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Purpose@#Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) has become the first-line treatment for advanced renal cell carcinoma, despite the lack of prognostic biomarkers. Cyclin-dependent kinase 5 (CDK5) affects the tumor microenvironment, which may influence the efficacy of TKI+IO. @*Materials and Methods@#Two cohorts from our center (Zhongshan Metastatic Renal Cell Carcinoma [ZS-MRCC] cohort, Zhongshan High-risk Localized Renal Cell Carcinoma [ZS-HRRCC] cohort) and one cohort from a clinical trial (JAVELIN-101) were enrolled. The expression of CDK5 of each sample was determined by RNA sequencing. Immune infiltration and T cell function were evaluated by flow cytometry and immunohistochemistry. Response and progression-free survival (PFS) were set as primary endpoints. @*Results@#Patients of low CDK5 expression showed higher objective response rate (60.0% vs. 23.3%) and longer PFS in both cohorts (ZS-MRCC cohort, p=0.014; JAVELIN-101 cohort, p=0.040). CDK5 expression was enhanced in non-responders (p < 0.05). In the ZS-HRRCC cohort, CDK5 was associated with decreased tumor-infiltrating CD8+ T cells, which was proved by immunohistochemistry (p < 0.05) and flow cytometry (Spearman’s ρ=–0.49, p < 0.001). In the high CDK5 subgroup, CD8+ T cells revealed a dysfunction phenotype with decreased granzyme B, and more regulatory T cells were identified. A predictive score was further constructed by random forest, involving CDK5 and T cell exhaustion features. The RFscore was also validated in both cohorts. By utilizing the model, more patients might be distinguished from the overall cohort. Additionally, only in the low RFscore did TKI+IO outperform TKI monotherapy. @*Conclusion@#High-CDK5 expression was associated with immunosuppression and TKI+IO resistance. RFscore based on CDK5 may be utilized as a biomarker to determine the optimal treatment strategy.
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Objective:To explore the risk factors of acute kidney injury(AKI) in patients after radical nephrectomy.Methods:We retrospectively collected clinical information of 920 patients with renal cell carcinoma who underwent radical nephrectomy at Zhongshan Hospital, Fudan University from February 2013 to September 2017. There were 612 male and 308 female patients included in this study, with a median age of 60 (range from 20-75 years). 313 patients (34.0%) had hypertension, 132 patients (14.3%) had diabetes, and 111 patients (12.1%) had smoking history. 829 cases (90.1%) were in stage 1-2 for preoperative renal function staging, and 91 cases (9.9%) were in stage 3-5. Preoperative hemoglobin was lower than the lower limit of normal in 391 cases (42.5%), white blood cell count increased in 66 cases (7.2%), and platelet increased in 72 cases (7.8%). Albumin was lower than the lower limit of normal in 65 cases (7.1%), lactate dehydrogenase increased in 73 cases (7.9%). blood urea nitrogen increased in 48 cases (5.2%), uric acid increased in 123 cases (13.4%), and urinary protein was positive in 88 cases (9.7%). 496 cases (53.9%) underwent open surgery and 424 (46.1%) underwent laparoscopic surgery. The changes in serum creatinine were followed up within 48 hours after surgery. AKI was defined according to the KDIGO standard. Logistic regression was used to analyze the risk factors for postoperative stage 2-3 AKI in patients.Results:Stage 1-3 AKI occurred on 627, 42 and 10 patients during hospitalization, respectively. Univariate analysis showed that diabetes ( OR=2.34, P=0.01), positive urine protein ( OR=2.22, P=0.04), and elevated white blood cell count ( OR=2.54, P=0.02) were significantly associated with postoperative stage 2-3 AKI. Multivariate logistic regression analysis showed that diabetes ( OR=2.51, P=0.01) and elevated white blood cell count ( OR=2.69, P=0.02) were independent risk factors for postoperative stage 2-3 AKI. Conclusion:Renal cell carcinoma patients with diabetes or preoperative elevated white blood cell count are more likely to develop stage 2-3 AKI after radical nephrectomy.
