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Objective: To analyze three different integrated scoring schemes of prostate biopsy and to compare their concordance with the scoring of radical prostatectomy specimens. Methods: A retrospective analysis of 556 patients with radical prostatectomy performed in Nanjing Drum Tower Hospital, Nanjing, China from 2017 to 2020. In these cases, whole organ sections were performed, the pathological data based on biopsy and radical prostatectomy specimens were summarized, and 3 integrated scores of prostate biopsy were calculated, namely the global score, the highest score and score of the largest volume. Results: Among the 556 patients, 104 cases (18.7%) were classified as WHO/ISUP grade group 1, 227 cases (40.8%) as grade group 2 (3+4=7); 143 cases (25.7%) as grade group 3 (4+3=7); 44 cases (7.9%) as grade group 4 (4+4=8) and 38 cases (6.8%) as grade group 5. Among the three comprehensive scoring methods for prostate cancer biopsy, the consistency of global score was the highest (62.4%). In the correlation analysis, the correlation between the scores of radical specimens and the global scores was highest (R=0.730, P<0.01), while the correlations of the scores based on radical specimens with highest scores and scores of the largest volume based on biopsy were insignificant (R=0.719, P<0.01; R=0.631, P<0.01, respectively). Univariate and multivariate analyses showed tPSA group and the three integrated scores of prostate biopsy were statistically correlated with extraglandular invasion, lymph node metastasis, perineural invasion and biochemical recurrence. Elevated global score was an independent prognostic risk factor for extraglandular invasion and biochemical recurrence in patients; increased serum tPSA was an independent prognostic risk factor for extraglandular invasion; increased hjighest score was an independent risk factor for perineural invasion. Conclusions: In this study, among the three different integrated scores, the overall score is most likely corresponded to the radical specimen grade group, but there is difference in various subgroup analyses. Integrated score of prostate biopsy can reflect grade group of radical prostatectomy specimens, thereby providing more clinical information for assisting in optimal patient management and consultation.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/cirurgia , Próstata/patologia , Estudos Retrospectivos , Prostatectomia/métodos , Biópsia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologiaRESUMO
Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.
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Angiomiolipoma , Carcinoma de Células Renais , Neoplasias Renais , Leucemia Mieloide Aguda , Humanos , Neoplasias Renais/patologia , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Angiomiolipoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Glicoproteínas de MembranaRESUMO
PURPOSE: To assess the causal effects of serum testosterone and sex hormone-binding globulin levels on brain volumetric measurements in women and men. METHODS: We performed a sex-stratified two-sample Mendelian randomization study using the random-effects inverse variance-weighted method as the primary analysis method. Sex-specific genetic instruments were obtained from a study with up to 194,453 men and 230,454 women. For testosterone, variants with dominant effects on both total and bioavailable testosterone but no aggregate effect on sex hormone-binding globulin were used as the main genetic instruments. Sex-specific summary-level data for magnetic resonance imaging brain volumetric measurements were obtained from a study with 11,624 women and 10,514 men. RESULTS: Analyses showed per standard deviation (approximately 3.7 nmol/L) higher testosterone levels in men were suggestively associated with larger gray matter volume (beta = 0.208, 95% confidence interval = 0.067 to 0.349, p = 0.004). The association remained in sensitivity analyses and multivariable analyses. Further analyses showed the effect was mainly act on peripheral cortical gray matter, but not on subcortical gray matter. Testosterone in men was not associated with hippocampal volume. Testosterone in women and sex hormone binding globulin in both sexes had no effect on all outcomes. CONCLUSION: Our findings overall support previous evidence that testosterone might have neuroprotective properties in elderly men. Future larger trials with long duration of intervention are warranted to assess the efficacy of testosterone for elderly men with cognitive impairment, especially in those with hypoandrogenism.
