ABSTRACT
Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.
ABSTRACT
Brachythrapy is a technique to implant radioactive isotype into or near tumors.The obvious properties of brachytherapy are a very high dose distribution of center,and rapid dose attenuation with the increasing of distance.Brachytherapy generally includes three major categories:low dose rate,high dose rate and pulse dose rate.The most significant clinical value of brachytherapy is that it could create dose distribution to tumor tissues,but decreased radiation injury of normal tissues close to tumor.The development of the clinical brachytherapy technique is always involved in the radiobiological characteristics.The basic concepts involving clinical brachytherapy radiobiology mainly includes:dose-rate effect,repair of radiation injury,re-oxygenation,cell cycle redistribution and repopulation.An amount of translational medical approach is needed to guide the application of clinical brachytherapy by exploring the interaction between brachytherapy radiobiology and clinical brachytherapy effect,as well as taking advantage of brachytherapy radiobiological characteristics.The ultimate goal is to improve tumor local control rate,reduce the occurrence of adverse reactions,and improve patients' overall survival.
ABSTRACT
Objective@#To explore the effects of oxidative stress on renal dopamine D1 receptor dysfunction in offspring of diabetic rat dams.@*Methods@#The pregnant Sprague Dawley (SD) rats (n=10) were randomly divided into the diabetic group (a single intraperitoneal injection of 35 mg/kg streptozotocin on day 0 of gestation) and control group (injected with the equal volume of 0.9% saline on day 0 of gestation) according to the random number table (n=5 each group). The offspring rats were divided into 4 groups including offspring of control dams treated with vehicle, offspring of control dams treated with antioxidant, offspring of diabetic dams treated with vehicle and offspring of diabetic dams treated with antioxidant (n=10 each group). After birth, the offspring rats were treated with normal drinking water or antioxidant (tempol, 1.0 mmol/L) from the age of 4 weeks until the end of the study (20 weeks). The blood pressure was monitored continuously by non-invasive tail-cuff method. The renal oxidative markers including superoxide dismutase (SOD) and malondialdehyde (MDA) activity and D1 receptor agonist (fenoldopam)-mediated urinary and sodium excretion were detected. Furthermore, the protein expression of renal G protein-coupled receptor kinase 2 (GRK2), GRK4, dopamine D1 receptor and the phosphorylation level of D1 receptor were detected.@*Results@#The mean arterial pressure of offspring from the diabetic dams treated with vehicle was significantly higher than that of offspring from control dams treated with vehicle (P=0.013), while the mean arterial pressure of offspring from diabetic dams treated with antioxidant was significantly lower than that of offspring from the diabetic dams treated with vehicle (P=0.038). The fenoldopam-mediated urinary flow and urinary sodium excretion rate were significantly lower in offspring of diabetic dams treated with vehicle than those in offspring of control dams treated with vehicle (P<0.01), which were significantly higher in offspring of diabetic dams treated with antioxidant as compared to offspring of diabetic dams treated with vehicle (both P<0.01). There was no significant difference in fenoldopam-mediated urinary flow and urinary sodium excretion rate in offspring of control dams treated with antioxidant or vehicle (urinary flow: P=0.772; urinary sodium excretion rate: P=0.716). Compared with offspring of control dams treated with vehicle, the renal MDA activity was significantly increased, while the SOD activity was significantly decreased in offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.013). The renal MDA activity was significantly decreased, while the SOD activity was significantly increased in offspring of diabetic dams treated with antioxidant in comparison with offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.035).The renal GRK2 and GRK4 protein expression in offspring of diabetic dams treated with vehicle were significantly higher than those in offspring of control dams treated with vehicle (P<0.01), while the expression levels of renal GRK2 and GRK4 in offspring of diabetic dams treated with antioxidant were significantly downregulated compared with offspring of diabetic dams treated with vehicle (P<0.01). There was no significant difference in the protein expression of dopamine D1 receptor among 4 groups (P=0.735). The level of dopamine D1 receptor phosphorylation in offspring of diabetic dams treated with vehicle was significantly higher than that in offspring of control dams treated with vehicle (P<0.01), while the dopamine D1 receptor phosphorylation level was significantly lower in offspring of diabetic dams treated with antioxidant compared to that in offspring of diabetic dams treated with vehicle (P<0.01).@*Conclusion@#Oxidative stress is involved in the dopamine D1 receptors dysfunction in the offspring of diabetic dams.
