The general theories of gray correction methods for the medical ultrasonic image are introduced in this paper, including gray level correction, gray level transformation and histogram correction. The dominant histogram equalization method is expatiated and modified against its disadvantages including inapparent enhancement of partial detail and non-interactivity. Series connections of several gray correction methods are used to treat with the ultrasonic image, and thus its utility is improved through the selective enhancement of the contrast of certain gray scope.

Objective To investigate the influence of m4-1BBL on the anti-tumor effects induced by truncated human prostate specific membrane antigen (tPSMA) gene in mice. Methods A eukaryotic expression plasmid encoding tPSMA and m4-1BBL (pDC316-tPSMA-IRES-m4-1BBL), pDC316-tPSMA and pDC316 were constructed. C57BL/6 mice were vaccinated in the quadriceps femoris, respectively. The CTL activity of spleen cells from the immunized mice against prostate cancer RM-1-tPSMA was detected by CCK-8 kit in vitro. The tumor growth was then observed. Results The target cell specific cytotoxicity rate induced by pDC316-tPSMA-IRES-m4-1BBL was 42.6%, compared to 24.8% in the pDC316-tPSMA group and 10.8% in the pDC316 group. The difference was significant (P<0.05). The volume of tumor in the pDC316 group was 2657.4mm3 7 d after vaccination, compared to 1334.5 mm3 in the pDC316-tPSMA group, 9 d after vaccination. In the pDC316-tPSMA-IRES-m4-1BBL group, the tumor volume was 445.8 mm3, 12d after vaccination. The difference was significant (P<0.05). Conclusion Gene vaccines co-expressing tPSMA gene and m4-1BBL gene could significantly enhance anti-prostate cancer effects in mice.

Objective To evaluate the application value of combined detection of PCA3 and PSA mRNA in peripheral blood of patients with prostate cancer(PCa) for evaluation of mien)metastasis. Methods PCA3 and PSA mRNA were detected by duplex real time quantitative RT-PCR in a total of 49 PCa and 71 benign protatic hyperplasia (BPH) patients' peripheral blood. The diagnostic value was analyzed by receiver operative characteristic(ROC) curve. Results The levels of PCA3 mRNA in PCa patients were significantly higher than those in BPH patients [2 362( <30-7 421 ) copies/ml vs <30 copies/M, Z = -6. 66, P < 0. 01 ], and the same to PSA mRNA [3 425 ( 908-36 639 ) copies/ml vs < 200 copies/ml, Z = - 6. 40, P<0. 01 ]. The positive rate of PCA3 and PSA mRNA in peripheral blood was positively correlated with clinical stage[clinical stage B: 30.0% (3/10), C: 60.0% (9/15) and 86.7% (13/15), D: 91.7% (22/24) and 91.7% (22/24) ,Chi-square = 13. 534 and 16. 541, P <0. 01, respectively]. Meanwhile, the positive rate of PCA3 mRNA and PSA mRNA was also increased with the increase of Gleason score[ Gleason score of 2 to 4 : 20.0% (1/5) and 40. 0% (2/5) ;5 to 7 : 66.7% (12/18) and 72. 2% ( 13/18 ) ;8 to 10 : 84. 6% (22/26) and 92.3% ( 24/26 ) ;Chi-square = 8. 895 and 8. 015, P < 0. 05, respectively ]. ROC analysis showed that the sensitivities for PCA3 and PSA mRNA were 69. 4% (34/49) and 81.7% (40/49) and the specificities was 90. 1% (64/71) and 77.5% (55/71), respectively, when the cut-off value was 846 copies/ml for PCA3 mRNA and 280 copies/ml for PSA mRNA. Meanwhile, the sensitivity can reach to 85.7% (42/49) when the detection of PCA3 and PSA mRNA were combined. However, the specificity was decreased to 76. 1% (54/71). For the diagnosis of PCa micrometastasis, the sensitivity and specificity for PCA3 mRNA was 90.9% (20/22) and 84.7% (11/13), respectively. Conclusions PCA3 and PSA mRNA in peripheral blood are useful markers for PCa diagnosis. Simultaneous detection for PCA3 and PSA mRNA is more helpful for PCa diagnosis. Meanwhile, detection of PCA3 mRNA is a useful marker for diagnosing PCa micrometastasis.

