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1.
Eur J Obstet Gynecol Reprod Biol ; 297: 30-35, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38574697

RESUMO

OBJECTIVE: Gastrointestinal dysfunction after cesarean section negatively affects postoperative recovery. Dexmedetomidine has been shown to improve postoperative gastrointestinal function in patients undergoing lumbar spinal fusion surgery and laparoscopic gastrectomy, but its role in cesarean section has not been fully elucidated. The study aimed to investigate the effect of dexmedetomidine on gastrointestinal function after cesarean section. STUDY DESIGN: 220 pregnant women who underwent elective cesarean section were randomized into group D and group S. Group D patients received a loading dose of 0.5 µg/kg of dexmedetomidine for 10 mins followed by a maintenance dose of 0.5 µg/kg/h intravenously immediately after the umbilical cord was cut intraoperatively, whereas the other group (group S) received an equivalent quantity of normal saline as loading and maintenance dose IV by infusion pump. The primary outcome was time to first flatus after surgery (hours). Secondary outcomes included time to first feces and first bowel sounds (hours), incidence rates of postoperative gastrointestinal complications, and the length of postoperative hospital stay (days). RESULTS: Modified intention-to-treat analysis showed that patients in Group D had a significantly shorter time to first flatus (21 [16 to 28.25] vs. 25 [18 to 32.25] h; P = 0.014), time to first feces (45.5 [35.75 to 55.25] vs. 53 [40 to 60] h; P = 0.019), and time to first bowel sounds (P = 0.010), a lower incidence of abdominal distension (21[20.6 %] vs. 36[34.3 %], P = 0.027), shorter length of postoperative hospital stay (P = 0.010) compared to patients in Group S. CONCLUSION: Intraoperative dexmedetomidine infusion reduces the time to first flatus, the incidence of abdominal distension, and shortens the length of hospital stay, promoting gastrointestinal function after cesarean section.

3.
Cereb Cortex ; 34(3)2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38436464

RESUMO

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Conectoma , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Medo
4.
Perioper Med (Lond) ; 13(1): 15, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38444044

RESUMO

BACKGROUND: Intravenous lidocaine could be a potential alternative adjuvant to propofol-based sedation for gastroscopy in elderly patients. This study aimed to evaluate the effect of intravenous lidocaine on the median effective dose (ED50) of propofol induction dose in elderly patients undergoing painless gastroscopy. METHODS: The study included 70 patients aged ≥ 60 years undergoing painless gastroscopy with 64 randomly assigned to either group L (2% lidocaine 1.5 mg/kg, n = 31) or group N (equal volume normal saline, n = 33). All patients received propofol induction following 0.1 µg/kg intravenous sufentanil. The Dixon "up-and-down" sequential method was used, with a 1.5 mg/kg initial induction dose of propofol followed by a 0.1 mg/kg sequential variable dose. The primary endpoint was the ED50 of the propofol induction dose. The total propofol dose, recovery time, adverse events, and local anesthetic intoxication reactions were also recorded. RESULTS: The ED50 of propofol induction dose was 0.670 (95% confidence interval [CI] 0.216-0.827) mg/kg in group L and 1.118 (95% CI 0.803-1.232) mg/kg in group N. There was a statistically significant difference between the two groups (p < 0.001). The incidence of hypotension and propofol injection pain were lower in group L than in group N (p < 0.05). Furthermore, the orientation recovery time in group L was shorter compared to group N (p < 0.05). None of the participants in group L observed local anesthetic intoxication reactions after receiving lidocaine. CONCLUSIONS: The administration of intravenous lidocaine to elderly patients undergoing painless gastroscopy resulted in a significant 40% reduction in the ED50 of propofol induction dose, which may be related to the decreased incidence of hypotension and injection pain, as well as the improved post-gastroscopy orientation recovery. TRIAL REGISTRATION: ChiCTR, ChiCTR2200065530. Registered on 08 November 2022.

