The dialysis method was employed to prepare blank and doxorubicin (DOX) loaded micelles formed by temperature- and pH- sensitive polyhistidine-co-polyDL-lactide-co-glycolide-co-polyethyleneglycol-co-polyDL-lactide-co-glycolide-co-polyhistidine (PHis-b-PLGA-b-PEG-b-PLGA-b-PHis). The critical micelle concentrations (CMC) of the copolymers were measured with Pyrene Fluorescent Probe Technique. The temperature- and pH- sensitive properties of the blank micelles solution were investigated by optical transmittance measurement. The morphology and diameter of DOX micelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The entrapment rate and drug-loading rate were determined with dialysis method. The in vitro release study was further performed to examine the temperature- and pH-responsive drug release behavior from DOX-loaded micelles. The results indicated that the CMC, entrapment efficiency and drug-loaded amount of the micelles were 7.5 x 10(-3) g x L(-1), 85.2 +/- 3.1% and 10.4 +/- 4.5%, respectively. The DOX micelle was globular-shaped with a mean diameter of 91.1 +/- 15.8 nm. The transmittance of micelle solution consistently increased with the increasing temperature or decreasing pH. In comparison to the drug release profile at physiological conditions (37 degrees C, pH 7.4), the DOX-loaded micelles showed faster drug release rate at higher temperature (41 degrees C), lower pH (pH 7.0, pH 6.5, pH 5.0) or higher temperature and lower pH (41 degrees C, pH 5.0). This indicated that the micelles showed a temperature and pH-triggered drug release pattern. Base on the above results, it can be concluded that PHis-b-PLGA-b-PEG-b-PLGA-b-PHis block copolymer micelles which respond to temperature and pH stimuli are promising smart carriers for anti-tumor drugs with the advantages of temperature- and pH- triggered drug release.

Objective To prevent the medical personnel from infection during aeromedical evacuation of fulminating respiratory infectious disease patients by exploring the changes of differential pressure between those in and out of the negative-pressure isolation capsule and analyzing the stability of the capsule during aeromedical evacuation.Methods A differential pressure monitor developed by Institute of Medical Equipment was used for real-time recording of the changes the differential pressure in and out of the capsule during five flight phases of the aircraft,and the safety of the capsule during aeromedical evacuation and corresponding considerations were investigated.Results The maximum and minimum values of the negative pressure in the capsule were-60 Pa and-120 Pa respectively during aeromedical evacuation,which were all less than the safety threshold-15 Pa.The negative pressure was is directly proportional to the flying altitude.Conclusion The capsule keeps negative pressure effectively during flight,and thus facilitates patient aeromedial evacuation greatly.

Objective To preliminarily investigate the methods,safety and short to medium-term effectiveness of the interventional ultrasound applying in the hybrid procedure to treat the thrombosis of arteriovenous graft(AVG).Methods Twenty patients with the thrombosis of AVG,who received the hybrid procedure defined as Fogarty catheter thrombectomy and percutaneous transluminal angioplasty (PTA) guided by the ultrasonography,were retrospectively investigated. The display effects of the ultrasonography were observed.The technical and clinical success rates were evaluated.All the cases were followed up every 3 months for at least 1 year to evaluate the post-interventional assisted primary patency and the post-interventional secondary patency.Results All the processes were clearly displayed and well guided by the interventional ultrasound during the procedure.The technical and the clinical success rates were both 100%.No major complications were recorded.The post-intervention assisted primary patency rate was 100%,92.9%,85.7%,71 .4% at 3,6,9,12 months,respectively.The post-intervention secondary patency was 100%,100%,89.5%,89.5% at the correspondent months.Conclusions This pilot research shows the hybrid procedure guided by the interventional ultrasound to treat the thrombosis of AVG has high success rate and satisfied patency in short to medium-term.The interventional ultrasound is an effective, safe and convenient guiding method to the hybrid procedure,and has the value for clinical application.

