Evasion of apoptosis is a hallmark of cancer, attributed in part to overexpression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). In a variety of cancer types, including lymphoma, Bcl-2 is overexpressed. Therapeutic targeting of Bcl-2 has demonstrated efficacy in the clinic and is the subject of extensive clinical testing in combination with chemotherapy. Therefore, the development of co-delivery systems for Bcl-2 targeting agents, such as small interfering RNA (siRNA), and chemotherapeutics, such as doxorubicin (DOX), holds promise for enabling combination cancer therapies. Lipid nanoparticles (LNPs) are a clinically advanced nucleic acid delivery system with a compact structure suitable for siRNA encapsulation and delivery. Inspired by ongoing clinical trials of albumin-hitchhiking doxorubicin prodrugs, here we developed a DOX-siRNA co-delivery strategy via conjugation of doxorubicin to the surface of siRNA-loaded LNPs. Our optimized LNPs enabled potent knockdown of Bcl-2 and efficient delivery of DOX into the nucleus of Burkitts' lymphoma (Raji) cells, leading to effective inhibition of tumor growth in a mouse model of lymphoma. Based on these results, our LNPs may provide a platform for the co-delivery of various nucleic acids and DOX for the development of new combination cancer therapies.

Objective To study the value of the semiquantitative-parameter analysis of wash out index of time-intensity curve (Swash-out) in evaluating the therapeutic effect of neoadjuvant chemotherapy for locally advanced breast cancer (LABC).Methods Fifty-nine women with LABC underwent dynamic contrast enhancedt MRI examination before chemotherapy,after the 2nd cycle and the 4th cycle of chemotherapy.All patients were divided into major histological response group (MHR) and non-major histological response group (NMHR) according to the final pathologic response.Swash-out and the variancetrends of Swash-out before NAC,after the 2nd cycle of NAC and after the 4th cycle of NAC were compared in each group and between the two groups.According to the gold standard of Miller & Payne criterion,Receiver operating characteristic curve (ROC) analysis was performed to evaluate the predicting effect of Swash-out for NAC response,and to compare it with Semi-quantitative TIC curve indicators Smax (steepest slope) and PPE (peak percent enhancement).Results Fifty-nine patients of LABC patients were divided into a MHR group of 34 patients and a NMHR group of 25 patients.Swash before NAC of MHR group was-16.99 (-56.72-41.20),Swash-out after the 2nd cycle of NAC was 5.66(-69.45-53.08),Swash-out after 4th cycle of NAC was 15.95 (-7.80-54.23).Swash-out before NAC of NMHR group was-23.08 (-64.24-34.39),Swash-out after the 2nd cycle of NAC of NMHR group was-23.01 (-52.72-28.70),Swash-out after 4th cycle of NAC of NMHR group was-11.45 (-50.49-50.93).Swash-out variance rate of MHR group after the 2nd and the 4th cycle of NAC were-1.18 (-31.32-60.86) and 1.50 (-86.27-3.61),respectively.Swash-out variance rate of NMHR group after the 2nd and the 4th cycle of NAC were-0.28(-3.24-9.46) and 0.27 (-5.34-3.11),respectively.Swash-out was not significantly different between the two groups before NAC (Z =-0.97,P ＞0.05).Swash-out and Swash-out variance rate of MHR group after the 2nd cycle of NAC were significant higher than that of NMHR group (Z =-3.97 and-3.02,P ＜0.01).Swash-out and Swash-out variance rate of MHR group after the 4th cycle of NAC were significant higher than that of NMHR group (Z =-3.96 and-3.16,P ＜ 0.01).Area under curve (Az) after the 2nd and the 4th cycle of NAC were 0.805 and 0.804,respectively,and no significant difference was found between them (Z =0.019,P ＞0.05).Diagnostic cut-off points were-8.670 for the 2nd cycle of NAC and 4.105 for the 4th cycle of NAC.Diagnostic sensitivity was 79.42％,specificity was 76.00％ and Youden index was 0.554,for after the 2nd and the 4th cycle of NAC.Conclusion Swash-out of TIC curve before NAC cannot predict the response of NAC,Swash-out of TIC curve after the 2nd cycle of NAC and after the 4th cycle of NAC are efficient in predicting the response of NAC.

