Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 398
Filtrar
1.
Front Psychiatry ; 15: 1377815, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736629

RESUMO

In the face of the unprecedented public health crisis caused by the novel coronavirus pneumonia epidemic, front-line health workers are under enormous mental pressure. This paper aims to explore the mental health challenges faced by front-line health workers in the early stages of a public health emergency, such as stress, anxiety, and depression. At the same time, the factors that increase their mental stress are analyzed, and practical measures are put forward to prevent and manage mental health problems, aiming at improving the quality of medical treatment during public health emergencies. This paper has some reference value for people engaged in mental health prevention.

2.
Psychoradiology ; 4: kkae005, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694267

RESUMO

Background: Schizophrenia is a polygenic disorder associated with changes in brain structure and function. Integrating macroscale brain features with microscale genetic data may provide a more complete overview of the disease etiology and may serve as potential diagnostic markers for schizophrenia. Objective: We aim to systematically evaluate the impact of multi-scale neuroimaging and transcriptomic data fusion in schizophrenia classification models. Methods: We collected brain imaging data and blood RNA sequencing data from 43 patients with schizophrenia and 60 age- and gender-matched healthy controls, and we extracted multi-omics features of macroscale brain morphology, brain structural and functional connectivity, and gene transcription of schizophrenia risk genes. Multi-scale data fusion was performed using a machine learning integration framework, together with several conventional machine learning methods and neural networks for patient classification. Results: We found that multi-omics data fusion in conventional machine learning models achieved the highest accuracy (AUC ~0.76-0.92) in contrast to the single-modality models, with AUC improvements of 8.88 to 22.64%. Similar findings were observed for the neural network, showing an increase of 16.57% for the multimodal classification model (accuracy 71.43%) compared to the single-modal average. In addition, we identified several brain regions in the left posterior cingulate and right frontal pole that made a major contribution to disease classification. Conclusion: We provide empirical evidence for the increased accuracy achieved by imaging genetic data integration in schizophrenia classification. Multi-scale data fusion holds promise for enhancing diagnostic precision, facilitating early detection and personalizing treatment regimens in schizophrenia.

3.
J Exp Bot ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506421

RESUMO

Modern tomatoes produce colourful mature fruits, but many wild tomato ancestors form green or gray green ripe fruits. In this study, tomato cultivar 'Lvbaoshi' (LBS) that produces green ripe fruits was found to contain three recessive loci that were responsible for development of green ripe fruits. The colourless peel of LBS fruits was caused by a 603-bp deletion in the promoter of SlMYB12. The candidate genes of the remaining two loci were identified as Stay-Green 1 (SlSGR1) and Phytoene Synthase 1 (SlPSY1). A single nucleotide substitution was present in sgr1 of LBS, resulting in disruption of mRNA splicing and truncation of the translated protein. A retrotransposon was found in the first exon of the psy1 locus in LBS, leading to the absence of any detectable PSY1 transcripts. Co-suppression of SGR1 and PSY1 by RNA interference (RNAi) converted the pink fruits into green ripe fruits in transgenic plants. An amino acid change in PSY1 and a deletion in the promoter of SGR1 were identified in many wild tomatoes bearing green or gray ripe fruits. Transgenic lines expressing ProSGR1::SGR1 from Solanum pennellii failed to convert the purple-flesh fruits into the red-flesh fruits. Overexpression of PSY1 from green ripe fruit wild tomatoes in LBS plants could only partially rescue the green ripe fruit phenotype of LBS. Downregulation of the Ripening Inhibitor (RIN) gene in the green-flesh (gf) plants led to development of green ripe fruits. This work uncovers a novel regulatory mechanism by which SlMYB12, SlPSY1 and SlSGR1 regulate fruit colour in cultivated tomatoes and some wild tomato species.