5.
Food Funct ; 15(8): 4365-4374, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38545932

RESUMO

Childhood malnutrition remains a serious global health concern, particularly in low-income nations like Uganda. This study investigated the impact of peanut supplementation on the compositions and functions of gut microbiome with nutritional improvement. School children aged 6-9 years from four rural communities were recruited, with half receiving roasted peanut snacks while the other half served as controls. Fecal samples were collected at the baseline (day 0), day 60, and day 90. Microbial DNA was extracted, and 16S rRNA sequencing was performed, followed by the measurement of SCFA concentration in fecal samples using UHPLC. Alpha and beta diversity analyses revealed significant differences between the control and supplemented groups after 90 days of supplementation. Leuconostoc lactis, Lactococcus lactis, Lactococcus garvieae, Eubacterium ventriosum, and Bacteroides thetaiotaomicron, associated with the production of beneficial metabolites, increased significantly in the supplemented group. Acetic acid concentration also increased significantly. Notably, pathogenic bacteria, including Clostridium perfringens and Leuconostoc mesenteroides, were decreased in the supplemented group. The study indicates the potential of peanut supplementation to modulate the gut metabolome, enrich beneficial bacteria, and inhibit pathogens, suggesting a novel approach to mitigating child malnutrition and improving health status.


Assuntos
Arachis , Bactérias , Suplementos Nutricionais , Fezes , Microbioma Gastrointestinal , Humanos , Arachis/microbiologia , Uganda , Criança , Masculino , Feminino , Fezes/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , RNA Ribossômico 16S/genética
6.
Heliyon ; 10(6): e27817, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545150

RESUMO

Terpene synthases (TPSs) regulate plant growth, development, and stress response. TPS genes have been identified in Arabidopsis thaliana and Zea mays. Cannabis sativa TPS genes were identified and analyzed using bioinformatics. Genomic data were downloaded from Plant Transcription Factor Database and National Center for Biotechnology Information database, and TPS genes were predicted, analyzed, and visualized using ExPASy, PlantCare, and other online websites along with TBtools, MEGA software, and other software. To verify its role, quantitative real-time polymerase chain reaction (qRT-PCR) tests were conducted. The Cannabis sativa TPS family comprises 41 elements distributed over 8 chromosomes and a single scaffold segment. The isoelectric point varied between 4.96 and 7.03, while the molecular weight spanned from 20705.90 to 102324.64 Da. The majority of genes were found in the cytoplasm and chloroplasts, with the remainder situated in the peroxisome, nucleus, plasma membrane, and mitochondria. Several cis-acting components associated with stress response were present in the gene's upstream promoter region. Data from RNA sequencing and qRT-PCR revealed specific expression of TPS genes in all five organs of female Cannabis sativa plants. Collinearity analysis showed 4 homologous gene pairs between the Cannabis sativa and Arabidopsis thaliana, with many pairs of homologous genes in other species, which was consistent with the dicotyledons evolutionary relationship. Furthermore, some genes may participate in Cannabis sativa growth and development and play a role in secondary metabolite synthesis. Therefore, bioinformatics analysis of the Cannabis sativa TPS gene family provides a theoretical basis for future research on the volatile terpene compounds of Cannabis sativa.

7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(2): 211-215, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38442942

RESUMO

Sepsis is a fatal organ dysfunction caused by the uncontrolled inflammatory response of the host to infection. Excessive inflammatory reaction is the core factor in the occurrence and development of sepsis, the degree of organ dysfunction is directly related to the prognosis of sepsis. Timely intervention of excessive inflammatory response and alleviation of organ function damage are essential to improve the prognosis of sepsis. Maresin-1 (MaR-1) is a newly discovered endogenous specific pro-inflammatory resolution mediator, which plays a role of anti-inflammatory, pro-inflammatory regression and organ protection in sepsis, and may be a new target for the treatment of sepsis. This article reviews the research progress of the role of MaR-1 in the regulation of inflammation and organ protection in sepsis, in order to provide reference for the clinical development of new drugs for the treatment of sepsis.


