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Objective:To study the efficacy of bisoprolol fumarate tablets combined with tiotropium bromide powder aerosol inhalation in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with pulmonary heart disease and its effect on high-sensitivity C-reactive protein (hs-CRP) and brain natriuretic peptide (BNP).Methods:From June 2016 to October 2021, 96 patients with AECOPD complicated with pulmonary heart disease admitted to the Affiliated Hospital of Jining Medical University were randomly divided into a control group and an observation group with 48 patients in each group. The patients in both groups were treated with oxygen inhalation, expectorant, cough relieving, asthma relieving and empirical antibiotics. The control group was treated with atomized inhalation of tiotropium bromide powder, and the observation group was treated with bisoprolol fumarate tablets on the basis of the control group. The left ventricular ejection fraction (LVEF), 6-minute walking distance (6MWD), 1 s forced expiratory volume (FEV 1), forced vital capacity (FVC), serum hs-CRP, BNP and other factors were compared between the two groups after treatment, and the total effective rate and adverse drug reaction of the two groups were counted. Results:After treatment, the total effective rates of the observation group and the control group were 91.67%(44/48) and 77.08%(37/48), respectively, with a statistically significant difference ( P<0.05). After treatment, the LVEF of the observation group and the control group were (43.15±6.04)% and (38.96±5.67)% respectively, the 6MWD was (294.86±30.11)m and (261.35±25.88)m, the FEV 1 was (2.36±0.69)L and (1.75±0.52)L, the FVC was (3.58±0.51)L and (2.96±0.45)L, the hs-CRP was (4.47±1.25)mg/L and (7.86±2.01)mg/L, and the BNP was (418.25±32.25)ng/ml and (496.52±43.21)ng/ml; ESR was (16.78±2.11)mm/h and (21.02±1.69)mm/h, ET-1 was (54.26±6.45)ng/ml and (73.21±8.24)ng/ml, and Interleukin 6 was (22.63±8.45)ng/L and (31.85±12.24)ng/L, respectively, with statistical significance ( P<0.05). The total incidence of adverse drug reaction in the observation group and the control group was 8.33%(4/48) and 4.17%(2/48), respectively, with no statistically significant difference ( P>0.05). Conclusions:Bisoprolol fumarate tablets combined with tiotropium bromide powder aerosol inhalation in the treatment of AECOPD complicated with cor pulmonale can improve the heart and lung function of patients, regulate the expression level of hs-CRP, BNP and other factors, improve the efficacy, and do not increase adverse reactions.
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Objective:To analyze and explore the independent risk factors of 28-day mortality in patients with septic myocardial injury.Methods:A retrospective cohort study was conducted to collect clinical data of 505 patients diagnosed with sepsis related myocardial injury admitted to the intensive care unit (ICU) of the Affiliated Hospital of Jining Medical University from January 2015 to December 2020. According to the 28-day survival status of patients, they were divided into survival group and death group. COX multivariate regression analysis was used to analyze the influencing factors of the 28-day mortality rate of sepsis related myocardial injury patients, and receiver operating characteristic (ROC) curves were drawn to evaluate the effectiveness of independent risk factors in predicting the 28-day mortality rate of sepsis related myocardial injury patients.Results:A total of 505 patients with sepsis myocardial injury were included, of which 282 survived on 28 days and 223 died, with a mortality rate of 44.16%. COX multivariate regression analysis showed that Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, blood lactate (LAC), oxygenation index (PaO 2/FiO 2), admission heart rate, and albumin were independent risk factors for sepsis associated myocardial injury mortality at 28 days (all P<0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of SOFA score was 0.766 2, and the 95% confidence interval (95% CI) was 0.724 5-0.807 9; The predictive value of 28-day mortality in sepsis associated myocardial injury patients was superior to APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin [The AUC values were 0.754 1(0.711 5-0.796 7), 0.752 6(0.710 1-0.795 1), 0.697 0(0.649 7-0.744 2), 0.623 2(0.573 7-0.672 7), and 0.620 3(0.570 8-0.669 7), respectively]. Conclusions:SOFA score, APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin are independent risk factors for the 28-day mortality rate of sepsis related myocardial injury. Clinical practice should identify these factors early, intervene early, and improve patient prognosis.