4.
Int J Surg ; 110(3): 1367-1375, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38484258

RESUMO

BACKGROUND: A diverting loop ileostomy (DLI) is performed in laparoscopic anterior rectal resection (LAR) surgery at high risk of anastomotic fistula. Minimally invasive surgery promotes postoperative recovery and cosmetics. To reduce abdominal trauma, specimen extraction through stoma incision (EXSI) is usually performed to avoid auxiliary abdominal incision with enlarged stomal incision. The traditional suture method (TSM) reduces the incision size by suturing the ends of the enlarged incision, leading to peristomal incisions and a higher risk of stomal complications. The study aimed to introduce the dumpling suture method (DSM) of PLI and compare this new method with TSM. MATERIALS AND METHODS: The authors propose a novel stoma suture technique, which utilized a method of skin folding suture to reduce the enlarged incision size. A retrospective analysis was conducted on 71 consecutive patients with rectal cancer who underwent LAR-DLI with EXSI, and the intraoperative details and postoperative outcomes of the two groups were measured. RESULTS: The DSM group showed a lower stomal complication rate (10.3 vs. 35.7%, P=0.016) than that of the TSM group. The scores of DET (Discoloration, Erosion, Tissue overgrowth), stomal pain, quality of life were all significantly lower in DSM group than in TSM group. In multivariate analysis, DSM was an independent protective factor for stoma-related complications. Operative time, time to first flatus, defecation and eat, nonstomal related postoperative complications were similar in both groups. CONCLUSION: DSM utilizes a method of skin folding suture to reduce the enlarged incision size, which is safe and effective in reducing the incidence of peristomal skin infections and stomal complications. This procedure offers a novel suturing approach for loop ileostomy with enlarged incision, effectively reducing the postoperative trauma and incidence of stomal complications.


Assuntos
Laparoscopia , Neoplasias Retais , Ferida Cirúrgica , Humanos , Ileostomia/métodos , Estudos Retrospectivos , Estudos de Coortes , Qualidade de Vida , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Anastomose Cirúrgica/efeitos adversos , Ferida Cirúrgica/complicações , Técnicas de Sutura/efeitos adversos , Suturas/efeitos adversos
5.
Cell Death Differ ; 31(5): 618-634, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38424148

RESUMO

IκB kinase (IKK) complex is central regulators of the NF-κB pathway, and dysregulation of IKK phosphorylation leads to hyperactivation of proinflammatory response in various chronic inflammatory diseases, including inflammatory bowel disease (IBD). However, the dynamic modulation of IKK phosphorylation and dephosphorylation in intestinal inflammation remains uncharacterized. Here, we found that autophagy/beclin-1 regulator 1 (AMBRA1) was highly expressed in inflamed colons in a colitis mouse model and in clinical IBD samples. Importantly, AMBRA1 deletion significantly decreased proinflammatory cytokine expression and enhanced the therapeutic effect of infliximab on intestinal inflammation. Mechanistically, the N-term F1 domain of AMBRA1 was required for AMBRA1 to competitively interact with protein phosphatase 4 regulatory subunit 1 (PP4R1) and catalytic protein phosphatase 4 (PP4c) to suppress their interactions with IKK, promote the dissociation of the PP4R1/PP4c complex, and antagonize the dephosphorylation activity of this complex towards the IKK complex. In response to TNF-α stimulation, IKKα phosphorylates AMBRA1 at S1043 to stabilize AMBRA1 expression by impairing its binding to Cullin4A (CUL4A) to decrease its CUL4A-mediated K48-linked ubiquitination. Overall, our study identifies an autophagy-independent function of AMBRA1 as a positive modulator of IKK phosphorylation to promote intestinal inflammation, thus providing a new targeted therapeutic strategy for patients with refractory IBD.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Autofagia , Quinase I-kappa B , Animais , Autofagia/efeitos dos fármacos , Camundongos , Humanos , Quinase I-kappa B/metabolismo , Fosforilação , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Camundongos Endogâmicos C57BL , Inflamação/metabolismo , Inflamação/patologia , Fosfoproteínas Fosfatases/metabolismo , Fosfoproteínas Fosfatases/genética , Colite/metabolismo , Colite/patologia , Colite/induzido quimicamente , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Células HEK293
6.
Heliyon ; 10(4): e25915, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404811