ABSTRACT
Objective To discuss the dosimetric advantage of computed tomography-guided interstitial brachytherapy compared with the conventional intracavitary brachytherapy for locally advanced cervical cancer,offering a more advantageous clinical treatment approach. Methods Twenty-eight locally advanced cervical cancer patients with bulky tumors ( tumor size>5 cm) after external beam radiotherapy received computed tomography-guided interstitial brachytherapy. Dosimetric outcomes of the current study, including the total dose ( external beam radiotherapy+ brachytherapy ) D90 for the HR-CTV and D2cc for the bladder,rectum, and sigmoid, were compared with a former patient group consisting of 30 patients who received the conventional intracavitary brachytherapy ( uterine tandem+ ovoid pairs ) . Results The mean D90 value for HR-CTV in the intracavitary brachytherapy group and interstitial brachytherapy group were (76.9±5. 7) and ( 88.1± 3. 3) Gy, respectively. The D2cc for the bladder, rectum, and sigmoid in the intracavitary brachytherapy group and interstitial brachytherapy group were (84.7±6. 8) Gy,(69.2±4. 2) Gy,(67.8±4. 5) Gy and (81.8±6. 5) Gy,(6.8±4. 0) Gy,(64.8±4. 1) Gy,respectively.1-year local tumor control rate in the intracavitary brachytherapy group and interstitial brachytherapy group were 59. 3％ and 85. 2％, respectively. Conclusions CT-guided interstitial brachytherapy shows a significant dosimetric advantage compared with the conventional intracavitary brachytherapy, and is, thereby, clinically possible feasible. However,the long term curative effect and toxicity need to be further investigated.
ABSTRACT
Objective To analyze the dosimetric advantages of CT-guided interstitial brachytherapy for recurrent cervical cancer. Methods A total of 16 patients with recurrent cervical cancer after radical surgery and adjuvant external beam radiotherapy received interstitial brachytherapy with CT-guided implantation of metal needles. The high-risk clinical target volume (HR-CTV) was given 36 Gy in 6 fractions.D90for HR-CTV in the brachytherapy and the cumulative D2 cm3values for the bladder,rectum,and sigmoid colon in the previous external beam radiotherapy and the brachytherapy were analyzed.Results The mean D90value for HR-CTV was 52.5±3.3 Gy. The cumulative D2 cm3values for the bladder, rectum, and sigmoid colon were 85.6±5.8 Gy,71.6±6.4 Gy,and 69.6±5.9 Gy,respectively.The mean number of metal needles was 6.1±1.5 in each brachytherapy. The actual 1-year overall survival and local control were 81% and 69%, respectively. Conclusions CT-guided interstitial brachytherapy for recurrent cervical cancer shows good dose-volume histogram parameters and few complications, so it may be clinically feasible. However,its long-term clinical efficacy needs further observation.
ABSTRACT
Objective: To observe therapeutic effects of ticagrelor combined tirofiban on patients with ST elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and their short-term prognosis.Methods: A total of 280 STEMI patients undergoing emergency PCI were selected.According to random number table, patients were randomly divided into clopidogrel group (received clopidogrel combined tirofiban therapy) and ticagrelor group (received ticagrelor combined tirofiban therapy).TIMI blood flow grade of infarct related arteries, platelet aggregation rate and P2Y12 reaction unit (PRU) before and after PCI, and incidence of major adverse cardiovascular events (MACE) within 30d follow-up, hemorrhage event and cardiac function were measured and compared between two groups.Results: Compared with clopidogrel group after PCI, there was significant rise in percentage of TIMI blood flow grade 3 (81.4% vs.91.4%), and significant reductions in platelet aggregation rate [(55.2±4.1)% vs.(50.8±4.4)%] and PRU [(196.2±15.1)U vs.(180.8±12.0)U] in ticagrelor group, P<0.05 all.Compared with clopidogrel group after 30d follow-up, there were significant reductions in incidence rates of re-myocardial infarction (5.0% vs.2.9%) and cardiogenic death (2.9% vs.0.7%), left ventricular end-diastolic dimension [(53.1±2.8)mm vs.(49.0±2.0)mm] and left ventricular end-systolic dimension [(40.2±2.1)mm vs.(37.4±1.8)mm], and significant rise in left ventricular ejection fraction [(51.8±2.7)% vs.(55.4±2.5)%] in ticagrelor group, P<0.05 all.There were no severe hemorrhage events in both groups, and no significant difference in incidence rate of mild hemorrhage (5.0% vs.6.4%) between clopidogrel group and ticagrelor group, P=0.591.Conclusion: For STEMI patients undergoing emergency PCI, ticagrelor combined tirofiban can effectively reduce platelet aggregation rate, improve TIMI blood flow of infarct related arteries, therapeutic effects and their short-term prognosis without increasing hemorrhage risk, which is worth extending.