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Análise da Randomização Mendeliana , Globulina de Ligação a Hormônio Sexual , Masculino , Humanos , Feminino , Idoso , Globulina de Ligação a Hormônio Sexual/análise , Testosterona , Causalidade , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismoRESUMO
Objective: To investigate the prevalence of atrial cardiomyopathy in patients with different types of acute ischemic stroke and its relationship with cryptogenic stroke. Methods: Patients with acute ischemic stroke within 7 days of onset who were admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January to September 2019 were prospectively and consecutively enrolled. All included patients were classified according to TOAST classification of ischemic stroke. Chi-square test was used to compare the prevalence of atrial cardiomyopathy among patients with different TOAST classifications. Multivariate logistic regression model was used to analyze the related factors of cryptogenic stroke. Results: A total of 1 098 patients with acute ischemic stroke were enrolled in the study, including 661 males and 437 females, with a median age [M(Q1,Q3)] of 61 (53, 68) years. The prevalence of atrial cardiomyopathy in patients with cryptogenic stroke[53.5% (46/86)] was higher than that in patients with large artery atherosclerosis [38.0%(63/166), P=0.018] and small vessel occlusion [19.4%(37/191), P<0.001], but was lower than that of patients in the cardioembolic group [97.3% (72/74), P<0.001]. Multivariate logistic regression analysis showed that atrial cardiomyopathy was an associated factor for cryptogenic stroke (OR=2.945, 95%CI: 1.766-4.911, P<0.001). Conclusions: Atrial cardiomyopathy is associated with cryptogenic stroke. The prevalence of atrial cardiomyopathy in patients with cryptogenic stroke is higher than that in patients with large artery atherosclerosis and small vessel occlusion, but lower than that in patients with cardiac embolism.
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Fibrilação Atrial , Cardiomiopatias , AVC Isquêmico , Humanos , Cardiomiopatias/epidemiologiaRESUMO
Objective: To investigate the relationship between plasma heat shock proteins 90α(Hsp90α) levels and the white matter hyperintensity(WMH) in patients with cerebral small vessel disease(SVD). Methods: Patients admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from March to August 2021 and diagnosed with WMH by magnetic resonance examination (MRI) were selected as the case group, matched with physical examination patients who visited the Department of Medical Examination during the same period and showed no WMH on MRI and no history of neurological diseases as the control group, and the level of plasma Hsp90α was quantitatively detected by enzyme-linked immunosorbent assay. Mann-Whitney U test was used to compare whether there was a difference in plasma Hsp90α levels between the control group and the case group.Multivariate logistic regression analysis was used to explore the related factors of WMH in patients with SVD. Results: Of the 183 subjects, the control group (n=73) consisted of 28 males and 45 females, aged (54±10) years, while the case group (n=110) consisted of 71 males and 39 females, aged (64±10) years old. Plasma Hsp90α level was higher in the case group than that of the control group [53.33(35.33, 70.09) ng/ml vs 35.02(18.51, 54.95) ng/ml, P<0.001]. After adjusting for confounding factors by multivariate analysis, the results showed that plasma Hsp90α levels greater than 58.34 ng/ml was associated with WMH (P=0.002, OR=5.931, 95%CI:1.955-17.995). Conclusion: Higher level of plasma Hsp90α is associated with WMH in patients with SVD.
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Doenças de Pequenos Vasos Cerebrais , Proteínas de Choque Térmico HSP90/metabolismo , Leucoaraiose , Substância Branca , Idoso , Feminino , Proteínas de Choque Térmico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Substância Branca/patologiaRESUMO
Patients with dementia with Lewy body(DLB), Alzheimer disease (AD), frontotemporal dementia (FTP), progressive supranuclear palsy (PSP) and healthy controls in the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from August 2019 to March 2021 were recruited, with 3 in each group. Phosphorylated α-synuclein from the skin of DLB patients was detected by skin micro-biopsy and compared with patients with AD, FTP, PSP and health controls. Phosphorylated α-synuclein was found in the skin nerves of the DLB patients, while no α-synuclein were detected in the skin samples of others. Skin phosphorylated α-synuclein may potentially become a diagnostic biomarker of DLB, however further studies are warranted to assess its sensitivity and specificity.
