ABSTRACT
Precisely delivering combinational therapeutic agents has become a crucial challenge for anti-tumor treatment. In this study, a novel redox-responsive polymeric prodrug (molecular weight, MW: 93.5 kDa) was produced by reversible addition-fragmentation chain transfer (RAFT) polymerization. The amphiphilic block polymer-doxorubicin (DOX) prodrug was employed to deliver a hydrophobic photosensitizer (PS), chlorin e6 (Ce6), and the as-prepared nanoscale system [NPs(Ce6)] was investigated as a chemo-photodynamic anti-cancer agent. The glutathione (GSH)-cleavable disulfide bond was inserted into the backbone of the polymer for biodegradation inside tumor cells, and DOX conjugated onto the polymer with a disulfide bond was successfully released intracellularly. NPs(Ce6) released DOX and Ce6 with their original molecular structures and degraded into segments with low MWs of 41.2 kDa in the presence of GSH. NPs(Ce6) showed a chemo-photodynamic therapeutic effect to kill 4T1 murine breast cancer cells, which was confirmed from a collapsed cell morphology, a lifted level in the intracellular reactive oxygen species, a reduced viability and induced apoptosis. Moreover, ex vivo fluorescence images indicated that NPs(Ce6) retained in the tumor, and exhibited a remarkable in vivo anticancer efficacy. The combinational therapy showed a significantly increased tumor growth inhibition (TGI, 58.53%). Therefore, the redox-responsive, amphiphilic block polymeric prodrug could have a great potential as a chemo-photodynamic anti-cancer agent.
ABSTRACT
Objective:To compare the clinical efficacy of high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) in the treatment of infants with severe respiratory syncytial virus (RSV) pneumonia.Methods:A prospective randomized controlled trial was conducted. The infants with severe RSV pneumonia who received invasive mechanical ventilation admitted to intensive care unit (ICU) of Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2018 to December 2019 were enrolled. According to the order of admission, each infant was assigned to HFOV group or CMV group by random number table. The basic data, pediatric critical score, blood gas analysis, ventilator parameters, oxygenation index [OI, OI = mean airway pressure (Pmean)×fraction of inspired oxygen (FiO 2)/arterial partial pressure of oxygen (PaO 2)×100], duration of mechanical ventilation, length of ICU stay, complications, prognosis, use of muscle relaxants and vasoactive drugs and other clinical indicators of the two groups were recorded. Results:A total of 28 infants were enrolled in the analysis, including 15 infants receiving CMV and 13 infants receiving HFOV. There were no significant differences in age, body weight, pediatric critical score and OI before enrollment, type Ⅱ respiratory failure, multiple organ dysfunction, basic diseases and laboratory examination indexes before enrollment between the two groups. Six hours after enrollment, compared with CMV group, heart rate (HR), respiratory rate (RR), case of transcutaneous oxygen saturation (SpO 2) decrease, case of HR decrease, case of cardiopulmonary resuscitation (CPR) and OI in HFOV group were significantly decreased [HR (bpm): 130 (125, 138) vs. 144 (140, 160), RR (times/min): 35 (34, 38) vs. 40 (35, 45), SpO 2 decrease (case: 1 vs. 10), HR decrease (case: 0 vs. 6), CPR (case: 0 vs. 4), OI: 6.5 (4.4, 8.9) vs. 9.3 (8.0, 12.8)], while case of use of muscle relaxants (case: 3 vs. 0) and volume of 7-day positive fluid balance [mL/kg: 167.1 (113.8, 212.6) vs. 90.8 (57.8, 112.7)] were significantly higher, the differences were statistically significant (all P < 0.05). There was no use of blood purification treatment, no severe complications such as pneumothorax and intracranial hemorrhage, and no death within 28 days in the two groups. Conclusion:Compared with CMV, HFOV in the treatment of infants with severe RSV pneumonia can improve the oxygenation level and clinical physiological indexes earlier, reduce the incidence of adverse events such as HR, SpO 2 decrease and CPR, increase the use of muscle relaxants and the positive fluid balance, and do not increase the incidence of severe complications such as pneumothorax and intracranial hemorrhage, so its clinical application is safe.
ABSTRACT
Objective To evaluate the effect of dexmedetomidine on renal functions during the anesthesia of renal transplantation.Methods Sixty patients (36 males, 24 females, aged 25-45 years, ASA physical status Ⅱ or Ⅲ), were randomly divided into two groups (n=30 each).Patients in dexmedetomidine group received a loading dose of dexmedetomidine 1 μg/kg within 10 min)and a continuous infusion of dexmedetomidine 0.6 μg·kg-1·h-1 until 30 min toward the end of surgery, while patients in control group received 0.9% sodium chloride injection to maintain equal capacity until 30 min before the end of surgery.Artery systolic blood pressure and heart rate were recorded before anesthesia induction (T1), before vascular anastomosis opening (T2), immediately after vascular anastomosis opening (T3), 30 min after vascular anastomosis opening (T4), after the surgery (T5), venous blood was collected in T2, T4, 24 h after surgery (T6) and 48 h after surgery (T7) to detect the blood urea nitrogen (BUN), serum creatinine (Cr), IL-18 and Cystatin C (Cys C);fluid infusion and urine were recorded.Results Compared with control group, HR of dexmedetomidine group was reduced at T3, SBP of dexmedetomidine group was elevated at T2, T3(P<0.05).Compared with T2, Cys C, BUN, Cr of two groups decreased significantly at T6, T7, and Cys C of dexmedetomidine group was lower than that of control group (P<0.05).Compared with T2, IL-18 of the two groups reduced significantly at T6 and T7, and lowered amplitude in the dexmedetomidine group was greater than that in the control group (P<0.05).Perioperative urine volume in the dexmedetomidine group was more than that in the control group (P<0.05).There was no difference in perioperative fluid infusion between the two groups.Conclusion Perioperative continuous infusion of dexmedetomidine might effectively improve the renal function of renal transplantation patients.