Objective To investigate the changes of blood-brain barrier (BBB) permeability and the correlation with cognitive function in patients with ischemic white matter disease with dynamic contrast-enhanced MRI (DCE-MRI).Methods Totally 71 subjects underwent routine MRI,DCE-MRI,mini-mental state examination (MMSE) and Fazekas scoring,and then were divided into patient group and control group according to the Fazekas scores.The leakage rate (K),area under the leakage curve (AUC) and fractional blood plasma volume (Vp) in cerebral white matter hyperintensities area and normal appearing white matter area were measured and compared between the two groups.The correlation between these parameters and MMSE scores were analyzed.Results K and AUC value of white matter hyperintensities area and normal appearing white matter area in patient group were significantly higher than those in control group (all P＜0.001).Vp value of normal appearing white matter area in patient group was lower than that in control group (P=0.015).K and AUC value of white matter hyperintensities area in patient group had significant negative correlation with MMSE scores (r=-0.440,--0.540,both P＜0.001).Conclusion BBB permeability increased in cerebral white matter hyperintensities and normal appearing white matter area in patients with ischemic white matter lesions,which correlated with cognitive function.

Objective:To explore the puncture management in hemodialysis patients with difficult new arteriovenous fistula based on the finest evidence-based best practice evidence and evaluate the clinical effects.Methods:A team was formed, according to theoretical framework basing on the evidence of continuous quality improvement model, the best evidence-based interventions were obtained by adopting evidence-based practice. Formulated review indicators, evaluated obstacles and promoting factors in the process of practice, and took corresponding action strategies. From February 2020 to June 2020, 30 patients admitted to the dialysis center of Sir Run Run Shaw Hospital of Zhejiang University were recruited in the baseline review group by convenience sampling method. From September 2020 to January 2021, 30 patients from September 2020 to January 2021 were recruited in the after-effect evaluation group. The baseline review group adopted the original difficult new arteriovenous fistula puncture management scheme, and the after-effect evaluation group adopted the difficult autologous new internal fistula puncture management scheme based on the best evidence. The success rate of one puncture of fistula, the incidence rate of hematoma during puncture and dialysis, the incidence rate of discontinuation of treatment and the compliance with examination indexes were compared in the patients before and after applying for the evidences.Results:Compared with the baseline review group, the success rate of one-time puncture of internal fistula in the aftereffect evaluation group increased from 36.7% (11/30) to 73.3% (22/30), the incidence rate of hematoma during puncture and dialysis were decreased from 33.3%(10/30) to 6.67%(2/30) and 40%(12/30) to 0, the incidence rate of discontinuation of treatment were decreased from 40%(12/30) to3.33% (1/30), the difference was statistically significant ( χ2 values were 6.67-11.88, P<0.05). The implementation rate of review indexes in the aftereffect evaluation group was higher than that in the baseline review group, and the difference was statistically significant ( P<0.05). Conclusions:Evidence-based practice can improve the success rate of difficult new arteriovenous fistula, and reduce the incidence of arteriovenous fistula hematoma, reduce treatment interruption, and better maintain the lifeline of patients.

Purpose: Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis. Materials and Methods: One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included. Results: Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea. Conclusion Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.

Amplifying "eat me signal" during tumor immunogenic cell death (ICD) cascade is crucial for tumor immunotherapy. Inspired by the indispensable role of adenosine triphosphate (ATP, a necessary "eat me signal" for ICD), a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy. Doxorubicin (DOX), ATP and ferrous ions (Fe²⁺) were co-assembled into nanosized amplifier (ADO-Fe) through π‒π stacking and coordination effect. Meanwhile, phenylboric acid-polyethylene glycol-phenylboric acid (PBA-PEG-PBA) was modified on the surface of ADO-Fe (denoted as PADO-Fe) by the virtue of d-ribose unit of ATP. PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction. In acidic microenvironment, PBA-PEG-PBA would dissociate from amplifier. Moreover, high H₂O₂ concentration would induce hydroxyl radical (·OH) and oxygen (O₂) generation through Fenton reaction by Fe²⁺. DOX and ATP would be released from the amplifier, which could induce ICD effect and "ICD adjuvant" to amplify this process. Together with programmed death ligands 1 (PD-L1) checkpoint blockade immunotherapy, PADO-Fe could not only activate immune response against primary tumor, but also strong abscopal effect against distant tumor. Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.