RESUMO
BACKGROUND: Scedosporium apiospermum (S. apiospermum) belongs to the asexual form of Pseudallescheria boydii and is widely distributed in various environments. S. apiospermum is the most common cause of pulmonary infection; however, invasive diseases are usually limited to patients with immunodeficiency. CASE PRESENTATION: A 54-year-old Chinese non-smoker female patient with normal lung structure and function was diagnosed with pulmonary S. apiospermum infection by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). The patient was admitted to the hospital after experiencing intermittent right chest pain for 8 months. Chest computed tomography revealed a thick-walled cavity in the upper lobe of the right lung with mild soft tissue enhancement. S. apiospermum was detected by the mNGS of BALF, and DNA sequencing reads were 426. Following treatment with voriconazole (300 mg q12h d1; 200 mg q12h d2-d20), there was no improvement in chest imaging, and a thoracoscopic right upper lobectomy was performed. Postoperative pathological results observed silver staining and PAS-positive oval spores in the alveolar septum, bronchiolar wall, and alveolar cavity, and fungal infection was considered. The patient's symptoms improved; the patient continued voriconazole for 2 months after surgery. No signs of radiological progression or recurrence were observed at the 10-month postoperative follow-up. CONCLUSION: This case report indicates that S. apiospermum infection can occur in immunocompetent individuals and that the mNGS of BALF can assist in its diagnosis and treatment. Additionally, the combined therapy of antifungal drugs and surgery exhibits a potent effect on the disease.
Assuntos
Pneumonia , Scedosporium , Humanos , Feminino , Pessoa de Meia-Idade , Scedosporium/genética , Voriconazol/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Antifúngicos/uso terapêutico , Pulmão/diagnóstico por imagem , Pneumonia/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
BACKGROUND: We previously treated small gastric submucosal tumors originating from the muscularis propria layer by precutting endoscopic band ligation but lacked precise pathological results. Then, precutting endoscopic band ligation was modified by additional snare resection after ligation to obtain tumor specimens, termed precutting endoscopic band ligation-assisted resection. AIMS: In this study, we aimed to explore the safety, feasibility, and efficacy of precutting endoscopic band ligation-assisted resection. METHODS: From 2021 to 2022, a total of 16 consecutive patients underwent precutting endoscopic band ligation-assisted resection to treat small gastric submucosal tumors originating from the muscularis propria. The clinical demography, perioperative data, and follow-up outcomes were retrospectively collected. RESULTS: With a mean operative time of 21.3 min, all lesions were successfully and completely resected, and no severe adverse events or local recurrences occurred postoperatively. More importantly, en bloc and R0 resection were achieved in all 16 patients. CONCLUSION: Precutting endoscopic band ligation-assisted resection is a safe, effective, and time-saving endoscopic technique for managing gastric small gastric submucosal tumors originating from the muscularis propria for both diagnosis and eradication.
Assuntos
Mucosa Gástrica , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Masculino , Feminino , Ligadura/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Mucosa Gástrica/cirurgia , Mucosa Gástrica/patologia , Idoso , Adulto , Resultado do Tratamento , Ressecção Endoscópica de Mucosa/métodos , Ressecção Endoscópica de Mucosa/efeitos adversos , Duração da Cirurgia , Gastroscopia/métodos , Estudos de ViabilidadeRESUMO
PURPOSE: To compare the difference in analgesic effect between femoral triangle block (FTB) and adductor canal block (ACB) during arthroscopic knee surgery. METHODS: Patients who underwent arthroscopic knee surgery were randomized preoperatively to FTB group or ACB group. For each group, 20 mL of 0.1% ropivacaine was injected. PRIMARY OUTCOMES: The numeric rating score (NRS) at 12 h after surgery at rest and during movement. SECONDARY OUTCOME: (1) The NRS at post anesthesia care unit (PACU) and 2, 24 h after surgery at rest and during movement; (2) The quadriceps muscle strength at PACU and 2, 12, 24 h after surgery; (3) Consumption of Rescue analgesia; (4) Incidence of adverse reactions. RESULTS: The NRS at 12 h after surgery at rest and during movement of ACB group were higher than FTB group. Among secondary outcomes, the NRS at PACU at rest and during movement, 2 h after surgery during movement of FTB group lower than ACB group; the quadriceps muscle strength at 2 h after surgery of FTB group stronger than ACB group. After multiple linear regression model analysis, the data showed additional statistically significant reduction NRS at 24 h after surgery at rest (0.757, p = 0.037) in FTB group. Other outcomes were similar between two groups. CONCLUSIONS: The FTB appears to provide superior pain control after knee arthroscopy than ACB, the FTB is superior to the ACB in quadriceps muscle strength at 2 h after surgery. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2300068765). Registration date: 28/02/2023.
