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Iron-based nanomaterials have shown great promise for tumor ferrotherapy in recent years. However, nanoparticle-induced ferroptosis has low therapeutic efficacy owing to unsatisfactory Fenton reaction activity in a typical tumor microenvironment. In this study, NIR light-activated Fe/PPy-RGD nanopolymers were developed to combine photothermal therapy and ferrotherapy and achieve enhanced antitumor activity. Importantly, Fe/PPy-RGD exhibited excellent therapeutic performance under NIR light activation both in vitro and in vivo. Under irradiation with NIR light, the heat generated by Fe/PPy-RGD not only induced a therapeutic photothermal effect but also enhanced the release of iron ions and the Fenton reaction by inducing ferroptosis. Additionally, by virtue of RGD conjugation and its ultrasmall size, Fe/PPy-RGD could effectively accumulate at tumor sites in living mice after systemic administration and could be monitored via MR imaging. Hence, this study provides a promising approach for integrating ferrotherapy with photothermal therapy to achieve enhanced tumor treatment., (© 2023 Wiley-VCH GmbH.)

Magnetic-based nanomaterials are promising for cancer diagnosis and treatment. Herein, we develop a self-assembled approach for the preparation of a porous magnetic nanosystem, DOX/Mn(0.25)-Fe 3 O 4 -III NPs, which can simultaneously achieve chemotherapy, ferroptosis therapy and MRI to improve the therapeutic efficacy. By tuning its porous structures, whole particle sizes and compositions, this nanosystem possesses both a high drug loading capacity and excellent Fenton reaction activity. Owing to the synergetic catalysis effect of iron and manganese ions, the Fenton catalytic activity of Mn(0.25)-Fe 3 O 4 -III NPs ( K cat = 1.2209 × 10 -2 min -1 ) was six times higher than that of pure porous Fe 3 O 4 NPs ( K cat = 1.9476 × 10 -3 min -1 ), making them greatly advantageous in ferroptosis-inducing cancer therapy. Moreover, we found out that these Mn(0.25)-Fe 3 O 4 -III NPs show a pH-dependent Fenton reaction activity. At acidic tumorous pH, this nanosystem could catalyze H 2 O 2 to produce the cytotoxic ˙OH to kill cancer cells, while in neutral physiological conditions it decomposed H 2 O 2 into biosafe species (H 2 O and O 2 ). In vivo studies demonstrated that DOX/Mn(0.25)-Fe 3 O 4 -III NPs exhibited a significant synergistic anticancer effect of combining chemotherapy and ferroptosis therapy and effective T 2 -weighted MRI with minimal side effects. Therefore, this porous magnetic nanoplatform has a great potential for combined diagnosis and therapy in future clinical applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Objective: To evaluate the effect of "psycho-cardiology" model in nursing care of acute stroke patients with depression., Methods: Seventy-eight acute stroke patients with depression were selected for this prospective study, and they were divided into two groups according to the random number table method. The control group (n=39) were given usual care, and the study group (n=39) were given nursing intervention of "psycho-cardiology" model in addition to usual care. The changes of mental state (Hamilton Depression Scale, HAMD; Hamilton Anxiety Scale, HAMA), the neurological function (National Institute of Health Stroke scale, NIHSS), and the cognitive function (Mini-Mental State Examination, MMSE), the prognostic indicator (Fugl-Meyer Assessment, FMA; Barthel Index, BI) were compared between the two groups before and after the intervention. The incidence of complications and nursing satisfaction were also compared between the two groups., Results: After nursing, the scores of HAMA and HAMD in the study group were significantly lower than those in the control group (P<0.05). The NIHSS score of the study group was significantly lower than that of the control group (P<0.05). The score of MMSE in the study group was significantly higher than that of the control group (P<0.05). The scores of FMA and BI in the study group were significantly higher than those of the control group (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). The nursing satisfaction of the study group was significantly higher than that of the control group (P<0.05)., Conclusion: Nursing intervention of "psycho-cardiology" model for acute stroke patients with depression can effectively alleviate the mental stress of patients, improve neurological function and cognitive function, reduce the occurrence of complications, improve prognosis and nursing satisfaction., Competing Interests: None., (AJTR Copyright © 2021.)

Developing of multifunctional nanoplateforms for simultaneous accurate cancer detection and target therapy is essential in cancer treatment. Herein, we present a facile synthesis of DOX/MNPs-FA nanocomposites for high-performance MRI and tumor-targeted drug delivery. In such core-shell structured DOX/MNPs-FA nanocomposite, the high magnetism of iron oxide core can be tuned and achieved by controlling the Zn 2+ dopant amount, making them suitable as excellent contrasts in T 2 -weighted MR imaging. The outer porous silica shell with large pores about 5.4 nm in diameter possesses high surface area and pore volume. Anticancer drug (DOX molecules) can be stored in the large pore channels and is triggered to be released under acidic condition (pH 4-6). Importantly, the presence of folic acid on the surface of DOX/MNPs-FA allows the targeted delivery of the DOX to tumor cells, and therefore improves tumor chemotherapy efficiency. Our in vitro studies also demonstrated that DOX/MNPs-FA could be efficiently internalized into HeLa cells via the folate receptor-mediated endocytosis, and generate a greater cytotoxicity toward cancer cells compared to free DOX and DOX/MNPs. Therefore, these DOX/MNPs-FA multifunctional nanocomposites have great potential applications for simultaneous tumor diagnosis and targeted chemotherapy.