RESUMO

Cognitive impairments in schizophrenia are pivotal clinical issues that need to be solved urgently. However, the mechanism remains unknown. It has been suggested that cognitive impairments in schizophrenia are associated with connectome damage, and are especially relevant to the disrupted hub nodes in the frontal and parietal lobes. Activating the dorsolateral prefrontal cortex (DLPFC) via repetitive transcranial magnetic stimulation (rTMS) could result in improved cognition. Based on several previous magnetic resonance imaging (MRI) studies on schizophrenia, we found that the first-episode patients showed connectome damage, as well as abnormal activation and connectivity of the DLPFC and inferior parietal lobule (IPL). Accordingly, we proposed that DLPFC-IPL pathway destruction might mediate connectome damage of cognitive impairments in schizophrenia. In the meantime, with the help of multimodal MRI and noninvasive neuromodulation tool, we may not only validate the hypothesis, but also find IPL as the potential intervention target for cognitive impairments in schizophrenia.

7.
Transl Psychiatry ; 14(1): 21, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38199983

RESUMO

High suicide risk represents a serious problem in patients with major depressive disorder (MDD), yet treatment options that could safely and rapidly ameliorate suicidal ideation remain elusive. Here, we tested the feasibility and preliminary efficacy of the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) in reducing suicidal ideation in patients with MDD. Thirty-two MDD patients with moderate to severe suicidal ideation participated in the current study. Suicidal ideation and depression symptoms were assessed before and after 5 days of open-label SAINT. The neural pathways supporting rapid-acting antidepressant and suicide prevention effects were identified with dynamic causal modelling based on resting-state functional magnetic resonance imaging. We found that 5 days of SAINT effectively alleviated suicidal ideation in patients with MDD with a high response rate of 65.63%. Moreover, the response rates achieved 78.13% and 90.63% with 2 weeks and 4 weeks after SAINT, respectively. In addition, we found that the suicide prevention effects of SAINT were associated with the effective connectivity involving the insula and hippocampus, while the antidepressant effects were related to connections of the subgenual anterior cingulate cortex (sgACC). These results show that SAINT is a rapid-acting and effective way to reduce suicidal ideation. Our findings further suggest that distinct neural mechanisms may contribute to the rapid-acting effects on the relief of suicidal ideation and depression, respectively.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Ideação Suicida , Hipocampo , Imageamento por Ressonância Magnética , Antidepressivos/uso terapêutico
8.
Gut Liver ; 18(1): 85-96, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36987383

RESUMO

Background/Aims: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as a radical surgery for refractory ulcerative colitis (UC). Definite results on the appropriate pouch length for an evaluation of the risk-to-benefit ratio regarding technical complications and long-term quality of life (QOL) are still scarce. Methods: Data on UC patients who underwent IPAA from 2008 to 2022 in four well-established pouch centers affiliated to China UC Pouch Center Union were collected. Results: A total of 208 patients with a median follow-up time of 6.0 years (interquartile range, 2.3 to 9.0 years) were enrolled. The median lengths of the patients' short and long pouches were 14.0 cm (interquartile range, 14.0 to 15.0 cm) and 22.0 cm (interquartile range, 20.0 to 24.0 cm), respectively. Patients with a short J pouch configuration were less likely to achieve significantly improved long-term QOL (p=0.015) and were prone to develop late postoperative complications (p=0.042), such as increased defecation frequency (p=0.003) and pouchitis (p=0.035). A short ileal pouch was an independent risk factor for the development of late postoperative complications (odds ratio, 3.100; 95% confidence interval, 1.519 to 6.329; p=0.002) and impaired longterm QOL improvement (odds ratio, 2.221; 95% confidence interval, 1.218 to 4.050, p=0.009). Conclusions: The length of the J pouch was associated with the improvement in long-term QOL and the development of late post-IPAA complications. A long J pouch configuration could be a considerable surgical option for pouch construction.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Humanos , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Bolsas Cólicas/efeitos adversos , Colite Ulcerativa/cirurgia , Colite Ulcerativa/complicações , Qualidade de Vida , Resultado do Tratamento , Estudos Retrospectivos , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
9.
Sci Total Environ ; 912: 169209, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38092211

