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Objective:To study the effect of miR-539-5p on apalutamide (ARN-509) sensitivity and malignant phenotype of androgen independent prostate cancer cell line C4-2B and related mechanisms.Methods:Castrated resistant prostate cancer, castrated sensitive prostate cancer and benign prostate tissue were obtained. C4-2B cell lines were divided into blank group, transfection group (miR-539-5p plasmid) and control group (control plasmid). qPCR was used to detect the expression of miR-539-5p, androgen receptor (AR) and HSBP1 in the tissues and 3 group of cells. The protein expressions of AR and HSBP1 were detected by western blot. Transwell assay was used to detect the invasion and migration ability of three groups of cells. CCK-8 assay was used to detect the proliferation ability and semi-inhibitory concentration (IC50) of AR antagonist ARN-509. The colony forming ability of the three groups of cells was detected by plate cloning experiment.Results:Tissue-qPCR indicated that, in the benign prostate tissue, tumor tissue of castration sensitive patients and tumor tissue of castration resistant patients, the expressions of miR-539-5p were 0.29 ± 0.04, 0.17 ± 0.02 and 0.07 ± 0.01, the expressions of AR were 0.13 ± 0.02, 0.28 ± 0.04 and 0.79 ± 0.11, and the expressions of HSBP1 were 0.20 ± 0.03, 0.38 ± 0.04 and 0.72 ± 0.11, respectively. Compared with benign prostate tissue and prostate cancer tissue, the expression of AR and HSBP1 gene was higher in prostate cancer tissues with castration resistance, and the expression of miR-539-5p was lower. Cell-qPCR demonstrated that the expressions of miR-539-5p in blank group, control group and transfection group were 1.00±0.09, 1.07±0.11 and 7.19±0.51, the expressions of AR were 1.00±0.10, 1.03±0.14 and 0.51±0.08, and the expressions of HSBP1 were 1.00±0.10, 0.96±0.12 and 0.97±0.11. The expression of miR-539-5p in the transfection cells was significantly higher than that in the control group and the blank group, the expression of AR gene was significantly lower than that in the control group and the blank group, and there was no significant difference in the expression of HSBP1. Western blot showed that, in blank group, control group and transfection group, the protein expressions of AR were 1.00±0.10, 1.12±0.22 and 0.72±0.16, and the expressions of HSBP1 were 1.00±0.10, 0.94±0.18 and 0.48±0.11. The protein expression of AR and HSBP1 in the transfection group was significantly lower than that in the control group and the blank group. Transwell experiment showed that the invasion and migration of cells in the transfection group were significantly lower than that in the control group and the blank group. CCK-8 assay and plate cloning experiment showed that the proliferative capacity and the number of clone formation in the transfection group were significantly lower than those in the control group and the blank group, and the expression of AR and HSBP1 in the transfection group was significantly lower than that in the control group and blank group. Compared with the control group and blank group, the IC50 value of ARN-509 decreased significantly in the transfection group.Conclusion:miR-539-5p may inhibit the malignant phenotype and castration resistance of cells via interfering with the translation level of HSBP1.
