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ALG6-congenital disorder of glycosylation (ALG6-CDG) is a complex of rare inherited disorders caused by mutations in the ALG6 gene, which encodes the α-1,3-glucosyltransferase enzyme required for N-glycosylation. ALG6-CDG affects multiple systems and exhibits clinical heterogeneity. Besides developmental delays and neurological signs and symptoms, behavioral and psychological symptoms are also an important group of clinical features of ALG6-CDG. Here, we present the case of a 17-year-old Chinese girl with ALG6-CDG who first visited the psychiatric department with apathy, language reduction, and substupor symptoms. The psychiatric assessments and treatment processes performed are described and discussed in this report. During diagnostic process, we found a novel mutation, c.849delT, in ALG6 by whole-exome sequencing. The patient's symptoms improved with escitalopram and risperidone treatment. However, above a certain dosage, she was sensitive to extrapyramidal side effects. This study accumulates clinical experience for diagnosing and treating ALG6-CDG and improves our understanding of this rare genetic disorder.
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Ageing and fertility are intertwined. Germline loss extends the lifespan in various organisms, termed gonadal longevity. However, the original longevity signal from the somatic gonad remains poorly understood. Here, we focused on the interaction between germline stem cells (GSCs) and their niche, the distal tip cells (DTCs), to explore the barely known longevity signal from the somatic gonad in C. elegans. We found that removing germline disrupts the cell adhesions between GSC and DTC, causing a significant transcriptomic change in DTC through hmp-2/ß-catenin and two GATA transcription factors, elt-3 and pqm-1 in this niche cell. Inhibiting elt-3 and pqm-1 in DTC suppresses gonadal longevity. Moreover, we further identified the TGF-ß ligand, tig-2, as the cytokine from DTC upon the loss of germline, which evokes the downstream gonadal longevity signalling throughout the body. Our findings thus reveal the source of the longevity signalling in response to germline removal, highlighting the stem cell niche as a critical signalling hub in ageing.
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Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery, posing significant challenges to orthopedic surgeons. Due to the lack of a definitive diagnostic gold standard, timely treatment initiation is problematic, resulting in substantial economic burdens on patients and society. In this review, we thoroughly analyze the complexities of PJI and emphasize the importance of accurate diagnosis and effective treatment. The article specifically focuses on the advancements in diagnostic techniques, ranging from traditional pathogen culture to advanced molecular diagnostics, and discusses their role in enhancing diagnostic accuracy. Additionally, we review the latest surgical management strategies, including everything from debridement to revision surgeries. Our summary aims to provide practical information for the diagnosis and treatment of PJI and encourages further research to improve diagnostic accuracy and treatment outcomes.
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Background: The use of pre- and perinatal risk factors as predictive factors may lower the age limit for reliable autism prediction. The objective of this study was to develop a clinical model based on these risk factors to predict autism. Methods: A stepwise logistic regression analysis was conducted to explore the relationships between 28 candidate risk factors and autism risk among 615 Han Chinese children with autism and 615 unrelated typically developing children. The significant factors were subsequently used to create a clinical risk score model. A chi-square automatic interaction detector (CHAID) decision tree was used to validate the selected predictors included in the model. The predictive performance of the model was evaluated by an independent cohort. Results: Five factors (pregnancy influenza-like illness, pregnancy stressors, maternal allergic/autoimmune disease, cesarean section, and hypoxia) were found to be significantly associated with autism risk. A receiver operating characteristic (ROC) curve indicated that the risk score model had good discrimination ability for autism, with an area under the curve (AUC) of 0.711 (95% CI=0.679-0.744); in the external validation cohort, the model showed slightly worse but overall similar predictive performance. Further subgroup analysis indicated that a higher risk score was associated with more behavioral problems. The risk score also exhibited robustness in a subgroup analysis of patients with mild autism. Conclusion: This risk score model could lower the age limit for autism prediction with good discrimination performance, and it has unique advantages in clinical application.