RESUMO

The partial pressure of ocean surface CO2 (pCO2) plays an important role in quantifying the carbon budget and assessing ocean acidification. For such a vast and complex ocean system as the global ocean, most current research practices tend to study the ocean into regions. In order to reveal the overall characteristics of the global ocean and avoid mutual influence between zones, a holistic research method was used to detect the correlation of twelve predictive factors, including chlorophyll concentration (Chlor_a), diffuse attenuation coefficient at 490 nm (Kd_490), density ocean mixed layer thickness (Mlotst), eastward velocity (East), northward velocity (North), salinity (Sal), temperature (Temp), dissolved iron (Fe), dissolved silicate (Si), nitrate (NO3), potential of hydrogen (pH), phosphate (PO4), at the global ocean scale. Based on measured data from the Global Surface pCO2 (LDEO) database, combined with National Aeronautics and Space Administration (NASA) Ocean Color satellite data and Copernicus Ocean reanalysis data, an improved optimized random forest (ORF) method is proposed for the overall reconstruction of global ocean surface pCO2, and compared with various machine learning methods. The results indicate that the ORF method is the most accurate in overall modeling at the global ocean scale (mean absolute error of 6.27µatm, root mean square error of 15.34µatm, R2 of 0.92). Based on independent observations from the LDEO dataset and time series observation stations, the ORF model was further validated, and the global ocean surface pCO2 distribution map of 0.25° × 0.25° for 2010 to 2019 was reconstructed, which is of significance for the global ocean carbon cycle and carbon assessment.

10.
Int J Obes (Lond) ; 48(3): 394-402, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38066333

RESUMO

BACKGROUND: Obesity is a common feature in women with polycystic ovary syndrome (PCOS) and is associated with multiple adverse reproductive outcomes. However, the impact of overweight and obesity on reproductive outcomes of women with PCOS who underwent in vitro fertilization-embryo transfer (IVF-ET) is currently controversial and appropriate body mass index (BMI) levels differ across ethnic groups. METHODS: This was a retrospective study including 1066 women with PCOS receiving IVF treatment at our institution between January 2018 and June 2021, among whom 960 underwent their first fresh or frozen embryo transfer. Participants were categorized according to BMI cut-off values proposed by the World Health Organization for Asian populations: normal weight (BMI < 23 kg/m2), overweight (BMI: 23-24.9 kg/m2), and obesity (BMI ≥ 25 kg/m2). The effect of BMI on clinical and embryological outcomes was evaluated by descriptive statistics and logistic regression models with confounders adjusted. The dose-response relationship between BMI as a continuous variable and IVF outcomes is also explored. INTERVENTIONS: no RESULTS: Increasing BMI was associated with significantly lower numbers of total oocytes retrieved, metaphase II oocytes, two pronuclear (2PN) zygotes, and good-quality embryos among women with PCOS. Patients with PCOS with a BMI ≥ 23 kg/m2 had significantly lower live birth rates (41.9% vs. 49.1%; adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], 0.57-0.97) and implantation rates (35.8% vs. 43.9%; aOR, 0.76; 95% CI, 0.61-0.93) than those with normal BMI. Moreover, BMI showed a non-linear relationship (p for nonlinearity <0.001) with the number of 2PN zygotes with the curve becoming steeper as BMI surpassed 22.4 kg/m2. CONCLUSIONS: Patients with PCOS with a BMI ≥ 23 kg/m2 have lower live birth rates than those with a BMI < 23 kg/m2. Defining obesity and overweight with ethnicity-specific BMI cut-offs may help to improve IVF outcomes among PCOS patients.


