"All about the value?" Decisional needs of breast reconstruction for breast cancer patients in the Chinese context: A mixed-methods study.

OBJECTIVE: To explore breast cancer (BC) patients' participation in breast reconstruction (BR) decision-making and specific decisional needs, especially the manifestations and causes of decisional conflicts, in China. METHODS: A mixed-methods study was conducted using triangulation of data from interviews and a questionnaire survey with health care professionals (HCPs) and BC patients with BR decision-making experience at 5 Beijing centers. The Ottawa Decision Support Framework guided (ODSF) the qualitative and quantitative data analyses. RESULTS: A total of 82.53% of Chinese BC patients would consider BR. Seven themes captured patients' BR decisional needs per the ODSF: inadequate support/resources (100%, 58.82%) and knowledge (75%, 52.94%) were most frequently cited. Health beliefs (unclear values) reflected Chinese characteristics. Patients had inadequate knowledge (M=19.99/50, SD=8.67) but positive BR attitudes (M=59.48/95, SD=10.45). CONCLUSIONS: BR decisions for Chinese BC patients are complex and often accompanied by decisional conflicts. Inadequate knowledge and inadequate support and resources contribute to these conflicts, emphasizing the need for culturally tailored information and support to promote SDM. PRACTICE IMPLICATIONS: HCPs need specialized training in SDM to guide patients in decision-making. It is essential to provide relevant resources and support that are culturally and clinically appropriate for Chinese patients.

Engineering a superwetting membrane with spider-web structured carboxymethyl cellulose gel layer for efficient oil-water separation based on biomimetic concept.

Superhydrophilic and underwater superoleophobic membranes have recently attracted significant interest as materials for effective oil-water emulsion separation. In this work, a superwetting membrane with a spider web structured gel layer was designed for efficient oil-water separation. Biomaterial, carboxymethyl cellulose (CMC), was used as the raw material, a spider web structured gel layer was constructed on the PVDF membrane surface by heat-treatment and chemical cross-linking. The hydrophilic gel layer imparted excellent superhydrophilic and underwater superoleophobic properties to the membrane, while the special spider web structure improved the membrane mechanical stability. The fabricated membrane exhibited superhydrophilicity and underwater superoleophobicity. Among different CMC concentration-modified membranes, the M-0.5 membrane containing 0.5 wt% CMC exhibited a flux of 612 L·m-2 h-1 during dichloromethane oil-water emulsion separation, which was 4.2-fold higher than that of the pristine PVDF membrane, while the membrane showed efficient oil-water separation capacity. Additionally, the water flux recovery reached as high as 93.3 %, and oil rejection attained 99.1 %. Meanwhile, the spiderweb-structured gel layer on the membrane surface displayed good mechanical stability. In summary, this novel membrane-modification method, inspired by the spider web structure, was simple, cost effective and environmentally friendly, thereby making it promising for future preparation of highly efficient oil-water emulsion separation membranes.

Assessment of the Endophytic Fungal Composition of Lactobacillus plantarum and Enterococcus faecalis-Fermented Astragalus membranaceus Using Single-Molecule, Real-Time Sequencing Technology.

Endophytic fungus represents microorganisms existing within the healthy plant organs, which can significantly influence metabolic product production in plants, a process with great research value and broad prospects for development. To investigate the effect of fermentation with probiotic cultures on the endophytic fungal diversity and composition of Astragalus membranaceus, we used single-molecular, real-time sequencing (Pacific Biosciences) for 18S ribosomal RNA (rRNA) sequencing. The results showed that the endophytic fungi of A. membranaceus mainly belonged to Aspergillus, Penicillium, Cystofilobasidium, Candida, Guehomyces, and Wallemia. Furthermore, the endophytic fungal diversity and abundance of A. membranaceus were more variable after fermentation with Enterococcus faecium and/or Lactobacillus plantarum. Our data lays a solid and comprehensive foundation for further exploration of endophytic fungi from A. membranaceus as potential sources of functional compounds.

The TARGET Nurses' health cohort study protocol: Towards a revolution in getting nurses' health ticked.

