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1.
BMC Cardiovasc Disord ; 24(1): 233, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689231

RESUMO

OBJECTIVE: This study aimed to examine the changes in absolute value and decline rate of early serum cardiac troponin T (cTnT) and N-terminal pro b-type natriuretic peptide (NT-proBNP) in neonates who received veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) support therapy within the first week of life. METHODS: We retrospectively collected clinical data and laboratory test results of 18 neonates who underwent V-A ECMO support within one week of birth, from July 2021 to June 2023, using the electronic medical record system. These patients were categorized into survival and death groups. Comparative analyses of the absolute values and decline rates of cTnT and NT-proBNP were made between the groups at baseline, and at 24, 48, and 72 h post-ECMO initiation. RESULTS: Out of the 18 neonates, 12 survived (survival rate: 66.7%), while 6 succumbed. The survival group exhibited significantly lower absolute values of cTnT and NT-proBNP than the death group, and their decline rates were significantly higher. Notably, all neonates without an early decline in cTnT and NT-proBNP levels were in the death group. CONCLUSION: The early changes in the absolute value and decline rate of serum cTnT and NT-proBNP in neonates undergoing V-A ECMO may serve as predictors of their prognosis.


Assuntos
Biomarcadores , Oxigenação por Membrana Extracorpórea , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Troponina T , Humanos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Peptídeo Natriurético Encefálico/sangue , Troponina T/sangue , Recém-Nascido , Fragmentos de Peptídeos/sangue , Estudos Retrospectivos , Masculino , Feminino , Biomarcadores/sangue , Fatores de Tempo , Resultado do Tratamento , Valor Preditivo dos Testes , Fatores de Risco
2.
Lipids Health Dis ; 23(1): 201, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937844

RESUMO

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. METHODS: A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg- 1), curcumin (Cur, 40 mg·kg- 1) and metformin (Met, 50 mg·kg- 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml- 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. RESULTS: The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. CONCLUSION: NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.


Assuntos
Aldo-Ceto Redutases , Curcumina , Hepatopatia Gordurosa não Alcoólica , Triglicerídeos , Curcumina/farmacologia , Curcumina/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Humanos , Células Hep G2 , Aldo-Ceto Redutases/metabolismo , Ratos , Masculino , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Acetil-CoA Carboxilase/metabolismo , Aldeído Redutase/metabolismo , Aldeído Redutase/antagonistas & inibidores , Dieta Hiperlipídica/efeitos adversos , Simulação de Acoplamento Molecular , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metformina/farmacologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Rodanina/análogos & derivados , Tiazolidinas
3.
Immunopharmacol Immunotoxicol ; 46(2): 192-198, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38147028

RESUMO

OBJECTIVE: Endoplasmic reticulum stress (ERS) and Toll-like receptor 2 (TLR2) signaling play an important role in inflammatory bowel disease (IBD); however, the link between TLR2 and ERS in IBD is unclear. This study investigated whether Thapsigargin (TG) -induced ER protein expression levels contributed to TLR2-mediated inflammatory response. METHODS: The THP-1 cells were treated with TLR2 agonist (Pam3CSK4), ERS inducer Thapsigargin (TG) or inhibitor (TUDCA). The mRNA expressions of TLR1-TLR10 were detected by qPCR. The production and secretion of inflammatory factors were detected by PCR and ELISA. Immunohistochemistry was used to detect the expressions of GRP78 and TLR2 in the intestinal mucosa of patients with Crohn's disease (CD). The IBD mouse model was established by TNBS in the modeling group. ERS inhibitor (TUDCA) was used in the treatment group. RESULTS: The expression of TLRs was detected via polymerase chain reaction (PCR) in THP-1 cells treated by ERS agonist Thapsigargin (TG). According to the findings, TG could promote TLR2 and TLR5 expression. Subsequently, in TLR2 agonist Pam3CSK4 induced THP-1 cells, TG could lead to increased expression of the inflammatory factors such as TNF-α, IL-1ß and IL-8, and ERS inhibitor (TUDCA) could block this effect. However, Pam3CSK4 did not significantly impact the GRP78 and CHOP expression. Based upon the immunohistochemical results, TLR2 and GRP78 expression were significantly increased in the intestinal mucosa of patients with Crohn's disease (CD). For in vivo experiments, TUDCA displayed the ability to inhibit intestinal mucosal inflammation and reduce GRP78 and TLR2 proteins. CONCLUSIONS: ERS and TLR2 is upregulated in inflammatory bowel disease, ERS may promote TLR2 pathway-mediated inflammatory response. Moreover, ERS and TLR2 signaling could be novel therapeutic targets for IBD.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Ácido Tauroquenodesoxicólico , Camundongos , Animais , Humanos , Receptor 2 Toll-Like/metabolismo , Chaperona BiP do Retículo Endoplasmático , Tapsigargina/farmacologia , Estresse do Retículo Endoplasmático
4.
Int J Eat Disord ; 56(7): 1353-1364, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36951235