Assuntos
Insuficiência de Múltiplos Órgãos , Sepse , Humanos , Insuficiência de Múltiplos Órgãos/prevenção & controle , Sepse/tratamento farmacológico , Inflamação
8.
BMC Psychol ; 12(1): 139, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475847

RESUMO

PURPOSE: The pathways underpinning suicide ideation (SI) and certain physical and psychological factors in patients with advanced breast cancer remain unclear. This study develops and validates a mediation model that delineates the associations between several multidimensional variables and SI in Chinese patients with advanced breast cancer. METHODS: Patients with advanced breast cancer (n = 509) were recruited as study participants from 10 regional cancer centers across China from August 2019 to December 2020. Participants were required to complete five questionnaires using an electronic patient-reported outcomes (ePRO) system: 9 item- Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), 5-level EQ-5D (EQ-5D-5L), and MD Anderson Symptom Inventory (MDASI). Risk factors for SI were identified using multivariable logistic regression, and inputted into serial multiple mediation models to elucidate the pathways linking the risk factors to SI. RESULTS: SI prevalence was 22.8% (116/509). After adjusting for covariates, depression (odds ratio [OR] = 1.384), emotional distress (OR = 1.107), upset (OR = 0.842), and forgetfulness (OR = 1.236) were identified as significant independent risk factors (all p < 0.05). The ORs indicate that depression and distress have the strongest associations with SI. Health status has a significant indirect effect (OR=-0.044, p = 0.005) and a strong total effect (OR=-0.485, p < 0.001) on SI, mediated by insomnia severity and emotional distress. CONCLUSIONS: There is a high SI prevalence among Chinese patients with advanced breast cancer. Our analysis revealed predictive pathways from poor health to heightened SI, mediated by emotional distress and insomnia. Regular management of distress and insomnia can decrease suicide risk in this vulnerable population.


Assuntos
Neoplasias da Mama , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Ideação Suicida , Depressão/psicologia , Fatores de Risco
9.
BMC Geriatr ; 24(1): 185, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395756

RESUMO

BACKGROUND: Little is understood about the association between psychosomatic symptoms and advanced cancer among older Chinese patients. METHODS: This secondary analysis was part of a multicenter cross-sectional study based on an electronic patient-reported outcome platform. Patients with advanced cancer were included between August 2019 and December 2020 in China. Participants (over 60 years) completed the MD Anderson Symptom Inventory (MDASI) and Hospital Anxiety and Depression Scale (HADS) to measure symptom burden. Network analysis was also conducted to investigate the network structure, centrality indices (strength, closeness, and betweenness) and network stability. RESULTS: A total of 1022 patients with a mean age of 66 (60-88) years were included; 727 (71.1%) were males, and 295 (28.9%) were females. A total of 64.9% of older patients with advanced cancer had one or more symptoms, and up to 80% had anxiety and depression. The generated network indicated that the physical symptoms, anxiety and depression symptom communities were well connected with each other. Based on an evaluation of the centrality indices, 'distress/feeling upset' (MDASI 5) appears to be a structurally important node in all three networks, and 'I lost interest in my own appearance' (HADS-D4) had the lowest centrality indices. The network stability was relatively high (> 0.7). CONCLUSION: The symptom burden remains high in older patients with advanced cancer in China. Psychosomatic symptoms are highly interactive and often present as comorbidities. This network can be used to provide targeted interventions to optimize symptom management in older patients with advanced cancer in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024957), registered on 06/12/2020.


Assuntos
Depressão , Neoplasias , Masculino , Feminino , Humanos , Idoso , Depressão/diagnóstico , Depressão/epidemiologia , Estudos Transversais , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Transtornos de Ansiedade
10.
Sci Rep ; 14(1): 4892, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418478

