RESUMO
Tuning fork, consisting of two fork arms and a fork handle, has a stable and rigid structure. Inspired by this structure, a tuning fork-shaped DNA (TF-DNA) fluorescence aptasensor was constructed to detect ochratoxin A (OTA) and aflatoxin B1 (AFB1). A TF-DNA double-stranded structure capable of attaching both OTA aptamer labeled with the FAM fluorescent group (FAM-Apt) and AFB1 aptamer labeled with the ROX fluorescent group (ROX-Apt) was designed and linked to magnetic beads. This TF-DNA double-stranded structure can provide a stable platform for dual-target detection. In the presence of OTA and AFB1, FAM-Apt and ROX-Apt preferentially bound to them and detached from the TF-DNA double-stranded structure. Dual-signal fluorescent probes were collected from the supernatant by magnetic separation, and achieved fluorescence enhancement at 520 nm and 607 nm, respectively. The linear ranges are 0.05 ng/mL to 100 ng/mL for OTA and 0.1 ng/mL to 100 ng/mL for AFB1, and the detection limits are 0.015 ng/mL and 0.045 ng/mL, respectively. The developed sensor has the advantages of simple and fast preparation, good specificity and reproducibility, which is promising for the simultaneous determination of multiple hazardous substances in food.
RESUMO
CXCL5 is overexpressed in colorectal cancer (CRC) and promotes distant metastasis and angiogenesis of tumors; however, the underlying mechanism that mediates CXCL5 overexpression in CRC remains unclear. Here, we successfully extracted and identified primary mesenchymal stromal cells (MSCs) and verified the promoting effects of tumor-associated MSCs on CRC proliferation and metastasis in vivo and in vitro. We found that MSCs not only promoted the expression of CXCL5 by secreting CCL7 but also secreted TGF-ß to inhibit this process. After secretion, CCL7/CCR1 activated downstream CBP/P300 to acetylate KLF5 to promote CXCL5 transcription, while TGF-ß reversed the effect of KLF5 on transcription activation by regulating SMAD4. Taken together, our results indicate that MSCs in the tumor microenvironment promoted the progression and metastasis of CRC and regulated the expression of CXCL5 in CRC cells by secreting CCL7 and TGF-ß. KLF5 is the key site of these processes and plays a dual role in CXCL5 regulation. MSCs and their secreted factors may serve as potential therapeutic targets in the tumor environment.
Assuntos
Neoplasias Colorretais , Células-Tronco Mesenquimais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CCL7 , Quimiocina CXCL5/genética , Quimiocina CXCL5/metabolismo , Quimiocina CXCL5/farmacologia , Neoplasias Colorretais/patologia , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Células-Tronco Mesenquimais/metabolismo , Metástase Neoplásica , Neovascularização Patológica/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: In laparoscopic low anterior resection for rectal cancer surgery, there has been controversy to whether the inferior mesenteric artery (IMA) should be ligated at the origin of its aorta (high ligation (HL)) or below the branches of the left colonic artery (LCA) (low ligation (LL)). This study was intended to clarify oncological outcome and long-term prognosis of retrospective analysis. METHODS: Analyzed the cases who underwent laparoscopic low anterior resection (LAR) in Shanghai Ruijin Hospital from January 2015 to December 2016, 357patients scheduled into 2 groups according to the level of IMA ligation: HL (n = 247) versus LL (n = 110). RESULTS: The primary endpoint is long-term outcomes, and the secondary endpoint is the incidence rate of major postoperative complications. There were no significant differences in 5-year overall survival (P = 0.92) and 5-year disease-free survival (P = 0.41). There were no differences between the clinical baseline levels in each group. The incidence of low anterior resection syndrome (LARS) in the two groups was statistically significant (P = 0.037). No significant differences were observed in operative time (P = 0.092) and intraoperative blood loss (P = 0.118). In the HL group, 6 cases (2.4%) had additional colonic excision due to poor anastomotic blood supply; none of the colonic anastomosis in the low ligation group had ischemic manifestations, and length from the proximal margin (P = 0.076), length from the distal margin (P = 0.184), the total number of lymph nodes excised (P = 0.065), and anastomotic leakage incidence (P = 0.33). CONCLUSION: Low ligation of the IMA which reserved LCA with vascular root lymph node dissection in laparoscopic low anterior resection for rectal cancer surgery may help protect the blood supply of the anastomosis, and will not increase postoperative complications while enhance recovery, without compromising radical excision and long-term prognosis.
Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Artéria Mesentérica Inferior/cirurgia , Neoplasias Retais/cirurgia , ChinaRESUMO
BACKGROUND: The surgical procedure for laparoscopic right colectomy (LRC) is not standardized. Some published studies show the superiority of ileocolic anastomosis (IIA), but the evidence so far is insufficient. This study aimed to investigate the potential advantages in postoperative recovery and safety of IIA in LRC. METHODS: A total of 114 patients who underwent LRC with IIA (n = 58) or extracorporeal ileocolic anastomosis (EIA, n = 56) between January 2019 and September 2021 were enrolled. We collected certain factors as clinical features, intraoperative characteristics, oncological outcomes, postoperative recovery, and short-term outcomes. Our primary outcome was time to gastrointestinal (GI) function recovery. Secondary outcomes were postoperative complications within 30 days, postoperative pain, and length of hospital stay. RESULTS: Faster GI recovery and less postoperative pain were observed in patients with IIA compared to EIA [time to first flatus: (2.4 ± 0.7) vs (2.8 ± 1.0) days, p < 0.01; time to liquid intake: (3.5 ± 0.7) vs (4.0 ± 1.1) days, p = 0.01; postoperative visual analogue scale score: (3.9 ± 1.0) vs (4.3 ± 0.6), p = 0.02]. No significant differences were detected in oncological outcomes or postoperative complications. IIA, rather than EIA, tended to be performed in patients with higher body mass index [(23.93 ± 3.52) vs (22.36 ± 2.87) kg/m2, p = 0.01]. CONCLUSIONS: IIA is associated with faster GI function recovery and less postoperative pain and may be more favorable for obese patients.
Assuntos
Neoplasias do Colo , Laparoscopia , Humanos , Estudos Retrospectivos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/complicações , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Colectomia/efeitos adversos , Colectomia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Dor Pós-Operatória/etiologia , Resultado do TratamentoRESUMO
OBJECTIVES: The current study aimed to develop a scale assessing knowledge about behavioral and psychological symptoms of dementia (KS-BPSD) among Chinese formal caregivers and to investigate its psychometric properties and factorial structure. METHODS: The scale was generated with a systematic development process, and 229 formal caregivers working at nursing homes were recruited to construct and assess the psychometric properties of the scale. The preliminary scale was reviewed by an expert panel and items were selected based on item discrimination, difficulty, and item-total correlation. RESULTS: The final KS-BPSD version consisted of 12 items, loaded into three factors (i.e., Disease Characteristics, Care and Risks, and Treatment Needs) following principal component analysis (PCA). The KS-BPSD showed good test-retest reliability, internal consistency, as well as construct and concurrent validity. CONCLUSIONS: The 12-item KS-BPSD was found to have high reliability and preliminary validity in assessing the level of knowledge about patient's BPSD among formal Chinese caregivers in nursing homes. CLINICAL IMPLICATIONS: KS-BPSD is a reliable tool to address the knowledge discrepancies and support needs among dementia caregivers, helping to develop and evaluate educational programs in the management of patient's BPSD.
Assuntos
Cuidadores , Demência , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Sintomas Comportamentais/diagnóstico , Cuidadores/psicologia , Demência/psicologia , População do Leste Asiático , Reprodutibilidade dos TestesRESUMO
STUDY OBJECTIVES: This study aims to investigate the extent to which sleep duration and efficiency are associated with plasma amyloid-ß (Aß) levels in non-demented older people. METHODS: This study is a cross-sectional analysis of 305 non-demented older people. Sleep duration and efficiency were assessed used the Pittsburgh Sleep Quality Index. Levels of plasma Aß were determined by sandwich enzyme-linked immunosorbent assay technique. Associations between sleep variables and plasma Aß levels were evaluated with multivariable linear regression analysis. RESULTS: Compared to those with sleep duration > 7 h, participants with sleep duration < 6 h had a higher plasma Aß42 level (ß = 0.495, 95% CI 0.077~0.913, p = 0.021) and Aß42/Aß40 ratio (ß = 0.101, 95% CI 0.058~0.144, p < 0.001). Compared to those with sleep efficiency ≥ 85%, participants with lower sleep efficiency (65~74%, <65%) had a higher level of plasma Aß42 (<65%: ß = 0.627, 95% CI 0.147~1.108, p = 0.011) and Aß42/Aß40 ratio (65~74%: ß = 0.052, 95% CI 0.007~0.097, p = 0.026; <65%: ß = 0.117, 95% CI 0.067~0.168, p < 0.001). CONCLUSIONS: These findings indicated that short sleep duration and low sleep efficiency were associated with a high level of Aß42. A better comprehending of the link between sleep and plasma Aß levels may lead to effective sleep-based intervention to reduce the risk of Alzheimer's disease.
