Pre-operative prognostic nutritional index as a predictive factor for prognosis in non-metastatic renal cell carcinoma treated with surgery / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the implications of the prognostic nutrition index (PNI) in non-metastatic renal cell carcinoma (RCC) patients treated with surgery and to compare it with other hematological biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune inflammation index (SII).@*METHODS@#A cohort of 328 non-metastatic RCC patients who received surgical treatment between 2010 and 2012 at Peking University First Hospital was analyzed retrospectively. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values of the hematological biomarkers. The Youden index was maximum for PNI was value of 47.3. So we divided the patients into two groups (PNI≤ 47. 3 and >47. 3) for further analysis. Categorical variables [age, gender, body mass index (BMI), surgery type, histological subtype, necrosis, pathological T stage and tumor grade] were compared using the Chi-square test and Student' s t test. The association of the biomarkers with overall survival (OS) and disease-free survival (DFS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model.@*RESULTS@#According to the maximum Youden index of ROC curve, the best cut-off value of PNI is 47. 3. Low level of PNI was significantly associated with older age, lower BMI and higher tumor pathological T stage (P < 0.05). Kaplan-Meier univariate analysis showed that lower PNI was significantly correlated with poor OS and DFS (P < 0.05). In addition, older age, lower BMI, tumor necrosis, higher tumor pathological T stage and Fuhrman grade were significantly correlated with poor OS (P < 0.05). Cox multivariate analysis showed that among the four hematological indexes, only PNI was an independent factor significantly associated with OS, whether as a continuous variable (HR=0.9, 95%CI=0.828-0.978, P=0.013) or a classified variable (HR=2.397, 95%CI=1.061-5.418, P=0.036).@*CONCLUSION@#Low PNI was a significant predictor for advanced pathological T stage, decreased OS, or DFS in non-metastatic RCC patients treated with surgery. In addition, PNI was superior to the other hematological biomar-kers as a useful tool for predicting prognosis of RCC in our study. It should be externally validated in future research before the PNI can be used widely as a predictor of RCC patients undergoing nephrectomy.

Comparison of safety and effectiveness between retroperitoneal laparoscopic tumor aspiration and laparoscopic partial nephrectomy in the treatment of renal angiomyolipoma / 北京大学学报(医学版)

OBJECTIVE@#To compare the safety and treatment effectiveness of retroperitoneal laparoscopic tumor aspiration and laparoscopic partial nephrectomy (LPN) in the treatment of renal angiomyolipoma (RAML).@*METHODS@#We retrospectively reviewed the clinical data of patients with pathologically confirmed RAML who received operation between August 2010 and August 2016 in the Department of Urology, Peking University First Hospital. Among them, a series of 121 patients were included in this trial according to the inclusion criteria, of which 74 cases could be collected and followed-up effectively. Based on the detailed surgical route, the 74 patients were divided into groups A and B: group A, which underwent retroperitoneal laparoscopic tumor aspiration, included 43 cases; group B, which received retroperitoneal LPN, included 31 cases. Patient demographics, intraoperative variables and postoperative outcomes were reported and compared between the groups.@*RESULTS@#No statistical difference was detected in both groups before the treatment. Intraoperatively, the mean estimated blood loss was 48.7 mL in group A and 102.9 mL in group B, and the mean operative time was 70.1 min (21.2 min of warm ischemia time included) in group A and 103.6 min (28.5 min of warm ischemia time included) in group B, which were both statistically different. In group A, no complications occurred and yet 2 complications of transfusion and 1 complication of urine leakage were discovered in group B, although all finally recovered only with conservative treatment. A statistical difference was observed in the complication rates. Post-operatively, the mean serum creatinine level was 1.13 mg/dL in group A, and the level was 1.08 mg/dL in group B, in which no evident difference was detected. In a mean 52.6-months' follow-up, a recurrence of 3 cases in group A (7.0%) and a recurrence of 2 cases in group B (6.5%) were reported. No evident difference was also detected between the groups in the tumor recurrence rates.@*CONCLUSION@#Due to the improvements in the intraoperative blood loss and operative time, retroperitoneal laparoscopic tumor aspiration may be provided with more potential advantages in the safety, also with equal efficacy of lower tumor recurrence rates when compared with the traditional retroperitoneal LPN in the treatment of RAML.