Assuntos
Sobrepeso , Síndrome do Ovário Policístico , Gravidez , Humanos , Feminino , Sobrepeso/complicações , Sobrepeso/epidemiologia , Síndrome do Ovário Policístico/complicações , Índice de Massa Corporal , Fertilização in vitro , Estudos Retrospectivos , Taxa de Gravidez , Obesidade/complicações , Obesidade/epidemiologia , China/epidemiologia
11.
Physiol Genomics ; 56(1): 32-47, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37955337

RESUMO

The microenvironment and cell populations within the myometrium play crucial roles in maintaining uterine structural integrity and protecting the fetus during pregnancy. However, the specific changes occurring at the single-cell level in the human myometrium between nonpregnant (NP) and term pregnant (TP) states remain unexplored. In this study, we used single-cell RNA sequencing (scRNA-Seq) and spatial transcriptomics (ST) to construct a transcriptomic atlas of individual cells in the myometrium of NP and TP women. Integrated analysis of scRNA-Seq and ST data revealed spatially distinct transcriptional characteristics and examined cell-to-cell communication patterns based on ligand-receptor interactions. We identified and categorized 87,845 high-quality individual cells into 12 populations from scRNA-Seq data of 12 human myometrium tissues. Our findings demonstrated alterations in the proportions of five subpopulations of smooth muscle cells in TP. Moreover, an increase in monocytic cells, particularly M2 macrophages, was observed in TP myometrium samples, suggesting their involvement in the anti-inflammatory response. This study provides unprecedented single-cell resolution of the NP and TP myometrium, offering new insights into myometrial remodeling during pregnancy.NEW & NOTEWORTHY Using single-cell RNA sequencing and spatial transcriptomics, the myometrium was examined at the single-cell level during pregnancy. We identified spatially distinct cell populations and observed alterations in smooth muscle cells and increased M2 macrophages in term pregnant women. These findings offer unprecedented insights into myometrial remodeling and the anti-inflammatory response during pregnancy. The study advances our understanding of pregnancy-related myometrial changes.


Assuntos
Miométrio , Útero , Gravidez , Feminino , Humanos , Miométrio/fisiologia , Miócitos de Músculo Liso , Anti-Inflamatórios
12.
Sci Total Environ ; 912: 168671, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-37996025

RESUMO

The implementation of roadside air purifiers has emerged as an effective active control measure to alleviate air pollution in urban street canyons. However, technical questions raised under real conditions remain challenging. In this study, we conducted a pilot-scale investigation involving seven units of self-designed roadside air purifiers in an urban street canyon in Hong Kong. The air cleaning effects were quantified with an air quality sensor network after rigorous quality control. The removal efficiencies of Nitrogen dioxide (NO2), Fine suspended particulates (PM2.5), Carbon monoxide (CO), and Nitric oxide (NO) were determined by comparing with simultaneously measured ambient concentrations, with hourly average efficiencies of 14.0 %-16.9 %, 3.5-10.0 %, 11.9 %-18.7 %, and 19.2 %-44.9 %, respectively. Generally, the purification effects presented variations depending on the ambient pollutants' levels. Higher ambient concentrations of NO2, PM2.5, CO correlated with increased purification effects, while NO presented the opposite trend. The influence of interval distance combined with spatial distribution indicated the operation of purifiers will induce local NO2 attenuation even at an interval distance of four meters. Statistical analysis delivered evidence the air cleaning ability exhibited optimal performance when relative humidity level is ranged from 70 % to 90 %, aligning with the prevailing conditions in Hong Kong. Additionally, improved purification effects were observed at the downwind direction, and their performance was enhanced when the wind speed exceeded 2.5 m/s. Moreover, we estimated the operational lifetime of the air purifiers to be approximately 130 days, offering crucial information regarding the filter replacement cycle. This work serves as a pioneering case study, showcasing the feasibility and deployment considerations of roadside air purifiers in effectively controlling air pollution in urban environments.