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The extrinsic diet and the intrinsic developmental programs are intertwined. Although extensive research has been conducted on how nutrition regulates development, whether and how developmental programs control the timing of nutritional responses remain barely known. Here, we report that a developmental timing regulator, BLMP-1/BLIMP1, governs the temporal response to dietary restriction (DR). At the end of larval development, BLMP-1 is induced and interacts with DR-activated PHA-4/FOXA, a key transcription factor responding to the reduced nutrition. By integrating temporal and nutritional signaling, the DR response regulates many development-related genes, including gska-3/GSK3ß, through BLMP-1-PHA-4 at the onset of adulthood. Upon DR, a precocious activation of BLMP-1 in early larval stages impairs neuronal development through gska-3, whereas the increase of gska-3 by BLMP-1-PHA-4 at the last larval stage suppresses WNT signaling in adulthood for DR-induced longevity. Our findings reveal a temporal checkpoint of the DR response that protects larval development and promotes adult health.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Restrição Calórica , Regulação da Expressão Gênica , Longevidade/genética , Fatores de Transcrição/metabolismo , Via de Sinalização WntRESUMO
BACKGROUND: Major depressive disorders (MDD) and bipolar disorders (BD) are the most common psychiatric diagnoses of suicide attempts (SA) in adolescents. However, little is known regarding the differences in incidence and clinical-related features of SA between these two disorders. The study aims to examine the SA incidence and related factors in adolescents with MDD versus BD. METHOD: A retrospective survey was conducted in outpatients. SA incidence, demographic characteristics and substance use history were collected. Symptom Checklist-90 was used to measure the severity of symptoms. The Revised Chinese internet addiction scale and Barratt Impulsiveness Scale-11 were utilized to assess the presence of internet addiction and impulsiveness. The Childhood Trauma Questionnaire was used to measure childhood maltreatment subtypes. RESULTS: 295 MDD and 205 BD adolescents were recruited. The incidence of SA for MDD and BD were 52.5 % and 56.4 %, respectively. BD adolescents who attempted suicide showed worse symptoms, higher rates of nicotine and alcohol use, higher motor and non-planning impulsivity, and a more childhood physical abuse proportion than MDD adolescents with SA. Physical abuse in childhood was found to be associated with SA in both disorders (OR = 1.998 for MDD; OR = 2.275 for BD), while higher anxiety (OR = 1.705), and alcohol use (OR = 2.094) were only associated with SA in MDD. LIMITATIONS: Retrospective, cross-sectional design cannot draw causality, and biases in self-report measurements cannot be ignored. CONCLUSIONS: The findings revealed some difference between BD and MDD for adolescents with SA, and it emphasize significance of prompt identification and exact distinction between BD and MDD in adolescents.
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Transtorno Bipolar , Transtorno Depressivo Maior , Testes Psicológicos , Autorrelato , Humanos , Adolescente , Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Tentativa de Suicídio/psicologia , Estudos Transversais , Estudos Retrospectivos , IncidênciaRESUMO
The choroid plexus is composed of epithelial cells situated on the basal layer. The tight junctions between adjacent choroid plexus epithelial cells establish the blood-cerebrospinal fluid barrier. This barrier, in conjunction with the blood-brain barrier, is crucial for the homeostasis of the brain microenvironment. The choroid plexus epithelium secretes cerebrospinal fluid, growth factors, neuropeptides, and lipids into the ventricles and also serves as a gateway for immune cells to enter the brain. The pathophysiology of aging and neurodegenerative diseases remains largely enigmatic, with an increasing body of research linking the choroid plexus to the etiology of these age-related disorders. In this review, we summarize the known relationship between the choroid plexus epithelium and age-related diseases, aiming to provide new therapeutic clues for these disorders.
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Barreira Hematoencefálica , Plexo Corióideo , Barreira Hematoencefálica/fisiologia , Encéfalo , Plexo Corióideo/metabolismo , Células Epiteliais/metabolismo , HumanosRESUMO
Ageing exhibits common and distinct features in various tissues, making it critical to decipher the tissue-specific ageing mechanisms. MiRNAs are essential regulators in ageing and are recently highlighted as a class of intercellular messengers. However, little is known about the tissue-specific transcriptomic changes of miRNAs during ageing. C. elegans is a well-established model organism in ageing research. Here, we profile the age-dependent miRNAomic changes in five isolated worm tissues. Besides the diverse ageing-regulated miRNA expression across tissues, we discover numerous miRNAs in the tissues without their transcription. We further profile miRNAs in the extracellular vesicles and find that worm miRNAs undergo inter-tissue trafficking via these vesicles in an age-dependent manner. Using these datasets, we uncover the interaction between body wall muscle-derived mir-1 and DAF-16/FOXO in the intestine, suggesting mir-1 as a messenger in inter-tissue signalling. Taken together, we systematically investigate worm miRNAs in the somatic tissues and extracellular vesicles during ageing, providing a valuable resource to study tissue-autonomous and nonautonomous functions of miRNAs in ageing.
