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Objective:To evaluate the efficacy and safety of linaclotide with polyethylene glycol in bowel preparation.Methods:From September 2021 to February 2022, 240 patients who visited the Department of Gastroenterology, Third People′s Hospital of Hubei Province, Jianghan University and underwent colonoscopy were selected. According to the random number table, in the ratio of 1 to 1, the patients were divided into the linaclotide with polyethylene glycol group and the simple polyethylene glycol group, with 120 cases in each group. The patients in the linaclotide with polyethylene glycol group took 580 μg linaclotide and 2 L polyethylene glycol electrolyte powder solution, and the patients in the simple polyethylene glycol group took 3 L polyethylene glycol electrolyte powder solution. The Boston bowel preparation scale(BBPS) score, the detection rate of polyps or adenomas, the insertion time of colonoscopy, the withdrawal time of colonoscopy, the time of the first defecation, the frequency of defecations, the success rate of cecal intubation, the occurrence of adverse effects and the satisfaction rate of patients were compared between the 2 groups. Independent sample t test and chi-square test were used for statistical analysis. Results:A total of 235 patients completed bowel preparation and accepted colonoscopy. There were no statistically significant differences in the BBPS score, the detection rate of polyps or adenomas, the insertion time of colonoscopy, the withdrawal time of colonoscopy, the success rate of cecal intubation and the frequency of defecations between the linaclotide with polyethylene glycol group and simple polyethylene glycol group(7.3±1.1 vs. 7.0±1.2; 58.1%, 68/117 vs. 60.2%, 71/118; 38.5%, 45/117 vs. 39.8%, 47/118; (4.2±1.9) min vs.(4.3±1.6) min; (5.9±2.7) min vs.(6.2±2.4) min; 100.0%, 117/117 vs. 100.0%, 118/118; 5.3±2.3 vs. 5.1±2.7; all P>0.05). The rate of adverse effects of the linaclotide with polyethylene glycol group was lower than that of simple polyethylene glycol group(25.6%, 30/117 vs. 39.8%, 47/118), the satisfaction rate of patients was higher than that of the simple polyethylene glycol group (93.2%, 109/117 vs. 76.3%, 90/118), and the differences were statistically significant( χ2=0.24 and 0.64, P=0.018 and 0.031). Conclusion:Compared with the 3 L polyethylene glycol regimen, 580 g linaclotide with 2 L polyethylene glycol regimen can achieve the same bowel preparation effect with higher safety and patient satisfaction, which is worthy of clinical application.
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Purpose@#The role of vacuolar protein sorting 34 (Vps34), an indispensable protein required for cell vesicular trafficking, in the biological behavior of hepatocellular carcinoma (HCC) has yet to be studied. @*Materials and Methods@#In the present study, the expression of Vps34 in HCC and the effect of Vps34 on HCC cell invasion was detected both in vivo and in vitro. Furthermore, by modulating the RILP and Rab11, which regulate juxtanuclear lysosome aggregation and recycling endosome respectively, the underlying mechanism was investigated. @*Results@#Vps34 was significantly decreased in HCC and negatively correlated with the HCC invasiveness both in vivo and in vitro. Moreover, Vps34 could promote lysosomal juxtanuclear accumulation, reduce the invasive ability of HCC cells via the Rab7-RILP pathway. In addition, the deficiency of Vps34 in HCC cells affected the endosome-lysosome system, resulting in enhanced Rab11 mediated endocytic recycling of cell surface receptor and increased invasion of HCC cells. @*Conclusion@#Our study reveals that Vps34 acts as an invasion suppressor in HCC cells, and more importantly, the endosome-lysosome trafficking regulated by Vps34 has the potential to become a target pathway in HCC treatment.
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Narcolepsy is a rare disease that presents with sleep-wake disorder, which divided into narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). NT1 accounts for more than 75%, which is characterized by excessive daytime sleepiness (EDS), cataplexy attacks and nocturnal sleep symptoms (e.g. sleep paralysis, hallucinations, sleep disruptions, sleep movement disorders, etc.), accompanied by metabolic, psychiatric and emotional disturbances. The main clinical manifestation of NT2 is EDS, without cataplexy and nonspecific other symptoms of NT1. The treatments of narcolepsy mainly include the treatments of EDS and cataplexy, as well as the improvement of nocturnal sleep. This article will elaborate the advances in clinical manifestations and treatments of narcolepsy.