RESUMO

Metastatic breast cancer could cause various psychological symptoms. Managing Cancer and Living Meaningfully (CALM) is a brief, manualized psychotherapy that has been validated for advanced cancer patients. We conducted a pilot randomized control trial (RCT) to verify the feasibility and preliminary efficacy of CALM therapy in this population. Patients who met the inclusion criteria were randomly assigned into CALM or Wait-list Control (WLC) groups. Patients in the CALM group received CALM therapy and usual care; patients in WLC group first received usual care and then underwent CALM therapy after completing all assessments. All patients were asked to complete three assessments: T0(baseline), T1(3 months), and T2(6 months). The primary outcomes was death anxiety; other outcomes were depression, distress, suicide ideation, attachment security, spiritual well-being and quality of life at the end of life. Analysis of Covariance (ANCOVA) and t-test were used for statistics analysis. Thirty-six patients were randomly assigned to either of the two groups, with 34 patients completing the three assessments. At six months, we found significant between group differences in suicide ideation, distress, and life completion between the CALM and WLC groups. At T2, patients in CALM group reported lower levels of depression (F = 5.016, p = 0.033, partial η2 = 0.143), distress (F = 7.969, p = 0.010, partial η2 = 0.257), attachment avoidance (F = 4.407, p = 0.044, partial η2 = 0.128), and better sense of life completion (F = 5.493, p = 0.026, partial η2 = 0.155) than patients in the WLC group. Compared with results of the T0 assessments, we found significant differences in socres for depression (T2&T0, t = - 2.689, p = 0.011, Cohen's d = 0.940) and distress (T2&T0, t = - 2.453, p = 0.022, Cohen's d = 0.965) between the two groups. CALM therapy was well received by the study population, and CALM therapy can reduce depression, distress, attachment avoidance while improving quality of life in Chinese metastatic breast cancer patients. A Phase III RCT was recommended to verify the impact of CALM therapy on psychological burden and survival in this population.Trial registration: This study is part of the "Preliminary application study for Managing Cancer and Living Meaningfully (CALM) therapy in Chinese advanced cancer patients" clinical trial, with the Trial Registration Number of ChiCTR1900023129 (13/05/2019) in the Chinese Clinical Trial Registry (ChiCTR) website. ( https://www.chictr.org.cn/index.html ).


Assuntos
Neoplasias da Mama , Humanos , Feminino , Projetos Piloto , Estudos de Viabilidade , Neoplasias da Mama/terapia , Qualidade de Vida , China
11.
Gen Hosp Psychiatry ; 87: 92-102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38382421

RESUMO

OBJECTIVE: Poor sleep quality is common in patients with cancer, but the prevalence rates varied widely across studies. This systematic review and meta-analysis examined the pooled prevalence of poor sleep quality among patients with cancer. METHODS: Systematic literature searches were independently conducted in the major databases (Web of Science, PubMed, EMBASE and PsycINFO). Studies that reported the prevalence of poor sleep quality in patients with cancer were analyzed using a random effects model. Funnel plots and Egger's tests were used to assess publication bias. Statistical analyses were performed using R software. RESULTS: A total of 59 epidemiological studies involving 16,223 patients were included. The pooled prevalence of poor sleep quality in patients with cancer was 57.4% [95% confidence interval (CI): 53.3% - 61.6%]. Additionally, three comparative studies with 372 patients and 412 healthy controls were included. Compared to healthy controls, patients with cancer had a significantly higher risk for poor sleep quality [odd ratio (OR) = 3.0; 95%CI: 1.2-7.2; P < 0.05]. Subgroup analyses of the studies revealed that studies from Middle East & North Africa region and low income countries, and on gynecological cancer as well as those with a lower cut-off value of sleep quality (all P < 0.01) reported a higher prevalence of poor sleep quality. Meta-regression analyses showed that higher prevalence of poor sleep quality was associated with higher prevalence of comorbid depression (P < 0.05) and anxiety (P < 0.01), but was associated with a lower education level (P < 0.05) and alcohol use ratio (P < 0.05). CONCLUSION: Poor sleep quality is common among patients with cancer. Considering the overall high prevalence rate and negative impact of poor sleep quality, appropriate measures to identify and improve poor sleep quality are needed to enhance the clinical outcomes in this group.


