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1.
Chinese Journal of Cancer Biotherapy ; (6): 590-597, 2021.
Article in Chinese | WPRIM | ID: wpr-882197

ABSTRACT

@#[摘 要] 目的:体内外实验探讨木鳖子单体化合物对羟基桂皮醛[Momordica cochinchinensis(Lour.)Spreng.p-hydroxycinnamaldehyde,CMSP]对小鼠黑色素瘤移植瘤生长和转移的影响及其作用机制。方法:建立荷瘤小鼠动物模型,并将18只C57BL/6小鼠随机分成3组(每组6只):对照组(腹腔注射0.1 ml生理盐水)、CMSP治疗组(分别腹腔注射0.1 ml 1、2 mg/ml CMSP),给药的第5天开始,每次给药前用卡尺分别测量和计算小鼠移植瘤的体积,实验结束后称量移植瘤的质量;H-E染色后光镜观察肝组织的病理学变化;免疫组织化学SP法观察移植瘤组织E-cadherin和vimentin蛋白的表达。采用细胞划痕和Transwell实验分别检测CMSP实验组(10、20 µg/ml)黑色素瘤B16细胞24、48 h的迁移能力,qPCR法检测CMSP处理24 h后B16细胞EMT相关mRNA表达,WB法检测CMSP处理B16细胞48 h后β-catenin、p-β-catenin(Ser675)、vimentin和E-cadherin蛋白的表达水平。结果:CMSP治疗组小鼠移植瘤平均体积和肿瘤质量明显降低(均P<0.05);对照组小鼠肝脏中转移灶的数量明显多于CMSP(1、2 mg/kg)治疗组(均P<0.05),CMSP(2 mg/kg)处理组小鼠的肝组织内未发现明显转移灶。CMSP治疗组(1、2 mg/kg)移植瘤组织中E-cadherin蛋白表达水平明显高于对照组(均P<0.05),而vimentin蛋白表达显著低于对照组(均P<0.01)。体外实验中,CMSP实验组(10、20 μg/ml)B16细胞24、48 h后划痕愈合率较对照组均明显降低(均P<0.05)。20 μg/ml CMSP处理B16细胞24、48 h后穿过Transwell小室的细胞数较对照组则显著下降(均P<0.01)。CMSP(10、20 μg/ml)处理B16细胞后β-catenin mRNA表达水平较对照组明显降低(均P<0.01),E-cadherin mRNA表达水平则明显升高(均P<0.05),而vimentin mRNA表达水平在10 μg/ml处理组与对照组相比差异无统计学意义(P>0.05),20 μg/ml处理组则明显降低(P<0.01)。与对照组相比,CMSP实验组(10、20 μg/ml)处理B16细胞后β-catenin、p-β-catenin和vimentin蛋白表达均显著降低(均P<0.01),而E-cadherin蛋白表达则明显升高(均P<0.01)。结论:CMSP能够抑制小鼠黑色素瘤移植瘤的生长和转移,其作用机制可能与抑制wnt/β-catenin通路的活性相关。

2.
Int. j. morphol ; 38(2): 415-422, abr. 2020. tab, graf
Article in English | LILACS | ID: biblio-1056456

ABSTRACT

This study aimed to investigate the sagittal spinal-pelvic morphological changes, as well as the relationship between pelvic anatomical changes and the spinal-pelvic plane in patients with adolescent idiopathic scoliosis (AIS), in order to provide guidelines for orthopedic surgery in AIS. X-ray data were collected for retrospective analysis from 30 patients diagnosed as AIS in the Departments of Radiology at the Second Affiliated Hospital of Inner Mongolia Medical University and the Inner Mongolia International Mongolian Medical Hospital from April 2014 to November 2018, along with 30 normal adolescents as control. Pelvic parameters, including pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS), a spinal parameter, lumbar lordosis (LL), and anatomical parameters, including sacral width (SW) and femoral head- sacrum distance (FH-S), were measured. The spinal-pelvic parameters were compared between AIS patients and normal controls and also between male and female AIS patients. Pearson correlation was performed to analyze correlation between spinal-pelvic parameters and between spinal-pelvic parameters and anatomical parameters in both AIS patients and normal controls. PT was significantly lower in AIS patients than in normal controls (P < 0.05), whereas no significant difference was found in the other spinal-pelvic parameters, i. e. , LL, PI, and SS. There was a significant difference in PT between sexes in AIS patients. SS was significantly correlated with LL in EIA patients (P < 0.05, r > 0.5). SS was significantly correlated with LL and PI, and PT with LL, PI, and SS in normal controls (all P < 0.05), and there was no significant correlation between the other sagittal spinal-pelvic parameters (P > 0.05). FH-S was significantly correlated with LL, PI, SS, and PT in AIS patients (all P < 0.05). AIS affects some of the sagittal spinalpelvic parameters and anatomical parameters. In AIS, there is a significant correlation between the spinal-pelvic parameters, and the anatomical parameter is significantly correlated with multiple spinal-pelvic parameters.