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Objective To investigate the effect of different enteral nutrition (EN) preparations on nutritional status and glucose metabolism in elderly heart failure (HF) patients. Methods Eighty-two elderly HF patients were consecutively admitted to Taizhou Enze Medical Center Group Enze Hospital from January 2017 to March 2018, and they were randomly divided into a study group and a control group, each group with 41 cases. The basic treatments were the same in two groups, while the patients in study group were treated with TPF-D emulsion, and those of control group were treated with SP emulsion. Nutritional status [serum albumin (Alb), proalbumin (PA) and transferrin (TF)], glucose metabolism indexes (glucose, Betatrophin and insulin dose), cardiac function [N-terminal B-type pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF)], high-sensitivity C-reactive protein (hs-CRP) in serum were compared between two groups after treatment, and the incidences of adverse reactions (gastric retention, diarrhea, constipation, electrolyte abnormality, pulmonary infection, dysfunction of liver) were also observed in the two groups. Results In the aspect of nutrition, no statistical significant differences in indexes were found at each time point between the two groups during the therapeutic course (all P > 0.05). In terms of glucose metabolism, the blood glucose levels in the study group were significantly lower than those in the control group on day 5 and day 7 after treatment (mmol/L: 9.73±3.69 vs. 11.56±3.78 on day 5, 8.35±2.17 vs. 10.41±2.38 on day 7, both P < 0.05); the serum Betatrophin levels in the study group were also significantly lower than those in the control group on 5 days and 7 days (μg/L: 5 days was 1.36±0.49 vs. 1.89±0.74, 7 days was 1.31±0.47 vs. 1.62±0.59, both P < 0.05); the doses of insulin used in the study group were obviously lower than those in the control group on 3, 5 and 7 days (U: 3 days was 37.86±8.49 vs. 47.84±10.33, 5 days was 29.33±7.45 vs. 38.56±9.69, 7 days was 13.35±8.56 vs. 28.49±9.77, all P < 0.05). In terms of cardiac function, the study group showed significant lower NT-proBNP levels on 3, 5 and 7 days (μg/L: 3 days was 5.8±0.8 vs. 6.2±1.0, 5 days was 3.7±0.7 vs. 4.4±0.9, 7 days was 1.9±0.5 vs. 3.1±0.7, all P <0.05]; significant higher level of LVEF in study group on 7 days (0.50±0.02 vs. 0.48±0.03, P < 0.05) and significant lower hs-CRP levels in study group on 5 days and 7 days (μg/L: 5 days was 27.12±10.58 vs. 34.41±12.69, 7 days was 15.33±9.87 vs. 22.71±11.45, both P < 0.05). In addition, compared with the control group, the incidence of gastric retention [17.07% (7/41) vs. 36.59% (15/41)], so of diarrhea [14.63% (6/41) vs. 34.15% (14/41)] and of electrolyte abnormalities [14.63% (6/41) vs. 39.02% (16/41)] were significantly lower in study group than those in the control group (all P <0.05). Conclusion Compared with SP, TPF-D not only can effectively improve the nutritional status, but also can superiorly control blood glucose, improve cardiac function and lower the incidence of adverse reactions in elderly HF patients.
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The pathogenesis of narcolepsy type 1 is characterized by massive loss of hypocretin neurons in the lateral hypothalamus.Due to the extensive interaction between the hypocretin signalling pathway and the autonomic nerve centre of brain stem and spinal cord,narcolepsy type 1 patients often showed autonomic nervous dysfunctions,such as circadian rhythms/sleep abnormalities,energy metabolism and body temperature regulation disorder,pupil adjustment disorder,sexual dysfunction and autonomic fluctuations during cataplexy.We reviewed the autonomic dysfunction of the narcolepsy type 1 patients in general and during cataplexy,in order to strengthen the attention to autonomic nervous dysfunction in narcolepsy type 1.