AIM: To evaluate the health status of nurses in China and explore the impact of work-related stress, work environment and lifestyle factors on their health outcomes. DESIGN: The Chinese Nurses' Health Study is a multicentred, prospective cohort study. METHODS: We plan to recruit approximately 80,000 registered nurses aged between 18 and 65 years. Eligible nurses will be introduced to complete a series of web-based questionnaires after obtaining their informed consent. Follow-up questionnaires will be completed at 2-year interval to continuously track subsequent exposures. Health-related indicators will be obtained through self-reporting by nurses and the provincial and national registry platforms such as National Central Cancer Registry. The funding was approved in July 2020 and Research Ethics Committee approval was granted in February 2021. DISCUSSION: The study is the first multicentred prospective cohort study that aims to assess the impact of work-related stress, work environment and lifestyle factors on the health of Chinese nurses. The results of the Chinese Nurses' Health Cohort Study will potentially draw a picture of the current situation of general health and well-being among nurses in China and their health risks. This will be critical in recommending locally tailored strategic preventive measures and policies to reduce health and well-being threats for nurses and potentially general public, thereby promoting the quality of healthcare in China and globally. IMPACT: This study will help to understand the health status and working environment characteristics of Chinese nurses, and provide valuable epidemiological evidence for improving working environment and promoting well-being. The results of this study are potentially of great significance for formulating targeted nursing strategies to promote the nurses' health, nursing quality and patient safety in China and even around the world. CLINICAL TRIAL REGISTRATION NUMBER AND NAME OF TRIAL REGISTER: ChiCTR.org (ID:ChiCTR2100043202), The Nurses' Health Cohort Study of Shandong.

Shared Decision-Making in Breast Reconstruction for Breast Cancer Patients: A Scoping Review.

For most breast cancer (BC) patients who have undergone a mastectomy, the decision whether to proceed with breast reconstruction (BR) is complicated and requires deliberation. Shared decision-making (SDM) helps to address those needs and promote informed value-based decisions. However, little is known about the SDM status for BR in BC patients. This scoping review describes: 1) basic characteristics of studies on BR SDM in BC patients; 2) factors influencing BR SDM in BC patients; 3) experience and perception of BR SDM in BC patients; and 4) outcome measures reported. This review was performed in accordance with the Arksey and O'Malley methodology. A total of 5 English and 4 Chinese databases were searched, as well as different sources from grey literature. The data extraction form was developed by referring to the objectives and the Ottawa Decision Support Framework (ODSF). Data was analyzed using thematic analysis, framework analysis and descriptive statistics, with findings presented in the tables and diagrams. A total of 1481 records were retrieved and 42 of these included after screening. In 21 (21/42, 50%) of the studies, patient decision aids (PDAs) were utilized, and in 17 (17/42, 40.48%) of the studies, the factors influencing the implementation of SDM were explored. Of these 17 studies, the factors influencing the implementation of SDM were categorized into the following: the patient level (17/17, 100%), the healthcare level (2/17, 11.76%) and the organizational and system level (7/17, 41.18%). A total of 8 (19.05%) of the 42 studies focused on patients' experiences and perceptions of SDM, and all studies used qualitative research methods. Of these 8 studies, a total of 7 (7/8, 87.50%) focused on patients' experiences of SDM participation, and 4 (4/8, 50.00%) focused on patients' perceptions of SDM. A total of 24 studies (24/42, 57.14%) involved quantitative outcome measures, where 49 items were divided into three classifications according to the outcomes of ODSF: the quality of the decision (17/24, 70.83%), the quality of the decision-making process (20/24, 83.33%), and impact (13/24, 54.17%). Although researchers have paid less attention to other research points in the field of SDM, compared to the design and application of SDM interventional tools, the research team still presents some equally noteworthy points through scoping review. For instance, the various factors influencing BC patients' participation in SDM for BR (especially at the healthcare provider level and at the organizational system level), patients' experiences and perceptions. Systematic reviews (SRs) should be conducted to quantify the impact of these different factors on BR SDM. Implementation of scientific theories and methods can inform the exploration and integration of these factors.

Decision coaching for people making healthcare decisions.

