Adverse effects of early-life stress:focus on the rodent neuroendocrine system

Early-life stress is associated with a high prevalence of mental illnesses such as post-traumatic stress disorders,attention-deficit/hyperactivity disorder,schizophrenia,and anxiety or depressive behavior,which constitute major public health problems.In the early stages of brain development after birth,events such as synaptogenesis,neuron maturation,and glial differentiation occur in a highly orchestrated manner,and external stress can cause adverse long-term effects throughout life.Our body utilizes multifaceted mechanisms,including neuroendocrine and neurotransmitter signaling pathways,to appropriately process external stress.Newborn individuals first exposed to early-life stress deploy neurogenesis as a stress-defense mechanism;however,in adulthood,early-life stress induces apoptosis of mature neurons,activation of immune responses,and reduction of neurotrophic factors,leading to anxiety,depression,and cognitive and memory dysfunction.This process involves the hypothalamus-pituitary-adrenal axis and neurotransmitters secreted by the central nervous system,including norepinephrine,dopamine,and serotonin.The rodent early-life stress model is generally used to experimentally assess the effects of stress during neurodevelopment.This paper reviews the use of the early-life stress model and stress response mechanisms of the body and discusses the experimental results regarding how early-life stress mediates stress-related pathways at a high vulnerability of psychiatric disorder in adulthood.

The Auxiliary Role of Large Language Models in Clinical Dialogues

In recent years,large language models(LLMs)have made significant progress in natural language processing(NLP).These models not only perform well in a variety of language tasks but also show great potential in the medical field.This paper aims to explore the application of LLMs in clinical dialogues,analyzing their role in improving the efficiency of doctor-patient communication,aiding in diagnosis and treatment,and providing emotional support.The paper also discusses the challenges and limitations of the model in terms of privacy protection,ethical issues,and practical applications.Through comprehensive analysis,we conclude that applying LLMs in clinical dialogues is promising.However,it requires careful consideration and caution by practitioners in practice.

Dysfunction of neuroendocrine system in sepsis and implication of hormone therapy

Sepsis and related syndromes are the major cause of multiple organ failure and death in patients with critical illnesses. Neuroendocrine dysfunction has long been thought to be an important event in sepsis. In clinic, optimal management of the hormones could alleviate severe complications in sepsis. In this article, we review the dysfunction ofneuroendocrine system as well as autonomic nervous system in sepsis, and summarize the respective therapy strategies.

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Practical hints for the diagnosis of mixed neuroendocrine-nonneuroendocrine neoplasms of the digestive system

In this editorial,a comment on the article by Díaz-López et al published in the recent issue of the 2024 is provided.We focus on the practical implications critical for providing a correct and complete diagnosis of mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)in the gastrointestinal system.The diagnosis of MiNEN begins with the recognition of neuroendocrine features in one component of a biphasic tumor.The non-neuroendocrine counterpart can be virtually represented by any neoplastic type,even though the most frequent histologies are glandular and squamous.However,qualification of the neuroendocrine component requires histological and immunohistochemical confirmation.Neuroendocrine tumors are characterized by a peculiar architectural organization and bland nuclei with granular“salt and pepper”chromatin.Although neuroendocrine carcinomas have multiple and variable presentations,they typically show a solid or organoid architecture.The histological aspect needs to be confirmed by immunohistochemistry,and a diagnosis is confirmed whenever the expression of keratin and neuroendocrine markers is observed.Once both histopathological and immunohistochemical features of neuroendocrine neoplasms are identified,it is important to consider the three major pitfalls of MiNEN diagnostics:(1)Entrapment of neuroendocrine non-neoplastic cells within the tumor mass;(2)Differential diagnosis with amphicrine neoplasms;and(3)Differential diagnosis of tumors that partially express neuroendocrine markers.According to the current guidelines for diagnosing digestive MiNEN,each component must represent at least 30%of the entire neoplastic mass.Although the high-grade histopathological subtype frequently determines disease prognosis,both components can significantly affect prognosis.Thus,if one of the components,either neuroendocrine or non-neuroendocrine,does not fulfill the volumetric criteria,the guidelines still encourage reporting it.These strict criteria are essential for correctly recognizing and characterizing digestive MiNENs.This task is essential because it has prognostic relevance and substantial potential value for guiding further studies in this field.In the future,systematic analyses should be performed to validate or reconsider the current 30%cutoff value.