Este estudio tuvo como objetivo investigar los cambios morfológicos sagitales de la columna vertebral-pélvica, así como la relación entre los cambios anatómicos pélvicos y el plano espinal-pélvico en pacientes con escoliosis idiopática adolescente (EIA), con el fin de proporcionar pautas para la cirugía ortopédica en AIS. Se obtuvieron los datos de rayos X para el análisis retrospectivo de 30 pacientes diagnosticados como EIA en los Departamentos de Radiología del hospital Second Affiliated Hospital of Inner Mongolia Medical University y el hospital Inner Mongolia International Mongolian Medical Hospital, desde abril de 2014 hasta noviembre del 2018, junto con 30 adolescentes normales como control. Se midieron los parámetros pélvicos, que incluyeron incidencia pélvica (IP), inclinación pélvica (P) y pendiente sacra (PS), un parámetro espinal, lordosis lumbar (LL) y parámetros anatómicos, que incluyeron el ancho sacro (AS) y la distancia del sacro cabeza femoral (FH-S). Los parámetros espinalpélvicos se compararon entre los pacientes con EIA y los controles normales, como también entre pacientes con EIA masculinos y femeninos. La correlación de Pearson se realizó para analizar la correlación entre los parámetros espinal-pélvicos y entre los parámetros espinal-pélvicos y los parámetros anatómicos tanto en pacientes con EIA como en controles normales. PT fue significativamente menor en pacientes con EIA que en los controles normales (P <0,05), mientras que no se encontraron diferencias significativas en los otros parámetros espinal-pélvicos, i. mi. , LL, PI y SS. Hubo una diferencia significativa en PT en pacientes de ambos sexos con EIA. SS se correlacionó significativamente con LL en pacientes con EIA (P <0,05, r> 0,5). SS se correlacionó significativamente con LL y PI, y PT con LL, PI y SS en controles normales (todos P <0,05), y no hubo correlación significativa entre los otros parámetros sagitales de la columna vertebral-pélvica (P> 0,05) FH-S se correlacionó significativamente con LL, PI, SS y PT en pacientes con EIA (todos P <0,05). EIA afecta algunos de los parámetros sagitales de la columna vertebral-pélvica y los parámetros anatómicos. En EIA, existe una correlación significativa entre los parámetros espinal-pélvicos, y el parámetro anatómico se correlaciona significativamente con múltiples parámetros espinales-pélvicos.


Subject(s)
Humans , Male , Female , Adolescent , Pelvic Bones/anatomy & histology , Scoliosis/pathology , Spine/anatomy & histology
3.
Chinese Journal of Cancer Biotherapy ; (6): 1018-1023, 2020.
Article in Chinese | WPRIM | ID: wpr-825754