RESUMO

OBJECTIVE: Bulimia nervosa (BN) is an eating disorder associated with the dysfunction of intrinsic brain networks. However, whether the network disruptions in BN patients manifest as dysconnectivity or imbalances of network modular segregation remains unclear. METHOD: We collected data from 41 women with BN and 41 matched healthy control (HC) women. We performed graph theory analysis based on resting-state functional magnetic resonance imaging (RS-fMRI) data; then, we computed the participation coefficient (PC) among brain modules to characterize the modular segregation for the BN and HC groups. The number of intra- and inter-modular connections was calculated to explain the PC changes. Additionally, we examined the potential associations of the measures mentioned above with clinical variables within the BN group. RESULTS: Compared with the HC group, the BN group showed significantly decreased PC in the fronto-parietal network (FPN), cingulo-opercular network (CON), and cerebellum (Cere). Additionally, the number of intra-modular connections of the default mode network (DMN) and the number of the inter-modular connections between the DMN and CON, FPN and Cere, and CON and Cere in the BN group were lower than those in the HC group. The nodal level analysis showed that the BN group had a decreased PC of the anterior prefrontal cortex (aPFC), dorsal frontal cortex (dFC), inferior parietal lobule (IPL), thalamus, and angular gyrus. Further, these metrics were significantly correlated with clinical variables in the BN group. DISCUSSION: These findings may provide novel insights to capture atypical topologies associated with pathophysiology mechanisms and clinical symptoms underlying BN.


Assuntos
Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Feminino , Bulimia Nervosa/diagnóstico por imagem , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Córtex Pré-Frontal , Mapeamento Encefálico
5.
BMC Geriatr ; 23(1): 774, 2023 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-38001406

RESUMO

OBJECTIVES: The purpose of this study was to assess the impact of polypharmacy, potentially inappropriate medications, and drug-drug interactions on in-hospital mortality in older COVID-19 inpatients. METHODS: A cross-sectional study was conducted using electronic medical data from a tertiary hospital in Chengdu from December 2022 to January 2023. The 2019 AGS/Beers criteria was used to evaluate the potentially inappropriate mediation (PIM) status of older COVID-19 inpatients (age ≥ 65 years), the drug-drug interactions were evaluated on Medscape, and multivariate logistic regression was used to identify the risk factors associated with in-hospital mortality. RESULTS: A total of 206 older COVID-19 inpatients were included in the study. The mean number of drugs per day was 13.04. The prevalence of PIM use based on the 2019 AGS Beers Criteria was 66.99%. The prevalence of drug-drug interactions was 61.65%. Logistic regression demonstrated that age ≥ 80 (OR: 10.321, 95% CI: 1.649, 64.579, P = 0.013), renal insufficiency (OR: 4.740, 95% CI: 1.366, 16.447, P = 0.014), long-term hospitalization (OR: 6.637, 95% CI: 1.030, 42.779, P = 0.046), severe pneumonia (OR: 50.230, 95% CI: 5.180, 487.041, P = 0.001) were influencing factors associated with in-hospital mortality in older COVID-19 inpatients. CONCLUSIONS: The polypharmacy, potentially inappropriate medications, and drug-drug interactions were seen in many older COVID-19 inpatients.