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Objective@#To investigate the expression and significance of ubiquitin-specific proteases 2-69(USP2-69) in invasive ductal carcinoma of breast.@*Methods@#Twenty-four cases of human breast tissue with invasive ductal carcinoma diagnosed at Huanshan Hospital, Fudan University from 2013 to 2015 were collected, and the expression of USP2-69 mRNA and protein was detected by molecular hybridization, Western blot and immunohistochemistry. USP2-69 was over-expressed in cultured human breast cancer cell line MCF-7 by USP2-69 plasmid transfection. The cellular proliferative activity was investigated in vitro.@*Results@#The USP2-69 mRNA and protein were highly expressed in breast invasive ductal carcinoma, compared to adjacent normal tissues (P<0.01). Ki-67 protein expression was also increased in cases with high USP2-69 protein level. Western blot showed significantly higher USP2-69 protein level in cancer tissue compared to the adjacent normal tissue. In the cultured tumor cells, there was increased S phase fraction, cellular proliferation rate, flat positive clones, cyclin D1 expression and decreased p27 expression in USP2-69-transfected MCF-7 cells.@*Conclusions@#USP2-69 is over-expressed in breast invasive ductal carcinoma, and is closely related to proliferation promoting effects. The data provide an important experimental basis for further study on the molecular mechanism of breast cancer cell proliferation.
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Objective To investigate the application of ultrasonic examination for patients with liver cirrhosis after transjugular intrahepatic portosystemic shunt (TIPS) in the stents in artificial channel (SIAC) and portal vein (PV).Methods The clinical data of 28 patients who were admitted into our hospital from January 2013 to February 2017 and received TIPS were analyzed.Scanned the stents in artificial channel and portal vein and their inner diameter through transabdominal probe,and then measured the blood flow velocity by doppler.ResultsAfter TIPS,the SIAC of cirrhosis patients showed parallel tubular high echo,smooth wall and clear vessel lumen.And the inner diameter of SIAC was (5.93±0.76)mm,the blood flow velocity was (97.14±28.46)cm/s,and the 95% reference value was 4.45 mm~7.41 mm and 41.36~152.92 cm/s respectively.And the inner diameter of PV was (12.40 mm±2.90)mm,the blood flow velocity was (38.33 cm±16.01)cm/s,and the 95% reference value was 6.72~18.08 mm and 22.32~49.34 cm/s respectively.Conclusion Ultrasonography can give objective evaluation of whether SIAC and PV is unobstructed after TIPS,and it can get their parameters of inner diameter and velocity.As a result, ultrasonography can be regard as a perfect means for follow-up checkup.
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Objective To explore the changes in the endogenous sulfur dioxide (SO2) pathway in the myocardial hypertrophy induced by the angiotensin Ⅱ (Ang Ⅱ) in mice.Methods Fourteen healthy C57BL mice,9 weeks old,were randomly divided into control group(n =7) and Ang Ⅱ group(n =7),and capsule osmotic pump with pre loaded 9 g/L saline and Ang Ⅱ was implanted into the back of each mouse subcutaneously.Mter 2 weeks,the mice were executed.The heart weight/body weight (HW/BW) and the left heart weight/full heart weight (LVW/HW) of the mice were measured.The microstructure of the cardiac myocyte was observed by hematoxylin-eosin (HE) staining under the microscope.The expression of myocardial alpha myosin heavy chain (α-MHC) was detected by immunohistochemistry and Western blot methods.SO2 enzymes aspartate aminotransferase 1 (AAT1) and AAT2 protein expression were detected by Western blot method.Myocardial SO2 content and AAT activity were measured by high performance liquid chromatography with fluorimetric detection and colometric method.Results Compared with control group,the HW/BW and LVW/HW in mice of Ang Ⅱ group were significantly increased (all P < 0.O1),the cardiac myocytes were hypertrophy,and α-MHC positive staining in the cytoplasm of myocardium was weakened.Moreover,Western blot data showed that α-MHC protein expression in heart tissue of Ang Ⅱ-treated mice was decreased significantly (allP < 0.05).Simultaneously,the data showed that AAT2 protein expression,SO2 content and AAT activity in heart tissue of Ang Ⅱ-treated mice were also decreased markedly[(1.093 ±0.131) μ mol/g protein vs.(0.737 ±0.233) μmol/g protein,P < 0.05;(7.979 ± 1.317) U/rmg protein vs.(6.470 ± O.516) U/mg protein,P < 0.01].Furthermore,there was a negative correlation between LVW/HW and cardiac SO2 content in heart tissue (r =-0.56,P < 0.05).Conclusions Myocardial endogenous SO2/AAT2 pathway is down-regulated in the development of myocardial hypertrophy induced by Ang Ⅱ in mice.
