The discovery of the key negative regulator MDM2 and the detailed mechanism of MDM2-P53 protein-protein interaction provide a great opportunity to activate P53 by inhibiting MDM2-P53 interaction with MDM2 inhibitor.In this article,the author will review the accomplishment in the area of MDM2 inhibitor treatment on tumors of urological system.The detailed mechanism and the signal pathways involved are summarized simultaneously.

OBJECTIVE:To investigate the protective effects of insulin-glucose on myocardium in patients receiving cardiac valve replacement under cardiopulmonary bypass. METHODS:Totally 120 patients receiving combined cardiac valve replacement under cardiopulmonary bypass were divided into control group and observation group according to random number table,with 60 cases in each group. All patients were given routine operation. Control group was given Thomas cardioplegia and oxygenated blood with a ratio of 1:4(V:V)to protect myocardium at 4 ℃. Besides that,the observation group was additionally given Insulin injec-tion 10 IU/L and Glucose injection 10 g/L added into Thomas cardioplegia at 4 ℃ to protect myocardium. The levels of plasma brain natriuretic peptide(BNP)and cardiac troponinⅠ(cTnⅠ)before anesthesia induction(T0),at the end of cardiopulmonary by-pass(T1),12 h(T2),24 h(T3),48 h(T4),and 72 h(T5)after surgery,the rate of recovery of automatic heartbeat after opening aor-ta,the application of vasoactive agent(dopamine)at T1 and the occurrence of postoperative complications were observed and com-pared between 2 groups. RESULTS:At T0,there was no statistical significance in the levels of plasma BNP and cTnⅠ between 2 groups(P>0.05). The levels of plasma BNP and cTnⅠin 2 groups at T1-5 were significantly higher than T0,with statistical signifi-cance(P<0.05);the levels of cTnⅠ began to decrease at T4 and cTnⅠbegan to decrease at T5. However,the levels of BNP and cTnⅠwere significantly lower in observation group than in control group at T1-5,with statistical significance(P<0.05). After open-ing aorta,there was no statistical significance in the rate of recovery of automatic heartbeat between 2 groups(P>0.05). The dos-age of dopamine (at T1) and the incidence of complications in observation group were statistically lower than control group,with statistical significance(P<0.05). No severe ADR was found in 2 groups during or after surgery. CONCLUSIONS:Insulin-glucose can alleviate myocardial damage, reduce the dosage of vasoactive agent and the incidence of postoperative complications in pa-tients receiving combined cardiac valve replacement under cardiopulmonary bypass with significant protective effect on myocardium with good safety.

Objective To observe the anti-proliferation effects of rapamycin and paclitaxel of different hu-man prostate cancer cells in vitro. Methods The methods of MTr and flow cytometry were respectively ap-plied to observe the effect of rapamycin, paclitaxel and rapamycin+paclitaxel on proliferation and apoptosis of different prostate cancer cell lines (LNCaP-C4, LNCaP-C4-2, PC-3). Results When the concentration of rapamycin was 0.01 μmol/L, the impressive effect showed a remarkable difference in contrast to the con-trol. While in group LNCaP-C4-2 and PC-3, the goal concentration of rapamycin was 0.001μmol/L. When the concentration of paclitaxel was 0. 2 ng/mL, the impressive effect showed a remarkable difference in con-trast to the control. In group rapamycin (10 nmol/L) and in group paclitaxel (1 ng/mL) there were signifi-cant differences in growth inhibition, compared with control. While in group rapamycin(5 nmoL/L)+pacli-taxel(0.5ng/mL) there was significant difference in growth inhibition, compared with rapamycin (10 nmol/L) and paclitaxel (1 ng/mL) respectively. After cultured with rapamycin or paclitaxel alone, more tumor cells induced apoptosis than control. While after cultured with rapamycin and paclitaxel simultaneously, more tumor cells induced apoptosis than with rapamycin or paclitaxel alone. Conclusions Both rapamycin and paclitaxel had a good impressive effect on the three prostate cell lines (LNCaP-CA, LNCaP-C4-2, PC-3) with dose-dependent manner. After cultured with rapamycin and paclitaxel simultaneously, more tumor cells were induced apoptosis than with rapamycin or paclitaxel alone.

