Dual drug-loaded metal-phenolic networks for targeted magnetic resonance imaging and synergistic chemo-chemodynamic therapy of breast cancer.

The development of nanomedicines with simplified compositions and synergistic theranostic functionalities remains a great challenge. Herein, we develop a simple method to integrate both atovaquone (ATO, a mitochondrial inhibitor) and cisplatin within tannic acid (TA)-iron (Fe) networks coated with hyaluronic acid (HA) for targeted magnetic resonance (MR) imaging-guided chemo-chemodynamic synergistic therapy. The formed TFP@ATO-HA displayed good colloidal stability with a mean size of 95.5 nm, which could accumulate at tumor sites after circulation and be specifically taken up by metastatic 4T1 cells overexpressing CD44 receptors. In the tumor microenvironment, TFP@ATO-HA could release ATO/cisplatin and Fe3+ in a pH-responsive manner, deplete glutathione, and generate reactive oxygen species with endogenous H2O2 for chemodynamic therapy (CDT). Additionally, ATO could enhance chemotherapeutic efficacy by inhibiting mitochondrial respiration, relieving hypoxia, and amplifying the CDT effect by decreasing intracellular pH and elevating Fenton reaction efficiency. In vivo experiments demonstrated that TFP@ATO-HA could effectively inhibit tumor growth and suppress lung metastases without obvious systemic toxicity. Furthermore, TFP@ATO-HA exhibited a r1 relaxivity of 2.6 mM-1 s-1 and targeted MR imaging of 4T1 tumors. Dual drug-loaded metal-phenolic networks can be easily prepared and act as effective theranostic nanoplatforms for targeted MR imaging and synergistic chemo-chemodynamic therapy.

Dendrimer/metal-phenolic nanocomplexes encapsulating CuO2 for targeted magnetic resonance imaging and enhanced ferroptosis/cuproptosis/chemodynamic therapy by regulating the tumor microenvironment.

The combination of ferroptosis, cuproptosis, and chemodynamic therapy (CDT) would be a potential strategy for tumor diagnosis and enhanced treatment. However, the therapeutic effect was severely limited by the lack of specific delivery of catalytic ions and the low Fenton reaction efficiency in tumor microenvironment (TME) with excess glutathione, limited acidity and insufficient endogenous hydrogen peroxide. In this work, p-carboxybenzenesulfonamide (BS), a carbonic anhydrase IX (CA IX) inhibitor, was modified on the surface of generation-5 poly(amidoamine) dendrimer to load copper peroxide nanoparticles, which were complexed with iron (Fe)-tannic acid (TF) networks for targeted magnetic resonance (MR) imaging and enhanced ferroptosis/cuproptosis/CDT by regulating TME. The formed CuO2@G5-BS/TF nanocomplexes with an average size of 39.4 nm could be specifically accumulated at tumor site and effectively internalized by metastatic 4T1 cells via the specific interaction between BS and CA IX over-expressed on tumor cells. Meanwhile, the inhibition of CA IX activity could not only decrease the intracellular pH to accelerate Fe3+/Cu2+ release, H2O2 self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity in TME. Moreover, the reduction of Fe3+/Cu2+ by intracellular glutathione (GSH) could further amplify ROS generation and enhance CDT efficacy, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy. In vivo experimental results demonstrated that CuO2@G5-BS/TF could provide better tumor MR imaging, effectively inhibit the growth and metastasis of 4T1 breast tumors, and be metabolized without significant systemic toxicity. Thus, CuO2@G5-BS/TF nanocomplexes provided a new approach for targeted MR imaging and enhanced ferroptosis/cuproptosis/CDT of triple-negative breast cancer. STATEMENT OF SIGNIFICANCE: Taking the advantage of dendrimer and metal-phenolic system, stable CuO2@G5-BS/TF nanocomplexes with an average size of 39.4 nm were synthesized to efficiently load Fe3+ and CuO2 nanoparticles for TNBC treatment and MR imaging. CuO2@G5-BS/TF nanocomplexes could target tumor cells overexpressing CAIX via the specific binding with BS, and the inhibition of CAIX activity could not only decrease the intracellular pH to accelerate Fe3+/Cu2+ release, H2O2 self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity. The reduction of Fe3+/Cu2+ by intracellular GSH could further amplify ·OH generation, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy by enhanced ferroptosis/cuproptosis/CDT via tumor microenvironment regulation.