Assuntos
Artroscopia , Nervo Femoral , Bloqueio Nervoso , Dor Pós-Operatória , Ultrassonografia de Intervenção , Humanos , Artroscopia/métodos , Masculino , Feminino , Método Duplo-Cego , Estudos Prospectivos , Ultrassonografia de Intervenção/métodos , Pessoa de Meia-Idade , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Adulto , Nervo Femoral/efeitos dos fármacos , Ropivacaina/administração & dosagem , Anestésicos Locais/administração & dosagem , Força Muscular/efeitos dos fármacos , Músculo Quadríceps , Articulação do Joelho/cirurgiaRESUMO
Dynamin 1 Like (DNM1L), a member of dynamin superfamily capable of mediating mitochondrial outer membrane division, plays a key role in the progression of different types of tumors. However, the prognostic value, clinical significance of DNM1L and its specific mechanism involved in tumorigenesis of hepatocellular carcinoma (HCC) have not been investigated clearly. In this study, we found that the expression of DNM1L were significantly higher in HCC tissues than adjacent/normal liver tissues based on multiple data sets obtained from TCGA, GEO and ONCOMINE database, also its protein expression form Drp1 is significantly higher in HCC tissues than adjacent tissues, and is related to the degree of differentiation. Kaplan-Meier curves suggested that high DNM1L expression prominently correlated with poorer overall survival, progression-free survival, relapse-free survival and disease-specific survival. Multivariate analysis showed that higher DNM1L expression was independent prognostic factors of shorter overall survival and disease-free survival. Kyoto Encyclopedia of Genes and Genomes and Gene set enrichment analysis analysis combined with validation experiments revealed the regulatory role of DNM1L on key molecules in the metabolism of xenobiotics by cytochrome p450 pathway, and DNM1L may also affects invasion and metastasis capability of HCC by mediating extracellular matrix -receptor interaction pathway. Moreover, analysis showed that higher DNM1L, CYP2C9, CYP3A4, CYP1A2 expression were associated with the resistance to sorafenib therapy. TIMER and CIBERSORT analysis indicated that the increase of DNM1L expression may affect the infiltration of immune cells in the tumor microenvironment. Taken together, the above results indicated that DNM1L could be able to serve as a promising independent predictor and therapeutic target for HCC patients.
Assuntos
Carcinoma Hepatocelular , Dinaminas , Neoplasias Hepáticas , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/genética , Prognóstico , Microambiente Tumoral , Dinaminas/genéticaRESUMO
OBJECTIVE: The stratification of microsatellite instability (MSI) status assists clinicians in making treatment decisions for colorectal cancer (CRC) patients. This study aimed to establish a CT-based radiomics signature to predict MSI status in patients with CRC. METHODS: A total of 837 CRC patients who underwent preoperative enhanced CT and had available MSI status data were recruited from two hospitals. Radiomics features were extracted from segmented tumours, and a series of data balancing and feature selection strategies were used to select MSI-related features. Finally, an MSI-related radiomics signature was constructed using a genetic algorithm-enhanced artificial neural network model. Combined and clinical models were constructed using multivariate logistic regression analyses by integrating the clinical factors with or without the signature. A Kaplan-Meier survival analysis was conducted to explore the prognostic information of the signature in patients with CRC. RESULTS: Ten features were selected to construct a signature which showed robust performance in both the internal and external validation cohorts, with areas under the curves (AUC) of 0.788 and 0.775, respectively. The performance of the signature was comparable to that of the combined model (AUCs of 0.777 and 0.767, respectively) and it outperformed the clinical model constituting age and tumour location (AUCs of 0.768 and 0.623, respectively). Survival analysis demonstrated that the signature could stratify patients with stage II CRC according to prognosis (HR: 0.402, p = 0.029). CONCLUSIONS: This study built a robust radiomics signature for identifying the MSI status of CRC patients, which may assist individualised treatment decisions. KEY POINTS: ⢠Our well-designed modelling strategies helped overcome the problem of data imbalance caused by the low incidence of MSI. ⢠Genetic algorithm-enhanced artificial neural network-based CT radiomics signature can effectively distinguish the MSI status of CRC patients. ⢠Kaplan-Meier survival analysis demonstrated that our signature could significantly stratify stage II CRC patients into high- and low-risk groups.
Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Humanos , Estudos Retrospectivos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/genética , Redes Neurais de Computação , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Pregnancy-related intracranial hemorrhage (ICH) is a rare but potentially life-threatening event with complex and varied cause, such as HELLP syndrome and hemophagocytic syndrome. CASE PRESENTATION: A 33-year-old patient underwent a cesarean section with a preliminary diagnosis of "severe preeclampsia and class3 HELLP syndrome ". The patient had poor response to language before surgery, and the catheter drainage fluid was hematuria. Later, the surgeon reported severe bleeding in the operation. Following thromboelastography (TEG) result and postoperative laboratory tests confirmed class1 HELLP syndrome and ICH occurred on the second day after the surgery, and hemophagocytic syndrome was diagnosed during subsequent treatments. CONCLUSION: For patients with HELLP syndrome, we should pay attention to their coagulation condition. The coagulation tests and platelet counts should be repeated if their clinical presentation changed. Those with neurological alarm signs should receive CT or MRI scan. If a pregnant woman had prolonged hemocytopenia and thrombocytopenia, not only the HELLP but also the hemophagocytic syndrome should be considered.