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Proteínas de Caenorhabditis elegans , MicroRNAs , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Envelhecimento/genética , Intestinos , MicroRNAs/metabolismo , Longevidade/genéticaRESUMO
BACKGROUND: It's difficult to treat segmental tibial fractures (STFs), which are intricate injuries associated with significant soft tissue damage. The aim of this study was to compare the clinical effect of hexaxial external fixator (HEF) and intramedullary nail (IMN) in treatment of STFs. METHODS: A total of 42 patients with STFs were finally recruited between January 2018 and June 2022. There were 25 males and 17 females with age range of 20 to 60 years. All fractures were classified as type 42C2 using the Arbeitsgemeinschaftfür Osteosythese/Orthopaedic Trauma Association (AO/OTA) classification. 22 patients were treated with HEF and 20 patients were treated with IMN. The condition of vascular and neural injuries, time of full weight bearing, bone union time and infection rate were documented and analyzed between the two groups. The mechanical medial proximal tibial angle (mMPTA), mechanical posterior proximal tibial angle (mPPTA), mechanical lateral distal tibial angle (mLDTA), mechanical anterior distal tibial angle (mADTA), hospital for special surgery (HSS) knee joint score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle joint score, range of motion (ROM) of flexion of keen joint and ROM of plantar flexion and dorsal flexion of ankle joint were compared between the two groups at the last clinical visit. RESULTS: There were no vascular and neural injuries or other severe complications in both groups. All 22 patients in HEF group underwent closed reduction but 3 patients in IMN group were treated by open reduction. The time of full weight bearing was (11.3 ± 3.2) days in HEF group and (67.8 ± 5.8) days in IMN group(P < 0.05), with bone union time for (6.9 ± 0.8) months and (7.7 ± 1.4) months, respectively(P < 0.05). There was no deep infection in both groups. In the HEF group and IMN group, mMPTA was (86.9 ± 1.5)° and (89.7 ± 1.8)°(P < 0.05), mPPTA was (80.8 ± 1.9)° and (78.6 ± 2.0)°(P < 0.05), mLDTA was (88.5 ± 1.7)° and (90.3 ± 1.7)°(P < 0.05), while mADTA was (80.8 ± 1.5)° and (78.4 ± 1.3)°(P < 0.05). No significant differences were found between the two groups at the last clinical visit concerning HSS knee joint score and AOFAS ankle joint score, ROM of flexion of keen joint and ROM of plantar flexion of ankle joint (P > 0.05). The ROM of dorsal flexion of ankle joint in IMN group was (30.4 ± 3.5)°, better than (21.6 ± 2.8)° in HEF group (P < 0.05). CONCLUSION: In terms of final clinical outcomes, the use of either HEF or IMN for STFs can achieve good therapeutic effects. While HEF is superior to IMN in terms of completely closed reduction, early full weight bearing, early bone union and alignment. Nevertheless, HEF has a greater impact on the ROM of dorsal flexion of the ankle joint, and much more care and adjustment are needed for the patients than IMN.
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Fraturas da Tíbia , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Fraturas da Tíbia/cirurgia , Fixadores Externos , Placas ÓsseasRESUMO
Morphological rearrangement of the endoplasmic reticulum (ER) is critical for metazoan mitosis. Yet, how the ER is remodeled by the mitotic signaling remains unclear. Here, we report that mitotic Aurora kinase A (AURKA) employs a small GTPase, Rab1A, to direct ER remodeling. During mitosis, AURKA phosphorylates Rab1A at Thr75. Structural analysis demonstrates that Thr75 phosphorylation renders Rab1A in a constantly active state by preventing interaction with GDP-dissociation inhibitor (GDI). Activated Rab1A is retained on the ER and induces the oligomerization of ER-shaping protein RTNs and REEPs, eventually triggering an increase of ER complexity. In various models, from Caenorhabditis elegans and Drosophila to mammals, inhibition of Rab1AThr75 phosphorylation by genetic modifications disrupts ER remodeling. Thus, our study reveals an evolutionarily conserved mechanism explaining how mitotic kinase controls ER remodeling and uncovers a critical function of Rab GTPases in metaphase.
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Aurora Quinase A , Mitose , Animais , Fosforilação , Aurora Quinase A/metabolismo , Transdução de Sinais , Retículo Endoplasmático/metabolismo , Mamíferos/metabolismoRESUMO
Non-suicidal self-injury (NSSI) is an issue primarily of concern in adolescents and young adults. Recent literature suggests that persistent, repetitive, and uncontrollable NSSI can be conceptualized as a behavioral addiction. The study aimed to examine the prevalence of NSSI with addictive features and the association of this prevalence with demographic and clinical variables using a cross-sectional and case-control design. A total of 548 outpatients (12 to 22 years old) meeting the criteria for NSSI disorder of DSM-5 were enrolled and completed clinical interviews by 4 psychiatrists. NSSI with addictive features were determined by using a single-factor structure of addictive features items in the Ottawa self-injury inventory (OSI). Current suicidality, psychiatric diagnosis, the OSI, the revised Chinese Internet Addiction Scale, the Childhood Trauma Questionnaire, and the 20-item Toronto Alexithymia Scale were collected. Binary logistic regression analyses were used to explore associations between risk factors and NSSI with addictive features. This study was conducted from April 2021 to May 2022. The mean age of participants was 15.93 (SD = 2.56) years with 418 females (76.3%), and the prevalence of addictive NSSI was 57.5% (n = 315). Subjects with addictive NSSI had a higher lifetime prevalence of nicotine and alcohol use, a higher prevalence of current internet addiction, suicidality, and alexithymia, and were more likely to have physical abuse/neglect, emotional abuse, and sexual abuse than NSSI subjects without addictive features. Among participants with NSSI, the strongest predictors of addictive features of NSSI were female (OR = 2.405, 95% CI 1.512-3.824, p < 0.0001), alcohol use (OR = 2.179, 95% CI 1.378-3.446, p = 0.001), current suicidality (OR = 3.790, 95% CI 2.351-6.109, p < 0.0001), and psysical abuse in childhood (OR = 2.470, 95% CI 1.653-3.690, p < 0.0001). Nearly 3 out of 5 patients (12-22 years old) with NSSI met the criteria of NSSI with addictive features in this psychiatric outpatients sample. Our study demonstrated the importance of the necessity to regularly assess suicide risk, and alcohol use, as well as focus more on females and subjects who had physical abuse in childhood to prevent addictive NSSI.
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Comportamento Aditivo , Testes Psicológicos , Autorrelato , Comportamento Autodestrutivo , Humanos , Feminino , Adolescente , Adulto Jovem , Criança , Adulto , Masculino , Pacientes Ambulatoriais , Estudos Transversais , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Comportamento Aditivo/epidemiologia , Fatores de RiscoRESUMO
Parkinson's disease (PD), one of the most devastating neurodegenerative brain disorders, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and deposits of α-synuclein aggregates. Currently, pharmacological interventions for PD remain inadequate. The cell necroptosis executor protein MLKL (Mixed-lineage kinase domain-like) is involved in various diseases, including inflammatory bowel disease and neurodegenerative diseases; however, its precise role in PD remains unclear. Here, we investigated the neuroprotective role of MLKL inhibition or ablation against primary neuronal cells and human iPSC-derived midbrain organoids induced by toxic α-Synuclein preformed fibrils (PFFs). Using a mouse model (Tg-Mlkl-/-) generated by crossbreeding the SNCA A53T synuclein transgenic mice with MLKL knockout (KO)mice, we assessed the impact of MLKL deficiency on the progression of Parkinsonian traits. Our findings demonstrate that Tg-Mlkl-/- mice exhibited a significant improvement in motor symptoms and reduced phosphorylated α-synuclein expression compared to the classic A53T transgenic mice. Furthermore, MLKL deficiency alleviated tyrosine hydroxylase (TH)-positive neuron loss and attenuated neuroinflammation by inhibiting the activation of microglia and astrocytes. Single-cell RNA-seq (scRNA-seq) analysis of the SN of Tg-Mlkl-/- mice revealed a unique cell type-specific transcriptome profile, including downregulated prostaglandin D synthase (PTGDS) expression, indicating reduced microglial cells and dampened neuron death. Thus, MLKL represents a critical therapeutic target for reducing neuroinflammation and preventing motor deficits in PD.
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Doença de Parkinson , Animais , Humanos , Camundongos , alfa-Sinucleína/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Camundongos Knockout , Camundongos Transgênicos , Doenças Neuroinflamatórias , Doença de Parkinson/metabolismo , Proteínas Quinases/metabolismo , Substância NegraRESUMO
BACKGROUND: Abnormal activation of microglia is involved in the pathogenesis of schizophrenia. Minocycline and antipsychotics have been reported to be effective in inhibiting the activation of microglia and thus alleviating the negative symptoms of patients with schizophrenia. However, the specific molecular mechanism by which minocycline and antipsychotics inhibit microglial activation is not clear. In this study, we aimed to explore the molecular mechanism of treatment effect of minocycline and antipsychotics on schizophrenia. METHODS: Microglia cells were activated by lipopolysaccharide (LPS) and further treated with minocycline, haloperidol, and risperidone. Then cell morphology, specific marker, cytokines, and nitric oxide production process, and the proteins in related molecular signaling pathways in LPS-activated microglia were compared among groups. RESULTS: The study found that minocycline, risperidone, and haloperidol significantly inhibited morphological changes and reduced the expression of OX-42 protein induced by LPS. Minocycline significantly decreased the production of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1ß). Risperidone also showed significant decrease in the production of IL-6 and TNF-α, while haloperidol only showed significant decrease in the production of IL-6. Minocycline, risperidone, and haloperidol were found to significantly inhibit nitric oxide (NO) expression, but had no effect on inducible nitric oxide synthase (iNOS) expression. Both minocycline and risperidone were effective in decreasing the activity of cJun Nterminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinases (MAPKs) signal pathway. Additionally, minocycline and risperidone were found to increase the activity of phosphorylated-p38. In contrast, haloperidol only suppressed the activity of ERK. Minocycline also suppressed the activation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), while risperidone and haloperidol only suppressed the activation of STAT3. CONCLUSIONS: The results demonstrated that minocycline and risperidone exert stronger anti-inflammatory and neuroprotective effects stronger than haloperidol, through MAPKs and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways in BV2 cells stimulated with LPS, revealing the underlying mechanisms of minocycline and atypical antipsychotics in the treatment of negative schizophrenia symptoms.
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Antipsicóticos , Humanos , Antipsicóticos/farmacologia , Microglia/metabolismo , Lipopolissacarídeos/farmacologia , Minociclina/farmacologia , Haloperidol/farmacologia , Risperidona/farmacologia , Fator de Necrose Tumoral alfa , Interleucina-6 , Óxido Nítrico/metabolismo , Transdução de Sinais , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/farmacologiaRESUMO
Image-text retrieval is a central problem for understanding the semantic relationship between vision and language, and serves as the basis for various visual and language tasks. Most previous works either simply learn coarse-grained representations of the overall image and text, or elaborately establish the correspondence between image regions or pixels and text words. However, the close relations between coarse- and fine-grained representations for each modality are important for image-text retrieval but almost neglected. As a result, such previous works inevitably suffer from low retrieval accuracy or heavy computational cost. In this work, we address image-text retrieval from a novel perspective by combining coarse- and fine-grained representation learning into a unified framework. This framework is consistent with human cognition, as humans simultaneously pay attention to the entire sample and regional elements to understand the semantic content. To this end, a Token-Guided Dual Transformer (TGDT) architecture which consists of two homogeneous branches for image and text modalities, respectively, is proposed for image-text retrieval. The TGDT incorporates both coarse- and fine-grained retrievals into a unified framework and beneficially leverages the advantages of both retrieval approaches. A novel training objective called Consistent Multimodal Contrastive (CMC) loss is proposed accordingly to ensure the intra- and inter-modal semantic consistencies between images and texts in the common embedding space. Equipped with a two-stage inference method based on the mixed global and local cross-modal similarity, the proposed method achieves state-of-the-art retrieval performances with extremely low inference time when compared with representative recent approaches. Code is publicly available: github.com/LCFractal/TGDT.
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In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.
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Proteínas Hedgehog , Receptores Acoplados a Proteínas G , Camundongos , Animais , Proteínas Hedgehog/genética , Receptores Acoplados a Proteínas G/metabolismo , Cílios/metabolismo , Cartilagem/metabolismo , RegeneraçãoRESUMO
Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms.
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Antipsicóticos , Hiperprolactinemia , Quinolonas , Esquizofrenia , Humanos , Amissulprida/uso terapêutico , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Benzodiazepinas/uso terapêutico , Doença Crônica , Hiperprolactinemia/induzido quimicamente , Olanzapina/efeitos adversos , Olanzapina/uso terapêutico , Piperazinas/efeitos adversos , Quinolonas/efeitos adversos , Recidiva , Esquizofrenia/tratamento farmacológicoRESUMO
Depression severely impairs psychosocial functioning and quality of life, which places a huge burden on patients and their families. However, the physiological mechanism of depression remains unknown. Treatment with existing antidepressant medications is effective in around 50% of patients according to various studies, but is associated with severe side effects including nausea and headaches. Chinese herbal medicine (CHM) has been approved and widely used for depression as an alternative medicine in Chinese culture for decades. It has certain advantages and potential in the prevention and treatment of depression. In this review, we summarize the currently available evidence for the efficacy of CHM for the treatment of depression and physiological diseases comorbid with depression. We further discuss the possible mechanisms of action of CHM and the relationships to our current understanding of depression. The majority of current evidence has suggested that the combined treatment with CHM and mainstream antidepressants improves the response rate and reduces the side effects, while CHM alone could be more effective than placebo. However, the results should be carefully interpreted due to the shortcomings of existing clinical trials and a high risk of bias in meta-analyses. Our review provides a summary of the current applications and understanding of widely used CHMs for depression.
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Medicamentos de Ervas Chinesas , Humanos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Depressão/tratamento farmacológico , Qualidade de Vida , FitoterapiaRESUMO
Introduction: Previous studies have suggested that the dysregulation of purine metabolism may be associated with autism spectrum disorder (ASD). Here, we adopted metabolomics and transcriptomics to verify and explore the underlying molecular mechanism of purine metabolism dysfunction in ASD and identify potential biomarkers within the purine metabolism pathway. Methods: Ultra-high-performance liquid chromatography-mass spectrometry was used to obtain the plasma metabolic profiles of 12 patients with ASD and 12 typically developing (TD) children. RNA sequencing was used to screen differentially expressed genes related to the purine metabolic pathway and purine receptor-coding genes in 24 children with ASD and 21 healthy controls. Finally, serum uric acid levels were compared in 80 patients with ASD and 174 TD children to validate the omics results. Results: A total of 66 identified metabolites showed significant between-group differences. Network analysis showed that purine metabolism was the most strongly enriched. Uric acid was one of the most highlighted nodes within the network. The transcriptomic study revealed significant differential expression of three purine metabolism-related genes (adenosine deaminase, adenylosuccinate lyase, and bifunctional enzyme neoformans 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase) (p < 0.01) and five purinergic receptor genes (P2X7, P2Y2, P2Y6, P2Y8, and P2Y10) (p < 0.05). In the validation sample, there was a significant difference in serum uric acid levels between the two groups (p < 0.001), and the area under the curve for uric acid was 0.812 (sensitivity, 82.5%; specificity, 63.8%). Discussion: Patients with ASD had dysfunctional purine metabolic pathways, and blood uric acid may be a potential biomarker for ASD.
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Most reinforced concrete structures serve under windy environments, and the carbonation resistance under that circumstance exhibits significant difference from that under the steady (no wind) environment. In this study, a windy environment was simulated using one self-developed wind tunnel, and alkali-activated slag/fly ash paste specimens were adopted for the carbonation under variant windy environments. Meanwhile, to reveal the effect of inner humidity on the carbonation, sliced alkali-activated materials (AAM) were mass-balanced first to variant humidity, and were then carbonated under a 2.5 m/s windy environment. With the assistance of computed tomography (CT), the structure of AAM at variant carbonation ages was rendered. The experimental result showed that wind is capable of promoting the exchange of moisture between the sample inside and the outer atmosphere, leading to faster carbonation as compared to that under no wind environment. When preconditioned to lower inner humidity, the carbonation rate of AAM was faster because the larger gaseous space benefited the intrusion of both CO2 and moisture. Furthermore, when preconditioned to lower humidity, the cracking extent of AAM was severer, which also contributed to the faster carbonation. Moreover, compared with ordinary Portland cement (OPC), the carbonation front on each instant 1D gray-scale value profile was broader, which suggested that the carbonation progress of AAM under windy environments was no longer controlled solely by diffusion. In addition, the gray-scale value on instant 1D profile fluctuated drastically, which verified cracking in AAM carbonated under windy environments. The current work not only deepens the understanding of the carbonation mechanism in-site (mostly under windy environments), but also helps to develop more environment-friendly construction material, with better durability performance.