ABSTRACT

@#[Abstract] Objective: To observe the effect of allogeneic platelets transfusion on the invasion and metastasis of human lung cancer A549 cells, and to preliminarily explore its mechanism of action. Methods: Eighty-nine patients with advanced lung cancer, who had received platelet transfusion in the Chemotherapy Department of Fourth Hospital of Hebei Medical University between January 2017 and December 2018, were enrolled in this study. The study cells were randomized into Ctrl group (A549 cells co-incubated with culture medium), Before group, and After group (A549 cells co-incubated with plasma Before and After platelet transfusion, respectively). The migration and invasion of A549 cells co-cultured with plasma before and after platelet transfection were detected by Scratch and Transwell experiments. The expression of MMPs, TIMPs and epithelial-mesenchymal transition (EMT) related proteins E-cadherin, N-cadherin and Vimentin, as well as vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR2) were detected by Western blotting (WB) method. Results: The scratch healing ability of A549 cells in After group was significantly higher than that of Ctrl group and Before group [(73.67±2.60)% vs (58.33±2.33)%, (35.33±2.03) %; P<0.01, vs Ctrl group; P<0.05, vs Before group], and there was also a significant difference between Before group and Ctrl group (P<0.05). The results of cell migration experiment showed that the number of transmembrane cells in After group was significantly higher than that in Ctrl group and Before group [(69.67±7.84) vs (18±2.08) and (39.33±2.03), all P<0.01]. The cell invasion experiment showed that the number of transmembrane cells in After group was significantly higher than that in Ctrl group and Before group [(59.34±3.46) vs (18.34±1.56) and (37.58±2.79), all P<0.01]. When A549 cells were co-incubated with plasma before and after platelet transfusion for 48 h, it was found that the expressions of MMP9 and MMP2 were increased (P<0.05), while their inhibitors TIMP1 and TIMP2 were decreased (P<0.01); the expressions of EMT-related proteins N-cadherin and Vimentin were increased (P<0.05), but E-cadherin was decreased (P<0.01); the expressions of angiogenesis related proteins VEGF and VEGFR2 were increased (P<0.05). Conclusion: Alloplatelets transfusion can promote the invasion and metastasis of lung cancer A549 cells, which may be realized by regulation of the expressions of EMT, metallomatrix protease and vascular growth factor-related proteins.

4.
Journal of Preventive Medicine ; (12): 4-5, 2020.
Article in Chinese | WPRIM | ID: wpr-822680

ABSTRACT

Objective@#To investigate the prevalence and influencing factors of abnormal ankle-branchial index(ABI)among community diabetic patients in Liangxi District of Wuxi. @*Methods@#From April to October 2018,the community patients with type 2 diabetes mellitus(T2DM)were selected from 12 streets in Liangxi District by convenient sampling method. The general information,body mass index(BMI),fasting blood glucose and ABI of the patients were collected by questionnaire survey,physical examination and laboratory test. The influencing factors for ABI abnormality were analyzed by multinomial logistic regression models.@*Results @#A total of 2 235 patients with T2DM were investigated,with an average age of(67.74±7.85)years old and an average course of disease of(10.25±7.38)years. There were 210 cases(9.40%)of low ABI,1 972 cases(88.23%)of normal ABI,and 53 cases(2.37%)of high ABI. The results of multinomial logistic regression analysis showed that systolic blood pressure(OR=1.021,95%CI:1.013-1.029),age(OR=1.081,95%CI:1.059-1.105),course of disease(OR=1.023,95%CI:1.004-1.041)and regular exercise(OR=0.499,95%CI:0.366-0.681)were influencing factors for low ABI;BMI(OR=1.120,95%CI:1.034-1.213)was a risk factor for high ABI. @*Conclusions@# The prevalence of abnormal ABI is high among community patients with T2DM in Liangxi District. Systolic blood pressure,age,course of disease,BMI and regular exercise are the influencing factors for ABI abnormality.

