Reexamining the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin.

Higher drug loading employed in nanoscale delivery platforms is a goal that researchers have long sought after. But such viewpoint remains controversial because the impacts that nanocarriers bring about on bodies have been seriously overlooked. In the present study we investigated the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin (PLD). We prepared PLDs with two different drug loading rates: high drug loading rate, H-Dox, 12.9% w/w Dox/HSPC; low drug loading rate, L-Dox, 2.4% w/w Dox/HSPC (L-Dox had about 5 folds drug carriers of H-Dox at the same Dox dose). The pharmaceutical properties and biological effects of H-Dox and L-Dox were compared in mice, rats or 4T1 subcutaneous tumor-bearing mice. We showed that the lowering of doxorubicin loading did not cause substantial shifts to the pharmaceutical properties of PLDs such as in vitro and in vivo stability (stable), anti-tumor effect (equivalent effective), as well as tissue and cellular distribution. Moreover, it was even more beneficial for mitigating the undesired biological effects caused by PLDs, through prolonging blood circulation and alleviating cutaneous accumulation in the presence of pre-existing anti-PEG Abs due to less opsonins (e.g. IgM and C3) deposition on per particle. Our results warn that the effects of drug loading would be much more convoluted than expected due to the complex intermediation between nanocarriers and bodies, urging independent investigation for each individual delivery platform to facilitate clinical translation and application.

First principles insights into the interaction mechanism of iron doped thermally activated kaolinite with Cd and Pb pollutants in organic solid waste incineration flue gas.

Incineration of organic solid wastes is accompanied by the heavy metal emission through flue gas. As an inexpensive and efficient heavy metal adsorbent, the improvement of kaolinite adsorption performance for heavy metals has drawn widespread interests. In this work, the interaction mechanisms between various kaolinite surfaces and Cd/Pb species are explored through first principles calculations. The results show that the combination of Fe doping and dehydroxylation enhances the activity of kaolinite surfaces, analysis of adsorption configurations reveal that both Cd and Pb species are immobilized through chemisorption on the -H + Fe surface. At the microscopic level, further electronic structure analysis shows that the composite modified kaolinite surface has more electron transfer and more pronounced orbital hybridization and overlap compared to the original kaolinite surface, demonstrating that the modification means of dehydroxylation and Fe doping indeed enhanced the activity of the kaolinite surface, especially the activity of the O atoms in the vicinity of the Fe atom and that the O atoms are more efficiently bonded as ionic connecting Cd/Pb species for the purpose of trapping Cd/Pb species. This study points out the research direction and provides basic theoretical support for the development of new kaolinite adsorbents in the future.

Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases.

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.

Identifying optimal candidates for induction chemotherapy among stage II-IVa nasopharyngeal carcinoma based on pretreatment Epstein-Barr virus DNA and nodal maximal standard uptake values of [18 F]-fluorodeoxyglucose positron emission tomography.

OBJECTIVE: This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II-IVa nasopharyngeal carcinoma (NPC) based on Epstein-Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax-N) of [18 F]-fluorodeoxyglucose positron emission tomography. PATIENTS AND MATERIALS: A total of 679 patients diagnosed with stage II-IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model. RESULTS: Both high levels of EBV DNA (>1500 copies/mL) and SUVmax-N (>12.3) indicated worse survival conditions. All patients were divided into low- and high-risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) (all p-values<0.05). The addition of IC to CCRT was associated with survival improvement in OS, PFS, and DMFS in high-risk patients, while no survival difference was found between CCRT and IC+CCRT in low-risk patients. CONCLUSIONS: Our study can help clinicians select stage II-IVa NPC patients who benefit from IC, which is important in guiding individual treatment.

Establishment of two new predictive models for prostate cancer to determine whether to require prostate biopsy when the PSA level is in the diagnostic gray zone (4-10 ng ml-1).

