The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo- neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus and their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly about its relationship with other hypothalamic- pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

Background: Online teaching has become increasingly common in higher education of the post-pandemic era. While a traditional face-to-face lecture or offline teaching remains very important and necessary for students to learn the medical knowledge systematically, guided by the BOPPPS teaching model, combination of online and offline learning approaches has become an unavoidable trend for maximizing teaching efficiency. However, in physiological education, the effectiveness of combined online teaching and offline teaching models remains poorly assessed. The present study aims at providing an assessment to the hybrid teaching model. Methods: The study was performed among undergraduate medical students of Class 2017 ~ 2019 in the Physiology course in Harbin Medical University during 2018-2020. Based on established offline teaching model with BOPPPS components in 2018, we incorporated online teaching contents into it to form a hybrid BOPPPS teaching model (HBOPPPS, in brief), preliminarily in 2019 and completely in 2020. HBOPPPS effectiveness was assessed through comparing the final examination scores of both objective (multi-choice and single answer questions) and subjective (short and long essays) questions between classes taught with different modalities. Results: The final examination score of students in Class 2019 (83.9 ± 0.5) who were taught with the HBOPPPS was significantly higher than that in Class 2017 (81.1 ± 0.6) taught with offline BOPPPS and in Class 2018 (82.0 ± 0.5) taught with immature HBOPPPS. The difference mainly attributed to the increase in average subjective scores (41.6 ± 0.3 in Class 2019, 41.4 ± 0.3 in Class 2018, and 38.2 ± 0.4 in Class 2017). In the questionnaire about the HBOPPPS among students in Class 2019, 86.2% responded positively and 79.4% perceived improvement in their learning ability. In addition, 73.5% of the students appreciated the reproducibility of learning content and 54.2% valued the flexibility of HBOPPPS. Lastly, 61.7% of the students preferred the HBOPPPS relative to BOPPPS in future learning. Conclusions: HBOPPPS is likely a more effective teaching model and useful for enhancing effectiveness of Physiology teaching. This is attributable to the reproducibility and flexibility as well as the increased learning initiatives.

Coronary artery disease (CAD) is a major cardiovascular disease responsible for high morbidity and mortality worldwide. The major pathophysiological basis of CAD is atherosclerosis in association with varieties of immunometabolic disorders that can suppress oxytocin (OT) receptor (OTR) signaling in the cardiovascular system (CVS). By contrast, OT not only maintains cardiovascular integrity but also has the potential to suppress and even reverse atherosclerotic alterations and CAD. These protective effects of OT are associated with its protection of the heart and blood vessels from immunometabolic injuries and the resultant inflammation and apoptosis through both peripheral and central approaches. As a result, OT can decelerate the progression of atherosclerosis and facilitate the recovery of CVS from these injuries. At the cellular level, the protective effect of OT on CVS involves a broad array of OTR signaling events. These signals mainly belong to the reperfusion injury salvage kinase pathway that is composed of phosphatidylinositol 3-kinase-Akt-endothelial nitric oxide synthase cascades and extracellular signal-regulated protein kinase 1/2. Additionally, AMP-activated protein kinase, Ca²⁺/calmodulin-dependent protein kinase signaling and many others are also implicated in OTR signaling in the CVS protection. These signaling events interact coordinately at many levels to suppress the production of inflammatory cytokines and the activation of apoptotic pathways. A particular target of these signaling events is endoplasmic reticulum (ER) stress and mitochondrial oxidative stress that interact through mitochondria-associated ER membrane. In contrast to these protective effects and machineries, rare but serious cardiovascular disturbances were also reported in labor induction and animal studies including hypotension, reflexive tachycardia, coronary spasm or thrombosis and allergy. Here, we review our current understanding of the protective effect of OT against varieties of atherosclerotic etiologies as well as the approaches and underlying mechanisms of these effects. Moreover, potential cardiovascular disturbances following OT application are also discussed to avoid unwanted effects in clinical trials of OT usages.

Oxytocin (OT), a nonapeptide, has a variety of functions. Despite extensive studies on OT over past decades, our understanding of its neural functions and their regulation remains incomplete. OT is mainly produced in OT neurons in the supraoptic nucleus (SON), paraventricular nucleus (PVN) and accessory nuclei between the SON and PVN. OT exerts neuromodulatory effects in the brain and spinal cord. While magnocellular OT neurons in the SON and PVN mainly innervate the pituitary and forebrain regions, and parvocellular OT neurons in the PVN innervate brainstem and spinal cord, the two sets of OT neurons have close interactions histologically and functionally. OT expression occurs at early life to promote mental and physical development, while its subsequent decrease in expression in later life stage accompanies aging and diseases. Adaptive changes in this OT system, however, take place under different conditions and upon the maturation of OT release machinery. OT can modulate social recognition and behaviors, learning and memory, emotion, reward, and other higher brain functions. OT also regulates eating and drinking, sleep and wakefulness, nociception and analgesia, sexual behavior, parturition, lactation and other instinctive behaviors. OT regulates the autonomic nervous system, and somatic and specialized senses. Notably, OT can have different modulatory effects on the same function under different conditions. Such divergence may derive from different neural connections, OT receptor gene dimorphism and methylation, and complex interactions with other hormones. In this review, brain functions of OT and their underlying neural mechanisms as well as the perspectives of their clinical usage are presented.