lnc-KCNQ1OT1在胃癌组织和细胞中的表达及其临床意义

目的:探讨长链非编码RNA-KCNQ1OT1(lnc-KCNQ1OT1)在胃癌组织和细胞中的表达及临床意义。方法:收集 2010年1月1日至2011年12月31日期间在哈尔滨医科大学附属肿瘤医院行手术治疗的163 例胃癌患者的临床资料，选取组织和细胞通过RT-PCR法检测lnc-KCNQ1OT1的表达情况，根据其表达情况及临床病例数据分析lnc-KCNQ1OT1在胃癌组织和细胞中的临床意义。结果:与癌旁组织比较，lnc-KCNQ1OT1在胃癌组织中的表达水平明显增高（P<0.05）。在胃癌细胞株HGC-27、MGC-803中，lnc-KCNQ1OT1表达水平较胃永生化上皮细胞株GES-1明显升高（P<0.05）。单因素分析显示lnc-KCNQ1OT1的表达与患者年龄、性别、肿瘤大小无关（P>0.05），与淋巴结转移（P<0.001）明显相关。K-M生存分析显示胃癌患者中lnc-KCNQ1OT1高表达者预后不良（P<0.05）。结论:在胃癌组织和细胞中lnc-KCNQ1OT1的表达量高，其高表达与胃癌患者淋巴结转移相关，并可导致胃癌患者预后不良。lnc-KCNQ1OT1可作为潜在的胃癌预后预测的分子标志物。     

Phoenixin-14 regulates proliferation and apoptosis of vascular smooth muscle cells by modulation of KCNQ1OT1/miR-183-3p/CTNNB1 axis

Phoenixin-14 has been reported to be implicated in the process of blood glucose metabolism, reproduction, lipid deposition and cardioprotection. However, the role of phoenixin-14 in vascular smooth muscle cells (VSMCs) remains unkown. In this study, we focused on the effects of phoenixin-14 on VSMCs under oxidized low-density lipoprotein (ox-LDL) treatment. The experimental results demonstrated that phoenixin-14 inhibited mRNA level and nuclear translocation of β-catenin. Functionally, phoenixin-14 inhibited cell proliferation and facilitated apoptosis of VSMCs under ox-LDL stimulation, and CTNNB1 overexpression reversed these effects. Mechanistically, KCNQ1OT1 interacted with miR-183-3p to upregulate CTNNB1 in VSMCs. Furthermore, CTNNB1 expression was negatively correlated with miR-183-3p but positively associated with KCNQ1OT1. Rescue assays indicated that KCNQ1OT1 overexpression or Lithium chloride (LiCl) treatment reversed the effects of phoenixin-14 on proliferation and apoptosis of ox-LDL-stimulated VSMCs. In summary, phoenixin-14 regulates proliferation and apoptosis of ox-LDL-treated VSMCs by regulating the KCNQ1OT1/miR-183-3p/CTNNB1 axis.     

Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior

The neuropeptides vasopressin (VP) and oxytocin (OT) and their receptors in the brain are involved in the regulation of various social behaviors and have emerged as drug targets for the treatment of social dysfunction in several sex-biased neuropsychiatric disorders. Sex differences in the VP and OT systems may therefore be implicated in sex-specific regulation of healthy as well as impaired social behaviors. We begin this review by highlighting the sex differences, or lack of sex differences, in VP and OT synthesis in the brain. We then discuss the evidence showing the presence or absence of sex differences in VP and OT receptors in rodents and humans, as well as showing new data of sexually dimorphic V1a receptor binding in the rat brain. Importantly, we find that there is lack of comprehensive analysis of sex differences in these systems in common laboratory species, and we find that, when sex differences are present, they are highly brain region- and species-specific. Interestingly, VP system parameters (VP and V1aR) are typically higher in males, while sex differences in the OT system are not always in the same direction, often showing higher OT expression in females, but higher OT receptor expression in males. Furthermore, VP and OT receptor systems show distinct and largely non-overlapping expression in the rodent brain, which may cause these receptors to have either complementary or opposing functional roles in the sex-specific regulation of social behavior. Though still in need of further research, we close by discussing how manipulations of the VP and OT systems have given important insights into the involvement of these neuropeptide systems in the sex-specific regulation of social behavior in rodents and humans.     

Hypoactive Sexual Desire Disorder: International Society for the Study of Women's Sexual Health (ISSWSH) Expert Consensus Panel Review

The objective of the International Society for the Study of Women's Sexual Health expert consensus panel was to develop a concise, clinically relevant, evidence-based review of the epidemiology, physiology, pathogenesis, diagnosis, and treatment of hypoactive sexual desire disorder (HSDD), a sexual dysfunction affecting approximately 10% of adult women. Etiologic factors include conditions or drugs that decrease brain dopamine, melanocortin, oxytocin, and norepinephrine levels and augment brain serotonin, endocannabinoid, prolactin, and opioid levels. Symptoms include lack or loss of motivation to participate in sexual activity due to absent or decreased spontaneous desire, sexual desire in response to erotic cues or stimulation, or ability to maintain desire or interest through sexual activity for at least 6 months, with accompanying distress. Treatment follows a biopsychosocial model and is guided by history and assessment of symptoms. Sex therapy has been the standard treatment, although there is a paucity of studies assessing efficacy, except for mindfulness-based cognitive behavior therapy. Bupropion and buspirone may be considered off-label treatments for HSDD, despite limited safety and efficacy data. Menopausal women with HSDD may benefit from off-label testosterone treatment, as evidenced by multiple clinical trials reporting some efficacy and short-term safety. Currently, flibanserin is the only Food and Drug Administration–approved medication to treat premenopausal women with generalized acquired HSDD. Based on existing data, we hypothesize that all these therapies alter central inhibitory and excitatory pathways. In conclusion, HSDD significantly affects quality of life in women and can effectively be managed by health care providers with appropriate assessments and individualized treatments.     

