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1.
Cancer Research on Prevention and Treatment ; (12): 622-627, 2023.
Artigo em Chinês | WPRIM | ID: wpr-986241

RESUMO

Metastasis is the main cause of cancer-related death. Growing evidence has shown that changes in glucose metabolism in nasopharyngeal carcinoma cells affect the invasion and metastasis of nasopharyngeal carcinoma through many pathways. This review summarizes the molecular mechanism underlying abnormal glucose metabolism in nasopharyngeal carcinoma cells and analyzes its relationship with the invasion and metastasis of nasopharyngeal carcinoma, including aerobic glycolysis, aerobic oxidation, and pentose phosphate pathway. The aim is to provide novel approaches using the relationships among glucose metabolism, invasion, and metastasis in the targeted therapy of nasopharyngeal carcinoma.

2.
Chinese Journal of Hepatobiliary Surgery ; (12): 659-663, 2018.
Artigo em Chinês | WPRIM | ID: wpr-708484

RESUMO

Objective To summarize our experience in the diagnosis and treatment of hepatic epithelioid angiomyolipoma (HEAML),with the aim to reduce the future misdiagnosis rate.Methods The PubMed,Medline,China Science Periodical Database (CSPD),and VIP Databases were searched from January 2000 to March 2018 on all reports on HEAML.Results There were 409 cases of HEAML in 97 reports.The ratio of men to women was 1∶4.84.The age ranged from 12 to 80 years and the median age was 44 years.61.9% of patients (205/331) were asymptomatic,while 34.7% (115/331) had upper or right upper quadrant abdominal discomfort.Some patients presented with abdominal mass,gastrointestinal reaction,low grade fever or weight loss.The clinical symptoms in 78 patients were not mentioned in the reports.The misdiagnostic rate of HEAML was as high as 40.3% (165/409).The imaging findings of HEAML were nonspecific.Ultrasound,CT and MRI scan usually showed contrast enhancement in the arterial phase.Most lesions were accompanied by central vessels with early drainage veins.The enhanced scans showed varied characteristics.The ratios of fast wash-in and fast wash-out,to fast wash-in and slow wash-out,and to delayed enhancement were roughly 4∶ 5∶ 1.A definitive diagnosis of HEAML is based on the pathological findings of epithelioid cells in the lesions and the expressions of HMB45,SMA,Melan-A and Actin on immunohistochemical staining.HEAML had a relatively low malignant rate of 3.9%.Surgical resection was the main treatment for HEAML.Conclusion HEAML was a rare and easily misdiagnosed disease.,which could be diagnosed by taking into account the clinical course,imaging,pathological and immunohistochemical findings.HEAML.

3.
Chinese Journal of Hepatobiliary Surgery ; (12): 150-154, 2018.
Artigo em Chinês | WPRIM | ID: wpr-708376

RESUMO

Objective To study liver transplantation in the treatment of alcoholic liver disease (ALD).Methods A retrospective study was conducted on 40 patients with ALD who underwent liver transplantation in the Changzheng Hospital of the Second Military Medical University from April 2005 to June 2017.The data were expressed as mean ± standard deviation ((-x) ±s) in populations with a normal distribution,and as median (min~max) in populations with an abnormal distribution.The survival rate was analyzed by life tables,and the Cox regression analysis was used for multivariate analysis.Results All patients were followed up until August 31,2017.The follow-up time was 2 ~ 4518 days,with a median of 997 days.Among the 40 patients,8 had already died (3 died of multiple organ failure,2 of biliary complications,1 of liver failure,1 of sepsis and 1 of recurrence of hepatocellular carcinoma (HCC).The 1-year survival rate was 81.0%,and the 5-year survival rate was 77.0%.Four of 40 patients developed tumor recurrence.The initial recurrence time was 189 ~ 337 days (median 236.5).The recurrence sites included the liver,colon combined with lungs,lungs,and lumbar vertebrae.Six of 40 (15.0%) patients had relapse in alcoholism.Multivariate analysis showed that age was a prognostic factor (RR =1.109,P <0.05).Years of drinking,daily amount of alcohol intake,abstinence,a previous history of upper gastrointestinal bleeding,a previous history of splenectomy,co-existing hepatocellular carcinoma,preoperative MELD score,preoperative Child-Pugh score,total operation time,anhepatic period,cold ischemia time,amount of intraoperative bleeding,postoperative alcoholism relapse,tumor recurrence or new onset of tumor were not significantly correlated with the postoperative survival rate (P>0.05).Conclusions ALD patients were mostly 40 ~ 60 years old.Age was an independent factor affecting survival.The younger the patient,the better the prognosis.Other factors were of no prognostic significance.

