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Activation of dopamine (DA) neurons is essential for the transition from sleep to wakefulness and maintenance of awakening, and sufficient to accelerate the emergence from general anesthesia in animals. Dopamine receptors (DR) are involve in arousal mediation. In the present study, we showed that the olfactory tubercle (OT) was active during emergence from isoflurane anesthesia, local injection of dopamine D1 receptor (D1R) agonist chloro-APB (1 mg/mL) and D2 receptor (D2R) agonist quinpirole (1 mg/mL) into OT enhanced behavioural and cortical arousal from isoflurane anesthesia, while D1R antagonist SCH-23390 (1 mg/mL) and D2R antagonist raclopride (2.5 mg/mL) prolonged recovery time. Optogenetic activation of DAergic terminals in OT also promoted behavioural and cortical arousal from isoflurane anesthesia. However, neither D1R/D2R agonists nor D1R/D2R antagonists microinjection had influences on the induction of isoflurane anesthesia. Optogenetic stimulation on DAergic terminals in OT also had no impact on the anesthesia induction. Our results indicated that DA signals in OT accelerated emergence from isoflurane anesthesia. Furthermore, the induction of general anesthesia, different from the emergence process, was not mediated by the OT DAergic pathways.

Locus coeruleus (LC) sends widespread outputs to many brain regions to modulate diverse functions, including sleep/wake states, attention, and the general anesthetic state. The paraventricular thalamus (PVT) is a critical thalamic area for arousal and receives dense tyrosine-hydroxylase (TH) inputs from the LC. Although anesthesia and sleep may share a common pathway, it is important to understand the processes underlying emergence from anesthesia. In this study, we hypothesize that LC TH neurons and the TH:LC-PVT circuit may be involved in regulating emergence from anesthesia. Only male mice are used in this study. Here, using c-Fos as a marker of neural activity, we identify LC TH expressing neurons are active during anesthesia emergence. Remarkably, chemogenetic activation of LC TH neurons shortens emergence time from anesthesia and promotes cortical arousal. Moreover, enhanced c-Fos expression is observed in the PVT after LC TH neurons activation. Optogenetic activation of the TH:LC-PVT projections accelerates emergence from anesthesia, whereas, chemogenetic inhibition of the TH:LC-PVT circuit prolongs time to wakefulness. Furthermore, optogenetic activation of the TH:LC-PVT projections produces electrophysiological evidence of arousal. Together, these results demonstrate that activation of the TH:LC-PVT projections is helpful in facilitating the transition from isoflurane anesthesia to an arousal state, which may provide a new strategy in shortening the emergence time after general anesthesia.

Background:Substantial substance use disorders and related health conditions emerged during the mid-20th century and continue to represent a remarkable 21st century global burden of disease. This burden is largely driven by the substance-dependence process, which is a complex process and is influenced by both genetic and environmental factors. During the past few decades, a great deal of progress has been made in identifying genetic variants associated with Substance Use and Dependence (SUD) through linkage, candidate gene association, genome-wide association and sequencing studies.Methods:Various statistical methods and software have been employed in different types of SUD genetic studies, facilitating the identification of new SUD-related variants.Conclusion:In this article, we review statistical methods and software that are currently available for SUD genetic studies, and discuss their strengths and limitations.

Objective: To evaluate the efficacy and toxicity of VMP regimen applied to the patients with low-risk gestational trophoblastic neoplasia (LR-GTN) treated in Anhui provincial hospital. Materials and methods: Between 2005 and 2017, 87 patients with low-risk gestational trophoblastic neoplasia received VMP regimen, consisted of vincristine (VCR), methotrexate (MTX) and platinum (cisplatin, carboplatin or nedaplatin), 68 of whom received VMP as their first-line chemotherapy, and 19 methotrexate-failed patients received VMP regimen as their second-line chemotherapy. The staging and scoring system was based on International Federation of Gynecology and Obstetrics (FIGO 2000) criteria. We describe and analyze their baseline characteristics, remission/resistance/recurrence rates, adverse reactions and prognosis. Results: The first-line VMP protocol can achieve an 83.8% remission rate and it tended to develop resistance when the pretreatment β-hCG reaches 7503.5 IU/L, and can achieve complete remission with FAV and EMA-CO as the salvage regimen. Among the 19 methotrexate-failed patients, 2 of whom were yet resistant to VMP regimen, followed by several courses of salvage chemotherapy such as FAV and EMP, and achieved 89.5% remission rate in second-line VMP group. Resistance to this regimen was obviously related with higher pre-treatment HCG whether used as primary or salvage treatment. Severe myelosuppression (grade 3 or 4) was shown in 4 (5.9%) of 68 cases, of which none was grade 4. Conclusion: For patients diagnosed with LR-GTN VMP regimen was a safe and effective treatment with a high rate of remission. Keywords: Low-risk gestational trophoblastic neoplasia, Vincristine, Methotrexate, Platinum, Efficacy

Normal sleep-wake behavior is extremely important for humans to maintain basic physiological and cognitive activities. However, the neural mechanisms underlying sleep-wake regulation are not fully understood. The paraventricular nucleus (PVN) of the hypothalamus has been classically defined as a region for the regulation of the hypothalamoneurohypophysial system and autonomic nervous system. Here, we identify the glutamatergic neurons in the PVN that play a unique role in sleep-wake regulation. Firstly using in vivo fiber photometry, we found altered calcium activities of PVN glutamatergic neurons during three sleep state transitions in freely behaving mice. The calcium activities of PVN glutamatergic neurons began to increase before non-rapid-eye movement (NREM) sleep to wake transitions and NREM sleep to rapid-eye-movement (REM) sleep transitions and began to decrease before wake to NREM sleep transitions. Then we used chemogenetic manipulations together with polysomnographic recordings, activation of PVN neurons increased wakefulness and decreased NREM sleep, while inhibition of PVN neurons caused a reduction in wakefulness and an increase in NREM sleep. Altogether, our findings revealed an important role for PVN glutamatergic neurons in the regulation of wake state.