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The main components and working principle of the fluid infusion and blood transfusion warmer were introduced,and the causes for the adverse events of the warmer were summarized based on National Medical Device Adverse Event Monitoring Information System and related literature in the world.The potential risks of the warmer were analyzed during operation,and the quality concerns and corresponding evaluation methods were proposed for the warmer from the aspects of device marking and documentation,structure,and temperature.References were provided for standard preparation,pre-market technical review and system verification of the fluid infusion and blood transfusion warmer.[Chinese Medical Equipment Journal,2023,44(10):76-80]
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Objective:The purpose of this case report is to improve the understanding of pulmonary arteriovenous malformation (PAVM) and its related complications by reviewing case data and literature.Methods:A case of huge PAVM complicated with brain abscess and paradoxical embolization of liver, spleen and kidney is reported, and then we summarize its clinical characteristics, diagnosis and treatment, and review the relevant references.Results:Brain abscess and paradoxical embolization are the most common complications of PAVM. The diagnosis and process of this patient was timely and clear. The patient received interventional embolization for PAVM and achieved good results.Conclusions:PAVM can cause brain abscess and paradoxical embolization. We should be vigilant to avoid missed diagnosis and misdiagnosis.
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Objective:To investigate the prevalence of anxiety and depression in patients undergoing thoracic tumor radiotherapy, preliminarily evaluate the nutritional risk of patients, and analyze the possible influential factors of anxiety and depression and their correlation with nutritional risk, providing a theoretical basis for further formulating a personalized psychological nursing plan for patients undergoing thoracic tumor radiotherapy.Methods:A total of 121 patients who underwent thoracic tumor radiotherapy between April 2019 and March 2020 in Cancer Hospital of The University of Chinese Academy of Sciences were selected for this study. We evaluated patients' psychological statuses using the Hospital Anxiety and Depression Scale and patients' nutritional risk using the Nutrition Risk Screening. We performed univariate analysis, unconditional logistic regression analysis, and contingency analysis to analyze the factors that affected the psychological status of patients undergoing thoracic tumor radiotherapy and correlate patients' psychological status with nutritional risk.Results:Among 121 patients, 99 (81.8%) patients undergoing thoracic tumor radiotherapy would develop or had developed anxiety, and 42 (34.7%) patients were at the boundary of depression or had depression. Correlation analysis revealed that nutritional risk was correlated with the prevalence of anxiety and depression. Logistic regression analysis showed that surgery, first radiotherapy, and nutritional risk were the factors that affected the prevalence of anxiety. Marital status, location of tumors, surgery, first radiotherapy, and nutritional risk affected the prevalence of depression.Conclusion:Patients undergoing thoracic tumor radiotherapy have serious psychological problems. Nutritional risk is positively correlated with the prevalence of anxiety and depression. Surgery and first radiotherapy are the factors that affect the prevalence of anxiety and depression.
