RESUMEN
Pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy, exhibits escalating incidence and mortality rates, underscoring the urgent need for the identification of novel therapeutic targets and strategies. The BAG3 protein, a multifunctional regulator involved in various cellular processes, notably plays a crucial role in promoting tumor progression and acts as a potential "bridge" between tumors and the tumor microenvironment. In this study, we demonstrate that PDAC cells secrete BAG3 (sBAG3), which engages the IFITM2 receptor to activate the MAPK signaling pathway, specifically enhancing pERK activity, thereby propelling PDAC growth. Furthermore, our preliminary investigation into the effects of sBAG3 on co-cultured NK cells intriguingly discovered that sBAG3 diminishes NK cell cytotoxicity and active molecule expression. In conclusion, our findings confirm the pivotal role of the sBAG3-IFITM2 axis in fostering PDAC progression, highlighting the potential significance of sBAG3 as a dual therapeutic target for both tumor and immune cells.
RESUMEN
BACKGROUND: Although only a few patients with severe mental disorders (SMD) can commit violent behaviour in the community, violent behaviour aggravates the stigma towards patients with SMD. Understanding the subtypes of violent behaviour may be beneficial for preventing violent behaviour among patients with SMD, but it has rarely been studied. METHODS: This longitudinal study investigated 1914 patients with SMD in the community at baseline, and the follow-up period ranged from February 2021 to August 2021. The Barratt Impulsiveness Scale Version-11, the Buss-Perry Aggression Questionnaire, the Impulsive/Premeditated Aggression Scale, the Personality Diagnostic Questionnaire and the MacArthur Community Violence Instrument were used at baseline. The Modified Overt Aggression Scale was used to assess the occurrence of violent behaviour (outcome) during the follow-up period. Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Latent class analysis was used to characterise the subtypes of patients with SMD who engaged in violent behaviour at follow-up. RESULTS: We found that 7.2% of patients with SMD presented violent behaviour within six months in the community. Younger age (OR = 0.98, 95% CI = 0.96-1.00, p = 0.016) and no economic source (OR = 1.60, 95% CI = 1.10-2.33, p = 0.014) were risk factors for violent behaviour. Patients with SMD who engaged in violent behaviour could be classified into three subtypes: one class characterised by a history of violence and impulsivity, another class characterised by high levels of aggression and motor impulsivity, and the last class characterised by median cognitive impulsivity. CONCLUSIONS: Socio-demographic factors were risk factors for violent behaviour among patients with SMD, which could eliminate the discrimination toward this group. Impulsivity played a vital role in identifying the three subtypes of patients with SMD who engaged in violent behaviour. These findings may be helpful for the development of a personalised violence risk management plan for patients with SMD who commit violent behaviour in the community.
Asunto(s)
Conducta Impulsiva , Vida Independiente , Trastornos Mentales , Violencia , Humanos , Masculino , Femenino , Estudios Longitudinales , Violencia/psicología , Adulto , Vida Independiente/psicología , Persona de Mediana Edad , Trastornos Mentales/psicología , Trastornos Mentales/epidemiología , Agresión/psicología , Factores de RiesgoRESUMEN
BACKGROUND: Leukocyte phytohemagglutinin (PHA-L), derived from the L4 tetramer of PHA, has been frequently employed as a mitogen to induce T lymphocyte proliferation in vitro. The biological application of PHA-L in cancer diagnosis and treatment has gained traction in recent years. However, it has been noted that PHA-L obtained using traditional procedures has a massive amount of impurities or toxic components, which interfere with the activity of PHA-L. Preparation of a monoclonal antibody against active PHA-L is a significant tool for studying PHA-L's function and therapeutic potential. RESULTS: We successfully prepared monoclonal antibodies against the active components of PHA-L based on the whole PHA-L protein as an antigen, and found that monoclonal antibody 3C1C6G11 can be employed in western blot, immunofluorescence, and immunohistochemistry detection. Importantly, preliminary result shows that the mAb 3C1C6G11 may prevent PHA-L-induced cell aggregation and AICD (activation-induced cell death). CONCLUSIONS: The monoclonal antibody mAb 3C1C6G11 prepared in this study can be used as an effective tool for detecting PHA-L active components, investigating PHA-L's function and antineoplastic application.
