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ObjectiveTo investigate the effect of kinesin family member 15 (KIF15) on the proliferation of hepatocellular carcinoma (HCC) cells and its mechanism of action. MethodsTCGA and GEPIA datasets were analyzed to determine the expression of KIF15 in HCC and its effect on tumor stage and survival. Quantitative real-time PCR and Western blot were used to measure the expression level of KIF15 in human-derived HCC cell lines (HepG2, Hep3B, MHCC-97H, and LM3) and human normal liver cell line L02 cultured in vitro, and Hep3B and HepG2 were selected for subsequent studies. CCK-8 assay, plate colony formation assay, and EdU staining were performed for Hep3B cells transfected with shRNA-NC or shRNA-KIF15 and HepG2 cells transfected with LV-vector or LV-KIF15 to evaluate the viability and proliferative capacity of these cells. GSEA was used to analyze the potential signaling pathways associated with KIF15 in HCC, and Western blot was used for detection. The independent-samples t test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsThe analysis of TCGA and GEPIA datasets showed that in HCC patients, the expression of KIF15 in HCC tissue was significantly higher than that in normal tissue, and the HCC patients with high KIF15 expression tended to have a poorer prognosis. Compared with sh-NC-Hep3B, sh3-Hep3B showed significant reductions in the mRNA and protein levels of KIF15 (P<0.05), cell viability, clone formation number, and EdU positive rate (all P<0.05). Compared with vector-HepG2, LV-KIF15-HepG2 showed significant increases in the mRNA and protein levels of KIF15 (P<0.05), cell viability, clone formation number, and EdU positive rate (all P<0.05). Subcutaneous tumor assay showed that compared with sh-NC-Hep3B, sh3-Hep3B showed reductions in tumor volume and tumor weight, as well as a significant reduction in the immunohistochemical score of Ki67 and a significant increase in the immunohistochemical score of TUNEL (P<0.05). GSEA analysis showed that the PI3K/AKT/mTOR pathway was positively correlated with KIF15 in HCC (NES=1.59, P<0.001). Western blot showed that LY294002 could inhibit the PI3K/AKT/mTOR pathway upregulated in LV-KIF15-HepG2, and compared with LV-KIF15-HepG2, LY294002+LV-KIF15-HepG2 showed significant reductions in cell viability, clone formation number, and EdU positive rate (all P<0.05). ConclusionKIF15 enhances the viability and proliferative capacity of HCC cells by upregulating the PI3K/AKT/mTOR signaling pathway.
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OBJECTIVE: To explore the effects of comprehensive nursing intervention on in vitro fertilization (IVF) and pregnancy outcomes in patients with polycystic ovary syndrome (PCOS). METHOD: A total of 130 patients with PCOS admitted to our hospital from April 2021 to March 2023 were selected as the research subjects. They were evenly divided according to a random number table method. The control group received routine care for the patients, while the study group received comprehensive care for the patients. The IVF, pregnancy outcomes, negative emotional changes, serum and follicular fluid (FF) amyloid-related protein and C-reactive protein (CRP) levels of the 2 groups of patients were compared. RESULT: The data on IVF rate and pregnancy rate in the study group were significantly better than those in the control group (P < .05). The SAS and SDS scores of the study group patients after intervention were significantly lower than those of the control group (P < .05). After intervention, the levels of serum and FF amyloid associated protein and CRP in the study group were significantly lower than those in the control group (P < .05). CONCLUSION: Patients with PCOS who receive comprehensive care can increase their probability of IVF, improve their pregnancy outcomes, and have a positive significance in reducing negative emotions.
