Radiotherapy-related Quality of Life in Nasopharyngeal Carcinoma Patients: a Systematic Review and Meta-analysis.

Introduction This systematic review and meta-analysis evaluated the quality of life (QoL) for nasopharyngeal carcinoma (NPC) patients with radiotherapy. Methods A systematic literature search was performed to identify relevant studies published until March 2022. Quality evaluation and data extraction were performed for the included studies, and meta-analysis was performed using Stata. Results Nine studies, including 1659 patients, were eligible. Most QoL scales developed at the end of the treatment course and then followed by a gradual recovery to 1 year and more than 1 year after treatment. However, some items have not changed significantly and have a deteriorating trend. Items of cognitive functioning and constipation in EORTC QLQ-C30, and sexuality, felt ill, and weight gain in EORTC QLQ- H&N35 showed that scales with follow-up of more than 1 year were worse than those within 1 year but still better than those after treatment. In the intensity-modulated radiotherapy (IMRT) subgroup in EORTC QLQ-C30, cognitive functioning was similar to those before, and there was no significant change in insomnia. There was no significant change in the teeth item in EORTC QLQ- H&N35. In the IMRT subgroup, scales of swallowing, felt ill, and weight gain with follow-up of more than 1 year were worse than those within 1 year. Conclusion The QoL of patients with NPC is significantly impaired after radiotherapy-treated compared to baseline, and most of these items will gradually improve.

Early clinical efficacy of pegylated interferon treatment in patients with different phases of chronic HBV infection: A real-world analysis.

Although there are therapeutic advantages for hepatitis B virus (HBV) withpegylated interferon alpha (peg-IFNα) treatment compared with nucleos(t)ide analog (NAs) therapy, the effect difference in infected population at different phases has not been well established. We studied the clinical efficacy of peg-IFNα in two populations with HBV infection, including inactive HBsAg carrier (IHC) and chronic hepatitis B (CHB). A total of 328 HBV-infected patients were included in this real-world analysis. Patients were divided into two groups according to the infected stages. Peg-IFNα monotherapy or combination therapy with NAs were used in IHCs, and peg-IFNα added-on NAs therapy was applied to patients with CHB. The primary efficacy endpoint was HBsAg loss at Week 24. Results: The Kaplan-Meier cumulative rates of HBsAg loss were 39.50% (n = 47/119) in IHC group and 28.71% (n = 60/209) in CHB group at Week 24 (p < .05). After Propensity Score Matching (PSM), the HBsAg loss rates were 36.84% (n = 35/95) and 32.63% (n = 31/95), respectively (p > .05). Patients with baseline HBsAg level < 100 IU/ml achieved higher rates of HBsAg clearance in IHC and CHB group (before PSM: 47.44% vs. 42.86%, after PSM: 49.12% vs. 45.83%, all p values > .05). Baseline HBsAg level and its level decline from baseline to Week 12 can be as the predictors for HBsAg loss at Week 24 in both groups. Hence, the efficacy of HBsAg clearance was broadly similar between IHCs and NA-treated CHB patients during the early peg-IFNα therapy. A significant downward trend of HBsAg level was observed in both groups during peg-IFNα therapy.

Dispersion Polymerization versus Emulsifier-Free Emulsion Polymerization for Nano-Object Fabrication: A Comprehensive Comparison.

Although the preparation of nano-objects by emulsifier-free controlled/living radical emulsion polymerization has drawn much attention, the morphologies of these formed objects are difficult to predict and to reproduce because of the much more complex nucleation mechanisms of emulsion polymerization compared to only one self-assembling nucleation mechanism of controlled radical dispersion polymerization. The present study compares dispersion polymerization with emulsifier-free emulsion polymerization in terms of nucleation mechanism, polymerization kinetics, and disappearance behavior of the macrochain transfer agent, gel permeation chromatograms curves of the obtained block copolymer as well as the structural and morphological differences between the produced nano-objects on the basis of published data. Moreover, the effects of the inherently heterogeneous nature of emulsion polymerization on the mechanism of reversible addition-fragmentation transfer polymerization and the nano-object morphology are examined, and efficient agitation and adequate solubility of the core-forming monomer in water are identified as the most crucial factors for the fabrication of nonspherical nano-objects.

