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[ Abstract] Objective To study the effect of sulodexide on the repair of diabetic retinopathy and the regulation of MAPK pathway in rats. Methods Totally 72 rats were randomly divided into normal control group, diabetic retinopathy group, low, middle and high dose of sulodexide group and metformin hydrochloride group. Except normal control group, other rats were intraperitoneally injected with streptozotocin to establish the rat model of diabetic retinopathy. Rats in the low, middle and high dose sulodexide groups were given sulodexide by intragastric administration of 10 mg / kg,20 mg / kg and 40 mg / kg, respectively. Metformin hydrochloride group was given metformin hydrochloride of 200 mg / kg, once a day for 12 weeks. The levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c) and serum levels of advanced glycation end products (AGEs), interleukin-6 (IL-6), IL-1β, and levels of glucose transporter 1 (GLUT-1), glucose transporter 3(GLUT-3), superoxide dismutase (SOD) and malondialdehyde (MDA) in retina were detected. The levels of p38 MAPK and phosphorylated p38 MAPK (p-p38 MAPK) in retina were detected by immunohistochemistry and Western blotting. Retinal pathological changes and ganglion cell count were examined by HE staining. Results The levels of FBG and HbA1c, serum AGEs, IL-6, IL-1 β, GLUT-1, GLUT-3, MDA and p38 MAPK mRNA, p38 MAPK, p-p38 MAPK / p38 MAPK and immunohistochemical integral optical density of retina in sulodexide group were significantly lower than those in diabetic retinopathy group (P < 0. 05), while the SOD level and ganglion cell number in retinal tissue were significantly higher than those in diabetic retinopathy group (P < 0. 05) . Conclusion Sulodexide can regulate blood glucose level and retinal glucose metabolism in diabetic retinopathy rats, and repair retinal pathological damage, and its mechanism may be related to the regulation of MAPK pathway.
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AIM:To investigate whether ceramide kinase-like protein(CERKL)alleviates oxidative stress injury of retinal pigment epithelial(RPE)cells induced by blue light via activating the silent information regulator 1(SIRT1)/E2F transcription factor 1(E2F1)axis. METHODS:Cultured human retinal pigment epithelial-19(ARPE-19)cells were irradiated with blue light to observe the morphological changes, and the expression of CERKL was detected by PCR and Western blot. ARPE-19 cells were transfected with siRNA-CERKL and pcDNA3.1-CERKL respectively. After exposure to blue light, cell viability was determined by MTT assay, apoptosis was detected by TUNEL assay, content of oxidative stress markers and the expression of SIRT1/E2F1 axis was analyzed. Then siRNA-SIRT1 was transfected into ARPE-19 cells, and the oxidative stress damage of ARPE-19 cells under blue light irradiation was detected again.RESULTS:ARPE-19 cells gradually contracted into spheres and appeared vacuoles after exposure to blue light. Blue light irradiation led to the increase of CERKL expression level(P<0.05), meanwhile, the rate of cell viability was decreased(P<0.05), the rate of the apoptosis was increased(P<0.05), contents of reactive oxygen species, malondialdehyde and 8-hydroxydeoxyguanosine were increased(P<0.05). Silence of CERKL aggravated this phenomenon, while up-regulation of CERKL could alleviate this change(P<0.05). Up-regulation of CERKL also activated the expression of SIRT1 and promoted the deacetylation of E2F1(P<0.05). Silencing SIRT1 could reverse the alleviating effect of up-regulating CERKL on oxidative stress injury of ARPE-19 cells induced by blue light(P<0.05). CONCLUSION: CERKL can reduce oxidative stress damage of ARPE-19 cells induced by blue light via activating SIRT1 expression and promoting the deacetylation of E2F1.