Effects of the online and offline hybrid continuous group care on maternal and infant health: a randomized controlled trial.

BACKGROUND: The group care is a well-established maternal care model that has been widely used in many developed countries, but in China, it is confined to prenatal care services. In addition, affected by traditional birth culture, Chinese women tend to focus more on their fetuses and newborns but lack attention to their own intrapartum and postpartum care. The aim of this study was to construct and implement a prenatal, intrapartum, and the postpartum continuous group care model that combines online and offline service in Hainan Province, China, and to evaluate the effect on maternal women and newborns. METHODS: This study was a randomized controlled trial involving 144 pregnant women in a first-class tertiary general hospital in Hainan Province, China. Women were divided into an intervention group and a control group using the random number table, with 72 women in each group. The control group received routine maternal care services, and the intervention group received the continuous group care based on the routine maternal care services. Count data such as rate of cesarean section and incidence rate of fetal macrosomia were analyzed with the chi-square test or Fisher's exact test, and the General Self-efficacy Scale scores were analyzed by repeated measures ANOVA. P < 0.05 was considered statistically significant, with two-sided probability values. RESULTS: Compared with the control group, the rate of excessive prenatal weight gain, cesarean section, and 42-day postpartum depression were significantly lower in the intervention group (P < 0.05), and higher General Self-efficacy Scale scores (in the expectant period and 42 days postpartum) and exclusive breastfeeding rate (42 days postpartum) (P < 0.05). The incidence of fetal macrosomia was significantly lower in the intervention group (P < 0.05). But there was no significant difference in birth weight, preterm birth, the incidence of low-birth-weight infants and 1-min Apgar score (P > 0.05). CONCLUSION: The continuous group care with online and offline service can effectively control the gestational weight gain, reduce the rate of cesarean section, macrosomia, and postpartum depression. It can improve the self-efficacy of women and the rate of exclusive breastfeeding effectively. TRIAL REGISTRATION: Chinese Clinical Trial Regestry (ChiCTR2200065765, 04/11/2022, Retrospectively registered).

Barriers and Facilitators to Exercise Compliance for Community Elders with COPD: A Cross-Sectional Study.

Background and Aim: Exercise compliance was known as important to improve long-term health conditions for Chronic obstructive pulmonary disease (COPD) patients, however, little was known about the determinants which affect their exercise compliance. This study aimed to investigate factors related to exercise compliance of COPD elderly patients. Methods: This cross-sectional study included elderly patients with stable COPD participants. Random cluster sampling and a survey, including the Exercise Compliance Scale, mMRC Dyspnea Index Scale, Social Support Scale, Anxiety Self-Assessment Scale, and Self-rating Depression Scale, were used. Data were analyzed using Spearman correlation and backward logistic regression. Results: 124 participants (45.90%) had poor exercise compliance while 146 had good compliance (54.10%). The backward logistic regression showed household monthly income (¥501-¥1500: OR=21.54, P<0.05; ¥3001-¥5000: OR=32.76, P<0.05), two chronic comorbidities (OR=17.13, P<0.05), and the moderate dyspnea (OR=16.87, P<0.05) might help to improve exercise compliance. While female COPD patients (OR=0.11, P<0.01) who had server dyspnea (OR=0.02, P<0.05) and depression (OR=0.84, P<0.05) might have more difficulties adhering to exercise. Conclusion: Low exercise compliance in community-dwelling elderly COPD patients could be affected by sex, monthly income level, number of chronic comorbidities, dyspnea, and depression.