Assuntos
COVID-19 , Lista de Medicamentos Potencialmente Inapropriados , Humanos , Idoso , Prescrição Inadequada , Polimedicação , Pacientes Internados , Estudos Transversais , Interações Medicamentosas , Fatores de Risco
6.
Int J Cancer ; 150(8): 1318-1328, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-34914096

RESUMO

Osimertinib, as a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), showed more potent efficacy against brain metastasis (BM) in untreated EGFR-mutant nonsmall cell lung cancer (NSCLC) in the FLAURA study. However, the overall survival (OS) benefit of osimertinib and clinical value of cranial local therapy (CLT) in these patients remain undetermined. Here we conducted a retrospective study involving untreated EGFR-mutant NSCLC patients with BMs receiving first-line osimertinib or first-generation EGFR-TKIs. Upfront CLT was defined as CLT performed before disease progression to the first-line EGFR-TKIs. Pattern of treatment failure and survival outcomes were extensively investigated. Among the 367 patients enrolled, first-generation EGFR-TKI was administered in 265, osimertinib in 102 and upfront CLT performed in 140. Patients receiving osimertinib had more (P < .001) and larger BMs (P = .003) than those receiving first-generation EGFR-TKIs. After propensity score matching, osimertinib was found to prolong OS (37.7 vs 22.2 months, P = .027). Pattern of failure analyses found that 51.8% of the patients without upfront CLT developed their initial progressive disease (PD) in the brain and 59.0% of the cranial PD occurred at the original sites alone, suggesting potential clinical value of upfront CLT. Indeed, upfront stereotactic radiosurgery (SRS) and/or surgery was associated with improved OS among those receiving first-generation EGFR-TKIs (P = .019) and those receiving osimertinib (P = .041). In summary, compared to first-generation EGFR-TKIs, osimertinib is associated with improved OS in untreated EGFR-mutant NSCLC with BMs. Meanwhile, upfront SRS and/or surgery may provide extra survival benefit, which needs to be verified in future studies.


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimiorradioterapia Adjuvante/métodos , Terapia Combinada/métodos , Irradiação Craniana/métodos , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Procedimentos Neurocirúrgicos/métodos , Radiocirurgia/métodos , Estudos Retrospectivos
7.
BMC Cancer ; 22(1): 198, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35189835

RESUMO

BACKGROUND: The clinical features, survival outcomes and patterns of treatment failure of advanced non-small cell lung cancer (NSCLC) patients harboring distinct subtypes of EGFR mutations and receiving first-line EGFR tyrosine kinases inhibitor (TKIs) are not fully understood. METHODS: Consecutive metastatic EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs from October 2010 to March 2020 were enrolled and classified into two main groups based on the EGFR mutation subtypes: common mutation (L858R or exon 19 deletion), uncommon mutation (other EGFR mutations). RESULTS: Of the 1081 patients included, 74 (6.8%) harbored uncommon mutations. The baseline characteristics were generally balanced between the two groups, except that bone metastasis developed less frequently in patients with uncommon mutations (p = 0.02). No significant difference of survival outcomes was found between the two groups, except that among patients with baseline brain metastasis, the intracranial time to progression was significantly shorter in patients with uncommon mutations. Nine of the 17 patients with de novo T790M mutation received Osimertinib, whose overall survival tended to be longer than the remaining 8 patients without Osimertinib treatment (p = 0.08). The patterns of treatment failure were generally consistent between the two groups, except which patients with uncommon mutations had a higher risk developing progressive disease in the brain. CONCLUSION: First-line EGFR-TKIs seemed to be less effective in controlling and preventing brain metastasis in patients with uncommon EGFR mutations and Osimertinib was associated with promising efficacy in patients with de novo T790M mutation, which warranted further validation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Acrilamidas/uso terapêutico , Idoso , Compostos de Anilina/uso terapêutico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Tirosina Quinases/antagonistas & inibidores , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
8.
Epidemiol Infect ; 150: e156, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35968710

