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We described an 82-year-old man who was taken to our emergency department after being found unconscious. His electrocardiogram (ECG) showed ST-segment elevation in leads V4-V6 and cardiac troponin I (cTnI) was abnormally elevated. In addition to ECG and cTnI changes, this patient was combined with unconsciousness, high fever, abnormal liver function, acute renal failure, and rhabdomyolysis. The initial diagnosis was heat stroke, so cooling measures were initiated immediately, but a concurrent myocardial infarction was suspected. Meanwhile, emergency coronary angiography was performed, but no severe coronary stenosis or thrombosis was found. We first evaluated quantitative flow ratio (QFR) and coronary angiography-derived index of microvascular resistance (ca-IMR) in patients with heat stroke. Ca-IMR was 260 mmHg*s/m in the left circumflex artery, indicating the presence of coronary microvascular dysfunction (CMD). After several days of treatment, the patient recovered from multiple organ damage. Therefore, ECG and troponin results should be interpreted carefully in patients with high fever and coma during high temperature seasons.
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Eletrocardiografia , Golpe de Calor , Infarto do Miocárdio , Troponina I , Humanos , Masculino , Golpe de Calor/sangue , Golpe de Calor/diagnóstico , Golpe de Calor/fisiopatologia , Golpe de Calor/complicações , Idoso de 80 Anos ou mais , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Troponina I/sangue , Diagnóstico DiferencialRESUMO
Developing advanced luminescent materials that are recognizable under specified conditions provides better opportunity for reliable optical anti-counterfeiting techniques. In this work, to the best of our knowledge, novel GdInO3:Tm,Yb perovskite phosphors with ultrafine sizes and rounded morphologies were successfully synthesized by a facile chemical precipitation route. Two-type perovskites with orthorhombic and hexagonal structures could be obtained by calcining the precursor at 850 and 1100 °C, respectively. Under 980â nm excitation, the two phosphors exhibited cyan-bluish emission at â¼460-565â nm, red emission at 645-680â nm, and near-infrared emission at 770-825â nm arising from 1G4 + 1D2â3H5,6, 3F2,3â3H6, and 3H4â3H6 transitions of Tm3+, respectively, where the hexagonal perovskite phosphor had relatively strong and sharp red emission as well as red-shifted cyan-bluish emission via successive cross relaxations. The Yb3+ sensitizer enhanced the upconversion luminescence via effective Yb3+âTm3+ energy transfer and the optimal Yb3+ concentrations were 10 at.% for orthorhombic perovskite and 5 at.% for hexagonal one. The upconversion mechanism mainly ascribed to two-photon processes while three-photon was also present. Upon excitation at 254â nm, their down-conversion spectra exhibited broad multibands in the wavelength range of 400-500â nm deriving from combined effects of the defect-induced emission of GdInO3 and the 1D2â3F4 + 4G4â3H6 emissions of Tm3+. The energy transfer from GdInO3 defect level to Tm3+ excitation state was observed for the first time. The unclonable security codes prepared by screen printing from those dual-mode emitting perovskite phosphors were almost invisible under natural light, which had promising potential for anti-counterfeiting application.