13.
Plant Biotechnol J ; 22(3): 698-711, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37929693

RESUMO

Flowering time, an important factor in plant adaptability and genetic improvement, is regulated by various genes in tomato (Solanum lycopersicum). In this study, we characterized a tomato mutant, EARLY FLOWERING (EF), that developed flowers much earlier than its parental control. EF is a dominant gain-of-function allele with a T-DNA inserted 139 bp downstream of the stop codon of FANTASTIC FOUR 1/2c (FAF1/2c). The transcript of SlFAF1/2c was at elevated levels in the EF mutant. Overexpressing SlFAF1/2c in tomato plants phenocopied the early flowering trait of the EF mutant. Knocking out SlFAF1/2c in the EF mutant reverted the early flowering phenotype of the mutant to the normal flowering time of the wild-type tomato plants. SlFAF1/2c promoted the floral transition by shortening the vegetative phase rather than by reducing the number of leaves produced before the emergence of the first inflorescence. The COP9 signalosome subunit 5B (CSN5B) was shown to interact with FAF1/2c, and knocking out CSN5B led to an early flowering phenotype in tomato. Interestingly, FAF1/2c was found to reduce the accumulation of the CSN5B protein by reducing its protein stability. These findings imply that FAF1/2c regulates flowering time in tomato by reducing the accumulation and stability of CSN5B, which influences the expression of SINGLE FLOWER TRUSS (SFT), JOINTLESS (J) and UNIFLORA (UF). Thus, a new allele of SlFAF1/2c was discovered and found to regulate flowering time in tomato.


Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Alelos , Mutação com Ganho de Função , Mutação , Flores/genética , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/genética
14.
medRxiv ; 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38077063

RESUMO

Striatal dopaminergic overactivity was hypothesized as the core pathophysiology of schizophrenia. However, morphological alterations of striatum in schizophrenia remains exclusive, largely because brain regional heterogeneity limited traditional group-mean based approach. Leveraging third-party brain maps of neurotransmitter and cognition behaviours, we developed a pattern-based representation feature score (ReFS) to investigate structural spatial pattern variation in schizophrenia. Structural ReFS of subcortical regions, particularly the striatum, were linked to schizophrenia diagnosis, symptom severity, and genetic susceptibility. Dopaminergic-ReFS of striatum was increased in schizophrenia patients and reliably reproduced across 13 datasets. The pattern-based ReFS effectively captured the shared genetic pathways underlying both schizophrenia and striatum. The results provide convergent, multimodal suggest the central role of striatal spatial patterns in schizophrenia psychopathologies and and open new avenues to develop individualized treatments for psychotic disorders.

15.
Sci Rep ; 13(1): 21523, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057383

RESUMO

The occurrence of systemic inflammatory response after percutaneous transhepatic gallbladder drainage brings great risks to patients and is one of the challenges faced by clinicians. Therefore, it is of great significance to find a suitable prediction method for clinicians to intervene early and reduce the transformation of serious complications. Easy-to-obtain and objectively measured clinical features were screened, and logistic regression was used to construct a prediction model. The predictive ability of the model was evaluated by using the receiver operating characteristic curve and the decision curve in the validation set and the training set, respectively. Nine clinical features (CRP, Fever, DBIL, Obstruction, Bile properties, PCT, Length, Width, and Volume factor) were used to construct the prediction model, and the validation results showed that the prediction model had good performance in the training set (AUC = 0.83) and the validation set (AUC = 0.81). The decision curve also showed that the predictive ability of the model incorporating nine clinical features is better than that of a single clinical feature. The model we constructed can accurately predict the occurrence of SIRS, which can guide clinicians to take treatment measures and avoid the deterioration of complications.


