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OBJECTIVE To investigate the in vitro anti-inflammatory effects and mechanisms of oblongifolins A (OA) extracted from Garcinia oblongifolia. METHODS RAW264.7 cells were used as the research subject and divided into control group (0.5% DMSO), lipopolysaccharide (LPS) group (1 μg/mL), DEX group (10 µmol/L DEX+1 μg/mL LPS), and low-, medium-, and high-concentration groups of OA (7.5, 15, 30 µmol/L OA+1 μg/mL LPS). Except for the control group, the remaining groups were first stimulated with LPS for 1 hour and then mixed with drugs for 24 hours. The morphological changes of cells were observed in each group. The contents of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, IL-4 and IL-10 were detected in cells of each group; mRNA expression levels of TNF-α, IL-6 and IL-1β were measured. The expression of key proteins in the nuclear factor κB (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathways in each group, as well as the nuclear translocation of NF-κB p65 and Nrf2 proteins in control group, LPS group and OA high-concentration group, were detected. RESULTS Compared to the LPS group, the number of spindle-shaped and irregular cells gradually decreased in OA groups, the contents of NO, ROS (except for OA low-concentration group), TNF-α, IL-6 and IL-1β, the mRNA expressions of TNF-α, IL-6 (except for OA low-concentration group) and IL-1β as well as the protein expressions of phosphorylated NF-κB p65 (p-NF-κB p65), p-IκBα, and Kelch-like ECH-associated protein 1 (Keap1) were decreased significantly (P<0.05). The contents of IL-4 and IL-10, protein expressions of IκBα, Nrf2 (except for OA low- and medium-concentration groups), HO-1 (except for OA low-concentration group) and NQO1 were all increased significantly (P<0.05). OA of high concentration could inhibit NF-κB p65 protein nuclear translocation and promote Nrf2 protein nuclear translocation. CONCLUSIONS OA can suppress LPS-induced inflammation in RAW264.7 macrophages. The underlying molecular mechanism likely entails the inhibition of the NF-κB signaling pathway, the activation of the Nrf2 signaling pathway and the reduction of ROS and inflammatory factor release.
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Objective:To verify the capability of small intestinal capsule endoscopy with intelligent assistant system based on deep convolutional neural network (DCNN) in the identification and diagnosis of small intestinal bleeding.Methods:A total of 158 235 small intestinal capsule endoscopy images of 1 970 patients were collected from ESView platform (including 3 765 images of 165 patients with small intestinal bleeding) for training of DCNN-based small intestinal capsule endoscopy with intelligent assistant system. In the validation phase, the capability of the system in identification and diagnosis of small intestinal bleeding was verified by images of 100 patients with small intestinal bleeding (10 cases of active bleeding, 31 cases of blood clot and 59 cases of submucosal hemorrhage).Results:Small intestinal bleeding lesions could be identified by the DCNN-based intelligent assistant system, and also could be displayed with mark on the original capsule endoscopy images. This system also could mark multiple bleeding images of the same lesion and multiple different bleeding lesions in the same image. With this system the average reading time of 100 cases of small intestinal bleeding of images the doctors used was (5.23±1.31) minutes per case. The sensitivity of the diagnosis of small intestinal bleeding was 99.00% (95% confidence interval 93.76% to 99.95%).Conclusions:The sensitivity of small intestinal bleeding identification by small intestinal capsule endoscopy with DCNN-based intelligent assistant system is high, which can be used to assist image reading doctors to identify and diagnose of small intestinal bleeding.