Assuntos
Síndrome HELLP , Linfo-Histiocitose Hemofagocítica , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Adulto , Síndrome HELLP/diagnóstico , Cesárea/efeitos adversos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Hemorragias IntracranianasRESUMO
BACKGROUND: Postoperative delirium (POD) is a common and severe complication in elderly hip-arthroplasty patients. AIM: This study aims to develop and validate a machine learning (ML) model that determines essential features related to POD and predicts POD for elderly hip-arthroplasty patients. METHODS: The electronic record data of elderly patients who received hip-arthroplasty surgery between January 2017 and April 2021 were enrolled as the dataset. The Confusion Assessment Method (CAM) was administered to the patients during their perioperative period. The feature section method was employed as a filter to determine leading features. The classical machine learning algorithms were trained in cross-validation processing, and the model with the best performance was built in predicting the POD. Metrics of the area under the curve (AUC), accuracy (ACC), sensitivity, specificity, and F1-score were calculated to evaluate the predictive performance. RESULTS: 476 Arthroplasty elderly patients with general anesthesia were included in this study, and the final model combined feature selection method mutual information (MI) and linear binary classifier using logistic regression (LR) achieved an encouraging performance (AUC = 0.94, ACC = 0.88, sensitivity = 0.85, specificity = 0.90, F1-score = 0.87) on a balanced test dataset. CONCLUSION: The model could predict POD with satisfying accuracy and reveal important features of suffering POD such as age, Cystatin C, GFR, CHE, CRP, LDH, monocyte count, history of mental illness or psychotropic drug use and intraoperative blood loss. Proper preoperative interventions for these factors could reduce the incidence of POD among elderly patients.
Assuntos
Artroplastia de Quadril , Delírio , Delírio do Despertar , Humanos , Idoso , Delírio do Despertar/etiologia , Delírio/diagnóstico , Delírio/etiologia , Artroplastia de Quadril/efeitos adversos , Fatores de Risco , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologiaRESUMO
PURPOSE: This current study aimed to explore whether gastrectomy history influenced surgical outcomes while undergoing laparoscopic cholecystectomy (LC). METHODS: The PubMed, Embase, and Cochrane Library databases were searched for eligible studies from inception to April 29, 2023. The Newcastle-Ottawa Scale (NOS) was adopted to assess the quality of included studies. The mean differences (MDs) and 95% confidence intervals (CIs) were calculated for continuous variables, and the odds ratios (ORs) and 95% CIs were calculated for dichotomous variables. RevMan 5.4 was used for data analysis. RESULTS: Seven studies enrolling 8193 patients were eligible for the final pooling up analysis (380 patients in the previous gastrectomy group and 7813 patients in the non-gastrectomy group). The patients in the gastrectomy group were older (MD = 11.11, 95%CI = 7.80-14.41, P < 0.01) and had a higher portion of males (OR = 3.74, 95%CI = 2.92-4.79, P < 0.01) than patients in the non-gastrectomy group patients. Moreover, the gastrectomy group had longer LC operation time (MD = 34.17, 95%CI = 25.20-43.14, P < 0.01), a higher conversion rate (OR = 6.74, 95%CI = 2.17-20.26, P = 0.01), more intraoperative blood loss (OR = 1.96, 95%CI = 0.59-3.32, P < 0.01) and longer postoperative hospital stays (MD = 1.07, 95%CI = 0.38-1.76, P < 0.01) than the non-gastrectomy group. CONCLUSION: Patients with a previous gastrectomy history had longer operation time, a higher conversion rate, more intraoperative blood loss, and longer postoperative hospital stays than patients without while undergoing LC. Surgeons should pay more attention to these patients and make prudent decisions to avoid worse surgical outcomes as much as possible.
Assuntos
Colecistectomia Laparoscópica , Laparoscopia , Neoplasias Gástricas , Humanos , Masculino , Perda Sanguínea Cirúrgica , Gastrectomia , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
Professional burnout refers to mental weariness caused by occupational stress. However, there is a lack of systematic studies on the prevalence of professional burnout among dentists. The purpose of this study was to investigate the prevalence of professional burnout among dentists. Databases including PubMed, PsycINFO, Embase, Cochrane, and Web of Science were systematically searched from inception to 28 October 2021. The random-effects model and forest plots were used to assess the pooled prevalence of professional burnout among dentists. A total of 15 studies with a total of 6038 study subjects were included in the meta-analysis, and the overall professional burnout among dentists was 13% (95%CI: 6-23). Subgroup analysis suggested a high prevalence of burnout in Europe, and the least in the Americas. The pooled burnout prevalence in cross-sectional surveys was significantly lower than that in longitudinal studies. In addition, the overall burnout prevalence in the last decade was significantly lower than that of a decade ago. This meta-analysis demonstrated that the prevalence of burnout was relatively low among dentists, and there was a downward trend. Therefore, it is important to continue to pay close attention to the mental health of dentists and effectively prevent and treat professional burnout to better maintain the provision of health care services.