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Background: This study aimed to explore the expression level and transcriptional regulation mechanism of Extra Spindle Pole Bodies Like 1 (ESPL1) in bladder cancer (BC). Methods: A multicentre database of samples (n = 1391) was assayed for ESPL1 mRNA expression in BC and validated at the protein level by immunohistochemical (IHC) staining of in-house samples (n = 202). Single-cell sequencing (scRNA-seq) analysis and enrichment analysis explored ESPL1 distribution and their accompanying molecular mechanisms. ATAC-seq, ChIP-seq and Hi-C data from multiple platforms were used to investigate ESPL1 upstream transcription factors (TFs) and potential epigenetic regulatory mechanisms. Immune-related analysis, drug sensitivity and molecular docking of ESPL1 were also calculated. Furthermore, upstream microRNAs and the binding sites of ESPL1 were predicted. The expression level and early screening efficacy of miR-299-5p in blood (n = 6625) and tissues (n = 537) were examined. Results: ESPL1 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 0.75; 95 % CI = 0.09, 1.40), and IHC staining of in-house samples verified this finding (p < 0.0001). ESPL1 was predominantly distributed in BC epithelial cells. Coexpressed genes of ESPL1 were enriched in cell cycle-related signalling pathways, and ESPL1 might be involved in the communication between epithelial and residual cells in the Hippo, ErbB, PI3K-Akt and Ras signalling pathways. Three TFs (H2AZ, IRF5 and HIF1A) were detected upstream of ESPL1 and presence of promoter-super enhancer and promoter-typical enhancer loops. ESPL1 expression was correlated with various immune cell infiltration levels. ESPL1 expression might promote BC growth and affect the sensitivity and therapeutic efficacy of paclitaxel and gemcitabine in BC patients. As an upstream regulator of ESPL1, miR-299-5p expression was downregulated in both the blood and tissues, possessing great potential for early screening. Conclusions: ESPL1 expression was upregulated in BC and was mainly distributed in epithelial cells. Elevated ESPL1 expression was associated with TFs at the upstream transcription start site (TSS) and distant chromatin loops of regulatory elements. ESPL1 might be an immune-related predictive and diagnostic marker for BC, and the overexpression of ESPL1 played a cancer-promoting role and affected BC patients' sensitivity to drug therapy. miR-299-5p was downregulated in BC blood and tissues and was also expected to be a novel marker for early screening.
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BACKGROUND: This study aimed to explore the expression, molecular mechanism and its biological function of potassium two pore domain channel subfamily K member 1 (KCNK1) in bladder cancer (BC). METHODS: We integrated large numbers of external samples (n = 1486) to assess KCNK1 mRNA expression levels and collected in-house samples (n = 245) for immunohistochemistry (IHC) experiments to validate at the KCNK1 protein level. Single-cell RNA sequencing (scRNA-seq) analysis was performed to further assess KCNK1 expression and cellular communication. The transcriptional regulatory mechanisms of KCNK1 expression were explored by ChIP-seq, ATAC-seq and ChIA-PET data. Highly expressed co-expressed genes (HECEGs) of KCNK1 were used to explore potential signalling pathways. Furthermore, the immunoassay, clinical significance and molecular docking of KCNK1 were calculated. RESULTS: KCNK1 mRNA was significantly overexpressed in BC (SMD = 0.58, 95% CI [0.05; 1.11]), validated at the protein level (p < 0.0001). Upregulated KCNK1 mRNA exhibited highly distinguishing ability between BC and control samples (AUC = 0.82 [0.78-0.85]). Further, scRNA-seq analysis revealed that KCNK1 expression was predominantly clustered in BC epithelial cells and tended to increase with cellular differentiation. BC epithelial cells were involved in cellular communication mainly through the MK signalling pathway. Secondly, the KCNK1 transcription start site (TSS) showed promoter-enhancer interactions in three-dimensional space, while being transcriptionally regulated by GRHL2 and FOXA1. Most of the KCNK1 HECEGs were enriched in cell cycle-related signalling pathways. KCNK1 was mainly involved in cellular metabolism-related pathways and regulated cell membrane potassium channel activity. KCNK1 expression was associated with the level of infiltration of various immune cells. Immunotherapy and chemotherapy (docetaxel, paclitaxel and vinblastine) were more effective in BC patients in the high KCNK1 expression group. KCNK1 expression correlated with age, pathology grade and pathologic_M in BC patients. CONCLUSIONS: KCNK1 was significantly overexpressed in BC. A complex and sophisticated three-dimensional spatial transcriptional regulatory network existed in the KCNK1 TSS and promoted the upregulated of KCNK1 expression. The high expression of KCNK1 might be involved in the cell cycle, cellular metabolism, and tumour microenvironment through the regulation of potassium channels, and ultimately contributed to the deterioration of BC.
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Regulação Neoplásica da Expressão Gênica , Canais de Potássio de Domínios Poros em Tandem , Neoplasias da Bexiga Urinária , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Simulação de Acoplamento Molecular , Canais de Potássio de Domínios Poros em Tandem/genética , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Transdução de Sinais , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1-4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research.