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Objective@#To establish a simple, reliable and reproducible animal model of neonatal hypoxic-ischemic encephalopathy (HIE) with similar clinical pathological process to neonates.@*Methods@#Seven days after birth, 180 Sprague-Dawley (SD) rats were randomly divided into six groups: blank control group, experimental control group and four hypoxia groups (8, 10, 12 and 14 min hypoxia groups). Those in the experimental groups were locally anesthetized with 5% lidocaine to separate their tracheas through blunt dissection, followed by tracheal clamping with vascular clamp for 8, 10, 12 and 14 min, respectively. Rats in the experimental control group were only treated with blunt dissection of trachea. No intervention was given to the blank control group. Due to significant reduction in rat survival rate after 14 min of hypoxia, no further morphological or behavioral examination was performed in this group. Rat brain tissue sections were stained with hematoxylin-eosin (HE) 12 h after modeling. Three days after modeling, the rat brain was weighted and the apoptosis of neural cells was detected with terminal deoxynucleotidyl transferase(TdT) mediated dUTP nick end labeling (TUNEL). Morris water maze was used to screen cognitive impairment in these rats at the age of two months. One-way analysis of variance was used for statistical analysis. SNK test and Dunnett 's T3 test were performed to compare homogeneous and non-homogeneous data between groups.@*Results@#Systemic cyanosis, loss of consciousness, paled body, urinary and fecal incontinence, twitching of the limbs and tail and other abnormal behavior were induced by hypoxia. Ischemic necrosis, bleeding, nucleus shrinkage in a large number of neurons and hyperchromatic nuclei were observed in the 8, 10 and 12 min hypoxia groups. Three days after modeling, brain weights of rats in the 8, 10 and 12 min hypoxia groups were lower than those of the blank control group and experimental control group [(1.16±0.07), (1.04±0.06), (0.97±0.12), (1.31±0.06) and (1.28±0.09) g, F=36.437, P<0.001]. However, the numbers of apoptotic cortical [(22.83±4.52), (30.25±3.02), (39.18±5.04), (7.96±2.24) and (8.86±2.49)/400 scope field, F=164.532, P<0.001] and hippocampal CA3 neurons of that three hypoxia groups were higher than those of the two control groups [(14.63±2.26), (20.25±3.02), (24.81±1.98), (4.75±2.66) and (6.67±1.78)/400 scope field, F=141.026, P<0.001]. At the age of two months, rats in the 8, 10 and 12 min hypoxia groups had longer escape latency [(17.99±6.48), (23.07±9.90), (38.94±32.46), (14.37±6.06) and (12.78±7.21) s, F=26.912, P<0.001] and fewer times of platform crossings than those in the control group and experimental control group [(5.00±1.41), (4.90±1.29), (3.75±1.83), (7.57±1.16) and (7.14±1.15) times, F=14.336, P<0.001].@*Conclusions@#Pathological changes in brain tissues and behaviors of rats after modeling are in line with the characteristics of classic animal model of HIE and similar to the clinical pathology and physiology of HIE, and this could be a new, simple, reliable and reproducible animal model of HIE, being capable of controlling the duration of hypoxia accurately.
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Objective To establish a simple, reliable and reproducible animal model of neonatal hypoxic-ischemic encephalopathy (HIE) with similar clinical pathological process to neonates.Methods Seven days after birth, 180 Sprague-Dawley (SD) rats were randomly divided into six groups: blank control group, experimental control group and four hypoxia groups (8, 10, 12 and 14 min hypoxia groups). Those in the experimental groups were locally anesthetized with 5% lidocaine to separate their tracheas through blunt dissection, followed by tracheal clamping with vascular clamp for 8, 10, 12 and 14 min, respectively. Rats in the experimental control group were only treated with blunt dissection of trachea. No intervention was given to the blank control group. Due to significant reduction in rat survival rate after 14 min of hypoxia, no further morphological or behavioral examination was performed in this group. Rat brain tissue sections were stained with hematoxylin-eosin (HE) 12 h after modeling. Three days after modeling, the rat brain was weighted and the apoptosis of neural cells was detected with terminal deoxynucleotidyl transferase(TdT) mediated dUTP nick end labeling (TUNEL). Morris water maze was used to screen cognitive impairment in these rats at the age of two months. One-way analysis of variance was used for statistical analysis. SNK test and Dunnett 's T3 test were performed to compare homogeneous and non-homogeneous data between groups.Results Systemic cyanosis, loss of consciousness, paled body, urinary and fecal incontinence, twitching of the limbs and tail and other abnormal behavior were induced by hypoxia. Ischemic necrosis, bleeding, nucleus shrinkage in a large number of neurons and hyperchromatic nuclei were observed in the 8, 10 and 12 min hypoxia groups. Three days after modeling, brain weights of rats in the 8, 10 and 12 min hypoxia groups were lower than those of the blank control group and experimental control group [(1.16±0.07), (1.04±0.06), (0.97±0.12), (1.31±0.06) and (1.28± 0.09) g,F=36.437,P<0.001]. However, the numbers of apoptotic cortical [(22.83±4.52), (30.25±3.02), (39.18±5.04), (7.96±2.24) and (8.86±2.49)/400 scope field,F=164.532,P<0.001]and hippocampal CA3 neurons of that three hypoxia groups were higher than those of the two control groups [(14.63±2.26), (20.25±3.02), (24.81±1.98), (4.75±2.66) and (6.67±1.78)/400 scope field,F=141.026,P<0.001]. At the age of two months, rats in the 8, 10 and 12 min hypoxia groups had longer escape latency [(17.99±6.48), (23.07±9.90), (38.94±32.46), (14.37±6.06) and (12.78±7.21) s,F=26.912,P<0.001]and fewer times of platform crossings than those in the control group and experimental control group [(5.00±1.41), (4.90±1.29), (3.75±1.83), (7.57±1.16) and (7.14±1.15) times,F=14.336,P<0.001].Conclusions Pathological changes in brain tissues and behaviors of rats after modeling are in line with the characteristics of classic animal model of HIE and similar to the clinical pathology and physiology of HIE, and this could be a new, simple, reliable and reproducible animal model of HIE, being capable of controlling the duration of hypoxia accurately.