Effectiveness of probiotic/prebiotic/synbiotic treatments on anxiety: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Anxiety can adversely affect human well-being. This meta-analysis aimed to evaluate the effects of interventions that alter the gut microbes (including probiotics, prebiotics, and synbiotics) on anxiety. METHODS: A systematic meta-analysis of the effects of probiotics, prebiotics, and synbiotics on anxiety was conducted by searching randomized controlled trials (RCTs) in 13 databases. The primary outcomes were the pre- and post-intervention anxiety scores in the intervention and placebo groups. Anxiety scores were extracted as standard mean differences (SMDs) and pooled based on a random effects model. Subgroup analyses of anxiety scales, health status, gastrointestinal symptoms, flora strains, treatment type, probiotic dose, region, and treatment duration were also performed. RESULTS: 29 RCTs (2035 participants) were included, revealing that both probiotics and synbiotics significantly reduced anxiety scores. Additionally, anxiety scores did not significantly reduce when comparing prebiotics and placebos. LIMITATIONS: Owing to the small combined effect size of probiotic/prebiotic/synbiotic treatments and the relatively few studies on prebiotics and synbiotics included in the analysis, the findings of probiotic/prebiotic/synbiotic treatments are preliminary. CONCLUSIONS: Our study indicated that probiotics and synbiotics can reduce anxiety scores; however, it might be premature to conclude their clinical efficacy in alleviating anxiety due to the small effect size. There is no consensus regarding the optimal dose, treatment duration, treatment type, or probiotic strain to improve anxiety. Moreover, the mechanisms by which probiotics and synbiotics improve anxiety remain unclear. More RCTs are needed to determine the mechanisms of action and to identify appropriate markers to clarify their effects.

Polydopamine-cloaked Fe-based metal organic frameworks enable synergistic multidimensional treatment of osteosarcoma.

One of the major challenges in effective cancer therapy arises because of the hypoxic microenvironment in the tumor. This compromises the efficacy of both chemo- and radiotherapy, and thus hinders patient outcomes. To solve this problem, we constructed polydopamine (PDA)-cloaked Fe-based metal organic frameworks (MOFs) loaded with d-arginine (d-Arg), glucose oxidase (GOX), and the chemotherapeutic drug tirapazamine (TPZ). These offer simultaneous multifaceted therapy combining chemodynamic therapy (CDT)/radiotherapy (RT)/starvation therapy (ST)/gas therapy (GT) and chemotherapy. The particles further can act as contrast agents in magnetic resonance imaging. GOX catalyses the conversion of endogenous glucose and O2 to hydrogen peroxide and gluconic acid, blocking the cells' energy supply and providing ST. With the resultant acidification of the local environment, the breakdown of the MOF releases TPZ (for chemotherapy) and Fe3+, which reacts with H2O2 to produce reactive oxygen species and thus stimulates the conversion of d-Arg to NO for GT and RT sensitization. The PDA coating not only seals the pores and chelates Fe3+ to enhance the T1-weighted magnetic resonance imaging (MRI) properties, but also is used to graft folate bovine serum albumin (FA-BSA) and thereby target the tumor site. The combined administration of low doses of X-ray irradiation and nanoparticles reduces the side effects on healthy tissue and can prevent lung metastases in mice. This work highlights the synergistic treatment of osteosarcoma via ST/GT/CDT/RT/MRI/ chemotherapy using a PDA-cloaked MOF system.

Ultrasound-enhanced theranostics of orthotopic breast cancer through a multifunctional core-shell tecto dendrimer-based nanomedicine platform.

Design of multifunctional nanoplatforms combined with ultrasound-targeted microbubble destruction (UTMD) technology for enhanced tumor accumulation is feasible to solve the bottleneck of theranostics. Herein, we present the development of zwitterion-modified gadolinium (Gd)-chelated core-shell tecto dendrimers (CSTDs) as a nanomedicine platform (PCSTD-Gd) for enhanced magnetic resonance (MR) imaging-guided chemo-gene therapy of orthotopic breast cancer with the assistance of UTMD. In our design, CSTDs synthesized via supramolecular recognition of ß-cyclodextrin and adamantane were covalently linked with tetraazacyclododecane tetraacetic acid-Gd(III) chelators, modified with 1,3-propane sultone to achieve good protein-resistance property, and used for co-delivery of an microRNA 21 inhibitor (miR 21i) and an anticancer drug doxorubicin (DOX). The overall design is quite advantageous and cooperative. The CSTDs with a greater size than single-generation core dendrimers have amplified the enhanced permeability and retention effect for better passive tumor targeting, with a larger r1 relaxivity for sensitive MR imaging and serum-enhanced gene delivery efficiency due to the better compaction ability as well as the protein resistance ability, and with larger interior space for improved drug loading. Through the unique design and the assistance of UTMD, the obtained PCSTD-Gd/DOX/miR 21i polyplexes enable enhanced MR imaging-guided combined chemo-gene therapy of an orthotopic breast cancer model in vivo.

