Background Krüppel‐like factors (KLFs) are zinc finger proteins which participate in transcriptional gene regulation. Although increasing evidence indicate that KLFs are involved in carcinogenesis and progression, its clinical significance and biological function in breast cancer are still limited. Methods We investigated all the expression of KLFs (KLF1-18) at transcriptional levels by using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). The mRNA and protein expression levels of KLFs were also determined by using RT-qPCR and immunohistochemistry, respectively. CBioPortal, GeneMANIA and STRING were used to comprehensive analysis of the molecular characteristics of KLFs. The clinical value of prognostic prediction based on the expression of KLFs was determined by using the KM plotter. The relevant molecular pathways of KLFs were further analyzed by using Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Finally, we investigated the effect of KLF2 and KLF15 on biological behavior of breast cancer cells in vitro. Results The expression of KLF2/4/6/8/9/11/15 was significantly down-regulated in breast cancer. The patients with high KLF2, KLF4 or KLF15 expression had a better outcome, while patients with high KLF8 or KLF11 had a poor prognosis. Furthermore, our results showed that KLF2 or KLF15 can be used as a prognostic factor independent on the other KLFs in patients with breast cancer. Overexpression of KLF2 or KLF15 inhibited cell proliferation and migration, and blocked cell cycle at G0/G1 phase, resulting in cell apoptosis. Conclusions KLF2 and KLF15 function as tumor suppressors in breast cancer and are potential biomarkers for prognostic prediction in patients with breast cancer.

Hydrogen sulfide (H2S), generally known as a new gas signal molecule after nitric oxide and carbon monoxide, has been found as an important endogenous gasotransmitter in the last few decades, and it plays a significant role in the cardiovascular system both pathologically and physiologically. In recent years, there is growing evidence that H2S provides myocardial protection against myocardial ischemia–reperfusion injury (MIRI), which resulted in an ongoing focus on the possible mechanisms of action accounting for the H2S cardioprotective effect. At present, lots of mechanisms of action have been verified through in vitro and in vivo models of I/R injury, such as S-sulfhydrated modification, antiapoptosis, effects on microRNA, bidirectional effect on autophagy, antioxidant stress, or interaction with NO and CO. With advances in understanding of the molecular pathogenesis of MIRI and pharmacology studies, the design, the development, and the pharmacological characterization of H2S donor drugs have made great important progress. This review summarizes the latest research progress on the role of H2S in MIRI, systematically explains the molecular mechanism of H2S affecting MIRI, and provides a new idea for the formulation of a myocardial protection strategy in the future.

Tamoxifen is commonly used for the treatment of patients with estrogen receptor-positive (ER+) breast cancer, but the acquired resistance to tamoxifen presents a critical challenge of breast cancer therapeutics. Recently, long noncoding RNA MIR497HG and its embedded miR-497 and miR-195 are proved to play significant roles in many types of human cancers, but their roles in tamoxifen-resistant breast cancer remain unknown. The results indicate that MIR497HG deficiency induces breast cancer progression and tamoxifen resistance by inducing downregulation of miR-497/195. miR-497/195 coordinately represses five positive PI3K-AKT regulators (MAP2K1, AKT3, BCL2, RAF1, and CCND1), resulting in inhibition of PI3K-AKT signaling, and PI3K-AKT inhibition in tamoxifen-resistant cells restored tamoxifen responsiveness. Furthermore, ER 𝜶 binds the MIR497HG promoter to activate its transcription in an estrogen-dependent manner. ZEB1 interacts with HDAC1/2 and DNMT3B at the MIR497HG promoter, resulting in promoter hypermethylation and histone deacetylation. The findings reveal that ZEB1-induced MIR497HG depletion contributes to breast cancer progression and tamoxifen resistance through PI3K-AKT signaling. MIR497HG can be used as a biomarker for predicting tamoxifen sensitivity in patients with ER+ breast cancer.

