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Objective:To explore the optimal local treatment pattern of supraclavicular lymph node in breast cancer patients with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM).Methods:Clinical data of 128 breast cancer patients with sISLM admitted to the Fourth Hospital of Hebei Medical University from 2010 to 2015 were retrospectively analyzed. Among them, 68 cases were treated with supraclavicular lymph node dissection combined with radiotherapy, and 60 cases received radiotherapy alone. The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were statistically compared between two groups.Results:Univariate analysis demonstrated that the 5-year LRFS, DMFS, PFS and OS did not significantly differ between two groups (all P>0.05). Multivariate analysis revealed that the local treatment pattern of supraclavicular lymph node was an independent prognostic factor for the 5-year DMFS, PFS and OS (all P<0.05). Subgroup analysis showed that when radiotherapy alone was performed, the 5-year OS of patients in the supraclavicular region radiation dose of>50 Gy group were significantly better than that in the 50 Gy group ( P=0.047). When supraclavicular lymph node dissection combined with radiotherapy was delivered, if the number of dissection was less than 10, the 5-year LRFS, DMFS, PFS, OS of patients in the>50 Gy group were all better than those in the 50 Gy group numerically without statistical significance (all P>0.05). If the number of dissection was ≥10, the 5-year LRFS, DMFS, PFS, OS in the 50 Gy group were better than those in the>50 Gy group numerically, whereas significant difference was only found in the 5-year DMFS ( P=0.028). Conclusions:Supraclavicular lymph node dissection combined with radiotherapy may be the optimal local treatment pattern for supraclavicular lymph node. When radiotherapy alone is performed, a radiation boost to the supraclavicular region may improve OS. When supraclavicular lymph node dissection combined with radiotherapy is performed, if the degree of dissection is low, a radiation boost to the supraclavicular region may bring clinical benefits. However, if the degree of dissection is high, a radiation boost to the supraclavicular region may not bring significant clinical benefits.
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Objective:To investigate effects of different doses of dexmedetomidine on postoperative cognitive function in elderly colon cancer patients undergoing the general anesthesia.Methods:A total of 80 elderly colorectal cancer patients aged 65 to 80 years old who received the surgery with the American Society of Anesthesiologists (ASA) grade Ⅱ-Ⅲ in Benxi Central Hospital of Liaoning Province were selected. According to the random number table, all patients were divided into 4 groups: the experiment group (group DD, group DM, group DX grouped by the dose of dexmedetomidine) and the control group. All groups were intravenously injected with 0.5 μg/kg loading dose dexmedetomidine in 10 minutes before induction of anesthesia; after induction of anesthesia, group DD was continuously pumped into 0.7 μg·kg -1·h -1, group DM was continuously pumped into 0.5 μg·kg -1·h -1, group DX was continuously pumped into 0.2 μg·kg -1·h -1, and all patients had drug withdrawal in 30 min before the end of the surgery. Under the same condition, group NS was injected with the same volume of 0.9% saline. The levels of serum S-100β protein and neuron specific enolase (NSE) of all groups were measured at the day before operation and 30 min, 3 h, 6 h, 12 h, 24 h after operation; Mini-mental state examination (MMSE) score was performed in all groups at the day before operation and 1 d, 3 d, 7 d after operation. The change of postoperative cognitive function and adverse reactions of all groups were also compared. Results:After screening, 72 out of 80 patients met the criteria (19 patients in group DD, 17 patients in group DM, 18 patients in group DX and 18 patients in the control group). There were no statistically significant differences in levels of serum S100β protein and NSE among 4 groups before operation (all P > 0.05), while there were statistically significant differences in levels of S100β protein and NSE at different time points after operation among all groups (all P < 0.05). The levels of S100β protein and NSE after operation in all groups at different time points were higher than those before operation (all P < 0.05). On the 1st day after operation, MMSE scores of 4 groups were significantly different ( P < 0.05); 3 d after operation, the difference in MMSE score was statistically significant when the control group was compared with group DD and group DX (all P < 0.05); 7 d after operation, the difference was statistically significant between the control group and group DX ( P < 0.05). Cognitive function decline or perioperative neurocognitive disorders (PND) occurred in 2 cases in group DD, 1 case in group DM, 2 cases in group DX, 8 cases in the control group. The rate of cognitive function changes in group DD, group DM and group DX was lower than that in the control group ( P < 0.05). Adverse reactions occurred in 9 patients in group DD, 7 patients in group DM, 4 patients in group DX, and 3 patients in the control group, and there was no significant difference in the incidence of adverse reactions among all groups ( P > 0.05). Conclusions:Dexmedetomidine can slow the decline in postoperative cognitive function after general anesthesia and reduce the incidence of PND for elderly patients with colorectal cancer. Furthermore, dexmedetomidine’s improvement on postoperative cognitive function has no dose-dependence.