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Doença de Alzheimer , Doença por Corpos de Lewy , Doença de Alzheimer/diagnóstico , Biópsia , Humanos , Doença por Corpos de Lewy/diagnóstico , PeleRESUMO
Temozolomide (TMZ) resistance is an important cause of clinical treatment failure and poor prognosis in gliomas. Increasing evidence indicates that cancer-derived exosomes contribute to chemoresistance; however, the specific contribution of glioma-derived exosomes remains unclear. The aim of this study was to explore the role and underlying mechanisms of exosomal macrophage migration inhibitory factor (MIF) on TMZ resistance in gliomas. We first demonstrated that MIF was upregulated in the exosomes of TMZ-resistant cells, engendering the transfer of TMZ resistance to sensitive cells. Our results indicated that exosomal MIF conferred TMZ resistance to sensitive cells through the enhancement of cell proliferation and the repression of cell apoptosis upon TMZ exposure. MIF knockdown enhanced TMZ sensitivity in resistant glioma cells by upregulating Metalloproteinase Inhibitor 3 (TIMP3) and subsequently suppressing the PI3K/AKT signaling pathway. Additionally, exosomal MIF promoted tumor growth and TMZ resistance of glioma cells in vivo, while IOS-1 (MIF inhibitor) promotes glioma TMZ sensitive in vivo. Taken together, our study demonstrated that exosome-mediated transfer of MIF enhanced TMZ resistance in glioma through downregulating TIMP3 and further activating the PI3K/AKT signaling pathway, highlighting a prognostic biomarker and promising therapeutic target for TMZ treatment in gliomas.
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Objective: To further improve socket shield technique. The treatment outcome and the key related factors in Asian population are evaluated by measuring the root fragment and alveolar crest parameters in immediate implant placement cases with socket shield. Methods: A total of 18 patients, with 21 implants placed using socket shield technique were included in this retrospective study. Fourteen implants of 11 cases were recruited from West China Hospital of Stomatology, Sichuan University, 7 implants of 7 cases were recruited from Stomatological Hospital of Chongqing Medical University. The relationship between the thickness of the root fragment, the vertical height of the root fragment and the dimensional changes of buccal alveolar bone in 6 months was analyzed respectively. The pink-white esthetic scores were evaluated. The complications were recorded, analyzed and preventive measures were put forward. Results: There is a negative correlation between the vertical height of tooth fragment and the buccal crest height reduction (r=-0.458, P=0.037). There were negative correlations between the thickness of the tooth fragment with the vertical dimensional changes (r=-0.574, P=0.007) and horizontal dimensional changes (r=-0.619, P=0.003) of buccal alveolar bone. Three cases with internal exposure were recorded during the treatment. No severe complications were observed. Every case achieved a satisfying pink-white esthetic outcome according to the existing treatment protocols. Conclusions: Rigorous case screening, delicate surgical procedures, and maintaining adequate thickness of the root are the key to achieve a good esthetic outcome of implant treatment with socket shield technique.
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Implantes Dentários para Um Único Dente , Carga Imediata em Implante Dentário , China , Implantação Dentária Endóssea , Estética Dentária , Humanos , Estudos Retrospectivos , Extração Dentária , Alvéolo Dental/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: The study aims to construct a multi-gene risk scoring model that can be used to predict the prognosis of patients with lung squamous cell carcinoma (LUSC). PATIENTS AND METHODS: RNA-seq data from 494 LUSC tumor samples and 49 peripheral lung tissue samples were obtained from TCGA_LUSC database. Differential analysis was conducted using edgeR to screen differentially expressed lncRNAs (DElncRNAs) between LUSC and normal samples. Univariate Cox regression analysis was used to screen lncRNAs that were significantly correlated with LUSC prognosis. LASSO regression model was built to reduce complexity. The LUSC prognostic model based on lncRNAs was established by multivariate Cox regression analysis, which was evaluated by ROC curves and survival analysis. ROC and Kaplan-Meier survival curves of each lncRNA in the model were plotted and compared. RESULTS: 2085 DElncRNAs were identified. Combined with univariate Cox regression analysis, 342 prognosis-related genes were screened. After LASSO regression analysis, 11 lncRNAs tightly related to LUSC prognosis were identified and a risk scoring model was constructed. ROC curve analysis proved the good performance of the model. The Kaplan-Meier survival curve showed that the mortality in high-risk group was significantly higher. The survival analysis results of each lncRNA were also consistent with the prediction in Cox regression. CONCLUSIONS: Our results suggested that the 11-lncRNA risk scoring model may provide a new insight for predicting prognosis of LUSC patients.