The overall prevalence of professional burnout among dentists was 13%.Subgroup analysis revealed that the prevalence of burnout differed in geographical regions, with the highest in Europe, followed by Asia, and the lowest in America.The pooled burnout prevalence in cross-sectional surveys was significantly lower than that in longitudinal studies. In addition, the overall burnout prevalence in the last decade was significantly lower than that of a decade ago.More attention should be paid to professional burnout among dentists to improve the provision of health care services.
Assuntos
Esgotamento Profissional , Estresse Ocupacional , Humanos , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Prevalência , Estudos Transversais , Odontólogos/psicologiaRESUMO
Heat shock protein 70 (HSP70) can regulate astrocyte viability under hypoxic and ischemic conditions. However, the protective mechanism involved is not completely clear. This study aimed to investigate whether HSP70 protects U87 glioma cells against hypoxic damage via the extracellular signal-regulated kinases 1/2 (ERK1/2) and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathways. Lentivirus-mediated HSP70-siRNA was used for HSP70 silencing. U87 glioma cells with lentiviral infection were exposed to hypoxia for 4, 8, 12, and 24 h, respectively, followed by a 24-h reoxygenation treatment. A Cell-Counting Kit-8 was then used to evaluate the viability of the U87 glioma cells. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine the mRNA and protein levels, respectively. The expression of HSP70, p-ERK1/2, p-AKT, and U87 cell viability were increased after 8 h of hypoxia/24 h of reoxygenation (P < 0.01). However, HSP70 silencing significantly decreased the U87 cell viability after the hypoxia/reoxygenation treatment (P < 0.01). The protein expressions of p-ERK1/2 and p-AKT also decreased in HSP70-silenced U87 cells (P < 0.01). In conclusion, HSP70 inhibition suppressed the viability of U87 glioma cells during hypoxia/reoxygenation (at least partially) by inhibiting the ERK1/2 and PI3K/AKT signaling pathways. This study may help to understand the molecular mechanisms underlying the progression and development of cerebral hypoxia-ischemia.
Assuntos
Hipóxia Celular/genética , Glioma/genética , Proteínas de Choque Térmico HSP70/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Glioma/patologia , Humanos , Camundongos , Transdução de SinaisRESUMO
BACKGROUND: Proper differentiation of trophoblasts in the human placenta is essential for a successful pregnancy, whereas abnormal regulation of this process may lead to adverse pregnancy outcomes, especially preeclampsia (PE). However, the underlying mechanism of trophoblast differentiation remains unclear. Previous studies have reported the involvement of alpha-actinin-4 (ACTN4) in the actin cytoskeleton dynamics and motility. Hence, we hypothesized that ACTN4 may act as an important regulator in the normal proliferation and differentiation of trophoblasts during early pregnancy. METHOD: To test this hypothesis, we collected villous tissues from women undergoing a legal pregnancy termination during 6-10 weeks of gestation and explanted them for cell culture and siRNA transfection. We also obtained placental tissues from PE patients and healthy pregnant women and isolated the primary cytotrophoblast (CTB) cells. The expression of ACTN4 in the CTBs of placental villi and during the differentiation of CTBs into STBs was detected by immunofluorescence, immunohistochemistry (IHC), and EdU proliferation assays. Besides, villous explant, Matrigel invasion, transwell migration assay, and Wound-healing assay were performed to identify the possible role of ACTN4 in the outgrowth of explants and the invasion, migration, and proliferation of cell column trophoblasts (CCTs). Western blot analysis was carried out to compare the protein expression level of AKT, Snail activities, and epithelial-to-mesenchymal transition (EMT) in the villi or HTR8/SVneo cells with ACTN4 knockdown. RESULTS: ACTN4 was highly expressed in CTB cells and interstitial extravillous trophoblast (iEVT) cells but not found in the syncytiotrophoblast (STB) cells in the first trimester villi. Downregulation of ACTN4 led to reduced trophoblast proliferation and explant outgrowth ex vivo, as well as iEVT invasion and migration in vitro due to disrupt of actin filaments organization. Such ACTN4 inhibition also decreased AKT and Snail activities and further impeded the EMT process. In addition, ACTN4 expression was found to be downregulated in the iEVTs from preeclamptic placentas. CONCLUSIONS: Our findings suggest that ACTN4 may act as an important regulator of trophoblast proliferation and differentiation during early pregnancy, and dysregulation of this protein may contribute to preeclampsia pathogenesis.