Assuntos
Peptídeos beta-Amiloides , Fragmentos de Peptídeos , Sono , Idoso , Doença de Alzheimer , Peptídeos beta-Amiloides/sangue , Biomarcadores , Estudos Transversais , Humanos , Fragmentos de Peptídeos/sangue , Qualidade do SonoRESUMO
BACKGROUND: The current study investigated the relationship between behavioural and psychological symptoms of dementia (BPSD) knowledge and positive aspects of caregiving (PAC), in addition, how caregiving attitude and self-efficacy mediate or moderate this relationship. METHODS: Two hundred twenty-nine formal caregivers (51males and 178females) who has worked in nursing homes for more than a month were recruited.With a cross-sectional, face-to-face survey, structural questionnaires were implemented to evaluate formal caregiver's BPSD knowledge, attitude, self-efficacy and PAC.A 13-item self-developed questionnaire was used to assess caregiver's BPSD knowledge about disease characteristics, care and risks, and treatment needs. Dementia attitude, self-efficacy and positive aspects of caregiving were measured by dementia attitude scale, the General self-efficacy scale, and Chinese version of positive aspects of caregiving respectively. Model 5 in the PROCESS micro was employed in order to verify the mediating effect of attitude and the moderating effect of self-efficacy on the relationship between BPSD knowledge and PAC. RESULTS: The results showed that greater BPSD knowledge was associated with increased PAC, and this relationship was fully mediated by increased friendly attitude toward people with dementia. Moreover, direct effect was moderated by self-efficacy, and that only among those with high self-efficacy, the direct effect of BPSD knowledge was found on promoting PAC. CONCLUSIONS: By elucidating the knowledge-attitude-practice pathway in handling patient's BPSD, the current study extends existing literature and provides insights for developing psychoeducation programs among formal caregivers.
Assuntos
Cuidadores , Demência , Cuidadores/psicologia , Efeitos Psicossociais da Doença , Estudos Transversais , Demência/diagnóstico , Demência/terapia , Humanos , AutoeficáciaRESUMO
Walking is a fundamental movement skill in humans. However, how the brain controls walking is not fully understood. In this functional magnetic resonance imaging study, the rhythmic, bilaterally alternating ankle movements were used as paradigm to simulate walking. In addition to the resting state, several motor tasks with different speeds were tested. Independent component analysis was performed to detect four components shared by all task conditions and the resting state. According to the distributed brain regions, these independent components were the cerebellum, primary auditory cortex-secondary somatosensory cortex-inferior parietal cortex-presupplementary motor area, medial primary sensorimotor cortex-supplementary area-premotor cortex-superior parietal lobule, and lateral primary somatosensory cortex-superior parietal lobule-dorsal premotor cortex networks, which coordinated limb movements, controlled the rhythm, differentiated speed, and performed a function as a basic actor network, respectively. These brain networks may be used as biomarkers of the neural control of normal human walking and as targets for neural modulation to improve different aspects of walking, such as rhythm and speed.