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Objective:To investigate the relationship between the arterial blood lactic acid level after entering the intensive care unit (ICU) and the 28-day mortality of patients with septic shock.Methods:The clinical data of 303 patients with septic shock hospitalized in the department of critical medicine of the Affiliated Hospital of Jining Medical College from April 2015 to June 2019 were analyzed retrospectively. According to the blood lactate (Lac) level, the patients were divided into <4 mmol/L group ( n=203), 4-10 mmol/L group ( n=69) and >10 mmol/L group ( n=31). The baseline characteristics of the patients were analyzed. Multiple logistic regression analysis was used to analyze the independent influencing factors of the 28-day mortality of patients with septic shock. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of the Lac level after entering the ICU for 28-day mortality, and Kaplan-Meier survival curve was performed according to the best cut-off value. Results:A total of 303 patients with septic shock were included, with 179 died in 28 days, and the total mortality was 59.08%. There were 203, 69, 31 patients in Lac<4 mmol/L, 4-10 mmol/L and >10 mmol/L group, respectively. There were significant differences in Acute Physiology and Chronic Health Evalution Ⅱ (APACHE Ⅱ), Sequential Organ Failure Assessment (SOFA), oxygenation index (PaO 2/FiO 2), abdominal infection, the proportion of vasoactive drugs use among the three groups ( P<0.05). Multiple logistic regression analysis showed that the independent influencing factor of the 28-day mortality of septic shock were age, SOFA, use of mechanical ventilation, lactic acid (Lac). ROC curve analysis showed that the area under the ROC curve (AUC) for predicting 28-day mortality of patients with septic shock was 0.604 5 (95% CI: 0.540 8-0.668 2). When the optimal cut-off value was 3.55 mmol/L, the sensitivity was 0.508 4, the specificity was 0.733 9, the positive likelihood ratio was 1.910 3 and the negative likelihood ratio was 0.669 9. According to the best cut-off value of entrance Lac, patients were divided into high Lac group (≥3.55 mmol/L) and low Lac group (<3.55 mmol/L), and their 28-day mortality rates were 73.39%(91/124) and 49.16%(88/179). Kaplan-Meier survival curve showed that the 28-day cumulative survival rate of the high Lac group was significantly lower than that of the low Lac group ( P<0.001). Multiple logistic regression analysis showed that after adjusting for confounding factors, the 28 d mortality increased to 1.22 times for each increase of 1 mmol/L of Lac [odds ratio ( OR)=1.22, 95% confidence interval (95% CI) was 1.08-1.37, P=0.001 4]. The 28 d mortality in high Lac group was 3.53 times higher than that in low Lac group ( OR=3.53, 95% CI was 1.36-7.09, P=0.000 4). Conclusions:In patients with ICU septic shock, the arterial blood Lac level after admission was associated with 28-day mortality. Patients with septic shock whose arterial blood Lac level exceeded 3.55 mmol/L within 1 hour of entering the room had a significantly increased risk of death.
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Objective:To compare the efficacy and safety of different treatment methods for thoracoabdominal aortic aneurysm(TAAA).Methods:The clinical data of 39 TAAA patients admitted to our department from Jan 2010 to Feb 2018 were retrospectively analyzed.Results:There were 25 patients in endovascular group, 11 in open group and 3 in hybrid group. The mean age in the endovascular group was significantly higher than that in the open group ( P<0.05). The blood loss and operation time in the endovascular group were significantly lower than those in the open group and the hybrid group ( P<0.05). There was no significant difference in the operation success rate, the complication rate in post-operative 30 days and the rate of re-intervention ( P>0.05) among the three groups. The post-operative 30 days mortality was significantly higher in the hybrid group than that in the endovascular group and open group ( P<0.05). During the follow-up period, the complication rate in the endovascular group was significantly higher than that in the open group ( P<0.05). Conclusion:Endovascular surgery is more suitable for elderly patients because of shorter operation time, less trauma and bleeding.
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E3 ubiquitin ligase TRIM21(tripartite motif containing 21) plays an important role in regulating cell biological functions and clinical prognosis as oncogene or tumor suppressor in different types of tumors. However,the biological functions and molecular mechanism of TRIM21 in hypopharyngeal squamous cell carcinoma (HPSCC) are still unclear.Our results showed that TRIM21 is highly expressed in moderately and well differentiated HPSCC, suggesting the role of TRIM21 in tumor differentiation. Overexpression and knockdown of TRIM21 inhibited or promoted cell proliferation and migration. Meanwhile, the expression of differentiation markers including KRT10 (keratin 10), IVL (involucrin) and TGM1 (transglutaminase 1) were increased and decreased upon TRIM21 overexpression or knockdown, respectively. The bioinformatics analysis of TRIM21 interacting protein identified by co-immunoprecipitation combined with mass spectrometry suggested that TRIM21 may be closely related to the regulation of cytoskeleton protein. We further demonstrated that TRIM21 interacted with KRT10. The inhibition of protein synthesis by cycloheximide led to upregulation of KRT10 in TRIM21 overexpressing FaDu cells, and ectopic expression of TRIM21 enhanced the ubiquitination level of KRT10. In summary, our results suggest that TRIM21 may promote the HPSCC differentiation by mediating ubiquitination of cytoskeleton proteins to improve the protein stability.