Asunto(s)
Anticuerpos Monoclonales , Phaseolus , Fitohemaglutininas/farmacología , Activación de LinfocitosRESUMEN
BACKGROUND: Soil salinity is a primary factor limiting soybean (Glycine max) productivity. Breeding soybean for tolerance to high salt conditions is therefore critical for increasing yield. To explore the molecular mechanism of soybean responses to salt stress, we performed a comparative transcriptome time-series analysis of root samples collected from two soybean cultivars with contrasting salt sensitivity. RESULTS: The salt-tolerant cultivar 'Qi Huang No.34' (QH34) showed more differential expression of genes than the salt-sensitive cultivar 'Dong Nong No.50' (DN50). We identified 17,477 genes responsive to salt stress, of which 6644 exhibited distinct expression differences between the two soybean cultivars. We constructed the corresponding co-expression network and performed Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The results suggested that phytohormone signaling, oxidoreduction, phenylpropanoid biosynthesis, the mitogen-activated protein kinase pathway and ribosome metabolism may play crucial roles in response to salt stress. CONCLUSIONS: Our comparative analysis offers a comprehensive understanding of the genes involved in responding to salt stress and maintaining cell homeostasis in soybean. The regulatory gene networks constructed here also provide valuable molecular resources for future functional studies and breeding of soybean with improved tolerance to salinity.
Asunto(s)
Glycine max , Transcriptoma , Fitomejoramiento , Estrés Salino/genética , Tolerancia a la Sal/genética , Glycine max/fisiologíaRESUMEN
BACKGROUND: Wheat processing quality is an important factor in evaluating overall wheat quality, and dough characteristics are important when assessing the processing quality of wheat. As a notable germplasm resource, semi-wild wheat has a key role in the study of wheat processing quality. RESULTS: In this study, four dough rheological characteristics were collected in four environments using a nested association mapping (NAM) population consisting of semi-wild and domesticated wheat varieties to identify quantitative trait loci (QTL) for wheat processing quality. A total of 49 QTL for wheat processing quality were detected, explaining 0.36-10.82% of the phenotypic variation. These QTL were located on all wheat chromosomes except for 2D, 3A, 3D, 6B, 6D and 7D. Compared to previous studies, 29 QTL were newly identified. Four novel QTL, QMlPH-1B.4, QMlPH-3B.4, QWdEm-1B.2 and QWdEm-3B.2, were stably identified in three or more environments, among which QMlPH-3B.4 was a major QTL. Moreover, eight important genetic regions for wheat processing quality were identified on chromosomes 1B, 3B and 4D, which showed pleiotropy for dough characteristics. In addition, out of 49 QTL, 15 favorable alleles came from three semi-wild parents, suggesting that the QTL alleles provided by the semi-wild parent were not utilized in domesticated varieties. CONCLUSIONS: The results show that semi-wild wheat varieties can enrich the existing wheat gene pool and provide broader variation resources for wheat genetic research.