The aim of this study was to explore the clinical characteristics of different sleep perception types of obstructive sleep apnea-hypopnea syndrome (OSAHS) patients and to analyze the correlation between sleep perception and polysomnography (PSG) indicators in OSAHS patients. Methods: We retrospectively analyzed 355 patients diagnosed with OSAHS by PSG at the Sleep Medicine Center of Shengjing Hospital of China Medical University. Patients saw a doctor due to snoring and daytime sleepiness from March 2017 to March 2018. We excluded the patients who are <18 years old, had a history of OSAHS treatment, had other sleep and psychiatric disorders, and could not provide complete data. According to the patients' explanation, medical history, PSG indicators, and morning questionnaire after PSG, the patients were divided into normal sleep perception (NSP), positive sleep perception abnormality (PSPA), and negative sleep perception abnormality (NSPA). We analyze the demographic characteristics and PSG of the three groups with ANOVA and non-parametric tests. In addition, we conducted correlation analysis between sleep perception and PSG indicators. Results: Of OSAHS patient, 55.5% had sleep perception abnormalities, of which 35.5% were positive-perception abnormalities and 20% were negative-perception abnormalities. From the analysis of PSG indicators, the sleep perception abnormality was related to the frequency of spontaneous arousal of the patient (P = 0.003) and was not related to the slight arousal caused by respiratory events, oxygen desaturations, and limb movement events. OSAHS patients with PSPA had a higher oxygen desaturation index (P = 0.046) but no significant difference in post hoc test. PSPA group had significantly lower rapid eye movement (REM) latency and sleep efficiency and more wake after sleep onset (WASO) than had the other sleep perception groups. Multivariate linear regression analyses after adjusting for age and sex revealed that sleep perception was related to lowest oxygen saturation (LSaO 2), TS90%, sleep efficiency, and WASO. Liu et al. Sleep Perception of OSAHS Patients Conclusion: Sleep perception abnormality is common in OSAHS patients. OSAHS patients with different sleep perception types have different PSG profiles. The OSAHS patients with PSPA have more severe hypoxia levels at night that require timely personalized treatment.

Background Breast cancer (BC) remains the leading cause of cancer‐related deaths worldwide. High recurrence risk Luminal BC receives adjuvant chemotherapy in addition to standard hormone therapy. Considering the heterogeneity of Luminal B BC, a more accurate classification model is urgently needed. Methods In this study, we retrospectively reviewed the data of 1603 patients who were diagnosed with HER2‐negative breast invasive ductal carcinoma. According to the expression level of PR and Ki‐67 index, the Luminal B (HER2‐negative) BCs were divided into three groups: ER+PR−Ki67 low (ER‐positive, PR‐negative, and Ki‐67 index <20%), ER+PR+Ki67 high (ER‐positive, PR‐positive, and Ki‐67 index ≥20%), and ER+PR−Ki67 high (ER‐positive, PR‐negative, and Ki‐67 index ≥20%). The cox proportional hazards regression model was used to evaluate the correlation between each variable and outcomes. Besides, discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve and log‐rank χ 2 value. Results The analysis results showed that there was a significant correlation between subtypes using this newly defined classification and overall survival ( p < 0.001) and disease‐free survival (DFS) ( p < 0.001). Interestingly, patients in the ER+PR−Ki67 high subgroup have the worst survival outcome in Luminal B (HER2‐negative) subtype, similar to Triple‐negative patients. Besides, the ER+PR+Ki67 high has worse 5‐year DFS compared with Luminal A group. There was a significant relationship between the regrouping subtype and the recurrence score index (RI) ( p < 0.001). Moreover, the results showed that patients in ER+PR–Ki67 high subtype were more likely to have high RI for distance recurrence (RI‐DR) and local recurrence (RI‐LRR). Our newly defined classification has a better discrimination ability to predict survival outcome and recurrence score of Luminal B (HER2‐negative) BC patients, which may help in clinical decision‐making for individual treatment.