RESUMO

Human immunodeficiency virus (HIV) has been widely prevalent among older men (aged ≥50 years old) in Sichuan Province. The study aimed to discover associated factors with the new HIV infection in older men, and provide a scientific basis for the prevention and control of acquired immunodeficiency syndrome (AIDS) in this group. A cross-sectional survey study of newly reported HIV/AIDS and general male residents aged 50 years and older was conducted between April and June 2019, with a resample of respondents to identify cases and controls, followed by a case-control study. Logistic regression was applied to analyse the association between the selected factors and new HIV infection among older men. At last, 242 cases and 968 controls were included. The results of multiple logistic regression suggested that many factors including living alone/concentrated (OR 1.56, 95% CI 1.20-2.04, P = 0.001), have a history of migrant worker (OR 2.10, 95% CI 1.61-2.73, P < 0.001), have commercial sexual behaviour (OR 1.71, 95% CI 1.32-2.22, P < 0.001), married (OR 0.48, 95% CI 0.37-0.64, P < 0.001), have a history of HIV antibody testing (OR 0.73, 95% CI 0.56-0.96, P = 0.026), HIV-related knowledge (OR 0.55, 95% CI 0.42-0.72, P < 0.001) were associated with new HIV infection among older men. The present study revealed some potential risky/protective factors altogether. The results highlighted the direction of HIV/AIDS prevention and control among older men, and it is a social issue that requires the joint participation of the whole society.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Idoso , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Sexual
9.
Phys Chem Chem Phys ; 24(12): 7293-7302, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35262152

RESUMO

Unraveling the photogenerated exciton dynamics of π-stacked molecular aggregates is of great importance for both fundamental studies and industrial applications. Among various π-stacked molecular aggregates, perylene tetracarboxylic acid bisimide (PBI) based aggregates are regarded as one of the prototypes due to their inherent high fluorescence quantum yield and excellent photostability and flexibility in controlling intermolecular forces via chemical modifications. However, the exciton dynamics of these PBI based aggregates remain elusive up to now. In this work, we have first employed LR-TDDFT-based nonadiabatic dynamics simulations and static electronic structure calculations to investigate the ultrafast exciton dynamics of a newly synthesized perylene bisimide quadruple (PBQ) π-stack. Upon photoexcitation, the S6 to S10 states are the most likely populated excited states, which can be regarded as a combination of local excited (LE) excitons and charge transfer (CT) excitons of those four PBI chromophores. Then, the excited PBQ π-stack relaxes ultrafast to the lowest lying excited S1 state within 500 fs, which is accompanied by the complicated exciton conversion as well as exciton localization/delocalization dynamics. In short, the initially populated hybrid LE and CT excitons convert to the LE excitons of B/C and A/D, in which the LE excitons of B/C contribute the most (∼0.44) while the LE excitons of A/D also have minor contributions (0.21), indicating the formation of the localized excimer state. We use the notations A/B/C/D here to represent the four PBI fragments of PBQ π-stacks along the direction perpendicular to the PBI molecular plane. Additionally, using a recently defined root mean square deviation (RMSD) of electron and hole spatial distributions along three Cartesian coordinates, we could investigate the exciton localization/delocalization dynamics in a quantitative way. Our simulation results indicate that the photoinduced electrons and holes of the PBQ π-stack exhibit an ultrafast localization(∼10 fs)-delocalization(∼60 fs)-localization(∼200 fs) dynamics, during which both LE and CT excitons play crucial roles. Our present work is not only consistent with previous experimental studies, but also provides more detailed insights into the relevant processes, which might be useful for the future design of PBI based optoelectronic devices with improved performances.

10.
Mol Med ; 27(1): 2, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407066

RESUMO

BACKGROUND: Although large artery atherosclerosis (LAA) is the most common type of cerebral infarction, non-LAA is not uncommon. The purpose of this paper is to investigate the prognosis of patients with non-LAA and to establish a corresponding nomogram. PATIENTS AND METHODS: Between June 2016 and June 2017, we had 1101 admissions for acute ischemic stroke (AIS). Of these, 848 were LAA and 253 were non-LAA. Patients were followed up every 3 months with a minimum of 1 year of follow-up. After excluding patients who were lost follow-up and patients who did not meet the inclusion criteria, a total of 152 non-LAA patients were included in this cohort study. After single-factor analysis and multifactor logistic regression analysis, the risk factors associated with prognosis were derived and different nomograms were developed based on these risk factors. After comparison, the best model is derived. RESULTS: Logistics regression found that the patient's National Institutes of Health Stroke Scale (NIHSS) score, ejection fraction (EF), creatine kinase-MB (CK-MB), age, neutrophil-to-lymphocyte ratio (NLR), aspartate aminotransferase (AST), and serum albumin were independently related to the patient's prognosis. We thus developed three models: model 1: single NIHSS score, AUC = 0.8534; model 2, NIHSS + cardiac parameters (CK-MB, EF), AUC = 0.9325; model 3, NIHSS + CK-MB + EF + age + AST + NLR + albumin, AUC = 0.9598. We compare the three models: model 1 vs model 2, z = - 2.85, p = 0.004; model 2 vs model 3, z = - 1.58, p = 0.122. Therefore, model 2 is considered to be the accurate and convenient model. CONCLUSIONS: Predicting the prognosis of patients with non-LAA is important, and our nomogram, built on the NIHSS and cardiac parameters, can predict the prognosis accurately and provide a powerful reference for clinical decision making.


