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This article reported a case of a patient with schizophrenia who experienced self-perceived fever and discomfort after taking atypical antipsychotic drugs with strong alpha 1 receptor antagonism， which included olanzapine， risperidone， paliperidone and clozapine. Such phenomenon was believed to be a medication side effect. Therefore， the patient switched to aripiprazole and the fever disappeared. This case report is intended to remind psychiatrists to pay attention to the side effects caused by atypical antipsychotic drugs with strong alpha 1 receptor antagonism as well as to suggest that various factors should be considered， including mechanisms of drug action， patient pathophysiology and individual differences， in order to improve treatment compliance and prognosis.
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Purpose@#We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.) Materials and Methods: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. @*Results@#2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245–0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0–48 hours vs. 48–53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. @*Conclusion@#EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.
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Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pediatric myofibroma/myofibromatosis of the soft tissue and bone. Methods: All cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone diagnosed between January 2011 and December 2018 were retrieved from the surgical pathology records in the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China. Clinical and radiological data were collected. H&E and immunohistochemistry were used to examine histological and immunophenotypic features and to make the diagnosis and differential diagnosis. The relevant literature was also reviewed. Results: Twenty-eight cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone were respectively collected. The patients' ages ranged from 2 months to 14 years, with a mean age of 7 years. There were 7 females and 21 males. There were 12 cases located in soft tissue, including the finger (n=9), upper arm (n=1) and foot (n=2). There were 14 cases located in the bone of limb, including the femur (n=8), tibia (n=4), clavicle (n=2), fibula (n=2) and radius (n=1). There were 2 cases of myofibromatosis involving multiple bones. Radiology showed lytic lesions in the bone. The proliferation of spindle-shaped myofibroblasts arranged in fascicles with indistinct eosinophilic cytoplasm and bland nuclei, with no pleomorphism and cytological atypia. The characteristic histologic structure was the biphasic nodular growth pattern with cellular and paucicellular regions. The tumors might arrange in a hemangiopericytoma-like pattern. The stroma varied between dense fibrosis and myxoid changes. The reactive new bone formation and inflammatory cell infiltration also existed. Immunohistochemical study showed that the SMA was positive. The surgical resections were performed. One of the patients had tumor recurrence as a result of 11-month follow-up. Conclusions: The pediatric myofibroma/myofibromatosis of the soft tissue and bone is a very rare benign tumor and has a good prognosis. It has a characteristic morphology and its differential diagnosis from other spindle cell tumors could be made with the immunohistochemical analysis.
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Child , Female , Humans , Infant , Male , Child, Preschool , Adolescent , Bone and Bones/pathology , Diagnosis, Differential , Leiomyoma , Myofibroma/diagnosis , Myofibromatosis/diagnosisABSTRACT
Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information,with its application to neuroscience termed neuroinformatics.Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms,which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases.Importantly,integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile.In this review,we first summarize data mining studies utilizing datasets from the individual type of omics analysis,including epigenetics/epigenomics,transcriptomics,proteomics,metabolomics,lipidomics,and spatial omics,pertaining to Alzheimer's disease,Parkinson's disease,and multiple sclerosis.We then discuss multi-omics integration approaches,including independent biological integration and unsupervised integra-tion methods,for more intuitive and informative interpretation of the biological data obtained across different omics layers.We further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain networks.Finally,we recommend a combination of high dimensional bio-informatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery,therapeutic development,and elucidation of disease mechanisms.We conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personalized medicine.
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Aim To investigate the potential protein post-translational modifications of psychedelic-induced Head-twith response and underling mechanism. Methods Psychedelics LSD, DOM, or Psilocin was administered to rats by intraperitoneal injection to induce head-twitch response, then the most effective dosage was identified to create animal models of head-twitch behavior. Western blot was performed in detecting the protein phosphorylation, acetylation, and ubiquitination in prefrontal cortex of SD rats after 10 min or 30 min injection. Results LSD (0.025 mg • kg~, i. p.), DOM (3 mg•kg
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The serotonin 2A receptor(5-HT
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Ketamine has been used clinically as an analgesic and anesthetic since 1970. Recently, it has been concerned due to its rapid and effective antidepressant effect. However, the psychiatric adverse reactions caused by ketamine such as addiction and hallucination limit its clinical application, yet the mechanism of the adverse reactions is still unclear. At present, it is generally believed that the pharmacological effects of ketamine are mainly mediated by N-methyl-D-aspartate acid (NMDA) receptors, but increasing numbers of research evidences suggest that the opioid receptor also play an important role in the pharmacological effects of ketamine. This review, based on the relevant literature published publicly in the past 20 years, summarizes the mechanisms of opioid receptors in the pharmacological effects of ketamine, such as anesthesia, analgesia, anti-depressant, anti-addiction and addiction, providing reference for revealing the mechanism of ketamine, and making beneficial exploration for solving the clinical side effects of ketamine.
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Over the past few years, the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health. Individuals with compromised immune function encounter distinctive challenges due to their heightened vulnerability to a diverse range of infectious diseases. This review aims to comprehensively explore and analyze the growing evidence regarding the role of the virome in immunocompromised disease status. By surveying the latest literature, we present a detailed overview of virome alterations observed in various immunodeficiency conditions. We then delve into the influence and mechanisms of these virome changes on the pathogenesis of specific diseases in immunocompromised individuals. Furthermore, this review explores the clinical relevance of virome studies in the context of immunodeficiency, highlighting the potential diagnostic and therapeutic gains from a better understanding of virome contributions to disease manifestations.
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Humans , Viruses , Virome , Microbiota , Immunologic Deficiency SyndromesABSTRACT
Although antiretroviral therapy (ART) can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus (HIV)-infected individuals, ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs. To achieve a functional cure for HIV infection, numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART. Early studies have tested adoptive T-cell therapies in HIV-infected individuals, but their effectiveness was limited. In recent years, with the technological progress and great success of chimeric antigen receptor (CAR) therapy in the treatment of hematological malignancies, CAR therapy has gradually shown its advantages in the field of HIV infection. Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells. Therefore, CAR therapy may be beneficial for enhancing HIV immunity, achieving HIV control, and eliminating HIV reservoirs, gradually becoming a promising strategy for achieving a functional HIV cure. In this review, we provide an overview of the design of anti-HIV CAR proteins, the cell types of anti-HIV CAR (including CAR T cells, CAR natural killer cells, and CAR-encoding hematopoietic stem/progenitor cells), the clinical application of CAR therapy in HIV infection, and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.
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Humans , Immunotherapy, Adoptive , HIV Infections/therapy , HIV-1ABSTRACT
BACKGROUND@#T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines.@*METHODS@#Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose.@*RESULTS@#Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W.@*CONCLUSIONS@#TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.