Neuroimmunomodulation最新文献

{"title":"Association of the biopsychosocial factors adverse childhood experiences, adult attachment style, emotion regulation and mitochondrial biogenesis with major depressive disorder.","authors":"Katharina Strecker, Eun-Jin Sim, Kathrin Woike, Carlos Schönfeldt-Lecuona, Peter Radermacher, Alexander Karabatsiakis, Markus Kiefer","doi":"10.1159/000544833","DOIUrl":"https://doi.org/10.1159/000544833","url":null,"abstract":"<p><strong>Introduction: </strong>Major depressive disorder (MDD) is one of the most prevalent mental disorders associated with various negative impacts such as lower overall quality of life, increased morbidity risk, and even premature mortality. According to the biopsychosocial model of health and disease, multiple factors contribute to the development and manifestation of MDD. Here, we assessed social, psychological, and biological variables and tested their power to predict MDD diagnosis using logistic regression models.</p><p><strong>Methods: </strong>In twenty-four patients with current MDD diagnosis and thirty-five healthy control participants, the following variables were measured to test for associations with MDD diagnosis: (1) emotional neglect and adult attachment style as social variables, (2) thought suppression and cognitive reappraisal as psychological variables, and (3) mitochondrial biogenesis (citrate synthase activity as a surrogate marker of mitochondrial density) measured in peripheral blood mononuclear cells (PBMC) as a biological variable.</p><p><strong>Results: </strong>The following biopsychosocial variables were associated with MDD diagnosis. Participants with greater emotional neglect (OR: 1.273, 95 % Cl: 1.059-1.645), higher levels of intrusive thoughts (OR: 1.738, 95 % Cl: 1.282-3.066), and decreased mitochondrial density in PBMC (OR: 0.298, 95 % Cl: 0.083-0.784) had a higher probability of belonging to the MDD group.</p><p><strong>Conclusions: </strong>In line with biopsychosocial models of depression, the present results indicate that variables at different level of analysis are conjointly related to MDD. These findings open new perspectives for the diagnosis and treatment of MDD, but they need to be replicated in larger samples in the future.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-21"},"PeriodicalIF":2.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KETO-MOOD: Ketogenic Diet for Microbiome Optimization and Overcoming Depression - A Protocol for a Randomized Controlled Trial.","authors":"Katarzyna Hongler, Astrid Lounici, Erin Maurer, Ueli Lanz, Orsolya Szathmari, Yvonne Reuter, Sandra Nussbaum, Ines Steinborn, Annika Haedrich, Melina A Mölling, Ulf Wein, Iona Bocek, Luca Hersberger, Annette B Brühl, Undine E Lang, Timur Liwinski","doi":"10.1159/000542979","DOIUrl":"10.1159/000542979","url":null,"abstract":"<p><strong>Introduction: </strong>Major depressive disorder (MDD) significantly impacts millions worldwide, with limited success in achieving remission for many patients, leading to high disease burden and increased suicide risk. Psychotherapy and antidepressants, although effective, do not provide relief for all, prompting the search for alternative treatments. Ketogenic diets have demonstrated positive effects on brain health. Our study aims to investigate the efficacy of the ketogenic diet in alleviating MDD symptoms, filling a critical gap in psychiatric treatment options and offering a novel dietary approach with potential to mitigate disease burden and enhance mental well-being.</p><p><strong>Methods: </strong>This phase 2 randomized controlled trial will evaluate the efficacy of a 10-week program of dietitian counseling and ketogenic meal provision versus an intervention with similar dietetic contact promoting a healthy, insulin-lowering, non-ketogenic diet. The primary outcome is the change in the Patient Health Questionnaire nine-item depression score. Secondary outcomes include cognitive and affective mindfulness, self-efficacy, sleep, cognitive function, work and social adjustment, and various immunological, metabolic, and microbiome markers at weeks 6 and 10.</p><p><strong>Conclusion: </strong>This study addresses a critical gap in depression treatment by exploring the ketogenic diet's potential as a metabolic mood enhancing intervention. Given the global impact of depression and limitations of current therapies, this research is valuable for exploring previously underappreciated neuroprotective and metabolic mechanisms and clinical benefits.