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Objective To study the safety and efficacy of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in elderly patients with biliary and pancreatic diseases under the concept of enhanced recovery after surgery (ERAS). Methods 320 patients were enrolled in ERCP operation. Both ERAS elderly group (experimental group A, n = 58, above 75 years) and young and middle-aged group (control group B, n=202,below 60 years)underwent enhanced recovery after surgery,meanwhile traditional elderly group(control group C, n = 60, above 75 years) received traditional perioperative management. It had compared multiple clinical indexes between group A with B and group A with C during the preoperative, intraoperative, and postoperative period. Results The incidence rate of cholangiocarcinoma, multiple complications, nutrition screening ≥ 3 points, ASA scored III degree and Child-Pugh scored A-level in preoperative ERAS elderly patients were higher than that of the young and middle-aged group (P < 0.05); And its incidence rate of nausea and vomiting and abdominal pain,nutritional screening < 3 points and ASA scored I degree were lower than that of the middle-aged group (P < 0.05);the fasting and water- deprivation time of the ERAS elderly group was shorter than that of the traditional elderly group (P < 0.05). The intraoperative operation time of the elderly ERAS group was slightly longer than that of the traditional elderly group (P < 0.05). The duration of electrocardiographic monitoring and the first aerofluxus time of the elderly patients with ERAS were longer than that of the young and middle-aged group (P < 0.05). The success, failure rate, and complication rate of the elderly patients with ERAS were 91.38% (53/58) and 8.62% (5 /58), 3.45% (2/58), meanwhile the young and middle-aged group were 96.53% (195/202), 3.47% (7/202), and 4.95% (10/202), and with no statistical difference (P > 0.05). The mild pain in ERAS elderly group was more than that of in traditional elderly group, while the moderate, and severe pain was less than that of traditional elderly group (P < 0.05); The opioid use rate, endoscopic nasobiliary indwelling, first-time ambulation and aerofluxus, total hospitalization, and postoperative hospitalization time of ERAS elderly group was less than the traditional elderly group (P < 0.05). Conclusions With ERAS, the treatment effect of ERCP in elderly patients is similar to that in young and middle-aged people, and it has good safety and effectiveness.
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Objective To investigate the correlation between normal ascending aortic elasticity and the left ventricular function by 256 slice iCT.Methods 105 subjects who underwent CTA and echocardiography inspection and diagnosed with normal coronary artery and without ascending aortic atherosclerosis were collected.Subjects were divided into three groups according to age and two groups according to gender respectively.Left ventricular function parameter values on CT were measured, including ESV,EDV,SV,EF,CO and MM.The aortic elasticity on CT and echocardiography was measured and calculated respectively on cross-sectional area at 15 mm above aortic valve.The relationship between ascending aortic elasticity and the left ventricular function was evaluated.Results Bland-Altman plot revealed that there was a good conformity between CT and echocardiography in measurement the value of ascending aortic elasticity(ICC=0.988,P<0.05).In different grougs of age,normal ascending aortic elasticity was positively correlated with EDV,ESV,SV,EF and negatively correlated with MM.There was no correlation with the CO.There was a negative relationship between aortic elasticity and age(r=-0.546,P<0.05)