Assuntos
Actinina/biossíntese , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Vilosidades Coriônicas/metabolismo , Trofoblastos/metabolismo , Actinina/antagonistas & inibidores , Actinina/genética , Adolescente , Adulto , Linhagem Celular Transformada , Células Cultivadas , Feminino , Técnicas de Silenciamento de Genes/métodos , Humanos , Gravidez , Adulto JovemRESUMO
BACKGROUND: Vitamin D deficiency is a global public health issue in women and children and is associated with adverse impacts on child growth, such as rickets. However, prior studies have mainly focused on measuring vitamin D levels in singleton pregnant women and their offspring, and very limited studies have revealed the prevalence of vitamin D deficiency in twin pregnant women and their offspring. The aim of this study was to investigate vitamin D levels in twin-pregnant women and their neonates. We also explored the correlation of maternal vitamin D levels with neonatal outcomes and infant growth. METHODS: A prospective subcohort investigation was carried out among 72 dichorionic, diamniotic twin-pregnant mothers and their twin offspring from the Longitudinal Twin Study. Peripheral blood was collected from the mothers in the third trimester, and cord blood was collected from neonates at birth to identify 25[OH]D levels. Data on the characteristics of the mothers and neonates were collected. Infant growth data and food sensitivities were also collected. RESULTS: The average maternal 25[OH]D level was 31.78 ng/mL, with 19.4% being deficient and 20.8% insufficient, while the average neonatal 25[OH]D level was 15.37 ng/mL, with 99.3% being deficiency or insufficient. A positive correlation was found between maternal and neonatal 25[OH]D levels (beta-value: 0.43, 95% CI: 0.37, 0.49). Interestingly, the higher the maternal 25[OH]D level was, the smaller the cotwin birthweight discordance (beta-value: -2.67, 95% CI: - 5.11, - 0.23). In addition, the infants of mothers with vitamin D deficiency were more likely to be allergic to foods at 6 months than those of mothers with vitamin D sufficiency. CONCLUSIONS: Twin neonates were at high risk of vitamin D deficiency, although their mothers' vitamin D deficiency partially improved. Higher maternal vitamin D levels were associated with smaller discordance of cotwin birthweight. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OOC-16008203 , 1st April 2016.
Assuntos
Sangue Fetal/química , Recém-Nascido/sangue , Gravidez de Gêmeos/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Adulto , China/epidemiologia , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Projetos Piloto , Gravidez , Estudos Prospectivos , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Adulto JovemRESUMO
OBJECTIVE: To further explore the role of BCL-2 associated anthanogen-1 (BAG-1) in neuronal apoptosis and whether the effect of BAG-1 depends on heat shock protein 70 (HSP70). METHODS: RNA interference (RNAi) technology was used to inhibit the expression of BAG-1 in SH-SY5Y cells. Hypoxia-reoxygenation injury model in the SH-SY5Y cells was established. Cell Counting Kit-8 (CCK-8) was performed for cell viability. Annexin V-APC/7-AAD double-staining followed by flow cytometry was used to measure cell apoptosis. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were used to detect the messenger RNA (mRNA) and protein expression of genes, respectively. RESULTS: BAG-1 gene silencing decreased SH-SY5Y cell viability and promoted SH-SY5Y cell apoptosis after hypoxia-reoxygenation. However, the down-regulation of BAG-1 had no effect on the mRNA and protein expression of HSP70. CONCLUSION: BAG-1 could protect SH-SY5Y cells from the hypoxia-reoxygenation injury without affecting HSP70 expression.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico HSP70/metabolismo , Neuroblastoma/patologia , RNA Interferente Pequeno/genética , Fatores de Transcrição/antagonistas & inibidores , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Choque Térmico HSP70/genética , Humanos , Neuroblastoma/genética , Neuroblastoma/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Células Tumorais CultivadasRESUMO
Preeclampsia (PE) is characterized by abnormal placentation in the early stages of pregnancy. Adequate migration and invasion of trophoblasts into the uterine wall and spiral arteries to form a functional maternal-fetal interface are pivotal for normal placentation, but the exact mechanism remains unclear. Growing evidence has revealed that special AT-rich sequence binding protein 1 (binds to nuclear matrix/scaffold-associating DNA) (SATB1) is a tumor promoter that participates in cancer cell migration and invasion. However, the expression and function of SATB1 in trophoblasts is unknown. Here, we characterize the stimulatory effect of SATB1 on the migration and invasion of trophoblasts and identify the regulatory events and downstream signaling components. Downregulated SATB1 was detected in PE placentae and villous explants cultured under hypoxia/reoxygenation (H/R) conditions. H/R-treated trophoblasts with lower SATB1 levels exhibited weaker invasive and growth capacities, whereas upregulation of the SATB1 level with recombinant SATB1 restored these impairments. This restoration was especially apparent with the sumoylation-deficient SATB1 variant, which contained a mutated site that blocked sumoylation. Moreover, the elevated concentration of SATB1 also increased the expression of ß-catenin, which is involved in human placental trophoblast invasion and differentiation is downregulated in PE. However, a specific activator, namely, lithium chloride (LiCl), increased ß-catenin expression but had no evident influence on SATB1 expression. Furthermore, upregulated SATB1 failed to restore trophoblast function when Wnt/ß-catenin was suppressed by dickkopf (Xenopus laevis) homolog 1, dickkopf 1 homolog (Xenopus laevis) (DKK1). Together, these data show that SATB1expression in the human placenta is affected by oxidative stress and might regulate the migration and invasion of trophoblasts via ß-catenin signaling.