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Objective To explore the relationship between the respiratory disturbance index (RDI) detected by cardiopulmonary coupling (CPC) and all parameters of polysomnography (PSG), and to analyze the correlation of the two different analytical techniques for the interpretation of sleep breathing events.Methods In this case-control study, the patients′ CPC and PSG were simultaneously recorded at the Sleep Clinic at Changzheng Hospital from Janunary 2016 to December 2016.Effective recordings were obtained from 292 patients (male/female: 173/119).According to PSG, these patients were divided into two groups: obstructive sleep apnea hyponea syndrome (OSAHS) group (n=173, aged (50.1±13.3) years) and non-OSAHS group (n=119, aged (50.5±11.7) years).All the PSG parameters and the RDI detected by CPC were compared between the two groups.Pearson correlation was used to analyze the relationship between the CPC-RDI and polysomnography parameters, and Bland-Altman chart was used to test the correlation of the two methods.The receiver operator characteristic curve was used to research the value of CPC-RDI in diagnosis of OSAHS.Results The OSAHS group showed higher levels of total sleep time (TST, (445.94±82.64) min), apnea times ((108.16±35.70)/h), hypopnea rate ((55.62±17.44)/h), apnea hyponea index (AHI, (22.78±20.73)/h), Epworth Sleeping Scale (ESS) scores ((11.21±5.30) scores), CPC-RDI ((32.98±22.19)/h) compared with the non-OSAHS group ((417.21±96.10) min,t=2.730;(7.89±5.41)/h,t=30.384;(11.05±2.23)/h, t=27.709;(5.51±3.11)/h,t=9.014;(7.61±2.29)scores,t=6.973;(11.16±8.63)/h,t=10.205, all P<0.01), and a significant decrease in N1 latency ((14.79±9.29) min vs (18.18±8.98)min, t=-3.106), N3% ((6.53±4.95)% vs(8.83±7.29)%,t=-3.212) and the lowest oxygen saturation (SaO2;(77.91±12.21)% vs(92.72±5.17)%, t=-12.479, all P<0.05 respectively).Pearson correlation analysis indicated that RDI was positively correlated with TST, N2 sleeping time, N3 sleeping time, AHI, microarousals index, leg movements index, and ESS scores (P<0.01 respectively).Remarkably, the correlation between CPC-RDI and PSG-AHI was excellent (r=0.801, P<0.01), and CPC-RDI was negatively correlated with lowest SaO2 (r=-0.765, P<0.01).Bland-Altman showed that the points in the limits of agreement accounted for more than 95% of all points.If CPC-RDI is higher than 18.95, the subjects were more likely with OSAHS.The sensitivity was 62.9% and the specificity was 88.7%.In addition, the enhanced low-frequency coupling parameters in the CPC analysis technique can clearly analyze the central respiratory rhythm disturbance.Conclusions CPC technology is an effective assessment technology to diagnose sleep-disordered breathing, and correlates well with AHI detected by traditional PSG.It shows the advantage of screening for central sleep apnea.
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Intraocular pressure detection has a great significance for understanding the status of eye health, prevention and treatment of diseases such as glaucoma. Traditional intraocular pressure detection needs to be held in the hospital. It is not only time-consuming to doctors and patients, but also difficult to achieve 24 hour-continuous detection. Microminiaturization of the intraocular pressure sensor and wearing it as a contact lens, which is convenient, comfortable and noninvasive, can solve this problem because the soft contact lens with an embedded micro fabricated strain gauge allows the measurement of changes in corneal curvature to correlate to variations of intraocular pressure. We fabricated a strain gauge using micro-electron mechanical systems, and integrated with the contact lens made of polydimethylsiloxane (PDMS) using injection molding. The experimental results showed that the sensitivity was 100. 7 µV/µm. When attached to the corneal surface, the average sensitivity of sensor response of intraocular pressure can be 125.8 µV/mm Hg under the ideal condition.