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"36-48"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Sex-Specific Effects of Early Life Adversity and Chronic Psychosocial Stress during Adulthood on Bone Are Mitigated by Mycobacterium vaccae NCTC 11659 in Mice.","authors":"Dorothea Gebauer, Tamara Schimmele, Giulia Mazzari, Benjamin T Krüger, Msgana Zemui, Anita Ignatius, Dominik Langgartner, Melanie Haffner-Luntzer, Stefan O Reber","doi":"10.1159/000543507","DOIUrl":"10.1159/000543507","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic stress is a major burden in our society and increases the risk for various somatic and mental diseases, in part via promoting chronic low-grade inflammation. Interestingly, the vulnerability for chronic stress during adulthood varies widely among individuals, with some being more resilient than others. For instance, women, relative to men, are at higher risk for developing typical stress-related diseases, including depression and post-traumatic stress disorder (PTSD). Moreover, the experience of early life adversity (ELA) may increase an individuals' vulnerability for chronic stress during adulthood (CAS), possibly due to its association with chronic inflammation. Because severe consequences of stress-induced immune activation are a dysregulated endochondral ossification, delayed long-bone growth, and bone regeneration following fracture, the aim of this study was to investigate the sex-specific effects of ELA alone or in combination with CAS on bone. As enhancement of an individuals' immunoregulatory potential by repeated administrations of a heat-inactivated preparation of Mycobacterium vaccae NCTC (National Collection of Type Cultures) 11659 has been shown to promote stress resilience in mice, we further aimed to investigate if M. vaccae NCTC 11659 also protects against the negative effects of ELA/CAS on bone.</p><p><strong>Methods: </strong>Male and female C57BL/6N mice were subjected to ELA using a maternal separation (MS) model. CAS was induced by either using the chronic subordinate colony housing (CSC) paradigm in males or the social instability paradigm (SIP) in females. The effects on bone were evaluated by µCT, histological, and gene expression analysis. M. vaccae NCTC 11659 was administered repeatedly s.c. prior to CAS.</p><p><strong>Results: </strong>No cumulative impact of ELA and CAS on bone could be detected. Female mice seem to be more susceptible to ELA while male mice to CAS. Importantly, repeated M. vaccae NCTC 11659 administrations were able to mitigate the negative consequences of stress on bone in both sexes.</p><p><strong>Conclusion: </strong>Our results support the hypotheses that the negative effects of ELA and CAS on bone are highly sex-dependent. Moreover, repeated s.c. administrations with immunoregulatory microorganisms might be a future therapeutic option for stress-related bone disorders.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"49-66"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Oral Administration of the Probiotic Lactobacillus rhamnosus GG on the Proteomic Profiles of Cerebrospinal Fluid and Immunoregulatory Signaling in the Hippocampus of Adult Male Rats.","authors":"Kelsey M Loupy, Lamya'a M Dawud, Cristian A Zambrano, Thomas Lee, Jared D Heinze, Ahmed I Elsayed, James E Hassell, Heather M D'Angelo, Matthew G Frank, Steven F Maier, Lisa A Brenner, Christopher A Lowry","doi":"10.1159/000544842","DOIUrl":"10.1159/000544842","url":null,"abstract":"<p><strong>Introduction: </strong>The microbiome-gut-brain axis, by modulating bidirectional immune, metabolic, and neural signaling pathways in the host, has emerged as a target for the prevention and treatment of psychiatric and neurological disorders. Oral administration of the probiotic bacterium Lactobacillus rhamnosus GG (LGG; ATCC 53103) exhibits anti-inflammatory effects, although the precise mechanisms by which LGG benefits host physiology and behavior are not known. The goal of this study was to explore the general effects of LGG on the cerebrospinal fluid (CSF) proteome and a biological signature of anti-inflammatory signaling in the central nervous system (CNS) of undisturbed, adult male rats.</p><p><strong>Methods: </strong>Liquid chromatography-tandem mass spectrometry-based proteomics were conducted using CSF samples collected after 21 days of oral treatment with live LGG (3.34 × 107 colony-forming units (CFU)/mL in the drinking water (resulting in an estimated delivery of ∼1.17 × 109 CFU/day/rat) or water vehicle. Gene enrichment analysis (using DAVID, v. 6.8) and protein-protein interactions (using STRING, v. 11) were used to explore physiological network changes in CSF. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was performed to assess gene expression changes of anti-inflammatory cytokines in the hippocampus. Genes associated with anti-inflammatory signaling that were analyzed included Il10, Tgfb1, Il4, and IL-4-responsive genes, Cd200, Cd200r1, and Mrc1 (Cd206).</p><p><strong>Results: </strong>Oral LGG administration altered the abundance of CSF proteins, increasing the abundance of five proteins (cochlin, NPTXR, reelin, Sez6l, and VPS13C) and decreasing the abundance of two proteins (CPQ, IGFBP-7) in the CSF. Simultaneously, LGG increased the expression of Il10 mRNA, encoding the anti-inflammatory cytokine interleukin 10, in the hippocampus.</p><p><strong>Conclusion: </strong>Oral LGG altered the abundance of CSF proteins associated with extracellular scaffolding, synaptic plasticity, and glutamatergic signaling. These data are consistent with the hypothesis that oral administration of LGG improves memory and cognition, and promotes a physiological resilience to neurodegenerative disease, by increasing glutamatergic signaling and promoting an anti-inflammatory environment in the brain.