Polymerization-Induced Self-Assembly of Functionalized Block Copolymer Nanoparticles and Their Application in Drug Delivery.

Drug delivery systems (DDS) based on functionalized polymeric nanoparticles have attracted considerable attention. Although great advances have been reported in the past decades, the fabrication efficiency and reproducibility of polymeric nanoparticles are barely satisfactory due to the intrinsic limitations of the traditional self-assembly method, which severely prevent further applications of the intelligent DDS. In the last decade, a new self-assembly method, which is usually called polymerization-induced self-assembly (PISA), has become a powerful strategy for the fabrication of the polymeric nanoparticles with bespoke morphology. The PISA strategy efficiently simplifies the fabrication of polymeric nanoparticles (combination of the polymerization and self-assembly in one pot) and allows the fabrication of polymeric nanoparticles at a relatively high concentration (up to 50 wt%), making it realistic for large-scale production of polymeric nanoparticles. In this review, the developments of PISA-based polymeric nanoparticles for drug delivery are discussed.

Hyperbranched Multicyclic Polymer Built from Tailored Multifunctional Monocyclic Prepolymer.

A simple and efficient method to construct a hyperbranched multicyclic polymer is introduced. First, a tailored trithiocarbonate with two terminal anthracene units and three azide groups is successfully synthesized, and this multifunctional trithiocarbonate is used as chain transfer agent (CTA) to afford anthracene-telechelic polystyrene (PS) via reversible addition-fragmentation chain transfer (RAFT) polymerization. After that, linear PS is irradiated under 365 nm UV light to achieve the cyclization process. The monocyclic polymer further reacts with sym-dibenzo-1,5-cyclooctadiene-3,7-diyne via "A2 +B3 " strategy based on a self-accelerating click reaction to produce hyperbranched multicyclic polymer. The structures and properties of the polymers are characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), UV-vis spectrophotometry, and triple-detection size-exclusion chromatography (TD-SEC). The number of monocyclic units of the resultant hyperbranched multicyclic polymer reaches about 21 based on multi-angle laser light scattering (MALLS) measurements. The plot of intrinsic viscosity versus molecular weight reveals that the α value of the unique hyperbranched multicyclic polymer is lower than both hyperbranched polymers and cyclic polymers.

Efficient Synthesis of Polymer Prodrug by Thiol-Acrylate Michael Addition Reaction and Fabrication of pH-Responsive Prodrug Nanoparticles.

In this study, an efficient method is proposed for the synthesis of polymer prodrug with acid-liable linkage via thiol-acrylate Michael addition reaction of the camptothecin with tethering acrylate group and polymer scaffold containing multiple thiol groups. The polymer scaffold P(HEO2MA)- b-P(HEMA-DHLA) is prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization of the methacrylate of lipoic acid (HEMA-LA) using poly(2-(2-hydroethoxy) ethyl methacrylate) (PHEO2MA) as macro-RAFT agent followed by reduction of the disulfides in lipoic acid (LA) groups to give polymer scaffold with dihydrolipoic acid (DHLA) pendent groups. Acrylate-tethering camptothecin (ACPT) is connected to P(HEO2MA)- b-P(HEMA-DHLA) via Michael addition reaction between thiol and acrylate with a high coupling efficiency (95%). Amphiphilic polymer prodrug P(HEO2MA)- b-P(HEMA-DHLA-CPT) spontaneously self-assembles into nanoparticles in an aqueous solution and exhibits a CPT loading content as high as 40.1%. The prodrug nanoparticles with the acid-liable ß-thiopropionate linkages can release CPT under acidic conditions, and the prodrug nanoparticles show similar cytotoxicity to HeLa cells as free CPT. Overall, the prodrug nanoparticles with high drug loading contents and acid-liable linkages are promising for pH-responsive anticancer therapy.