This study investigated the effects of altered CXCL12/CXCR4 axis on the bone morphogenetic protein 2 (BMP-2)/Smad/runt-related transcription factor 2 (Runx2)/Osterix (Osx) signal axis and osteogenic gene expression during osteogenic differentiation of mesenchymal stem cells (MSCs), to gain understanding of the link between migration and osteogenic differentiation signal axis and MSCs osteogenic differentiation mechanisms. The pHBAd-MCMV- CXCL12-GFP vector (Ad-CXCL12) was constructed and quantitative polymerase chain reaction (qPCR)/western blotting used to determine CXCL12 expression in Ad-CXCL12-transfected MSCs. MSCs were treated with Ad-CXCL12 and AMD3100 (CXCL12 inhibitor) to detect BMP-2/Smad/Runx2/Osterix expression, bone sialoprotein (BSP), osteocalcin (OCN) and osteopontin (OPN) mRNA expression, and alkaline phosphatase (ALP) activity. PCR and sequencing confirmed successful construction of Ad-CXCL12. qPCR and enzyme-linked immunosorbent assay indicated that Ad-CXCL12 transfection promoted CXCL12 expression in MSCs. At 72 hours, Runx2 and Osterix, and Smad1/5/8 mRNA and protein expressions were significantly higher in the Ad-CXCL12 group than in the control group ( P < 0.01). At 1 and 2 weeks, ALP activity and BSP mRNA expression were significantly higher in the Ad-CXCL12 group than in the control group ( P < 0.01), respectively. No significant difference in OCN and OPN mRNA expression was determined between Ad-CXCL12 and control groups ( P > 0.05). At 3 weeks, no significant difference in mineralized nodule staining was observed between groups ( P > 0.05). Changes in the CXCL12/CXCR4 migration axis affected the BMP-2/Smad/Runx2/Osterix axis and BSP , OCN and OPN mRNA expression in early-stage, but not mid-/latestage, MSCs osteogenic differentiation, therefore affecting the ability of MSCs to undergo osteogenic differentiation., Competing Interests: None.

Bone marrow derived mesenchymal stem cells (BM-MSCs) belong a type of pluripotent stem cells and can be induced to differentiate into osteoblasts (OB). Runt-related transcription factor 2 (Runx2) is an osteogenesis specific transcription factor and plays an important role in osteogenesis of BM-MSCs. It can promote the expression of osteogenesis related genes, regulate cell cycle progression, improve bone microenvironment and affect functions of chondrocytes and osteoclasts, which have involvement of a large amount of signal molecules including TGF-β, BMP, Notch, Wnt, Hedgehog, FGF and microRNA. In this paper, we summarize the mechanisms underlying the Runx2 induced osteogenesis of BM-MSCs.

Objective: To observe the method of mechanical ventilation in the chest compressions during cardiopulmonary resuscitation (CPR), and to explore the influence of the flow pattern selection of square-wave and decelerating-wave on airway pressure of patients., Methods: A prospective self-pairing study was conducted. Forty patients undergoing CPR admitted to Department of Emergency of Lishui City Central Hospital from January 2011 to February 2013 were enrolled. Using Respironics Eisprit ventilator, the working mode and parameters of ventilator were set reasonably according to previous research, while the chest compressions was performed in a stable state by the same doctor,. Each patient received different flow, waves, including square-wave and decelerating-wave, and the highest peak airway pressure was recorded as a pair of data when the time-pressure and time-flow waveform were frozen. Two pairs of data by different doctors were collected in each patient. Eighty pairs of data from 40 patients were collected for statistical analysis by paired t test., Results: The highest peak airway pressure of decelerating-wave was (38.15 ± 5.99) cmH₂O (1 cmH₂O=0.098 kPa), which was (5.71 ± 1.98) cmH₂O lower than that of square wave [(43.86 ± 6.68) cmH₂O] with significantly statistical difference (t=22.010, P=0.000). 73.75% patients undergoing square wave with peak airway pressure over 40 cmH₂O were found, but only 45.00% patients were found in decelerating-wave., Conclusions: Because decelerating-wave used in mechanical ventilation during CPR can obviously reduce the peak airway pressure, the occurrence of barotrauma, and the probability of triggering high pressure ventilator alarm, and improve the compliance of ventilator, so decelerating-wave is more reasonable than square-wave.

The oral administration of amphotericin B (AmB) has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO) cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2) was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB.

In this work, we have demonstrated that mesoporous silica-coated Pd@Ag nanoparticles (Pd@Ag@mSiO 2 ) can be used as an excellent nanoplatform for photodynamic therapy (PDT) drug delivery. Photosensitizer molecules, Chlorin e6 (Ce6), are covalently linked to the mesoporous shell and the prepared Pd@Ag@mSiO 2 -Ce6 nanoparticles exhibit excellent water solubility, good stability against leaching and high efficiency in photo-generating cytotoxic singlet oxygen. More importantly, the photothermal effect of Pd@Ag nanoplates under the irradiation of a NIR laser can enhance the uptake of Pd@Ag@mSiO 2 -Ce6 nanoparticles by cells, further increasing the PDT efficiency toward cancer cells. The photothermally enhanced PDT effects were demonstrated both in vitro and in vivo. When the Pd@Ag@mSiO 2 -Ce6 nanoparticles were injected intratumorally into the S180 tumor-bearing mice, the tumors were completely destroyed without recurrence of tumors upon irradiation with both 808 nm and 660 nm lasers, while the irradiation with 808 nm or 660 nm alone did not. These results indicate that the Pd@Ag@mSiO 2 nanoparticles may be a valuable new tool for application in cancer phototherapy.