Objective To evaluate the feasibility of assessing osteoarthritis (OA) in hip dysplasia using 3D delayed gadolinium-enhanced MRI of cartilage (dGEMRIC).Methods Thirty-five hips in 20 patients with radiographic evidence of hip dysplasia underwent 3D-dGEMRIC scanning.Clinical symptoms were assessed with the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) questionnaire.Radiographic measurement of lateral center-edge angle and T(o)nnis grading were performed on the X-rays.Hips of T(o)nnis grade 1were included in the group of hips with early OA,while the hips with no evidence of OA and without pain symptom were included in the group of hips with normal morphology.The 3D-dGEMRC scans were completed on a 1.5 T MR scanner.The data of 3D-dGEMRIC was reconstructed radically.The dGEMRIC indices were measured on six sites of periphery zones of hip cartilage on reconstructed images.The dGEMRIC indices among different groups were analyzed by non-parametric tests.The differences of dGEMRIC indices among six sites in the group of early OA or the group of normal morphology were analyzed by Wilcoxon test.Results The mean dGEMRIC indices of six sites were lower in group of T(o)nnis grade 1than in group of T(o)nnis grade 0 ( Z =- 2.149,P =0.032 ),and lower in group of T(o)nnis grade 2 than in group of T(o)nnis grade 1( Z =- 1.990,P =0.047 ).The dGEMRIC indices of the anterior site,anterosuperior site,superior-anterior site,and superior site were significantly different between the group of hips with early OA and the group of hips with normal morphology (Z =-2.333--2.041,all of the P values were lower than 0.05).In the group of hips with normal morphology,the dGEMRIC indices of superior-anterior site of hip were lower than superior site(P =0.028).In the group of hips with early OA,the dGEMRIC indices of superior-anterior site were lower than the other sites except for anterior-superior site ( Z =- 3.041- - 2.277,all of the P values were lower than 0.05 ).Conclusions 3 D-dGEMRIC might be a sensitive technique for detection of glycosaminoglycans alteration in early OA and staging of OA in hip dysplasia.Radial reconstruction could provide an accurate assessment of OA,and the results demonstrated that early cartilage alteration could be detected in the anterior to superior sites of hips,and the earliest cartilage alteration may occur in the superior-anterior site of hips.

ObjectiveStudy the ADC value and the maximal diameter and their changes of breast cancer before and after neoadjuvant chemotherapy,to determine the relationship with different expression level of Ki-67.Methods Forty eight patients with breast cancer confirmed by biopsy underwent MR DWI and enhanced scan before and after 4 cyclesneoadjuvant chemotherapy.ReviewtheMRimages retrospectively.The ADC value and the maximum diameter( D)of the cancer foci were measured before and after chemotherapy,and the rate of their changes △ADC％ and △D％ were calculated.Using different Ki-67 index level,all the foci were divided into three groups:group A with Ki-67 ＜ 20％,group B with Ki-67 between 20％ and 60％,and group C with Ki-67 ＞ 60％.Using nonparameter test to compare the ADC values,△ADC％,D and △D％ of the three groups before and after chemotherapy,determine whether there were differences.ResultsBefore chemotherapy,the ADC value of group A ( n = 15 ) was 1.1 ×10-3 mm2/s[ (0.9 × 10-3—1.2 × 10-3) mm2/s],which was higher than that of group B[n = 8,0.9 ×10-3 mm2/s(0.9 × 10-3-1.0 × 10-3) mm2/s] and C [n =25,0.9 × 10-3 mm2/s(0.7 × 10-3—1.2 ×10-3) mm2/s],and the difference was statistically significant (P ＜0.05 ) ; while the ADC value of group C after chemotherapy was 1.3 × 10 -3 mm2/s[ (0.2 × 10 -3—1.4 × 10 -3 ) mm2/s],which was higher than that of group A [1.1 × 10-3 mm2/s,(1.0 × 10-3—1.2 × 10-3) mm2/s] and B[1.1 × 10-3 mm2/s,( 1.0 × 10-3-1.1 × 10 -3 ) mm2/s],and the differences were statistically significance ( P ＜ 0.01 ) ; the ADC change rate( △ADC％ ) of group C was 45.5％ ( - 12.0％ —78.6％ ),which was greater than group A [45.5％ ( - 12.0％—78.6％ ) ] and B [ 45.5％ ( - 12.0％—78.6％ ) ],the difference was significant (P ＜ 0.01 ).The maximum diameters of group A were 2.2 cm (2.0—2.4 cm)and 1.0 cm(0.0—1.4 cm)before and after chemotherapy,lower than those of group B [ 3.7 cm ( 3.6—3.9 cm ) before NAC,2.9 cm (0.0-3.1 em) after NAC] and group C[3.4 cm(2.7—4.2 cm) before NAC,1.9 cm(0.0—2.2 cm) after NAC ],and the differences were statistically significant ( P ＜ 0.05 ) ; the change rate of the maximum diameter in group B was 21.6％ ( - 15.2％—27.5％ ),which was less than group A [52.7％ ( -23.6％—72.1％)] (P＜0.01) and C [51.2％ ( -10.3％—92.6％)] (P ＜0.05),and the difference was statistically significant.Conclusion The ADC values and the maximal diameter of breast cancer differed with different expression levels of Ki-67 index before and after neoadjuvant chemotherapy,and the response to neoadjuvant chemotherapy of which varied as well.