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Possible mechanisms by which Polygonati rhizoma opposes atherosclerosis (AS) were identified by network pharmacology and molecular docking analyses. The Traditional Chinese Medicine Database (TCMD) and the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to identify the likely active components of Polygonati rhizoma. The potential targets set of Polygonati rhizoma were predicted with the PharmaDB database and the Swiss TargetPrediction database. The targets set for AS was retrieved by OMIM, DisGeNET and NCBI Gene database. We used the STRING platform to construct a protein-protein interaction network of the intersectional targets and performed visual analysis in Cytoscape. The key targets of Polygonati rhizoma in AS were searched by network topology and the resulting GO and KEGG enrichment was analyzed by Clue GO. In addition, the key targets were verified by molecular docking in Discovery Studio 4.0. A total of 45 active ingredients and 51 potential targets were obtained in the treatment of AS. The results of the topology analysis included five key targets: serum albumin, mitogen-activated protein kinase 3, mitogen-activated protein kinase 1, proto-oncogene tyrosine-protein kinase Src and matrix metalloproteinase-9. The 131 GO items showed that the biological process mainly involved the steroid receptor, cell response to steroid stimulation, the phosphatidylinositol-3 kinase signal pathway, and others. The KEGG pathway analysis included 37 pathways, which were closely related to peroxisome proliferation activated receptor signaling pathway, platelet activation pathway, vascular endothelial growth factor pathway, hypoxia inducible factor pathway and adhesion connection pathway. The results of molecular docking proved that the combined activity of the components with potential key targets is excellent. This study proposes mechanisms by which Polygonati rhizoma might act to reverse or minimize AS and provides a scientific basis for clinical research on Polygonati rhizoma.
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OBJECTIVE:To systematically evaluate the effectiveness and safety of dexmedetomidine versus other controlled hypotension drugs for functional nasal endoscopic surgery ,and to provide evidence-based reference for clinic. METHODS : Retrieved from PubMed ,EBSCO,Springer,Ovid,Cochrane library ,CJFD,VIP,Wanfang database ,relevant journals and references of the included literature were also searched manually. RCTs about the effectiveness and safety of dexmedetomidine (trial group)versus other controlled hypotension drugs (control group )for functional nasal endoscopic surgery were collected. After data extraction of included literatures ,quality evaluation with modified Jada quality scoring method ,Meta-analysis was performed by using Rev Man 5.3 software. RERULTS :A total of 8 RCTs involving 497 patients were included. Meta-analysis results showed that compared with control group ,the ratio patients of hypotensive drug supplement [OR =-0.37,95%CI(0.21,0.65),P=0.000 6] and the bleeding volume [MD =-77.74,95%CI(-99.52,-55.96),P<0.001] of trial groups were lower ;hemodynamics such as MAP during extubation [MD =-13.40,95%CI(-16.24,-10.56),P<0.001] and heart rate during extubation [MD =-33.13, 95%CI(-33.40,-26.87),P<0.001] was more stable during extubation ;quality score of Fromme surgical field was higher [MD = -0.80,95%CI(-0.96,-0.65),P<0.001];while the incidence of chill [OR =0.37,95%CI(0.18,0.75),P=0.006],nausea and vomit [OR =0.28,95%CI(0.14,0.59),P=0.008] were lower. CONCLUSIONS :Dexmedetomidine has a certain advantage than routine drugs for controlled hypotension during nasal endoscopic surgery ,and with better safety.
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Dexmedetomidine (DEX) has neuroprotective effects and its efficacy was determined in propofol-treated pups. Postnatal day (P) 7 rats were exposed to propofol and DEX to investigate the induced apoptosis-related gene expression. Furthermore, synaptic structural changes at the cellular level were observed by electron microscopy. Induction of hippocampal long-term potentiation (LTP) of P30 rats and long-lasting performance of spatial discrimination at P30 and P60 were evaluated. After a single propofol exposure to P7 rats, DEX pretreatment effectively rescued the profound apoptosis seen in hippocampal neurocytes, and strongly reversed the aberrant expression levels of Bcl2-like 1 (BCL2L1), matrix metallopeptidase 9 (MMP-9) and cleaved caspase 3 (CC3), and sharply enhanced synaptic plasticity. However, there were no significant differences in escape latency or crossing times in a probe test. This was accompanied by no obvious reduction in search strategies among the rat groups. No impairment of long-term learning and memory in P30 or P60 rats was detected when using a single dose propofol treatment during the most vulnerable period of brain development. DEX was shown to ameliorate the rodent developmental neurotoxicity caused by a single neonatal propofol challenge, by altering MMP-9, BCL2L1 and CC3 apoptotic signaling.