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Objective:To investigate the clinical value of plasma presepsin level in early severity evaluation for acute pancreatitis (AP) patients.Methods:The clinical data of 67 patients with AP admitted in Second Affiliated Hospital of Wenzhou Medical University from December 2016 to January 2019 were prospectively selected. The patients were divided into mild AP group (MAP, n=36) and moderately severe and severe AP group (MSAP+ SAP, n=31) according to CTSI and with or without organ dysfunction and local or systemic complications on admission. Another 20 healthy normal subjects were selected as the control group. Plasma presepsin, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), serum amylase and calcium levels were measured within 2 hours, and the APACHEⅡ score was calculated within 24 hours of admission. Receiver operating characteristic curves(ROC) were plotted and the area under the curve (AUC) was calculated to assess the clinical value of presepsin, CRP, PCT, WBC, serum amylase and calcium for predicting the severity of AP patients, respectively. Results:The plasma presepsin level in MAP, MSAP+ SAP and control group was (439.59±74.23)ng/L, (1097.82±93.15)ng/L and (97.31±21.57)ng/L, respectively. Plasma presepsin level in MAP and MSAP+ SAP patients with biliary pancreatitis were obviously higher than those patients with other etiological factors, and plasma presepsin level in MSAP+ SAP patients with hyperlipidemia-associated pancreatitis was significantly higher than those in the MAP group, and the difference was statistically significant ( P<0.05). The AUC of plasma presepsin in the diagnosis of MSAP+ SAP was 0.873(95% CI 0.734-0.922), which was greater than the AUC values of CRP, PCT, WBC and serum calcium; the optimal cut-off value was 951.94 ng/L; the diagnostic sensitivity was 85.6%, which was superior to CRP, PCT, WBC and serum calcium; and the specificity was 76.2%, which was second to 78.9% of serum calcium. Conclusions:Plasma presepsin level can be used as a sensitive indicator for early severity evaluation of AP patients, with a specificity only second to serum calcium.
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Objective@#To investigate the clinical value of plasma presepsin level in early severity evaluation for acute pancreatitis (AP) patients.@*Methods@#The clinical data of 67 patients with AP admitted in Second Affiliated Hospital of Wenzhou Medical University from December 2016 to January 2019 were prospectively selected. The patients were divided into mild AP group (MAP, n=36) and moderately severe and severe AP group (MSAP+ SAP, n=31) according to CTSI and with or without organ dysfunction and local or systemic complications on admission. Another 20 healthy normal subjects were selected as the control group. Plasma presepsin, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), serum amylase and calcium levels were measured within 2 hours, and the APACHEⅡ score was calculated within 24 hours of admission. Receiver operating characteristic curves(ROC) were plotted and the area under the curve (AUC) was calculated to assess the clinical value of presepsin, CRP, PCT, WBC, serum amylase and calcium for predicting the severity of AP patients, respectively.@*Results@#The plasma presepsin level in MAP, MSAP+ SAP and control group was (439.59±74.23)ng/L, (1097.82±93.15)ng/L and (97.31±21.57)ng/L, respectively. Plasma presepsin level in MAP and MSAP+ SAP patients with biliary pancreatitis were obviously higher than those patients with other etiological factors, and plasma presepsin level in MSAP+ SAP patients with hyperlipidemia-associated pancreatitis was significantly higher than those in the MAP group, and the difference was statistically significant (P<0.05). The AUC of plasma presepsin in the diagnosis of MSAP+ SAP was 0.873(95% CI 0.734-0.922), which was greater than the AUC values of CRP, PCT, WBC and serum calcium; the optimal cut-off value was 951.94 ng/L; the diagnostic sensitivity was 85.6%, which was superior to CRP, PCT, WBC and serum calcium; and the specificity was 76.2%, which was second to 78.9% of serum calcium.@*Conclusions@#Plasma presepsin level can be used as a sensitive indicator for early severity evaluation of AP patients, with a specificity only second to serum calcium.
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BACKGROUND@#Positive surgical margins are independent risk factor for biochemical recurrence, local recurrence, and distant metastasis after radical prostatectomy. However, limited predictive tools are available. This study aimed to develop and validate a preoperative nomogram for predicting positive surgical margins after laparoscopic radical prostatectomy (LRP).@*METHODS@#From January 2010 to March 2016, a total of 418 patients who underwent LRP without receiving neoadjuvant therapy at Peking University Third Hospital were retrospectively involved in this study. Clinical and pathological results of each patient were collected for further analysis. Univariable and multivariable logistic regression (backward stepwise method) were used for the nomogram development. The concordance index (CI), calibration curve analysis and decision curve analysis were used to evaluate the performance of our model.@*RESULTS@#Of 418 patients involved in this study, 142 patients (34.0%) had a positive surgical margin on final pathology. Based on the backward selection, four variables were included in the final multivariable regression model, including the percentage of positive cores in preoperative biopsy, clinical stage, free prostate specific antigen (fPSA)/total PSA (tPSA), and age. A nomogram was developed using these four variables. The concordance index (C-index) of the nomogram was 0.722 in the development cohort and 0.700 in the bootstrap validations. The bias-corrected calibration plot showed a limited departure from the ideal line with a mean absolute error of 2.0%. In decision curve analyses, the nomogram showed net benefits in the range from 0.2 to 0.7.@*CONCLUSION@#A nomogram to predict positive surgical margins after LRP was developed and validated, which could help urologists plan surgical procedures.