BACKGROUND: Decision coaching is non-directive support delivered by a healthcare provider to help patients prepare to actively participate in making a health decision. 'Healthcare providers' are considered to be all people who are engaged in actions whose primary intent is to protect and improve health (e.g. nurses, doctors, pharmacists, social workers, health support workers such as peer health workers). Little is known about the effectiveness of decision coaching. OBJECTIVES: To determine the effects of decision coaching (I) for people facing healthcare decisions for themselves or a family member (P) compared to (C) usual care or evidence-based intervention only, on outcomes (O) related to preparation for decision making, decisional needs and potential adverse effects. SEARCH METHODS: We searched the Cochrane Library (Wiley), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), CINAHL (Ebsco), Nursing and Allied Health Source (ProQuest), and Web of Science from database inception to June 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) where the intervention was provided to adults or children preparing to make a treatment or screening healthcare decision for themselves or a family member. Decision coaching was defined as: a) delivered individually by a healthcare provider who is trained or using a protocol; and b) providing non-directive support and preparing an adult or child to participate in a healthcare decision. Comparisons included usual care or an alternate intervention. There were no language restrictions. DATA COLLECTION AND ANALYSIS: Two authors independently screened citations, assessed risk of bias, and extracted data on characteristics of the intervention(s) and outcomes. Any disagreements were resolved by discussion to reach consensus. We used the standardised mean difference (SMD) with 95% confidence intervals (CI) as the measures of treatment effect and, where possible, synthesised results using a random-effects model. If more than one study measured the same outcome using different tools, we used a random-effects model to calculate the standardised mean difference (SMD) and 95% CI. We presented outcomes in summary of findings tables and applied GRADE methods to rate the certainty of the evidence. MAIN RESULTS: Out of 12,984 citations screened, we included 28 studies of decision coaching interventions alone or in combination with evidence-based information, involving 5509 adult participants (aged 18 to 85 years; 64% female, 52% white, 33% African-American/Black; 68% post-secondary education). The studies evaluated decision coaching used for a range of healthcare decisions (e.g. treatment decisions for cancer, menopause, mental illness, advancing kidney disease; screening decisions for cancer, genetic testing). Four of the 28 studies included three comparator arms.  For decision coaching compared with usual care (n = 4 studies), we are uncertain if decision coaching compared with usual care improves any outcomes (i.e. preparation for decision making, decision self-confidence, knowledge, decision regret, anxiety) as the certainty of the evidence was very low.  For decision coaching compared with evidence-based information only (n = 4 studies), there is low certainty-evidence that participants exposed to decision coaching may have little or no change in knowledge (SMD -0.23, 95% CI: -0.50 to 0.04; 3 studies, 406 participants). There is low certainty-evidence that participants exposed to decision coaching may have little or no change in anxiety, compared with evidence-based information. We are uncertain if decision coaching compared with evidence-based information improves other outcomes (i.e. decision self-confidence, feeling uninformed) as the certainty of the evidence was very low. For decision coaching plus evidence-based information compared with usual care (n = 17 studies), there is low certainty-evidence that participants may have improved knowledge (SMD 9.3, 95% CI: 6.6 to 12.1; 5 studies, 1073 participants). We are uncertain if decision coaching plus evidence-based information compared with usual care improves other outcomes (i.e. preparation for decision making, decision self-confidence, feeling uninformed, unclear values, feeling unsupported, decision regret, anxiety) as the certainty of the evidence was very low. For decision coaching plus evidence-based information compared with evidence-based information only (n = 7 studies), we are uncertain if decision coaching plus evidence-based information compared with evidence-based information only improves any outcomes (i.e. feeling uninformed, unclear values, feeling unsupported, knowledge, anxiety) as the certainty of the evidence was very low. AUTHORS' CONCLUSIONS: Decision coaching may improve participants' knowledge when used with evidence-based information. Our findings do not indicate any significant adverse effects (e.g. decision regret, anxiety) with the use of decision coaching. It is not possible to establish strong conclusions for other outcomes. It is unclear if decision coaching always needs to be paired with evidence-informed information. Further research is needed to establish the effectiveness of decision coaching for a broader range of outcomes.

Design and identification of two novel resveratrol derivatives as potential LSD1 inhibitors.