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"94-109"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Perinatal Microbiota-Gut-Brain Axis: Implications for Postpartum Depression.","authors":"Marie Armbruster, Paul Forsythe","doi":"10.1159/000543691","DOIUrl":"10.1159/000543691","url":null,"abstract":"<p><strong>Background: </strong>Pregnancy and childbirth are accompanied by widespread maternal physiological adaptations and hormonal shifts that have been suggested to result in a period of vulnerability for the development of mood disorders such as postpartum depression (PPD). There is also evidence of peripartum changes in the composition of the gut microbiota, but the potential contribution of intestinal microbes to the adaptations, or subsequent vulnerabilities, during this period are unknown.</p><p><strong>Summary: </strong>Here, we outline key pathways involved in peripartum adaptations including GABAergic signaling, oxytocin, and immunomodulation that are also associated with susceptibility to mood disorders and present evidence that these pathways are modulated by gut microbes. We also discuss the therapeutic potential of the microbiota-gut-brain axis in PPD and identify future directions for research to help realize this potential.</p><p><strong>Key messages: </strong>Peripartum adaptations are associated with shifts in gut microbial composition. Disruption of GABAergic, oxytocin, and immunomodulatory pathways may contribute to vulnerability of mood disorders including PPD. These key adaptive pathways are modulated by intestinal microbes suggesting a role for the gut microbiota in determining susceptibility to PPD. More research is needed to confirm relationship between gut microbes and PPD and to gain the mechanistic understanding required to realize the therapeutic potential of microbiota-gut-brain axis in this mood disorder.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"67-82"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The saNeuroGut Initiative: Investigating the Gut Microbiome and Symptoms of Anxiety, Depression, and Posttraumatic Stress.","authors":"Michaela A O'Hare, Patricia C Swart, Stefanie Malan-Müller, Leigh L van den Heuvel, Erine Bröcker, Soraya Seedat, Sian M J Hemmings","doi":"10.1159/000542696","DOIUrl":"10.1159/000542696","url":null,"abstract":"<p><strong>Introduction: </strong>Common mental disorders, such as anxiety disorders, depression, and posttraumatic stress disorder (PTSD), present a substantial health and economic burden. The gut microbiome has been associated with these psychiatric disorders via the microbiome-gut-brain axis. However, previous studies have focused on the associations between the gut microbiome and common mental disorders in European, North American, and Asian populations. As part of the saNeuroGut Initiative, we assessed associations between gut microbial composition and self-reported symptoms of anxiety, depression, and posttraumatic stress (PTS) among South African adults.</p><p><strong>Methods: </strong>Participants completed validated, online self-report questionnaires to evaluate symptoms of state anxiety, trait anxiety, depression, and PTSD. Eighty-six stool-derived microbial DNA samples underwent sequencing of the V4 region of the 16S rRNA gene to characterise gut bacterial taxa in the sample.</p><p><strong>Results: </strong>No significant associations were observed between symptom severity scores and alpha (Shannon and Simpson indices) and beta (Aitchison distances) diversity metrics. Linear regression models revealed that the abundances of Catenibacterium, Collinsella, and Holdemanella were significantly positively associated with the severity of PTS symptoms.</p><p><strong>Conclusion: </strong>Catenibacterium, Collinsella, and Holdemanella have each previously been associated with various psychiatric disorders, with Catenibacterium having been positively associated with symptoms of PTSD in another South African cohort. This study sheds light on the relationship between the human gut microbiome and symptoms of anxiety, depression, and PTS in a South African adult sample.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-15"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological Approaches in the Diagnosis and Treatment of Psychiatric Disorders: A Historical Overview.","authors":"Norbert Müller","doi":"10.1159/000542784","DOIUrl":"10.1159/000542784","url":null,"abstract":"<p><strong>Background: </strong>For over 130 years, scientists have been suggesting that infection and inflammation may play a role in psychosis and other psychiatric disorders. First attempts to treat psychosis by immune-modulating therapies were made early in the last century; however, after the development of antipsychotics in the 1950s, scientific interest shifted away from immunological aspects of psychiatric disorders to the involvement of catecholamines, in particular dopamine, in psychosis.