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Histonas , Fenótipo , Humanos , Masculino , Feminino , Histonas/genética , Criança , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia , Pré-Escolar , Adolescente , Adulto , Deficiência Intelectual/genética , Deficiência Intelectual/patologiaRESUMO
BACKGROUND: Fibrosis has important pathoetiological and prognostic roles in chronic liver disease. This study evaluates the role of radiomics in staging liver fibrosis. METHOD: After literature search in electronic databases (Embase, Ovid, Science Direct, Springer, and Web of Science), studies were selected by following precise eligibility criteria. The quality of included studies was assessed, and meta-analyses were performed to achieve pooled estimates of area under receiver-operator curve (AUROC), accuracy, sensitivity, and specificity of radiomics in staging liver fibrosis compared to histopathology. RESULTS: Fifteen studies (3718 patients; age 47 years [95% confidence interval (CI): 42, 53]; 69% [95% CI: 65, 73] males) were included. AUROC values of radiomics for detecting significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4) were 0.91 [95%CI: 0.89, 0.94], 0.92 [95%CI: 0.90, 0.95], and 0.94 [95%CI: 0.93, 0.96] in training cohorts and 0.89 [95%CI: 0.83, 0.91], 0.89 [95%CI: 0.83, 0.94], and 0.93 [95%CI: 0.91, 0.95] in validation cohorts, respectively. For diagnosing significant fibrosis, advanced fibrosis, and cirrhosis the sensitivity of radiomics was 84.0% [95%CI: 76.1, 91.9], 86.9% [95%CI: 76.8, 97.0], and 92.7% [95%CI: 89.7, 95.7] in training cohorts, and 75.6% [95%CI: 67.7, 83.5], 80.0% [95%CI: 70.7, 89.3], and 92.0% [95%CI: 87.8, 96.1] in validation cohorts, respectively. Respective specificity was 88.6% [95% CI: 83.0, 94.2], 88.4% [95% CI: 81.9, 94.8], and 91.1% [95% CI: 86.8, 95.5] in training cohorts, and 86.8% [95% CI: 83.3, 90.3], 94.0% [95% CI: 89.5, 98.4], and 88.3% [95% CI: 84.4, 92.2] in validation cohorts. Limitations included use of several methods for feature selection and classification, less availability of studies evaluating a particular radiological modality, lack of a direct comparison between radiology and radiomics, and lack of external validation. CONCLUSION: Although radiomics offers good diagnostic accuracy in detecting liver fibrosis, its role in clinical practice is not as clear at present due to comparability and validation constraints.
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Radiologia , Radiômica , Masculino , Humanos , Pessoa de Meia-Idade , Cirrose Hepática/diagnóstico por imagem , Área Sob a Curva , Bases de Dados FactuaisRESUMO
The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.
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Anti-Hipertensivos , Transtorno do Deficit de Atenção com Hiperatividade , Comportamento Animal , Captopril , Microbioma Gastrointestinal , Efeitos Tardios da Exposição Pré-Natal , Ratos Endogâmicos SHR , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Gravidez , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Feminino , Anti-Hipertensivos/farmacologia , Captopril/farmacologia , Masculino , Ratos , Comportamento Animal/efeitos dos fármacos , Labetalol/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipertensão Induzida pela Gravidez/induzido quimicamente , Dopamina/metabolismoRESUMO
Soil quality is an important determinant of soil-use efficiency in the Loess Plateau. However, there is no in-depth study on the soil quality of the Loess Plateau. The present study compared the quality of the 0-20 cm soil layer (T0-20) and the 20-40 cm soil layer (T20-40) from the Guyuan region located in the Loess Plateau. The analysis revealed that T0-20 had a higher content of total N, total P, available P, and organic matter, and the activities of microbial enzymes, especially ß-grape-glycosidase (ß-GC) and sucrase (SC), than T20-40, indicating that soil quality in T0-20 was better than T20-40. Amplicon sequencing found that Pseudombrophila from Ascomycota was the most abundant microbial species and significantly differed between T0-20 (34.2%) and T20-40 (48.7%). This species and another 19 microbial species, such as Ceratobasidiaceae and Mortierellaceae, determined the diversity of soil microorganism. Further analysis of the phenotype and other parameters of pepper seedlings subjected to P. capsici infection isolated from test soil revealed that decreased organic matter content in deep soil layer is related to happening of pepper blight, and 3 h after infection was the critical time point for infection. The peroxidase (POD) activity increased after P. capsici infection and was positively correlated with infection time, suggesting this enzyme may be an indicator of pepper blight occurrence. These findings provide a theoretical foundation for planning pepper blight management and crop cultivation strategies in the Guyuan region.