Assuntos
Movimento Celular/fisiologia , Regulação para Baixo , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Estresse Oxidativo/fisiologia , Pré-Eclâmpsia/metabolismo , Trofoblastos/metabolismo , beta Catenina/metabolismo , Feminino , Humanos , Hipóxia/metabolismo , Cloreto de Lítio/farmacologia , Proteínas de Ligação à Região de Interação com a Matriz/genética , Placenta/efeitos dos fármacos , Placenta/metabolismo , Placentação/fisiologia , Pré-Eclâmpsia/genética , Gravidez , Transdução de Sinais/fisiologia , Trofoblastos/efeitos dos fármacos , beta Catenina/genéticaRESUMO
BCL-2-associated athanogene-1(BAG-1) is a multifunctional and anti-apoptotic protein that was first identified as a binding partner of BCL-2. But the effects and mechanisms for BAG-1 against hypoxic damage is unclear up to now. Whether BAG-1 could protect the human brain against hypoxic damage through up-regulating 70 kDa heat shock proteins (HSP70) and PI3K/AKT pathway activation? In present study, we examined the changes of HSP70 and AKT and p-AKT protein level in SH-SY5Y cells with BAG-1L gene over-expression subjected to hypoxia/re-oxygenation injury. BAG-1L over-expression increased neuronal viability, and it reduced apoptosis of neurons after hypoxia/re-oxygenation for 8 h. BAG-1L over-expression enhanced the HSP70 protein levels and increased p-AKT/total AKT ratio after hypoxia/re-oxygenation for 8 h. These results suggest that BAG-1L over-expression protects against hypoxia/re-oxygenation injury, at least in part, by interacting with HSP70, and by accelerating the activation of PI3K/AKT pathways.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição/metabolismo , Apoptose/efeitos dos fármacos , Hipóxia Celular , Linhagem Celular Tumoral , Humanos , Neuroblastoma/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacosRESUMO
OBJECTIVE: To explore the role of specific AT rich sequence binding protein 1(SATB1) and wnt/ß-catenin signaling pathways in the regulation of trophoblast invasion and its effect in the pathogenesis of preeclampsia. METHODS: From March 2013 to March 2014, 20 cases of human villous tissues (early pregnancy group) from women of 8-10 gestational weeks who received artificial abortion at the First Affiliated Hospital of Chongqing Medical University, 18 cases of placental tissues (mid-pregnancy group) from women of 18-20 gestational weeks who had labor induction by water bag, 20 cases of placental tissues (normal full-term group) from healthy full-term pregnancy women and 20 cases of placental tissues (preeclamptic group) from women with preeclampsia who received elective c-section in were collected. Immunohistochemical SP method was utilized to determine the position of SATB1 and beta-catenin in villous tissues or placental tissues. Western blot was performed to analyze the expression level of SATB1 and beta-catenin in villous tissues or placental tissues. Immunofluorescence assay was used to determine the location of SATB1 and ß-catenin in HTR8/SVneo cells. Western blot was performed to detect the expression level of SATB1 and beta-catenin in HTR8/SVneo cells cultured in normoxia and hypoxia reoxygenation (H/R) condition. Co-Immunoprecipitation detection was used to evaluate the interaction between SATB1 and ß-catenin in placental tissues in preeclamptic group and HTR8/SVneo cells in H/R group. Gelatin zymography analysis was used to measure the activity of matrix metalloproteinases (MMP)-2 and 9 in placental tissues from preeclamptic group and HTR8/SVneo cells in H/R group. RESULTS: (1) In the normal full-term group, rare syncytiotrophoblastic nodule, less fibrinoid necrosis and abundant numbers of capillary could be observed in placental tissues. In comparison, there were obvious vacuolation in the cytoblast of syncytiotrophoblast, rich fibrinoid necrosis and poor numbers of villous capillary in placental tissues from preeclamptic group. (2) SATB1 could be found by immunochemical staining in placenta or villous tissues from all the groups. The staining intensity of SATB1 were more weakening in preeclamptic group than in the normal full-term group. (3) ß-catenin could be found by immunochemical staining in placenta or villous tissues from all the groups. The staining intensity of ß-catenin were more weakening in preeclamptic group than in the normal full-term group. (4) The protein expression levels of SATB1 in early pregnancy group, mid-pregnancy group, normal full-term group and preeclamptic group were 0.300 ± 0.009, 0.271±0.015, 0.238±0.018 and 0.153±0.007, respectively. The protein levels of ß-catenin among the above groups were 0.743±0.041, 0.648±0.021, 0.549±0.069 and 0.269±0.047, respectively. Both the expression of SATB1 and ß-catenin protein were significant decreased in placental tissues from preeclamptic group compared with the other three groups. (5) The SATB1 and ß-catenin protein was located in nucleus of trophoblast and a small amount was in the cytoplasm. The fluorescence intensity of both SATB1 and ß-catenin in the H/R group were significantly decreasing when compared to the normoxia group. (6) HTR8/SVneo cells in H/R group showed a significant decrease in both SATB1 and ß-catenin protein levels when compared to the normoxia group. The protein level of SATB1 in the normoxia group was 0.213±0.005, while was 0.083±0.021 in the H/R group. The protein level of ß-catenin in the normoxia group was 0.797±0.081, and was 0.543±0.131 in the H/R group. (7) There was an interaction between SATB1 and ß-catenin in placental tissues from the preeclamptic group and HTR8/SVneo cells exposed by H/R. (8) The enzymatic activity of MMP-2 and MMP-9 protein were decreased significantly in placental tissues from the preeclamptic group (2.251±0.310, 1.447±0.102, respectively) when compared to the normal full-term group (7.098±0.451, 5.502±0.197, respectively). MMP-2 and MMP-9 were significantly decreased in the H/R group (0.471±0.104, 0.297±0.103, respectively) when compared to the normoxia group (0.842±0.209, 0.595±0.100, respectively). CONCLUSION: The expression of SATB1 decreased in the placenta of preeclampsia. This may influence the activity of MMP-2 and 9 by regulating Wnt/ß-catenin signaling pathways, affect trophoblast invasion and eventually result in preeclampsia.