Microfluidic synthesis of fibronectin-coated polydopamine nanocomplexes for self-supplementing tumor microenvironment regulation and MR imaging-guided chemo-chemodynamic-immune therapy.

Development of nanomedicines to overcome the hindrances of tumor microenvironment (TME) for tumor theranostics with alleviated side effects remains challenging. We report here a microfluidic synthesis of artesunate (ART)-loaded polydopamine (PDA)/iron (Fe) nanocomplexes (NCs) coated with fibronectin (FN). The created multifunctional Fe-PDA@ART/FN NCs (FDRF NCs) with a mean size of 161.0 â€‹nm exhibit desired colloidal stability, monodispersity, r1 relaxivity (4.96 â€‹mM-1s-1), and biocompatibility. The co-delivery of the Fe2+ and ART enables enhanced chemodynamic therapy (CDT) through improved intracellular reactive oxygen species generation via a cycling reaction between Fe3+ and Fe2+ caused by the Fe3+-mediated glutathione oxidation and Fe2+-mediated ART reduction/Fenton reaction for self-supplementing TME regulation. Likewise, the combination of ART-mediated chemotherapy and the Fe2+/ART-regulated enhanced CDT enables noticeable immunogenic cell death, which can be collaborated with antibody-mediated immune checkpoint blockade to exert immunotherapy having significant antitumor immunity. The combined therapy improves the efficacy of primary tumor therapy and tumor metastasis inhibition by virtue of FN-mediated specific targeting of FDRF NCs to tumors with highly expressed αvß3 integrin and can be guided through the Fe(III)-rendered magnetic resonance (MR) imaging. The developed FDRF NCs may be regarded as an advanced nanomedicine formulation for chemo-chemodynamic-immune therapy of different tumor types under MR imaging guidance.

The application of a continuous partnership-based birth plan in China: A randomized controlled trial.

BACKGROUND: The cesarean section rate is as high as 36.7% in China, much higher than the average cesarean section rate of 27% in Asia. With the implementation of the two-children and three-children policy, the primipara with cesarean will also face the choice of repeated or even multiple cesareans, which will increase the risk of maternal perinatal mortality and serious fetal pulmonary morbidity. To reduce the cesarean section rate, a series of midwifery service measures such as the birth plan have been taken in China and it has played a certain role in improving the birth outcome and maternal birth experience. However, the areas carrying out birth plan are often economically developed with advanced medical conditions. the application effect of birth plan in economically underdeveloped areas with limited medical conditions in China is unknown. OBJECTIVE: To evaluate the effects of a continuous partnership-based birth plan on local women's birth outcomes and experience in Haikou which is an economically underdeveloped city in China. DESIGN: A randomized controlled trial study design was used. PARTICIPANTS: 90 primiparous women who received pregnancy service from the obstetrics clinic of one of tertiary hospitals in Haikou city, Hainan Province between July 2020 and December 2020 and planned to give birth in this hospital were recruited. METHODS: After eligibility was determined, consents obtained and baseline surveys completed, 90 participants were randomly allocated to study groups with concealed opaque envelopes by a blinded research assistant and each group were 45 participants. Participants in control group received routine obstetric health service and nursing care, while participants in the experimental group received the continuous partnership service of midwives on the basis of routine care. At the same time, the birth plan was formulated and implemented, and the relevant indicators were recorded and analyzed during and after birth, including cesarean section rate, non-medical indication cesarean section rate, oxytocin use rate, perineal lateral resection rate and anxiety degree. RESULTS: The cesarean rate in the experiment and control groups were 20.45% and 57.14%, of which the non-medical indication cesarean rate in the experiment and control groups were 22.22% and 50.00%, respectively, whereby the difference of cesarean rate and nonmedically indicated cesarean section rate between the groups was statistically significant (χ2 = 12.231, p < 0.001;χ2 = 9.101, p = 0.003). Besides, the differences in anxiety degree, neonatal NICU transfer rate and satisfaction of birth between the two groups were statistically significant (p < 0.05). While there was no significant difference in oxytocin use rate, perineal lateral resection rate, neonatal 1-min and 5-min Alzheimer's score between the two groups (P > 0.05). CONCLUSION: The birth plan based on continuous partnership can reduce medical intervention, improve birth outcomes, reduce anxiety and optimize maternal birth experience of women, which is worthy of promotion in economically underdeveloped areas of China.

