Cardiovascular toxicities following the use of tyrosine kinase inhibitors in hepatocellular cancer patients: a retrospective, pharmacovigilance study.

BACKGROUND: Cardiac adverse events (AEs) are common in tyrosine kinase inhibitors(TKIs). This study explored the cardiac AEs of TKIs through the Food and Drug Administration's Adverse Event Reporting System (FAERS). METHODS: Disproportionality analysis and Bayesian analysis were utilized for data mining of the suspected cardiac AEs of TKIs, based on FAERS data from January 2004 to December 2021. RESULTS: A total of 4708 cardiac AEs reports of sorafenib, regorafenib, lenvatinib, and cabozantinib were identified. Hypertension accounts for the most reported cardiac AE. Lenvatinib appears to induce cardiac failure with the highest signals strength [ROR = 7.7 (3.46,17.17)]. Acute myocardial infarction was detected in lenvatinib [ROR = 7.91 (5.64,11.09)] and sorafenib [ROR = 2.22 (1.74, 2.84)]. Acute coronary syndrome was detected in lenvatinib [ROR = 11.57 (6.84, 19.58)] and sorafenib [ROR = 2.81 (1.87,4.24)]. Atrial fibrillation was detected in sorafenib [ROR = 1.82 (1.55,2.14)] and regorafenib [ROR = 1.36 (1.03,1.81)]. Meanwhile, aortic dissections were detected in sorafenib [ROR = 5.08 (3.31,7.8)] and regorafenib [ROR = 3.39 (1.52,7.56)]. Most patients developed hypertension and cardiac failure within 30 days of initiating TKI treatments. Patients taking lenvatinib had an increased incidence of developing acute coronary syndrome after 180 days of treatment. CONCLUSION: Analysis of FAERS data provides a precise profile on the characteristics of cardiac AEs associated with different TKI regimens. Distinct monitoring and appropriate management are needed in the care of TKI recipients.

[Molecular Genetic Characteristics of Acute Myeloid Leukemia Patients with CBFß-MYH11 Positive].

OBJECTIVE: To explore mutational characteristics of acute myeloid leukemia (AML) patients with CBFß-MYH11+ and analyze the correlation between the mutations and partial clinical characteristics. METHODS: A total of 62 AML patients with CBFß-MYH11+ were included and 51 candidate genes were screened for their mutations using targeted next-generation sequencing (NGS). The exon 12 of NPM1 , FLT3-ITD , and TAD, bZIP domains of CEBPA were detected by genomic DNA-PCR combined with sanger sequencing. RESULTS: Compared with RUNX1-RUNX1T1 + group, the patients with CBFß-MYH11+ showed higher age, peripheral WBC level, initial induced complete remission (CR) rate, more commonly carried chromosomal abnormalities such as +22, and lower deletion ratio of sex chromosome (-X or -Y) (P<0.05). In AML patients with CBFß-MYH11+, the most common mutation was NRAS , followed by KIT, KRAS , and FLT3-TKD . Compared with RUNX1-RUNX1T1+ group, NRAS and FLT3-TKD were more frequently mutated in patients with CBFß-MYH11+ (51.6% vs 18.7%, 17.7% vs 3.8%) (P<0.05). CONCLUSION: The genomic landscape and clinical characteristics of AML patients with CBFß-MYH11+ are different from patients with RUNX1-RUNX1T1 +.

[Inhibitory effect of chloroquine on airway hyperresponsiveness in asthmatic mice].

OBJECTIVE: To investigate the effect of chloroquine on airway hyperresponsiveness in asthmatic mice and explore the possible mechanism. METHODS: Balb/c mouse models of asthma established using OVA received intraperitoneal injections of chloroquine, dexamethasone, or both prior to OVA challenge. Within 24 h after the final challenge, airway hyper- responsiveness (AHR) of the mice was assessed, and the total cell count and the counts of different cell populations in the bronchoalveolar lavage fluid (BALF) were determined under light microscopy. The severity of lung inflammation was evaluated using HE staining, and the concentrations of IL-6 and PGF2α in the BALF were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Chloroquine pretreatment significantly decreased AHR (P<0.001) in the asthmatic mice and reduced the total cell count (P<0.01), eosinophils (P<0.001), neutrophils (P<0.01), and PGF2α levels in the BALF. Chloroquine combined with low-dose dexamethasone significantly lessened inflammations around the bronchioles (P<0.05) and blood vessels (P<0.01) in the lung tissue, and obviously lowered IL-6 (P<0.05) and PGF2α (P<0.001) in the BALF in the asthmatic mice. CONCLUSION: Chloroquine can inhibit AHR in asthmatic mice and produce better anti-inflammatory effect when combined with dexamethasone for treatment of neutrophilic asthma.

[Effects of puerarin on proliferation and differentiation of umbilical cord mesenchymal stem cells into osteoblasts in vitro].

This study is to investigate the effects of puerarin on the proliferation and differentiation of umbilical cord mesenchymal stem cells (MSCs) into osteoblasts. Umbilical cord MSCs were cultured by tissue adherence and the third passage of cells was used in the experiment. The effect of puerarin on proliferation of umbilical cord MSCs was measured with MTT. The effects of puerarin on umbilical cord MSCs were evaluated by ALP immunohistochemisty and von kossa staining. The OD value decreased with the increase of puerarin concentration. On 7th day, ALP expression of puerarin group was higher than that of control group. On 14th day, ALP staining showed that the positive rate of puerarin group was higher than that of control group. Von kossa staining showed the quantity of calcium nodules was higher in puerarin group than that of control group. Puerarin can promote the umbilical cord MSCs to differentiate into osteoblasts and has an effect on the proliferation of umbilical cord MSCs.

catena-Poly[[(2,2'-bipyridine)-nickel(II)]-µ-2,4'-oxydibenzoato].

In the title compound, [Ni(C(14)H(8)O(5))(C(10)H(8)N(2))](n), the Ni(II) atom is six-coordinated in a slightly distorted octa-hedral geometry by four O atoms from two chelating carboxyl-ate groups of symmetry-related 2,4'-oxydibenzoate anions and by two N atoms from a 2,2'-bipyridine ligand. The Ni(II) atoms are bridged by the 2,4'-oxydibenzoate anions, resulting in the formation of helical chains parallel to [010] with a repeating unit of 15.039 (2) Å.