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With the widespread use of traditional Chinese medicine(TCM) and the integration of TCM and western medicine, drug-drug interaction(DDI) is considered as a major cause of therapeutic failures and side effects. Cytochrome P450 enzymes(CYPs) are responsible for large number of drug metabolism. CYP3 A4 and CYP2 D6, two important CYP isoforms, are responsible for about 80% drug metabolism of CYPs super family. The inhibition of CYPs is likely to be the most common factor leading to adverse DDI. Therefore, it is of great significance to predict potential CYP3 A4 and CYP2 D6 inhibitors to prevent the DDI. A fast and low-cost me-thod for calculating and predicting CYP inhibiting components was established in this paper, namely support vector machine(SVM) and molecular docking technology which are used to predict and screen drugs. Firstly, 12 qualitative models of two targets were established by using SVM, and the optimal model was selected to predict the compounds in traditional Chinese medicine database(TCMD). Then, molecular docking technology was used to establish docking model. By analyzing the key amino acids involved in drug-target interactions and combining with SVM model, potential inhibitors of CYP3 A4 and CYP2 D6 were found. From the computational results, astin D and epiberberine exhibited inhibition effect on CYP3 A4 and CYP2 D6, respectively. Astin D was only found in astins family from Aster tataricus, while epiberberine was considered to be the active constituent of Coptidis Rhizoma. Therefore, for the risk of DDI, extra attention should be paid to the source of these potential inhibitors, Asteris Radix et Rhizoma and Coptidis Rhizoma. This computational method provides technical support for discovering potential natural inhibitors of CYPs from Chinese herbs by using SVM and molecular docking model, and it is also helpful to recognize the CYPs-mediated DDI existing in TCM, providing research ideas for further pharmacovigilance of integrated therapy.
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Inhibidores Enzimáticos del Citocromo P-450/análisis , Sistema Enzimático del Citocromo P-450 , Medicamentos Herbarios Chinos/química , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Plantas Medicinales/químicaRESUMEN
Objective To compare the effects of oral use of Compound Danshen Dripping Pills and Mecobalamin Tablets on hemorheology and nerve conduction velocity of diabetic peripheral neuropathy patients. Methods A total of 70 diabetic peripheral neuropathy patients were randomized into treatment group and control group, 35 cases in each group. Both groups were given fundamental treatment for controlling blood glucose, blood lipids and blood pressure, and additionally the treatment group was treated with Compound Danshen Dripping Pills orally and the control group was treated with Mecobalamin Tablets orally. The treatment for the two groups lasted 3 continuous months. The changes of hemorheology and nerve conduction velocity of the two groups were observed before and after treatment. Results After treatment, indexes of hemorheology and nerve conduction velocity of the two groups were much improved(P<0.05 compared with those before treatment). The improvement of hemorheology indexes in the treatment group was superior to that in the control group (P < 0.05), but the difference of improvement of nerve conduction velocity was insignificant between the two groups (P > 0.05). Conclusion The effects of oral use of Compound Danshen Dripping Pills on the nerve conduction velocity of diabetic peripheral neuropathy patients are similar to those of Mecobalamin Tablets, but the pills have better effects on improving hemorheology than the tablets. The results indicated that Compound Danshen Dripping Pills are effective on improving blood flow and nerve conduction velocity of the limbs of the patients.
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BACKGROUND: Human placental mesenchymal stem cells can improve the blood glucose level of diabetes mellitus rats and gestational diabetes rats, but little is reported on its effect on glucagon, adiponectin, and tumor necrosis factor-α in the serum and placental tissues. OBJECTIVE: To investigate the effects of human placental mesenchymal stem cells on the levels of glucagon, adiponectin and tumor necrosis factor-α in the serum and placental tissues in gestational diabetes rats. METHODS: A rat model of gestational diabetes was made by high-fat and high-sugar diet plus low-dose injection of streptozotocin. Passage 3 human placental mesenchymal stem cell suspension (1×1010 cells/L, 0.5 mL) was injected into gestational diabetes rats at gestational days 4 and 11 (4- and 11-day intervention groups). Meanwhile, control rats were given the same amount of normal saline. At 20 days of gestation, blood samples from the abdominal aorta were extracted, and then cesarean section was made to remove the placenta in the gestational diabetes rats. ELISA and real-time PCR were used to detect the levels of glucagon, adiponectin and tumor necrosis factor-α in the serum and placental tissues, respectively. RESULTS AND CONCLUSION: (1) The serum and placental levels of glucagon, adiponectin and tumor necrosis factor-α showed no differences between the 4- and 11-day intervention groups (P > 0.05). (2) Compared with the control group, significantly increased serum adiponectin level and significantly decreased placental glucagon mRNA expression were found in the 4-day intervention group (P < 0.05). (3) Compared with the control group, the serum adiponectin level and the placental glucagon level both had a significant decrease in the 11-day intervention group (P < 0.01), while the serum level of tumor necrosis factor-α was significantly decreased (P < 0.01). To conclude, transplantation of human placental mesenchymal stem cells can vary the adiponectin and glucagon levels, which provides a new research idea and basis for the further study on the possible mechanism of placental mesenchymal stem cells to improve blood glucose level in gestational diabetes rats. Additionally, it is worthy while to notice that gestational diabetes rats given placental mesenchymal stem cells in the early or late pregnancy show no effects on the above indicators.
