed in the leaves of E. ulmoides, while EuGT-5 was highly expressed in the stems. Under 200 mmol·L~(-1) NaCl treatment, most EuGTs genes exhibited an initial increase followed by a decrease in expression, significantly responding to salt stress. This study provides important genetic resources for further exploration of EuGTs gene functions and germplasm innovation in E. ulmoides.
Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Eucommiaceae/chemistry* ; Phylogeny ; Multigene Family/genetics* ; Gene Expression Profiling ; Transcription Factors/metabolism* ; Genome, Plant/genetics*

This study was aimed at understanding the genome-wide characterization and variations for three imported novel coronavirus(SARS-CoV-2)strains from different sources in the same period in Jinan at the viral genome level,to provide a sci-entific basis for further improving the prevention and control of COVID-19 outbreaks at Jinan port.We selected nasal and pha-ryngeal swab samples from three cases of imported asymptomatic COVID-19infectionat Jinan port;performed second-genera-tion whole-genome sequencing;and analyzed the variant loci and homology withvarious bioinformatics software.The whole ge-nome sequence of SARS-CoV-2 was successfully obtained from three samples of asymptomatic infected cases,and had full lengths ranging from 29 835 bp to 29 844 bp.Pangolin typing results indicated that the genotypes of the three samples were O-micron BQ.1,BQ.1.1,and BQ.1.12.Compared with the original Wuhan strain,the three samples produced mutations at 77,80,and 78 base sites,respectively,involving 60-63 non-synonymous mutations,mainly in the S and ORF1ab genes.Omicron BQ.1 is an imported variant of the SARS-CoV-2 virus and was detected for the first time at Jinan port.From a molecular biolo-gy perspective,this study provides a theoretical basis for the source tracing and prevention and control of COVID-19 at theport.

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

Hexane is a widely used organic solvent in industry, and chronic hexane poisoning is the main occupational toxic lesion in China. In particular, axonal and myelin lesions in the distal thick fibers of the peripheral nervous system may be caused by 2, 5-hexanedione (2, 5-HD), an intermediate metabolite of n-hexane in humans. Hexane has toxic effects not only on the nervous system but also on the liver, kidneys, and reproductive organs. In this paper, we review the progress of research on the mechanism of n-hexane toxic neuropathy.
Humans ; Hexanes/toxicity* ; Hexanones ; Industry ; Solvents

Objective:To compare the effects of anterograde elastic stable intramedullary nailing (ESIN-A), retrograde K-wires fixation (KW-R) and retrograde precision shaping of elastic stable intramedullary nailing (ESIN-RPS) in the treatment of fractures of distal radial metaphyseal diaphyseal junction (DRMDJ) in children.Methods:A retrospective study was conducted to analyze the data of 112 eligible children with DRMDJ fracture who had been treated at Department of Orthopedics, Children's Hospital, Anhui Medical University and Department of Orthopedics, The People's Hospital of Fuyang City,Anhui Medical University, from January 2016 to May 2022. There were 64 males and 48 females, with an age of (8.4±2.3) years. The children were divided into 3 groups according to different surgical fixation methods: group ESIN-A of 36 cases, group KW-R of 52 cases, and group ESIN-RPS of 24 cases. The operation time, intraoperative bleeding, fluoroscopy times, alignment rates and residual angulations by the anteroposterior and lateral X-ray films immediately after reduction were compared among the 3 groups. The Gartland-Werley evaluation of wrist function and complications were compared at the last follow-up.Results:There was no statistically significant difference in the preoperative general data among the 3 groups, indicating comparability ( P>0.05). In the operation time, group KW-R [(71.2±9.2) min] > group ESIN-A [(65.1±13.1) min] > group ESIN-RPS [(51.7±17.1) min]; in the fluoroscopy times, group KW-R [(13.9±6.3) times] > group ESIN-A [(9.0±2.8) times] > group ESIN-RPS [(6.4±2.0) times]; in the alignment rates by the anteroposterior and lateral X-ray films immediately after reduction, group ESIN-RPS (93.1%±4.6% and 95.2%±3.3%) > group KW-R (82.1%±11.0% and 88.1%±7.4%) > group ESIN-A (80.4%±9.9% and 86.7%±6.9%); in the residual angulations by the anteroposterior and lateral X-ray films immediately after reduction, group ESIN-RPS (3.3°±1.8° and 2.9°±2.1°) < group ESIN-A (5.2°±1.0° and 5.0°±3.2°) < group KW-R (6.6°±1.6°and 7.5°±2.7°). Pairwise comparisons in the above items were statistically significant ( P<0.05). In group ESIN-A, the incision length [(1.8±0.3) cm] was significantlylonger than that in group ESIN-RPS [(1.4±0.2) cm], and the intraoperative blood loss [(8.3±2.2) mL] significantly larger than that in group ESIN-RPS [(5.5±1.6) mL] ( P<0.05). One year after operation, the excellent and good rate by the Gartland-Werley evaluation of wrist function in groups ESIN-RPS, ESIN-A and KW-R, respectively, were 95.8% (23/24), 86.5% (31/36) and 86.1% (46/52), showing no statistically significant difference between the 3 group ( P>0.05), and the major incidence of complications in group KW-R (25.0%, 13/52) and in group ESIN-A (25.0%, 9/36) were significantly higher than that in group ESIN-RPS (4.2%, 1/24) ( P<0.05). Conclusion:In the treatment of DRMDJ fractures in children, compared with ESIN-A and KW-R, ESIN-RPS is an effective choice due to its advantages of shorter operation time, less intraoperative blood loss, less radiation, better alignment, and fewer complications.