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Objective To investigate the principles of diagnosis and treatment of non-hereditary bilateral synchronous renal cell carcinoma.Methods This retrospective study analyzed 36 cases of non-hereditary bilateral synchronous renal cell carcinoma in our hospital from January 2008 to December 2016,including 30 males and 6 females.A total of 74 renal tumors were found,in which 34 patients had bilateral single kidney tumor and 2 patients had two tumors in one kidney.The diameter of tumors ranged from 1 cm to 11 cm,with an average of (6.8 ±4.1)cm.The patients that underwent nephron-sparing surgery(NSS) got 4-12 points,with an average of (6.1 ±3.4) points in R.E.N.A.L.score and 3-13 points,with an average of (6.9 ± 3.7) points in Zhongshan score.The patients are classified into 4 groups according to operation methods.In group A,16 patients underwent bilateral NSS,which the preoperative creatinine was 63-103 μmol/L with an average of (80.9 ± 11.4) μmol/L.In group B,7 patients underwent one side of NSS before contralateral radical nephrectomy (RN),which preoperative creatinine was 59-87 μmol/L with an average of (75.7 ± 8.9)μmol/L.In group C,7 patients underwent one side of RN before contralateral NSS,preoperative creatinine was 57-107 μmol/L,with an average of (77.6 ± 19.2) μmol/L.In group D,6 patients underwent one side of NSS or RN and spare the contralateral side,2 of which shifted from NSS to RN after finding tumor invaded pelvis and upper ureter during surgery.Of all the 16 patients with bilateral NSS,4 patients underwent surgery on the side where tumor had a higher score in the first phase and then the side where tumor had a lower score in the second phase,11 underwent surgeries in an opposite order.One patient underwent bilateral NSS simultaneously.Group A,B and C are taken into final analysis.Result All the 30 patients underwent surgery successfully.The operation time of NSS ranged from 60 to 110 min with an average of (88.6 ± 23.6) min and RN ranged from 40 to 90 min with an average of (72.3 ± 21.4) min.The warm ischemia time of NSS was 12-40 mins with an average of (29.5 ± 9.7)min.The creatinine of Group A was 62-117 μmol/L with an average of (89.4 ± 15.8) μmol/L and 57-392 μmol/L with an average of (129.6 ±74.9)μmol/L one month after the first and second surgery respectively.The creatinine of Group B was 64-115 μmol/L with an average of (94 ± 14.4) μmol/L and 93-453 μmol/L with an average of (190.4 ± 117.2)μ mol/L one month after the first and second surgery respectively.The creatinine of Group C was 84-113 μmol/L with an average of (90.1 ± 12.1) μ mol/L and 88-156 μmol/L with an average of (121.4 ± 24.8)μmol/L one month after the first and second surgery respectively.One patient in Group B and C developed lung metastases.One patient in Group B occurred oliguria after the second stage of surgery,and gradually improved after one week of hemodialysis.The creatine showed no significant difference among Group A,B and C before operation,after the first and second stage (P ＞ 0.05).Postoperative hospital stay after the first stage surgery was 3-16 days with an average of (6.7 ± 3.4) d,and 3-16 d with an average of (6.2 ± 3.2)d after the second stage,respectively.Conclusions In principle,bilateral renal tumors should be treated with NSS,wbich can protect renal functions as much as possible.Among patients who can undergo bilateral NSS,the first-stage surgery should be operated on the simpler and easier side to preserve the kidney of one side as much as possible to lay a good foundation for the second stage surgery.Among patients who undergo one side of RN and the other side of NSS,NSS is recommended for the first stage,and RN for the contralateral second stage after the renal function of the operated side was restored.
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Background and purpose: Gene chip is a nucleic acid sequence analysis method which is based on hybridization. It is a high-through put assay which can widely detect the level of gene expression in different tissues and cell types. This study aimed to compare and bioinformatically analyze differentially expressed genes between higher malignant degree of prostate cancer tissues and prostate inflammation tissues. Methods: The total RNAs were isolated from tissues of prostate cancer and prostate inflammation by TRIzol method and then purified, reversely tran-scribed to cDNA with incorporating biotin labeling probe, hybridized with Affymetrix Human U133 Plus 2.0 (covering 47000 transcripts,representing 38500 distinct genes). Picture signals of fluorescence in gene array were scanned and differential expression of gene in two tissues were compared by Command Console Software 4.0. These differential expressed genes were analyzed by bioinformatics methods finally. Results: According to the fold change ≥2, P<0.05, 1819 differential expression genes including 1025 up-regulated genes and 794 down-regulated genes were discovered. GO enrichment analysis displayed that these differentially expressed genes were mainly involved in cell cycle, cell metabolism, etc. KEGG pathway analysis found that these genes were mainly involved in some metabolism pathways including purine nucleotide metabolism. The interactions between the proteins encoded by these genes were analyzed by STING. Twenty key nodes genes including TPX2, ANLN, NUSAP1, MELK, DLGAP5, KIF11, TOP2A, RRM2 were dis-covered. Then this study revealed CEP55 and ANLN might be related to the occurrence and metastasis of prostate cancer by looking through literature. Conclusion: During the development of prostate cancer, the activation of genes related to cell cycle and cell migration, the abnormalities of genes related to metabolism and the inhibition of genes related to cell adhesion play critical roles in the development of prostate cancer. CEP55 and ANLN were related to the occurrence and prognosis of prostate cancer by systematic analysis which provided a valuable clue for the next experiment.