Asunto(s)
Pan , Mapeo Cromosómico , Productos Agrícolas/genética , Calidad de los Alimentos , Sitios de Carácter Cuantitativo , Reología , Triticum/genética , China , Cromosomas de las Plantas , Genes de Plantas , Variación Genética , Estudio de Asociación del Genoma Completo , Genotipo , FenotipoRESUMEN
OBJECTIVES: To investigate the epidemiological characteristics of antisocial personality disorder (ASPD) in young men in Chengdu and explore the characteristics and risks of violence. METHODS: Stratified random sampling was used to conduct a self-assessment questionnaire survey in 4 108 males aged from 18 to 34 in Chengdu, including general demographic characteristics, structured clinical interview for the diagnostic and statistical manual of mental disorders-â £ axis â ¡ disorders (SCID-â ¡) personality disorder screen questionnaire, violence questionnaire, psychosis screening questionnaire (PSQ), Alcohol Use Disorders Identification Test (AUDIT) and drug use. χ2 test, univariate and multivariate logistic regression were used for analysis and odds ratio (OR) was calculated. RESULTS: The positive rate of ASPD was 5.91%, which was associated with young age, unmarried, unemployment state, low educational level, violent behavior, psychotic symptoms, alcohol and drug use (P<0.05). Young men with ASPD also had a risk (P<0.05) of violence (OR was 8.51), multiple violence (OR was 16.57), injury (OR was 6.68), intentional violence (OR was 11.41), etc., the risk decreased after controlling for psychotic symptoms and substance abuse, but was still statistically significant. CONCLUSIONS: The risk of violence, severe violence and intentional violence in young men in Chengdu is high, and psychotic symptoms and substance abuse increase the risk of ASPD violence and relate characteristics.
Asunto(s)
Alcoholismo , Trastornos Relacionados con Sustancias , Alcoholismo/epidemiología , Trastorno de Personalidad Antisocial/diagnóstico , Trastorno de Personalidad Antisocial/epidemiología , Comorbilidad , Humanos , Masculino , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/epidemiología , Encuestas y CuestionariosRESUMEN
Understanding the violence behaviors in schizophrenia patients has always been the focus of forensic psychiatry. Although many studies show gut microbiota could regulate behavior, to our knowledge, no studies have profiled the gut microbiota structure in schizophrenia patients with violence. We profiled the characteristics of gut microbiota structure in 26 schizophrenia patients with violence (V.SCZ) by comparing with that of 16 schizophrenia patients without violence (NV.SCZ) under the control of confounders, and found the differences of gut microbiota structure between the two groups. Violence was assessed by the MacArthur Community Violence Instrument. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale. The 16S rRNA gene sequencing was used to identify and relatively quantify gut microbial composition. Bioinformatics analysis was used to find differential gut microbial composition between the V.SCZ and NV.SCZ groups. Fifty-nine differential microbial taxonomic compositions were found between the two groups. Fifteen gut microbial compositions were the key microbial taxonomic compositions responsible for the differences between the V.SCZ and NV.SCZ groups, including five enriched microbial taxonomic compositions (p_Bacteroidetes, c_Bacteroidia, o_Bacteroidales, f_Prevotellaceae, s_Bacteroides_uniformis), and ten impoverished microbial taxonomic compositions (p_Actinobacteria, c_unidentified_Actinobacteria, o_Bifidobacteriales, f_ Enterococcaceae, f_Veillonellaceae, f_Bifidobacteriaceae, g_Enterococcus, g_Candidatus_Saccharimonas, g_Bifidobacterium, and s_Bifidobacterium_pseudocatenulatum). This study profiled the differences of gut microbiota between schizophrenia patients with violence and without violence. These results could enrich the etiological understanding of violence in schizophrenia and might be helpful to violence management in the future.