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Objective To evaluate the role of ibuprofen and hydrocortisone in early treatment of patent ductus arteriosus ( PDA ) in premature infants with low cortisol level . Method A prospective randomized controlled trial on 144 very low birth weight infants in the Hospital within 24 hours after birth with gestational age of 28~32 weeks and birth weight of 1000~1499 grams,who had asymptomatic PDA diagnosed by echocardiography , introducing early administration of drugs including ibuprofen and /or hydrocortisone within the first 24 ~48 hours after birth.According to the baseline of serum cortisol level measured prior to the administration of drugs , the preterm were assigned into two groups .The low cortisol level group ( the cortisol level <150μg/L) were further subdivided into four groups each being allocated to hydrocortisone or ibuprofen or both of hydrocortisone and ibuprofen combined or placebo treatment .The high cortisol level group ( the cortisol level≥150μg/L) were allocated to either ibuprofen or placebo treatment in randomization.Diameter of ductus arteriosus and cortisol value were measured again after treatment , and the follow-ups were undertaken till discharge .All data was collected and analyzed by statistical software .Result A total of 91 cases were in low cortisol level group ( 22 cases of hydrocortisone , 23 cases of ibuprofen , 21 cases of both hydrocortisone and ibuprofen , and 25 cases of placebo ) and 53 cases in high cortisol level group (26 cases of placebo and 27 cases of Ibuprofen ).Low cortisol level group , combined therapy , closure of the ductus at a rate of 81.0%, was higher than other methods of therapy ( P<0.05);high cortisol level group, the ductus arteriosus closed in 20 patients of ibuprofen therapy ( 74.1%) and in 13 patients of placebo treatment (50.0%) (P<0.05).Early treatment did not significantly increase the drug adverse effects, including impaired renal function , gastrointestinal bleeding , hyperglycemia and others. After comparisons between laboratory changes in early targeted groups and non-early targeted groups after treatment, findings were as follows: decrease in the incidence of apnea , myocardial damage , feeding intolerance , intraventricular hemorrhage and reduce the duration of phototherapy .Conclusion This trial proved the efficacy and safety of early therapy with ibuprofen and hydrocortisone for closure of ductus arteriosus in premature infants with low cortisol level and the decreasing incidence of complications due to PDA without increasing the risk of adverse effects .
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Objective To study the clinical characteristics of inherited metabolic disease(IMD) in the neonatal intensive care unit and to improve the ability of early diagnosis of the disease.Methods A total of 5 590 newborns were hospitalized in the Neonatal Intensive Care Unit (NICU),Fujian Maternity and Children Hospital between January 2012 and April 2015,and 340 neonates who were suspected of IMD consecutively were recruited.Tandem mass spectrometry and gas chromatography-tandem mass spectrometry were used to diagnose IMD.A retrospective study of analyzing the clinical characteristics of the patients of IMD in the NICU was conducted.Results Fifteen neonates were diagnosed as IMD,among whom methylmalonic academia,maple syrup urine disease,hyperphenylalaninemia,citrin deficiency,propionic acidemia,glutaric academia,ornithine transcarbamylase deficiency and primary carnitine deficiency were 5,2,2,2,1,1,1 and 1,respectively.Sixty-six point seven percent (10/15 cases) of IMD onset in the first week after birth were severe.Clinical presentations include the nervous was severe,digestive system and respiratory system symptoms,such as poor response,coma,lethargy,dystonia,convulsion,shortness of breath,dyspnea,milk refusal,diarrhea,jaundice,and so on.The main early manifestations were anorexia,lethargy,seizures and shortness of breath,which were nonspecific.Conclusions Clinical manifestations of IMD are nonspecific.The earlier onset of the disease is more serious,and early tandem mass spectrometry and gas phase chromatography-mass spectrometry are useful for early diagnosis and may guide early clinical intervention.