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Síndrome del Ovario Poliquístico , Embarazo , Femenino , Humanos , Fertilización In Vitro/métodos , Resultado del Embarazo , Índice de Embarazo , Líquido Folicular/metabolismoRESUMEN
This study aims to explore the effect of "Trichosanthis Fructus-Allii Macrostemonis" combination(GX) on the activation of NOD-, LRR-, and pyrin domain-containing protein 3(NLRP3) inflammasome, the release of inflammatory cytokines, and the level of autophagy in RAW264.7 macrophage damaged by lipopolysaccharide(LPS), and the mechanism of GX against inflammatory response in macrophages. To be specific, LPS was used to induce the injury of RAW264.7 cells. Cell Counting Kit-8(CCK-8) assay was employed to measure the survival rate of cells, and Western blot to detect the protein expression of NLRP3, apoptosis-associated speck-like protein(ASC), cysteine-aspartic acid protease(caspase)-1, interleukin(IL)-18, IL-1β, microtubule-associated protein light chain 3(LC3)-Ⅱ, and selective autophagy junction protein p62/sequestosome 1 in RAW264.7 macrophages. ELISA was used to measure the levels of IL-18 and IL-1β in RAW264.7 cells. Transmission electron microscopy was applied to observe the number of autophagosomes in RAW264.7 cells. Immunofulourescence staining was used to detect the expression of LC3-Ⅱ and p62 in RAW264.7 cells. The result showed that GX significantly reduced the protein expression of NLRP3, ASC, and caspase-1 in RAW264.7 cells, significantly increased the protein expression of LC3Ⅱ, decreased the expression of p62, significantly inhibited the secretion of IL-18 and IL-1β, significantly increased the number of autophagosomes, significantly enhanced the immunofluorescence of LC3Ⅱ, and reduced the immunofluorescence of p62. Furthermore, 3-methyladenine(3-MA) could reverse the inhibitory effect of GX on NLRP3, ASC, and caspase-1 and reduce the release of IL-18 and IL-1β. In summary, GX can increase of the autophagy activity of RAW264.7 and inhibit the activation of NLRP3 inflammasome, thereby reducing the release of inflammatory cytokines and suppressing inflammatory response in macrophages.
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Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-18/metabolismo , Lipopolisacáridos/farmacología , Macrófagos , Citocinas/metabolismo , Caspasa 1/metabolismo , Autofagia , Interleucina-1beta/metabolismoRESUMEN
Objective:To analyze the expression and relationship of miR-379 and human kinesin family member 4A (KIF4A) in triple-negative breast cancer (TNBC).Methods:A total of 52 patients diagnosed with TNBC in breast department at Puji Branch of Dongguan People′s Hospital between January 2016 and November 2019 were retrospectively selected as the study group. Meanwhile, 70 patients with non-triple-negative breast cancer (NTNBC) diagnosed in the same period were selected as the control group. The expression levels of miR-379 and KIF4A in both groups were detected. The receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) of miR-379 and KIF4A predicting TNBC was calculated; The relationship between the expression levels of miR-379 and KIF4A and clinicopathological parameters, and the correlation between the expression level of miR-379 and KIF4A were analyzed.Results:The expression level of KIF4A in study group was higher than that in control group [(6.93±0.43) vs (3.75±0.25), P<0.05], and the expression level of miR-379 in study group was lower than that in control group [(0.54±0.17) vs (0.87±0.32), P<0.05]. MiR-379 combined with KIF4A expression had the greatest diagnostic value for TNBC: AUC 0.823 (95% CI: 0.730- 0.917), specificity 0.785, sensitivity 0.950; Univariate analysis showed that there were significant difference in the expression of miR-379 in TNBC patients with different clinical stages, tumor diameter, and lymph node metastasis (all P<0.05); There were significant difference in the expression of KIF4A in TNBC patients with different clinical stages and tumor diameter (all P<0.05). Pearson correlation analysis showed that miR-379 expression was negatively correlated with KIF4A expression in TNBC ( r=-0.349, P<0.05). Conclusions:The expression of miR-379 is down-regulated, while the expression of KIF4A is up-regulated in patients with TNBC. The two are related to poor clinicopathological characteristics, which indicates that they can be used for condition evaluation of the patients.
