OBJECTIVE: Todevelop a rapid and sensitive UHPLC-Q-orbitrap method for the identification of chemical constituents in Nelumbinis Folium. METHODS: Thermo Scientific Hypersil GOLD aQ(2.1 mm×100 mm,1.9 μm) was used with 0.1% formic acid-acetonitrile solution and 0.1% formic acid-water solution as the mobile phase in gradient elution. The extract was detected by Q-orbitrapmass spectrometry equipped with an ESI ion source in both positiveand negative mode. RESULTS: Based on the accurate mass-to-charge measurements, retention time, mass fragmentation patterns, compound discoverer software which can link to local compound database of Traditional Chinese Medicine from Thermo Scientific and online compound database from mzCloud, using Mass Frontier software to explain the fragmentations, a total of 53 compounds were screened and characterized, including 21 flavonoids,5 terpenes,13 alkaloids, 3 coumarins, 3 amino acids, 2 lignans and 6 other compounds. CONCLUSION: These results are helpful for the comprehensive quality control, better comprehension of the metabolism, and further study of the pharmacodynamic substances from Nelumbinis Folium.

Objective To discuss the feasibility, efficacy and complications of CT-guided 125I seed implantation for the treatment of lymph node metastasis nearby the iliac vessels.Methods The clinical data of twelve patients with para-iliac vessel lymph node metastasis, who had been treated with CT-guided 125I seed implantation, were retrospectively analyzed. A total of 12 lesions were detected; the diameter ≤6 cm was seen in seven lesions, and the diameter >6 cm was seen in five lesions. Using computer treatment planning system, the source distribution was calculated. Under CT guidance 125I seeds with the activity of 0.4-0.7 mci were implanted into the metastatic lymph nodes with a seed interval of 0.5-1.0 cm. CT scan was performed immediately after implantation to check the distribution of seeds as well as the possible complications. After the treatment, D90 (90%prescription dose received by target volume) was ≥75 Gy in 6 patients and <75 Gy in other 6 patients. Two months after the treatment CT reexamination was employed, and imaging evaluation was conducted according to WHO Response Evaluation Criteria in Solid Tumors. Results CT-guided 125I seed implantation was successfully accomplished in all 12 patients. Two months after the treatment, the evaluation of the therapeutic effect showed that complete remission (CR) was obtained in 0 patient, partial remission (PR) in 8 patients, stable disease in 3 patients and progress disease in one patient;and the total effect rate(CR+PR) was 66.7%. The local control rate was 91.7%. In eight patients the pain that was caused by metastatic lymph nodes was significantly relieved within 1-14 days after 125I implantation treatment. Before the treatment three patients had lower limb edema, and in two of them the lower limb edema was obviously relieved within 1-14 days after the treatment. All patients were followed up for 3-39 months, and the median follow-up time was 11 months. One-year survival rate was 41.7%. No severe complications such as massive hemorrhage, infection, myelosuppression or seed displacement occurred. Conclusion For the treatment of para-iliac vessel lymph node metastasis, CT-guided 125I seed implantation is safe and feasible. Better curative effect may be achieved when the diameter of the metastatic lymph node is<6 cm and the peripheral radiation dose is>75 Gy.

Objective To investigate the surrounding and central dosimetric distribution difference of the same activity, same number of 125I seeds. Methods 3D treatment planning system (3D-TPS) was used to separately sketch out 7 cubes with side length of 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm and 5 cm;simulations of different tumor sizes were established, into which 125I seeds with activity of 0.5 mCi were respectively loaded. All seeds were distributed at the periphery of the tumor (peripheral group) with the prescribed dose of 145 Gy. The dose volume histogram (DVH) was printed and the 90% of target volume absorbed dose (D90), 90% of prescription dose coverage target volume percentage (V90), the maximum dose and mean dose were determined. Then the seeds in every cube were distributed into the center (central group) and the above parameters were calculated by using the same method. Results The mean D90 of the peripheral and central group was (147.29 ±0.58) Gy and (106.08 ±9.40) Gy respectively, the difference between the two groups was statistically significant (t=-4.292, P=0.005). The mean V90 of the peripheral and central group was (95.46±0.44)% and (79.07±4.19)% respectively, the difference between the two groups was statistically significant (t=-3.831, P=0.009). The mean maximum dose of the peripheral and central group was (1 224.65 ±12.7) Gy and (1 532.48 ±48.54) Gy respectively, the difference between the two groups was statistically significant (t=6.823, P=0.000). The mean value of average dose of the peripheral and central group was (192.14 ±2.89) Gy and (179.81 ±5.40) Gy respectively, the difference between the two groups was statistically significant (t=-2.847, P=0.029). Conclusion The dose distribution is directly influenced by the distribution pattern of the 125I seeds. When the number and activity of the 125I seeds are the same, the peripheral seeds implantation has a better dose distribution.