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Objective To compare the efficacy and safety of oral ibuprofen and indomethacin for the closure of patent ductus arteriosus (PDA) in preterm infants and investigate the factors affecting the effect of indomethacin.Methods Two hundred and four preterm infants with symptomatic PDA were enrolled in this retrospective study.They were divided into two groups accroding to the admission date.From Jan.1,2007 to Dec.30,2009,44 infants orally administered ibuprofen (one course:first dose was 10 mg/kg,followed by two doses of 5 mg/kg at 24 h intervals) were as ibuprofen group.From Dec.31,2009 to Jan.31,2011,160 infants orally administered indomethacin (one course:0.2 mg/kg,at 12 h and 24 h intervals for three times) were as indomethacin group.Chisquare test,t test and rank sum test were used to compare the rate of ductal closure,side effects and complications of two groups.Influence factors of indomethacin therapy were analyzed with Logistic regression.Results There were no differences of overall ductal closure rate [77.3% (34/44) vs 70.6% (113/160),x2 =0.757,P>0.05],one course therapy [68.2% (30/44) vs 63.8%(102/160),x2=0.297,P>0.05] and two courses therapy closure rate [9.1% (4/44) vs 6.9%(11/160),x2 =0.030,P>0.05] between i buprofen group and indomethacin group.The incidences of oliguria [<1 ml/(kg ? h)] and high serum creatinine (>88 μmol/L) of indomethacin group were higher than those in ibuprofen group [21.3% (34/160) vs 6.8% (3/44),x2=4.841,P=0.028;26.9% (43/160) vs 9.1% (4/44),x2=6.156,P=0.013].Logistic regression analysis showed that small gestational age (OR=2.563,95%CI:1.099-5.976,P=0.029),neonatal respiratory distress syndrome (OR=2.407,95%CI:1.023-5.664,P=0.044)and septicemia (OR=4.575,95%CI:1.782-26.768,P=0.009) were unfavorable factors for ductal closure in preterm infants underwent indomcthacin therapy,while antenatal steroid (OR=0.530,95%CI:0.312-0.901,P=0.018) was a favorable factor.Conclusions Oral ibuprofen have the same effects as indomethacin on PDA treatment in preterm infants,but with fewer side effects on renal function in terms of urine output and serum creatinine level.Some factors such as septicemia may affect the theraputic effects.
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Objective To investigate the treatment of symptomatic patent ductus arteriosus (PDA) in very low birth weight preterm infants. Methods From January 1, 2008 to December 31, 2010, 78 very low birth weight preterm infants (birth weight<1500 g) were diagnosed as symptomatic PDA. Among which, 42 cases administered orally with indomethacin (0.2 mg/kg, every 12 hrs for three times) were taken as treatment group, while five cases in this group who failed to indomethacin treatment were interrupted with video-assisted thoracoscopic surgery. And 36 cases who did not receive treatment for ductus arteriosus were taken as control group. The clinical outcomes, complications and prognosis of these patients were observed. Results There were no significant differences between the gentle percentage, gestational age, diameter of ductus arteriosus, rate of complicated with heart failure, sepsis, neonatal respiratory distress syndrome and intraventricular hemorrhage of two groups (P>0.05, respectively). The ductus arteriosus closed in 33 patients of treatment group (78.6%) and in nine patients of control group (25.0%)(χ2=22.39,P=0.000). There were no significant differences in serum creatinine level and platelet count between before and after the treatment in treatment group(P>0.05). Compared with control group, the treatment group had lower incidence of intraventricular hemorrhage (z=1.167, P=0.030), shorter duration of oxygen therapy [(8.0±5.5) d vs (13.3±9.3) d, t=2.225, P=0.032] and shorter hospital stay [(39.0±7.7) d vs (43.6±10.6) d, t=2.229, P=0.029]; while the incidence of bronchopulmonary dysplasia and necrotizing enterocolitis were similar (P>0.05). The five cases of PDA who received video-assisted thoracoscopic surgery were successfully interrupted with no residual shunt left, while three of them had lung infections and one had pleural effusion, but no pneumothorax and infant death associated with surgery occurred. Conclusions Symptomatic PDA of very low birth weight preterm infants should be treated actively. Oral indomethacin was an effective and safe method to cure the PDA in these infants. Surgical ligation under video-assisted thoracoscopic surgery after failure of indomethacin treatment might be a good option.