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Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Laparoscopia , Métodos , Margens de Excisão , Nomogramas , Prostatectomia , Métodos , Neoplasias da Próstata , Cirurgia Geral , Curva ROC , Estudos RetrospectivosRESUMO
OBJECTIVE@#To investigate the safety and feasibility of laparoscopic treatment for renal carcinoma with Mayo 0-2 level venous thrombosis.@*METHODS@#From January 2015 to February 2018, 58 renal carcinoma cases with venous thrombus underwent laparoscopic radical nephrectomy with inferior vena cava thrombectomy in Department of Urology, Peking University Third Hospital, of which, 51 cases were male, and 7 female, aged 29-82 years. According to the Mayo grade classification, 20 cases were level 0, 20 cases were level 1, and 18 cases were level 2, with left side being 22 cases, and right side 36 cases. The patients except for those complicated with hemorrhagic diseases, cardiac and pulmonary insufficiency, or those who could not tolerate anesthesia and surgical contraindications, underwent the operation after comprehensive examinations.@*RESULTS@#The 58 cases of renal tumor with venous tumor emboli were successfully completed with the surgeries, including 50 cases of totally laparoscopic surgery, 8 cases of laparoscopy surgery from convert to open (among the patients who were converted to open surgery, 7 were complicated with grade 2 tumor thrombus and 1 with grade 1 tumor thrombus). The main reasons for converting to open surgery were huge tumors (the largest of which was about 16 cm in diameter), severe adhesion and difficulty of separation. For different patients, different surgical methods and procedures were adopted according to the tumor direction and the different grade of tumor thrombus. Radical nephrectomy combined with vena cava tumor thrombus removal was performed in 55 cases and segmental resection of vena cava in 3 cases. The operation time was 132-557 min, and blood loss was 20-3 000 mL. Post-operative pathological types: 51 cases were clear cell carcinoma, 5 cases were type 2 of papillary carcinoma, 1 case was squamous cell carcinoma, and 1 case was chromophobe cell tumor. In the study, 47 cases were followed up for 1-36 months, and 4 cases died (the survival time was 5-15 months, with an average of 10.2 months).@*CONCLUSION@#Laparoscopic radical nephrectomy with inferior vena cava thrombectomy is a reasonable choice for renal tumor with Mayo 0-2 level venous thrombosis. For different tumor directions and different grades of tumor thrombus, an appropriate operation plan can give the maxim benefit to the patients with skillful surgeons.
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Renais , Neoplasias Renais/complicações , Laparoscopia , Nefrectomia/métodos , Estudos Retrospectivos , Trombectomia/métodos , Trombose/cirurgia , Veia Cava InferiorRESUMO
Objective@#To evaluate the safety, efficacy and tolerability of China-made sildenafil citrate (Jinge) in the treatment of ED.@*METHODS@#We conducted a multi-center, randomized, double-blind and placebo-controlled clinical trial among 222 ED patients in five urological or andrological clinics of China. The patients were randomly assigned to receive sildenafil citrate (SC, n = 111) or placebo (n = 111) for 8 weeks. We obtained and analyzed the demographic and clinical characteristics of the patients, the scores of International Index of Erectile Function (IIEF), the success rate of sexual intercourse, and the incidence of adverse events.@*RESULTS@#No statistically significant differences were found between the patients of the SC and those of the placebo group in the mean age (［47.2±11.32］ yr vs ［46.67±13.08］ yr, P>0.05), psychological etiology (27.93% vs 23.42%, P>0.05), organic etiology (21.62% vs 29.73%, P>0.05) or mixed etiology (50.45% vs 46.85%, P>0.05), nor in height, weight, nationality, or history of smoking, drinking or allergy. Compared with the placebo controls, the SC-treated patients showed significant increases in the excellence rate of effectiveness (29.91% vs 78.90%, P<0.01), success rate of sexual intercourse (29.16% vs 63.87%, P<0.01), and total effectiveness rate (34.58% vs 77.98%, P<0.01). The effectiveness rates on organic, psychogenic and mixed types ED were remarkably higher in the SC group (64.52%, 83.33%, and 82.14%) than in the placebo control (46.15%, 21.21%, and 25.00%) (P<0.01). Mild or temporary adverse events were observed in 32 cases in the SC group as compared with 13 in the placebo control.@*CONCLUSIONS@#China-made sildenafil citrate is an effective, safe and well-tolerated drug for ED of different etiologies in the Chinese population.