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Objective To determine the value of procalcitonin (PCT) as an early marker of postoperative infection after cardiac surgery with cardiopulmonary bypass (CPB).Methods A retrospective study was conducted. Patients with systemic inflammatory response syndrome (SIRS) after cardiac surgery with CPB admitted to intensive care unit (ICU) of Peking Union Medical College Hospital from November 2014 to January 2017 were enrolled. The cardiac surgery types and intraoperative conditions, the treatments in ICU, postoperative 28-day mortality and hospital mortality of the patients; the levels of plasma PCT measured at ICU admission, postoperative 1, 3, and 5 days were collected. According to whether patients with postoperative infection or not, they were divided into infection group and non-infection group. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of plasma PCT levels at different time points in patients with infection.Results Eighty-two patients were included in this study, 25 (30.5%) had microbiological evidence of pneumonia. The levels of plasma PCT were increased with a peak 1 day after cardiac surgery in all patients, then significantly decreased 5 days after operation. Compared with patients without infection, the levels of plasma PCT were significantly increased in patients with infection at immediate and 1, 3, 5 days post operation in ICU [μg/L: 10.0 (6.0, 64.5) vs. 5.0 (1.0, 10.0), 31.0 (10.0, 116.2) vs. 5.0 (1.0, 10.0), 34.7 (10.0, 60.4) vs. 2.9 (0.7, 9.3), 15.8 (7.7, 29.4) vs. 0.7 (0.5, 2.6), allP < 0.01]. The area under the ROC curve (AUC) of the plasma PCT levels at ICU admission, and 1, 3, 5 days thereafter to predict infection for critically ill patients with SIRS after CPB was 0.77, 0.82, 0.86, and 0.91, respectively (allP < 0.01), cut-off values were 6.8, 9.4, 9.2 and 3.9μg/L, with the sensitivities of 76.0%, 84.0%, 79.2%, and 88.0%, and the specificities of 66.7%, 68.4%, 75.4%, and 78.9%, respectively.Conclusions In the presence of SIRS, elevated plasma PCT levels correlated with evidence of infection in early stage post operation in the ICU patients after cardiac surgery with use of CPB. The level of plasma PCT exceeded the cut-off value in different time points, suggesting infection, and it is helpful to predict the occurrence of infection early after operation.
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Objective To determine the value of procalcitonin (PCT) as an early marker of postoperative infection after cardiac surgery with cardiopulmonary bypass (CPB).Methods A retrospective study was conducted. Patients with systemic inflammatory response syndrome (SIRS) after cardiac surgery with CPB admitted to intensive care unit (ICU) of Peking Union Medical College Hospital from November 2014 to January 2017 were enrolled. The cardiac surgery types and intraoperative conditions, the treatments in ICU, postoperative 28-day mortality and hospital mortality of the patients; the levels of plasma PCT measured at ICU admission, postoperative 1, 3, and 5 days were collected. According to whether patients with postoperative infection or not, they were divided into infection group and non-infection group. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of plasma PCT levels at different time points in patients with infection.Results Eighty-two patients were included in this study, 25 (30.5%) had microbiological evidence of pneumonia. The levels of plasma PCT were increased with a peak 1 day after cardiac surgery in all patients, then significantly decreased 5 days after operation. Compared with patients without infection, the levels of plasma PCT were significantly increased in patients with infection at immediate and 1, 3, 5 days post operation in ICU [μg/L: 10.0 (6.0, 64.5) vs. 5.0 (1.0, 10.0), 31.0 (10.0, 116.2) vs. 5.0 (1.0, 10.0), 34.7 (10.0, 60.4) vs. 2.9 (0.7, 9.3), 15.8 (7.7, 29.4) vs. 0.7 (0.5, 2.6), allP < 0.01]. The area under the ROC curve (AUC) of the plasma PCT levels at ICU admission, and 1, 3, 5 days thereafter to predict infection for critically ill patients with SIRS after CPB was 0.77, 0.82, 0.86, and 0.91, respectively (allP < 0.01), cut-off values were 6.8, 9.4, 9.2 and 3.9μg/L, with the sensitivities of 76.0%, 84.0%, 79.2%, and 88.0%, and the specificities of 66.7%, 68.4%, 75.4%, and 78.9%, respectively.Conclusions In the presence of SIRS, elevated plasma PCT levels correlated with evidence of infection in early stage post operation in the ICU patients after cardiac surgery with use of CPB. The level of plasma PCT exceeded the cut-off value in different time points, suggesting infection, and it is helpful to predict the occurrence of infection early after operation.