Objective To understand the status of knowledge and attitude of schistosomiasis control among the human populafion in schistosomiasis transmission-controlled area of Changqiu mountainous areas.Methods The subjects were selected by the random cluster sampling method among residents and students in these alias,then they were investigated by questionnaire.Resuits A total of 150 residents and 209 students were selected.There were 60% of the residents whose awareness rates of the knowledge on schistosomiasis control were above 90%.The correction rates of the questions in residents were between 99.30% and 100%.and the awareness rates about the questionswhether re-infection would occure after schistosomiasis was cured and the remedy for schistosomiasisof female adults were both 75.40%.The correction rates of the two question8 on attitude and behaviour of schistosomiasis control in adults were above 80.00%.In students'questionnaires.the awareness rates of knowledge on schistosomiasis control were above 90%.except the two questions on the shape of the snailand the infection-risk months of schistosomiasis.The correction rates of attitude and behaviour of schistosomiasis control were aslo above 80%.Conclusion The correction rates of knowledge,attitude and behaviour of schistosomiasis control of adults and students have reached the national goal of schistosomiasis control in 2008.

Objective To quantitatively analyze and testify the diagnostic value of combined MRS and DWI for prostate cancer based on sextant localization.Methods Patients who underwent prostate MR examinations in our hospital had MRS and DWI scanning in addition to conventional MRI.The(choline+creatine)/citrate(CC/C)value in each measurable voxel and the minimal ADC value(ADC_(mini))in each sextant were measured.Taking CC/C of no less than 0.911 as the cutoff value for prostate cancer,the ratios of positive voxel(PVR)in sextants were calculated.The selected patients were divided into 2 groups according to the date of examination,for the quantitative analysis and the verification respectively.Group 1 was from Feb,2006 to Dec,2006,and group 2 from Jan,2007 to Jul,2007.The diagnostic efficacy of PVR,ADC_(mini) and their combination was tested by ROC analysis.Results There were 40 patients in group 1 and group 2 respectively for the linear discrimination of the cluster analysis,including 20 patients with prostate cancer and 20 patients without prostate cancer.The linear discrimination equation calculated from group 1 was 'D=3.264×ADC_(mini)-0.205×PVR-4.407'.The areas under curve(Az)of ROC for PVR,ADC_(mini) and D were 0.769,0.910 and 0.909,respectively.In group 2,the Az of ROC for PVR,ADC_(mini) and D were 0.838,0.912 and 0.915,respectively.There were no statistical difference between ADC_(mini)-alone and D in both groups(X~2=0.32 and 1.50,P＞0.05).Conclusions Quantitative prostate DWI had higher diagnostic value than MRS.The combined use of MRS and DWI was not superior to the DWI-alone in the diagnostic efficacy of prostate cancer.