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Idoso , Humanos , Masculino , China , Coito , Método Duplo-Cego , Composição de Medicamentos , Disfunção Erétil , Tratamento Farmacológico , Inibidores da Fosfodiesterase 5 , Usos Terapêuticos , Citrato de Sildenafila , Usos Terapêuticos , Fumar , Resultado do TratamentoRESUMO
A total of 178 patients with the time of mechanical ventilation beyond 48 hours in the second affiliated hospital of Wenzhou medical college from January 2010 to December 2013 were enrolled in this study,and there were fifty-six patients with ventilator-associated tracheobronchitis (VAT).The associated factors included age,sex,blood pressure,blood glucose,BMI,the time of mechanical ventilation,tracheal intubation methods,raise head to 30-45°,proton pump inhibitors (PPI),prophylactic antibiotic treatment,glasgow coma scale (GCS),acute physiology and chronic health evaluation (APECHE) Ⅱ score.The related factors of VAT were evaluated by using univariate logistical regression analysis,and the statistical significant variables were analyzed by using multivariate logistical regression analysis.By using univariate logistical regression analysis age,blood glucose,the time of mechanical ventilation,raise head to 30-45°,prophylactic antibiotic treatment,GCS and APECHE Ⅱ score were the important factors of VAT (P ＜ 0.05),but sex,blood pressure,BMI,tracheal intubation methods and PPI were insignificant related to VAT(P ＞ 0.05).By using multivariate logistical regression analysis the time of mechanical ventilation (OR =4.072,95％ CI 2.036-8.146),GCS[2.198(1.155-4.184)],age[2.128 (1.119-4.046)],APECHE Ⅱ score [2.109 (1.084-4.104)] and raise head to 30-45 ° [0.488 (0.243-0.979)] were associated independently with the VAT.The time of mechanical ventilation,GCS,age over 60 years,APECHE Ⅱ score and raise head to 30-45°were the independent factors associated with VAT.
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AlM:To investigate the protective effect of astaxanthin (AST) on human retinal pigment epithelial (RPE) cells against oxidative damage induced by hydrogen peroxide (H2O2).METHODS:Human RPE cells were subcultured, cell activity was detected by MTT, rate of apoptosis was detected by flow cytometry and cell ultrastructure changes were observed under transmission electron microscope. RESULTS: MTT results showed that cell activity elevated to ( 53. 66%± 3. 25% and 70. 43%± 2. 38% after 10-8 mol/L and 10-4 mol/L AST treated. The difference had statistically significant (P<0. 05) compared with oxidative injury group (38. 76%± 3. 74%). Flow cytometry results showed that the apoptosis rate of RPE cells decreased to 30. 23%± 1. 91% and 12. 58%± 2. 12% in AST pretreated group, the difference was significant (P<0. 05) compared with oxidative injury group ( 42. 50%± 1. 94%); Electron microscopy showed that the morphology of cells gradually improved accompanied with the concentration of AST elevated.CONCLUSlON:AST may inhibit hydrogen peroxide-induced apoptosis of RPE cells, it can provide reliable evidence for pursue effective medicine to prevent and treat retina injury.