Asunto(s)
Agresión , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S , Psicología del Esquizofrénico , Heces/microbiología , Genética Forense , Psicología Forense , Humanos , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
PURPOSE: Knife carrying has caused considerable public concern in the UK. But little is known of the epidemiology and characteristics of men who carry knives. We investigated associations with socioeconomic deprivation, area-level factors, and psychiatric morbidity. METHODS: Cross-sectional surveys of 5005 British men, 18-34 years, oversampling Black and Minority Ethnic (BME) men, lower social grades, and in London Borough of Hackney and Glasgow East. Participants completed questionnaires covering violent behaviour and psychiatric morbidity using standardised self-report instruments. Socioeconomic deprivation measured at small area level. RESULTS: Prevalence of knife carrying was 5.5% (4.8-6.9) and similar among white and BME subgroups. However, prevalence was twice the national rate in Glasgow East, and four times higher among Black men in Hackney, both areas with high levels of background violence and gang activity. Knife carrying was associated with multiple social problems, attitudes encouraging violence, and psychiatric morbidity, including antisocial personality disorder (AOR 9.94 95% CI 7.28-13.56), drug dependence (AOR 2.96 95% CI 1.90-4.66), and paranoid ideation (AOR 6.05 95% CI 4.47-8.19). There was no evidence of a linear relationship with socioeconomic deprivation. CONCLUSION: Men who carry knives represent an important public health problem with high levels of health service use. It is not solely a criminal justice issue. Rates are increased in areas where street gangs are active. Contact with the criminal justice system provides opportunity for targeted violence prevention interventions involving engagement with integrated psychiatric, substance misuse, and criminal justice agencies.
Asunto(s)
Trastornos Relacionados con Sustancias , Violencia , Agresión , Trastorno de Personalidad Antisocial , Estudios Transversales , Humanos , Masculino , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
KEY MESSAGE: Eight environmentally stable QTL for grain yield-related traits were detected by four RIL populations, and two of them were validated by a natural wheat population containing 580 diverse varieties or lines. Yield and yield-related traits are important factors in wheat breeding. In this study, four RIL populations derived from the cross of one common parent Yanzhan 1 (a Chinese domesticated cultivar) and four donor parents including Hussar (a British domesticated cultivar) and three semi-wild wheat varieties in China were phenotyped for 11 yield-related traits in eight environments. An integrated genetic map containing 2009 single-nucleotide polymorphism (SNP) markers generated from a 90 K SNP array was constructed to conduct quantitative trait loci (QTL) analysis. A total of 161 QTL were identified, including ten QTL for grain yield per plant (GYP) and yield components, 49 QTL for spike-related traits, 43 QTL for flag leaf-related traits, 22 QTL for plant height (PH), and 37 QTL for heading date and flowering date. Eight environmentally stable QTL were validated in individual RIL population where the target QTL was notably detected, and six of them had a significant effect on GYP. Furthermore, Two QTL, QSPS-2A.4 and QSL-4A.1, were also validated in a natural wheat population containing 580 diverse varieties or lines, which provided valuable resources for further fine mapping and genetic improvement in yield in wheat.
Asunto(s)
Grano Comestible/genética , Sitios de Carácter Cuantitativo , Triticum/genética , Alelos , China , Mapeo Cromosómico , Cromosomas de las Plantas , Grano Comestible/crecimiento & desarrollo , Flores/genética , Flores/crecimiento & desarrollo , Flores/fisiología , Ligamiento Genético , Genoma de Planta , Genotipo , Fenotipo , Fitomejoramiento , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/fisiología , Polimorfismo de Nucleótido Simple , Triticum/crecimiento & desarrolloRESUMEN
BACKGROUND: Many studies have related biochemical characteristics to violence and have reported schizophrenia could elevated the risk of violent behaviour. However, the metabolic characteristics of schizophrenia patients with violence (V.SC) are unclear. METHODS: To explore the metabolic characteristics of schizophrenia with violence and to identify potential biomarkers, untargeted metabolomics was performed by using gas chromatography time-of-flight mass spectrometry to analyse the plasma metabolites of fifty-three V.SC and twenty-four schizophrenia patients without violence (NV.SC). Multivariate and univariate analyses were performed to identify differential metabolites and biomarkers. Violence was assessed by the MacArthur Violence Assessment Study method. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale. RESULTS: Multivariate analysis was unable to distinguish V.SC from NV.SC. Glycerolipid metabolism and phenylalanine, tyrosine and tryptophan biosynthesis were the differential metabolic pathways between V.SC and NV.SC. We confirmed ten metabolites and five metabolites as metabolic biomarkers of V.SC by random forest and support vector machine analysis, respectively. The biomarker panel, including the ratio of L-asparagine to L-aspartic acid, vanillylmandelic acid and glutaric acid, yielded an area under the receiver operating characteristic curve of 0.808. CONCLUSIONS: This study gives a holistic view of the metabolic phenotype of schizophrenia with violence which is characterized by the dysregulation of lipids and amino acids. These results might provide information for the aetiological understanding and management of violence in schizophrenia; however, this is a preliminary metabolomics study about schizophrenia with violence, which needs to be repeated in future studies.