Background: Overexpression of LSD1 is associated with the occurrence of many diseases, including cancers, which makes LSD1 a significant target for anticancer drug research. Methodology & Results: With the aid of 3D quantitative structure-activity relationship models established with 34 reported resveratrol derivative LSD1 inhibitors, derivatives 35-40 were designed. Absorption, distribution, metabolism and excretion calculations showed that they may have good bioavailability and drug likeness. Additionally, 35 and 37 presented good antitumor effects in an in vitro antiproliferative assay. Molecular docking and molecular dynamics simulation results indicated that 35 and 37 can establish extensive interactions with LSD1. Conclusion: The results of computational prediction and experimental validation suggest that 35 and 37 are effective antitumor inhibitors, which provides some ideas and directions for the development of new anticancer LSD1 inhibitors.

Preparation of PU/Fibrin Vascular Scaffold with Good Biomechanical Properties and Evaluation of Its Performance in vitro and in vivo.

PURPOSE: The development of tissue-engineered blood vessels provides a new source of donors for coronary artery bypass grafting and peripheral blood vessel transplantation. Fibrin fiber has good biocompatibility and is an ideal tissue engineering vascular scaffold, but its mechanical property needs improvement. METHODS: We mixed polyurethane (PU) and fibrin to prepare the PU/fibrin vascular scaffolds by using electrospinning technology in order to enhance the mechanical properties of fibrin scaffold. We investigated the morphological, mechanical strength, hydrophilicity, degradation, blood and cell compatibility of PU/fibrin (0:100), PU/fibrin (5:95), PU/fibrin (15:85) and PU/fibrin (25:75) vascular scaffolds. Based on the results in vitro, PU/fibrin (15:85) was selected for transplantation in vivo to repair vascular defects, and the extracellular matrix formation, vascular remodeling, and immune response were evaluated. RESULTS: The results indicated that the fiber diameter of the PU/fibrin (15:85) scaffold was about 712nm. With the increase of PU content, the mechanical strength of the composite scaffolds increased, however, the degradation rate decreased gradually. The PU/fibrin scaffold showed good hydrophilicity and hemocompatibility. PU/fibrin (15:85) vascular scaffold could promote the adhesion and proliferation of mesenchymal stromal cells (MSCs). Quantitative RT-PCR experimental results showed that the expression of collagen, survivin and vimentin genes in PU/fibrin (15:85) was higher than that in PU/fibrin (25:75). The results in vivo indicated the mechanical properties and compliance of PU/fibrin grafts could meet clinical requirements and the proportion of thrombosis or occlusion was significantly lower. The graft showed strong vasomotor response, and the smooth muscle cells, endothelial cells, and ECM deposition of the neoartery were comparable to that of native artery after 3 months. At 3 months, the amount of macrophages in PU/fibrin grafts was significantly lower, and the secretion of pro-inflammatory and anti-inflammatory cytokines decreased. CONCLUSION: PU/fibrin (15:85) vascular scaffolds had great potential to be used as small-diameter tissue engineering blood vessels.

3D-QSAR, molecular docking, and molecular dynamics simulation study of thieno[3,2-b]pyrrole-5-carboxamide derivatives as LSD1 inhibitors.

Histone Lysine Specific Demethylase 1 (LSD1) is overexpressed in many cancers and becomes a new target for anticancer drugs. In recent years, small molecule inhibitors with various structures targeting LSD1 have been reported. Here we report the binding interaction modes of a series of thieno[3,2-b]pyrrole-5-carboxamide LSD1 inhibitors using molecular docking, and three-dimensional quantitative structure-activity relationships (3D-QSAR). Comparative molecular field analysis (CoMFA q 2 = 0.783, r 2 = 0.944, r pred 2 = 0.851) and comparative molecular similarity indices analysis (CoMSIA q 2 = 0.728, r 2 = 0.982, r pred 2 = 0.814) were used to establish 3D-QSAR models, which had good verification and prediction capabilities. Based on the contour maps and the information of molecular docking, 8 novel small molecules were designed in silico, among which compounds D4, D5 and D8 with high predictive activity were subjected to further molecular dynamics simulations (MD), and their possible binding modes were explored. It was found that Asn535 plays a crucial role in stabilizing the inhibitors. Furthermore, ADME and bioavailability prediction for D4, D5 and D8 were carried out. The results would provide valuable guidance for designing new reversible LSD1 inhibitors in the future.