4.
Organ Transplantation ; (6): 220-224, 2017.
Artigo em Chinês | WPRIM | ID: wpr-731683

RESUMO

Objective To summarize the clinical experience of diagnosis and treatment of nontuberculosismycobacterium (NTM) infection after liver transplantation. Methods Clinical experience of effective treatment of 1 case with NTM at 7th month after liver transplantation at the Shanghai Changzheng Hospital affiliated to the Second Military Medical University was summarized and literature review was performed. Results Following liver transplantation, the NTMpatient was clinically manifested with fever in the afternoon. CT scan prompted the progression of the disease. The lesions were enlarged and fused with thin-walled cavity in the right upper lung. The diagnosis of NTM infection was validated by fiberoptic bronchoscopy (brush or lavage approach), spot test of T cells infected with mycobacterium tuberculosis (T-SPOT. TB), multiple phlegm culture and empirical anti-tuberculosis therapy. The patient was effectively treated and successfullydischarged after diagnostic quadruple anti-tuberculosis therapy. The patient was followed up until the day of manuscript submission. The patient was physically stable without the symptoms of fever and cough with asthma. The liver function was normal. Conclusions The incidence of NTM infection is rare and inneglectable after liver transplantation. Application of fibrobronchoscopy via brush or lavage approach can enhance the positive diagnostic rate. Diagnostic quadruple antituberculosis therapy is efficacious for NTM infection.

5.
Journal of Clinical Hepatology ; (12): 1977-1980, 2017.
Artigo em Chinês | WPRIM | ID: wpr-664049

RESUMO

Objective To investigate the clinical effect of liver transplantation in the treatment of hepatolenticular degeneration (HLD) and the prognosis of HLD patients.Methods A retrospective analysis was performed for the clinical data of 15 HLD patients who underwent liver transplantation in Changzheng Hospital of Second Military Medical University from June 2003 to January 2017.Friedman test of K related samples test was used for comparison of data between groups,and Wilcoxon one-sample test of 2 related samples test was used for comparison of data between two groups.Results Of all patients,13 underwent standard orthotopic liver transplantation,and 2 underwent modified piggyback liver transplantation.One patient died of multiple organ failure during the perioperative period and 2 were lost to follow-up at half a year after surgery.Of all patients,one lived for 14 months,one lived for 5 years and 8 months,and the other ten patients were still alive up to now.Six patients suffered from acute rejection reaction (AR),among whom four were improved after conventional hormone pulse therapy,one was improved and discharged after antiviral therapy with ganciclovir for cytomegalovirus infection,and the other one patient was improved and discharged after the second liver transplantation at 5 months after surgery due to poor response to hormone pulse therapy and chronic rejection reaction.Ten patients had varying degrees of improvement in positive Kayser-Fleischer ring,and three patients achieved varying degrees of improvement in severe neuropsychiatric symptoms and had a basically normal neuropsychiatric state at half a year to one year after surgery.One patient died in the perioperative period,and the other 14 patients had a significant improvement in liver function at 1 month after surgery,and the level of ceruloplasmin gradually increased to a normal level.Conclusion Orthotopic liver transplantation can effectively improve copper metabolism,liver function,and neuropsychiatric symptoms in HLD patients and increase their quality of life and long-term survival rates.