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Intracranial arterial dolichoectasia (IADE), also known as dilated cerebral artery disease, is manifested as an increase in the length and diameter of one or more intracranial arteries, the affected arteries being enlarged and dilated significantly, or even with winding and tortuosity. The diagnosis and prognostic evaluation of IADE are mainly based on the diameter and curvature of the intracranial artery. IADE can be manifested as ischemic stroke, transient ischemic attack, hydrocephalus, and hemorrhagic stroke. The review focuses on IADE, including the concept, diagnostic criteria, etiology, pathogenesis, pathology, clinical manifestations, treatment, and prognosis.
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Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.
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Niño , Femenino , Humanos , Lactante , Masculino , Aneurisma Coronario/etiología , Inmunoglobulinas Intravenosas/uso terapéutico , Infliximab/efectos adversos , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
Objective: To explore the effects and potential mechanism of Foshou Powder on Parkinson’s disease. Methods: Reserpine was injected in KM mice to establish Parkinson’s disease model, and hypothermia and akinesia were measured to evaluate the effects of volatile oil of Angelica sinensis, Ligusticum chuanxiong and combination. The human monoamine oxidase (hMAO) activity and inhibition mode were measured by fluorescence spectrophotometry in vitro with kynuramine as the common substrate of human monoamine oxidase A (hMAO-A) and human monoamine oxidase B (hMAO-B). On this basis, the 2 × 4 factorial design was applied to research the interaction between Angelica sinensis volatile oil and Ligusticum chuanxiong volatile oil. Results: The antagonistic experiments of reserpine showed that the application of Angelica sinensis volatile oil and Ligusticum chuanxiong volatile oil significantly improved hypothermia and akinesia. Enzyme activity test revealed that volatile oil of Angelica sinensis and Ligusticum chuanxiong had competitive inhibitory effects on hMAO-A and hMAO-B, and the combination of the two substances had significant synergistic effect on the activity of both hMAO. Conclusion: Angelica sinensis and Ligusticum chuanxiong in Foshou Powder have significant synergistic effects in the prevention and treatment of Parkinson’s disease, which may be related to the inhibition of MAO activity.
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To enhance the accuracy of computer-aided diagnosis of adolescent depression based on electroencephalogram signals, this study collected signals of 32 female adolescents (16 depressed and 16 healthy, age: 16.3 ± 1.3) with eyes colsed for 4 min in a resting state. First, based on the phase synchronization between the signals, the phase-locked value (PLV) method was used to calculate brain functional connectivity in the θ and α frequency bands, respectively. Then based on the graph theory method, the network parameters, such as strength of the weighted network, average characteristic path length, and average clustering coefficient, were calculated separately (
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Adolescente , Femenino , Humanos , Encéfalo/diagnóstico por imagen , Diagnóstico por Computador , Electroencefalografía , Máquina de Vectores de SoporteRESUMEN
BACKGROUND: Both stroke and depression are multi-factorial diseases, with both genetic and environmental factors likely to participate in their pathogenesis. Post stroke depression (PSD) is a common complication after stroke leading to poor functional outcome, increased physical disability and mortality. Although several genes have been associated with PSD, the genetic basis of PSD remains poorly understood. METHOD: A 2-stage candidate gene study by targeted sequencing was conducted involving stroke patients with or without depression and health controls. In the discovery stage (121 PSD, 131 non-PSD and 639 HC), logistic regression was used to test associations respectively in PSD and non-PSD groups. In