Objective To analyze the correlation between preoperative oxidative stress levels and reperfusion arrhythmia(RA)in post-PCI patients with acute myocardial infarction(AMI).Methods A total of 120 AMI patients undergoing PCI in our hospital from May 2022 to May 2024 were recruited,and according to the occurrence of RA,they were divided into a RA group(46 cases)and a non-RA group(74 cases).The general clinical data were collected in all patients.Multivariate logistic regression was used to screen the influencing factors for the occurrence of RA after PCI in AMI patients.ROC curve analysis was applied to determine the predictive value of the preoperative oxidative stress levels for the occurrence of RA after PCI.Results The RA group had significantly larger proportions of onset-to-PCI time＜6 h,inferior wall infarction,and culprit vessel at thrombolysis in myocardial infarction(TIMI)grade 0 than the non-RA group(P＜0.01).The preoperative level of malondialdehyde(MDA)was obviously higher,while that of superoxide dismutase(SOD)was notably lower in the RA group than the non-RA group(P＜0.01).Multivariate logistic regression analysis showed that culprit vessel at TIMI grade 0(OR=3.484,95％CI:1.043-11.633,P=0.042),onset-to-PCI time＜6 h(OR=4.143,95％CI:1.227-13.989,P=0.022),inferior wall infarction(OR=54.265,95％CJ:2.027-1450.950,P=0.017),and preoperative MDA(OR=2.495,95％CI:1.570-3.966,P=0.001)were risk factors for RA after PCI in AMI patients;preoperative SOD(OR=0.823,95％CI:0.749-0.905,P=0.001)was a protective factor.ROC curve analysis indicated that the AUC value of preoperative MDA and pre-operative SOD in predicting RA after PCI in AMI patients was 0.809 and 0.849,respectively(P＜0.001).Conclusion Culprit vessel at TIMI grade 0,onset-to-PCI time＜6 h,inferior wall infarc-tion,and preoperative MDA and SOD are all influencing factors for RA in post-PCI AMI patients.Moreover,preoperative MDA and SOD levels can effectively predict the risk of RA after PCI in the patients.

Objective:To investigate the the differential expression of EIF5A2 in intrahepatic cholangiocarcinoma cell lines RBE,HCCC9810,and HUCCT1,and its effects on HCCC9810 cell migration and invasion,epithelial mesenchymal transition,and PI3K/AKT signaling pathway.Methods:The differential expression of EIF5A2 in RBE,HCCC9810,and HUCCT1 cell lines was detected using WB method.The HCCC9810 cell line,with the highest expression of EIF5A2,was selected for this experiment.The expression of EIF5A2 in HCCC9810 cell line was silenced by transient transfection of small interfering RNA.The best silencing effect of small interfering RNA was screened by WB.Scratch assay and Tran-swell migration invasion assay were used to detect the effect of silencing EIF5A2 on the migration and invasion ability of HCCC9810 cells.WB was used to detect the effect of silencing EIF5A2 on PI3K/AKT signaling pathway and epithelial mesenchymal transition in HCCC9810 cells.Results:The WB results showed that EIF5A2 had the highest expression in the HCCC9810 cell line,and siRNA1 had the best silencing effect on EIF5A2 in the HCCC9810 cell line.Scratch assay and Transwell migration invasion assay results showed that silencing EIF5A2 in the HCCC9810 cell line resulted in a decrease in cell invasion and metastasis ability(P＜0.05).At the same time,the expression of p-PI3K and p-AKT in the PI3K/AKT signaling pathway was significantly decreased(P＜0.05),while the epithelial cell marker E-cadherin expression increased(P＜0.05)and the stromal cell marker N-cadherin expression decreased(P＜0.05).Conclusion:EIF5A2 may promote epi-thelial mesenchymal transition and enhance the migration and invasion ability of intrahepatic cholangiocarcinoma cells through the PI3K/AKT signaling pathway.

Objective:To investigate the the differential expression of EIF5A2 in intrahepatic cholangiocarcinoma cell lines RBE,HCCC9810,and HUCCT1,and its effects on HCCC9810 cell migration and invasion,epithelial mesenchymal transition,and PI3K/AKT signaling pathway.Methods:The differential expression of EIF5A2 in RBE,HCCC9810,and HUCCT1 cell lines was detected using WB method.The HCCC9810 cell line,with the highest expression of EIF5A2,was selected for this experiment.The expression of EIF5A2 in HCCC9810 cell line was silenced by transient transfection of small interfering RNA.The best silencing effect of small interfering RNA was screened by WB.Scratch assay and Tran-swell migration invasion assay were used to detect the effect of silencing EIF5A2 on the migration and invasion ability of HCCC9810 cells.WB was used to detect the effect of silencing EIF5A2 on PI3K/AKT signaling pathway and epithelial mesenchymal transition in HCCC9810 cells.Results:The WB results showed that EIF5A2 had the highest expression in the HCCC9810 cell line,and siRNA1 had the best silencing effect on EIF5A2 in the HCCC9810 cell line.Scratch assay and Transwell migration invasion assay results showed that silencing EIF5A2 in the HCCC9810 cell line resulted in a decrease in cell invasion and metastasis ability(P＜0.05).At the same time,the expression of p-PI3K and p-AKT in the PI3K/AKT signaling pathway was significantly decreased(P＜0.05),while the epithelial cell marker E-cadherin expression increased(P＜0.05)and the stromal cell marker N-cadherin expression decreased(P＜0.05).Conclusion:EIF5A2 may promote epi-thelial mesenchymal transition and enhance the migration and invasion ability of intrahepatic cholangiocarcinoma cells through the PI3K/AKT signaling pathway.