Assuntos
Neoplasias , Qualidade do Sono , Humanos , Prevalência , Comorbidade , Consumo de Bebidas Alcoólicas , Neoplasias/epidemiologia
12.
Mol Genet Genomic Med ; 12(2): e2385, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38337174

RESUMO

BACKGROUND: Oculocutaneous albinism type 4 (OCA4) is a rare autosomal recessive disorder characterized by a reduction of pigmentation in skin, hair, and eyes, and OCA4 is mainly seen in the SLC45A2 gene variants. OBJECTIVE: To report a Chinese patient suspected of oculocutaneous albinism and identify the causing mutation. METHODS: Genomic DNA was extracted from the peripheral blood samples of the patient, his parents, and elder brother. Whole exome sequencing was performed in the family, and Sanger sequencing was then used to verify the mutations. RESULTS: Compound heterozygous variants, c.1304C>A (p.S435Y) and c.301C>G (p.R101G) in SLC45A2 gene, were detected in the proband, which were inherited from his father and mother respectively. Based on the ACMG guidelines, we can interpret the c.1304C>A (p.S435Y) variant as a suspected pathogenic variant and the c.301C>G (p.R101G) variant as a clinically significant unspecified variant. The diagnosis of OCA4 is confirmed. CONCLUSION: We firstly reported this case of OCA4 with the compound heterozygous variants in the SLC45A2 gene. Our findings further enrich the reservoir of SLC45A2 mutations in OCA4.


Assuntos
Albinismo Oculocutâneo , Masculino , Humanos , Idoso , Mutação , Albinismo Oculocutâneo/genética , Albinismo Oculocutâneo/diagnóstico , DNA , China , Antígenos de Neoplasias/genética , Proteínas de Membrana Transportadoras/genética
13.
Environ Toxicol ; 39(5): 2596-2609, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38205898

RESUMO

Cell senescence, glycolysis, and mitochondrial deficit jointly regulate the development of septic acute kidney injury (SAKI). This study aimed to explore the role of circular RNA HIPK3 (circHIPK3) in mitochondrial function in SAKI. The SAKI mouse model was established by Candida albicans infection, followed by Western blot assay, measurements of serum lactate, and adenosine triphosphate (ATP), 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1) staining and flow cytometry. Human renal tubular epithelial cells were treated with lipopolysaccharide to establish the SAKI cell model, followed by cell counting kit-8 assay, tests of hexokinase activity, lactate production, oxygen consumption rate, extracellular acidification rate, ATP, and JC-1 staining, and Western blot assay. The roles of mitochondrial pyruvate carrier 1 (MPC1) were validated by kidney function tests, hematoxylin and eosin staining, periodic acid-Schiff staining, and SA-ß-gal staining. circHIPK3 downregulation reduced glycolysis and mitochondrial dysfunction both in vivo and in vitro through the microRNA (miR)-148b-3p/DNMT1/3a/Klotho axis. Inhibition of miR-148b-3p or Klotho increased glycolysis and mitochondrial dysfunction. Knockdown of MPC1 increased lactate content and decreased ATP levels and MMP both in vivo and in vitro. Collectively, circHIPK3, in concert with the miR-148b-3p/DNMT1/3a/Klotho axis, increased glycolysis, and inhibited the negative regulation of lactate production by MPC1, and aggravated mitochondrial dysfunction and cell senescence in SAKI.


Assuntos
Injúria Renal Aguda , Benzimidazóis , Carbocianinas , MicroRNAs , Doenças Mitocondriais , Camundongos , Animais , Humanos , RNA Circular/genética , MicroRNAs/genética , Mitocôndrias , Injúria Renal Aguda/genética , Trifosfato de Adenosina , Lactatos
14.
Transl Psychiatry ; 14(1): 17, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195555