the replication stage (200 PSD, 218 non-PSD and 983 HC), 54 selected SNPs were again genotyped in an independent cohort. Fixed-effects inverse variance-weighted meta-analysis was used in the combined samples. RESULTS: The study identified 2 novel genes associated with PSD [HTR3D (rs55674402, pâ¯=â¯0.002512, odds ratio (OR)â¯=â¯0.7431); NEUROG3 (rs144643855, pâ¯=â¯0.00325, ORâ¯=â¯0.6523)] and 3 risk SNPs in one risk gene associated with non-PSD [PIK3C2B (rs17406271, pâ¯=â¯0.0006801, ORâ¯=â¯1.446; rs2271419, pâ¯=â¯0.0005836, ORâ¯=â¯1.497; rs2271420, pâ¯=â¯0.001031, ORâ¯=â¯1.431)] in the Chinese sample. NEUROG3 shows highest expression level in hippocampus. Functional enrichment analysis shows that susceptibility genes for PSD are mostly enriched in chemical synaptic transmission and regulation of lipid synthetic process. LIMITATIONS: The sample size was not sufficient to reach a genome-wide p value level. To overcome this shortage, some unique strategies were applied during the selection of SNPs for replication. Secondly, the age, gender composition and depressive severity between two stages were not well-matched. Different sample sources should be blamed, and to minimizing the influence, gender was corrected as co-variant in logistic regression. CONCLUSION: This study identified that HTR3D and NEUROG3 were linked with the susceptibility of PSD and PIK3C2B with stroke in the Chinese Han population. Further replication of these findings in a larger and better matched sample is warranted. Functional analysis suggests that the pathogenesis of PSD may be implicated in 5-HT synaptic transmission, neural plasticity and lipid metabolism, and therapeutic interventions targeting these pathways may be effective approaches for PSD treatment.
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Trastorno Depresivo/genética , Accidente Cerebrovascular/genética , Anciano , Pueblo Asiatico/genética , Estudios de Casos y Controles , Fosfatidilinositol 3-Quinasas Clase II/genética , Estudios de Cohortes , Trastorno Depresivo/epidemiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUNDS: To investigate alterations in histone modification and histone deacetylases (HDACs) in patients with oral lichen planus (OLP), and to evaluate correlations with inflammatory cytokine production. METHODS: Global histone H3/H4 acetylation and HDAC activity in CD4+ T cells from 23 patients with OLP and 10 healthy control subjects were examined using spectrophotometry. The mRNA levels of eight members of four classes of HDAC genes were measured by real-time quantitative polymerase chain reaction. Forty cytokines involved in inflammation were examined with a cytokine array. The correlation between histone modification and cytokine production was analyzed. RESULTS: Global histone H3 hypo-acetylation was observed in OLP patients. Patients with OLP had significantly higher HDACs activity,and higher HDAC6 and HDAC7 mRNA level compared with the controls. Of the 40 cytokines in the cytokine array, eight were significantly increased in OLP patients: interleukin (IL)-4, IL-8, IL-1ra, tumor necrosis factor receptor II (TNFR II), macrophage inflammatory protein 1b (MIP-1b), fibrosis-associated tissue inhibitors of metalloproteinase 1 (TIMP)-1, monocyte chemotactic protein 1 (MCP-1), and eotaxin-2. In the OLP group, the acetylation level of histone H3 was negatively correlated with IL-4 and MCP-1 production, and the expression of HDAC6 mRNA was positively correlated with MCP-1 production. In the non-erosive subgroup, acetylation of histone H3 was negatively correlated with IL-4, IL-16, and TIMP-2 production. In the erosive OLP subgroup, the expression of HDAC7 mRNA was positively correlated with MIP-1a production. CONCLUSION: Aberrant histone modification of CD4+ T cells in peripheral blood could occur in OLP patients, and possibly affects inflammatory cytokine production.