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Objective To evaluate the efficacy of using dual laser system in off clamp nephronsparing surgery.Methods We used dual laser system in the patients who underwent off-clamp NSS between Jan 2016 and Apr 2016 in our institution.There were 16 males and 8 females with average age of 49 years.Mean tumor size was 1.9 cm (range 0.8-3.2 cm).The mean R.E.N.A.L.score was 3.8 (range 3-6).The mean Zhongshan score was 3.5(range 3-5).The mean ZⅡ(zero ischemia index)was 1.6(range 1-4).The Evolve Dual (980 nm/1 470 nm) laser system set at 60 W in continuous mode was used.Results Offclamp NSS was successfully performed in 22 patients except for renal artery occlusion in 2 case.Mean operative time was 74 min(range 50-100 min);The average estimated blood loss was 52.9 ml(range 10-200 ml);Mean postoperative drainage was 65.4 ml(range 20-150ml);Mean postoperative hospital stay was 5.2 days (range:4-7days).No severe post-operative complication was found.The mean pre-and postoperative serum creatinine levels were 76.2 μmol/L(range:48-112μ mol/L) and 81.5μ mol/L(range:54-122 μ mol/L) with no significant difference(P ＞0.05).The postoperative pathology indicated that 20 cases of clear cell carcinomas,3 cases of chromophobe renal cell carcinomas,one case of papillary carcinoma.Conclusions Dual laser system can be used in off clamp nephron-sparing surgery safely and effectively.
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Objective To evaluate the effect and feasibility of mini-flank approach for open partial nephrectomy (MI-OPN) in complex renal tumors with high Zhongshan Score (ZS Score ≥8).Methods Between January 2012 and December 2014, the data from 25 patients with renal tumors , including 18 male and 7 female patients, were retrospectively reviewed.The average age was 50.2 years(range 26-75 years) and the average body mass index was 24.5 kg/m2(range 21.3-30.1 kg/m2).The initial symptom included asymptom in 17 cases, hematuria in 6 cases and other presentation in 2 cases.Bilateral renal tumors were found in 4 cases.Fifteen cases suffered with contralateral urinary stone , renal cyst or hydronephrosis .The preoperative serum creatinine level was 76.9 μmol/L ( range 47 -132 μmol/L ) and the preoperative estimated glomerular filtration rate (eGFR) was 103.8 ml/(min· 1.73 m2)(range 36.5-173.9).The ZS Score was 8 in 11 cases, 9 in 3 cases, 10 in 5 cases, 11 in 2 cases, 12 in 2 cases, and 13 in 2 cases.Mean maximum tumor size was 4.9 cm ( range 2.5-8.1 cm) in CT scan.The average length of incision was 8.0 cm( 7.5 -10.0 cm ) .During the operation , the mass and around normal renal tissue were exposed after opening the Gerota fascia.Along the dorsal of kidney , the renal artery was dissected and clamped .Then, the mass was completely removed along margin of 0.5-1.0 cm normal renal tissue.The vascular end was closed by 3-0 absorbable suture.The entire wound of kidney was U shaped closed by 2-0 absorbable suture.The operative time, ischemia time, estimate blood loss, pathology parameters, operative and short-term (2 -3 months) postoperative complications were recorded .Renal function was recorded 2 -3 months after operation.Results MI-OPN was successfully performed in 23 cases.Radical nephrectomy was performed in 1 cases due to the tumor invasion into the renal pelvis and ureteropelvic junction .Another radical nephrectomy was performed for suspection of positive margin .Mean operative time was 100.2 min ( range 75-150 min) , mean warm ischemia time was 28.3 min( range 21-39 min) and mean estimated blood loss was 63.6 ml(range 10-400 ml).Only 1 case accepted blood transfusion.Mean postoperative hospital stay was 6.6 days (range 5-9 days).Postoperative complications were found in 1 patient, who was found the fluid in surgical region and relieved after the drainage . The pathological diagnosis included clear cell carcinoma in 21 cases, papillary carcinoma in 3 cases and chromophobe cell tumor in 1 case.The mean postoperative serum creatinine level was 88.9μmol/L( range 61-189μmol/L) and the mean postoperative eGFR was 86.3 ml/( min· 1.73 m2 ) ( range 34.0-149.6 ) .There was significant difference between pre and postoperative renal function ( P<0.01 ) .During the average follow-up period of 13.7 months ( range 6-24 months ) , no local recurrence or metastasis occurred .Conclusion MI-OPN is an innovation of traditional OPN and suitable for the complex renal tumors with high ZS score .