While substantial progress has been made in finding genetic variants associated with nicotine dependence (ND), a large proportion of the genetic variants remain undiscovered. The current research focuses have shifted toward uncovering rare variants, gene-gene/gene-environment interactions, and structural variations predisposing to ND, the impact of genetic heterogeneity in ND has been nevertheless paid less attention. The study of genetic heterogeneity in ND not only could enhance the power of detecting genetic variants with heterogeneous effects in the population but also improve our understanding of genetic etiology of ND. As an initial step to understand genetic heterogeneity in ND, we applied a newly developed heterogeneity weighted U (HWU) method to 26 ND-related genes, investigating heterogeneous effects of these 26 genes in ND. We found no strong evidence of genetic heterogeneity in genes such as CHRNA5. However, results from our analysis suggest heterogeneous effects of CHRNA6 and CHRNB3 on nicotine dependence in males and females. Following the gene-based analysis, we further conduct a joint association analysis of two gene clusters, CHRNA5-CHRNA3-CHRNB4 and CHRNB3-CHRNA6. While both CHRNA5-CHRNA3-CHRNB4 and CHRNB3-CHRNA6 clusters are significantly associated with ND, there is a much stronger association of CHRNB3-CHRNA6 with ND when considering heterogeneous effects in gender (p-value = 2.11E-07).

Palygorskite is an environmentally friendly, inexpensive, and promising silicate mineral. In this research, nanoscale palygorskite additive powders (NPA) were prepared by high energy ball milling with the modifier γ-aminopropyltriethoxysilane (KH550). The NPA was sustainably dispersed in base oil 150 N, exhibiting no particle sedimentation for one week. The self-healing behavior and tribological performance of NPA as lubricant additive were investigated by a ring-on-disc tribometer under different concentrations for 50 h. The results indicate that NPA possesses excellent friction-reducing and anti-wear performance. The 3.0 wt.% and 4.0 wt.% concentrations of NPA displayed the best friction-reducing and anti-wear effects, respectively. The average friction coefficient and wear mass loss decreased by 31.93% and 26.92%, in contrast to that of base oil 150 N. It was also found that different NPA concentrations possessed different friction states. A tribo-film with bilayer structure was formed during the friction process, the first one of which contained compound made up of multiple elements, and the second one of which contained NPA nanoparticles deposited on the friction interface. Moreover, the friction coefficient increased dramatically during the formation of the tribo-film.

Steroid cell tumors (SCT), not otherwise specified (NOS) are particularly rare ovarian sex cord-stromal tumors, which comprise

Prostaglandin E2 (PGE2) is the most common prostaglandin in the human body, meaning that its malfunction impacts on the development of numerous diseases. Prostaglandin E synthase 2 (PTGES2) is involved in the synthesis of PGE2. In the present study, immunohistochemistry of PTGES2 was performed in 152 patients with endometrial cancer and in 66 patients with normal endometria. The results indicate a notable association among increased expression of PTGES2 and age (P=0.0092) and the depth of myometrial invasion (P

Summary Epithelial ovarian cancer is composed of a diverse group of tumors that can be derived from the fallopian tube, endometrium, or ovary. In this study, we explored the expression levels of LATS family members in ovarian tumors using normal ovaries, fallopian tubes, and endometrium as controls. Immunohistochemistry studies of LATS1, LATS2, Pax8, and calretinin were performed on normal ovary, fallopian tube, normal endometrium, and ovarian tumor sections. Statistical analyses were conducted using the χ 2 test, Fisher exact test, or Kruskal-Wallis H test. Patient survival was analyzed using the Kaplan-Meier method. LATS1 was expressed in normal ovarian epithelia, endometrium, and fallopian tubes, whereas LATS2 expression was observed in the normal fallopian tubes and endometrium. High expressions of LATS1 and LATS2 in serous cystadenomas gradually decreased in borderline cystadenomas and carcinomas, respectively. However, an opposite expression pattern was observed in mucinous tumors. Low expressions of LATS1 and LATS2 were also detected in clear cell carcinoma. Both LATS1 and LATS2 expression levels significantly correlated with recurrence and stage; LATS1 levels were also related with tumor grades in serous carcinoma. However, univariate and multivariate Cox regression analyses revealed that high expression of LATS1 was associated with better prognosis in patients with serous carcinoma. Both LATS1 and LATS2 were not related with the clinical variables in mucinous and clear cell carcinoma. LATS1 expression levels might be a valuable survival indicator in ovarian serous carcinoma.

Based on 1982-1999 satellite sensings, meteorological data and observations of crop growth/development, a study is conducted on seasonal and interannual variations in vegetation NDVI (normalized difference vegetation index), its response to climate change and its relationship with crop growth/development during the period in Zhengzhou region of Henan province. Evidence suggests that the interannual change is not so pronounced in the regional NDVI, exhibiting, on the whole, an unsteadily increasing trend; stronger seasonality is shown in the annual variation, with a more significant rising trend in spring as opposed to those for summer and autumn; NDVI change is in positive correlation both to temperature and precipitation (stronger response to temperature), with its change subject dominantly to temperature and rainfall in spring and summer, respectively, under varying effect of temperature and precipitation in autumn, and largely under the impacts of heat in winter and during the growth of winter wheat and summer-sown corn the NDVI is positively correlated to the crop height and density (the number of crop individuals per unit area) in their milking stage, the latter acting as a principal factor of NDVI change.