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Citocinas/metabolismo , Código de Histonas , Mediadores de Inflamación/metabolismo , Liquen Plano Oral/genética , Liquen Plano Oral/inmunología , Acetilación , Adulto , Linfocitos T CD4-Positivos/enzimología , Femenino , Histona Desacetilasas/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Objective To evaluate the effect of transversus abdominis plane (TAP) block on postoperative cognitive function in elderly patients undergoing laparoscopic surgery under general anesthesia.Methods Forty-eight male patients undergoing laparoscopic tension-free repair of inguinal hernia under general anesthesia,aged 65-75 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,with body mass index of 20-28 kg/m2,were divided into 2 groups (n =24 each) using a random number table method:TAP block combined with general anesthesia group (group TG) and general anesthesia group (group G).Anesthesia was induced with midazolam,cisatracurium besylate,sufentanil and etomidate,and the patients were mechanically ventilated after laryngeal mask airway insertion.TAP block was performed through the anterior superior iliac spine approach,and 0.25% ropivacaine 30 ml was injected in group TG.Anesthesia was maintained by target-controlled infusion of propofol and remifentanil and muscle relaxation by intravenously injecting cisatracurium.The occurrence of cerebral regional oxygen saturation (rSO2) and low rSO2 events (rSO2 <60%) was recorded at 1 min before anesthesia induction (T0),5 min after inserting the laryngeal mask airway (T1),at skin incision (T2),30 min after skin incision (T3),and at the end of surgery (T4).The consumption of propofol and remifentanil was recorded during surgery.Montreal Cognitive Assessment (MoCA) was used to evaluate the cognitive function of patients at 1 day before surgery and 7 days after surgery,and the development of postoperative cognitive dysfunction (POCD,MoCA scores< 26) was recorded.Results Compared with group G,the intraoperative consumption of propofol and remifentanil was significantly reduced,rSO2 was increased at T2~,and the incidence of low rSO2 events was decreased,MoCA scores were increased at 7 days after surgery,and the incidence of POCD was decreased in group TG (P<0.05).Conclusion TAP block can reduce the incidence of POCD in elderly patients undergoing laparoscopic surgery under general anesthesia.
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Objective To investigate the effect of repeated application of low-frequency transcranial magne-tic stimulation ( rTMS) when combined with hyperbaric oxygen ( HBO) in the treatment non-fluent aphasia after a stroke. Methods Forty-eight stroke survivors with non-fluent aphasia were randomly assigned to a control group, an HBO group or an observation group, each of 16. All received conventional rehabilitation therapy consisting of drug therapy, speech training and conventional physical exercises, while the HBO and observation groups were additionally given HBO and rTMS combined with HBO respectively. The 1 Hz rTMS was applied over the Broca's homologues of the unaffected hemisphere. Before and after 4 weeks of treatment, the Western Aphasia Battery ( WAB) was used to evaluate the subjects' language function and the Modified Barthel Index ( MBI) was used to assess their ability in the activities of daily living. Results There was no significant difference in the average WAB scores among the three groups before the treatment. After 4 weeks of treatment the average WAB and MBI scores of the HBO group and the observation group had improved significantly, and there was then a significant difference among the three groups. The observation group was performing significantly better than the HBO group and the control group in spontaneous speech, auditory comprehension, repetition, naming, AQ score and MBI score. Pairwise comparisons showed that the observation group's average WAB score, spontaneous speech, auditory comprehension, repetition, naming, AQ score and MBI score were the best, followed by those of the HBO group and then those of the control group. All of the differences were statistically significant. Conclusions Low-frequency rTMS combined with HBO can significantly improve the language function and the quality of life of patients with non-fluent aphasia. Such combined therapy is worthy of clinical promotion and application.