PURPOSE: The purpose of this study is to construct a recombinant adenovirus vector carrying mouse 4-1BBL and observe its effects in dendritic cells. MATERIALS AND METHODS: Mouse 4-1BBL cDNA was taken from the plasmid pcDNA3-m4-1BBL and subcloned into adenovirus shuttle plasmid pAdTrack-CMV, and then transformed into competent BJ5183 with plasmid pAdEasy-1. After recombination in E. coli, Ad-4-1BBL was packaged and amplified in HEK 293 cells. The expression of 4-1BBL in Ad-4-1BBL-transfected mouse prostate cancer cell line RM-1 was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. After the co-culture of dendritic cells (DCs) with Ad-4-1BBL-transfected RM-1 cells, interleukin (IL)-6 and IL-12 production were assessed by enzyme-linked immunosorbent assay (ELISA) and co-stimulatary moleculs (CD80 and CD86) on DCs were analyzed by flow cytometry. RESULTS: The levels of IL-6 (3,960 pg/mL) and IL-12 (249 pg/mL) production in Ad-m4-1BBL-pulsed DCs were more than those in none-pulsed DCs. The differences were statistically significant (p < 0.05). The expression of co-stimulatary molecules (CD80 and CD86) was up-regulated in Ad-m4-1BBL-pulsed DCs. CONCLUSION: The results indicated the recombinant mouse 4-1BBL can effectively activate DCs.

Objective To study the expressions of DD3 mRNA and PSA mRNA in the prostate tissues and its diagnostic value in prostate cancer (PCa). Methods DD3 mRNA and PSA mRNA were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction ( FQ-RT-PCR) based on Taqman technique in the tissues of 21 cases of PCa and 39 cases of BPH. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of DD3 mRNA, PSA mRNA and DD3 mRNA/PSA mRNA. Results The expressions of DD3 mRNA and PSA mRNA, and DD3 mRNA/ PSA mRNA were significantly higher in PCa tissues than those in BPH tissues ( P 0.05 for all). The AUC-ROC of DD3 mRNA,PSA mRNA and DD3 mRNA/PSA mRNA were 0. 937 (95% CI,0. 879 -0. 995) , 0.755(95% CI,0.629 -0.880) and 0.839 (95%CI,0.738 -0.940),respectively. The sensitivity for DD3 mRNA,PSA mRNA and DD3 mRNA/PSA mRNA was 90. 5% ,81. 0% and 81. 0% , respectively, and the specificity was 85.0% ,62.0% and 66.7% at cutoff value of 1.4?105 copies/mg tissue,3.0?107 copies/ mg tissue and 5. 0?10-3,respectively. The sensitivity and specificity of simultaneous detection for DD3 mRNA and PSA mRNA were 100% and 85.0%. Conclusions Both DD3 mRNA and PSA mRNA expressions were significantly higher in PCa tissues than those in BPH tissues; and the quantitative detection of DD3 mRNA is more helpful for the diagnosis. The simultaneous detection of DD3 mRNA and PSA mRNA can improve the sensitivity in the diagnosis of PCa.

The clinical data of 1 patient with long-term survival metastatic prostate cancer were analyzed retrospectively, and the related literature was reviewed and discussed. The patient, male, 70 years old, was admitted to the hospital in 2009 due to dysuria with lower abdominal pain for one month.Blood PSA>1 000 ng/ml. The pathology of prostate biopsy was prostatic adenocarcinoma, Gleason score was 8 points (4+ 4), and was diagnosed as prostate cancer (T 4N 0M 1b) with bone metastasis. The patient underwent combined androgen-blocked treatment(castration and bicalutamide 50mg) for four years, then progressed to mCRPC. The initial treatment was continued in the fifth year due to the absence of novel therapeutic agents, and then symptoms progressed. The regimens were adjusted successively to increased anti-androgen (castration and bicalutamide 150 mg) from Jan 2015, then switch to another anti-androgen (Flutamide 250 mg) from Aug 2015, and then withdraw the anti-androgens from Feb 2016. All these treatments showed limited benefit for a relatively short time. The t-PSA increased steadily to over 1 000 ng/ml with persistent symptoms. In April 2017, he started the treatment with the original abiraterone acetate and underwent a PSA flare-up in the following month.tPSA decreased sharply since May 2017, less than 0.02ng/ml in Aug 2017. Meanwhile, the regimen relieved the ostealgia. He could take care of himself in daily life. raditional CAB therapy can maintain PSA-free progression and symptom-free progression for several years for some metastatic prostate cancer patients. After disease progression, the increased dosage of anti-androgens, the substitution of anti-androgen, and the withdrawal of anti-androgens showed limited benefit within a short time. However, the novel hormone therapy is still effective in relieving clinical symptoms and prolonging patients' survival time.