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Objective To explore the clinical effectiveness of pressure-controlled ventilation-volume guar-anteed(PCV-VG)in obese patients with obstructive sleep apnea syndrome(OSAS)during uvulopalatopharyngo-plasty. Methods 40 obese patients(BMI≥30 kg/m2)with OSAS scheduled for uvulopalatopharyngoplasty under general anesthesia were randomly divided into two groups of volume-controlled ventilation(group V,n = 20)and pressure-controlled ventilation-volume guaranteed(group P,n=20). The heart rate(HR),mean arterial pressure (MAP),arterial partial pressure of oxygen(PaO2)and arterial partial pressure of carbondioxide(PaCO2)were recorded before induction of anesthesia without oxygen inhalation(T0),30 min(T1)and 1 h(T2)after tracheal intubation,and 30 min after extubation(T3). The peak airway pressure(Ppeak),airway resistance(Raw),thoracic compliance (CL),oxygenation index (OI) and respiratory index (RI) were also calculated at T1 and T2 under observation of recovery. Results There were no obvious differences between the two groups of patients before anesthesia and after recovery. Compared with the group V ,PaCO2 ,PPEAK ,Raw at T1 ,T2 and RI at T1 ~ T3 of the group P decreased(P<0.05),while CL at T1,T2 and PaO2,OI at T1~T3 increased(P<0.05). There were no sig-nificant differences in HR ,MAP at the above time points. Conclusions Compared with volume-controlled venti-lation,PCV-VG can effectively enhance thoracic compliance,lower inspiratory pressure and airway resistance ,and decrease intrapulmonary shunt ,which is conductive to improve arterial oxygenation and gas exchange in obese patients with OSAS.
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Objective To study the effect of aqueous extract from Araliae Echinocaulis Radicis et Cortex (AEAE) on expression of TGF-β/BMPs signaling pathway in osteoblasts.Methods The fracture model of rat was established and randomly divided into model group,AEAE low,middle and high dose (3.6,1.8,0.9 g/kg) group.After ig administration for 7 d,the blood was taken from abdominal aorta and the serum was separated.The rats primary osteoblasts were cultured and qualified after alkaline phosphatase staining and alizarin red staining.The osteoblasts were cultured continuously for 48 h in animal serum of the corresponding group.The contents of BMP-2,TGF-β,Smad-1 and Smad-2 were detected by qRT-PCR and Western blotting method.Results Compared with model group,the mRNA level ofBMP-2,TGF-β and Smad-1 in AEAE low,middle and high dose group,Smad-2 mRNA level in middle and high dose group,and the protein level of BMP-2,TGF-β,Smad-1 and Smad-2 in low,middle and high dose groupwere significantly higher than those in model group (P<0.05 and 0.01).Conclusion AEAE can promote the proliferation ofosteoblasts by up-regulating the expression of BMP-2,TGF-β,Smad-1 and Smad-2 in TGF-β/BMPs signaling pathway.