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Objective To investigate the influence of estimated glomerular filtration rate (eGFR) in rehabilitation of motor function and short-term prognoses in patients with acute middle cerebral artery (MCA) infarction. MethodsSeventy-four patients with acute MCA infarction, admitted to Department of Neurology from March 2016 to September 2018, and then, accepted rehabilitation training for 4 weeks in Department of Rehabilitation medicine, were recruited. Modification of Diet in Renal Disease was used to evaluate the eGFR instead of renal function; according to the results, these patients were divided into normal renal function group and mild-moderate renal dysfunction group. National Institute of Health Stroke Scale (NIHSS) was used to assess the neurologic function. Fazekas scale was used to assess degrees of leukoaraiosis. Fugl-Meyer Motor Function Assessment (FMA) was used to assess motor functions before rehabilitation treatment and 90 d after onset. Modified Barthel Index (MBI) was used to assess activity of daily living 90 d after onset. According to MBI scores, the patients were divided into good prognosis group (MBI scores>60) and poor prognosis group (MBI scores≤60); multivariate Logistic regression analysis was used to confirm the risk factors affecting prognoses 90 d after onset.ResultsAmong 74 enrolled patients, 40 were classified as normal renal function group and 34 as mild-moderate renal dysfunction group; patients in the mild-moderate renal dysfunction group had significantly higher level of blood urea nitrogen, proportion of silent lacunar cerebral infarction and Fazekas scale scores, and had statistically lower FMA scores and MBI 90 d after onset than normal renal function group (P<0.05). Among the 74 patients, good prognosis was found in 32 patients and poor prognosis in 42 patients; multivariate Logistic regression analysis found that age, eGFR (OR=0.944,P= 0.011, 95%CI: 0.903-0.987), baseline NIHSS scores, and Fazekas scale scores were risk factors affecting prognoses 90 d after onset.ConclusionIn acute MCA infarction patients, eGFR can influence the rehabilitation of motor function and short-term prognoses.
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Objective To study the value of MSCT in the diagnosis of neonatal type (Ⅲ) congenital esophageal atresia.Methods MSCT data of 25 cases with neonatal type (Ⅲ) congenital esophageal atresia confirmed by surgery and pathology were analyzed retrospectively.The full preparation before examination and the image post-processing function were checked,and MSCT data were compared with the findings of surgery.Results By full preparation and application of M PR,SSD technology after scanning,the esophageal proximal blind end,and the distance between the two esophageal blind ends were clearly displayed,furthermore,the opening position,morphology and diameter of the distal tracheoesophageal fistula were also showed,and bronchial tree morphology and inflammation in the lung can be visible.Conclusion MSCT full preparation and application of image post processing function are potential to the clinical diagnosis of congenital esophageal atresia and tracheoesophageal fistula.
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Objective@#To investigate the histone acetylation level and histone deacetylase (HDAC) activity of peripheral blood CD4+ T lymphocytes in patients with oral lichen planus (OLP). @*Methods @#Twenty-three OLP patients were selected from August 2016 to January 2017 from the Stomatological Hospital, Southern Medical University. The diagnosis was confirmed by pathology, and the lesions were divided into a nonerosive OLP group (11 cases) and an erosive OLP group (12 cases). Ten healthy sex- and age-matched volunteers served as controls. Immunomagnetic beads were used to separate CD4+ T lymphocytes, and histones and nucleoproteins were extracted. The global histone H3/H4 acetylation levels and HDAC activity of CD4+ T lymphocytes from all subjects were detected by ELISA. The differences between the OLP and control groups were statistically analyzed. @*Results@#Global histone H3 hypoacetylation was observed in the OLP group compared with the control group (u = -2.410, P = 0.012). However, there was no significant difference in the serum CD4+ T lymphocyte histone H4 acetylation level between the OLP and control group (u = -1.412, P = 0.158). HDAC activity was significantly higher in the OLP group than in the healthy control group (F = 5.749, P = 0.023), and much higher HDAC activity was observed in the erosive group than in the nonerosive (P = 0.014) and healthy control groups (P = 0.001). The degree of histone H3 acetylation correlated negatively with increased HDAC activity in the OLP group (rs = -0.771, P < 0.001). There was no correlation between the level of histone H3 acetylation and HDAC activity in the healthy control group (rs = 0.382,P = 0.276). The histone H4 acetylation level in the OLP group showed no correlation with HDAC activity (rs = 0.149, P = 0.498), and the histone H4 acetylation level in the control group also showed no correlation with HDAC activity (rs = 0.527, P = 0.117).@*Conclusion @#Abnormal histone acetylation of CD4+ T lymphocytes in the peripheral blood of patients with OLP was identified and could be related to HDAC activity, suggesting that the epigenetic modification of histone acetylation may play a role in the pathogenesis of OLP.