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Ascomicetos , Solo , Alimentos , China , Carbono/análiseRESUMO
Cell senescence deters the activation of various oncogenes. Induction of senescence is, therefore, a potentially effective strategy to interfere with vital processes in tumor cells. Sphingosine-1-phosphate receptor 1 (S1PR1) has been implicated in various cancer types, including ovarian cancer. The mechanism by which S1PR1 regulates ovarian cancer cell senescence is currently elusive. In this study, we demonstrate that S1PR1 was highly expressed in human ovarian cancer tissues and cell lines. S1PR1 deletion inhibited the proliferation and migration of ovarian cancer cells. S1PR1 deletion promoted ovarian cancer cell senescence and sensitized ovarian cancer cells to cisplatin chemotherapy. Exposure of ovarian cancer cells to sphingosine-1-phosphate (S1P) increased the expression of 3-phosphatidylinositol-dependent protein kinase 1 (PDK1), decreased the expression of large tumor suppressor 1/2 (LATS1/2), and induced phosphorylation of Yes-associated protein (p-YAP). Opposite results were obtained in S1PR1 knockout cells following pharmacological inhibition. After silencing LATS1/2 in S1PR1-deficient ovarian cancer cells, senescence was suppressed and S1PR1 expression was increased concomitantly with YAP expression. Transcriptional regulation of S1PR1 by YAP was confirmed by chromatin immunoprecipitation. Accordingly, the S1PR1-PDK1-LATS1/2-YAP pathway regulates ovarian cancer cell senescence and does so through a YAP-mediated feedback loop. S1PR1 constitutes a druggable target for the induction of senescence in ovarian cancer cells. Pharmacological intervention in the S1PR1-PDK1-LATS1/2-YAP signaling axis may augment the efficacy of standard chemotherapy.
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Neoplasias Ovarianas , Proteínas Quinases , Feminino , Humanos , Receptores de Esfingosina-1-Fosfato/genética , Neoplasias Ovarianas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Senescência Celular/genética , Proliferação de Células/genéticaRESUMO
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common disorders in child and adolescent psychiatry, with a prevalence of more than 5%. Despite extensive research on ADHD in the last 10 to 20 years, effective treat-ments are still lacking. Instead, the concept of ADHD seems to have become broader and more heterogeneous. Therefore, the diagnosis and treatment of ADHD remains challenging for clinicians. AIM: To investigate the effects of a multimodal integrated intervention for children with ADHD. METHODS: Between March 2019 and September 2020, a total of 100 children with ADHD who were diagnosed and treated at our hospital were assessed for eligibility, two of whom revoked their consent. A case-control study was conducted in which the children were equally assigned, using a randomized number table, to either a medication group (methylphenidate hydrochloride extended-release tablets and atomoxetine hydrochloride tablets) or a multimodal integrated intervention group (medication + parent training + behavior modification + sensory integration therapy + sand tray therapy), with 49 patients in each group. The clinical endpoint was the efficacy of the different intervention modalities. RESULTS: The two groups of children with ADHD had comparable patient characteristics (P > 0.05). Multimodal integrated intervention resulted in a significantly higher treatment efficacy (91.84%) than medication alone (75.51%) (P < 0.05). Children who received the multimodal integrated intervention showed lower scores in the Conners Parent Symptom Questionnaire and the Weiss Functional Impairment Rating Scale than those treated with medication alone (P < 0.05). The Sensory Integration Scale scores of children in the multimodal integrated intervention group were higher than those of children in the medication group (P < 0.05). Children who received the multimodal integrated intervention had higher compliance and family satisfaction and a lower incidence of adverse events than those treated with medication alone (P < 0.05). CONCLUSION: Multimodal integrated intervention effectively alleviated symptoms associated with ADHD in children. It enhanced their memory and attention with high safety and parental satisfaction, demonstrating good potential for clinical promotion.