Objective To analyze the correlation between preoperative oxidative stress levels and reperfusion arrhythmia(RA)in post-PCI patients with acute myocardial infarction(AMI).Methods A total of 120 AMI patients undergoing PCI in our hospital from May 2022 to May 2024 were recruited,and according to the occurrence of RA,they were divided into a RA group(46 cases)and a non-RA group(74 cases).The general clinical data were collected in all patients.Multivariate logistic regression was used to screen the influencing factors for the occurrence of RA after PCI in AMI patients.ROC curve analysis was applied to determine the predictive value of the preoperative oxidative stress levels for the occurrence of RA after PCI.Results The RA group had significantly larger proportions of onset-to-PCI time＜6 h,inferior wall infarction,and culprit vessel at thrombolysis in myocardial infarction(TIMI)grade 0 than the non-RA group(P＜0.01).The preoperative level of malondialdehyde(MDA)was obviously higher,while that of superoxide dismutase(SOD)was notably lower in the RA group than the non-RA group(P＜0.01).Multivariate logistic regression analysis showed that culprit vessel at TIMI grade 0(OR=3.484,95％CI:1.043-11.633,P=0.042),onset-to-PCI time＜6 h(OR=4.143,95％CI:1.227-13.989,P=0.022),inferior wall infarction(OR=54.265,95％CJ:2.027-1450.950,P=0.017),and preoperative MDA(OR=2.495,95％CI:1.570-3.966,P=0.001)were risk factors for RA after PCI in AMI patients;preoperative SOD(OR=0.823,95％CI:0.749-0.905,P=0.001)was a protective factor.ROC curve analysis indicated that the AUC value of preoperative MDA and pre-operative SOD in predicting RA after PCI in AMI patients was 0.809 and 0.849,respectively(P＜0.001).Conclusion Culprit vessel at TIMI grade 0,onset-to-PCI time＜6 h,inferior wall infarc-tion,and preoperative MDA and SOD are all influencing factors for RA in post-PCI AMI patients.Moreover,preoperative MDA and SOD levels can effectively predict the risk of RA after PCI in the patients.

With the rapid development of nanotechnology, the research and development of nanomedicines have become one of the development directions of drug innovation. Nanomedicines have special physical and chemical properties, such as nanoscale effects and nanostructure effects, so they have special biological properties, which may change the pharmacokinetic profiles such as absorption and tissue distribution of drug molecules, and thus affect their safety and effectiveness. There are many special concerns on the non-clinical safety evaluation of nanomedicines at the basis of ordinary drug because of the particularity of nanomedicines. On August 25, 2021, China issued Guidance on Non-clinical Safety Evaluation for Nanomedicines(interim). This article interprets comprehensively the guidance, focuses on the key points of non-clinical safety evaluation for nanomedicines, and expounds combined with some cases, aiming to provide reference for drug researchers.

OBJECTIVE: To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies. METHODS: The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated. RESULTS: A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027). CONCLUSION The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Multiple Myeloma/complications* ; Leukemia, Plasma Cell ; Retrospective Studies ; Esophageal Neoplasms/complications* ; Esophageal Squamous Cell Carcinoma/complications* ; Prognosis ; Neoplasms, Second Primary

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m² and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m² or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