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<p><b>BACKGROUND</b>Passive leg raising (PLR) represents a "self-volume expansion (VE)" that could predict fluid responsiveness, but the influence of systolic cardiac function on PLR has seldom been reported. This study aimed to investigate whether systolic cardiac function, estimated by the global ejection fraction (GEF) from transpulmonary-thermodilution, could influence the diagnostic value of PLR.</p><p><b>METHODS</b>This prospective, observational study was carried out in the surgical Intensive Care Unit of the First Affiliated Hospital of Sun Yat-sen University from December 2013 to July 2015. Seventy-eight mechanically ventilated patients considered for VE were prospectively included and divided into a low-GEF (<20%) and a near-normal-GEF (≥20%) group. Within each group, baseline hemodynamics, after PLR and after VE (250 ml 5% albumin over 30 min), were recorded. PLR-induced hemodynamic changes (PLR-Δ) were calculated. Fluid responders were defined by a 15% increase of stroke volume (SV) after VE.</p><p><b>RESULTS</b>Twenty-five out of 38 patients were responders in the GEF <20% group, compared to 26 out of 40 patients in the GEF ≥20% group. The thresholds of PLR-ΔSV and PLR-Δ cardiac output (PLR-ΔCO) for predicting fluid responsiveness were higher in the GEF ≥20% group than in the GEF <20% group (ΔSV: 12% vs. 8%; ΔCO: 7% vs. 6%), with increased sensitivity (ΔSV: 92% vs. 92%; ΔCO: 81% vs. 80%) and specificity (ΔSV: 86% vs. 70%; ΔCO: 86% vs. 77%), respectively. PLR-Δ heart rate could predict fluid responsiveness in the GEF ≥20% group with a threshold value of -5% (sensitivity 65%, specificity 93%) but could not in the GEF <20% group. The pressure index changes were poor predictors.</p><p><b>CONCLUSIONS</b>In the critically ill patients on mechanical ventilation, the diagnostic value of PLR for predicting fluid responsiveness depends on cardiac systolic function. Thus, cardiac systolic function must be considered when using PLR.</p><p><b>TRIAL REGISTRATION</b>Chinese Clinical Trial Register, ChiCTR-OCH-13004027; http://www.chictr.org.cn/showproj.aspx?proj=5540.</p>
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Objective @#To study the clinical periodontal status of patients with desquamative gingivitis (DG) and analyze the factors that influence clinical periodontal indicators.@*Methods @#A purposive sampling method was used to obtain 42 subjects for a DG case group and a control group. Periodontal clinical indicators were detected, and related factors were analyzed. @*Results @#The DG patients were primarily middle-aged women. Periodontal clinical indicators were more prevalent in individuals with oral lichen planus (OLP) and mucous membrane pemphigoid (MMP) than in the control group. Probing depth (PD) (χ2=53.058, P<0.001; χ2=32.989, P<0.001), clinical attachment (χ2=30.292, P<0.001; χ2=32.470, P<0.001) and the positive rate of bleeding on probing (BOP) (χ2=50.003, P<0.001; χ2=36.236, P<0.001) were higher in the OLP and MMP group than in the control group. The time interval between the onset and treatment of DG was correlated with PD (rs=0.523, P<0.001) and the rate of positive BOP sites (rs=0.377, P=0.014). @*Conclusion@# Patients with DG have obvious periodontal lesions. Early medical intervention is helpful for diagnosing and treating DG-related oral and systemic disease.