Objective To study the growth suppressive effect of demethylation drug 5-aza-2'-deoxycytidine on bladder tumor cells. Methods The growth suppressive effect of DAC on 4 transitional cell carcinoma (TCC) cell lines was measured using the Cell Proliferation Reagent WST-1 assay.The effects of DAC on apoptosis induction and cell cycle arrest were analyzed by flow cytometric analysis. Caspase 3, 9 activities were analyzed by APOPCYTO Caspase Colorimetric Assay Kit and PCNA expression was also investigated by Western blot to clarify the mechanism of DAC against TCC. Results DAC inhibited the growth of all TCC cell lines tested in a dose-dependant manner, however,growth suppressive effect of DAC was independent of p53 status in TCC. DAC inhibited proliferation via inducing G2/M cell cycle arrest but not via inducing apoptosis. After treated with 0, 1 and 8 μmol/L DAC, cells of RTl 12 in G2/M phase was (36.3 ± 3.4) %, (46.2 ± 4.6) % and (56.5 ±6.2) %, TCCsup was (37.5 ± 3.8) %, (48.4 ±4.9) % and (60.1 ± 6.7) %, respectively. The expression of PCNA was decreased by DAC, but caspase3, 9 activities were not activated. Conclusion DAC could suppress the growth of TCC cells and might be a new strategy to treat bladder malignancy in the future.

Objective To study long-term post-liver-transplantation hyperuricemia (HUA) and the influence of urate-lowering therapyon renal functions of adult patients.Methods Among 428 cases undergoing liver transplantations during March 2011 to December 2013,206 patients,whose followup periods were above 1 year,were selected as the objects of study.Those whose two-time serum uric acid (SUA) levels tested not in the same day one year after operation ＞420 μmol/L (male),or female ＞360 μmol/L (female) were divided into HUA group,and non-HUA group.The serum creatinine (SCr) concentrations and glomerular filtration rate (eGFR) were analyzedin the two groups at their peak SUA to find whether there was any difference between the two groups.Meanwhile,27 HUA patients with abnormal renal function were given urate-lowering therapy and the differences in SCr and eGFR after the therapy were observed.Results 49.5％ patients sufferedlong-term HUA after liver transplantations.As compared with non-HUA group,SCrconcentrations were increased statistically (P＜0.05),and eGFR was reduced statistically in HUA group (P＜0.05).After 8-week uratelowering therapy among 27 patients,SUA level in 24 cases (88.9％,24/27) returned to the normal standard and SCr concentrations in 21 cases (77.8％,21/27) decreased for a certain degree.SUA levels were decreased to (349.93 ± 22.85)μmol/L from (532.94 ± 93.91) μmol/L (P＜0.001).SCr concentrations were decreased to (129.52 ± 19.06)μmol/L from (144.95 ± 13.51) μmol/L (P =0.016).The eGFR increased to (56.30 ± 11.46) ml · min-1 · 1.73 m-2 from (46.46 ± 8.11) ml·min-1 ·1.73 m-2(P =0.012),which showed a certain degree of improvement in their renal functions.Conclusion HUA is a long-term common complication in liver transplanted adult patients,which has a negative influence on patients' renal functions,so we need to pay enough attention to this.Urate-lowing therapy has a positive influence on the improvement of renal function if other factors were excluded from the treatment.