Asunto(s)
Aminoácidos , Esquizofrenia , Biomarcadores , Cromatografía de Gases y Espectrometría de Masas , Humanos , Metabolómica , ViolenciaRESUMEN
Polymer dispersed liquid crystals (PDLCs) have kindled a spark of interest because of their unique characteristic of electrically controlled switching. However, some issues including high operating voltage, low contrast ratio and poor mechanical properties are hindering their practical applications. To overcome these drawbacks, some measures were taken such as molecular structure optimization of the monomers and liquid crystals, modification of PDLC and doping of nanoparticles and dyes. This review aims at detailing the recent advances in the process, preparations and applications of PDLCs over the past six years.
Asunto(s)
Cristales Líquidos/química , Polímeros/química , Carbono , Colorantes/química , Cristales Líquidos/ultraestructura , Membranas Artificiales , Nanoestructuras , Óptica y Fotónica/instrumentación , Óptica y Fotónica/métodos , Fosfatidiletanolaminas/química , Polimerizacion , Relación Estructura-ActividadRESUMEN
KEY MESSAGE: The quantitative trait loci (QTLs) for grain morphological traits were identified via nested association mapping and validated in a natural wheat population via haplotype analysis. Grain weight, one of the three most important components of crop yield, is largely determined by grain morphological traits. Dissecting the genetic bases of grain morphology could facilitate the improvement of grain weight and yield production. In this study, four wheat recombinant inbred line populations constructed by crossing the modern variety Yanzhan 1 with three semi-wild wheat varieties (i.e., Chayazheda, Yutiandaomai, and Yunnanxiaomai from Xinjiang, Tibet, and Yunnan, respectively) and one exotic accession Hussar from Great Britain were investigated for grain weight and eight morphological traits in seven environments. Eighty-eight QTLs for all measured traits were totally identified through nested association mapping utilizing 14,643 high-quality polymorphic single nucleotide polymorphism (SNP) markers generated by 90 K SNP array. Among them, 64 (72.7%) QTLs have the most favorable alleles donated by semi-wild wheat varieties. For 14 QTL clusters affecting at least two grain morphological traits, nine QTL clusters were located in similar position with known genes/QTL, and the other five were novel. Three important novel QTLs (i.e., qTGW-1B.1, qTGW-1B.2, and qTGW-1A.1) were further validated in a natural wheat population via haplotype analysis. The favorable haplotypes for these three QTLs might be used in marker-assisted selection for the improvement of wheat yield by modifying morphological traits.
