Mediating effect of circadian rhythm between work stress and sleep quality in Chinese shift-working nurses: A cross-sectional survey.

AIM: This study examined the mediating effect of circadian rhythm amplitude (LV) and stability (FR) between work stress and sleep quality among Chinese shift-working nurses (SWNs). DESIGN: A cross-sectional study. METHODS: Three-hundred and seventy-nine nurses working in shifts were investigated by convenient sampling from six hospitals in Shanghai, China. The mediating effect was analysed using the structural equation model with bootstrapping procedures. RESULTS: Work stress could directly affect shift nurses' sleep quality and indirectly affect sleep quality through circadian rhythm amplitude and stability. The total indirect effects of work stress on sleep quality accounted for 36.7% of the total effect. The study revealed that poor sleep quality is very common among SWNs, which deserves attention. The mediating effect of the circadian rhythm provides new insights to improve sleep quality, not only by lightening the work stress but also by improving circadian rhythm in SWNs.

Difficult Journey to Find the Best Treatment for Homozygous Familial Hypercholesterolemia: Case Report.

Homozygous familial hypercholesterolemia (HoFH) is a rare autosomal recessive genetic disorder. It is difficult to diagnose and treat it at early stage. We present a nine-year-old boy with HoFH from China. At the beginning, he was misdiagnosed as xanthomatosis in the dermatology department of the local hospital, but the disease did not alleviate after three laser ablation operations. Later, blood lipid monitoring, ultrasound of heart and carotid artery were further added in our hospital, and finally the boy was diagnosed with HoFH by genetic testing. A biallelic mutations was observed in the fourth exon of low density lipoprotein receptor (LDLR): c.418G>A (p.E140K). Our patient achieved a relatively satisfactory therapeutic results after a series of lipid-lowering therapies including atorvastatin monotherapy, lipoprotein apheresis and double-filtration plasma pheresis. We found that LDL-C levels obtained 57% reduction from baseline after atorvastatin combined with double-filtration plasma pheresis (DFPP). It was observed that regression of carotid intima-media thickness (cIMT), valve regurgitation and xanthoma occurred after a series of Intensive lipid-lowering therapy.

Vitamin E D-alpha-tocopheryl polyethylene glycol 1000 succinate-conjugated liposomal docetaxel reverses multidrug resistance in breast cancer cells.

OBJECTIVES: Multidrug resistance (MDR) remains a primary challenge in breast cancer treatment. In the present study, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS)-coated docetaxel-loaded liposomes were developed as a novel drug delivery system to reverse MDR and enhance breast cancer therapy compared with the traditional liposomes, DSPE-mPEG-coated liposomes (stealth liposomes) and commercial Taxotere® . KEY FINDINGS: Liposomes were prepared by thin - film dispersion method. Evaluations were performed using human breast cancer MCF-7 and resistant MCF-7/ADR cells. The reversal multidrug-resistant effect was assessed by P-gp inhibition assay, cytotoxicity, cellular uptake and apoptosis assay. RESULTS: The TPGS-chol-liposomes were of an appropriate particle size (140.0 ± 6.0 nm), zeta potential (-0.196 ± 0.08 mv), high encapsulation efficiency (99.0 ± 0.9) and favourable in vitro sustained release. The TPGS-coated liposomes significantly improved cytotoxicity and increased the intracellular accumulation of docetaxel in both types of breast cancer cells. The TPGS-coated liposomes were confirmed to induce apoptosis via a synergistic effect between docetaxel and TPGS. It was demonstrated that TPGS enhanced the intracellular accumulation of drug by inhibiting overexpressed P-glycoprotein. CONCLUSIONS: The TPGS-conjugated liposomes showed significant advantages in vitro compared with the PEG-conjugated liposomes. The TPGS-conjugated liposomes could reverse the MDR and enhance breast cancer therapy.

Synchronized release of bufadienolides in a stable Lutrol F127 based solid dispersion prepared with spray congealing.

OBJECTIVE: The objective of this study was to design and prepare a novel solid dispersion using spray congealing to achieve fast and synchronous dissolution of bufalin, cinobufagin, and resibufogenin, three therapeutically complementary drugs. METHODS: The solid dispersion was characterized with dissolution, X-ray diffractometry, and fourier transform infrared spectroscopy after preparation and storage for four weeks at different temperatures and relative humidity. RESULTS: It was found that all drugs were molecularly dispersed within matrix and had a significant enhancement (∼4-fold higher) of dissolution rate. Furthermore, synchronized release of different drugs from a single carrier was achieved due to the highly molecular dispersibility and the excellent solubilization properties of F127. In addition, the solid dispersion was physically stable for at least four weeks at controlled conditions. But for samples under stress conditions, the results showed that drug-rich phase was formed and storage temperature was the dominant factor in determining stability of the solid dispersion (SD). CONCLUSIONS: These findings highlight the fitness of spray congealing to co-deliver multiple drugs, which open new perspectives for the development of more advanced combination of multiple therapeutic agents, presumably improving the bioavailability and therapeutic efficacy.

Cationic DDA/TDB liposome as a mucosal vaccine adjuvant for uptake by dendritic cells in vitro induces potent humoural immunity.

The cationic dimethyldioctadecylammonium/trehalose 6,6,9-dibehenate (DDA/TDB) liposome is as a strong adjuvant system for vaccines, with remarkable immunostimulatory activity. The mucosal administration of vaccines is a potential strategy for inducing earlier and stronger mucosal immune responses to infectious diseases. In this study, we assessed whether the intranasal administration of cationic DDA/TDB liposomes combined with influenza antigen A (H3N2) can be used as a highly efficacious vaccine to induce mucosal and systemic antibody responses. Confocal laser scanning microscopy and a flow-cytometric analysis showed that the uptake of the cationic DDA/TDB liposome carrier was significantly higher than that of neutral 1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol (DSPC/Chol) or cationic 1,2-dioleoyl-3-trimethylammonium-propane/3ß-(N-[N',N'-dimethylaminoethane]-carbamoyl (DOTAP/DC-Chol) liposomes. Our results indicate that the cationic DDA/TDB liposome is more effective in facilitating its uptake by dendritic cells (DCs) in vitro than the DSPC/Chol or DOTAP/DC-Chol liposome. DCs treated with DDA/TDB liposomes strongly expressed CD80, CD86, and MHC II molecules, whereas those treated with DSPC/Chol or DOTAP/DC-Chol liposomes did not. C57BL/6 mice intranasally immunized with H3N2-encapsulating cationic DDA/TDB liposomes had significantly higher H3N2-specific s-IgA levels in their nasal wash fluid than those treated with other formulations. The DDA/TDB liposomes also simultaneously enhanced the serum IgG IgG2a, IgG1, and IgG2b antibody responses. In summary, DDA/TDB liposomes effectively facilitated their uptake by DCs and DCs maturation in vitro, and induced significantly higher mucosal IgA, systemic IgG, IgG1, and IgG2b antibody titres than other formulations after their intranasal administration in vivo. These results indicate that DDA/TDB liposomes are a promising antigen delivery carrier for clinical antiviral applications.