The intracellular trafficking and subcellular distribution of exogenous gene is very important for gene delivery. A successful gene vehicle should overcome various barriers including endosomal membrane barriers to delivery gene to the target organelle. Traditional nonviral vehicle is unable to avoid endosomal pathway efficiently, so the efficiency of gene delivery is low and the application of gene drugs is limited. In order to achieve efficient nonviral gene delivery, a lot of researches based on endosomal escape have been carried out and some agents with the function of endsomal escape have been found. These agents facilitate the endsomal escape via various mechanisms, such as fusion into the lipid bilayer of endosomes, pore formation in the endosomal membrane, proton sponge effect and photochemical methods to rupture the endosomal membrane. In this review, various reported strategies for endsomal escape are described according to the escape mechanisms, and their applications in intracellular gene delivery are also discussed.

OBJECTIVETo investigate the expression of zinc finger E-box binding homebox 1 (ZEB1) in the prepuce of hypospadias children and its relationship to the incidence of hypospadias.

METHODSPrepuce tissues were collected from 37 children aged 6-15 months undergoing hypospadias repair and 11 age-matched controls receiving circumcision. Based on the position of the urethral meatus, the hypospadias cases were classified as severe (n = 13) and mild-moderate (n = 24). The mRNA and protein expressions of ZEB1 were determined by immunohistochemistry and RT-PCR.

RESULTSThe expression of the ZEB1 protein was remarkably higher in the severe (100% [13/13]) and mild-moderate hypospadias patients (75.0% [18/24]) than in the controls (9.1% [1/11]), with statistically significant differences between any two groups (P < 0.05). RT-PCR showed the integrated density value (IDV) of the ZEB1 mRNA expression to be (0.67 ± 0.21), (0.81 ± 0.24), and (1.55 ± 0.29) in the control, mild-moderate, and severe hypospadias patients, respectively, significantly higher in the severe hypospadias than in the control and mild-moderate hypospadias groups (P < 0.05), but with no significant difference between the latter two (P = 0.64).

CONCLUSIONThe expression of ZEB1 is significantly increased in hypospadias patients, and its upregulation is positively correlated with the severity of hypospadias, which suggests that the overexpression of ZEB1 may contribute to the development of hypospadias.

Biomarkers ; metabolism ; Case-Control Studies ; Circumcision, Male ; Foreskin ; metabolism ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Hypospadias ; classification ; etiology ; metabolism ; Immunohistochemistry ; Infant ; Male ; Penis ; RNA, Messenger ; metabolism ; Transcription Factors ; genetics ; metabolism ; Up-Regulation ; Urethra ; Zinc Finger E-box-Binding Homeobox 1

OBJECTIVETo compare the effect and impact of holmium laser enucleation of the prostate (HoLEP) and 120-W thulium: YAG vapoenucleation of the prostate (ThuVEP) on erectile function in the treatment of benign prostatic hyperplasia (BPH).

METHODSWe retrospectively analyzed 93 cases of symptomatic BPH treated by HoLEP or 120 W ThuVEP. We made comparisons between the two groups of patients in the baseline and postoperative clinical and surgical indexes as well as their IPSS, quality of life (QOL), maximum flow rate (Qmax), postvoid residual urine volume (PVR), and IIEF-EF scores before surgery and during the 12-month follow-up.

RESULTSThuVEP, in comparison with HoLEP, achieved a significantly shorter operation time ([57.6 +/- 12. 8] vs. [70.4 +/- 21.8] min, P = 0.001) and a higher laser efficiency ([0.71 +/- 0.18] vs. [0.62 +/- 0.19] g/min, P = 0. 021). At 1, 6, or 12 months of follow-up, no significant differences were observed in IPSS, OOL, Omax, and PVR between the two groups (P > 0.05). Both the HoLEP and ThuVEP groups showed low incidences of complications and remarkably improved IIEF-EF scores at 12 months postoperatively, but with no significant differences (both P > 0.05). However, in those with relatively normal erectile functions before operation, the mean IIEF-EF score was reduced from 22.8 +/- 2.2 preoperatively to 21.0 +/- 2.7 after HoLEP, (P = 0.036).