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Objective:To analyze the risk factors for postoperative one-year mortality in elderly patients with femoral intertrochanteric fracture following multidisciplinary treatment (MDT) by intramedullary nailing.Methods:The clinical data were retrospectively analyzed of the 158 elderly patients with femoral intertrochanteric fracture who had undergone MDT by proximal femoral intramedullary nailing between January 2018 and August 2020 at Department of Orthopedics, Trauma Center, Zhongda Hospital Affiliated to Southeast University. There were 41 males and 117 females with an average age of 82.5 years (from 65 to 95 years). By the modified Evans classification, there were 15 cases of type Ⅰ, 16 cases of type Ⅱ, 35 cases of type Ⅲ, 81 cases of type Ⅳ, and 11 cases of type Ⅴ. The one-year mortality was documented in the patients after surgery. To screen for risk factors, univariate analysis was conducted of gender, age, body mass index (BMI), modified Evans classification of fractures, time from injury to operation, American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI) and comorbidities, as well as preoperative hemoglobin (Hb), serum albumin (ALB) and total lymphocyte count (TLC). The factors with P<0.05 were included in the multivariate logistic regression model analysis to determine the risk factors. Results:A total of 13 patients died within one year after surgery, yielding a mortality of 8.2% (13/158). Univariate analysis showed significant differences in age, body mass index, modified Evans classification of fractures, CCI and Hb between the surviving and dead patients ( P<0.05). Multivariate logistic regression analysis showed that age >85 years ( OR=0.122, 95% CI: 0.018 to 0.834, P=0.032), BMI>23.9 kg/m 2 ( OR=0.083, 95% CI: 0.013 to 0.510, P=0.007), CCI≥3 points ( OR=0.051, 95% CI: 0.090 to 0.275, P=0.001) and preoperative Hb<90 g/L ( OR=4.733, 95% CI: 1.036 to 21.624, P=0.045) were the independent risk factors for postoperative one-year mortality in the elderly patients with intertrochanteric fracture following MDT by proximal femoral intramedullary nailing. Conclusions:After MDT by proximal femoral intramedullary nailing of femoral intertrochanteric fractures, the geriatric patients with an age >85 years, BMI>23.9 kg/m 2, CCI≥3 points and Hb<90 g/L are likely to die. Therefore, special care should be taken for them.
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Objective:To explore the effect of low expression of human epidermal growth factor-like domain protein 6 (EGFL6) gene in human bladder cancer cell 5637 on its proliferation ability in vitro and in vivo.Methods:Human bladder cancer cells 5637 were divided into experimental group and control group. The experimental group cells targeted human EGFL6 gene with small interfering RNA (siRNA) , and the control group cells were transfected with Mock-siRNA. The cells in the experimental group and the control group were detected by real-time quantitative PCR. The content of EGFL6 mRNA in the medium. CCK8 was used to detect the proliferation ability of cells. Nude mice were injected subcutaneously with human bladder cancer cells 5637 in the experimental and control groups respectively, and the proliferation ability of the cells in vivo was detected by subcutaneous transplantation tumor assay in nude mice. The expression of EGFL6, p-P13K, and p-AKT was detected by western blotting.Results:The expression of EGFL6 was 0.19±0.03 and 0.91±0.11 in the experimental and control groups, respectively. siRNA-EGFL6 decreased the protein expression of EGFL6 in human bladder cancer 5637 cells in the experimental group. CCK8 results showed that the absorbance of the experimental group and the control group were 1.558±0.152 and 2.287±0.182, respectively. The results of subcutaneous tumor transplantation in nude mice showed that the volume of tumor in experimental group and control group was (1192.07±250.9) μm 3 and (2280.5±600.1) μm 3, respectively. The mass were (0.66±0.31) g and (1.52±0.48) g, respectively. The tumor volume and mass of the experimental group decreased after 4 weeks. The results of protein immunoblotting experiments revealed that the expression of p-P13K was 0.79±0.14 and 0.33±0.09 in the control and experimental groups, respectively, and the expression of p-AKT was 0.93±0.13 and 0.28±0.06, respectively, confirming that the expression of p-P13K and p-AKT were decreased in the experimental group of cells compared with the control group. Conclusion:The low expression of EGFL6 can inhibit the proliferation of human bladder cancer cell 5637 in vivo and in vitro through the P13K-AKT signaling pathway.