Advances in the study of aptamer-based drug for targeting therapy / 药学学报

Aptamers are randomly selected from single-stranded oligonucleotide libraries by systematic evolution of ligands technology exponential enrichment (SELEX). They bind to various targets like metal ions, nucleic acids, proteins, small organic compounds, and even entire organisms. Candidate aptamers are predicted to be highly effective in producing targeting effects for certain diseases like cancer, macular degeneration, acute coronary syndrome, von Willebrand factor related disorder disease and so on. Aptamers may also serve as drug-carriers helping drugs to be released in specific regions and tissues. Compared with other types of targeting ligands, aptamers have an array of unique advantageous features, which make them promising to develop aptamer-drug conjugates (ApDCs) for targeted-oriented therapy. Deep investigation into ApDCs discovery and development may promote the process of biological and biomedical analysis. In this review, we summarize the advances of drug discovery and drug delivery using aptamers in basic and clinical trials in recent years, and meanwhile analyze its advantages and challenges in biomedical studies.

Advances in the research of anti-CD20 therapeutic monoclonal antibodies / 药学学报

As targeted drugs to B-cell malignancies, anti-CD20 monoclonal antibodies have been proved to be important in therapeutic antibody field. With three generations in more than ten years' development, the structures of these drugs have been improved, and many new indications have been found. Nowadays, these kinds of antibodies are not only used in the treatment of lymphoid malignancies, but also been proved to be useful in some autoimmune diseases treatment, and their new indications are still being expanded. With the optimization of their clinical dosage regimens, drug reaction has been increased, thus, therapeutic and side effects of anti-CD20 monoclonal antibody have been further improved as well. However, the exact mechanism of action of their combination therapy with other chemical drugs is still unclear, which remains to be further studied. This article reviewed new development of anti-CD20 therapeutic monoclonal antibodies research in recent years.

Advance in the study of targeting delivery system for siRNA mediated by aptamers / 药学学报

RNA interference (RNAi), as a new technology of gene therapy, has been used in the studies of many diseases in vitro, however, targeting delivery of small interference RNA (siRNA) is still a bottleneck for clinical therapy of siRNA agents. Aptamer is a group of oligonucleotides with high affinity and targeting, and is becoming another important means of delivery for siRNA. In this review, we summarized siRNA delivery obstacles in vivo and recent attractive developments increatively using cell-internalizing aptamers to deliver siRNAs to target cells.

Pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites in rhesus monkeys / 药学学报

To study the pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites after iv gtt administration in rhesus monkeys, a dual solid phase extraction pretreatment method coupling with non-gel sieving capillary electrophoresis analysis method was used for determination of cantide and its metabolites in plasma and their pharmacokinetic parameters were calculated. The pharmacokinetic behavior of cantide and its metabolites (M1 and M2) after iv gtt administration (8, 16 and 24 mg kg(-1)) in rhesus monkeys were investigated. After iv gtt administration of cantide to rhesus monkeys, cantide in plasma was eliminated rapidly and the terminal elimination half-life (t1/2) was 57.91-77.97 min, the correlation coefficients (r) to the dose of Cmax AUC(o-inf) and AUC(0-t) of the prototype was 0.9918, 0.9568 and 0.9773, respectively. The metabolites of cantide reached the Cmax following cantide immediately and the Cmax of metabolites were lower than that of the prototype. The CL(S) of cantide and its metabolites (M1 and M2) were 1.60-2.19, 5.92-8.58 and 6.07-8.78 mL min(-1) kg(-1), respectively. So, it is concluded that the Cmax of cantide and its metabolites increased with the dose, which is the same as their AUC(0-inf) and AUC(0-t). The CL(S) of metabolites were higher than that of the prototype. The MRT and t1/2 of metabolites in the high dose group increased obviously.

Establishment of euglycemic clamp technique in beagle dogs / 军事医学科学院院刊

Objective To establish a euglycemic clamp technique in beagle dogs. Methods The euglycemic clamp technique was applied in healthy beagle dogs and the blood glucose, insulin, C-peptide, insulin and glucagon were monitored during the clamp. Results The blood glucose was controlled within the basal level.The coefficient of variation was less than 5% during the clamp. The serum insulin concentration finally reached(40.0±3.8)mIU/L stably and a significant inhibition was shown in endogenous insulin by the determination of C-peptide. But there was no significant increase in serum glucagon compared with basal values.Conclusion Methodology confirmed that the euglycemic clamp technique is successful in beagle dogs and can be applied in the study of pharmacodynamics of insulin preparations.

