Sorafenib and tetrakis (4-carboxyphenyl) porphyrin assembled nanoparticles for synergistic targeted chemotherapy and sonodynamic therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is characterized by a high degree of malignancy and mortality. Sorafenib (SOR), a multi-kinase inhibitor, is clinically used in the treatment of HCC. However, SOR suffers from serious side effects and drug resistance. The development of novel therapeutic strategies for HCC therapy is urgently needed. Sonodynamic therapy (SDT) has unique advantages in treating deep tumors due to the merits of deep tissue penetration, low side effects, and the absence of drug resistance. Here, we developed multifunctional nanoparticles (NPs) termed SOR-TCPP@PEG-FA by assembling SOR, tetrakis (4-carboxyphenyl) porphyrin (TCPP), and folic acid (FA)-modified DSPE-PEG. The FA group enhances the tumor targeting capability of these NPs, while TCPP generates ROS under ultrasound (US) irradiation, which are toxic to tumor cells, and SOR with chemotherapeutic effects is released, thus realizing the synergistic SDT and chemotherapy of tumors.

Calcium-enriched carbon nanoparticles loaded with indocyanine green for near-infrared fluorescence imaging-guided synergistic calcium overload, photothermal therapy, and glutathione-depletion-enhanced photodynamic therapy.

Combining phototherapy with other treatments has significantly advanced cancer therapy. Here, we designed and fabricated calcium-enriched carbon nanoparticles (Ca-CNPs) that could effectively deplete glutathione (GSH) and release calcium ions in tumors, thereby enhancing the efficacy of photodynamic therapy (PDT) and the calcium overload effect that leads to mitochondrial dysfunction. Due to the electrostatic interaction, π-π stacking interaction, multiple hydrogen bonds, and microporous structures, indocyanine green (ICG) was loaded onto the surface of Ca-CNPs with a high loading efficiency of 44.7 wt%. The obtained Ca-CNPs@ICG can effectively improve the photostability of ICG while retaining its ability to generate singlet oxygen (1O2) and undergo photothermal conversion (Ca-CNPs@ICG vs. ICG, 45.1% vs. 39.5%). In vitro and in vivo experiments demonstrated that Ca-CNPs@ICG could be used for near-infrared fluorescence imaging-guided synergistic calcium overload, photothermal therapy, and GSH depletion-enhanced PDT. This study sheds light on the improvement of 1O2 utilization efficiency and calcium overload-induced mitochondrial membrane potential imbalance in tumor cells.

The experiences of nurses and midwives who provide surgical abortion care: A qualitative systematic review.

AIM: To synthesize qualitative evidence on nurses' and midwives' experiences in the provision of surgical abortion care. We address three specific questions: (a) what are the experiences of nurses and midwives in surgical abortion care? (b) what are their responses and coping strategies? (c) what are the deficiencies in surgical abortion care? DESIGN: Qualitative studies were synthesized using Thomas and Harden's qualitative thematic synthesis method. DATA SOURCES: Electronic databases, including PubMed, Embase, CINAHL, PsycINFO, Scopus and Web of Science were searched. Grey literature using ProQuest was searched. The databases were searched from inception to 5 August 2020. REVIEW METHODS: The SPIDER (Sample, Phenomenon of Interest, Design, Evaluation and Research type) search tool was used in the literature search. Data synthesis was conducted using the three-stage thematic synthesis method described by Thomas and Harden. RESULTS: 966 studies were identified in the initial search and 18 studies were included. Four analytical themes were generated: 'Providing abortion care requires high emotional labour'; 'Professionalism of abortion care providers'; 'Initiatives in professional development' and 'Improving directions for high-quality abortion care'. CONCLUSION: Nurses and midwives indicated that they require support to enhance psychological health and improve professional skills. Hospital managers should organize regular debriefing or structured group workshops for exchange of practical experiences and strengthening emotional support. More research is required to establish comprehensive training related to abortion care for nurses and midwives. The findings demonstrate that optimization of abortion services should start from hospital management models, pain management and bereavement care. IMPACT: Understanding the experiences of nurses and midwives in abortion provision will inform future clinical practice in surgical abortion care, which would be helpful in improving the professionalism and confidence of abortion providers. Our findings have implications for the training, development of policies and standards for surgical abortion care for nurses and midwives.

SLEEP-GOAL: A multicenter success criteria outcome study on 302 obstructive sleep apnoea (OSA) patients.

