Objective To investigate the relationships of the expression of microRNA-487a-3p (miR-487a-3p) and A kinase-interacting protein 1 (AKIP1) mRNA in the endometrial cancer (EC) tissue with the patient survival within 5 years after surgery. Methods The EC tissue and adjacent normal tissue samples were collected from 130 EC patients who underwent surgical treatment at the Fourth Hospital of Shijiazhuang from September 2016 to April 2019.qRT-PCR was employed to determine the expression levels of miR-487a-3p and AKIP1 mRNA.The patients were followed up for 5 years after surgery to record the survival status.After removal of the patients who missed follow-up,78 surviving patients were recorded as the EC survival group,and 34 deceased patients were recorded as the EC death group.The dual luciferase reporter gene assay was conducted to verify the targeting relationship between miR-487a-3p and AKIP1 mRNA.Comparison was conducted for the expression levels of miR-487a-3p and AKIP1 mRNA between adjacent normal tissue and EC tissue,the expression levels of miR-487a-3p and AKIP1 mRNA in the EC tissue among patients with different clinical pathological parameters,and the clinical pathological parameters and the expression levels of miR-487a-3p and AKIP1 mRNA in the EC tissue between the EC survival group and the EC death group.The correlations of miR-487a-3p and AKIP1 mRNA levels in the EC tissue with the degree of tumor differentiation,International Federation of Gynecology and Obstetrics (FIGO) stage,lymph node metastasis,and depth of muscle invasion were analyzed.The relationships of miR-487a-3p and AKIP1 mRNA with patient prognosis and the risk factors affecting the survival of EC patients within 5 years after surgery were analyzed to evaluate the value of miR-487a-3p and AKIP1 mRNA levels in predicting the survival of EC patients within 5 years after survival. Results The EC tissue showed lower miR-487a-3p level (0.41±0.08 vs. 1.00±0.05;t=71.306,P<0.001) and higher AKIP1 mRNA level (2.35±0.37 vs. 1.00±0.03;t=41.465,P<0.001) than the adjacent normal tissue.The miR-487a-3p low expression group and AKIP1 mRNA high expression group had higher proportions of patients with low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,and deep invasion of muscle layer than the miR-487a-3p high expression group and AKIP1 mRNA low expression group,respectively (all P<0.05).The results of dual luciferase reporter gene assay showed that the relative activity of luciferase in the miR-487a-3p small interfering RNA (siRNA)+AKIP1 mRNA-wild type (WT) group was higher than that in the miR-487a-3p empty vector+AKIP1 mRNA-WT group (2.85±0.19 vs. 1.00±0.04;t=23.339,P<0.001).There was no significant difference in the relative activity of luciferase between the miR-487a-3p empty vector+AKIP1 mRNA-mutant type (MUT) group and the miR-487a-3p siRNA+AKIP1 mRNA-MUT group (1.04±0.05 vs. 1.05±0.03;t=0.420,P=0.683).MiR-487a-3p in the EC tissue had negative correlations with AKIP1 mRNA,FIGO stage,lymph node metastasis,and depth of muscle invasion and a positive correlation with the degree of tumor differentiation (all P<0.001).AKIP1 mRNA had positive correlations with FIGO stage,lymph node metastasis,and depth of muscle invasion and a negative correlation with the degree of tumor differentiation (all P<0.001).The 5-year overall survival rates in the miR-487a-3p high expression group and AKIP1 mRNA low expression group (89.47% and 84.91%) were higher than those in the miR-487a-3p low expression group and AKIP1 mRNA high expression group (49.09% and 55.93%),respectively (both P<0.05).The EC death group had higher proportions of patients with low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,and deep invasion of muscle layer,higher AKIP1 mRNA level in the EC tissue,and lower miR-487a-3p level than the EC survival group (all P<0.05).Low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,deep invasion of muscle layer,low miR-487a-3p level,and high AKIP1 mRNA level were independent risk factors for the survival of EC patients within 5 years after surgery (all P<0.05).The area under curve (AUC) values of miR-487a-3p and AKIP1 mRNA alone (0.785 and 0.789,respectively) were lower than that of their combination (0.908) in predicting the survival of EC patients within 5 years after surgery (both P<0.05). Conclusion The EC tissue has a low miR-487a-3p level and a high AKIP1 mRNA level,both of which are correlated with clinicopathological parameters and prognosis and can be used to predict the survival of EC patients within 5 years after surgery.
Humans ; Female ; Endometrial Neoplasms/pathology* ; MicroRNAs/genetics* ; RNA, Messenger/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Middle Aged ; Survival Rate ; Nuclear Proteins