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Objective:To investigate differences in serum uric acid levels between elderly patients with prostate cancer and patients with benign prostatic hyperplasia(BPH).Methods:A total of 300 prostate cancer patients admitted to the urology department of our hospital between Feb.2010 and Jun.2019 were retrospectively analyzed.During the same period, 240 BPH patients and 400 elderly men with normal prostate size were enrolled as the control group.Serum uric acid and prostate-specific antigen(PSA)levels, C-reactive protein(CRP), neutrophil count and lymphocyte count were determined.Serum uric acid concentrations were monitored in prostate cancer patients with different clinicopathological characteristics.Results:CRP and Neu/Lym levels were higher in the prostate cancer group than in the BPH and control groups( P<0.05). The serum uric acid level was (327.0±58.3)μmol/L in the prostate cancer group, lower than in the BPH group(375.2±68.4)μmol/L and the control group(377.8±73.2)μmol/L( F=55.69, P<0.001). Multivariable Logistic regression analysis indicated that serum uric acid was a protective factor for prostate cancer( OR=0.593, 95% CI: 0.542-0.718, P=0.004). There were significant differences in serum uric acid levels between prostate cancer patients with different ages and pathological grades( t=-4.63, F=12.73, P<0.001). However, serum uric acid levels were not significantly correlated with clinical staging or lymph node metastasis( F=-2.72 and 0.77, P=0.068 and 0.460). Conclusions:Compared with BPH patients and healthy males, serum uric acid levels are reduced and inflammatory markers are increased in prostate cancer patients, indicating that serum uric acid may be a risk factor for the occurrence and progression of prostate cancer in the elderly.
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Objective:To examine the risk of long-term cognitive impairment in elderly prostate cancer patients aged 75 years and older undergoing androgen deprivation therapy(DAT), and to analyze the correlation between DAT and cognitive impairment.Methods:This was a retrospective cohort study.Elderly prostate cancer patients aged 75 years and older in the National Cancer Database(SEER)from 1996-2003 were included.According to whether ADT was received, patients were divided into the ADT group(n=82 514)and the control group(n=121 856). Baseline clinical data were compared between the two groups. Kaplan- Meier survival analysis and the Log- rank test were used to compare the incidence of cognitive impairment(dementia and Alzheimer's disease)between the two groups. Cox risk ratio regression analysis was used to assess the relationship between ADT and cognitive impairment. Results:A total of 204 370 patients were enrolled in this study.The mean age of patients was(79.2±4.6)years.Compared with the control group, the ADT group was older and had higher prostate specific antigen levels, higher proportions of poorly differentiated tumors, more complications and a higher proportion of patients receiving radiotherapy( P<0.05). During the follow-up of(12.1±3.3)years, a total of 41 661 cases of dementia were diagnosed, including 13 634 in the ADT group and 28 027 in the control group, and 28 945 cases of Alzheimer's disease were diagnosed, including 9 372 in the ADT group and 19 573 in the control group.Kaplan-Meier survival analysis and the log-rank test showed that the incidence of dementia in the ADT group was higher than that in the control group( χ2=8.10, P=0.004), and the incidence of Alzheimer's disease was also higher in the ADT group than in the control group( χ2=5.06, P=0.024). Cox regression analysis results showed that ADT significantly increased the risk of dementia( HR=1.71, 95% CI: 1.14-2.57, P=0.01)and Alzheimer's disease( HR=1.63, 95% CI: 1.08-2.46, P=0.02), compared with treatment that did not include ADT. Conclusions:The risk of dementia and Alzheimer's disease is increased in elderly prostate cancer patients aged 75 years and older after ADT.
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Objective To investigate the effect of postoperative analgesia with oxycodone on T cell function after operative of cesarean section with chronic hepatitis B.Methods Sixty cesarean sec-tion women with chronic hepatitis B undergoing CS,aged 22-35,were randomly divided into two groups:oxycodone group (group O)and morphine group (group M).The changes of immune cells (Th1,Th2)and liver function were recorded after the analgesia (immediate,postoperative 24 h,48 h,72 h).The total number of pressing analgesia pump and the cumulative amount of PCA were re-corded.Results The Th1 of group O was higher than that of group M at 24 h,48 h after operation (P <0.05),while there was no significant difference of Th1 and Th2 in group M.The total patient-controlled pressing times and accumulated amount of PCA of group O were significantly lower than those in group M (P <0.05).There was no significant difference in the incidence of adverse reactions between the two groups.Conclusion Oxycodone can activate T cell function in postoperative analge-sia,while morphine causes the inhibition of Th1 cells.