Assuntos
Aspartato Aminotransferases/metabolismo , Aterosclerose/complicações , AVC Isquêmico/fisiopatologia , Nomogramas , Albumina Sérica Humana/metabolismo , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , Estudos de Coortes , Análise Fatorial , Feminino , Humanos , AVC Isquêmico/etiologia , AVC Isquêmico/metabolismo , Modelos Logísticos , Perda de Seguimento , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Prognóstico , Volume Sistólico
11.
Cancer Cell Int ; 21(1): 568, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702269

RESUMO

BACKGROUND: Pelvic lymph node metastasis (LNM) is a crucial independent prognostic factor in cervical cancer (CCa) and serves as an indicator for radiation therapy as the primary or an adjuvant treatment option. However, preoperative diagnosis of LNM remains challenging. Thus, we aimed to identify biomarkers of LNM in patients with presumed early-stage CCa. METHODS: The differentially expressed genes (DEGs) between tumours with different lymph node statuses were identified by using The Cancer Genome Atlas database. Then, univariate Cox regression analysis and Kaplan-Meier analyses were utilized to screen overall survival (OS)-associated genes. Multivariate Cox analysis and logistical analysis were utilized to evaluate independent risk factors for OS and LNM, respectively. Subsequently, the protein level of fatty acid binding protein 4 (FABP4) was detected in normal cervical and CCa tissues by immunohistochemistry assays. EdU assays were performed to determine whether FABP4 altered the proliferation of cervical cancer cells. Wound healing and Transwell assays were conducted to explore the effects of FABP4 depletion on migratory and invasive abilities of cervical cancer cells. F-actin fluorescence staining were performed to investigate morphological change and Western blotting analyses were performed to determine epithelial mesenchymal transition-related marker expression and downstream signalling pathways. RESULTS: A total of 243 DEGs, including 55 upregulated and 188 downregulated DEGs, were found in CCa patients with LNM versus those without LNM. Among these, FABP4 was found to be closely associated with poor OS. Multivariate analysis uncovered that FABP4 was an independent risk factor for OS and LNM in patients with CCa. The immunohistochemical results verified dramatically increased FABP4 expression in CCa tissues compared to normal cervical epithelia and its association with poor OS and LNM. In vitro, The proliferation, migration and invasion of cervical cancer cells were significantly inhibited after knocking down of FABP4, which was accompanied by elevated expression of E-cadherin and downregulated expression of N-cadherin, Vimentin and p-AKT. CONCLUSIONS: FABP4 might be a promising biomarker of LNM and survival in patients with early-stage CCa and therefore could significantly contribute to the development of personalized prognosis prediction and therapy optimization.