Dual-Responsive Core-Shell Tecto Dendrimers Enable Efficient Gene Editing of Cancer Cells to Boost Immune Checkpoint Blockade Therapy.

Immune checkpoint blockade (ICB) therapy has become a promising strategy in treating multiple tumor types, but the therapeutic efficacy is still unsatisfactory due to the temporary and inefficient blocking and the poor immune responsiveness. Herein, we report the development of dual reactive oxygen species (ROS)- and pH-responsive core-shell tecto dendrimers loaded with gold nanoparticles (for short, Au CSTDs) to deliver a plasmid-clustered regularly interspersed short palindromic repeats (CRISPR)/Cas9 system for the permanent disruption of the programmed death ligand 1 (PD-L1) gene in cancer cells to boost cancer immunotherapy. In our work, Au CSTDs were constructed using lactobionic acid (LA)-modified generation 5 poly(amidoamine) dendrimers entrapped with gold nanoparticles as cores and phenylboronic acid (PBA)-conjugated generation 3 dendrimers as shells via the formation of responsive phenylborate ester bonds between PBA and LA. The plasmid-CRISPR/Cas9 system can be efficiently compacted and specifically taken up by cancer cells overexpressing sialic acids due to the PBA-mediated targeting and be responsively released in cancer cells by the responsive dissociation of the Au CSTDs, leading to the successful endosomal escape and the efficient knockout of the PD-L1 gene. Further in vivo delivery in a mouse melanoma model reveals that the developed Au CSTDs/plasmid-CRISPR/Cas9 complexes can be specifically accumulated at the tumor site for enhanced computed tomography (CT) imaging of tumors, owing to the X-ray attenuation effect of Au, and disrupt the PD-L1 expression in tumor cells, thus promoting the ICB-based antitumor immunity. The designed dual-responsive Au CSTDs may be developed as a versatile tool for genetic engineering of other cell types to achieve different therapeutic effects for expanded space of biomedical applications.

The use of Kumpfer's resilience framework in understanding the breastfeeding experience of employed mothers after returning to work: a qualitative study in China.

BACKGROUND: The increasing numbers of women in the workforce is an inevitable trend in China. More and more employed women stop breastfeeding because of working stressors. Many mothers, however, overcome the challenges and insist on breastfeeding after returning to work. Their individual experience of breastfeeding may provide a new insight to promote and support breastfeeding on employed mothers. This study sought to understand mothers' experience with insisting on breastfeeding after returning to work based on Kumpfer's Resilience Framework in Chinese context. METHODS: This qualitative study was designed with semi-structured interviews. Purposive sampling and snowball sampling were employed to recruit 13 full-time working mothers with a stable job in the public sector who continued to breastfeed for 1 month or longer after returning to work in Haikou, Hainan Province, China. Interviews were conducted from January to March 2020 to capture participants' experiences of breastfeed after returning to work. Grounded theory and Kumpfer's Resilience Framework were used to analyze data via a systematic and iterative process. RESULTS: Employed mothers built resilience while continuing to breastfeed after returning to work. The core concept was "dynamic interaction". Other categories were the background and explanation of this phenomenon. For working mothers who continued to breastfeed, resilience involved "dynamic interaction", which started from "experiencing stressors" and "obtaining support", two environmental factors interacted with the individual to "build resilience qualities", which interact with environment led to "behavioral resilience". And then the ongoing dynamic interaction between behavioral resilience and environment ultimately led to three different "weaning processes", including natural weaning, active weaning, and forced weaning. CONCLUSIONS: This study identified the framework of resilience in mothers who were in the adversity of breastfeeding after returning to work based on Kumpfer's Resilience Framework. It provided a new insight into the resilience of employed mothers around the world to continue breastfeeding and showed the different culture of breastfeeding on employed mothers.