5.
Chinese Journal of Cancer Biotherapy ; (6): 623-631, 2019.
Article in Chinese | WPRIM | ID: wpr-798308

ABSTRACT

@#Objective: To investigate the expression of miR-1269a in esophageal squamous cell carcinoma (ESCC) tissues and its effect on the malignant biological behaviors of ESCC KYSE30 cells, as well as to explore the underlying mechanism. Methods: Ninety specimens of ESCC tissues and adjacent para-cancerous tissues were obtained from patients underwent surgery in Fourth Hospital, Hebei Medical University. In addition, normal esophageal immortalized epithelial cells and esophageal cancer cell lines were also collected. The expression level of miR-1269a in above mentioned tissues and cell lines was examined by Real-time fluorescent quantitative PCR. After being transfected with miR-1269a mimics and inhibitors, the effects of miR-1269a on proliferation, migration, invasion and colony formation of KYSE30 cells were detected by MTS, Transwell and colony formation assay, respectively. The bioinformatics tool was used to predict the possible target genes of miR-1269a. Then the regulation effect of miR-1269a on target gene expression was validated by WB and Dual-luciferase reporter assay. After being transfected with SOX6 plasmid, the effects of SOX6 on the proliferation, migration, invasion and colony formation of KYSE30 cells were detected by MTS, Transwell and colony formation assay, respectively. At last, rescue assay was used to confirm the results. Results: The expression level of miR-1269a in ESCC tissues was significantly higher than that in adjacent para-cancerous tissues (P<0.05), and the expression level of miR-1269a in ESCC cell lines was significantly elevated compared with the normal epithelial cells (P<0.05 or P<0.01). The capacities of proliferation, invasion, migration and colony formation of KYSE30 cells in miR-1269a mimics transfection group were obviously higher than those in mimics NC group, while those abilities in miR-1269a inhibitor transfection group were significantly lower than those in inhibitor NC group (P<0.05 or P<0.01). Bioinformatics analysis showed that miR-1269a could combine with 3’UTR region at SOX6 gene; and after miR-1269a over-expression, the expression level of SOX6 and luciferase activity in KYSE30 cells were significantly reduced (P<0.05). Rescue assay showed that miR1269a over-expression could promote the proliferation, invasion and migration of KYSE 30 cells, while simultaneous transfection of SOX6 could partially reverse the promotion effect of miR-1269a mimics. Conclusion: The expression level of miR-1269a in ESCC tissues and cell lines is significantly increased, and it could enhance proliferation, migration, invasion and colony formation of KYSE30 cell line.And its mechanism may be related to the suppression of its target gene SOX6.

6.
Chinese Journal of Cancer Biotherapy ; (6): 993-998, 2019.
Article in Chinese | WPRIM | ID: wpr-793299

ABSTRACT

@#Objective: To detect the expression of non-coding RNA snord105b in gastric cancer (GC) tissues, sera and cell lines, and its correlation with clinicopathological characteristics of patients with GC as well as its effect on the proliferation of GC cells. Methods: One hundred and twenty pairs of GC tissues and corresponding para-cancerous tissues from patients, who underwent surgery at Department of Surgery, the Fourth Hospital of Hebei Medical University between 2016 and 2017, were collected for this study. The presurgical sera samples from GC patients (n=50) and peripheral venous blood samples from healthy donors (n=30), as well as five gastric cancer cell lines (SGC-7901, AGS, MGC-803, BGC-823, HGC-27) and gastric mucosa normal epithelial GES-1 cells were also obtained. qPCR assay was adopted to detect the expression of snord105b in GC tissues, sera and cell lines. The correlation between snord105b and patients’clinicopathological features was investigated. MTS assay was adopted to detect the effect of snord105b silence or over-expressionon in vitro proliferation of four GC cells. Results: qPCR assay demonstrated that the expression of snord105b in GC tissues, sera and cell lines were significantly higher than that of para-cancerous tissues, sera from healthy donors and GES-1 cells (all P< 0.05). Expression level of snord105b was obviously associated with age,tumor size, differentiation and TNM stages of patients (all P<0.05). MTS assay demonstrated that knockdown of snord105b could suppress the proliferation of GC cells (P< 0.05), while forced-expression of snord105b could promote the proliferation of GC cells (P< 0.05). Conclusion: non-coding RNA snord105b aberrantly expressed in GC tissues, sera, and cells, and its expression was obviously correlated with patients’age, tumor size, differentiation and TNM stages. Snord105b could significantly promote the proliferation of GC cells, which may be used as a potential clinical biomaker for early diagnosis and prognosis of GC.