Assuntos
Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Conectoma , Atividade Motora/fisiologia , Rede Nervosa/fisiologia , Adulto , Tornozelo/fisiologia , Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem , Caminhada/fisiologiaRESUMO
BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive performance and the modulation of several metabolic parameters in some disease models, but its potential roles in successful aging remain unclear. We herein sought to define the putative correlation between BDNF Val66Met and several metabolic risk factors including BMI, blood pressure, fasting plasma glucose (FPG) and lipid levels in a long-lived population inhabiting Hongshui River Basin in Guangxi. METHODS: BDNF Val66Met was typed by ARMS-PCR for 487 Zhuang long-lived individuals (age ≥ 90, long-lived group, LG), 593 of their offspring (age 60-77, offspring group, OG) and 582 ethnic-matched healthy controls (aged 60-75, control group, CG) from Hongshui River Basin. The correlations of genotypes with metabolic risks were then determined. RESULTS: As a result, no statistical difference was observed on the distribution of allelic and genotypic frequencies of BDNF Val66Met among the three groups (all P > 0.05) except that AA genotype was dramatically higher in females than in males of CG. The HDL-C level of A allele (GA/AA genotype) carriers was profoundly lower than was non-A (GG genotype) carriers in the total population and the CG (P = 0.009 and 0.006, respectively), which maintained in females, hyperglycemic and normolipidemic subgroup of CG after stratification by gender, BMI, glucose and lipid status. Furthermore, allele A carriers, with a higher systolic blood pressure, exhibited 1.63 folds higher risk than non-A carriers to be overweight in CG (OR = 1.63, 95% CI: 1.05 - 2.55, P = 0.012). Multiple regression analysis displayed that the TC level of LG reversely associated with BDNF Val66Met genotype. CONCLUSIONS: These data suggested that BDNF 66Met may play unfavorable roles in blood pressure and lipid profiles in the general population in Hongshui River area which might in part underscore their poorer survivorship versus the successful aging individuals and their offspring.
Assuntos
Pressão Sanguínea/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Metabolismo dos Lipídeos/genética , Longevidade , Doenças Metabólicas , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Etnicidade , Feminino , Genótipo , Humanos , Longevidade/genética , Longevidade/fisiologia , Masculino , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/genética , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
BACKGROUND: The +294T/C polymorphism in the peroxisome proliferator-activated receptor delta (PPARD) gene is associated with hyperlipidemia in several younger populations, but results are still inconsistence across ethnic groups and its possible impact on the lipid profiles of long-lived individuals remains unexploited. Here, we aimed to evaluate the possible correlation between PPARD +294T/C and serum lipid levels in a long-lived population in Bama, a region known for longevity situated in Guangxi, China. METHODS: Genotyping of PPARD +294T/C polymorphism was conducted in 505 long-lived inhabitants (aged 90 and above, long-lived group, LG) and 468 healthy controls (aged 60-75, non-long-lived group, non-LG) recruited from Bama area. RESULTS: No difference in allelic and genotypic frequencies was found between the two groups (P>0.05). However, C-allele and C-genotype (TC and CC) were significantly more frequent in the females of non-LG than were LG after sex stratification. CC carriers exhibited higher LDL-C level in LG (P<0.05) but lower TC, TG and LDL-C in non-LG (P<0.05 for each) than TT carriers; C allele carriers (TC/CC) in LG exhibited higher TC, TG, and LDL-C levels as compared with the same genotype and the same lipid parameter in non-LG (P<0.05 for each). LDL-C in LG was correlated with genotypes while TC, TG, and LDL-C in non-LG were correlated with genotypes (P<0.05-0.001). CONCLUSION: Our results suggest that there were different impact patterns of PPARD +294T/C polymorphism on lipid profiles between long-lived cohort and average population in Bama area and this may be one of the genetic bases of its longevity.