Objective To explore convenient and practical semi-quantitative MRS indicators in diagnosis of prostate cancer.Methods One hundred patients with completer MRS data and clinical data were enrolled in the study.The following parameters were assessed to evaluate their efficacy in diagnosis of prostate cancer, (Cho + Cr)/Cit of single voxel, mean (Cho + Cr)/Cit of the whole area and (Cho + Cr)/ Cit positive voxel ratio at the sextant level.Similarly, all the parameters mentioned above and mean (Cho +Cr)/Cit positive voxel ratios of the whole gland were assessed at the whole gland level.Pearson test and Kappa test were used in the research.Results Two thousand nine hundred and forty-five voxels were assessed including 1203 in cancer positive region and 1742 in cancer negative regioa The range of the (Cho + Cr) /Cit ratio in cancer positive region was from 0.22 to 8.00 (median, 1.87), and that in cancer negative region was from 0.11 to 8.00 (median, 0.53).The (Cho + Cr)/Cit ratio in cancer positive region was higher than that in cancer negative region (Z =28.48, P<0.01) with partial overlap.On the level of sextant, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (Cho + Cr)/Cit ratio> 0.911 to diagnose prostate cancer were 81.4% (179/220),64.2% (194/302), 62.4% (179/287) 、82.6% (194/235) 、71.5% (373/522) respectively; those of mean (Cho + Cr)/Cit ratio>0.911 were 77.3% (170/220),77.2% (233/302),71.1% (170/239),82.3% (233/283),77.2% (403/522) respectively; those of positive voxel ratio>0.519 were 73.2% (161/220),80.8% (244/302)、 73.5% (161/219),80.8% (244/302), 77.6% (405/522) respectively; the consistency between mean (Cho + Cr) /Cit ratio and positive voxel ratio was high (Kappa=0.907).On the level of the whole prostate, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (Cho + Cr)/ Cit ratio>0.911 to diagnose prostate cancer were 94.3% (50/53),40.4% (19/47),64.1% (50/78), 86.4% (19/22),69.0% (69/100) respectively; those of mean (Cho + Cr)/Cit ratio>0.911 were73.6% (39/53),83.0% (39/47), 83.0% (39/47), 73.6% (39/53), 78.0% (78/100) respectively; those of maximum positive voxel ratio> 0.519 were 88.7% (47/53),61.7% (29/47),72.3% (47/65),82.9% (29/35),76.0% (76/100) respectively; those of mean positive voxel ratio>0.519 were 62.3% (33/53), 85.1% (40/47), 82.5% (33/40), 66.7% (40/60), 73.0% (73/100) respectively; the consistency between mean (Cho + Cr)/Cit ratio and mean positive voxel ratio was fairly high (Kappa =0.818).Conclusion Single voxel criteria were suggested to diagnose clinically suspected prostate cancer.Maximum positive voxel ratio criteria were suggested to guide localization in biopsy.

Objective To investigate the clinical value of tumor's longest diameter and volume in assessing pathologic response in locally advanced breast cancer treated with neoadjuvant chemotherapy(NAC).Methods A prospective study was undertaken in women undergoing NAC for locally advanced breast cancer in order to determine the ability of quantitative MRI to assess the final pathologic response. 36 cases with pathologically confirmed locally advanced breast cancer who had been undergone four courses of NAC underwent preoperative breast MRI three times during the NAC. Pathologic response was assessed according Miller & Payne grading system, of which grade 4 and 5 defined as major histological response (MHR), and grade 1 to 3 as non-major histological response (NMHR). The tumor's longest diameters and volumes in MHR were compared with those in NMHR by Mann-Whitney U test before, after the second and fourth cycle of NAC. Concordance correlation coefficient (CCC) were assessed to evaluate the agreement between the two method. Receiver operating characteristic curve (ROC) analysis was carried out to assess the clinical value of tumor size and the change rate.Results Before,after the second and the fourth cycle of NAC, the difference of tumor's longest diameters and their first change rate between MHR [(2.75±1.16) cm,(2.19±1.07) cm ,(1.58±0.75) cm and (21.70±15.09)%]respectively,and NMHR [(2.71±1.10) cm,(2.33±0.90) cm,(2.01±0.94) cm and (11.68±10.27)%] respectively were not significant(P>0.05). The second change rate of tumor's longest diameter in MHR [(39.00±15.38)% ] was significantly higher than that in NMHR[ (25.83±21.77)% ](P=0.04). Before, after the second and the fourth cycly of NAC, the differences of tumor volumes and their first change rate between MHR [ median 14.00 cm~3 ( range 2.96～83.41 cm~3 ) , median 7.31 cm~3 (range 0.05～55.35 cm~3), median 2.69 cm~3 (range 0～33.40 cm~3 ) , median 48.65% (range 33.64%～98.48%) ] and NMHR [median 4.25 cm~3 (range 4.78～106.55 cm~3), median 10.53 cm~3 (range 1.72～42.85 cm~3), median 7.56 cm~3 (range 0.68～156.58 cm~3), median 52.04% (range-35.79%～78.31%) ] were not significant. The second changing rate of tumor's volume in MHR [median 85.37% (ranged 27.52%～100%)] was significantly higher than that in NMHR [median 68.80% (ranged -289.60%～94.24%)](P=0.01). CCC was computed before and (0.82), after the second cycle (0.67) and after the fourth cycle (0.55), in all examinations pooled together (0.78).The second change rates of tumor's longest diameter and volume were equal to predict the final pathologic response, and the area under curve were 0.75 and 0.80, respectively (P=0.61). Conclusion The agreement between the tumor's longest diameters and tumor's volumes is good in all in breast carcinoma. The assessment efficacy of the change rate of tumor's longest diameter and that of volume were low.