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Objective To evaluate the effectiveness of Percu Twist (PT) tracheostomy comparing with that of operative tracheostomy(OT)in intensive care unit(ICU). Methods Related data were retrieved from CBM,CNKI,Wanfang Data,VIP,PubMed,EMBASE,CENTRAL,and Web of Science from the time of their establishment to May 15th 2014,and the data of randomized controlled trials(RCTs)concerning PT and OT were selected. The risk of bias assessment and data extraction were performed by two independent reviewers. Meta analysis was conducted using RevMan 5.2 software. Results A total of 12 RCTs were identified,and 893 patients in ICU were involved. The results of Meta-analysis showed that PT could significantly shorten the operation time〔mean difference (MD)=-15.11,95% confidence interval(95%CI)=-17.14 to -13.07,P<0.000 01〕,reduce the volume of blood loss(MD=-17.59,95%CI=-21.90 to-13.28,P<0.000 01),reduce the size of incision(MD=-2.20, 95%CI=-2.57 to -1.82,P<0.000 01),shor ten the time of healing(MD=-3.60,95%CI=-4.15 to -3.05, P<0.000 01),and reduce complications such as infection of the wound〔odds ratio(OR)=0.20,95%CI=0.10-0.44,P<0.000 1〕and cutaneous emphysema/mediastinal emphysema(OR=0.22,95%CI=0.10-0.47,P<0.000 1)compared with OT group. The funnel plot suggested that publication bias might be found among 12 researches. Conclusions PT was shown to be more effective than OT in ICU with lower incidence of complications. As number of RCT cases is still small with unsatis factory quality,further clinical use is warranted for a better assessment.
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Objective To observe the efficacy of growth hormone ( GH) co-treatment in poor responders undergoing IVF-ET.Methods To analyze all the ovaries low response patients treated by IVF/ICSI,80 cases were ran-domly divided into two groups:40 patients in GH group were given GH along with Gn daily until the HCG administra-tion.40 patients in the control group received the same treatment protocol except the GH co -treatment.The catching spawn number and MⅡova,fertile rate,the number of perfect embryos ,pregnant rate were observed .The serum con-centrations of IGF-I,IGFBP-3 were detected by ELISA and compared between the two groups .Results The number of oocytes retrieved ,number of MII oocytes ,cleavage ,number of embryos available of GH group were increased without statistical significance(all P>0.05 ).The serum IGFBP-3 level of 2 groups had no statistical significance .The fertile rate,pregnant rate ,serum IGF-I level were significantly higher in GH group than those in the control group ( all P<0.05).Conclusion GH co-treatment in poor responders could improve the outcome of IVF-ET,which imply that GH could improve the quality of oocytes and embryos related to the elevated IGF-1 level in serum .
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Neuropeptide Y (NPY), a sympathetic neurotransmitter, is highly associated with baroreflex dysfunction and multiple cardiac diseases such as diabetic myocardiopathy. In the present study, we aimed to explore the role of peripheral NPY Y1 receptor (Y1R) and Y2 receptor (Y2R), which are dominantly present in peripheral cardiovascular control, in baroreflex sensitivity (BRS) of streptozotocin (STZ)-induced diabetic rats. Peripheral Y1R and Y2R were antagonized by specific antagonists (BIBP 3226 and BIIE 0246, respectively) from subcutaneously implanted ALZET mini-osmotic pump in STZ-induced diabetic rats for 4 weeks. Then baseline systolic blood pressure, heart rate, cardiac function, BRS, plasma NPY and lipid levels were evaluated. We found that STZ led to increased plasma NPY and lipid level. And the STZ-increased lipid levels were reduced by BIBP 3226 and BIIE 0246. BIBP 3226 ameliorated the aberrant BRS, but had little effect on the impaired cardiac function of the STZ rats. BIIE 0246 alleviated sodium nitroprusside (SNP)-induced but not phenylephrine (PE)-induced aberrant baroreflex control of heart rate in the STZ rats. In addition, BIIE 0246 alleviated the bradycardia, but further impaired cardiac contractility in the STZ rats. These results suggest that peripheral Y1R and Y2R play different roles in STZ-induced impairment of BRS.