Assuntos
Lipídeos/sangue , Longevidade/genética , PPAR delta/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
Alzheimer's Disease (AD) accounts for the majority of dementia, and Mild Cognitive Impairment (MCI) is the early stage of AD. Early and accurate diagnosis of dementia plays a vital role in more targeted treatments and effectively halting disease progression. However, the clinical diagnosis of dementia requires various examinations, which are expensive and require a high level of expertise from the doctor. In this paper, we proposed a classification method based on multi-modal data including Electroencephalogram (EEG), eye tracking and behavioral data for early diagnosis of AD and MCI. Paradigms with various task difficulties were used to identify different severity of dementia: eye movement task and resting-state EEG tasks were used to detect AD, while eye movement task and delayed match-to-sample task were used to detect MCI. Besides, the effects of different features were compared and suitable EEG channels were selected for the detection. Furthermore, we proposed a data augmentation method to enlarge the dataset, designed an extra ERPNet feature extract layer to extract multi-modal features and used domain-adversarial neural network to improve the performance of MCI diagnosis. We achieved an average accuracy of 88.81% for MCI diagnosis and 100% for AD diagnosis. The results of this paper suggest that our classification method can provide a feasible and affordable way to diagnose dementia.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Redes Neurais de Computação , Diagnóstico PrecoceRESUMO
Background: Although neoadjuvant therapy has brought numerous benefits to patients, not all patients can benefit from it. Chemokines play a crucial role in the tumor microenvironment and are closely associated with the prognosis and treatment of colorectal cancer. Therefore, constructing a prognostic model based on chemokines will help risk stratification and providing a reference for the personalized treatment. Methods: Employing LASSO-Cox predictive modeling, a chemokine-based prognostic model was formulated, harnessing the data from TCGA and GEO databases. Then, our exploration focused on the correlation between the chemokine signature and elements such as the immune landscape, somatic mutations, copy number variations, and drug sensitivity. CXCL10+M1 macrophages identified via scRNA-seq. Monocle2 showed cell pseudotime trajectories, CellChat characterized intercellular communication. CytoTRACE analyzed neoadjuvant therapy stemness, SCENIC detected cell type-specific regulation. Lastly, validation was performed through multiplex immunofluorescence experiments. Results: A model based on 15 chemokines was constructed and validated. High-risk scores correlated with poorer prognosis and advanced TNM and clinical stages. Individuals presenting elevated risk scores demonstrated an increased propensity towards the development of chemotherapy resistance. Subsequent scRNA-seq data analysis indicated that patients with higher presence of CXCL10+ M1 macrophages in tumor tissues are more likely to benefit from neoadjuvant therapy. Conclusion: We developed a chemokine-based prognostic model by integrating both single-cell and bulk RNA-seq data. Furthermore, we revealed epithelial cell heterogeneity in neoadjuvant outcomes and identified CXCL10+ M1 macrophages as potential therapy response predictors. These findings could significantly contribute to risk stratification and serve as a key guide for the advancement of personalized therapeutic approaches.
Assuntos
Quimiocina CXCL10 , Neoplasias Colorretais , Terapia Neoadjuvante , Microambiente Tumoral , Humanos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Terapia Neoadjuvante/métodos , Prognóstico , Microambiente Tumoral/imunologia , Biomarcadores Tumorais , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Feminino , Masculino , Resultado do Tratamento , Quimiocinas/metabolismo , Quimiocinas/genéticaRESUMO
Neurological and psychiatric diseases can lead to motor, language, emotional disorder, and cognitive, hearing or visual impairment By decoding the intention of the brain in real time, the Brain-computer interface (BCI) can first assist in the diagnosis of diseases, and can also compensate for its damaged function by directly interacting with the environment; In addition, provide output signals in various forms, such as actual motion, tactile or visual feedback, to assist in rehabilitation training; Further intervention in brain disorders is achieved by close-looped neural modulation. In this article, we envision the future BCI digital prescription system for patients with different functional disorders and discuss the key contents in the prescription the brain signals, coding and decoding protocols and interaction paradigms, and assistive technology. Then, we discuss the details that need to be specially included in the digital prescription for different intervention technologies. The third part summarizes previous examples of intervention, focusing on how to select appropriate interaction paradigms for patients with different functional impairments. For the last part, we discussed the indicators and influencing factors in evaluating the therapeutic effect of BCI as intervention.
Assuntos
Encefalopatias , Interfaces Cérebro-Computador , Doenças do Sistema Nervoso , Humanos , Doenças do Sistema Nervoso/terapia , Encéfalo , Eletroencefalografia/métodosRESUMO
OBJECTIVE: To assess the association between SIRT1 gene polymorphisms and the longevity phenomena in Yongfu region of Guangxi. In this case-control study, 500 individuals from Yongfu region of Guangxi were recruited. The subjects were divided into a longevity group (n=223, average age=93.17 U+00B1 3.08 yr) and a healthy control group (n=277, average age=46.92 U+00B1 17.12 yr). Polymerase chain reaction-high resolution melting curve (PCR-HRM) and DNA sequencing were used to determine the allelic and genotypic frequencies of rs3758391, rs3740051, rs2273773, rs4746720 and rs10997870 polymorphisms of SIRT1 gene in the two groups. The association between above polymorphisms and longevity was assessed. RESULTS: In the longevity group, CT genotype of the rs4746720 locus was significantly more common than CC and TT genotypes (P=0.000, OR=2.098, 95%CI:1.412-4.117). However, no significant difference was found in the allelic and genotypic frequencies of rs3758391, rs3740051 and rs2273773 between the two groups. CONCLUSION: There is an association between rs4746720 of SIRT1 gene and longevity in Yongfu region of Guangxi.