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Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , RNA Longo não Codificante/análise , Biomarcadores Tumorais/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , Curva ROC , Análise de Regressão , Fatores de RiscoRESUMO
Objective: To explore the therapeutic efficacy of nasal Continuous Positive Airway Pressure (CPAP) and aerobic exercise of different intensity in patients with Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) and Type 2 Diabetes Mellitus (T2DM). Methods: A total of 112 patients with OSAHS and T2DM, including 53 males and 59 females, with a mean age of (66.9±7.8) years old, from the Fourth Rehabilitation Hospital of Shanghai and the Second Affiliated Hospital of Soochow University from January 2017 to December 2018 were enrolled prospectively. There were divided into two groups based on whether received nasal CPAP therapy: 50 cases in nasal CPAP+aerobic exercise group and 62 cases in aerobic exercise group. Subsequently, patients in nasal CPAP+aerobic exercise group were randomly divided into two subgroups: moderate and low intensity aerobic exercise (26 and 24 cases respectively). All patients completed nasal CPAP and (or) aerobic exercise of different intensity for 20 weeks. The therapeutic efficacy of polysomnography (PSG) parameters, glycolipid metabolism, 6 minutes walking distance (6 MWD), and rate of perceived exertion (RPE) were compared between each group before and after treatment. Results: Pre-and post-intervention, PSG parameters, body mass index (BMI) [(26.6±3.7) vs (24.3±2.8) kg/m(2)], RPE [(16.4±1.3) vs (12.2±2.6) score], 6 MWD [(372.6±59.7) vs (441.5±75.6) m] and glucolipid metabolism indexes were improved significantly in nasal CPAP+aerobic exercise group (all P<0.05), such as fasting blood glucose [(7.4±2.4) vs (6.2±1.6) mmol/L], glycosylated hemoglobin [(7.6±1.2)% vs (6.6±0.7)%], fasting insulin [(10.8±4.4) vs (6.9±3.4) µU/L], insulin resistance index [(3.5±1.9) vs (1.9±1.2)], total cholesterol [(4.0±0.9) vs (3.5±0.9) mmol/L], low density lipoprotein cholesterol [(4.2±0.6) vs (3.1±0.8) mmol/L]; BMI, exercise endurance, some glucolipid metabolism indexes and PSG parameters were also improved in aerobic exercise group (P<0.05). After 20 weeks' intervention, it showed statistically significant differences in PSG parameters, glycometabolism, some lipid metabolism indexes and RPE (all P<0.05), and no significantly difference in BMI [(24.3±2.7) vs (24.3±2.8) kg/m(2)] between the two groups. Compared with the low intensity subgroup, there were significant improvement in 2 hours' postprandial insulin, insulin resistance index, low density lipoprotein cholesterol, lipoprotein A, RPE, 6 MWD in moderate subgroup (P<0.05). Conclusion: Nasal CPAP combined with moderate intensity aerobic exercise can effectively improve the glucolipid metabolism, insulin resistance and exercise tolerance in patients with OSAHS and T2DM.
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Diabetes Mellitus Tipo 2 , Apneia Obstrutiva do Sono , Idoso , China , Pressão Positiva Contínua nas Vias Aéreas , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Unfortunately, there are errors that occurred in the name and manufacture of the growth hormone (GH) received by the patients in the GH group on page two, Table 1 and figure 1 on page three.
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PURPOSE: To investigate whether growth hormone (GH) could improve pregnancy rates of patients with thin endometrium by clinical study and laboratory experiments. MATERIALS AND METHODS: Ninety-three patients were randomized to either the GH-received group (40) or the routine exogenous administration of estrogens control group (53) for clinical study. The human endometrial carcinoma cell line RL95-2 was used for testing the role of GH with Western blot and real-time PCR by exposure to various concentrations of GH (0.1 nM,1 nM,10 nM,100 nM). RESULTS: Patients treated with GH had a significantly (P < 0.05) greater endometrium thickness on day 3 (7.87±0.72 vs 6.34±0.86), higher implantation rates (24.4% vs 10.5%) and greater clinical pregnancy rates (42.5% vs 18.9%) compared with the control group. No adverse events were associated with the use of GH. Administration of GH significantly up-regulated the expression of VEGF, ItgB3 and IGF-I expression in RL95-2 cells at both mRNA and protein levels (P < 0.05). AG490, an inhibitor of JAK2, nearly completely inhibited the up-regulative effect of GH through the JAK2-STAT5 pathway, and GH-induced effects could be mediated through autocrine IGF-I together with its hepatic counterpart. IGF-I mRNA was detected in the RL95-2 cells. CONCLUSION: GH may improve pregnancy outcomes of patients with thin endometrium who undergo frozen embryo transfer by acting on human endometrial cells to promote proliferation and vascularization and to up-regulate receptivity-related molecular expression.