6.
Pakistan Journal of Medical Sciences. 2015; 31 (6): 1361-1365
em Inglês | IMEMR | ID: emr-175109

RESUMO

Objective: To investigate the clinical features of epistaxis in the posterior fornix of the inferior nasal meatus and compare the treatment outcomes of endoscopic surgery and conventional nasal packing for this intractable form of epistaxis


Methods: Between August 2011 and August 2014, the medical records of 53 adult patients with idiopathic epistaxis in the posterior fornix of the inferior nasal meatus diagnosed by nasal endoscopy were obtained from our department. Of these, 38 patients underwent endoscopic surgery [surgery group] and 15 received a nasal pack [packing group]. The patients' background characteristics, incidence of re-bleeding, extent of discomfort after treatment as assessed using a 10-point visual analogue scale [VAS] and incidence of nasal cavity adhesion after treatment were analysed


Results: There were no significant differences in background characteristics between the two groups. The incidence of re-bleeding [0/38 vs. 4/15, surgery vs. control, P = 0.001], VAS score for discomfort [2.4 +/- 1.4 vs. 7.6 +/- 1.0, surgery vs. control, P = 0.001] and incidence of nasal cavity adhesion after treatment [2/38 vs. 7/15, surgery vs. control, P = 0.007] were significantly lower in the surgery group than in the packing group


Conclusion: Endoscopic surgery is superior to conventional nasal packing for the management of epistaxis in the posterior fornix of the inferior nasal meatus. During surgery, it is crucial to expose the bleeding sites by shifting the inferior turbinate inward by fracture


Assuntos
Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Endoscopia , Administração Intranasal
7.
Organ Transplantation ; (6): 222-226, 2014.
Artigo em Chinês | WPRIM | ID: wpr-731544

RESUMO

Objective To investigate the prognosis of patients underwent liver transplantation (LT) for end-stage autoimmune liver disease (AILD). Methods Clinical data of 48 patients with end-stage AILD undergoing LT from May 1996 to April 2013 in Affiliated Changzheng Hospital of the Second Military Medical University were analyzed retrospectively. The postoperative cumulative survival rates of the recipients were calculated,and the cause of death was analyzed. The postoperative rejections,new-onset viral hepatitis and AILD recurrence were analyzed. Results In 48 AILD recipients,38 cases survived and the postoperative 5-year cumulative survival rate was 76%. Causes of death for the 10 dead cases were multiple organ failure, liver graft failure,sepsis,pulmonary infection,hemorrhage,hepatic artery embolization and renal failure. In 48 AILD recipients,9 cases (19%) suffered acute rejection after operation,3 cases suffered new-onset hepatitis B infection in 1-2 years after operation,2 recipients suffered primary disease (primary biliary cirrhosis)recurrence 2 years after operation and all survived for a long term after positive treatments.Conclusions Most liver transplant recipients with end-stage AILD can obtain a long-term survival. Attentions should be paid on the immunosuppressive regimens in early period after LT,prevention of infection,rejection and postoperative new-onset viral hepatitis,timely diagnosis of primary disease recurrence.

8.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 680-685, 2012.
Artigo em Inglês | WPRIM | ID: wpr-233100

RESUMO

The normal range of oral mucosal cell apoptosis and proliferation rate through a larger sample of non-malnourished crowd was investigated, and the nutritional status of clinical patients was assessed. Of 194 clinical patients selected according to "NRS2002" guidance, there were 167 non-malnourished patients and 27 malnourished cases, respectively. Twelve patients with toxic reactions of grade III after postoperative chemotherapy (POC) were chosen. The oral mucosal epithelial apoptosis and proliferation rate were measured by using flow cytometry. The statistical significance was processed by using unpaired t-test. The results showed that there was no significant difference in gender, age and body weight between malnourished and non-malnourished groups. The normal range of oral mucosal epithelial apoptosis and the proliferation rate was (27.50±1.50)% and (15.12±1.68)% in non-malnourished patients, and that was (19.90±4.14)% and (6.66±5.83)% in the malnourished patients, respectively. It is concluded that the normal range of oral mucosa cell apoptosis and proliferation rate is achieved, which can not be influenced by gender, age, weight and other factors, and could be used as a sensitive and accurate index to assess the nutritional status of clinical patients.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoptose , Fisiologia , Proliferação de Células , Mucosa Bucal , Patologia , Fisiologia , Estado Nutricional , Fisiologia
9.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 680-5, 2012.
Artigo em Inglês | WPRIM | ID: wpr-636613