Asunto(s)
Genética de Población , Sitios de Carácter Cuantitativo , Semillas/anatomía & histología , Triticum/genética , Alelos , China , Mapeo Cromosómico , Genotipo , Haplotipos , Fenotipo , Polimorfismo de Nucleótido Simple , Tibet , Reino UnidoRESUMEN
BACKGROUND: A body of studies has focused on the olfactory impairment among people with schizophrenia. The effect of sex on this relationship has attracted the attention of researchers. These issues have not been studied much in Chinese schizophrenia patients. METHODS: We conducted a case-control study of 110 first-episode antipsychotic medicine naïve schizophrenia patients aged 18-35 years and 110 controls, matched by age and sex. Odour threshold, discrimination and identification were assessed by the "Sniffin' Sticks" test. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). RESULTS: The odour threshold, discrimination and identification scores of patients with schizophrenia were significantly lower than those of the healthy control group. The difference in identification score had statistical significance between male and female patients with schizophrenia (t = - 2.45, P < 0.05). Controlling for confounding factor, in male schizophrenia participants, the negative subscale score was significantly and inversely correlated with the discrimination (γ = - 0.37, p < 0.008), identification (γ = - 0.45, p < 0.008) and TDI (γ = - 0.50, p < 0.008) scores; the general psychopathology subscale score was inversely and significantly correlated with the identification (γ = - 0.47, p < 0.008) and TDI (γ = - 0.41, p < 0.008) scores. For female schizophrenia patients, positive and general psychopathology subscale scores had a significant inverse correlation with the identification score (positive: γ = - 0.47, p < 0.008; general psychopathology: γ = - 0.42, p < 0.008). CONCLUSIONS: Controlling for confounder, negative symptoms were related to impaired odour discrimination and identification in male schizophrenia patients, while positive symptoms were correlated with impaired odour identification in female schizophrenia patients. This sex dimorphism could provide useful information for future studies aiming to finding biomarkers of schizophrenia.
Asunto(s)
Trastornos del Olfato/psicología , Trastornos Psicóticos/psicología , Esquizofrenia/complicaciones , Caracteres Sexuales , Adolescente , Adulto , Antipsicóticos/uso terapéutico , Estudios de Casos y Controles , Discriminación en Psicología , Femenino , Humanos , Masculino , Odorantes , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND: Little is known about the characteristics of people with and without schizophrenia who have been charged with homicide in China. AIMS AND RESEARCH QUESTION: Our research question was what differences are there between alleged homicide offenders with and without psychosis? METHOD: All archival records of alleged homicide cases referred for assessment to the West China Forensic Central Medical Service during 1998-2006 were retrieved. The centre serves a large catchment area in the mainly rural province of Sichuan. A random 20% of cases with schizophrenia and all cases without psychosis were selected for comparison. Demographic, criminological and mental health data were extracted from the records, and violence was rated by using the Violence Risk Scale (Chinese version). RESULTS: The two groups differed significantly in age, education, occupation, marital status and relationships to victim. The estimated risk of reoffending was higher in the schizophrenia group than the non-psychotic group, even after controlling for demographic differences. Despite many individuals reporting long histories of mental illness, about 40% of those with schizophrenia had never had any psychiatric treatment and less than 4% were in treatment at the time of the alleged homicide. CONCLUSIONS: The tendency for homicidal people with schizophrenia to be older, less educated and more socially isolated than their non-psychotic peers is similar to experience in Western countries, but the apparently higher risk scale scores of the Chinese schizophrenia group and their greater tendency to attack strangers are different. The lack of reported previous engagement with mental health services by a clearly ill and risky group of people is a likely explanation. Similar rural problems compared with better served urban areas have been reported in the Chuvash Republic. The case for better rural mental health services seems strong. Copyright © 2017 John Wiley & Sons, Ltd.