CONCLUSIONBoth HoLEP and 120W ThuVEP are effective and safe in the treatment of BPH. Compared with HoLEP, 120 W ThuVEP has even a higher laser efficiency. However, neither can significantly improve erectile function, and HoLEP may have a short-term negative impact on the relatively normal erectile function of the patient.

Aged ; Holmium ; Humans ; Laser Therapy ; adverse effects ; methods ; Lasers, Solid-State ; therapeutic use ; Male ; Middle Aged ; Penile Erection ; Prostatectomy ; adverse effects ; methods ; Prostatic Hyperplasia ; surgery ; Quality of Life ; Retrospective Studies ; Thulium ; Transurethral Resection of Prostate ; Treatment Outcome ; Urine

Objective To evaluate the expressions of estrogen receptor (ER) α and β in human prostate cancer and adjacent non-cancerous tissues,and to evaluate the correlation between the expression and the clinicopathological features and prognosis.Methods Immunohistochemical staining was used to detect ERα and ERβ in 85 prostate adenocarcinoma tissues,adjacent non-cancerous tissues,and 29 benign prostatic hyperplasia (BPH) tissues.The correlation between the expression and the clinicopathological features was analyzed by Spearman's coefficient.Cox's proportional hazards regression model was used to identify the risk factors for biological recurrence.Results There were significant differences between the expression of ERα in prostate cancer,adjacent non-cancerous tissues,and BPH [epithelial cell 0 (0/85),11.8％ (10/85) and 24.1％ (7/29),P=0.000; and in stromal cell 52.9％ (45/85),67.1％ (57/85),31.0％ (9/29),P =0.003].There were significant differences between the expression of ERβ in these groups [epithelial cell 36.5％ (31/85),61.2％ (52/85),100.0％ (29/29),P =0.000; and in stromal cell 49.4％ (42/85),72.9％ (62/85),79.3％ (23/29),P =0.001].The ERα expression in cancerous stromal cells was positively correlated with the PSA level (r =0.296,P =0.006) and Gleason score (r =0.404,P =0.000).The ERβ expression was negatively correlated with Gleason score in cancerous epithelial cells (r =-0.254,P =0.019) and stromal cells (r =-0.315,P =0.003).Multivariate analysis revealed that negative expression was an independent poor prognostic factor for the biological recurrence free survival after radical prostatectomy (HR =0.107,95.0％ CI 0.019-0.592,P =0.010).Conclusions There were significant differences between the expression of ERα and ERβ in prostate cancer,adjacent non-cancerous tissues,and BPH.ERα in cancerous stromal cells,ERβ in cancerous epithelial and stromal cells were related to the differentiation of prostate adenocarcinoma.ERβ in cancerous epithelial cells can be used as an independent prognostic factor for biological recurrence after radical surgery.

OBJECTIVETo investigate the impact of in utero exposure to di-n-butyl phthalate (DBP) on the apoptosis of testicular cells in the pubertal male rat offspring.

METHODSTen pregnant SD rats were randomly divided into a control and an experimental group to be treated intragastrically with olive oil (1 ml per day) and DBP (500 mg per kg of body weight per day) respectively between gestation days 12 and 19. At the pubertal age (postnatal day 45, PND 45), the testes of the male rat offspring were removed for observation of the cell structure under the transmission electron microscope and the development of different spermatogenetic cells by HE staining. The apoptosis of testicular cells was detected by the TUNEL method, the expressions of the apoptosis-regulating proteins Bcl-2, Bcl-XL, Bax and p53 were determined by immunohistochemistry and Western blot, and the data obtained were compared between the two groups by t-test.

RESULTSTransmission electron microscopy revealed increased apoptosis and vacuolization of testicular cells in the PND-45 rat offspring, HE staining showed markedly decreased numbers of different spermatogenetic cells, TUNEL manifested significantly increased apoptosis of testicular cells in the experimental group as compared with the control (12.00 ± 5. 22 vs 3.17 ± 1.47, P < 0.01), and immunohistochemistry and Western blot exhibited remarkably higher expressions of Bax and p53 in the former than in the latter group (P < 0.05).

CONCLUSIONIn utero exposure to DBP can increase the apoptosis of germ cells and Sertoli cells, induce the vacuolization of testicular cells, and significantly elevate the expressions of the apoptosis-promoting proteins Bax and p53 in the pubertal male rat offspring.