Investigating the Binding Mode of Reversible LSD1 Inhibitors Derived from Stilbene Derivatives by 3D-QSAR, Molecular Docking, and Molecular Dynamics Simulation.

Overexpression of lysine specific demethylase 1 (LSD1) has been found in many cancers. New anticancer drugs targeting LSD1 have been designed. The research on irreversible LSD1 inhibitors has entered the clinical stage, while the research on reversible LSD1 inhibitors has progressed slowly so far. In this study, 41 stilbene derivatives were studied as reversible inhibitors by three-dimensional quantitative structure-activity relationship (3D-QSAR). Comparative molecular field analysis (CoMFA q 2 = 0.623, r 2 = 0.987, r pred 2 = 0.857) and comparative molecular similarity indices analysis (CoMSIA q 2 = 0.728, r 2 = 0.960, r pred 2 = 0.899) were used to establish the model, and the structure-activity relationship of the compounds was explained by the contour maps. The binding site was predicted by two different kinds of software, and the binding modes of the compounds were further explored. A series of key amino acids Val288, Ser289, Gly314, Thr624, Lys661 were found to play a key role in the activity of the compounds. Molecular dynamics (MD) simulations were carried out for compounds 04, 17, 21, and 35, which had different activities. The reasons for the activity differences were explained by the interaction between compounds and LSD1. The binding free energy was calculated by molecular mechanics generalized Born surface area (MM/GBSA). We hope that this research will provide valuable information for the design of new reversible LSD1 inhibitors in the future.

Dual-targeting nanoparticles with core-crosslinked and pH/redox-bioresponsive properties for enhanced intracellular drug delivery.

Multifunctional nanoparticles (NPs) with high blood-stability, tumor-targeting ability, and stimuli-bioresponsive drug release behaviors are urgently demanded. Herein, folic acid (FA) and galactose (GAL) functionalized, core-crosslinked NPs (CC NPs) with dual-targeting and pH/redox-bioresponsive properties were developed based on amphiphilic FA-poly(6-O-methacryloyl-d-galactopyranose)-b-poly[2-(diisopropylamino) ethyl methacrylate-co-pyridyl disulfide methylacrylate] [FA-PMAgGP-b-P(DPA-co-PDEMA), termed as FA-PMgDP] block copolymers, and then investigated for facilitated hepatoma-targeting delivery of doxorubicin (DOX). A series of PMgDP copolymers were synthesized though two-step RAFT copolymerization followed by acid-induced acetal deprotection reaction. Their well-defined chemical structures and compositions were characterized by 1H NMR and gel permeation chromatography. Nano-sized, non-crosslinked PMgDP NPs (PMgDP NC NPs) with sizes of less than 25 nm in aqueous solution were self-assembled via the solvent exchange method, and PMgDP CC NPs were readily prepared in the presence of dithiothreitol. The drug-loading content of PMgDP CC NPs was up to 15.8% and its entrapment efficiency was 89.0%. In normal physiological conditions, 11.6% of DOX was released from DOX-loaded PMgDP CC NPs at 25 h, whereas in analogous intracellular microenvironment, 95.5% was released at 11 h owing to the acid-induced protonation of tertiary amine and reductive cleavage of disulfide bond in the hydrophobic core. In a cellular uptake study, FA and GAL-mediated, active, dual-targeted DOX-loaded FA-PMgDP CC NPs showed a 3.54-fold increase in cellular uptake efficiency to HepG2 cells compared to that of shown by single GAL-targeted, DOX-loaded PMgDP NC NPs. Results of in vitro cytotoxicity study showed that blank FA-PMgDP CC NPs exhibited good biocompatibility, whereas dual-targeting DOX-loaded FA-PMgDP CC NPs increased cell apoptosis. Therefore, the above results indicated that the well-constructed FA-PMgDP CC NPs with multi-synergistic effect may serve as new nanocarriers in the field of precise hepatoma-targeting drug delivery.

Hyperbranched Zwitterionic Polymer-Functionalized Underwater Superoleophobic Microfiltration Membranes for Oil-in-Water Emulsion Separation.

Inspired by mussel adhesion chemistry, a kind of hydrophilic poly(vinylidene fluoride) (PVDF) microfiltration membrane with underwater superoleophobicity was prepared using thiolated hyperbranched zwitterionic poly(sulfobetaine methacrylate) (HPS) as a nanoscale surface modifier. The HPS was first synthesized via reversible addition fragmentation chain transfer (RAFT) copolymerization and followed by sulfonation reaction and then coated onto polydopamine (PD) adhesive PVDF membranes via thiol-mediated Michael addition reaction. The successful and uniform coating of HPS onto the membrane surface was demonstrated by X-ray photoelectron spectroscopy and by using an energy dispersive X-ray detector. The surface micro-nano morphology and increased roughness of the PD/HPS-modified (M-PD/HPS) membrane were also investigated by using a field emission scanning electron microscope and an atomic force microscope. The M-PD/HPS membrane could be wetted completely by water, and the underwater oil contact angles were about 160°, indicating the M-PD/HPS membrane has excellent hydrophilicity and underwater superoleophobicity. Compared with the pure PVDF membrane, the M-PD/HPS membrane for hexane-in-water emulsion separation exhibited an enhanced water filtration flux of 10 707 L m-2 h-1 (0.1 MPa), and the oil rejection ratio was above 99.9%. Besides, the excellent antifouling ability and recyclable properties of the M-PD/HPS membranes would make them suitable for long-time use. Thus, the approach of mussel adhesion chemistry employing the RAFT-mediated nanosized hyperbranched zwitterionic polymers as postmodification reagents showed a good application prospect in purification of oily waste water and oil recovery.

Temperature-responsive in situ nanoparticle hydrogels based on hydrophilic pendant cyclic ether modified PEG-PCL-PEG.

Thermo-sensitive injectable hydrogels based on poly(ε-caprolactone)/poly(ethylene glycol) (PCL/PEG) block copolymers have attracted considerable attention for sustained drug release and tissue engineering applications. Previously, we have reported a thermo-sensitive hydrogel of P(CL-co-TOSUO)-PEG-P(CL-co-TOSUO) (PECT) triblock copolymers modified by hydrophilic cyclic ether pendant groups 1,4,8-trioxa-[4.6]spiro-9-undecanone (TOSUO). Unfortunately, the low gel modulus of PECT (only 50-70 Pa) may limit its applications. Herein, another kind of thermogelling triblock copolymer of a pendant cyclic ether-modified caprolactonic poloxamer analog, PEG-P(CL-co-TOSUO)-PEG (PECTE), was successfully prepared by control of the hydrophilicity/hydrophobicity balance and chemical compositions of the copolymers. PECTE powder could directly disperse in water to form a stable nanoparticle (NP) aqueous dispersion and underwent sol-gel-sol transition behavior at a higher concentration with the temperature increasing from ambient or lower temperatures. Significantly, the microstructure parameters (e.g., different chemical compositions of the hydrophobic block and topology) played a critical role in the phase transition behavior. Furthermore, comparison studies on PECTE and PEG-PCL-PEG (PECE) showed that the introduction of pendant cyclic ether groups into PCL blocks could avoid unexpected ahead-of-time gelling of the PECE aqueous solution. In addition, the rheological analysis of PECTE and PECT indicated that the storage modulus of the PECTE hydrogel could be 100 times greater than that of the PECT hydrogel under the same mole ratios of TOSUO/CL and lower molecular weight. Consequently, PECTE thermal hydrogel systems are believed to be promising as in situ gel-forming biomaterials for drug delivery and tissue engineering.

Graft copolymer nanoparticles with pH and reduction dual-induced disassemblable property for enhanced intracellular curcumin release.

Nanoparticle (NP)-assisted drug delivery systems with disassemblable behaviors in response to intracellular microenvironment are urgently demanded in systemic cancer chemotherapy for enhanced intracellular drug release. Curcumin (CUR), an effective and safe anticancer agent, was limited by its water insolubility and poor bioavailability. Herein, pH and reduction dual-induced disassemblable NPs for high loading efficiency and improved intracellular release of CUR were developed based on an acid degradable cyclic benzylidene acetal groups (CBAs)-functionalized poly(2,4,6-trimethoxybenzylidene-1,1,1-tris(hydroxymethyl)ethane methacrylate)-g-SS-poly(ethylene glycol) (PTTMA-g-SS-PEG) graft copolymer, which was readily prepared via RAFT copolymerization and coupling reaction. The NPs self-assembled from PTTMA-g-SS-PEG copolymers were stable at physiological pH, and quickly disassembled in mildly acidic and reductive environments because of the hydrolysis of CBAs in hydrophobic PTTMA core and the cleavage of disulfide-linked detachable PEG shell. PTTMA-g-SS-PEG NPs exhibited excellent CUR loading capacity with drug loading content up to 19.2% and entrapment efficiency of 96.0%. Within 20 h in vitro, less than 15.0% of CUR was released from the CUR-loaded NPs in normal physiological conditions, whereas 94.3% was released in the presence of reductive agent and mildly acidic conditions analogous to the microenvironment in endosome/lysosome and cytoplasm. Confocal fluorescence microscopies revealed that the CUR-loaded PTTMA-g-SS-PEG NPs exhibited more efficiently intracellular CUR release for EC-109 cells than that of CUR-loaded reduction-unresponsive PTTMA-g-PEG NPs and free CUR. In vitro cytotoxicity studies displayed blank PTTMA-g-SS-PEG NPs showed low toxicity at concentrations up to 1.0 mg/mL, whereas CUR-loaded PTTMA-g-SS-PEG NPs demonstrated more efficient growth inhibition toward EC-109 and HepG-2 cells than reduction-unresponsive controls and free CUR. Therefore, the above results indicated that pH and reduction dual-induced disassemblable PTTMA-g-SS-PEG NPs may have emerged as superior nanocarriers for active loading and promoted intracellular drug delivery in systemic cancer chemotherapy.

Comb-like amphiphilic copolymers bearing acetal-functionalized backbones with the ability of acid-triggered hydrophobic-to-hydrophilic transition as effective nanocarriers for intracellular release of curcumin.

The pH-responsive micelles have enormous potential as nanosized drug carriers for cancer therapy due to their physicochemical changes in response to the tumor intracellular acidic microenvironment. Herein, a series of comb-like amphiphilic copolymers bearing acetal-functionalized backbone were developed based on poly[(2,4,6-trimethoxybenzylidene-1,1,1-tris(hydroxymethyl) ethane methacrylate-co-poly(ethylene glycol) methyl ether methacrylate] [P(TTMA-co-mPEGMA)] as effective nanocarriers for intracellular curcumin (CUR) release. P(TTMA-co-mPEGMA) copolymers with different hydrophobic-hydrophilic ratios were prepared by one-step reversible addition fragmentation chain transfer (RAFT) copolymerization of TTMA and mPEGMA. Their molecular structures and chemical compositions were confirmed by (1)H NMR, Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). P(TTMA-co-mPEGMA) copolymers could self-assemble into nanosized micelles in aqueous solution and displayed low critical micelle concentration (CMC). All P(TTMA-co-mPEGMA) micelles displayed excellent drug loading capacity, due to the strong π-π conjugate action and hydrophobic interaction between the PTTMA and CUR. Moreover, the hydrophobic PTTMA chain could be selectively hydrolyzed into a hydrophilic backbone in the mildly acidic environment, leading to significant swelling and final disassembly of the micelles. These morphological changes of P(TTMA-co-mPEGMA) micelles with time at pH 5.0 were determined by DLS and TEM. The in vitro CUR release from the micelles exhibited a pH-dependent behavior. The release rate of CUR was significantly accelerated at mildly acidic pH of 4.0 and 5.0 compared to that at pH 7.4. Toxicity test revealed that the P(TTMA-co-mPEGMA) copolymers exhibited low cytotoxicity, whereas the CUR-loaded micelles maintained high cytotoxicity for HepG-2 and EC-109 cells. The results indicated that the novel P(TTMA-co-mPEGMA) micelles with low CMC, small and tunable sizes, high drug loading, pH-responsive drug release behavior, and good biocompatibility may have potential as hydrophobic drug delivery nanocarriers for cancer therapy with intelligent delivery.

Expression of connexin 43 and E-cadherin protein and mRNA in non-small cell lung cancers in Chinese patients.