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Humans , Contact Lenses, Hydrophilic , Dimethylpolysiloxanes , Glaucoma , Intraocular Pressure , Tonometry, OcularABSTRACT
MicroRNA has speciifc biological and expression properties in transcription level, which has more potential than genomic DNA in the identification for forensic body fluid, species and degraded crime biological materials. Here we introduce the speciifc research of forensic body lfuid identiifcation, research strategies and applied perspectives with forensic miRNA, expecting to provide the application and study of miRNA analysis for reference.
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Using of high throughput sequencing technology to study the microbial diversity in complex samples has become one of the hottest issues in the field of microbial diversity research. In this study, the soil and sheep rumen chyme samples were used to extract DNA, respectively. Then the 25 ng total DNA was used to amplify the 16S rRNA V3 region with 20, 25, 30 PCR cycles, and the final sequencing library was constructed by mixing equal amounts of purified PCR products. Finally, the operational taxonomic unit (OUT) amount, rarefaction curve, microbial number and species were compared through data analysis. It was found that at the same amount of DNA template, the proportion of the community composition was not the best with more numbers of PCR cycle, although the species number was much more. In all, when the PCR cycle number is 25, the number of species and proportion of the community composition were the most optimal both in soil or chyme samples.
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Animals , Bacteria , Classification , DNA, Bacterial , Genetics , Gene Library , High-Throughput Nucleotide Sequencing , Polymerase Chain Reaction , Methods , RNA, Ribosomal, 16S , Genetics , Rumen , Microbiology , Sheep , Soil MicrobiologyABSTRACT
Molecular targeted therapy (MTT) refers to a new therapy designed to interfere with a specific molecular target or signaling pathway that may have a significant influence in tumor growth or progression. MTT can inhibit cell proliferation and induce apoptosis by specific interventions in the signaling pathways of tumor cells. MTT exhibits potential as an effective treatment against cancer. This approach can improve the ability to kill cancer cells and reduce damage to normal tissues. MTT has gradually been used clinically in treating cancer and shown advantages over traditional methods. This paper reviews research progress in this targeted therapy to treat gynecological cancer.
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Hespintor is an unknown function protein that was got from hepatoblastoma cell lines HepG2 by suppression subtractive hybridization technique (SSH), sequence analysis showed that the protein is a new member of secretory type of Kazal type serine protease inhibitor (Serpin) family, and has high homology with esophageal cancer related gene 2 (ECRG2). The coding sequence of Hespintor's Kazal domain was subcloned into prokaryotic expression vector pET-40b(+), then transformed into Rosetta (DE3). A recombinant protein about 42 kDa in the form of inclusion body was optimization expressed by inducing with 0.25 mmol/L IPTG, 30 degrees C for 5 h. and its specificity was confirmed via Western blotting. The recombinant protein was purified by metal chelate affinity chromatography (MCAC) and anion-exchange chromatography. The preliminary experimental result showed that the recombinant protein can inhibit trysin hydrolysis activity specifically. The result clearly demonstrated that Hespintor, as a novel member of Serpin, would be valuable in developing anti-tumor agents.