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<p><b>OBJECTIVE</b>To explore clinical effects of suturing-assisted locking plate in treating elderly proximal humeral fractures.</p><p><b>METHODS</b>From January 2005 to January 2013, 55 elderly patients with three- and four-part fractures of proximal humeral fractures were divided into treatment group and control group. In treatment group, there were 31 patients including 12 males, and 19 females aged from 65 to 85 with an average of (74.00±5.42) years old, and treated with suturing-assisted locking plates; 19 patients were Neer 3-part fractures, and 12 patients were Neer 4-part fractures of proximal humerus; 23 patients were suffered from low-energy injuries and 8 patients were caused by high-energy injuries. In control group, there were 24 patients including 7 males, and 17 females aged from 65 to 85 with an average of (72.79±5.34) years old, and treated with locking plates; 16 patients were Neer 3-part fractures, and 8 patients were Neer 4-part fractures of proximal humerus; 17 patients were suffered from low-energy injuries and 7 patients were caused by high-energy injuries. Operative time, blood loss during operation, and bone healing time between two groups were observed and compared. Postoperative Neer scoring were used to evaluate recovery of shoulder joint function.</p><p><b>RESULTS</b>All patients were followed up from 6 to 24 months with an average of 16.1 months. In treatment group, blood loss was (495.806±143.150) ml, function of Neer scoring was 22.645±2.443, range of action was 18.194±2.613, anatomy was 7.935±1.504 and total score of Neer scoring was 77.161±8.335; while in control group, blood loss was (641.667±169.851) ml, function of Neer scoring was 13.958±1.989, range of action was 13.083±2.165, anatomy was 5.500±1.978 and total score of Neer scoring was 58.792±7.313. There were sigificant difference between two groups in these indexes.</p><p><b>CONCLUSION</b>Suturing-assisted locking plate for the treatment of proximal humerus fractures in elderly, has advantages of less blood loss, simple fracture reduction and rapid recovery of shoulder joint, and is a effective method.</p>
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Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Placas Ósseas , Estudos de Casos e Controles , Recuperação de Função Fisiológica , Fraturas do Ombro , Cirurgia Geral , Articulação do Ombro , SuturasRESUMO
<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and prognosis in breast cancer with brain metastasis (BCBM).</p><p><b>METHODS</b>The clinical data of 137 BCBM from June 2002 to June 2008 was reviewed and analyzed. Their molecular subtypes were categorized based on detection of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression. The focal area included 35 cases of triple-negative breast cancer (TNBC), 38 cases of HR (ER and PR) (-)/HER-2(+), 40 cases of HR(+)/HER-2(-), 24 cases of HR(+)/HER-2(+). The clinical characteristics and the outcome in patients with influence were analyzed.</p><p><b>RESULTS</b>In 137 BCBM, the median overal survival after brain metastasis was 6.5 month. The median survivals of TNBC, HR(-)/HER-2(+), HR(+)/HER-2(-) and HR(+)/HER-2(+) were 5.0, 5.5, 10.0 and 9.5 months, respectively. The median survivals after brain metastasis of the breast cancer patients who received the combination therapy of whole brain radiation therapy (WBRT) and neurosurgery and/or stereotactic radiosurgery, received WBRT but not combination therapy and didn't receive WBRT were 15.0, 9.5 and 4.0 months, respectively. In univariate survival analysis, substyle, number of brain metastasis, brain metastasis as initial recurrence or not, brain-only metastases or not, the combination therapy status after brain metastasis were obviously correlated with the prognosis (χ(2) = 6.891 to 29.414, P < 0.05). Substyle (RR = 1.234, 95%CI: 1.057 to 1.440) and the combination therapy status after brain metastasis (RR = 1.838, 95%CI: 1.389 to 2.431) were independent prognostic factor in multivariable analysis (P < 0.05).</p><p><b>CONCLUSIONS</b>TNBC confers a high risk of death after brain metastases. Systemic treatment via combined modalities are helpful for breast cancer patients, even after the detection of brain metastases.</p>
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Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Encéfalo , Patologia , Neoplasias Encefálicas , Terapêutica , Neoplasias da Mama , Patologia , Terapêutica , Terapia Combinada , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas , Patologia , TerapêuticaRESUMO