Objective To investigate the dose distribution of esophageal stents carrying different diameters of radioactive 125I seeds in tumor target area. Methods A laser scanner was used to scan a piece of blank paper on which circles of 12 mm, 14 mm and 16 mm diameter and a 5 cm scale were drawn. The data were stored in JPEF format on the computer desktop. According to the circular diameter, simulations of the corresponding esophageal stents were established, which were divided into group A, group B and group C. By using image conversion program, 17 images with 5 mm slice-distance were created for each group; the images were transmitted to the computer treatment planning system (TPS) to simulate the 8 cm long esophageal stents of different diameters. TPS was used to sketch the gross tumor volume (GTV) in order to simulate the esophageal stent border that was used as the inner boundary of GTV, which was expanded 0.5 cm outward to be used as the external boundary of GTV. Beginning from the fifth level, the 4 cm-long GTV was drawn with circles. Setting the same prescription dose, from the fifth level to the thirteenth level the 125I seeds with 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 and 0.9 mCi were successively loaded on the simulation of the esophageal stents. The distance between 125I seed layers was 1 cm; the average number of seeds distributed on each layer was 4 particles. The dose volume histogram (DVH) was obtained. The D90 (the dose received by 90% of the target) and V90 (the percentage of the GTV volume receiving 90% the prescription dose) were recorded.Result s The arithmetic mean D90 of group A, B and C was (77.24 ±19.92) Gy, (69.56 ±25.27) Gy and (56.38±20.08) Gy respectively, and no statistically significant differences existed between each other among the three groups (F=0.84,P=0.44). The V90 of group A, B and C was (77.76±30.73)%,(76.79±25.92)%and (64.10 ±32.49)% respectively, and no statistically significant differences existed between each other among the three groups (F=0.46,P=0.64). Conclusion When the diameter of radioactive esophageal stent is 12 mm, the activity of 125I seed of 0.6 mCi is recommended. When the diameter of radioactive esophageal stent is 14 mm or 16 mm, the activity of 125I seed of 0.7 mCi is recommended. Nevertheless, when the diameter of radioactive esophageal stent is 16 mm, distribution of every five 125I seeds on each layer is strongly recommended. These three kinds of esophageal stent diameter have no significant effect on the dosimetric parameters.

Objective To investigate the safety and feasibility of different puncturing approaches in the performance of CT-guided 125I seed implantation for the treatment of retroperitoneal malignant tumors. Methods The clinical data of twenty-five patients with retroperitoneal malignant tumors, who had underwent CT-guided 125I seed implantation, were retrospectively analyzed. The puncturing approaches included trans-hepatic route, trans-gastric route, trans-duodenal route, and through mesentery and through thoracolumbar iliocostalis. The malignant tumors included retroperitoneal lymph node metastases (n=21) and pancreatic cancer (n=4). Preoperative full bowel preparation was carried out in all patients, and treatment planning was formulated by using treatment planning system (TPS) before the procedure. Under CT guidance, proper puncturing approach was selected according to lesion's location. One to 3 needles were used to implant 125I seeds. Immediately after 125I seed implantation, CT scanning was performed to check the distribution of 125I seeds. Results CT-guided 125I seed implantation was successfully completed in all patients. The puncturing approaches used in this series included trans-hepatic route (n=21), trans-gastric route (n=9), trans-duodenal route (n=2), through mesentery (n=2) and through thoracolumbar iliocostalis (n=5). After the operation, no procedure-related complications such as bleeding, peritonitis, hematemesis or melena occurred in all patients. The postoperative 125I particle number, total activity and peripheral dose (D90) were not significantly different from the preoperative data. Conclusion The use of the five puncturing approaches mentioned above is clinically safe and feasible. Strict perioperative management measures should be carefully executed when through cavity organ implantation is employed.