Objective To compare the diagnostic value of MRS acquired by body coil(BODY)and endorectal Coil(ERC)in the detection of prostate cancer.Methods MRI and 3D MRS were performed in 12 patients with prostate disease,in which 6 of them were proved to have prostate cancer and the other 6 noncancerous disease.Both BODY and ERC MRS were performed in 7 patients,and only BODY MRS was performed in the other 5 patients.All MRS data were quantitatively assessed with a per-sextant method.The metabolic ratio of(Choline+Creatine)/Citrate[(Cho+Cre)/Cit]was measured in each ROI.ROC analysis was carried out to assess and to compare the diagnostic value of BODY and ERC MRS in patients with prostate cancer with Wilcoxon test.Results (1)The ratios of(Cho+Cre)/Cit in the prostate cancer group(median 1.744,0.295 to 7.998)was statistically higher than that in the non-prostate cancer group (median 0.412,0.112 to 2.113)acquired by using BODY MRS(Z=-9.159,P＜0.01).(2)The ratios of(Cho+Cre)/Cit in the prostate cancer group(median 1.975,0.479 to 7.998)was statistically higher than that in the lion-prostate cancer group(median 0.400,0.104 to 2.232)acquired by using ERC MRS(Z=-9.200,P＜0.01).(3)The mean ratios of(Cho+Cre)/Cit in the prostate cancer group and in the non-prostate cancer group acquired by using both coils were not of statistically significant difference(P＞0.05).(4)ROC analysis for diagnosing prostate cancer showed no significant difference(P=0.851)between the areas under the curve of BODY and that of ERC MRS(Az=0.93 1 and 0.935 respectively).Conclusion The BODY MRS could provide comparable diagnostic efficacy to ERC MRS in patients with prostate cancer.

Objective To study the changes of the apparent diffusion coefficient (ADC) values and the association with serum prostate specific antigen (PSA) in prostate cancer patients. Methods Diffusion-weighted echo-planar imaging (EPI) sequences were performed in 47 patients with biopsy proved locally confined prostate cancer,age ranged from 56 to 86 years.t-PSA range,f-PSA range and F/T range in serum of all patients were 1.41-603.16 ng/ml,0.10-12.29 ng/ml and 0.01-0.36,respectively.The patients'clinical staging were 2 cases of stage A,18 cases of stage B and 27 cases of stage C,among which 1 cases were well differentiated (Gleason 2-4), 23 were moderately differentiated (Gleason 5-7) and 23 were poorly differentiated(Gleason 8-10),respectively.Images were obtained with a diffusion factor of 800 s/mm2.According to the pathological results obtained by ultrasound guided systemic biopsy,the locations of the prostate cancerous region were marked as one or more of the sextants.The ADC values of every region and whole gland were measured and analyzed with ROC curve.Correlations between the ADC and t-PSA,f-PSA,F/T ratios were analyzed.Results Acceptable images for ADC measurement were obtained in all cases.The mean ADC values of cancerous and noncancerous regions in 47 prostate patients were(1.29±0.28)×10-3mm2/s and (1.78+0.32)×10-3mm2/s and significant difference was noted in ADC values between cancerous and noncancerous regions(t=13.58,P＜0.01).Negative correlation was found between the ADC values and t-PSA,f-PSA,(γ=-0.353,P＜0.01;γ=-O.401.P＜0.01).There were no significant associations between the ADC values and F/T(γ=-0.123,P＞0.05). Conclusions The ADC values in cancerous regions were negatively correlated with t-PSA,f-PSA. Measurement of ADCs,combined with serum PSA,might be useful to accurate location and preoperative assessment of tumor.