Efficient Fabrication of Photosensitive Polymeric Nano-objects via an Ingenious Formulation of RAFT Dispersion Polymerization and Their Application for Drug Delivery.

An ingenious formulation of RAFT dispersion polymerization based on photosensitive monomers of 2-nitrobenzyl methacrylate (NBMA) and 7-(2-methacryloyloxy-ethoxy)-4-methyl-coumarin (CMA) is reported herein. Various morphologies, such as spherical micelle, nanoworm, lamella, and vesicle, are fabricated at up to 20% solids content. Photoinduced cleavage of the NBMA moieties and dimerization of the coumarin moieties are simultaneously triggered upon UV (365 nm) irradiation. The former endows the cores of the nano-objects with abundant carboxyl groups, resulting in the transformation of the hydrophobic cores to hydrophilic ones. The latter induces the core-cross-linking of the nano-objects, which endows the nano-objects with enhanced structural stability and prevents the nanoparticle-to-unimer disassembly. The resultant nano-objects exhibit superior structural stability and excellent performances for drug delivery, including high drug loadings, pH-stimuli release, and high-efficient endosomal escape.

Fabrication of Reductive-Responsive Prodrug Nanoparticles with Superior Structural Stability by Polymerization-Induced Self-Assembly and Functional Nanoscopic Platform for Drug Delivery.

A highly efficient strategy, polymerization-induced self-assembly (PISA) for fabrication of the polymeric drug delivery systems in cancer chemotherapy is reported. Diblock prodrug copolymer, PEG-b-P(MEO2MA-co-CPTM) was used as the macro-RAFT agent to fabricate prodrug nanoparticles through PISA. The advantages of fabricating intelligent drug delivery system via this approach are as following: (1) Simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation in one-pot at relatively high concentration (100 mg/mL); (2) Almost complete monomer conversion allows direct application of the resultant prodrug nanoparticles without further purification; (3) Robust structures of the resultant prodrug nanoparticles, because the cross-linker was used as the comonomer, resulted in core-cross-linking simultaneously with the formation of the prodrug nanoparticles; (4) The drug content in the resultant prodrug nanoparticles can be accurately modulated just via adjusting the feed molar ratio of MEO2MA/CPTM in the synthesis of PEG-b-P(MEO2MA-co-CPTM). The prodrug nanoparticles with similar diameters but various drug contents were obtained using different prodrug macro-CTA. In consideration of the long-term biological toxicity, the prodrug nanoparticles with higher drug content exhibit more excellent anticancer efficiency due to that lower dosage of them are enough for effectively killing HeLa cells.

Protective Role of tert-Butylhydroquinone Against Sodium Fluoride-Induced Oxidative Stress and Apoptosis in PC12 Cells.

The neurotoxicity of fluoride is associated with oxidative stress due to imbalance between production and removal of reactive oxygen species (ROS). In contrast, induction of detoxifying and antioxidant genes through activation of NF-E2-related factor 2 (Nrf2) has been implicated in preventing oxidative stress and apoptosis in neurodegenerative diseases. The present study aimed to investigate the possible neuroprotective role of tert-butylhydroquinone (tBHQ), a general Nrf2 activator, on sodium fluoride (NaF)-induced oxidation damage and apoptosis in neuron-like rat pheochromocytoma (PC12) cells. Pretreatment with tBHQ protected PC12 cells against NaF-induced cytotoxicity as measured by MTT assay and apoptosis detection, simultaneously, inhibited NaF-induced overproduction of intracellular ROS and reduction of total glutathione content. Furthermore, NaF or tBHQ induced the stabilization of Nrf2, and enhanced expression of heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCS) as a consequence of Nrf2 inducing. These findings indicated that tBHQ pretreatment conferred protective effect on PC12 cells against NaF-induced apoptotic cell death and oxidation-redox imbalance through stabilization of Nrf2 and elevation of downstream HO-1 and γ-GCS expressions.

Formation of Hexagonally Packed Hollow Hoops and Morphology Transition in RAFT Ethanol Dispersion Polymerization.

Similar to the traditional self-assembly strategy, polymerization induced self-assembly and reorganization (PISR) can produce a myriad of polymeric morphologies through morphology transitions. Besides the chain length ratio (R) of the hydrophobic to the hydrophilic blocks, the chain mobility in the intermediate nano-objects, which is a requisite for morphology transition, is a determining factor in the formation of the final morphology. Although various morphologies have been fabricated, hexagonally packed hollow hoops (HHHs) with highly ordered internal structure have not, to the best of our knowledge, been prepared by PISR. In this article, the fabrication of HHHs through morphology transition from large compound vesicles to HHHs is reported. HHHs with highly regular internal structure may have significance in theoretical research and practical applications of nanomaterials.

Galactose-based amphiphilic block copolymers: synthesis, micellization, and bioapplication.

Redox-responsive amphiphilic diblock copolymers, poly(6-O-methacryloyl-D-galactopyranose-co-2-(N,N-dimethylaminoethyl) methacrylate)-b-poly(pyridyl disulfide ethyl methylacrylate) (P(MAGP-co-DMAEMA)-b-PPDSMA) were obtained by deprotection of poly((6-O-methacryloyl-1,2:3,4-di-O-isopropylidene-D-galactopyranose)-co-DMAEMA)-b-PPDSMA [P(MAlpGP-co-DMAEMA)-b-PPDSMA], which were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization of PDSMA using P(MAlpGP-co-DMAEMA) as macro-RAFT agent. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies showed that diblock copolymers P(MAGP-co-DMAEMA)-b-PPDSMA can self-assemble into micelles. Doxorubicin (DOX) could be encapsulated by P(MAGP-co-DMAEMA)-b-PPDSMA upon micellization and released upon adding glutathione (GSH) into the micelle solution. The galactose functional groups in the PMAGP block had specific interaction with HepG2 cells, and P(MAGP-co-DMAEMA)-b-PPDSMA can act as gene delivery vehicle. So, this kind of polymer has potential applications in hepatoma-targeting drug and gene delivery and biodetection.

One-pot synthesis of redox-responsive polymers-coated mesoporous silica nanoparticles and their controlled drug release.

A versatile one-pot strategy for the preparation of reversibly cross-linked polymer-coated mesoporous silica nanoparticles (MSNs) via surface reversible addition-fragmentation chain transfer (RAFT) polymerization is presented for the first time in this paper. The less reactive monomer oligo(ethylene glycol) acrylate (OEGA) and the more reactive cross-linker N,N'-cystaminebismethacrylamide (CBMA) are chosen to be copolymerized on the external surfaces of RAFT agent-functionalized MSNs to form the cross-linked polymer shells. Owing to the reversible cleavage and restoration of disulfide bonds via reduction/oxidation reactions, the polymer shells can control the on/off switching of the nanopores and regulate the drug loading and release. The redox-responsive release of doxorubicin (DOX) from this drug carrier is realized. The protein adsorption, in vitro cytotoxicity assays, and endocytosis studies demonstrate that this biocompatible vehicle is a potential candidate for delivering drugs. It is expected that this versatile grafting strategy may help fabricate satisfying MSN-based drug delivery systems for clinical application.

A unique aliphatic tertiary amine chromophore: fluorescence, polymer structure, and application in cell imaging.

Although photoluminescence of tertiary aliphatic amines has been extensively studied, the usage of this fundamental chromophore as a fluorescent probe for various applications has unfortunately not been realized because their uncommon fluorescence is easily quenched, and strong fluorescence has been observed only in vapor phase. The objective of this study is how to retain the strong fluorescence of tertiary amines in polymers. Tertiary amines as branching units of the hyperbranched poly(amine-ester) (HypET) display relatively strong fluorescence (Φ = 0.11-0.43). The linear polymers with tertiary amines in the backbone or as the side group are only very weakly fluorescent. The tertiary amine of HypET is easily oxidized under ambient conditions, and red-shifting of fluorescence for the oxidized products has been observed. The galactopyranose-modified HypET exhibits low cytotoxicity and bright cell imaging. Thus, this study opens a new route of synthesizing fluorescent materials for cell imaging, biosensing, and drug delivery.

Spiropyran-based hyperbranched star copolymer: synthesis, phototropy, FRET, and bioapplication.

Photo- and pH-responsive amphiphilic hyperbranched star copolymers, poly(6-O-methacryloyl-1,2;3,4-di-O-isopropylidene-d-galactopyranose)[poly(2-(N,N-dimethylaminoethyl) methacrylate)-co-poly(1'-(2-methacryloxyethyl)-3',3'-dimethyl-6-nitro-spiro(2H-1-benzo-pyran-2,2'-indoline))](n)s [HPMAlpGP(PDMAEMA-co-PSPMA)(n)], were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of the DMAEMA and the SPMA using hyperbranched PMAlpGP as a macro RAFT agent. In aqueous solution, the copolymers self-assembled to form core-shell micelles with HPMAlpGP core and PDMAEMA-co-PSPMA shell. The hydrophobic fluorescent dye nitrobenzoxadiazolyl derivative (NBD) was loaded into the spiropyran-containing micelles. The obtained micelles not only have the photochromic properties, but also modulate the fluorescence of NBD through fluorescence resonance energy transfer (FRET), which was also observed in living cells. Slight fluorescence intensity decrease of the spiropyran in merocyanine (ME) form was observed after five UV-visible light irradiation cycles. The cytotoxicity of the HPMAlpGP(PDMAEMA-co-PSPMA)(n) micelles was lower than that of 25k PEI. All the results revealed that these photoresponsive nanoparticles are a good candidate for cell imaging and may find broad applications in biological areas such as biological diagnosis, imaging, and detection.

Biocompatible zwitterionic sulfobetaine copolymer-coated mesoporous silica nanoparticles for temperature-responsive drug release.

A novel nanocontainer, which could regulate the release of payloads, has been successfully fabricated by attaching zwitterionic sulfobetaine copolymer onto the mesoporous silica nanoparticles (MSNs). RAFT polymerization is employed to prepare the hybrid poly(2-(dimethylamino)ethyl methacrylate)-coated MSNs (MSN-PDMAEMA). Subsequently, the tertiary amine groups in PDMAEMA are quaternized with 1,3-propanesultone to get poly(DMAEMA-co-3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate)-coated MSNs [MSN-Poly(DMAEMA-co-DMAPS)]. The zwitterionic PDMAPS component endows the nanocarrier with biocompatibility, and the PDMAEMA component makes the copolymer shell temperature-responsive. Controlled release of loaded rhodamine B has been achieved in the saline solutions.

Spiropyran-based polymeric vesicles: preparation and photochromic properties.

A direct access to photochromic polymeric vesicles was demonstrated via polymerization-induced self-assembly and reorganization (PISR). The resulting vesicles displayed interesting photochromic behaviors different from that of their free polymer chains in DMF, and the vesicles exhibited stronger fluorescence and excellent photostability due to confinement of conformational flexibility of the polymer chains in aggregates.

Minimally invasive co-injection of modular micro-muscular and micro-vascular tissues improves in situ skeletal muscle regeneration.

Various conventional treatment strategies for volumetric muscle loss (VML) are often hampered by the extreme donor site morbidity, the limited availability of quality muscle flaps, and complicated, as well as invasive surgical procedures. The conventional biomaterial-based scaffolding systems carrying myoblasts have been extensively investigated towards improving the regeneration of the injured muscle tissues, as well as their injectable forms. However, the applicability of such designed systems has been restricted due to the lack of available vascular networks. Considering these facts, here we present the development of a unique set of two minimally invasively injectable modular microtissues, consisting of mouse myoblast (C2C12)-laden poly(lactic-co-glycolic acid) porous microspheres (PLGA PMs), or the micro-muscles, and human umbilical vein endothelial cell (HUVEC)-laden poly(ethylene glycol) hollow microrods (PEG HMs), or the microvessels. Besides systematic in vitro investigations, the myogenic performance of these modular composite microtissues, when co-injected, was explored in vivo using a mouse VML model, which confirmed improved in situ muscle regeneration and remolding. Together, we believe that the construction of these injectable modular microtissues and their combination for minimally invasive therapy provides a promising method for in situ tissue healing.