OBJECTIVE: To demonstrate SLEEP-GOAL as a more holistic and comprehensive success criterion for Obstructive Sleep Apnoea (OSA) treatment. METHODS: A prospective 7-country clinical trial of 302 OSA patients, who met the selection criteria, and underwent nose, palate and/or tongue surgery. Pre- and post-operative data were recorded and analysed based on both the Sher criteria (apnoea hypopnea index, AHI reduction 50% and <20) and the SLEEP-GOAL. RESULTS: There were 229 males and 73 females, mean age of 42.4±17.3 years, mean BMI 27.9±4.2. The mean VAS score improved from 7.7±1.4 to 2.5±1.7 (p<0.05), mean Epworth score (ESS) improved from 12.2±4.6 to 4.9±2.8 (p<0.05), mean body mass index (BMI) decreased from 27.9±4.2 to 26.1±3.7 (p>0.05), gross weight decreased from 81.9±14.3kg to 76.6±13.3kg. The mean AHI decreased 33.4±18.9 to 14.6±11.0 (p<0.05), mean lowest oxygen saturation (LSAT) improved 79.4±9.2% to 86.9±5.9% (p<0.05), and mean duration of oxygen <90% decreased from 32.6±8.9 minutes to 7.3±2.1 minutes (p<0.05). The overall success rate (302 patients) based on the Sher criteria was 66.2%. Crosstabulation of respective major/minor criteria fulfilment, based on fulfilment of two major and two minor or better, the success rate (based on SLEEP-GOAL) was 69.8%. Based solely on the Sher criteria, 63 patients who had significant blood pressure reduction, 29 patients who had BMI reduction and 66 patients who had clinically significant decrease in duration of oxygen <90% would have been misclassified as "failures". CONCLUSION: AHI as a single parameter is unreliable. Assessing true success outcomes of OSA treatment, requires comprehensive and holistic parameters, reflecting true end-organ injury/function; the SLEEP-GOAL meets these requirements.

Chemistry and bioactivity of Flos Magnoliae, a Chinese herb for rhinitis and sinusitis.

Flos Magnoliae (FM, Chinese name: Xin-yi) is one of the most commonly used Chinese medicinal herbs. It has a long history of clinical use for managing rhinitis, sinusitis and headache. More than 20 different FM species have been used clinically, which makes species identification and evaluation of pharmacological effects of individual chemical ingredients difficult. In this review, we have summarized the current knowledge on FM phytochemistry and its bioactivity activities. The bioactive compounds in FM include both lipid and water-soluble components. More than 90% of the essential components of FM species are terpenoids, including monoterpenes and sesquiterpenes. Lignans and neolignans including tetrahydrofurofuran, tetrahydrofuran and aryltetralin are also present in FM species. A small number of water-soluble compounds have been isolated from Magnolia flower buds, including a benzylisoquinoline alkaloid magnoflorine, an ester ethyl-E-p-hydroxyl-cinnamate and a flavonoid biondnoid. A wide range of pharmacological actions of FM have been reported, including anti-allergy, anti-inflammation and anti-microbial activity. The structure-activity relationship analysis revealed the influence of methylation at position 5 on the 3,7-dioxabicyclo-(3,3,0)-octane backbone of six lignans in antagonistic activities against platelet-activating factor. In addition, the trans stereoisomer fargesin had a much lower bioactivity than the cis stereoisomer demethoxyaschantin. Recent studies have been directed towards the isolation of other bioactive compounds. Further studies on FM may help to develop new anti-inflammatory and anti-allergic drugs.

Inhibitions of mast cell-derived histamine release by different Flos Magnoliae species in rat peritoneal mast cells.

Flos Magnoliae (FM) is a commonly used Chinese medicinal herb for symptomatic relief of allergic rhinitis, sinusitis and headache. A number of FM species have been used as substitutes or adulterants for clinical application, although the differences in their pharmacological actions have not been reported. The present study investigated the effects of six identified FM species M. biondii, M. denudata, M. kobus, M. liliflora, M. sargentiana and M. sprengeri, as well as the marker compounds magnolin and fargesin on compound 48/80-induced histamine release in rat peritoneal mast cells (RPMC) in vitro. Ethanolic extracts of all FM species produced a concentration-dependent inhibition of compound 48/80-induced histamine release in RPMC. The rank order of the IC(50)s was M. biondii

Tracking the development of the N1 from age 3 to adulthood: an examination of speech and non-speech stimuli.