Assuntos
Vesícula Biliar , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Vesícula Biliar/cirurgia , Curva ROC , Modelos Logísticos , Drenagem/efeitos adversos , Drenagem/métodos , Estudos Retrospectivos
16.
Nat Commun ; 14(1): 6532, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848452

RESUMO

N6-methyladenosine (m6A) maintains maternal RNA stability in oocytes. One regulator of m6A, ALKBH5, reverses m6A deposition and is essential in RNA metabolism. However, the specific role of ALKBH5 in oocyte maturation remains elusive. Here, we show that Alkbh5 depletion causes a wide range of defects in oocyte meiosis and results in female infertility. Temporal profiling of the maternal transcriptomes revealed striking RNA accumulation in Alkbh5-/- oocytes during meiotic maturation. Analysis of m6A dynamics demonstrated that ALKBH5-mediated m6A demethylation ensures the timely degradation of maternal RNAs, which is severely disrupted following Alkbh5-/- depletion. A distinct subset of transcripts with persistent m6A peaks are recognized by the m6A reader IGF2BP2 and thus remain stabilized, resulting in impaired RNA clearance. Additionally, reducing IGF2BP2 in Alkbh5-depleted oocytes partially rescued these defects. Overall, this work identifies ALKBH5 as a key determinant of oocyte quality and unveil the facilitating role of ALKBH5-mediated m6A removal in maternal RNA decay.


Assuntos
Oócitos , Oogênese , Feminino , Humanos , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Meiose/genética , Metilação , Oócitos/metabolismo , Oogênese/genética , Oogênese/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
17.
Adv Sci (Weinh) ; 10(32): e2303378, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37786278

RESUMO

Although the MAPK/MEK/ERK pathway is prevalently activated in colorectal cancer (CRC), MEK/ERK inhibitors show limited efficiency in clinic. As a downstream target of MAPK, ELK4 is thought to work primarily by forming a complex with SRF. Whether ELK4 can serve as a potential therapeutic target is unclear and the transcriptional regulatory mechanism has not been systemically analyzed. Here, it is shown that ELK4 promotes CRC tumorigenesis. Integrated genomics- and proteomics-based approaches identified SP1 and SP3, instead of SRF, as cooperative functional partners of ELK4 at genome-wide level in CRC. Serum-induced phosphorylation of ELK4 by MAPKs facilitated its interaction with SP1/SP3. The pathological neoangiogenic factor LRG1 is identified as a direct target of the ELK4-SP1/SP3 complex. Furthermore, targeting the ELK4-SP1/SP3 complex by combination treatment with MEK/ERK inhibitor and the relatively specific SP1 inhibitor mithramycin A (MMA) elicited a synergistic antitumor effect on CRC. Clinically, ELK4 is a marker of poor prognosis in CRC. A 9-gene prognostic model based on the ELK4-SP1/3 complex-regulated gene set showed robust prognostic accuracy. The results demonstrate that ELK4 cooperates with SP1 and SP3 to transcriptionally regulate LRG1 to promote CRC tumorigenesis in an SRF-independent manner, identifying the ELK4-SP1/SP3 complex as a potential target for rational combination therapy.


Assuntos
Neoplasias Colorretais , Regulação da Expressão Gênica , Humanos , Regiões Promotoras Genéticas , Neoplasias Colorretais/genética , Carcinogênese/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Proteínas Elk-4 do Domínio ets/genética , Glicoproteínas
18.
BMC Med ; 21(1): 250, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37424013