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Humans , Escherichia coli , Genetics , Metabolism , Genetic Vectors , Genetics , Hep G2 Cells , Proteinase Inhibitory Proteins, Secretory , Recombinant Proteins , Genetics , Serine Peptidase Inhibitors, Kazal Type , Serine Proteinase Inhibitors , Classification , GeneticsABSTRACT
Objective To study the effects of sleep inertia (SI) of different time course sleeps on sleep stages and cognitions in healthy men after 30 h sleep deprivation,and also to investigate the mechanism of cognitive functions impairment in sleep inertia stages and the influential factors of sleep inertia.Methods Ten healthy men (age,(20.8 ±2.1) years) participated in the program.The program was divided into 2 stages.First,participants attended a series of tests after 20 min nap(20 min nap group)after 30 h sleep deprivation.The testing series included 3 parts:the continuous performance task,the Stroop Tests,and the Addition Tests.The series of tests were done 3 times immediately after the volunteers were awoken and each lasted about 15 minutes with an interval of 10 minutes between each test.The polysomnogram (PSG) was recorded during the nap.The following 7 days was set as washing-out period to ensure a complete recovery.Participants repeated the similar processes with 2 h nap(2 h nap group) instead of 20 min nap.The cognitive performance of each group was compared with each other along with the best cognitive performance in awakening to estimate whether or not the cognitive abilities regained the normal condition.Results ( 1 ) Sleep latency became shortened in both groups after 30 h sleep deprivation.There were no slow wave sleep (SWS) and rapid eye movement sleep (REM) sleep stages in the 20 min naps,while the percentage of SWS was increased and percentage of REM declined in 2 h naps.(2)In the early of SI (5 min after awaking),cognitive tasks showed that the abilities of continuous attention,selected attention and addition ability were all impaired (continuous performance task:(371.8 ± 21.3 ) times/3 min vs (334.4 ± 22.4) times/3 min,( 373.2 ± 19.0) times/3 min vs ( 323.7 ± 23.8) times/3 min,t =10.443,7.774,both P<0.01; Stroop tests:(20.3 ±1.5) points vs(17.3 ± 1.0) points,(21.5 ±0.8)points vs( 16.1 ± 1.4 ) points,t =8.478,4.934,both P < 0.05 ; Addition Tests:( 222.2 ± 13.2 ) s vs ( 266.6 ±23.7 ) s,( 226.3 ± 10.9) s vs ( 267.6 ± 23.4 ) s,t =5.748,6.685,both P < 0.01 ).The cognitive functions impairments of 2 h nap group were more severe at the initiation of sleep inertia,but regained the normal condition more quickly.Different cognitive tasks recovered at different speeds.The dispersion of SI needed 30 min.Conclusions ( 1 ) There are difference in the sleep construction and awaked sleep stage between 20 min nap and 2 h nap groups.(2) SI exerts negative influences on cognitive performances of continuous attention,selected attention and addition after sleep deprivation.Many factors may influence the dispersion of SI,including sleep debt,compensation of sleep debt and others.(3) Fragments of sleep are unfavorable to the recovery of body.
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Objective To study the clinical significance of the change of plasma BNP levels in patients with grades sepsis and its correlation with the left ventricular ejection fraction.Methods One hundred patients of sepsis who were admitted in intensive care unit of Taizhou hospital were selected.It was divided into four groups:30 patients with septic shock,40 patients with severe sepsis,30 patients with sepsis and 20 persons without disease as control group.The concentration of plasma BNP was determined using sandwich immunoflurescence,and ultrasonic cardiogram was used to evaluate heart function and clinical features in all groups.To compare with the differences of the concentration of plasma BNP and the correlation between the concentration of Plasma BNP and LVEF in all groups,the data of clinical features,28-day mortality,prognostic values of BNP and the length of stay (ROG) in ICU were collected and compared.Result Plasma BNP levels in patients with septic shock[ (976.3 ± 160.7) pg/ml] were obvious higher than severe sepsis[ (648.4 ± 267.3) pg/ml ],sepsis [ (217.2 ± 89.7) pg/ml ] and control group [ (50.3 ± 25.4)pg/ml] (P <0.01).LVEF in patients with septic shock [ (48.2 ±9.6)% ] was obvious lower than severe sepsis[ (52.8 ±9.4)% ],sepsis[ (61.3 ± 8.9)% ] and control group[ (66.4 ±9.3)% ] (P <0.05 or P <0.01).It appeared to be inverse relationship between LVEF and the plasma BNP levels (r =-0.876,-0.724,P <0.01).BNP levels were significantly higher in non-survivors compared with survivors[ (1367.6±506.4)pg/ml vs (420.3 ±82.6)pg/ml,P <0.01 ].The receiver operating characteristic (ROG) curves indicated that values of areas under the curve of plasma BNP levels for 28-days mortality were 0.918(P <0.01).Conclusion The concentration of plasma BNP in patients was different in different grades of sepsis.It appeared to be negative correlation between the concentration of plasma BNP and LVEF.Plasma BNP levels had predictive value to the patients with sepsis.