Different lymph node staging systems for predicting the prognosis of colorectal neuroendocrine neoplasms

BACKGROUND Colorectal neuroendocrine neoplasms(NENs)are a rare malignancy that primarily arises from the diffuse distribution of neuroendocrine cells in the colon and rectum.Previous studies have pointed out that the status of lymph node may be used to predict the prognosis.AIM To investigate the predictive values of lymph node ratio(LNR),positive lymph node(PLN),and log odds of PLNs(LODDS)staging systems on the prognosis of colorectal NENs treated surgically,and compare their predictive values.METHODS This cohort study included 895 patients with colorectal NENs treated surgically from the Surveillance,Epidemiology,and End Results database.The endpoint was mortality of patients with colorectal NENs treated surgically.X-tile software was utilized to identify most suitable thresholds for categorizing the LNR,PLN,and LODDS.Participants were selected in a random manner to form training and testing sets.The prognosis of surgically treating colorectal NENs was examined using multivariate cox analysis to assess the associations of LNR,PLN,and LODDS with the prognosis of colorectal NENs.C-index was used for assessing the predictive effectiveness.We conducted a subgroup analysis to explore the different lymph node staging systems’predictive values.RESULTS After adjusting all confounding factors,PLN,LNR and LODDS staging systems were linked with mortality in patients with colorectal NENs treated surgically(P<0.05).We found that LODDS staging had a higher prognostic value for patients with colorectal NENs treated surgically than PLN and LNR staging systems.Similar results were obtained in the different G staging subgroup analyses.Furthermore,the area under the receiver operating characteristic curve values for LODDS staging system remained consistently higher than those of PLN or LNR,even at the 1-,2-,3-,4-,5-and 6-year follow-up periods.CONCLUSION LNR,PLN,and LODDS were found to significantly predict the prognosis of patients with colorectal NENs treated surgically.

Drama for Language Learning to Adult Learners Through Co-generative Dialogues

Drama is a motivational, powerful, and feasible technique and tool for language learning. Interactions in the class play an important role. Thus, teachers exploit a number of opportunities to give chance to participants for communication. Writing drama and enacting it can be a good space for generating discussion to develop language skills. Analysis of language interaction in drama focuses on negotiations of language. Co-generative dialogues help participants to focus on the social aspects of life. The interaction and communication to environment play a vital role as it conveys a positive message through performance and fulfills the socio effective requirement. As English Language teaching teachers, we always look for innovative and motivational ideas for language learning and thus, “Drama for language learning through co-generative dialogues” helped me to expand the repertoire of dynamics in the classroom. Drama included co-generative dialogues stage production and performance. It is a powerful and innovative medium for exploring and learning language. It communicated response, moods, and information to the audience. The research explored the effect of drama for language learning through co-generative dialogues, to build cultural awareness, create bondage, meet people, and solve problems.

Three Hypotheses on the Performance of Plato＇s Dialogues

This article examines some ideas on reading Plato by three scholars, dating from different decades of the 20th century and setting off from various theoretical starting points, who explored an alternative possibility by suggesting theories that incorporate the element of＂dramatic＂ performance. According to Auguste Diès the written dialogue is a literary version of a dialectical duel actually held in the Academy between a distinguished visitor and a selected group of students. Through the so-called process of＂transposition＂, Plato transforms a real life event into an artful piece of literature recreating the original scene for educational purposes. Gilbert Ryle, on the other hand, held that the dialogues were primarily intended for dramatic recitation in public, with Plato himself delivering the words of Socrates. They were delivered orally to audiences, as a rule in the context of literary competitions, in which the other Socratics also took part. Finally, Holger Thesleff has once suggested that the （re）performance of the dialogues as an established activity in the Academy constitutes a necessary stage in the composition of new works and the revision of the old ones. In view of his conviction that Plato was the inventor of the dramatic philosophical dialogue he also seemed to have been the first one who explicitly, however cautiously, entertained the idea of theatrical presentation of Plato＇s dialogues-though he later changed his mind and fallen back to the theory of public reading.