7.
Chinese Journal of Cancer Biotherapy ; (6): 1282-1289, 2018.
Article in Chinese | WPRIM | ID: wpr-801643

ABSTRACT

@# Objective: To investigate the expression of miR-1269 in non-small-cell lung cancer (NSCLC) tissues, and to explore its effect on the cellular biological characteristics of NSCLC A549 cells and the underlying mechanism. Methods: 34 pairs of NSCLC tissues and the corresponding adjacent para-cancerous tissues obtained from the patients, who underwent surgery in the Department of Breast Surgery, the Fourth Hospital of Hebei Medical University from Jan. 2017 to Jan. 2018, were collected for this study. The expression level of miR-1269 in above tissue specimens was examined by real-time fluorescent quantitative PCR.After transfection with miR1269 mimics and mimics NC (negative control), the proliferation, migration and invasion of A549 cells were detected by MTS, Wound healing and Transwell assay, respectively; and the changes in cell cycle distribution of A549 cells were examined by flow cytometry. The bioinformatics tool was used to predict the possible target gene of miR-1269, and the regulation effect of miR-1269 on target gene was then validated by Western blotting and Dual-luciferase reporter assay. In the meanwhile, the protein expressions of cyclin depen dent kinase inhibitor p21, Cyclin D2, and EMT-related proteins (E-cadherin and ZEB2) in the transfected A549 cells were measured by Western blotting. Results: The expression level of miR-1269 in NSCLC tissues was significantly higher than that in paracancerous tissues (2.81±2.27 vs 1.61±1.36, P <0.05). The capacities of proliferation, migration and invasion ofA549 cells in miR-1269 mimics transfection group were significantly higher than those in mimics NC group and blank control group (all P <0.01). And the cell proportion at S-phase in miR-1269-mimics group was obviously higher than that in mimics NC group [(46.54±1.57)% vs (23.32±3.15)%, P<0.01]. Bioinformatics analysis showed that miR-1269 could combine with 3’UTR of FOXO1 gene. After transfection with miR-1269 mimics, the expression level and luciferase activity of FOXO1 protein in A549 cells were significantly reduced (all P <0.01). Moreover, the protein expressions of p21 and E-cadherin were significantly decreased after over-expression of miR-1269 (all P <0.05), while the expressions of ZEB2 and Cyclin D2 were up-regulated (all P <0.05). Conclusion: The expression level of miR-1269 in NSCLC tissues was significantly increased, and it could enhance the proliferation, cell cycle progression, migration and invasion ofA549 cells. The possible mechanism may be related to its targeted regulation of FOXO1.

8.
Braz. j. med. biol. res ; 51(7): e7220, 2018. tab, graf
Article in English | LILACS | ID: biblio-889115

ABSTRACT

An abnormality in the Lin28/let-7a axis is relevant to the progression of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), which could be a novel therapeutic target for this malignant tumor. The present study aimed to investigate the antiproliferative and anti-invasive effects of urolithin A in a stable full-length HBV gene integrated cell line HepG2.2.15 using CCK-8 and transwell assays. The RNA and protein expressions of targets were assessed by quantitative PCR and western blot, respectively. Results revealed that urolithin A induced cytotoxicity in HepG2.2.15 cells, which was accompanied by the cleavage of caspase-3 protein and down-regulation of Bcl-2/Bax ratio. Moreover, urolithin A suppressed the protein expressions of Sp-1, Lin28a, and Zcchc11, and elevated the expression of microRNA let-7a. Importantly, urolithin A also regulated the Lin28a/let-7a axis in transient HBx-transfected HCC HepG2 cells. Furthermore, urolithin A decelerated the HepG2.2.15 cell invasion, which was involved in suppressing the let-7a downstream factors HMGA2 and K-ras. These findings indicated that urolithin A exerted the antiproliferative effect by regulating the Lin28a/let-7a axis and may be a potential supplement for HBV-infected HCC therapy.


Subject(s)
Humans , RNA-Binding Proteins/drug effects , Carcinoma, Hepatocellular/drug therapy , Coumarins/pharmacology , MicroRNAs/drug effects , Liver Neoplasms/drug therapy , Reference Values , Sincalide/analysis , Time Factors , Virus Replication/drug effects , Cell Survival/drug effects , Blotting, Western , Reproducibility of Results , Analysis of Variance , RNA-Binding Proteins/analysis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , MicroRNAs/analysis , Cell Proliferation/drug effects , Hep G2 Cells , Real-Time Polymerase Chain Reaction , Liver Neoplasms/genetics , Liver Neoplasms/virology
9.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 319-325, 2017.
Article in Chinese | WPRIM | ID: wpr-333480