Assuntos
Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/metabolismo , Western Blotting , Estudos de Casos e Controles , Núcleo Celular , Citoplasma , Feminino , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pré-Eclâmpsia/genética , Gravidez , Terceiro Trimestre da Gravidez , Trofoblastos/metabolismoRESUMO
The orientation and shape of ceramics grains was always neglected, resulting in a lot of information during sintering has not been excavated. In this study, a modified phase-field model in order to express the anisotropy of grain boundary energy is developed. The effects of the anisotropy of grain boundary energy on the grain orientation and shape evolution are investigated in detail. The ferroelectric ceramic thick films are prepared by tape casting. The comparison of experiment and simulation results shows that the anisotropy of grain boundary energy results in uneven grain orientation and bimodal grain size distribution. The quantitative analysis of grain microstructures helps to establish a relationship with the degree of anisotropy of grain boundary energy. Our findings provide a new way to judge the degree of anisotropy by calculating the relevant parameters in the SEM images of ceramics materials.
RESUMO
PURPOSE: To explore the capability of preoperative CT imaging features, in combination with clinical indicators, for predicting vessels that encapsulate tumor clusters (VETC) pattern and prognosis in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From January 2015 to May 2022, patients with HCC who underwent curative resection and preoperative enhanced CT were retrospectively included. Clinical indicators and imaging featuresassociated with the VETC pattern were determined by logistic regression analyses. The early recurrence (ER) rate was determined using the Kaplan-Meier survival curve. Factors associated with ER after surgical resection were identified by Cox regression analyses. RESULT: A total of 243 patients with HCCwere evaluated. The total bilirubin > 17.1 µmol/L (odds ratio [OR] 3.43, 95 % Confidence Interval [CI] 1.70, 6.91, p = 0.001), serum α-fetoprotein > 100 ng/mL (OR 2.41, 95 % CI 1.25, 4.67, p = 0.009), intratumor artery (IA) (OR 2.00, 95 % CI 1.04, 3.86,p = 0.039) and arterial peritumoral enhancement (OR 2.60, 95 % CI 1.13, 5.96, p = 0.025) were independent risk factors for VETC+-HCC. The VETC+status andCT feature ofIA were associated with an increased risk of recurrence, with a shorter median RFS, compared to those without these factors (p < 0.001 and p = 0.019, respectively). In multivariable Cox regression analysis, the VETC+(hazard ratio [HR] 2.60, 95 % CI 1.66, 4.09, p < 0.001), morphological patterns of confluent multinodular growth (HR 1.79, 95 % CI 1.10, 2.91,p = 0.019), the number of the tumors (≥2) (HR 2.69, 95 % CI 1.56, 4.65, p < 0.001), and the IA (HR 1.73, 95 % CI 1.12, 2.66, p = 0.013) were independent predictors of ER in patients with HCC after surgical resection. CONCLUSION: Preoperative CT features combined with clinical indicators could predict VETC pattern, and the CT features, along with VETC status, were of prognostic significance for early postoperative recurrence in patients with HCC. CLINICAL RELEVANCE STATEMENT: Preoperative CT features combined with clinical indicators could predict VETC pattern, and the CT features, along with VETC status, were of prognostic significance for early recurrence in patients with HCC after surgical resection.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Cuidados Pré-Operatórios/métodos , Idoso , Prognóstico , AdultoRESUMO
OBJECTIVES: This study aimed to compare the analgesic effects of continuous femoral nerve block (FNB), femoral triangle block (FTB), and adductor canal block (ACB) following total knee arthroplasty (TKA). The goal was to identify the most effective nerve block technique among these. METHODS: Patients undergoing TKA were randomly assigned to 1 of 3 groups: FNB, FTB, or ACB. Nerve blocks were administered preoperatively, with catheters placed for patient-controlled nerve analgesia (PCNA). The primary end point was the Numeric Rating Scale (NRS) score at movement at 24 hours postsurgery. Secondary end points included NRS scores at rest and movement, quadriceps strength, Timed Up and Go (TUG) test performance, range of motion, effective PCNA utilization, and opioid consumption at various postsurgery time points. RESULTS: Of the 94 valid data sets analyzed (FNB: 31, FTB: 31, ACB: 32), significant differences were observed in the primary end point (H=7.003, P =0.03). Post hoc analysis with Bonferroni correction showed that the FNB group had a significantly lower median pain score (3 [2 to 4]) compared with the ACB group (4 [3 to 5], Bonferroni-adjusted P =0.03). Regarding secondary end points, both the FNB and FTB groups had significantly lower NRS scores than the ACB group at various time points after surgery. Quadriceps strength and TUG completion were better in the FTB and ACB groups. There were no statistically significant differences among the groups for the other end points. DISCUSSION: Continuous FTB provides postoperative analgesia comparable to FNB but with the advantage of significantly less impact on quadriceps muscle strength, a benefit not seen with FNB. Both FTB and ACB are effective in preserving quadriceps strength postoperatively.