BackgroundOur previous study showed that erythropoietin (EPO) protects the photoreceptor from apoptosis in retinal detachment(RD) rat,but its signal transduction pathway remains unknown.Objective The present study was to investigate the effects of EPO on signal transduction pathway in RD.MethodsTwentyfour albino clean Sprague-Dawley(SD) rats were randomly divided into 4 groups.5 μl PBS was injected into vitreous cavity of rats in RD+PBS group,and 400 ng EPO(5 μl) was used at the same way in RD+EPO group.Three days later,the rats were sacrificed and the retina was isolated in each group.The expression levels of Janus kinase 2 (JAK2),p-JAK2,Akt,p-Akt,extracellular regulated protein kinase-1/2 ( ERK-1/2 ),p-ERK-1/2,signal transducer and activator of transcription 5 ( STAT5 ),p-STAT5,nuclear factor-kB (NF-sB) and p-NF-kB were detected by Western blot assay.The administration of experimental animals followed the Standard of ARVO.ResultsThree days after RD,the expression levels of JAK2,Akt and ERK-1,ERK-2 in retinas among normal group,RD,RD+PBS,RD+EPO groups were statistically insignificant different ( F =0.298,P =0.826 ; F =0.681,P =0.588 ; F =0.978,P=0.450;F=1.115,P=0.399 ),but the levels of p-JAK2,p-Akt,p-Erk-1 and p-Erk-2 among these 4 groups were significant difference ( F=24.435,P =0.000; F=48.163,P =0.000;F =19.092,P =0.001; F =14.393,P=0.001 ),and those in RD+EPO group was significantly higher than that in RD and RD+PBS groups( P＜0.05 ).The expression levels of STAT5 and NF-kB among the 4 groups were no significantly differences (F =1.136,P=0.391 ;F=0.696,P=0.580),but after the phosphorylation of STAT5 and NF-kB,the differences was significant ( F =14.189,P =0.001 ; F =40.103,P =0.000 ).Those in RD,RD + PBS,RD + EPO groups did not increase either (P＞0.05).Although the levels of p-STAT5 and p-NF-kB in RD,RD+PBS,RD+EPO groups were significantly higher than those in normal control group( P＜0.05 ),the level of p-STAT5 in RD+EPO group was not significantly higher than that in RD and RD + PBS groups (P ＞ 0.05 ). Conclusions PI3K/Akt and MAPK/ERK-1/2 signal transduction pathways might participate in the protecting process of EPO to photoreceptor in RD rats.
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Objective: To evaluate the molecular biological characteristics of bilateral primary breast cancer (BPBC). Methods: The clinicopathological characteristics of 325 patients with BPBC and 650 patients with unilateral breast cancer (UBC) were retrospectively analyzed. The evidence of molecular biology related to the occurrence of BPBC was evaluated by univariate analysis and multivariate Logistic regression analysis. Results: The early occurrence of first primary breast cancer, a family history of breast cancer, a maximum tumor diameter of more than 5 cm, and clinical stage III were more frequent in BPBC patients than in UBC patients (P 0.05). The characteristics including a family history of breast cancer, a maximum tumor diameter of more than 5 cm and positive expression of p53 in BPBC were independent risk factors. The patients with positive ER or positive PR had a lower risk of BPBC. Conclusion: There are differences in biological characteristics between BPBC and UBC. The breast cancer patients with the characteristics including young woman, a family history of breast cancer, negative expression of hormone receptor, positive expression of p53, and high expression of Ki67 should pay attention to the occurrence of contralateral breast cancer. Copyright© 2011 by TUMOR.
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Erythropoietin(EPO) has an anti-apoptotic effect,and promotes the proliferation and differentiation of erythroid progenitor cells. Several studies have indicated that EPO can protect photoreceptor cells from the lightinduced retinal degeneration ;protect retinal neurons from ischemia-reperfusion injury and retinal ganglion cells after acute and chronic ocular hypertension; promote ganglion cell survival and axonal regeneration after optic nerve transaction; attenuate inflammation in multiple sclerosis optic neuritis; reduce the permeability of the retinal barrier and protect retinal neurons in diabetic retinopathy; enhance the stability of hypoxic retinal vessels in retinopathy of prematurity. Herein,we review the distribution of EPO and its receptor in retina,their expression in animal model of retinal diseases,and their effects and mechanisms in protection of retinal neurons and optic nerve.
