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Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

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Neural Regeneration Research 2024年第10期19卷 2202-2211页

作者： Chika Fujii Charles F.Zorumski Yukitoshi Izumi department of psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

关键词： allopregnanolone fluvoxamine ketamine neurosteroids postpartum depression quercetin

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Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

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Neural Regeneration Research 2024年第10期19卷 2212-2218页

作者： Yukitoshi Izumi Kazuko A.O'Dell Charles F.Zorumski department of psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

关键词： cognitive impairment glyphosate microglia neuroinflammation roundup toll-like receptor 4 zinc chelation

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Event segmentation in ADHD:neglect of social information and deviant theta activity point to a mechanism underlying ADHD

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General psychiatry 2024年第3期37卷 431-439页

作者： Astrid Prochnow Xianzhen Zhou Foroogh Ghorbani Veit Roessner Bernhard Hommel Christian Beste Cognitive neurophysiology Department of Child and Adolescent PsychiatryFaculty of MedicineTU DresdenDresdenGermany Faculty of Psychology Shandong Normal UniversityJinanShandongChina

Background Attention-deficit/hyperactivity disorder(ADHD)is one of the most frequently diagnosed psychiatric conditions in children and *** the symptoms appear to be well described,no coherent conceptual mechanistic framework integrates their occurrence and variance and the associated problems that people with ADHD *** The current study proposes that altered event segmentation processes provide a novel mechanistic framework for understanding deficits in *** Adolescents with ADHD and neurotypically developing(NT)peers watched a short movie and were then asked to indicate the boundaries between meaningful segments of the *** recorded electroencephalography(EEG)data were analysed for differences in frequency band activity and effective connectivity between brain *** Compared with their NT peers,the ADHD group showed less dependence of their segmentation behaviour on social information,indicating that they did not consider social information to the same extent as their unaffected *** divergence was accompanied by differences in EEG theta band activity and a different effective connectivity network architecture at the source ***,NT adolescents primarily showed error signalling in and between the left and right fusiform gyri related to social information processing,which was not the case in the ADHD *** the ADHD group,the inferior frontal cortex associated with attentional sampling served as a hub instead,indicating problems in the deployment of attentional *** This study shows that adolescents with ADHD perceive events differently from their NT peers,in association with a different brain network architecture that reflects less adaptation to the situation and problems in attentional sampling of environmental *** results call for a novel conceptual view of ADHD,based on event segmentation theory.

关键词： instead meaningful primarily

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Emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of Emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie department of Emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA department of psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

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Novel insights in phosphodiesterase 4 subtype inhibition to target neuroinflammation and stimulate remyelination

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Neural Regeneration Research 2024年第3期19卷 493-494页

作者： Melissa Schepers Tim Vanmierlo department of neuroscience Biomedical Research InstituteFaculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium department of psychiatry and neuropsychology School for Mental Health and NeuroscienceMaastricht UniversityMaastrichtNetherlands University MS Center(UMSC)Hasselt-Pelt HasseltBelgium

In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is ***,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon *** to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in ***,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.

关键词： impaired inflammation Marie

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Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri H.Juárez Adalberto Merighi department of Veterinary Sciences University of TurinGrugliascoTOItaly department of psychiatry and neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical *** have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue *** enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC *** increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

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Different concentrations of hyaluronic acid eye drops for dry eye syndrome: a systematic review and Meta-analysis

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1110-1119页

作者： Xiao-Wei Ouyang Sheng Fang Yun-Min Yi Shi-Peng Zou Qi-Yu Hu Zi-Xuan Huang Qing-Xia Li Jin-Yan Luo department of Ophthalmology Nanchang Hongdu Hospital of Traditional Chinese MedicineNanchang 330000Jiangxi ProvinceChina department of Ophthalmology Jiangxi Hospital of Integrated Traditional Chinese and Western MedicineNanchang 330000Jiangxi ProvinceChina department of Cataract Nanchang University Affiliated Eye HospitalNanchang 330000Jiangxi ProvinceChina department of neuro-ophthalmology Nanchang University Affiliated Eye HospitalNanchang 330000Jiangxi ProvinceChina

AIM:To compare high or low concentration of hyaluronic acid eye drops(HY)for dry eye syndromes(DES).METHODS:Randomized controlled trials(RCTs)comparing various concentrations of HY were searched in PubMed,Embase,Web of Science,Cochrane,SinoMed,CNKI,Wanfang Database,CQVIP,and Chinese journals databases between inception and July *** standardized mean differences(SMD)or weighted mean difference(WMD)with 95%confidence intervals(CI)from RCTs evaluating Schirmer’s I test(SIT),corneal fluorescein staining score(CFS),tear breakup time(TBUT),DES score(DESS),and Ocular Surface Disease Index(OSDI)were *** analysis,Egger’s test and Meta-regression analysis were performed for all ***:We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria,involving 1796 ***-concentrations group significantly improved the outcome of CFS according to random effects modelling(SMD,-3.37;95%CI,-5.25 to-1.48;P=0.0005).The rest of the results were not statistically significant,including indicators such as SIT,TBUT,DESS and ***:For dry eyes with positive corneal staining,a high concentration of HY is recommended,whereas in other cases,a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