Animals ; Apoptosis ; Body Weight ; Dibutyl Phthalate ; adverse effects ; Female ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Sertoli Cells ; cytology ; pathology ; Spermatogenesis ; Testis ; cytology ; pathology ; Tumor Suppressor Protein p53 ; metabolism ; bcl-2-Associated X Protein ; metabolism

Objective To investigate the clinical significance of retinal binding protein (RBP) and Cystatin C in blood and urine in patients with chronic kidney disease (CKD).Methods One hundred and twenty-one patients with CKD in Nephrology Laboratory of The People's Hospital of Xinjiang Uygur Autonomous Region from Aug.2012 to Jan.2013 were served as the case group.Sixty healthy check-up people were considered as control group.Enzyme linked immunosorbent assay was used to detect RBP and Cystatin C in urine,and the immune turbidimetry testing was applied to detect RBP and Cystatin C in blood.The receiveroperating characteristic (ROC) curve and area under curve (AUC) were applied to evaluate the sensibility and diagnostic value of indexes in CKD.Results The positive rate of RBP,Cystatin C in urine and blood were 89.6％,92.6％,52.5％,59.5％ respectively of 12 patients in case group,higher than those in control group (all value were 0,P ＜0.001).ROC curve showed that the sensitivity of urine RBP and Cystatin C were higher than that in blood of case group.AUC of RBP,Cystatin C level in urine and blood were 0.915,0.974,.655,and 0.623 respectively.And 95％ confidence interval were 0.877-0.954,0.956-0.992,0.575-0.736,0.543-0.702 respectively,and the differences are statistically significant (P ＜ 0.001).Conclusion The sensitivity of urine cystatin C and RBP are significantly higher than that in blood,which might be served as a diagnostic marker of CKD and can provide important basis for clinical diagnosis.

Abdominal Neoplasms ; secondary ; surgery ; Abdominal Wall ; Antiporters ; metabolism ; Choriocarcinoma ; pathology ; Diagnosis, Differential ; Epithelioid Cells ; pathology ; Female ; Gestational Trophoblastic Disease ; metabolism ; pathology ; secondary ; surgery ; Humans ; Pregnancy ; Uterine Neoplasms ; metabolism ; pathology ; surgery ; Young Adult

The intracellular trafficking and subcellular distribution of exogenous gene is very important for gene delivery. A successful gene vehicle should overcome various barriers including endosomal membrane barriers to delivery gene to the target organelle. Traditional nonviral vehicle is unable to avoid endosomal pathway efficiently, so the efficiency of gene delivery is low and the application of gene drugs is limited. In order to achieve efficient nonviral gene delivery, a lot of researches based on endosomal escape have been carried out and some agents with the function of endsomal escape have been found. These agents facilitate the endsomal escape via various mechanisms, such as fusion into the lipid bilayer of endosomes, pore formation in the endosomal membrane, proton sponge effect and photochemical methods to rupture the endosomal membrane. In this review, various reported strategies for endsomal escape are described according to the escape mechanisms, and their applications in intracellular gene delivery are also discussed.
Cell Membrane ; metabolism ; Endosomes ; metabolism ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; Humans

Objective Acute renal failure (ARF) requiring renal replacement therapy (RRT) was reported in 0.33％to 9.5％ patients after cardiac surgery.This study was designed to assess the clinical usefulness and accuracy of 3 clinical tools for the prediction of ARF after cardiac surgery in Chinese patients.Methods Five hundred and four eligible patients with complete clinical data in our institution received prospective assessment for RRT and acute kidney injury (AKI) between June,2009 and November,2010.The clinical tools used were Cleveland ARF Score,acute kidney injury prediction following elective cardiac surgery(AKICS) and Simplified Renal Index(SRI).Hosmer—Lemeshow goodness-of-fit test was used to estimate the calibration.Discrimination was determined with receiver operating characteristic (ROC) curves and area under a ROC curve (AUC).Results Follow-up was completed in all 504 patients.The overall incidence of postoperative RRT was 3.17％(16/504) with a mortality of 37.5％,and the incidence of AKI was 5.36％ ( 27/504 ).Discrimination for the prediction of RRT and AKI was good for SRI measured with AUROCs:0.759 (95％ CI,0.643-0.874) for RRT and 0.773 (95％ CI,0.677-0.868 ) for AKI.SRI score performed better in terms of discrimination than Cleveland ARF score and AKICS in our study,which did not consist with results reported by other centers.Conclusion SRI scoring system is the most useful among three tools for predicting postoperative RRT and should be the first choice in Chinese patients for whom a cardiac surgery is planned.It can also be used in predicting the composite end point of AKI with an extended application in patients at risk for postoperative kidney dysfunction.