Assuntos
Artroplastia do Joelho , Nervo Femoral , Bloqueio Nervoso , Dor Pós-Operatória , Humanos , Bloqueio Nervoso/métodos , Feminino , Masculino , Dor Pós-Operatória/tratamento farmacológico , Nervo Femoral/efeitos dos fármacos , Idoso , Pessoa de Meia-Idade , Medição da Dor , Resultado do Tratamento , Analgesia Controlada pelo Paciente , Força Muscular/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the effect of prone position on the prognosis of patients with severe pneumonia in intensive care unit (ICU). METHODS: A retrospective cohort study was conducted. The patients with severe pneumonia admitted to the ICU of Qingdao Municipal Hospital from May 2022 to August 2023 were enrolled. The general information, etiology, underlying diseases, vital signs and laboratory indicators at ICU admission, clinical treatment and prognosis during ICU hospitalization were collected. The above clinical data of patients with different prognosis were compared. Multifactorial Logistic regression analysis was used to screen the related factors affecting survival during ICU in patients with severe pneumonia. The change in oxygenation index (PaO2/FiO2) of patients with severe pneumonia were observed at 1 hour before the first prone position, 1 hour after the first prone position, and 1 hour after the end of the first prone position. The effect of prone position on oxygenation in patients with severe pneumonia was analyzed. Spearman correlation analysis was used to investigate the correlation between the duration to first prone position and the change in the PaO2/FiO2 before and after prone position in patients with severe pneumonia. RESULTS: Finally, a total of 144 patients with severe pneumonia were enrolled, 45 survived and 99 died during ICU hospitalization, with a mortality of 68.8%. Compared with the survival group, the patients in the death group were older [years old: 81.00 (70.75, 86.00) vs. 71.00 (60.50, 81.50), P < 0.01], the proportion of pre-existing lung disease, heart rate (HR), respiratory rate (RR), blood lactic acid (Lac) and the ratio of continuous renal replacement therapy (CRRT) were higher [ratio of pre-existing lung disease: 23.2% (23/99) vs. 8.9% (4/45), HR (bpm): 99.61±22.47 vs. 91.49±18.76, RR (times/min): 22.50 (19.75, 29.25) vs. 20.00 (17.50, 24.50), Lac (mmol/L): 2.00 (1.55 , 3.25) vs. 1.60 (1.20, 1.95), CRRT ratio: 25.3% (25/99) vs. 6.7% (3/45), all P < 0.05], and the proportion of prone position was lower [41.4% (41/99) vs. 68.9% (31/45), P < 0.01]. Multifactorial Logistic regression analysis showed that age [odds ratio (OR) = 0.946, 95% confidence interval (95%CI) was 0.912-0.980, P = 0.002] and Lac (OR = 0.563, 95%CI was 0.340-0.930, P = 0.025) were negatively correlated with survival during ICU hospitalization in severe pneumonia patients, while prone position was positively correlated with survival (OR = 2.551, 95%CI was 1.067-6.095, P = 0.035), indicating that prone position was beneficial for improving ICU prognosis in severe pneumonia patients. The results of PaO2/FiO2 at different time points in prone position showed that PaO2/FiO2 at 1 hour of the first prone position in the patients with severe pneumonia was significantly higher than that at 1 hour before the first prone position [mmHg (1 mmHg ≈ 0.133 kPa): 146.69 (113.92, 257.25) vs. 111.75 (70.15, 212.20), P < 0.01], indicating that the prone position had a relevant effect on the improvement of oxygenation in patients. Spearman correlation analysis showed that the duration of the first prone position in patients with severe pneumonia was significantly and positively correlated with the improvement of oxygenation at 1 hour of the first prone position (r = 0.565, P < 0.001). CONCLUSIONS: The prone position is a therapeutic measure that can independently influence the prognosis of patients with severe pneumonia during ICU hospitalization. The prone position effectively improves oxygenation in patients with severe pneumonia and the first change in oxygenation in patients is related to the duration of the prone position.