Analysis of Application of Relevance Theory in Listening Long Dialogues--Taking Long Dialogues in CET-4 Listening as Examples

Long dialogue listening is an important part of listening testin CET-4.Thispaper discussesthe explanatory power of Relevance Theory in the process of solving 16 listening long dialoguesin CET-4 listening testthrough quantitative and qualitative analysis.It adopts Relevance Theory to predict the context and listening problemsduring the pre-listening process.Then it uses Relevance Theory to analyze the turn-taking in conversationand understand the content of the long dialogues during the while-listening process.The application of Relevance Theory to CET-4 listening comprehension provides us with new inspiration for improving listening comprehension and listening teaching.

Pragmatic Analysis of the Dialogues in the Film The Great Gatsby

The Great Gatsby,is well acknowledged as Francis Scott Fitzgerald's masterpiece.It is so popular that it has been made into films for five times.This paper is trying to analysis the dialogues in the latest film version of it from the pragmatic perspective based on Grice 's conversational implicature,cooperative principle and Leech's politeness principle.

Pragmatic Analysis of Dialogues in Chinese and Foreign Films--On the Basis of Cooperative Principle

People speaking English and Chinese have their own ways of communication,which is reflected evidently in the mov ies.Movies are reaching their communicative purpose through the way of dialogues,mirroring the distinct cultures.this article is going to analyze the adjacency pairs from the movies The Devil Wears Prada(American) and Go LaLa Go!(China).How the CP is observed and broken differently by English and Chinese speakers respectively due to different cultural background in the adja cency pairs of the movies is going to be the main topic of our discussion.

An investigation of Communication Strategies used in Dialogues by Chinese English Major Students

This paper,through analyzing students'conversations based on SWECCL(Wen Qiufang etc,2005),makes an attempt to examine the use of CSs(Communication Strategies)by Chinese students in English major.The results show that the students are not competent in employing CSs,which is easily seen in their heavy reliance on Stalling and Reduction CSs.What's more,the CSs of L2-based are rarely employed in students' conversations.Apart from the above CSs,students who are in high proficiency group have more inclination to use Cooperation CS,while those who are in low proficiency group are more likely to turn to the CSs of Reduction,Substitution,and Literal Translation.

An Analysis of Fictional Dialogues of Love in a Fallen City in the Light of Relevance Theory

Although literary works are imaginary,they are based on careful observations of the real world.The fictional world is an imitation of the real world.So there is a strong similarity between them.The character utterances in fictions may be artificial in reality,but they are true in fictions.Therefore,pragmatic theories also have validity for literary interaction in theory.The au thor analyzes the fictional dialogues in Eileen Chang' s novel——Love in a Fallen City under the framework of the communica tion model based on Relevance Theory.In the academic field,Relevance Theory has been applied to explain a wide range of phenomena in translation,stylistics,phonology,and English teaching.However,the researches on mass communication discourse are still on the development.

Non-traditional Dialogues between Thoughts

The article considers a new and non-traditional form of dialogue. Calling it a ＂spiritual dialogue＂ or the intersection of thoughts, the author comments on this type of dialogue as a basis for interreligious, intercultural and intercivilizational dialogues, seeing it as their main motive force. In this study, firstly, traditional and non-traditional dialogues are compared and indicate their specific features on the basis of the work of the Eastern and the West thinkers. Then, the nontraditional dialogue has been considered in the context of modern information chaos. The last section of the article is devoted to the analysis of the basic principles of non-traditional dialogue, emphasizing the role of language. The conclusion of the article once again highlights the importance of non-traditional dialogue that starts in the inner world of the human being, which gives him a possibility to observe an object from two viewpoints and merge and these different views in the mind.