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Transferência Embrionária/métodos , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Hormônio do Crescimento/administração & dosagem , Taxa de Gravidez/tendências , Adulto , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Didrogesterona/administração & dosagem , Transferência Embrionária/tendências , Endométrio/patologia , Estradiol/administração & dosagem , Feminino , Humanos , Gravidez , Progesterona/administração & dosagem , Resultado do TratamentoRESUMO
Objective: To discuss the affect of glycosylated hemoglobin (HbA1c) level for the onset of nonalcoholic fatty liver disease (NAFLD) in cohort population. Methods: An epidemiological survey of the relationship between HbA1c and NAFLD conducted in 2012 was based at cohort baseline, and three follow-up sessions conducted in 2013, 2014 and 2015. In total 2 811 subjects were included in the study after exclusion of NAFLD patients at baseline and those who lost their lives due to relocation, and death. The Cox proportional hazard model was used to analyze the relationship between glycosylated hemoglobin and other risk factors of NAFLD. Continuous variables were compared using the t-test or the Mann-Whitney test. χ (2)-test was used for the measurement of categorical data. Results: A total of 2 811 subjects with mean age of 59 (58.2±9.8) years old, including 1 664 males and 1 147 females. Age, waist circumference, body mass index, systolic blood pressure, γ-glutamyltransferase and fasting blood glucose level of HbA1c abnormal group were higher than normal group. The incidence of NAFLD in the abnormal HbA1c level group (25.4%) was higher than normal group (14.9 %), and diastolic blood pressure, high-density lipoprotein cholesterol was lower than normal group and the differences were statistically significant. During the three follow-up intervals, there were 440 new cases of NAFLD, consisting 285 males and 155 females with cumulative incidence of 15.7% (440/2 811). Multivariate Cox regression analysis showed that patients with elevated HbA1c had a higher risk of developing NAFLD (HR 1.796; 95% CI 1.335~2.418; P < 0.01), and the increased HbA1c level after adjustment for gender, age, and metabolic syndrome-related factors remained an independent risk factors for NAFLD (HR 1.580; 95.0% CI 1.161-2.152; P < 0.01). Conclusion: An elevated HbA1c levels have a positive predictive value for the onset of NAFLD.
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Hemoglobinas Glicadas/análise , Hepatopatia Gordurosa não Alcoólica , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Feminino , Humanos , Masculino , Síndrome Metabólica , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Fatores de Risco , Circunferência da CinturaRESUMO
OBJECTIVE: The effect of lipoxin receptor agonist BML-111 on acute kidney injury and AKI in rats with hemorrhagic shock (HS) and its mechanism were investigated. MATERIALS AND METHODS: A model of hemorrhagic shock in Sprague-Dawley (SD) rats was established, and recovered after 30 min of shock. 1 mg/kg BML-111 was intraperitoneally injected at the beginning of resuscitation in group BML-111. The concentration of serum creatinine, serum KIM-1 content, NGAL and inflammatory factors were detected. Renal tissue injury was examined by HE staining; TUNEL staining was used to detect the apoptosis of rat kidney cells. Western blot was performed for the detection of the expression level of MAPK (mitogen-activated protein kinase), Bax, cytochrome C and caspase-3,9 in rat renal tissue. RESULTS: HE staining showed pathological changes in groups group comparing to sham group. BML-111 group had a significant decrease in renal tissue injury. The scores of renal injury in each group were in accordance with the histological changes. The expression level of inflammatory factors in HS group was significantly higher than that in sham group (p<0.05). After BML-111 intervention, the levels of inflammatory factors in renal tissue were significantly lower than those in HS group (p<0.05). Meanwhile, NGAL and KIM-1 also showed the same trend. TUNEL staining showed that compared with sham group, the number of apoptotic cells in renal tissue of HS group increased significantly, and the apoptosis rate of renal tissue cells in group BML-111 decreased significantly. Western blot showed that the expression level of JNK, p38MAPK, and apoptosis-related protein in HS group was significantly increased, whereas the expression level of p38MAPK and JNK in group BML-111 was significantly decreased. CONCLUSIONS: BML-111 can reduce the inflammatory response and apoptosis of renal tissue by inhibiting the activation of MAPK signaling pathway in acute renal injury induced by hemorrhagic shock.