Clinical validity of hinge position to expansive semi open-door laminoplasty / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate and compare the efficacy and clinical results of cervical expansive open door laminoplasty (EOLP) with different hinge position.</p><p><b>METHODS</b>From February 2006 to February 2007, a total of 102 cases with cervical spondylotic myelopathy were assessed in this randomized controlled trial. Fifty-seven patients underwent EOLP with the hinge located at the inner margin of the lateral mass classified as wide-open group. Forty-five cases who underwent EOLP with the hinge positioned at the lamina margin served as narrow-open group. The clinical results and radiological examinations of both groups were evaluated 24 months after surgery.</p><p><b>RESULTS</b>There were no significant differences in operation time, bleeding quantity and recovery rate of Japanese Orthopaedic Association (JOA) scores. The incidence of C(5) palsy and severity of axial symptoms in the wide-open group were significantly lower than those in the narrow-open group (P < 0.05). There were no significant differences in cervical curvature index and range of motion between the two groups.</p><p><b>CONCLUSIONS</b>Well-suited and appropriated inwardly shift the hinge could promote clinical outcomes after EOLP, especially decrease the incidence of the C(5) palsy and the severity of axial symptom, but it is contraindication for patients with ossification of posterior longitudinal ligament, ossification of ligament flavum and fluorosis cervical stenosis.</p>

The feasibility and mechanism of recombinant adenovirus Ad - p 14 ARF in gene therapy of liver cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the feasibility and mechanism of recombinant adenovirus Ad-pl4ARF in cancer gene therapy.</p><p><b>METHODS</b>The proliferation of different liver cancer cells was assessed by morphology and trypan blue assay. Cell apoptosis was confirmed by detecting phosphatidylserine (PS) externalization with Annexin V/PI double staining. The expression of related proteins was analyzed by Western bloting. Nude mouse model bearing subcutaneous transplanted BEL7402 tumor was established to study the therapeutic ability of Ad-pl4ARF.</p><p><b>RESULTS</b>Ad-pl4ARF suppressed cell growth and proliferation, and promoted cell apoptosis of cancer cell lines with different genetic background. Ad-pl4ARF inhibited growth of liver cancer cells ( HepG2, BEL7402) in a dose-dependent manner. Ad-pl4ARF lead to overexpression of Bax and p21, the downstream regulating genes of p53. In the experimental therapy on nude mice bearing subcutaneous transplanted BEL7402 tumor, Ad-pl4ARF suppressed tumor growth significantly.</p><p><b>CONCLUSION</b>pl4ARF is a short gene and with powerful function, which are consistent with the requirements for tumor suppressor genes used in gene therapy. It may play an important role in gene therapy against malignancies in the future.</p>

Metabolism, Distribution and Excretion of Recombinant Human Thrombopoietin in Mice / 中国实验血液学杂志

The metabolism, distribution and excretion profiles of recombinant human thrombopoietin (rhTPO) in mice were studied by means of (125)I-labeled rhTPO ((125)I-rhTPO) combined with size exclusive high performance liquid chromatography (SHPLC) or trichloroacetic acid (TCA) precipitation analysis. (125)I-rhTPO was prepared by iodogen method. Purification was performed on Sephacryl S-200 HR gel. Radioactive-purity of (125)I-rhTPO identified by SHPLC was (96.9 +/- 1.5)% (n = 3). The proliferation effect of TPO dependent cell line (TD-3) and the increase of peripheral platelet counts in mouse by (125)I-rhTPO demonstrated that (125)I-labeled protein maintained the biological activities of TPO both in vitro and in vivo. SHPLC analysis of serum and urine samples taken after sc 1 micro g/mouse (345 kBq/mouse) of (125)I-rhTPO revealed that there were two lower molecular weight (125)I-degradation metabolites ((125)I-MI and (125)I-MII) other than parent molecule. (125)I-MI was mainly found in urine, and (125)I-MII was detected both in serum and in urine. The maximal concentration of (125)I-rhTPO was reached at 2 hours after injection. The terminal half-life was 10.8 hours, which was much longer than those of other peptides. TCA precipitable radioactivity in tissue showed that the radioactivity in bone marrow was rather high. The highest level was found in urinary system. Levels in adrenals, lymph nodes, and fat were near to that in serum. Lowest was found in brain. The main excretion route was urinary system and (98 +/- 5.6)% of (125)I-rhTPO was excreted within 72 hours after dosing.