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Background: Circular RNAs (circRNA) play an essential role in the tumorigenesis of non-small cell lung cancer (NSCLC). CircDTL is a novel identified circRNA with little information regarding its biological role. However, the role of circDTL in NSCLC has not been investigated yet.Method: In this study, the levels of circDTL in tissues and cells were measured by RT-PCR. Cell viability was measured by the CCK-8 assay. Cell migration and invasion were evaluated using the wound healing assay and transwell assay, respectively. Cell death was measured by the cell death ELISA kit. The levels of Fe2+, ROS, MDA and GSH were measured using the commercial kits. The interactions between miR-1287-5p and circDTL/3′UTR GPX4 were verified by dual-luciferase activity assay. The effects of circDTL on tumor growth were evaluated in vivo.Results: CircDTL was found to be upregulated and acted as an oncogene in NSCLC cells. Knockdown of circDTL promoted both apoptosis and ferroptosis of NSCLC cells. It was identified that circDTL exerts its oncogenic effects via the circDTL/miR-1287-5p/GPX4 axis and GPX4 inhibits both ferroptosis and apoptosis. Finally, this study showed that silencing of circDTL promoted the sensitivity of NSCLC cells to chemotherapeutic agents and inhibited the growth of tumors in vivo.Conclusion: CircDTL acts as an oncogene and exerts its effects via the miR-1287-5p/GPX4 axis in NSCLC, providing a potential therapeutic target for NSCLC cancer therapy.

Purpose: Oxcarbazepine (OXC) is widely used in anti-epileptic treatment. Cytochrome P450 3A4 (CYP3A4), cytochrome P450 3A5(CYP3A5), and ATP-binding cassette sub-family B member 1 (ABCB1) are potential genes involved in OXC metabolisms and transport in vivo. This study aims to examine the genetic effects of CYP3A4, CYP3A5, and ABCB1 on OXC metabolism and transport in Chinese epileptic patients using OXC as monotherapy and bitherapy with lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA). Methods: Sixty-six Chinese epileptic patients were recruited from Xiangya Hospital Central South University, of whom 40 patients were receiving OXC monotherapy, 11 patients were placed in the OXC bitherapy group combined with one enzyme-inducing anti-epileptic drugs (LTG or LEV), and 15 patients were placed in the OXC bitherapy group combined with VPA. Oxcarbazepine and its main metabolite 10-hydrocarbazepine (MHD) plasma concentrations were measured using high performance liquid chromatography (HPLC)-UV method. In addition, eight single nucleotide polymorphisms (SNPs) in CYP3A4, CYP3A5, ABCB1 gene were genotyped by polymerase chain reaction-improved multiple ligase detection reaction (PCR-iMLDR). Results: In the OXC+VPA group, ABCB1 rs2032582 and rs2032582-rs10234411-rs1045642 TAG haplotype were associated with MHD and MHD+OXC plasma concentration before permutation test. In OXC monotherapy and OXC+ LTG/LEV groups, no significant association between genetic polymorphisms in CYP3A4/5, ABCB1 gene and OXC plasma concentration parameters were observed. Conclusion: CYP3A4/5 and ABCB1 genetic variants might not take part in the metabolism and transport of MHD and OXC among epileptic patients using OXC monotherapy and bitherapy in combination with LEV, LTG or VPA. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Background: Hemorrhagic transformation is one of the most serious complications in intravenous thrombolysis. Studies show that the existence of more than 10 cerebral microbleeds is strongly associated with hemorrhagic transformation. The current study attempts to develop and validate a clinical prediction model of more than 10 cerebral microbleeds. Methods: We reviewed the computed tomography markers of cerebral small vessel diseases and the basic clinical information of acute ischemic stroke patients who were investigated using susceptibility weighted imaging from 2018 to 2021. A clinical prediction model of more than 10 cerebral microbleeds was established. Discrimination, calibration, and the net benefit of the model were assessed. Finally, a validation was conducted to evaluate the accuracy and stability of the model. Results: The multivariate logistic regression model showed hypertension, and some computed tomography markers (leukoaraiosis, lacunar infarctions, brain atrophy) were independent risk factors of more than 10 cerebral microbleeds. These risk factors were used for establishing the clinical prediction model. The area under the receiver operating characteristic curve (AUC) was 0.894 (95% CI: 0.870–0.919); Hosmer–Lemeshow chi-squared test yielded χ2 = 3.946 (P = 0.862). The clinical decision cure of the model was higher than the two extreme lines. The simplified score of the model ranged from 0 to 12. The model in the internal and external validation cohort also had good discrimination (AUC 0.902, 95% CI: 0.868–0.937; AUC 0.914, 95% CI: 0.882–0.945) and calibration (P = 0.157, 0.247), and patients gained a net benefit from the model. Conclusions: We developed and validated a simple scoring tool for acute ischemic stroke patients with more than 10 cerebral microbleeds; this tool may be beneficial for paradigm decision regarding intravenous recombinant tissue plasminogen activator therapy of acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Meige syndrome (MS) is cranial dystonia characterized by the combination of upper and lower cranial involvement and including binocular eyelid spasms (blepharospasm; BSP) and involuntary movements of the jaw muscles (oromandibular dystonia; OMD). The etiology and pathogenesis of this disorder of the extrapyramidal system are not well-understood. Neurologic and ophthalmic examinations often reveal no abnormalities, making diagnosis difficult and often resulting in misdiagnosis. A small proportion of patients have a family history of the disease, but to date no causative genes have been identified to date and no cure is available, although botulinum toxin A therapy effectively mitigates the symptoms and deep brain stimulation is gaining increasing attention as a viable alternative treatment option. Here we review the history and progress of research on MS, BSP, and OMD, as well as the etiology, pathology, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

Extremely low nucleotide diversity of modern horse Y-chromosome has been reported, and only poor phylogenetic resolution could be resulted from limited Y-chromosome markers. In this study, three types of horse Y-chromosome markers, including Single-nucleotide polymorphisms (SNPs), copy number variants (CNVs), and allele-specific CNVs, were developed by screening more than 300 male horses from 23 indigenous Chinese horse populations and 4 imported horse breeds. Fourteen segregating sites including a novel SNP in the AMELY gene were found in approximately 53 kb of male-specific Y-chromosome sequences. CNVs were detected at 11 of 14 sites, while allele-specific CNVs at 6 polymorphic sites in repeated fragments were also determined. The phylogenetic analyses with the SNPs identified in this study and previously published 51 SNPs obtained mainly from European horses showed that indigenous Chinese horses exhibit much deeper divergence than European and Middle Eastern horses, while individuals of Chinese horses with the C allele of the AMELY gene constituted the most ancient group. Via SNPs, CNVs, and allele-specific CNVs, much higher diversity of paternal lines can be detected than those identified with merely SNPs. Our results indicated that there are ancient paternal horse lines preserved in southwestern China, which sheds new light on the domestication and immigration of horses, and suggest that the priorities of the conservation should be given to the ancient and rare paternal lines. These three marker types provided finer phylogenetic resolution of horse patrilineal lines, and the strategies used in the present study also provide valuable reference for the genetic studies of other mammalian patrilineages. [ABSTRACT FROM AUTHOR]