</p><p><strong>Summary: </strong>Antipsychotic treatment was not as successful as expected, so the 1990s saw renewed interest in inflammation and psychoneuroimmunological research in schizophrenia and beyond. In parallel, advances in immunological research methods allowed immunological and inflammatory mechanisms to be studied in more detail.</p><p><strong>Key messages: </strong>Clinical studies and meta-analyses have demonstrated positive effects of anti-inflammatory treatment in certain patients with psychiatric disorders. More research is needed to elucidate exactly how immunological mechanisms result in disease pathophysiology, with the aim to improve anti-inflammatory and personalized treatments.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"16-23"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regular Positive Human Contacts Do Not Improve Pigs' Response to a Lipopolysaccharide Immune Challenge.","authors":"Oceane Schmitt, Christian Knecht, Birgit Sobczak, Hana Volkmann, Ulrike Gimsa, Jean-Loup Rault","doi":"10.1159/000544748","DOIUrl":"10.1159/000544748","url":null,"abstract":"<p><strong>Introduction: </strong>Little is known about the effects of a positive human-animal relationship on animal health and resilience. This study investigated the effects of regular positive human-animal interactions on pigs' response to an immune challenge.</p><p><strong>Methods: </strong>Twenty-four female pigs were recruited at weaning (5 weeks old), and siblings of similar weights were allocated to either the positive contact treatment with positive contacts given by a human to groups of 3 pigs in their home pen or the control treatment only exposed to a human standing immobile and silently in front and outside their home pen. Treatment sessions were applied over 9 consecutive weeks, lasted 10 min per group, and occurred twice daily (morning and afternoon), 3 days a week. At 16 weeks of age, pigs were submitted to an immune challenge, which consisted of a single intravenous administration of lipopolysaccharide (LPS; 2 µg/kg). The sickness behaviours of pigs were observed using scan sampling every 5 min over 6 h post-administration, recording somnolence, vomiting, diarrhoea, cramping, shivering, and panting. Blood samples were taken before the LPS administration, after 1 h and 3 h. Blood plasma was analysed to quantify tumour necrosis factor alpha, interleukins 6 and 10, immunoglobulin A, and cortisol concentrations, and blood serum was analysed to quantify a brain-derived neurotrophic factor. Behavioural and physiological data were statistically analysed using general linear models in R.</p><p><strong>Results: </strong>Both treatments showed signs of sickness behaviour following LPS administration, but the two treatments did not differ in the frequency, severity of sickness behaviours, or length of recovery or in the blood plasma concentration of cytokines and cortisol measured.</p><p><strong>Conclusion: </strong>Therefore, regular exposure to positive contacts with a human over several weeks, although leading to the development of a positive human-animal relationship, did not enhance the pigs' response to this immune challenge or the immune parameters measured in this study.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"83-93"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Brief Historic Review of Research on Early Life Stress and Inflammation across the Lifespan.","authors":"Sonja Entringer, Christine Heim","doi":"10.1159/000542676","DOIUrl":"10.1159/000542676","url":null,"abstract":"<p><strong>Background: </strong>Extensive evidence from animal and human studies indicates that exposure to stress during sensitive developmental periods significantly increases the risk for psychiatric and physical disorders, resulting in reduced longevity. Chronic immune activation has been suggested as one pathway through which early adverse experiences may become biologically embedded. This paper highlights selected key findings and questions that first emerged in the literature and founded the field and then examines how research methods and questions have evolved over time.</p><p><strong>Summary: </strong>During the past decades, evidence from preclinical, clinical, and epidemiological studies has accumulated suggesting consequences of early life stress (ELS) exposure for immune function, particularly increased chronic inflammation or inflammatory responses. Scientific approaches to study the effects of ELS on the immune system have changed since the first studies on this topic were published.</p><p><strong>Key messages: </strong>Across different study designs, species, and methods, a consistent association between childhood adversity and a pro-inflammatory phenotype has been reported. We critically discuss which topics warrant further consideration and how current findings could be used to develop targeted interventions to prevent or reverse the biological embedding of ELS and resultant disease manifestations.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"24-35"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000542667","DOIUrl":"10.1159/000542667","url":null,"abstract":"","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1"},"PeriodicalIF":2.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}