ABSTRACT

Esophageal cancer is a common malignant tumor,whose pathogenesis and prognosis factors are not fully understood.This study aimed to discover the gene clusters that have similar functions and can be used to predict the prognosis of esophageal cancer.The matched microarray and RNA sequencing data of 185 patients with esophageal cancer were downloaded from The Cancer Genome Atlas (TCGA),and gene co-expression networks were built without distinguishing between squamous carcinoma and adenocarcinoma.The result showed that 12 modules were associated with one or more survival data such as recurrence status,recurrence time,vital status or vital time.Furthemaore,survival analysis showed that 5 out of the 12 modules were related to progression-free survival (PFS) or overall survival (OS).As the most important module,the midnight blue module with 82 genes was related to PFS,apart from the patient age,tumor grade,primary treatment success,and duration of smoking and tumor histological type.Gene ontology enrichment analysis revealed that "glycoprotein binding" was the top enriched function of midnight blue module genes.Additionally,the blue module was the exclusive gene clusters related to OS.Platelet activating factor receptor (PTAFR) and feline Gardner-Rasheed (FGR) were the top hub genes in both modeling datasets and the STRING protein interaction database.In conclusion,our study provides novel insights into the prognosis-associated genes and screens out candidate biomarkers for esophageal cancer.

10.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 1-10, 2017.
Article in Chinese | WPRIM | ID: wpr-238410

ABSTRACT

This meta-analysis was carried out to evaluate the relationship between NM23 expression and the prognosis of patients with colorectal cancer.We searched PubMed,EMBASE and Web of Science for relevant articles.The pooled odd ratios (ORs) and corresponding 95%CI were calculated to evaluate the prognostic value of NM23 expression in patients with colorectal cancer,and the association between NM23 expression and clinicopathological factors.In total,2289 patients were pooled from 24 available studies.The incorporative OR combined by 16 studies with overall survival showed that high NM23 expression was associated with better overall survival (OR=0.67,95%CI:0.49-0.93,P=0.02,I2=56%,Ph=0.004).And a new estimate without heterogeneity was produced when only combining high-quality studies (OR=0.70,95%CI:0.56-0.86,P=0.0007,I2=46%).In disease free survival (DFS),we also obtained a good prognosis (OR=0.30,95%CI:0.14-0.68,P=0.004).Although we failed to find any significance in N status (P=0.10),elevated NM23 expression was related to well tumor differentiation (OR=0.60,95%CI:0.44-0.820,P=0.001) and Dukes' A&B (OR=0.55,95%CI:0.32-0.95,P=0.03).These results indicated that over-expressed NM23 might be an indicator of good prognosis,well tumor differentiation and Dukes' A&B of patients with colorectal cancer,but no significance was found in N status.

11.
International Eye Science ; (12): 1399-1402, 2014.
Article in Chinese | WPRIM | ID: wpr-641965

ABSTRACT

AIM: To investigate the efficacy of intravitreal ranibizumab combined with laser therapy in the treatment of macular edema caused by branch retinal vein occlusion ( BRVO) . METHODS:There were 78 patients (78 eyes) who were diagnosed with macular edema caused by BRVO using fundus fluorescence angiography ( FFA ) and optical coherence tomography ( OCT ) . Group A: randomly selected 26 cases ( 26 eyes ) were given grid laser photocoagulation ( GLP) . Group B: randomly selected 26 cases (26 eyes) were given GLP first, and then received intravitreal ranibizumab 1wk later. Group C: randomly selected 26 cases ( 26 eyes ) undergone intravitreal ranibizumab first, and then given GLP 1wk later. There was no significant difference in macular edema. We analyzed the changes in the best corrected visual activity ( BCVA ) , central macular thickness ( CMT ) before and 1wk, 1,6mo after treatment. RESULTS: Compared with before treatment, 1wk after treatment: mean value changes of BCVA and CMT were no significant difference in group A (P>0. 05);mean value changes of BCVA was improved and mean value of CMT was decreased in groups B and C, the difference was statistically significant (P0.05) between groups A and B after 6mo treatment;mean BCVA improved and CMT average value was decreased in group C, the difference was statistically significant ( PCONCLUSION: Intravitreal injection ranibizumab combined laser therapy can effectively reduce BRVO induced macular edema, enhance vision acuity. Compared with GLP, combination therapy has more rapid onset of treatment, and reduce macular edema better; Intravitreal ranibizumab should be given in front of the GLP, and the treatment effect is more precise, more stability.

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