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Objective To assess the efficacy and safety of tolterodine on late-onset overactive bladder symptoms after prostate brachytherapy due to prostate carcinoma.Methods Twenty-six prostate cancer patients diagnosed by biopsy,who underwent prostate brachytherapy using iodine-125,were recrui(t)ed in this trial.All cascs complained of overactive bladder symptoms 6 months postoperatively.The 26 patients were divided into 2 groups:14 men in tolterodine group (TR group) who were given tolterodine 2 mg twice a day; 12 men in tamsulosin group (TS group) who were given tamsulosin 0.2 mg once a day.Efficacy was assessed by changes in IPSS,OABSS and nighttime voiding at 2 weeks and 4 weeks after medical treatment respectively.Safety was assessed by postvoid residual (PVR) and acute urinary retention (AUR),dry mouth,constipation and tachycardia at the fourth week after medical treatment.Results The age,tumor staging,GS,PSA,initial prostate volume,IPSS,OABSS,nighttime voiding,iodine-125 seeds implanted and needles punctured of both groups were comparable.IPSS,OABSS and nighttime voiding were significantly improved in TR group after 2 weeks of medical treatment and the above parameters were significantly improved than TS group (14.4 vs 18.3,5.9 vs8.4,1.4 vs2.5).OAB symptoms of TR group were also significantly improved than TS group after 4 weeks of therapy.There were no significant differences of PVR and AUR,dry mouth,constipation and tachycardia between both groups.Conclusions Tolterodine is effective and safe in treating late-onset OAB symptoms after prostate brachytherapy,although the occurence of dry mouth and tachycardia might be increased.
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ObjectiveTo investigate the expression and activity of histone deacetylase (HDAC) in prostate cancer.Methodshe pathological samples of 37 cases of PCa were collected. The mean age of the patients was 73 (53 - 88 ) years, the preoperative t-PSA was 81.69 ( 3.13 - 2000 ) ng/ml, Gleason score: 13 cases were ≤7, 24 cases were ＞7. Twenty-seven cases of BPH were set as controls. The mean age of the BPH patients was 69 (52 - 84) years, the preoperative t-PSA was 10.93 ( 1.11 - 55.07 ) ng/ml.Western blotting and colorimetric Assay kits were used to determine the HDAC expression and activity. The difference of HDAC activity in benign prostatic hyperplasia and prostate cancer was statistically analyzed.The correlation of the HDAC expression level and values of PSA and Gleason score was also assessed.ResultsHDACs were over-expressed in most cases of prostate cancer, the expression rates were HDAC1 :57％, HDAC2: 68％, HDAC3: 84％ and HDAC4: 73％, respectively. The HDAC activity (P ＜0.05)was significantly different between the prostate cancer and benign prostatic hyperplasia groups. The expression level of HDAC did not correlate with the values of PSA and Gleason score.ConclusionsHDAC was highly expressed and strongly active in prostate cancer. The results suggest that HDAC might be a potential target for the management of prostate cancer patients.