Assuntos
Povo Asiático/genética , Longevidade/genética , Polimorfismo de Nucleotídeo Único , Sirtuína 1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Sequência de Bases , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Ordem dos Genes , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Amnestic mild cognitive impairment (aMCI) is regarded as a transitional state of Alzheimer's disease, with working memory (WM) impairment. OBJECTIVE: To investigate the brain activity in aMCI patients during WM tasks with the functional near-infrared spectroscopy (fNIRS) technique, as well as explore the association between brain activity and cognitive function in multiple domains. METHODS: This study is a case-control study of 54 aMCI patients and 33 cognitively healthy elderly (NC). All participants underwent neuropsychological assessments. fNIRS was applied to examine the brain activation during the WM task. Multivariable linear regression analysis was applied to evaluate associations between brain activation and cognitive function in multiple domains. RESULTS: Compared to NC subjects, aMCI patients had lower activation in the bilateral prefrontal, parietal, and occipital cortex during the WM task. Additionally, activation in the left prefrontal, bilateral parietal, and occipital cortex during the encoding and maintenance phase was positively associated with memory function. During memory retrieval, higher activity in the left prefrontal, parietal, and occipital cortex were correlated with higher memory scores. Besides, a positive association also formed between attention function and the activation in the left prefrontal, parietal, and occipital cortex during the WM task. CONCLUSION: These findings demonstrated that reduced activation in the prefrontal, parietal and occipital cortex during WM might reflect the risk of cognitive impairment, especially memory and attention function in aMCI patients. Given the brain activation visualization, fNIRS may be a convenient and alternative tool for screening the risk of Alzheimer's disease.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Memória de Curto Prazo/fisiologia , Doença de Alzheimer/psicologia , Estudos de Casos e Controles , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Atenção , Transtornos da Memória , Testes Neuropsicológicos , Imageamento por Ressonância Magnética/métodosRESUMO
Locally advanced colorectal cancer requires preoperative chemotherapy to reduce local recurrence and metastasis rates, but it remains difficult to predict the tumor will be sensitive to which treatments. The patient-derived organoids (PDOs) are considered an effective platform for predicting tumor drug responses in precision oncology. However, it has the limitation of being time-consuming in practical applications, especially in neoadjuvant treatment. Here we used cancer tissue-originated spheroids (CTOS) method to establish organoids from a heterogeneous population of colorectal cancer specimens, and evaluated the capacity of CTOS to predict clinical drug responses. By analyzing the relationship of the activities of drug-treated CTOS, drug targets and target-related pathways, tumor intrinsic effective-target-related pathways can be identified. These pathways were highly matched to the abnormal pathways indicated by whole-exome sequencing. Based on this, we used half effective concentration gradients to classify CTOS as sensitive or resistant to chemotherapy regimens within a week, for predicting neoadjuvant treatment outcomes for colorectal cancer patients. The drug sensitivity test results are highly matched to the clinical responses to treatment in individual patients. Thus, our data suggested that CTOS models can be effectively screened ex vivo to identify pathways sensitive to chemotherapies. These data also supported organoid research for personalized clinical medication guidance immediately after diagnosis in patients with advanced colorectal cancer.