RESUMO

The normal range of oral mucosal cell apoptosis and proliferation rate through a larger sample of non-malnourished crowd was investigated, and the nutritional status of clinical patients was assessed. Of 194 clinical patients selected according to "NRS2002" guidance, there were 167 non-malnourished patients and 27 malnourished cases, respectively. Twelve patients with toxic reactions of grade III after postoperative chemotherapy (POC) were chosen. The oral mucosal epithelial apoptosis and proliferation rate were measured by using flow cytometry. The statistical significance was processed by using unpaired t-test. The results showed that there was no significant difference in gender, age and body weight between malnourished and non-malnourished groups. The normal range of oral mucosal epithelial apoptosis and the proliferation rate was (27.50±1.50)% and (15.12±1.68)% in non-malnourished patients, and that was (19.90±4.14)% and (6.66±5.83)% in the malnourished patients, respectively. It is concluded that the normal range of oral mucosa cell apoptosis and proliferation rate is achieved, which can not be influenced by gender, age, weight and other factors, and could be used as a sensitive and accurate index to assess the nutritional status of clinical patients.

10.
Chinese Journal of Hepatobiliary Surgery ; (12): 758-760, 2010.
Artigo em Chinês | WPRIM | ID: wpr-386404

RESUMO

Objective To explore the relationship between ATP content in CD4+ T lymphocytes and acute rejection after liver transplantation(LT). Methods This study contained 77 patients who received LT from February to October 2009, They were divided into AR (acute rejection) and NAR (non-acute rejection) groups while 56 healthy people were enrolled to serve as the control group.Blood specimens were collected preoperatively and at 1, 2 and 4 weeks postoperatively. For the AR group, specimens were also collected on the day when AR occurred and 1 week after steroid bump together with that of the healthy people. ImmuKnowTM test kits for immune cell function were used to assay the ATP value. Results ATP values within CD4+T lymphocytes were elevated significantly in each group compared with those preoperatively. Peak level was reached in the AR group and was significantly higher than that of the contemporary NAR group (P<0.05). ROC curve analysis showed that the obvious elevation of the ATP value within CD4+ T lymphocytes 1 week postoperatively had better sensitivity and specificity in diagnosing AR. The ATP sensitivity rate for early AR was 84.6 %and specificity rate 81 %. The ATP value within CD4+ T lymphocytes on the day of AR occurrence had a positive relationship with the rejection acting index(RAI), while relative index (r) was 0. 876(P<0.05). After the steroid dump treatment, AR in all the patients was reversed and the ATP value declined significantly as compared with the control group and the day when AR occurred(P<0. 05).Conclusion During the postoperative period, the dynamic change of ATP value within CD4 + T lymphocyte had a close relationship with acute rejection after liver transplantation. Thus, it might be used as a feasible and noninvasive monitoring index for diagnosing AR and the effectiveness of the anti-rejection treatment.

11.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 751-756, 2010.
Artigo em Inglês | WPRIM | ID: wpr-349749

RESUMO

In this study, CD133+ subpopulations were isolated from 41 primary colorectal cancer tissues, the proliferation and cell cycle distribution of the cells were examined without in vitro expansion, and then compared to those of cell lines. The detection of CD133 in colorectal cancer tissues, isolation of CD133+ and CD133- epithelial subpopulations, Ki-67/DNA multiparameter assay and cell volume analysis were flow cytometrically conducted. The results showed that Ki-67 expression was correlated with CD133 level in primary cancer tissues, while cell cycle G2/M phase distribution or clinicopathological characteristics was not. In addition, the CD133+ cells showed larger cell volume and higher Ki-67 expression as compared with CD133- cells. But there was no statistically significant difference in G(2)/M phase distribution between the two subpopulations. Our results demonstrated that the CD133+ subpopulation in colorectal cancer tissue contained more actively cycling and proliferating cells, which was not correlated to clinicopathological factors but might contribute to tumor progression and poor clinical outcome.