AIM: Connexin 43 (Cx43) and E-cadherin are important biomarkers related with cancer. Their expression at protein and mRNA levels was here investigated in 50 primary lung carcinoma tissues and 20 samples of adjacent normal tissue of Chinese patients with non-small cell lung cancer (NSCLC). METHODS: Protein and mRNA expression were evaluated by ABC immunohistochemistry and RT-PCR. RESULTS: (1) The positive expression rates of Cx43 and E-cadherin protein were higher in the adjacent normal tissues than those in the primary lung carcinoma tissues; (2) the positive expression rates of Cx43 and E-cadherin protein decreased with NSCLC progression; (3) the expression of E-cadherin protein was not related with the pathological type of NSCLC; and (4) the relative quantity of the Cx43 or E-cadherin mRNA expression was correlated with the the histological type, clinical stage, cancer cell differentiation and the lymph node metastasis. CONCLUSION: The data suggested that the Cx43 and E-cadherin are reduced with NSCLC progression, and might be important biomarkers for judging the metastasis and prognosis.

Sequential thermo-induced self-gelation and acid-triggered self-release process of drug-conjugated nanoparticles: a strategy for the sustained and controlled drug delivery to tumors.

A novel strategy was purposed to sustainedly deliver drug-loaded nanoparticles (NPs) to tumor sites and further enhance intracellular drug release. NPs with the ability of sequential self-gelation and self-release in response to a tumor-specific microenvironment were developed, which involved the conjugation of doxorubicin (DOX) on a thermosensitive amphiphilic copolymer (poly(ε-caprolactone)-b-poly(ethylene glycol)-b-poly(ε-caprolactone), PCEC) via acid-cleavable hydrazone linkages. The conjugate (PCEC-co-DOX) can self-assemble into micelle-like NPs in water. Moreover, the freeze-dried PCEC-co-DOX NP powder with good dispersibility in water can easily be constructed into an injectable NP aqueous dispersion at ambient temperature, making it convenient for storage and clinical applications. After injection, the dispersion can in situ thermosensitively self-gelate, anchoring large amounts of NPs at the tumor site. Subsequently, the formed NP self-supported gel can sustainedly release NPs themselves in an acidic tumor microenvironment. The released DOX-co-PCEC NPs were taken up by tumor cells and finally realized in intracellular drug release by the acid-triggered cleavage of the hydrazone bond. Compared with the repeated injection of free DOX, a single peritumoral injection of DOX-co-PCEC NP aqueous dispersion achieved a similar tumor inhibition effect but exhibited lower systemic toxicity. In vivo biodistribution studies indicated that DOX delivered by the DOX-co-PCEC NP hydrogel accumulated mainly in tumor tissue rather than in healthy tissue in mice treated with a single peritumoral injection. These results suggest that the design presented here provides a promising nanomedicine platform for cancer therapy.

[Modified minimally invasive percutaneous pedicle screws osteosynthesis for the treatment of thoracolumbar fracture without neural impairment].

OBJECTIVE: To explore the feasibility and efficacy of modified minimally invasive percutaneous pedicle screws osteosynthesis for the treatment of thoracolumbar vertebral compression fracture. METHODS: Twenty cases of thoracolumbar fracture without neural impairment were enrolled. None needed laminotomy decompression. With the aid of C-arm image intensifier, the GSS II pedicle screws were inserted through four small longitudinal incisions and modified surgical instruments. Perioperative parameters and postoperative imaging indices were compared with those undergoing conventional open pedicle screws osteosynthesis in other 20 cases. RESULTS: There was no significant difference in operative time between minimal invasive group and conventional group (P > 0.05); but the length of incisions, length of hospital stay, the volume of operative hemorrhage and post-operative drainage in minimal invasive group were significantly shorter than those in conventional group (P < 0.05); in each group, the comparisons of Cobb's angle, anterior vertebral height and disc height between pre and post-operation were all significantly different (P > 0.05); The incidence rate of chronic lower back pain in minimal invasive group was obviously lower than conventional group during the follow-up visit. CONCLUSION: The percutaneous internal pedicle screw fixation using modified instruments has the advantages of simple manipulation, less trauma and hemorrhage, quicker recovery, less pain, shorter hospital stay and a lower incidence rate of chronic lower back pain.