Objective Based on 25 indicators including immune factors, cell count classification, and smear results of the knee joint fluid, machine learning models were established to distinguish between osteoarthritis (OA) and rheumatoid arthritis (RA). Methods 100 OA and 40 RA patients scheduled for total knee arthroplasty were enrolled respectively. Each patient's knee joint fluid was collected preoperatively. Nucleated cells were counted and classified. The expression levels of immune factors, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-8, IL-15, matrix metalloproteinase 3 (MMP3), MMP9, MMP13, rheumatoid factor (RF), serum amyloid A (SAA), C-reactive protein (CRP), and others were measured. Smears and microscopic classification of all the immune factors were performed. Independent influencing factors for OA or RA were identified using univariate binary logistic regression, Lasso regression, and multivariate binary logistic regression. Based on the independent influencing factors, three machine learning models were constructed which are logistic regression, random forest, and support vector machine. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to evaluate and compare the models. Results A total of 5 indicators in the knee joint fluid were screened out to distinguish OA and RA, which were IL-1β(odds ratio(OR)=10.512, 95× confidence interval (95×CI) was 1.048-105.42, P=0.045), IL-6 (OR=1.007, 95×CI was 1.001-1.014, P=0.022), MMP9 (OR=3.202, 95×CI was 1.235-8.305, P=0.017), MMP13 (OR=1.002, 95× CI was 1-1.004, P=0.049), and RF (OR=1.091, 95×CI was 1.01-1.179, P=0.026). According to the results of ROC, calibration curve and DCA, the accuracy (0.979), sensitivity (0.98) and area under the curve (AUC, 0.996, 95×CI was 0.991-1) of the random forest model were the highest. It has good validity and feasibility, and its distinguishing ability is better than the other two models. Conclusion The machine learning model based on immune factors in the knee joint fluid holds significant value in distinguishing OA and RA. It provides an important reference for the clinical early differential diagnosis, prevention and treatment of OA and RA.
Humans ; Arthritis, Rheumatoid/metabolism* ; Machine Learning ; Male ; Female ; Middle Aged ; Aged ; Synovial Fluid/immunology* ; Osteoarthritis, Knee/metabolism* ; Knee Joint/metabolism* ; ROC Curve ; Diagnosis, Differential

The early diagnosis and precise treatment of esophageal squamous cell carcinoma (ESCC) hold significant clinical value in improving patient survival rate. Current diagnostic methods for early-stage ESCC primarily rely on invasive procedures and endoscopy, which can cause discomfort and financial burden for patients. Therefore, non-invasive biomarkers with high sensitivity and specificity present a more suitable alternative for early tumor diagnosis. Tumor associated autoantibodies (TAAb), identified as potential biomarkers, have considerable clinical implications for the early diagnosis, treatment monitoring, and prognosis assessment of ESCC. Here in we aim to summarize recent research on ESCC-related autoantibodies, including their background, types and development, analyze the potential of those autoantibodies in clinical diagnosis, treatment monitoring, and prognosis assessment, and also discuss the limitations of existing research and future directions. The goal is to provide a theoretical foundation for the early diagnosis and personalized treatment of ESCC.
Humans ; Autoantibodies/immunology* ; Esophageal Neoplasms/therapy* ; Esophageal Squamous Cell Carcinoma/immunology* ; Biomarkers, Tumor/immunology* ; Prognosis ; Carcinoma, Squamous Cell/diagnosis* ; Animals