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno AC133 , Antígenos CD , Metabolismo , Ciclo Celular , Fisiologia , Proliferação de Células , Neoplasias Colorretais , Patologia , Glicoproteínas , Metabolismo , Antígeno Ki-67 , Metabolismo , Células-Tronco Neoplásicas , Metabolismo , Patologia , Peptídeos , Metabolismo , Prognóstico
12.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 751-6, 2010.
Artigo em Inglês | WPRIM | ID: wpr-634959

RESUMO

In this study, CD133+ subpopulations were isolated from 41 primary colorectal cancer tissues, the proliferation and cell cycle distribution of the cells were examined without in vitro expansion, and then compared to those of cell lines. The detection of CD133 in colorectal cancer tissues, isolation of CD133+ and CD133- epithelial subpopulations, Ki-67/DNA multiparameter assay and cell volume analysis were flow cytometrically conducted. The results showed that Ki-67 expression was correlated with CD133 level in primary cancer tissues, while cell cycle G2/M phase distribution or clinicopathological characteristics was not. In addition, the CD133+ cells showed larger cell volume and higher Ki-67 expression as compared with CD133- cells. But there was no statistically significant difference in G(2)/M phase distribution between the two subpopulations. Our results demonstrated that the CD133+ subpopulation in colorectal cancer tissue contained more actively cycling and proliferating cells, which was not correlated to clinicopathological factors but might contribute to tumor progression and poor clinical outcome.

13.
Chinese Journal of Gastrointestinal Surgery ; (12): 210-212, 2010.
Artigo em Chinês | WPRIM | ID: wpr-259307

RESUMO

<p><b>OBJECTIVE</b>To investigate the clinical features of Crohn disease according to the Montreal classification.</p><p><b>METHODS</b>Clinical data of 43 surgical patients with Crohn disease (surgical group) and 125 non-surgical patients with Crohn disease (non-surgical group) were retrospectively analyzed and compared between two groups. The Montreal classification was used.</p><p><b>RESULTS</b>In the surgical group, 28 patients (65.1%) were A2, 14 (32.6%) were A3 and only one was A1, which was not significantly different as compared to the non-surgery group. The proportions of L1, L2, L3, and L4 subtype in the surgical group were 41.9%, 25.6%, 30.2%, and 2.3%, respectively, which was not significantly different as compared to that in the non-surgery group. In the surgical group,B1 disease was found in 1 case (2.3%), B2 in 26 cases (60.5%), and B3 in 16 cases (37.2%), while in the non-surgical group, B1 was found in 79 cases (63.2%), B2 in 44 cases (35.2%) and B3 in 2 cases (1.6%). Differences were significant between two groups in disease behavior (P=0.001, P=0.004, P=0.001).</p><p><b>CONCLUSIONS</b>Most surgical patients of Crohn disease are A2. L1 and L3 are the main lesion location. As disease behavior, B2 and B3 are the main reasons for operation.</p>


Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Doença de Crohn , Classificação , Patologia , Cirurgia Geral , Padrões de Referência , Estudos Retrospectivos
14.
Chinese Journal of Biotechnology ; (12): 610-615, 2010.
Artigo em Chinês | WPRIM | ID: wpr-292230

RESUMO

Using the polymmerse chain reaction (PCR), we amplified the phytase gene phyA from Pichia pastoris GS115-phyA in Aspergillus niger NRRL3135 without the signal peptide sequence and intron sequence,. Then, it was cloned into pINA1297 vector to generate a recombinant vector of pINA1297-phyA. pINA1297-phyA was linearized and transformed into Yarrowia lipolytica po1h by the lithium acetate method. The positive transformants were obtained by YNB(casa) and PPB plates, after induced in YM medium at 28 degrees C for 6 day. The activity of the expressed phytase phyA reached 636.23 U/mL. The molecular weight of the enzyme was 130 kDa measured with SDS-PAGE analysis, whereas its molecular size reduced to 51 kDa after deglycosylation which is correspond with theoretical value. The enzymatic analysis of the recombinant phytase phyA revealed its optimal pH and temperature was 5.5 and 55 degrees C, which had high activity after incubated in pH ranged from 2.0 to 8.0 for 1 h. Moreover, its activity remained 86.08% after exposure to 90 degrees C for 10 min. It also was resistant to pepsin or trypsin treatment.