关键词： dry eye hyaluronic acid concentration Meta-analysis

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Prevalence of prolonged grief disorder and its symptoms among bereaved individuals in China:a systematic review and meta-analysis

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General psychiatry 2024年第2期37卷 177-188页

作者： Meng-Di Yuan Jun-Fa Liu Bao-Liang Zhong Research Center for Psychological and Health Sciences China University of Geosciences(Wuhan)WuhanHubeiChina department of psychiatry Wuhan Mental Health CentreWuhanHubeiChina

Background The prevalence of prolonged grief disorder(PGD)and its symptoms among the bereaved population in China vary *** This meta-analysis aims to estimate the prevalence of PGD and its symptoms among bereaved individuals in *** We conducted a literature search in major Chinese and English databases from their inception to 4 October 2023,for cross-sectional studies on the prevalence of PGD or its symptoms in bereaved Chinese *** risk of bias of the included studies and certainty of the evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data(‘JBI checklist’)and the Grading of Recommendations,Assessment,Development and Evaluations(GRADE),***‘metaprop’package in R V.4.1.2 was used to synthesise the *** A total of 28 studies involving 10994 bereaved individuals were included in the analysis,with JBI checklist scores between 3 and *** combined prevalence(95%confidence interval)of PGD and its symptoms was 8.9%(4.2%to 17.6%)and 32.4%(18.2%to 50.8%),*** and its symptoms were most prevalent among those who had lost their only child(22.7%)and those bereaved by earthquakes(80.4%),*** GRADE system assigned a very low certainty level to the evidence for the pooled prevalence of PGD and its *** The pooled prevalence of PGD and its symptoms indicate a potential high need for grief counselling services among bereaved individuals in *** need is particularly pronounced in those who have lost their only child and those bereaved due to *** methodologically rigorous studies are needed to provide more accurate prevalence *** registration number CRD42023432553.

关键词： symptoms prevalence analysis

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Liquid biopsy for gastric cancer:Techniques,applications,and future directions

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World Journal of Gastroenterology 2024年第12期30卷 1680-1705页

作者： Cristina Díaz del Arco M Jesús Fernández Aceñero Luis Ortega Medina department of Surgical Pathology Health Research Institute of the Hospital Clínico San CarlosHospital Clínico San CarlosMadrid 28040Spain department of Legal Medicine Psychiatry and PathologyUniversidad Complutense de MadridMadrid 28040Spain

After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular vesicles,tumor-educated platelets,and other ***,research has extended to include the examination of samples other than blood or plasma,such as saliva,gastric juice,urine,or *** techniques are diverse,intricate,and *** must be highly sensitive,and pre-analytical,patient,and tumor-related factors significantly influence the detection threshold,diagnostic method selection,and potential ***,the implementation of LB in clinical practice still faces several *** potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases,monitoring treatment response,early identification of relapses,or assessing patient *** the other hand,gastric cancer(GC)is a disease often diagnosed at advanced *** recent advances in molecular understanding,the currently available treatment options have not substantially improved the prognosis for many of these *** application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these *** this comprehensive review,from a pathologist’s perspective,we provide an overview of the main options available in LB,delve into the fundamental principles of the most studied techniques,explore the potential utility of LB application in the context of GC,and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

关键词： Liquid biopsy Gastric cancer Circulating tumor cells Cell-free DNA Circulating tumor DNA Molecular

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Deciding on life-saving treatment after a violent suicide attempt:an ethical case report

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General psychiatry 2024年第2期37卷 289-291页

作者： Robert Wichers Hanna M Heller Sisco van Veen department of Child and Adolescent psychiatry&Psychosocial Care Amsterdam University Medical CenterLocation AMCAmsterdamThe Netherlands Amsterdam Public Health Mental Health programAmsterdamThe Netherlands department of Hospital psychiatry Amsterdam University Medical CenterLocation VUmcAmsterdamThe Netherlands Research department 113 Suicide PreventionAmsterdamThe Netherlands department of psychiatry&department of Ethics Law and HumanitiesAmsterdam University Medical CenterAmsterdamThe Netherlands GGZ inGeest Mental Health Care AmsterdamThe Netherlands

To the editor:In the USA alone,there were 1.7 million suicide attempts in 2021.1 Although the majority of suicide attempts are not fatal,immediate medical attention is often necessary,especially when violent methods are used.2 These methods include jumping from heights,using a firearm,crashing a motor vehicle,and lying down or jumping in front of a moving object.

关键词： treatment editor alone

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