The purpose of this study is to prepare T7 and TAT dual modified liposomes (T7-TAT-LIP) to penetrate through blood brain barrier and target to brain tumor cells. The liposomes were prepared with CFPE, T7 modified PEG-DSPE, TAT modified PEG-DSPE, soybean phospholipid, PEG-DSPE and cholesterol. The CFPE was used to track the cellular uptake efficiency. The density of T7 and TAT and the length of PEG were optimized, and then the liposomes were characterized by particle size, zeta potential, morphology and stability. Afterwards, the cellular uptake by bEnd.3 and C6 cells were evaluated. The results showed that the optimized parameters were 6% of T7, 0.5% of TAT, the molecular weight of PEG for T7 was 2000 and the molecular weight of PEG for TAT was 1000. After optimization, the particle size of T7-TAT-LIP was 118 nm, the zeta potential was -6.32 mV and the particles were spherical. The turbidity and particle size of liposomes were not obviously changed after 24 h incubation in PBS at 37 °C. The particle size and polydispersity index were also stable during 1 month incubation at 4-8 °C. The cellular uptake by both bEnd.3 and C6 cells of T7-TAT-LIP was higher than that of T7 or TAT modified liposomes, suggesting dual modified liposomes possessed better blood brain barrier targeting ability and brain tumor targeting ability than the single ligand modified liposomes.
Biological Transport ; Blood-Brain Barrier ; Brain Neoplasms ; drug therapy ; Cell-Penetrating Peptides ; pharmacology ; Cholesterol ; Liposomes ; Particle Size ; Phosphatidylethanolamines ; Polyethylene Glycols

OBJECTIVETo evaluate the efficacy and safety of heated humidified high-flow nasal cannula (HHHFNC) in preventing extubation failure in neonates.

METHODSA literature search was performed using PubMed, Cochrane Library, FMRS, and CNKI to collect the randomized controlled trials (RCTs) and quasi-RCTs which compared the clinical efficacy of HHHFNC and nasal continuous positive airway pressure (NCPAP) in preventing extubation failure in neonates. The identified studies were finally selected after full-text search and quality assessment and then subjected to a Meta analysis using RevMan 5.3.

RESULTSFive eligible trials involving 1040 neonates were included in the Meta analysis. The Meta analysis showed that there was no significant difference in treatment failure rate between the HHHFNC and the NCPAP groups. The HHHFNC group had significantly lower incidence rates of nasal trauma (OR=0.49, 95% CI: 0.34-0.71, P=0.0001) and pneumothorax (OR=0.27, 95% CI: 0.07-0.97, P=0.04) than the NCPAP group, but there were no significant differences in the duration to reach full oral feedings and the incidence rates of serious adverse events or other complications between the two groups, such as in-hospital mortality, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity.

CONCLUSIONSHHHFNC is safe and effective in preventing extubation failure in neonates.

Airway Extubation ; methods ; Catheters ; Continuous Positive Airway Pressure ; methods ; Hot Temperature ; Humans ; Infant, Newborn ; Nasal Cavity ; Noninvasive Ventilation ; methods

Objective To explore medium and long term efficacy of oblique lateral interbody fusion(OLIF)in treating lumbar specific infection.Methods From October 2017 to January 2021,24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation,including 15 males and 9 females,aged from 27 to 61 years old with an average of(43.0±15.0)years old;the courses of disease ranged from 6 to 24 months with an average of(14.0±7.0)months;7 patients with L2-L3,12 patients with L3-L4 and 5 patients with L4-L5;19 patients with tuberculosis infection and 5 patients with brucella infection.The amount of intraoperative blood loss,operative time and complications were recorded,and erythro-cyte sedimentation rate(ESR),C-reactive protein(CRP),visual analogue scale(VAS),Japanese Orthopaedic Association(JOA)score and American Spinal Injury Association(ASIA)rating were compared before and one month after opertaion.Re-sults All patients were followed up from 9 to 24 months with an average of(13.0±6.0)months.Operative time was(132.5±21.4)min,and intraoperative blood loss was(227.3±43.1)ml.ESR and CRP were decreased from(82.34±18.62)mmol·h-1 and(53.08±21.84)mg·L-1 before operation to(33.52±17.31)mmol·h-1 and(15.48±8.36)mg·L-1 at one month after opera-tion,respectively(P＜0.05).VAS was decreased from(7.52±1.36)before opertaion to(1.74±0.87)at one month after opera-tion(P＜0.05).JOA was increased from(17.86±3.95)before operation to(24.72±3.19)at one month after operation(P＜0.05).Four patients had neurological symptoms before operation,and were classified to grade D according to ASIA classifica-tion,who were recovered to grade E at 1 month after operation.One patient was suffered from psoas major muscle injury after operation,and returned to normal at 3 weeks.One patient was suffered from abdominal distension and difficulty in defecation,and relieved after gastrointestinal decompression and enema.No complications such as abdominal organ injury and poor wound healing occurred in all patients.Conclusion OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection,especially the lesion located on the middle lumbar vertebra.It has advantages of less trauma,short operation time,less blood loss,convenient operation,complete removal of the lesion,safety and effectiveness,and has good medium-and long-term efficacy for lumbar specific infection.