Rare Occurrence of Acute Hematogenous Periprosthetic Joint Infection Due to Fusobacterium Nucleatum in the Background of a Dental Procedure: A Case Report.

OBJECTIVE: Fusobacterium nucleatum is an anaerobic gram-negative bacilli that is one of the oral and other mucosal surface microbiota. It involves a wide range of human diseases and was first found in periodontal diseases, but reports of bone-related infections caused by F. nucleatum are rare, especially periprosthetic joint infections (PJI). METHODS: Here, we present the first case of acute hematogenous PJI of the hip joint caused by F. nucleatum, and debridement, antibiotics, and implant retention (DAIR) was performed. RESULTS: The patient was successfully treated with DAIR, identification of isolates by metagenomics next-generation sequencing was confirmed by polymerase chain reaction. CONCLUSIONS: For stable acute hematogenous PJI after hip replacement, quick and accurate diagnosis, the identification of pathogenic microorganisms, and the use of DAIR combined with sufficient sensitive antibiotics have a certain clinical effect and can achieve the purpose of both preserving the prosthesis and infection control.

Silver Nanoparticles Covered with pH-Sensitive Camptothecin-Loaded Polymer Prodrugs: Switchable Fluorescence "Off" or "On" and Drug Delivery Dynamics in Living Cells.

A unique drug delivery system, in which silver nanoparticles (AgNPs) are covered with camptothecin (CPT)-based polymer prodrug, has been developed, and the polymer prodrug, in which the CPT is linked to the polymer side chains via an acid-labile ß-thiopropionate bond, is prepared by RAFT polymerization. For poly(2-(2-hydroxyethoxy)ethyl methacrylate-co-methacryloyloxy-3-thiahexanoyl-camptothecin)@AgNPs [P(HEO2MA-co-MACPT)@AgNPs], the polymer thickness on the AgNP surface is around 5.9 nm (TGA method). In vitro tests in buffer solutions at pH = 7.4 reveal that fluorescence of the CPT in the hybrid nanoparticles is quenched due to the nanoparticle surface energy transfer (NSET) effect, but under acidic conditions, the CPT fluorescence is gradually recovered with gradual release of the CPT molecules from the hybrid nanoparticles through cleavage of the acid-labile bond. The NSET "on" and "off" is induced by the CPT-AgNP distance change. This unique property makes it possible to track the CPT delivery and release process from the hybrid nanoparticles in the living cells in a real-time manner. The internalization and intracellular releasing tests of the hybrid nanoparticles in the HeLa cells demonstrate that the lysosome containing the hybrid nanoparticles displays CPT blue fluorescence due to release of the CPT under acidic conditions, and the drug-releasing kinetics shows fluorescence increase of the released CPT with incubation time. The cytotoxicity of hybrid nanoparticles is dependent on activity of the acid-labile bond. Therefore, this is a potential efficient drug delivery system in cancer therapy and a useful approach to study the mechanism of release process in the cells.

Synthesis, characterization and thermal sensitivity of chitosan-based graft copolymers.

Novel chitosan-based graft copolymers (CECTS-g-PDMA) were synthesized through homogeneous graft copolymerization of (N,N-dimethylamino)ethyl methacrylate (DMA) onto N-carboxyethylchitosan (CECTS) in aqueous solution by using ammonium persulfate (APS) as the initiator. The effect of polymerization variables, including initiator concentration, monomer concentration, reaction time and temperature, on grafting percentage was studied. XRD, FTIR, DSC and TGA were used to characterize the graft copolymers. Surface-tension measurements, turbidity measurements and temperature-variable (1)H NMR analysis were combined to investigate the thermal sensitivity of CECTS-g-PDMAs in aqueous solution.