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Objective To evaluate the effect of low-dose norepinephrine on the efficacy of FloTrac∕Vigileo system in guiding goal-directed fluid therapy(GDT)in neurosurgical procedures. Methods Ninety American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes, aged 18-64 yr, with body mass index of 18-24 kg∕m2, of New York Heart Association class Ⅰ or Ⅱ, with left ven-tricular ejection fraction>50%, were divided into 3 groups(n=30 each)using a random number table:control group(group C), group GDT and low-dose norepinephrine plus GDT group(group NE+GDT). The total volume of fluid infused was calculated according to the 4-2-1 rule, and routine fluid therapy was performed in group C. Fluid therapy was performed according to stroke volume variation(SVV)under the guidance of FloTrac∕Vigileo system in group GDT. In group NE+GDT, fluid therapy was performed accord-ing to SVV under FloTrac∕Vigileo system guidance, and norepinephrine 0.01-0.03 μg·kg-1·min-1was intravenously infused at the same time. The total volume of fluid infused, amount of crystalloid solution and colloid solution infused, blood loss, urine volume and requirement for ephedrine were recorded during op-eration. The pH value, base excess, blood lactate and hemoglobin(Hb)were recorded immediately be-fore skin incision and at the end of operation. Results Compared with group C, the amount of crystalloid solution infused and urine volume were significantly reduced, the amount of colloid solution infused was in-creased, the requirement for ephedrine was reduced, the concentration of blood lactate was decreased at the end of operation, and the concentration of Hb was increased in group GDT(P<0.05 or 0.01). There were no significant differences between GDT group and NE+GDT group in the total volume of fluid infused, a-mount of crystalloid solution and colloid solution infused, blood loss, urine volume, blood lactate concen-tration at each time point, pH value, base excess or Hb concentrations(P> 0.05). Conclusion Appli-cation of low-dose norepinephrine(0.01-0.03 μg· kg-1·min-1)in neurosurgical procedures does not affect the efficacy of FloTrac∕Vigileo system in guiding GDT.
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Objective To evaluate the effect of sleep deprivation on cognitive function in the rats undergoing propofol anesthesia.Methods Sixty healthy male Sprague Dawley rats,aged 14-18 weeks,weighing 200-250 g,were randomly assigned into 3 groups (n=20 each) using a random number table:control group (group C),propofol anesthesia group (group P),and sleep deprivation + propofol anesthesia group (group SDP).Propofol was given as a bolus of 15 mg/kg followed by an infusion of 40 mg · kg-1 · h-1 for 2 h in group P.After the rats were subjected to rapid eye movement sleep deprivation for 24 h,the rats received propofol anesthesia in group SDP.Before sleep deprivation,after sleep deprivation,and at 1,3 and 7 days after anesthesia,Morris water maze test was used to assess the learning and memory function,and the escape latency and frequency of crossing the original platform were recorded.Ten rats randomly selected from each group at 1 and 7 days after anesthesia were sacrificed,and brains were removed to observe the morphology of nerve cells in the hippocampal CA1 region (by Nissl's staining) and to detect the expression of phosphorylated Tau at Thr231 (Tau-pThr231) in the hippocampal CA1 region (by immunohistochemisty).Results Compared with group C,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the expression of Tau-pThr231 in the hippocampal CA1 region was up-regulated at 1 day after anesthesia in P and SDP groups (P<0.05),especially in group SDP (P<0.05),and there was no significant difference between the groups at the other time points (P>0.05).The pathological changes were aggravated at 1 day after anesthesia in group SDP compared with group P,and there was no significant difference at 3 and 7 days after anesthesia between group SDP and group P.Conclusion Sleep deprivation can aggravate the transient cognitive dysfunction after propofol anesthesia,and the mechanism is related to promotion of Tau phosphorylation in the rats.
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Objective To investigate the effects of sevoflurane anesthesia in diabetic pregnant rats on the cognitive function of the offspring rats. Methods Forty female Sprague?Dawley rats and 5 male rats, weighing 200-250 g, were used in the study. Twenty pregnant rats at 7 weeks of gestation were randomly selected, and diabetes mellitus was induced by intraperitoneal streptozotocin 45 mg∕kg and confirmed by blood glucose level>10.4 mmol∕L. Twenty pregnant rats at 20 days of gestation, in which diabetes mellitus was not induced, were selected and divided into 2 groups ( n=10 each) using a random number table:sevoflurane group (group S) and control group (group C). Twenty pregnant rats at 20 days of gestation with diabetes mellitus were selected and divided into 2 groups ( n=10 each) using a random number table:sevoflurane group (group DS) and control group ( group DC). In DS and S groups, the pregnant rats were placed in a self?made anesthetic box and inhaled 2% sevoflurane for 2 h. At 6 weeks after birth, the offspring rats were selected, and Morris water maze test was performed. The rats were sacrificed, brains were removed, and the hippocampi and cortex were removed for determination of phosphorylated cyclic a?denosine monophosphate response element?binding protein ( p?CREB) expression using immuno?histochem?istry. Results Compared with group C, the escape latency was significantly prolonged, and the frequency of crossing the original platform was significantly decreased in S and DC groups ( P<0.05) . Compared with group DC, the escape latency was significantly prolonged, and the frequency of crossing the original plat?form was significantly decreased in group DS (P<0.01). Compared with group S, the escape latency was significantly prolonged, the frequency of crossing the original platform was significantly decreased ( P<0.05) , and lighter staining for p?CREB was found, and the number of p?CREB positive cells was decreased in the hippocampus and cortex in group DS. Conclusion Sevoflurane anesthesia?induced cognitive dys?function is aggravated in the offspring rats of diabetic pregnant rats, and the mechanism is related to inhibi?tion of CREB phosphorylation.
