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Objective:To evaluate the role of nuclear factor-erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase-4 (GPX4) signaling pathway-mediated ferroptosis in midazolam-induced reduction of hypoxic-ischemic brain damage (HIBD) in neonatal rats.Methods:Ninety healthy 7-day-old neonatal rats, weighing 16-20 g, were divided into 6 groups ( n=15 each) using the random number table method: sham operation group (Sham group), HIBD group, low-dose midazolam (10 mg/kg) group (group L), medium-dose midazolam (20 mg/kg) group (group M), high-dose midazolam (40 mg/kg) group (group H), and Nrf2 inhibitor ML385 group (group I). The HIBD model was developed by ligating the left carotid artery and exposing to a hypoxic condition for 2 h in anesthetized animals. Starting from 2nd day after developing the model, the corresponding doses of midazolam were intraperitoneally injected in midazolam groups, the equal volume of normal saline was intraperitoneally injected in Sham and HIBD groups, midazolam 40 mg/kg and Nrf2 inhibitor ML385 30 mg/kg were intraperitoneally injected once a day for 8 consecutive days in group I. The rats were weighed and subjected to the Morris water maze test after the end of administration. Blood samples were taken from the abdominal aorta after the end of the Morris water maze test, and then the animals were sacrificed to remove the brain for determination of the concentrations of serum iron, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), contents of iron and GSH in hippocampal tissues (by ultraviolet spectrophotometry and micro method), the number of Nrf2/neuronal nuclear antigen (NeuN) and GPX4/NeuN positive cells (by immunofluorescent staining), and expression of Nrf2, GPX4, and 4-hydroxynonaenoic acid (4-HNE) in hippocampal tissues and for microscopic examination of the pathological changes of hippocampal neurons in brain tissues (after HE staining and Nissl staining). Results:Compared with Sham group, the first time to arrival at platform was significantly prolonged, the number of crossing the origional platform was reduced, and the time of staying at the target quadrant was shortened, the iron content in the hippocampal tissues was increased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were decreased, the expression of Nrf2 and GPX4 was down-regulated, the expression of 4-HNE was up-regulated, the concentrations of serum iron, IL-6 and TNF-α were increased, and the injury to hippocampal neurons was marked in HIBD group ( P<0.05). Compared with HIBD group, the first time to arrival at platform was significantly shortened, the number of crossing the origional platform was increased, and the time of staying at the target quadrant was prolonged, the iron content in the hippocampus tissues was decreased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were increased, the expression of Nrf2 and GPX4 was up-regulated, the expression of 4-HNE was down-regulated, the concentrations of serum iron, IL-6 and TNF-α were decreased ( P<0.05), and the injury to hippocampal neurons was significantly reduced in H, M and L groups. Compared with group H, the first time to arrival at platform was significantly prolonged, the number of crossing the origional platform was reduced, and the time of staying at the target quadrant was shortened, the iron content in the hippocampus tissue was increased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were decreased, the expression of Nrf2 and GPX4 was down-regulated, the expression of 4-HNE was up-regulated, the concentrations of serum iron, IL-6 and TNF-α were increased ( P<0.05), and the injury to hippocampal neurons was aggravated in group I. Conclusions:The mechanism by which midazolam reduces HIBD may be related to activation of the Nrf2/GPX4 signaling pathway and inhibition of hippocampal neuronal ferroptosis in neonatal rats.
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With the concepts of minimal invasive surgery and precision medicine embedding deeply in modern medicine, traditional clinical treatment strategies are constantly updated due to the rapid progression of medical research. Systematic dissection of the regional lymph nodes is a key component in the surgical therapy of gynecologic malignancies, however it may result in a series of complications, such as lower extremity lymphedema, deep venous thrombosis, immune disorders and so on, which seriously impact the patients' quality of life. The necessity of systematic lymphadenectomy and the extent of lymph nodes resection have always been one of the most controversial issues in gynecologic oncology. In recent years, the extensive application of sentinel lymph node (SLN) technology has been increasingly used in the treatment of gynecologic malignancies, which may provide important guidance on this issue. This article reviews the clinical application status, detection methods, detection efficiency, and current controversies regarding SLN mapping and biopsy in cervical cancer, endometrial cancer, ovarian cancer and vulvar cancer, discussing the application value of SLN technology in gynecologic oncology.
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OBJECTIVE:To study the effects of particle size of ticagrelor crude drug on in vitro dissolution behavior of Ticagre-lor tablets. METHODS:Ticagrelor crude drug and different particle size of ticagrelor powder A,B,C,D,E after smashing for dif-ferent time(15,30,40,60 s)were used to prepare the tablet by wet granulation method. Accumulative in vitro dissolution rate of prepared tablets within 60 min were determined by UV spectrophotometry at 300 nm(using 0.2% tween as medium,paddle meth-od). Using original tablet as reference preparation,the similarity factor(f2)method was used to compare the similarity of dissolu-tion behavior between 5 prepared tablets and original tablet. RESULTS:d(0.9)of powder A,B,C,D,E were 69.181,40.778, 24.805,12.611,3.083 μm,respectively. The corresponding f2 were 27.77,36.79,50.06,67.68,79.99. CONCLUSIONS:The par-ticle size of ticagrelor crude drug is much smaller,and the dissolution behavior of prepared tablet is closer to that of original tablet. The in vitro dissolution rate of Ticagrelor tablets is improved remarkably by micronization technology. In order to produce Ticagre-lor tablets with the same bioavailability as original tablet,particle size of ticagrelor crude drug powder should be controlled with d(0.9)≤20μm.