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Injúria Renal Aguda/metabolismo , Apoptose/efeitos dos fármacos , Ácidos Heptanoicos/farmacologia , Rim/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Choque Hemorrágico/metabolismo , Injúria Renal Aguda/complicações , Injúria Renal Aguda/patologia , Proteínas de Fase Aguda , Animais , Western Blotting , Caspase 3 , Moléculas de Adesão Celular/sangue , Creatinina/sangue , Mediadores da Inflamação/sangue , Rim/metabolismo , Rim/patologia , Lipocalina-2 , Lipocalinas/sangue , Masculino , Proteínas Proto-Oncogênicas/sangue , Ratos , Ressuscitação , Choque Hemorrágico/complicações , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The endoplasmic reticulum (ER) stress occurs frequently in cancers. The unfolded protein response (UPR) is activated to cope with ER stress. This has generated widespread interest in targeting UPR as therapeutic strategies. Inositol-requiring transmembrane kinase/endonuclease 1α (IRE1α), an ER stress sensor, is a key component of UPR. However, the role of IRE1α in tumorigenesis remains unclear. The purpose of this work is to investigate the role of IRE1α in colon cancer and to determine whether IRE1α could serve as a target for therapy. We found that knockdown of IRE1α suppressed the proliferation of colon cancer cells in vitro and xenograft growth in vivo. Inhibition of expression of IRE1α decreased stemness of colon cancer stem cells (CSCs) and attenuated growth of intestinal organoids. Genetic ablation of IRE1α prevented the colitis-associated colonic tumorigenesis in mice. The mechanistic study indicates that knockdown of IRE1α repressed the expression of ß-catenin, a key factor that drives colonic tumorigenesis, through activating pancreatic ER kinase/eukaryotic translation initiation factor 2α signaling. We found that the IRE1a-specific inhibitor 4µ8C could suppress the production of ß-catenin, inhibited the proliferation of colon cancer cells, repressed colon CSCs and prevented xenograft growth. The results suggest that IRE1α has a critical role in colonic tumorigenesis and IRE1α targeting might be a strategy for treatment of colon cancers.
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Neoplasias do Colo/enzimologia , Endorribonucleases/genética , Proteínas Serina-Treonina Quinases/genética , beta Catenina/metabolismo , Animais , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Colite/enzimologia , Colite/patologia , Endorribonucleases/metabolismo , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Nus , Transplante de Neoplasias , Células-Tronco Neoplásicas/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Carga TumoralRESUMO
Objective: To explore correlation between chest CT score and oxygenation index in patients with acute hydrogen sulphide poisoning, whether CT score can be applied to assess acute lung injury after acute hydrogen sulfide poisoning and provide basis and reference. Methods: The clinic and a series of CT datas of 32 acute hydrogen sulphide poisoning cases were retrospectively analysed and compared, According to GBZ31-2002 (the diagnostic standard of occupational H(2)S acute poisoning) , these patients were divided into 2 grouds including moderate groud and severe groud; The CT score were improved, referenceing the scoring criteria of the chest X-ray; The difference of the CT score and the oxygenation index were analyzed between moderate and severe group in the acute phase and the disperse phase; The correlation between CT score and oxygenation index were analyzed. Results: The CT score in moderate poisoning group were lower than severe group (2.26±1.37 vs 10.44±2.55, 1.34±0.65 vs 4.55±2.45, all P<0.05) in the acute phase and the dissipation phase.The oxygen index of the 19 cases in the acute phase were 307.55±28.29, and the oxygen index of the 8 cases in the dissipation phase was 435.75±37.00; The oxygen index of the 9 cases in the acute phase and the dissipation phase were respectively 193.17±36.41, 347.67±44.49. The oxygen partial pressure and oxygenation index in severe group were significantly lower than those in moderate group (all P<0.01) in the acute phase and the dissipation phase. Pearman correlation analysis showed that the CT score were negatively correlated to the oxygen index in the acute phase and the dissipation phase, respectively (r=-0.97ã-0.75, all P<0.01) . Conclusions: The CT score of lung injury and oxygenation index is negatively correlated. The CT score can be used to evaluate the degree of lung injury, and can be used in the evaluation of acute lung injury after acute hydrogen sulfide poisoning.