Asunto(s)
Criminales/psicología , Homicidio/psicología , Esquizofrenia/complicaciones , Psicología del Esquizofrénico , Adolescente , Adulto , China , Femenino , Humanos , Masculino , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Esquizofrenia/patología , Adulto JovenRESUMEN
PURPOSE: Public health psychiatry has a key role in violence prevention. Cross-national comparisons of violence and associated psychiatric morbidity can indicate targets for preventive interventions. METHOD: Data on young adult men in households, 18-34 years, were drawn from the Second Men's Modern Lifestyles survey in Great Britain (n = 2046) and from a corresponding survey in Chengdu, China (n = 4132), using a translated questionnaire. Binary logistic regression models were carried out to estimate the cross-national differences for different types of violence and to identify explanatory variables. RESULTS: Chinese men were less likely to report violence in the past 5 years (AOR 0.59, 95% CI 0.48-0.72, P < 0.001). All levels of violence were lower among Chinese men except intimate partner violence (AOR 2.43, 95% CI 1.65-3.59, P < 0.001) and a higher proportion of Chinese men were only violent towards their partners (AOR 7.90, 95% CI 3.27-19.07, P < 0.001). CONCLUSIONS: Cross-national differences were explained by British men's reports of early violence persisting into adulthood, confidence in fighting ability, perception that violence is acceptable behaviour, and experience of violent victimization. More British men screened positive for antisocial personality disorder and substance misuse. Attitudes which condone violence and a serious problem of alcohol-related, male-on-male violence are key targets for preventive interventions among British men. The higher prevalence of life course-persistent antisocial behaviour among British men is of concern and requires further investigation. Higher prevalence of intimate partner violence among Chinese men reflects patriarchal approaches to conflict resolution and confirms an important public health problem in China which requires further cross-national investigation.
Asunto(s)
Trastorno de Personalidad Antisocial/epidemiología , Comparación Transcultural , Características Culturales , Violencia/estadística & datos numéricos , Adolescente , Adulto , China/epidemiología , Humanos , Violencia de Pareja/estadística & datos numéricos , Masculino , Prevalencia , Encuestas y Cuestionarios , Reino Unido/epidemiología , Adulto JovenRESUMEN
Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this disorder. However, the PFC functional connectivity patterns during illness onset and its longitudinal progression remain uncharacterized. Emerging evidence suggests that early-course schizophrenia involves increased PFC glutamate, which might elevate PFC functional connectivity. To test this hypothesis, we examined 129 non-medicated, human subjects diagnosed with early-course schizophrenia and 106 matched healthy human subjects using both whole-brain data-driven and hypothesis-driven PFC analyses of resting-state fMRI. We identified increased PFC connectivity in early-course patients, predictive of symptoms and diagnostic classification, but less evidence for "hypoconnectivity." At the whole-brain level, we observed "hyperconnectivity" around areas centered on the default system, with modest overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a subset of the sample followed longitudinally (n = 25), which also predicted immediate symptom improvement. Biologically informed computational modeling implicates altered overall connection strength in schizophrenia. The initial hyperconnectivity, which may decrease longitudinally, could have prognostic and therapeutic implications.
Asunto(s)
Red Nerviosa/fisiología , Corteza Prefrontal/fisiología , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Adolescente , Adulto , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Adulto JovenRESUMEN
Purpose To determine whether the brain functional abnormalities of drug-naive first-episode schizophrenia are reduced after 1 year of undergoing antipsychotic treatment and whether pretreatment resting-state functional magnetic resonance (MR) imaging parameters are associated with longitudinal changes in clinical symptoms. Materials and Methods This prospective study was approved by the local ethical committee, and written informed consent was obtained from all participants. Twenty antipsychotic-naive first-episode patients with schizophrenia and 16 healthy individuals were recruited and underwent resting-state functional MR imaging at baseline and again at 1-year follow-up, by which time significant clinical improvement was seen. The amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were analyzed with analysis of covariance. Results The amount of ALFF in the right inferior parietal lobule (IPL) and orbitofrontal cortex (OFC) and the amount of FC between the bilateral IPLs significantly increased over the follow-up period, and the amount of ALFF in the right occipital gyrus was reduced (P < .050, AlphaSim corrected [ http://afni.nimh.nih.gov/pub/dist/doc/manual/AlphaSim.pdf ]), returning toward normal levels. Furthermore, the degree of alteration in ALFF values in the right OFC (P = .037) and occipital gyrus (P = .002) at baseline was significantly correlated with the magnitude of the normalization in those regions at 1-year follow-up. In contrast, abnormalities of ALFF in the bilateral thalamus, ventral medial prefrontal cortex, precuneus, and right amygdala and of FC between the right OFC and the dorsal medial prefrontal cortex at baseline did not improve in patients at 1-year follow-up. Conclusion These findings show that some, but not all, neurophysiologic alterations that occur during the acute phase of schizophrenia are normalized in the context of clinical improvement and suggest therapeutic implications for exploration of which alterations in regional and network-level brain function evolve over time in patients with schizophrenia and which reflect persistent pathologic traits. Online supplemental material is available for this article.