Spinal cord injury (SCI) represents a complex pathophysiological process involving the interaction of multiple cell types. Conventional sequencing methods can only detect the average gene expression level of the damaged local cell populations, which is difficult to reflect its heterogeneity. Therefore, new technologies are needed to reveal the intercellular heterogeneity and the complex intercellular interactions of the damaged lesions. The single-cell RNA sequencing (scRNA-seq) technique facilitates high-resolution profiling of gene expression at the single-cell level, providing insights into cellular heterogeneity and function, potential molecular pathways, cell fate transitions, and the intercellular interactions pertinent to disease progression. This technology generates valuable gene expression data that support both basic and translational research efforts aiming at the identification of therapeutic targets for intervention. The scRNA-seq technique and its multifaceted application in the local immune microenvironment of injury after SCI were discussed, which will contribute to a more comprehensive understanding of the pathophysiological processes in the immune microenvironment of SCI.
Spinal Cord Injuries/genetics* ; Humans ; Single-Cell Analysis/methods* ; Sequence Analysis, RNA/methods* ; Animals ; Gene Expression Profiling/methods* ; Cellular Microenvironment/genetics*

Objective To explore the application value of low-flow rate and-contrast injection scheme for pulmonary artery computed tomography angiography(CTA)in the elderly patients.Methods Sixty elderly patients undergoing pulmonary artery CTA in some hospital from April 2020 to January 2023 were selected and divided into a control group(30 cases)and an experimental group(30 cases)according to the contrast agent injection schemes.A conventional contrast injection scheme was used for the control group,and an optimized contrast injection scheme with low flow rate and low contrast dose was designed for the experimental group.The two gorups were observed and subjectively scored in terms of the degree of pulmonary artery enhancement,the display of pulmonary artery trunks and branches and the sharpness of image vessel edges,and objectively evaluated for the degree of contrast sclerosis artifacts in the superior vena cava and the enhancement CT values of the pulmonary artery trunks and the left and the right pulmonary veins.The extravasation of the contrast agent was recorded for the patients in the 2 groups.SPSS 25.0 software was used for statistical analysis.Results The two groups had no significant differences in score pulmonary artery CTA image quality(P＞0.05);the experimental group had the socre of contrast sclerosis artifacts in the superior vena cava statistically lower than that of the control group(P＜0.05).The two groups had no obvious differences in the CT values of the pulmonary artery trunks and the left and the right pulmonary veins(P＞0.05).There were no patients with the extravasation of the contrast agent found in the experimental group,while there one case with severe extravasation and 4 cases with mild or moderate extravasation in the control group.Conclusion Low-flow rate and-contrast injection scheme for pulmonary artery CTA of the elderly patients contributes to avoiding contrast agent extrava-sation while ensuring image quality,enhancing patient experience and safety.[Chinese Medical Equipment Journal,2024,45(10):66-70]

Objective To investigate a convenient and quantitative solution to activation levels and functional characterization of CAR-T cells by inserting T cell activity-responsive promoter (TARP) nanoluciferase reporter gene system into a lentiviral plasmid containing the gene encoding the chimeric antigen receptor (CAR). Methods The recombinant plasmid was constructed by using whole gene synthesis and molecular cloning techniques. The lentivirus was packaged and was infected with human primary T lymphocytes. Flow cytometry was used to detected the positive rate of lentivirus-infected T cells. The functional characterization of CAR-T cells was identified by luciferase reporter gene system, Western blot, flow cytometry, and small animal live imaging techniques. Results The results of enzyme digestion identification and the plasmid sequencing showed that the recombinant plasmids were constructed, and flow cytometry displayed the normal preparation of CAR-T cells. This system could dynamically respond to the activation of CAR-T cells by luciferase reporter gene system. The functional assay in vitro confirmed that the system could reflect the exhaustion of CAR-T cells, and the small animal live imaging results demonstrated that the system can be used as a tracer of CAR-T cells in mice. Conclusion TARP nanoluciferase reporter gene system provides a more convenient, sensitive and quantitative method for evaluating CAR-T cells activation level, exhaustion phenotype and tracing.
Humans ; Animals ; Mice ; T-Lymphocytes ; Cell Line, Tumor ; Receptors, Chimeric Antigen/genetics* ; Promoter Regions, Genetic ; Immunotherapy, Adoptive/methods*