Core-Shell Tecto Dendrimers Enable Enhanced Tumor MR Imaging through an Amplified EPR Effect.

Development of nanoplatforms that can amplify the passive tumor targeting effect based on enhanced permeability and retention (EPR) effect is crucial for precision cancer nanomedicine applications. Herein, we present the development of core-shell tecto dendrimers (CSTDs) as a platform for enhanced tumor magnetic resonance (MR) imaging through an amplified EPR effect. In this work, poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5) were decorated with ß-cyclodextrin (CD) and then assembled with G3 PAMAM dendrimers premodified with adamantane (Ad) via supramolecular recognition of CD and Ad. The formed G5-CD/Ad-G3 CSTDs were conjugated with tetraazacyclododecane tetraacetic acid (DOTA)-Gd(III) chelators and further acetylated to neutralize the remaining CSTD periphery amines. We reveal that the formed CSTD.NHAc-DOTA(Gd) (CSTD-D-Gd) complexes have a narrow size distribution and satisfactory colloidal stability, and are cytocompatible within the concentration range studied. Compared to the single dendrimer counterpart of G5.NHAc-DOTA(Gd) (G5-D-Gd) complexes, the CSTD-D-Gd complexes with a higher molecular weight and volume possess a longer rotation correlation time, hence having a longitudinal relaxivity (r1) of 7.34 mM-1 s-1, which is 1.5 times larger than that of G5-D-Gd complexes (4.92 mM-1 s-1). More importantly, the CSTD-D-Gd complexes display better permeability in the three-dimensional (3D) cell spheroids in vitro through fluorescence imaging and a more significant EPR effect for improved tumor MR imaging in vivo than the G5-DOTA-Gd complexes. The generated CSTD-D-Gd complexes may be adopted for enhanced tumor MR imaging through an amplified passive EPR effect and also be further extended for different cancer theranostic applications.

A cascaded enzyme-loaded Fe-hemoporfin framework for synergistic sonodynamic-starvation therapy of tumors.

Enzyme-loaded nanosystems with multimodal therapeutic functions have received increasing attention in the treatment of malignant tumors. Herein, we designed and prepared cascaded dual-enzyme-augmented Fe-hemoporfin framework nanosonosensitizers for synergistic sonodynamic-starvation therapy of tumors. Amorphous Fe-hemoporfin frameworks (FeHF) with an average size of ∼85 nm were synthesized by assembling the clinical drug hemoporfin with Fe3+ ions. Then, FeHF was used to load dual enzymes (glucose oxidase (GOx) and catalase (CAT)) and modified by PEGylated folic acid-conjugated lipids. The dual-enzyme loaded FeHF (FeHF-GOx/CAT) exhibited higher efficiency not only for glucose depletion but also for ultrasound (US)-triggered 1O2 generation than that of pure FeHF, resulting from the cascaded catalytic reaction from the dual-enzyme system. As observed by magnetic resonance imaging, the intravenously injected FeHF-GOx/CAT was accumulated within tumors. The FeHF-GOx/CAT + US exhibited the highest inhibition effect compared to the FeHF-CAT + US (only SDT) or FeHF-GOx/CAT (only starvation therapy), due to the synergistic effects of SDT and starvation therapy. Therefore, the cascaded dual-enzyme loading strategy can increase the SDT efficiency of FeHF, which may guide further works in the development of efficient nanosonosensitizers.