12.
BMC Neurol ; 21(1): 36, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499823

RESUMO

BACKGROUND: Hemorrhagic transformation (HT) is a serious neurological complication of acute ischemic stroke (AIS) after revascularization. The majority of AIS patients do not have atrial fibrillation (AF) which could also develop into HT. In this study, we aimed to explore whether hemostasis parameters are risk factors of HT in non-AF patients. METHODS: We consecutively enrolled 285 AIS patients with HT. Meanwhile, age- and sex-matched 285 AIS patients without HT were included. The diagnosis of HT was determined by brain CT or MRI during hospitalization. All patients were divided into two subgroups based on the presence of AF and explore the differences between the two subgroups. Blood samples were obtained within 24 h of admission, and all patients were evenly classified into three tertiles according to platelet counts (PLT) levels. RESULTS: In this study, we found the first PLT tertile (OR = 3.509, 95%CI = 1.268-9.711, P = 0.016) was independently associated with HT in non-AF patients, taking the third tertile as a reference. Meanwhile, we also found mean platelet volume (MPV) (OR = 0.605, 95%CI = 0.455-0.805, P = 0.001) and fibrinogen (FIB) (OR = 1.928, 95%CI = 1.346-2.760, P < 0.001) were significantly associated with HT in non-AF patients. But in AF patients, hemostasis parameters showed no significant difference. Meanwhile, we found the MPV (OR = 1.314, 95%CI = 1.032-1.675, P = 0.027) and FIB (OR = 1.298, 95%CI = 1.047-1.610, P = 0.018) were significantly associated with long-term outcomes in non-AF HT patients. CONCLUSIONS: Low PLT, low MPV, and high FIB levels were independently associated with HT in non-AF patients. Additionally, MPV and FIB levels were significantly associated with unfavorable long-term outcomes in non-AF HT patients. Our study showed that hemostasis functions at admission may be beneficial for clinicians to recognize patients with a high risk of HT at an early stage and improve unfavorable long-term outcomes in non-AF patients.


Assuntos
Hemorragia Cerebral/sangue , Hemorragia Cerebral/etiologia , Hemostasia/fisiologia , AVC Isquêmico/sangue , AVC Isquêmico/complicações , Idoso , Fibrilação Atrial , Estudos de Casos e Controles , Feminino , Fibrinogênio , Humanos , Imageamento por Ressonância Magnética , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Fatores de Risco
13.
BMC Gastroenterol ; 21(1): 209, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964873

RESUMO

BACKGROUND: Hepatitis C virus (HCV) is one of the major causes of chronic liver disease, cirrhosis, and liver cancer. Most of the infected people have no clinical symptoms. The current strategy for HCV elimination includes test and treatment. In this study, we aimed to evaluate the campaign for retrieving patients who were lost to follow-up, for subsequent re-evaluation. METHODS: From January 2020 to October 2020, patients who had prior tests for positive anti-HCV antibody in 2010-2018 in our hospital were enrolled for our patient callback campaign. Patients who had unknown HCV RNA status or no documented successful antiviral therapy history were selected for anti-HCV therapy re-evaluation. To facilitate patient referral in the hospital, we developed an electronic reminding system and called the candidate patients via telephone during the study period. RESULTS: Through the hospital electronic system, 3783 patients with positive anti-HCV antibody documentation were identified. Among them, 1446 (38.22%) had tested negative for HCV RNA or had anti-HCV therapy, thereby excluded. Of the 2337 eligible patients, 1472 (62.99%) were successfully contacted and called back during the study period for subsequent HCV RNA testing and therapy. We found that 42.19% of the patients had positive HCV RNA and 88% received subsequent anti-HCV therapy. CONCLUSIONS: A significant number of patients with positive HCV serology were lost for HCV confirmatory test or therapy in the hospital. Therefore, this targeted HCV callback approach in the hospital is feasible and effective in achieving microelimination.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Anticorpos Anti-Hepatite C , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Estudos Retrospectivos
14.
Int J Geriatr Psychiatry ; 36(4): 493-499, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33108011

RESUMO

OBJECTIVES: Depression is the most common mental complication in stroke survivors with about one-third of patients suffering from poststroke depression (PSD). This was the first prospective study aimed to compare the prevalence of PSD and its symptoms between two cohorts of patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). METHODS: Both AIS and ICH patients were simultaneously enrolled in the study. Depression symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17) after a 1-month follow-up. Patients were diagnosed with PSD according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition and the HAMD-17 (HAMD scores >7). RESULTS: The prevalence of PSD (42.3%) in the ICH group was significantly higher than that (22.9%) in the AIS group (p < 0.001). After adjustment for conventional confounding factors, the odds ratio of PSD was 2.65 (95% CI, 1.34-5.24, p = 0.005) for ICH compared to AIS. Depressive symptoms consisting of anxiety, loss of interest, insomnia, and fatigue were more frequent in patients with ICH than in AIS patients. CONCLUSIONS: PSD was more prevalent, and the risk was over twofold higher in patients with ICH than AIS.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral Hemorrágico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Depressão/epidemiologia , Depressão/etiologia , Humanos , Estudos Prospectivos , Acidente Vascular Cerebral/complicações
15.
Lung ; 199(4): 389-394, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34415400