Self-Report of Outpatient Therapy Dose at 6 and 12 Months After Severe Traumatic Brain Injury

Objective

Determine agreement between self-reported dose and dose reflected in administrative records of outpatient physical, occupational, and speech therapies at 6 and 12 months after severe traumatic brain injury (TBI), for the purpose of examining accuracy and predictors of accuracy of self-reported health care utilization in this population.

Does a thoracoscopic approach provide better outcomes for pulmonary metastases?

Traditional open thoracotomy (OT) is the gold standard treatment for patients with pulmonary metastases. However, it remains controversial whether video-assisted thoracic surgery (VATS) can provide comparable outcomes to OT. We conducted this review to compare the outcomes of VATS with OT in pulmonary metastasectomy (PM). Relevant studies published up to November 2019 were identified from PubMed data base and screened. Studies were then selected by the researchers based on our selection criteria. Data including the type of study, patient groups, outcomes and key results were extracted from the included studies and summarized. Screening of 2,788 papers identified 9 that were relevant to our research question. The authors, dates of publication, journal details, type of study, patient groups, outcomes and key results from these papers were summarized. All 9 studies documented the survival rate (1-, 3- and 5-year survival). Metastases from colorectal cancer were investigated in three studies, and metastases from sarcoma were investigated in one study. The overall survival rate of VATS was not inferior to that of OT in patients with pulmonary metastases. VATS was also associated with better perioperative results compared with OT. In conclusion, VATS is suitable as an alternative surgical technique for PM.     

CB1 modulation of hormone secretion, neuronal activation and mRNA expression following extracellular volume expansion

The endocannabinoid system includes important signaling molecules that are involved in several homeostatic and neuroendocrine functions. In the present study, we evaluated the effects of the type 1 cannabinoid (CB₁) receptor antagonist, rimonabant (10 mg/kg, p.o.), on hormone secretion, neuronal activation and mRNA expression in the hypothalamus following isotonic (I-) or hypertonic (H-) extracellular volume expansion (EVE). The total nitrate content in the PVN and SON was also assessed under the same experimental conditions. Our results showed that OT and AVP plasma concentrations were increased in response to H-EVE, while decreased AVP levels were found following I-EVE. Accordingly, both I- and H-EVE stimulated oxytocinergic neuronal activation, as evidenced by the increased number of c-Fos/OT double labeled neurons in the hypothalamus. The vasopressinergic cells of the PVN and SON, however, were only activated in response to H-EVE. Furthermore, increased amounts of both AVP and OT mRNAs were found in the hypothalamus following EVE. Pretreatment with rimonabant significantly potentiated hormone secretion and also vasopressinergic and oxytocinergic neuronal activation induced by EVE, although decreased AVP and OT mRNA expression was found in the hypothalami of rimonabant pretreated groups. In addition, the nitrate content in the PVN and SON was not altered in response to EVE or rimonabant pretreatment. Taken together, these results suggest that the CB₁ receptor may modulate several events that contribute to the development of appropriate responses to increased fluid volume and osmolality.     

Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat

We have analyzed at high resolution the neuroanatomical connections of the juxtaparaventricular region of the lateral hypothalamic area (LHAjp); as a control and in comparison to this, we also performed a preliminary analysis of a nearby LHA region that is dorsal to the fornix, namely the LHA suprafornical region (LHAs). The connections of these LHA regions were revealed with a coinjection tract-tracing technique involving a retrograde (cholera toxin B subunit) and anterograde (Phaseolus vulgaris leucoagglutinin) tracer. The LHAjp and LHAs together connect with almost every major division of the cerebrum and cerebrospinal trunk, but their connection profiles are markedly different and distinct. In simple terms, the connections of the LHAjp indicate a possible primary role in the modulation of defensive behavior; for the LHAs, a role in the modulation of ingestive behavior is suggested. However, the relation of the LHAjp and LHAs to potential modulation of these behaviors, as indicated by their neuroanatomical connections, appears to be highly integrative as it includes each of the major functional divisions of the nervous system that together determine behavior, i.e., cognitive, state, sensory, and motor. Furthermore, although a primary role is indicated for each region with respect to a particular mode of behavior, intermode modulation of behavior is also indicated. In summary, the extrinsic connections of the LHAjp and LHAs (so far as we have described them) suggest that these regions have a profoundly integrative role in which they may participate in the orchestrated modulation of elaborate behavioral repertoires.     

Protein turnover in normal and degenerating visual pathway of the frog and the rat, an autoradiographic study

Radioactivity above background level can be detected in the contralateral visual pathway of normal rats as long as 250 days after intraocular injection of tritiated proline. Silver grains disappear first from the retina, and last from the superior colliculus. In the optic tectum and the isthmic nucleus of the frog, more than 500 days are necessary to reach background level of radioactivity, when labelled retinal fibres are undergoing Wallerian degeneration. The intensity of label in tectal laminae formed by myelinated fibres is markedly reduced 12 days after the removal of the labelled eye. In the laminae of unmyelinated fibres, the decrease in the number of silver grains is less than 50% during a 150-day degeneration period. In the isthmic nucleus radioactivity was less intense, when labelled retinal fibres were degenerating in the tectum, as compared to that in normal animals. Radioactivity in the superior colliculus decreased 3 times faster than in the tectum after removal of the labelled eye. We conclude that proline is reutilized for protein synthesis. Unmyelinated fibres degenerate slower than myelinated ones in frogs, and transneuronal transport cannot be enhanced by increased protein breakdown.