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Animaux , Rats , Arginine , Pharmacologie , Baroréflexe , Benzazépines , Pharmacologie , Pression sanguine , Bradycardie , Diabète expérimental , Traitement médicamenteux , Rythme cardiaque , Contraction myocardique , Neuropeptide Y , Sang , Récepteur neuropeptide Y , StreptozocineRésumé
Glucosamine, a naturally occurring amino monosaccharide, has been reported to play a role in the regulation of apoptosis more than half century. However the effect of glucosamine on tumor cells and the involved molecular mechanisms have not been thoroughly investigated. Glucosamine enters the hexosamine biosynthetic pathway (HBP) downstream of the rate-limiting step catalyzed by the GFAT (glutamine:fluctose-6-phosphate amidotransferase), providing UDP-GlcNAc substrates for O-linked beta-N-acetylglucosamine (O-GlcNAc) protein modification. Considering that O-GlcNAc modification of proteasome subunits inhibits its activity, we examined whether glucosamine induces growth inhibition via affecting proteasomal activity. In the present study, we found glucosamine inhibited proteasomal activity and the proliferation of ALVA41 prostate cancer cells. The inhibition of proteasomal activity results in the accumulation of ubiquitinated proteins, followed by induction of apoptosis. In addition, we demonstrated that glucosamine downregulated proteasome activator PA28gamma and overexpression of PA28gamma rescued the proteasomal activity and growth inhibition mediated by glucosamine. We further demonstrated that inhibition of O-GlcNAc abrogated PA28gamma suppression induced by glucosamine. These findings suggest that glucosamine may inhibit growth of ALVA41 cancer cells through downregulation of PA28gamma and inhibition of proteasomal activity via O-GlcNAc modification.
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Humains , Mâle , Acétyl-glucosamine/composition chimique , Alloxane/pharmacologie , Apoptose/effets des médicaments et des substances chimiques , Autoantigènes/génétique , Lignée cellulaire tumorale , Prolifération cellulaire/effets des médicaments et des substances chimiques , Régulation de l'expression des gènes tumoraux , Glucosamine/pharmacologie , Phosphorylation , Tumeurs de la prostate/enzymologie , Proteasome endopeptidase complex/antagonistes et inhibiteurs , Petit ARN interférent/génétique , Protéines ubiquitinées/métabolismeRésumé
Down syndrome (DS) is the most common cause of cognitive impairment associated with a congenital chromosomal abnormality, trisomy of chromosome 21. Mental retardation and congenital heart defects are key features of DS. All DS individuals develop early-onset Alzheimer's disease-like neuropathology. Intersectin 1 gene is localized on human chromosome 21, the critical region of DS, and it has higher expression in the brain of DS patients than in normal individuals. So fully understanding functions of intersectin 1 is critical for revealing the pathogenesis of DS. Intersectin 1 protein has two isoforms: intersectin 1-L and intersectin 1-S. This review will focus on the distribution, expression characters and functions of intersectin 1 in the central nervous system.