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Objective To evaluate the effects of fluid restriction in combination with small dose of norepinephrine on cerebral oxygen metabolism in elderly patients undergoing gastrointestinal surgery.Methods Forty elderly patients of both sexes,aged 65-80 yr,with body mass index of 18-24 kg/m2,of ASA physical status Ⅰ or Ⅱ (NYHA Ⅰ or Ⅱ),with left ventricular ejection fraction≥50%,undergoing elective gastrointestinal surgery,were randomly divided into 2 groups (n =20 each) using a random number table:routine fluid administration group (group S) and restricted fluid administration + small dose of norepinephrine group (group RN).In group S,lactated Ringer's solution was given routinely,ephedrine 5 mg (per time) was injected intravenously,and MAP was maintained ≥ 65 mmHg during operation.In group RN,lactated Ringer's solution was infused intravenously at 5 ml · kg-1 · h-1 starting from 30 min before anesthesia,norepinephrine was infused intravenously at 0.01-0.03 μg · kg-1 · min-1 after induction of anesthesia,and MAP was maintained ≥ 65 mmHg.Intraoperative blood loss was replaced with the equal volume of 6% hydroxyethyl starch 130/0.4 sodium chloride injection in both groups.At 5 min before skin incision,1 and 2 h after skin incision and postanesthesia care unit discharge time,arterial and jugular bulb venous blood samples were obtained for blood gas analysis,and arterial oxygen content,jugular bulb venous oxygen content,arteriovenous oxygen content difference,cerebral oxygen extraction rate,and the ratio of cerebral blood flow to cerebral oxygen metabolic rate were calculated.Results There were no significant differences between the two groups in arterial oxygen content,jugular bulb venous oxygen content,arteriovenous oxygen content difference,cerebral oxygen extraction rate,and the ratio of cerebral blood flow to cerebral oxygen metabolic rate.Conclusion Fluid restriction combined with small dose of norepinephrine produces no effects on cerebral oxygen metabolism in elderly patients undergoing gastrointestinal surgery.
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Objective To evaluate the role of heparanase in endotoxemia-induced destruction of vascular endothelial glycocalyx in rats.Methods Forty-eight pathogen-free male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were randomly divided into 3 groups (n=16 each) using a random number table: control group (group C), lipopolysaccharide (LPS) group (group L) and LPS+ heparin group (group LH).Endotoxemia was induced by intravenous LPS 15 mg/kg in L and LH groups, and heparin sodium 100 U · kg-1 · h-1 was infused simultaneously in group LH.At 3 and 6 h after LPS injection, blood samples were collected from the femoral vein for determination of the serum concentrations of serum heparin sulfate (HS), syndecan-1, E-selectin and intercellular adhesion molecule-1 (ICAM-1) concentrations.The rats were then sacrificed, and lungs were removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio).Results Compared with group C, the serum HS, syndecan-1, E-selectin and ICAM-1 concentrations and W/D ratio were significantly increased in group L, and the serum HS and ICAM-1 concentrations were increased in group LH (P<0.05).Compared with group L, the serum HS, syndecan-1, E-selectin and ICAM-1 concentrations and W/D ratio were significantly decreased in group LH (P<0.05).The pathological changes of lungs were obvious in group L, and were significantly mitigated in group LH.Conclusion Heparanase is involved in endotoxemiainduced destruction of vascular endothelial glycocalyx in rats.
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Objective To evaluate the effects of ethyl gallate (EG ) on sepsis-induced acute lung injury (ALI) in rats .Methods Forty-eight healthy male Wistar rats ,aged 10-12 weeks ,weighing 150-250 g ,were randomly divided into 3 groups (n=16 each) using a random number table :control group (group C) ,group ALI , and group EG .The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg .Sepsis was induced by cecal ligation and puncture (CLP) .EG 1 ml/h (50 mg·kg-1 ·h-1 ) was infused intravenously via the femoral vein for 4 h starting from 6 h after CLP in group EG .The equal volume of normal saline was given instead in group ALI . The rats were sacrificed at 10 and 24 h after CLP (T1 ,2 ) , and the lungs were removed for determination of wet/dry lung weight ratio (W/D ratio ) , superoxide dismutase (SOD ) activity , contents of malondialdehyde (MDA ) and glutathione (GSH ) , and 3-NT expression (by immuno-histochemistry ) in lung tissues .The pathological changes of the lung were examined with light microscope .Results Compared with group C ,the W/D ratio ,MDA content and 3-NT expression were significantly increased and GSH content was decreased at T1 ,2 ,the SOD activity was significantly decreased at T2 in group ALI ,and the MDA content and 3-NT expression were increased at T1 ,and the W/D ratio ,MDA content and 3-NT expression were increased and GSH content was decreased at T2 in group EG ( P<0.05) .Compared with group ALI ,the MDA content was significantly decreased at T1 ,and the W/D ratio ,MDA content and 3-NT expression were decreased ,and GSH content and SOD activity were increased at T2 in group EG ( P<0.05) .The pathological changes of the lung were obvious in group ALI , and significantly attenuated in group EG .Conclusion EG can attenuate sepsis-induced ALI by antioxidative effects in rats .