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Objective To establish an animal model of rapid eye movement (REM) sleep deprivation (SD) and an animal model for perifornical nucleus microdialysis and investigate the change of cognition, hypocretinergic system and GABAergic system in rats' hypothalamus after various degrees of REM sleep deprivation and sleep revival and two GABAergic drugs intervention. Methods The modified multiple platform method (MMPM)was used to establish sleep deprivation model and the cognitive function was assessed by Morris' water maze. Immunofluorescence technique was used to analyze the number of Hypocretin (Hcrt) immunoreactive neurons, total Fos immunoreactive neurons, Hcrt and Fos colabeled neurons, and the integrated optical density ( IA ) of GABAA Rαl immunoreactive area in rats' hypothalamus.High performance liquid chromatograph (HPLC) was used to quantitatively analyze the level of GABA and Gluin in the rats' hypothalamus. Two GABAergic drugs, a selective GABAA R antagonist, SR-95531, and a selective blocker of type 1 GABA transporter (uptake blocker), NO-711, were used for perifornical nucleus microdialysis. Results There was no statistically significant difference in tests between CC and TC ( Define CC and TC). There was a significant decrease (P < 0. 05 ) of cognitive function measured by Morris maze test in SD 3 d, SD 5 d and RS 6 h of SD groups compared with CC and TC groups. Number of Fos immunoreactive, F+ &H+ immunoreactive neuronsand IA of GABAA Rαl immunoreactive area were all significantly increased ( P < 0. 05 ). Content of GABA measured by HPLC was also increased ( P < 0. 05 ). However, all these changes were partly reversed by sleep revival SR-95531 and NO-711 had different effect on these changes. Conclusions Sleep deprivation, no matter mild or severe, has adverse effects on cognitive function. Activities of both GABAergic and Hcrtergic system are increased during REMSD. These two neurons system could be regulated by each other and the relationship between them is positive correlation. GABAergic system also had self-regulation during REMSD, but microdialysision of either SR-95531 or NO-711 acquired adverse effects on cognitive function of rats. So GABAergic system is not an optimal therapeutic target. Because GABAergic and Hcrtergic system has inhibitory effect on each other,suppressing activity of Hcrtergic system might be a promising therapeutic target.
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Objective To evaluate the efficacy of eszopiclone for patients with acute insomnia and the impact of premedication with eszopiclone on sleep structure of patients with acute insomnia.Methods In an open-label,self-control trial was conducted at Changzheng Hospital Sleep Centers,and patients (n =32) with acute insomnia (12 men,20 women; mean age,36.2 years) were administered eszopiclone 3 mg for three consecutive nights.Sleep was monitored via polysomnography.The insomnia severity index (ISI),and mini-mental state examination (MMSE) were used to assess the degree of insomnia and impact of drugs on cognitive function during the day.Results Eszopiclone can shorten sleep latency ( before treatment:(52.92 ± 11.71 ) min,after treatment:(28.2 ± 10.11 ) min; t =-4.376,P <0.01 ),prolong total sleep time(before treatment:(365.22 ±30.13) min,after treatment:(429.18 ±26.93 ) min; t =4.102,P < 0.01 ),decrease wake up times( before treatment:( 5.00 ± 1.92 ) times,after treatment:( 2.73 ± 0.91 )times; t =- 4.592,P < 0.01 ),improve sleep efficiency ( before treatment:72.69% ± 6.32%,after treatment:82.67% ± 4.16% ; t =3.371,P < 0.01 ),reduce awake time ( before treatment:( 88.51 ±17.48) min,after treatment:(65.93 ±21.l0)min; t =-4.592,P <0.01 ),decrease light sleep ( NREM1 period) the percentage of time ( before treatment:12.54% ± 2.10%,after treatment:7.30% ± 2.90% ;t=-3.155,P < 0.01 ),and increase the percentage of slow wave sleep (before treatment:8.03% ±5.37%,after treatment:9.31% ±5.29%; t =4.228,P <0.01).No effect was observed on the percentage of NERM2 period (t =0.731,P >0.05) and REM period (t =-0.813,P >0.05).Eszopiclone can improve the quality of subjective assessment of sleep ( ISI score decreased,t =- 2.551,P < 0.05) and has no significant effect on cognitive function on first the morning after patients taking the medication.Conclusion Eszopiclone can positively regulate the sleep structure in patients with acute insomnia and improve subjective assessment of sleep quality.It is safe and has no significant effect on cognitive function.