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Background Erythropoietin (EPO) has a protective effect on retinal neurons in many retinal diseases,but regarding the effect of EPO on apoptosis of retinal photoreceptor cells in retinal detachment (RD) is uncompletely clear.Objective This study was to investigate the protective effect of endogenous EPO on photoreceptors in a rat model of RD and explore its possible mechanism.Methods Seventy-two Sprague- Dawley (SD) rats were randomly assigned to control group,RD group,RD+PBS group,RD+erythropoietin soluble receptor (EPOsR) 2, 20, 200ng groups with 12 rats for each group.1.4% hyaluronic acid was slowly injected into the subretinal space to induce RD in rats,and PBS or 2,20 or 200ng EPOsR was then injected into the vitreous space.On day 3 after RD,apoptotic photoreceptors were detected using transferase-mediated dUTP nickend labeling (TUNEL),and caspase-3 activity was assessed by Western-blot and immunofluorescence staining.On day 14 after RD,retinal histopathologic examination was carried out and outer nuclear layer (ONL) thickness was measured under the light microscope.The use of animals complied with the Statement of Association for Research in Vision and Ophthalmology. Results Apoptotic photoreceptors were seen in ONL of rats of the RD group.Apoptotic photoreceptors were gradually increased with the elevation of EPOsR dose in the vitreous cavity.Western blot and immunofluorescence consistently showed that the gray scale of caspase-3 activity was 0.15±0.04,0.49±0.03,0.50±0.07,0.63±0.03,0.69±0.04 and 0.83±0.04 in the normal group,RD group,RD +PBS group,RD+EPOsR 2,20,200ng groups respectively with statistically significant differences (F=76.016;P=0.000),and caspase-3 activity was considerably stronger in the RD+EPOsR 200ng group than the other groups (P＜0.01).On day 14 after RD,the ONL thicknesses in the normal control group,RD group,RD+PBS group,RD+EPOsR 2,20,200ng groups were (47.39±3.39)μm,(33.96±3.54)μm,(31.83±5.21)μm,(31.40±2.63)μm,(24.99±2.06)μm and (19.30±3.71)μm,showing significant differences among these groups (F=44.733,P=0.000).ONL thicknesses the groups treated with different doses of EPOsR were markedly thinner than that of the RD group and RD +PBS group (P＜0.01).Conclusion EPOsR induces apoptosis of retinal cells and enhances the activity of caspase-3 in a dose-dependent manner.Endogenous EPO can protect photoreceptors against anoxia-mediated damage in RD eyes through decreasing caspase-3 activity and inhibiting apoptosis.
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<p><b>OBJECTIVE</b>To investigate the effects of curcumin on the expression of nuclear factor-kappaB (NF-kappaB) and intercellular adhesion molecular 1 (ICAM-1) in rats with cerebral ischemia-reperfusion (IR) injury.</p><p><b>METHODS</b>A total of 160 SD rats were randomized equally into sham-operated group, IR model group, curcumin treatment group and solvent control group. Global cerebral ischemia/reperfusion injury was induced in the latter 3 groups with subsequent corresponding treatment. At 6 h and 1, 3, and 7 days after the injury, 10 rats from each group were sacrificed, and brain sections were prepare for HE staining, immunohistochemical staining for NF-kappaB, and enzyme-linked immunosorbent assay for ICAM-1 expression.</p><p><b>RESULTS</b>In the IR model group, the contour of the pyramidal cells in hippocampal CA1 region was almost indistinguishable after the injury, whereas more than 70% of the pyramidal cells retained distinct cell contour and nuclear boundary in curcumin treatment group. At 6 h and 1, 3, and 7 days after the IR injury, the expression of NF-kappaB in curcumin treatment group showed significantly reduction in comparison with that in the IR model and solvent control groups (P<0.05), and the content of ICAM-1 protein was also reduced, which was especially obvious at 1 and 3 days (P<0.05).</p><p><b>CONCLUSION</b>Curcumin can ameliorate cerebral pathological changes in the event of IR injury by suppressing the expressions of NF-kappaB and ICAM-1.</p>
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Animais , Masculino , Ratos , Isquemia Encefálica , Metabolismo , Patologia , Curcumina , Farmacologia , Regulação para Baixo , Molécula 1 de Adesão Intercelular , Genética , Metabolismo , NF-kappa B , Genética , Metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Traumatismo por Reperfusão , MetabolismoRESUMO
Objective To investigate the effect of mechanical ventilation in acute organophosphorous pesticide poisoning(AOPP) with respiratry failure. Methods Forty from forty-two AOPP patients with respiratry failure were treated with mechanical ventilation(MV) ,gastrolavage and other methods. Five minutes before mechanical ventilation and two hours after mechanical ventilation, patients' heart rate (HR), systolic blood pressure (SBP), arterial partial blood pH, oxygenation index, the pressure of carbon dioxide (PaCO2) were compared. Results Patients' HR was increased ( P＜0. 05 ), SBP was increased ( P＜0. 01 ), arterial partial blood pH was increased( P＜0. 01 ), oxygenation index was increased(P＜0. 01 ) ,PaCO2 was decreased(P＜0.01 ). Thirty nine cases were cured,three cases dided. Conclusion Mechanical ventilation can effectively treat the AOPP patients with respiratry failure.
