Aim To develop a HPLC method for the determination of the concentration of 1,8-TMP rhein in rat plasma and study the pharmacokinetics of 1,8-TMP rhein in rat plasma after single dose i. v. administration of 1,8-TMP rhein (2, 4, 8 mg·kg - 1 ). Methods Emodin was used as an internal standard. Plasma sam-ples were extracted with methanol and analyzed by HPLC. The mobile phase was methanol - 0. 1% for-mic acid water (78 ∶ 22, V/ V), with a flow rate of 1. 0 mL·min - 1 and UV 275 nm as the detection wave-length. The plasma concentration of 1,8-TMP rhein in rats was determined by HPLC after single-dose intrave-nous injection in rats with 2,4 and 8 mg·kg - 1 of 1,8-TMP rhein, and the pharmacokinetic parameters were caclulated by DAS 2. 1. Results The result of cali-bration curve was linear over the range of 0. 05 ~ 10. 00 mg·L - 1 (r = 0. 996 2). The lower limit of quantifica-tion was 0. 05 mg · L - 1 . The intra-day and inter-day precision (RSD% ) were both lower than 6% , and the extraction recoveries were higher than 88% , respec-tively. The validated method was successfully applied to a pharmacokinetic study after i. v. administration of 1,8-TMP rhein in rats with a dose of 2,4 and 8 mg· kg - 1 . The T1 / 2 was (68. 35 ± 1. 36), (69. 32 ± 2. 1) and (69. 32 ± 2. 03) min, respectively. The AUC0 - t was ( 101. 03 ± 24. 90 ), ( 144. 79 ± 3. 29 ) and (231. 92 ± 19. 30 ) min · mg · L - 1 , respectively. Conclusion A simple and specific HPLC method for the analysis of 1,8-TMP rhein is successfully developed and applied to a pharmacokinetic study in rat plasma.

Objective To analyze the outcomes of catheter ablation for persistent atrial fibrillation(AF)and the independent risk factors for its recurrence in the elderly.Methods A total of 194 patients with persistent AF who underwent catheter ablation at our department from January 2019 to December 2021 were enrolled in this study.They were divided into elderly group(≥60 years old,99 cases)and non-elderly group(＜60 years old,95 cases).Their surgical characteris-tics,postoperative complications and recurrence were compared between the two groups,and the independent risk factors for postoperative recurrence were analyzed in the elderly group.Results Advanced age,higher B-type natriuretic peptide,larger proportions of hypertension and coronary heart disease,and increased CHA2DS2-VASc and HAS-BLED scores,while lower male ratio and estimated glomerular filtration rate were observed in the elderly group than the non-elderly group(P＜0.05,P＜0.01).The elderly group had a higher proportion of left atrial fibrosis than the non-elderly group(30.3％vs 8.4％,P=0.001).Postoperative complications in the elderly group in-cluded 1 case of pericardial effusion and 2 cases of hematoma at the puncture site,and all of these were improved after treatment.There were no significant differences in the 1-year success rate(71.7％vs 69.5％,P=0.763)or recurrence rate during blanking period(21.2％vs 21.1％,P=0.981)between the elderly and non-elderly groups.AF duration(HR=1.020,95％CI:1.007-1.032,P=0.002)and recurrence during blanking period(HR=6.781,95％CI:3.078-14.935,P=0.001)were independent risk factors for postoperative recurrence in the elderly group.Conclu-sion Catheter ablation is safe and effective in the treatment of persistent AF in the elderly.The elderly patients with long duration of AF and recurrences during blanking period are more likely to experience recurrences within 1 year after ablation.

Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX₃CR1⁺CCR2^-Ly6C^-MHCII^- (MP1), CX₃CR1^lowCCR2^lowLy6C^-MHCII^- (MP2), CX₃CR1^-CCR2⁺Ly6C⁺MHCII^- (MP3), and CX₃CR1⁺CCR2^-Ly6C^-MHCII⁺ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.

Antibodies, Antiphospholipid ; Antiphospholipid Syndrome ; Female ; Humans ; Killer Cells, Natural ; Pregnancy ; Pregnancy Complications

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.
Humans ; Glycosylation ; Pancreatic Neoplasms/pathology* ; Adenocarcinoma ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Glycoproteins ; Mass Spectrometry ; Biomarkers/metabolism* ; Polysaccharides