Our goal was to establish two new predictive models of prostate cancer to determine whether to require a prostate biopsy when the prostate-specific antigen level is in the diagnostic gray zone. A retrospective analysis of 197 patients undergoing prostate biopsy with prostate-specific antigens between 4 and 10 ng ml-1 was conducted. Of these, 47 patients were confirmed to have cancer, while the remaining 150 patients were diagnosed with benign prostate disease after examining biopsy pathology. Two multivariate logistic regression models were established including age, prostate volumes, free/total prostate-specific antigen ratio, and prostate-specific antigen density using SPSS 19.0 to obtain the predicted probability and Logit P, and then, two receiver operating characteristic (ROC) curves were drawn to obtain the best cutoff value for prostate biopsy: one for the group of all the prostate cancers and one for the group of clinically significant prostate cancers. The best cutoff value for prostate biopsy was 0.25 from the multivariate logistic regression ROC curve model of all the prostate cancers, which gave a sensitivity of 75.4% and a specificity of 75.8%. The best cutoff value for prostate biopsy was 0.20 from the multivariate logistic regression model of clinically significant prostate cancers, which gave a sensitivity of 76.7% and a specificity of 80.1%. We identified the best cutoff values for prostate biopsy (0.25 for all prostate cancers and 0.20 for clinically significant prostate cancers) to determine whether to require prostate biopsy when the PSA level is in the diagnostic gray zone.

[Safeguard and management of the heart vales in congenital heart disease procedure].

OBJECTIVE: To summarize the experience in performing reoperation of valve dysfunction after congenital heart disease procedure. METHODS: From 1994 to 2001 we reviewed the data of 13 patients with valve dysfunction after congenital heart disease operation, in which 8 patients after ventricular septal defect, 3 after atrioventricular canal and 2 after respectively tetralogy of Fallot and atrial septal defect were corrected. Before the first operation, 6 patients had presented the mild to moderate mitral regurgitation, 1 had aortic regurgitation. Other 6 patients had valves dysfunction occurring after the first operation, among them, 2 suffered from respectively residual shunt of the ventricular septal defect, 2 had anterior chordae rupture of tricuspid valve, one had an operative injured aortic valve and one had surviving of right ventricular outlet obstruction. Thirteen patients were reoperated, including mitral valve replacement in 6, tricuspid valve replacement in 2, aortic valve replacement in one, aortic valve replacement consists with mitral valve repair and tricuspid valve repair in one and tricuspid valve repair in 3. Concomitant procedures were performed. RESULTS: Low cardiac output occurred in 3 cases and there were 2 early deaths, due to cerebral air-embolism, respiratory and circulatory failure respectively. Other 11 cases discharged and were followed up well. CONCLUSIONS: It is important to safeguard and repair the valvular construction and function during the operation in congenital heart disease. Reoperation should be performed timely for obtaining recurrent and a good results.

[Effect of cariporide on immature rabbit heart].

OBJECTIVE: To investigate the protective effects of Cariporide on immature rabbit heart, and to search for the protective mechanism of the Na(+)/H(+) exchange inhibitor on immature rabbit hearts. METHODS: New Zealand immature rabbits were randomly divided into two groups (n = 12 in each group). The isolated rabbit heart model was involved in this study. The hearts were submitted to 60 minutes of normothermic ischemia with cardioplegia per 20 minutes of reperfusion. Group I received St. Thomas No2 as cardioprotective solution. Group II received St. Thomas No2 with addition of cariporide (10 micro mol/L). The left ventricular function was recorded, including left ventricular systolic pressure (LVSP), left ventricular dystolic pressure (LVDP), coronary artery flow (CAF), mean aortic pressure (MAP), aortic flow (AF) and dp/dt max. The levels of creatine phosphokinase (CK), lactic dehydrogenase (LDH) of coronary sinus venous solution were measured. The ventricular cardiomyocytes isolated from other 6 immature rabbit hearts were subdivided into 3 groups of each heart, which were attained by means of collagenase-perfusion. All cells were incubated with calcium fluoresence indicator Fluo-3/AM, and then the intracellular free calcium was measured under the laser scanning con-focal microscopy. The baseline was measured after isolation without anoxic/re-oxygenation. The control group received anoxic conditions for 60 minutes and re-oxygenation for 30 minutes, then was measured. The experiment group received the same conditions as control group with addition of Cariporide (1 micromol/L). RESULTS: After ischaemia/reperfusion, the percentage of recovery of myocardial function in group II was much better than group I; the LVDP, LVSP, MAP, AF, CAF and dp/dt max showed markedly better recovery in group II. The release of CK, LDH was significantly increased in Group I. After anoxic/re-oxygenation, the intracellular free calcium of isolated immature rabbit ventricular myocytes in control group increased significantly than baseline (P < 0.01); there were no significant difference of immature myocardial [Ca(2+)]i between experiment group and baseline (P > 0.05); and the experiment group myocardial [Ca(2+)]i reduced significantly than control (P < 0.01). CONCLUSIONS: Cariporide demonstrates significant cardio-protective effects for immature myocardium ischemia/reperfusion, and the protective mechanism may be due to the inhibition of the intracellular free calcium overload.