Objective To compare the safety , surgery effects , pain scores of the close-distance-two-port video-assisted lobectomy and systematic dissection of the mediastinal nodes , and single-port video-assisted thora-coscopic surgery (VATS). Methods Between October 2012 and January 2015 in Peking University First Hospi-tal and Beijing Hospital , 269 patients who were going to be performed lobectomy and systematic lymph node dissection, were gathered and 205 patients were included in this study finally. Of the total, 122 patients were performed close-distance-two-port VATS , and 83 patients underwent single-port VATS. The clinical data were gathered, and statistically analyzed. Result In both groups, no severe postoperative complications or death oc-curred. No significant differences existed between the two groups in terms of intraoperative blood loss , duration and volume of chest tube drainage , postoperative pain score , hospital stay after surgery and hospitalization ex-penses (P > 0.05) but the data about operating time, number of dissected lymph nodes, complications(subcuta-neous emphysema , air-leak from the port of drainage tube and poor wound healing ) were significantly different (P < 0.05). Conclusions Compared with the single-port VATS, the method of close-distance-two-port video-as-sistant lobectomy and systematic dissection of the mediastinal nodes is safe and practicable with definite thera-peutic effect, less operation difficulty and complications.

Objective To explore the role of VEGF positive expression in tumor tissue in the prognosis of liver transplantation for hepatocellular carcinoma (HCC).Method Fifty cases of liver transplant recipients with HCC confirmed immunohistochemically were enrolled in this study.The MaxVisionTM two-step method was applied to detect the expression of vascular endothelial growth factor(VEGF),and the microvessel density (MVD) was measured in para-cancerous tissues by using DAB staining.The correlation of the VEGF tumor tissue in tumor tissue with Child-Pugh,MELD,tumor diameter and number,differentiation,MVD,Milan criteria and UCSF criteria for HCC liver transplantation was analyzed.Result In the HCC tissue,the VEGF positive expression rate was 52％(26/50).The one-year survival of recipients positive and negative for VEGF was 78％ and 100％,respectively,and one-year recurrence rate was 32％ and 12％,respectively,with the difference being significant (P =0.043 and P =0.048 respectively).The expression of VEGF was associated with Child-Pugh,tumor diameter,MVD,Milan criteria and UCSF criteria (P＜0.05 for all).Logistic regression analysis showed that low differentiation and VEGF positive expression were independent prognostic factors for HCC recurrence after liver transplantation.Conclusion VEGF has a certain reference value to judge HCC invasiveness and prognosis of liver transplantation.

With the development of the health service in china,the old talent-training program for clinical medicine major was failed in meeting higher demands for talents of clinical medicine. To create the new talent-training program,therefore,has become the main content of teaching reform for medical col-leges and universities. Taking University of South China as an example,the paper analyzed the changing trend of talent-training program for five-year clinical medicine majors from talent-training goal,curriculum system,practical teaching and content of courses,which proposed some thoughts on the optimization of training program for clinical medicine majors.

Objective To compare the therapeutic efficacies of fire-needle acupuncture and Halometasone cream in treating sub-acute and chronic eczema. Method Totally 114 patients were divided into a treatment group and a control group. The treatment group was intervened by using fire-needle acupuncture, and the control group was by Halometasone cream. Itchy score and Eczema Area and Severity Index (EASI) were used for comparison before and after intervention. Result There were significant differences in comparing the markedly-effective rate and total effective rate between the fire-needle acupuncture group and the Halometasone control group according to the itchy score (P＜0.01). There were no significant differences in comparing the markedly-effective rate and total effective rate between the two groups according to EASI (P>0.05). Conclusion Fire-needle acupuncture is superior to Halometasone cream for acute and chronic eczema in relieving itch, action time and effect-sustaining duration.