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Objective To analyze the changes in number and biological ability of endothelial progenitor cells (EPCs) from peripheral blood of SLE patients. Methods Mononuclear cells (MNCs) were isolated by Ficoll density gradient centrifugation from peripheral blood of 20 female SLE patients and 20 healthy female controls. EPCs were identified by double staining using antibodies to CD34 and CD133, or antibodies to CD133 and vascular endothelial growth factor receptor 2 (VEGFR2). Phycoerythrin (PE) conjugated antiCD34, fluorescein isothiocyanate (FITC) conjugated anti-CD133 and APC conjugated anti-VEGFR2 antibodies were used in a three color flow cytometric analysis to determine the percentage of EPCs in peripheral MNCs.The proliferation and migration ability of EPCs were measured by MTT assay and modified millicell chamber assay, respectively. The adhesion activity of EPCs was evaluated by counting the number of adherent cells.Results The percentage and proliferation rate of EPCs in peripheral MNCs from female SLE patients were significantly lower than those from the healthy controls(4.49% ± 1.66% vs 20.81% ± 4.14%, 23.11% ± 3.16%vs 35.65% ± 1.74%, both P ＜ 0.01 ). The migration and adhesion ability of EPCs from SLE patients was impaired compared with those from the healthy controls (12.00 ± 2.12 vs 23.60 ± 3.0 cells/field, 22.43 ± 4.43vs 36.43 ± 3.69 cells/filed, both P ＜ 0.01 ). Conclusion There is a decrease in the number and an impairment in biological ability of EPCs in SLE patients.
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Objective To study the role of P38 mitogen-activated protein kinase(P38 MAPK) activation in high level glucose-induced microvascular hyperpermeability.Methods Rats were induced to diabetis by intraperitoneal injection of streptozotocin(STZ).The rats were divided into 5 groups,including normal,diabetes,control,MKK6b(A) and MKK6b(E) groups.The permeability coefficient to albumin(Pa) was measured in venules of in vivo mesenterium using a fluorescence ratio technique;Morphological changes of microvascular endothelial cell were monitored by observing fluorescence of F-actin stained with rhodamine-phalloidin.Results The permeability of diabetic rats was obviously increased.The activation of P38 MAPK by MKK6b(E) could increase microvascular permeability in normal rats,and the inhibition of P38 MAPK by MKK6b(A) could inhibit hyperpermeability of diabetic rats.Conclusion The activation of P38 MAPK induced by hyperglycemia may play a role in diabetic microvascular hyperpermeability.
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Objective To evaluate the indications,complications and efficacy of permanent interstitial brachytherapy in the treatment of clinically localized prostate cancer. Methods Five patients (mean age,73 years;range,59~84 years) with clinically localized stage T 2b to T 3 adenocarcinoma of the prostate were treated with iodine-125 brachytherapy using the transrectal ultrasound guided transperineal implantation technique and Prowess 2.42 treatment planning system.The follow-up period ranged from 12 to 18 months. Results After implantation,the PSA levels of the 5 patients were decreased significantly and were all less than 0.5 ng/ml at 12th post-implant month;and the prostate volume shrunk from the third month. In the early period after the implantation all the patients complained of some voiding problems and had a noticed increase of International Prostate Symptom Score (IPSS),with the decrease of urinary flow rate.But the conditions improved gradually from the third month. No serious complications such as hematuria, bloody stool and rectal ulcer were found in this group. Conclusions Permanent interstitial brachytherapy has better efficacy,fewer complications and more radiation safety in the treatment of clinically localized prostate cancer.
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Objective To study collagen changes in dermis of hairless mice that were exposed to ultraviolet. Methods The hairless mice was irradiated under UVA, UVB and the combination of the two for 20 weeks, total dose of UVA was 222J/cm~2, and that of UVB was 5.9J/cm~2. After irradiation, the dorsal skin's collagens of animals were analysed by computer imaging analysis system, histopathologic examination, specific stains and electorn microscopy. Results The hairless mice exposed to ultraviolet A were unchanged in dermis collagen. The hairless mice was irradiated under UVB and the both UVA and UVB, and the content of collagen was decreased with less affinity for collagen staining. These findings were supported by electron microscopy, which showed fraying, thickened, and proliferating collagen, coalesced into extensive denaturalization. The ratio of types Ⅲ/Ⅰ+Ⅲ collagen was significantly increased. Conclusion The qualitative and quantitative changes of the collagen in the ultraviolet irradiated skin of hairless mice are related to ultraviolet B but not to UVA. UVB is a key factor of skin collagen damage in UV-irradiation.