OBJECTIVE: To examine the expression of chemokine receptor CCR10 on monocytes/macrophages in the joints of patients with rheumatoid arthritis (RA), and to investigate the role of chemokine CCL28 and its receptor CCR10 in the migration of RA monocytes and its mechanism. METHODS: The expression of CCR10 in synovial tissues from 8 RA patients, 4 osteoarthritis (OA) patients, and 4 normal controls was analyzed by immunohistochemistry, and cell staining was scored on a 0-5 scales. Flow cytometry was used to measure the percentage of CCR10 positive cells in CD14⁺ monocytes from peripheral blood of 26 RA patients and 20 healthy controls, as well as from synovial fluid of 15 RA patients. The chemotactic migration of monocytes from RA patients and healthy controls in response to CCL28 was evaluated using an in vitro Transwell system. Western blotting was conducted to assess phosphorylation of the extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) pathways in RA monocytes upon CCL28 treatment. RESULTS: CCR10 was predominantly expressed in RA synovial lining cells and sublining macrophages, endothelial cells, and lymphocytes. CCR10 expression was significantly increased on lining cells and sublining macrophages in RA synovial tissue compared with OA and normal synovial tissue (both P < 0.01). The patients with RA had markedly elevated expression of CCR10 on peripheral blood CD14⁺ monocytes compared with the healthy controls [(15.6±3.0)% vs. (7.7±3.8)%, P < 0.01]. CCR10 expression on synovial fluid monocytes from the RA patients was (32.0±15.0)%, which was significantly higher than that on RA peripheral blood monocytes (P < 0.01). In vitro, CCL28 caused significant migration of CD14⁺ monocytes from peripheral blood of the RA patients and the healthy controls at concentrations ranging from 10-100 μg/L (all P < 0.01). The presence of neutralizing antibody to CCR10 greatly suppressed CCL28-driven chemotaxis of RA monocytes (P < 0.01). Stimulation of RA monocytes with CCL28 induced a remarkable increase in phosphorylation of ERK and Akt (both P < 0.05). ERK inhibitor (U0126) and phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) strongly reduced the migration of RA monocytes in response to CCL28 (both P < 0.01). CONCLUSION RA patients had increased CCR10 expression on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages. CCL28 ligation to CCR10 promoted RA monocyte migration through activation of the ERK and PI3K/Akt signaling pathways. The CCL28-CCR10 pathway could participate in monocyte recruitment into RA joints, thereby contributing to synovial inflammation and bone destruction.
Humans ; Monocytes/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Endothelial Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Arthritis, Rheumatoid ; Synovial Membrane ; Chemokines, CC/metabolism* ; Synovial Fluid ; Osteoarthritis ; Receptors, CCR10/metabolism*

OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; Multiple Myeloma/genetics* ; Mutation

ObjectiveTo assess the predictive performance of four creatinine-based equations for estimated glomerular filtration rate （eGFR）： 2012 chronic kidney disease epidemiology collaboration （CKD-EPIcr） equation ， 2021CKD-EPIcr equation， Xiangya equation and European kidney function consortium （EKFC） equation. MethodsA total of 198 patients with chronic kidney disease from the Third Affiliated Hospital of Sun Yat-sen University and the Kiang Wu Hospital in Macau were enrolled. We compared the GFR measured （mGFR） by iohexol plasma clearance and the eGFR calculated by four equations. The agreement between mGFR and eGFR was analyzed by Bland-Altman plots， concordance correlation coefficient （CCC）， coverage probability （CP） and total deviation index （TDI）. The performance of eGFR equations， including their bias， precision， root square mean error （RSME）， and percentage of estimates within 30% deviation of measured GFR （P₃₀）， were evaluated. Bootstrap method （2 000 samples） was used to calculate bias， interquartile range （IQR）， RSME， and 95% confidence intervals （CI） for P_30. After selecting the optimal eGFR equation as the reference， we statisticlly tested other equations by ① Wilcoxon signed-rank test for bias； ② McNemar-Bowker test for P₃₀； ③ comparing RMSE and IQR with independent samples t test after 2 000 bootstrap samples were obtained. ResultsThe median mGFR and four eGFR equations （EKFC， 2012CKD-EPIcr， 2021CKD-EPIcr and Xiangya equation） in the overall population were 56.2 mL·min^-1·（1.73m²）^-1， 67.1 mL·min^-1·（1.73m²）^-1， 73.0 mL·min^-1·（1.73m²）^-1， 66.9 mL·min^-1·（1.73m²）^-1 and 63.8 mL·min^-1·（1.73m²）^-1， respectively. The Bland-Altman plots showed that EKFC equation had the lowest mean difference and the narrowest 95% limit of agreement. The EKFC equation had the optimal performance on CCC， TDI and CP with values of 0.90， 24.41 and 0.50， respectively. Overall， the bias， accuracy， P₃₀ and RSME from the EKFC equation was -0.99， 14.64， 0.80， and 14.68， respectively， with 95% CI ranging from -2.53 to 0.94， 11.82 to 17.35， 0.73 to 0.85， and 12.69 to 17.35， respectively， which were superior to those values from other three eGFR equations. The differences were statistically significant （all P < 0.05）. The results in the mGFR subgroups were basically consistent with the overall trend. ConclusionsOf the four eGFR equations validated in this study， the EKFC equation comprehensively surpasses 2012CKD-EPIcr equation， 2021CKD-EPIcr equation， and Xiangya equation. With P₃₀>75%， the EKFC equation can meet clinical diagnostic needs. Therefore， the EKFC equation is recommended for estimating GFR in a Chinese population， but more participants need be included to further support this conclusion.