Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE)intervention timing and liver injury periodization in patients with exertional heat stroke(EHS).Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected,then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT,AST,TBIL and DBIL.According to propensity score matching analysis,11 patients in the survival group and 12 patients in the death group were included in the statistical analysis,and 20 of them were treated with TPE.The changes in indicators and clinical outcomes before and after TPE were observed,in order to evaluate the impact of intervention timing on prognosis.Results Among the 23 patients,14 had no liver injury or could progress to the repair phase,resulting in 3 deaths(with the mortality rate of 21.43%),while 9 patients failed to pro-gress to the repair phase,resulting in 9 deaths(with the mortality rate of 100%),with significant differences(P＜0.05).The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13),while that of interven-tion after reaching or exceeding the third stage was 85.71%(6/7),and the difference was statistically significant(P＜0.05).Conclusion TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes,thereby improving prognosis and reducing mortality.

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans ; Male ; Middle Aged ; Aged ; Coronary Artery Disease/diagnostic imaging* ; Stroke Volume ; Myocardial Perfusion Imaging ; Retrospective Studies ; Ventricular Function, Left ; Myocardial Ischemia

Objective: To construct chimeric antigen receptor (CAR) T cells targeting CD52 (CD52 CAR-T) and validate the effect of CD52 CAR-T cells on CD52-positive leukemia. Methods: A second-generation CD52-targeting CAR bearing 4-1BB costimulatory domain was ligated into a lentiviral vector through molecular cloning. Lentivirus was prepared and packaged by 293 T cells with a four-plasmid system. Fluorescein was used to label cell surface antigens to evaluate the phenotype of CD52 CAR-T cells after infection. Flow cytometry and ELISA were used to evaluate the specific cytotoxicity of CD52 CAR-T cells to CD52-positive cell lines in vitro. Results: ①A pCDH-CD52scFv-CD8α-4-1BB-CD3ζ-GFP expressing plasmid was successfully constructed and used to transduce T cells expressing a novel CD52-targeting CAR. ②On day 6, CD52-positive T cells were almost killed by CD52-targeted CAR-T post lentivirus transduction [CD52 CAR-T (4.48 ± 4.99) %, vs Vector-T (56.58±19.8) %, P=0.011]. ③T cells transduced with the CAR targeting CD52 showed low levels of apoptosis and could be expanded long-term ex vivo. ④The CD52 CAR could promote T cell differentiation into central and effector memory T cells, whereas the proportion of T cells with a CD45RA(+) effector memory phenotype were reduced. ⑤CD52 CAR-T cells could specifically kill CD52-positive HuT78-19t cells but had no killing effect on CD52-negative MOLT4-19t cells. For CD52 CAR-T cells, the percentage of residual of HuT78-19t cells was (2.66±1.60) % at an the E:T ratio of 1∶1 for 24 h, while (56.66±5.74) % of MOLT4-19t cells survived (P<0.001) . ⑥The results of a degranulation experiment confirmed that HuT78-19t cells significantly activated CD52 CAR-T cells but not MOLT4-19t cells[ (57.34±11.25) % vs (13.06± 4.23) %, P<0.001]. ⑦CD52 CAR-T cells released more cytokines when co-cultured with HuT78-19t cells than that of vector-T cells [IFN-γ: (3706±226) pg/ml, P<0.001; TNF-α: (1732±560) pg/ml, P<0.01]. Conclusions: We successfully prepared CD52 CAR-T cells with anti-leukemia effects, which might provide the foundation for further immunotherapy.
CD52 Antigen ; Cell Line, Tumor ; Humans ; Immunotherapy, Adoptive/methods* ; Lentivirus/genetics* ; Leukemia ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen/genetics*