Objective:To quantify the fat of extraocular muscle in TAO patients with MRI fat-water separation technique.Methods:66 patients (129 eyes) with TAO were included in this study from November 2017 to July 2019. The age, gender, course of disease, disease activity and severity were collected. Fat fraction(FF) of the heaviest inflamed extraocular muscle was used as FFmax, the average FF of each orbital was recorded as FFmean. FF differences between groups of severity and activity were compared, the correlation between FF and clinical characteristics was also analyzed. Meanwhile, the changes of FF in follow-up patients before and after treatment were compared.Results:FFmean and FFmax of mild group were higher than moderate-to-severe as well as sight-threatening group. In male patients, active group′s FFmean and FFmax were lower. FF was different in groups which based on disease course ( P<0.05). Spearman correlation analysis showed a positive correlation between FF and disease course. Besides, there was a negative correlation between FF, disease activity, and disease severity ( P < 0.05). FF increased after treatment(FFmean: 34.03%±6.75% vs 32.26%±6.06%, P=0.040; FFmax: 33.43%±9.44% vs 29.04%±8.45%, P=0.006). Conclusion:MRI fat fraction can quickly and objectively quantify the fat of extraocular muscle, providing a new reference index for TAO′s disease evaluation.

Objective Constructing a risk prediction model of IgA nephropathy proteinuria treated by traditional Chinese medicine based on random survival forest model,Screening prognostic risk factors of IgA nephropathy proteinuria.Methods Collecting retrospectively clinical data of 129 cases diagnosed with IgA nephropathy,randomly divided them into training set(60%)and test set(40%).The risk prediction model of IgA nephropathy proteinuria was constructed in the training set with the random survival forest model,and the prognostic risk factors were screened by VIMP method.The accuracy of risk prediction model was validated in the test set with time-dependent ROC curve(tdROC).Results According to the result of VIMP,the prognostic risk factors for IgA nephropathy proteinuria are in the order of eGFR,hypertension,traditional Chinese medicine,24 hUPRO>1 g,genomo sclerosis ratio,Lee grading,fat,hyperlipidemia,hypertrophymia,hyparmane ledmia,Anemia,age and gender.The eGFR was negatively and non-linearly associated with the risk rate of developing persistent proteinuria.Glomerulosclerosis ratio greater than 0.3 is approximately linearly and positively associated with the risk rate of persistent proteinuria.Conclusion Random survival forest model has good predictive performance in the risk prediction model of IgA nephropathy proteinuria treated by traditional Chinese medicine.This risk model can determine the result of IgA nephropathy treated by traditional Chinese medicine,and which is helpful for clinical follow-up monitoring and formulation of individualized treatment plans.

ObjectiveTo explore the mechanism of Yishen Huoxue prescription in renal interstitial fibrosis （RIF） from the perspective of endothelial cell and cell energy metabolism. MethodThe model was successfully established by unilateral ureteral obstruction （UUO）. Seventy-five SPF C57BL/6 mice were randomly divided into a model group， a resveratrol group （50 mg·kg^-1·d^-1）， three Yishen Huoxue prescription low， medium， and high-dose groups （7.1， 14.2， 28.4 g·kg^-1·d^-1）， with 15 mice in each group. In addition， another 15 mice were used to prepare sham operation model. Mice in the sham operation group and the model group were gavaged with equal volume of normal saline. All mice were sacrificed on 7， 14， and 21 d after modeling. The protein expression of platelet endothelial cell adhesion molecule 31 （CD31） was detected by immunohistochemical S-P method. The expression of α-smooth muscle actin （α-SMA）， collagen Ⅳ （Col-Ⅳ）， angiopoietin 1（Ang-1） and tyrosine kinase receptors 2 （Tie-2）， vascular endothelial growth factor （VEGF）， vascular endothelial cadherin （VE-cadherin）， and occludin in renal tissues was detected by Western blotting. The mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin in renal tissues were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the levels of reactive oxygen species （ROS） in mice were detected by enzyme linked immunosorbent assay （ELISA）. ResultAs compared with the sham operation group， the expression of CD31 in renal tissues of the model group was significantly decreased and worsened with the extension of modeling time （P<0.05）， α-SAM and Col-Ⅳ protein expression levels were significantly increased （P<0.01）， but the expression of CD31 was stable in 14-21 d. ROS levels were significantly increased （P<0.01）， and the protein and mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin were significantly down-regulated （P<0.01）. As compared with the model group， the expression of CD31 was increased （P<0.05）， and α-SAM and Col-Ⅳ in the resveratrol group and the medium and high-dose Yishen Huoxue prescription groups were significantly decreased （P<0.01）. The ROS content was significantly decreased （P<0.01）， and the protein and mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin were up-regulated （P<0.01）， As compared with the resveratrol group， the protein expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin in the medium and low-dose Yishen Huoxue prescription groups were significantly different （P<0.01）. There was no significant difference in the mRNA expressions of CD31 and Ang-1/Tie-2 in the high-dose Yishen Huoxue prescription group， and no significant difference in the ROS level in the medium-dose Yishen Huoxue prescription group. ConclusionThe anti-RIF effect of Yishen Huoxue prescription may be related to promoting vascular endothelial repair， regulating mitochondrial ROS to reduce oxidative stress， protecting the integrity of renal endothelial structure， delaying cell apoptosis， and maintaining cell energy metabolism.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.