RESUMO

PURPOSE: Vitronectin (VTN), a multifunctional glycoprotein, is involved in various biological and pathological processes. The purpose of this study was to explore the effect of VTN on mesenchymal-epithelial transition (MET) of pulmonary fibroblast cells. METHODS: Lentivirus encoding for VTN-specific shRNA was constructed and infected into the cultured fibroblast WI-38 cells. Real-time PCR and Western blot were applied to examine the expression of VTN in WI-38 cells. MTT assay was used to assess cell proliferation. Western blot was conducted to examine the expression of MET-related and apoptosis-related proteins. RESULTS: The knockdown of VTN significantly inhibited the growth of WI-38 cells compared to the control group. Meanwhile, knockdown of VTN remarkably increased the expression of Bax and Caspase 3 compared with the control group. Furthermore, knockdown of VTN significantly promoted the expression of E-cadherin in comparison to control group. CONCLUSIONS: Knockdown of VTN promoted the expression of apoptosis-related factors, meanwhile, facilitated the MET process of fibroblast cells by regulating the expression of relevant factors. In sum, VTN performed a potential regulator in cell growth and MET of pulmonary fibroblast cells, which can be considered as a potential target for diagnose and therapy of relevant diseases.


Assuntos
Fibroblastos , Vitronectina , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal , Pulmão
16.
Neurosurg Rev ; 44(1): 571-577, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32040777

RESUMO

This study aimed to establish an effective prognostic nomogram for microvascular decompression (MVD)-treated trigeminal neuralgia (TN). The nomogram was based on a retrospective cohort study of 1054 patients with TN. During the period 2005-2014, 845 patients at our department treated TN with MVD and served as a development cohort. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The model was externally validated by 209 TN patients during 2014-2016. Multivariate cox analysis suggested that the patient's age, atypical pain, vascular type, number of offending vessels, and second MVD were significant factors influencing the prognosis of MVD-treated TN. The C index of nomogram in the development cohort was 0.767 (95% CI, 0.739-0.794), and 0.749 (95% CI, 0.688-0.810) in the validation cohort. We developed and validated a nomogram to predict 3-year overall remission rate after MVD treatment of TN. The nomogram can be used in clinical trials to determine the likelihood of pain recurrence in TN patients treated with MVD for 3 years to aid in the comprehensive treatment of TN.


Assuntos
Cirurgia de Descompressão Microvascular , Nomogramas , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neuralgia do Trigêmeo/diagnóstico , Neuralgia do Trigêmeo/mortalidade
17.
J Neuroinflammation ; 16(1): 20, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30700305

RESUMO

Stroke is the most common cerebrovascular disease, the second leading cause of death behind heart disease and is a major cause of long-term disability worldwide. Currently, systemic immunomodulatory therapy based on intravenous cells is attracting attention. The immune response to acute stroke is a major factor in cerebral ischaemia (CI) pathobiology and outcomes. Over the past decade, the significant contribution of the spleen to ischaemic stroke has gained considerable attention in stroke research. The changes in the spleen after stroke are mainly reflected in morphology, immune cells and cytokines, and these changes are closely related to the stroke outcomes. Autonomic nervous system (ANS) activation, release of central nervous system (CNS) antigens and chemokine/chemokine receptor interactions have been documented to be essential for efficient brain-spleen cross-talk after stroke. In various experimental models, human umbilical cord blood cells (hUCBs), haematopoietic stem cells (HSCs), bone marrow stem cells (BMSCs), human amnion epithelial cells (hAECs), neural stem cells (NSCs) and multipotent adult progenitor cells (MAPCs) have been shown to reduce the neurological damage caused by stroke. The different effects of these cell types on the interleukin (IL)-10, interferon (IFN), and cholinergic anti-inflammatory pathways in the spleen after stroke may promote the development of new cell therapy targets and strategies. The spleen will become a potential target of various stem cell therapies for stroke represented by MAPC treatment.