OBJECTIVETo evaluate the clinical value of magnetic resonance (MR) diffusion-weighted imaging (DWI) for diagnosing radiation-induced liver injury (RILI) and detecting changes in hepatic pathology at different post-irradiation times.

METHODSMale New Zealand white rabbits received no irradiation (C0, control group; n = 10) or irradiation of 50 Gy/10F once every other day by virtual three dimensional conformal radiotherapy (3D-CRT) for one day (C1; n = 10), three days (C2; n = 10), two weeks (C3; n = 10), one month (C4; n = 10) or two months (C5; n = 10). One member of all groups were sacrificed for DWI examination and pathologic study on post-irradiation day 1, day 3, week 2, month 1 and month 2. The apparent diffusion coefficient (ADC) values were measured using a range of b values (50, 300, 600, 800 and 1000 s/mm2).

RESULTSHematoxylin-eosin (H-E) staining showed that livers of rabbits in the C3, C4 and C5 groups had the characteristic features of veno-occlusive disease. DWI examination showed that the irradiated livers of rabbits in C2, C3, C4 and C5 groups had significantly lower ADC values than the livers of the non-irradiated rabbits at b values of 300, 600, 800 and 1000 s/mm2 (P less than 0.05). When the b value was 600 s/mm2, the best negative correlation between ADC values and pathological stage was seen for the irradiated livers (Spearman's rank, r = -0.459, P less than 0.01). The threshold ADC value to distinguish the normal group (C0) from an irradiated group (more than or equal toC1) was 1.955 * 10-3 mm2/s at 600 s/mm2 b value. When the b value was 1000 s/mm2, the threshold ADC value to predict an irradiated group with normal H-E staining (C1) from an irradiated group with abnormal H-E staining (more than or equal toC2) was 1.5250 * 10-3 mm2/s; the ADC threshold value was 1.5150 * 10-3 mm2/s to predict groups C0-2 and groups C3-5.

CONCLUSIONDWI has high sensitivity for detecting RILI at three days after irradiation with proper b values. Use of the ADC value is feasible for estimating the evolutionary process of pathological features of RILI damage. DWI may represent an important clinical tool for detection of early pathological changes in RILI.

OBJECTIVETo characterize DNA-PKcs and Ku70 expressions in hepato- and cholangio-neoplastic tissues and the association with the degree of malignancy and invasiveness of the tumors.

METHODSThe expression of DNA-PKcs and Ku70 was examined in 47 cases of hepato- or cholangio-neoplasm by immunohistochemistry.

RESULTSKu70 was expressed in all of the neoplastic tissues examined and with a little variation in levels. The highest expression was observed in adenocarcinomas and adenomas. There was no statistically significant association between Ku70 expression level and the degree of their malignancy extent or invasiveness. In contrast to Ku 70, a wide variation in expression levels of DNA-Pkcs was observed among different types of neoplastic tissues. The highest ratio of positive expressing cells was detected in hepatocellular carcinomas (92.1%), which was significantly higher than that in cholangioadeno carcinomas (65.3%) and biliary cystadenocarcinomas (51.9%). Low or no expression level was detected in papillary adenoma cases. DNA-PKcs expression of invasive adenomas and adeno-carcinomas (61.2%) was significantly higher than that of non-invasive adenomas and adeno-carcinomas (30.4%). There was no expression observed in the normal tissues adjacent to the tumors.

CONCLUSIONDNA-PKcs is expressed in hepato- and cholangio-neoplasms and its variable level of expression is associated with the types of the tumor and their degree of malignancy and invasiveness. DNA-PKcs could be recognized as a new biomarker for liver neoplasm.

Adenocarcinoma ; enzymology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Nuclear ; biosynthesis ; genetics ; Bile Duct Neoplasms ; enzymology ; Bile Ducts, Intrahepatic ; enzymology ; Biomarkers, Tumor ; biosynthesis ; genetics ; Carcinoma, Hepatocellular ; enzymology ; DNA-Activated Protein Kinase ; biosynthesis ; genetics ; DNA-Binding Proteins ; biosynthesis ; genetics ; Female ; Humans ; Ku Autoantigen ; Liver Neoplasms ; enzymology ; Male ; Middle Aged

As a standard method for early stage prostate cancer, 125Ⅰ seed implantations are used widely in America. Although there are guidelines from American Brachytherapy Society and American Association of Physicists in Medicine, some hospitals still cannot implant the seeds properly according to the guidelines. Complications were observed inevitably. The medical events about seeds implantation in America from 2002 were investigated and the reasons were analyzed in this paper. Additionally, some solutions were given to avoid the medical events, so that the practitioners in China can learn from it and make sure the 125Ⅰ seeds implantation can be developed healthily and smoothly.