Asunto(s)
Imagen por Resonancia Magnética , Esquizofrenia/diagnóstico por imagen , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiopatología , Estudios Prospectivos , Esquizofrenia/fisiopatología , Adulto JovenRESUMEN
We conducted a national survey among medical students in China to estimate the prevalence of depressive symptoms and explore associated risk factors based on an established questionnaire composed of demographic information, life events in the past four weeks before survey, and the validated Chinese version of the 21-item Beck's Depression Inventory (BDI). The mean age of enrolled 9010 students was 20.7 (standard deviation: 1.6) years. BDI scores indicated that 19.9% had depressive symptoms based on the cut-off score of 14. Socioeconomic factors and student characteristics such as male sex, low monthly income per capita, father's poor education background, and higher year of study were associated with higher prevalence of depressive symptoms among medical students. Students who studied in comprehensive universities were more likely to have depressive symptoms compared with those from medical universities. Habitual smoking and alcohol drinking, sleep deprivation, and hospitalization or medication for one week or more in the last four weeks also predisposed students to higher risk of depressive symptoms. Our results indicate that depressive symptoms are becoming a highly prevalent health problem among Chinese medical students. Primary and secondary prevention should be prioritized to tackle this issue based on potential risk factors.
Asunto(s)
Depresión/epidemiología , Estudiantes de Medicina/estadística & datos numéricos , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , China/epidemiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Renta , Masculino , Pobreza/estadística & datos numéricos , Prevalencia , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Factores Sexuales , Privación de Sueño/epidemiología , Fumar/epidemiología , Factores Socioeconómicos , Encuestas y Cuestionarios , Universidades , Adulto JovenRESUMEN
BACKGROUND: Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. METHODS: Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. RESULTS: Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal-limbic-thalamic-striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. LIMITATIONS: The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. CONCLUSION: The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD.
Asunto(s)
Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Sincronización Cortical/fisiología , Trastorno Depresivo Mayor/fisiopatología , Encéfalo/irrigación sanguínea , Mapeo Encefálico , Humanos , DescansoRESUMEN
Chemotherapy is still a prevalent strategy for clinical lung cancer treatment. However, the inevitable emerged drug resistance has become a great hurdle to therapeutic effect. Studies have demonstrated that the primary cause of drug resistance is a decrease in the chemotherapeutic medicine concentration. Several lectins have been confirmed to be effective as chemotherapy adjuvants, enhancing the anti-tumor effects of chemotherapy drugs. Here, we combined phytohemagglutinin (PHA), which has been reported possess anti-tumor effects, with chemotherapy drugs Cisplatin (DDP) and Adriamycin (ADM) on lung cancer cells to detect the sensitivities of PHA as a chemotherapy adjuvant. Our results demonstrated that the PHA significantly enhanced the sensitivity of lung cancer cells to DDP and ADM, and Western blot showed that PHA combined with DDP or ADM enhance cytotoxic effects by inhibiting autophagy and promoting apoptosis. More importantly, we found PHA enhanced the chemotherapeutic drugs cytotoxicity by changing the cell membrane to increase the intracellular chemotherapeutic drugs concentration. Besides, the combination of PHA and ADM increased the ADM concentration in the multidrug-resistant strain A549-R cells and achieved the drug sensitization effect. Our results suggest that PHA combined with chemotherapy can be applied in the treatment of lung cancer cells and lung cancer multidrug-resistant strains, and provide a novel strategy for clinical tumor chemotherapy and a new idea to solve the problem of drug resistance in clinical lung cancer.