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Objective To study the changes of skin wrinkles in hairless mice while exposed to ultraviolet. Methods The hairless mice were irradiated under long-wave ultraviolet ray (UVA), medium-frequency wave ultraviolet ray (UVB) and the combination of the two for 20 weeks. Total dose of UVA was 222J/cm~2, and that of UVB was 5.9J/ cm~2. After irradiation, the skin wrinkling of animals were analysed by the naked eye, dermatoglyphics enlarges and applied color skin system of pathologic portrait quantitative analysis. Results Control group: The hairless mice skin were fine and delicate, the ditch and ridge of skin distributed even, and had no the obvious cornification. Long wave ultraviolet ray (UVA) set: The skin was slightly rough, skin ditch and ridge distributed still even, and had no obvious cornification; quantitative analysis had no the obvious difference from that of control group. Medium-frequency wave ultraviolet ray (UVB) set: The dermatoglyphics were disorderly, and the skin ditch deepened, widened, and the skin ridge increased the breadth and obvious cornification, and quantitative analysis had obvious difference from that of control group. Long wave and medium-frequency wave ultraviolet ray (UVA+ UVB) set: The dermatoglyphics was disorderly, and the skin ditch deepened, widened, the skin ridge increased the breadth, skin cornification was more obvious, quantitative analysis had obvious difference from that of control group. Conclusions The qualitative and quantitative changes of the wrinkles in the ultraviolet irradiated skin of hairless mice are related to ultraviolet B but not to UVA. UVB is a key factor of skin wrinkling in UV-irradiation.
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Objective To promote the use of chemical peeling in facial rejuvenation with the phenol and croton oil peeling agents to the UVA/B-irradiated skin of hairless mice, and to provide the experimental evidence for the clinical application of the treatment of irradiated skin.Methods Sixty BALB/C hairless mice were photo-aged by use of chronic ultraviolet A and ultraviolet B irradiation for 20 weeks. After irradiation the animals were randomly divided into two groups:untreated (10 mice) and treated (50 mice). The phenol and croton oil chemical peeling agents were applied to the dorsal skin of treated animal group while it was full anesthetized. Punch biopsies were taken at 7, 14, 30, 60, and 90 days after peel for histological analysis. At 60 days after irradiation, the skin wrinkling of animals were analyzed by macroscopy, cleavage line amplification, and computer imaging analysis system. Results The treated areas of irradiated skin recovered rejuvenation and exhibited a unique connective tissue layer composed of fine collagen fibers beneath the epidermis. Conclusion The mixture of phenol-croton oil may reverses the visible stigmata of photoaging skin. Our results will be of great help to promote the use of chemical peeling in facial rejuvenation.
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AIM: To investigate the effect of advanced glycosylation end products(AGEs) modified protein on morphological changes of actin cytoskeleton in primary endothelial cells and the role of MAPK signaling pathways in this pathological procedure.METHODS: Human umbilical vein endothelial cells(HUVECs) were incubated with AGEs modified human serum albumin(AGE-HSA) at concentrations of 12.5,25,50,and 100 mg/L,respectively,for 2,4,8,12 and 24 hours.The cells were treated with different chemical compounds of inhibitors,or adenoviral deliver approach(either dominant positive or negative adenoviral constructs) of MAP kinases to specifically block or activate certain signal transduction pathways under above situations.As control,HSA of the same concentration was administered to cells at the same time.The treated cells were incubated with FITC-phalloidin to stain F-actin.RESULTS: F-actin in HUVECs was rearranged greatly by AGEs in a concentration and time-dependent manners.The unmodified HSA did not influence Factin distributions.The AGEs-induced changes were blocked by pretreatment with SB203580,PD98059 for 30 min,or pre-infection with recombinant virus of dominant negative form of MKK 6b [MKK6b(A)],MEK1 [MEK1(A)] for 24 h,while SP600125 and dominant negative form of MKK7 [MKK7(A)] failed to inhibit the effects of AGEs.Furthermore,the infection of recombinant virus of constitutive active form of MKK6b [MKK6b(E)] or MEK1 [MEK1(E)] could also induced re-arrangement of F-actin,respectively,while the effect elicited by [MKK6b(E)] was abolished by co-infection with recombinant adeno-virus of dominant negative p38?. CONCLUSION: AGEs-induced morphological changes of F-actin in endothelial cells are mediated by p38-and ERK MAPK signal pathways.