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Objective To evaluate the effect of dexmedetomidine on hippocampal neuronal apoptosis in endotoxemic rats.Methods Twenty-four pathogen-free male Sprague-Dawley rats,aged 6 weeks,weighing 200-250 g,were randomly divided into 3 groups(n=8 each)using a random number table:control group (group C),endotoxemia group (group E),and dexmedetomidine group (group D).Dexmedetomidine 50 μg/kg was injected intraperitoneally,and lipopolysaccharide 5 mg/kg was injected via the caudal vein 30 min later in group D.Normal saline 2 ml was injected intraperitoneally,and lipopolysaccharide 5 mg/kg was injected via the caudal vein 30 min later in group E.Normal saline 2 ml was injected intraperitoneally,and normal saline 2 ml was injected via the caudal vein 30 min later in group C.At 12 h after the model was successfully established,Morris water maze test was used to assess the cognitive function.The escape latency,swimming distance and frequency of crossing the original platform were recorded,and the swimming speed was calculated.The rats were then sacrificed,and hippocampi were harvest for determination of neuronal apoptosis (by TUNEL) and expression of glucose-regulated protein 78 (GRP78),CAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12 (by immunohistochemistry).The apoptosis index (AI) was calculated.Results There was no significant difference in the swimming speed between the 3 groups (P>0.05).Compared with group C,the escape latency and swimming distance were significantly prolonged,the frequency of crossing the original platform was significantly decreased,and the AI was significantly increased,and the expression of GRP78,CHOP,and caspase-12 was significantly up-regulated in E and D groups (P<0.05).Compared with group E,the escape latency and swimming distance were significantly shortened,the frequency of crossing the original platform was significantly increased,and the AI was significantly decreased,and the expression of GRP78,CHOP,and caspase-12 was significantly down-regulated in group D (P < 0.05).Conclusion Dexmedetomidine reduces cognitive dysfunction probably through reducing hippocampal neuronal apoptosis mediated by endoplasmic reticulum stress in endotoxemic rats.
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<p><b>OBJECTIVE</b>To identify the incidence and risk factors of perioperative major adverse cardiac events (MACE) in elderly patients with coronary heart disease (CHD) undergoing non-cardiac surgery.</p><p><b>METHODS</b>We prospectively analyzed the clinical data of 360 CHD patients who aged 75 years or older undergoing elective intermediate-to high-risk surgery in five medical centers across China from January 2008 to January 2010. The clinical variables included the 12-lead ECG and Troponin I levels after surgery. The combined outcome was defined as all the perioperative MACE in hospital. The risk factors of MACE and their indexes were analyzed with univariate analysis and multivariable logistic regression in SPSS software,together with a risk scoring and stratification system established.</p><p><b>RESULTS</b>Perioperative MACE occurred in 11.94% of elderly CHD patients undergoing non-cardiac surgery. Seven independent risk factors of perioperative MACE for this population were identified,which included angina within 6 months (P=0.001), hypertension(P=0.014), preoperative haematocrit (HCT) <40% (P=0.050), serum creatinine (Scr)>150 mmol/L (P=0.014), ejection fraction(EF) <50% (P=0.019), intraoperative hyoxemia (P=0.019), and operative time>150 min (P=0.001). The risk indexes of these factors were 4,3,3,6,4,5, and 4, respectively. The rate of perioperative MACE increased significantly as the level of risk stratification elevated.</p><p><b>CONCLUSIONS</b>Elderly CHD patients undergoing non-cardiac surgery are at high risk of perioperative MACE. Angina within 6 months,hypertension, preoperative HCT<40%, Scr>150 mmol/L, EF<50%, intraoperative hyoxemia, and operative time>150 min can increase the risk of MACE. The risk scoring and stratification system based on the risk factor index can be a valuable parameter for assessing the perioperative cardiac risk of noncardiac surgery for elderly CHD patients.</p>
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Anciano , Humanos , China , Enfermedad Coronaria , Procedimientos Quirúrgicos Electivos , Electrocardiografía , Incidencia , Modelos Logísticos , Atención Perioperativa , Factores de RiesgoRESUMEN
Objective To evaluate the effect of edaravone on apoptosis in hippocampal cells in a rat model of endotoxic shock.Methods Thirty-six male Sprague-Dawley rats, weighing 200-250 g, aged 6 weeks, were randomly divided into 3 groups (n=12 each) using a random number table: control group (group C), endotoxic shock group (group ES), and edaravone group (group E).Lipopolysaccharide 10 mg/kg was injected via the femoral vein to establish the model of endotoxic shock in ES and E groups, while the equal volume of normal saline was given in group C.In group E, edaravone 3 mg/kg was intravenously injected immediately after establishment of the model once every 2 h until the animals were sacrificed.The equal volume of normal saline was given instead of edaravone in C and ES groups.At 6 and 12 h after administration of edaravone, 6 rats in each group were sacrificed, and the hippocampi were isolated for determination of malondialdehyde (MDA) content (using thiobarbituric acid method) , tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) contents (using enzyme-linked immunosorbent assay), and cell apoptosis in hippocampal CA1 region (by TUNEL assay).The apoptotic index was calculated.Results Compared with group C, the MDA, TNF-α and IL-6 contents were significantly increased at 6 and 12 h after administration of edaravone, and the apoptotic index was increased at 12 h after administration of edaravone in ES and E groups.Compared with group ES, the MDA, TNF-α and IL-6 contents were significantly decreased at 6 and 12 h after administration of edaravone, and the apoptotic index was decreased at 12 h after administration of edaravone in group E.Conclusion Edaravone can reduce apoptosis in hippocampal cells, and the mechanism is associated with the reduced oxidative stress and inflammatory responses in a rat model of endotoxic shock.