Objective To evaluate the effect of different tube voltages on the radiation dose and image quality of a full field digital mammography system.Methods Both experiments were performed under manual exposure mode.In one experiment,the tube voltages were kept constant at 25,28 and 31 kVp,and the CIRS 015 phantom was exposed at three target/filter combinations molybdenum/molybdenum (Mo/Mo),molybdenum/rhodium (Mo/Rh),and rhodium/rhodium (Rh/Rh) and at tube current-exposure time products of 32-140mAs.The entrance skin exposure (ESE) and average glandular dose (AGD) were recorded,the signal-to-noise ratio(SNR) and contrast-to-noise ratio (CNR) and figure of merit (FOM) were measured to evaluate the influences of different tube voltages on dose and image quality at same target/filter combination.The univariate of randomized completed block-design was used for statistics.In second experiment,the phantom were exposed using Mo/Rh combination when the tube current-exposure time product was kept constant at 56 mAs,and the tube voltage varied between 23 and 33 kVp in 1-kVp increments.The ESE and AGD were recorded,the SNR,CNR and FOM were measured for plotting the curves against tube voltages.Results At Mo/Mo combination,the AGD,ESE,SNR,CNR and FOM of 25,28 and31 kVp were(1.25 ±0.56) mGy,(6.46±2.86) mGy,71.52±8.37,1.91 ±0.26,3.21 ± 0.68; (1.94 ±0.85) mGy,(9.18±4.07) mGy,144.46 ± 11.31,2.41 ±0.28,3.37 ±0.96 and (3.01 ±1.38) mGy,(12.60±5.59) mGy,128.89 ±15.29,2.47 ±0.31,2.31 ±0.76 respectively; at Mo/Rh combination were (1.23 ±0.55) mGy,(5.26 ±2.33) mGy,67.31 ±4.11,1.82 ±0.19,3.01 ± 0.82; (1.86 ±0.84) mGy,(7.57 ±3.34) mGy,139.54 ± 12.16,2.30 ±0.25,3.23 ±0.92 and (2.81 ±1.24) mGy,(10.48 ±4.62) mGy,127.77 ±15.14,2.59 ±0.31,2.67 ±0.68; and at Rh/Rh were(1.09 ±0.48) mGy,(4.89 ±2.16) mGy,67.46 ±2.23,1.48 ±0.72,3.08 ± 1.69; (1.75 ± 0.78) mGy,(6.88 ±3.03) mGy,137.74 ± 14.65,2.37 ±0.26,3.62 ± 1.07 and (2.59 ± 1.13) mGy,(9.32 ± 4.12) mGy,117.91 ± 19.05,2.51 ± 0.31,2.74 ± 0.84.Both experiments indicated that,for a given target/filter combination,the AGD,ESE and CNR increased,but the ESE/AGD decreased with the tube voltage increasing; The first experiment indicated both SNR and FOM of 28 kVp were higher than that of 25 kVp and 31 kVp; the second experiment showed both SNR and FOM decreased with tube voltages increasing.The differences of AGD、ESE、ESE/AGD、SNR、CNR and FOM among the three tube voltages were significant (F =4.391-528.848,P ＜ 0.05) ; but the difference of CNR between 28 and 31 kVp at Mo/Mo and Rh/Rh had no statistical significance (P ＞ 0.05) ; and the differences of FOM between 25 and 28 kVp at the three target/filter combinations were not statistically significant (P ＞ 0.05).Conclusion For a breast with 4.2 cm thickness and 50％ adipose 50％ glandular composition,different tube voltages have significant effects on the radiation dose and image quality.