Vinorelbine administration impedes the timely progression of meiotic maturation and induces aneuploidy in mouse oocytes.

Vinorelbine is a commonly used drug to treat various malignancies, such as breast cancer, non-small cell lung cancer, and metastatic pleural mesothelioma. Its side effects include severe neutropenia, local phlebitis, gastrointestinal reactions, and neurotoxicity. In view of the scarcity of research on vinorelbine's reproductive toxicity, this study evaluated the impact of vinorelbine ditartrate, a commonly used form of vinorelbine, on oocyte maturation in vitro. Our investigation revealed that vinorelbine ditartrate had no effect on oocyte meiotic resumption. However, it did reduce the rate of first polar body extrusion, suggesting that it could significantly impede the meiotic maturation of oocytes. Vinorelbine ditartrate exposure was found to disturb the regular spindle assembly and chromosome alignment, leading to the continuous activation of the spindle assembly checkpoint (SAC) and a delayed activation of the anaphase-promoting complex/cyclosome (APC/C), ultimately causing aneuploidy in oocytes. Consequently, the administration of vinorelbine is likely to result in oocyte aneuploidy, which can be helpful in providing a drug reference and fertility guidance in a clinical context.

[Pollution Characteristics of Macrolide Antibiotics During Drinking Water Treatment and Their Chlorination Reaction Mechanism].

Antibiotic contamination in drinking water has attracted widespread attention. The pollution condition of six macrolide antibiotics (erythromycin-H2[KG-*2/5]O, clarithromycin, oleandomycin, roxithromycin, leucomycin, and tylosin) in two drinking water treatment plants was monitored, and the reaction mechanism of tylosin, a typical macrolide antibiotic, during chlorination disinfection treatment was investigated. The results showed that the six macrolide antibiotics can be widely detected in the drinking water treatment processes; however, their concentrations were generally very low. The concentrations of macrolide antibiotics in the influents and effluents ranged from 0.18 ng·L-1 to 3.97 ng·L-1 and 0.02 ng·L-1 to 1.91 ng·L-1, respectively. The removal rates of the six macrolides in the drinking water treatment were different, ranging from 18% (oleandomycin) to 100% (erythromycin- H2[KG-*2/5]O). The degradation of the six macrolides during chlorination was slow and greatly affected by water quality parameters. The chlorination degradation of tylosin followed the second-order reaction kinetic mode, with the kinetic rate constant of 0.77 L·(mol·s)-1 at pH 7.0. Nine chlorination degradation products of tylosin were detected, and the reaction pathways primarily included tertiary amine hydroxylation, aromatic oxidation, and epoxy addition.

Risk factors for mortality within 6 mo in patients with diabetes undergoing urgent-start peritoneal dialysis: A multicenter retrospective cohort study.

BACKGROUND: The risk of early mortality of patients who start dialysis urgently is high; however, in patients with diabetes undergoing urgent-start peritoneal dialysis (USPD), the risk of, and risk factors for, early mortality are unknown. AIM: To identify risk factors for mortality during high-risk periods in patients with diabetes undergoing USPD. METHODS: This retrospective cohort study enrolled 568 patients with diabetes, aged ≥ 18 years, who underwent USPD at one of five Chinese centers between 2013 and 2019. We divided the follow-up period into two survival phases: The first 6 mo of USPD therapy and the months thereafter. We compared demographic and baseline clinical data of living and deceased patients during each period. Kaplan-Meier survival curves were generated for all-cause mortality according to the New York Heart Association (NYHA) classification. A multivariate Cox proportional hazard regression model was used to identify risk factors for mortality within the first 6 mo and after 6 mo of USPD. RESULTS: Forty-one patients died within the first 6 mo, accounting for the highest proportion of mortalities (26.62%) during the entire follow-up period. Cardiovascular disease was the leading cause of mortality within 6 mo (26.83%) and after 6 mo (31.86%). The risk of mortality not only within the first 6 mo but also after the first 6 mo was higher for patients with obvious baseline heart failure symptoms than for those with mild or no heart failure symptoms. Independent risk factors for mortality within the first 6 mo were advanced age [hazard ratio (HR: 1.908; 95%CI: 1.400-2.600; P < 0.001), lower baseline serum creatinine level (HR: 0.727; 95%CI: 0.614-0.860; P < 0.001), higher baseline serum phosphorus level (HR: 3.162; 95%CI: 1.848-5.409; P < 0.001), and baseline NYHA class III-IV (HR: 2.148; 95%CI: 1.063-4.340; P = 0.033). Independent risk factors for mortality after 6 mo were advanced age (HR: 1.246; 95%CI: 1.033-1.504; P = 0.022) and baseline NYHA class III-IV (HR: 2.015; 95%CI: 1.298-3.130; P = 0.002). CONCLUSION: To reduce the risk of mortality within the first 6 mo of USPD in patients with diabetes, controlling the serum phosphorus level and improving cardiac function are recommended.

Association Between Self-Perceived Stigma and Quality of Life Among Urban Chinese Older Adults: The Moderating Role of Attitude Toward Own Aging and Traditionality.