OBJECTIVE: To investigate the clinical significance of SFRP1 gene and its methylation in childhood acute lymphoblastic leukemia (ALL) . METHODS: Methylation-specific PCR (MSP) was used to detect the methylation status of SFRP1 gene in bone marrow mononuclear cells of 43 children with newly diagnosed ALL before chemotherapy (primary group) and when the bone marrow reached complete remission d 46 after induction of remission chemotherapy (remission group), the expression of SFRP1 mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR), the expression of SFRP1 protein was detected by Western blot, and clinical data of children were collected, the clinical significance of SFRP1 gene methylation in children with ALL was analyze. RESULTS: The positive rate of SFRP1 gene promoter methylation in the primary group (44.19%) was significantly higher than that in the remission group (11.63%) (χ2=11.328, P<0.05). The relative expression levels of SFRP1 mRNA and protein in bone marrow mononuclear cells of children in the primary group were significantly lower than those in the remission group (P<0.05). Promoter methylation of SFRP1 gene was associated with risk level (χ2=15.613, P=0.000) and survival of children (χ2=6.561, P=0.010) in the primary group, children with SFRP1 hypermethylation had significantly increased risk and shortened event-free survival time, but no significant difference in other clinical data. CONCLUSION Hypermethylation of SFRP1 gene promoter may be involved in the development of childhood ALL, and its hypermethylation may be associated with poor prognosis.
Child ; Humans ; Clinical Relevance ; DNA Methylation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Bone Marrow/metabolism* ; RNA, Messenger/metabolism* ; Membrane Proteins/genetics* ; Intercellular Signaling Peptides and Proteins/metabolism*

OBJECTIVE: To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients. METHODS: The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively. RESULTS: A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival. CONCLUSION In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.
Humans ; East Asian People ; Hematologic Neoplasms/complications* ; Lymphoma/complications* ; Multiple Myeloma/complications* ; Neoplasms, Second Primary ; Retrospective Studies ; Survival Analysis

OBJECTIVE: To explore the efficacy of tyrosine kinase inhibitor (TKI) combined with decitabine, homoharringtonine, and interferon regimen as maintenance therapy for blast phase chronic myeloid leukemia (CML-BP). METHODS: The clinical data of CML-BP patients who received the first major hematological response after induction therapy at The Affiliated Cancer Hospital of Zhengzhou University from June 2015 to December 2021 were analyzed retrospectively. The event-free survival, duration of remission, and overall survival of patients in TKI combined with decitabine, homoharringtonine, interferon group(n=18) and TKI combined with conventional chemotherapy group(n=10) were compared by log-rank test. RESULTS: A total of 28 patients were included, with a median age of 46 (24-58) years old. Kaplan-Meier survival analysis showed that patients in TKI combined with decitabine, homoharringtonine, interferon group had longer event-free survival (7.4 vs 4.3 months, P=0.043, HR＝0.44, 95% CI: 0.17-1.14), duration of overall remission (16.1 vs 6.6 months, P=0.005, HR＝0.32, 95% CI: 0.11-0.89), overall survival (34.3 vs 13.5 months, P=0.006, HR＝0.29, 95% CI: 0.10-0.82) compared with patients in TKI combined with conventional chemotherapy group. CONCLUSION The TKI combined with decitabine, homoharringtonine and interferon regimen can significantly prolong the survival of CML-BP patients who obtained the major hematological response compared with TKI combined with conventional chemotherapy regimen.
Humans ; Middle Aged ; Blast Crisis/drug therapy* ; Homoharringtonine/therapeutic use* ; Decitabine/therapeutic use* ; Interferons/therapeutic use* ; Tyrosine Protein Kinase Inhibitors ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; Treatment Outcome

Since the outbreak of corona virus disease 2019 (COVID-19), viral strains have mutated and evolved. Vaccine research is the most direct and effective way to control COVID-19. According to different production mechanisms, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines included inactivated virus vaccine, live attenuated vaccine, mRNA vaccine, DNA vaccine, viral vector vaccine, virus-like particle vaccine and protein subunit vaccine. Among them, viral protein subunit vaccine has a wide application prospect due to its high safety and effectiveness. Viral nucleocapsid protein has high immunogenicity and low variability which could be a new direction for vaccine production. We summarized the current development of vaccine research by reviewing the current progress, vaccine safety and vaccine immune efficiency. It is hoped that the proposed possible development strategies could provide a reference for epidemic prevention work in future.
Humans ; SARS-CoV-2/genetics* ; COVID-19/prevention & control* ; Protein Subunits ; Vaccines, DNA ; Nucleocapsid Proteins