Assuntos
6-Fitase , Genética , Aspergillus niger , Genética , Metabolismo , Pichia , Genética , Proteínas Recombinantes , Genética , Yarrowia , Genética , Metabolismo
15.
Journal of Central South University(Medical Sciences) ; (12): 1047-1050, 2007.
Artigo em Chinês | WPRIM | ID: wpr-813952

RESUMO

OBJECTIVE@#To construct the plasmid of human vascular endothelial cell growth factor165 and green fluorescence protein report gene eukaryotic expression vector of fusion protein pEGFP /hVEGF165, and to detect its expression in vascular endothelial cells.@*METHODS@#We amplified full-length of gene VEGF165 by PCR, cloned in direction in multiple clone sites of pEGFP-N1, constructed recombinant plasmid of pEGFP/hVEGF165. Through enzyme digestion, PCR, and sequencing analysis, we also performed liposome-mediated transfection of vascular endothelial cells of in vitro cultivation, and detected the expression of fusion protein pEGFP/hVEGF165 using fluorescence microscope, RT-PCR, and Western blot.@*RESULTS@#Both gene VEGF165 and multiple clone site of pEGFP-N1 confirmed by PCR, enzyme digestion, and sequence analysis. EGFP/VEGF protein was expressed in vascular endothelial cells after pEGFP/VEGF165 recombinant plasmid transfected vascular endothelial cells.@*CONCLUSION@#Fusion protein eukaryotic plasmid of report gene EGFP and VEGF165 is successfully constructed, and EGFP/VEGF can be expressed in vascular endothelial cells, which lays a foundation for the application of VEGF gene in treating ischemia vascular diseases.


Assuntos
Humanos , Células Cultivadas , Células Endoteliais , Metabolismo , Expressão Gênica , Vetores Genéticos , Proteínas de Fluorescência Verde , Genética , Plasmídeos , RNA Mensageiro , Proteínas Recombinantes de Fusão , Genética , Metabolismo , Transfecção , Fator A de Crescimento do Endotélio Vascular , Genética , Metabolismo
16.
Journal of Central South University(Medical Sciences) ; (12): 295-298, 2007.
Artigo em Chinês | WPRIM | ID: wpr-813891

RESUMO

OBJECTIVE@#To observe the effect of ranitidine on gastric acid, plasma endothelin, and calcitonin gene-related peptide (CGRP) in patients undergoing the brain operation, and to explore the possible pathogenesis of ranitidine on preventing from gastric mucosal injury under the stress.@*METHODS@#Thirty patients who underwent brain surgery were randomly divided into 2 groups: Fifteen patients in the control group did not use ranitidine and the other 15 in the treatment group received ranitidine 150 mg intravenously twice daily besides the routine therapy. We continuously monitored the gastric pH value from 4 hours pre-operatively to 72 hours post-operatively in the 30 patients. We also determined the plasma endothelin and CGRP levels of the patients at the 4th hour pre-operatively and at the 4th, 24th, and 72nd hours post-operatively.@*RESULTS@#In the control group there was no significant difference between the mean intra-gastric pH values pre-operatively and post-operatively (P> 0.05). In the treatment group the level of intra-gastric pH was much higher than that in the control group (P< 0.05). In the control group, the level of plasma endothelin significantly higher and the level of calcitonin gene-related peptide significantly lower than that pre-operatively (P< 0.01), but the level of plasma endothelin significantly was lower and the level of calcitonin gene-related peptide obviously higher in the post-operative treatment group than that pre-operatively (P< 0.01).@*CONCLUSION@#The brain operation obviously influences the endogenous plasma endothelin and CGRP levels, but its influence on the intra-gastric acid is not visible. Ranitidine can obviously decrease the level of intra-gastric acid, and improve the macrocirculation of gastric mucous membrane by decreasing ET and increasing the CGRP level.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antiulcerosos , Usos Terapêuticos , Encéfalo , Cirurgia Geral , Peptídeo Relacionado com Gene de Calcitonina , Sangue , Endotelina-1 , Sangue , Ácido Gástrico , Metabolismo , Infusões Intravenosas , Complicações Pós-Operatórias , Ranitidina , Usos Terapêuticos , Úlcera Gástrica
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