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71.
Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d ‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability. 相似文献
72.
《Clinical lung cancer》2020,21(2):160-170
IntroductionPulmonary carcinosarcoma (PC) is a rare malignant neoplasm composed of epithelial and mesenchymal components. It accounts for < 1% of thoracic cancers and is not fully understood. This study examined Surveillance, Epidemiology, and End Results (SEER) data to describe demographic and clinical characteristics of patients with PC and assessed survival outcomes by treatment modality and stage.Patients and MethodsSEER data were reviewed to identify patients diagnosed with primary PC (1973-2012). Overall survival (OS) and disease-specific survival (DSS) were analyzed by univariate/multivariable Cox proportional hazards models and Kaplan-Meier methods.ResultsA total of 411 patients were included. Median age was 67 (range, 24-96) years. Disease stage at the time of initial diagnosis was known for 74.7% of the identified patients (307/411). Of these patients, 23.1% had localized disease. Survival was significantly better for patients with localized disease (OS: 31 vs. 6 months, P < .001; DSS: 54 vs. 8 months, P < .001). Additionally, patients who received surgery alone had significantly improved OS (20 months; P < .001) and DSS (32 months; P < .001) compared to patients who received combined surgery and radiotherapy (OS: 7 months; DSS: 8 months) or radiotherapy alone (OS: 4 months; DSS: 4 months).ConclusionTreatment with surgery alone resulted in superior survival outcomes compared to other treatment modality combinations, regardless of patient age and disease stage. Within the limitations of this study, providers may wish to consider these findings when devising patient treatment plans. 相似文献
73.
Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth 下载免费PDF全文
Nurul Fathiyatul Nabila JaffarMuhammad Shahidan Muhammad SakriHasnan JaafarWan Faiziah Wan Abdul RahmanTengku Ahmad Damitri Al-Astani Tengku Din 《Asian Pacific journal of cancer prevention》2020,21(10):2919-2925
Objective: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib. Methods: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis. Results: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring. Conclusion: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment. 相似文献
74.
Hiroki Toyoda 《Synapse (New York, N.Y.)》2019,73(7)
The insular cortex plays essential roles in nicotine addiction. However, much is still unknown about its cellular and synaptic mechanisms responsible for nicotine addiction. We have previously shown that in layer 5 pyramidal neurons of the mouse insular cortex, activation of the nicotinic acetylcholine receptors (nAChRs) suppresses synaptic potentiation through enhancing GABAergic synaptic transmission, although it enhances both glutamatergic and GABAergic synaptic transmission. In the present study, we examined whether dopamine receptors might contribute to the nicotine‐induced inhibition of synaptic potentiation. The nicotine‐induced inhibition of synaptic potentiation was decreased in the presence of a D1 dopamine receptor antagonist SCH23390 irrespective of the presence of a D2 dopamine receptor antagonist sulpiride, suggesting that D1 dopamine receptors are involved in nicotine‐induced inhibition. We also investigated how dopamine receptors might contribute to the nAChR‐induced enhancement of glutamatergic and GABAergic synaptic transmission. The nAChR‐induced enhancement of GABAergic synaptic transmission was decreased in the presence of SCH23390 irrespective of the presence of sulpiride, whereas that of glutamatergic synaptic transmission was not altered in the presence of SCH23390 and sulpiride. These results suggest that D1 dopamine receptors are involved in the nAChR‐induced enhancement of GABAergic synaptic transmission while dopamine receptors are not involved in that of glutamatergic synaptic transmission. These observations indicate that the interaction between nAChRs and D1 dopamine receptors plays critical roles in synaptic activities in layer 5 pyramidal neurons of the mouse insular cortex. These insular synaptic changes might be associated with nicotine addiction. 相似文献
75.
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77.
心力衰竭是一种慢性疾病,是心脏无法泵出足够的血液为其他身体器官提供氧气,从而引发呼吸短促、疲劳和水肿等症状。目前其治疗包括病因治疗、一般治疗、药物治疗及非药物治疗等,其中血管紧张素受体脑啡肽酶抑制剂(ARNI)是当前新研发出的一类抗心衰药物,沙库巴曲缬沙坦是其代表药物,具有阻断肾素-血管紧张-醛固酮系统(RAAS)及抑制脑啡肽酶(NEP)的双重作用,新的欧美指南均推荐用于射血分数降低心力衰竭(HFrEF)的治疗。本文现就沙库巴曲缬沙坦在心力衰竭治疗中的作用机理、临床试验、药物安全性作一综述,旨在为该病的临床治疗提供参考。 相似文献
78.
Serum Folate Levels and Lung Cancer Risk: A Meta- Epidemiological Study of Population-based Case-Control Studies 下载免费PDF全文
Jong-Myon Bae 《Asian Pacific journal of cancer prevention》2020,21(6):1829-1833
Objective: While it has been claimed that lung cancer occurs due to epigenetic mechanisms, four systematic reviews were reported to investigate the association between serum folate levels and lung cancer risk. Considering some methodological problems founded in the systematic review, a meta-epidemiological study was conducted. Methods: The selection criteria of this study were defined that a case-control study was conducted to determine the risk of lung cancer occurrence according to the concentration of serum folate and its results showed odds ratio and its 95% confidence interval. Additional paper was explored from cited lists of 4 papers selected by previous systematic reviews. Random effect model was applied if I-squared value was over 50%. Results: For 5 case-control studies selected, the summary odds ratios (and their 95% confidence intervals) were 0.82 (0.74-0.90) in men, 0.70 (0.62-0.79) in former smokers, and 0.86 (0.75-1.00) in non-smokers. Conclusion: Higher foliate levels can decrease lung cancer risk in men and former smokers. Especially, the protective effect was highest in former smokers compared in non-smokers and current smokers. Based on these facts, folate fortification programs to reduce lung cancer risk would be focused on former smokers in men. And some epidemiological studies are needed to provide a hypothesis to explain the sex differences in the association between folate and lung cancer risk. 相似文献
79.
80.
《Clinical neurophysiology》2020,131(1):213-224
ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology. 相似文献