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Animaux , Humains , Protéines adaptatrices du transport vésiculaire , Génétique , Métabolisme , Système nerveux central , Biologie cellulaire , Métabolisme , Chromosomes humains de la paire 21 , Troubles mentaux , Génétique , Métabolisme , Neurones , MétabolismeRésumé
<p><b>OBJECTIVE</b>To investigate the effect of specific blockage of mutant p53 gene by individualized antisense RNA in vitro.</p><p><b>METHODS</b>Mutation status of p53 in human breast cancer cell lines was determined by immunocytochemical staining, PCR-SSCP and sequencing. Single strand antisense transcription system targeting specific p53 mutation site (mt-p53) was constructed, and corresponding antisense RNA was prepared. The hybridization of antisense RNA with its corresponding mt-p53 gene was confirmed by in-situ hybridization. Human breast cancer cells were transfected with antisense RNA by cationic liposome-mediated method. Time course of effects of antisense RNA was investigated by immunocytochemical staining and cell growth inhibiting assay. Expression of mt-p53 protein was examined by Western blot. Cell proliferation was evaluated by MTT assay and cell cycle distribution was determined by flow cytometry (FCM). Apoptosis was determined by TUNEL assay.</p><p><b>RESULTS</b>Mutation of p53 exon 8 was found in MDA-MB-231 cells and antisense transcription system (pGEM3zf (+/-) p53exon8) was then constructed successfully. In transfected MDA-MB-231 cells, hybridization signals were observed in cytoplasm. Fourth-eight hours after transfection, the antisense RNA (ASp53exon8'RNA) had a significant retarding effect on p53 related proliferation inhibition, along with a decrease of p53 protein expression.</p><p><b>CONCLUSIONS</b>ASp53exon8'RNA specifically blocks mt-p53 gene expression, resulting in an inhibition of MDA-MB-231 cell proliferation. Such an approach may be used as a therapeutic option against human malignancy.</p>
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Femelle , Humains , Apoptose , Séquence nucléotidique , Tumeurs du sein , Métabolisme , Anatomopathologie , Lignée cellulaire tumorale , Prolifération cellulaire , Codon , Régulation de l'expression des gènes tumoraux , Données de séquences moléculaires , Mutation , Plasmides , ARN antisens , Protéines recombinantes , Métabolisme , Transfection , Protéine p53 suppresseur de tumeur , Génétique , MétabolismeRésumé
<p><b>OBJECTIVE</b>To study on mutations in D-loop region which is gene control region of mitochondrial genome in patients with familial breast cancer.</p><p><b>METHODS</b>Twenty-three breast cancer patients came from twenty-one families of breast cancer, and eighteen healthy controls participated in the study. PCR amplification of D-loop region in mitochondrial DNA was performed and then the product was sequenced to analyze mutations.</p><p><b>RESULTS</b>One hundred and twenty-six mutations in D-loop region were found in twenty-three patients with familial breast cancer, and four mutations were new. In all of twenty-three patients, thirty-seven mutations were found in D310 which was hot spot of D-loop region in mitochondrial DNA. In these mutations, T>C in 310, TC insert in 311-312, CA deletion in 522-523 and C>G in 527 were multi-presentation mutations in patients with familial breast cancer. Mutations had no difference in the same family member of breast cancer family except that occurrence in the region of D310. In the same family, mutations in D310 of patients were different from controls.</p><p><b>CONCLUSION</b>Mutations in D310 of familial breast cancer patients may enhance their susceptibility to breast cancer.</p>
Sujets)
Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Séquence nucléotidique , Tumeurs du sein , Génétique , ADN mitochondrial , Chimie , Génétique , Prédisposition génétique à une maladie , Génome humain , Génétique , Région de contrôle de locus , Génétique , Mutation , PedigreeRésumé
<p><b>OBJECTIVE</b>To investigate the changes and clinical value of circulating endothelial cells (CEC) in the peripheral blood of advanced NSCLC patient.</p><p><b>METHODS</b>Sixty-seven advanced NSCLC patients were randomly divided into either the treatment group with NP plus endostatin or control group with NP alone. Level of CEC and cytokeratin (CK) in the peripheral blood were measured by flow cytometry.</p><p><b>RESULTS</b>The response rate and benefit rate was 44.4%, 80.0% in the treatment group, and 27.3%, 50.0% in the control group, respectively (P = 0.176 and P = 0.012). Time to tumor progression (TTP) was 146.7 days in the treatment group and 91.1 days in the control group (P = 0.061). However, when the cut-off of TTP was defined as > 170 days, there was a significant difference between two groups (cut-off = 170, P = 0.034; cut-off = 180, P = 0.009). The number of CEC decreased by 0.29 +/- 0.47 in the treatment group and by 0.01 +/- 0.43 in the control group (P = 0.033). The correlation between CEC and CK was found to be positive either before (r = 0.381, P = 0.013) or after the treatment (r = 0.450, P = 0.004).</p><p><b>CONCLUSION</b>Chemotherapy combined with endostatin is superior to chemotherapy alone in the treatment of NSCLC. CEC, as a biomarker, may be useful in predicting the efficacy of the combined treatment.</p>