Objective To establish the pharmacokinetic model of linezolid in neonates,and to optimize the administration regimen. Methods A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy,and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected,and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features. Results The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination,and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h,respectively. The results of goodness of fit,visualization verification,and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows:6 mg/kg,q8h,at 28 weeks of gestational age (GA);8 mg/kg,q8h,at 32 weeks of GA;9 mg/kg,q8h,at 34-37 weeks of GA;11 mg/kg,q8h,at 40 weeks of GA. Conclusions The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

Accumulating evidence supports the significance of aberrant alternative splicing (AS) events in cancer; however, genome-wide profiling of progression-free survival (PFS)-related AS events in testicular germ cell tumors (TGCT) has not been reported. Here, we analyzed high-throughput RNA-sequencing data and percent-spliced-in values for 150 patients with TGCT. Using univariate and multivariate Cox regression analysis and a least absolute shrinkage and selection operator method, we identified the top 15 AS events most closely associated with disease progression. A risk-associated AS score (ASS) for the 15 AS events was calculated for each patient. ASS, pathological stage, and T stage were significantly associated with disease progression by univariate analysis, but only ASS and pathological stage remained significant by multivariate analysis. The ability of these variables to predict 5-year progression was assessed using receiver operating characteristic curve analysis. ASS had stronger predictive value than a combination of age, pathological stage, and T stage (area under the curve = 0.899 and 0.715, respectively). Furthermore, Kaplan-Meier analysis of patients with low and high ASS demonstrated that high ASS was associated with significantly worse PFS than low ASS (P = 1.46 × 10

ObjectiveProlonged storage of packed red blood cells （PRBC） is reportedly associated with poor clinical outcomes in critically ill， trauma， and cardiac surgery patients. However， the impact of PRBC’s age on long-term oncological outcomes in cancer patients remains poorly defined. Here we retrospectively evaluated the effect of PRBC’s age on overall survival and biochemical recurrence in patients undergoing curative resection of hepatocellular carcinoma. MethodsA total of 1 221 qualified patients undergoing curative hepatectomy for HCC between August 1， 2008 and June 30， 2012 at the Sun Yat-sen University Cancer Center （Guangzhou， PR China） were divided into nontransfused or transfused group. Transfused patients were further divided according to PRBC storage duration （fresh PRBC group， ≤ 14 days； old PRBC group， > 14 days）. Overall survival （OS）， intrahepatic recurrence-free survival （IRFS）， extrahepatic metastasis-free survival （EMFS） were assessed and multivariate analyses were performed to evaluate the association of PRBC storage duration with cancer outcomes. ResultsA total of 251 （20.6%） patients received intraoperative PRBC transfusion. Of these， 112 and 125 patients were grouped in the fresh and the old PRBC groups， respectively. The Kaplan–Meier curves showed that both fresh PRBC group and old PRBC group had worse OS， IRFS， and EMFS than nontransfused group （P<0.001）. Cox regression analyses further indicated that old PRBC transfusion was an independent prognostic factor of OS （HR=1.417， P=0.049）， IRFS （HR=1.519， P=0.013） for patients with HCC； conversely， new PRBC transfusion was not. ConclusionIn patients undergoing curative hepatectomy， intraoperative transfusions of PRBC that had been stored for more than 2 weeks is independently associated with a significantly increased risk of intrahepatic recurrence and reduced overall survival.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors