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BACKGROUND: The efficacy of pharmacological and nutritional interventions in individuals at clinical high risk for psychosis (CHR-P) remains elusive. This study aims to investigate the efficacy of pharmacological and nutritional interventions in CHR-P and whether these interventions can enhance the efficacy of psychological treatments. METHODS: We systematically reviewed data from 5 databases until July 24, 2021: PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, and WanFang Data. The primary outcome was the transition to psychosis. Network meta-analyses were conducted at 3 time points (6, 12, and ≥24 months) considering both pharmacological/nutritional interventions alone and its combination with psychotherapy. RESULTS: Out of 11 417 identified references, 21 studies were included, comprising 1983 participants. CHR-P participants receiving omega-3 polyunsaturated fatty acids treatment were associated with a lower probability of transition compared with placebo/control at 6 months (odds ratio [OR] = 0.07, 95% confidence interval [CI] = .01 to .054), 12 months (OR = 0.14, 95% CI = .03 to .66), and ≥24 months (OR = 0.16, 95% CI = .05 to .54). Moreover, risperidone plus psychotherapy was associated with a lower likelihood of transition at 6 months compared with placebo/control plus psychotherapy, but this result was not sustained over longer durations. CONCLUSION: Omega-3 polyunsaturated fatty acids helped in preventing transitions to psychosis compared with controls. PROSPERO REGISTRATION NUMBER: CRD42021256209.
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Ácidos Graxos Ômega-3 , Metanálise em Rede , Transtornos Psicóticos , Humanos , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Transtornos Psicóticos/prevenção & controle , Transtornos Psicóticos/terapia , Psicoterapia/métodos , Antipsicóticos/uso terapêutico , Antipsicóticos/administração & dosagemRESUMO
The reactivity of pyridine is a complex topic due to its unique electronic structure. The reactions of atomic boron with pyridine molecules in solid neon have been investigated using matrix isolation infrared absorption spectroscopy. Three products (marked as A, B, and C) were observed and characterized through 10B, D and 15N isotopic substitution pyridine regents as well as quantum chemical calculations. In the reaction, the ground-state boron atom can attack the lone pair electrons of the nitrogen atom in the pyridine molecule, resulting in the formation of a 1-boropyridinyl radical (A). Alternatively, addition to the aromatic π-system of pyridine can occur in a [1,4] type, leading to the formation of a B[η2(1,4)-C5H5N] complex (B). Under UV-visible light (280 < λ < 580 nm) irradiation, these two compounds can further undergo photo-isomerization to form BN-embedded seven-membered azaborepin compounds (C). The observation of species A, B, and the subsequent photo-isomerization to species C is consistent with theoretical predictions, indicating that these reactions are kinetically favorable. This research provides valuable insights into the future design and synthesis of corresponding BN heterocyclic derivatives.
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BACKGROUND AND PURPOSE: The gut microbiome has been reported to be closely related to Alzheimer's disease (AD) progression. Here, a comprehensive meta-analysis of gut microbial characteristics in AD, mild cognitive impairment (MCI) and subjective cognitive decline (SCD) was performed to compare gut microbial alterations at each stage. METHODS: A total of 10 databases (CNKI, WanFang, VIP, SinoMed, WOS, PubMed, Embase, Cochrane Library, PsycINFO and Void) were searched and 34 case-control studies were included. α and ß diversity and the relative abundance of gut microbiota were analysed as outcome indices. Data analysis was performed using Review Manager (5.4.1) and R. RESULTS: Chao1 and Shannon index levels in AD were significantly lower compared with healthy controls (HCs), and the Chao1 index was significantly lower in MCI compared with HCs. There was a significant difference in ß diversity of gut microbiomes in patients (SCD, MCI, AD) compared with HCs. The relative abundance of Firmicutes at the phylum level was significantly lower in patients with AD and MCI than HCs. However, the relative abundance of Bacteroidetes at the phylum level was significantly higher in patients with MCI than HCs. There was an increasing trend for Enterobacteriaceae and a decreasing trend for Ruminococcaceae, Lachnospiraceae and Lactobacillus during AD; Lactobacillus showed a decreasing trend early in SCD. CONCLUSION: Our results indicated that there were gut microbiological abnormalities in AD, even as early as the SCD stage. The dynamic, consistent changes in gut microbes with the disease process showed that they might serve as potential biomarkers for early identification and diagnosis of AD.
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OBJECTIVE: To update the prevalence of eating disorders in the general population before 2021 and to analyze the distribution characteristics at different times and in different regions and sexes, as well as the diagnostic criteria. METHODS: Based on the method from a previous report by the authors, studies were identified from the following databases: PubMed/Medline, PsycINFO, ISI Web of Knowledge, Ovid and the 4 most important Chinese databases. Articles in English and Chinese before 2021 were retrieved. The data retrieved at this time were pooled with the data from a previous report for analyses. RESULTS: Thirty-three studies were identified, which included 18 studies supplemented in this retrieval. The pooled lifetime and 12-month prevalence of eating disorders were 0.91% (95% CI, 0.48-1.71) and 0.43% (95% CI, 0.18-0.78), respectively. The pooled lifetime and 12-month prevalence of the subgroup EDs (any), which covers all types of eating disorders, were 1.69% and 0.72%, respectively. The lifetime prevalence of AN, BN and BED was 0.16% (95% CI, 0.06-0.31), 0.63% (95% CI, 0.33-1.02) and 1.53% (95% CI, 1.00-2.17), respectively. The lifetime prevalence of EDs in Western countries was 1.89%, and was high at 2.58% in females. Prevalence studies using DSM-5 criteria were scarce. CONCLUSIONS: The prevalence of eating disorders might be underestimated thus far. Not all types of EDs were included in a majority of epidemiological surveys, and the prevalence rates of the new types of EDs were significantly higher. Eating disorders were especially common in Western countries and in females. New diagnostic criteria should be used to comprehensively assess all types of eating disorders. LEVEL OF EVIDENCE: 1, systematic review and meta-analysis.
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Anorexia Nervosa , Transtorno da Compulsão Alimentar , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Anorexia Nervosa/diagnóstico , Transtorno da Compulsão Alimentar/diagnóstico , Bulimia Nervosa/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Humanos , PrevalênciaRESUMO
BACKGROUND: Negative symptoms are the core of schizophrenia, but whether antipsychotics are efficacious for their treatment is unclear. Moreover, there is debate whether patients in relevant trials should have predominant negative symptoms or whether prominent negative symptoms are also acceptable. METHODS: We systematically reviewed randomised, blinded antipsychotic drug trials in patients with schizophrenia and either predominant or prominent negative symptoms (last search Dec 12, 2017). Separate pairwise meta-analyses were conducted in these two populations. The primary outcome was negative symptoms. Depressive, symptoms, positive symptoms, and extrapyramidal side-effects were analysed as causes of secondary negative symptoms. FINDINGS: We included 21 randomized-controlled trials with 3451 participants which revealed the following significant differences in the primary outcome: in patients with predominant negative symptoms amisulpride was superior to placebo (N = 4; n = 590, SMD 0.47, CI 0.23, 0.71), olanzapine was superior to haloperidol in a small trial (n = 35) and cariprazine outperformed risperidone (N = 1, n = 456, SMD - 0.29, CI - 0.48, - 0.11). In patients with prominent negative symptoms, olanzapine and quetiapine were superior to risperidone in single trials. Overall, studies in prominent negative symptoms were potentially more confounded by improvements of secondary negative symptoms. INTERPRETATION: Amisulpride is the only antipsychotic that outperformed placebo in the treatment of predominant negative symptoms, but there was a parallel reduction of depression. Cariprazine was better than risperidone in a large trial that was well-controlled for secondary negative symptoms, but the trial was sponsored by its manufacturer. Future trials should apply scientifically developed definitions such as the deficit syndrome and the persistent negative symptoms concept.
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Antipsicóticos/farmacologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , HumanosRESUMO
OBJECTIVE: The argument surrounding the safety and effectiveness of interventions for the population of individuals at a clinical high risk of developing psychosis has been ongoing for the past 30 years. However, few studies have assessed the needs of this special young population, who are struggling with the recent onset of psychotic symptoms. METHOD: The sample consisted of 171 family members of 108 clinical high-risk individuals included from the ShangHai at Risk for Psychosis research programme. A 'WeChat' group was established to provide mutual support. There were 22,007 valid messages sent within the group between 1 April 2015 and 27 June 2016. Chat records were subsequently analysed to determine the needs of families during intervention at the early stages of psychosis. RESULTS: Families of clinical high-risk individuals were highly involved in the entire medical process, and the major concerns of the families of clinical high-risk individuals focused on both functional recovery and medication. The themes of 'take medication', 'go to school' and 'study in school' were often discussed within the group. CONCLUSION: A family-focused intervention targeting functional recovery and real-time professional explanations of medication would meet the major needs of families of Chinese clinical high-risk individuals.
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Família , Necessidades e Demandas de Serviços de Saúde , Redes Sociais Online , Sistemas de Apoio Psicossocial , Transtornos Psicóticos/terapia , Grupos de Autoajuda , Adolescente , Adulto , China , Feminino , Humanos , Masculino , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/reabilitação , Risco , Adulto JovemRESUMO
BACKGROUND: Schizotypal personality disorder (SPD) is linked to schizophrenia in terms of shared genetics, biological markers and phenomenological characteristics. In the current study, we aimed to determine whether the previously reported altered functional connectivity (FC) with precuneus in patients with schizophrenia could be extended to individuals with SPD. METHODS: Twenty subjects with SPD and 19 healthy controls were recruited from 4461 freshmen at a university in Shanghai and received a resting-state scan of MRI. All participants were evaluated by the Chinese version of Schizotypal Personality Questionnaire (SPQ) and the Chinese version of Symptom Checklist (SCL-90). The imaging data were analysed using the seed-based functional connectivity method. RESULTS: Compared with the controls, SPD subjects exhibited reduced FC between bilateral precuneus and contralateral parahippocampus. In SPD group, SPQ total score was negatively correlated with FC between right precuneus and left parahippocampus (r = -0.603, p = 0.006); there was a negative trend between SPQ subscale score of suspiciousness and FC between left precuneus and right parahippocampus (r = -0.553, p = 0.014); and a positive trend was found between SPQ subscale score of odd or eccentric behaviour and FC between left precuneus and right superior temporal gyrus (r = 0.543, p = 0.016). As for the SCL-90 score, a similar negative trend was found between SCL-90 subscale score of suspiciousness and FC between right precuneus and left parahippocampus (r = -0.535, p = 0.018) in SPD group. CONCLUSIONS: Our findings suggest that the decreased functional connectivity between precuneus and contralateral parahippocampus might play a key role in the pathophysiology of schizophrenia spectrum disorder.
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Giro Para-Hipocampal/fisiopatologia , Lobo Parietal/fisiopatologia , Transtorno da Personalidade Esquizotípica/fisiopatologia , Lobo Temporal/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , NeuroimagemRESUMO
There is a growing body of evidence suggesting that patients with psychosis show impaired theory of mind (ToM). However, much remains to be understood as to whether ToM deficits occur in the premorbid or post-onset period of psychosis. Our primary aim was to examine empirically impairment on ToM tasks in a group of individuals with clinical high risk (CHR) of psychosis. Fifty CHR participants identified through the Structured Interview for Prodromal Syndromes and 52 age-/education-matched controls were assessed with a complete standard neuropsychological battery (the MCCB, MATRICS Consensus Cognitive Battery) and a social cognition assessment (Faux Pas Test, FPT). We then examined the association of baseline FPT performance with conversion to psychosis at 12-month follow-up. Compared with controls, the CHR group showed significantly poorer performances on the FPT and most MCCB domains. Significant positive correlations were found between faux pas detection and the MCCB domains of Attention/Vigilance and Working Memory in CHR participants when controlling for age and years of education. Mean scores on the FPT in 14 converters who were diagnosed with full-blown psychosis within 12 months were significantly lower than they were for non-converters. Impairments in ToM ability are acquired earlier in the prodromal stage of psychosis, along with general cognition (such as memory function) deficits. Declines in ToM ability may overlap with the progress of psychosis (the gradual loss insight), sharing similar neural substrates, and reflected by impairments in basic cognitive function.
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Transtornos Cognitivos/etiologia , Comportamento de Busca de Ajuda , Transtornos Psicóticos , Reconhecimento Psicológico/fisiologia , Teoria da Mente , Adolescente , Adulto , Transtornos Cognitivos/diagnóstico , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Fatores de Risco , Estatísticas não Paramétricas , Inquéritos e Questionários , Adulto JovemRESUMO
The relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and suicide risk in patients with mental disorders remains controversial. We conducted a network meta-analysis to examine the effects of SSRIs on suicide risk in patients with mental disorders. A comprehensive search was conducted across PubMed, Web of Science, PsycINFO, CENTRAL, Wanfang Database, and China National Knowledge Infrastructure for articles published until December 19, 2023. The main outcomes were suicidal ideation and instances of suicidal behavior. We included 29 double-blind randomized trials in our analysis. The findings suggest that SSRIs primarily offer short-term protection against suicidal ideation. By week 2, paroxetine, fluoxetine, escitalopram, and non-SSRI treatments were linked to a decreased suicide risk compared with a placebo, with the exception of sertraline. This protective effect was diminished by week 8. In contrast, studies on instances of suicidal behavior from weeks 1 to 10 found no significant difference in efficacy between SSRIs, non-SSRIs, and placebo. These results indicate that SSRIs may offer short-term protection against suicidal ideation. However, their long-term effectiveness in mitigating suicidal ideation and preventing suicidal behaviors is limited.
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Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores Seletivos de Recaptação de Serotonina , Ideação Suicida , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Humanos , Método Duplo-Cego , Suicídio/estatística & dados numéricos , Suicídio/psicologia , Transtornos Mentais/tratamento farmacológicoRESUMO
BACKGROUND AND HYPOTHESIS: Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. STUDY DESIGN: We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1. STUDY RESULTS: Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of -0.66 (95% CI: -0.90; -0.43) for olanzapine, -0.64 (-0.80; -0.48) for aripiprazole, -0.62 (-0.76; -0.48) for risperidone and -0.42 (-0.53; -0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations. CONCLUSIONS: SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.
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Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/efeitos adversos , Palmitato de Paliperidona/efeitos adversos , Aripiprazol/efeitos adversos , Olanzapina/uso terapêutico , Risperidona/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/induzido quimicamenteRESUMO
BACKGROUND: Yoga is gradually being explored as a potential complementary intervention in addition to psychiatric drugs for schizophrenia. However, there are conflicts on the efficacy of yoga for schizophrenia. This meta-analysis was aimed to evaluate the association of yoga intervention with reductions on clinical symptoms and improvements in quality of life (QoL) as well as social functioning among schizophrenia. METHOD: Systematic literature search was undertaken to identify all RCTs that compared yoga with active or passive controls for patients with schizophrenia from inception to July 2023. The outcomes were measurements of positive symptoms, negative symptoms, QoL and social functioning. Random-effects models were performed to calculate the effect sizes in the standardized mean differences reporting as Hedges' s g statistic. RESULTS: 19 studies enrolling 1274 participants with schizophrenia were included. Yoga had a medium effect on positive symptoms in the short term (Hedges's g = 0.31) and small effect in the long term (Hedges's g = 0.18). Medium significant effects were also found on negative symptoms in both the short term (Hedges's g = 0.44) and the long term (Hedges's g = 0.35). Yoga had a significant impact on improving both total QoL (Hedges's g = 0.34) and social functioning (Hedges's g = 0.45) with medium effect sizes. CONCLUSIONS: Yoga was associated with significant reductions on negative and positive symptoms, and significant improvements in QoL as well as social functioning in patients with schizophrenia. Future research should explore the long-term efficacy of yoga for schizophrenia, encompassing more diverse populations.
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Esquizofrenia , Yoga , Humanos , Qualidade de Vida , Esquizofrenia/terapia , Interação SocialRESUMO
Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase.
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Antipsicóticos , Preparações de Ação Retardada , Metanálise em Rede , Esquizofrenia , Humanos , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Administração Oral , Esquizofrenia/tratamento farmacológico , Preparações de Ação Retardada/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Injeções , Resultado do TratamentoRESUMO
BACKGROUND: Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia. METHODS: We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach. DISCUSSION: Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO-ID CRD42023410645.
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Metanálise em Rede , Esquizofrenia Resistente ao Tratamento , Revisões Sistemáticas como Assunto , Estimulação Transcraniana por Corrente Contínua , Humanos , Esquizofrenia Resistente ao Tratamento/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Antipsicóticos/uso terapêutico , Estimulação Magnética Transcraniana/métodos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/terapiaRESUMO
More than one hundred studies have used the mainland Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) to assess cognition in schizophrenia, but the results of these studies, the quality of the reports, and the strength of the evidence provided in the reports have not been systematically assessed. We identified 114 studies from English-language and Chinese-language databases that used the Chinese MCCB to assess cognition in combined samples of 7394 healthy controls (HC), 392 individuals with clinical high risk for psychosis (CHR-P), 4922 with first-episode schizophrenia (FES), 1549 with chronic schizophrenia (CS), and 2925 with schizophrenia of unspecified duration. The mean difference (MD) of the composite MCCB T-score (-13.72) and T-scores of each of the seven cognitive domains assessed by MCCB (-14.27 to -7.92) were significantly lower in individuals with schizophrenia than in controls. Meta-analysis identified significantly greater cognitive impairment in FES and CS than in CHR-P in six of the seven domains and significantly greater impairment in CS than FES in the reasoning and problem-solving domain (i.e., executive functioning). The only significant covariate of overall cognitive functioning in individuals with schizophrenia was a negative association with the severity of psychotic symptoms. These results confirm the construct validity of the mainland Chinese version of MCCB. However, there were significant limitations in the strength of the evidence provided about CHR-P (small pooled sample sizes) and the social cognition domain (inconsistency of results across studies), and the quality of many reports (particularly those published in Chinese) was rated 'poor' due to failure to report sample size calculations, matching procedures or methods of handling missing data. Moreover, almost all studies were cross-sectional studies limited to persons under 60 with at least nine years of education, so longitudinal studies of under-educated, older individuals with schizophrenia are needed.
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The incidence rate of colorectal cancer (CRC) has been increasing significantly in recent years, and it is urgent to develop novel drugs that have more effects for its treatment. It has been reported that many molecules extracted from the root bark of Morus alba L. (also known as Cortex Mori) have antitumor activities. In our study, we identified morusinol as a promising anticancer agent by selecting from 30 molecules extracted from Morus alba L. We found that morusinol treatment suppressed cell proliferation and promoted apoptosis of CRC cells in vitro. Besides this, we observed that morusinol induced cytoprotective autophagy. The GO analysis of differentially expressed genes from RNA-seq data showed that morusinol affected cholesterol metabolism. Then we found that key enzyme genes in the cholesterol biosynthesis pathway as well as the sterol regulatory element binding transcription factor 2 (SREBF2) were significantly downregulated. Furthermore, additional cholesterol treatment reversed the anti-CRC effect of morusinol. Interestingly, we also found that morusinol treatment could promote forkhead box O3 (FOXO3a) nuclear accumulation, which subsequently suppressed SREBF2 transcription. Then SREBF2-controlled cholesterol biosynthesis was blocked, resulting in the suppression of cell proliferation, promotion of apoptosis, and production of autophagy. The experiments in animal models also showed that morusinol significantly impeded tumor growth in mice models. Our results suggested that morusinol may be used as a candidate anticancer drug for the treatment of CRC.
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Antineoplásicos , Neoplasias Colorretais , Morus , Camundongos , Animais , Proliferação de Células , Antineoplásicos/farmacologia , Autofagia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Linhagem Celular Tumoral , Apoptose , Morus/químicaRESUMO
The characteristics of the cognitive processing of food, body and emotional information in patients with anorexia nervosa (AN) are debatable. We reviewed functional magnetic resonance imaging studies to assess whether there were consistent neural basis and networks in the studies to date. Searching PubMed, Ovid, Web of Science, The Cochrane Library and Google Scholar between January 1980 and May 2012, we identified 17 relevant studies. Activation likelihood estimation was used to perform a quantitative meta-analysis of functional magnetic resonance imaging studies. For both food stimuli and body stimuli, AN patients showed increased hemodynamic response in the emotion-related regions (frontal, caudate, uncus, insula and temporal) and decreased activation in the parietal region. Although no robust brain activation has been found in response to emotional stimuli, emotion-related neural networks are involved in the processing of food and body stimuli among AN. It suggests that negative emotional arousal is related to cognitive processing bias of food and body stimuli in AN.
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Anorexia Nervosa/fisiopatologia , Encéfalo/fisiopatologia , Emoções/fisiologia , Imageamento por Ressonância Magnética , Anorexia Nervosa/psicologia , Mapeamento Encefálico , Alimentos , Neuroimagem Funcional , Humanos , Estimulação LuminosaRESUMO
Background: Eye movement abnormality in schizophrenia has been studied for several decades. However, patient differences in eye movements across phases of schizophrenia from eye-tracking studies have not been well documented. Aims: This pilot study used eye-tracking technology to investigate attentive bias towards interpersonal communication information across different clinical phases of schizophrenia. Methods: This study included 78 persons at clinical high risk (CHR) for schizophrenia, 68 first-episode (FEZ) patients, and 39 chronically ill patients from the Shanghai At Risk for Psychosis Extending Project (SHARP Extending cohort) as well as 74 healthy controls (HCs). The experiment was an unguided-viewing task composed of 24 trials showing three types of pictures which varied in the degree of interpersonal communication. Type 1 was a scenery picture without people, type 2 was a picture with four people not communicating, and type 3 was a picture with four people communicating. We used two measures: (1) initial fixation duration and (2) total fixation duration. Results: A ratio for both measures was calculated between measures for pictures with more or less interpersonal communication. The ratio of initial fixation duration for pictures with people communicating versus pictures with people not communicating was lowest in chronically ill patients (0.13 (0.34))compared with HCs (0.31 (0.36)), FEZ patients (0.31 (0.46)), and CHR patients (0.36 (0.42)). The difference in the ratios of initial fixation duration for type 2 and type 3 pictures was also significant for female participants (HCs vs chronically ill patients, t=2.706, p=0.009; CHR patients vs chronically ill patients, t=4.079, p<0.001). In addition, the ratio of initial fixation duration on pictures with people not communicating versus pictures without people negatively correlated with participants' high-risk symptoms (r=-0.35, p=0.002) among the CHR group and also correlated with the negative symptom subscore on the Positive and Negative Syndrome Scale (PANSS) among chronically ill patients (r=-0.33, p=0.037). The ratio of initial fixation duration between type 1 and type 3 pictures was associated with PANSS negative symptoms only in female patients with schizophrenia (r=-0.46, p=0.004). Conclusions: These findings suggest an altered attentive bias towards pictures with a high degree of interpersonal communication information across different clinical phases in schizophrenia. The ratio of initial attentive orienting was associated with negative symptoms in female patients.
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OBJECTIVE: This study aimed to provide insight into the efficacy of cognitive-behavioral therapy for psychosis (CBTp) in patients with "clinical high risk of psychosis (CHR-P)". METHODS: Major scientific databases were searched up to April 17, 2020. Randomized controlled trials in CHR-P individuals, comparing CBTp with needs-based interventions (NBI, including treatment as usual or nonspecific control treatment) were included, following PRISMA guidelines. The primary outcome (efficacy) was transition to psychosis by 6 months, 12 months, 24 months, and over 24 months. Secondary outcomes were change in attenuated psychotic symptoms, depression, distress, improvements in functioning, and quality of life. RESULTS: Ten randomized controlled studies met inclusion criteria. The comparisons included 1128 participants. CBTp was significantly more efficacious in reducing rate of transition to psychosis by 6 months (after post-hoc sensitivity analysis) (relative risk [RR] = 0.44, 95% confidence interval [CI]: 0.26, 0.73), 12 months (RR = 0.44, 95% CI: 0.30, 0.64), 12 months (RR = 0.46, 95%CI: 0.30, 0.69), and over 24 months (RR = 0.58, 95% CI: 0.35, 0.95) after treatment, compared with those receiving NBI. CBTp was also associated with more reduced attenuated psychotic symptoms by 12 months (SMD = -0.17, 95% CI: -0.33, -0.02) and by 24 months (SMD = -0.24, 95% CI: -0.43, -0.06). No beneficial effects on functioning, depression, quality of life, or distress were observed favoring CBTp. CONCLUSIONS: CBTp is effective in reducing both psychosis transition rates and attenuated psychotic symptoms for the prodromal stage of psychosis. It is a promising intervention at the preventative stage.
Assuntos
Terapia Cognitivo-Comportamental , Progressão da Doença , Avaliação de Resultados em Cuidados de Saúde , Sintomas Prodrômicos , Transtornos Psicóticos/terapia , Qualidade de Vida , HumanosRESUMO
China's population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated, especially Alzheimer's disease (AD) and related dementias (ADRD). AD's incidence rate, morbidity, and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals, families and society. The 'Healthy China Action' plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD. This report describes related epidemiological trends, evaluates the economic burden of the disease, outlines current clinical diagnosis and treatment status and delineates existing available public health resources. More specifically, it examines the public health impact of ADRD, including prevalence, mortality, costs, usage of care, and the overall effect on caregivers and society. In addition, this special report presents technical guidance and supports for the prevention and treatment of AD, provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.
RESUMO
To investigate the immediate and lasting effects of transcranial electrical stimulation (tES) on working memory (WM) in schizophrenia. We performed a literature search to identify randomized controlled trials (RCTs) evaluating the ability of tES to ameliorate WM. Twelve studies were included: 215 patients in the active stimulation group and 214 in the sham stimulation group. Meta-analysis demonstrated a significant efficacy of tES on WM in follow up, a summary of one or more assessments weeks after the last tES session (standardized mean difference (SMD) 0.33, 95% confidence interval (CI) 0.04 to 0.62; p = 0.02; n = 190, 4 studies; I2 = 33%) compared to sham tES, while non-significant results were observed for WM assessed immediately after the last tES session (SMD 0.14, 95% CI -0.12 to 0.41; p = 0.30; n = 417, 11 studies; I2 = 41%) in schizophrenia. There was no significant difference between the two groups in tolerability and dropouts. Evidence of low quality indicates that effects of tES on WM in schizophrenia may appear a few weeks after the last tES session, but not always be present when tested immediately after the last tES session. Further large-scale RCTs with a parallel-group design, sample size estimation and a longer follow-up period are needed.