RESUMO

Several lines of evidence support the involvement of transcriptomic and epigenetic mechanisms in the brain structural deficits of major depressive disorder (MDD) separately. However, research in these two areas has remained isolated. In this study, we proposed an integrative strategy that combined neuroimaging, brain-wide gene expression, and peripheral DNA methylation data to investigate the genetic basis of gray matter abnormalities in MDD. The MRI T1-weighted images and Illumina 850 K DNA methylation microarrays were obtained from 269 patients and 416 healthy controls, and brain-wide transcriptomic data were collected from Allen Human Brain Atlas. The between-group differences in gray matter volume (GMV) and differentially methylated CpG positions (DMPs) were examined. The genes with their expression patterns spatially related to GMV changes and genes with DMPs were overlapped and selected. Using principal component regression, the associations between DMPs in overlapped genes and GMV across individual patients were investigated, and the region-specific correlations between methylation status and gene expression were examined. We found significant associations between the decreased GMV and DMPs methylation status in the anterior cingulate cortex, inferior frontal cortex, and fusiform face cortex regions. These DMPs genes were primarily enriched in the neurodevelopmental and synaptic transmission process. There was a significant negative correlation between DNA methylation and gene expression in genes associated with GMV changes of the frontal cortex in MDD. Our findings suggest that GMV abnormalities in MDD may have a transcriptomic and epigenetic basis. This imaging-transcriptomic-epigenetic integrative analysis provides spatial and biological links between cortical morphological deficits and peripheral epigenetic signatures in MDD.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/genética , Epigenômica , Multiômica , Encéfalo/diagnóstico por imagem , Perfilação da Expressão Gênica
15.
Clin Chim Acta ; 552: 117698, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38072301

RESUMO

BACKGROUND: Infective endocarditis is a life-threatening uncommon infectious disease, and we aimed to explore the clinical utility of venous or arterial blood-based metagenomic next-generation sequencing (mNGS) approaches to diagnose left-sided infective endocarditis (LSIE). METHODS: We prospectively studied 79 LSIE patients who received valvular surgery in our hospital. Results of blood culture, valve culture, venous blood-based mNGS, arterial blood-based mNGS, venous blood-based mNGS plus blood culture, and arterial blood-based mNGS plus blood culture were evaluated and compared. RESULTS: Both venous blood- and arterial blood-based mNGS methods displayed significantly higher positive detection rates than blood culture and valve culture (43.0 %, 49.4 % vs. 32.9 %, 19.0 %; P < 0.001). Strikingly, when combining blood-based mNGS and blood culture, the positive rate could be further improved to more than 60 %. Moreover, we found mNGS LSIE detection was closely associated with preoperative leukocyte (P = 0.027), neutrophil value (P = 0.018), vegetation ≥ 14 mm (P = 0.043), and vegetations in aortic valve (P = 0.048). In addition, we discovered that blood-based mNGS had a superir capacity over blood culture to detect gram-negative bacteria, fungi, Bartonella Quintana, and mixed infections than blood culture. CONCLUSION: This study indicates that venous blood- and arterial blood-based mNGS displayed high positive rate in the rapid detection of pathogens in high-risk LSIE patients.


Assuntos
Endocardite , Veias , Humanos , Estudos Prospectivos , Endocardite/diagnóstico , Leucócitos , Sequenciamento de Nucleotídeos em Larga Escala , Sensibilidade e Especificidade
16.
Oncotarget ; 14: 997-1008, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38117531

RESUMO

To evade cell cycle controls, malignant cells rely upon rapid expression of select proteins to mitigate proapoptotic signals resulting from damage caused by both cancer treatments and unchecked over-proliferation. Cyclin-dependent kinase 9 (CDK9)-dependent signaling induces transcription of downstream oncogenes promoting tumor growth, especially in hyperproliferative 'oncogene-addicted' cancers, such as human hematological malignancies (HHMs). GFH009, a potent, highly selective CDK9 small molecule inhibitor, demonstrated antiproliferative activity in assorted HHM-derived cell lines, inducing apoptosis at IC50 values below 0.2 µM in 7/10 lines tested. GFH009 inhibited tumor growth at all doses compared to controls and induced apoptosis in a dose-dependent manner. Twice-weekly injections of GFH009 maleate at 10 mg/kg significantly prolonged the survival of MV-4-11 xenograft-bearing rodents, while their body weight remained stable. There was marked reduction of MCL-1 and c-MYC protein expression post-drug exposure both in vitro and in vivo. Through rapid 'on-off' CDK9 inhibition, GFH009 exerts a proapoptotic effect on HHM preclinical models triggered by dynamic deprivation of crucial cell survival signals. Our results mechanistically establish CDK9 as a targetable vulnerability in assorted HHMs and, along with the previously shown superior class kinome selectivity of GFH009 vs other CDK9 inhibitors, strongly support the rationale for currently ongoing clinical studies with this agent in acute myeloid leukemia and other HHMs.