Synthesis of one-for-all type Cu5FeS4 nanocrystals with improved near infrared photothermal and Fenton effects for simultaneous imaging and therapy of tumor.

CuS materials exhibit excellent near infrared (NIR) photoabsorption and photothermal effect, but they are lack of magnetic resonance imaging (MRI) ability. Fe-based nanomaterials possess MRI capacity, but they usually exhibit poor NIR photoabsorption. In order to solve the above problems, we synthesize three kinds of CuxFeySz samples, including FeS2, CuFeS2 and Cu5FeS4 nanomaterials. With the Cu/Fe ratios increase from 0/1.0 to 1.0/1.0 and 5.0/1.0, the localized surface plasmon resonances (LSPRs) characteristic peaks shift to longer wavelength, and the photothermal transduction efficiencies go up from 24.4% to 36.6% and 45.9%. Thus, Cu5FeS4 is found to be the most excellent sample. Especially, Cu5FeS4 exhibits photothermal-enhanced Fenton effect, which can produce hydroxyl radical (·OH) under a wide pH range (e.g., pH = 5.4-7.4) to realize the chemodynamic effect. In addition, Cu5FeS4 can be employed as an efficient MRI contrast agent. When Cu5FeS4 dispersion is intravenously injected into the mouse, the tumor can be detected by MRI as well as thermal imaging, and eliminated through photothermal-enhanced chemodynamic effect. Therefore, Cu5FeS4 can be used as an efficient "one-for-all" type agent for MRI-guided photothermal-enhanced chemodynamic therapy of tumor.

Long-term clinical benefit of Peg-IFNα and NAs sequential anti-viral therapy on HBV related HCC.

Analysis of the value of long-term antiviral therapy using sequential Peg-IFN therapy and nucleos(t)ide analogues (NAs) improves the prognosis of HBV-related HCC. HBV-related HCC patients were classified into sequential therapy with Peg-IFNα-2a and NAs, and NAs therapy alone. All patients were followed up for 5 years. The survival rate, HCC recurrence rate, Child-Pugh score, and side effects of drugs were evaluated. Firstly, the early and late cumulative survival rate was higher in patients receiving antiviral therapy compared with the control patients (p<0.05). Patients receiving sequential therapy with Peg-IFNα-2a and NAs showed a higher late cumulative survival rate and significantly reduced early and late recurrence rate, compared to those in the NA-alone group (p<0.05). Single NAs therapy only reduced the late recurrence rate in HCC-patients. Secondly, NAs therapy significantly increased the Child-Pugh score after five years of therapy (five-year therapy 7.03±1.50 vs. initial score 6.63±0.85; p<0.05), whereas the sequential therapy with Peg-IFNα-2a and NAs did not greatly alter the Child-Pugh score (6.88±1.26; p>0.05). Compared to the control patients, patients receiving antiviral therapy (NAs alone or sequential therapy with Peg-IFNα-2a and NAs) exhibited a significantly decreased Child-Pugh score (p<0.05). Compared to NAs alone, sequential therapy with Peg-IFNα-2a and NAs provided a more efficient strategy for improving both the five-year survival rate and the two-year or five-year recurrence rate in patients.

Multifunctional Core-Shell Tecto Dendrimers Incorporated with Gold Nanoparticles for Targeted Dual Mode CT/MR Imaging of Tumors.

