The isothermal crystallization behavior and morphology of neat poly(L-lactic acid) (PLLA) and its blends with poly(D-lactic acid) (PDLA) and PDLA-b-poly(ethylene glycol) (PEG)-b-PDLA have been investigated. The glass transition temperature of the PLLA/PDLA blend, and especially the PLLA/PDLA-b-PEG-b-PDLA blend, is much lower than that of neat PLLA, indicating the plasticization effect of both low molecular weight PDLA and flexible PEG block. Both the PLLA/PDLA and PLLA/PDLA-b-PEG-b-PDLA blends can form stereocomplex (SC) crystals. However, the PDLA in the PLLA/PDLA blend postponed the crystallization rate of the blend, whereas the PEG chains in PLLA/PDLA-b-PEG-b-PDLA not only promoted the formation of SC crystals but also facilitated the crystallization of the PLLA matrix. The evolution of the crystal structure and morphologies of PLLA and its blends during the isothermal crystallization process have revealed the significant role of flexible PEG chains in the stereocomplex crystallization.
Advanced pancreatic cancer has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells (DC-CIK) administered with the chemotherapy (CT) S-1 in this malignancy. Consecutive patients ( = 47) with advanced pancreatic cancer were treated with either DC-CIK + S-1, DC-CIK alone, S-1 alone, or best supportive care. DC-CIK plus S-1 produced significantly longer median OS and PFS (212 and 136 days) compared with DC-CIK (128 and 85 days), CT (141 and 92 days), or supportive care only (52 and 43 days; < 0.001). After adjusting for competing risk factors, DC-CIK combined with S-1 and receipt of 2 or more cycles of DC-CIK treatment remained independent predictors of disease-free and overall survival ( < 0.05). Phenotypic analysis of PBMCs demonstrated that the CD3, CD3/CD4, and CD8/CD28 T-cell subsets were elevated ( < 0.05), while the CD3/CD8, CD3/CD16/CD56 and CD4/CD25 cell subsets were significantly decreased after DC-CIK cell therapy ( < 0.05). There were no grade 3 or 4 toxicities. In addition, the mutational frequency in cell-free tumor DNA (cfDNA) declined in 4 of 14 patients who received DC-CIK, and was associated with a more favorable survival. Treatment of advanced pancreatic cancer with combined DC-CIK infusions and S-1 was safe, resulted in favorable PFS and OS, and modulated the peripheral blood immune repertoire. .
Background: HPV persistent infection is a strong carcinogenic factor that can induce cervical cancer. Investigation of HPV epidemiology and genotype distribution is of great meaning for the development of cervical cancer prevention and control strategies. Methods: By using PCR-based hybridization gene chip assay, HPV genotype was detected from 14,185 women that came from HEC (Health Examination Center) or OGOC (Obstetrics and Gynecology Outpatient Clinics) between 2015 and 2017 in Sichuan area. The epidemiology and genotype distribution as well as the relationship between HPV infection and histology/cytology abnormalities were analyzed. Results: The positivity rate of HPV was 23.84%. The HPV-positive rate of OGOC group (37.62%) was significantly higher than that of HEC group (15.29%), p < 0.05. The prevalence of HPV reached peak at age 41-50 (5.86%) in HEC group, but at age 21-30 (14.74%) in OGOC group. Of all the HPV positive women, single genotype infection was the most common form in both HEC and OGOC group (62.06% in total screening population, 74.36% in HEC group and 54.01% in OGOC group). Three most prevalent HPV types were HPV-52 (5.02%), 58 (3.61%), and 16 (3.24%) in total screening population. Of all the HPV positive women, the top three types were HPV-52 (20.93%), CP8304 (15.32%), and 58 (14.42%) in HEC group, while were HPV-52 (21.14%), 16 (16.34%), and 58 (15.61%) in OGOC group. HPV 52/16/58 accounted for 41.84% of cytology and 56.52% of histological abnormalities. Conclusions: Women in Sichuan area were facing the great threat of HPV infection, especially the women aged between 21~30 or 41-50 years old. The priority HPV types were HPV 52, 58, and 16 in OGOC group, while were HPV 52, CP8304, and 58 in HEC group. HPV 52/16/58 accounted for the majority of cytology and histological abnormalities. Our analysis was found to be valuable for providing a scientific basis for the prevention and control strategies of cervical cancer in Sichuan area.
Star-shaped PCL with one to five arms were synthesized by ROP. They have the same crystal structure as linear PCL, indicating that the central cores are located in amorphous regions. The influence of arm length and number on crystallization and melting behavior were studied by DSC, POM, and through the Avrami equation. A model is proposed to analyze the enzymatic degradation process of star-shaped polymers. The multi-arm structure and the limitation of the central cores on the chain mobility of each arm are considered to be the primary factors influencing the characteristic crystallization and enzymatic degradation behavior of star-shaped PCLs.
Microvessels of the blood–brain barrier (BBB) exclusively express the major facilitator superfamily domain‐containing protein 2a (Mfsd2a), which is the key transporter for docosahexaenoic acid uptake into the brain. Mfsd2a suppresses caveolae‐mediated transcytosis to regulate BBB transcellular permeability via controlling lipid composition of BBB endothelial cells. It is speculated that Mfsd2a can restrain BBB crossing efficiency and brain accumulation efficiency of brain‐targeting drug delivery systems, which penetrate the BBB often through the receptor‐mediated transcytosis pathway. Transcytosis across the BBB is a crucial bottleneck for targeted chemotherapy of brain metastases. To overcome this issue, a pair of priming nanoparticles (NPs) and following drug‐loaded NPs are designed. Tunicamycin‐(TM)‐loaded transcytosis‐targeting‐peptide‐(TTP)‐decorated NPs (TM@TTP) are used to boost BBB transcytosis via inhibiting Mfsd2a. Doxorubicin (DOX)‐loaded TTP and CD44‐specific hyaluronic acid (HA)‐comodified NPs (DOX@TTP–HA) are designed as following drug‐loaded NPs. The brain accumulation efficacy of following DOX@TTP–HA with priming is 4.30‐fold higher than that without priming through the enhanced transcytosis pathway rather than the tight junction opening. Effective BBB crossing and brain accumulation, selective tumor uptake, excellent antitumor efficacy, and low hepatotoxicity are achieved by TM@TTP and DOX@TTP–HA, suggesting this tactic as a significant therapeutic strategy against breast cancer brain metastases.
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