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Objective To evaluate the optimum ratio of medicine dosage for dexmedetomidine mixed with sufentanil used for patient?controlled intravenous analgesia ( PCIA) after Nuss procedure in pedi?atric patients with pectus excavatum. Methods Sixty pediatric patients diagnosed with pectus excavatum, aged 5-12 yr, weighing 18-50 kg, of ASA physical statusⅠorⅡ, scheduled for elective Nuss procedure under general anesthesia, were randomly divided into 3 equal groups using a random number table:different ratios of medicine dosage while dexmedetomidine was added to sufentanil groups ( SD1-3 groups) . Postopera?tive analgesia was as follows: group SD1 received sufentanil 1 μg∕kg + dexmedetomidine 2 μg∕kg; group SD2 received sufentanil 1 μg∕kg + dexmedetomidine 3 μg∕kg; group SD3 received sufentanil 1 μg∕kg +dexmedetomidine 4 μg∕kg. A mixture of tropisetron 0?1 mg∕kg and dexamethasone 0?1 mg∕kg ( in 100 ml of normal saline) was added in each group. The PCA pump was programmed to deliver 0?5 ml with a lockout interval of 15 min and background infusion at 2 ml∕h. The PCA pump was connected immediately after the end of operation, and sufentanil with a dosage of 0?1μg∕kg was used as a rescue analgesic within 48 h post?operatively. The VAS score was maintained below 4. The requirement for rescue analgesics was recorded. The Ramsay sedation scores was recorded at 4, 8, 12, 24 and 48 h postoperatively, and the occurrence of adverse reactions such as nausea and vomiting, bradycardia, over?sedation, respiratory depression, agitation and shivering was recorded within 48 h after surgery. Results No pediatric patients developed nausea and vomiting, respiratory depression, bradycardia, over?sedation, and shivering. No pediatric patients required rescue analgesics in SD2 and SD3 groups. Compared with group SD1 , the requirement for rescue analgesics and incidence of agitation were significantly decreased, and Ramsay sedation scores were increased at 4 and 8 h after operation in SD2 and SD3 groups. Ramsay sedation scores were significantly higher at 4 h after oper?ation in SD3 group than in SD2 group. Conclusion Dexmedetomidine 3 μg∕kg mixed with sufentanil 1μg∕kg is the optimum ratio of medicine dosage when used for PCIA after Nuss procedure in pediatric patients with pectus excavatum.
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Objective To compare the accuracy of bispectral index (BIS),Narcotrend index (NI),index of consciousness (IoC) versus auditory evoked potential index (AAI) in monitoring the depth of sedation induced by propofol.Methods Sixty ASA physical status Ⅰ or Ⅱ patients of both sexes,aged 41-64 yr,with body mass index 20-30 kg/m2,scheduled for elective surgeries under general anesthesia,were enrolled in the study.Propofol was given by target-controlled infusion (TCI) with the initial target effect-site concentration (Ce) of 0.8 μg/ml using Marsh pharmacokinetic model,and then the Ce of propofol was increased by 0.1 μg/ml,and OAA/S was performed.Before TCI of propofol,the values of BIS,NI,IoC and AAI were recorded,and at the same time the value of OAA/S score was 5.During TCI of propofol,when OAA/S score reached 4,3,2 and 1 in turn,the Ce of propofol was recorded,the sequence for determination of the values of BIS,NI,IoC and AAI was determined using a random number table,and the values were then recorded for 5 s after the values were stable and then averaged.The parameters for vital signs were maintained within the normal range.Pearson correlation of BIS,NI,IoC and AAI values with Ce of propofol was analyzed.Results The correlation coefficients of BIS,NI,IoC and AAI values with the Ce of propofol were rBIs-Ce =-0.829,rSI-Ce =-0.886,rloC-Ce =-0.881 and rAAI-Ce =-0.791,respectively.There was no significant difference between rBIS-Ce,rNI-Ce,rIoC-Ce and rAAI-Ce.Conclusion There are no significant differences in the accuracy of BIS,NI,IoC or AAI in monitoring the depth of sedation induced by propofol in middle-aged patients with non-noxious stimuli.
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Objective To investigate general and clinicopathological characteristics of male breast cancer and analyze the factors affecting the outcomes of the patients.Methods Fifty-nine male breast cancer patients treated at Cancer Hospital of Zhengzhou University from January 2002 to December 2011 were included into the study.The clinicopathologic features and 5-year survival rate were retrospectively analyzed.The clinicopathologieal characteristics were investigated by univariate analysis to evaluate the impact of these factors on patient survival.Results The median age at diagnosis was 64 years old in these patients.The positive rate of ER/PR was 74.6 ％ (44/59).The patients were followed up for 9-123 months.The 5-year survival rate was 61％.Patients in stages Ⅰ and Ⅱ had better overall survival than those in stages Ⅲ and Ⅳ.Conclusion The male breast cancer patient has special clinical characteristics.TNM stage is a significant predictor of the overall survival.