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BACKGROUND: Long-term treatment of attention deficit/hyperactivity disorder (ADHD) is associated with adverse events, such as nausea and vomiting, dizziness, and sleep disturbances, and poor maintenance of late ADHD medication compromises treatment outcomes and prolongs the recovery of patients' social functioning. AIM: To evaluate the effect of non-pharmacological treatment on the full recovery of social functioning in patients with ADHD. METHODS: A total of 90 patients diagnosed with ADHD between May 2019 and August 2020 were included in the study and randomly assigned to either the pharmacological group (methylphenidate hydrochloride and tomoxetine hydrochloride) or the non-pharmacological group (parental training, behavior modification, sensory integration therapy, and sand tray therapy), with 45 cases in each group. Outcome measures included treatment compliance, Swanson, Nolan, and Pelham, Version IV (SNAP-IV) scores, Conners Parent Symptom Questionnaire (PSQ) scores, and Weiss Functional Impairment Rating Scale (WFIRS) scores. RESULTS: The non-pharmacological interventions resulted in significantly higher compliance in patients (95.56%) compared with medication (71.11%) (P < 0.05). However, no significant differences in SNAP-IV and PSQ scores, in addition to the learning/school, social activities, and adventure activities of the WFIRS scores were observed between the two groups (P > 0.05). Patients with non-pharmacological interventions showed higher WFIRS scores for family, daily life skills, and self-concept than those in the pharmacological group (P < 0.05). CONCLUSION: Non-pharmacological interventions, in contrast to the potential risks of adverse events after long-term medication, improve patient treatment compliance, alleviate patients' behavioral symptoms of attention, impulsivity, and hyperactivity, and improve their cognitive ability, thereby improving family relationships and patient self-evaluation.
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BACKGROUND: Hydrogen sulfide (H2S) is widely distributed throughout the nervous system with various antioxidant and anti-inflammatory properties. Hypertension involves an increase in reactive oxygen species (ROS) and inflammation in the hypothalamic paraventricular nucleus (PVN). However, it is unclear how H2S in PVN affects hypertension. METHODS: Our study used spontaneously hypertensive rats (SHR) and control Wistar Kyoto (WKY) rats, microinjected with adenovirus-associated virus (AAV)-CBS (cystathionine beta-synthase overexpression) or AAV-ZsGreen in bilateral PVN, or simultaneously injected with virus-carrying nuclear factor erythroid 2-related factor 2 (Nrf2)-shRNA for 4 weeks. Blood pressure (BP) and plasma noradrenaline level were detected, and the PVN was collected. Finally, levels of CBS, H2S, Nrf2, Fra-LI, ROS, gp91phox, p47phox, superoxide dismutase 1, interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor-α, tyrosine hydroxylase, and glutamate decarboxylase 67 were measured. RESULTS: We found that AAV-CBS increased H2S in the PVN, and BP, neuronal activation, oxidative stress, and inflammation of PVN were substantially reduced. Furthermore, endogenous H2S in the PVN activated Nrf2 and corrected the PVN's imbalance of excitatory and inhibitory neurotransmitters. However, Nrf2 knockdown in the PVN was similarly observed to abolish the beneficial effect of H2S on hypertension. CONCLUSIONS: The findings imply that endogenous H2S in SHR PVN is reduced, and PVN endogenous H2S can alleviate hypertension via Nrf2-mediated antioxidant and anti-inflammatory effects.