ABSTRACT
Objective To examine the dosimetric advantages of three-dimensional (3D) computed tomography (CT)-guided interstitial brachytherapy (BT) for target volume and surrounding normal tissue in patients with locally advanced cervical cancer,and to provide a simple and effective clinical treatment approach.Methods A total of 52 patients who had poor tumor response to external beam radiotherapy (EBRT) with a residual tumor greater than 5 cm at the time of BT were included.The patients were treated by 3D CT-guided interstitial BT using a hybrid applicator comprised of uterine tandem and free metal needles.The high-risk clinical target volume (HR-CTV),intermediate-risk clinical target volume (IR-CTV),and organs at risk (OAR) were contoured.The total dose,including external beam radiotherapy and high dose-rate BT,was biologically normalized to conventional 2 Gy fractions (EQD2).D90and D100for both HR-CTV and IR-CTV,and D2 ccfor the bladder,rectum,and sigmoid were analyzed.Results The mean D90value for HR-CTV was 88.4±3.5 Gy.The D2 ccfor the bladder,rectum,and sigmoid were 81.1±5.6,65.7±5.1,and 63.1±5.4 Gy,respectively.D2 cc≤90 Gy for the bladder and D2 cc≤70 Gy for the sigmoid were observed in all the patients.D2 cc≤70 Gy for the rectum was observed in 89% of patients.Conclusions 3DCT-guided interstitial BT has a significant dosimetric advantage for target volume accompanied by few minor complications,and thereby may be clinically feasible for treating locally advanced cervical cancer.However,its long-term efficacy and possible toxicities will require further clinical observation.
ABSTRACT
Objective To investigate the effect of the high mobility group protein 1 (HMGB1), cancer embryonic antigen (CEA) and squamous cell carcinoma antigen ( SCC-Ag) by paclitaxel combined with cisplatin chemotherapy in the treatment of advanced esophageal cancer patients .Methods 43 cases advanced esophageal cancer patients from our hospital were selected and randomly divided into the control group and the experiment group.19 cases in the control group were treated by surgery combined with postoperative chemotherapy , 24 cases in the experimental group were treated with surgery and chemotherapy.The clinical efficacy and high mobility group protein 1 ( HMGB1 ) , cancer embryonic antigen ( CEA ) and squamous cell carcinoma antigen ( SCC-Ag ) levels were compared between the two groups before and after treatment.Results The total effective rate of the experimental group was (91.7%) higher than that of the control group (57.9%), the difference was statistically significant (P <0.05).After treatment, the serum levels of SCC-Ag, CEA and HMGB1 were decreased in the two groups, compared with the control group, the experimental group SCC-Ag, CEA and HMGB1 levels were lower, the difference was statistically significant ( P <0.05 ) .There was no significant difference in adverse reactions between the two groups.Conclusion Paclitaxel combined with cisplatin in the treatment of advanced esophageal cancer patients with good results, presumably with the decrease of serum SCC-Ag, CEA and HMGB1 levels in patients with.