OBJECTIVES: To examine developmental changes in the N1a, N1b and N1c evoked by a tone and a speech consonant (/da/). METHODS: Subjects (n=70 for tones; n=69 for /da/) were grouped into 2 year intervals (age 3-16) and adults. They listened to a tone (2 kHz; 36 ms; 77 dB SL; ISI=600 ms; n=346) or a speech consonant /da/ (female voice recording; 7 ms VOT; 212 ms; 72 dB SL; ISI=600 ms; n=349) while watching a Disney((R)) screensaver. EEG was recorded from 26 electrodes referenced to Cz. An averaged reference was computed off-line. Amplitude and latency data were analyzed with repeated-measures ANOVAs for agexelectrode, and agexN1 component, respectively. RESULTS: Left hemisphere N1a was mature before age 3 whereas the right hemisphere N1a matured around 7-8 years. The vertex N1b showed a parietal distribution which shifted anteriorly with age. The N1c showed age- and stimulus-related changes. The N1c measured over the left hemisphere matured earlier than the N1c over the right hemisphere. The N1c to /da/ matured earlier than that to tones. CONCLUSIONS: Auditory processing undergoes steady and subtle developmental changes. These changes follow different maturational patterns depending on the type of stimuli. The evidence suggests earlier development of the left hemisphere and earlier development of the generators underlying speech processing.

Elevated plasma vitamers of vitamin B6 in patients with chronic renal failure on regular haemodialysis.

Plasma pyridoxal-5'-phosphate (PL-5'-P), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA) were measured by high-performance liquid chromatography (HPLC) in 39 patients (15 male, 24 female) with chronic fenal failure undergoing regular haemodialysis and 46 healthy controls (28 male, 18 female). All three vitamers of vitamin B6 and the metabolite were significantly elevated in the haemodialysis patients. Mean PL-5'-P and PN concentrations were 20 times the mean in controls. Only one patient took a vitamin B6 supplement. In view of the neurotoxicity of supranutritional intakes of PN in normal humans we suggest that supplements of PN be carefully monitored when administered to patients with chronic renal failure.

Erythrocyte eicosapentaenoic acid versus docosahexaenoic acid as a marker for fish and fish oil consumption.

The fatty acid composition of erythrocyte membranes was investigated in 21 healthy men after 6 wk of varying intakes of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). In one experiment, 12 subjects were fed three diets in a 3 x 3 crossover design: an essentially fish-free control diet, a fish diet (0.15 g EPA/d, 0.41 g DHA/d) and the same fish-based diet supplemented with 5 g/d fish oil (Fish + Oil: 0.99 g EPA/d, 0.99 g DHA/d). A 6 wk wash-out period was allowed between each diet. In another experiment, 11 subjects were supplemented with 5 g/d fish oil alone for 6 wk (0.84 g EPA/d, 0.48 g DHA/d). After fish or fish oil feeding, the percent proportion of EPA and DHA in the erythrocyte membranes rose at the expense of linoleic and arachidonic acids. After 6 wk on the fish-based diets, EPA incorporation approached saturation, with the incremental increases being proportional to the amounts supplied by the diets. In contrast, parallel increases were observed for erythrocyte DHA even though the Fish + Oil diet was supplying twice as much DHA as the fish alone diet. These observations imply different metabolic rates for EPA and DHA and their importance is discussed in terms of the value of erythrocyte EPA versus DHA as markers for fish and fish oil consumption.

Persistent changes in the fatty acid composition of erythrocyte membranes after moderate intake of n-3 polyunsaturated fatty acids: study design implications.

To examine the incorporation of n-3 polyunsaturated fatty acids (PUFAs) into erythrocyte membranes during and after moderate n-3 PUFA intake, 12 healthy men were fed three diets for 6-wk periods in a 3 x 3 crossover design, supplying different amounts of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3): a control diet, a fish diet (0.15 g EPA/d, 0.41 g DHA/d), and a fish + oil diet (5 g fish oil/d; 0.99 g EPA/d and 0.99 g DHA/d). A 6-wk washout period was allowed between diets. Between 6 and 12 wk after the fish + oil diet, erythrocyte EPA and DHA were still declining and it was only after 18 wk that erythrocyte EPA had returned to baseline whereas DHA had not. Investigators examining variables that are influenced by altered membrane fatty acid composition should be aware of these prolonged effects when designing studies. Protracted washout periods (greater than 18 wk) make the classic crossover design prohibitive and a parallel design becomes essential.