RESUMO
Background and objectives: Initial shunt failure following ventriculoperitoneal (VP) shunt surgery has a significant impact on the working time of the shunt. However, there are few studies regarding factors affecting VP shunt longevity. Hence, in this study, we aimed to build a nomogram to predict the longevity of the replacement VP shunt in patients with initial shunt failure. Methods: From 2011 to 2021, 142 patients with initial VP failure who underwent VP shunt revision were enrolled and relevant clinical and demographic factors were analyzed. Univariate and multivariate Cox proportional hazard regression models were used to choose predictors, and a nomogram was constructed using nine independent prognostic variables: sex, age, hydrocephalus type, intensive care unit admission, tracheostomy, decompressive craniectomy, craniotomy, lumbar cisterna drainage, and ventricular drainage. The prediction models' discrimination, accuracy, calibration, and clinical value were evaluated using Harrell's C-index, a calibration plot, and decision curve analysis. Results: At 1 month, 3 months, and 5 years, the nomogram's C-index was 0.680, 0.708, and 0.694, respectively. The nomogram's calibration plot provided a good fit for the overall prediction over the course of 1 year. Decision curve analysis predicted that 1-3 months after surgery will yield good net benefits between 30 and 50% probability thresholds. Conclusion: A preoperative nomogram may be an effective tool for assessing VP shunt longevity after initial VP shunt placement.
RESUMO
Introduction: The role of tumour secretory cytokines and peripheral circulatory cytokines in tumour progression has received increasing attention; however, the role of tumour-related inflammatory cytokines in colorectal cancer (CRC) remains unclear. In this study, the concentrations of various cytokines in the peripheral blood of healthy controls and patients with CRC at different stages were compared. Methods: Peripheral blood samples from 4 healthy participants and 22 colorectal cancer patients were examined. Luminex beads were used to evaluate concentration levels of 40 inflammatory cytokines in peripheral blood samples. Results: In peripheral blood, compared with healthy controls and early stage (I + II) CRC patients, advanced CRC (III + IV) patients had increased concentrations of mononuclear/macrophage chemotactic-related proteins (CCL7, CCL8, CCL15, CCL2, and MIF), M2 polarization-related factors (IL-1ß, IL-4), neutrophil chemotactic and N2 polarization-related cytokines (CXCL2, CXCL5, CXCL6, IL-8), dendritic cells (DCs) chemotactic-related proteins (CCL19, CCL20, and CCL21), Natural killer (NK) cell related cytokines (CXCL9, CXCL10), Th2 cell-related cytokines (CCL1, CCL11, CCL26), CXCL12, IL-2, CCL25, and CCL27, and decreased IFN-γ and CX3CL1 concentrations. The differential upregulation of cytokines in peripheral blood was mainly concentrated in CRC patients with distant metastasis and was related to the size of the primary tumour; however, there was no significant correlation between cytokine levels in peripheral blood and the propensity and mechanism of lymph node metastasis. Discussion: Different types of immune cells may share the same chemokine receptors and can co-localise in response to the same chemokines and exert synergistic pro-tumour or anti-tumour functions in the tumour microenvironment. Chemokines and cytokines affect tumour metastasis and prognosis and may be potential targets for treatment.
Assuntos
Neoplasias Colorretais , Citocinas , Humanos , Citocinas/metabolismo , Macrófagos/metabolismo , Neoplasias Colorretais/patologia , Microambiente TumoralRESUMO
Background: Early detection of mild cognitive impairment is crucial in the prevention of Alzheimer's disease (AD). This study aims to explore the changes in gait and brain co-functional connectivity between cognitively healthy and cognitively impaired groups under dual-task walking through the functional near-infrared spectroscopy (fNIRS) and gait analysis devices. Method: This study used fNIRS device and gait analysis devices to collect the data of 54 older adults. According to the Mini-mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scales, the older adults were cognitively healthy (control group) and cognitively impaired (experimental group), of which 38 were in the control group and 16 were in the experimental group. The experiment was divided into a total of three sets of task experiments: a walking-only experiment, a dual-task walking-easy (DTW-easy) experiment, and a dual-task walking-difficult (DTW-difficult) experiment. Main Result: For the cognitively impaired and cognitively healthy populations, there were no significant differences in overall functional connectivity, region of interest (ROI) connection strength, and gait performance during single-task walking between the two groups.Whereas the performances of DTW differed significantly from the single-task walking in terms of between-group variability of functional connectivity strength change values, and ROI connection strength change values in relation to the dual-task cost of gait. Finally, the cognitively impaired group was significantly more affected by DTW-difficult tasks than the cognitively healthy group. Conclusion: This study provides a new approach to assist in the diagnosis of people with cognitive impairment and provides a new research pathway for the identification of cognitive impairment.