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ObjectiveTo investigate the effects of norepinephrine on oxygen metabolism and postoperative outcomes in the elderly patients undergoing fluid-restored abdominal surgery.MethodsAfter hospital ethics committee approval,and written informed consent was obtained from all patients,40 elderly patients,aged > 64 yr,with a body mass index of 18-24 kg/m2,undergoing elective colorectal surgery,were randomly divided into 2 groups (n =20 each):routine fluid administration group (group A) and restricted fluid administration group (group B).In group A,lactated Ringer's solution was given routinely.Lactated Ringer's solution was given at a rate of 5 ml· kg- 1 · h- 1 and small dose of norepinephrine was infused intravenously at 0.01-0.03 μg· kg- 1 · h - 1 simultaneously during the surgery,and MAP was maintained ≥65 mm Hg in group B.Intraoperative blood loss was replaced with the equal volume of 6% hydroxyethyl starch 130/0.4.Before the surgery ( baseline),1 and 2 h after beginning of the surgery,and while leaving postanesthesia care unit,mean arterial pressure (MAP),heart rate (HR),cardiac index (CI) and central venous pressure (CVP) were recorded,and arterial and central venous blood samples were drawn for blood gas analysis.Oxygen delivery index (DO2 I ),oxygen consumption index (YO2I) and oxygen extraction ratio (ERO2) were calculated.The gastric mucosal pH was determined before the surgery and 1 h after beginning of the surgery.Blood samples were taken form the peripheral vein to determine the concentration of Hb,serum albumin,blood urea nitrogen (BUN) and creatinine (Cr) concentrations before the surgery and 1 day after the surgery.The extubation time,duration of stay in hospital,the time when the patients passed the flatus,pulmonary complications,gastrointestinal complications,and wound infections were recorded.ResultsCompared with group A,CI,Hb,ScvO2 and DO2I were significantly increased,CVP and ERO2 were decreased during the surgery,the concentrations of Hb and serum albumin were significantly increased,1 day after the surgery,and the incidence of pulmonary complications and wound infections was significantly decreased after the surgery in group B (P < 0.05 ).There were no significant differences in gastric muscosal pH,the indexes of renal function,extubatiotn time,the time when the patients passed the flatus,duration of stay in hospital and the incidence of gastrointestinal complications between the two groups ( P > 0.05).ConclusionWhen small dose of norepinephrine is used to treat perioperative hypotension induced by fluid restriction,it can increase oxygen delivery,and reduce the incidence of postoperative complications,and has no adverse effects on gastrointestinal microcirculation and oxygen consumption in the elderly patients undergoing colorectal surgery.
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Objective To investigate the relationship between lipopolysaccharide binding protein(LBP) in serum and degree of hepatic inflammation. Methods The levels of LBP in serum of 99 patients with chronic viral hepatitis (CVH) were detected by ELISA. The levels of LBP in 33 of all patients with chronic severe viral hepatitis were further detected 2~4 weeks after treatment. Results The serum levels of LBP in patients with chronic viral hepatitis were higher than that in normal patients [(79.62?45.52) ng/ml vs (50.22?31.44) ng/ml, P=0.001]. The serum levels of LBP in patients with chronic severe viral hepatitis were significantly higher than that in patients with moderate degree CVH group, severe degree CVH group, and normal group (P