ABSTRACT
Objective To investigate the dosimetric difference between inverse planning simulated annealing(IPSA)and manual optimized plan for isodose line in interstitial brachytherapy for locally advanced cervical cancer and to provide a better optimization method for clinical application. Methods A total of 104 patients with cervical cancer were enrolled in this study. They received pelvic external beam radiotherapy and interstitial brachytherapy in five fractions. Both IPSA and manual optimized plan for isodose line were used to optimize the dose in each fraction. Dose volume parameters of the two plans were compared to analyze the dosimetric outcome by paired t-test. Results There were no significant differences in mean D 90and D 100for high-risk clinical target volume(HR-CTV)and D 90for intermediate-risk clinical target volume(IR-CTV)between the two groups(P>0.05). The IPSA group had a significantly higher D 100for IR-CTV than the manual optimized group(58.36±2.06 Gy vs. 53.99±2.17 Gy, P=0.025). For organs at risk,the IPSA group had a significantly lower mean rectum D 2ccand a significantly higher bladder D 2ccthan the manual optimized group(68.53± 2.85 Gy vs. 71.77± 1.79 Gy, P=0.002;80.49± 3.36 Gy vs. 78.71± 2.64 Gy,P=0.034). There was no significant difference in sigmoid D 2ccbetween the two groups(P>0.05). The IPSA group had significantly higher relative dose homogeneity index(HI)and conformity index (CI)of radiation dose for target volume than the manual optimized group(P<0.05), and there was no significant difference in overdose volume index(OI)between the two groups(P= 0. 1 0 7).Conclusions Compared with manual optimized plan for isodose line, IPSA can improve the dose distribution of tumor tissue,reduce mean rectum D 2cc,and increase CI and HI,so it is a preferable optimized treatment planning method in clinical application.
ABSTRACT
BACKGROUND:Myocardial fibrosis following myocardial infarction is an important mechanism of ventricle reconstitution. However, there are few reports concerning effects of myocardial transplantation related to stern cells on this process. OBJECTIVE: To investigate the effects of auto-skeletal muscle satellite cells implanted into ischemic myocardium on myocardial fibrosis in rats with myocardial infarction and their mechanisms.DESIGN, TIME AND SETTING: The randomized controlled animal study was performed at the Third Research Room, Research Institute of Surgery, Daping Hospital, Third Military Medical University of Chinese PLA from July to September 2007. MATERIALS: A total of 45 Wistar rats, of both genders, weighing 150-200 g, were used in this study. Of them, 30 rats were used to establish models of myocardial infarction.METHODS: A total of 45 rats were assigned to 3 groups (n=15). Rats in the myocardial infarction group received ligation of the left anterior descending coronary artery to induce myocardial infarction. 2 weeks later, 0.2 mL serum-free M199 medium was infused into the juncture between infarct region and normal myocardium through multiple points. In the transplantation group, following model induction, 0.2 mL auto-skeletal muscle satellite cells in rats after 2-weeks in vitro culture were transplanted into the surrounding of infarct region. Rats in the sham operation group were not induced to create models, only injected with 0.2 mL saline in the heart anterior wall surrounding the left anterior descending branch through multiple points. MAIN OUTCOME MEASURES: Four weeks after injection, vascular endothelial growth factor mRNA and vascular endothelial growth factor protein expression in the ischemic myocardium was demonstrated. Capillary density changes in the ischemic myocardium were detected. Growth and proliferation of myocardial cells in the infarct region were observed using hematoxylin-eosin staining.RESULTS: Vascular endothelial growth factor mRNA and vascular endothelial growth factor protein expression was significantly decreased in the sham operation and myocardial infarction groups compared with the transplantation group at 4 weeks following satellite cell transplantation (P<0.01). Capillary density was greater in the myocardial infarction group compared with the sham operation group (P<0.05). Capillary density was significantly higher in the rat ischemic myocardium in the transplantation group compared with the sham operation and myocardial infarction groups (P<0.01). Hematoxylin-eosin staining demonstrated that myocardial morphology was normal in rats of the sham operation group, with clear structure, orderly myocardial fibrosis. There were no fibroblastaggregation and hyperplasia among myocardial fibrosis. Fibroblast hyperplasia and collagent formation were found in the rat myocardium in the myocardial infarction group, with disorderly myocardial structure. Myocardial cells with transverse striation and many nuclei were observed in the rat infarct region of the transplantation group, with orderly arrangement. Fibrous tissue was significantly less in the transplantation group compared with the myocardial infarction group.CONCLUSION: Satellite cells can proliferate and differentiate into striated muscle-like cells with flexible and systolic functions in the infarct region. Satellite cells secrete vascular endothelial growth factor and promote blood capillary hyperplasia in ischemic myocardium by autocrine and paracrine, which finally effectively inhibits fibrosis progress in the ischomic myocardium.
