Patients with chronic pain have significantly higher incidences of depression and anxiety than the average person. However, the mechanism underlying this link has not been elucidated in terms of how chronic pain causes significant mood changes and further develops into severe anxiety or depression. The serotonergic system in the raphe nuclei is an important component in both pain processing and the pathogenesis of depression. Since the lateral habenular nucleus (LHb) controls the raphe nuclei, it may participate in the regulation of pain-associated depression. Thus, the aim of the current study was to investigate the role of the LHb in this pathophysiological process. We used chronic constriction injury (CCI) of the sciatic nerve in rats as a model for neuropathic pain and assessed the changes potentially related to the mood disorders. The forced swim test (FST) and sucrose preference test (SPT) were performed to determine the behavioral changes 28 days after pain surgery. Expression of β calmodulin-dependent protein kinase type II (βCaMKII) in the LHb, cytochrome-c oxidase (COX) activity in the LHb and dorsal raphe nucleus (DRN) and serotonin (5-HT) levels in the DRN were measured. We found an increasing in LHb activity and βCaMKII expression, and a decrease in neuronal activity in the DRN and 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratios in the CCI rats. These effects were accompanied by the depression-like behaviors. Lesions in the LHb improved the pain threshold and depression-like behavior in the rats. These results suggest that the LHb may play a role in pain-associated depression by affecting the activity of 5-HT neurons in the DRN. Furthermore, we showed that increases in the LHb-DRN pathway activity were a common neurobiological mechanisms for pain and depression, which may explain the coexistence of pain and depression.

Papillary thyroid cancer (PTC) is a common malignancy in endocrine system worldwide.Increasing evidence has shown that dysregulation of circular RNAs (circRNAs) could contribute to PTC tumorigenesis. The aims of this project are to investigate the potential role and molecular mechanism of hsa_circ_0039411 in PTC. In the project, RT-qPCR was performed to measure the expression profile of hsa_circ_0039411 in PTC tissues and cells.Cell counting kit-8, clonogenic, flow cytometric, and transwell experiments were used to identify the biological role of hsa_circ_0039411 on PTC cell progression. Bioinformatics methods, along with the dual-luciferase reporter test, was used to identify the potential mechanism of hsa_circ_0039411. Hsa_circ_0039411 was identified as enhanced in PTC tissues/cells. Gain-of-function experiments indicated that hsa_circ_0039411 facilitated PTC cell growth, migration, and invasion and inhibited cell apoptosis. Knockdown of hsa_circ_0039411 caused the opposite effects mentioned above. The mechanism exploration showed that hsa_circ_0039411 functioned as a sponge for miR-1179 and miR-1205 to elevate ATP-binding cassette transporter A9 (ABCA9) and metastasisassociated 1 (MTA1) expression at the post-transcriptional level, respectively. Further investigation confirmed that the functions of hsa_circ_0039411 are dependent on its modulation of ABCA9 and MTA1 in PTC cells. This study uncovered a mechanism of hsa_circ_0039411 in PTC, which might act as a novel therapeutic target for PTC. K E Y W O R D SATP-binding cassette transporter A9, circular RNA, hsa_circ_0039411, metastasis-associated 1, miR-1179, miR-1205, papillary thyroid cancer

BACKGROUND: Peripheral nerve block (PNB) with perineural local anesthetic is used for anesthesia or analgesia with many benefits. To extend these benefits, various adjuvant drugs have been used to prolong the duration of analgesia. We aimed to evaluate the effectiveness of various adjuvants at prolonging the duration of sensory and motor blockade for PNB. METHODS: A network meta-analysis of placebo-controlled and active randomized controlled trials was performed comparing 10 adjuvants. Embase, PubMed, Web of Science, and Cochrane library were searched, with articles before May 21, 2020 included. Two authors independently selected studies and extracted data. The primary outcomes were sensory block (SB) and motor block (MB) time, and the secondary outcome was time of first analgesia rescue (FAR). Effect size measures were described as mean differences (MD) with 95% confidence intervals (CIs). Confidence in evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The study protocol was preregistered with the prospectively registered systematic reviews in health and social care international database (PROSPERO), as number CRD42020187866. RESULTS: Overall 16,364 citations were identified, of which 53 studies were included with data for 3649 patients. In network meta-analyses, 4 of 7 included treatment strategies were associated with more efficacious analgesia compared with placebo therapy, including dexamethasone (SB time: 5.73 hours, 95% CI, 4.16–7.30; MB time: 4.20 hours, 95% CI, 2.51–5.89; time of FAR: 8.71 hours, 95% CI, 6.63–10.79), dexmedetomidine (SB time: 4.51 hours, 95% CI, 3.52–5.50; MB time: 4.04 hours, 95% CI, 2.98–5.11; time of FAR: 5.25 hours, 95% CI, 4.08–6.43), fentanyl (SB time: 3.59 hours, 95% CI, 0.11–7.06; MB time: 4.42 hours, 95% CI, 0.78–8.06), and clonidine (SB time: 2.75 hours, 95% CI, 1.46–4.04; MB time: 2.93 hours, 95% CI, 1.69–4.16; time of FAR: 3.35 hours, 95% CI, 1.82–4.87). In a subgroup analysis, addition of dexamethasone to ropivacaine significantly increased the time of FAR when compared to dexmedetomidine (time of FAR: 5.23 hours, 95% CI, 2.92–7.54) or clonidine (time of FAR: 6.61 hours, 95% CI, 4.29–8.92) with ropivacaine. CONCLUSIONS: These findings provide evidence for the consideration of dexmedetomidine, dexamethasone, and clonidine as adjuvants to prolong the duration of PNB. The addition of dexamethasone to ropivacaine has a longer time of FAR compared with clonidine or dexmedetomidine.

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The glycocalyx is a gel‐like layer covering the luminal surface of vascular endothelial cells. It comprises of membrane‐attached proteoglycans, glycosaminoglycan chains, glycoproteins, and adherent plasma proteins. The glycocalyx maintains homeostasis of the vasculature, which includes controlling vascular permeability and microvascular tone, preventing microvascular thrombosis, and regulating leukocyte adhesion. In the past decades, the number of studies on endothelial glycocalyx has steadily grown. Glycocalyx emerged as an essential part of blood vessels involved in multiple physiological functions. Damage to glycocalyx is associated with many types of diseases. The structure and physiology and pathophysiology of the glycocalyx, as well as the clinical effects of glycocalyx degradation, are addressed throughout this study. We strive in particular to define therapeutic approaches for the survival or reparation of the glycocalyx.