OBJECTIVETo evaluate the anti-angiogenic activity of peptide 21 obtained by modification of tumstatin, and its inhibitory effect on the growth and metastasis of human ovarian cancer transplanted in nude mice.

METHODSThe peptide 21 was purified by affinity chromatography. Human ovarian cancer SKOV3 cells were inoculated in nude mice and the transplanted tumor was treated with the peptide 21 to observe the tumor growth and metastasis. The microvessel density (MVD) and immunohistochemical staining index of PCNA, VEGF and MMP-2 and TIMP-2 were performed to assess the inhibitory effect of the peptide 21.

RESULTSIn the nude mice at 21 days after peptide 21 treatment, the inhibition rate of tumor growth was 53.17%, the tumor microvessel density was significantly reduced (P <0.05), the expression of PCNA, VEGF and MMP-2 were significantly lower (P <0.01), and TIMP-2 expression was significantly higher (P <0.01) in comparison with that of control group.

CONCLUSIONThe peptide 21 generated in this study has a significant anti-angiogenetic activity, showing significant inhibitory effect on the growth of human ovarian cancer transplanted in nude mice. The mechanism of its inhibitory action on ovarian cancer growth may be mediated by reduction of neovascularization and reduction of expression of angiogenetic factors.

Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Antigens, CD34 ; metabolism ; Antineoplastic Agents ; chemistry ; pharmacology ; Autoantigens ; chemistry ; pharmacology ; Cell Line, Tumor ; Collagen Type IV ; chemistry ; pharmacology ; Female ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neovascularization, Pathologic ; pathology ; prevention & control ; Ovarian Neoplasms ; metabolism ; pathology ; Peptides ; chemistry ; pharmacology ; Proliferating Cell Nuclear Antigen ; metabolism ; Recombinant Proteins ; chemistry ; pharmacology ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Tumor Burden ; drug effects ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

AIMTo investigate the differences in microvessel densities (MVD) and the expressions of vascular endothelial growth factor (VEGF), VEGF-C and VEGF receptor-3 (VEGFR-3) between prostate cancer (PCa) tissues and adjacent benign tissues, and to explore the correlations among MVD, Jewett-Whitmore staging, Gleason scores and expressions of VEGF, VEGF-C and VEGFR-3 in the progression of PCa.

METHODSAn immunohistochemical approach was adopted to detect the expressions of CD34, VEGF, VEGF-C and VEGFR-3 in both cancer areas and peripheral benign areas of 71 primary prostatic adenocarcinoma specimens. A statistic analysis was then performed according to the experimental and clinic data.

RESULTSSignificantly upregulated expressions of VEGF, VEGF-C and VEGFR-3 were all found in malignant epithelium/cancer cells compared with adjacent benign epithelium (P<0.01). Patients in stage D had a significantly higher score than patients in stage A, B or C when comparing the expression of VEGF-C or VEGFR-3 in the tumor area (P<0.01). In addition, significant correlations were observed between Jewett-Whitmore staging and VEGF-C (r(s)=0.738, P<0.01), clinical staging and VEGFR-3 (r(s)=0.410, P<0.01), VEGF-C and Gleason scores (r(s)=0.401, P<0.01), VEGFR-3 and Gleason scores (r(s)=0.581, P<0.001) and MVD and VEGF (r(s)=0.492, P<0.001).

CONCLUSIONIncreased expressions of VEGF and VEGF-C were closely associated with progression of PCa. The main contribution of increased VEGF expression for PCa progression was to upregulate MVD, which maintained the growth advantage of tumor tissue. However, the chief role of increased expressions of VEGF-C and VEGFR-3 was to enhance lymphangiogenesis and provide a main pathway for cancer cells to disseminate.

Aged ; Aged, 80 and over ; Antigens, CD34 ; analysis ; Disease Progression ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Prostatic Neoplasms ; blood supply ; physiopathology ; Vascular Endothelial Growth Factor A ; biosynthesis ; Vascular Endothelial Growth Factor C ; biosynthesis ; Vascular Endothelial Growth Factor Receptor-3 ; biosynthesis