ABSTRACT
Objective To investigate the effect of auto-skeletal muscle satellite cell implantation into ischemic myocardium on cardiac function and the mechanisms.Methods Approximately 10 7 to 10 9 muscle satellite cells(SCs)were cultivated in vitro.The left anterior descending(LAD)artery was ligated in Wistar rats to create myocardial infarction(MI).Some rats only underwent sham operation served as control.Two weeks after MI,autologous SCs,serum-free culture medium and sodium chloride injection were injected into ischemic myocardium of implantation rats(n=15),control rats(n=15)and myocardium around LAD of sham operation rats(SO,n=15),respectively.Four weeks after injection,hemodynamic parameters and cardiac function in all groups were evaluated by polygraph system,capillary density in the ischemic myocardium was demonstrated by immunohistochemical method,serum VEGF concentration was examined by ELISA,and the differentiated myofibers from SCs in the infarcted site were observed by pathologic examination and immunohistochemical method.Results Four weeks after injection,the SCs had progressively differentiated into striated muscle fibers in the myocardial infarction site,and immunohistochemical analysis confirmed their skeletal muscle origin.Compared with the SO rats,systolic blood pressure(SBP),diastolic blood pressure(DBP),mean ar-tery pressure(MAP),left ventricular systolic pressure(LVSP)and dp/dtmaxwere markedly decreased(P
ABSTRACT
Objective To evaluate the effects on blood pressure and vascular endothelial-1 function of combined therapy of atrovastin and nifedipine controlled released tablet in essential hypertension.Methods A randomized,double-blind,controlled trial was performed.Eighty-two patients with essential hypertension were randomly divided into two groups,receiving nifedipine controlled released tablet 30 mg once daily,or atrovastin 10 mg once daily and nifedipine controlled released tablet 30 mg once daily for 12 weeks.Another 30 subjects with normal blood pressure served as normal blood pressure control.Antihypertensive efficiency was observed during the whole study period.The concentration of plasma endothelin-1(ET-1) nitric oxide(NO) were measured before and after treatment.Results Blood pressure decreased significantly in both groups,but more significant in combined therapy group.In the combined therapy group,atrovastin resulted in a significant reduction of plasma ET-1 and a rise of nitric oxide(NO)(P
ABSTRACT
@#Bricker operation was used to treat advanced paraplegia with severe upper uninary tract deterioration, bilateral ureterohydronephrosis, recurrence urinary tract infection, and chronic renal failure.Three cases have good results. The operation is an extensive and complex procedure,indication should be strict.
ABSTRACT
AIM: To investigate the changes of intracellular calcium ion (Ca2+) concentration in mouse H9c2 (2-1) cells transfected with or without FK506 binding protein 12.6(FKBP12.6) gene by ultrasound mediated destruction of microbubbles. METHODS: The pcDNA3.1-FKBP12.6 plasmid, mingled with albumin-coated microbubbles agents, was transfected into H9c2 (2-1) cells by ultrasound-mediated destruction of microbubbles. The H9c2 (2-1) cell growth state was investigated by inverted microscope. The changes of intracellular Ca2+ concentration was determined by laser scanning confocal microscope. The FKBP12.6 protein expression was checked by immunohistochemistry. RESULTS: As compared with control cells, the H9c2 (2-1) cells, transfected with FKBP12.6 gene, grew better, had higher gross intracellular Ca2+ concentration. CONCLUSION: FKBP12.6 gene augments Ca2+ concentration in mouse H9c2 (2-1) cells, enhances the contractibility of the myocardial cell, which may be helpful to improve the myocardial dysfunction.