Assuntos
Antineoplásicos , Quinase 9 Dependente de Ciclina , Neoplasias Hematológicas , Humanos , Antineoplásicos/farmacologia , Apoptose , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Neoplasias Hematológicas/tratamento farmacológico , Oncogenes
17.
Artigo em Inglês | MEDLINE | ID: mdl-37934311

RESUMO

Adolescent psychotic mood disorder (MDP) is a specific phenotype that characterized by more severe symptoms and prognosis compared to nonpsychotic mood disorder (MDNP). But the underlying neural mechanisms remain unknown, and graph theory analysis can help to understand possible mechanisms of psychotic symptoms from the perspective of functional networks. A total of 177 adolescent patients with mood disorders were recruited, including 61 MDP and 116 MDNP. Functional networks were constructed, and topological properties were compared between the two groups at baseline and after treatment, and the association between properties changes and symptom improvement was explored. Compared to the MDNP group, the MDP group exhibited higher small-world properties (FDR q = 0.003) and normalized clustering coefficients (FDR q = 0.008) but demonstrated decreased nodal properties in the superior temporal gyrus (STG), Heschl's gyrus, and medial cingulate gyrus (all FDR q < 0.05). These properties were found to be correlated with the severity of psychotic symptoms. Topological properties also changed with improvement of psychotic symptoms after treatment, and changes in degree centrality of STG in the MDP was significantly positive correlated with improvement of psychotic symptoms (r = 0.377, P = 0.031). This study indicated that functional networks are more severely impaired in patients with psychotic symptoms. Topological properties, particularly those associated with the STG, hold promise as emerging metrics for assessing symptoms and treatment efficacy in patients with psychotic symptoms.

18.
BJA Open ; 8: 100237, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37942055

RESUMO

Background: The type of anaesthesia and choice of anaesthetic drugs may affect the quality of recovery after surgery. Remimazolam is a new benzodiazepine with rapid onset and offset, specifically antagonised by flumazenil. This study aimed to compare remimazolam with propofol on the quality of recovery in patients undergoing ambulatory arthroscopic surgery. Methods: Patients aged 18-65 yr and scheduled for ambulatory arthroscopic meniscus repair were recruited and randomly assigned to receive either continuous i.v. infusion of remimazolam or plasma target-controlled infusion of propofol. The quality of recovery-15 (QoR-15) scale was administered on postoperative day 1 (POD1) as the primary outcome. Secondary outcomes included the Athens Insomnia Scale (AIS) scores and cardiovascular variables. Results: In total, 120 patients were randomly assigned to the remimazolam or propofol groups and 114 patients were included in the analysis. The remimazolam group had higher total QoR-15 scores on POD1 (125 [120-127.5] vs 121.5 [119-124], with a median difference of 3 (95% confidence interval: 1-5; P=0.002). Physical independence and psychological support were higher in the remimazolam group (8.5 [8-10] vs 8 [7-9], P=0.043; 17 [13-17] vs 12.5 [12-14], P<0.001). Remimazolam lowered the number of awakenings during the first postoperative night (P=0.042) and the incidence of hypotension (P=0.04). Conclusions: Remimazolam-based total i.v. anaesthesia was associated with small improvements in the quality of recovery; however, the improvement was less than the minimally clinically important difference. Clinical trial registration: ChiCTR2100053014.