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<p><b>OBJECTIVE</b>To study the effects of perinatal recurrent infection on the brain development in immature mice.</p><p><b>METHODS</b>Six pregnant C57BL6 mice were randomly assigned to three groups: intrauterine infection, perinatal recurrent infection and control. The intrauterine infection group was intraperitoneally injected with LPS (0.5 mg/kg) on the 18th day of pregnancy. The perinatal recurrent infection group was injected with LPS (0.5 mg/kg) on the 18th day of pregnancy and their offsprings were intraperitoneally injected with the same dose of LPS daily from postnatal day 3 to 12. The control group was administered with normal saline at the same time points as the recurrent infection group. The short-time neurobehaviors were assessed on postnatal day 13. The mice were then sacrificed to measure brain weights and neuropathological changes using cresyl violet staining. Western blot was used to evaluate the expression of TNF-α, Caspase-3 and myelin basic protein (MBP).</p><p><b>RESULTS</b>The brain weights of the recurrent infection group were significantly lower than the control and intrauterine infection groups (P<0.05) and the recurrent infection group displayed significant neuropathological changes. Perinatal recurrent infection resulted in increased expression levels of TNF-α and Caspase-3, and decreased expression level of MBP compared with the intrauterine infection and control groups (P<0.01). The neurobehavior test showed that the recurrent infection group used longer time in gait reflex, right reflex and geotaxis reflex compared with the control and intrauterine infection groups on postnatal day 13 (P<0.05).</p><p><b>CONCLUSIONS</b>Perinatal recurrent infection may exacerbate inflammatory response and cell death in the immature brain, which may be one of the important factors for perinatal brain injury.</p>
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Animales , Femenino , Ratones , Embarazo , Animales Recién Nacidos , Infecciones Bacterianas , Peso Corporal , Encéfalo , Patología , Caspasa 3 , Ratones Endogámicos C57BL , Proteína Básica de Mielina , Recurrencia , ReflejoRESUMEN
Objective To evaluate the effects of volume resuscitation with different fluids on expression of aquaporin 1 (AQP-1) in pulmonary capillary endothelial cells of endotoxemic rats.Methods Fifty pathogen-free male Sprague-Dawley,rats,weighing 250-300 g,aged 6-8 weeks,were randomly divided into 4 groups (n =10 each):control group (group C),lipopolysaccharide group (group LPS),NaCl group (group NS),6% hydroxyethyl starch 130/0.4 group (group HES) and hypertonic hydroxyethyl starch 40 group (group HSH).Sepsis was induced with LPS 5 mg/kg injected via the femoral vein.At l0 min after the model was successfully established,the corresponding fluids were infused into the femoral vein at a constant speed (15 ml/kg over 6 h) via a pump.At 0,3 and 6 h after LPS administration,blood samples were collected from the femoral artery for measurement of serum tumor necrosis factor-α (TNF-α) concentrations and for blood gas analysis.PaO2 and lactate (Lac) concentrations were recorded and oxygenation index (PaO2/FiO2) was calculated.The rats were sacrificed at 6 h after LPS administration,and lungs were removed for determination of AQP-1 expression in pulmonary capillary endothelial cells and wet-to-dry lung weight ratio (W/D ratio),and for microscopic examination of the pathological changes which were scored.Results Compared with group C,W/D ratio,serum TNF-α and Lac concentrations,and pathological scores were significantly increased,AQP-1 expression was down-regulated,and PaO2 and oxygenation index were decreased in LPS,NS,HES and HSH groups.Compared with group LPS,W/D ratio,serum TNF-a and Lac concentrations,and pathological scores were significantly decreased,AQP-1 expression was up-regulated,and PaO2 and oxygenation index were increased in NS,HES and HSH groups.Compared with group NS,W/D ratio,serum TNF-α and Lac concentrations,and pathological scores were significantly decreased,AQP-1 expression was up-regulated,and PaO2 and oxygenation index were increased in HES and HSH groups.Compared with group HES,the blood Lac concentrations were significantly decreased,and no significant changes were found in the other parameters in group HSH.Conclusion Volume resuscitation with NaC1,hydroxyethyl starch 130/0.4 and hypertonic hydroxyethyl starch 40 can reduce the lung injury effectively in endotoxemic rats,and hypertonic hydroxyethyl starch 40 provides more significant efficacy,and up-regulated AQP-1 expression in pulmonary capillary endothelial cells is involved in the mechanism.