Objective:To explore the promoting effects of slit guidance ligand 2 (Slit2) on the repair of corneal epithelium and nerve damage in diabetic mice and possible molecular mechanism.Methods:Sixty SPF C57BL/6 mice aged 5-6 weeks were divided into normal control group, diabetes model group and Slit2 injection group according to the random number table method, 20 for each group.Diabectic model was prepared by intraperitoneal injection of streptozotocin in the diabetes model group and Slit2 injection group.A mouse corneal epithelial injury repair model was established using electric epithelial scraper, and Slit2 recombinant protein was subconjunctivally injected immediately following modeling in the Slit2 injection group.The equal volume of phosphate buffer saline (PBS) was used in a same way in the diabetes model group.No intervention was performed in the normal control group.Corneal epithelial healing were examined at 24, 48 and 72 hours after corneal epithelial defect by corneal fluorescin staining.Real-time fluorescent quantitative PCR was used to detect the expression of Slit2 and its related receptors in the corneal epithelium of normal and diabetic model mice.Fluorescence staining of corneal wholemount with β-tubulin Ⅲ was used to observe the changes in corneal nerve morphology.Immunofluorescence staining was performed to detect the expression and distribution of Slit2 in mouse corneal epithelium in normal control group and diabetes model group, as well as the expression and distribution of Slit2, epidermal growth factor receptor (EGFR), extracellular-signal-regulated kinase (ERK), threonine protein kinase (AKT), β-catenin and Ki67 in the healing corneal epithelium of mice after corneal epithelium damage in different groups.The mouse corneal epithelial stem/progenitor cell line (TKE2) was divided into normal control group, high-glucose group and Slit2 treatment group.Western blot was performed to detect the expression of p-EGFR/EGFR and p-AKT/AKT in the TKE2 of the three groups.The expression of p-EGFR/EGFR and p-AKT/AKT in high glucose-cultured TKE2 with 0.01, 0.1 and 0.5 μg/ml Slit2 treatment for 10 minutes, and before and 10, 20, 30, 60, 120 minutes after 0.5 μg/ml Slit2 treatment was detected by Western blot.The effects of Slit2 on the axon regeneration of mouse trigeminal ganglion cells (TGs) were observed by immunofluorescence staining.The use and care of animals complied with the ARVO statement.This study protocol was approved by an Ethics Committee of Qingdao Eye Hospital of Shandong First Medical University (No.[2020]57).Results:At 48 and 72 hours after corneal epithelial scraping, the speed of corneal epithelial repair was significantly slowed down in diabetes model group in comparison with the normal control group and Slit2 injection group.The relative expression levels of Slit2 and its receptors Robo1, Robo2 and Robo4 mRNA in the normal corneal epithelium in the diabetes model group were significantly higher than those of the normal control group (all at P<0.05). The fluorescence intensity of Slit2 in normal corneal epithelium in diabetes model group was similar to the normal control group, and the fluorescence intensity of Slit2 in damaged corneal epithelium in diabetic mice was significantly weaker than that in normal control group.Corneal nerve plexus was denser at 7 days after corneal epithelial injury and the nerve fibers were increased with more branches in Slit2 injection group compared with diabetic group.The fluorescence intensity of p-EGFR, p-ERK, β-catenin and Ki67 in damaged corneal epithelium in normal control group and Slit2 injection group was stronger than that of the diabetes model group.The relative expression levels of p-EGFR/EGFR, p-AKT/AKT, and β-catenin in TKE2 in high-glucose group were significantly lower than those in normal control group and Slit2 treatment group (all at P<0.05). The relative expression levels of p-EGFR/EGFR and p-AKT/AKT in high glucose-cultured TKE2 after Slit2 treatment were significantly increased in comparison with before Slit2 treatment (both at P<0.05), and the relative expression levels of p-EGFR/EGFR and p-AKT/AKT in TKE2 were elevated as the increase of Slit2 concentration.The activation effect of 0.5 μg/ml Slit2 on EGFR and AKT pathways was most obvious.The synapse length of TGs cultured by high glucose was (40.52±5.44) μm, which was significantly shortened than (72.14±9.48) μm in normal control group and (73.04±4.66) μm in Slit2 injection group (both at P<0.05). Conclusions:Slit2 can protect the corneal epithelium by activating EGFR signaling pathway and play a protective role to neurons by increasing the density of corneal subepithelial plexus and promoting the growth of TGs axons in diabetic mice.