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Objective To reveal the protective effects of atorvastatin against atherosclerosis independent of cholesterol-lowering effect, we investigated the effects of atorvastation on the expression of protein kinase C (PKC) and C-reactive protein in experimental atherosclerosis of rats.Method Fifty female Sprague-Dawley rats were randomly divided into normal diet group (n = 10, control group), vitamin D3 injection and high cholesterol diet group (n = 40). After 8 weeks, vitamin D3 injection and high cholesterol diet rats were randomized to receive either atorvastatin (5 mg. kg-1. d-1) (n = 20, atorvastatin group) or normal diet (n = 20, model group). Another eight weeks later, all rats were killed and part of their aortas were examined by light and electron microscope and the left were removed for western blot analysis to measure PKC; At the begin and end of experiment, serumcollected for lipid and C-reactive protein determining determination.Results Cholesterol, low-density lipoprotein, triglyceride levels in atorvastatin group were significantly lower than those in model group but higher than control group. The pathologic changes in atorvastatin group were less severe than those in model group, there showed no any pathological changes in control group. The levels of C-reactive protein in model group[(18.64 ± 0.94) mg/L] were higher than those in control group [(9.21 ± 0.21)mg/L] (P<0.05). C-reactive protein levels also differed significantly between control and atorvastatin group (12.52 ± 0.65 mg/L)( P<0.05). PKC levels were significantly higher in model group (7786.12 ± 264.75)and atorvastatin group (4267.57 ± 233.94) than in control group (2468.75 ± 145.53)(all P<0.05). But compared with model group, PKC levels were markedly lower in the atorvastatin group ( P<0.01 ).Conclusions Atorvastatin may be useful not only as a cholesterol-lowering agents but also as anti-arteriosclerotic agent that provide vascular protection by inhibition PKC expression and inflammatory reaction.
RESUMO
<p><b>OBJECTIVE</b>To observe the histopathological changes of a novel small-caliber vascular graft after implantation in canine theca interna under scanning electron microscope.</p><p><b>METHOD</b>A 3 cm segment of the vascular graft (diameter of 4 mm) was implanted in an end-to-end fashion to bridge the severed carotid artery in 19 healthy dogs. Color Doppler sonography was performed 2 weeks after the operation to observe the patency rate of artificial blood vessel. At 1, 8, 12 and 24 week postimplantation, the arteries (4, 4, 6 and 5, respectively) were collected for optical and scanning electron microscopies after angiography to observe the patency of the arteries.</p><p><b>RESULTS</b>Of the total of 19 arteries, occlusion occurred in 1 at 12 weeks and 1 at 24 weeks. Optical and electron microscopies showed that 1 week after implantation, slight fibroplasias and formation of red thrombus could be seen at the vascular anastomosis without endothelial cell lining. At 8 weeks, the host tissue grew into the lumen of the graft through the pores to form uniform neointima consisting of plenty of collagen fibers, but still without endothelial cells. At 12 weeks, discontinuous endothelial cells were seen to grow on the surface of the neointima. In the middle segment of the vascular graft, immature endothelial cells were found to grow in clusters. The structure of the neointima was loose in comparison with that at the anastomosis, with occasional inflammation cells. Twenty-four weeks after grafting, endothelial cells grew over the entire inner wall of the patent graft, and the surface of the neointima at the anastomosis was lined with continuous endothelial cells.</p><p><b>CONCLUSION</b>The vascular graft can be useful for reconstruction of canine carotid artery defect and achieves good endothelialization 24 weeks after implantation.</p>