19.
Support Care Cancer ; 31(12): 698, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37964024

RESUMO

OBJECTIVE: To evaluate the efficacy and feasibility of utilizing Traditional Chinese Medicine (TCM) combined group psychotherapy intervention on psychological distress management and gut micro-biome regulation for colorectal (CRC) survivors. METHODS: A single-arm phase I clinical trial was conducted between December 2020 and December 2021 in Xiyuan Hospital and Beijing Cancer Hospital in China. Inclusion criteria included stage I-III CRC survivors after radical surgery with age between 18 and 75. The intervention was a 6-week online TCM combined group psychotherapy intervention including 90-min communication, TCM lifestyle coaching, self-acupressure guidance, and mindfulness practice led by TCM oncologist and psychiatrist each week. Outcomes were measured by Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Fear of Cancer Recurrence Inventor (FCRI), and Quality of Life Questionnaire (QLQ-C30). Fecal samples before and after intervention were collected for 16Sr RNA analysis. RESULTS: We recruited 40 CRC survivors and 38 of them finally completed all interventions with average age of 58±13 years' old. Paired t-test showed that SAS at week 2(35.4±5.8), week 4 (37.9±10.5) and week 6 (31.3±6.4) during the intervention was significantly lower than baseline (42.1±8.3, p<0.05 respectively). SDS score also declined substantially from baseline (38.8±10.7) to week 2 (28.3±8.8, p<0.001) and week 6 (25.4±7.7, p<0.001). FCRI decreased from 19.4±7.2 at baseline to 17.5±7.1 at week 4 (p=0.038) and 16.3±5.8 at week 6 (p=0.008). Although changes of QLQ-C30 were not statistically prominent, symptom burden of insomnia and fatigue significantly alleviated. The abundances of gut microbiota Intestinibacter, Terrisporobacter, Coprobacter, and Gordonibacter were all significantly elevated after intervention. CONCLUSIONS: TCM combined group psychotherapy intervention is feasible and effective to reduce CRC survivors' psychological distress and modulate certain gut bacteria which might be associated with brain-gut axis effect. It is necessary to carry out with phase II randomized controlled clinical trial.


Assuntos
Neoplasias Colorretais , Psicoterapia de Grupo , Humanos , Pessoa de Meia-Idade , Idoso , Adolescente , Adulto Jovem , Adulto , Medicina Tradicional Chinesa , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Neoplasias Colorretais/terapia , Neoplasias Colorretais/psicologia
20.
J Agric Food Chem ; 71(44): 16752-16762, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37822021

RESUMO

Fumonisin B1 (FB1) is a representative form of fumonisin and is widely present in food and feed. Hydrolyzed fumonisin B1 (HFB1) emerges as a breakdown product of FB1, which is accompanied by FB1 alterations. While previous studies have primarily focused on the liver or kidney toxicity of FB1, with limited studies existing on its neurotoxicity and even fewer on the toxicity of HFB1, this study focuses on the neurotoxicity of FB1 and HFB1 exposure in mice investigated by the open field test, Morris water maze test, histopathological analysis, and nontargeted metabolomics. Further, the levels of oxidative stress-related indices, neurotransmitters, and sphingolipids in the brain were measured to analyze their correlation with behavioral outcomes. The results showed that both FB1 (5 mg/kg) and HFB1 (2.8 mg/kg) reduced autonomous exploratory behavior in mice, impaired spatial learning and memory, and caused mild abnormalities in the brain structure. Quantitative analysis further indicated that exposure to FB1 and HFB1 disrupted neurotransmitter homeostasis, exacerbated oxidative stress, and significantly increased the sphinganine/sphingosine (Sa/So) ratio. Moreover, HFB1 exhibited neurotoxic effects similar to those of FB1, emphasizing the need to pay attention to the neurotoxicity effect of HFB1. These findings underscore the importance of understanding the risks and potential neurological damage associated with FB1 and HFB1 exposure, highlighting the necessity for further research in this crucial field.


Assuntos
Fumonisinas , Camundongos , Animais , Fumonisinas/análise , Memória Espacial , Esfingolipídeos , Fígado/metabolismo
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