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Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accu-mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi-esis and ultimately resulting in bone marrow failure. Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years (5.3%)and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML. Saponins are amphipathic glycosides found in traditional Chinese medicines. In the present study, we isolated a panel of saponins from Paris forrestii (Takht.) H. Li, a unique plant found in Tibet and Yunnan provinces, China. By examining their activities in suppressing acute myeloid leukemia cell proliferation, total saponins from Paris forrestii (TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines. TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg-ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa-tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con-firmed by the inactivation of 4EBP-1 and p70S6K,two typical downstream signal molecules in the AKT/mTOR pathway. More specifically, TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6, a recently identified oncogene in AML. RNF6 activated AKT/mTOR, and consistently, knockdown of RNF6 led to inactivation of the AKT/mTOR pathway. Furthermore, TSPf suppressed the growth of AML xenografts in nude mice models. Oral administration of 100 mg·kg-1 body weight almost fully suppressed tumor growth within 14 d, without gross toxicity. This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway. Given its low toxicity,TSPf could be developed for the treatment of AML.
RESUMEN
AIM: To investigate the impact of silencing of the PTEN gene using siRNA on the invasion, proliferation, cell cycle, and epithelial-mesenchymal transition of the Tca8113 cell line. METHODS: The established Tca8113 cell model with siRNA interference to silence the PTEN gene was used. The transfection efficiency was examined by RT-qPCR and Western blot analysis. CCK-8 assay was utilized to analyze the proliferation of Tca8113 cells and cell invasion was evaluated using a transwell assay. The cell cycle distribution was analyzed by flow cytometry. The protein expression levels of the epithelial-mesenchymal transition (EMT) markers E-cadherin and Vimentin and the EMT-related proteins ß-catenin and TGF-ß1 were analyzed by Western blot. RESULTS: The expression level of PTEN was significantly reduced in the PTEN-siRNA group. The invasiveness and proliferation rate of Tca8113 cells in the PTEN-siRNA group were significantly greater than those of the control and negative control groups. The expression levels of E-cadherin and ß-catenin were reduced, whereas the expression levels of vimentin and TGFß-1 were elevated in the PTEN-siRNA group compared with those of control and negative groups. These results were significantly different. CONCLUSION: The silencing of PTEN by siRNA increased the proliferation and promoted cell invasion of Tca8113 cells. PTEN gene silencing may accelerate the EMT in Tca8113 cells.
Asunto(s)
Carcinoma de Células Escamosas/patología , Transición Epitelial-Mesenquimal/fisiología , Silenciador del Gen , Neoplasias de la Boca/patología , Fosfohidrolasa PTEN/genética , ARN Interferente Pequeño , Antígenos CD , Cadherinas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Humanos , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Invasividad Neoplásica/genética , Fosfohidrolasa PTEN/fisiología , Transfección , Factor de Crecimiento Transformador beta1/metabolismo , beta Catenina/metabolismoRESUMEN
Objective@# To detect the expression of vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in oral lichen planus (OLP).@*Methods @#Thirty OLP patients and fifteen healthy subjects were enrolled in the study. Serum were collected from 15 healthy volunteers as controls. Normal tissues were collected from surgical department as immunohistochemical analysis. The levels of VEGF, ICAM-1, VCAM-1 in serum were measured by ELISA. Immunohistochemical analysis of VEGF, ICAM-1, VCAM-1 were carried out by the means of primary antibodies and anti-VEGF, anti-CD106 antigen (VCAM-1) and anti-CD54 antigen (ICAM-1). @*Results@# ELISA results showed no expression differences for VEGF between the two groups. Whereas, the levels of ICAM-1, VCAM-1 in OLP group were significantly higher than those in control group (P < 0.05). Immunohistochemical results reveal the presence of a significant angiogenesis in OLP patients through the immunoexpression of VEGF, ICAM-1, VCAM-1 according to the percentage of stained cells (P < 0.05).@*Conclusion @# Regarding the results, it seems that high expression of VCAM-1 and ICAM-1 are related to oral lichen planus.