Development of multifunctional nanoprobes with an excellent imaging performance for precision tumor imaging still remains a great challenge. Here, we report the creation of multifunctional core-shell tecto dendrimers (CSTDs) incorporated with gold nanoparticles (Au NPs) as a platform for dual-mode computed tomography (CT)/magnetic resonance (MR) imaging of tumors. In this work, ß-cyclodextrin (CD)-modified generation 5 poly(amidoamine) (PAMAM) dendrimers were synthesized and entrapped with Au NPs as the core. Then, adamantine (Ad)-modified generation 3 PAMAM dendrimers acted as a shell to form Au NP-entrapped CSTDs (for short, Au CSTDs) through supramolecular host-guest recognition between CD and Ad. The formed Au CSTDs were sequentially modified with Arg-Gly-Asp (RGD) peptide through a spacer of polyethylene glycol (PEG), Gd chelator, and 1,3-propane sultone, followed by chelating Gd (III) ions. The synthesized multifunctional Au CSTDs with a mean size of 11.61 nm possess good colloidal stability, high X-ray attenuation property and high r1 relaxivity (9.414 mM-1 s-1), good antifouling property, and desired cytocompatibility. Due to the RGD-mediated targeting specificity to αvß3 integrin-overexpressing cancer cells, the multifunctional Au CSTDs enable targeted CT/MR dual mode imaging of a breast cancer model in vivo and can be cleared out of body through metabolization pathway with good biosafety profile. The developed multifunctional CSTDs may be applied as an effective CT/MR dual mode imaging probe for accurate diagnosis of various αvß3 integrin-overexpressing cancer types.

Peg-interferon and nucleos(t)ide analogue combination at inception of antiviral therapy improves both anti-HBV efficacy and long-term survival among HBV DNA-positive hepatocellular carcinoma patients after hepatectomy/ablation.

Antiviral therapy has been shown to improve the prognosis of hepatitis B virus (HBV) DNA-positive hepatocellular carcinoma (HCC) after radical treatment, but antiviral treatments require further optimization. This study aimed to evaluate the efficacies of different antiviral strategies with HCC patients after hepatectomy/ablation. This prospective, randomized, controlled and multi-centre trial enrolled HBV DNA-positive primary HCC patients after hepatectomy/ablation between January 2007 and January 2009. Patients were divided into four groups: early combination (entecavir plus Peg-interferon [IFN]α-2a co-administration during year 1); late combination (addition of Peg-IFNα-2a for 48 weeks after 1 year of entecavir); nucleos(t)ide analogue[NA] monotherapy; and non-antiviral treatment. Primary endpoints included recurrence-free survival and overall survival. A total of 447 patients were enrolled. The 2-year and 8-year recurrence-free survival and 8-year overall survival rates were significantly higher in the early combination group than in the other two antiviral groups (P < .05). After 48-week treatment, more patients achieved an HBsAg reduction >1500 IU/mL and the mean HBsAg level was significantly lower in the early combination group compared with the late combination and NA monotherapy groups (P < .05). Multivariate analysis showed that early combination therapy and a reduction in HBsAg by >1500 IU/mL after 48 weeks of therapy correlated with reduced mortality and disease recurrence. Early introduction of combination antiviral treatment may represent a more effective therapeutic strategy for patients with HBV DNA-positive HCC after hepatectomy/ablation. A reduction in HBsAg by >1500 IU/mL after 48-week treatment is associated with reduced mortality and disease recurrence of HBV DNA-positive HCC patients after hepatectomy/ablation.

Expression of protein disulfide isomerase A3 precursor in colorectal cancer.

INTRODUCTION: Over 20% of colorectal cancer (CRC) patients seek medical attention for the first time when they are in the advanced stages of CRC. Thus, early and reliable detection of CRC is critical to early diagnosis of CRC. Protein disulfide isomerase A3 precursor (PDIA3) has been implicated in various types of cancers. However, little is known about PDIA3 in CRC. METHODS: In this study, we screened PDIA3 expression in CRC tissues and cell lines. Small interfering RNA (siRNA) was introduced into SW480 cells to knockdown PDIA3 expression. The effect of PDIA3 in cell growth was evaluated. RESULTS: Significant upregulation of PDIA3 expression was found in CRC tissues as compared with adjacent non-cancer tissues, and was found in established CRC cell lines (SW480, HCT116, CACO2, NCM460 and HT-29). In SW480 cells, knockdown of PDIA3 expression with siRNA resulted in subcellular morphological change, reduced cell proliferation and increased apoptosis. CONCLUSION: PDIA3 inhibition could suppress CRC, likely through inducing apoptosis. PDIA3 could be a potential therapeutic target for CRC.