RESUMO

BACKGROUND: Inflammation has been implicated in the pathology of schizophrenia and may cause neuronal cell death and dendrite loss. Neuroimaging studies have highlighted longitudinal brain structural changes in patients with schizophrenia, yet it is unclear whether this is related to inflammation. We aim to address this question, by relating brain structural changes with the transcriptional profile of inflammation markers in the early stage of schizophrenia. METHODS: Thirty-eight patients with first-episode schizophrenia and 51 healthy controls were included. High-resolution T1-weighted magnetic resonance imaging (MRI) and clinical assessments were performed at baseline and 2 ~ 6 months follow-up for all subjects. Changes in the brain structure were analyzed using surface-based morphological analysis and correlated with the expression of immune cells-related gene sets of interest reported by previous reviews. Transcriptional data were retrieved from the Allen Human Brain Atlas. Furthermore, we examined the brain structural changes and peripheral inflammation markers in association with behavioral symptoms and cognitive functioning in patients. RESULTS: Patients exhibited accelerated cortical thickness decrease in the left frontal cortices, less decrease or an increase in the superior parietal lobule and right lateral occipital lobe, and increased volume in the bilateral pallidum, compared with controls. Changes in cortical thickness correlated with the transcriptional level of monocyte across cortical regions in patients (r = 0.54, p < 0.01), but not in controls (r = - 0.05, p = 0.76). In addition, cortical thickness change in the left superior parietal lobule positively correlated with changes in digital span-backward test scores in patients. CONCLUSIONS: Patients with schizophrenia exhibit regional-specific cortical thickness changes in the prefrontal and parietooccipital cortices, which is related to their cognitive impairment. Inflammation may be an important factor contributing to cortical thinning in first-episode schizophrenia. Our findings suggest that the immunity-brain-behavior association may play a crucial role in the pathogenesis of schizophrenia.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cognição , Córtex Cerebral/patologia
19.
Pak J Med Sci ; 39(4): 936-940, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492320

RESUMO

Objective: To observe the anesthesia and clinical efficacy of inhalation anesthesia and intravenous anesthesia in patients with trigeminal neuralgia undergoing surgery. Methods: This is a retrospective study. Eighty patients with trigeminal neuralgia admitted to the Affiliated Hospital of Beihua University from July 2018 to July 2021 were selected and divided into two groups according to different anesthesia methods: inhalation group and intravenous group, with 40 cases in each group. Patients in the inhalation group were given inhalation anesthesia with sevoflurane, while those in the intravenous group were given intravenous anesthesia. Hemodynamics, intubation and extubation time, postoperative consciousness recovery, adverse reactions and clinical effects of surgery were compared between the two groups during anesthesia. Results: During the induction of anesthesia, after induction and after surgery, the levels of hemodynamic parameters in the two groups increased compared with those before induction of anesthesia, and the increase in the inhalation group was smaller (P<0.05). Patients in the inhalation group had a long time from anesthesia to endotracheal intubation but had a short time from completion of surgery to intubation, which was statistically significant compared with the intravenous group (P<0.05). Compared with the intravenous group, the postoperative consciousness recovery time of the inhalation group was significantly shorter and the incidence of adverse reactions was significantly lower (P<0.05). Conclusion: Inhalation anesthesia with sevoflurane is more effective than intravenous anesthesia in trigeminal neuralgia patients treated with trigeminal nerve balloon avulsion, boasting satisfactory safety, less impact on hemodynamics, and shorter recovery time of consciousness.

20.
BMC Psychiatry ; 23(1): 526, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37479996

RESUMO

BACKGROUND: Cognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia. METHODS: 136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects' cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia. RESULTS: Grouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P < 0.05). We found a negative correlation between the backward digit span task score and fALFF of the left IPL in healthy controls (r = - 0.388, P = 0.003), which was not seen in patients (r = 0.203, P = 0.020). In addition, none of the other analyses were statistically significant (P > 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia. CONCLUSION: Our study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment.


Assuntos
Disfunção Cognitiva , Esquizofrenia , Adulto , Humanos , Disfunção Cognitiva/complicações , Estudos Transversais , Diacilglicerol Quinase , Lobo Parietal , Esquizofrenia/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...