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Increasing evidence indicated that N6-methyl-adenosine (M6A) played a key role in a variety of pathophysiological processes. Methylases could promote the processing of mature mi-RNA in a M6A-dependent manner, thereby participating in the pathological cells' occurrence and development. However, the regulatory mechanism of M6A in atherosclerosis (AS) was still unclear.Quantificational Real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of M6A, methyltransferase, demethylase transferase, miR-19a and other mi-RNA in atherosclerotic vascular endothelial cells (ASVEC). Cell Counting Kit (CCK8) was used to detect cell proliferation, the expression of PCNA was measured by Western Blot (WB) and qRT-PCR. Transwell assays were used to detect the invasion ability of ASVEC. Co-immunoprecipitation (Co-IP) was used to detect the binding of METTL14 to DGCR8. RNA Immunoprecipitation (RIP) was used to detect the binding of METTL14 to miR-19a.M6A modification levels and METTL14 methylation transferase were significantly overexpressed in ASVEC. Silencing METTL14 inhibited the proliferation and invasion of ASVEC. Low expression of METTL14 suppressed the binding of methylated RNA and RNA splicing related protein DGCR8. Moreover, silencing METTL14 significantly inhibited the expression of miR-19a while promoted the expression of primary pre-miR-19a. However, high expression of METTL14 obviously increased the expression of DGCR8 and methylated m6A. Furthermore, silencing miR-19a inhibited the proliferation and invasion of ASVEC.METTL14 increased the M6A modification of pri-miR-19a and promoted the processing of mature miR-19a, thus promoting the proliferation and invasion of ASVEC. These results suggested that METTL14/ M6A/ miR-19a signaling pathway may be a new target for atherosclerosis treatment.

Recently, we hypothesized that supraspinal structures may have important functions in discriminating between noxious mechanically and heat mediated nociception through distinct functions: facilitation and inhibition. In this study, conducted in conscious rats, we explored the role of different thalamic nuclei: the mediodorsal (MD) nucleus, the central medial (CM) nucleus, the submedius (SM) nucleus, the ventralmedial (VM) nucleus and the ventral posterolateral (VPL) nucleus, in the descending control of secondary and contralateral mechanical hyperalgesia and heat hypoalgesia occurring in intramuscularly hypertonic (HT, 5.8%) saline-induced muscle nociception. We found that the MD nuclei participated in the descending facilitation of mechanical hyperalgesia, and that the VM nuclei were specifically involved in the descending inhibition of heat hypoalgesia. Neither descending facilitation nor descending inhibition was affected after electrolytic lesion of the thalamic CM, SM, and VPL nuclei. This descending facilitatory and inhibitory modulation of nociception was strengthened by glutamate, and weakened by GABA, microinjected into the thalamic MD and VM nuclei. It is suggested that (1) thalamic MD nucleus and VM nucleus form two distinct endogenous systems in the control of noxious mechanically and heat evoked responses, and (2) the strengthening of descending inhibition and the weakening of descending facilitation by means of up regulation and down regulation of appropriate receptor expression in the VM and MD nuclei may provide a new strategic policy in treating pathological pain.

To explore the value of morphological classification in predicting malignant transformation in multiple exostoses (ME).The imaging data of 116 patients (totally 190 tumors) with ME were retrospectively analyzed. All the tumors were pathology confirmed after surgical resection, including 175 exostoses from 101 patients, and 15 exostotic chondrosarcomas in 15 cases. Based on the ratio of diameter between tumor tip and tumor base (R1), tumors were classified into two types: cauliflower-like tumor (R1 ≥ 1.0) and non-cauliflower-like tumor (R11.0). In addition, non-cauliflower-like tumors were further classified into two subtypes according to the ratio of tumor height to tumor base diameter: sessile type (R21.0) and pedunculated type (R2 ≥ 1.0). The relationship between tumor shape and malignant transformation was studied.Of all the 175 exostoses from 101 patients, 27 were cauliflower-like tumors and 148 were non-cauliflower-like tumors. Of all the 15 exostotic chondrosarcomas in 15 cases, most tumors were cauliflower-like (c2 = 38.0075, p0.05). Cauliflower-like tumor for the prediction of exostotic chondrosarcoma, the sensibility, specificity, positive predictive value, negative predictive value were 86.7%, 84.6%, 32.5%, 98.7%, respectively.Tumor malignant transformation was more common in cauliflower-like tumors than in non-cauliflower-like tumors. The morphological classification and preventive resection of cauliflower-like tumors maybe helpful in preventing the malignant transformation of ME.

Effect of muscle spindle afferent invoked by intraarterial injection of succinylcholine (Sch) on respiration was assessed by changes in unit discharge of respiration related neurons and phrenic nerve of 63 anesthetized, bilaterally vagotomized and artificially ventilated rabbits. The results are as follows. (1) Intra~arterial injection of Sch prolonged inspiratory duration (Ti) or decreased expiratory duration (Te) and augmented respiratory frequency (RF). (2) 66% (37/56) of the medullary inspiratory neurons were excited and 10/17 of the expiratory neurons were inhibited by intraarterial injection of Sch, reaching maximum respectively at 1 2 and 2 3 min after injection, while non-respiration related neurons were not affected. (3) This effect of Sch was suppressed or abolished when muscle spindles were destroyed by intramuscular injection of bupivacaine.