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Sulfeto de Hidrogênio , Hipertensão , Ratos , Animais , Anti-Hipertensivos/uso terapêutico , Ratos Endogâmicos SHR , Núcleo Hipotalâmico Paraventricular/metabolismo , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Ratos Endogâmicos WKY , Anti-Inflamatórios/farmacologia , Inflamação/metabolismoRESUMO
BACKGROUND: Standardized chemotherapy for breast cancer can improve the survival of patients, but during the process, it is accompanied by a variety of symptoms. OBJECTIVE: To explore the dynamic changes of symptoms and quality of life in breast cancer patients at different time points during chemotherapy, and to explore the correlation with quality of life. METHOD: A prospective study method was used to collect 120 breast cancer patients undergoing chemotherapy as the research objects. The general information questionnaire, the Chinese version of the M.D. Anderson Symptom inventory (MDASI-C), and the European Organization for Cancer Research and Treatment (EORTC) Quality of Life questionnaire were used in the first week (T1), first month (T2), three month (T3) and 6 months after chemotherapy (T4) to conduct dynamic investigation. RESULTS: The symptoms of breast cancer patients at four time points during chemotherapy period were: psychological symptoms, pain-related symptoms, perimenopausal symptoms, impaired self-image, and neurological related symptoms etc. At T1, it exhibited 2 symptoms, however as moving along the chemotherapy process, the symptoms are increasing. The severity is (F= 76.32, P< 0.001), life of quality (F= 117.64, P< 0.001) vary. At T3, there were 5 symptoms, and at T4 symptom number increased to 6 with worsening quality of life. It exhibited positive correlation with scores in multiple domains of quality of life (P< 0.05), and the above symptoms showed positive correlation with multiple domains of QLQ-C30 (P< 0.05). CONCLUSION: After T1-T3 of chemotherapy in breast cancer patients, the symptoms become more serious and the quality of life reduced. Therefore, medical staff should pay attention to the occurrence and development of patient's symptoms, create a reasonable plan from the perspective of symptom management and carry out personalized interventions to improve patient's quality of life.
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Antineoplásicos , Neoplasias da Mama , Qualidade de Vida , Feminino , Humanos , Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Estudos Prospectivos , Inquéritos e Questionários , Antineoplásicos/uso terapêuticoRESUMO
Previous studies have shown that reduced sleep duration, sleep fragmentation, and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling. At the same time, blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease. However, currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency. This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital. Patients were divided into two groups: those with insufficient sleep (sleep duration ≤ 6 hours, n = 19, age 61.58 ± 8.54 years, 10 men) and those with normal sleep durations (sleep duration > 6 hours, n = 31, age 63.19 ± 10.09 years, 18 men). Demographic variables were collected to evaluate cognitive function, neuropsychiatric symptoms, and activities of daily living. The levels of orexin, its receptor proteins, and several blood-brain barrier factors were measured in cerebrospinal fluid. Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains. Furthermore, levels of orexin and its receptors were upregulated in the cerebrospinal fluid, and the blood-brain barrier was destroyed. Both these events precipitated each other and accelerated the progression of Alzheimer's disease. These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation. Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.
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This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type â ¡ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1ß, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1ß, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.
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Artrite Experimental , Artrite Reumatoide , Codonopsis , Extratos Vegetais , Animais , Bovinos , Masculino , Ratos , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Peso Corporal , Codonopsis/química , Interleucina-6/sangue , NF-kappa B/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Extratos Vegetais/uso terapêutico , Ratos Sprague-Dawley , Transdução de Sinais , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Acute myocardial infarction (AMI) and acute ischemic stroke (AIS) are the main causes of disability and mortality worldwide. Although reperfusion therapy is the most effective treatment for the two diseases, it is still a great challenge for treating the two diseases at the same time. Here we share 2 cases: one patient was hospitalized for AMI, developed AIS after receiving percutaneous coronary intervention (PCI), and suffered from cardiac rupture after alteplase thrombolytic therapy. The other patient was admitted for AIS, who had sudden chest pain during the thrombolytic process of alteplase. Considering AMI, emergency PCI was performed, and he was finally discharged.
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One of the most significant environmental factors affecting plant growth, development and productivity is salt stress. The damage caused by salt to plants mainly includes ionic, osmotic and secondary stresses, while the plants adapt to salt stress through multiple biochemical and molecular pathways. Tomato (Solanum lycopersicum L.) is one of the most widely cultivated vegetable crops and a model dicot plant. It is moderately sensitive to salinity throughout the period of growth and development. Biotechnological efforts to improve tomato salt tolerance hinge on a synthesized understanding of the mechanisms underlying salinity tolerance. This review provides a comprehensive review of major advances on the mechanisms controlling salt tolerance of tomato in terms of sensing and signaling, adaptive responses, and epigenetic regulation. Additionally, we discussed the potential application of these mechanisms in improving salt tolerance of tomato, including genetic engineering, marker-assisted selection, and eco-sustainable approaches.