Rhetorical Devices in Dialogues of The Big Bang Theory

This paper analyzes the effect of rhetorical devices, such as irony, sarcasm, parody, hyperbole, pun, antonomasia, etc., in dialogues of the American TV series The Big Bang Theory （2007） with an aim to help improve English learners＇ awareness and appreciation of rhetorical means in English-based literary works. Instances are cited with the use of such rhetoric means in the dialogue transcriptions. It is discovered that integrated use of a variety of rhetorical devices is a significant means for vivid and impressive characterization in literature. Such an analysis is a rewarding journey on either an academic or entertainment basis, and a process of discovery and learning that may particularly be well-received with EFL （English as a Foreign Language） learners

A Pragmatic-Stylistic Analysis of Fictional Dialogues in Kazuo Ishiguro’s Short Story“Come Rain or Come Shine”

This study investigates the applicability and effectiveness of pragmatic-stylistic analysis in fictional dialogues.Taking Kazuo Ishiguro’s short story“Come Rain or Come Shine”in Nocturnes:Five Stories of Music and Nightfall as a case study,a detailed analysis of four fictional dialogues in this story has been conducted in the light of the cooperative principle,the im/politeness theory,and the turn-taking theory.The study has shown that pragmatic-stylistics offers a useful analytical tool in guiding readers to stylistically read character speech forms and interpret textual cues in conversation so as to gain a better insight into the characters’traits,their power relationships as well as the acceleration and deceleration in the narrative development.

A Study of Dialogues about Human Nature in Lord of the Flies

Lord of the Flies is Golding’s most famous and representative novel,which contains many types of dialogues between the characters.Dialogue is a way to communicate and show one’s opinion on a certain topic,which reveals the characters’characteristics,ultimately the human nature.Based on Bakhtin’s three dialogic devices—the syncrisis,the anacrisis and the diatribe,this thesis analyses the dialogues between the characters in Lord of the Flies which reflect the end of innocence and the darkness of human nature.

The Translation of Fictional Dialogues in the Light of Conversational Implicature Theory——A Case Study of The Outstation

This paper is intended to focus on the translation of fictional dialogues,and to explore the specific translation methods in the choice of emotional words to convey the speaker’s conversational implicature in the fiction The Outstation under the guidance of conversational implicature theory.

Progress in immunotherapy for neuroendocrine neoplasm of the digestive system

Neuroendocrine neoplasms(NENs)are rare heterogeneous tumors that can develop in almost any organ,with the digestive organs,including the gastrointestinal tract and pancreas being the most commonly affected sites.Despite the fact that advances in initial therapies have progressed,there is presently no recognized effective treatment for advanced NEN.Immune checkpoint inhibitors(ICIs)have shown superior efficacy in treating several types of solid tumors.Despite their successful role in the treatment of partial NENs,such as small cell lung cancer,and Merkel cell carcinoma,the role of ICIs in most of the NENs remains limited.Nevertheless,due to their specific anti-tumor mechanisms and acceptable safety profile,ICIs are a promising avenue for further study in NENs therapy.Recent clinical trials have illustrated that combination therapy with ICI is more efficient than monotherapy,and multiple clinical trials are constantly ongoing to evaluate the efficacy and safety of these combination therapies.Therefore,the purpose of this review is to provide a comprehensive summary of the clinical progress of immunotherapy in NENs affecting the digestive system,with a specific emphasis on the application of programmed cell death protein 1/programmed death receptor ligand 1 inhibitor.Furthermore,this review has an exploration of the potential beneficiary population and the inherent value of utilizing immunotherapy in the management of NENs.

Mixed neuroendocrine non-neuroendocrine tumors:The quest for evidence

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are rare mixed tumors containing both neuroendocrine and non-neuroendocrine components that occupy at least 30%of the whole tumor.Biologically,both components appear to derive from an identical cellular precursor undergoing early dual differentiation or late transdifferentiation.While our understanding of MiNENs has improved in recent years,many areas of uncertainty remain.In this context,setting diagnostic criteria capable of capturing the continuum of disease biology while providing clinically meaningful information in terms of prognosis and response to treatments appears vital to advance the field and improve patients’outcomes.Evidence is needed to generate robust classification schemes,and multi-institutional cooperation will likely play a crucial role in building adequately powered cohorts to address some of the most pressing questions discussed in this Editorial.What is the minimum representation for each component needed to define MiNENs?How can the epidemiology of MiNENs change according to different diagnostic definitions?How can we generate the clinical evidence nee-ded to optimize the management of MiNENs?