ObjectiveTo explore the carcinogenic mechanism of Campylobacter jejuni. MethodsEighteen female C57BL/6 Apc^Min/+ mice were randomly divided into the C. jejuni-infected group and the non-infection control group， each group with nine mice. Colorectal cancer of Apc^Min/+ mice was induced by dextran sulfate sodium and gavage of C. jejuni （or PBS as a control）. At the end of the experiment， the number of tumors in colorectal tissues of mice in each group was counted， and RNA was extracted from colorectal tumors， along with para-cancer tissues as controls. Transcriptome sequencing was performed by RNA-Seq technology， and data were analyzed for differentially expressed genes （DEGs）. Further， selected DEGs were subjected to GO （gene ontology） enrichment analysis and KEGG pathway enrichment analysis. ResultsCompared with that of the non-infection control group， the incidence of tumor in C. jejuni-infected group was significantly higher （P < 0.01）， which indicated the success of recreating the C. jejuni-induced CRC model. RNA-seq results showed that there were 394 and 501 DEGs （fold change > 4 and P < 0.05） in the C. jejuni-infected group compared with the two control groups， respectively. In GO enrichment analysis， DEGs were mainly enriched in immune response regulation and activation pathways， multiple protein transport pathways and receptor binding pathways. Cancer-related pathways and metabolic pathways were significant enriched in KEGG pathway enrichment analysis. Among these DEGs， 17 genes were found in comparisons with both control groups. The 17 genes were further selected， resulting in 14 “core” DEGs. In further validation of qRT-PCR， 9 genes were significantly differentially expressed， among which 3 genes were up-regulated （Gm1987， Saxo1 and Plekhs1） and 6 were down-regulated （Lrp2， Serpina3c， Fabp4， Tmem52， Lrrn4 and Upk3b）. ConclusionThis study emphasizes 9 host genes that may play important and unique roles in the occurrence and development of colorectal cancer induced by C. jejuni， which provides new insights for further studies on the carcinogenic mechanism of C. jejuni.

Objective::To study whether long-term administration of Gastrodiae Rhizoma powder can improve the learning and memory ability of APPswe/PSldE9 double transgenic (APP/PS1) Alzheimer' s disease(AD) model mice and delay the progress of AD whether these effects are related to the regulation of antioxidant stress pathway in Kelch-like epoxylopropylamine-related protein 1(Keap1)-nuclear factor E2 related factor 2 (Nrf2)/heme oxygenase(HO)-1, and further explore the neuroprotective mechanism of Gastrodiae Rhizoma powder and its role in the prevention and treatment of AD. Method::APP/PS1 double transgenic mice model, the mice consisted of five groups: normal, normal administration group, model group, Gastrodiae Rhizoma powder prevention group, Gastrodiae Rhizoma powder treatment group.The mice in the normal administration group and the Gastrodiae Rhizoma powder prevention group were given the same dose of Gastrodiae Rhizoma powder (1.5 g·kg^-1) daily at the age of 8 weeks.The normal group and model group were given the same amount of normal saline at the same time, until 24 weeks old, Morris water maze was used to test the learning and memory ability of mice, and the treatment group was treated with Gastrodiae Rhizoma powder at 22 weeks old.The mice were given the same dose of Gastrodiae Rhizoma powder (1.5 g·kg^-1) every day for 2 weeks.The number of crossing platform, escape latency and platform residence time of mice were detected by Morris water maze from 24 weeks old to 24 weeks old.RNA, Real-time PCR was extracted from mouse hippocampus to detect the mRNA level of Nrf2, HO-1, Keap1, and Western blot was used to detect the expression of Nrf2, HO-1, Keap1 protein in mouse hippocampus. Result::Compared with normal group, the water maze test showed that the learning and memory ability of model group was lower than that of the model group (P<0.01), and the learning and memory ability of Gastrodiae Rhizoma powder prevention group and Gastrodiae Rhizoma powder treatment group was significantly higher than that of model group (P<0.01). Compared with normal group, the levels of Nrf2, HO-1 and protein in the hippocampus in model group decreased in varying degrees (P<0.05). Compared with model group, Gastrodiae Rhizoma powder prevented Nrf2, in the hippocampus of mice in model group.The level of HO-1 in mRNA and protein increased in different degrees (P<0.05, P<0.01). Levels of Nrf2, HO-1 mRNA in Gastrodiae Rhizoma powder treatment group was significantly higher than that in Gastrodiae Rhizoma powder group (P<0.05). There was no significant difference in the expression of Nrf2, HO-1 protein.There was no significant difference in mRNA and protein levels of Keap1 among different groups. Conclusion::Morris water maze test and other results showed that Gastrodiae Rhizoma powder could improve the learning and memory ability of APP/PS1 mice, and it may enhance the expression of downstream antioxidant genes by regulating Keap1-Nrf2/HO-1 pathway.And then improve the learning and memory ability of APP/PS1 mice.