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Objective To observe changes in the working memory and brain functional imaging on functional magnetic resonance imaging(fMRI) after 36 hours sleep deprivation (SD) in healthy volunteers and to explore the possible mechanism of the changes.Methods FMRI scannings were performed in ten male healthy young volunteers before and after 36 hours SD and results were analyzed using SPM2 software.Subjects were also tested LTR and PLUS task to measure the persistence and operation of working memory before and after 36 hours SD.Results The reaction time of LTR task after 36 hours SD ( (866 ± 102) ms)was significantly longer than that before SD ( (754 ± 91 ) ms, t = 2.59, P < 0.01 ).The reaction time of PLUS task after SD ( (848 ± 94) ms) was significantly longer ( t = 2.37, P < 0.05 ) than that before SD ( (756 ± 79) ms).The error rate of LTR task after SD (95.3% ± 3.56% ) was significantly higher (t=3.52,P < 0.01 ) than that before SD (84.8% ± 8.71% ).The error rate of PLUS task after SD (95.7% ±4.72% ) was significantly higher (t =3.38 ,P <0.01 ) than that before SD (84.2% ±9.66% ).There were no significant differences between the two tasks.The frontal and parietal lobes, anterior cingulate gyrus and thalamus were activated during memory tasks testing before SD.Brain activation was broader and stronger in PLUS task than in LTR task.After SD, activation in parietal lobe was decreased and activation in prefrontal and thalamus was increased significantly.Conclusions The working memory performance decreased after SD.Both LTR and PLUS tasks of working memory activate frontal and parietal lobes, anterior cingulate gyrus and thalamus.The activation of parietal lobe decreased and the activation of prefrontal lobe and thalamus increased after 36 hours SD.This is the possible mechanism of SD to causes the cognition decline.
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The reversing effect of wild-type PTEN gene on resistance of CI3K cells to cisplatin and its inhibitory effect on the phosphorylation of protein kinase B (AKT) were studied. The expression of PTEN mRNA and protein in OV2008 cells and C13K cells were semi-quantitatively detected by using RT-PCR and Western blotting. Recombinant eukaryotic expression plasmid containing human wild-type PTEN gene was transfected into C13K cells by lipofectamine2000. The expression of PTEN mRNA was monitored by RT-PCR and the expression of PTEN, Akt, p-Akt protein were ana- lyzed by Western blotting in PTEN-transfected and non-transfected CI3K cells. Proliferation and chemosensitivity of cells to DDP were measured by MTT, and cell apoptosis was detected by flow cytometry after treatment with cisplatin. The expression of PTEN mRNA and protein in OV2008 cells were significantly higher than those in C13K cells. After transfection with PTEN gene for 48 h, the expression of PTEN mRNA and protein in C13K cells were 2.04±0.10, 0.94±0.04 respectively and the expression of p-Akt protein (0.94±0.07) was lower than those in control groups (1.68±0.14, 1.66±0.10) (P<0.05). The IC50 of DDP to C13K cells transfected with PTEN (7.2±0.3 μmol/L) was obviously lower than those of empty-vector transfected cells and non-transfected cells (12.7±0.4 μmol/l, 13.0±0.3 μmol/L) (P<0.05). The apopototis ratio of wild-type PTEN-transfected, empty vector transfected and non-transfected C13K cells were (41.65±0.87)%, (18.61±0.70)% and (15.28 ±0.80)% respectively, and the difference was statistically significant (P<0.05). PTEN gene plays an important role in ovarian cancer multidrug resistance. Transfection of PTEN could increase the ex- pression of PTEN and restore drug sensitivity to cisplatin in human ovarian cancer cell line C13K with multidrug-resistance by decreasing the expression of p-Akt.