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Objective To investigate the effects of preoperative sleep disturbance on the efficacy of flurbiprofen for postoperative analgesia in patients undergoing endoscopic nasal surgery.Methods Ninety-six ASA Ⅰ or Ⅱ patients of both sexes (aged 20-60 years and weighing 50-80 kg) undergoing endoscopic nasal surgery were enrolled in this study.Pittsburg sleep quality index was used to evaluate the long-term sleep quality before hospitalization and Athens sleep quality index was used to evaluate the short-term sleep quality in hospital.The patients were divided into four groups according to the types of preoperative sleep disturbance (n =24 each):no sleep disturbance (group Ⅰ),long-term sleep disturbance (group Ⅱ),acute short-term sleep disturbance (group Ⅲ),and long-term + acute short-term sleep disturbance (group Ⅳ).Anesthesia was induced with sufentanil,propofol and cis-atracurium and maintained with intravenous infusion of remifentanil and propofol.Then the patients received endotracheal intubation and mechanical ventilation.The end-tidal pressure of carbon dioxide was maintained at 30-35 mm Hg.Controlled hypotension was performed with nicardipine,and the mean arterial blood pressure was maintained at 50-70 mm Hg and heart rate at 60-90 bpm during operation.The patients received intravenous injection of flurbiprofen 50 mg 15 minutes before the end of operation for postoperative analgesia.When the visual analogue scale score was more than 3 during the first 6 hours after operation,flurbiprofen 50 mg was given intravenously as rescue analgesia.Results The incidence of rescue analgesia administered after operation was significantly greater in groups Ⅱ,Ⅲ and Ⅳ than in group Ⅰ,and greater in group Ⅳ than in groups Ⅱ and Ⅲ.There was no significant difference in the incidence of rescue analgesia administered during the first 6 hours after operation between groups Ⅱ and Ⅲ.Conclusion Preoperative sleep disturbance has adverse effects on the efficacy of flurbiprofen for postoperative analgesia in patients undergoing endoscopic nasal surgery.
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BACKGROUND:Gene therapy has become a new trend for disease therapy and brought promise for some refractory diseases. The key point is to choose the proper cell, gene and vector. OBJECTIVE:To investigate the effectiveness and feasibility of bone morphogenetic protein 2 (BMP2) gene transfected into endothelial progenitor cells (EPCs) from rat bone marrow for gene therapy. METHODS:The EPCs were isolated, cultured and identified from the bone marrow of Sprague-Dawley rats. Empty vector (LV-eGFP) or BMP2 gene (LV-eGFP-BMP2) was transferred into EPCs by the constructed lentiviral vector (LV). We examined the transfection efficiency by eGFP fluorescence, BMP2 secretion by ELISA, BMP2 expression by Western blot, and compared the capacities of migration, proliferation and anti-apoptosis after transfection in the three groups of normal EPCs, empty vector-EPCs, and BMP2-EPCs. RESULTS AND CONCLUSION:The transfection efficiency of lentiviral vector was 90%. BMP2 gene-transferred EPCs secreted and expressed more BMP2 proteins (P0.05). After successful transfection with lentivirus-BMP2 gene, EPCs can secrete and express more BMP2 protein and show enhanced anti-apoptotic ability without obvious influence on the proliferation and migration capacity.