Assuntos
Baço/fisiologia , Transplante de Células-Tronco/métodos , Acidente Vascular Cerebral/cirurgia , Animais , Citocinas/metabolismo , Humanos
18.
J Geriatr Psychiatry Neurol ; 32(6): 291-297, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31480980

RESUMO

This study was performed to compare the treatment status between older (≥65 years) and younger adults (18-64 years) with severe mental illness (SMI) and explore factors associated with treatment status in rural China. Persons with SMI were identified in one mental health survey in 2015 in 6 townships of Xinjin County, Chengdu, China. Logistic regressions were conducted to explore factors associated with treatment status. Older adults with SMI, especially major depressive disorder, reported significantly lower rates of treatment than younger group. Older age, longer duration of illness, and poor mental status were risk factors for never-treated status in these patients. Never-treated status (46.3%) and poor treatment status in these older patients are serious issues. Different treatment statuses in these patients had various influencing factors. It is crucial to develop culture-specific, community-based mental health services to improve early identification, diagnosis, treatment, and recovery of older adults with SMI in rural China.


Assuntos
Transtornos Mentais/terapia , Adolescente , Adulto , China , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Fatores de Risco , População Rural , Inquéritos e Questionários , Adulto Jovem
19.
Proc Natl Acad Sci U S A ; 113(45): 12850-12855, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27791169

RESUMO

Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most devastating insect pests of rice (Oryza sativa L.). Currently, 30 BPH-resistance genes have been genetically defined, most of which are clustered on specific chromosome regions. Here, we describe molecular cloning and characterization of a BPH-resistance gene, BPH9, mapped on the long arm of rice chromosome 12 (12L). BPH9 encodes a rare type of nucleotide-binding and leucine-rich repeat (NLR)-containing protein that localizes to the endomembrane system and causes a cell death phenotype. BPH9 activates salicylic acid- and jasmonic acid-signaling pathways in rice plants and confers both antixenosis and antibiosis to BPH. We further demonstrated that the eight BPH-resistance genes that are clustered on chromosome 12L, including the widely used BPH1, are allelic with each other. To honor the priority in the literature, we thus designated this locus as BPH1/9 These eight genes can be classified into four allelotypes, BPH1/9-1, -2, -7, and -9 These allelotypes confer varying levels of resistance to different biotypes of BPH. The coding region of BPH1/9 shows a high level of diversity in rice germplasm. Homologous fragments of the nucleotide-binding (NB) and leucine-rich repeat (LRR) domains exist, which might have served as a repository for generating allele diversity. Our findings reveal a rice plant strategy for modifying the genetic information to gain the upper hand in the struggle against insect herbivores. Further exploration of natural allelic variation and artificial shuffling within this gene may allow breeding to be tailored to control emerging biotypes of BPH.

20.
Hum Brain Mapp ; 39(3): 1438-1448, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29266498

RESUMO

Complex motor sequencing and sensory integration are two key items in scales assessing neurological soft signs. However, the underlying neural mechanism and heritability of these two functions is not known. Using a healthy twin design, we adopted two functional brain imaging tasks focusing on fist-edge-palm (FEP) complex motor sequence and audiovisual integration (AVI). Fifty-six monozygotic twins and 56 dizygotic twins were recruited in this study. The pre- and postcentral, temporal and parietal gyri, the supplementary motor area, and the cerebellum were activated during the FEP motor sequence, whereas the precentral, temporal, and fusiform gyri, the thalamus, and the caudate were activated during AVI. Activation in the supplementary motor area during FEP motor sequence and activation in the precentral gyrus and the thalamic nuclei during AVI exhibited significant heritability estimates, ranging from 0.5 to 0.62. These results suggest that activation in cortical motor areas, the thalamus and the cerebellum associated with complex motor sequencing and audiovisual integration function may be heritable.


Assuntos
Percepção Auditiva/fisiologia , Encéfalo/fisiologia , Destreza Motora/fisiologia , Percepção Visual/fisiologia , Adolescente , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Humanos , Padrões de Herança , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto Jovem
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