BACKGROUND: Ageism is a global challenge, which leads to a range of adverse outcomes for elderly people worldwide, which maybe more severe among urban older adults in a competitive society. However, how self-perceived ageism influences the quality of life in a sample of urban older adults remains inconclusive. OBJECTIVES: The current study aims to assess the status of self-perceived stigma among urban Chinese older adults, identify its relationship with quality of life, and further explore whether both attitude toward own aging and traditionality moderate this relationship. MATERIALS AND METHODS: Primary data were collected through cross-sectional surveys among urban older adults in three provinces of China from October 2019 to December 2020. A total of 764 urban older adults were valid participants (effective response rate = 81.28%) and completed questionnaires via anonymous face-to-face interviews. Socio-demographic factors, self-perceived stigma, attitude toward own aging, traditionality, and quality of life were assessed using questionnaires that included the Self-perceived Stigma, Attitude Toward Own Aging, Traditionality, and SF-8 Scales. RESULTS: For urban Chinese older adults, the average score of self-perceived stigma was 2.041 ± 0.726. Self-perceived stigma (ß = -0.391, p < 0.05) and attitude toward own aging (ß = -0.211, p < 0.05) both influenced quality of life. Additionally, attitude toward own aging (ß = -0.530, p < 0.05) and traditionality (ß = -0.525, p < 0.05) moderated the association between self-perceived stigma and quality of life. Simple slope analysis revealed that when the level of negative attitude toward own aging and traditionality was higher, the strength of the influence of self-perceived stigma on quality of life was stronger. CONCLUSION: Urban Chinese older adults were aware of the self-perceived stigma, which contributes to decreased quality of life. Attitude toward own aging and traditionality could moderate the association between self-perceived stigma and quality of life. When negative attitudes toward own aging and traditionality are higher, self-perceived stigma has a greater effect on the quality of life. More interventions related to relieving self-perceived stigma, traditionality, and negative attitude toward own aging should be considered to build a new modern society that emphasizes health, friendliness, well-being, and dignity for all ages.

[Corrigendum] TLR4 mediates inflammation and hepatic fibrosis induced by chronic intermittent hypoxia in rats.

Following the publication of the above article, the authors have realized that the first grant number featured in the Funding section of the Declarations on p. 658 appeared incorrectly: The text here should have been written as 'grant nos. 2018J01199, 2018Y0032 and 2016J01441' instead of 'grant nos. 2018J0105, 2018Y0032 and 2016J01441'. The authors regret their oversight in providing this incorrect information in the Funding section of their paper. They thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership of the Journal and to the funding body in question for any inconvenience caused. [the original article was published in Molecular Medicine Reports 22: 651­660, 2020; DOI: 10.3892/mmr.2020.11134].

TLR4 mediates inflammation and hepatic fibrosis induced by chronic intermittent hypoxia in rats.

Obstructive sleep apnea syndrome (OSAS) is a common and complex disorder that is associated with liver injury. Moreover, previous studies have revealed that chronic intermittent hypoxia (CIH) is associated with the development of non­alcoholic fatty liver disease and hepatic fibrosis. However, the underlying molecular mechanisms remain largely unknown. The present study aimed to investigate whether chronic intermittent hypoxia induced hepatic fibrosis, in addition to determining its underlying mechanisms, in CIH model rats using immunohistochemistry, western blotting and reverse transcription­quantitative PCR. The present results suggested that CIH caused hepatic fibrosis and increased the expression levels of interleukin (IL)­1ß, IL­8, monocyte chemotactic­1, tumor necrosis factor­α, intercellular adhesion molecule­1 and vascular cell adhesion molecule­1 in the liver; these conditions could be reversed by Toll­like receptor 4 (TLR4) short hairpin RNA lentivirus treatment. Moreover, immunohistochemistry and western blotting results indicated that TLR4 and NF­κB expression levels were significantly increased in the CIH and CIH­TLR4 empty vector lentivirus group. However, protein expression levels of TLR4, NF­κB, inhibitor of NF­κB and phosphorylated­mitogen­activated protein kinase (MAPK)­1 in the hypoxia/reoxygenation group were significantly higher compared with the control group (P<0.05), and these results were reversed by the MAPK inhibitor U0126 in vitro. Collectively, the present preliminary results suggested that inflammation and the TLR4/NF­κB/MAPK signaling pathway may be involved in CIH­induced liver fibrosis.

BMP8A promotes survival and drug resistance via Nrf2/TRIM24 signaling pathway in clear cell renal cell carcinoma.

There is increasing evidence that bone morphogenetic proteins (BMP) are involved in the proliferation and drug tolerance of kidney cancer. However, the molecular mechanism of BMP8A in renal cell proliferation and drug tolerance is not clear. Here we showed that BMP8A was highly expressed in renal cell carcinoma, which suggests a poor prognosis of ccRCC. Promotion of cell proliferation and inhibition of apoptosis were detected by CCK-8 assay, Trypan Blue staining, flow cytometry and bioluminescence. BMP8A promoted resistance of As2 O3 by regulating Nrf2 and Wnt pathways in vitro and in vivo. Mechanistically, BMP8A enhanced phosphorylation of Nrf2, which, in turn, inhibited Keap1-mediated Nrf2 ubiquitination and, ultimately, promoted nuclear translocation and transcriptional activity of Nrf2. Nrf2 regulates the transcription of TRIM24 detected by ChIP-qPCR. BMP8A was highly expressed in ccRCC, which suggests a poor prognosis. BMP8A was expected to be an independent prognostic molecule for ccRCC. On the one hand, activated Nrf2 regulated reactive oxygen balance, and on the other hand, by regulating the transcription level of TRIM24, it was involved in the regulation of the Wnt pathway to promote the proliferation, invasion and metastasis of ccRCC and the resistance of As2 O3 . Taken together, our findings describe a regulatory axis where BMP8A promotes Nrf2 phosphorylation and activates TRIM24 to promote survival and drug resistance in ccRCC.